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  1. Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system.

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    Arriola Apelo, Sebastian I; Neuman, Joshua C; Baar, Emma L; Syed, Faizan A; Cummings, Nicole E; Brar, Harpreet K; Pumper, Cassidy P; Kimple, Michelle E; Lamming, Dudley W

    2016-02-01

    Inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway by the FDA-approved drug rapamycin has been shown to promote lifespan and delay age-related diseases in model organisms including mice. Unfortunately, rapamycin has potentially serious side effects in humans, including glucose intolerance and immunosuppression, which may preclude the long-term prophylactic use of rapamycin as a therapy for age-related diseases. While the beneficial effects of rapamycin are largely mediated by the inhibition of mTOR complex 1 (mTORC1), which is acutely sensitive to rapamycin, many of the negative side effects are mediated by the inhibition of a second mTOR-containing complex, mTORC2, which is much less sensitive to rapamycin. We hypothesized that different rapamycin dosing schedules or the use of FDA-approved rapamycin analogs with different pharmacokinetics might expand the therapeutic window of rapamycin by more specifically targeting mTORC1. Here, we identified an intermittent rapamycin dosing schedule with minimal effects on glucose tolerance, and we find that this schedule has a reduced impact on pyruvate tolerance, fasting glucose and insulin levels, beta cell function, and the immune system compared to daily rapamycin treatment. Further, we find that the FDA-approved rapamycin analogs everolimus and temsirolimus efficiently inhibit mTORC1 while having a reduced impact on glucose and pyruvate tolerance. Our results suggest that many of the negative side effects of rapamycin treatment can be mitigated through intermittent dosing or the use of rapamycin analogs. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  2. Biphasic Rapamycin Effects in Lymphoma and Carcinoma Treatment.

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    Liu, Yang; Pandeswara, Srilakshmi; Dao, Vinh; Padrón, Álvaro; Drerup, Justin M; Lao, Shunhua; Liu, Aijie; Hurez, Vincent; Curiel, Tyler J

    2017-01-15

    mTOR drives tumor growth but also supports T-cell function, rendering the applications of mTOR inhibitors complex especially in T-cell malignancies. Here, we studied the effects of the mTOR inhibitor rapamycin in mouse EL4 T-cell lymphoma. Typical pharmacologic rapamycin (1-8 mg/kg) significantly reduced tumor burden via direct suppression of tumor cell proliferation and improved survival in EL4 challenge independent of antitumor immunity. Denileukin diftitox (DD)-mediated depletion of regulatory T cells significantly slowed EL4 growth in vivo in a T-cell-dependent fashion. However, typical rapamycin inhibited T-cell activation and tumor infiltration in vivo and failed to boost DD treatment effects. Low-dose (LD) rapamycin (75 μg/kg) increased potentially beneficial CD44hiCD62L + CD8 + central memory T cells in EL4 challenge, but without clinical benefit. LD rapamycin significantly enhanced DD treatment efficacy, but DD plus LD rapamycin treatment effects were independent of antitumor immunity. Instead, rapamycin upregulated EL4 IL2 receptor in vitro and in vivo, facilitating direct DD tumor cell killing. LD rapamycin augmented DD efficacy against B16 melanoma and a human B-cell lymphoma, but not against human Jurkat T-cell lymphoma or ID8agg ovarian cancer cells. Treatment effects correlated with IL2R expression, but mechanisms in some tumors were not fully defined. Overall, our data define a distinct, biphasic mechanisms of action of mTOR inhibition at doses that are clinically exploitable, including in T-cell lymphomas. Cancer Res; 77(2); 520-31. ©2016 AACR. ©2016 American Association for Cancer Research.

  3. Rapamycin treatment is associated with an increased apoptosis rate in experimental vein grafts.

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    Schachner, Thomas; Oberhuber, Alexander; Zou, Yping; Tzankov, Alexandar; Ott, Harald; Laufer, Günther; Bonatti, Johannes

    2005-02-01

    Rapamycin is an immunosuppressive agent with marked antiproliferative properties and is effective in reducing in stent restenosis and vein graft neointimal hyperplasia. Apoptosis is one mechanism counterbalancing cellular proliferation. We therefore investigated the role of apoptosis in rapamycin treated vein grafts in a mouse model. C57BL6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a cuff technique. In the treatment group 200 microg of rapamycin were applied locally in pluronic gel. The control group did not receive local treatment. Vein grafts were harvested at 4 weeks postoperatively and underwent morphometric analysis as well as immunohistochemical analysis for apoptosis (TUNEL). In grafted veins without treatment (controls) neointimal thickness was 50 (12-58) microm at 4 weeks postoperatively. In 200 microg rapamycin treated grafts the neointimal thickness was 17 (5-55) microm. Rapamycin treated vein grafts showed a significantly increased rate of apoptosis in the adventitia as compared with controls (P=0.032). In the neointima the apoptosis rate was lower in both groups with no significant difference between rapamycin treated grafts and controls. We conclude that treatment of experimental vein grafts with rapamycin is associated with an increased apoptosis rate in the vascular wall and a trend towards reduction of neointimal hyperplasia. These results suggest that apoptosis may be a beneficial antiproliferative component for the treatment of vein graft disease.

  4. Synergism between the mTOR inhibitor rapamycin and FAK down-regulation in the treatment of acute lymphoblastic leukemia

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    Pei-Jie Shi

    2016-02-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is an aggressive malignant disorder of lymphoid progenitor cells in both children and adults. Although improvements in contemporary therapy and development of new treatment strategies have led to dramatic increases in the cure rate in children with ALL, the relapse rate remains high and the prognosis of relapsed childhood ALL is poor. Molecularly targeted therapies have emerged as the leading treatments in cancer therapy. Multi-cytotoxic drug regimens have achieved success, yet many studies addressing targeted therapies have focused on only one single agent. In this study, we attempted to investigate whether the effect of the mammalian target of rapamycin (mTOR inhibitor rapamycin is synergistic with the effect of focal adhesion kinase (FAK down-regulation in the treatment of ALL. Methods The effect of rapamycin combined with FAK down-regulation on cell proliferation, the cell cycle, and apoptosis was investigated in the human precursor B acute lymphoblastic leukemia cells REH and on survival time and leukemia progression in a non-obese diabetic/severe combined immunodeficiency (NOD/SCID mouse model. Results When combined with FAK down-regulation, rapamycin-induced suppression of cell proliferation, G0/G1 cell cycle arrest, and apoptosis were significantly enhanced. In addition, REH cell-injected NOD/SCID mice treated with rapamycin and a short-hairpin RNA (shRNA to down-regulate FAK had significantly longer survival times and slower leukemia progression compared with mice injected with REH-empty vector cells and treated with rapamycin. Moreover, the B-cell CLL/lymphoma-2 (BCL-2 gene family was shown to be involved in the enhancement, by combined treatment, of REH cell apoptosis. Conclusions FAK down-regulation enhanced the in vitro and in vivo inhibitory effects of rapamycin on REH cell growth, indicating that the simultaneous targeting of mTOR- and FAK-related pathways might offer a novel

  5. Negative Effects of Chronic Rapamycin Treatment on Behavior in a Mouse Model of Fragile X Syndrome

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    Rachel M. Saré

    2018-01-01

    Full Text Available Fragile X syndrome (FXS, the most common form of inherited intellectual disability, is also highly associated with autism spectrum disorders (ASD. It is caused by expansion of a CGG repeat sequence on the X chromosome resulting in silencing of the FMR1 gene. This is modeled in the mouse by deletion of Fmr1 (Fmr1 KO. Fmr1 KO mice recapitulate many of the behavioral features of the disorder including seizure susceptibility, hyperactivity, impaired social behavior, sleep problems, and learning and memory deficits. The mammalian target of rapamycin pathway (mTORC1 is upregulated in Fmr1 KO mice and is thought to be important for the pathogenesis of this disorder. We treated Fmr1 KO mice chronically with an mTORC1 inhibitor, rapamycin, to determine if rapamycin treatment could reverse behavioral phenotypes. We performed open field, zero maze, social behavior, sleep, passive avoidance, and audiogenic seizure testing. We found that pS6 was upregulated in Fmr1 KO mice and normalized by rapamycin treatment, but, except for an anxiogenic effect, it did not reverse any of the behavioral phenotypes examined. In fact, rapamycin treatment had an adverse effect on sleep and social behavior in both control and Fmr1 KO mice. These results suggest that targeting the mTOR pathway in FXS is not a good treatment strategy and that other pathways should be considered.

  6. Effects of rapamycin treatment after controlled cortical impact injury on neurogenesis and synaptic reorganization in the mouse dentate gyrus

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    Corwin R Butler

    2015-11-01

    Full Text Available Post-traumatic epilepsy (PTE is one consequence of traumatic brain injury (TBI. A prominent cell signaling pathway activated in animal models of both TBI and epilepsy is the mammalian target of rapamycin (mTOR. Inhibition of mTOR with rapamycin has shown promise as a potential modulator of epileptogenesis in several animal models of epilepsy, but cellular mechanisms linking mTOR expression and epileptogenesis are unclear. In this study, the role of mTOR in modifying functional hippocampal circuit reorganization after focal TBI induced by controlled cortical impact was investigated. Rapamycin (3 or 10 mg/kg, an inhibitor of mTOR signaling, was administered by intraperitoneal injection beginning on the day of injury and continued daily until tissue collection. Relative to controls, rapamycin treatment reduced dentate granule cell area in the hemisphere ipsilateral to the injury two weeks post-injury. Brain injury resulted in a significant increase in doublecortin immunolabeling in the dentate gyrus ipsilateral to the injury, indicating increased neurogenesis shortly after TBI. Rapamycin treatment prevented the increase in doublecortin labeling, with no overall effect on Fluoro-Jade B staining in the ipsilateral hemisphere, suggesting that rapamycin treatment reduced posttraumatic neurogenesis but did not prevent cell loss after injury. At later times post-injury (8-13 weeks, evidence of mossy fiber sprouting and increased recurrent excitation of dentate granule cells was detected, which were attenuated by rapamycin treatment. Rapamycin treatment also diminished seizure prevalence relative to vehicle-treated controls after TBI. Collectively, these results support a role for adult neurogenesis in PTE development and suggest that suppression of epileptogenesis by mTOR inhibition includes effects on post-injury neurogenesis.

  7. Prenatal Mechanistic Target of Rapamycin Complex 1 (m TORC1) Inhibition by Rapamycin Treatment of Pregnant Mice Causes Intrauterine Growth Restriction and Alters Postnatal Cardiac Growth, Morphology, and Function.

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    Hennig, Maria; Fiedler, Saskia; Jux, Christian; Thierfelder, Ludwig; Drenckhahn, Jörg-Detlef

    2017-08-04

    Fetal growth impacts cardiovascular health throughout postnatal life in humans. Various animal models of intrauterine growth restriction exhibit reduced heart size at birth, which negatively influences cardiac function in adulthood. The mechanistic target of rapamycin complex 1 (mTORC1) integrates nutrient and growth factor availability with cell growth, thereby regulating organ size. This study aimed at elucidating a possible involvement of mTORC1 in intrauterine growth restriction and prenatal heart growth. We inhibited mTORC1 in fetal mice by rapamycin treatment of pregnant dams in late gestation. Prenatal rapamycin treatment reduces mTORC1 activity in various organs at birth, which is fully restored by postnatal day 3. Rapamycin-treated neonates exhibit a 16% reduction in body weight compared with vehicle-treated controls. Heart weight decreases by 35%, resulting in a significantly reduced heart weight/body weight ratio, smaller left ventricular dimensions, and reduced cardiac output in rapamycin- versus vehicle-treated mice at birth. Although proliferation rates in neonatal rapamycin-treated hearts are unaffected, cardiomyocyte size is reduced, and apoptosis increased compared with vehicle-treated neonates. Rapamycin-treated mice exhibit postnatal catch-up growth, but body weight and left ventricular mass remain reduced in adulthood. Prenatal mTORC1 inhibition causes a reduction in cardiomyocyte number in adult hearts compared with controls, which is partially compensated for by an increased cardiomyocyte volume, resulting in normal cardiac function without maladaptive left ventricular remodeling. Prenatal rapamycin treatment of pregnant dams represents a new mouse model of intrauterine growth restriction and identifies an important role of mTORC1 in perinatal cardiac growth. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  8. Effects of rapamycin and curcumin treatment on the development of epilepsy after electrically induced status epilepticus in rats

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    Drion, Cato M.; Borm, Lars E.; Kooijman, Lieneke; Aronica, Eleonora; Wadman, Wytse J.; Hartog, Aloysius F.; van Vliet, Erwin A.; Gorter, Jan A.

    2016-01-01

    Inhibition of the mammalian target of rapamycin (mTOR) pathway has been suggested as a possible antiepileptogenic strategy in temporal lobe epilepsy (TLE). Here we aim to elucidate whether mTOR inhibition has antiepileptogenic and/or antiseizure effects using different treatment strategies in the

  9. Effects of rapamycin and curcumin treatment on the development of epilepsy after electrically induced status epilepticus in rats.

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    Drion, C.M.; Borm, L.E.; Kooijman, L.; Aronica, E.; Wadman, W.J.; Hartog, A.F.; van Vliet, E.A.; Gorter, J.A.

    2016-01-01

    OBJECTIVE: Inhibition of the mammalian target of rapamycin (mTOR) pathway has been suggested as a possible antiepileptogenic strategy in temporal lobe epilepsy (TLE). Here we aim to elucidate whether mTOR inhibition has antiepileptogenic and/or antiseizure effects using different treatment

  10. Co-delivery of rapamycin- and piperine-loaded polymeric nanoparticles for breast cancer treatment.

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    Katiyar, Sameer S; Muntimadugu, Eameema; Rafeeqi, Towseef Amin; Domb, Abraham J; Khan, Wahid

    2016-09-01

    P-glycoprotein (P-gp) efflux is the major cause of multidrug resistance (MDR) in tumors when using anticancer drugs, moreover, poor bioavailability of few drugs is also due to P-gp efflux in the gut. Rapamycin (RPM) is in the clinical trials for breast cancer treatment, but its P-gp substrate property leads to poor oral bioavailability and efficacy. The objective of this study is to formulate and evaluate nanoparticles of RPM, along with a chemosensitizer (piperine, PIP) for improved oral bioavailability and efficacy. Poly(d,l-lactide-co-glycolide) (PLGA) was selected as polymer as it has moderate MDR reversal activity, which may provide additional benefits. The nanoprecipitation method was used to prepare PLGA nanoparticles with particle size below 150 nm, loaded with both drugs (RPM and PIP). Prepared nanoparticles showed sustained in vitro drug release for weeks, with initial release kinetics of zero order with non-Fickian transport, subsequently followed by Higuchi kinetics with Fickian diffusion. An everted gut sac method was used to study the effect of P-gp efflux on drug transport. This reveals that the uptake of the RPM (P-gp substrate) has been increased in the presence of chemosensitizer. Pharmacokinetic studies showed better absorption profile of RPM from polymeric nanoparticles compared to its suspension counterpart and improved bioavailability of 4.8-folds in combination with a chemosensitizer. An in vitro cell line study indicates higher efficacy of nanoparticles compared to free drug solution. Results suggest that the use of a combination of PIP with RPM nanoparticles would be a promising approach in the treatment of breast cancer.

  11. Topical rapamycin as a treatment for fibrofolliculomas in Birt-Hogg-Dubé syndrome: a double-blind placebo-controlled randomized split-face trial.

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    Lieke M C Gijezen

    Full Text Available Birt-Hogg-Dubé syndrome (BHD is a rare autosomal dominant disorder characterised by the occurrence of benign, mostly facial, skin tumours called fibrofolliculomas, multiple lung cysts, spontaneous pneumothorax and an increased renal cancer risk. Current treatments for fibrofolliculomas have high rates of recurrence and carry a risk of complications. It would be desirable to have a treatment that could prevent fibrofolliculomas from growing. Animal models of BHD have previously shown deregulation of mammalian target of rapamycin (mTOR. Topical use of the mTOR inhibitor rapamycin is an effective treatment for the skin tumours (angiofibromas in tuberous sclerosis complex, which is also characterised by mTOR deregulation. In this study we aimed to determine if topical rapamycin is also an effective treatment for fibrofolliculomas in BHD.We performed a double blinded, randomised, facial left-right controlled trial of topical rapamycin 0.1% versus placebo in 19 BHD patients. Trial duration was 6 months. The primary outcome was cosmetic improvement as measured by doctors and patients. Changes in fibrofolliculoma number and size were also measured, as was occurrence of side effects.No change in cosmetic status of fibrofolliculomas was reported in the majority of cases for the rapamycin treated (79% by doctors, 53% by patients as well as the placebo treated facial sides (both 74%. No significant differences between rapamycin and placebo treated facial halves were observed (p = 1.000 for doctors opinion, p = 0.344 for patients opinion. No significant difference in fibrofolliculoma number or change in size of the fibrofolliculomas was seen after 6 months. Side effects occurred more often after rapamycin treatment (68% of patients than after placebo (58% of patients; p = 0.625. A burning sensation, erythema, itching and dryness were most frequently reported.This study provides no evidence that treatment of fibrofolliculomas with topical

  12. Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment.

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    Wang, Tina; Tsui, Brian; Kreisberg, Jason F; Robertson, Neil A; Gross, Andrew M; Yu, Michael Ku; Carter, Hannah; Brown-Borg, Holly M; Adams, Peter D; Ideker, Trey

    2017-03-28

    Global but predictable changes impact the DNA methylome as we age, acting as a type of molecular clock. This clock can be hastened by conditions that decrease lifespan, raising the question of whether it can also be slowed, for example, by conditions that increase lifespan. Mice are particularly appealing organisms for studies of mammalian aging; however, epigenetic clocks have thus far been formulated only in humans. We first examined whether mice and humans experience similar patterns of change in the methylome with age. We found moderate conservation of CpG sites for which methylation is altered with age, with both species showing an increase in methylome disorder during aging. Based on this analysis, we formulated an epigenetic-aging model in mice using the liver methylomes of 107 mice from 0.2 to 26.0 months old. To examine whether epigenetic aging signatures are slowed by longevity-promoting interventions, we analyzed 28 additional methylomes from mice subjected to lifespan-extending conditions, including Prop1 df/df dwarfism, calorie restriction or dietary rapamycin. We found that mice treated with these lifespan-extending interventions were significantly younger in epigenetic age than their untreated, wild-type age-matched controls. This study shows that lifespan-extending conditions can slow molecular changes associated with an epigenetic clock in mice livers.

  13. Four-week rapamycin treatment improves muscular dystrophy in a fukutin-deficient mouse model of dystroglycanopathy.

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    Foltz, Steven J; Luan, Junna; Call, Jarrod A; Patel, Ankit; Peissig, Kristen B; Fortunato, Marisa J; Beedle, Aaron M

    2016-01-01

    Secondary dystroglycanopathies are a subset of muscular dystrophy caused by abnormal glycosylation of α-dystroglycan (αDG). Loss of αDG functional glycosylation prevents it from binding to laminin and other extracellular matrix receptors, causing muscular dystrophy. Mutations in a number of genes, including FKTN (fukutin), disrupt αDG glycosylation. We analyzed conditional Fktn knockout (Fktn KO) muscle for levels of mTOR signaling pathway proteins by Western blot. Two cohorts of Myf5-cre/Fktn KO mice were treated with the mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) for 4 weeks and evaluated for changes in functional and histopathological features. Muscle from 17- to 25-week-old fukutin-deficient mice has activated mTOR signaling. However, in tamoxifen-inducible Fktn KO mice, factors related to Akt/mTOR signaling were unchanged before the onset of dystrophic pathology, suggesting that Akt/mTOR signaling pathway abnormalities occur after the onset of disease pathology and are not causative in early dystroglycanopathy development. To determine any pharmacological benefit of targeting mTOR signaling, we administered RAPA daily for 4 weeks to Myf5/Fktn KO mice to inhibit mTORC1. RAPA treatment reduced fibrosis, inflammation, activity-induced damage, and central nucleation, and increased muscle fiber size in Myf5/Fktn KO mice compared to controls. RAPA-treated KO mice also produced significantly higher torque at the conclusion of dosing. These findings validate a misregulation of mTOR signaling in dystrophic dystroglycanopathy skeletal muscle and suggest that such signaling molecules may be relevant targets to delay and/or reduce disease burden in dystrophic patients.

  14. FK506 Binding Protein Mediates Glioma Cell Growth and Sensitivity to Rapamycin Treatment by Regulating NF-κB Signaling Pathway

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    Wei Jiang

    2008-03-01

    Full Text Available FK506 binding protein 5 (FKBP5 belongs to a family of immunophilins named for their ability to bind immunosuppressive drugs, also known as peptidyl-prolyl cis-trans isomerases, and also with chaperones to help protein folding. Using glioma cDNA microarray analysis, we found that FKBP5 was overexpressed in glioma tumors. This finding was further validated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. The roles of FKBP5 in glioma cells were then examined. We found that cell growth was suppressed after FKBP5 expression was inhibited by short interfering RNA transfection and enhanced by FKBP5 overexpression. Electrophoretic mobility shift assay showed that nuclear factor-kappa B (NF-κB and DNA binding was enhanced by FKBP5 overexpression. The expression level of I-kappa B alpha and phosphorylated NF-κB was regulated by the expression of FKBP5. These data suggest that FKBP5 is involved in NF-κB pathway activation in glioma cells. In addition, FKBP5 overexpression in rapamycin-sensitive U87 cells blocked the cells' response to rapamycin treatment, whereas rapamycin-resistant glioma cells, both PTEN-positive and -negative, were synergistically sensitive to rapamycin after FKBP5 was knocked down, suggesting that the FKBP5 regulates glioma cell response to rapamycin treatment. In conclusion, our study demonstrates that FKBP5 plays an important role in glioma growth and chemoresistance through regulating signal transduction of the NF-κB pathway.

  15. A randomized controlled trial to establish effects of short-term rapamycin treatment in 24 middle-aged companion dogs.

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    Urfer, Silvan R; Kaeberlein, Tammi L; Mailheau, Susan; Bergman, Philip J; Creevy, Kate E; Promislow, Daniel E L; Kaeberlein, Matt

    2017-04-01

    Age is the single greatest risk factor for most causes of morbidity and mortality in humans and their companion animals. As opposed to other model organisms used to study aging, dogs share the human environment, are subject to similar risk factors, receive comparable medical care, and develop many of the same age-related diseases humans do. In this study, 24 middle-aged healthy dogs received either placebo or a non-immunosuppressive dose of rapamycin for 10 weeks. All dogs received clinical and hematological exams before, during, and after the trial and echocardiography before and after the trial. Our results showed no clinical side effects in the rapamycin-treated group compared to dogs receiving the placebo. Echocardiography suggested improvement in both diastolic and systolic age-related measures of heart function (E/A ratio, fractional shortening, and ejection fraction) in the rapamycin-treated dogs. Hematological values remained within the normal range for all parameters studied; however, the mean corpuscular volume (MCV) was decreased in rapamycin-treated dogs. Based on these results, we will test rapamycin on a larger dog cohort for a longer period of time in order to validate its effects on cardiac function and to determine whether it can significantly improve healthspan and reduce mortality in companion dogs.

  16. Long-term effects of rapamycin treatment on insulin mediated phosphorylation of Akt/PKB and glycogen synthase activity

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    Varma, Shailly; Shrivastav, Anuraag; Changela, Sheena; Khandelwal, Ramji L.

    2008-01-01

    Protein kinase B (Akt/PKB) is a Ser/Thr kinase that is involved in the regulation of cell proliferation/survival through mammalian target of rapamycin (mTOR) and the regulation of glycogen metabolism through glycogen synthase kinase 3β (GSK-3β) and glycogen synthase (GS). Rapamycin is an inhibitor of mTOR. The objective of this study was to investigate the effects of rapamycin pretreatment on the insulin mediated phosphorylation of Akt/PKB phosphorylation and GS activity in parental HepG2 and HepG2 cells with overexpression of constitutively active Akt1/PKB-α (HepG2-CA-Akt/PKB). Rapamycin pretreatment resulted in a decrease (20-30%) in the insulin mediated phosphorylation of Akt1 (Ser 473) in parental HepG2 cells but showed an upregulation of phosphorylation in HepG2-CA-Akt/PKB cells. Rictor levels were decreased (20-50%) in parental HepG2 cells but were not significantly altered in the HepG2-CA-Akt/PKB cells. Furthermore, rictor knockdown decreased the phosphorylation of Akt (Ser 473) by 40-60% upon rapamycin pretreatment. GS activity followed similar trends as that of phosphorylated Akt and so with rictor levels in these cells pretreated with rapamycin; parental HepG2 cells showed a decrease in GS activity, whereas as HepG2-CA-Akt/PKB cells showed an increase in GS activity. The changes in the levels of phosphorylated Akt/PKB (Ser 473) correlated with GS and protein phoshatase-1 activity

  17. Combined treatment of rapamycin and dietary restriction has a larger effect on the transcriptome and metabolome of liver.

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    Fok, Wilson C; Bokov, Alex; Gelfond, Jonathan; Yu, Zhen; Zhang, Yiqiang; Doderer, Mark; Chen, Yidong; Javors, Martin; Wood, William H; Zhang, Yongqing; Becker, Kevin G; Richardson, Arlan; Pérez, Viviana I

    2014-04-01

    Rapamycin (Rapa) and dietary restriction (DR) have consistently been shown to increase lifespan. To investigate whether Rapa and DR affect similar pathways in mice, we compared the effects of feeding mice ad libitum (AL), Rapa, DR, or a combination of Rapa and DR (Rapa + DR) on the transcriptome and metabolome of the liver. The principal component analysis shows that Rapa and DR are distinct groups. Over 2500 genes are significantly changed with either Rapa or DR when compared with mice fed AL; more than 80% are unique to DR or Rapa. A similar observation was made when genes were grouped into pathways; two-thirds of the pathways were uniquely changed by DR or Rapa. The metabolome shows an even greater difference between Rapa and DR; no metabolites in Rapa-treated mice were changed significantly from AL mice, whereas 173 metabolites were changed in the DR mice. Interestingly, the number of genes significantly changed by Rapa + DR when compared with AL is twice as large as the number of genes significantly altered by either DR or Rapa alone. In summary, the global effects of DR or Rapa on the liver are quite different and a combination of Rapa and DR results in alterations in a large number of genes and metabolites that are not significantly changed by either manipulation alone, suggesting that a combination of DR and Rapa would be more effective in extending longevity than either treatment alone. © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  18. Comparison of three rapamycin dosing schedules in A/J Tsc2+/- mice and improved survival with angiogenesis inhibitor or asparaginase treatment in mice with subcutaneous tuberous sclerosis related tumors

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    Dabora Sandra L

    2010-02-01

    Full Text Available Abstract Background Tuberous Sclerosis Complex (TSC is an autosomal dominant tumor disorder characterized by the growth of hamartomas in various organs including the kidney, brain, skin, lungs, and heart. Rapamycin has been shown to reduce the size of kidney angiomyolipomas associated with TSC; however, tumor regression is incomplete and kidney angiomyolipomas regrow after cessation of treatment. Mouse models of TSC2 related tumors are useful for evaluating new approaches to drug therapy for TSC. Methods In cohorts of Tsc2+/- mice, we compared kidney cystadenoma severity in A/J and C57BL/6 mouse strains at both 9 and 12 months of age. We also investigated age related kidney tumor progression and compared three different rapamycin treatment schedules in cohorts of A/J Tsc2+/- mice. In addition, we used nude mice bearing Tsc2-/- subcutaneous tumors to evaluate the therapeutic utility of sunitinib, bevacizumab, vincristine, and asparaginase. Results TSC related kidney disease severity is 5-10 fold higher in A/J Tsc2+/- mice compared with C57BL/6 Tsc2+/- mice. Similar to kidney angiomyolipomas associated with TSC, the severity of kidney cystadenomas increases with age in A/J Tsc2+/- mice. When rapamycin dosing schedules were compared in A/J Tsc2+/- cohorts, we observed a 66% reduction in kidney tumor burden in mice treated daily for 4 weeks, an 82% reduction in mice treated daily for 4 weeks followed by weekly for 8 weeks, and an 81% reduction in mice treated weekly for 12 weeks. In the Tsc2-/- subcutaneous tumor mouse model, vincristine is not effective, but angiogenesis inhibitors (sunitinib and bevacizumab and asparaginase are effective as single agents. However, these drugs are not as effective as rapamycin in that they increased median survival only by 24-27%, while rapamycin increased median survival by 173%. Conclusions Our results indicate that the A/J Tsc2+/- mouse model is an improved, higher through-put mouse model for future TSC

  19. Rapamycin Synergizes with Cisplatin in Antiendometrial Cancer Activation by Improving IL-27–Stimulated Cytotoxicity of NK Cells

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    Wen-Jie Zhou

    2018-01-01

    Full Text Available Natural killer (NK cell function is critical for controlling initial tumor growth and determining chemosensitivity of the tumor. A synergistic relationship between rapamycin and cisplatin in uterine endometrial cancer (UEC in vitro has been reported, but the mechanism and the combined therapeutic strategy for endometrial cancer (EC are still unknown. We found a positive correlation between the level of IL-27 and the differentiated stage of UEC. The increase of IL-27 in uterine endometrial cancer cell (UECC lines (Ishikawa, RL95-2 and KLE led to a high cytotoxic activity of NK cells to UECC in the co-culture system. Exposure with rapamycin enhanced the cytotoxicity of NK cells by upregulating the expression of IL-27 in UECC and IL-27 receptors (IL-27Rs: WSX-1 and gp130 on NK cells and further restricted the growth of UEC in Ishikawa-xenografted nude mice. In addition, treatment with rapamycin resulted in an increased autophagy level of UECC, and IL-27 enhanced this ability of rapamycin. Cisplatin-mediated NK cells' cytotoxic activity and anti-UEC activation were independent of IL-27; however, the combination of rapamycin and cisplatin led to a higher cytotoxic activity of NK cells, smaller UEC volume and longer survival rate in vivo. These results suggest that rapamycin and cisplatin synergistically activate the cytotoxicity of NK cells and inhibit the progression of UEC in both an IL-27–dependent and –independent manner. This provides a scientific basis for potential rapamycin-cisplatin combined therapeutic strategies targeted to UEC, especially for the patients with low differentiated stage or abnormally low level of IL-27.

  20. The mTOR inhibitor rapamycin has limited acute anticonvulsant effects in mice.

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    Adam L Hartman

    Full Text Available The mammalian target of rapamycin (mTOR pathway integrates signals from different nutrient sources, including amino acids and glucose. Compounds that inhibit mTOR kinase activity such as rapamycin and everolimus can suppress seizures in some chronic animal models and in patients with tuberous sclerosis. However, it is not known whether mTOR inhibitors exert acute anticonvulsant effects in addition to their longer term antiepileptogenic effects. To gain insights into how rapamycin suppresses seizures, we investigated the anticonvulsant activity of rapamycin using acute seizure tests in mice.Following intraperitoneal injection of rapamycin, normal four-week-old male NIH Swiss mice were evaluated for susceptibility to a battery of acute seizure tests similar to those currently used to screen potential therapeutics by the US NIH Anticonvulsant Screening Program. To assess the short term effects of rapamycin, mice were seizure tested in ≤ 6 hours of a single dose of rapamycin, and for longer term effects of rapamycin, mice were tested after 3 or more daily doses of rapamycin.The only seizure test where short-term rapamycin treatment protected mice was against tonic hindlimb extension in the MES threshold test, though this protection waned with longer rapamycin treatment. Longer term rapamycin treatment protected against kainic acid-induced seizure activity, but only at late times after seizure onset. Rapamycin was not protective in the 6 Hz or PTZ seizure tests after short or longer rapamycin treatment times. In contrast to other metabolism-based therapies that protect in acute seizure tests, rapamycin has limited acute anticonvulsant effects in normal mice.The efficacy of rapamycin as an acute anticonvulsant agent may be limited. Furthermore, the combined pattern of acute seizure test results places rapamycin in a third category distinct from both fasting and the ketogenic diet, and which is more similar to drugs acting on sodium channels.

  1. Mammalian Target of Rapamycin Inhibition With Rapamycin Mitigates Radiation-Induced Pulmonary Fibrosis in a Murine Model

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    Chung, Eun Joo [Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); Sowers, Anastasia; Thetford, Angela [Radiation Biology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); McKay-Corkum, Grace; Chung, Su I. [Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); Mitchell, James B. [Radiation Biology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States); Citrin, Deborah E., E-mail: citrind@mail.nih.gov [Radiation Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland (United States)

    2016-11-15

    Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a late toxicity of therapeutic radiation. Signaling of the mammalian target of rapamycin drives several processes implicated in RIPF, including inflammatory cytokine production, fibroblast proliferation, and epithelial senescence. We sought to determine if mammalian target of rapamycin inhibition with rapamycin would mitigate RIPF. Methods and Materials: C57BL/6NCr mice received a diet formulated with rapamycin (14 mg/kg food) or a control diet 2 days before and continuing for 16 weeks after exposure to 5 daily fractions of 6 Gy of thoracic irradiation. Fibrosis was assessed with Masson trichrome staining and hydroxyproline assay. Cytokine expression was evaluated by quantitative real-time polymerase chain reaction. Senescence was assessed by staining for β-galactosidase activity. Results: Administration of rapamycin extended the median survival of irradiated mice compared with the control diet from 116 days to 156 days (P=.006, log-rank test). Treatment with rapamycin reduced hydroxyproline content compared with the control diet (irradiation plus vehicle, 45.9 ± 11.8 μg per lung; irradiation plus rapamycin, 21.4 ± 6.0 μg per lung; P=.001) and reduced visible fibrotic foci. Rapamycin treatment attenuated interleukin 1β and transforming growth factor β induction in irradiated lungs compared with the control diet. Type II pneumocyte senescence after irradiation was reduced with rapamycin treatment at 16 weeks (3-fold reduction at 16 weeks, P<.001). Conclusions: Rapamycin protected against RIPF in a murine model. Rapamycin treatment reduced inflammatory cytokine expression, extracellular matrix production, and senescence in type II pneumocytes.

  2. Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island.

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    Arriola Apelo, Sebastian I; Lamming, Dudley W

    2016-07-01

    Rapamycin (sirolimus) is a macrolide immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) protein kinase and extends lifespan in model organisms including mice. Although rapamycin is an FDA-approved drug for select indications, a diverse set of negative side effects may preclude its wide-scale deployment as an antiaging therapy. mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Over the past decade, it has become clear that although genetic and pharmacological inhibition of mTORC1 extends lifespan and delays aging, inhibition of mTORC2 has negative effects on mammalian health and longevity and is responsible for many of the negative side effects of rapamycin. In this review, we discuss recent advances in understanding the molecular and physiological effects of rapamycin treatment, and we discuss how the use of alternative rapamycin treatment regimens or rapamycin analogs has the potential to mitigate the deleterious side effects of rapamycin treatment by more specifically targeting mTORC1. Although the side effects of rapamycin are still of significant concern, rapid progress is being made in realizing the revolutionary potential of rapamycin-based therapies for the treatment of diseases of aging. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Prevention of age-related macular degeneration-like retinopathy by rapamycin in rats.

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    Kolosova, Nataliya G; Muraleva, Natalia A; Zhdankina, Anna A; Stefanova, Natalia A; Fursova, Anzhela Z; Blagosklonny, Mikhail V

    2012-08-01

    Age-related macular degeneration, a neurodegenerative and vascular retinal disease, is the most common cause of blindness in the Western countries. Evidence accumulates that target of rapamycin is involved in aging and age-related diseases, including neurodegeneration. The target of rapamycin inhibitor, rapamycin, suppresses the senescent cell phenotype and extends life span in diverse species, including mice. Rapamycin decreases senescence-associated phenotypes in retinal pigment epithelial cells in culture. Herein, we investigated the effect of rapamycin on spontaneous retinopathy in senescence-accelerated OXYS rats, an animal model of age-related macular degeneration. Rats were treated with either 0.1 or 0.5 mg/kg rapamycin, which was given orally as a food mixture. In a dose-dependent manner, rapamycin decreased the incidence and severity of retinopathy. Rapamycin improved some (but not all) histological abnormalities associated with retinopathy. Thus, in retinal pigment epithelial cell layers, rapamycin decreased nuclei heterogeneity and normalized intervals between nuclei. In photoreceptor cells, associated neurons, and radial glial cells, rapamycin prevented nuclear and cellular pyknosis. More important, rapamycin prevented destruction of ganglionar neurons in the retina. Rapamycin did not exert any adverse effects on the retina in control disease-free Wistar rats. Taken together, our data suggest the therapeutic potential of rapamycin for treatment and prevention of retinopathy. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Feasibility of LED-Assisted CMOS Camera: Contrast Estimation for Laser Tattoo Treatment

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    Ngot Thi Pham

    2018-04-01

    Full Text Available Understanding the residual tattoo ink in skin after laser treatment is often critical for achieving good clinical outcomes. The current study aims to investigate the feasibility of a light-emitting diode (LED-assisted CMOS camera to estimate the relative variations in tattoo contrast after the laser treatment. Asian mice were tattooed using two color inks (black and red. The LED illumination was a separate process from the laser tattoo treatment. Images of the ink tattoos in skin were acquired under the irradiation of three different LED colors (red, green, and blue for pre- and post-treatment. The degree of contrast variation due to the treatment was calculated and compared with the residual tattoo distribution in the skin. The black tattoo demonstrated that the contrast consistently decreased after the laser treatment for all LED colors. However, the red tattoo showed that the red LED yielded an insignificant contrast whereas the green and blue LEDs induced a 30% (p < 0.001 and 26% (p < 0.01 contrast reduction between the treatment conditions, respectively. The proposed LED-assisted CMOS camera can estimate the relative variations in the image contrast before and after the laser tattoo treatment.

  5. Rapamycin potentiates cytotoxicity by docetaxel possibly through downregulation of Survivin in lung cancer cells

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    Li Hui

    2011-03-01

    Full Text Available Abstract Background To elucidate whether rapamycin, the inhibitor of mTOR (mammalian target of rapamycin, can potentiate the cytotoxic effect of docetaxel in lung cancer cells and to probe the mechanism underlying such enhancement. Methods Lung cancer cells were treated with docetaxel and rapamycin. The effect on the proliferation of lung cancer cells was evaluated using the MTT method, and cell apoptosis was measured by flow cytometry. Protein expression and level of phosphorylation were assayed using Western Blot method. Results Co-treatment of rapamycin and docetaxel was found to favorably enhance the cytotoxic effect of docetaxel in four lung cancer cell lines. This tumoricidal boost is associated with a reduction in the expression and phosphorylation levels of Survivin and ERK1/2, respectively. Conclusion The combined application of mTOR inhibitor and docetaxel led to a greater degree of cancer cell killing than that by either compound used alone. Therefore, this combination warrants further investigation in its suitability of serving as a novel therapeutic scheme for treating advanced and recurrent lung cancer patients.

  6. The rapamycin-binding domain of the protein kinase mammalian target of rapamycin is a destabilizing domain.

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    Edwards, Sarah R; Wandless, Thomas J

    2007-05-04

    Rapamycin is an immunosuppressive drug that binds simultaneously to the 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR) kinase. The resulting ternary complex has been used to conditionally perturb protein function, and one such method involves perturbation of a protein of interest through its mislocalization. We synthesized two rapamycin derivatives that possess large substituents at the C-16 position within the FRB-binding interface, and these derivatives were screened against a library of FRB mutants using a three-hybrid assay in Saccharomyces cerevisiae. Several FRB mutants responded to one of the rapamycin derivatives, and twenty of these mutants were further characterized in mammalian cells. The mutants most responsive to the ligand were fused to yellow fluorescent protein, and fluorescence levels in the presence and absence of the ligand were measured to determine stability of the fusion proteins. Wild-type and mutant FRB domains were expressed at low levels in the absence of the rapamycin derivative, and expression levels rose up to 10-fold upon treatment with ligand. The synthetic rapamycin derivatives were further analyzed using quantitative mass spectrometry, and one of the compounds was found to contain contaminating rapamycin. Furthermore, uncontaminated analogs retained the ability to inhibit mTOR, although with diminished potency relative to rapamycin. The ligand-dependent stability displayed by wild-type FRB and FRB mutants as well as the inhibitory potential and purity of the rapamycin derivatives should be considered as potentially confounding experimental variables when using these systems.

  7. Development of a method for the characterization and operation of UV-LED for water treatment.

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    Kheyrandish, Ataollah; Mohseni, Madjid; Taghipour, Fariborz

    2017-10-01

    Tremendous improvements in semiconductor technology have made ultraviolet light-emitting diodes (UV-LEDs) a viable alternative to conventional UV sources for water treatment. A robust and validated experimental protocol for studying the kinetics of microorganism inactivation is key to the further development of UV-LEDs for water treatment. This study proposes a protocol to operate UV-LEDs and control their output as a polychromatic radiation source. In order to systematically develop this protocol, the results of spectral power distribution, radiation profile, and radiant power measurements of a variety of UV-LEDs are presented. A wide range of UV-LEDs was selected for this study, covering various UVA, UVB, and UVC wavelengths, viewing angles from 3.5° to 135°, and a variety of output powers. The effects of operational conditions and measurement techniques were investigated on these UV-LEDs using a specially designed and fabricated setup. Operating conditions, such as the UV-LED electrical current and solder temperature, were found to significantly affect the power and peak wavelength output. The measurement techniques and equipment, including the detector size, detector distance from the UV-LED, and potential reflection from the environment, were shown to influence the results for many of the UV-LEDs. The results obtained from these studies were analyzed and applied to the development of a protocol for UV-LED characterization. This protocol is presented as a guideline that allows the operation and control of UV-LEDs in any structure, as well as accurately measuring the UV-LED output. Such information is essential for performing a reliable UV-LED assessment for the inactivation of microorganisms and for obtaining precise kinetic data. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Stomatitis associated with mammalian target of rapamycin inhibition: A review of pathogenesis, prevention, treatment, and clinical implications for oral practice in metastatic breast cancer.

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    Chambers, Mark S; Rugo, Hope S; Litton, Jennifer K; Meiller, Timothy F

    2018-04-01

    Patients with metastatic breast cancer may develop oral morbidities that result from therapeutic interventions. Mammalian target of rapamycin (mTOR) inhibitor-associated stomatitis (mIAS) is a common adverse event (AE), secondary to mTOR inhibitor therapy, that can have a negative impact on treatment adherence, quality of life, and health care costs. A multidisciplinary team approach is important to minimize mIAS and to maximize treatment benefits to patients with breast cancer. In this review, we discuss the pathophysiology, diagnosis, and natural history of mIAS. Current and new management strategies for the prevention and treatment of mIAS are described in the context of fostering a coordinated team care approach to optimizing patient care. The authors conducted a PubMed search from 2007 through 2017 using the terms "stomatitis," "mIAS," "everolimus," "mTOR," "metastatic breast cancer," and "oral care." They selected articles published in peer-reviewed journals that reported controlled trials and evidence-based guidelines. mIAS can be distinguished from mucositis caused by cytotoxic chemotherapy or radiotherapy on the basis of cause, clinical presentation, and treatment paradigms. Specific preventive and therapeutic management strategies can be implemented across the continuum of patient oral health care. Oral health care providers are on the frontline of oral health care for patients with metastatic breast cancer and are uniquely positioned to provide patient education, advocate accurate reporting of mIAS, and support early identification, monitoring, and prompt intervention to mitigate the severity and duration of this manageable, potentially dose-limiting AE. Copyright © 2018 American Dental Association. Published by Elsevier Inc. All rights reserved.

  9. A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects.

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    Kraig, Ellen; Linehan, Leslie A; Liang, Hanyu; Romo, Terry Q; Liu, Qianqian; Wu, Yubo; Benavides, Adriana D; Curiel, Tyler J; Javors, Martin A; Musi, Nicolas; Chiodo, Laura; Koek, Wouter; Gelfond, Jonathan A L; Kellogg, Dean L

    2018-05-01

    Inhibition of the mechanistic target of rapamycin (mTOR) pathway by rapamycin (RAPA), an FDA-approved immunosuppressive drug used as a clinical therapy to prevent solid organ allograft rejection, enhances longevity in mice. Importantly, RAPA was efficacious even when initiated in relatively old animals, suggesting that mTOR inhibition could potentially slow the progression of aging-associated pathologies in older humans (Harrison et al., 2009; Miller et al., 2011). However, the safety and tolerability of RAPA in older human subjects have not yet been demonstrated. Towards this end, we undertook a placebo-controlled pilot study in 25 generally healthy older adults (aged 70-95 years); subjects were randomized to receive either 1 mg RAPA or placebo daily. Although three subjects withdrew, 11 RAPA and 14 controls completed at least 8 weeks of treatment and were included in the analysis. We monitored for changes that would indicate detrimental effects of RAPA treatment on metabolism, including both standard clinical laboratory assays (CBC, CMP, HbA1c) and oral glucose tolerance tests (OGTTs). We also monitored parameters typically associated with aging that could potentially be modified by RAPA; these included cognitive function which was assessed by three different tools: Executive Interview-25 (EXIT25); Saint Louis University Mental Status Exam (SLUMS); and Texas Assessment of Processing Speed (TAPS). In addition, physical performance was measured by handgrip strength and 40-foot timed walks. Lastly, changes in general parameters of healthy immune aging, including serum pro-inflammatory cytokine levels and blood cell subsets, were assessed. Five subjects reported potential adverse side effects; in the RAPA group, these were limited to facial rash (1 subject), stomatitis (1 subject) and gastrointestinal issues (2 subjects) whereas placebo treated subjects only reported stomatitis (1 subject). Although no other adverse events were reported, statistically

  10. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

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    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  11. Paradoxical effects of rapamycin on experimental house dust mite-induced asthma.

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    Karin Fredriksson

    Full Text Available The mammalian target of rapamycin (mTOR modulates immune responses and cellular proliferation. The objective of this study was to assess whether inhibition of mTOR with rapamycin modifies disease severity in two experimental murine models of house dust mite (HDM-induced asthma. In an induction model, rapamycin was administered to BALB/c mice coincident with nasal HDM challenges for 3 weeks. In a treatment model, nasal HDM challenges were performed for 6 weeks and rapamycin treatment was administered during weeks 4 through 6. In the induction model, rapamycin significantly attenuated airway inflammation, airway hyperreactivity (AHR and goblet cell hyperplasia. In contrast, treatment of established HDM-induced asthma with rapamycin exacerbated AHR and airway inflammation, whereas goblet cell hyperplasia was not modified. Phosphorylation of the S6 ribosomal protein, which is downstream of mTORC1, was increased after 3 weeks, but not 6 weeks of HDM-challenge. Rapamycin reduced S6 phosphorylation in HDM-challenged mice in both the induction and treatment models. Thus, the paradoxical effects of rapamycin on asthma severity paralleled the activation of mTOR signaling. Lastly, mediastinal lymph node re-stimulation experiments showed that treatment of rapamycin-naive T cells with ex vivo rapamycin decreased antigen-specific Th2 cytokine production, whereas prior exposure to in vivo rapamycin rendered T cells refractory to the suppressive effects of ex vivo rapamycin. We conclude that rapamycin had paradoxical effects on the pathogenesis of experimental HDM-induced asthma. Thus, consistent with the context-dependent effects of rapamycin on inflammation, the timing of mTOR inhibition may be an important determinant of efficacy and toxicity in HDM-induced asthma.

  12. Longitudinal imaging studies of tumor microenvironment in mice treated with the mTOR inhibitor rapamycin.

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    Keita Saito

    Full Text Available Rapamycin is an allosteric inhibitor of mammalian target of rapamycin, and inhibits tumor growth and angiogenesis. Recent studies suggested a possibility that rapamycin renormalizes aberrant tumor vasculature and improves tumor oxygenation. The longitudinal effects of rapamycin on angiogenesis and tumor oxygenation were evaluated in murine squamous cell carcinoma (SCCVII by electron paramagnetic resonance imaging (EPRI and magnetic resonance imaging (MRI to identify an optimal time after rapamycin treatment for enhanced tumor radioresponse. Rapamycin treatment was initiated on SCCVII solid tumors 8 days after implantation (500-750 mm(3 and measurements of tumor pO(2 and blood volume were conducted from day 8 to 14 by EPRI/MRI. Microvessel density was evaluated over the same time period by immunohistochemical analysis. Tumor blood volume as measured by MRI significantly decreased 2 days after rapamycin treatment. Tumor pO(2 levels modestly but significantly increased 2 days after rapamycin treatment; whereas, it decreased in non-treated control tumors. Furthermore, the fraction of hypoxic area (pixels with pO(2<10 mm Hg in the tumor region decreased 2 days after rapamycin treatments. Immunohistochemical analysis of tumor microvessel density and pericyte coverage revealed that microvessel density decreased 2 days after rapamycin treatment, but pericyte coverage did not change, similar to what was seen with anti-angiogenic agents such as sunitinib which cause vascular renormalization. Collectively, EPRI/MRI co-imaging can provide non-invasive evidence of rapamycin-induced vascular renormalization and resultant transient increase in tumor oxygenation. Improved oxygenation by rapamycin treatment provides a temporal window for anti-cancer therapies to realize enhanced response to radiotherapy.

  13. Nurse led, primary care based antiretroviral treatment versus hospital care: a controlled prospective study in Swaziland

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    Bailey Kerry A

    2010-08-01

    Full Text Available Abstract Background Antiretroviral treatment services delivered in hospital settings in Africa increasingly lack capacity to meet demand and are difficult to access by patients. We evaluate the effectiveness of nurse led primary care based antiretroviral treatment by comparison with usual hospital care in a typical rural sub Saharan African setting. Methods We undertook a prospective, controlled evaluation of planned service change in Lubombo, Swaziland. Clinically stable adults with a CD4 count > 100 and on antiretroviral treatment for at least four weeks at the district hospital were assigned to either nurse led primary care based antiretroviral treatment care or usual hospital care. Assignment depended on the location of the nearest primary care clinic. The main outcome measures were clinic attendance and patient experience. Results Those receiving primary care based treatment were less likely to miss an appointment compared with those continuing to receive hospital care (RR 0·37, p p = 0·001. Those receiving primary care based, nurse led care were more likely to be satisfied in the ability of staff to manage their condition (RR 1·23, p = 0·003. There was no significant difference in loss to follow-up or other health related outcomes in modified intention to treat analysis. Multilevel, multivariable regression identified little inter-cluster variation. Conclusions Clinic attendance and patient experience are better with nurse led primary care based antiretroviral treatment care than with hospital care; health related outcomes appear equally good. This evidence supports efforts of the WHO to scale-up universal access to antiretroviral treatment in sub Saharan Africa.

  14. Novel synergistic antitumor effects of rapamycin with bortezomib on hepatocellular carcinoma cells and orthotopic tumor model

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    Wang Cun

    2012-05-01

    Full Text Available Abstract Background Despite recent advances in the treatment of hepatocellular carcinoma (HCC, the chemotherapy efficacy against HCC is still unsatisfactory. The mammalian target of rapamycin (mTOR has been emerged as an important cancer therapeutic target. However, HCC cells often resistant to rapamycin because of the paradoxical activation of Akt by rapamycin. In this study, we investigated whether bortezomib could enhance the antitumor effects of rapamycin. Methods The effects of rapamycin and bortezomib on HCC proliferation, apoptosis, migration, and invasiveness in vitro were assessed by CCK-8 analysis, flow cytometry, Hoechst 33342 staining and transwell assays, respectively. Total and phosphorylated protein levels of Akt were detected by Western blotting. The effects of rapamycin and/or bortezomib on the mRNA expression levels of p53, p27, p21 and Bcl-2 family in HCCLM3 cells were evaluated by RT-PCR. The roles of rapamycin and bortezomib on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. The effects of rapamycin and bortezomib on cell proliferation and apoptosis in vivo were test by PCNA and TUNEL staining. Results Bortezomib synergized with rapamycin to reduce cell growth, induce apoptosis, and inhibit cell mobility in vitro. Further mechanistic studies showed that bortezomib inhibited rapamycin-induced phosphorylated Akt, which in turn enhanced apoptosis of HCC cell lines. The alteration of the mRNA expression of cell cycle inhibitors p53, p27, p21 and apoptosis associated genes Bcl-2, Bax were also involved in the synergistic antitumor effects of rapamycin and bortezomib. P53 inhibitor PFT-α significantly attenuate the effect of rapamycin and bortezomib on cell apoptosis, which indicated that the pro-apoptotic effect of rapamycin and bortezomib may be p53-dependent. Treatment of HCCLM3-R bearing nude mice with rapamycin and bortezomib significantly enhanced tumor growth

  15. Eukaryotic initiation factor 2α--a downstream effector of mammalian target of rapamycin--modulates DNA repair and cancer response to treatment.

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    Liron Tuval-Kochen

    Full Text Available In an effort to circumvent resistance to rapamycin--an mTOR inhibitor--we searched for novel rapamycin-downstream-targets that may be key players in the response of cancer cells to therapy. We found that rapamycin, at nM concentrations, increased phosphorylation of eukaryotic initiation factor (eIF 2α in rapamycin-sensitive and estrogen-dependent MCF-7 cells, but had only a minimal effect on eIF2α phosphorylation in the rapamycin-insensitive triple-negative MDA-MB-231 cells. Addition of salubrinal--an inhibitor of eIF2α dephosphorylation--decreased expression of a surface marker associated with capacity for self renewal, increased senescence and induced clonogenic cell death, suggesting that excessive phosphorylation of eIF2α is detrimental to the cells' survival. Treating cells with salubrinal enhanced radiation-induced increase in eIF2α phosphorylation and clonogenic death and showed that irradiated cells are more sensitive to increased eIF2α phosphorylation than non-irradiated ones. Similar to salubrinal--the phosphomimetic eIF2α variant--S51D--increased sensitivity to radiation, and both abrogated radiation-induced increase in breast cancer type 1 susceptibility gene, thus implicating enhanced phosphorylation of eIF2α in modulation of DNA repair. Indeed, salubrinal inhibited non-homologous end joining as well as homologous recombination repair of double strand breaks that were induced by I-SceI in green fluorescent protein reporter plasmids. In addition to its effect on radiation, salubrinal enhanced eIF2α phosphorylation and clonogenic death in response to the histone deacetylase inhibitor--vorinostat. Finally, the catalytic competitive inhibitor of mTOR--Ku-0063794--increased phosphorylation of eIF2α demonstrating further the involvement of mTOR activity in modulating eIF2α phosphorylation. These experiments suggest that excessive phosphorylation of eIF2α decreases survival of cancer cells; making eIF2α a worthy target for

  16. Improving insomnia in primary care patients: A randomized controlled trial of nurse-led group treatment.

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    Sandlund, Christina; Hetta, Jerker; Nilsson, Gunnar H; Ekstedt, Mirjam; Westman, Jeanette

    2017-07-01

    Insomnia is a common health problem, and most people who seek help for insomnia consult primary care. In primary care, insomnia treatment typically consists of hypnotic drugs, although cognitive behavioral therapy for insomnia is the recommended treatment. However, such treatment is currently available to few primary care patients. To evaluate the effects of a group treatment program for insomnia led by nurses in primary care. were the Insomnia Severity Index, a 2-week sleep diary, and a questionnaire on frequency of hypnotic drug use. A randomized controlled trial with pre- and post-treatment assessment and a 1-year post-treatment follow-up of the intervention group. Routine primary health care; 7 primary care centers in Stockholm, Sweden. Patients consulting primary care for insomnia were assessed for eligibility. To be included, patients had to have insomnia disorder and be 18 years or older. Patients were excluded if they if they worked night shifts or had severe untreated somatic and/or mental illness, bipolar disorder, or untreated sleep disorder other than insomnia. One-hundred and sixty-five patients 20 to 90 years were included. Most were women, and many had co-existing somatic and/or mental health problems. The post-treatment dropout rate was 20%. The intervention was a nurse-led group treatment for insomnia based on the techniques of cognitive behavioral therapy for insomnia. The nurses had 2days of training in how to deliver the program. Ninety patients were randomized to the intervention and 75 to the control group (treatment as usual). Data from 82 in the intervention and 71 in the control group were analyzed in accordance with intention-to-treat principles. Fifty-four of the 72 in the intervention group who participated in the group treatment program were followed up after 1year. Mean Insomnia Severity Index score decreased significantly from 18.4 to 10.7 after group treatment but remained unchanged after treatment as usual (17.0 to 16.6). The effect

  17. Rapamycin causes growth arrest and inhibition of invasion in human chondrosarcoma cells.

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    Song, Jian; Wang, Xiaobo; Zhu, Jiaxue; Liu, Jun

    2016-01-01

    Chondrosarcoma is a highly malignant tumor that is characterized by a potent capacity to invade locally and cause distant metastasis and notable for its lack of response to conventional chemotherapy or radiotherapy. Rapamycin, the inhibitor of mammalian target of rapamycin (mTOR), is a valuable drug with diverse clinical applications and regulates many cellular processes. However, the effects of rapamycin on cell growth and invasion of human chondrosarcoma cells are not well known. We determined the effect of rapamycin on cell proliferation, cell cycle arrest and invasion by using MTS, flow cytometry and invasion assays in two human chondrosarcoma cell lines, SW1353 and JJ012. Cell cycle regulatory and invasion-related genes' expression analysis was performed by quantitative RT-PCR (qRT-PCR). We also evaluated the effect of rapamycin on tumor growth by using mice xenograph models. Rapamycin significantly inhibited the cell proliferation, induced cell cycle arrest and decreased the invasion ability of human chondrosarcoma cells. Meanwhile, rapamycin modulated the cell cycle regulatory and invasion-related genes' expression. Furthermore, the tumor growth of mice xenograph models with human chondrosarcoma cells was significantly inhibited by rapamycin. These results provided further insight into the role of rapamycin in chondrosarcoma. Therefore, rapamycin targeted therapy may be a potential treatment strategy for chondrosarcoma.

  18. LED; Zum Thema LED

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    This collection of articles on the subject of light emitting diodes (LED) provides technical information on LED technology, examines latest developments and provides examples of LED use in practice. An 'ABC' of LED technology is presented and fifteen common LED mistakes are noted. The chances and risks of LED use are discussed as is the retrofitting of lighting installations with LEDs. The use of LEDs in street lighting is examined. The journal also includes interviews with architects and a lighting designer. Practical examples of the use of LEDs include the refurbished parliamentary library in Berne, their use in the bird sanctuary headquarters in Sempach, Switzerland, as well as LED use in sales outlets. Also, the use of LED lighting in a spa gazebo in Lucerne is examined.

  19. Tomato FK506 Binding Protein 12KD (FKBP12 mediates the interaction between rapamycin and Target of Rapamycin (TOR

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    Fangjie Xiong

    2016-11-01

    Full Text Available Target of Rapamycin (TOR signaling is an important regulator in multiple organisms including yeast, plants and animals. However, the TOR signaling in plants is much less understood as compared to that in yeast and animals. TOR kinase can be efficiently suppressed by rapamycin in the presence of functional FK506 Binding Protein 12KD (FKBP12 in yeast and animals. In most examined higher plants rapamycin fails to inhibit TOR kinase due to the non-functional FKBP12. Here we find that tomato plants showed obvious growth inhibition when treated with rapamycin and the inhibitory phenotype is similar to suppression of TOR causing by active-site TOR inhibitors (asTORis such as KU63794, AZD8055 and Torin1. The chemical genetic assays using TOR inhibitors and heterologous expressing SlFKBP12 in Arabidopsis indicated that the TOR signaling is functional in tomato. The protein gel shifting and TOR inhibitors combination assays showed that SlFKBP12 can mediate the interaction between rapamycin and TOR. Furthermore, comparative expression profiling analysis between treatments with rapamycin and KU63794 identified highly overlapped Differentially Expressed Genes (DEGs which are involved in many anabolic and catabolic processes, such as photosynthesis, cell wall restructuring, and senescence in tomato. These observations suggest that SlFFBP12 is functional in tomato. The results provided basic information of TOR signaling in tomato, and also some new insights into how TOR controls plant growth and development through reprogramming the transcription profiles

  20. Tomato FK506 Binding Protein 12KD (FKBP12) Mediates the Interaction between Rapamycin and Target of Rapamycin (TOR).

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    Xiong, Fangjie; Dong, Pan; Liu, Mei; Xie, Gengxin; Wang, Kai; Zhuo, Fengping; Feng, Li; Yang, Lu; Li, Zhengguo; Ren, Maozhi

    2016-01-01

    Target of Rapamycin (TOR) signaling is an important regulator in multiple organisms including yeast, plants, and animals. However, the TOR signaling in plants is much less understood as compared to that in yeast and animals. TOR kinase can be efficiently suppressed by rapamycin in the presence of functional FK506 Binding Protein 12 KD (FKBP12) in yeast and animals. In most examined higher plants rapamycin fails to inhibit TOR kinase due to the non-functional FKBP12. Here we find that tomato plants showed obvious growth inhibition when treated with rapamycin and the inhibitory phenotype is similar to suppression of TOR causing by active-site TOR inhibitors (asTORis) such as KU63794, AZD8055, and Torin1. The chemical genetic assays using TOR inhibitors and heterologous expressing SlFKBP12 in Arabidopsis indicated that the TOR signaling is functional in tomato. The protein gel shifting and TOR inhibitors combination assays showed that SlFKBP12 can mediate the interaction between rapamycin and TOR. Furthermore, comparative expression profile analysis between treatments with rapamycin and KU63794 identified highly overlapped Differentially Expressed Genes (DEGs) which are involved in many anabolic and catabolic processes, such as photosynthesis, cell wall restructuring, and senescence in tomato. These observations suggest that SlFFBP12 is functional in tomato. The results provided basic information of TOR signaling in tomato, and also some new insights into how TOR controls plant growth and development through reprogramming the transcription profiles.

  1. Rapamycin Rescues the Poor Developmental Capacity of Aged Porcine Oocytes

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    Seung Eun Lee

    2014-05-01

    Full Text Available Unfertilized oocytes age inevitably after ovulation, which limits their fertilizable life span and embryonic development. Rapamycin affects mammalian target of rapamycin (mTOR expression and cytoskeleton reorganization during oocyte meiotic maturation. The goal of this study was to examine the effects of rapamycin treatment on aged porcine oocytes and their in vitro development. Rapamycin treatment of aged oocytes for 24 h (68 h in vitro maturation [IVM]; 44 h+10 μM rapamycin/24 h, 47.52±5.68 or control oocytes (44 h IVM; 42.14±4.40 significantly increased the development rate and total cell number compared with untreated aged oocytes (68 h IVM, 22.04±5.68 (p<0.05. Rapamycin treatment of aged IVM oocytes for 24 h also rescued aberrant spindle organization and chromosomal misalignment, blocked the decrease in the level of phosphorylated-p44/42 mitogen-activated protein kinase (MAPK, and increased the mRNA expression of cytoplasmic maturation factor genes (MOS, BMP15, GDF9, and CCNB1 compared with untreated, 24 h-aged IVM oocytes (p<0.05. Furthermore, rapamycin treatment of aged oocytes decreased reactive oxygen species (ROS activity and DNA fragmentation (p<0.05, and downregulated the mRNA expression of mTOR compared with control or untreated aged oocytes. By contrast, rapamycin treatment of aged oocytes increased mitochondrial localization (p<0.05 and upregulated the mRNA expression of autophagy (BECN1, ATG7, MAP1LC3B, ATG12, GABARAP, and GABARAPL1, anti-apoptosis (BCL2L1 and BIRC5; p<0.05, and development (NANOG and SOX2; p<0.05 genes, but it did not affect the mRNA expression of pro-apoptosis genes (FAS and CASP3 compared with the control. This study demonstrates that rapamycin treatment can rescue the poor developmental capacity of aged porcine oocytes.

  2. Beneficial role of rapamycin in experimental autoimmune myositis.

    Directory of Open Access Journals (Sweden)

    Nicolas Prevel

    Full Text Available We developed an experimental autoimmune myositis (EAM mouse model of polymyositis where we outlined the role of regulatory T (Treg cells. Rapamycin, this immunosuppressant drug used to prevent rejection in organ transplantation, is known to spare Treg. Our aim was to test the efficacy of rapamycin in vivo in this EAM model and to investigate the effects of the drug on different immune cell sub-populations.EAM is induced by 3 injections of myosin emulsified in CFA. Mice received rapamycin during 25 days starting one day before myosin immunization (preventive treatment, or during 10 days following the last myosin immunization (curative treatment.Under preventive or curative treatment, an increase of muscle strength was observed with a parallel decrease of muscle inflammation, both being well correlated (R(2 = -0.645, p<0.0001. Rapamycin induced a general decrease in muscle of CD4 and CD8 T cells in lymphoid tissues, but spared B cells. Among T cells, the frequency of Treg was increased in rapamycin treated mice in draining lymph nodes (16.9 ± 2.2% vs. 9.3 ± 1.4%, p<0.001, which were mostly activated regulatory T cells (CD62L(lowCD44(high: 58.1 ± 5.78% vs. 33.1 ± 7%, treated vs. untreated, p<0.001. In rapamycin treated mice, inhibition of proliferation (Ki-67(+ is more important in effector T cells compared to Tregs cells (p<0.05. Furthermore, during preventive treatment, rapamycin increased the levels of KLF2 transcript in CD44(low CD62L(high naive T cell and in CD62L(low CD44(high activated T cell.Rapamycin showed efficacy both as curative and preventive treatment in our murine model of experimental myositis, in which it induced an increase of muscle strength with a parallel decrease in muscle inflammation. Rapamycin administration was also associated with a decrease in the frequency of effector T cells, an increase in Tregs, and, when administered as preventive treatment, an upregulation of KFL2 in naive and activated T cells.

  3. A new LED device used for photodynamic therapy in treatment of moderate to severe acne vulgaris.

    Science.gov (United States)

    Dong, Yiyun; Zhou, Guoyu; Chen, Jinan; Shen, Lingyue; Jianxin, Zhao; Xu, Qing; Zhu, Yulan

    2016-03-01

    This study investigated the efficacy and safety of a newly designed LED device used in photodiagnosis and photodynamic therapy of moderate to severe acne vulgaris in Chinese patients. Forty-six patients with moderate to severe facial acne showing high degrees of fluorescence by ultraviolet light examination were illuminated during ALA-PDT with two wavelengths of light (543-548 nm, and 630±6 nm, respectively) after 2 h of incubation with ALA. Each patient received treatment once every 30 days for two or three sessions. Two independent investigators assigned an acne severity score at baseline, one week after each treatment, as well as 4, 8, and 12 weeks after the completion of treatment. Adverse effects were recorded during and after each treatment. All patients rated their satisfaction with the results of treatment at a 12-week follow up visit. The ALA-PDL treatment regimen showed an overall effectiveness rate of 89.13% (41/46 patients). Some degree of clinical efficacy was seen in 71.42%, 86.67%, and 95.83% of patients with grades IV, V, and VI acne, respectively, and the rate of clinical effectiveness increased with increasing acne severity. When compared with baseline scores, significant reductions in acne scores were obtained at 8, and 12 weeks after completion of treatment. Maximum efficacy was shown at the 12 week follow up. No severe adverse events were observed. ALA-PDT administered with the newly designed LED device was an effective treatment for moderate to severe acne vulgaris, and side effects were mild and reversible. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Treatment with beta-blockers in nurse-led heart failure clinics

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Schou, Morten; Videbaek, Lars

    2007-01-01

    BACKGROUND: Beta-blockers (BBs) are a cornerstone in the treatment of chronic heart failure (HF), but several surveys have documented that many patients are not offered treatment or are not titrated to target doses. In part to address this problem, specialized, nurse-led HF clinics have been......% of the patients were being treated with a BB. Mean dose (relative to target dose) was 63 (+/-35)% in patients receiving a BB and target dose was reached by 21%. Patients who were not on BBs were more often female, elderly and in NYHA class III-IV. In a multivariable model only lower age predicted BB use at three...... months (PElderly patients appear to be less likely to receive treatment....

  5. Application of Photocatalysts and LED Light Sources in Drinking Water Treatment

    Directory of Open Access Journals (Sweden)

    Gopal Achari

    2013-09-01

    Full Text Available This study investigates a cross-section of TiO2 compositions for which existing evidence suggests the prospect of improved performance compared to standard Degussa P25. In the context of a program aimed toward a 365 nm LED based photo-reactor, the question is whether a distinctly superior photocatalyst composition for drinking water treatment is now available that would shape design choices. An answer was sought by synthesizing several photocatalysts with reported high reactivity in some context in the literature, and by performing photocatalysts reactivity tests using common pollutants of water system including Natural Organic Matter (NOM and Emerging Contaminants (ECs from the pesticide and pharmaceutical classes. 365 nm Light Emitting Diodes (LEDs were used as the irradiation source. Since LEDs are now available in the UV, we did not examine the TiO2 modifications that bring band gap excitation into the region beyond 400 nm. The results suggest that the choice of the photocatalyst should be best made to fit the reactor design and photocatalyst mounting constraints such as mass transport, reactive surface, and light field. No photocatalyst composition overall, superior for all classes emerged.

  6. Rapamycin exerts antifungal activity in vitro and in vivo against Mucor circinelloides via FKBP12-dependent inhibition of Tor.

    Science.gov (United States)

    Bastidas, Robert J; Shertz, Cecelia A; Lee, Soo Chan; Heitman, Joseph; Cardenas, Maria E

    2012-03-01

    The zygomycete Mucor circinelloides is an opportunistic fungal pathogen that commonly infects patients with malignancies, diabetes mellitus, and solid organ transplants. Despite the widespread use of antifungal therapy in the management of zygomycosis, the incidence of infections continues to rise among immunocompromised individuals. In this study, we established that the target and mechanism of antifungal action of the immunosuppressant rapamycin in M. circinelloides are mediated via conserved complexes with FKBP12 and a Tor homolog. We found that spontaneous mutations that disrupted conserved residues in FKBP12 conferred rapamycin and FK506 resistance. Disruption of the FKBP12-encoding gene, fkbA, also conferred rapamycin and FK506 resistance. Expression of M. circinelloides FKBP12 (McFKBP12) complemented a Saccharomyces cerevisiae mutant strain lacking FKBP12 to restore rapamycin sensitivity. Expression of the McTor FKBP12-rapamycin binding (FRB) domain conferred rapamycin resistance in S. cerevisiae, and McFKBP12 interacted in a rapamycin-dependent fashion with the McTor FRB domain in a yeast two-hybrid assay, validating McFKBP12 and McTor as conserved targets of rapamycin. We showed that in vitro, rapamycin exhibited potent growth inhibitory activity against M. circinelloides. In a Galleria mellonella model of systemic mucormycosis, rapamycin improved survival by 50%, suggesting that rapamycin and nonimmunosuppressive analogs have the potential to be developed as novel antifungal therapies for treatment of patients with mucormycosis.

  7. Rapamycin Exerts Antifungal Activity In Vitro and In Vivo against Mucor circinelloides via FKBP12-Dependent Inhibition of Tor

    Science.gov (United States)

    Bastidas, Robert J.; Shertz, Cecelia A.; Lee, Soo Chan; Heitman, Joseph

    2012-01-01

    The zygomycete Mucor circinelloides is an opportunistic fungal pathogen that commonly infects patients with malignancies, diabetes mellitus, and solid organ transplants. Despite the widespread use of antifungal therapy in the management of zygomycosis, the incidence of infections continues to rise among immunocompromised individuals. In this study, we established that the target and mechanism of antifungal action of the immunosuppressant rapamycin in M. circinelloides are mediated via conserved complexes with FKBP12 and a Tor homolog. We found that spontaneous mutations that disrupted conserved residues in FKBP12 conferred rapamycin and FK506 resistance. Disruption of the FKBP12-encoding gene, fkbA, also conferred rapamycin and FK506 resistance. Expression of M. circinelloides FKBP12 (McFKBP12) complemented a Saccharomyces cerevisiae mutant strain lacking FKBP12 to restore rapamycin sensitivity. Expression of the McTor FKBP12-rapamycin binding (FRB) domain conferred rapamycin resistance in S. cerevisiae, and McFKBP12 interacted in a rapamycin-dependent fashion with the McTor FRB domain in a yeast two-hybrid assay, validating McFKBP12 and McTor as conserved targets of rapamycin. We showed that in vitro, rapamycin exhibited potent growth inhibitory activity against M. circinelloides. In a Galleria mellonella model of systemic mucormycosis, rapamycin improved survival by 50%, suggesting that rapamycin and nonimmunosuppressive analogs have the potential to be developed as novel antifungal therapies for treatment of patients with mucormycosis. PMID:22210828

  8. A nurse- and pharmacist-led treatment advice clinic for patients attending an HIV outpatient clinic.

    Science.gov (United States)

    Griffiths, C; Miles, K; Aldam, D; Cornforth, D; Minton, J; Edwards, S; Williams, I

    2007-05-01

    This paper is a report of a study to map care pathways, examine the approach of different treatment advisors and explore the acceptability of a nurse- and pharmacist-led treatment advice clinic in order to aid decision-making for the future development and evaluation of the clinic. High levels of adherence to antiretroviral drugs are a prerequisite for a successful and durable virological and immunological response to HIV. Treatment guidelines acknowledge that adherence is a process, not a single event, and that adherence support must be integrated into clinical follow-up for all patients receiving these drugs. Data were collected between September 2004 and January 2005 through 17 consultation observations and 10 patient interviews in a specialist treatment advice clinic located within a central London HIV outpatient clinic providing care for over 2200 patients, of whom more than 1300 are taking highly active antiretroviral therapy. The nurses and pharmacist had similar consultation approaches, although follow-up care varied in extent. Benefits of the clinic approach included permitting patients to observe real tablets, tailoring regimens to lifestyles and telephone follow-up. These factors, particularly telephone support, were perceived by patients to assist with adherence. The role of telephone support, perceived to assist with initial adherence, requires further investigation. Future work is also needed to explore the health economics of this approach and to determine the actual impact of the clinic on clinical and adherence outcomes.

  9. Inhibition of repopulation is not a determining factor for the radiosensitizing effects of rapamycin

    International Nuclear Information System (INIS)

    Sarkaria, J.N.; Carlson, B.L.; Mladek, A.C.

    2003-01-01

    The mammalian target of rapamycin (mTOR) is a key downstream effector of the PI3K-Akt signaling pathway, and we have previously shown that inhibition of mTOR by rapamycin significantly enhances the efficacy of prolonged fractionated radiation in U87 glioma cells grown as xenografts or spheroids. To test whether inhibition of repopulation between radiation fractions contributes to the sensitizing effects of rapamycin, the efficacy of our previous protracted radiation schedule was compared with an accelerated regimen in U87 spheroids. Regrowth of individual spheroids was tracked over time following treatment with either accelerated or protracted radiation in the presence or absence of rapamycin. As in our previous studies, treatment with 10 nM rapamycin significantly increased the time required for U87 spheroids to regrow to 10 times their original volume (22 ± 2 days [mean ± 95% CI]) compared to control (7 ± 1 days). Regrowth after protracted radiation (2 Gy every 3 days x 4; 9 ± 2 days)did not significantly differ from control treatment, while accelerated radiation (2 Gy every 4 hours x 4) modestly delayed spheroid regrowth (12 ± 2 days). Specific to our model, the relatively small difference in regrowth time between the two radiation fractionation schedules suggests that repopulation is not a major detrimental factor in the protracted radiation schedule. Interestingly, the combination of rapamycin with either protracted or accelerated RT significantly enhanced the efficacy of the radiation with regrowth times of 31 ± 4 days and 29 ± 4 days, respectively. Consistent with this in vitro data, preliminary results from an animal study suggest that treatment with a rapamycin analog and daily radiation is as effective as protracted radiation/ rapamycin schedules. Thus, any effects of rapamycin on repopulation in our model systems do not contribute significantly to the sensitizing effects of rapamycin

  10. The Rapamycin-Binding Domain of the Protein Kinase mTOR is a Destabilizing Domain*

    Science.gov (United States)

    Edwards, Sarah R.; Wandless, Thomas J.

    2013-01-01

    Rapamycin is an immunosuppressive drug that binds simultaneously to the 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding domain (FRB) of the mammalian target of rapamycin (mTOR) kinase. The resulting ternary complex has been used to conditionally perturb protein function, and one such method involves perturbation of a protein of interest through its mislocalization. We synthesized two rapamycin derivatives that possess large substituents at the C16 position within the FRB-binding interface, and these derivatives were screened against a library of FRB mutants using a three-hybrid assay in Saccharomyces cerevisiae. Several FRB mutants responded to one of the rapamycin derivatives, and twenty of these mutants were further characterized in mammalian cells. The mutants most responsive to the ligand were fused to yellow fluorescent protein, and fluorescence levels in the presence and absence of the ligand were measured to determine stability of the fusion proteins. Wild-type and mutant FRB domains were expressed at low levels in the absence of the rapamycin derivative, and expression levels rose up to ten-fold upon treatment with ligand. The synthetic rapamycin derivatives were further analyzed using quantitative mass spectrometry, and one of the compounds was found to contain contaminating rapamycin. Furthermore, uncontaminated analogs retain the ability to inhibit mTOR, albeit with diminished potency relative to rapamycin. The ligand-dependent stability displayed by wildtype FRB and FRB mutants as well as the inhibitory potential and purity of the rapamycin derivatives should be considered as potentially confounding experimental variables when using these systems. PMID:17350953

  11. Divergent tissue and sex effects of rapamycin on the proteasome-chaperone network of old mice

    Directory of Open Access Journals (Sweden)

    Karl Andrew Rodriguez

    2014-11-01

    Full Text Available Rapamycin, an allosteric inhibitor of the mTOR kinase, increases longevity in mice in a sex-specific manner. In contrast to the widely accepted theory that a loss of proteasome activity is detrimental to both life- and healthspan, biochemical studies in vitro reveal that rapamycin inhibits 20S proteasome peptidase activity. We tested if this unexpected finding is also evident after chronic rapamycin treatment in vivo by measuring peptidase activities for both the 26S and 20S proteasome in liver, fat, and brain tissues of old, male and female mice fed encapsulated chow containing 2.24mg/kg (14 ppm rapamycin for 6 months. Further we assessed if rapamycin altered expression of the chaperone proteins known to interact with the proteasome-mediated degradation system (PMDS, heat shock factor 1 (HSF1, and the levels of key mTOR pathway proteins. Rapamycin had little effect on liver proteasome activity in either gender, but increased proteasome activity in female brain lysates and lowered its activity in female fat tissue. Rapamycin-induced changes in molecular chaperone levels were also more substantial in tissues from female animals. Furthermore, mTOR pathway proteins showed more significant changes in female tissues compared to those from males. These data show collectively that there are divergent tissue and sex effects of rapamycin on the proteasome-chaperone network and that these may be linked to the disparate effects of rapamycin on males and females. Further our findings suggest that rapamycin induces indirect regulation of the PMDS/heat-shock response through its modulation of the mTOR pathway rather than via direct interactions between rapamycin and the proteasome.

  12. Potential use of rapamycin in HIV infection

    DEFF Research Database (Denmark)

    Donia, Marco; McCubrey, James A; Bendtzen, Klaus

    2010-01-01

    The strong need for the development of alternative anti-HIV agents is primarily due to the emergence of strain-resistant viruses, the need for sustained adherence to complex treatment regimens and the toxicity of currently used antiviral drugs. This review analyzes proof of concept studies......, the evidence presented in this review suggests that RAPA may be a useful drug that should be evaluated for the prevention and treatment of HIV-1 infection....... indicating that the immunomodulatory drug rapamycin (RAPA) possesses anti-HIV properties both in vitro and in vivo that qualifies it as a potential new anti-HIV drug. It represents a literature review of published studies that evaluated the in vitro and in vivo activity of RAPA in HIV. RAPA represses HIV-1...

  13. Potential use of rapamycin in HIV infection

    DEFF Research Database (Denmark)

    Donia, Marco; McCubrey, James A; Bendtzen, Klaus

    2010-01-01

    The strong need for the development of alternative anti-HIV agents is primarily due to the emergence of strain-resistant viruses, the need for sustained adherence to complex treatment regimens and the toxicity of currently used antiviral drugs. This review analyzes proof of concept studies...... indicating that the immunomodulatory drug rapamycin (RAPA) possesses anti-HIV properties both in vitro and in vivo that qualifies it as a potential new anti-HIV drug. It represents a literature review of published studies that evaluated the in vitro and in vivo activity of RAPA in HIV. RAPA represses HIV-1...... replication in vitro through different mechanisms including, but not limited, to down regulation of CCR5. In addition RAPA synergistically enhances the anti-HIV activity of entry inhibitors such as vicriviroc, aplaviroc and enfuvirtide in vitro. RAPA also inhibits HIV-1 infection in human peripheral blood...

  14. Suppression of Th17-polarized airway inflammation by rapamycin.

    Science.gov (United States)

    Joean, Oana; Hueber, Anja; Feller, Felix; Jirmo, Adan Chari; Lochner, Matthias; Dittrich, Anna-Maria; Albrecht, Melanie

    2017-11-10

    Because Th17-polarized airway inflammation correlates with poor control in bronchial asthma and is a feature of numerous other difficult-to-treat inflammatory lung diseases, new therapeutic approaches for this type of airway inflammation are necessary. We assessed different licensed anti-inflammatory agents with known or expected efficacy against Th17-polarization in mouse models of Th17-dependent airway inflammation. Upon intravenous transfer of in vitro derived Th17 cells and intranasal challenge with the corresponding antigen, we established acute and chronic murine models of Th17-polarised airway inflammation. Consecutively, we assessed the efficacy of methylprednisolone, roflumilast, azithromycin, AM80 and rapamycin against acute or chronic Th17-dependent airway inflammation. Quantifiers for Th17-associated inflammation comprised: bronchoalveolar lavage (BAL) differential cell counts, allergen-specific cytokine and immunoglobulin secretion, as well as flow cytometric phenotyping of pulmonary inflammatory cells. Only rapamycin proved effective against acute Th17-dependent airway inflammation, accompanied by increased plasmacytoid dendritic cells (pDCs) and reduced neutrophils as well as reduced CXCL-1 levels in BAL. Chronic Th17-dependent airway inflammation was unaltered by rapamycin treatment. None of the other agents showed efficacy in our models. Our results demonstrate that Th17-dependent airway inflammation is difficult to treat with known agents. However, we identify rapamycin as an agent with inhibitory potential against acute Th17-polarized airway inflammation.

  15. Brain Injury-Induced Synaptic Reorganization in Hilar Inhibitory Neurons Is Differentially Suppressed by Rapamycin.

    Science.gov (United States)

    Butler, Corwin R; Boychuk, Jeffery A; Smith, Bret N

    2017-01-01

    Following traumatic brain injury (TBI), treatment with rapamycin suppresses mammalian (mechanistic) target of rapamycin (mTOR) activity and specific components of hippocampal synaptic reorganization associated with altered cortical excitability and seizure susceptibility. Reemergence of seizures after cessation of rapamycin treatment suggests, however, an incomplete suppression of epileptogenesis. Hilar inhibitory interneurons regulate dentate granule cell (DGC) activity, and de novo synaptic input from both DGCs and CA3 pyramidal cells after TBI increases their excitability but effects of rapamycin treatment on the injury-induced plasticity of interneurons is only partially described. Using transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed in the somatostatinergic subset of hilar inhibitory interneurons, we tested the effect of daily systemic rapamycin treatment (3 mg/kg) on the excitability of hilar inhibitory interneurons after controlled cortical impact (CCI)-induced focal brain injury. Rapamycin treatment reduced, but did not normalize, the injury-induced increase in excitability of surviving eGFP+ hilar interneurons. The injury-induced increase in response to selective glutamate photostimulation of DGCs was reduced to normal levels after mTOR inhibition, but the postinjury increase in synaptic excitation arising from CA3 pyramidal cell activity was unaffected by rapamycin treatment. The incomplete suppression of synaptic reorganization in inhibitory circuits after brain injury could contribute to hippocampal hyperexcitability and the eventual reemergence of the epileptogenic process upon cessation of mTOR inhibition. Further, the cell-selective effect of mTOR inhibition on synaptic reorganization after CCI suggests possible mechanisms by which rapamycin treatment modifies epileptogenesis in some models but not others.

  16. Magneto-LED therapy in the treatment of inflammatory lesions and erosions of the glans penis – case report

    Directory of Open Access Journals (Sweden)

    Jarosław Pasek

    2016-10-01

    Full Text Available Introduction . Inflammatory lesions and erosions of the glans penis defined as balanitis or balanoposthitis constitute a disease in which the effectiveness of conservative treatment is not sufficient. Objective. To present the therapeutic efficacy of magneto-LED therapy in the treatment, and to present a patient with inflammatory lesions and erosions of the glans penis. Case report. The patient, 68 years old with inflammatory lesions and erosions of the glans penis of 2–4 years duration, was previously treated with various methods of local therapy without effect. As a result of a 32-week long magneto-LED therapy cycle, complete resolution of skin lesions with subsidence of the burning sensation during urination and reduced swelling and inflammatory erythema of the glans, as well as disappearance of the white coating and unpleasant smell, was achieved. Conclusions . Magneto-LED therapy is an efficient method of treatment of inflammatory lesions and erosions of the glans penis.

  17. Inhibition of Akt enhances the chemopreventive effects of topical rapamycin in mouse skin

    Science.gov (United States)

    Dickinson, Sally E; Janda, Jaroslav; Criswell, Jane; Blohm-Mangone, Karen; Olson, Erik R.; Liu, Zhonglin; Barber, Christie; Rusche, Jadrian J.; Petricoin, Emmanuel; Calvert, Valerie; Einspahr, Janine G.; Dickinson, Jesse; Stratton, Steven P.; Curiel-Lewandrowski, Clara; Saboda, Kathylynn; Hu, Chengcheng; Bode, Ann M.; Dong, Zigang; Alberts, David S.; Bowden, G. Timothy

    2016-01-01

    The PI3Kinase/Akt/mTOR pathway has important roles in cancer development for multiple tumor types, including UV-induced non-melanoma skin cancer. Immunosuppressed populations are at increased risk of aggressive cutaneous squamous cell carcinoma (SCC). Individuals who are treated with rapamycin, (sirolimus, a classical mTOR inhibitor) have significantly decreased rates of developing new cutaneous SCCs compared to those that receive traditional immunosuppression. However, systemic rapamycin use can lead to significant adverse events. Here we explored the use of topical rapamycin as a chemopreventive agent in the context of solar simulated light (SSL)-induced skin carcinogenesis. In SKH-1 mice, topical rapamycin treatment decreased tumor yields when applied after completion of 15 weeks of SSL exposure compared to controls. However, applying rapamycin during SSL exposure for 15 weeks, and continuing for 10 weeks after UV treatment, increased tumor yields. We also examined whether a combinatorial approach might result in more significant tumor suppression by rapamycin. We validated that rapamycin causes increased Akt (S473) phosphorylation in the epidermis after SSL, and show for the first time that this dysregulation can be inhibited in vivo by a selective PDK1/Akt inhibitor, PHT-427. Combining rapamycin with PHT-427 on tumor prone skin additively caused a significant reduction of tumor multiplicity compared to vehicle controls. Our findings indicate that patients taking rapamycin should avoid sun exposure, and that combining topical mTOR inhibitors and Akt inhibitors may be a viable chemoprevention option for individuals at high risk for cutaneous SCC.

  18. High efficiency GaN-based LEDs using plasma selective treatment of p-GaN surface

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Young-Bae; Naoi, Yoshiki; Sakai, Shiro [Department of Electrical and Electronic Engineering, University of Tokushima, 2-1 Minami-josanjima, Tokushima 770-8506 (Japan); Takaki, Ryohei; Sato, Hisao [Nitride Semiconductor Co., Ltd., 115-7 Itayajima, Akinokami, Seto-cho, Naruto, Tokushima 771-0360 (Japan)

    2003-11-01

    We have studied a new method of increasing the extraction efficiency of a GaN-based light-emitting diode (LED) using a plasma surface treatment. In this method, prior to the evaporation of a semitransparent p-metal, the surface of a p-GaN located beneath a p-pad is selectively exposed to a nitrogen plasma in a reactive ion etching (RIE) chamber. The electrical characteristics of the plasma treated p-GaN remarkably changes its resistivity into semi-insulator without any parasitic damage. Since the LEDs with a new method have no light absorption in a p-pad region, a higher optical power can be extracted compared to a conventional LEDs without plasma selective treatment on the p-GaN surface. (copyright 2003 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  19. Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats I: Magnetic resonance imaging.

    Science.gov (United States)

    van Vliet, Erwin A; Otte, Willem M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A

    2016-01-01

    The mammalian target of rapamycin (mTOR) pathway has received increasing attention as a potential antiepileptogenic target. Treatment with the mTOR inhibitor rapamycin after status epilepticus reduces the development of epilepsy in a rat model. To study whether rapamycin mediates this effect via restoration of blood-brain barrier (BBB) dysfunction, contrast-enhanced magnetic resonance imaging (CE-MRI) was used to determine BBB permeability throughout epileptogenesis. Imaging was repeatedly performed until 6 weeks after kainic acid-induced status epilepticus in rapamycin (6 mg/kg for 6 weeks starting 4 h after SE) and vehicle-treated rats, using gadobutrol as contrast agent. Seizures were detected using video monitoring in the week following the last imaging session. Gadobutrol leakage was widespread and extensive in both rapamycin and vehicle-treated epileptic rats during the acute phase, with the piriform cortex and amygdala as the most affected regions. Gadobutrol leakage was higher in rapamycin-treated rats 4 and 8 days after status epilepticus compared to vehicle-treated rats. However, during the chronic epileptic phase, gadobutrol leakage was lower in rapamycin-treated epileptic rats along with a decreased seizure frequency. This was confirmed by local fluorescein staining in the brains of the same rats. Total brain volume was reduced by this rapamycin treatment regimen. The initial slow recovery of BBB function in rapamycin-treated epileptic rats indicates that rapamycin does not reduce seizure activity by a gradual recovery of BBB integrity. The reduced BBB leakage during the chronic phase, however, could contribute to the decreased seizure frequency in post-status epilepticus rats treated with rapamycin. Furthermore, the data show that CE-MRI (using step-down infusion with gadobutrol) can be used as biomarker for monitoring the effect of drug therapy in rats. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

  20. Magneto-LED therapy in the treatment of inflammatory lesions and erosions of the glans penis – case report

    OpenAIRE

    Jarosław Pasek; Tomasz Pasek; Grzegorz Cieślar; Aleksander Sieroń

    2016-01-01

    Introduction . Inflammatory lesions and erosions of the glans penis defined as balanitis or balanoposthitis constitute a disease in which the effectiveness of conservative treatment is not sufficient. Objective. To present the therapeutic efficacy of magneto-LED therapy in the treatment, and to present a patient with inflammatory lesions and erosions of the glans penis. Case report. The patient, 68 years old with inflammatory lesions and erosions of the glans penis of 2–4 years...

  1. Compressive strength measurements of hybrid dental composites treated with dry heat and light emitting diodes (LED post cure treatment

    Directory of Open Access Journals (Sweden)

    Jenny Krisnawaty

    2014-11-01

    Full Text Available Hybrid composites are mostly used on large cavities as restorative dental materials, whether it is used directly or indirectly. The mechanical properties of composite resin shall increase if it is treated with post cure treatment. The aim of this study is to evaluate compressive strength differences between dry heat and Light Emitting Diodes (LED treatment on the hybrid dental composite. A quasi-experimental was applied on this research with a total of 30 samples that were divided into two groups. Each sample was tested using LLOYD Universal Testing Machine with 1 mm/min speed to evaluate the compressive strength. The compressive strength results were marked when the sample was broken. The results of two groups were then analyzed using t-test statistical calculation. The results of this study show that post cure treatment on hybrid composite using LED light box (194.138 MPa was lower than dry heat treatment (227.339 MPa, which was also significantly different from statistical analysis. It can be concluded that compressive strength of LED light box was lower than dry heat post-cure treatment on the hybrid composite resin.

  2. Addition of rapamycin and hydroxychloroquine to metronomic chemotherapy as a second line treatment results in high salvage rates for refractory metastatic solid tumors: a pilot safety and effectiveness analysis in a small patient cohort.

    Science.gov (United States)

    Chi, Kwan-Hwa; Ko, Hui-Ling; Yang, Kai-Lin; Lee, Cheng-Yen; Chi, Mau-Shin; Kao, Shang-Jyh

    2015-06-30

    Autophagy is an important oncotarget that can be modulated during anti-cancer therapy. Enhancing autophagy using chemotherapy and rapamycin (Rapa) treatment and then inhibiting it using hydroxychloroquine (HCQ) could synergistically improve therapy outcome in cancer patients. It is still unclear whether addition of Rapa and HCQ to chemotherapy could be used for reversing drug resistance. Twenty-five stage IV cancer patients were identified. They had no clinical response to first-line metronomic chemotherapy; the patients were salvaged by adding an autophagy inducer (Rapa, 2 mg/day) and an autophagosome inhibitor (HCQ, 400 mg/day) to their current metronomic chemotherapy for at least 3 months. Patients included 4 prostate, 4 bladder, 4 lung, 4 breast, 2 colon, and 3 head and neck cancer patients as well as 4 sarcoma patients. Chemotherapy was administered for a total of 137 months. The median duration of chemotherapy cycles per patient was 4 months (95% confidence interval, 3-7 months). The overall response rate to this treatment was of 40%, with an 84% disease control rate. The most frequent and clinically significant toxicities were myelotoxicities. Grade ≥3 leucopenia occurred in 6 patients (24%), grade ≥3 thrombocytopenia in 8 (32%), and anemia in 3 (12%). None of them developed febrile neutropenia. Non-hematologic toxicities were fatigue (total 32%, with 1 patient developing grade 3 fatigue), diarrhea (total 20%, 1 patient developed grade 3 fatigue), reversible grade 3 cardiotoxicity (1 patient), and grade V liver toxicity from hepatitis B reactivation (1 patient). Our results of Rapa, HCQ and chemotherapy triplet combination suggest autophagy is a promising oncotarget and warrants further investigation in phase II studies.

  3. Rapamycin Influences the Efficiency of Fertilization and Development in the Mouse: A Role for Autophagic Activation

    Directory of Open Access Journals (Sweden)

    Geun-Kyung Lee

    2016-08-01

    Full Text Available The mammalian target of rapamycin (mTOR regulates cellular processes such as cell growth, metabolism, transcription, translation, and autophagy. Rapamycin is a selective inhibitor of mTOR, and induces autophagy in various systems. Autophagy contributes to clearance and recycling of macromolecules and organelles in response to stress. We previously reported that vitrified-warmed mouse oocytes show acute increases in autophagy during warming, and suggested that it is a natural response to cold stress. In this follow-up study, we examined whether the modulation of autophagy influences survival, fertilization, and developmental rates of vitrified-warmed mouse oocytes. We used rapamycin to enhance autophagy in metaphase II (MII oocytes before and after vitrification. The oocytes were then subjected to in vitro fertilization (IVF. The fertilization and developmental rates of vitrified-warmed oocytes after rapamycin treatment were significantly lower than those for control groups. Modulation of autophagy with rapamycin treatment shows that rapamycin-induced autophagy exerts a negative influence on fertilization and development of vitrified-warmed oocytes.

  4. Rapamycin sensitizes T-ALL cells to dexamethasone-induced apoptosis

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    Mu Dezhi

    2010-11-01

    Full Text Available Abstract Background Glucocorticoid (GC resistance is frequently seen in acute lymphoblastic leukemia of T-cell lineage (T-ALL. In this study we investigate the potential and mechanism of using rapamycin to restore the sensitivity of GC-resistant T-ALL cells to dexamethasone (Dex treatment. Methods Cell proliferation was detected by 3-(4,5-dimethylthiazol-2-yl- 2,5-diphenyltetrazolium bromide (MTT assay. Fluorescence-activated cell sorting (FACS analysis was used to analyze apoptosis and cell cycles. Western blot analysis was performed to test the expression of the downstream effector proteins of mammalian target of rapamycin (mTOR, the cell cycle regulatory proteins, and apoptosis associated proteins. Results 10 nM rapamycin markedly increased GC sensitivity in GC-resistant T-ALL cells and this effect was mediated, at least in part, by inhibition of mTOR signaling pathway. Cell cycle arrest was associated with modulation of G1-S phase regulators. Both rapamycin and Dex can induce up-regulation of cyclin-dependent kinase (CDK inhibitors of p21 and p27 and co-treatment of rapamycin with Dex resulted in a synergistic induction of their expressions. Rapamycin did not obviously affect the expression of cyclin A, whereas Dex induced cyclin A expression. Rapamycin prevented Dex-induced expression of cyclin A. Rapamycin had a stronger inhibition of cyclin D1 expression than Dex. Rapamycin enhanced GC-induced apoptosis and this was not achieved by modulation of glucocorticoid receptor (GR expression, but synergistically up-regulation of pro-apoptotic proteins like caspase-3, Bax, and Bim, and down-regulation of anti-apoptotic protein of Mcl-1. Conclusion Our data suggests that rapamycin can effectively reverse GC resistance in T-ALL and this effect is achieved by inducing cell cycles arrested at G0/G1 phase and activating the intrinsic apoptotic program. Therefore, combination of mTOR inhibitor rapamycin with GC containing protocol might be an attracting

  5. Cholestasis and regulation of genes related to drug metabolism and biliary transport in rat liver following treatment with cyclosporine A and sirolimus (Rapamycin)

    DEFF Research Database (Denmark)

    Bramow, S; Ott, P; Thomsen Nielsen, F

    2001-01-01

    then analysed as were hepatic mRNA levels of canalicular transport proteins (Mrp2, Bsep, Mdr1b and Mdr2), sinusoidal transport proteins (Ntcp, Oatp1 and Oatp2), GSH related enzymes (gamma-glutamylcysteine synthetase light (GCSlc) and heavy (GCShc) chain subunits and glutathione-S-transferase) and CYPs (CYP3A9...... secondary to cyclosporine A could be related to reduction in mRNA expression of GSH synthesising enzymes and Mrp2, leading to reduced protection against oxidative stress and reduced bile acid-independent bile flow. After sirolimus treatment, Mrp2 mRNA was also reduced together with reduced levels of most...... CYPs and increased Oatp2, possibly leading to accumulation of toxic metabolites in the hepatocytes. The enhanced cholestatic effect of the combination treatment could be related to reduced GSH synthesising enzymes and even more pronounced reduction in Mrp2 mRNA and increase of Oatp2 mRNA....

  6. Differential effects of rapamycin and dexamethasone in mouse models of established allergic asthma.

    Directory of Open Access Journals (Sweden)

    Elizabeth M Mushaben

    Full Text Available The mammalian target of rapamycin (mTOR plays an important role in cell growth/differentiation, integrating environmental cues, and regulating immune responses. Our lab previously demonstrated that inhibition of mTOR with rapamycin prevented house dust mite (HDM-induced allergic asthma in mice. Here, we utilized two treatment protocols to investigate whether rapamycin, compared to the steroid, dexamethasone, could inhibit allergic responses during the later stages of the disease process, namely allergen re-exposure and/or during progression of chronic allergic disease. In protocol 1, BALB/c mice were sensitized to HDM (three i.p. injections and administered two intranasal HDM exposures. After 6 weeks of rest/recovery, mice were re-exposed to HDM while being treated with rapamycin or dexamethasone. In protocol 2, mice were exposed to HDM for 3 or 6 weeks and treated with rapamycin or dexamethasone during weeks 4-6. Characteristic features of allergic asthma, including IgE, goblet cells, airway hyperreactivity (AHR, inflammatory cells, cytokines/chemokines, and T cell responses were assessed. In protocol 1, both rapamycin and dexamethasone suppressed goblet cells and total CD4(+ T cells including activated, effector, and regulatory T cells in the lung tissue, with no effect on AHR or total inflammatory cell numbers in the bronchoalveolar lavage fluid. Rapamycin also suppressed IgE, although IL-4 and eotaxin 1 levels were augmented. In protocol 2, both drugs suppressed total CD4(+ T cells, including activated, effector, and regulatory T cells and IgE levels. IL-4, eotaxin, and inflammatory cell numbers were increased after rapamycin and no effect on AHR was observed. Dexamethasone suppressed inflammatory cell numbers, especially eosinophils, but had limited effects on AHR. We conclude that while mTOR signaling is critical during the early phases of allergic asthma, its role is much more limited once disease is established.

  7. Rapamycin down-regulates LDL-receptor expression independently of SREBP-2

    International Nuclear Information System (INIS)

    Sharpe, Laura J.; Brown, Andrew J.

    2008-01-01

    As a key regulator of cholesterol homeostasis, sterol-regulatory element binding protein-2 (SREBP-2) up-regulates expression of genes involved in cholesterol synthesis (e.g., 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) Reductase) and uptake (the low density lipoprotein (LDL)-receptor). Previously, we showed that Akt, a critical kinase in cell growth and proliferation, contributes to SREBP-2 activation. However, the specific Akt target involved is unknown. A potential candidate is the mammalian target of rapamycin, mTOR. Rapamycin can cause hyperlipidaemia clinically, and we hypothesised that this may be mediated via an effect of mTOR on SREBP-2. Herein, we found that SREBP-2 activation and HMG-CoA Reductase gene expression were unaffected by rapamycin treatment. However, LDL-receptor gene expression was decreased by rapamycin, suggesting that this may contribute to the hyperlipidaemia observed in rapamycin-treated patients. Rapamycin did not affect mRNA stability, so the decrease in LDL-receptor gene expression is likely to be occurring at the transcriptional level, although independently of SREBP-2

  8. Rapamycin and Glucose-Target of Rapamycin (TOR) Protein Signaling in Plants*

    Science.gov (United States)

    Xiong, Yan; Sheen, Jen

    2012-01-01

    Target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator that integrates energy, nutrients, growth factors, and stress signals to promote survival and growth in all eukaryotes. The reported land plant resistance to rapamycin and the embryo lethality of the Arabidopsis tor mutants have hindered functional dissection of TOR signaling in plants. We developed sensitive cellular and seedling assays to monitor endogenous Arabidopsis TOR activity based on its conserved S6 kinase (S6K) phosphorylation. Surprisingly, rapamycin effectively inhibits Arabidopsis TOR-S6K1 signaling and retards glucose-mediated root and leaf growth, mimicking estradiol-inducible tor mutants. Rapamycin inhibition is relieved in transgenic plants deficient in Arabidopsis FK506-binding protein 12 (FKP12), whereas FKP12 overexpression dramatically enhances rapamycin sensitivity. The role of Arabidopsis FKP12 is highly specific as overexpression of seven closely related FKP proteins fails to increase rapamycin sensitivity. Rapamycin exerts TOR inhibition by inducing direct interaction between the TOR-FRB (FKP-rapamycin binding) domain and FKP12 in plant cells. We suggest that variable endogenous FKP12 protein levels may underlie the molecular explanation for longstanding enigmatic observations on inconsistent rapamycin resistance in plants and in various mammalian cell lines or diverse animal cell types. Integrative analyses with rapamycin and conditional tor and fkp12 mutants also reveal a central role of glucose-TOR signaling in root hair formation. Our studies demonstrate the power of chemical genetic approaches in the discovery of previously unknown and pivotal functions of glucose-TOR signaling in governing the growth of cotyledons, true leaves, petioles, and primary and secondary roots and root hairs. PMID:22134914

  9. Developing LED UV fluorescence sensors for online monitoring DOM and predicting DBPs formation potential during water treatment.

    Science.gov (United States)

    Li, Wen-Tao; Jin, Jing; Li, Qiang; Wu, Chen-Fei; Lu, Hai; Zhou, Qing; Li, Ai-Min

    2016-04-15

    Online monitoring dissolved organic matter (DOM) is urgent for water treatment management. In this study, high performance size exclusion chromatography with multi-UV absorbance and multi-emission fluorescence scans were applied to spectrally characterize samples from 16 drinking water sources across Yangzi River and Huai River Watersheds. The UV absorbance indices at 254 nm and 280 nm referred to the same DOM components and concentration, and the 280 nm UV light could excite both protein-like and humic-like fluorescence. Hence a novel UV fluorescence sensor was developed out using only one UV280 light-emitting diode (LED) as light source. For all samples, enhanced coagulation was mainly effective for large molecular weight biopolymers; while anion exchange further substantially removed humic substances. During chlorination tests, UVA280 and UVA254 showed similar correlations with yields of disinfection byproducts (DBPs); the humic-like fluorescence obtained from LED sensors correlated well with both trihalomethanes and haloacetic acids yields, while the correlation between protein-like fluorescence and trihalomethanes was relatively poor. Anion exchange exhibited more reduction of DBPs yields as well as UV absorbance and fluorescence signals than enhanced coagulation. The results suggest that the LED UV fluorescence sensors are very promising for online monitoring DOM and predicting DBPs formation potential during water treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Biological constraints limit the use of rapamycin-inducible FKBP12-Inp54p for depleting PIP2 in dorsal root ganglia neurons.

    Science.gov (United States)

    Coutinho-Budd, Jaeda C; Snider, Samuel B; Fitzpatrick, Brendan J; Rittiner, Joseph E; Zylka, Mark J

    2013-09-08

    Rapamycin-induced translocation systems can be used to manipulate biological processes with precise temporal control. These systems are based on rapamycin-induced dimerization of FK506 Binding Protein 12 (FKBP12) with the FKBP Rapamycin Binding (FRB) domain of mammalian target of rapamycin (mTOR). Here, we sought to adapt a rapamycin-inducible phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phosphatase (Inp54p) system to deplete PIP2 in nociceptive dorsal root ganglia (DRG) neurons. We genetically targeted membrane-tethered CFP-FRBPLF (a destabilized FRB mutant) to the ubiquitously expressed Rosa26 locus, generating a Rosa26-FRBPLF knockin mouse. In a second knockin mouse line, we targeted Venus-FKBP12-Inp54p to the Calcitonin gene-related peptide-alpha (CGRPα) locus. We hypothesized that after intercrossing these mice, rapamycin treatment would induce translocation of Venus-FKBP12-Inp54p to the plasma membrane in CGRP+ DRG neurons. In control experiments with cell lines, rapamycin induced translocation of Venus-FKBP12-Inp54p to the plasma membrane, and subsequent depletion of PIP2, as measured with a PIP2 biosensor. However, rapamycin did not induce translocation of Venus-FKBP12-Inp54p to the plasma membrane in FRBPLF-expressing DRG neurons (in vitro or in vivo). Moreover, rapamycin treatment did not alter PIP2-dependent thermosensation in vivo. Instead, rapamycin treatment stabilized FRBPLF in cultured DRG neurons, suggesting that rapamycin promoted dimerization of FRBPLF with endogenous FKBP12. Taken together, our data indicate that these knockin mice cannot be used to inducibly deplete PIP2 in DRG neurons. Moreover, our data suggest that high levels of endogenous FKBP12 could compete for binding to FRBPLF, hence limiting the use of rapamycin-inducible systems to cells with low levels of endogenous FKBP12.

  11. Outcome of treatment seeking rural gamblers attending a nurse-led cognitive-behaviour therapy service: A pilot study

    Directory of Open Access Journals (Sweden)

    Barry Tolchard

    2016-03-01

    Full Text Available Objectives: Little is known about the differences between urban and rural gamblers in Australia, in terms of comorbidity and treatment outcome. Health disparities exist between urban and rural areas in terms of accessibility, availability, and acceptability of treatment programs for problem gamblers. However, evidence supporting cognitive-behaviour therapy as the main treatment for problem gamblers is strong. This pilot study aimed to assess the outcome of a Cognitive-Behavioural Therapy (CBT treatment program offered to urban and rural treatment-seeking gamblers. Methods: People who presented for treatment at a nurse-led Cognitive-Behavioural Therapy (CBT gambling treatment service were invited to take part in this study. A standardised clinical assessment and treatment service was provided to all participants. A series of validated questionnaires were given to all participants at (a assessment, (b discharge, (c at a one-month, and (d at a 3-month follow-up visit. Results: Differences emerged between urban and rural treatment-seeking gamblers. While overall treatment outcomes were much the same at three months after treatment, rural gamblers appeared to respond more rapidly and to have sustained improvements over time. Conclusion: This study suggests that rural problem gamblers experience different levels of co-morbid anxiety and depression from their urban counterparts, but once in treatment appear to respond quicker. ACBT approach was found to be effective in treating rural gamblers and outcomes were maintained. Ensuring better availability and access to such treatment in rural areas is important. Nurses are in a position as the majority health professional in rural areas to provide such help. Keywords: Evidence based health care, Health program evaluation, Models of care, Rural health services delivery, Rural mental health

  12. A system for treatment of diabetic foot ulcers using led irradiation and natural latex

    Directory of Open Access Journals (Sweden)

    Gustavo Adolfo Marcelino de Almeida Nunes

    Full Text Available Abstract Introduction: We developed and tested a new system for inducing the healing of diabetic foot ulcers. The system relies on the regenerative properties of its two components: an insole with a sheet of natural latex and a device that contains a matrix of light emitting diodes with wavelength of 635 nm. Methods The electronic and latex based devices were developed, and a four weeks test was performed in one control group (CG of five ulcers and one experimental group (EG of eight ulcers. The CG was treated with a standard approach, based on a silver-releasing foam dressing, and the EG was treated with the system under test. For each ulcer, an index for quantifying the percentage ulcer recovery, named CRU(%, has been calculated; a CRU(% = 0% means no healing, and a CRU(% = 100% means total healing. Results There were statistically significant increases of CRU(% of 51.8% (p = 0.022, for the CG, and of 78.4% (p < 0.001, for the EG. The increase in the EG was higher than the increase in the CG, and the difference was statistically significant (p < 0.001. The results showed that the proposed method had, for these particular sets of ulcers, faster healing rates, than for the standard method. Conclusion The results hint that the proposed method seems promising as a future treatment method. However, the technique must undergo further testing before it can be considered for extensive clinical applications.

  13. Restoration of Corticosteroid Sensitivity in Chronic Obstructive Pulmonary Disease by Inhibition of Mammalian Target of Rapamycin.

    Science.gov (United States)

    Mitani, Akihisa; Ito, Kazuhiro; Vuppusetty, Chaitanya; Barnes, Peter J; Mercado, Nicolas

    2016-01-15

    Corticosteroid resistance is a major barrier to the effective treatment of chronic obstructive pulmonary disease (COPD). Several molecular mechanisms have been proposed, such as activations of the phosphoinositide-3-kinase/Akt pathway and p38 mitogen-activated protein kinase. However, the mechanism for corticosteroid resistance is still not fully elucidated. To investigate the role of mammalian target of rapamycin (mTOR) in corticosteroid sensitivity in COPD. The corticosteroid sensitivity of peripheral blood mononuclear cells collected from patients with COPD, smokers, and nonsmoking control subjects, or of human monocytic U937 cells exposed to cigarette smoke extract (CSE), was quantified as the dexamethasone concentration required to achieve 30% inhibition of tumor necrosis factor-α-induced CXCL8 production in the presence or absence of the mTOR inhibitor rapamycin. mTOR activity was determined as the phosphorylation of p70 S6 kinase, using Western blotting. mTOR activity was increased in peripheral blood mononuclear cells from patients with COPD, and treatment with rapamycin inhibited this as well as restoring corticosteroid sensitivity. In U937 cells, CSE stimulated mTOR activity and c-Jun expression, but pretreatment with rapamycin inhibited both and also reversed CSE-induced corticosteroid insensitivity. mTOR inhibition by rapamycin restores corticosteroid sensitivity via inhibition of c-Jun expression, and thus mTOR is a potential novel therapeutic target for COPD.

  14. The rapamycin-regulated gene expression signature determines prognosis for breast cancer

    Directory of Open Access Journals (Sweden)

    Tsavachidis Spiridon

    2009-09-01

    Full Text Available Abstract Background Mammalian target of rapamycin (mTOR is a serine/threonine kinase involved in multiple intracellular signaling pathways promoting tumor growth. mTOR is aberrantly activated in a significant portion of breast cancers and is a promising target for treatment. Rapamycin and its analogues are in clinical trials for breast cancer treatment. Patterns of gene expression (metagenes may also be used to simulate a biologic process or effects of a drug treatment. In this study, we tested the hypothesis that the gene-expression signature regulated by rapamycin could predict disease outcome for patients with breast cancer. Results Colony formation and sulforhodamine B (IC50 in vitro and in vivo gene expression data identified a signature, termed rapamycin metagene index (RMI, of 31 genes upregulated by rapamycin treatment in vitro as well as in vivo (false discovery rate of 10%. In the Miller dataset, RMI did not correlate with tumor size or lymph node status. High (>75th percentile RMI was significantly associated with longer survival (P = 0.015. On multivariate analysis, RMI (P = 0.029, tumor size (P = 0.015 and lymph node status (P = 0.001 were prognostic. In van 't Veer study, RMI was not associated with the time to develop distant metastasis (P = 0.41. In the Wang dataset, RMI predicted time to disease relapse (P = 0.009. Conclusion Rapamycin-regulated gene expression signature predicts clinical outcome in breast cancer. This supports the central role of mTOR signaling in breast cancer biology and provides further impetus to pursue mTOR-targeted therapies for breast cancer treatment.

  15. A Signal-On Fluorosensor Based on Quench-Release Principle for Sensitive Detection of Antibiotic Rapamycin

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    Hee-Jin Jeong

    2015-03-01

    Full Text Available An antibiotic rapamycin is one of the most commonly used immunosuppressive drugs, and also implicated for its anti-cancer activity. Hence, the determination of its blood level after organ transplantation or tumor treatment is of great concern in medicine. Although there are several rapamycin detection methods, many of them have limited sensitivity, and/or need complicated procedures and long assay time. As a novel fluorescent biosensor for rapamycin, here we propose “Q’-body”, which works on the fluorescence quench-release principle inspired by the antibody-based quenchbody (Q-body technology. We constructed rapamycin Q’-bodies by linking the two interacting domains FKBP12 and FRB, whose association is triggered by rapamycin. The fusion proteins were each incorporated position-specifically with one of fluorescence dyes ATTO520, tetramethylrhodamine, or ATTO590 using a cell-free translation system. As a result, rapid rapamycin dose-dependent fluorescence increase derived of Q’-bodies was observed, especially for those with ATTO520 with a lowest detection limit of 0.65 nM, which indicates its utility as a novel fluorescent biosensor for rapamycin.

  16. A signal-on fluorosensor based on quench-release principle for sensitive detection of antibiotic rapamycin.

    Science.gov (United States)

    Jeong, Hee-Jin; Itayama, Shuya; Ueda, Hiroshi

    2015-03-26

    An antibiotic rapamycin is one of the most commonly used immunosuppressive drugs, and also implicated for its anti-cancer activity. Hence, the determination of its blood level after organ transplantation or tumor treatment is of great concern in medicine. Although there are several rapamycin detection methods, many of them have limited sensitivity, and/or need complicated procedures and long assay time. As a novel fluorescent biosensor for rapamycin, here we propose "Q'-body", which works on the fluorescence quench-release principle inspired by the antibody-based quenchbody (Q-body) technology. We constructed rapamycin Q'-bodies by linking the two interacting domains FKBP12 and FRB, whose association is triggered by rapamycin. The fusion proteins were each incorporated position-specifically with one of fluorescence dyes ATTO520, tetramethylrhodamine, or ATTO590 using a cell-free translation system. As a result, rapid rapamycin dose-dependent fluorescence increase derived of Q'-bodies was observed, especially for those with ATTO520 with a lowest detection limit of 0.65 nM, which indicates its utility as a novel fluorescent biosensor for rapamycin.

  17. TORC1 Inhibition by Rapamycin Promotes Antioxidant Defences in a Drosophila Model of Friedreich's Ataxia.

    Directory of Open Access Journals (Sweden)

    Pablo Calap-Quintana

    Full Text Available Friedreich's ataxia (FRDA, the most common inherited ataxia in the Caucasian population, is a multisystemic disease caused by a significant decrease in the frataxin level. To identify genes capable of modifying the severity of the symptoms of frataxin depletion, we performed a candidate genetic screen in a Drosophila RNAi-based model of FRDA. We found that genetic reduction in TOR Complex 1 (TORC1 signalling improves the impaired motor performance phenotype of FRDA model flies. Pharmacologic inhibition of TORC1 signalling by rapamycin also restored this phenotype and increased the lifespan and ATP levels. Furthermore, rapamycin reduced the altered levels of malondialdehyde + 4-hydroxyalkenals and total glutathione of the model flies. The rapamycin-mediated protection against oxidative stress is due in part to an increase in the transcription of antioxidant genes mediated by cap-n-collar (Drosophila ortholog of Nrf2. Our results suggest that autophagy is indeed necessary for the protective effect of rapamycin in hyperoxia. Rapamycin increased the survival and aconitase activity of model flies subjected to high oxidative insult, and this improvement was abolished by the autophagy inhibitor 3-methyladenine. These results point to the TORC1 pathway as a new potential therapeutic target for FRDA and as a guide to finding new promising molecules for disease treatment.

  18. Target of rapamycin (TOR) plays a critical role in triacylglycerol accumulation in microalgae.

    Science.gov (United States)

    Imamura, Sousuke; Kawase, Yasuko; Kobayashi, Ikki; Sone, Toshiyuki; Era, Atsuko; Miyagishima, Shin-Ya; Shimojima, Mie; Ohta, Hiroyuki; Tanaka, Kan

    2015-10-01

    Most microalgae produce triacylglycerol (TAG) under stress conditions such as nitrogen depletion, but the underlying molecular mechanism remains unclear. In this study, we focused on the role of target of rapamycin (TOR) in TAG accumulation. TOR is a serine/threonine protein kinase that is highly conserved and plays pivotal roles in nitrogen and other signaling pathways in eukaryotes. We previously constructed a rapamycin-susceptible Cyanidioschyzon merolae, a unicellular red alga, by expressing yeast FKBP12 protein to evaluate the results of TOR inhibition (Imamura et al. in Biochem Biophys Res Commun 439:264-269, 2013). By using this strain, we here report that rapamycin-induced TOR inhibition results in accumulation of cytoplasmic lipid droplets containing TAG. Transcripts for TAG synthesis-related genes, such as glycerol-3-phosphate acyltransferase and acyl-CoA:diacylglycerol acyltransferase (DGAT), were increased by rapamycin treatment. We also found that fatty acid synthase-dependent de novo fatty acid synthesis was required for the accumulation of lipid droplets. Induction of TAG and up-regulation of DGAT gene expression by rapamycin were similarly observed in the unicellular green alga, Chlamydomonas reinhardtii. These results suggest the general involvement of TOR signaling in TAG accumulation in divergent microalgae.

  19. Mechanical activation of mammalian target of rapamycin pathway is required for cartilage development

    OpenAIRE

    Guan, Yingjie; Yang, Xu; Yang, Wentian; Charbonneau, Cherie; Chen, Qian

    2014-01-01

    Mechanical stress regulates development by modulating cell signaling and gene expression. However, the cytoplasmic components mediating mechanotransduction remain unclear. In this study, elimination of muscle contraction during chicken embryonic development resulted in a reduction in the activity of mammalian target of rapamycin (mTOR) in the cartilaginous growth plate. Inhibition of mTOR activity led to significant inhibition of chondrocyte proliferation, cartilage tissue growth, and express...

  20. Enhanced antitumor activity of 3-bromopyruvate in combination with rapamycin in vivo and in vitro.

    Science.gov (United States)

    Zhang, Qi; Pan, Jing; Lubet, Ronald A; Komas, Steven M; Kalyanaraman, Balaraman; Wang, Yian; You, Ming

    2015-04-01

    3-Bromopyruvate (3-BrPA) is an alkylating agent and a well-known inhibitor of energy metabolism. Rapamycin is an inhibitor of the serine/threonine protein kinase mTOR. Both 3-BrPA and rapamycin show chemopreventive efficacy in mouse models of lung cancer. Aerosol delivery of therapeutic drugs for lung cancer has been reported to be an effective route of delivery with little systemic distribution in humans. In this study, 3-BrPA and rapamycin were evaluated in combination for their preventive effects against lung cancer in mice by aerosol treatment, revealing a synergistic ability as measured by tumor multiplicity and tumor load compared treatment with either single-agent alone. No evidence of liver toxicity was detected by monitoring serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes. To understand the mechanism in vitro experiments were performed using human non-small cell lung cancer (NSCLC) cell lines. 3-BrPA and rapamycin also synergistically inhibited cell proliferation. Rapamycin alone blocked the mTOR signaling pathway, whereas 3-BrPA did not potentiate this effect. Given the known role of 3-BrPA as an inhibitor of glycolysis, we investigated mitochondrial bioenergetics changes in vitro in 3-BrPA-treated NSCLC cells. 3-BrPA significantly decreased glycolytic activity, which may be due to adenosine triphosphate (ATP) depletion and decreased expression of GAPDH. Our results demonstrate that rapamycin enhanced the antitumor efficacy of 3-BrPA, and that dual inhibition of mTOR signaling and glycolysis may be an effective therapeutic strategy for lung cancer chemoprevention. ©2015 American Association for Cancer Research.

  1. Rapamycin Eye Drops Suppress Lacrimal Gland Inflammation In a Murine Model of Sjögren's Syndrome

    Science.gov (United States)

    Shah, Mihir; Edman, Maria C.; Reddy Janga, Srikanth; Yarber, Frances; Meng, Zhen; Klinngam, Wannita; Bushman, Jonathan; Ma, Tao; Liu, Siyu; Louie, Stan; Mehta, Arjun; Ding, Chuanqing; MacKay, J. Andrew; Hamm-Alvarez, Sarah F.

    2017-01-01

    Purpose To evaluate the efficacy of topical rapamycin in treating autoimmune dacryoadenitis in a mouse model of Sjögren's syndrome. Methods We developed rapamycin in a poly(ethylene glycol)-distearoyl phosphatidylethanolamine (PEG-DSPE) micelle formulation to maintain solubility. Rapamycin or PEG-DSPE eye drops (vehicle) were administered in a well-established Sjögren's syndrome disease model, the male nonobese diabetic (NOD) mice, twice daily for 12 weeks starting at 8 weeks of age. Mouse tear fluid was collected and tear Cathepsin S, a putative tear biomarker for Sjögren's syndrome, was measured. Lacrimal glands were retrieved for histological evaluation, and quantitative real-time PCR of genes associated with Sjögren's syndrome pathogenesis. Tear secretion was measured using phenol red threads, and corneal fluorescein staining was used to assess corneal integrity. Results Lymphocytic infiltration of lacrimal glands from rapamycin-treated mice was significantly (P = 0.0001) reduced by 3.8-fold relative to vehicle-treated mice after 12 weeks of treatment. Rapamycin, but not vehicle, treatment increased tear secretion and decreased corneal fluorescein staining after 12 weeks. In rapamycin-treated mice, Cathepsin S activity was significantly reduced by 3.75-fold in tears (P eye. PMID:28122086

  2. Mechanical activation of mammalian target of rapamycin pathway is required for cartilage development.

    Science.gov (United States)

    Guan, Yingjie; Yang, Xu; Yang, Wentian; Charbonneau, Cherie; Chen, Qian

    2014-10-01

    Mechanical stress regulates development by modulating cell signaling and gene expression. However, the cytoplasmic components mediating mechanotransduction remain unclear. In this study, elimination of muscle contraction during chicken embryonic development resulted in a reduction in the activity of mammalian target of rapamycin (mTOR) in the cartilaginous growth plate. Inhibition of mTOR activity led to significant inhibition of chondrocyte proliferation, cartilage tissue growth, and expression of chondrogenic genes, including Indian hedgehog (Ihh), a critical mediator of mechanotransduction. Conversely, cyclic loading (1 Hz, 5% matrix deformation) of embryonic chicken growth plate chondrocytes in 3-dimensional (3D) collagen scaffolding induced sustained activation of mTOR. Mechanical activation of mTOR occurred in serum-free medium, indicating that it is independent of growth factor or nutrients. Treatment of chondrocytes with Rapa abolished mechanical activation of cell proliferation and Ihh gene expression. Cyclic loading of chondroprogenitor cells deficient in SH2-containing protein tyrosine phosphatase 2 (Shp2) further enhanced mechanical activation of mTOR, cell proliferation, and chondrogenic gene expression. This result suggests that Shp2 is an antagonist of mechanotransduction through inhibition of mTOR activity. Our data demonstrate that mechanical activation of mTOR is necessary for cell proliferation, chondrogenesis, and cartilage growth during bone development, and that mTOR is an essential mechanotransduction component modulated by Shp2 in the cytoplasm. © FASEB.

  3. Synthesis of I-125 labeled photoaffinity rapamycin analogs

    International Nuclear Information System (INIS)

    Shu, A.Y.L.; Yamashita, D.S.; Holt, D.A.; Heys, J.R.

    1996-01-01

    Two no-carrier-added 125 I-labelled photoaffinity rapamycin analogs were prepared: 7-demethoxy-7-(4-azido-3- 125 I-benzyloxy) rapamycin and its C 28 -C 29 seco analog. The key reactions of the synthesis were substitution of the C 7 methoxyl of rapamycin with 4-azido-3-tributylstannylbenzyloxy group, exchange of tributyltin with 125 I using Na 125 I and Chloramine-T, and a ZnCl 2 mediated retro-Aldol cleavage of the C 28 -C 29 bond of rapamycin. (author)

  4. Performance optimization of AlGaN-based LEDs by use of ultraviolet-transparent indium tin oxide: Effect of in situ contact treatment

    Science.gov (United States)

    Tu, Wenbin; Chen, Zimin; Zhuo, Yi; Li, Zeqi; Ma, Xuejin; Wang, Gang

    2018-05-01

    Ultraviolet (UV)-transparent indium tin oxide (ITO) grown by metal–organic chemical vapor deposition (MOCVD) is used as the current-spreading layer for 368 nm AlGaN-based light-emitting diodes (LEDs). By performing in situ contact treatment on the LED/ITO interface, the morphology, resistivity, and contact resistance of electrodes become controllable. Resistivity of 2.64 × 10‑4 Ω cm and transmittance at 368 nm of 95.9% are realized for an ITO thin film grown with Sn-purge in situ treatment. Therefore, the high-power operating voltage decreases from 3.94 V (without treatment) to 3.83 V (with treatment). The improved performance is attributed to the lowering of the tunneling barrier at the LED/ITO interface.

  5. Synergistic Effect of Rapamycin and Metformin Against Age-Dependent Oxidative Stress in Rat Erythrocytes.

    Science.gov (United States)

    Singh, Abhishek Kumar; Garg, Geetika; Singh, Sandeep; Rizvi, Syed Ibrahim

    2017-10-01

    Erythrocytes are particularly vulnerable toward age-dependent oxidative stress-mediated damage. Caloric restriction mimetics (CRMs) may provide a novel strategy for the maintenance of redox balance as well as effective treatment of age-associated diseases. Herein, we have investigated the beneficial effect of cotreatment with CRM-candidate drugs, rapamycin (an immunosuppressant drug and inhibitor of mammalian target of rapamycin) and metformin (an antidiabetic biguanide and activator of adenosine monophosphate kinase), against aging-induced oxidative stress in erythrocytes and plasma of aging rats. Male Wistar rats of age 4 (young) and 24 months (old) were coexposed to rapamycin (0.5 mg/kg body weight [b.w.]) and metformin (300 mg/kg b.w.), and data were compared with the response of rats receiving an independent exposure to these chemicals at similar doses. The exposure of individual candidate drugs significantly reversed the age-dependent alterations in the endpoints associated with oxidative stress such as reactive oxygen species, ferric reducing ability of plasma, malondialdehyde, reduced glutathione, plasma membrane redox system, plasma protein carbonyl, and acetyl cholinesterase in erythrocytes and plasma of aging rats. However, the cotreatment with rapamycin and metformin showed a significant augmented effect compared with individual drug interventions on reversal of these age-dependent biomarkers of oxidative stress, suggesting a synergistic response. Thus, the findings open up further possibilities for the design of new combinatorial therapies to prevent oxidative stress- and age-associated health problems.

  6. Effects of blue diode laser (445 nm) and LED (430-480 nm) radiant heat treatments on dental glass ionomer restoratives

    Science.gov (United States)

    Dionysopoulos, Dimitrios; Tolidis, Kosmas; Strakas, Dimitrios; Gerasimou, Paris; Sfeikos, Thrasyvoulos; Gutknecht, Norbert

    2018-02-01

    The purpose of this in vitro study was to evaluate the effect of two radiant heat treatments on water sorption, solubility and surface roughness of three conventional glass ionomer cements by using a blue diode laser (445 nm) and a light emitting diode (LED) unit (430-480 nm). Thirty disk-shaped specimens were prepared for each tested GIC (Equia Fil, Ketac Universal Aplicap and Riva Self Cure). The experimental groups (n = 10) of the study were as follows: Group 1 was the control group, in Group 2 the specimens were irradiated for 60 s at the top surface using a LED light-curing unit and in Group 3 the specimens were irradiated for 60 s at the top surface using a blue light diode laser. Statistical analysis was performed using one-way ANOVA and Tukey post hoc tests at a level of significance of a = 0.05. Radiant heat treatments with both laser and LED devices significantly decreased water sorption and solubility (p tested GICs. Blue diode laser treatment was seemed to be more effective compared to LED treatment for some of the tested materials. There were no changes in surface roughness of the GICs after the treatments (p > 0.05). Among the tested materials there were differences in water sorption and solubility (p 0.05). The use of the blue diode laser for this radiant heat treatment was harmless for the surface of the tested GICs and may be advantageous for the longevity of their restorations.

  7. Rapamycin inhibits poly(ADP-ribosyl)ation in intact cells

    International Nuclear Information System (INIS)

    Fahrer, Joerg; Wagner, Silvia; Buerkle, Alexander; Koenigsrainer, Alfred

    2009-01-01

    Rapamycin is an immunosuppressive drug, which inhibits the mammalian target of rapamycin (mTOR) kinase activity inducing changes in cell proliferation. Synthesis of poly(ADP-ribose) (PAR) is an immediate cellular response to genotoxic stress catalyzed mostly by poly(ADP-ribose) polymerase 1 (PARP-1), which is also controlled by signaling pathways. Therefore, we investigated whether rapamycin affects PAR production. Strikingly, rapamycin inhibited PAR synthesis in living fibroblasts in a dose-dependent manner as monitored by immunofluorescence. PARP-1 activity was then assayed in vitro, revealing that down-regulation of cellular PAR production by rapamycin was apparently not due to competitive PARP-1 inhibition. Further studies showed that rapamycin did not influence the cellular NAD pool and the activation of PARP-1 in extracts of pretreated fibroblasts. Collectively, our data suggest that inhibition of cellular PAR synthesis by rapamycin is mediated by formation of a detergent-sensitive complex in living cells, and that rapamycin may have a potential as therapeutic PARP inhibitor.

  8. Rapamycin inhibits poly(ADP-ribosyl)ation in intact cells

    Energy Technology Data Exchange (ETDEWEB)

    Fahrer, Joerg, E-mail: joerg.fahrer@uni-ulm.de [Molecular Toxicology Group, Department of Biology, University of Konstanz (Germany); Wagner, Silvia [Clinic of General, Visceral- and Transplantation Surgery, ZMF, University Hospital Tuebingen (Germany); Buerkle, Alexander [Molecular Toxicology Group, Department of Biology, University of Konstanz (Germany); Koenigsrainer, Alfred [Clinic of General, Visceral- and Transplantation Surgery, ZMF, University Hospital Tuebingen (Germany)

    2009-08-14

    Rapamycin is an immunosuppressive drug, which inhibits the mammalian target of rapamycin (mTOR) kinase activity inducing changes in cell proliferation. Synthesis of poly(ADP-ribose) (PAR) is an immediate cellular response to genotoxic stress catalyzed mostly by poly(ADP-ribose) polymerase 1 (PARP-1), which is also controlled by signaling pathways. Therefore, we investigated whether rapamycin affects PAR production. Strikingly, rapamycin inhibited PAR synthesis in living fibroblasts in a dose-dependent manner as monitored by immunofluorescence. PARP-1 activity was then assayed in vitro, revealing that down-regulation of cellular PAR production by rapamycin was apparently not due to competitive PARP-1 inhibition. Further studies showed that rapamycin did not influence the cellular NAD pool and the activation of PARP-1 in extracts of pretreated fibroblasts. Collectively, our data suggest that inhibition of cellular PAR synthesis by rapamycin is mediated by formation of a detergent-sensitive complex in living cells, and that rapamycin may have a potential as therapeutic PARP inhibitor.

  9. LED Technology for Dental Applications

    DEFF Research Database (Denmark)

    Argyraki, Aikaterini; Ou, Yiyu; Soerensen, L. H.

    LEDs have a large potential in many dental and oral applications. Areas such as photo polymerization, fluorescence imaging, photodynamic therapy, and photoactivated disinfection are important future candidates for LED based diagnostics and treatment in dentistry.......LEDs have a large potential in many dental and oral applications. Areas such as photo polymerization, fluorescence imaging, photodynamic therapy, and photoactivated disinfection are important future candidates for LED based diagnostics and treatment in dentistry....

  10. Activation of the unfolded protein response in sarcoma cells treated with rapamycin or temsirolimus.

    Directory of Open Access Journals (Sweden)

    Joseph W Briggs

    Full Text Available Activation of the unfolded protein response (UPR in eukaryotic cells represents an evolutionarily conserved response to physiological stress. Here, we report that the mTOR inhibitors rapamycin (sirolimus and structurally related temsirolimus are capable of inducing UPR in sarcoma cells. However, this effect appears to be distinct from the classical role for these drugs as mTOR inhibitors. Instead, we detected these compounds to be associated with ribosomes isolated from treated cells. Specifically, temsirolimus treatment resulted in protection from chemical modification of several rRNA residues previously shown to bind rapamycin in prokaryotic cells. As an application for these findings, we demonstrate maximum tumor cell growth inhibition occurring only at doses which induce UPR and which have been shown to be safely achieved in human patients. These results are significant because they challenge the paradigm for the use of these drugs as anticancer agents and reveal a connection to UPR, a conserved biological response that has been implicated in tumor growth and response to therapy. As a result, eIF2 alpha phosphorylation and Xbp-1 splicing may serve as useful biomarkers of treatment response in future clinical trials using rapamycin and rapalogs.

  11. Systemic inhibition of mTOR kinase via rapamycin disrupts consolidation and reconsolidation of auditory fear memory.

    Science.gov (United States)

    Mac Callum, Phillip E; Hebert, Mark; Adamec, Robert E; Blundell, Jacqueline

    2014-07-01

    The mammalian target of rapamycin (mTOR) kinase is a critical regulator of mRNA translation and is known to be involved in various long lasting forms of synaptic and behavioural plasticity. However, information concerning the temporal pattern of mTOR activation and susceptibility to pharmacological intervention during both consolidation and reconsolidation of long-term memory (LTM) remains scant. Male C57BL/6 mice were injected systemically with rapamycin at various time points following conditioning or retrieval in an auditory fear conditioning paradigm, and compared to vehicle (and/or anisomycin) controls for subsequent memory recall. Systemic blockade of mTOR with rapamycin immediately or 12h after training or reactivation impairs both consolidation and reconsolidation of an auditory fear memory. Further behavioural analysis revealed that the enduring effects of rapamycin on reconsolidation are dependent upon reactivation of the memory trace. Rapamycin, however, has no effect on short-term memory or the ability to retrieve an established fear memory. Collectively, our data suggest that biphasic mTOR signalling is essential for both consolidation and reconsolidation-like activities that contribute to the formation, re-stabilization, and persistence of long term auditory-fear memories, while not influencing other aspects of the memory trace. These findings also provide evidence for a cogent treatment model for reducing the emotional strength of established, traumatic memories analogous to those observed in acquired anxiety disorders such as posttraumatic stress disorder (PTSD) and specific phobias, through pharmacologic blockade of mTOR using systemic rapamycin following reactivation. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. New dental applications with LEDs

    DEFF Research Database (Denmark)

    Argyraki, A.; Ou, Yiyu; Petersen, Paul Michael

    Visible and ultraviolet LEDs will in the future give rise to new dental applications. Fluorescence imaging, photodynamic therapy and photoactivated disinfection are important future candidates for diagnostics and treatment in dentistry.......Visible and ultraviolet LEDs will in the future give rise to new dental applications. Fluorescence imaging, photodynamic therapy and photoactivated disinfection are important future candidates for diagnostics and treatment in dentistry....

  13. Integrated aerobic biological-chemical treatment of winery wastewater diluted with urban wastewater. LED-based photocatalysis in the presence of monoperoxysulfate.

    Science.gov (United States)

    Solís, Rafael R; Rivas, Francisco Javier; Ferreira, Leonor C; Pirra, Antonio; Peres, José A

    2018-01-28

    The oxidation of Winery Wastewater (WW) by conventional aerobic biological treatment usually leads to inefficient results due to the presence of organic substances, which are recalcitrant or toxic in conventional procedures. This study explores the combination of biological and chemical processes in order to complete the oxidation of biodegradable and non-biodegradable compounds in two sequential steps. Thus, a biological oxidation of a diluted WW is carried out by using the activated sludge process. Activated sludge was gradually acclimated to the Diluted Winery Wastewater (DWW). Some aspects concerning the biological process were evaluated (kinetics of the oxidation and sedimentation of the sludge produced). The biological treatment of the DWW led to a 40-50% of Chemical Oxygen Demand (COD) removal in 8 h, being necessary the application of an additional process. Different chemical processes combining UVA-LEDs radiation, monoperoxysulfate (MPS) and photocatalysts were applied in order to complete the COD depletion and efficient removal of polyphenols content, poorly oxidized in the previous biological step. From the options tested, the combination of UVA, MPS and a novel LaCoO 3 -TiO 2 composite, with double route of MPS decomposition through heterogeneous catalysis and photocatalysis, led to the best results (95% of polyphenol degradation, and additional 60% of COD removal). Initial MPS concentration and pH effect in this process were assessed.

  14. Online, social media and mobile technologies for psychosis treatment: a systematic review on novel user-led interventions.

    Science.gov (United States)

    Alvarez-Jimenez, M; Alcazar-Corcoles, M A; González-Blanch, C; Bendall, S; McGorry, P D; Gleeson, J F

    2014-06-01

    Internet and mobile-based interventions provide a unique opportunity to deliver cost-effective, accessible, time-unlimited support to people with psychosis. The aims of this study were to systematically compile and analyze the evidence on the acceptability, feasibility, safety and benefits of online and mobile-based interventions for psychosis. Systematic review of peer-reviewed studies examining the usability, acceptability, feasibility, safety or efficacy of user-led, Internet or mobile-based interventions, with at least 80% of participants diagnosed with schizophrenia-spectrum disorders. Of 38 potentially relevant articles, 12 were eligible for inclusion. Interventions included web-based psycho-education; web-based psycho-education plus moderated forums for patients and supporters; integrated web-based therapy, social networking and peer and expert moderation; web-based CBT; personalized advice based on clinical monitoring; and text messaging interventions. Results showed that 74-86% of patients used the web-based interventions efficiently, 75-92% perceived them as positive and useful, and 70-86% completed or were engaged with the interventions over the follow-up. Preliminary evidence indicated that online and mobile-based interventions show promise in improving positive psychotic symptoms, hospital admissions, socialization, social connectedness, depression and medication adherence. Internet and mobile-based interventions for psychosis seem to be acceptable and feasible and have the potential to improve clinical and social outcomes. The heterogeneity, poor quality and early state of current research precludes any definite conclusions. Future research should investigate the efficacy of online and mobile interventions through controlled, well-powered studies, which investigate intervention and patient factors associated with take-up and intervention effects. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Sqstm1 knock-down causes a locomotor phenotype ameliorated by rapamycin in a zebrafish model of ALS/FTLD.

    Science.gov (United States)

    Lattante, Serena; de Calbiac, Hortense; Le Ber, Isabelle; Brice, Alexis; Ciura, Sorana; Kabashi, Edor

    2015-03-15

    Mutations in SQSTM1, encoding for the protein SQSTM1/p62, have been recently reported in 1-3.5% of patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration (ALS/FTLD). Inclusions positive for SQSTM1/p62 have been detected in patients with neurodegenerative disorders, including ALS/FTLD. In order to investigate the pathogenic mechanisms induced by SQSTM1 mutations in ALS/FTLD, we developed a zebrafish model. Knock-down of the sqstm1 zebrafish ortholog, as well as impairment of its splicing, led to a specific phenotype, consisting of behavioral and axonal anomalies. Here, we report swimming deficits associated with shorter motor neuronal axons that could be rescued by the overexpression of wild-type human SQSTM1. Interestingly, no rescue of the loss-of-function phenotype was observed when overexpressing human SQSTM1 constructs carrying ALS/FTLD-related mutations. Consistent with its role in autophagy regulation, we found increased mTOR levels upon knock-down of sqstm1. Furthermore, treatment of zebrafish embryos with rapamycin, a known inhibitor of the mTOR pathway, yielded an amelioration of the locomotor phenotype in the sqstm1 knock-down model. Our results suggest that loss-of-function of SQSTM1 causes phenotypic features characterized by locomotor deficits and motor neuron axonal defects that are associated with a misregulation of autophagic processes. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Effect of a Cooling Step Treatment on a High-Voltage GaN LED During ICP Dry Etching

    Science.gov (United States)

    Lin, Yen-Sheng; Hsiao, Sheng-Yu; Tseng, Chun-Lung; Shen, Ching-Hsing; Chiang, Jung-Sheng

    2017-02-01

    In this study, a lower dislocation density for a GaN surface and a reduced current path are observed at the interface of a SiO2 isolation sidewall, using high-resolution transmission electron microscopy. This is grown using a 3-min cooling step treatment during inductivity coupled plasma dry etching. The lower forward voltage is measured, the leakage current decreases from 53nA to 32nA, and the maximum output power increases from 354.8 W to 357.2 W for an input current of 30 mA. The microstructure and the optoelectronic properties of high-voltage light-emitting-diodes is proven to be affected by the cooling step treatment, which allows enough time to release the thermal energy of the SiO2 isolation well.

  17. A controlled trial of the Litebook light-emitting diode (LED light therapy device for treatment of Seasonal Affective Disorder (SAD

    Directory of Open Access Journals (Sweden)

    Telner John

    2007-08-01

    Full Text Available Abstract Background Recent research has emphasized that the human circadian rhythm system is differentially sensitive to short wavelength light. Light treatment devices using efficient light-emitting diodes (LEDs whose output is relatively concentrated in short wavelengths may enable a more convenient effective therapy for Seasonal Affective Disorder (SAD. Methods The efficacy of a LED light therapy device in the treatment of SAD was tested in a randomized, double-blind, placebo-controlled, multi-center trial. Participants aged 18 to 65 with SAD (DSM-IV major depression with seasonal pattern were seen at Baseline and Randomization visits separated by 1 week, and after 1, 2, 3 and 4 weeks of treatment. Hamilton Depression Rating Scale scores (SIGH-SAD were obtained at each visit. Participants with SIGH-SAD of 20 or greater at Baseline and Randomization visits were randomized to active or control treatment: exposure to the Litebook LED treatment device (The Litebook Company Ltd., Alberta, Canada which delivers 1,350 lux white light (with spectral emission peaks at 464 nm and 564 nm at a distance of 20 inches or to an inactivated negative ion generator at a distance of 20 inches, for 30 minutes a day upon awakening and prior to 8 A.M. Results Of the 26 participants randomized, 23 completed the trial. Mean group SIGH-SAD scores did not differ significantly at randomization. At trial end, the proportions of participants in remission (SIGH-SAD less than 9 were significantly greater (Fisher's exact test, and SIGH-SAD scores, as percent individual score at randomization, were significantly lower (t-test, with active treatment than with control, both in an intent-to-treat analysis and an observed cases analysis. A longitudinal repeated measures ANOVA analysis of SIGH-SAD scores also indicated a significant interaction of time and treatment, showing superiority of the Litebook over the placebo condition. Conclusion The results of this pilot study support

  18. Efficacy of Polyphenon E, Red Ginseng, and Rapamycin on Benzo(apyrene-Induced Lung Tumorigenesis in A/J Mice

    Directory of Open Access Journals (Sweden)

    Ying Yan

    2006-01-01

    Full Text Available The objective of this investigation was to determine the efficacy of several novel agents in preventing lung tumorigenesis in mice. We evaluated polyphenon E, red ginseng, and rapamycin in A/J mice treated with the tobacco-specific carcinogen benzo(apyrene for their ability to inhibit pulmonary adenoma formation and growth. We found that treatment with polyphenon E exhibited a significant reduction on both tumor multiplicity and tumor load (tumor multiplicity × tumor volume in a dose-dependent fashion. Polyphenon E (2% wt/wt in the diet reduced tumor multiplicity by 46% and tumor load by 94%. This result provided key evidence in support of a phase II clinical chemoprevention trial of lung cancer. Administration of red ginseng in drinking water decreased tumor multiplicity by 36% and tumor load by 70%. The mammalian target of rapamycin inhibitor rapamycin showed significant efficacy against lung tumor growth in the tumor progression protocol and reduced tumor load by 84%. The results of these investigations demonstrate that polyphenon E, red ginseng, and rapamycin significantly inhibit pulmonary adenoma formation and growth in A/J mice.

  19. Improving the diagnosis and treatment of osteoporosis using a senior-friendly peer-led community education and mentoring model: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Kloseck M

    2017-05-01

    Full Text Available Marita Kloseck,1,2 Deborah A Fitzsimmons,1,3,4 Mark Speechley,5 Marie Y Savundranayagam,1 Richard G Crilly1,2 1Sam Katz Community Health and Aging Research Unit, 2Division of Geriatric Medicine, Western University, London, ON, Canada; 3School of Nursing and Allied Health, Liverpool John Moores University, Liverpool, 4School of Health and Related Research, The University of Sheffield, Sheffield, UK; 5Department of Epidemiology and Biostatistics, Western University, London, ON, Canada Background: This randomized controlled trial (RCT evaluated a 6-month peer-led community education and mentorship program to improve the diagnosis and management of osteoporosis.Methods: Ten seniors (74–90 years of age were trained to become peer educators and mentors and deliver the intervention. In the subsequent RCT, 105 seniors (mean age =80.5±6.9; 89% female were randomly assigned to the peer-led education and mentorship program (n=53 or control group (n=52. Knowledge was assessed at baseline and 6 months. Success was defined as discussing osteoporosis risk with their family physician, obtaining a bone mineral density assessment, and returning to review their risk profile and receive advice and/or treatment.Results: Knowledge of osteoporosis did not change significantly. There was no difference in knowledge change between the two groups (mean difference =1.3, 95% confidence interval [CI] of difference −0.76 to 3.36. More participants in the intervention group achieved a successful outcome (odds ratio 0.16, 95% CI 0.06–0.42, P<0.001.Conclusion: Peer-led education and mentorship can promote positive health behavior in seniors. This model was effective for improving osteoporosis risk assessment, diagnosis, and treatment in a community setting. Keywords: prevention, seniors, mentor, bone mineral density, capacity building, community knowledge translation

  20. Improving the diagnosis and treatment of osteoporosis using a senior-friendly peer-led community education and mentoring model: a randomized controlled trial.

    Science.gov (United States)

    Kloseck, Marita; Fitzsimmons, Deborah A; Speechley, Mark; Savundranayagam, Marie Y; Crilly, Richard G

    2017-01-01

    This randomized controlled trial (RCT) evaluated a 6-month peer-led community education and mentorship program to improve the diagnosis and management of osteoporosis. Ten seniors (74-90 years of age) were trained to become peer educators and mentors and deliver the intervention. In the subsequent RCT, 105 seniors (mean age =80.5±6.9; 89% female) were randomly assigned to the peer-led education and mentorship program (n=53) or control group (n=52). Knowledge was assessed at baseline and 6 months. Success was defined as discussing osteoporosis risk with their family physician, obtaining a bone mineral density assessment, and returning to review their risk profile and receive advice and/or treatment. Knowledge of osteoporosis did not change significantly. There was no difference in knowledge change between the two groups (mean difference =1.3, 95% confidence interval [CI] of difference -0.76 to 3.36). More participants in the intervention group achieved a successful outcome (odds ratio 0.16, 95% CI 0.06-0.42, P seniors. This model was effective for improving osteoporosis risk assessment, diagnosis, and treatment in a community setting.

  1. Bone growth during rapamycin therapy in young rats

    Directory of Open Access Journals (Sweden)

    He Yu-Zhu

    2009-01-01

    Full Text Available Abstract Background Rapamycin is an effective immunosuppressant widely used to maintain the renal allograft in pediatric patients. Linear growth may be adversely affected in young children since rapamycin has potent anti-proliferative and anti-angiogenic properties. Methods Weanling three week old rats were given rapamycin at 2.5 mg/kg daily by gavage for 2 or 4 weeks and compared to a Control group given equivalent amount of saline. Morphometric measurements and biochemical determinations for serum calcium, phosphate, iPTH, urea nitrogen, creatinine and insulin-growth factor I (IGF-I were obtained. Histomorphometric analysis of the growth plate cartilage, in-situ hybridization experiments and immunohistochemical studies for various proteins were performed to evaluate for chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption. Results At the end of the 2 weeks, body and tibia length measurements were shorter after rapamycin therapy associated with an enlargement of the hypertrophic zone in the growth plate cartilage. There was a decrease in chondrocyte proliferation assessed by histone-4 and mammalian target of rapamycin (mTOR expression. A reduction in parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP and an increase in Indian hedgehog (Ihh expression may explain in part, the increase number of hypertrophic chondrocytes. The number of TRAP positive multinucleated chondro/osteoclasts declined in the chondro-osseous junction with a decrease in the receptor activator of nuclear factor kappa β ligand (RANKL and vascular endothelial growth factor (VEGF expression. Although body and tibial length remained short after 4 weeks of rapamycin, changes in the expression of chondrocyte proliferation, chondrocyte differentiation and chondro/osteoclastic resorption which were significant after 2 weeks of rapamycin improved at the end of 4 weeks. Conclusion When given to young rats, 2 weeks of rapamycin

  2. Mammalian target of rapamycin activity is required for expansion of CD34(+) hematopoietic progenitor cells

    NARCIS (Netherlands)

    Geest, Christian R.; Zwartkruis, Fried J.; Vellenga, Edo; Coffer, Paul J.; Buitenhuis, Miranda

    Background The mammalian target of rapamycin is a conserved protein kinase known to regulate protein synthesis, cell size and proliferation. Aberrant regulation of mammalian target of rapamycin activity has been observed in hematopoietic malignancies, including acute leukemias and myelodysplastic

  3. Disruption of mammalian target of rapamycin complex 1 in macrophages decreases chemokine gene expression and atherosclerosis

    NARCIS (Netherlands)

    Ai, Ding; Jiang, Hongfeng; Westerterp, Marit; Murphy, Andrew J.; Wang, Mi; Ganda, Anjali; Abramowicz, Sandra; Welch, Carrie; Almazan, Felicidad; Zhu, Yi; Miller, Yury I.; Tall, Alan R.

    2014-01-01

    The mammalian target of rapamycin complex 1 inhibitor, rapamycin, has been shown to decrease atherosclerosis, even while increasing plasma low-density lipoprotein levels. This suggests an antiatherogenic effect possibly mediated by the modulation of inflammatory responses in atherosclerotic plaques.

  4. GSK-3/Rb12 Pathway as a Novel Target of Rapamycin in Prostate Cancer

    National Research Council Canada - National Science Library

    Litovchick, Larissa

    2005-01-01

    .... Rapamycin exerts its effects through inhibition of mammalian Target of Rapamycin (mTOR) protein kinase resulting in a decreased expression of a subset of proteins essential for cell cycle progression...

  5. Giant Bilateral Renal Angiomyolipomas and Lymphangioleiomyomatosis Presenting after Two Successive Pregnancies Successfully Treated with Surgery and Rapamycin

    Directory of Open Access Journals (Sweden)

    Ramón Peces

    2011-01-01

    Full Text Available We report the case of a 25-year-old woman who presented with abdominal and flank pain with two successive pregnancies and was diagnosed of giant bilateral renal AMLs and pulmonary LAM associated with TSC in the post-partum of her second pregnancy. This case illustrates that in women with TSC rapid growth from renal AMLs and development of LAM may occur with successive pregnancies. It also stresses the potential for preservation of renal function despite successive bilateral renal surgery of giant AMLs. Moreover, the treatment with a low-dose rapamycin may be an option for LAM treatment. Finally, a low-dose rapamycin may be considered as an adjuvant treatment together to kidney-sparing conservative surgery for renal AMLs.

  6. Fototerapia (LEDs 660/890nm no tratamento de úlceras de perna em pacientes diabéticos: estudo de caso Phototherapy (LEDs 660/890nm in the treatment of leg ulcers in diabetic patients: case study

    Directory of Open Access Journals (Sweden)

    Débora Garbin Minatel

    2009-07-01

    Full Text Available Avaliou-se a fototerapia na cicatrização de úlceras de perna (UP mistas em dois pacientes diabéticos (tipo 2, hipertensos. O aparelho apresentava sonda 1 (S1 (1 LED de 660nm, 5mW aplicado em 3 UP e sonda 2 (S2 (32 LEDs de 890nm e 4 LEDs de 660nm, 500mW em 6 UP. Após antissepsia,úlceras foram tratadas com sondas a 3J/cm2, 30seg, 2x/semana seguido pelo curativo diário com sulfadiazina de prata a 1% por 12 semanas. Pela análise com software Image J®, as UP com S2 tiveram índices de cicatrização médios de 0,6; 0,7 e 0,9 enquanto S1 foi de 0,2; 0,4 e 0,6 no 30º, 60º e 90º dias, respectivamente. A fototerapia acelerou a cicatrização das úlceras de perna em pacientes diabéticos.This study evaluated the use of phototherapy in the healing of mixed leg ulcers in two diabetic patients (type 2 with arterial hypertension. The device had probe 1 (one 660nm LED, 5mW applied in 3 ulcers and probe 2 (32 890nm LEDs associated with 4 660nm LEDs, 500mW in 6 ulcers. After asepsis, ulcers were treated with probes to 3 J/cm2, 30sec per point, twice a week, followed by topical daily dressing with 1% silver sulphadiazine during 12 weeks. The following analyses of ulcers with software Image J showed that probe 2 presented mean healing rates of 0.6; 0.7 and 0.9, whereas probe 1 had 0.2;0.4 and 0.6 at 30, 60 and 90 days, espectively. Phototherapy accelerated wound healing of leg ulcers in diabetic patients.

  7. Rapamycin-based inducible translocation systems for studying phagocytosis.

    Science.gov (United States)

    Bohdanowicz, Michal; Fairn, Gregory D

    2011-01-01

    Phagocytosis is an immune receptor-mediated process whereby cells engulf large particles. The process is dynamic and requires several localized factors acting in concert with and sequentially after the engagement of immune receptors to envelope the particle. Once the particle is internalized, the nascent -phagosome undergoes a series of events leading to its maturation to the microbicidal phagolysosome. Investigating these dynamic and temporally controlled series of events in live cells requires noninvasive methods. The ability to rapidly recruit the proteins of interest to the sites of phagocytosis or to nascent phagosomes would help dissect the regulatory mechanisms involved during phagocytosis. Here, we describe a general approach to express in RAW264.7 murine macrophages, a genetically encoded rapamycin--induced heterodimerization system. In the presence of rapamycin, tight association between FK506-binding protein (FKBP) and FKBP rapamycin-binding protein (FRB) is observed. Based on this principle, a synthetic system consisting of a targeting domain attached to FKBP can recruit a protein of interest fused to FRB upon the addition of rapamycin. Previously, this technique has been used to target lipid-modifying enzymes and small GTPases to the phagosome or plasma membrane. The recruitment of the FRB module can be monitored by fluorescent microscopy if a fluorescent protein is fused to the FRB sequence. While the focus of this chapter is on phagocytic events, this method can be employed to study any organelle of interest when the appropriate targeting sequence is used.

  8. Photobiomodulation versus light-emitting diode (LED) therapy in the treatment of temporomandibular disorder: study protocol for a randomized, controlled clinical trial.

    Science.gov (United States)

    Langella, Luciana G; Silva, Paula F C; Costa-Santos, Larissa; Gonçalves, Marcela L L; Motta, Lara J; Deana, Alessandro M; Fernandes, Kristianne P S; Mesquita-Ferrari, Raquel A; Bussadori, Sandra Kalil

    2018-01-26

    Temporomandibular disorder (TMD) is described as a subgroup of orofacial pain with a set of signs and symptoms that involve the temporomandibular joint, masticatory muscles, ears, and neck. TMD can occur unilaterally or bilaterally and approximately 70% of the population is affected with at least one sign. The disorder progresses with orofacial pain, muscle pain involving the masticatory and cervical muscles, joint noises (clicks and pops), joint block, mandibular dysfunction, and headache. The etiology can be abnormal occlusion and/or posture, trauma involving local tissues, repetitive microtrauma, parafunctional habits, and an increase in emotional stress. Studies have demonstrated that phototherapy is an efficient option for the treatment of TMD, leading to improvements in pain and orofacial function. The aim of the proposed study is to compare the effects of two sources of photobiomodulation in individuals with TMD. A randomized, controlled, double-blind, clinical trial is proposed, which will involve 80 individuals aged 18-65 years allocated to either a laser group or light-emitting diode (LED) group submitted to 12 sessions of phototherapy. The Research Diagnostic Criteria for TMDs will be used to evaluate all participants. Pain will be measured using the visual analog scale and maximum vertical mandibular movement will be determined with the aid of digital calipers. This study compares the effects of two modalities of laser therapy on the pain and orofacial function of patients with TMD dysfunction. Photobiomodulation and LED therapy are treatment options for reducing the inflammatory process and pain as well as inducing the regeneration of the target tissue. ClinicalTrials.gov, NCT03257748 . Registered on 8 August 2017.

  9. The Effect of Different Dosing Schedules of Intravitreal Sirolimus, a Mammalian Target of Rapamycin (mTOR) Inhibitor, in the Treatment of Non-Infectious Uveitis (An American Ophthalmological Society Thesis).

    Science.gov (United States)

    Nguyen, Quan Dong; Sadiq, Mohammad Ali; Soliman, Mohamed Kamel; Agarwal, Aniruddha; Do, Diana V; Sepah, Yasir J

    2016-08-01

    To determine if two different doses of intravitreal sirolimus, an mTOR inhibitor, can decrease inflammation and is safe in eyes with non-infectious posterior, intermediate, or panuveitis in the Sirolimus as a Therapeutic Approach UVEitis: Protocol-2 (SAVE-2) Study. SAVE-2 is a prospective randomized, phase II, open-label interventional clinical trial conducted at 4 clinical centers in the United States. Eligible subjects were randomized into one of two treatments. Group 1 received 440µg of intravitreal sirolimus in study eyes on days 0, 30, 60, 90, 120, and 150; group 2 received 880µg of intravitreal sirolimus on days 0, 60, and 120. Fellow eyes were also eligible to receive sirolimus (of opposite dose to that of study eye). Primary endpoint of the study was at month 6 (M6). 24 subjects have been randomized in SAVE-2 and are included in the analysis. Vitreous haze decreased by ≥2 steps in 63.6% and 50% of patients in groups 1 and 2, respectively at M6 (p=0.695). Mean change in best-corrected visual acuity for subjects was +3.66 and -2.91 ETDRS letters in group 1 and 2, respectively. Among subjects with macular edema at baseline (n=13), the mean change in foveal thickness was -89.42µm in group 1 and +81.5µm in group 2 at M6. Both low and high doses of intravitreal sirolimus were found to decrease vitreous haze in eyes with non-infectious uveitis. Low dose (440µg) sirolimus administered monthly may be more efficacious in reducing uveitic macular edema than high dose (880µg) administered every 2 months.

  10. Meta-Analysis of 29 Experiments Evaluating the Effects of Rapamycin on Life Span in the Laboratory Mouse.

    Science.gov (United States)

    Swindell, William R

    2017-08-01

    Rapamycin has favorable effects on aging in mice and may eventually be applied to encourage "healthy aging" in humans. This study analyzed raw data from 29 survival studies of rapamycin- and control-treated mice, with the goals of estimating summary statistics and identifying factors associated with effect size heterogeneity. Meta-analysis demonstrated significant heterogeneity across studies, with hazard ratio (HR) estimates ranging from 0.22 (95% confidence interval [CI]: 0.06-0.82) to 0.92 (95% CI: 0.65-1.28). Sex was the major factor accounting for effect size variation, and mortality was decreased more in females (HR = 0.41; 95% CI: 0.35-0.48) as compared with males (HR = 0.63; 95% CI: 0.55-0.71). Rapamycin effects were also genotype dependent, however, with stronger survivorship increases in hybrid mice (14.4%; 95% CI: 12.5-16.3%) relative to pure inbred strains (8.8%; 95% CI: 6.2-11.6%). Number needed to treat was applied as an effect size metric, which consistently identified early senescence as the age of peak treatment benefit. These results provide synthesis of existing data to support the potential translation of findings from mouse to primate species. Because rapamycin's effect on survival depends on sex and genotype, further work is justified to understand how these factors shape treatment response. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. A central role for the mammalian target of rapamycin in LPS-induced anorexia in mice.

    Science.gov (United States)

    Yue, Yunshuang; Wang, Yi; Li, Dan; Song, Zhigang; Jiao, Hongchao; Lin, Hai

    2015-01-01

    Bacterial lipopolysaccharide (LPS), also known as endotoxin, induces profound anorexia. However, the LPS-provoked pro-inflammatory signaling cascades and the neural mechanisms underlying the development of anorexia are not clear. Mammalian target of rapamycin (mTOR) is a key regulator of metabolism, cell growth, and protein synthesis. This study aimed to determine whether the mTOR pathway is involved in LPS-induced anorexia. Effects of LPS on hypothalamic gene/protein expression in mice were measured by RT-PCR or western blotting analysis. To determine whether inhibition of mTOR signaling could attenuate LPS-induced anorexia, we administered an i.c.v. injection of rapamycin, an mTOR inhibitor, on LPS-treated male mice. In this study, we showed that LPS stimulates the mTOR signaling pathway through the enhanced phosphorylation of mTOR(Ser2448) and p70S6K(Thr389). We also showed that LPS administration increased the phosphorylation of FOXO1(Ser256), the p65 subunit of nuclear factor kappa B (Panorexia by decreasing the phosphorylation of p70S6K(Thr389), FOXO1(Ser256), and FOXO1/3a(Thr) (24) (/) (32). These results suggest promising approaches for the prevention and treatment of LPS-induced anorexia. © 2015 Society for Endocrinology.

  12. Rapamycin attenuates bleomycin-induced pulmonary fibrosis in rats and the expression of metalloproteinase-9 and tissue inhibitors of metalloproteinase-1 in lung tissue.

    Science.gov (United States)

    Jin, Xiaoguang; Dai, Huaping; Ding, Ke; Xu, Xuefeng; Pang, Baosen; Wang, Chen

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is the most common and devastating form of interstitial lung disease (ILD) in the clinic. There is no effective therapy except for lung transplantation. Rapamycin is an immunosuppressive drug with potent antifibrotic activity. The purpose of this study was to examine the effects of rapamycin on bleomycin-induced pulmonary fibrosis in rats and the relation to the expression of metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1). Sprague-Dawley rats were treated with intratracheal injection of 0.3 ml of bleomycin (5 mg/kg) in sterile 0.9% saline to make the pulmonary fibrosis model. Rapamycin was given at a dose of 0.5 mg/kg per gavage, beginning one day before bleomycin instillation and once daily until animal sacrifice. Ten rats in each group were sacrificed at 3, 7, 14, 28 and 56 days after bleomycin administration. Alveolitis and pulmonary fibrosis were semi-quantitatively assessed after HE staining and Masson staining under an Olympus BX40 microscope with an IDA-2000 Image Analysis System. Type I and III collagen fibers were identified by Picro-sirius-polarization. Hydroxyproline content in lung tissue was quantified by a colorimetric-based spectrophotometric assay, MMP-9 and TIMP-1 were detected by immunohistochemistry and by realtime quantitative reverse transcriptase polymerase chain reaction (RT-PCR). Bleomycin induced alveolitis and pulmonary fibrosis of rats was inhibited by rapamycin. Significant inhibition of alveolitis and hydroxyproline product were demonstrated when daily administration of rapamycin lasted for at least 14 days. The inhibitory efficacy on pulmonary fibrosis was unremarkable until rapamycin treatment lasted for at least 28 days (P pulmonary fibrosis, which is associated with decreased expression of MMP-9 and TIMP-1.

  13. LED-roulette : LED's vervangen balletje

    NARCIS (Netherlands)

    Goossens, P.

    2007-01-01

    Iedereen waagt wel eens een gokje, in een loterij of misschien ook in een casino. Wie droomt er immers niet van om op een gemakkelijke manier rijk te worden? Met de hier beschreven LED-roulette valt weliswaar weinig te winnen, maar het is wel een uitstekende manier om het roulettespel thuis te

  14. Broadband Radiometric LED Measurements

    OpenAIRE

    Eppeldauer, G. P.; Cooksey, C. C.; Yoon, H. W.; Hanssen, L. M.; Podobedov, V. B.; Vest, R. E.; Arp, U.; Miller, C. C.

    2016-01-01

    At present, broadband radiometric measurements of LEDs with uniform and low-uncertainty results are not available. Currently, either complicated and expensive spectral radiometric measurements or broadband photometric LED measurements are used. The broadband photometric measurements are based on the CIE standardized V(��) function, which cannot be used in the UV range and leads to large errors when blue or red LEDs are measured in its wings, where the realization is always poor. Reference irr...

  15. Broadband radiometric LED measurements

    Science.gov (United States)

    Eppeldauer, G. P.; Cooksey, C. C.; Yoon, H. W.; Hanssen, L. M.; Podobedov, V. B.; Vest, R. E.; Arp, U.; Miller, C. C.

    2016-09-01

    At present, broadband radiometric LED measurements with uniform and low-uncertainty results are not available. Currently, either complicated and expensive spectral radiometric measurements or broadband photometric LED measurements are used. The broadband photometric measurements are based on the CIE standardized V(λ) function, which cannot be used in the UV range and leads to large errors when blue or red LEDs are measured in its wings, where the realization is always poor. Reference irradiance meters with spectrally constant response and high-intensity LED irradiance sources were developed here to implement the previously suggested broadband radiometric LED measurement procedure [1, 2]. Using a detector with spectrally constant response, the broadband radiometric quantities of any LEDs or LED groups can be simply measured with low uncertainty without using any source standard. The spectral flatness of filtered-Si detectors and low-noise pyroelectric radiometers are compared. Examples are given for integrated irradiance measurement of UV and blue LED sources using the here introduced reference (standard) pyroelectric irradiance meters. For validation, the broadband measured integrated irradiance of several LED-365 sources were compared with the spectrally determined integrated irradiance derived from an FEL spectral irradiance lamp-standard. Integrated responsivity transfer from the reference irradiance meter to transfer standard and field UV irradiance meters is discussed.

  16. Dansk LED - Museumsbelysning

    DEFF Research Database (Denmark)

    Poulsen, Peter Behrensdorff; Dam-Hansen, Carsten; Thorseth, Anders

    Projektet har til formål at anvende dansk forskning inden for optik og lys til at realisere innovative energieffektive LED lyssystemer til museumsbranchen.......Projektet har til formål at anvende dansk forskning inden for optik og lys til at realisere innovative energieffektive LED lyssystemer til museumsbranchen....

  17. The post-therapeutic effect of rapamycin in mild traumatic brain-injured rats ensuing in the upregulation of autophagy and mitophagy.

    Science.gov (United States)

    Wang, Changxing; Hu, Zhiying; Zou, Yang; Xiang, Mingjun; Jiang, Yuting; Botchway, Benson O A; Huo, Xue; Du, Xiaoxue; Fang, Marong

    2017-09-01

    Mild traumatic brain injury (mTBI), common in juveniles, has been reported to be caused by sports-related concussion. Many young children may suffer from post-concussion syndrome. mTBI, in early stages of life, could play a part in neuron apoptosis and degeneration, cognitive and motor coordination impairment, as well as dementia. Our study was aimed at further investigating the post-therapeutic efficacy of rapamycin in the recuperation of mTBI while at the same time investigating the metamorphosis in both autophagy and mitophagy in mTBI. We created a weight-drop rat mTBI model with the administration of rapamycin at 4 h after every mTBI. Behavioral tests of beam walking and open field task indicated the expected improvement of cognitive and motor coordination functions. Both Western blot and immunofluorescence examinations revealed increased Beclin-1 and PINK1 in the treated rats as well as reduction of caspase-3 and cytochrome C (Cyt C). More so, the TUNEL staining evidenced curtailment of apoptotic cells following treatment with rapamycin. The upregulation of Beclin-1 and PINK1 and the downregulation of caspase-3 and Cyt C extrapolate that rapamycin plays neuroprotective as well as anti-apoptotic role via interposition of both autophagy and mitophagy. © 2017 International Federation for Cell Biology.

  18. Brassinosteriod Insensitive 2 (BIN2) acts as a downstream effector of the Target of Rapamycin (TOR) signaling pathway to regulate photoautotrophic growth in Arabidopsis.

    Science.gov (United States)

    Xiong, Fangjie; Zhang, Rui; Meng, Zhigang; Deng, Kexuan; Que, Yumei; Zhuo, Fengping; Feng, Li; Guo, Sundui; Datla, Raju; Ren, Maozhi

    2017-01-01

    The components of the target of rapamycin (TOR) signaling pathway have been well characterized in heterotrophic organisms from yeast to humans. However, because of rapamycin insensitivity, embryonic lethality in tor null mutants and a lack of reliable ways of detecting TOR protein kinase in higher plants, the key players upstream and downstream of TOR remain largely unknown in plants. Using engineered rapamycin-sensitive Binding Protein 12-2 (BP12-2) plants, the present study showed that combined treatment with rapamycin and active-site TOR inhibitors (asTORis) results in synergistic inhibition of TOR activity and plant growth in Arabidopsis. Based on this system, we revealed that TOR signaling plays a crucial role in modulating the transition from heterotrophic to photoautotrophic growth in Arabidopsis. Ribosomal protein S6 kinase 2 (S6K2) was identified as a direct downstream target of TOR, and the growth of TOR-suppressed plants could be rescued by up-regulating S6K2. Systems, genetic, and biochemical analyses revealed that Brassinosteriod Insensitive 2 (BIN2) acts as a novel downstream effector of S6K2, and the phosphorylation of BIN2 depends on TOR-S6K2 signaling in Arabidopsis. By combining pharmacological with genetic and biochemical approaches, we determined that the TOR-S6K2-BIN2 signaling pathway plays important roles in regulating the photoautotrophic growth of Arabidopsis. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  19. Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury.

    Science.gov (United States)

    Wang, Xiaoping; Li, Xiaojia; Huang, Bin; Ma, Shuai

    2016-01-01

    Spinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K) pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP) in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

  20. Rapamycin Induces Heme Oxygenase-1 in Liver but Inhibits Bile Flow Recovery after Ischemia

    NARCIS (Netherlands)

    Kist, Alwine; Wakkie, Joris; Madu, Max; Versteeg, Ruth; ten Berge, Judith; Nikolic, Andrej; Nieuwenhuijs, Vincent B.; Porte, Robert J.; Padbury, Robert T. A.; Barritt, Greg J.

    Background/Aims. Rapamycin, which is employed in the management of patients undergoing liver surgery, induces the synthesis of heme oxygenase-1 (HO-1) in some non-liver cell types. The aim was to investigate whether rapamycin can induce HO-1 expression in the liver, and to test the effects of

  1. Rapamycin preconditioning attenuates transient focal cerebral ischemia/reperfusion injury in mice.

    Science.gov (United States)

    Yin, Lele; Ye, Shasha; Chen, Zhen; Zeng, Yaoying

    2012-12-01

    Rapamycin, an mTOR inhibitor and immunosuppressive agent in clinic, has protective effects on traumatic brain injury and neurodegenerative diseases. But, its effects on transient focal ischemia/reperfusion disease are not very clear. In this study, we examined the effects of rapamycin preconditioning on mice treated with middle cerebral artery occlusion/reperfusion operation (MCAO/R). We found that the rapamycin preconditioning by intrahippocampal injection 20 hr before MCAO/R significantly improved the survival rate and longevity of mice. It also decreased the neurological deficit score, infracted areas and brain edema. In addition, rapamycin preconditioning decreased the production of NF-κB, TNF-α, and Bax, but not Bcl-2, an antiapoptotic protein in the ischemic area. From these results, we may conclude that rapamycin preconditioning attenuate transient focal cerebral ischemia/reperfusion injury and inhibits apoptosis induced by MCAO/R in mice.

  2. The antiaging activity and cerebral protection of rapamycin at micro-doses.

    Science.gov (United States)

    Qi, Haiyan; Su, Feng-Yun; Wan, Shan; Chen, Yongjie; Cheng, Yan-Qiong; Liu, Ai-Jun

    2014-11-01

    The immunosuppressant drug rapamycin was reported to have an antiaging activity, which was attributed to the TORC1 inhibition that inhibits cell proliferation and increases autophagy. However, rapamycin also exhibits a number of harmful adverse effects. Whether rapamycin can be developed into an antiaging agent remains unclear. We demonstrated that rapamycin at micro-doses (below the TORC1 inhibiting concentration) exhibits a cell-protective activity: (1) It protects cultured neurons against neurotoxin MPP(+) and H2O2. (2) It increases survival time of neuron in culture. (3) It maintains the nonproliferative state of cultured senescent human fibroblasts and prevents cell death induced by telomere dysfunction. (4) In animal models, it decreased the cerebral infarct sizes induced by acute ischemia and dramatically extended the life span of stroke prone spontaneously hypertensive rats (SHR-SPs). We propose that rapamycin at micro-dose can be developed into an antiaging agent with a novel mechanism. © 2014 John Wiley & Sons Ltd.

  3. Rapamycin prevents drug seeking via disrupting reconsolidation of reward memory in rats.

    Science.gov (United States)

    Lin, Jue; Liu, Lingqi; Wen, Quan; Zheng, Chunming; Gao, Yang; Peng, Shuxian; Tan, Yalun; Li, Yanqin

    2014-01-01

    The maladaptive drug memory developed between the drug-rewarding effect and environmental cues contributes to difficulty in preventing drug relapse. Established reward memories can be disrupted by pharmacologic interventions following their reactivation. Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) kinase, has been proved to be involved in various memory consolidation. However, it is less well characterized in drug memory reconsolidation. Using a conditioned place preference (CPP) procedure, we examined the effects of systemically administered rapamycin on reconsolidation of drug memory in rats. We found that systemically administered rapamycin (0.1 or 10 mg/kg, i.p.) after re-exposure to drug-paired environment, dose dependently decreased the expression of CPP 1 d later, and the effect lasted for up to 14 d and could not be reversed by a priming injection of morphine. The effect of rapamycin on morphine-associated memory was specific to drug-paired context, and rapamycin had no effect on subsequent CPP expression when rats were exposed to saline-paired context or homecage. These results indicated that systemic administration of rapamycin after memory reactivation can persistently inhibit the drug seeking behaviour via disruption of morphine memory reconsolidation in rats. Additionally, the effect of rapamycin on memory reconsolidation was reproduced in cocaine CPP and alcohol CPP. Furthermore, rapamycin did not induce conditioned place aversion and had no effect on locomotor activity and anxiety behaviour. These findings suggest that rapamycin could erase the acquired drug CPP in rats, and that mTOR activity plays an important role in drug reconsolidation and is required for drug relapse.

  4. Rapamycin up-regulates triglycerides in hepatocytes by down-regulating Prox1.

    Science.gov (United States)

    Kwon, Sora; Jeon, Ji-Sook; Kim, Su Bin; Hong, Young-Kwon; Ahn, Curie; Sung, Jung-Suk; Choi, Inho

    2016-02-27

    Although the prolonged use of rapamycin may cause unwanted side effects such as hyperlipidemia, the underlying mechanism remains unknown. Prox1 is a transcription factor responsible for the development of several tissues including lymphatics and liver. There is growing evidences that Prox1 participates in metabolism in addition to embryogenesis. However, whether Prox1 is directly related to lipid metabolism is currently unknown. HepG2 human hepatoma cells were treated with rapamycin and total lipids were analyzed by thin layer chromatography. The effect of rapamycin on the expression of Prox1 was determined by western blotting. To investigate the role of Prox1 in triglycerides regulation, siRNA and overexpression system were employed. Rapamycin was injected into mice for 2 weeks and total lipids and proteins in liver were measured by thin layer chromatography and western blot analysis, respectively. Rapamycin up-regulated the amount of triglyceride and down-regulated the expression of Prox1 in HepG2 cells by reducing protein half-life but did not affect its transcript. The loss-of-function of Prox1 was coincident with the increase of triglycerides in HepG2 cells treated with rapamycin. The up-regulation of triglycerides by rapamycin in HepG2 cells reverted to normal levels by the compensation of Prox1 using the overexpression system. Rapamycin also down-regulated Prox1 expression but increased triglycerides in mouse liver. This study suggests that rapamycin can increase the amount of triglycerides by down-regulating Prox1 expression in hepatocytes, which means that the mammalian target of rapamycin (mTOR) signaling is important for the regulation of triglycerides by maintaining Prox1 expression.

  5. Rapamycin-binding FKBP25 associates with diverse proteins that form large intracellular entities

    International Nuclear Information System (INIS)

    Galat, Andrzej; Thai, Robert

    2014-01-01

    Highlights: • The hFKBP25 interacts with diverse components of macromolecular entities. • We show that the endogenous human FKBP25 is bound to polyribosomes. • The endogenous hFKBP25 co-immunoprecipitated with nucleosomal proteins. • FKBP25 could induce conformational switch in macromolecular complexes. - Abstract: In this paper, we show some evidence that a member of the FK506-binding proteins, FKBP25 is associated to diverse components that are part of several different intracellular large-molecular mass entities. The FKBP25 is a high-affinity rapamycin-binding immunophilin, which has nuclear translocation signals present in its PPIase domain but it was detected both in the cytoplasm compartment and in the nuclear proteome. Analyses of antiFKBP25-immunoprecipitated proteins have revealed that the endogenous FKBP25 is associated to the core histones of the nucleosome, and with several proteins forming spliceosomal complexes and ribosomal subunits. Using polyclonal antiFKBP25 we have detected FKBP25 associated with polyribosomes. Added RNAs or 0.5 M NaCl release FKBP25 that was associated with the polyribosomes indicating that the immunophilin has an intrinsic capacity to form complexes with polyribonucleotides via its charged surface patches. Rapamycin or FK506 treatments of the polyribosomes isolated from porcine brain, HeLa and K568 cells caused a residual release of the endogenous FKBP25, which suggests that the immunophilin also binds to some proteins via its PPIase cavity. Our proteomics study indicates that the nuclear pool of the FKBP25 targets various nuclear proteins that are crucial for packaging of DNA, chromatin remodeling and pre-mRNA splicing whereas the cytosolic pool of this immunophilin is bound to some components of the ribosome

  6. Rapamycin-binding FKBP25 associates with diverse proteins that form large intracellular entities

    Energy Technology Data Exchange (ETDEWEB)

    Galat, Andrzej, E-mail: galat@dsvidf.cea.fr; Thai, Robert

    2014-08-08

    Highlights: • The hFKBP25 interacts with diverse components of macromolecular entities. • We show that the endogenous human FKBP25 is bound to polyribosomes. • The endogenous hFKBP25 co-immunoprecipitated with nucleosomal proteins. • FKBP25 could induce conformational switch in macromolecular complexes. - Abstract: In this paper, we show some evidence that a member of the FK506-binding proteins, FKBP25 is associated to diverse components that are part of several different intracellular large-molecular mass entities. The FKBP25 is a high-affinity rapamycin-binding immunophilin, which has nuclear translocation signals present in its PPIase domain but it was detected both in the cytoplasm compartment and in the nuclear proteome. Analyses of antiFKBP25-immunoprecipitated proteins have revealed that the endogenous FKBP25 is associated to the core histones of the nucleosome, and with several proteins forming spliceosomal complexes and ribosomal subunits. Using polyclonal antiFKBP25 we have detected FKBP25 associated with polyribosomes. Added RNAs or 0.5 M NaCl release FKBP25 that was associated with the polyribosomes indicating that the immunophilin has an intrinsic capacity to form complexes with polyribonucleotides via its charged surface patches. Rapamycin or FK506 treatments of the polyribosomes isolated from porcine brain, HeLa and K568 cells caused a residual release of the endogenous FKBP25, which suggests that the immunophilin also binds to some proteins via its PPIase cavity. Our proteomics study indicates that the nuclear pool of the FKBP25 targets various nuclear proteins that are crucial for packaging of DNA, chromatin remodeling and pre-mRNA splicing whereas the cytosolic pool of this immunophilin is bound to some components of the ribosome.

  7. [LED lights in dermatology].

    Science.gov (United States)

    Noé, C; Pelletier-Aouizerate, M; Cartier, H

    2017-04-01

    The use in dermatology of light-emitting diodes (LEDs) continues to be surrounded by controversy. This is due mainly to poor knowledge of the physicochemical phases of a wide range of devices that are difficult to compare to one another, and also to divergences between irrefutable published evidence either at the level of in vitro studies or at the cellular level, and discordant clinical results in a variety of different indications: rejuvenation, acne, wound healing, leg ulcers, and cutaneous inflammatory or autoimmune processes. Therapeutic LEDs can emit wavelengths ranging from the ultraviolet, through visible light, to the near infrared (247-1300 nm), but only certain bands have so far demonstrated any real value. We feel certain that if this article remains factual, then readers will have a different, or at least more nuanced, opinion concerning the use of such LED devices in dermatology. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Therapeutic Targeting of the IL-6 Trans-Signaling/Mechanistic Target of Rapamycin Complex 1 Axis in Pulmonary Emphysema.

    Science.gov (United States)

    Ruwanpura, Saleela M; McLeod, Louise; Dousha, Lovisa F; Seow, Huei J; Alhayyani, Sultan; Tate, Michelle D; Deswaerte, Virginie; Brooks, Gavin D; Bozinovski, Steven; MacDonald, Martin; Garbers, Christoph; King, Paul T; Bardin, Philip G; Vlahos, Ross; Rose-John, Stefan; Anderson, Gary P; Jenkins, Brendan J

    2016-12-15

    The potent immunomodulatory cytokine IL-6 is consistently up-regulated in human lungs with emphysema and in mouse emphysema models; however, the mechanisms by which IL-6 promotes emphysema remain obscure. IL-6 signals using two distinct modes: classical signaling via its membrane-bound IL-6 receptor (IL-6R), and trans-signaling via a naturally occurring soluble IL-6R. To identify whether IL-6 trans-signaling and/or classical signaling contribute to the pathogenesis of emphysema. We used the gp130 F/F genetic mouse model for spontaneous emphysema and cigarette smoke-induced emphysema models. Emphysema in mice was quantified by various methods including in vivo lung function and stereology, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to assess alveolar cell apoptosis. In mouse and human lung tissues, the expression level and location of IL-6 signaling-related genes and proteins were measured, and the levels of IL-6 and related proteins in sera from emphysematous mice and patients were also assessed. Lung tissues from patients with emphysema, and from spontaneous and cigarette smoke-induced emphysema mouse models, were characterized by excessive production of soluble IL-6R. Genetic blockade of IL-6 trans-signaling in emphysema mouse models and therapy with the IL-6 trans-signaling antagonist sgp130Fc ameliorated emphysema by suppressing augmented alveolar type II cell apoptosis. Furthermore, IL-6 trans-signaling-driven emphysematous changes in the lung correlated with mechanistic target of rapamycin complex 1 hyperactivation, and treatment of emphysema mouse models with the mechanistic target of rapamycin complex 1 inhibitor rapamycin attenuated emphysematous changes. Collectively, our data reveal that specific targeting of IL-6 trans-signaling may represent a novel treatment strategy for emphysema.

  9. An emerging role for the mammalian Target of Rapamycin (mTOR in 'pathological' protein translation: relevance to cocaine addiction

    Directory of Open Access Journals (Sweden)

    Christopher V Dayas

    2012-02-01

    Full Text Available Complex neuroadaptations within key nodes of the brain’s ‘reward circuitry’ are thought to underpin long-term vulnerability to relapse. A more comprehensive understanding of the molecular and cellular signalling events that subserve relapse vulnerability may lead to pharmacological treatments that could improve treatment outcomes for psychostimulant-addicted individuals. Recent advances in this regard include findings that drug-induced perturbations to neurotrophin, metabotropic glutamate receptor and dopamine receptor signalling pathways perpetuate plasticity impairments at excitatory glutamatergic synapses on ventral tegmental area (VTA and nucleus accumbens (NAC neurons. In the context of addiction, much previous work, in terms of downstream effectors to these receptor systems, has centered on the extracellular-regulated MAP kinase (ERK signalling pathway. The purpose of the present review is to highlight the evidence of an emerging role for another downstream effector of these addiction-relevant receptor systems - the mammalian target of rapamycin complex 1 (mTORC1. mTORC1 functions to regulate synaptic protein translation and is a potential critical link in our understanding of the neurobiological processes that drive addiction and relapse behavior. The precise cellular and molecular changes that are regulated by mTORC1 and contribute to relapse vulnerability are only just coming to light. Therefore, we aim to highlight evidence that mTORC1 signalling may be dysregulated by drug-exposure and that these changes may contribute to aberrant translation of synaptic proteins that appear critical to increased relapse vulnerability, including AMPARs. The importance of understanding the role of this signalling pathway in the development of addiction vulnerability is underscored by the fact that the mTORC1 inhibitor rapamycin reduces drug-seeking in preclinical models and preliminary evidence indicating that rapamycin suppresses drug craving in

  10. Overexpression of TOR (target of rapamycin) inhibits cell proliferation in Dictyostelium discoideum.

    Science.gov (United States)

    Swer, Pynskhem Bok; Mishra, Himanshu; Lohia, Rakhee; Saran, Shweta

    2016-05-01

    TOR (target of rapamycin) protein kinase acts as a central controller of cell growth and development of an organism. Present study was undertaken to find the expression pattern and role of TOR during growth and development of Dictyostelium discoideum. Failures to generate either knockout and/or knockdown mutants indicate that interference with its levels led to cellular defects. Thus, the effects of TOR (DDB_G0281569) overexpression specifically, cells expressing Dd(Δ211-TOR)-Eyfp mutant was analyzed. Elevated expression of (Δ211-TOR)-Eyfp reduced both cell size and cell proliferation. DdTOR was found to be closer to fungus. mRNA level of TOR was found maximally in the freshly starved/aggregate cells that gradually declined. This was also strengthened by the expression patterns observed by in situ and the analysis of β-galactosidase reporter driven by the putative TOR promoter. The TOR protein was found to be highest at the aggregate stage. The fusion protein, (Δ211-TOR)-Eyfp was localized to the cell membrane, cytosol, and the nucleus. We suggest, DdTOR to be an essential protein and high TOR expression inhibits cell proliferation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. LED system reliability

    NARCIS (Netherlands)

    Driel, W.D. van; Yuan, C.A.; Koh, S.; Zhang, G.Q.

    2011-01-01

    This paper presents our effort to predict the system reliability of Solid State Lighting (SSL) applications. A SSL system is composed of a LED engine with micro-electronic driver(s) that supplies power to the optic design. Knowledge of system level reliability is not only a challenging scientific

  12. Rapamycin protects kidney against ischemia reperfusion injury through recruitment of NKT cells.

    Science.gov (United States)

    Zhang, Chao; Zheng, Long; Li, Long; Wang, Lingyan; Li, Liping; Huang, Shang; Gu, Chenli; Zhang, Lexi; Yang, Cheng; Zhu, Tongyu; Rong, Ruiming

    2014-08-19

    NKT cells play a protective role in ischemia reperfusion (IR) injury, of which the trafficking in the body and recruitment in injured organs can be influenced by immunosuppressive therapy. Therefore, we investigated the effects of rapamycin on kidneys exposed to IR injury in early stage and on trafficking of NKT cells in a murine model. Balb/c mice were subjected to kidney 30 min ischemia followed by 24 h reperfusion. Rapamycin (2.5 ml/kg) was administered by gavage daily, starting 1 day before the operation. Renal function and histological changes were assessed. The proportion of NKT cells in peripheral blood, spleen and kidney was detected by flow cytometry. The chemokines and corresponding receptor involved in NKT cell trafficking were determined by RT-PCR and flow cytometry respectively. Rapamycin significantly improved renal function and ameliorated histological injury. In rapamycin-treated group, the proportion of NKT cells in spleen was significantly decreased but increased in peripheral blood and kidney. In addition, the CXCR3+ NKT cell in the kidney increased remarkably in the rapamycin-treated group. The chemokines, CXCL9 and CXCL10, as the ligands of CXCR3, were also increased in the rapamycin-treated kidney. Rapamycin may recruit NKT cells from spleen to the IR-induced kidney to ameliorate renal IR injury in the early stage.

  13. Icotinib combined with rapamycin in a renal transplant recipient with epidermal growth factor receptor-mutated non-small cell lung cancer: A case report

    OpenAIRE

    ZHAO, QIONG; WANG, YINA; TANG, YEMIN; PENG, LING

    2013-01-01

    As kidney transplant recipients are at increased risk of developing cancer, regular monitoring should be undertaken to monitor the balance between immunosuppression and graft function and to identify malignancy. The present study reports the outcome of the treatment of adenocarcinoma of the lung (T1aN0M1a, stage IV) using the molecular-targeted therapy, icotinib, in a 66-year-old male renal transplant patient receiving rapamycin and prednisolone as ongoing renal immunosuppressive therapy. An ...

  14. Evaluation of the Effectiveness of Nurse-Led Continence Care Treatments for Chinese Primary Care Patients with Lower Urinary Tract Symptoms.

    Directory of Open Access Journals (Sweden)

    Edmond P H Choi

    Full Text Available The aim of this study was to evaluate whether community-based nurse-led continence care interventions are effective in improving outcomes for adult Chinese primary care patients with lower urinary tract symptoms (LUTS.A case-controlled intervention study was conducted. An intervention group of 360 primary care patients enrolled into a nurse-led continence care programme were recruited by consecutive sampling. A control group of 360 primary care patients with LUTS identified by screening were recruited from the waiting rooms of primary care clinics by consecutive sampling. Both groups were monitored at baseline and at 12 months.Outcome measures included symptom severity, health-related quality of life (HRQOL, self-efficacy, global health and self-reported health service utilization at 12-months. The effect of the continence care programme on symptom severity and HRQOL was assessed by the difference-in-difference estimation, using independent t-test and multiple liner regression. Chi-square test was used to compare the self-efficacy, global health and self-reported health service utilization between the two groups at 12-months.After adjusting for baseline severity and socio-demographics, the intervention group had significant improvements in LUTS severity (P<0.05 and HRQOL (P<0.05. Improvements in the amount of urine leakage were not significantly different between the two groups. A higher proportion of subjects in the intervention group reported increased self-efficacy (43.48% vs. 66.83%, improved global health condition (17.74% vs. 41.5%, having doctor consultation (18.5% vs. 8.06, having medication due to LUTS (26.50% vs.11.29% and having non-drug therapy due to LUTS (59.5% vs.9.68%.Community-based nurse-led continence care can effectively alleviate symptoms, improve health-related quality of life, and enhance self-efficacy and the global health condition of Chinese male and female primary care patients with LUTS.

  15. Primary intestinal lymphangiectasia treated with rapamycin in a child with tuberous sclerosis complex (TSC).

    Science.gov (United States)

    Pollack, Sarah F; Geffrey, Alexandra L; Thiele, Elizabeth A; Shah, Uzma

    2015-09-01

    Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by a congenital malformation of the lymphatic vessels of the small intestine causing insufficient drainage and leakage of lymph fluid. Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas in multiple organ systems. While the lymphatic system has been implicated in TSC through lymphangioleiomyomatosis (LAM) and lymphedema, this paper reports the first case of PIL in TSC, a female patient with a TSC2 mutation. She developed persistent and significant abdominal distension with chronic diarrhea during her first year of life. Due to lack of treatment options and the involvement of the mTOR pathway in TSC, a trial of an mTOR inhibitor, rapamycin, was initiated. This treatment was highly effective, with improvement in clinical symptoms of PIL as well as abnormal laboratory values including VEGF-C, which was elevated to over seven times the normal upper limit before treatment. This case suggests that PIL is a rare manifestation of TSC, warranting the use of mTOR inhibitors in future studies. © 2015 Wiley Periodicals, Inc.

  16. Thermal management for LED applications

    CERN Document Server

    Poppe, András

    2014-01-01

    Thermal Management for LED Applications provides state-of-the-art information on recent developments in thermal management as it relates to LEDs and LED-based systems and their applications. Coverage begins with an overview of the basics of thermal management including thermal design for LEDs, thermal characterization and testing of LEDs, and issues related to failure mechanisms and reliability and performance in harsh environments. Advances and recent developments in thermal management round out the book with discussions on advances in TIMs (thermal interface materials) for LED applications, advances in forced convection cooling of LEDs, and advances in heat sinks for LED assemblies. This book also: Presents a comprehensive overview of the basics of thermal management as it relates to LEDs and LED-based systems Discusses both design and thermal management considerations when manufacturing LEDs and LED-based systems Covers reliability and performance of LEDs in harsh environments Has a hands-on applications a...

  17. The Treatment Advocacy Program: A Randomized Controlled Trial of a Peer-Led Safer Sex Intervention for HIV-Infected Men Who Have Sex with Men

    Science.gov (United States)

    McKirnan, David J.; Tolou-Shams, Marina; Courtenay-Quirk, Cari

    2010-01-01

    Objective: Primary care may be an effective venue for delivering behavioral interventions for sexual safety among HIV-positive men who have sex with men (MSM); however, few studies show efficacy for such an approach. We tested the efficacy of the Treatment Advocacy Program (TAP), a 4-session, primary-care-based, individual counseling intervention…

  18. A photocleavable rapamycin conjugate for spatiotemporal control of small GTPase activity.

    Science.gov (United States)

    Umeda, Nobuhiro; Ueno, Tasuku; Pohlmeyer, Christopher; Nagano, Tetsuo; Inoue, Takanari

    2011-01-12

    We developed a novel method to spatiotemporally control the activity of signaling molecules. A newly synthesized photocaged rapamycin derivative induced rapid dimerization of FKBP (FK-506 binding protein) and FRB (FKBP-rapamycin binding protein) upon UV irradiation. With this system and the spatially confined UV irradiation, we achieved subcellularly localized activation of Rac, a member of small GTPases. Our technique offers a powerful approach to studies of dynamic intracellular signaling events.

  19. Rapamycin delays growth of Wnt-1 tumors in spite of suppression of host immunity

    International Nuclear Information System (INIS)

    Svirshchevskaya, Elena V; Mariotti, Jacopo; Wright, Mollie H; Viskova, Natalia Y; Telford, William; Fowler, Daniel H; Varticovski, Lyuba

    2008-01-01

    Rapamycin, an inhibitor of mammalian target of Rapamycin (mTOR), is an immunosuppressive agent that has anti-proliferative effects on some tumors. However, the role of Rapamycin-induced immune suppression on tumor progression has not been examined. We developed a transplantation model for generation of mammary tumors in syngeneic recipients that can be used to address the role of the immune system on tumor progression. We examined the effect of Rapamycin on the immune system and growth of MMTV-driven Wnt-1 mammary tumors which were transplanted into irradiated and bone marrow-reconstituted, or naïve mice. Rapamycin induced severe immunosuppression and significantly delayed the growth of Wnt-1 tumors. T cell depletion in spleen and thymus and reduction in T cell cytokine secretion were evident within 7 days of therapy. By day 20, splenic but not thymic T cell counts, and cytokine secretion recovered. We determined whether adoptive T cell therapy enhances the anti-cancer effect using ex vivo generated Rapamycin-resistant T cells. However, T cell transfer during Rapamycin therapy did not improve the outcome relative to drug therapy alone. Thus, we could not confirm that suppression of T cell immunity contributes to tumor growth in this model. Consistent with suppression of the mTOR pathway, decreased 4E-BP1, p70 S6-kinase, and S6 protein phosphorylation correlated with a decrease in Wnt-1 tumor cell proliferation. Rapamycin has a direct anti-tumor effect on Wnt-1 breast cancer in vivo that involves inhibition of the mTOR pathway at doses that also suppress host immune responses

  20. Rapamycin inhibits mTOR/p70S6K activation in CA3 region of the hippocampus of the rat and impairs long term memory.

    Science.gov (United States)

    Lana, D; Di Russo, J; Mello, T; Wenk, G L; Giovannini, M G

    2017-01-01

    The present study was aimed at establishing whether the mTOR pathway and its downstream effector p70S6K in CA3 pyramidal neurons are under the modulation of the cholinergic input to trigger the formation of long term memories, similar to what we demonstrated in CA1 hippocampus. We performed in vivo behavioral experiments using the step down inhibitory avoidance test in adult Wistar rats to evaluate memory formation under different conditions. We examined the effects of rapamycin, an inhibitor of mTORC1 formation, scopolamine, a muscarinic receptor antagonist or mecamylamine, a nicotinic receptor antagonist, on short and long term memory formation and on the functionality of the mTOR pathway. Acquisition was conducted 30min after i.c.v. injection of rapamycin. Recall testing was performed 1h, 4h or 24h after acquisition. We found that (1) mTOR and p70S6K activation in CA3 pyramidal neurons were involved in long term memory formation; (2) rapamycin significantly inhibited mTOR and of p70S6K activation at 4h, and long term memory impairment 24h after acquisition; (3) scopolamine impaired short but not long term memory, with an early increase of mTOR/p70S6K activation at 1h followed by stabilization at longer times; (4) mecamylamine and scopolamine co-administration impaired short term memory at 1h and 4h and reduced the scopolamine-induced increase of mTOR/p70S6K activation at 1h and 4h; (5) mecamylamine and scopolamine treatment did not impair long term memory formation; (6) unexpectedly, rapamycin increased mTORC2 activation in microglial cells. Our results demonstrate that in CA3 pyramidal neurons the mTOR/p70S6K pathway is under the modulation of the cholinergic system and is involved in long-term memory encoding, and are consistent with the hypothesis that the CA3 region of the hippocampus is involved in memory mechanisms based on rapid, one-trial object-place learning and recall. Furthermore, our results are in accordance with previous reports that selective

  1. Blocking mammalian target of rapamycin (mTOR improves neuropathic pain evoked by spinal cord injury

    Directory of Open Access Journals (Sweden)

    Wang Xiaoping

    2016-01-01

    Full Text Available Spinal cord injury (SCI is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E–binding protein 4 (4E-BP1 and p70 ribosomal S6 protein kinase 1 (S6K1 in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

  2. Color homogeneity in LED spotlights

    NARCIS (Netherlands)

    Prins, C.R.

    2013-01-01

    Color variation in the light output of white LEDs is a common problem in LED lighting. We aim to design LED spotlights with a uniform color output while keeping the cost of the system low and the energy efficiency high. Therefore we design a special optic to eliminate the color variation of the LED.

  3. Icotinib combined with rapamycin in a renal transplant recipient with epidermal growth factor receptor-mutated non-small cell lung cancer: A case report.

    Science.gov (United States)

    Zhao, Qiong; Wang, Yina; Tang, Yemin; Peng, Ling

    2014-01-01

    As kidney transplant recipients are at increased risk of developing cancer, regular monitoring should be undertaken to monitor the balance between immunosuppression and graft function and to identify malignancy. The present study reports the outcome of the treatment of adenocarcinoma of the lung (T1aN0M1a, stage IV) using the molecular-targeted therapy, icotinib, in a 66-year-old male renal transplant patient receiving rapamycin and prednisolone as ongoing renal immunosuppressive therapy. An initial partial response to icotinib was achieved, and graft function remained good. However, the patient subsequently developed interstitial pneumonitis. The plasma concentrations of rapamycin and icotinib were within the normal ranges, which excluded the possibility of a pharmacokinetic drug interaction and indicated that the interstitial pneumonitis was likely to be associated with the side-effects of icotinib. Drug therapy was discontinued and the patient underwent a segmentectomy. Tacrolimus was administered for ongoing renal graft immunosuppression. To the best of our knowledge, this is the first report of the concomitant administration of icotinib and rapamycin in post-transplant de novo lung cancer. It is also the first report of interstitial pneumonitis associated with icotinib in a post-transplant patient.

  4. ‘No Blue’ White LED

    DEFF Research Database (Denmark)

    Ou, Haiyan; Corell, Dennis Dan; Dam-Hansen, Carsten

    2010-01-01

    This paper explored the feasibility of making a white LED light source by color mixing method without using the blue color. This ‘no blue’ white LED has potential applications in photolithography room illumination, medical treatment and biophotonics research. A no-blue LED was designed......-2005. Even after 15 days of illumination, no effect was observed. So this LED-based solution was demonstrated to be a very promising light source for photolithography room illumination due to its better color rendering in addition to energy efficiency, long life time and design flexibility. Additionally......, and the prototype was fabricated. The spectral power distribution of both the LED bulb and the yellow fluorescent tube was measured. Based on that, colorimetric values were calculated and compared on terms of chromatic coordinates, correlated color temperature, color rendering index, and chromatic deviation...

  5. Ketamine Exhibits Different Neuroanatomical Profile After Mammalian Target of Rapamycin Inhibition in the Prefrontal Cortex: the Role of Inflammation and Oxidative Stress.

    Science.gov (United States)

    Abelaira, Helena M; Réus, Gislaine Z; Ignácio, Zuleide M; Dos Santos, Maria Augusta B; de Moura, Airam B; Matos, Danyela; Demo, Júlia P; da Silva, Júlia B I; Danielski, Lucineia G; Petronilho, Fabricia; Carvalho, André F; Quevedo, João

    2017-09-01

    Studies indicated that mammalian target of rapamycin (mTOR), oxidative stress, and inflammation are involved in the pathophysiology of major depressive disorder (MDD). Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been identified as a novel MDD therapy; however, the antidepressant mechanism is not fully understood. In addition, the effects of ketamine after mTOR inhibition have not been fully investigated. In the present study, we examined the behavioral and biochemical effects of ketamine in the prefrontal cortex (PFC), hippocampus, amygdala, and nucleus accumbens after inhibition of mTOR signaling in the PFC. Male adult Wistar rats received pharmacological mTOR inhibitor, rapamycin (0.2 nmol) or vehicle into the PFC and then a single dose of ketamine (15 mg/kg, i.p.). Immobility was assessed in forced swimming tests, and then oxidative stress parameters and inflammatory markers were evaluated in the brain and periphery. mTOR activation in the PFC was essential to ketamine's antidepressant-like effects. Ketamine increased lipid damage in the PFC, hippocampus, and amygdala. Protein carbonyl was elevated in the PFC, amygdala, and NAc after ketamine administration. Ketamine also increased nitrite/nitrate in the PFC, hippocampus, amygdala, and NAc. Myeloperoxidase activity increased in the hippocampus and NAc after ketamine administration. The activities of superoxide dismutase and catalase were reduced after ketamine administration in all brain areas studied. Inhibition of mTOR signaling pathways by rapamycin in the PFC was required to protect against oxidative stress by reducing damage and increasing antioxidant enzymes. Finally, the TNF-α level was increased in serum by ketamine; however, the rapamycin plus treatment group was not able to block this increase. Activation of mTOR in the PFC is involved in the antidepressant-like effects of ketamine; however, the inhibition of this pathway was able to protect certain brain areas against

  6. Surgical trauma induces overgrowth in lower limb gigantism: regulation with use of rapamycin is promising.

    Science.gov (United States)

    Pinto, Rohan Sebastian; Harrison, William David; Graham, Kenneth; Nayagam, Durai

    2018-01-04

    We describe an unclassified overgrowth syndrome characterised by unregulated growth of dermal fibroblasts in the lower limbs of a 35-year-old woman. A PIK3CA gene mutation resulted in lower limb gigantism. Below the waist, she weighed 117 kg with each leg measuring over 100 cm in circumference. Her total adiposity was 50% accounted for by her legs mainly. Liposuction and surgical debulking were performed to reduce the size of the limbs but had exacerbated the overgrowth in her lower limbs. Systemic sepsis from an infected foot ulcer necessitated treatment by an above-knee amputation. Postoperatively, the stump increased in size by 19 kg. A trial of rapamycin to reverse the growth of the stump has shown promise. We discuss the clinical and genetic features of this previously unclassified disorder and the orthopaedic considerations involved. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Advances in the therapeutic use of mammalian target of rapamycin (mTOR) inhibitors in dermatology.

    Science.gov (United States)

    Fogel, Alexander L; Hill, Sharleen; Teng, Joyce M C

    2015-05-01

    Significant developments in the use of mammalian target of rapamycin (mTOR) inhibitors (mTORIs) as immunosuppressant and antiproliferative agents have been made. Recent advances in the understanding of the mTOR signaling pathway and its downstream effects on tumorigenesis and vascular proliferation have broadened the clinical applications of mTORIs in many challenging disorders such as tuberous sclerosis complex, pachyonychia congenita, complex vascular anomalies, and inflammatory dermatoses. Systemic mTORI therapy has shown benefits in these areas, but is associated with significant side effects that sometimes necessitate drug holidays. To mitigate the side effects of systemic mTORIs for dermatologic applications, preliminary work to assess the potential of percutaneous therapy has been performed, and the evidence suggests that percutaneous delivery of mTORIs may allow for effective long-term therapy while avoiding systemic toxicities. Additional large placebo-controlled, double-blinded, randomized studies are needed to assess the efficacy, safety, duration, and tolerability of topical treatments. The objective of this review is to provide updated information on the novel use of mTORIs in the management of many cutaneous disorders. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  8. Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs.

    Science.gov (United States)

    Larson, Jeanne C; Allstadt, Sara D; Fan, Timothy M; Khanna, Chand; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Legendre, Alfred M; Galyon, Gina D; LeBlanc, Amy K; Martin-Jimenez, Tomas

    2016-01-01

    To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. 5 healthy purpose-bred hounds. The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.

  9. Labor Inhibits Placental Mechanistic Target of Rapamycin Complex 1 Signaling

    Science.gov (United States)

    LAGER, Susanne; AYE, Irving L.M.H.; GACCIOLI, Francesca; RAMIREZ, Vanessa I.; JANSSON, Thomas; POWELL, Theresa L.

    2014-01-01

    Introduction Labor induces a myriad of changes in placental gene expression. These changes may represent a physiological adaptation inhibiting placental cellular processes associated with a high demand for oxygen and energy (e.g., protein synthesis and active transport) thereby promoting oxygen and glucose transfer to the fetus. We hypothesized that mechanistic target of rapamycin complex 1 (mTORC1) signaling, a positive regulator of trophoblast protein synthesis and amino acid transport, is inhibited by labor. Methods Placental tissue was collected from healthy, term pregnancies (n=15 no-labor; n=12 labor). Activation of Caspase-1, IRS1/Akt, STAT, mTOR, and inflammatory signaling pathways was determined by Western blot. NFκB p65 and PPARγ DNA binding activity was measured in isolated nuclei. Results Labor increased Caspase-1 activation and mTOR complex 2 signaling, as measured by phosphorylation of Akt (S473). However, mTORC1 signaling was inhibited in response to labor as evidenced by decreased phosphorylation of mTOR (S2448) and 4EBP1 (T37/46 and T70). Labor also decreased NFκB and PPARγ DNA binding activity, while having no effect on IRS1 or STAT signaling pathway. Discussion and conclusion Several placental signaling pathways are affected by labor, which has implications for experimental design in studies of placental signaling. Inhibition of placental mTORC1 signaling in response to labor may serve to down-regulate protein synthesis and amino acid transport, processes that account for a large share of placental oxygen and glucose consumption. We speculate that this response preserves glucose and oxygen for transfer to the fetus during the stressful events of labor. PMID:25454472

  10. Suppression of AKT phosphorylation restores rapamycin-based synthetic lethality in SMAD4-defective pancreatic cancer cells.

    Science.gov (United States)

    Le Gendre, Onica; Sookdeo, Ayisha; Duliepre, Stephie-Anne; Utter, Matthew; Frias, Maria; Foster, David A

    2013-05-01

    mTOR has been implicated in survival signals for many human cancers. Rapamycin and TGF-β synergistically induce G1 cell-cycle arrest in several cell lines with intact TGF-β signaling pathway, which protects cells from the apoptotic effects of rapamycin during S-phase of the cell cycle. Thus, rapamycin is cytostatic in the presence of serum/TGF-β and cytotoxic in the absence of serum. However, if TGF-β signaling is defective, rapamycin induced apoptosis in both the presence and absence of serum/TGF-β in colon and breast cancer cell lines. Because genetic dysregulation of TGF-β signaling is commonly observed in pancreatic cancers-with defects in the Smad4 gene being most prevalent, we hypothesized that pancreatic cancers would display a synthetic lethality to rapamycin in the presence of serum/TGF-β. We report here that Smad4-deficient pancreatic cancer cells are killed by rapamycin in the absence of serum; however, in the presence of serum, we did not observe the predicted synthetic lethality with rapamycin. Rapamycin also induced elevated phosphorylation of the survival kinase Akt at Ser473. Suppression of rapamycin-induced Akt phosphorylation restored rapamycin sensitivity in Smad4-null, but not Smad4 wild-type pancreatic cancer cells. This study shows that the synthetic lethality to rapamycin in pancreatic cancers with defective TGF-β signaling is masked by rapamycin-induced increases in Akt phosphorylation. The implication is that a combination of approaches that suppress both Akt phosphorylation and mTOR could be effective in targeting pancreatic cancers with defective TGF-β signaling. ©2013 AACR.

  11. Are invertebrates relevant models in ageing research? Focus on the effects of rapamycin on TOR.

    Science.gov (United States)

    Erdogan, Cihan Suleyman; Hansen, Benni Winding; Vang, Ole

    2016-01-01

    Ageing is the organisms increased susceptibility to death, which is linked to accumulated damage in the cells and tissues. Ageing is a complex process regulated by crosstalk of various pathways in the cells. Ageing is highly regulated by the Target of Rapamycin (TOR) pathway activity. TOR is an evolutionary conserved key protein kinase in the TOR pathway that regulates growth, proliferation and cell metabolism in response to nutrients, growth factors and stress. Comparing the ageing process in invertebrate model organisms with relatively short lifespan with mammals provides valuable information about the molecular mechanisms underlying the ageing process faster than mammal systems. Inhibition of the TOR pathway activity via either genetic manipulation or rapamycin increases lifespan profoundly in most invertebrate model organisms. This contribution will review the recent findings in invertebrates concerning the TOR pathway and effects of TOR inhibition by rapamycin on lifespan. Besides some contradictory results, the majority points out that rapamycin induces longevity. This suggests that administration of rapamycin in invertebrates is a promising tool for pursuing the scientific puzzle of lifespan prolongation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Color homogeneity in LED spotlights

    NARCIS (Netherlands)

    Prins, C.R.; Tukker, T.W.; IJzerman, W.L.; Thije Boonkkamp, ten J.H.M.

    2014-01-01

    LED is a rising technology in the field of lighting. Halogen spotlights are nowadays replaced by LED spotlights because of their energy efficiency and long lifetime. However, color variation in the light output is a common problem. Poorly designed LED spotlights tend to have yellowish or bluish

  13. Deep UV LEDs

    Science.gov (United States)

    Han, Jung; Amano, Hiroshi; Schowalter, Leo

    2014-06-01

    Deep ultraviolet (DUV) photons interact strongly with a broad range of chemical and biological molecules; compact DUV light sources could enable a wide range of applications in chemi/bio-sensing, sterilization, agriculture, and industrial curing. The much shorter wavelength also results in useful characteristics related to optical diffraction (for lithography) and scattering (non-line-of-sight communication). The family of III-N (AlGaInN) compound semiconductors offers a tunable energy gap from infrared to DUV. While InGaN-based blue light emitters have been the primary focus for the obvious application of solid state lighting, there is a growing interest in the development of efficient UV and DUV light-emitting devices. In the past few years we have witnessed an increasing investment from both government and industry sectors to further the state of DUV light-emitting devices. The contributions in Semiconductor Science and Technology 's special issue on DUV devices provide an up-to-date snapshot covering many relevant topics in this field. Given the expected importance of bulk AlN substrate in DUV technology, we are pleased to include a review article by Hartmann et al on the growth of AlN bulk crystal by physical vapour transport. The issue of polarization field within the deep ultraviolet LEDs is examined in the article by Braut et al. Several commercial companies provide useful updates in their development of DUV emitters, including Nichia (Fujioka et al ), Nitride Semiconductors (Muramoto et al ) and Sensor Electronic Technology (Shatalov et al ). We believe these articles will provide an excellent overview of the state of technology. The growth of AlGaN heterostructures by molecular beam epitaxy, in contrast to the common organo-metallic vapour phase epitaxy, is discussed by Ivanov et al. Since hexagonal boron nitride (BN) has received much attention as both a UV and a two-dimensional electronic material, we believe it serves readers well to include the

  14. TOR (target of rapamycin) is a key regulator of triacylglycerol accumulation in microalgae.

    Science.gov (United States)

    Imamura, Sousuke; Kawase, Yasuko; Kobayashi, Ikki; Shimojima, Mie; Ohta, Hiroyuki; Tanaka, Kan

    2016-01-01

    Most microalgae abundantly accumulate lipid droplets (LDs) containing triacylglycerols (TAGs) under several stress conditions, but the underlying molecular mechanism of this accumulation remains unclear. In a recent study, we found that inhibition of TOR (target of rapamycin), a highly conserved protein kinase of eukaryotes, by rapamycin resulted in TAG accumulation in microalgae, indicating that TOR negatively regulates TAG accumulation. Here, we show that formation of intracellular LDs and TAG accumulation were also induced in the unicellular green alga Chlamydomonas reinhardtii after exposure to Torin1 or AZD8055, which are novel TOR inhibitors that inhibit TOR activity in a manner different from rapamycin. These results supported quite well our previous conclusion that TOR is a central regulator of TAG accumulation in microalgae.

  15. The Inhibitory Effect of Rapamycin on Toll Like Receptor 4 and Interleukin 17 in the Early Stage of Rat Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Ruichao Yu

    2016-02-01

    activation of Th17 cells. Rapamycin may attenuate DN via reduction of the TLR4 signaling pathway and Th17 cells signaling. Although the underlying mechanisms need to be explored, the observed increase of TLR4 and IL-17 during the early stages of DN and their suppression with rapamycin treatment suggest the importance of TLR4 and IL-17 in DN pathophysiology.

  16. Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs: A pilot study

    Science.gov (United States)

    Larson, Jeanne C.; Allstadt, Sara D.; Fan, Timothy M.; Khanna, Chand; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Legendre, Alfred M.; Galyon, Gina D.; LeBlanc, Amy K.; Martin-Jimenez, Tomas

    2017-01-01

    Objective To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. Animals 5 healthy purpose-bred hounds. Procedures The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and non-compartmental analyses. Results Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Conclusions and Clinical Relevance Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in ng/mL. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, needs to be determined. PMID:26709938

  17. Paradigmenwechsel in der Anti-Aging-Medizin: Hormesis, Target-of-Rapamycin-Komplex und erste Anti-Aging-Pillen // Paradigm Shift in Anti-Aging Medicine: Hormesis, Target of Rapamycin Complex and First Human Anti-Aging-Pills

    Directory of Open Access Journals (Sweden)

    Römmler A

    2016-01-01

    Full Text Available Studies in model organisms have shown that some drugs and lifestyle practices (calorie-restricted diets, regular exercise, e.g. can extend life and health span and protect against the onset of age-related chronic diseases by targeting physiological pathways.brA common mode of action was found via mTOR (mechanistic Target Of Rapamycin pathway signalling. This intracellular protein kinase complex plays a key role in stimulating anabolic and cell growth promoting processes, while inhibiting autophagy. On the other hand, downregulation results in antiproliferative, anticancer and intensive cell-repairing effects leading to life and health span extension and stress resistance. The mTOR complex regulates such basic cell activities and integrates signals from nutrition sensing, energy metabolism, insulin and growth factors, stress and hypoxia.brImportantly, mTOR can be inhibited by some molecules and their analogs (rapamycin, resveratrol, metformin, e.g., which are released naturally from plants, yeast or bacteria to protect against natural enemies. Its dosage resembles an adaptive hormetic response relationship, as high concentrations are toxic and mild doses are associated with anticancer and antiaging effects. This opens up new avenues for their use as „anti-aging pills“ in humans.brRecent human data suggest that metformin, rapamycin and other mTOR-inhibitors could delay heart disease, cancer, cognitive decline and improve survival time in people with diabetes mellitus. In addition, response to influenca vaccine was enhanced by rapamycin in adults with immunosenescence, indicating beneficial anti-aging effects in the elderly.br“Treat aging” is an actual call to recognize aging as an indication appropriate for clinical trials and treatments, as it was recently approved by the Federal Drug Administration (FDA USA. p bKurzfassung/b: Die ansteigende Morbidität und Invalidität in alternden Industrienationen stößt an die Grenzen der Ressourcen

  18. Nuclear PIM1 confers resistance to rapamycin-impaired endothelial proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Walpen, Thomas; Kalus, Ina [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Schwaller, Juerg [Department of Biomedicine, University of Basel, 4031 Basel (Switzerland); Peier, Martin A. [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Battegay, Edouard J. [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), 8057 Zuerich (Switzerland); Humar, Rok, E-mail: Rok.Humar@usz.ch [Research Unit, Division Internal Medicine, University Hospital Zuerich, 8091 Zuerich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), 8057 Zuerich (Switzerland)

    2012-12-07

    Highlights: Black-Right-Pointing-Pointer Pim1{sup -/-} endothelial cell proliferation displays increased sensitivity to rapamycin. Black-Right-Pointing-Pointer mTOR inhibition by rapamycin enhances PIM1 cytosolic and nuclear protein levels. Black-Right-Pointing-Pointer Truncation of Pim1 beyond serine 276 results in nuclear localization of the kinase. Black-Right-Pointing-Pointer Nuclear PIM1 increases endothelial proliferation independent of rapamycin. -- Abstract: The PIM serine/threonine kinases and the mTOR/AKT pathway integrate growth factor signaling and promote cell proliferation and survival. They both share phosphorylation targets and have overlapping functions, which can partially substitute for each other. In cancer cells PIM kinases have been reported to produce resistance to mTOR inhibition by rapamycin. Tumor growth depends highly on blood vessel infiltration into the malignant tissue and therefore on endothelial cell proliferation. We therefore investigated how the PIM1 kinase modulates growth inhibitory effects of rapamycin in mouse aortic endothelial cells (MAEC). We found that proliferation of MAEC lacking Pim1 was significantly more sensitive to rapamycin inhibition, compared to wildtype cells. Inhibition of mTOR and AKT in normal MAEC resulted in significantly elevated PIM1 protein levels in the cytosol and in the nucleus. We observed that truncation of the C-terminal part of Pim1 beyond Ser 276 resulted in almost exclusive nuclear localization of the protein. Re-expression of this Pim1 deletion mutant significantly increased the proliferation of Pim1{sup -/-} cells when compared to expression of the wildtype Pim1 cDNA. Finally, overexpression of the nuclear localization mutant and the wildtype Pim1 resulted in complete resistance to growth inhibition by rapamycin. Thus, mTOR inhibition-induced nuclear accumulation of PIM1 or expression of a nuclear C-terminal PIM1 truncation mutant is sufficient to increase endothelial cell proliferation

  19. Rapamycin causes activation of protein phosphatase-2A1 and nuclear translocation of PCNA in CD4+ T cells

    International Nuclear Information System (INIS)

    Morrow, Peter W.; Tung, H.Y. Lim; Hemmings, Hugh C.

    2004-01-01

    Rapamycin is a powerful immunosuppressant that causes cell cycle arrest in T cells and several other cell types. Despite its important clinical role, the mechanism of action of rapamycin is not fully understood. Here, we show that rapamycin causes the activation of protein phosphatase-2A 1 which forms a complex with proliferation cell nuclear antigen (PCNA) in a CD 4+ T cell line. Rapamycin also induces PCNA translocation from the cytoplasm to the nucleus, an effect which is antagonized by okadaic acid, an inhibitor of type 2A protein phosphatases. These findings provide evidence for the existence of a signal transduction pathway that links a rapamycin-activated type 2A protein phosphatase to the control of DNA synthesis, DNA repair, cell cycle, and cell death via PCNA

  20. Combined image guided monitoring the pharmacokinetics of rapamycin loaded human serum albumin nanoparticles with a split luciferase reporter

    Science.gov (United States)

    Wang, Fu; Yang, Kai; Wang, Zhe; Ma, Ying; Gutkind, J. Silvio; Hida, Naoki; Niu, Gang; Tian, Jie

    2016-02-01

    Imaging guided techniques have been increasingly employed to investigate the pharmacokinetics (PK) and biodistribution of nanoparticle based drug delivery systems. In most cases, however, the PK profiles of drugs could vary significantly from those of drug delivery carriers upon administration in the blood circulation, which complicates the interpretation of image findings. Herein we applied a genetically encoded luciferase reporter in conjunction with near infrared (NIR) fluorophores to investigate the respective PK profiles of a drug and its carrier in a biodegradable drug delivery system. In this system, a prototype hydrophobic agent, rapamycin (Rapa), was encapsulated into human serum albumin (HSA) to form HSA Rapa nanoparticles, which were then labeled with Cy5 fluorophore to facilitate the fluorescence imaging of HSA carrier. Meanwhile, we employed transgenetic HN12 cells that were modified with a split luciferase reporter, whose bioluminescence function is regulated by Rapa, to reflect the PK profile of the encapsulated agent. It was interesting to discover that there existed an obvious inconsistency of PK behaviors between HSA carrier and rapamycin in vitro and in vivo through near infrared fluorescence imaging (NIFRI) and bioluminescence imaging (BLI) after treatment with Cy5 labeled HSA Rapa. Nevertheless, HSA Rapa nanoparticles manifested favorable in vivo PK and tumor suppression efficacy in a follow-up therapeutic study. The developed strategy of combining a molecular reporter and a fluorophore in this study could be extended to other drug delivery systems to provide profound insights for non-invasive real-time evaluation of PK profiles of drug-loaded nanoparticles in pre-clinical studies.Imaging guided techniques have been increasingly employed to investigate the pharmacokinetics (PK) and biodistribution of nanoparticle based drug delivery systems. In most cases, however, the PK profiles of drugs could vary significantly from those of drug delivery

  1. Induction of biogenic magnetization and redox control by a component of the target of rapamycin complex 1 signaling pathway.

    Directory of Open Access Journals (Sweden)

    Keiji Nishida

    Full Text Available Most organisms are simply diamagnetic, while magnetotactic bacteria and migratory animals are among organisms that exploit magnetism. Biogenic magnetization not only is of fundamental interest, but also has industrial potential. However, the key factor(s that enable biogenic magnetization in coordination with other cellular functions and metabolism remain unknown. To address the requirements for induction and the application of synthetic bio-magnetism, we explored the creation of magnetism in a simple model organism. Cell magnetization was first observed by attraction towards a magnet when normally diamagnetic yeast Saccharomyces cerevisiae were grown with ferric citrate. The magnetization was further enhanced by genetic modification of iron homeostasis and introduction of ferritin. The acquired magnetizable properties enabled the cells to be attracted to a magnet, and be trapped by a magnetic column. Superconducting quantum interference device (SQUID magnetometry confirmed and quantitatively characterized the acquired paramagnetism. Electron microscopy and energy-dispersive X-ray spectroscopy showed electron-dense iron-containing aggregates within the magnetized cells. Magnetization-based screening of gene knockouts identified Tco89p, a component of TORC1 (Target of rapamycin complex 1, as important for magnetization; loss of TCO89 and treatment with rapamycin reduced magnetization in a TCO89-dependent manner. The TCO89 expression level positively correlated with magnetization, enabling inducible magnetization. Several carbon metabolism genes were also shown to affect magnetization. Redox mediators indicated that TCO89 alters the intracellular redox to an oxidized state in a dose-dependent manner. Taken together, we demonstrated that synthetic induction of magnetization is possible and that the key factors are local redox control through carbon metabolism and iron supply.

  2. Combination of rapamycin, CI-1040, and 17-AAG inhibits metastatic capacity of prostate cancer via Slug inhibition.

    Directory of Open Access Journals (Sweden)

    Guanxiong Ding

    Full Text Available Though prostate cancer (PCa has slow progression, the hormone refractory (HRCP and metastatic entities are substantially lethal and lack effective treatments. Transcription factor Slug is critical in regulating metastases of various tumors including PCa. Here we studied targeted therapy against Slug using combination of 3 drugs targeting 3 pathways respectively converging via Slug and further regulating PCa metastasis. Using in vitro assays we confirmed that Slug up-regulation incurred inhibition of E-cadherin that was anti-metastatic, and inhibited Bim-regulated cell apoptosis in PCa. Upstream PTEN/Akt, mTOR, Erk, and AR/Hsp90 pathways were responsible for Slug up-regulation and each of these could be targeted by rapamycin, CI-1040, and 17-AAG respectively. In 4 PCa cell lines with different traits in terms of PTEN loss and androgen sensitivity we tested the efficacy of mono- and combined therapy with the drugs. We found that metastatic capacity of the cells was maximally inhibited only when all 3 drugs were combined, due to the crosstalk between the pathways. 17-AAG decreases Slug expression via blockade of HSP90-dependent AR stability. Combination of rapamycin and CI-1040 diminishes invasiveness more potently in PCa cells that are androgen insensitive and with PTEN loss. Slug inhibited Bim-mediated apoptosis that could be rescued by mTOR/Erk/HSP90 inhibitors. Using mouse models for circulating PCa DNA quantification, we found that combination of mTOR/Erk/HSP90 inhibitors reduced circulating PCa cells in vivo significantly more potently than combination of 2 or monotherapy. Conclusively, combination of mTOR/Erk/Hsp90 inhibits metastatic capacity of prostate cancer via Slug inhibition.

  3. Activated mammalian target of rapamycin is a potential therapeutic target in gastric cancer

    International Nuclear Information System (INIS)

    Xu, Da-zhi; Sun, Xiao-wei; Guan, Yuan-xiang; Li, Yuan-fang; Lin, Tong-yu; Geng, Qi-rong; Tian, Ying; Cai, Mu-yan; Fang, Xin-juan; Zhan, You-qing; Zhou, Zhi-wei; Li, Wei; Chen, Ying-bo

    2010-01-01

    The mammalian target of rapamycin (mTOR) plays a key role in cellular growth and homeostasis. The purpose of our present study is to investigate the expression of activated mTOR (p-mTOR) in gastric cancer patients, their prognostic significance and the inhibition effect of RAD001 on tumor growth and to determine whether targeted inhibition of mTOR could be a potential therapeutic strategy for gastric cancer. The expression of p-mTOR was detected in specimens of 181 gastric cancers who underwent radical resection (R0) by immunohistochemistry. The correlation of p-mTOR expression to clinicopathologic features and survival of gastric cancer was studied. We also determined the inhibition effect of RAD001 on tumor growth using BGC823 and AGS human gastric cancer cell lines. Immunostaining for p-mTOR was positive in 93 of 181 (51.4%) gastric cancers, closely correlated with lymph node status and pTNM stage. Patients with p-mTOR positive showed significantly shorter disease-free survival (DFS) and overall survival (OS) rates than those with p-mTOR-negative tumors in univariable analyses, and there was a trend toward a correlation between p-mTOR expression and survival in multivariable analyses. RAD001 markedly inhibited dose-dependently proliferation of human gastric carcinoma cells by down-regulating expression of p70s6k, p-p70s6k, C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53. In gastric cancer, p-mTOR is a potential therapeutic target and RAD001 was a promising treatment agent with inducing cell cycle arrest and apoptosis by down-regulating expression of C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53

  4. Effects of chronic Akt/mTOR inhibition by rapamycin on mechanical overload-induced hypertrophy and myosin heavy chain transition in masseter muscle.

    Science.gov (United States)

    Umeki, Daisuke; Ohnuki, Yoshiki; Mototani, Yasumasa; Shiozawa, Kouichi; Fujita, Takayuki; Nakamura, Yoshiki; Saeki, Yasutake; Okumura, Satoshi

    2013-01-01

    To examine the effects of the Akt/mammalian target of rapamycin (mTOR) pathway on masseter muscle hypertrophy and myosin heavy chain (MHC) transition in response to mechanical overload, we analyzed the effects of bite-opening (BO) on the hypertrophy and MHC composition of masseter muscle of BO-rats treated or not treated with rapamycin (RAPA), a selective mTOR inhibitor. The masseter muscle weight in BO-rats was significantly greater than that in controls, and this increase was attenuated by RAPA treatment. Expression of slow-twitch MHC isoforms was significantly increased in BO-rats with/without RAPA treatment, compared with controls, but the magnitude of the increase was much smaller in RAPA-treated BO-rats. Phosphorylation of p44/42 MAPK (ERK1/2), which preserves fast-twitch MHC isoforms in skeletal muscle, was significantly decreased in BO-rats, but the decrease was abrogated by RAPA treatment. Calcineurin signaling is known to be important for masseter muscle hypertrophy and fast-to-slow MHC isoform transition, but expression of known calcineurin activity modulators was unaffected by RAPA treatment. Taken together, these results indicate that the Akt/mTOR pathway is involved in both development of masseter muscle hypertrophy and fast-to-slow MHC isoform transition in response to mechanical overload with inhibition of the ERK1/2 pathway and operates independently of the calcineurin pathway.

  5. Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance

    DEFF Research Database (Denmark)

    Widlund, Anne Lykkegaard; Vang, Ole; Ye, Lan

    2013-01-01

    mitochondrial transcripts were decreased, particularly in the highly oxidative soleus muscle, we found no consistent change in mitochondrial DNA or protein levels. In agreement with the lack of change in mitochondrial components, rapamycin-treated mice had endurance equivalent to that of untreated controls...

  6. Rapamycin blocks the antidepressant effect of ketamine in task-dependent manner

    Czech Academy of Sciences Publication Activity Database

    Holubová, Kristína; Kletečková, Lenka; Škurlová, Martina; Říčný, J.; Stuchlík, Aleš; Valeš, Karel

    2016-01-01

    Roč. 233, č. 11 (2016), s. 2077-2097 ISSN 0033-3158 R&D Projects: GA MZd(CZ) NT13403 Institutional support: RVO:67985823 Keywords : ketamine * rapamycin * antidepressants * anxiety * cognitive deficit * bulbectomy * mTOR * BDNF Subject RIV: FH - Neurology Impact factor: 3.308, year: 2016

  7. The Immunosuppressive drug – Rapamycin – Electroanalytical Sensing Using Boron- Doped Diamond electrode

    International Nuclear Information System (INIS)

    Stanković, Dalibor M.; Kalcher, Kurt

    2015-01-01

    Graphical abstract: Display Omitted -- Abstract: This paper presents for the first time the study of electrochemical behavior of well known immunosuppressant drug – rapamycin (sirolimus) using boron-doped diamond electrode. Rapamycin provided single and oval-shaped oxidation peak at +1.1 V vs. Ag/AgCl electrode in Britton–Robinson buffer solution at pH 3 confirming highly irreversible behavior of analyte at boron-doped diamond electrode. A differential pulse voltammetry was used for quantification of tested drug under the optimum experimental conditions. The calibration curve was linear over the range from 0.5 to 19.5 μM (R 2 = 0.9976) with detection limit of 0.22 μM. Repeatability of ten successfully measurements of three different concentrations (5, 10 and 15 μM) was 2.5, 1.9 and 1,7 %, respectively. Influence of most common biomolecules presented in urine samples was evaluated. The suggested analytical methodology was successfully applied for determination of rapamycin in four urine samples with excellent recoveries. The developed approach could be beneficial in analysis of rapamycin in biological samples using boron-doped diamond electrode as up-to-date electrochemical sensor and could represent inexpensive analytical alternative to separation methods

  8. Surface Engineering of Porous Silicon Microparticles for Intravitreal Sustained Delivery of Rapamycin

    Science.gov (United States)

    Nieto, Alejandra; Hou, Huiyuan; Moon, Sang Woong; Sailor, Michael J.; Freeman, William R.; Cheng, Lingyun

    2015-01-01

    Purpose. To understand the relationship between rapamycin loading/release and surface chemistries of porous silicon (pSi) to optimize pSi-based intravitreal delivery system. Methods. Three types of surface chemical modifications were studied: (1) pSi-COOH, containing 10-carbon aliphatic chains with terminal carboxyl groups grafted via hydrosilylation of undecylenic acid; (2) pSi-C12, containing 12-carbon aliphatic chains grafted via hydrosilylation of 1-dodecene; and (3) pSiO2-C8, prepared by mild oxidation of the pSi particles followed by grafting of 8-hydrocarbon chains to the resulting porous silica surface via a silanization. Results. The efficiency of rapamycin loading follows the order (micrograms of drug/milligrams of carrier): pSiO2-C8 (105 ± 18) > pSi-COOH (68 ± 8) > pSi-C12 (36 ± 6). Powder X-ray diffraction data showed that loaded rapamycin was amorphous and dynamic drug-release study showed that the availability of the free drug was increased by 6-fold (compared with crystalline rapamycin) by using pSiO2-C8 formulation (P = 0.0039). Of the three formulations in this study, pSiO2-C8-RAP showed optimal performance in terms of simultaneous release of the active drug and carrier degradation, and drug-loading capacity. Released rapamycin was confirmed with the fingerprints of the mass spectrometry and biologically functional as the control of commercial crystalline rapamycin. Single intravitreal injections of 2.9 ± 0.37 mg pSiO2-C8-RAP into rabbit eyes resulted in more than 8 weeks of residence in the vitreous while maintaining clear optical media and normal histology of the retina in comparison to the controls. Conclusions. Porous silicon–based rapamycin delivery system using the pSiO2-C8 formulation demonstrated good ocular compatibility and may provide sustained drug release for retina. PMID:25613937

  9. Surface engineering of porous silicon microparticles for intravitreal sustained delivery of rapamycin.

    Science.gov (United States)

    Nieto, Alejandra; Hou, Huiyuan; Moon, Sang Woong; Sailor, Michael J; Freeman, William R; Cheng, Lingyun

    2015-01-22

    To understand the relationship between rapamycin loading/release and surface chemistries of porous silicon (pSi) to optimize pSi-based intravitreal delivery system. Three types of surface chemical modifications were studied: (1) pSi-COOH, containing 10-carbon aliphatic chains with terminal carboxyl groups grafted via hydrosilylation of undecylenic acid; (2) pSi-C12, containing 12-carbon aliphatic chains grafted via hydrosilylation of 1-dodecene; and (3) pSiO2-C8, prepared by mild oxidation of the pSi particles followed by grafting of 8-hydrocarbon chains to the resulting porous silica surface via a silanization. The efficiency of rapamycin loading follows the order (micrograms of drug/milligrams of carrier): pSiO2-C8 (105 ± 18) > pSi-COOH (68 ± 8) > pSi-C12 (36 ± 6). Powder X-ray diffraction data showed that loaded rapamycin was amorphous and dynamic drug-release study showed that the availability of the free drug was increased by 6-fold (compared with crystalline rapamycin) by using pSiO2-C8 formulation (P = 0.0039). Of the three formulations in this study, pSiO2-C8-RAP showed optimal performance in terms of simultaneous release of the active drug and carrier degradation, and drug-loading capacity. Released rapamycin was confirmed with the fingerprints of the mass spectrometry and biologically functional as the control of commercial crystalline rapamycin. Single intravitreal injections of 2.9 ± 0.37 mg pSiO2-C8-RAP into rabbit eyes resulted in more than 8 weeks of residence in the vitreous while maintaining clear optical media and normal histology of the retina in comparison to the controls. Porous silicon-based rapamycin delivery system using the pSiO2-C8 formulation demonstrated good ocular compatibility and may provide sustained drug release for retina. Copyright 2015 The Association for Research in Vision and Ophthalmology, Inc.

  10. A pilot randomised controlled trial of personalised care after treatment for prostate cancer (TOPCAT-P): nurse-led holistic-needs assessment and individualised psychoeducational intervention: study protocol

    Science.gov (United States)

    Stanciu, Marian Andrei; Morris, Caroline; Makin, Matt; Watson, Eila; Bulger, Jenna; Evans, Richard; Hiscock, Julia; Hoare, Zoë; Edwards, Rhiannon Tudor; Neal, Richard David; Wilkinson, Clare

    2015-01-01

    Introduction Prostate cancer is common and the incidence is increasing, but more men are living longer after diagnosis, and die with their disease rather than of it. Nonetheless, specific and substantial physical, sexual, emotional and mental health problems often lead to a poor quality of life. Urology services increasingly struggle to cope with the demands of follow-up care, and primary care is likely to play the central role in long-term follow-up. The present phase II trial will evaluate the feasibility and acceptability of a nurse-led, person-centred psychoeducational intervention, delivered in community or primary care settings. Methods and analysis Prostate cancer survivors diagnosed in the past 9–48 months and currently biochemically stable will be identified from hospital records by their treating clinician. Eligible men would have either completed radical treatment, or would be followed up with prostate specific antigen monitoring and symptom reporting. We will recruit 120 patients who will be randomised to receive either an augmented form of usual care, or an additional nurse-led intervention for a period of 36 weeks. Following the health policy in Wales, the intervention is offered by a key worker, is promoting prudent healthcare and is using a holistic needs assessment. Outcome measures will assess physical symptoms, psychological well-being, confidence in managing own health and quality of life. Healthcare service use will be measured over 36 weeks. Feedback interviews with patients and clinicians will further inform the acceptability of the intervention. Recruitment, attrition, questionnaire completion rates and outcome measures variability will be assessed, and results will inform the design of a future phase III trial and accompanying economic evaluation. Ethics and dissemination Ethics approval was granted by Bangor University and North Wales REC (13/WA/0291). Results will be reported in peer-reviewed publications, at scientific

  11. The effect of the immunophilin ligands rapamycin and FK506 on proliferation of mast cells and other hematopoietic cell lines.

    Science.gov (United States)

    Hultsch, T; Martin, R; Hohman, R J

    1992-01-01

    The immunosuppressive drugs FK506 and cyclosporin A have an identical spectrum of activities with respect to IgE receptor (Fc epsilon RI)-mediated exocytosis from mast cells and T cell receptor-mediated transcription of IL-2. These findings suggest a common step in receptor-mediated signal transduction leading to exocytosis and transcription and imply that immunosuppressive drugs target specific signal transduction pathways, rather than specific cell types. This hypothesis is supported by studies on the effect of rapamycin on IL-3 dependent proliferation of the rodent mast cell line PT18. Rapamycin inhibits proliferation of PT18 cells, achieving a plateau of 80% inhibition at 1 nM. This inhibition is prevented in a competitive manner by FK506, a structural analogue of rapamycin. Proliferation of rat basophilic leukemia cells and WEHI-3 cells was also inhibited, at doses comparable to those shown previously to inhibit IL-2-dependent proliferation of cytotoxic T lymphocyte line (CTLL) cells. In contrast, proliferation of A-431 cells, a epidermoid cell line, was not affected by rapamycin. DNA histograms indicate that complexes formed between the rapamycin-FK506-binding protein (FKBP) and rapamycin arrest-proliferating PT18 cells in the G0/G1-phase. It is concluded that FKBP-rapamycin complexes may inhibit proliferative signals emanating from IL-3 receptors, resulting in growth arrest of cytokine-dependent, hematopoietic cells. PMID:1384815

  12. Rapamycin enhances the anti-angiogenesis and anti-proliferation ability of YM155 in oral squamous cell carcinoma.

    Science.gov (United States)

    Li, Kong-Liang; Wang, Yu-Fan; Qin, Jia-Ruo; Wang, Feng; Yang, Yong-Tao; Zheng, Li-Wu; Li, Ming-Hua; Kong, Jie; Zhang, Wei; Yang, Hong-Yu

    2017-06-01

    YM155, a small molecule inhibitor of survivin, has been studied in many tumors. It has been shown that YM155 inhibited oral squamous cell carcinoma through promoting apoptosis and autophagy and inhibiting proliferation. It was found that YM155 also inhibited the oral squamous cell carcinoma-mediated angiogenesis through the inactivation of the mammalian target of rapamycin pathway. Rapamycin, a mammalian target of rapamycin inhibitor, played an important role in the proliferation and angiogenesis of oral squamous cell carcinoma cell lines. In our study, cell proliferation assay, transwell assay, tube formation assay, and western blot assay were used to investigate the synergistic effect of rapamycin on YM155 in oral squamous cell carcinoma. Either in vitro or in vivo, rapamycin and YM155 exerted a synergistic effect on the inhibition of survivin and vascular endothelial growth factor through mammalian target of rapamycin pathway. Overall, our results revealed that low-dose rapamycin strongly promoted the sensitivity of oral squamous cell carcinoma cell lines to YM155.

  13. The Role of mTOR Inhibitors for the Treatment of B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Pinelopi Argyriou

    2012-01-01

    Full Text Available Despite the fact that the majority of lymphomas initially respond to treatment, many patients relapse and die from disease that is refractory to current regimens. The need for new treatment strategies in lymphomas has led to the investigation and evaluation of novel agents that target cellular pathways. The mammalian target of rapamycin (mTOR is a representative pathway that may be implicated in lymphomagenesis. Rapamycin and especially its derivatives (temsirolimus, everolimus, and deforolimus represent the first described mTOR inhibitors. These agents have shown promising results in the treatment of lymphoid malignancies. On the other hand, new ATP-competitive mTOR inhibitors that provoke a broader inhibition of mTOR activity are in early stages of clinical development. The purpose of this paper is to summarize the existing knowledge about mTOR inhibitors and their use in the treatment of B-cell lymphomas. Relevant issues regarding mTOR biology in general as well as in B-cell lymphoid neoplasms are also discussed in short.

  14. Practical lighting design with LEDs

    CERN Document Server

    Lenk, Ron

    2016-01-01

    The second edition of Practical Lighting Design with LEDs has been revised and updated to provide the most current information for developing light-emitting diodes products. The authors, noted authorities in the field, offer a review of the most relevant topics including optical performance, materials, thermal design, and modeling and measurement. Comprehensive in scope, the text covers all the information needed to design LEDs into end products.

  15. Standardization of UV LED measurements

    Science.gov (United States)

    Eppeldauer, G. P.; Larason, T. C.; Yoon, H. W.

    2015-09-01

    Traditionally used source spectral-distribution or detector spectral-response based standards cannot be applied for accurate UV LED measurements. Since the CIE standardized rectangular-shape spectral response function for UV measurements cannot be realized with small spectral mismatch when using filtered detectors, the UV measurement errors can be several times ten percent or larger. The UV LEDs produce broadband radiation and both their peaks or spectral bandwidths can change significantly. The detectors used for the measurement of these LEDs also have different spectral bandwidths. In the discussed example, where LEDs with 365 nm peak are applied for fluorescent crack-recognition using liquid penetrant (non-destructive) inspection, the broadband radiometric LED (signal) measurement procedure is standardized. A UV LED irradiance-source was calibrated against an FEL lamp standard to determine its spectral irradiance. The spectral irradiance responsivity of a reference UV meter was also calibrated. The output signal of the reference UV meter was calculated from the spectral irradiance of the UV source and the spectral irradiance responsivity of the reference UV meter. From the output signal, both the integrated irradiance (in the reference plane of the reference meter) and the integrated responsivity of the reference meter were determined. Test UV meters calibrated for integrated responsivity against the reference UV meter, can be used to determine the integrated irradiance from a field UV source. The obtained 5 % (k=2) measurement uncertainty can be decreased when meters with spectral response close to a constant value are selected.

  16. A pilot randomised controlled trial of personalised care after treatment for prostate cancer (TOPCAT-P): nurse-led holistic-needs assessment and individualised psychoeducational intervention: study protocol.

    Science.gov (United States)

    Stanciu, Marian Andrei; Morris, Caroline; Makin, Matt; Watson, Eila; Bulger, Jenna; Evans, Richard; Hiscock, Julia; Hoare, Zoë; Edwards, Rhiannon Tudor; Neal, Richard David; Wilkinson, Clare

    2015-06-25

    Prostate cancer is common and the incidence is increasing, but more men are living longer after diagnosis, and die with their disease rather than of it. Nonetheless, specific and substantial physical, sexual, emotional and mental health problems often lead to a poor quality of life. Urology services increasingly struggle to cope with the demands of follow-up care, and primary care is likely to play the central role in long-term follow-up. The present phase II trial will evaluate the feasibility and acceptability of a nurse-led, person-centred psychoeducational intervention, delivered in community or primary care settings. Prostate cancer survivors diagnosed in the past 9-48 months and currently biochemically stable will be identified from hospital records by their treating clinician. Eligible men would have either completed radical treatment, or would be followed up with prostate specific antigen monitoring and symptom reporting. We will recruit 120 patients who will be randomised to receive either an augmented form of usual care, or an additional nurse-led intervention for a period of 36 weeks. Following the health policy in Wales, the intervention is offered by a key worker, is promoting prudent healthcare and is using a holistic needs assessment. Outcome measures will assess physical symptoms, psychological well-being, confidence in managing own health and quality of life. Healthcare service use will be measured over 36 weeks. Feedback interviews with patients and clinicians will further inform the acceptability of the intervention. Recruitment, attrition, questionnaire completion rates and outcome measures variability will be assessed, and results will inform the design of a future phase III trial and accompanying economic evaluation. Ethics approval was granted by Bangor University and North Wales REC (13/WA/0291). Results will be reported in peer-reviewed publications, at scientific conferences, and directly through national cancer and primary care networks

  17. Rapamycin-ameliorated diabetic symptoms involved in increasing adiponectin expression in diabetic mice on a high-fat diet.

    Science.gov (United States)

    Gong, Fang-Hua; Ye, Yan-Na; Li, Jin-Meng; Zhao, Hai-Yang; Li, Xiao-Kun

    2017-07-01

    Recent studies showed that rapamycin improved diabetic complications. Here, we investigated the metabolic effects of rapamycin in type 2 diabetes model (T2DM) mice. Mice were treated with a daily intraperitoneal injection of rapamycin at 2 mg/kg or vehicle only for 3 weeks and were maintained on a high-fat diet. The treated diabetic mice exhibited decreased body weight, blood glucose levels, and fat mass. FGF21 expression was suppressed in C57B/L6 mice, but adiponectin expression increased both in FGF21 KO and C57B/L6 mice. These results suggest that rapamycin may alleviate FGF21 resistance in mice on a high-fat diet. The reduction of adipose tissue mass of the diabetic mice may be due to the increased adiponectin. Copyright © 2017. Published by Elsevier Taiwan.

  18. Saccharomyces cerevisiae FKBP12 binds Arabidopsis thaliana TOR and its expression in plants leads to rapamycin susceptibility.

    Science.gov (United States)

    Sormani, Rodnay; Yao, Lei; Menand, Benoît; Ennar, Najla; Lecampion, Cécile; Meyer, Christian; Robaglia, Christophe

    2007-06-01

    The eukaryotic TOR pathway controls translation, growth and the cell cycle in response to environmental signals such as nutrients or growth-stimulating factors. The TOR protein kinase can be inactivated by the antibiotic rapamycin following the formation of a ternary complex between TOR, rapamycin and FKBP12 proteins. The TOR protein is also found in higher plants despite the fact that they are rapamycin insensitive. Previous findings using the yeast two hybrid system suggest that the FKBP12 plant homolog is unable to form a complex with rapamycin and TOR, while the FRB domain of plant TOR is still able to bind to heterologous FKBP12 in the presence of rapamycin. The resistance to rapamycin is therefore limiting the molecular dissection of the TOR pathway in higher plants. Here we show that none of the FKBPs from the model plant Arabidopsis (AtFKBPs) is able to form a ternary complex with the FRB domain of AtTOR in the presence of rapamycin in a two hybrid system. An antibody has been raised against the AtTOR protein and binding of recombinant yeast ScFKBP12 to native Arabidopsis TOR in the presence of rapamycin was demonstrated in pull-down experiments. Transgenic lines expressing ScFKBP12 were produced and were found to display a rapamycin-dependent reduction of the primary root growth and a lowered accumulation of high molecular weight polysomes. These results further strengthen the idea that plant resistance to rapamycin evolved as a consequence of mutations in plant FKBP proteins. The production of rapamycin-sensitive plants through the expression of the ScFKBP12 protein illustrates the conservation of the TOR pathway in eukaryotes. Since AtTOR null mutants were found to be embryo lethal 1, transgenic ScFKBP12 plants will provide an useful tool for the post-embryonic study of plant TOR functions. This work also establish for the first time a link between TOR activity and translation in plant cells.

  19. Saccharomyces cerevisiae FKBP12 binds Arabidopsis thaliana TOR and its expression in plants leads to rapamycin susceptibility

    Directory of Open Access Journals (Sweden)

    Meyer Christian

    2007-06-01

    Full Text Available Abstract Background The eukaryotic TOR pathway controls translation, growth and the cell cycle in response to environmental signals such as nutrients or growth-stimulating factors. The TOR protein kinase can be inactivated by the antibiotic rapamycin following the formation of a ternary complex between TOR, rapamycin and FKBP12 proteins. The TOR protein is also found in higher plants despite the fact that they are rapamycin insensitive. Previous findings using the yeast two hybrid system suggest that the FKBP12 plant homolog is unable to form a complex with rapamycin and TOR, while the FRB domain of plant TOR is still able to bind to heterologous FKBP12 in the presence of rapamycin. The resistance to rapamycin is therefore limiting the molecular dissection of the TOR pathway in higher plants. Results Here we show that none of the FKBPs from the model plant Arabidopsis (AtFKBPs is able to form a ternary complex with the FRB domain of AtTOR in the presence of rapamycin in a two hybrid system. An antibody has been raised against the AtTOR protein and binding of recombinant yeast ScFKBP12 to native Arabidopsis TOR in the presence of rapamycin was demonstrated in pull-down experiments. Transgenic lines expressing ScFKBP12 were produced and were found to display a rapamycin-dependent reduction of the primary root growth and a lowered accumulation of high molecular weight polysomes. Conclusion These results further strengthen the idea that plant resistance to rapamycin evolved as a consequence of mutations in plant FKBP proteins. The production of rapamycin-sensitive plants through the expression of the ScFKBP12 protein illustrates the conservation of the TOR pathway in eukaryotes. Since AtTOR null mutants were found to be embryo lethal 1, transgenic ScFKBP12 plants will provide an useful tool for the post-embryonic study of plant TOR functions. This work also establish for the first time a link between TOR activity and translation in plant cells

  20. Optical characterization of ultrabright LEDs

    International Nuclear Information System (INIS)

    Benavides, Juan Manuel; Webb, Robert H.

    2005-01-01

    Ultrabright light emitting diodes (LEDs) are a new light source for visual psychophysics and microscopy. The new LEDs are intended primarily for room and exterior illumination, and the manufacturers' specifications are adequate for that. However, we use them as light sources in situations where a more complete characterization may be useful. For one set of LEDs we have measured the radiometric intensity and its distribution in space and wavelength, and we have tested for interactions of these variables and their dependence on driver configuration. We describe techniques for making these measurements and give a link to a simple calculator for converting among radiometric and photometric measures, as well as an evaluation of the safety considerations these very bright sources demand

  1. Descending serotonergic facilitation mediated by spinal 5-HT3 receptors engages spinal rapamycin-sensitive pathways in the rat

    Science.gov (United States)

    Asante, Curtis O.; Dickenson, Anthony H.

    2010-01-01

    We have recently reported the importance of spinal rapamycin-sensitive pathways in maintaining persistent pain-like states. A descending facilitatory drive mediated through spinal 5-HT3 receptors (5-HT3Rs) originating from superficial dorsal horn NK1-expressing neurons and that relays through the parabrachial nucleus and the rostroventral medial medulla to act on deep dorsal horn neurons is known be important in maintaining these pain-like states. To determine if spinal rapamycin-sensitive pathways are activated by a descending serotonergic drive, we investigated the effects of spinally administered rapamycin on responses of deep dorsal horn neurons that had been pre-treated with the selective 5-HT3R antagonist ondansetron. We also investigated the effects of spinally administered cell cycle inhibitor (CCI)-779 (a rapamycin ester analogue) on deep dorsal horn neurons from rats with carrageenan-induced inflammation of the hind paw. Unlike some other models of persistent pain, this model does not involve an altered 5-HT3R-mediated descending serotonergic drive. We found that the inhibitory effects of rapamycin were significantly reduced for neuronal responses to mechanical and thermal stimuli when the spinal cord was pre-treated with ondansetron. Furthermore, CCI-779 was found to be ineffective in attenuating spinal neuronal responses to peripheral stimuli in carrageenan-treated rats. Therefore, we conclude that 5-HT3R-mediated descending facilitation is one requirement for activation of rapamycin-sensitive pathways that contribute to persistent pain-like states. PMID:20709148

  2. Semiconductor lasers and herterojunction leds

    CERN Document Server

    Kressel, Henry

    2012-01-01

    Semiconductor Lasers and Heterojunction LEDs presents an introduction to the subject of semiconductor lasers and heterojunction LEDs. The book reviews relevant basic solid-state and electromagnetic principles; the relevant concepts in solid state physics; and the p-n junctions and heterojunctions. The text also describes stimulated emission and gain; the relevant concepts in electromagnetic field theory; and the modes in laser structures. The relation between electrical and optical properties of laser diodes; epitaxial technology; binary III-V compounds; and diode fabrication are also consider

  3. White LED motorcycle headlamp design

    Science.gov (United States)

    Sun, Wen-Shing

    2015-09-01

    The motorcycle headlamp is composed of a white LED module, an elliptical reflector, a parabolic reflector and a toric lens. We use non-sequential ray to improve the optical efficiency of the compound reflectors. Using the toric lens can meet ECE_113 regulation and obtain a good uniformity.

  4. Architecture-Led Safety Process

    Science.gov (United States)

    2016-12-01

    Contents Acknowledgments iv Abstract v 1 Introduction 1 2 Architecture -Led Processes and ALSA 2 3 ALSA Practices 5 3.1 Example System 8 4 Identify... Architecture Models 13 5 Identify Operational Hazards and Hazard Contributors 15 5.1 System Partitioning 15 5.2 Operational Context as a Control

  5. LED licht van de toekomst

    NARCIS (Netherlands)

    Zeiler, W.

    2009-01-01

    De gloeilamp is verleden tijd, na ongeveer 125 jaar na de ontdekking door Thomas Edison valt langzaam maar zeker binnen een decennium het doek. Australië heeft de klassieke gloeilamp al in de ban gedaan en vele landen volgen deze trend. De rol van de klassieke gloeilamp wordt overgenomen door LED.

  6. Testing intravitreal toxicity of rapamycin in rabbit eyes Toxicidade intravítrea da rapamicina em olhos de coelhos

    Directory of Open Access Journals (Sweden)

    Roberta Pereira de Almeida Manzano

    2009-02-01

    Full Text Available PURPOSE: To evaluate retinal toxicity of varying doses of rapamycin when injected intravitreally in rabbits. Rapamycin is a potent immunosuppressive agent with significant antitumor and antiangiogenic properties, clinically approved for prevention of organ transplant rejection. METHODS: Twelve New Zealand albino rabbits were divided into four groups. Four different doses of rapamycin were prepared in 0.1 ml: 20 µg, 50 µg, 200 µg, and 1000 µg. Each concentration was injected in one eye of three rabbits, and 0.1 ml volume of sterile BSS was injected into the contralateral eye of the three rabbits. Slit-lamp and fundoscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, and toxicity. A baseline ERG was performed before drug treatment and at day 14, after which the rabbits were euthanized. Histology of the enucleated eyes was studied to look for retinal toxicity. RESULTS: ERG results showed some decrease in scotopic response; however this was not dose related. ERG results were normal at 20 µg. Histological results showed no retinal toxicity in all groups. CONCLUSION: Although ERG changes were identified at dosages between 50-1000 µg, the histology of all groups up to 1000 µg did not show any discernable abnormalities.OBJETIVO: Avaliar a toxicidade da injeção intravítrea de diferentes doses de rapamicina para a retina de coelhos. Rapamicina é uma potente droga imunossupressora aprovada clinicamente para a prevenção da rejeição de transplantes de orgãos. MÉTODOS: Doze coelhos albinos da Nova Zelândia foram usados neste estudo. Foram divididos em quatro grupos. Quatro diferentes doses de rapamicina foram preparadas nas seguintes concentrações: 20 µg, 50 µg, 200 µg, 1000 µg. Foram realizadas injeções intravítreas de 0,1 ml de cada concentração em um olho de três coelhos e 0,1 ml de solução salina foi injetada no olho contralateral de cada coelho. Foram

  7. LED lamp color control system and method

    Science.gov (United States)

    Gaines, James; Clauberg, Bernd; Van Erp, Josephus A.M.

    2013-02-05

    An LED lamp color control system and method including an LED lamp having an LED controller 58; and a plurality of LED channels 60 operably connected to the LED controller 58, each of the plurality of LED channels 60 having a channel switch 62 in series with at least one shunted LED circuit 83, the shunted LED circuit 83 having a shunt switch 68 in parallel with an LED source 80. The LED controller 58 determines whether the LED source 80 is in a feedback controllable range, stores measured optical flux for the LED source 80 when the LED source 80 is in the feedback controllable range, and bypasses storing the measured optical flux when the LED source 80 is not in the feedback controllable range.

  8. LED lamp power management system and method

    Science.gov (United States)

    Gaines, James; Clauberg, Bernd; Van Erp, Josephus A. M.

    2013-03-19

    An LED lamp power management system and method including an LED lamp having an LED controller 58; a plurality of LED channels 60 operably connected to the LED controller 58, each of the plurality of LED channels 60 having a channel switch 62 in series with at least one shunted LED circuit 83, the shunted LED circuit 83 having a shunt switch 68 in parallel with an LED source 80. The LED controller 58 reduces power loss in one of the channel switch 62 and the shunt switch 68 when LED lamp electronics power loss (P.sub.loss) exceeds an LED lamp electronics power loss limit (P.sub.lim); and each of the channel switches 62 receives a channel switch control signal 63 from the LED controller 58 and each of the shunt switches 68 receives a shunt switch control signal 69 from the LED controller 58.

  9. Branched Chain Amino Acid Suppresses Hepatocellular Cancer Stem Cells through the Activation of Mammalian Target of Rapamycin

    Science.gov (United States)

    Nishitani, Shinobu; Horie, Mayumi; Ishizaki, Sonoko; Yano, Hirohisa

    2013-01-01

    Differentiation of cancer stem cells (CSCs) into cancer cells causes increased sensitivity to chemotherapeutic agents. Although inhibition of mammalian target of rapamycin (mTOR) leads to CSC survival, the effect of branched chain amino acids (BCAAs), an mTOR complex 1 (mTORC1) activator remains unknown. In this study, we examined the effects of BCAA on hepatocellular carcinoma (HCC) cells expressing a hepatic CSC marker, EpCAM. We examined the effects of BCAA and/or 5-fluorouracil (FU) on expression of EpCAM and other CSC-related markers, as well as cell proliferation in HCC cells and in a xenograft mouse model. We also characterized CSC-related and mTOR signal-related molecule expression and tumorigenicity in HCC cells with knockdown of Rictor or Raptor, or overexpression of constitutively active rheb (caRheb). mTOR signal-related molecule expression was also examined in BCAA-treated HCC cells. In-vitro BCAA reduced the frequency of EpCAM-positive cells and improved sensitivity to the anti-proliferative effect of 5-FU. Combined 5-FU and BCAA provided better antitumor efficacy than 5-FU alone in the xenograft model. Stimulation with high doses of BCAA activated mTORC1. Knockdown and overexpression experiments revealed that inhibition of mTOR complex 2 (mTORC2) or activation of mTORC1 led to decreased EpCAM expression and little or no tumorigenicity. BCAA may enhance the sensitivity to chemotherapy by reducing the population of cscs via the mTOR pathway. This result suggests the utility of BCAA in liver cancer therapy. PMID:24312415

  10. Branched chain amino acid suppresses hepatocellular cancer stem cells through the activation of mammalian target of rapamycin.

    Directory of Open Access Journals (Sweden)

    Shinobu Nishitani

    Full Text Available Differentiation of cancer stem cells (CSCs into cancer cells causes increased sensitivity to chemotherapeutic agents. Although inhibition of mammalian target of rapamycin (mTOR leads to CSC survival, the effect of branched chain amino acids (BCAAs, an mTOR complex 1 (mTORC1 activator remains unknown. In this study, we examined the effects of BCAA on hepatocellular carcinoma (HCC cells expressing a hepatic CSC marker, EpCAM. We examined the effects of BCAA and/or 5-fluorouracil (FU on expression of EpCAM and other CSC-related markers, as well as cell proliferation in HCC cells and in a xenograft mouse model. We also characterized CSC-related and mTOR signal-related molecule expression and tumorigenicity in HCC cells with knockdown of Rictor or Raptor, or overexpression of constitutively active rheb (caRheb. mTOR signal-related molecule expression was also examined in BCAA-treated HCC cells. In-vitro BCAA reduced the frequency of EpCAM-positive cells and improved sensitivity to the anti-proliferative effect of 5-FU. Combined 5-FU and BCAA provided better antitumor efficacy than 5-FU alone in the xenograft model. Stimulation with high doses of BCAA activated mTORC1. Knockdown and overexpression experiments revealed that inhibition of mTOR complex 2 (mTORC2 or activation of mTORC1 led to decreased EpCAM expression and little or no tumorigenicity. BCAA may enhance the sensitivity to chemotherapy by reducing the population of cscs via the mTOR pathway. This result suggests the utility of BCAA in liver cancer therapy.

  11. Survival benefit with proapoptotic molecular and pathologic responses from dual targeting of mammalian target of rapamycin and epidermal growth factor receptor in a preclinical model of pancreatic neuroendocrine carcinogenesis.

    Science.gov (United States)

    Chiu, Christopher W; Nozawa, Hiroaki; Hanahan, Douglas

    2010-10-10

    Pancreatic neuroendocrine tumors (PNETs), although rare, often metastasize, such that surgery, the only potentially curative therapy, is not possible. There is no effective systemic therapy for patients with advanced PNETs. Therefore, new strategies are needed. Toward that end, we investigated the potential benefit of dual therapeutic targeting of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR) kinases, using a preclinical mouse model of PNET. Rapamycin and erlotinib, inhibitors of mTOR and EGFR, respectively, were used to treat RIP-Tag2 transgenic mice bearing advanced multifocal PNET. Tumor growth and survival were monitored, and tumors were surveyed for potential biomarkers of response to the therapeutics. Rapamycin monotherapy was notably efficacious, prolonging survival concomitant with tumor stasis (stable disease). However, the tumors developed resistance, as evidenced by eventual relapse to progressive tumor growth. Erlotinib monotherapy slowed tumor growth and elicited a marginal survival benefit. In combination, there was an unprecedented survival benefit in the face of this aggressive multifocal cancer and, in contrast to either monotherapy, the development of adaptive resistance was not apparent. Additionally, the antiapoptotic protein survivin was implicated as a biomarker of sensitivity and beneficial responses to the dual targeted therapy. Preclinical trials in a mouse model of endogenous PNET suggest that combined targeting of the mTOR and EGFR signaling pathways could have potential clinical benefit in treating PNET. These results have encouraged development of an ongoing phase II clinical trial aimed to evaluate the efficacy of this treatment regimen in human neuroendocrine tumors.

  12. Rapamycin combined with anti-CD45RB mAb and IL-10 or with G-CSF induces tolerance in a stringent mouse model of islet transplantation.

    Directory of Open Access Journals (Sweden)

    Nicola Gagliani

    Full Text Available BACKGROUND: A large pool of preexisting alloreactive effector T cells can cause allogeneic graft rejection following transplantation. However, it is possible to induce transplant tolerance by altering the balance between effector and regulatory T (Treg cells. Among the various Treg-cell types, Foxp3(+Treg and IL-10-producing T regulatory type 1 (Tr1 cells have frequently been associated with tolerance following transplantation in both mice and humans. Previously, we demonstrated that rapamycin+IL-10 promotes Tr1-cell-associated tolerance in Balb/c mice transplanted with C57BL/6 pancreatic islets. However, this same treatment was unsuccessful in C57BL/6 mice transplanted with Balb/c islets (classified as a stringent transplant model. We accordingly designed a protocol that would be effective in the latter transplant model by simultaneously depleting effector T cells and fostering production of Treg cells. We additionally developed and tested a clinically translatable protocol that used no depleting agent. METHODOLOGY/PRINCIPAL FINDINGS: Diabetic C57BL/6 mice were transplanted with Balb/c pancreatic islets. Recipient mice transiently treated with anti-CD45RB mAb+rapamycin+IL-10 developed antigen-specific tolerance. During treatment, Foxp3(+Treg cells were momentarily enriched in the blood, followed by accumulation in the graft and draining lymph node, whereas CD4(+IL-10(+IL-4(- T (i.e., Tr1 cells localized in the spleen. In long-term tolerant mice, only CD4(+IL-10(+IL-4(- T cells remained enriched in the spleen and IL-10 was key in the maintenance of tolerance. Alternatively, recipient mice were treated with two compounds routinely used in the clinic (namely, rapamycin and G-CSF; this drug combination promoted tolerance associated with CD4(+IL-10(+IL-4(- T cells. CONCLUSIONS/SIGNIFICANCE: The anti-CD45RB mAb+rapamycin+IL-10 combined protocol promotes a state of tolerance that is IL-10 dependent. Moreover, the combination of rapamycin+G-CSF induces

  13. Colorimetric characterization of LED luminaires

    International Nuclear Information System (INIS)

    Costa, C L M; Vieira, R R; Pereira, R C; Silva, P V M; Oliveira, I A A; Sardinha, A S; Viana, D D; Barbosa, A H; Souza, L P; Alvarenga, A D

    2015-01-01

    The Optical Metrology Division of Inmetro – National Institute of Metrology, Quality and Technology has recently started the colorimetric characterization of lamps by implementing Correlated Color Temperature (CCT) and Color Rendering Index (CRI) measurements of incandescent lamps, followed by the CFL, and LED lamps and luminaires. Here we present the results for the verification of the color characterization of samples of SSL luminaires for public as well as indoor illumination that are sold in Brazil

  14. Celebrity-led development organisations

    DEFF Research Database (Denmark)

    Budabin, Alexandra Cosima; Rasmussen, Louise Mubanda; Richey, Lisa Ann

    2017-01-01

    The past decade has seen a frontier open up in international development engagement with the entrance of new actors such as celebrity-led organisations. We explore how such organisations earn legitimacy with a focus on Madonna’s Raising Malawi and Ben Affleck’s Eastern Congo Initiative. The study...... for funding, endorsements, and expertise. We argue that the ways in which celebrity-led organisations establish themselves as legitimate development actors illustrate broader dynamics of the machinery of development.......The past decade has seen a frontier open up in international development engagement with the entrance of new actors such as celebrity-led organisations. We explore how such organisations earn legitimacy with a focus on Madonna’s Raising Malawi and Ben Affleck’s Eastern Congo Initiative. The study...... draws from organisational materials, interviews, mainstream news coverage, and the texts of the celebrities themselves to investigate the construction of authenticity, credibility, and accountability. We find these organisations earn legitimacy and flourish rapidly amid supportive elite networks...

  15. Triolimus: A Multi-Drug Loaded Polymeric Micelle Containing Paclitaxel, 17-AAG, and Rapamycin as a Novel Radiosensitizer.

    Science.gov (United States)

    Tomoda, Keishiro; Tam, Yu Tong; Cho, Hyunah; Buehler, Darya; Kozak, Kevin R; Kwon, Glen S

    2017-01-01

    Triolimus is a multi-drug loaded polymeric micelle containing paclitaxel (PTX), 17-allylamino-17-demethoxygeldanamycin (17-AAG), and rapamycin (RAP). This study examines the radiosensitizing effect of Triolimus in vitro and in vivo. Radiosensitizing effects of Triolimus on A549 cells are dose dependent and at 2 × 10 -9 m, Triolimus shows significant radiosensitization even at low radiation doses (2 Gy). By sensitivity enhancement ratio, PTX alone, dual drug combinations, and Triolimus treatment at 2 × 10 -9 m have radiosensitizing effects with potency as follows: PTX alone (PTX) > PTX and RAP (P/R) > Triolimus (TRIO) > PTX and 17-AAG (P/17) >17-AAG and RAP (17/R). In vivo, fractionated radiation of 15 Gy preceded by infusion of PTX alone, dual drug combinations, or an intermediate dose of Triolimus (Int. TRIO: PTX/17-AAG/RAP at 15/15/7.5 mg kg -1 ) strongly inhibits A549 tumor growth. Notably, pretreatment with high dose of Triolimus (High TRIO: PTX/17-AAG/RAP at 60/60/30 mg kg -1 ) before the fractionated radiation leads to tumor control for up to 24 weeks. An enhanced radiosensitizing effect is observed without an increase in acute toxicity compared to PTX alone or radiation alone. These results suggest that further investigations of Triolimus in combination with radiation therapy are merited. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Warm white LEDs lighting over Ra=95 and its applications

    Science.gov (United States)

    Kobashi, Katsuya; Taguchi, Tsunemasa

    2007-02-01

    We have for the first time developed warm white LEDs lighting using a combination of near ultraviolet LED and three-band (red, green and blue) white phosphors. This LED has the average color-rendering index Ra=96. Moreover, special color-rendering index R9 (red) and R15 (face color of Japanese) are estimated to be 95 and 97, respectively. We will describe the results of evaluation on the medical lighting applications such as operation, treatment and endoscope experiments, application to the LED fashions and application to the Japanese antique art (ink painting) lighting.

  17. Rapamycin targeting mTOR and hedgehog signaling pathways blocks human rhabdomyosarcoma growth in xenograft murine model

    Energy Technology Data Exchange (ETDEWEB)

    Kaylani, Samer Z. [Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, 1600 7th Avenue South, ACC 414, Birmingham, AL 35233 (United States); Xu, Jianmin; Srivastava, Ritesh K. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, Bethesda (United States); Pressey, Joseph G. [Division of Hematology and Oncology, Department of Pediatrics, University of Alabama at Birmingham, 1600 7th Avenue South, ACC 414, Birmingham, AL 35233 (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, 1530 3rd Avenue South, VH 509, Birmingham, AL 35294-0019 (United States)

    2013-06-14

    Graphical abstract: Intervention of poorly differentiated RMS by rapamycin: In poorly differentiated RMS, rapamycin blocks mTOR and Hh signaling pathways concomitantly. This leads to dampening in cell cycle regulation and induction of apoptosis. This study provides a rationale for the therapeutic intervention of poorly differentiated RMS by treating patients with rapamycin alone or in combination with other chemotherapeutic agents. -- Highlights: •Rapamycin abrogates RMS tumor growth by modulating proliferation and apoptosis. •Co-targeting mTOR/Hh pathways underlie the molecular basis of effectiveness. •Reduction in mTOR/Hh pathways diminish EMT leading to reduced invasiveness. -- Abstract: Rhabdomyosarcomas (RMS) represent the most common childhood soft-tissue sarcoma. Over the past few decades outcomes for low and intermediate risk RMS patients have slowly improved while patients with metastatic or relapsed RMS still face a grim prognosis. New chemotherapeutic agents or combinations of chemotherapies have largely failed to improve the outcome. Based on the identification of novel molecular targets, potential therapeutic approaches in RMS may offer a decreased reliance on conventional chemotherapy. Thus, identification of effective therapeutic agents that specifically target relevant pathways may be particularly beneficial for patients with metastatic and refractory RMS. The PI3K/AKT/mTOR pathway has been found to be a potentially attractive target in RMS therapy. In this study, we provide evidence that rapamycin (sirolimus) abrogates growth of RMS development in a RMS xenograft mouse model. As compared to a vehicle-treated control group, more than 95% inhibition in tumor growth was observed in mice receiving parenteral administration of rapamycin. The residual tumors in rapamycin-treated group showed significant reduction in the expression of biomarkers indicative of proliferation and tumor invasiveness. These tumors also showed enhanced apoptosis

  18. Critical analysis of the potential for therapeutic targeting of mammalian target of rapamycin (mTOR in gastric cancer

    Directory of Open Access Journals (Sweden)

    Inokuchi M

    2014-04-01

    Full Text Available Mikito Inokuchi,1 Keiji Kato,1 Kazuyuki Kojima,2 Kenichi Sugihara1 1Department of Surgical Oncology, 2Department of Minimally Invasive Surgery, Tokyo Medical and Dental University, Tokyo, Japan Abstract: Multidisciplinary treatment including chemotherapy has become the global standard of care for patients with metastatic gastric cancer (mGC; nonetheless, survival remains poor. Although many molecular-targeted therapies have been developed for various cancers, only anti-HER2 treatment has produced promising results in patients with mGC. Mammalian target of rapamycin (mTOR plays a key role in cell proliferation, antiapoptosis, and metastasis in signaling pathways from the tyrosine kinase receptor, and its activation has been demonstrated in gastric cancer (GC cells. This review discusses the clinical relevance of mTOR in GC and examines its potential as a therapeutic target in patients with mGC. Preclinical studies in animal models suggest that suppression of the mTOR pathway inhibits the proliferation of GC cells and delays tumor progression. The mTOR inhibitor everolimus has been evaluated as second- or third-line treatment in clinical trials. Adverse events were well tolerated although the effectiveness of everolimus alone was limited. Everolimus is now being evaluated in combination with chemotherapy in Phase III clinical studies in this subgroup of patients. Two Phase III studies include exploratory biomarker research designed to evaluate the predictive value of the expression or mutation of molecules related to the Akt/mTOR signaling pathway. These biomarker studies may lead to the realization of targeted therapy for selected patients with mGC in the future. Keywords: gastric cancer, mTOR, everolimus

  19. Phosphoproteomic profiling of in vivo signaling in liver by the mammalian target of rapamycin complex 1 (mTORC1.

    Directory of Open Access Journals (Sweden)

    Gokhan Demirkan

    Full Text Available Our understanding of signal transduction networks in the physiological context of an organism remains limited, partly due to the technical challenge of identifying serine/threonine phosphorylated peptides from complex tissue samples. In the present study, we focused on signaling through the mammalian target of rapamycin (mTOR complex 1 (mTORC1, which is at the center of a nutrient- and growth factor-responsive cell signaling network. Though studied extensively, the mechanisms involved in many mTORC1 biological functions remain poorly understood.We developed a phosphoproteomic strategy to purify, enrich and identify phosphopeptides from rat liver homogenates. Using the anticancer drug rapamycin, the only known target of which is mTORC1, we characterized signaling in liver from rats in which the complex was maximally activated by refeeding following 48 hr of starvation. Using protein and peptide fractionation methods, TiO(2 affinity purification of phosphopeptides and mass spectrometry, we reproducibly identified and quantified over four thousand phosphopeptides. Along with 5 known rapamycin-sensitive phosphorylation events, we identified 62 new rapamycin-responsive candidate phosphorylation sites. Among these were PRAS40, gephyrin, and AMP kinase 2. We observed similar proportions of increased and reduced phosphorylation in response to rapamycin. Gene ontology analysis revealed over-representation of mTOR pathway components among rapamycin-sensitive phosphopeptide candidates.In addition to identifying potential new mTORC1-mediated phosphorylation events, and providing information relevant to the biology of this signaling network, our experimental and analytical approaches indicate the feasibility of large-scale phosphoproteomic profiling of tissue samples to study physiological signaling events in vivo.

  20. FOXO3a reactivation mediates the synergistic cytotoxic effects of rapamycin and cisplatin in oral squamous cell carcinoma cells

    International Nuclear Information System (INIS)

    Fang Liang; Wang Huiming; Zhou Lin; Yu Da

    2011-01-01

    FOXO3a, a well-known transcriptional regulator, controls a wide spectrum of biological processes. The Phosphoinositide-3-kinase (PI3K)/Akt signaling pathway inactivates FOXO3a via phosphorylation-induced nuclear exclusion and degradation. A loss or gain of FOXO3a activity has been correlated with efficiency of chemotherapies in various cancers including oral squamous cell carcinoma (OSCC). Therefore, in the current study, we have investigated the FOXO3a activity modulating and antitumor effects of rapamycin and cisplatin in OSCC cells. Cisplatin inhibited proliferation and induced apoptosis in a dose-dependent way in OSCC Tca8113 cells. Rapamycin alone had no effect on cell proliferation and apoptosis. Rapamycin downregulated the expression of S-phase kinase associated protein-2 (Skp2) and increased the FOXO3a protein stability but induced the upregulation of feedback Akt activation-mediated FOXO3a phosphorylation. Cisplatin decreased the phosphorylation of FOXO3a via Akt inhibition. Rapamycin combined with cisplatin as its feedback Akt activation inhibitor revealed the most dramatic FOXO3a nuclear localization and reactivation with the prevention of its feedback loop and exposed significant synergistic effects of decreased cell proliferation and increased apoptosis in vitro and decreased tumor size in vivo. Furthermore, the downstream effects of FOXO3a reactivation were found to be accumulation of p27 and Bim. In conclusion, rapamycin/cisplatin combination therapy boosts synergistic antitumor effects through the significant FOXO3a reactivation in OSCC cells. These results may represent a novel mechanism by which rapamycin/cisplatin combination therapy proves to be a potent molecular-targeted strategy for OSCC.

  1. Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals.

    Science.gov (United States)

    Weisman, Ronit

    2016-10-01

    All organisms can respond to the availability of nutrients by regulating their metabolism, growth, and cell division. Central to the regulation of growth in response to nutrient availability is the target of rapamycin (TOR) signaling that is composed of two structurally distinct complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). The TOR genes were first identified in yeast as target of rapamycin, a natural product of a soil bacterium, which proved beneficial as an immunosuppressive and anticancer drug and is currently being tested for a handful of other pathological conditions including diabetes, neurodegeneration, and age-related diseases. Studies of the TOR pathway unraveled a complex growth-regulating network. TOR regulates nutrient uptake, transcription, protein synthesis and degradation, as well as metabolic pathways, in a coordinated manner that ensures that cells grow or cease growth in response to nutrient availability. The identification of specific signals and mechanisms that stimulate TOR signaling is an active and exciting field of research that has already identified nitrogen and amino acids as key regulators of TORC1 activity. The signals, as well as the cellular functions of TORC2, are far less well understood. Additional open questions in the field concern the relationships between TORC1 and TORC2, as well as the links with other nutrient-responsive pathways. Here I review the main features of TORC1 and TORC2, with a particular focus on yeasts as model organisms.

  2. Construction of a mutant of Actinoplanes sp. N902-109 that produces a new rapamycin analog.

    Science.gov (United States)

    Huang, He; Gao, Ping; Zhao, Qi; Hu, Hai-Feng

    2018-03-01

    In the present study, we introduced point mutations into Ac_rapA which encodes a polyketide synthase responsible for rapamycin biosynthesis in Actinoplanes sp. N902-109, in order to construct a mutant with an inactivated enoylreductase (ER) domain, which was able to synthesize a new rapamycin analog. Based on the homologous recombination induced by double-strand breaks in chromosome mediated by endonuclease I-SceI, the site-directed mutation in the first ER domain of Ac_rapA was introduced using non-replicating plasmid pLYERIA combined with an I-SceI expression plasmid. Three amino acid residues of the active center, Ala-Gly-Gly, were converted to Ala-Ser-Pro. The broth of the mutant strain SIPI-027 was analyzed by HPLC and a new peak with the similar UV spectrum to that of rapamycin was found. The sample of the new peak was prepared by solvent extraction, column chromatography, and crystallization methods. The structure of new compound, named as SIPI-rapxin, was elucidated by determining and analyzing its MS and NMR spectra and its biological activity was assessed using mixed lymphocyte reaction (MLR). An ER domain-deficient mutant of Actinoplanes sp. N902-109, named as SIPI-027, was constructed, which produced a novel rapamycin analog SIPI-rapxin and its structure was elucidated to be 35, 36-didehydro-27-O-demethylrapamycin. The biological activity of SIPI-rapxin was better than that of rapamycin. In conclusion, inactivation of the first ER domain of rapA, one of the modular polyketide synthase responsible for macro-lactone synthesis of rapamycin, gave rise to a mutant capable of producing a novel rapamycin analog, 35, 36-didehydro-27-O-demethylrapamycin, demonstrating that the enoylreductase domain was responsible for the reduction of the double bond between C-35 and C-36 during rapamycin synthesis. Copyright © 2018 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  3. Expression and mechanism of mammalian target of rapamycin in age-related renal cell senescence and organ aging.

    Science.gov (United States)

    Zhuo, Li; Cai, Guangyan; Liu, Fuyou; Fu, Bo; Liu, Weiping; Hong, Quan; Ma, Qiang; Peng, Youming; Wang, Jianzhong; Chen, Xiangmei

    2009-10-01

    The mammalian target of rapamycin (mTOR) is relevant to cell senescence and organismal aging. This study firstly showed that the level of mTOR expression increased with aging in rat kidneys, rat mesangial cells and WI-38 cells (P aging-related phenotypes were all reduced in cells treated with rapamycin (an inhibitor of mTOR) than in control cells (P aging, and that mTOR may promote cellular senescence by regulating the cell cycle through p21(WAF1/CIP1/SDI1), which might provide a new target for preventing renal aging.

  4. PEGylated lipid bilayer-wrapped nano-graphene oxides for synergistic co-delivery of doxorubicin and rapamycin to prevent drug resistance in cancers

    Science.gov (United States)

    Thapa, Raj Kumar; Byeon, Jeong Hoon; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2017-07-01

    Nano-graphene oxide (nGO) is a carbon allotrope studied for its potential as carrier for chemotherapeutic delivery and its photoablation effects. However, interaction of nGO with blood components and the subsequent toxicities warrant a hybrid system for effective cancer drug delivery. Combination chemotherapy aids in effective cancer treatment and prevention of drug resistance. Therefore, in this study, we attempted to prepare polyethylene glycosylated (PEGylated) lipid bilayer-wrapped nGO co-loaded with doxorubicin (DOX) and rapamycin (RAPA), GOLDR, for the prevention and treatment of resistant cancers. Our results revealed a stable GOLDR formulation with appropriate particle size (∼170 nm), polydispersity (∼0.19) and drug loading. Free drug combination (DOX and RAPA) presented synergistic anticancer effects in MDA-MB-231, MCF-7, and BT474 cells. Treatment with GOLDR formulation maintained this synergism in treated cancer cells, which was further enhanced by the near infrared (NIR) laser irradiation-induced photothermal effects of nGO. Higher chromatin condensation and apoptotic body formation, and enhanced protein expression of apoptosis-related markers (Bax, p53, p21, and c-caspase 3) following GOLDR treatment in the presence of NIR laser treatment clearly suggests its superiority in effective chemo-photothermal therapy of resistant cancers. The hybrid nanosystem that we developed provides a basis for the effective use of GOLDR treatment in the prevention and treatment of resistant cancer types.

  5. MicroRNA-99a inhibits insulin-induced proliferation, migration, dedifferentiation, and rapamycin resistance of vascular smooth muscle cells by inhibiting insulin-like growth factor-1 receptor and mammalian target of rapamycin

    International Nuclear Information System (INIS)

    Zhang, Zi-wei; Guo, Rui-wei; Lv, Jin-lin; Wang, Xian-mei; Ye, Jin-shan; Lu, Ni-hong; Liang, Xing; Yang, Li-xia

    2017-01-01

    Patients with type 2 diabetes mellitus (T2DM) are characterized by insulin resistance and are subsequently at high risk for atherosclerosis. Hyperinsulinemia has been associated with proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) during the pathogenesis of atherosclerosis. Moreover, insulin-like growth factor-1 receptor (IGF-1R) and mammalian target of rapamycin (mTOR) have been demonstrated to be the underlying signaling pathways. Recently, microRNA-99a (miR-99a) has been suggested to regulate the phenotypic changes of VSMCs in cancer cells. However, whether it is involved in insulin-induced changes of VSCMs has not been determined. In this study, we found that insulin induced proliferation, migration, and dedifferentiation of mouse VSMCs in a dose-dependent manner. Furthermore, the stimulating effects of high-dose insulin on proliferation, migration, and dedifferentiation of mouse VSMCs were found to be associated with the attenuation of the inhibitory effects of miR-99a on IGF-1R and mTOR signaling activities. Finally, we found that the inducing effect of high-dose insulin on proliferation, migration, and dedifferentiation of VSMCs was partially inhibited by an active mimic of miR-99a. Taken together, these results suggest that miR-99a plays a key regulatory role in the pathogenesis of insulin-induced proliferation, migration, and phenotype conversion of VSMCs at least partly via inhibition of IGF-1R and mTOR signaling. Our results provide evidence that miR-99a may be a novel target for the treatment of hyperinsulinemia-induced atherosclerosis. - Highlights: • Suggesting a new mechanism of insulin-triggered VSMC functions. • Providing a new therapeutic strategies that target atherosclerosis in T2DM patients. • Providing a new strategies that target in-stent restenosis in T2DM patients.

  6. LEDs light up the world

    Energy Technology Data Exchange (ETDEWEB)

    Mather, N.

    2004-06-30

    A lighting system using light-emitting diodes, and privately financed by a Canadian engineering professor at the University of Calgary, has been set up in a village in Nepal in 2000. Since then, through the efforts of the 'Light Up The World' Foundation, established by Dr. Irvine-Halliday, projects have lit up thousands of homes in the Philippines, India, Afghanistan, the Galapagos Islands, Mexico, Sri Lanka, and Angola. Although the goal of the project is primarily to provide lighting for reading and writing for school-children, the project has been the source of many other advantages; creation of enterprise, increased employment, enhanced income, gender equality, and improvements in health and safety among them. Since LED lamps in most cases replace kerosene lamps, the system also has significant environmental benefits. The system as originally envisioned creates electricity by pedal-powered generator, or by solar panels connected to a battery, depending on what is available at each home. Each home is connected to the power supply and supplied with low-energy diode lamps. The lights are extremely efficient and many homes can be equipped with them using less energy than it takes to power a single 100-watt light bulb. 5 photos.

  7. The interaction between early life epilepsy and autistic-like behavioral consequences: a role for the mammalian target of rapamycin (mTOR pathway.

    Directory of Open Access Journals (Sweden)

    Delia M Talos

    Full Text Available Early life seizures can result in chronic epilepsy, cognitive deficits and behavioral changes such as autism, and conversely epilepsy is common in autistic children. We hypothesized that during early brain development, seizures could alter regulators of synaptic development and underlie the interaction between epilepsy and autism. The mammalian Target of Rapamycin (mTOR modulates protein translation and is dysregulated in Tuberous Sclerosis Complex, a disorder characterized by epilepsy and autism. We used a rodent model of acute hypoxia-induced neonatal seizures that results in long term increases in neuronal excitability, seizure susceptibility, and spontaneous seizures, to determine how seizures alter mTOR Complex 1 (mTORC1 signaling. We hypothesized that seizures occurring at a developmental stage coinciding with a critical period of synaptogenesis will activate mTORC1, contributing to epileptic networks and autistic-like behavior in later life. Here we show that in the rat, baseline mTORC1 activation peaks during the first three postnatal weeks, and induction of seizures at postnatal day 10 results in further transient activation of its downstream targets phospho-4E-BP1 (Thr37/46, phospho-p70S6K (Thr389 and phospho-S6 (Ser235/236, as well as rapid induction of activity-dependent upstream signaling molecules, including BDNF, phospho-Akt (Thr308 and phospho-ERK (Thr202/Tyr204. Furthermore, treatment with the mTORC1 inhibitor rapamycin immediately before and after seizures reversed early increases in glutamatergic neurotransmission and seizure susceptibility and attenuated later life epilepsy and autistic-like behavior. Together, these findings suggest that in the developing brain the mTORC1 signaling pathway is involved in epileptogenesis and altered social behavior, and that it may be a target for development of novel therapies that eliminate the progressive effects of neonatal seizures.

  8. Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application.

    Science.gov (United States)

    Zhao, Pan; Sui, Bing-Dong; Liu, Nu; Lv, Ya-Jie; Zheng, Chen-Xi; Lu, Yong-Bo; Huang, Wen-Tao; Zhou, Cui-Hong; Chen, Ji; Pang, Dan-Lin; Fei, Dong-Dong; Xuan, Kun; Hu, Cheng-Hu; Jin, Yan

    2017-10-01

    Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects. © 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  9. Renal function in heart transplant patients after switch to combined mammalian target of rapamycin inhibitor and calcineurin inhibitor therapy

    Directory of Open Access Journals (Sweden)

    Helmschrott M

    2017-06-01

    Full Text Available Matthias Helmschrott,1 Rasmus Rivinius,1 Thomas Bruckner,2 Hugo A Katus,1 Andreas O Doesch1 1Department of Cardiology, Angiology, Pneumology, 2Institute for Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany Background: A calcineurin inhibitor (CNI-based immunosuppression combined with mammalian target of rapamycin inhibitors (mTORs seems to be attractive in patients after heart transplantation (HTX in special clinical situations, for example, in patients with adverse drug effects of prior immunosuppression. Previous studies in patients after HTX detected advantageous effects regarding renal function of a tacrolimus (TAC-based vs cyclosporine-A (CSA-based immunosuppression (in combination with mycophenolate mofetil. However, data regarding renal function after HTX in mTOR/CNI patients remain limited. Aim: Primary end point of the present study was to analyze renal function in HTX patients 1 year after switch to an mTOR/CNI-based immunosuppression. Methods: Data of 80 HTX patients after change to mTOR/CNI-based immunosuppression were retrospectively analyzed. Renal function was assessed by measured serum creatinine and by estimated glomerular filtration rate (eGFR calculated from Modification of Diet in Renal Disease equation. Results: Twenty-nine patients received mTOR/CSA-based treatment and 51 patients received mTOR/TAC-based therapy. At time of switch and at 1-year follow-up, serum creatinine and eGFR did not differ significantly between both study groups (all P=not statistically significant. Analysis of variances with repeated measurements detected a similar change of renal function in both study groups. Conclusion: The present study detected no significant differences between both mTOR/CNI study groups, indicating a steady state of renal function in HTX patients after switch of immunosuppressive regimen. Keywords: heart transplantation, cyclosporine A, tacrolimus, risk factors

  10. Neuroprotective effect of rapamycin on spinal cord injury via activation of the Wnt/β-catenin signaling pathway

    Directory of Open Access Journals (Sweden)

    Kai Gao

    2015-01-01

    Full Text Available The Wnt/β-catenin signaling pathway plays a crucial role in neural development, axonal guidance, neuropathic pain remission and neuronal survival. In this study, we initially examined the effect of rapamycin on the Wnt/β-catenin signaling pathway after spinal cord injury, by intraperitoneally injecting spinal cord injured rats with rapamycin over 2 days. Western blot analysis and immunofluorescence staining were used to detect the expression levels of β-catenin protein, ca-spase-3 protein and brain-derived neurotrophic factor protein, components of the Wnt/β-catenin signaling pathway. Rapamycin increased the levels of β-catenin and brain-derived neurotrophic factor in the injured spinal cord, improved the pathological morphology at the injury site, reduced the loss of motor neurons, and promoted motor functional recovery in rats after spinal cord injury. Our experimental findings suggest that the neuroprotective effect of rapamycin intervention is mediated through activation of the Wnt/β-catenin signaling pathway after spinal cord injury.

  11. Target of rapamycin signalling mediates the lifespan-extending effects of dietary restriction by essential amino acid alteration

    NARCIS (Netherlands)

    Emran, S.; Yang, M.Y.; He, X.L.; Zandveld, J.; Piper, M.D.W.

    2014-01-01

    Dietary restriction (DR), defined as a moderate reduction in food intake short of malnutrition, has been shown to extend healthy lifespan in a diverse range of organisms, from yeast to primates. Reduced signalling through the insulin/IGF-like (IIS) and Target of Rapamycin (TOR) signalling pathways

  12. Mechanistic target of rapamycin (MTOR) protein expression in the tumor and its microenvironment correlates with more aggressive pathology at cystectomy

    NARCIS (Netherlands)

    Winters, B.R. (Brian R.); Vakar-Lopez, F. (Funda); Brown, L. (Lisha); Montgomery, B. (Bruce); Seiler, R. (Roland); P.C. Black (Peter C.); J.L. Boormans (Joost); Dall′Era, M. (Marc); Davincioni, E. (Elai); Douglas, J. (James); Gibb, E.A. (Ewan A.); B.W. van Rhijn (Bas); M.S. van der Heijden (Michiel); Hsieh, A.C. (Andrew C.); Wright, J.L. (Jonathan L.); Lam, H.-M. (Hung-Ming)

    2018-01-01

    textabstractBackground: The mechanistic target of rapamycin (mTOR) has been implicated in driving tumor biology in multiple malignancies, including urothelial carcinoma (UC). We investigate how mTOR and phosphorylated mTOR (pmTOR) protein expression correlate with chemoresponsiveness in the tumor

  13. Blue LED irradiation to hydration of skin

    Science.gov (United States)

    Menezes, Priscila F. C.; Requena, Michelle B.; Lizarelli, Rosane F., Z.; Bagnato, Vanderlei S.

    2015-06-01

    Blue LED system irradiation shows many important properties on skin as: bacterial decontamination, degradation of endogenous skin chromophores and biostimulation. In this clinical study we prove that the blue light improves the skin hydration. In the literature none authors reports this biological property on skin. Then this study aims to discuss the role of blue light in the skin hydration. Twenty patients were selected to this study with age between 25-35 years old and phototype I, II and III. A defined area from forearm was pre determined (A = 4.0 cm2). The study was randomized in two treatment groups using one blue light device (power of 5.3mW and irradiance of 10.8mW/cm2). The first treatment group was irradiated with 3J/cm2 (277seconds) and the second with 6J/cm2 (555 seconds). The skin hydration evaluations were done using a corneometer. The measurements were collected in 7, 14, 21 and 30 days, during the treatment. Statistical test of ANOVA, Tukey and T-Student were applied considering 5% of significance. In conclusion, both doses were able to improve the skin hydration; however, 6J/cm2 has kept this hydration for 30 days.

  14. The dynamics of histone H2A ubiquitination in HeLa cells exposed to rapamycin, ethanol, hydroxyurea, ER stress, heat shock and DNA damage.

    Science.gov (United States)

    Nakata, Shiori; Watanabe, Tadashi; Nakagawa, Koji; Takeda, Hiroshi; Ito, Akihiro; Fujimuro, Masahiro

    2016-03-25

    Polyubiquitination plays key roles in proteasome-dependent and independent cellular events, whereas monoubiquitination is involved in gene expression, DNA repair, protein-protein interaction, and protein trafficking. We previously developed an FK2 antibody, which specifically recognizes poly-Ub moieties but not free Ub. To elucidate the role of Ub conjugation in response to cellular stress, we used FK2 to investigate whether chemical stress (rapamycin, ethanol, or hydroxyurea), ER stress (thapsigargin or tunicamycin), heat shock or DNA damage (H2O2 or methyl methanesulfonate) affect the formation of Ub conjugates including histone H2A (hH2A) ubiquitination. First, we found that all forms of stress tested increased poly-ubiquitinated proteins in HeLa cells. Furthermore, rapamycin and hydroxyurea treatment, and ER stress increased ubiquitination of hH2A, while methyl methanesulfonate (MMS) treatment induced deubiquitination of hH2A. The ethanol and H2O2 treatments, and heat shock transiently induced hH2A de-ubiquitination, although deubiquitinated hH2A were ubiquitinated again by subsequent cultivation. We also revealed that FK2 reacts with not only polyubiquitinated proteins but also mono-ubiquitinated hH2A. With the exception of MMS, all forms of stress tested increased the acetylation of K5-hH2A, K9-hH3 and K8-hH4 in addition to ubiquitination. K118 and K119 of hH2A were ubiquitinated in cells under normal conditions, and K119 was the major ubiquitination site. The MMS-treatment and heat shock induced the deubiquitination of both K118 and K119-histone H2A. Interestingly, MMS treatment did not affect cell HeLa cell viability expressing double-mutant hH2A (KK118,119AA-hH2A), while heat shock slightly but significantly decreased viability of double-mutant hH2A expressing cells, indicating that ubiquitination of both sites associates with recovery from heat shock but not MMS treatment. Thus, we characterized FK2 reactivity and demonstrated that various stresses alter

  15. Rapamycin-induced oligomer formation system of FRB-FKBP fusion proteins.

    Science.gov (United States)

    Inobe, Tomonao; Nukina, Nobuyuki

    2016-07-01

    Most proteins form larger protein complexes and perform multiple functions in the cell. Thus, artificial regulation of protein complex formation controls the cellular functions that involve protein complexes. Although several artificial dimerization systems have already been used for numerous applications in biomedical research, cellular protein complexes form not only simple dimers but also larger oligomers. In this study, we showed that fusion proteins comprising the induced heterodimer formation proteins FRB and FKBP formed various oligomers upon addition of rapamycin. By adjusting the configuration of fusion proteins, we succeeded in generating an inducible tetramer formation system. Proteins of interest also formed tetramers by fusing to the inducible tetramer formation system, which exhibits its utility in a broad range of biological applications. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  16. Fokusgruppeinterview som led i en evalueringsproces

    DEFF Research Database (Denmark)

    Andersen-Mølgaard, Hanna; Harrit, Ole

    2006-01-01

    Teoretiske begrundelser og perspektiver, responsiv-konstruktivistisk evaluering, fokusgruppeinterview som led i BIKVAmodellen, eksempler, vurdering og perspektivering......Teoretiske begrundelser og perspektiver, responsiv-konstruktivistisk evaluering, fokusgruppeinterview som led i BIKVAmodellen, eksempler, vurdering og perspektivering...

  17. Goniometric characterization of LED based greenhouse lighting

    DEFF Research Database (Denmark)

    Thorseth, Anders; Lindén, Johannes; Corell, Dennis Dan

    2015-01-01

    This paper describes a demonstration of goniospectroradiometry for characterizations of new light emitting diode (LED) based luminaries for enhanced photosynthesis in greenhouses. It highlights the differences between measurement of the traditional high pressure sodium (HPS) luminaries and the LED...

  18. Protection against methanol-induced retinal toxicity by LED photostimulation

    Science.gov (United States)

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

    2002-06-01

    We have initiated experiments designed to test the hypothesis that 670-nm Light-Emitting Diode (LED) exposure will attenuate formate-induced retinal dysfunction in a rodent model of methanol toxicity. Methanol intoxication produces toxic injury to the retina. The toxic metabolite formed in methanol intoxication is formic acid, a mitochondrial toxin known to inhibit cytochrome oxidase activity. 670-nm LED light has been hypothesized to act by stimulating cytochrome oxidase activity. To test this hypothesis, one group of animals was intoxicated with methanol, a second group was intoxicated with methanol and LED-treated and a third group was untreated. LED treatment (670 nm for 1 min 45 seconds equals 50 mW/cm2, 4 joules/cm2) was administered at 5, 25, and 50 hours after the initial dose of methanol. At 72 hours of methanol intoxication, retinal function was assessed by measurement of ERG responses and retinas were prepared for histologic analysis. ERG responses recorded in methanol-intoxicated animals revealed profound attenuation of both rod-dominated and UV-cone mediated responses. In contrast, methanol- intoxicated animals exposed to LED treatment exhibited a nearly complete recovery of rod-dominated ERG responses and a slight improvement of UV-cone mediated ERG responses. LED treatment also protected the retina against the histopathologic changes produced by formate in methanol intoxication. These data provide evidence that LED phototherapy protects the retina against the cytotoxic actions of formate and are consistent with the hypothesis that LED photostimulation improves mitochondrial respiratory chain function.

  19. An approach to analyse the specific impact of rapamycin on mRNA-ribosome association

    Directory of Open Access Journals (Sweden)

    Jaquier-Gubler Pascale

    2008-08-01

    Full Text Available Abstract Background Recent work, using both cell culture model systems and tumour derived cell lines, suggests that the differential recruitment into polysomes of mRNA populations may be sufficient to initiate and maintain tumour formation. Consequently, a major effort is underway to use high density microarray profiles to establish molecular fingerprints for cells exposed to defined drug regimes. The aim of these pharmacogenomic approaches is to provide new information on how drugs can impact on the translational read-out within a defined cellular background. Methods We describe an approach that permits the analysis of de-novo mRNA-ribosome association in-vivo during short drug exposures. It combines hypertonic shock, polysome fractionation and high-throughput analysis to provide a molecular phenotype of translationally responsive transcripts. Compared to previous translational profiling studies, the procedure offers increased specificity due to the elimination of the drugs secondary effects (e.g. on the transcriptional read-out. For this pilot "proof-of-principle" assay we selected the drug rapamycin because of its extensively studied impact on translation initiation. Results High throughput analysis on both the light and heavy polysomal fractions has identified mRNAs whose re-recruitment onto free ribosomes responded to short exposure to the drug rapamycin. The results of the microarray have been confirmed using real-time RT-PCR. The selective down-regulation of TOP transcripts is also consistent with previous translational profiling studies using this drug. Conclusion The technical advance outlined in this manuscript offers the possibility of new insights into mRNA features that impact on translation initiation and provides a molecular fingerprint for transcript-ribosome association in any cell type and in the presence of a range of drugs of interest. Such molecular phenotypes defined pre-clinically may ultimately impact on the evaluation of

  20. Measurement of the photometric characteristics of LEDs

    International Nuclear Information System (INIS)

    Nazarenko, L.A.; Zubkov, D.P.

    2015-01-01

    Proposed and implemented a method for measuring LEDs, which is based on self-calibration of the LED goniophotometer facility by using a trap-detector. Designed and manufactured automated goniophotometer, which provides a measurement of high power LEDs at a specified junction temperature. Designed and experimentally researched the photometer with a photometric sphere based diffuser, which meets all requirements of CIE for photometric measurements of LEDs

  1. Effect of Led Lighting Colors for Laying Japanese Quails

    Directory of Open Access Journals (Sweden)

    KC Nunes

    Full Text Available ABSTRACT Time of exposure and light intensity rearing house may affect the performance and egg quality of laying quails. This research aimed at evaluating the live performance, egg quality, biometry of the reproductive system, and the gastrointestinal tract of Japanese quails (Coturnix coturnix japonica exposed to artificial light-emitting diodes (LED of different colors in comparison with fluorescent lamps. A total of 240 Japanese quails were distributed in completely randomized experimental design with four treatments (fluorescent lamp, and green, red, or blue LED lamps with six replicates of 10 birds each. Average egg weight and eggshell thickness were different (p0.05. The oviduct of 64-d-old hens exposed to green LED lighting was shorter (p<0.05 than those exposed to the fluorescent lamp. Red LED can be used to replace the fluorescent lamps, as they promote the same live performance, egg quality, and morphological development of the reproductive tract of laying Japanese quails.

  2. Plant growth with Led lighting systems

    International Nuclear Information System (INIS)

    Campiotti, C.A.; Bernardini, A.; Di Carlo, F.; Scoccianti, M.; Alonzo, G.; Carlino, M.; Dondi, F.; Bibbiani, C.

    2009-01-01

    Leds lighting is highly relevant for the horticultural industry. Compared to other light sources used for plant production, leds have several properties which are potentially useful in relation to horticulture. However, although LEDs technology has raised strong interest in research for extraterrestrial agriculture, current LEDs panel costs are still too high for commercial adoption in greenhouse sector, and their electrical efficacies do not compete with those of high-pressure sodium lamps, but several manufactures are working to address these issues. When LEDs become practical, their ability to based light sources specifically suitable for photosynthesis and other horticulturally relevant plant properties (i.e. low radiated heat; lighting from within the canopy) will render the narrow band spectrum of LEDs of particular interest for providing light to greenhouse horticulture. A general description of LEDs application and their technical characteristics is briefly reported. [it

  3. Generation of solar spectrum by using LEDs

    Science.gov (United States)

    Lu, Pengzhi; Yang, Hua; Pei, Yanrong; Li, Jing; Xue, Bin; Wang, Junxi; Li, Jinmin

    2016-09-01

    Light emitting diode (LED) has been recognized as an applicable light source for indoor and outdoor lighting, city beautifying, landscape facilities, and municipal engineering etc. Conventional LED has superior characteristics such as long life time, low power consumption, high contrast, and wide viewing angle. Recently, LED with high color-rendering index and special spectral characteristics has received more and more attention. This paper is intended to report a solar spectrum simulated by multichip LED light source. The typical solar spectrum of 5500k released by CIE was simulated as a reference. Four types of LEDs with different spectral power distributions would be used in the LED light source, which included a 430nm LED, a 480nm LED, a 500nm LED and a white LED. In order to obtain better simulation results, the white LED was achieved by a 450nm LED chip with the mixture of phosphor. The phosphor combination was prepared by mixing green phosphor, yellow phosphor and red phosphor in a certain proportion. The multichip LED light source could provide a high fidelity spectral match with the typical solar spectrum of 5500k by adjusting injection current to each device. The luminous flux, CIE chromaticity coordinate x, y, CCT, and Ra were 104.7 lm, 0.3337, 0.3681, 5460K, and 88.6, respectively. Because of high color-rendering index and highly match to the solar spectrum, the multichip LED light source is a competitive candidate for applications where special spectral is required, such as colorimetric measurements, visual inspection, gemstone identification and agriculture.

  4. Cryogenic characterization of LEDs for space application

    Science.gov (United States)

    Carron, Jérôme; Philippon, Anne; How, Lip Sun; Delbergue, Audrey; Hassanzadeh, Sahar; Cillierre, David; Danto, Pascale; Boutillier, Mathieu

    2017-09-01

    In the frame of EUCLID project, the Calibration Unit of the VIS (VISible Imager) instrument must provide an accurate and well characterized light source for in-flight instrument calibration without noise when it is switched off. The Calibration Unit consists of a set of LEDs emitting at various wavelengths in the visible towards an integrating sphere. The sphere's output provides a uniform illumination over the entire focal plane. Nine references of LEDs from different manufacturers were selected, screened and qualified under cryogenic conditions. Testing this large quantity of samples led to the implementation of automated testing equipment with complete in-situ monitoring of optoelectronic parameters as well as temperature and vacuum values. All the electrical and optical parameters of the LED have been monitored and recorded at ambient and cryogenic temperatures. These results have been compiled in order to show the total deviation of the LED electrical and electro-optical properties in the whole mission and to select the best suitable LED references for the mission. This qualification has demonstrated the robustness of COTS LEDs to operate at low cryogenic temperatures and in the space environment. Then 6 wavelengths were selected and submitted to an EMC sensitivity test at room and cold temperature by counting the number of photons when LEDs drivers are OFF. Characterizations were conducted in the full frequency spectrum in order to implement solutions at system level to suppress the emission of photons when the LED drivers are OFF. LEDs impedance was also characterized at room temperature and cold temperature.

  5. A pilot trial of the mTOR (mammalian target of rapamycin) inhibitor RAD001 in patients with advanced B-CLL.

    Science.gov (United States)

    Decker, Thomas; Sandherr, Michael; Goetze, Katharina; Oelsner, Madlen; Ringshausen, Ingo; Peschel, Christian

    2009-03-01

    Although B-cell chronic lymphocytic leukemia (CLL) is treatable, it remains an incurable disease and most patients inevitably suffer relapse. Many therapeutic options exist for those requiring therapy, including monoclonal antibodies and stem cell transplantation, but remissions tend to last shorter in the course of the disease. Targeting the cell cycle has recently been realized to be an attractive therapeutic approach in solid and hematological malignancies, and the proliferative nature of B-CLL is increasingly accepted. Here, we report data on a phase II pilot trial with the oral mammalian target of rapamycin (mTOR) inhibitor RAD001 5 mg/daily in patients with advanced B-CLL who had progressive disease after at least two lines of treatment. After treatment of seven patients, this trial was stopped because of toxicity concerns, although some degree of activity was observed (one partial remission, three patients with stable disease). Interestingly, cyclin E expression decreased in responding patients. Further strategies of mTOR inhibition by RAD001 in B-CLL should focus on different treatment schedules, adequate anti-infectious prophylaxis, or combinations with cytotoxic drugs.

  6. PENGEMBANGAN LAMPU LED DENGAN TEKNOLOGI PHOTOVOLTAIC (LED-PV SEBAGAI ALAT BANTU PENGUMPUL IKAN PADA PERIKANAN BAGAN

    Directory of Open Access Journals (Sweden)

    Mochamad Arief Sofijanto

    2015-03-01

    mengetahui perbedaan jumlah hasil tangkapan pada bagan tancap akibat perlakuan warna lampu LED yang berbeda. Metode penelitian yang digunakan adalah deskriptif dan experimental fishing dimana rancangan penelitiannya adalah Rancangan Acak Lengkap (RAL dengan perlakuan warna lampu LED sebanyak 5 jenis warna yaitu merah (A, kuning (B, hijau (C, biru (D, dan putih (E dengan 6 kali ulangan. Secara deskriptif hasil penelitian menunjukkan lampu LED dapat digunakan untuk menggantikan lampu petromaks dan lampu LHE. Diperoleh 17 jenis ikan laut yang tertarik pada cahaya lampu LED yang digunakan. Hasil analisis statistik menunjukkan terdapat perbedaan nyata terhadap hasil tangkapan bagan dengan perlakuan warna lampu LED. Berdasarkan Uji Nyata Terkecil dinyatakan bahwa bagan yang menggunakan warna lampu LED biru mendapatkan hasil tangkapan tertinggi kemudian diikuti oleh warna kuning, hijau, putih dan merah.  The set ‘bagan’ (liftnet fishing gear is a kind of fishing gears which using atificial light as fishes gathering. This fishing gear uses an electric generator to turn on the energy saving lamp which hang on under the set ‘bagan’. The price of gasoline more expensive due to the Indonesia government’s fuel subsidy reduced and this make fishing operation costs more expensive for fishermen. This research using the LED lamps that do not use gasoline as fuel because the LED lamps can use the photovoltaic technology (solar cell system. The purposes of this study were: 1 to find out whether the LED lamps can replace the kerosene lamps and saving energy lamps, 2 to know the different in cath using different colours of LED lamps. The reserach methods are descriptive and experimental fishing which used Completely Randomized Design with LED lamps colour treatments i.e: red (A, yellow (B, green (C, blue (D, and white (E, the number of replications are 6 times. LED lamps can be used to replace the kerosene and saving energy lamps. There were 17 species of

  7. White LED visible light communication technology research

    Science.gov (United States)

    Yang, Chao

    2017-03-01

    Visible light communication is a new type of wireless optical communication technology. White LED to the success of development, the LED lighting technology is facing a new revolution. Because the LED has high sensitivity, modulation, the advantages of good performance, large transmission power, can make it in light transmission light signal at the same time. Use white LED light-emitting characteristics, on the modulation signals to the visible light transmission, can constitute a LED visible light communication system. We built a small visible optical communication system. The system composition and structure has certain value in the field of practical application, and we also research the key technology of transmitters and receivers, the key problem has been resolved. By studying on the optical and LED the characteristics of a high speed modulation driving circuit and a high sensitive receiving circuit was designed. And information transmission through the single chip microcomputer test, a preliminary verification has realized the data transmission function.

  8. System Reliability for LED-Based Products

    Energy Technology Data Exchange (ETDEWEB)

    Davis, J Lynn; Mills, Karmann; Lamvik, Michael; Yaga, Robert; Shepherd, Sarah D; Bittle, James; Baldasaro, Nick; Solano, Eric; Bobashev, Georgiy; Johnson, Cortina; Evans, Amy

    2014-04-07

    Results from accelerated life tests (ALT) on mass-produced commercially available 6” downlights are reported along with results from commercial LEDs. The luminaires capture many of the design features found in modern luminaires. In general, a systems perspective is required to understand the reliability of these devices since LED failure is rare. In contrast, components such as drivers, lenses, and reflector are more likely to impact luminaire reliability than LEDs.

  9. The effect of LED illumination on endodontic biofilms

    DEFF Research Database (Denmark)

    Markvart, Merete

    Within endodontics photodynamic therapy (PDT) has been suggested as a disinfectant procedure during root canal treatment. A photoactive dye (photosensitizer), methylene blue or toluidine blue, are activated by a light source, usually lasers or light emitting diodes (LEDs), thereby forming free...

  10. Projecting LED product life based on application

    Science.gov (United States)

    Narendran, Nadarajah; Liu, Yi-wei; Mou, Xi; Thotagamuwa, Dinusha R.; Eshwarage, Oshadhi V. Madihe

    2016-09-01

    LED products have started to displace traditional light sources in many lighting applications. One of the commonly claimed benefits for LED lighting products is their long useful lifetime in applications. Today there are many replacement lamp products using LEDs in the marketplace. Typically, lifetime claims of these replacement lamps are in the 25,000-hour range. According to current industry practice, the time for the LED light output to reach the 70% value is estimated according to IESNA LM-80 and TM-21 procedures and the resulting value is reported as the whole system life. LED products generally experience different thermal environments and switching (on-off cycling) patterns when used in applications. Current industry test methods often do not produce accurate lifetime estimates for LED systems because only one component of the system, namely the LED, is tested under a continuous-on burning condition without switching on and off, and because they estimate for only one failure type, lumen depreciation. The objective of the study presented in this manuscript was to develop a test method that could help predict LED system life in any application by testing the whole LED system, including on-off power cycling with sufficient dwell time, and considering both failure types, catastrophic and parametric. The study results showed for the LED A-lamps tested in this study, both failure types, catastrophic and parametric, exist. The on-off cycling encourages catastrophic failure, and maximum operating temperature influences the lumen depreciation rate and parametric failure time. It was also clear that LED system life is negatively affected by on-off switching, contrary to commonly held belief. In addition, the study results showed that most of the LED systems failed catastrophically much ahead of the LED light output reaching the 70% value. This emphasizes the fact that life testing of LED systems must consider catastrophic failure in addition to lumen depreciation, and

  11. Role of everolimus in the treatment of renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Saby George

    2009-08-01

    Full Text Available Saby George1, Ronald M Bukowski21University of Texas Health Sciences Center, MC-8221, Division of Hematology and Oncology, San Antonio, Texas, USA; 2CCF Lerner College of Medicine Division of Hematology and Oncology, Cleveland, Ohio, USAAbstract: The therapeutic options in metastatic renal cell carcinoma have been recently expanded by the discovery of the VHL gene, the mutation of which is associated with development of clear cell carcinoma, and overexpression of the angiogenesis pathway, resulting in a very vascular tumor. This breakthrough in science led to the development of a variety of small molecules inhibiting the VEGF-dependent angiogenic pathway, such as sunitinib and sorafenib. These agents prolong overall and progression-free survival, respectively. The result was the development of robust front-line therapies which ultimately fail and are associated with disease progression. In this setting, there existed an unmet need for developing second-line therapies for patients with refractory metastatic renal cell carcinoma (MRCC. Everolimus (RAD 001 is an oral inhibitor of the mammalian target of rapamycin (mTOR pathway. The double-blind, randomized, placebo-controlled phase III trial of everolimus (RECORD-1 conducted in MRCC patients after progression on sunitinib or sorafenib, or both, demonstrated a progression-free survival benefit favoring the study drug (4.9 months vs 1.9 months, HR 0.33, 95% CI 0.25 to 0.43, P ≤ 0 0.001. Everolimus thus established itself as a standard of care in the second-line setting for patients with MRCC who have failed treatment with VEGF receptor inhibitors.Keywords: mTOR inhibitor, mammalian target of rapamycin inhibitor, signal transduction inhibitor, renal cell carcinoma, targeted therapy

  12. The Drosophila FoxA ortholog Fork head regulates growth and gene expression downstream of Target of rapamycin.

    Directory of Open Access Journals (Sweden)

    Margret H Bülow

    2010-12-01

    Full Text Available Forkhead transcription factors of the FoxO subfamily regulate gene expression programs downstream of the insulin signaling network. It is less clear which proteins mediate transcriptional control exerted by Target of rapamycin (TOR signaling, but recent studies in nematodes suggest a role for FoxA transcription factors downstream of TOR. In this study we present evidence that outlines a similar connection in Drosophila, in which the FoxA protein Fork head (FKH regulates cellular and organismal size downstream of TOR. We find that ectopic expression and targeted knockdown of FKH in larval tissues elicits different size phenotypes depending on nutrient state and TOR signaling levels. FKH overexpression has a negative effect on growth under fed conditions, and this phenotype is not further exacerbated by inhibition of TOR via rapamycin feeding. Under conditions of starvation or low TOR signaling levels, knockdown of FKH attenuates the size reduction associated with these conditions. Subcellular localization of endogenous FKH protein is shifted from predominantly cytoplasmic on a high-protein diet to a pronounced nuclear accumulation in animals with reduced levels of TOR or fed with rapamycin. Two putative FKH target genes, CG6770 and cabut, are transcriptionally induced by rapamycin or FKH expression, and silenced by FKH knockdown. Induction of both target genes in heterozygous TOR mutant animals is suppressed by mutations in fkh. Furthermore, TOR signaling levels and FKH impact on transcription of the dFOXO target gene d4E-BP, implying a point of crosstalk with the insulin pathway. In summary, our observations show that an alteration of FKH levels has an effect on cellular and organismal size, and that FKH function is required for the growth inhibition and target gene induction caused by low TOR signaling levels.

  13. Targeting Rapamycin to Podocytes Using a Vascular Cell Adhesion Molecule-1 (VCAM-1-Harnessed SAINT-Based Lipid Carrier System.

    Directory of Open Access Journals (Sweden)

    Ganesh Ram R Visweswaran

    Full Text Available Together with mesangial cells, glomerular endothelial cells and the basement membrane, podocytes constitute the glomerular filtration barrier (GFB of the kidney. Podocytes play a pivotal role in the progression of various kidney-related diseases such as glomerular sclerosis and glomerulonephritis that finally lead to chronic end-stage renal disease. During podocytopathies, the slit-diaphragm connecting the adjacent podocytes are detached leading to severe loss of proteins in the urine. The pathophysiology of podocytopathies makes podocytes a potential and challenging target for nanomedicine development, though there is a lack of known molecular targets for cell selective drug delivery. To identify VCAM-1 as a cell-surface receptor that is suitable for binding and internalization of nanomedicine carrier systems by podocytes, we investigated its expression in the immortalized podocyte cell lines AB8/13 and MPC-5, and in primary podocytes. Gene and protein expression analyses revealed that VCAM-1 expression is increased by podocytes upon TNFα-activation for up to 24 h. This was paralleled by anti-VCAM-1 antibody binding to the TNFα-activated cells, which can be employed as a ligand to facilitate the uptake of nanocarriers under inflammatory conditions. Hence, we next explored the possibilities of using VCAM-1 as a cell-surface receptor to deliver the potent immunosuppressant rapamycin to TNFα-activated podocytes using the lipid-based nanocarrier system Saint-O-Somes. Anti-VCAM-1-rapamycin-SAINT-O-Somes more effectively inhibited the cell migration of AB8/13 cells than free rapamycin and non-targeted rapamycin-SAINT-O-Somes indicating the potential of VCAM-1 targeted drug delivery to podocytes.

  14. Anti‐aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application

    OpenAIRE

    Zhao, Pan; Sui, Bing‐Dong; Liu, Nu; Lv, Ya‐Jie; Zheng, Chen‐Xi; Lu, Yong‐Bo; Huang, Wen‐Tao; Zhou, Cui‐Hong; Chen, Ji; Pang, Dan‐Lin; Fei, Dong‐Dong; Xuan, Kun; Hu, Cheng‐Hu; Jin, Yan

    2017-01-01

    Summary Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical ad...

  15. Led Zeppelin reklaamib Narvat / Anti Ronk

    Index Scriptorium Estoniae

    Ronk, Anti

    2007-01-01

    Ilmus Narva-teemaline kahest CD-st koosnev album, kus ühel plaadil on 60 minutit videot linna vaatamisväärsuste ja informatsiooniga, teisel - briti rockansambli Led Zeppelini teosed Narva sümfooniaorkestri ja rockansambli Led R esituses

  16. The Role of the Mammalian Target of Rapamycin (mTOR) in Pulmonary Fibrosis

    Science.gov (United States)

    Nho, Richard

    2018-01-01

    The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-dependent pathway is one of the most integral pathways linked to cell metabolism, proliferation, differentiation, and survival. This pathway is dysregulated in a variety of diseases, including neoplasia, immune-mediated diseases, and fibroproliferative diseases such as pulmonary fibrosis. The mTOR kinase is frequently referred to as the master regulator of this pathway. Alterations in mTOR signaling are closely associated with dysregulation of autophagy, inflammation, and cell growth and survival, leading to the development of lung fibrosis. Inhibitors of mTOR have been widely studied in cancer therapy, as they may sensitize cancer cells to radiation therapy. Studies also suggest that mTOR inhibitors are promising modulators of fibroproliferative diseases such as idiopathic pulmonary fibrosis (IPF) and radiation-induced pulmonary fibrosis (RIPF). Therefore, mTOR represents an attractive and unique therapeutic target in pulmonary fibrosis. In this review, we discuss the pathological role of mTOR kinase in pulmonary fibrosis and examine how mTOR inhibitors may mitigate fibrotic progression. PMID:29518028

  17. The antidepressant sertraline inhibits translation initiation by curtailing mammalian target of rapamycin signaling.

    Science.gov (United States)

    Lin, Chen-Ju; Robert, Francis; Sukarieh, Rami; Michnick, Stephen; Pelletier, Jerry

    2010-04-15

    Sertraline, a selective serotonin reuptake inhibitor, is a widely used antidepressant agent. Here, we show that sertraline also exhibits antiproliferative activity. Exposure to sertraline leads to a concentration-dependent decrease in protein synthesis. Moreover, polysome profile analysis of sertraline-treated cells shows a reduction in polysome content and a concomitant increase in 80S ribosomes. The inhibition in translation caused by sertraline is associated with decreased levels of the eukaryotic initiation factor (eIF) 4F complex, altered localization of eIF4E, and increased eIF2alpha phosphorylation. The latter event leads to increased REDD1 expression, which in turn impinges on the mammalian target of rapamycin (mTOR) pathway by affecting TSC1/2 signaling. Sertraline also independently targets the mTOR signaling pathway downstream of Rheb. In the Emu-myc murine lymphoma model where carcinogenesis is driven by phosphatase and tensin homologue (PTEN) inactivation, sertraline is able to enhance chemosensitivity to doxorubicin. Our results indicate that sertraline exerts antiproliferative activity by targeting the mTOR signaling pathway in a REDD1-dependent manner. (c) 2010 AACR.

  18. Mammalian target of rapamycin inhibition in polycystic kidney disease: From bench to bedside

    Directory of Open Access Journals (Sweden)

    Hyun-Jung Kim

    2012-09-01

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is the most common life-threatening hereditary disease in the USA resulting in chronic kidney disease and the need for dialysis and transplantation. Approximately 85% of cases of ADPKD are caused by a mutation in the Pkd1 gene that encodes polycystin-1, a large membrane receptor. The Pkd1 gene mutation results in abnormal proliferation in tubular epithelial cells, which plays a crucial role in cyst development and/or growth in PKD. Activation of the proliferative mammalian target of rapamycin (mTOR signaling pathway has been demonstrated in polycystic kidneys from rodents and humans. mTOR inhibition with sirolimus or everolimus decreases cysts in most animal models of PKD including Pkd1 and Pkd2 gene deficient orthologous models of human disease. On the basis of animal studies, human studies were undertaken. Two large randomized clinical trials published in the New England Journal of Medicine of everolimus or sirolimus in ADPKD patients were very unimpressive and associated with a high side-effect profile. Possible reasons for the unimpressive nature of the human studies include their short duration, the high drop-out rate, suboptimal dosing, lack of randomization of “fast” and “slow progressors” and the lack of correlation between kidney size and kidney function in ADPKD. The future of mTOR inhibition in ADPKD is discussed.

  19. Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

    Science.gov (United States)

    Jesus, Tito T; Oliveira, Pedro F; Sousa, Mário; Cheng, C Yan; Alves, Marco G

    2017-06-01

    Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermatogenesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system.

  20. A comprehensive review of everolimus clinical reports: a new mammalian target of rapamycin inhibitor.

    Science.gov (United States)

    Gurk-Turner, Cheryle; Manitpisitkul, Wana; Cooper, Matthew

    2012-10-15

    As new immunosuppressive agents are introduced to the market, clinicians are faced with the daunting task of sifting through the published literature to decide the value that the agent will add to their own practice. We often must extrapolate information provided through study in other solid-organ transplantation populations than our specific area of interest as we interpret the results and outcomes. With these challenges in mind, this compilation of published work for the newest mammalian target of rapamycin inhibitor everolimus (Certican; Novartis Pharmaceuticals, Hanover, NJ) (Zortress; Novartis Pharmaceuticals, Basel, Switzerland) is intended to provide a concise but thorough presentation of available literature so that the reader who may be unfamiliar with the agent can make their own judgment. Both Ovid and PubMed search engines were queried with a particular focus on high-impact articles noted in the Web of Science or Citation Index. Work described solely in abstract or case report form was excluded, as well as meta-analyses or those that were editorial or commentary in nature. Included were publications presented using the English language that described adult human subjects who received a heart, lung, kidney, or liver allograft. The goal of this strategy was to allow for the inclusion of pertinent literature in an unbiased fashion. Tables are provided that outline trial specific information, leaving a discussion of major outcomes to the text of the review.

  1. GTPase ROP2 binds and promotes activation of target of rapamycin, TOR, in response to auxin.

    Science.gov (United States)

    Schepetilnikov, Mikhail; Makarian, Joelle; Srour, Ola; Geldreich, Angèle; Yang, Zhenbiao; Chicher, Johana; Hammann, Philippe; Ryabova, Lyubov A

    2017-04-03

    Target of rapamycin (TOR) promotes reinitiation at upstream ORFs (uORFs) in genes that play important roles in stem cell regulation and organogenesis in plants. Here, we report that the small GTPase ROP2, if activated by the phytohormone auxin, promotes activation of TOR, and thus translation reinitiation of uORF-containing mRNAs. Plants with high levels of active ROP2, including those expressing constitutively active ROP2 (CA-ROP2), contain high levels of active TOR ROP2 physically interacts with and, when GTP-bound, activates TOR in vitro TOR activation in response to auxin is abolished in ROP-deficient rop2 rop6 ROP4 RNAi plants. GFP-TOR can associate with endosome-like structures in ROP2-overexpressing plants, indicating that endosomes mediate ROP2 effects on TOR activation. CA-ROP2 is efficient in loading uORF-containing mRNAs onto polysomes and stimulates translation in protoplasts, and both processes are sensitive to TOR inhibitor AZD-8055. TOR inactivation abolishes ROP2 regulation of translation reinitiation, but not its effects on cytoskeleton or intracellular trafficking. These findings imply a mode of translation control whereby, as an upstream effector of TOR, ROP2 coordinates TOR function in translation reinitiation pathways in response to auxin. © 2017 The Authors.

  2. Rictor/mammalian target of rapamycin complex 2 promotes macrophage activation and kidney fibrosis.

    Science.gov (United States)

    Ren, Jiafa; Li, Jianzhong; Feng, Ye; Shu, Bingyan; Gui, Yuan; Wei, Wei; He, Weichun; Yang, Junwei; Dai, Chunsun

    2017-08-01

    Mammalian target of rapamycin (mTOR) signalling controls many essential cellular functions. However, the role of Rictor/mTOR complex 2 (mTORC2) in regulating macrophage activation and kidney fibrosis remains largely unknown. We report here that Rictor/mTORC2 was activated in macrophages from the fibrotic kidneys of mice. Ablation of Rictor in macrophages reduced kidney fibrosis, inflammatory cell accumulation, macrophage proliferation and polarization after unilateral ureter obstruction or ischaemia/reperfusion injury. In bone marrow-derived macrophages (BMMs), deletion of Rictor or blockade of protein kinase Cα inhibited cell migration. Additionally, deletion of Rictor or blockade of Akt abolished interleukin-4-stimulated or transforming growth factor (TGF)-β1-stimulated macrophage M2 polarization. Furthermore, deletion of Rictor downregulated TGF-β1-stimulated upregulation of multiple profibrotic cytokines, including platelet-derived growth factor, vascular endothelial growth factor and connective tissue growth factor, in BMMs. Conditioned medium from TGF-β1-pretreated Rictor -/- macrophages stimulated fibroblast activation less efficiently than that from TGF-β1-pretreated Rictor +/+ macrophages. These results demonstrate that Rictor/mTORC2 signalling can promote macrophage activation and kidney fibrosis. Targeting this signalling pathway in macrophages may shine light on ways to protect against kidney fibrosis in patients with chronic kidney diseases. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  3. Advances in LEDs for automotive applications

    Science.gov (United States)

    Bhardwaj, Jy; Peddada, Rao; Spinger, Benno

    2016-03-01

    High power LEDs were introduced in automotive headlights in 2006-2007, for example as full LED headlights in the Audi R8 or low beam in Lexus. Since then, LED headlighting has become established in premium and volume automotive segments and beginning to enable new compact form factors such as distributed low beam and new functions such as adaptive driving beam. New generations of highly versatile high power LEDs are emerging to meet these application needs. In this paper, we will detail ongoing advances in LED technology that enable revolutionary styling, performance and adaptive control in automotive headlights. As the standards which govern the necessary lumens on the road are well established, increasing luminance enables not only more design freedom but also headlight cost reduction with space and weight saving through more compact optics. Adaptive headlighting is based on LED pixelation and requires high contrast, high luminance, smaller LEDs with high-packing density for pixelated Matrix Lighting sources. Matrix applications require an extremely tight tolerance on not only the X, Y placement accuracy, but also on the Z height of the LEDs given the precision optics used to image the LEDs onto the road. A new generation of chip scale packaged (CSP) LEDs based on Wafer Level Packaging (WLP) have been developed to meet these needs, offering a form factor less than 20% increase over the LED emitter surface footprint. These miniature LEDs are surface mount devices compatible with automated tools for L2 board direct attach (without the need for an interposer or L1 substrate), meeting the high position accuracy as well as the optical and thermal performance. To illustrate the versatility of the CSP LEDs, we will show the results of, firstly, a reflector-based distributed low beam using multiple individual cavities each with only 20mm height and secondly 3x4 to 3x28 Matrix arrays for adaptive full beam. Also a few key trends in rear lighting and impact on LED light

  4. Pharmacist-led medication review in an acute admissions unit

    DEFF Research Database (Denmark)

    Hansen, Trine Graabæk; Bonnerup, Dorthe Krogsgaard; Kjeldsen, Lene Juel

    2015-01-01

    of principles and methodologies, and the practical procedure is seldom described in detail, which makes reproducing study findings difficult. The objective of this paper is to provide a detailed description of a procedure developed and used for pharmacist-led medication review in acute admissions units......) collection of information about the patient's medical treatment, (3) patient interview, (4) critical examination of the patient's medications and (5) recommendations for the hospital physician.Conclusions We have provided a detailed description of a procedure for pharmacist-led medication review. We do so...

  5. Harmonics Monitoring Survey on LED Lamps

    Directory of Open Access Journals (Sweden)

    Abdelrahman Ahmed Akila

    2017-03-01

    Full Text Available Light Emitting Diode (LED lamps are being increasingly used in many applications. These LED lamps operate using a driver, which is a switching device. Hence, LED lamps will be a source of harmonics in the power system. These harmonics if not well treated, may cause severe performance and operational problems. In this paper, harmonics (amplitude and phase angles generated by both LED lamps and conventional fluorescent lamps will be studied practically. Then they will be analyzed and evaluated. Compared to each other harmonics generated by both LED and conventional florescent lamps, self mitigation may occur based on the phase angle of these harmonics. All data will be measured using power analyzer and will be done on a sample of actual lamps.

  6. White LEDs with limit luminous efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Lisitsyn, V. M.; Stepanov, S. A., E-mail: stepanovsa@tpu.ru; Yangyang, Ju [National Research Tomsk Polytechnic University, 30 Lenin Av., Tomsk, 634050 (Russian Federation); Lukash, V. S. [JSC Research Institute of Semiconductor Devices, 99a Krasnoarmeyskaja St., Tomsk, 634050 (Russian Federation)

    2016-01-15

    In most promising widespread gallium nitride based LEDs emission is generated in the blue spectral region with a maximum at about 450 nm which is converted to visible light with the desired spectrum by means of phosphor. The thermal energy in the conversion is determined by the difference in the energies of excitation and emission quanta and the phosphor quantum yield. Heat losses manifest themselves as decrease in the luminous efficacy. LED heating significantly reduces its efficiency and life. In addition, while heating, the emission generation output and the efficiency of the emission conversion decrease. Therefore, the reduction of the energy losses caused by heating is crucial for LED development. In this paper, heat losses in phosphor-converted LEDs (hereinafter chips) during spectrum conversion are estimated. The limit values of the luminous efficacy for white LEDs are evaluated.

  7. Mammalian-target of rapamycin inhibition with temsirolimus in myelodysplastic syndromes (MDS) patients is associated with considerable toxicity: results of the temsirolimus pilot trial by the German MDS Study Group (D-MDS).

    Science.gov (United States)

    Wermke, Martin; Schuster, Claudia; Nolte, Florian; Al-Ali, Haifa-Kathrin; Kiewe, Philipp; Schönefeldt, Claudia; Jakob, Christiane; von Bonin, Malte; Hentschel, Leopold; Klut, Ina-Maria; Ehninger, Gerhard; Bornhäuser, Martin; Baretton, Gustavo; Germing, Ulrich; Herbst, Regina; Haase, Detelef; Hofmann, Wolf K; Platzbecker, Uwe

    2016-12-01

    The mammalian-target of rapamycin (also termed mechanistic target of rapamycin, mTOR) pathway integrates various pro-proliferative and anti-apoptotic stimuli and is involved in regulatory T-cell (TREG) development. As these processes contribute to the pathogenesis of myelodysplastic syndromes (MDS), we hypothesized that mTOR modulation with temsirolimus (TEM) might show activity in MDS. This prospective multicentre trial enrolled lower and higher risk MDS patients, provided that they were transfusion-dependent/neutropenic or relapsed/refractory to 5-azacitidine, respectively. All patients received TEM at a weekly dose of 25 mg. Of the 9 lower- and 11 higher-risk patients included, only 4 (20%) reached the response assessment after 4 months of treatment and showed stable disease without haematological improvement. The remaining patients discontinued TEM prematurely due to adverse events. Median overall survival (OS) was not reached in the lower-risk group and 296 days in the higher-risk group. We observed a significant decline of bone marrow (BM) vascularisation (P = 0·006) but were unable to demonstrate a significant impact of TEM on the balance between TREG and pro-inflammatory T-helper-cell subsets within the peripheral blood or BM. We conclude that mTOR-modulation with TEM at a dose of 25 mg per week is accompanied by considerable toxicity and has no beneficial effects in elderly MDS patients. © 2016 John Wiley & Sons Ltd.

  8. Design of an Oximeter Based on LED-LED Configuration and FPGA Technology

    OpenAIRE

    Stojanovic, Radovan; Karadaglic, Dejan

    2013-01-01

    A fully digital photoplethysmographic (PPG) sensor and actuator has been developed. The sensing circuit uses one Light Emitting Diode (LED) for emitting light into human tissue and one LED for detecting the reflectance light from human tissue. A Field Programmable Gate Array (FPGA) is used to control the LEDs and determine the PPG and Blood Oxygen Saturation (SpO2). The configurations with two LEDs and four LEDs are developed for measuring PPG signal and Blood Oxygen Saturation (SpO2). N-LEDs...

  9. White LED with High Package Extraction Efficiency

    International Nuclear Information System (INIS)

    Yi Zheng; Stough, Matthew

    2008-01-01

    The goal of this project is to develop a high efficiency phosphor converting (white) Light Emitting Diode (pcLED) 1-Watt package through an increase in package extraction efficiency. A transparent/translucent monolithic phosphor is proposed to replace the powdered phosphor to reduce the scattering caused by phosphor particles. Additionally, a multi-layer thin film selectively reflecting filter is proposed between blue LED die and phosphor layer to recover inward yellow emission. At the end of the project we expect to recycle approximately 50% of the unrecovered backward light in current package construction, and develop a pcLED device with 80 lm/W e using our technology improvements and commercially available chip/package source. The success of the project will benefit luminous efficacy of white LEDs by increasing package extraction efficiency. In most phosphor-converting white LEDs, the white color is obtained by combining a blue LED die (or chip) with a powdered phosphor layer. The phosphor partially absorbs the blue light from the LED die and converts it into a broad green-yellow emission. The mixture of the transmitted blue light and green-yellow light emerging gives white light. There are two major drawbacks for current pcLEDs in terms of package extraction efficiency. The first is light scattering caused by phosphor particles. When the blue photons from the chip strike the phosphor particles, some blue light will be scattered by phosphor particles. Converted yellow emission photons are also scattered. A portion of scattered light is in the backward direction toward the die. The amount of this backward light varies and depends in part on the particle size of phosphors. The other drawback is that yellow emission from phosphor powders is isotropic. Although some backward light can be recovered by the reflector in current LED packages, there is still a portion of backward light that will be absorbed inside the package and further converted to heat. Heat generated

  10. LED-driven backlights for automotive displays

    Science.gov (United States)

    Strauch, Frank

    2007-09-01

    As a light source the LED has some advantage over the traditionally used fluorescence tube such as longer life or lower space consumption. Consequently customers are asking for the LED lighting design in their products. We introduced in a company owned backlight the white LED technology. This step opens the possibility to have access to the components in the display market. Instead of having a finalized display product which needs to be integrated in the head unit of a car we assemble the backlight, the glass, own electronics and the housing. A major advantage of this concept is the better control of the heat flow generated by the LEDs to the outer side because only a common housing is used for all the components. Also the requirement for slim products can be fulfilled. As always a new technology doesn't come with advantages only. An LED represents a point source compared to the well-known tube thus requiring a mixing zone for the multiple point sources when they enter a light guide. This zone can't be used in displays because of the lack of homogeneity. It's a design goal to minimize this zone which can be helped by the right choice of the LED in terms of slimness. A step ahead is the implementation of RGB LEDs because of their higher color rendering abilities. This allows for the control of the chromaticity point under temperature change but as a drawback needs a larger mixing zone.

  11. High Power UV LED Industrial Curing Systems

    Energy Technology Data Exchange (ETDEWEB)

    Karlicek, Robert, F., Jr; Sargent, Robert

    2012-05-14

    UV curing is a green technology that is largely underutilized because UV radiation sources like Hg Lamps are unreliable and difficult to use. High Power UV LEDs are now efficient enough to replace Hg Lamps, and offer significantly improved performance relative to Hg Lamps. In this study, a modular, scalable high power UV LED curing system was designed and tested, performing well in industrial coating evaluations. In order to achieve mechanical form factors similar to commercial Hg Lamp systems, a new patent pending design was employed enabling high irradiance at long working distances. While high power UV LEDs are currently only available at longer UVA wavelengths, rapid progress on UVC LEDs and the development of new formulations designed specifically for use with UV LED sources will converge to drive more rapid adoption of UV curing technology. An assessment of the environmental impact of replacing Hg Lamp systems with UV LED systems was performed. Since UV curing is used in only a small portion of the industrial printing, painting and coating markets, the ease of use of UV LED systems should increase the use of UV curing technology. Even a small penetration of the significant number of industrial applications still using oven curing and drying will lead to significant reductions in energy consumption and reductions in the emission of green house gases and solvent emissions.

  12. Preliminary investigations of piezoelectric based LED luminary

    DEFF Research Database (Denmark)

    Nielsen, Dennis; Andersen, Michael A. E.; Meyer, Kaspar Sinding

    2011-01-01

    , modulation schemes, LEDs and LED driving conditions are analyzed. A prototype radial mode PT optimized for ZVS (Zero Voltage Switching) is designed. FEM (Final Element Method) and measurements validates the PT design. A prototype PT based AC/DC converter operating from european mains is proposed......This paper presents a preliminary study of PT (Piezoelectric Transformer) based SMPS’s (Switch Mode Power Supplies) for LED luminary. The unique properties of PTs (efficiency, power density and EMI) make them highly suitable for this application. Power stage topologies, rectifiers circuits...

  13. Transforming Growth Factor β1-induced Apoptosis in Podocytes via the Extracellular Signal-regulated Kinase-Mammalian Target of Rapamycin Complex 1-NADPH Oxidase 4 Axis.

    Science.gov (United States)

    Das, Ranjan; Xu, Shanhua; Nguyen, Tuyet Thi; Quan, Xianglan; Choi, Seong-Kyung; Kim, Soo-Jin; Lee, Eun Young; Cha, Seung-Kuy; Park, Kyu-Sang

    2015-12-25

    TGF-β is a pleiotropic cytokine that accumulates during kidney injuries, resulting in various renal diseases. We have reported previously that TGF-β1 induces the selective up-regulation of mitochondrial Nox4, playing critical roles in podocyte apoptosis. Here we investigated the regulatory mechanism of Nox4 up-regulation by mTORC1 activation on TGF-β1-induced apoptosis in immortalized podocytes. TGF-β1 treatment markedly increased the phosphorylation of mammalian target of rapamycin (mTOR) and its downstream targets p70S6K and 4EBP1. Blocking TGF-β receptor I with SB431542 completely blunted the phosphorylation of mTOR, p70S6K, and 4EBP1. Transient adenoviral overexpression of mTOR-WT and constitutively active mTORΔ augmented TGF-β1-treated Nox4 expression, reactive oxygen species (ROS) generation, and apoptosis, whereas mTOR kinase-dead suppressed the above changes. In addition, knockdown of mTOR mimicked the effect of mTOR-KD. Inhibition of mTORC1 by low-dose rapamycin or knockdown of p70S6K protected podocytes through attenuation of Nox4 expression and subsequent oxidative stress-induced apoptosis by TGF-β1. Pharmacological inhibition of the MEK-ERK cascade, but not the PI3K-Akt-TSC2 pathway, abolished TGF-β1-induced mTOR activation. Inhibition of either ERK1/2 or mTORC1 did not reduce the TGF-β1-stimulated increase in Nox4 mRNA level but significantly inhibited total Nox4 expression, ROS generation, and apoptosis induced by TGF-β1. Moreover, double knockdown of Smad2 and 3 or only Smad4 completely suppressed TGF-β1-induced ERK1/2-mTORactivation. Our data suggest that TGF-β1 increases translation of Nox4 through the Smad-ERK1/2-mTORC1 axis, which is independent of transcriptional regulation. Activation of this pathway plays a crucial role in ROS generation and mitochondrial dysfunction, leading to podocyte apoptosis. Therefore, inhibition of the ERK1/2-mTORC1 pathway could be a potential therapeutic and preventive target in proteinuric and chronic

  14. Drosophila insulin and target of rapamycin (TOR pathways regulate GSK3 beta activity to control Myc stability and determine Myc expression in vivo

    Directory of Open Access Journals (Sweden)

    Parisi Federica

    2011-09-01

    Full Text Available Abstract Background Genetic studies in Drosophila melanogaster reveal an important role for Myc in controlling growth. Similar studies have also shown how components of the insulin and target of rapamycin (TOR pathways are key regulators of growth. Despite a few suggestions that Myc transcriptional activity lies downstream of these pathways, a molecular mechanism linking these signaling pathways to Myc has not been clearly described. Using biochemical and genetic approaches we tried to identify novel mechanisms that control Myc activity upon activation of insulin and TOR signaling pathways. Results Our biochemical studies show that insulin induces Myc protein accumulation in Drosophila S2 cells, which correlates with a decrease in the activity of glycogen synthase kinase 3-beta (GSK3β a kinase that is responsible for Myc protein degradation. Induction of Myc by insulin is inhibited by the presence of the TOR inhibitor rapamycin, suggesting that insulin-induced Myc protein accumulation depends on the activation of TOR complex 1. Treatment with amino acids that directly activate the TOR pathway results in Myc protein accumulation, which also depends on the ability of S6K kinase to inhibit GSK3β activity. Myc upregulation by insulin and TOR pathways is a mechanism conserved in cells from the wing imaginal disc, where expression of Dp110 and Rheb also induces Myc protein accumulation, while inhibition of insulin and TOR pathways result in the opposite effect. Our functional analysis, aimed at quantifying the relative contribution of Myc to ommatidial growth downstream of insulin and TOR pathways, revealed that Myc activity is necessary to sustain the proliferation of cells from the ommatidia upon Dp110 expression, while its contribution downstream of TOR is significant to control the size of the ommatidia. Conclusions Our study presents novel evidence that Myc activity acts downstream of insulin and TOR pathways to control growth in Drosophila. At

  15. Drosophila insulin and target of rapamycin (TOR) pathways regulate GSK3 beta activity to control Myc stability and determine Myc expression in vivo.

    Science.gov (United States)

    Parisi, Federica; Riccardo, Sara; Daniel, Margaret; Saqcena, Mahesh; Kundu, Nandini; Pession, Annalisa; Grifoni, Daniela; Stocker, Hugo; Tabak, Esteban; Bellosta, Paola

    2011-09-27

    Genetic studies in Drosophila melanogaster reveal an important role for Myc in controlling growth. Similar studies have also shown how components of the insulin and target of rapamycin (TOR) pathways are key regulators of growth. Despite a few suggestions that Myc transcriptional activity lies downstream of these pathways, a molecular mechanism linking these signaling pathways to Myc has not been clearly described. Using biochemical and genetic approaches we tried to identify novel mechanisms that control Myc activity upon activation of insulin and TOR signaling pathways. Our biochemical studies show that insulin induces Myc protein accumulation in Drosophila S2 cells, which correlates with a decrease in the activity of glycogen synthase kinase 3-beta (GSK3β ) a kinase that is responsible for Myc protein degradation. Induction of Myc by insulin is inhibited by the presence of the TOR inhibitor rapamycin, suggesting that insulin-induced Myc protein accumulation depends on the activation of TOR complex 1. Treatment with amino acids that directly activate the TOR pathway results in Myc protein accumulation, which also depends on the ability of S6K kinase to inhibit GSK3β activity. Myc upregulation by insulin and TOR pathways is a mechanism conserved in cells from the wing imaginal disc, where expression of Dp110 and Rheb also induces Myc protein accumulation, while inhibition of insulin and TOR pathways result in the opposite effect. Our functional analysis, aimed at quantifying the relative contribution of Myc to ommatidial growth downstream of insulin and TOR pathways, revealed that Myc activity is necessary to sustain the proliferation of cells from the ommatidia upon Dp110 expression, while its contribution downstream of TOR is significant to control the size of the ommatidia. Our study presents novel evidence that Myc activity acts downstream of insulin and TOR pathways to control growth in Drosophila. At the biochemical level we found that both these pathways

  16. Device-based local delivery of siRNA against mammalian target of rapamycin (mTOR) in a murine subcutaneous implant model to inhibit fibrous encapsulation.

    Science.gov (United States)

    Takahashi, Hironobu; Wang, Yuwei; Grainger, David W

    2010-11-01

    Fibrous encapsulation of surgically implanted devices is associated with elevated proliferation and activation of fibroblasts in tissues surrounding these implants, frequently causing foreign body complications. Here we test the hypothesis that inhibition of the expression of mammalian target of rapamycin (mTOR) in fibroblasts can mitigate the soft tissue implant foreign body response by suppressing fibrotic responses around implants. In this study, mTOR was knocked down using small interfering RNA (siRNA) conjugated with branched polyethylenimine (bPEI) in fibroblastic lineage cells in serum-based cell culture as shown by both gene and protein analysis. This mTOR knock-down led to an inhibition in fibroblast proliferation by 70% and simultaneous down-regulation in the expression of type I collagen in fibroblasts in vitro. These siRNA/bPEI complexes were released from poly(ethylene glycol) (PEG)-based hydrogel coatings surrounding model polymer implants in a subcutaneous rodent model in vivo. No significant reduction in fibrous capsule thickness and mTOR expression in the foreign body capsules were observed. The siRNA inefficacy in this in vivo implant model was attributed to siRNA dosing limitations in the gel delivery system, and lack of targeting ability of the siRNA complex specifically to fibroblasts. While in vitro data supported mTOR knock-down in fibroblast cultures, in vivo siRNA delivery must be further improved to produce clinically relevant effects on fibrotic encapsulation around implants. Copyright © 2010 Elsevier B.V. All rights reserved.

  17. LED photochemotherapy against Staphylococcus aureus: an in vitro study

    Science.gov (United States)

    de Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Pires-Santos, Gustavo M.; Sampaio, Fernando José Pires; Soares, Luiz Guilherme P.; Soares, Amanda P.; Pinheiro, Antônio L. B.

    2018-02-01

    Bacterial resistance to antibiotics is reality and need for alternative treatments is urgent. The aim of this work was to evaluate, in vitro, the effect of LED photochemotherapy on Staphylococcus aureus (ATCC 23529) using 25 μg / mL of phenothiazine compound combined with LED light (λ632 +/- 2ηm) using 12 J/cm2 energy density. The experiments were carried out in triplicate and the samples were divided into groups: Control, Irradiated (treated only with light), Photosensitizer (treated only in the presence of the dye), LED-Photochemotherapy (treatment with light associated with dye). Counts of the colony forming units and the data obtained were statistically analyzed (ANOVA, Tukey's test, p<0.05). The present study demonstrated that the efficacy of LED-Photochemotherapy as the use of 25 μg/mL x 12 J/cm2 caused 91.57 % of inhibition of bacterial growth. It is concluded that using energy density of 12 J/cm2 associated to 25 μg/mL caused high in vitro inhibition of S. aureus.

  18. LED til væksthuse

    DEFF Research Database (Denmark)

    Dam-Hansen, Carsten; Thorseth, Anders; Rosenqvist, Eva

    2012-01-01

    Den teknologiske udvikling indenfor Lys Emitterende Dioder (LED) går imod stadig større lysmængder og stadig større effektivitet. Kombineret med fordele som lang levetid, dæmpbarhed og ingen varmestråling gør det, at LED baserede lyskilder/lamper i stigende grad benyttes til belysningsformål og kan...

  19. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells

    International Nuclear Information System (INIS)

    Li, Kuiqing; Chen, Xu; Liu, Cheng; Gu, Peng; Li, Zhuohang; Wu, Shaoxu; Xu, Kewei; Lin, Tianxin; Huang, Jian

    2015-01-01

    Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinase p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients. - Highlights: • Pirarubicin induced autophagy in bladder cancer cells. • Inhibition of autophagy enhanced pirarubicin-induced apoptosis. • Pirarubicin induced autophagy through inhibition of mTOR signaling pathway

  20. Pirarubicin induces an autophagic cytoprotective response through suppression of the mammalian target of rapamycin signaling pathway in human bladder cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Kuiqing; Chen, Xu [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Liu, Cheng [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Gu, Peng; Li, Zhuohang; Wu, Shaoxu [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Xu, Kewei [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Lin, Tianxin, E-mail: tianxinl@sina.com [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China); Huang, Jian, E-mail: urolhj@sina.com [Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120 (China)

    2015-05-01

    Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinase p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients. - Highlights: • Pirarubicin induced autophagy in bladder cancer cells. • Inhibition of autophagy enhanced pirarubicin-induced apoptosis. • Pirarubicin induced autophagy through inhibition of mTOR signaling pathway.

  1. Characterization of the metabolic phenotype of rapamycin-treated CD8+ T cells with augmented ability to generate long-lasting memory cells.

    Directory of Open Access Journals (Sweden)

    Shan He

    Full Text Available BACKGROUND: Cellular metabolism plays a critical role in regulating T cell responses and the development of memory T cells with long-term protections. However, the metabolic phenotype of antigen-activated T cells that are responsible for the generation of long-lived memory cells has not been characterized. DESIGN AND METHODS: Using lymphocytic choriomeningitis virus (LCMV peptide gp33-specific CD8(+ T cells derived from T cell receptor transgenic mice, we characterized the metabolic phenotype of proliferating T cells that were activated and expanded in vitro in the presence or absence of rapamycin, and determined the capability of these rapamycin-treated T cells to generate long-lived memory cells in vivo. RESULTS: Antigen-activated CD8(+ T cells treated with rapamycin gave rise to 5-fold more long-lived memory T cells in vivo than untreated control T cells. In contrast to that control T cells only increased glycolysis, rapamycin-treated T cells upregulated both glycolysis and oxidative phosphorylation (OXPHOS. These rapamycin-treated T cells had greater ability than control T cells to survive withdrawal of either glucose or growth factors. Inhibition of OXPHOS by oligomycin significantly reduced the ability of rapamycin-treated T cells to survive growth factor withdrawal. This effect of OXPHOS inhibition was accompanied with mitochondrial hyperpolarization and elevation of reactive oxygen species that are known to be toxic to cells. CONCLUSIONS: Our findings indicate that these rapamycin-treated T cells may represent a unique cell model for identifying nutrients and signals critical to regulating metabolism in both effector and memory T cells, and for the development of new methods to improve the efficacy of adoptive T cell cancer therapy.

  2. Risk evaluation and mitigation strategies: a focus on the mammalian target of rapamycin inhibitors.

    Science.gov (United States)

    Gabardi, Steven

    2013-03-01

    To review the history of risk evaluation and mitigation strategies (REMS) with the mammalian target of rapamycin (mToR) inhibitors, evaluate their required REMS elements, and delineate the reasons for them being released from their REMS requirements. Articles were identified through a literature search of MEDLINE and EMBASE (January 2007-July 2012) using the search terms: risk evaluation and mitigation strategies, REMS, everolimus, sirolimus and organ transplant (individual organs also were searched). Information from the Federal Register, the Food and Drug Administration, and the manufacturers of the mToR inhibitors was also evaluated. REMS are strategies implemented to manage known or potential risks associated with medications and to ensure ongoing pharmacovigilance throughout the life of a pharmaceutical product. The mToR inhibitors have been associated with several potential risks, including proteinuria, graft thrombosis, and wound-healing complications. The Food and Drug Administration approved REMS programs for both sirolimus and everolimus. The manufacturers of both medications complied with the components of their approved REMS, but after less than 2 years, both medications have been relieved of their REMS obligations. The only element of the sirolimus REMS was a medication guide, whereas the everolimus REMS consisted of a medication guide and a communication plan. The sirolimus REMS was implemented more than 10 years after its initial approval by the Food and Drug Administration, but was released from its REMS requirement within 7 months of its implementation. The everolimus REMS was instituted upon initial approval and was removed approximately 2 years later. Both medications' REMS were always intended to educate health care providers and patients about the potential risks associated with this transplant immunosuppressant. Transplant practitioners should be familiar with the mToR inhibitors' associated risks and properly educate patients regarding the

  3. Rapamycin inhibits BMP-7-induced osteogenic and lipogenic marker expressions in fetal rat calvarial cells.

    Science.gov (United States)

    Yeh, Lee-Chuan C; Ma, Xiuye; Ford, Jeffery J; Adamo, Martin L; Lee, John C

    2013-08-01

    Bone morphogenetic proteins (BMPs) promote osteoblast differentiation and bone formation in vitro and in vivo. BMPs canonically signal through Smad transcription factors, but BMPs may activate signaling pathways traditionally stimulated by growth factor tyrosine kinase receptors. Of these, the mTOR pathway has received considerable attention because BMPs activate P70S6K, a downstream effector of mTOR, suggesting that BMP-induced osteogenesis is mediated by mTOR activation. However, contradictory effects of the mTOR inhibitor rapamycin (RAPA) on bone formation have been reported. Since bone formation is thought to be inversely related to lipid accumulation and mTOR is also important for lipid synthesis, we postulated that BMP-7 may stimulate lipogenic enzyme expression in a RAPA-sensitive mechanism. To test this hypothesis, we determined the effects of RAPA on BMP-7-stimulated expression of osteogenic and lipogenic markers in cultured fetal rat calvarial cells. Our study showed that BMP-7 promoted the expression of osteogenic and lipogenic markers. The effect of BMP-7 on osteogenic markers was greater in magnitude than on lipogenic markers and was temporally more sustained. RAPA inhibited basal and BMP-7-stimulated osteogenic and lipogenic marker expression and bone nodule mineralization. The acetyl CoA carboxylase inhibitor TOFA stimulated the expression of osteoblast differentiation markers, whereas palmitate suppressed their expression. We speculate that the BMP-7-stimulated adipogenesis is part of the normal anabolic response to BMPs, but that inappropriate activation of the lipid biosynthetic pathway by mTOR could have deleterious effects on bone formation and could explain paradoxical effects of RAPA to promote bone formation. Copyright © 2013 Wiley Periodicals, Inc.

  4. Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

    International Nuclear Information System (INIS)

    Zhang, Pengpeng; Shan, Tizhong; Liang, Xinrong; Deng, Changyan; Kuang, Shihuan

    2014-01-01

    Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor flox/flox mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor flox/flox mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function

  5. Pulsed and Continuous UV LED Reactor for Water Treatment

    Data.gov (United States)

    U.S. Environmental Protection Agency — Numerical data represented in the figures which are graphs. This dataset is associated with the following publication: Spencer, M., M. Miller, J. Richwine, K....

  6. Refrigerating liquid prototype for LED's thermal management

    International Nuclear Information System (INIS)

    Faranda, Roberto; Guzzetti, Stefania; Lazaroiu, George Cristian; Leva, Sonia

    2012-01-01

    The heat management is the critical factor for high performance operation of LED. A new heat management application of refrigerating liquid integrated within a fabricated prototype is proposed and investigated. A series of experiments considering different heights of liquid level were performed to evaluate the heat dissipation performance and optical characteristics of the refrigerating liquid based prototype. The results reveal that the junction temperature decreases as the level of refrigerating liquid increases. The experimental results report that the refrigerating liquid reduces the junction temperature, and can positively influence the luminous radiation performances. An optimization investigation of the proposed solution was carried out to find an optimum thermal performance. The experiments indicated that refrigerating liquid cooling is a powerful way for heat dissipation of high power LEDs, and the fabrication of prototype was feasible and useful. - Highlights: ► New heat management application of refrigerating liquid on a fabricated LED prototype. ► Thermal models setup and comparison between the classical and the new solutions. ► The impact of refrigerating liquid level on LED thermal and luminous performances. ► The relationship between different levels of liquid with LED prototype performances.

  7. Rapamycin and CHIR99021 Coordinate Robust Cardiomyocyte Differentiation From Human Pluripotent Stem Cells Via Reducing p53-Dependent Apoptosis.

    Science.gov (United States)

    Qiu, Xiao-Xu; Liu, Yang; Zhang, Yi-Fan; Guan, Ya-Na; Jia, Qian-Qian; Wang, Chen; Liang, He; Li, Yong-Qin; Yang, Huang-Tian; Qin, Yong-Wen; Huang, Shuang; Zhao, Xian-Xian; Jing, Qing

    2017-10-02

    Cardiomyocytes differentiated from human pluripotent stem cells can serve as an unexhausted source for a cellular cardiac disease model. Although small molecule-mediated cardiomyocyte differentiation methods have been established, the differentiation efficiency is relatively unsatisfactory in multiple lines due to line-to-line variation. Additionally, hurdles including line-specific low expression of endogenous growth factors and the high apoptotic tendency of human pluripotent stem cells also need to be overcome to establish robust and efficient cardiomyocyte differentiation. We used the H9-human cardiac troponin T-eGFP reporter cell line to screen for small molecules that promote cardiac differentiation in a monolayer-based and growth factor-free differentiation model. We found that collaterally treating human pluripotent stem cells with rapamycin and CHIR99021 during the initial stage was essential for efficient and reliable cardiomyocyte differentiation. Moreover, this method maintained consistency in efficiency across different human embryonic stem cell and human induced pluripotent stem cell lines without specifically optimizing multiple parameters (the efficiency in H7, H9, and UQ1 human induced pluripotent stem cells is 98.3%, 93.3%, and 90.6%, respectively). This combination also increased the yield of cardiomyocytes (1:24) and at the same time reduced medium consumption by about 50% when compared with the previous protocols. Further analysis indicated that inhibition of the mammalian target of rapamycin allows efficient cardiomyocyte differentiation through overcoming p53-dependent apoptosis of human pluripotent stem cells during high-density monolayer culture via blunting p53 translation and mitochondrial reactive oxygen species production. We have demonstrated that mammalian target of rapamycin exerts a stage-specific and multifaceted regulation over cardiac differentiation and provides an optimized approach for generating large numbers of functional

  8. Serotonin induces memory-like, rapamycin-sensitive hyperexcitability in sensory axons of aplysia that contributes to injury responses.

    Science.gov (United States)

    Weragoda, Ramal M S; Walters, Edgar T

    2007-09-01

    The induction of long-term facilitation (LTF) of synapses of Aplysia sensory neurons (SNs) by serotonin (5-HT) has provided an important mechanistic model of memory, but little is known about other long-term effects of 5-HT on sensory properties. Here we show that crushing peripheral nerves results in long-term hyperexcitability (LTH) of the axons of these nociceptive SNs that requires 5-HT activity in the injured nerve. Serotonin application to a nerve segment induces local axonal (but not somal) LTH that is inhibited by 5-HT-receptor antagonists. Blockade of crush-induced axonal LTH by an antagonist, methiothepin, provides evidence for mediation of this injury response by 5-HT. This is the first demonstration in any axon of neuromodulator-induced LTH, a phenomenon potentially important for long-lasting pain. Methiothepin does not reduce axonal LTH induced by local depolarization, so 5-HT is not required for all forms of axonal LTH. Serotonin-induced axonal LTH is expressed as reduced spike threshold and increased repetitive firing, whereas depolarization-induced LTH involves only reduced threshold. Like crush- and depolarization-induced LTH, 5-HT-induced LTH is blocked by inhibiting protein synthesis. Blockade by rapamycin, which also blocks synaptic LTF, is interesting because the eukaryotic protein kinase that is the target of rapamycin (TOR) has a conserved role in promoting growth by stimulating translation of proteins required for translation. Rapamycin sensitivity suggests that localized increases in translation of proteins that promote axonal conduction and excitability at sites of nerve injury may be regulated by the same signals that increase translation of proteins that promote neuronal growth.

  9. Platelet-derived growth factor regulates vascular smooth muscle phenotype via mammalian target of rapamycin complex 1

    International Nuclear Information System (INIS)

    Ha, Jung Min; Yun, Sung Ji; Kim, Young Whan; Jin, Seo Yeon; Lee, Hye Sun; Song, Sang Heon; Shin, Hwa Kyoung; Bae, Sun Sik

    2015-01-01

    Mammalian target of rapamycin complex (mTORC) regulates various cellular processes including proliferation, growth, migration and differentiation. In this study, we showed that mTORC1 regulates platelet-derived growth factor (PDGF)-induced phenotypic conversion of vascular smooth muscle cells (VSMCs). Stimulation of contractile VSMCs with PDGF significantly reduced the expression of contractile marker proteins in a time- and dose-dependent manner. In addition, angiotensin II (AngII)-induced contraction of VSMCs was completely blocked by the stimulation of VSMCs with PDGF. PDGF-dependent suppression of VSMC marker gene expression was significantly blocked by inhibition of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and mTOR whereas inhibition of p38 MAPK had no effect. In particular, inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked the PDGF-dependent phenotypic change of VSMCs whereas silencing of Rictor had no effect. In addition, loss of AngII-dependent contraction by PDGF was significantly retained by silencing of Raptor. Inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked PDGF-induced proliferation of VSMCs. Taken together, we suggest that mTORC1 plays an essential role in PDGF-dependent phenotypic changes of VSMCs. - Graphical abstract: Regulation of VSMC phenotype by PDGF-dependent activation of mTORC1. - Highlights: • The expression of contractile marker proteins was reduced by PDGF stimulation. • PDGF-dependent phenotypic conversion of VSMCs was blocked by inhibition of mTOR. • PDGF-induced proliferation of VSMCs was attenuated by inhibition of mTORC1. • mTORC1 plays a critical role in PDGF-dependent phenotypic conversion of VSMCs

  10. Platelet-derived growth factor regulates vascular smooth muscle phenotype via mammalian target of rapamycin complex 1

    Energy Technology Data Exchange (ETDEWEB)

    Ha, Jung Min; Yun, Sung Ji; Kim, Young Whan; Jin, Seo Yeon; Lee, Hye Sun [Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine, Yangsan (Korea, Republic of); Song, Sang Heon [Department of Internal Medicine, Pusan National University Hospital, Busan (Korea, Republic of); Shin, Hwa Kyoung [Department of Anatomy, Pusan National University School of Korean Medicine, Yangsan (Korea, Republic of); Bae, Sun Sik, E-mail: sunsik@pusan.ac.kr [Medical Research Institute, Department of Pharmacology, Pusan National University School of Medicine, Yangsan (Korea, Republic of)

    2015-08-14

    Mammalian target of rapamycin complex (mTORC) regulates various cellular processes including proliferation, growth, migration and differentiation. In this study, we showed that mTORC1 regulates platelet-derived growth factor (PDGF)-induced phenotypic conversion of vascular smooth muscle cells (VSMCs). Stimulation of contractile VSMCs with PDGF significantly reduced the expression of contractile marker proteins in a time- and dose-dependent manner. In addition, angiotensin II (AngII)-induced contraction of VSMCs was completely blocked by the stimulation of VSMCs with PDGF. PDGF-dependent suppression of VSMC marker gene expression was significantly blocked by inhibition of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and mTOR whereas inhibition of p38 MAPK had no effect. In particular, inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked the PDGF-dependent phenotypic change of VSMCs whereas silencing of Rictor had no effect. In addition, loss of AngII-dependent contraction by PDGF was significantly retained by silencing of Raptor. Inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked PDGF-induced proliferation of VSMCs. Taken together, we suggest that mTORC1 plays an essential role in PDGF-dependent phenotypic changes of VSMCs. - Graphical abstract: Regulation of VSMC phenotype by PDGF-dependent activation of mTORC1. - Highlights: • The expression of contractile marker proteins was reduced by PDGF stimulation. • PDGF-dependent phenotypic conversion of VSMCs was blocked by inhibition of mTOR. • PDGF-induced proliferation of VSMCs was attenuated by inhibition of mTORC1. • mTORC1 plays a critical role in PDGF-dependent phenotypic conversion of VSMCs.

  11. Mechanistic Target of Rapamycin-Independent Antidepressant Effects of (R)-Ketamine in a Social Defeat Stress Model.

    Science.gov (United States)

    Yang, Chun; Ren, Qian; Qu, Youge; Zhang, Ji-Chun; Ma, Min; Dong, Chao; Hashimoto, Kenji

    2018-01-01

    The role of the mechanistic target of rapamycin (mTOR) signaling in the antidepressant effects of ketamine is controversial. In addition to mTOR, extracellular signal-regulated kinase (ERK) is a key signaling molecule in prominent pathways that regulate protein synthesis. (R)-Ketamine has a greater potency and longer-lasting antidepressant effects than (S)-ketamine. Here we investigated whether mTOR signaling and ERK signaling play a role in the antidepressant effects of two enantiomers. The effects of mTOR inhibitors (rapamycin and AZD8055) and an ERK inhibitor (SL327) on the antidepressant effects of ketamine enantiomers in the chronic social defeat stress (CSDS) model (n = 7 or 8) and on those of ketamine enantiomers in these signaling pathways in mouse brain regions were examined. The intracerebroventricular infusion of rapamycin or AZD8055 blocked the antidepressant effects of (S)-ketamine, but not (R)-ketamine, in the CSDS model. Furthermore, (S)-ketamine, but not (R)-ketamine, significantly attenuated the decreased phosphorylation of mTOR and its downstream effector, ribosomal protein S6 kinase, in the prefrontal cortex of susceptible mice after CSDS. Pretreatment with SL327 blocked the antidepressant effects of (R)-ketamine but not (S)-ketamine. Moreover, (R)-ketamine, but not (S)-ketamine, significantly attenuated the decreased phosphorylation of ERK and its upstream effector, mitogen-activated protein kinase/ERK kinase, in the prefrontal cortex and hippocampal dentate gyrus of susceptible mice after CSDS. This study suggests that mTOR plays a role in the antidepressant effects of (S)-ketamine, but not (R)-ketamine, and that ERK plays a role in (R)-ketamine's antidepressant effects. Thus, it is unlikely that the activation of mTOR signaling is necessary for antidepressant actions of (R)-ketamine. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Mammalian target of rapamycin is required for phrenic long-term facilitation following severe but not moderate acute intermittent hypoxia.

    Science.gov (United States)

    Dougherty, Brendan J; Fields, Daryl P; Mitchell, Gordon S

    2015-09-01

    Phrenic long-term facilitation (pLTF) is a persistent increase in phrenic nerve activity after acute intermittent hypoxia (AIH). Distinct cell-signaling cascades give rise to pLTF depending on the severity of hypoxemia within hypoxic episodes. Moderate AIH (mAIH; three 5-min episodes, PaO2 ∼35-55 mmHG) elicits pLTF by a serotonin (5-HT)-dependent mechanism that requires new synthesis of brain-derived neurotrophic factor (BDNF), activation of its high-affinity receptor (TrkB), and ERK MAPK signaling. In contrast, severe AIH (sAIH; three 5-min episodes, PaO2 ∼25-30 mmHG) elicits pLTF by an adenosine-dependent mechanism that requires new TrkB synthesis and Akt signaling. Although both mechanisms require spinal protein synthesis, the newly synthesized proteins are distinct, as are the neurochemicals inducing plasticity (serotonin vs. adenosine). In many forms of neuroplasticity, new protein synthesis requires translational regulation via mammalian target of rapamycin (mTOR) signaling. Since Akt regulates mTOR activity, we hypothesized that mTOR activity is necessary for sAIH- but not mAIH-induced pLTF. Phrenic nerve activity in anesthetized, paralyzed, and ventilated rats was recorded before, during, and 60 min after mAIH or sAIH. Rats were pretreated with intrathecal injections of 20% DMSO (vehicle controls) or rapamycin (0.1 mM, 12 μl), a selective mTOR complex 1 inhibitor. Consistent with our hypothesis, rapamycin blocked sAIH- but not mAIH-induced pLTF. Thus spinal mTOR activity is required for adenosine-dependent (sAIH) but not serotonin-dependent (mAIH) pLTF, suggesting that distinct mechanisms regulate new protein synthesis in these forms of spinal neuroplasticity. Copyright © 2015 the American Physiological Society.

  13. Response of Eustoma Leaf Phenotype and Photosynthetic Performance to LED Light Quality

    Directory of Open Access Journals (Sweden)

    Md Zohurul Kadir Roni

    2017-10-01

    Full Text Available In a controlled environment, light from light-emitting diodes (LEDs has been associated with affecting the leaf characteristics of Eustoma. LEDs help plant growth and development, yet little is known about photosynthetic performance and related anatomical features in the early growth stage of Eustoma leaves. In this study, we examined the effects of blue (B, red (R, and white (W LEDs on the photosynthetic performance of Eustoma leaves, as well as leaf morphology and anatomy including epidermal layer thickness, palisade cells, and stomatal characteristics. Leaves grown under B LEDs were thicker and had a higher chlorophyll content than those grown under the R and W LEDs. Leaves under B LEDs had greater net photosynthetic rates (A, stomatal conductance (gs, and transpiration rates (E, especially at a higher photon flux density (PPFD, that resulted in a decrease in the intercellular CO2 concentration (Ci, than leaves under the W and R LEDs. B LEDs resulted in greater abaxial epidermal layer thickness and palisade cell length and width than the R and W LED treatments. The palisade cells also developed a more cylindrical shape in response to the B LEDs. B LED leaves also showed greater guard cell length, breadth, and area, and stomatal density, than W or R LEDs, which may contribute to increased A, gs and E at higher PPFDs.

  14. High-power LEDs for plant cultivation

    Science.gov (United States)

    Tamulaitis, Gintautas; Duchovskis, Pavelas; Bliznikas, Zenius; Breive, Kestutis; Ulinskaite, Raimonda; Brazaityte, Ausra; Novickovas, Algirdas; Zukauskas, Arturas; Shur, Michael S.

    2004-10-01

    We report on high-power solid-state lighting facility for cultivation of greenhouse vegetables and on the results of the study of control of photosynthetic activity and growth morphology of radish and lettuce imposed by variation of the spectral composition of illumination. Experimental lighting modules (useful area of 0.22 m2) were designed based on 4 types of high-power light-emitting diodes (LEDs) with emission peaked in red at the wavelengths of 660 nm and 640 nm (predominantly absorbed by chlorophyll a and b for photosynthesis, respectively), in blue at 455 nm (phototropic function), and in far-red at 735 nm (important for photomorphology). Morphological characteristics, chlorophyll and phytohormone concentrations in radish and lettuce grown in phytotron chambers under lighting with different spectral composition of the LED-based illuminator and under illumination by high pressure sodium lamps with an equivalent photosynthetic photon flux density were compared. A well-balanced solid-state lighting was found to enhance production of green mass and to ensure healthy morphogenesis of plants compared to those grown using conventional lighting. We observed that the plant morphology and concentrations of morphologically active phytohormones is strongly affected by the spectral composition of light in the red region. Commercial application of the LED-based illumination for large-scale plant cultivation is discussed. This technology is favorable from the point of view of energy consumption, controllable growth, and food safety but is hindered by high cost of the LEDs. Large scale manufacturing of high-power red AlInGaP-based LEDs emitting at 650 nm and a further decrease of the photon price for the LEDs emitting in the vicinity of the absorption peak of chlorophylls have to be achieved to promote horticulture applications.

  15. Packaging technology of LEDs for LCD backlights

    International Nuclear Information System (INIS)

    Fan Manning; Liang Meng; Wang Guohong

    2009-01-01

    We design a package patterned with red and green emitting phosphors excited by a blue LED to emit tri-basic mixing color. For high backlight display quality, we compare several phosphors. According to our measurements, green phosphors 0752G, 0753G and red phosphor 0763R are preferred for producing a good backlight source. Compared to RGB-LED backlight units, this frame typically benefits the lighting uniformity, and can simplify the structures. It also provides higher color render and better CCT than the traditional package method of a yellow phosphor with a blue chip. However, its light efficiency needs to be further improved for the use of backlights for LCDs.

  16. Intelligent styring af dynamisk LED belysning

    DEFF Research Database (Denmark)

    Thorseth, Anders; Corell, Dennis Dan; Hansen, Søren Stentoft

    Denne slutrapport giver en kort beskrivelse af arbejdet, der er udført af DTU Fotonik i projektet ”Intelligent styring af dynamisk LED belysning” støttet af EUDP. Arbejdet er udført i perioden 2011‐2012 i samarbejde med Lighten.......Denne slutrapport giver en kort beskrivelse af arbejdet, der er udført af DTU Fotonik i projektet ”Intelligent styring af dynamisk LED belysning” støttet af EUDP. Arbejdet er udført i perioden 2011‐2012 i samarbejde med Lighten....

  17. Freeform lens design for LED collimating illumination.

    Science.gov (United States)

    Chen, Jin-Jia; Wang, Te-Yuan; Huang, Kuang-Lung; Liu, Te-Shu; Tsai, Ming-Da; Lin, Chin-Tang

    2012-05-07

    We present a simple freeform lens design method for an application to LED collimating illumination. The method is derived from a basic geometric-optics analysis and construction approach. By using this method, a highly collimating lens with LED chip size of 1.0 mm × 1.0 mm and optical simulation efficiency of 86.5% under a view angle of ± 5 deg is constructed. To verify the practical performance of the lens, a prototype of the collimator lens is also made, and an optical efficiency of 90.3% with a beam angle of 4.75 deg is measured.

  18. Null bactericidal effect of ultraviolet radiation emitted by LEDs.

    Directory of Open Access Journals (Sweden)

    Francisco Alcántara Muñoz

    2016-11-01

    Full Text Available This research has aimed to assess the bactericidal effect of ultraviolet light emitted by LEDS on the growth on Petri dishes of microorganisms whose legal limits in foods have been established. An electrically fed apparatus has been designed with precise timing and a camera to prevent light spillage, in which two ultraviolet radiation emission devices were connected by LED technology at different wavelengths: through an array of LEDS emitting at around 350nm, and a single specific emission LED at 280nm. 1000 cfu of E. Coli and S. aureus sown on PCA were used as prototypes of gram negative and positive bacteria, respectively, onto which ultraviolet light was radiated at different time intervals, by means of both devices, with the whole experiment being carried out in triplicate . In none of the three series of treatments at the two wavelengths were reductions in microbial growth observed. The series of sowings on PCA were done on unseeded plates in order to be able to discard the likelihood of subsequent recontamination.

  19. Geriatric and Student Perceptions following Student-led Educational Sessions

    Directory of Open Access Journals (Sweden)

    Kristin Janzen

    2018-01-01

    Full Text Available Objective: The objective of this study was to measure the effect of student-led educational events on geriatric patient and student participant perceptions in a community setting. Methods: Students led three events at a senior community center, focusing on learning and memory, sleep hygiene, and arthritis pain. The participants were geriatric patients who themselves were providers of support to homebound peers (“clients” through an independently organized program. Geriatric participants completed pre- and post-event surveys to measure changes in familiarity with the topics. Student participants also completed pre- and post-event surveys that tracked changes in their comfort in working with the geriatric population. Results: Each event demonstrated at least one positive finding for geriatric patients and/or their clients. Students reported increased comfort in working with and teaching the geriatric population following the first and third events, but not the second. Conclusion: Student-led educational sessions can improve perceived health-related knowledge of geriatric participants while simultaneously exposing students to the geriatric patient population. Overall, both students and geriatric participants benefited from these events. Practice Implications: Incorporation of single, student-led educational events could be mutually beneficial to students and the elderly population in the community and easily incorporated into any healthcare curriculum. Funding:This work was supported by a Butler University Innovation Fund Grant. Treatment of Human Subjects: IRB review/approval required and obtained   Type: Original Research

  20. Design of an Oximeter Based on LED-LED Configuration and FPGA Technology

    Directory of Open Access Journals (Sweden)

    Radovan Stojanovic

    2013-01-01

    Full Text Available A fully digital photoplethysmographic (PPG sensor and actuator has been developed. The sensing circuit uses one Light Emitting Diode (LED for emitting light into human tissue and one LED for detecting the reflectance light from human tissue. A Field Programmable Gate Array (FPGA is used to control the LEDs and determine the PPG and Blood Oxygen Saturation (SpO2. The configurations with two LEDs and four LEDs are developed for measuring PPG signal and Blood Oxygen Saturation (SpO2. N-LEDs configuration is proposed for multichannel SpO2 measurements. The approach resulted in better spectral sensitivity, increased and adjustable resolution, reduced noise, small size, low cost and low power consumption.

  1. Final report LED solutions for public lighting; Eindrapportage LED oplossingen voor openbare verlichting

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-04-15

    This report examines if and how LED can be used for public lighting on a large scale. Pilot projects in 29 municipalities were assessed to test the usefulness of LED lighting. This final report provides answers to the questions that relate to the feasibility of the deployment of LED in public lighting and provides some practical pointers. [Dutch] Er is onderzocht of, en zo ja op welke wijze, LED grootschalig toegepast kan worden in de openbare verlichting (OVL). In 29 gemeenten in Nederland zijn proefprojecten geevalueerd om LED verlichting te toetsen op bruikbaarheid. Deze eindrapportage geeft antwoord op vragen die betrekking hebben op de haalbaarheid van de toepassing van LED binnen de OVL en geeft wat praktische aandachtspunten.

  2. Design of an oximeter based on LED-LED configuration and FPGA technology.

    Science.gov (United States)

    Stojanovic, Radovan; Karadaglic, Dejan

    2013-01-04

    A fully digital photoplethysmographic (PPG) sensor and actuator has been developed. The sensing circuit uses one Light Emitting Diode (LED) for emitting light into human tissue and one LED for detecting the reflectance light from human tissue. A Field Programmable Gate Array (FPGA) is used to control the LEDs and determine the PPG and Blood Oxygen Saturation (S(p)O(2)). The configurations with two LEDs and four LEDs are developed for measuring PPG signal and Blood Oxygen Saturation (S(p)O(2)). N-LEDs configuration is proposed for multichannel S(p)O(2) measurements. The approach resulted in better spectral sensitivity, increased and adjustable resolution, reduced noise, small size, low cost and low power consumption.

  3. Mechanistic Target of Rapamycin Is a Novel Molecular Mechanism Linking Folate Availability and Cell Function.

    Science.gov (United States)

    Silva, Elena; Rosario, Fredrick J; Powell, Theresa L; Jansson, Thomas

    2017-07-01

    Folate deficiency has been linked to a wide range of disorders, including cancer, neural tube defects, and fetal growth restriction. Folate regulates cellular function mediated by its involvement in the synthesis of nucleotides, which are needed for DNA synthesis, and its function as a methyl donor, which is critical for DNA methylation. Here we review current data showing that folate sensing by mechanistic target of rapamycin (mTOR) constitutes a novel and distinct pathway by which folate modulates cell functions such as nutrient transport, protein synthesis, and mitochondrial respiration. The mTOR signaling pathway responds to growth factors and changes in nutrient availability to control cell growth, proliferation, and metabolism. mTOR exists in 2 complexes, mTOR complex (mTORC) 1 and mTORC2, which have distinct upstream regulators and downstream targets. Folate deficiency in pregnant mice caused a marked inhibition of mTORC1 and mTORC2 signaling in multiple maternal and fetal tissues, downregulation of placental amino acid transporters, and fetal growth restriction. In addition, folate deficiency in primary human trophoblast (PHT) cells resulted in inhibition of mTORC1 and mTORC2 signaling and decreased the activity of key amino acid transporters. Folate sensing by mTOR in PHT cells is independent of the accumulation of homocysteine and requires the proton-coupled folate transporter (PCFT; solute carrier 46A1). Furthermore, mTORC1 and mTORC2 regulate trophoblast folate uptake by modulating the cell surface expression of folate receptor α and the reduced folate carrier. These findings, which provide a novel link between folate availability and cell function, growth, and proliferation, may have broad biological significance given the critical role of folate in normal cell function and the multiple diseases that have been associated with decreased or excessive folate availability. Low maternal folate concentrations are linked to restricted fetal growth, and we

  4. Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Pengpeng [Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Shan, Tizhong; Liang, Xinrong [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States); Deng, Changyan [Key Laboratory of Swine Genetics and Breeding, Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070 (China); Kuang, Shihuan, E-mail: skuang@purdue.edu [Department of Animal Sciences, Purdue University, West Lafayette, IN 47907 (United States)

    2014-09-12

    Highlights: • mTOR is a critical regulator of many biological processes yet its function in heart is not well understood. • MCK-Cre/Mtor{sup flox/flox} mice were established to delete Mtor in cardiomyocytes. • The mTOR-mKO mice developed normally but die prematurely within 5 weeks after birth due to heart disease. • The mTOR-mKO mice had dilated myocardium and increased cell death. • mTOR-mKO hearts had reduced expression of metabolic genes and activation of mTOR target proteins. - Abstract: Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtor{sup flox/flox} mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function.

  5. Differential responses of human regulatory T cells (Treg and effector T cells to rapamycin.

    Directory of Open Access Journals (Sweden)

    Laura Strauss

    Full Text Available BACKGROUND: The immunosuppressive drug rapamycin (RAPA promotes the expansion of CD4(+ CD25(highFoxp3(+ regulatory T cells via mechanisms that remain unknown. Here, we studied expansion, IL-2R-gamma chain signaling, survival pathways and resistance to apoptosis in human Treg responding to RAPA. METHODOLOGY/PRINCIPAL FINDINGS: CD4(+CD25(+ and CD4(+CD25(neg T cells were isolated from PBMC of normal controls (n = 21 using AutoMACS. These T cell subsets were cultured in the presence of anti-CD3/CD28 antibodies and 1000 IU/mL IL-2 for 3 to 6 weeks. RAPA (1-100 nM was added to half of the cultures. After harvest, the cell phenotype, signaling via the PI3K/mTOR and STAT pathways, expression of survival proteins and Annexin V binding were determined and compared to values obtained with freshly-separated CD4(+CD25(high and CD4(+CD25(neg T cells. Suppressor function was tested in co-cultures with autologous CFSE-labeled CD4(+CD25(neg or CD8(+CD25(neg T-cell responders. The frequency and suppressor activity of Treg were increased after culture of CD4(+CD25(+ T cells in the presence of 1-100 nM RAPA (p<0.001. RAPA-expanded Treg were largely CD4(+CD25(highFoxp3(+ cells and were resistant to apoptosis, while CD4(+CD25(neg T cells were sensitive. Only Treg upregulated anti-apoptotic and down-regulated pro-apoptotic proteins. Treg expressed higher levels of the PTEN protein than CD4(+CD25(neg cells. Activated Treg+/-RAPA preferentially phosphorylated STAT5 and STAT3 and did not utilize the PI3K/mTOR pathway. CONCLUSIONS/SIGNIFICANCE: RAPA favors Treg expansion and survival by differentially regulating signaling, proliferation and sensitivity to apoptosis of human effector T cells and Treg after TCR/IL-2 activation.

  6. Portrait of a Teacher-Led School

    Science.gov (United States)

    Nazareno, Lori

    2013-01-01

    Imagine a school with no principal and with a leadership structure that holds teachers accountable for the learning of all students. About 50 such teacher-led schools currently operate across the United States, and this article tells the story of one of them. The Mathematics and Science Leadership Academy (MSLA) in Denver, Colorado, serves about…

  7. A community led tobacco free city

    Directory of Open Access Journals (Sweden)

    Najith Duminda Galmangoda Guruge

    2018-03-01

    Community led initiatives based on Health Promotion approach are effective in establishing 'Tobacco-free' cities. The community empowerment processes linked with such approaches can reduce the exposure to passive smoking, generating “smoke free cities” as well. Continuous vigilance at ground level and supportive actions from the national level are needed to sustain the results and enhance long term outcomes.

  8. Student-Led Conferences: Students Taking Responsibility

    Science.gov (United States)

    Nauss, Sherri A.

    2010-01-01

    One of the many challenges that face middle grade students, parents, and teachers is the student's lack of ownership of their academic achievements. Student-led conferences are a unique way to engage the student and the parent in the academic progress. Parents and teachers discuss the student's attitude toward the work, the student's work ethic in…

  9. LED Lighting in a Performing Arts Building

    Energy Technology Data Exchange (ETDEWEB)

    Miller, N. J.; Kaye, S. M. [Univ. of Florida, Gainesville, FL (United States); Coleman, P. M. [Univ. of Florida, Gainesville, FL (United States); Wilkerson, A. M.; Perrin, T. E.; Sullivan, G. P. [Efficiency Solutions, Inc., Richland, WA (United States)

    2014-07-31

    At the University of Florida in Gainesville, the DOE Solid-State Lighting GATEWAY program evaluated LED architectural and theatrical lighting in four academic/performance-related spaces within the Nadine McGuire Theatre + Dance Pavilion. Due to a wise choice of products and luminaire light distributions, the change brought significant quality improvements including improved controllability and color.

  10. Photobiocatalytic alcohol oxidation using LED light sources

    NARCIS (Netherlands)

    Rauch, M.C.R.; Schmidt, S.; Arends, I.W.C.E.; oppelt, K.; Kara, S; Hollmann, F.

    2016-01-01

    The photocatalytic oxidation of NADH using a flavin photocatalyst and a simple blue LED light source is reported. This in situ NAD+ regeneration system can be used to promote biocatalytic, enantioselective oxidation reactions. Compared to the traditional use of white light bulbs this method enables

  11. Electrical efficiency and droop in MQW LEDs

    Science.gov (United States)

    Malyutenko, V. K.

    2014-02-01

    It is believed that low power conversion efficiency in commercial MQW LEDs occurs as a result of efficiency droop, current-induced dynamic degradation of the internal quantum efficiency, injection efficiency, and extraction efficiency. Broadly speaking, all these "quenching" mechanisms could be referred to as the optical losses. The vast advances of high-power InGaN and AlGaInP MQW LEDs have been achieved by addressing these losses. In contrast to these studies, in this paper we consider an alternative approach to make high-power LEDs more efficient. We identify current-induced electrical efficiency degradation (EED) as a strong limiting factor of power conversion efficiency. We found that EED is caused by current crowding followed by an increase in current-induced series resistance of a device. By decreasing the current spreading length, EED also causes the optical efficiency to degrade and stands for an important aspect of LED performance. This paper gives scientists the opportunity to look for different attributes of EED.

  12. Effects of ketamine administration on mTOR and reticulum stress signaling pathways in the brain after the infusion of rapamycin into prefrontal cortex.

    Science.gov (United States)

    Abelaira, Helena M; Réus, Gislaine Z; Ignácio, Zuleide M; Dos Santos, Maria Augusta B; de Moura, Airam B; Matos, Danyela; Demo, Júlia P; da Silva, Júlia B I; Michels, Monique; Abatti, Mariane; Sonai, Beatriz; Dal Pizzol, Felipe; Carvalho, André F; Quevedo, João

    2017-04-01

    Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC. Male adult Wistar rats received pharmacological mTOR inhibitor, rapamycin (0.2 nmol), or vehicle into the PFC and then a single dose of ketamine (15 mg/kg, i.p.). The immunocontent of mTOR, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), eukaryotic elongation factor 2 kinase (eEF2K) homologous protein (CHOP), PKR-like ER kinase (PERK) and inositol-requiring enzyme 1 (IRE1) - alpha were determined in the brain. The mTOR levels were reduced in the rapamycin group treated with saline and ketamine in the PFC; p4EBP1 levels were reduced in the rapamycin group treated with ketamine in the PFC and nucleus accumbens; the levels of peEF2K were increased in the PFC in the vehicle group treated with ketamine and reduced in the rapamycin group treated with ketamine. The PERK and IRE1-alpha levels were decreased in the PFC in the rapamycin group treated with ketamine. Our results suggest that mTOR signaling inhibition by rapamycin could be involved, at least in part, with the mechanism of action of ketamine; and the ketamine antidepressant on ER stress pathway could be also mediated by mTOR signaling pathway in certain brain structures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Intrathecal administration of rapamycin inhibits the phosphorylation of DRG Nav1.8 and attenuates STZ-induced painful diabetic neuropathy in rats.

    Science.gov (United States)

    He, Wan-You; Zhang, Bin; Xiong, Qing-Ming; Yang, Cheng-Xiang; Zhao, Wei-Cheng; He, Jian; Zhou, Jun; Wang, Han-Bing

    2016-04-21

    The mammalian target of rapamycin (mTOR) is a key regulator of mRNA translation and protein synthesis, and it is specifically inhibited by rapamycin. In chronic pain conditions, mTOR-mediated local protein synthesis is crucial for neuronal hyperexcitability and synaptic plasticity. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 plays a major role in action potential initiation and propagation and cellular excitability in DRG (dorsal root ganglion) neurons. In this study, we investigated if mTOR modulates the phosphorylation of Nav1.8 that is associated with neuronal hyperexcitability and behavioral hypersensitivity in STZ-induced diabetic rats. Painful diabetic neuropathy (PDN) was induced in Sprague-Dawley rats by intraperitoneal injection with streptozotocin (STZ) at 60mg/kg. After the onset of PDN, the rats received daily intrathecal administrations of rapamycin (1μg, 3μg, or 10μg/day) for 7 days; other diabetic rats received the same volumes of dimethyl sulfoxide (DMSO). Herein, we demonstrate a marked increase in protein expression of total mTOR and phospho-mTOR (p-mTOR) together with the up-regulation of phosphor-Nav1.8 (p-Nav1.8) prior to the mechanical withdrawal threshold reaching a significant reduction in dorsal root ganglions (DRGs). Furthermore, the intrathecal administration of rapamycin, inhibiting the activity of mTOR, suppressed the phosphorylation of DRG Nav1.8, reduced the TTX-R current density, heightened the voltage threshold for activation and lowered the voltage threshold for inactivation and relieved mechanical hypersensitivity in diabetic rats. An intrathecal injection (i.t.) of rapamycin inhibited the phosphorylation and enhanced the functional availability of DRG Nav1.8 attenuated STZ-induced hyperalgesia. These results suggest that rapamycin is a potential therapeutic intervention for clinical PDN. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry

    Directory of Open Access Journals (Sweden)

    Maria Elena Maccari

    2018-03-01

    Full Text Available Activated phosphoinositide 3-kinase (PI3K δ Syndrome (APDS, caused by autosomal dominant mutations in PIK3CD (APDS1 or PIK3R1 (APDS2, is a heterogeneous primary immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical and immunological manifestations, questions about long-term disease evolution and response to therapy remain. The prospective European Society for Immunodeficiencies (ESID-APDS registry aims to characterize the disease course, identify outcome predictors, and evaluate treatment responses. So far, 77 patients have been recruited (51 APDS1, 26 APDS2. Analysis of disease evolution in the first 68 patients pinpoints the early occurrence of recurrent respiratory infections followed by chronic lymphoproliferation, gastrointestinal manifestations, and cytopenias. Although most manifestations occur by age 15, adult-onset and asymptomatic courses were documented. Bronchiectasis was observed in 24/40 APDS1 patients who received a CT-scan compared with 4/15 APDS2 patients. By age 20, half of the patients had received at least one immunosuppressant, but 2–3 lines of immunosuppressive therapy were not unusual before age 10. Response to rapamycin was rated by physician visual analog scale as good in 10, moderate in 9, and poor in 7. Lymphoproliferation showed the best response (8 complete, 11 partial, 6 no remission, while bowel inflammation (3 complete, 3 partial, 9 no remission and cytopenia (3 complete, 2 partial, 9 no remission responded less well. Hence, non-lymphoproliferative manifestations should be a key target for novel therapies. This report from the ESID-APDS registry provides comprehensive baseline documentation for a growing cohort that will be followed prospectively to establish prognostic factors and identify patients for treatment studies.

  15. A novel strategy inducing autophagic cell death in Burkitt's lymphoma cells with anti-CD19-targeted liposomal rapamycin

    International Nuclear Information System (INIS)

    Ono, K; Sato, T; Iyama, S; Tatekoshi, A; Hashimoto, A; Kamihara, Y; Horiguchi, H; Kikuchi, S; Kawano, Y; Takada, K; Hayashi, T; Miyanishi, K; Sato, Y; Takimoto, R; Kobune, M; Kato, J

    2014-01-01

    Relapsed or refractory Burkitt's lymphoma often has a poor prognosis in spite of intensive chemotherapy that induces apoptotic and/or necrotic death of lymphoma cells. Rapamycin (Rap) brings about autophagy, and could be another treatment. Further, anti-CD19-targeted liposomal delivery may enable Rap to kill lymphoma cells specifically. Rap was encapsulated by anionic liposome and conjugated with anti-CD19 antibody (CD19-GL-Rap) or anti-CD2 antibody (CD2-GL-Rap) as a control. A fluorescent probe Cy5.5 was also liposomized in the same way (CD19 or CD2-GL-Cy5.5) to examine the efficacy of anti-CD19-targeted liposomal delivery into CD19-positive Burkitt's lymphoma cell line, SKW6.4. CD19-GL-Cy5.5 was more effectively uptaken into SKW6.4 cells than CD2-GL-Cy5.5 in vitro. When the cells were inoculated subcutaneously into nonobese diabetic/severe combined immunodeficiency mice, intravenously administered CD19-GL-Cy5.5 made the subcutaneous tumor fluorescent, while CD2-GL-Cy5.5 did not. Further, CD19-GL-Rap had a greater cytocidal effect on not only SKW6.4 cells but also Burkitt's lymphoma cells derived from patients than CD2-GL-Rap in vitro. The specific toxicity of CD19-GL-Rap was cancelled by neutralizing anti-CD19 antibody. The survival period of mice treated with intravenous CD19-GL-Rap was significantly longer than that of mice treated with CD2-GL-Rap after intraperitoneal inoculation of SKW6.4 cells. Anti-CD19-targeted liposomal Rap could be a promising lymphoma cell-specific treatment inducing autophagic cell death

  16. Targeting the phosphatidylinositol 3-kinase/Akt/mechanistic target of rapamycin signaling pathway in B-lineage acute lymphoblastic leukemia: An update.

    Science.gov (United States)

    Simioni, Carolina; Martelli, Alberto M; Zauli, Giorgio; Vitale, Marco; McCubrey, James A; Capitani, Silvano; Neri, Luca M

    2018-04-18

    Despite considerable progress in treatment protocols, B-lineage acute lymphoblastic leukemia (B-ALL) displays a poor prognosis in about 15-20% of pediatric cases and about 60% of adult patients. In addition, life-long irreversible late effects from chemo- and radiation therapy, including secondary malignancies, are a growing problem for leukemia survivors. Targeted therapy holds promising perspectives for cancer treatment as it may be more effective and have fewer side effects than conventional therapies. The phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) signaling pathway is a key regulatory cascade which controls proliferation, survival and drug-resistance of cancer cells, and it is frequently upregulated in the different subtypes of B-ALL, where it plays important roles in the pathophysiology, maintenance and progression of the disease. Moreover, activation of this signaling cascade portends a poorer prognosis in both pediatric and adult B-ALL patients. Promising preclinical data on PI3K/Akt/mTOR inhibitors have documented their anticancer activity in B-ALL and some of these novel drugs have entered clinical trials as they could lead to a longer event-free survival and reduce therapy-associated toxicity for patients with B-ALL. This review highlights the current status of PI3K/Akt/mTOR inhibitors in B-ALL, with an emphasis on emerging evidence of the superior efficacy of synergistic combinations involving the use of traditional chemotherapeutics or other novel, targeted agents. © 2018 Wiley Periodicals, Inc.

  17. Enhanced genetic modification of adult growth factor mobilized peripheral blood hematopoietic stem and progenitor cells with rapamycin.

    Science.gov (United States)

    Li, Lijing; Torres-Coronado, Mónica; Gu, Angel; Rao, Anitha; Gardner, Agnes M; Epps, Elizabeth W; Gonzalez, Nancy; Tran, Chy-Anh; Wu, Xiwei; Wang, Jin-Hui; DiGiusto, David L

    2014-10-01

    Genetic modification of adult human hematopoietic stem and progenitor cells (HSPCs) with lentiviral vectors leads to long-term gene expression in the progeny of the HSPCs and has been used to successfully treat several monogenic diseases. In some cases, the gene-modified cells have a selective growth advantage over nonmodified cells and eventually are the dominant engrafted population. However, in disease indications for which the gene-modified cells do not have a selective advantage, optimizing transduction of HSPC is paramount to successful stem cell-based gene therapy. We demonstrate here that transduction of adult CD34+ HSPCs with lentiviral vectors in the presence of rapamycin, a widely used mTORC1 inhibitor, results in an approximately threefold increase in stable gene marking with minimal effects on HSPC growth and differentiation. Using this approach, we have demonstrated that we can enhance the frequency of gene-modified HSPCs that give rise to clonogenic progeny in vitro without excessive increases in the number of vector copies per cell or changes in integration pattern. The genetic marking of HSPCs and expression of transgenes is durable, and transplantation of gene-modified HSPCs into immunodeficient mice results in high levels of gene marking of the lymphoid and myeloid progeny in vivo. The prior safe clinical history of rapamycin in other applications supports the use of this compound to generate gene-modified autologous HSPCs for our HIV gene therapy clinical trials. ©AlphaMed Press.

  18. The crosstalk between Target of Rapamycin (TOR) and Jasmonic Acid (JA) signaling existing in Arabidopsis and cotton.

    Science.gov (United States)

    Song, Yun; Zhao, Ge; Zhang, Xueyan; Li, Linxuan; Xiong, Fangjie; Zhuo, Fengping; Zhang, Chaojun; Yang, Zuoren; Datla, Raju; Ren, Maozhi; Li, Fuguang

    2017-04-04

    Target of rapamycin (TOR) acts as an important regulator of cell growth, development and stress responses in most examined diploid eukaryotes. However, little is known about TOR in tetraploid species such as cotton. Here, we show that TORC1-S6K-RPS6, the major signaling components, are conserved and further expanded in cotton genome. Though the cotton seedlings are insensitive to rapamycin, AZD8055, the second-generation inhibitor of TOR, can significantly suppress the growth in cotton. Global transcriptome analysis revealed that genes associated with jasmonic acid (JA) biosynthesis and transduction were significantly altered in AZD8055 treated cotton seedlings, suggesting the potential crosstalk between TOR and JA signaling. Pharmacological and genetic approaches have been employed to get further insights into the molecular mechanism of the crosstalk between TOR and JA. Combination of AZD8055 with methyl jasmonate can synergistically inhibit cotton growth, and additionally JA levels were significantly increased when cotton seedlings were subjected to AZD8055. JA biosynthetic and signaling mutants including jar1, coi1-2 and myc2-2 displayed TOR inhibitor-resistant phenotypes, whereas COI1 overexpression transgenic lines and jaz10 exhibited sensitivity to AZD8055. Consistently, cotton JAZ can partially rescue TOR-suppressed phenotypes in Arabidopsis. These evidences revealed that the crosstalk between TOR and JA pathway operates in cotton and Arabidopsis.

  19. Perceived Learning Effectiveness of a Course Facebook Page: Teacher-Led versus Student-Led Approach

    Science.gov (United States)

    Tugrul, Tugba Orten

    2017-01-01

    This research aims to compare the perceived effectiveness of teacher-led and student-led content management approaches embraced in a course Facebook page designed to enhance traditional classroom learning. Eighty-five undergraduate marketing course students voluntarily completed a questionnaire composed of two parts; a depiction of a course…

  20. CooLED - efficient LED bulbs with custrom optics - final report

    DEFF Research Database (Denmark)

    Wolff, Jesper; Corell, Dennis Dan; Dam-Hansen, Carsten

    Denne rapport indeholder en beskrivelse af arbejdet udført i og resultaterne af forsknings- og udviklingsprojektet EUDP 64012-0226, CooLED – en ny generation LED Lyskilde for det tidsløse high-end marked....

  1. Sustainable LED Fluorescent Light Replacement Technology

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2011-09-30

    Ilumisys and the National Center for Manufacturing Sciences (NCMS) partnered on a three-year project awarded by the United States (U.S.) Department of Energy (DOE), to quantify the impacts of LED lamps, incandescent lamps and fluorescent benchmark lamps over a product lifecycle – i.e. to develop a sustainable design and manufacturing strategy that addresses product manufacturing, use, recycling and disposal scenarios for LED-based lighting. Based on the knowledge gained from extensive product tear-down studies of fluorescent and screw-in lighting products, lifecycle assessment tools, and accelerated lifecycle testing protocols, an interactive Sustainable LED Design Guide has been developed to aid architectural and lighting designers and engineers in making design decisions that consider three important environmental impacts (greenhouse gas emissions, energy use and mercury emission) across all phases of the life of an LED lighting product. Critical information developed for the lifecycle analysis and product feature comparisons is the useful life of the lighting product as well as its performance. The Design Guide is available at www.ncms.org, and was developed based on operational and durability testing of a variety of lighting products including power consumption, light output, and useful life of a lamp in order to allow a more realistic comparison of lamp designs. This report describes the main project tasks, results and innovative features of the lifecycle assessment (LCA)-based design tools, and the key considerations driving the sustainable design of LED lighting systems. The Design Guide incorporates the following three novel features for efficiently evaluating LED lighting features in value-chains: Bill-of-Materials (BOM) Builder – Designers may import process data for each component and supply functional data for the product, including power, consumption, lumen output and expected useful life: Environmental Impact Review – Designs are comparable

  2. LED i Københavns Kommunes gadebelysning

    DEFF Research Database (Denmark)

    Bülow, Katja

    2016-01-01

    Artiklen i denne udgivelse formidler resultatet af en undersøgelse, hvor de visuelle forhold i Københavns Kommunes gader undersøges som resultat af gadens belysning. Der lægges vægt på metoden bag undersøgelsen og på hvordan indførelsen af LED forandrer belysningen i gaderne.......Artiklen i denne udgivelse formidler resultatet af en undersøgelse, hvor de visuelle forhold i Københavns Kommunes gader undersøges som resultat af gadens belysning. Der lægges vægt på metoden bag undersøgelsen og på hvordan indførelsen af LED forandrer belysningen i gaderne....

  3. EVALUATING THE CULTURE-LED REGENERATION

    Directory of Open Access Journals (Sweden)

    D'Angelo Francesca

    2010-12-01

    Full Text Available The aim of the paper is to propose a new approach to urban planning, evaluating the culture-led regeneration processes. In the last few years, the cultural turn in urban planning played a central role in the urban studies. In this way we try to elaborate a more robust perspective interpreting the complex phenomenology emerging from the culture-led regeneration processes. Within the concept of complexity we discuss about the metabolic process that are the processes necessary to transform energy, material and information in goods and service functional to the complex urban system life. The approach that will be employed is the MuSIASEM that is based on several novel concept and an innovative methods never applied in this research field.

  4. Uniform LED illuminator for miniature displays

    Science.gov (United States)

    Medvedev, Vladimir; Pelka, David G.; Parkyn, William A.

    1998-10-01

    The Total Internally Reflecting (TIR) lens is a faceted structure composed of prismatic elements that collect a source's light over a much larger angular range than a conventional Fresnel lens. It has been successfully applied to the efficient collimation of light from incandescent and fluorescent lamps, and from light-emitting diodes (LEDs). A novel LED-powered collimating backlight is presented here, for uniformly illuminating 0.25'-diagonal miniature liquid- crystal displays, which are a burgeoning market for pagers, cellular phones, digital cameras, camcorders, and virtual- reality displays. The backlight lens consists of a central dual-asphere refracting section and an outer TIR section, properly curved with a curved exit face.

  5. Notes on LED Installations in Street Illumination

    Directory of Open Access Journals (Sweden)

    Elisabeta Spunei

    2014-09-01

    Full Text Available The paper presents a study made on choosing LED street lighting installations, such that the quality requirements for exterior artificial lighting are fulfilled. We analyze two types of LED street lighting installations from a technical point of view, together with lighting level and brightness values obtained during the measurements. Following on the field measurements, the lighting quality parameters are calculated, and, for the lighting installation with the best performance, optimal mounting suggestions are made. The optimal quality parameters are calculated by simulations using the Dialux software. The same software and the same light sources we also compute an optimal street lighting by determining the size of the installation that provides the best lighting parameter values.

  6. Optical design of a LED searchlight system

    Science.gov (United States)

    Gong, Chen; Xu, Haiping; Liang, Jinhua; Liu, Yunfei; Yuan, Zengquan

    2018-01-01

    A 1200m visible searchlight system is designed based on photometry and application of geometric optics. To generate intensity distribution of this relatively powerful light beam we propose to use a high power LED and several refractive optical elements, which are composed of two plane-convex lenses and a conventional Fresnel lens. Two plane-convex lenses enable refraction of the side rays from the LED to the front direction which incident on the Fresnel lens. Fresnel lens, in its turn, concentrate the light flux and provide a nearly collimated beam to meet the requirement of forming a well-illuminated area across the road in the far field. Simulation data shows that this searchlight allow generating an appropriate illumination distribution for the long range requirements. A proof-of-concept prototype producing acceptable illuminance is developed.

  7. Weaknesses of 'wage-led growth'

    OpenAIRE

    Skott, Peter

    2016-01-01

    The emphasis in post-Keynesian macroeconomics on wage- versus profit- led growth may not have been helpful. The profit share is not an exogenous variable, and the correlations between the pro.t share and economic growth can be positive for some exogenous shocks but negative for others. The terminology, second, suggests a unidirectional causality from distribution to aggregate demand while in fact distribution can itself be directly affected by shifts in aggregate demand. The reduced form corr...

  8. Etude par génétique inverse du gène codant la protéine TARGET OF RAPAMYCIN d'Arabidopsis thaliana (AtTOR), l'homologue d'une kinase contrôlant la croissance cellulaire chez les eucaryotes

    OpenAIRE

    Menand, Benoit

    2002-01-01

    TOR (target of rapamycin) protein kinases were identified in yeast, mammals and Drosophila as central controllers of cell growth. Thu, G1 to S phases progression through the cell cycle is blocked by rapamycin, a drug which specifically inhibits TOR activity by forming a ternary complex with the peptidyl-prolyl isomerase FKBP12 (FK506 and rapamycin binding protein), and the FKBP-rapamycin binding domain (FRB) of TOR proteins. This work presents the study, the Arabidopsis homologue of yeast and...

  9. Light out-coupling from LEDs by means of metal nanoparticles; Lichtauskopplung aus LEDs mittels Metallnanoteilchen

    Energy Technology Data Exchange (ETDEWEB)

    Goehler, Tino

    2010-12-17

    The external quantum efficiency of light-emitting diodes (LEDs) based on Al- GaAs/InGaAlP is limited by total internal reflection because of the high refractive index (typically between 3 and 4) of the semiconductor. Metal nanoparticles (MNP) deposited on the surface of the LED can be used as dipole scatterers in order to enhance the emission of the LED. In this thesis, first, single gold nanoparticles of various sizes deposited on such an LED were investigated. A clear enhancement is detected as long as the dipole plasmon resonance of the particle is at a shorter wavelength than the LED emission. If the plasmon resonance coincides with the LED emission or is at a larger wavelength, the enhancement turns into suppression. Numerical simulations indicate that this latter effect is mainly caused by the particle quadrupole resonance producing extra absorption. Arrays of MNPs can be produced by a special mask technique called ''Fischer pattern nanolithography'' and manipulated in shape and size by additional steps. Originally, the MNPs produced by this technique are triangular in shape and turn out to suppress the LED emission. After transformation of the particles to spheres, a clear enhancement was detected. Light that would otherwise remain trapped inside the substrate is coupled out by resonant plasmonic scattering. Investigations on analogous structures on a transparent high-index material (GaP) indicate a stronger coupling between the particles than expected on the basis of literature data. (orig.)

  10. Plant growth regulation by the light of LEDs; LED ko wo tsukatta shokubutsu saibai gijutsu

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, H. [Mitsubishi Chemical Co., Tokyo (Japan). Yokohama Research Center

    1996-03-01

    Light Emitting Diode (LED) has not only an excellent display function for the luminescent device but also a superior feature without other lamps as light source for plant growth. It was National Aeronautics and Space Administration (NASA) to find out such merit for this light source for plant growth and try at first to use for plant growth at the space. They began to examine the LED application to the light source for the plant growth at the space since a stage at high cost of the LED, to develop some researches centered at cultivation of lettuce, wheat, and others. Finding out future possibility of cost-down of the LEDs on the cost/performance and large merits of the LEDs for control of the plant growth and plant physiology, authors have conducted some cultivation experiments of the plants using the LEDs for light source some years ago. In this papers, characterizations, actual possibility, and future developments of the LEDs for the light sources of the plant growth, are introduced. 5 refs., 4 figs.

  11. A new approach to preparation of standard LEDs for luminous intensity and flux measurement of LEDs

    Science.gov (United States)

    Park, Seung-Nam; Park, Seongchong; Lee, Dong-Hoon

    2006-09-01

    This work presents an alternative approach for preparing photometric standard LEDs, which is based on a novel functional seasoning method. The main idea of our seasoning method is simultaneously monitoring the light output and the junction voltage to obtain quantitative information on the temperature dependence and the aging effect of the LED emission. We suggested a general model describing the seasoning process by taking junction temperature variation and aging effect into account and implemented a fully automated seasoning facility, which is capable of seasoning 12 LEDs at the same time. By independent measurements of the temperature dependence, we confirmed the discrepancy of the theoretical model to be less than 0.5 % and evaluate the uncertainty contribution of the functional seasoning to be less than 0.5 % for all the seasoned samples. To demonstrate assigning the reference value to a standard LED, the CIE averaged LED intensity (ALI) of the seasoned LEDs was measured with a spectroradiometer-based instrument and the measurement uncertainty was analyzed. The expanded uncertainty of the standard LED prepared by the new approach amounts to be 4 % ~ 5 % (k=2) depending on color without correction of spectral stray light in the spectroradiometer.

  12. Lifetime prediction of LED lighting systems considering thermal coupling between LED sources and drivers

    DEFF Research Database (Denmark)

    Alfarog, Azzarn Orner; Qu, Xiaohui; Wang, Huai

    2017-01-01

    and accelerate the failure. In this paper, a new thermal model concerning the thermal coupling is proposed with Finite Element Method (FEM) simulation for parameter acquirement. The proposed model has a better estimation of the thermal stresses of key components in the LED lamps and therefore an improved...... separately, and then the thermal design is also optimized independently. In practice, the LED source and driver are usually compacted in a single fixture. The heat dissipated from LED source and driver will be coupled together and affect the heat transfer performance, which may degrade the whole system...

  13. mTORC1 activity as a determinant of cancer risk--rationalizing the cancer-preventive effects of adiponectin, metformin, rapamycin, and low-protein vegan diets.

    Science.gov (United States)

    McCarty, Mark F

    2011-10-01

    Increased plasma levels of adiponectin, metformin therapy of diabetes, rapamycin administration in transplant patients, and lifelong consumption of low-protein plant-based diets have all been linked to decreased risk for various cancers. These benefits may be mediated, at least in part, by down-regulated activity of the mTORC1 complex, a key regulator of protein translation. By boosting the effective availability of the translation initiator eIF4E, mTORC1 activity promotes the translation of a number of "weak" mRNAs that code for proteins, often up-regulated in cancer, that promote cellular proliferation, invasiveness, and angiogenesis, and that abet cancer promotion and chemoresistance by opposing apoptosis. Measures which inhibit eIF4E activity, either directly or indirectly, may have utility not only for cancer prevention, but also for the treatment of many cancers in which eIF4E drives malignancy. Since eIF4E is overexpressed in many cancers, strategies which target eIF4E directly--some of which are now being assessed clinically--may have the broadest efficacy in this regard. Many of the "weak" mRNAs coding for proteins that promote malignant behavior or chemoresistance are regulated transcriptionally by NF-kappaB and/or Stat3, which are active in a high proportion of cancers; thus, regimens concurrently targeting eIF4E, NF-kappaB, and Stat3 may suppress these proteins at both the transcriptional and translational levels, potentially achieving a very marked reduction in their expression. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Transcranial LED therapy for cognitive dysfunction in chronic, mild traumatic brain injury: two case reports

    Science.gov (United States)

    Naeser, Margaret A.; Saltmarche, Anita; Krengel, Maxine H.; Hamblin, Michael R.; Knight, Jeffrey A.

    2010-02-01

    Two chronic, traumatic brain injury (TBI) cases are presented, where cognitive function improved following treatment with transcranial light emitting diodes (LEDs). At age 59, P1 had closed-head injury from a motor vehicle accident (MVA) without loss of consciousness and normal MRI, but unable to return to work as development specialist in internet marketing, due to cognitive dysfunction. At 7 years post-MVA, she began transcranial LED treatments with cluster heads (2.1" diameter with 61 diodes each - 9x633nm, 52x870nm; 12-15mW per diode; total power, 500mW; 22.2 mW/cm2) on bilateral frontal, temporal, parietal, occipital and midline sagittal areas (13.3 J/cm2 at scalp, estimated 0.4 J/cm2 to brain cortex per area). Prior to transcranial LED, focused time on computer was 20 minutes. After 2 months of weekly, transcranial LED treatments, increased to 3 hours on computer. Performs nightly home treatments (now, 5 years, age 72); if stops treating >2 weeks, regresses. P2 (age 52F) had history of closed-head injuries related to sports/military training and recent fall. MRI shows fronto-parietal cortical atrophy. Pre-LED, was not able to work for 6 months and scored below average on attention, memory and executive function. Performed nightly transcranial LED treatments at home (9 months) with similar LED device, on frontal and parietal areas. After 4 months of LED treatments, returned to work as executive consultant, international technology consulting firm. Neuropsychological testing (post- 9 months of transcranial LED) showed significant improvement in memory and executive functioning (range, +1 to +2 SD improvement). Case 2 reported reduction in PTSD symptoms.

  15. Perceived learning effectiveness of a course Facebook page: teacher-led versus student-led approach

    Directory of Open Access Journals (Sweden)

    Tugba Orten Tugrul

    2017-01-01

    Full Text Available This research aims to compare the perceived effectiveness of teacher -led and student-led content management approaches embraced in a course Facebook page designed to enhance traditional classroom learning. Eighty-five undergraduate marketing course students voluntarily completed a questionnaire composed of two parts; a depiction of a course Facebook page where both teacher and students can share instructional contents, and questions about perceived learning effectiveness. The findings indicate that students have more favorable evaluations of a student-led approach in sharing instructional contents on a course Facebook Page than a teacher-led approach. Additionally, it is shown that instructional contents posted by both teacher and students enhance the overall learning effectiveness of a course Facebook page incorporated into a traditional classroom teaching.

  16. SUMO modification through rapamycin-mediated heterodimerization reveals a dual role for Ubc9 in targeting RanGAP1 to nuclear pore complexes

    International Nuclear Information System (INIS)

    Zhu Shanshan; Zhang Hong; Matunis, Michael J.

    2006-01-01

    SUMOs (small ubiquitin-related modifiers) are eukaryotic proteins that are covalently conjugated to other proteins and thereby regulate a wide range of important cellular processes. The molecular mechanisms by which SUMO modification influences the functions of most target proteins and cellular processes, however, remain poorly defined. A major obstacle to investigating the effects of SUMO modification is the availability of a system for selectively inducing the modification or demodification of an individual protein. To address this problem, we have developed a procedure using the rapamycin heterodimerizer system. This procedure involves co-expression of rapamycin-binding domain fusion proteins of SUMO and candidate SUMO substrates in living cells. Treating cells with rapamycin induces a tight association between SUMO and a single SUMO substrate, thereby allowing specific downstream effects to be analyzed. Using RanGAP1 as a model SUMO substrate, the heterodimerizer system was used to investigate the molecular mechanism by which SUMO modification targets RanGAP1 from the cytoplasm to nuclear pore complexes (NPCs). Our results revealed a dual role for Ubc9 in targeting RanGAP1 to NPCs: In addition to conjugating SUMO-1 to RanGAP1, Ubc9 is also required to form a stable ternary complex with SUMO-1 modified RanGAP1 and Nup358. As illustrated by our studies, the rapamycin heterodimerizer system represents a novel tool for studying the molecular effects of SUMO modification

  17. Sustained activation of the mammalian target of rapamycin nutrient sensing pathway is associated with hepatic insulin resistance, but not with steatosis, in mice

    NARCIS (Netherlands)

    Korsheninnikova, E.; van der Zon, G. C. M.; Voshol, P. J.; Janssen, G. M.; Havekes, L. M.; Grefhorst, A.; Kuipers, F.; Reijngoud, D. -J.; Romijn, J. A.; Ouwens, D. M.; Maassen, J. A.

    2006-01-01

    Aims/hypothesis Activation of nutrient sensing through mammalian target of rapamycin (mTOR) has been linked to the pathogenesis of insulin resistance. We examined activation of mTOR-signalling in relation to insulin resistance and hepatic steatosis in mice. Materials and methods Chronic hepatic

  18. Sustained activation of the mammalian target of rapamycin nutrient sensing pathway is associated with hepatic insulin resistance, but not with steatosis, in mice

    NARCIS (Netherlands)

    Korsheninnikova, E.; van der Zon, G. C. M.; Voshol, P. J.; Janssen, G. M.; Havekes, L. M.; Grefhorst, A.; Kuipers, F.; Reijngoud, D.-J.; Romijn, J. A.; Ouwens, D. M.; Maassen, J. A.

    2006-01-01

    Activation of nutrient sensing through mammalian target of rapamycin (mTOR) has been linked to the pathogenesis of insulin resistance. We examined activation of mTOR-signalling in relation to insulin resistance and hepatic steatosis in mice. Chronic hepatic steatosis and hepatic insulin resistance

  19. Are nurse-led chemotherapy clinics really nurse-led? : an ethnographic study

    OpenAIRE

    Farrell, Carole; Walshe, Catherine Elizabeth; Molassiotis, Alex

    2017-01-01

    Background: The number of patients requiring ambulatory chemotherapy is increasing year on year, creating problems with capacity in outpatient clinics and chemotherapy units. Although nurse-led chemotherapy clinics have been set up to address this, there is a lack of evaluation of their effectiveness. Despite a rapid expansion in the development of nursing roles and responsibilities in oncology, there is little understanding of the operational aspects of nurses’ roles in nurse-led clinics. Ob...

  20. Moral Issues in Intelligence-led Policing

    DEFF Research Database (Denmark)

    The core baseline of Intelligence-led Policing is the aim of increasing efficiency and quality of police work, with a focus on crime analysis and intelligence methods as tools for informed and objective decisions both when conducting targeted, specialized operations and when setting strategic...... technological measures, increased private partnerships and international cooperation challenging the core nature of police services as the main providers of public safety and security? This book offers new insights by exploring dilemmas, legal issues and questions raised by the use of new policing methods...

  1. LED-technologies for bright light therapy

    Science.gov (United States)

    Kukhta, M. S.; Sidorenko, E. V.; Simutkin, G. G.; Khomushku, O. M.; Glushkov, G. S.

    2018-05-01

    The significance of the LED-based medical equipment design is caused by the need to make up for the sunshine shortfall in many areas of Russia (Siberia, the Far East, the Extreme North) that will allow reducing dramatically the risk of seasonal affective disorders. The sunshine is the essential synchronizer of the human biological rhythms, the abnormality of which plays an important role in the seasonal affective disorder nature. The study allows proving the object database development able to meet the human demand for a comfortable and high-quality placemaking as well as the health potential recoverability.

  2. Someone Has Led This Child To Believe

    OpenAIRE

    Louise, Regina

    2015-01-01

    ABSTRACTSOMEONE HAS LED THIS CHILD TO BELIEVE is a true story and continuation of the best-selling memoir Somebody’s Someone. After 12 year-old Regina Louise, tired of being beaten, battles and escapes an illegal guardian; she jumps from a two-story window and runs to a local police station where she is taken into custody, locked in a holding cell, and delivered to the Edgar Children’s Shelter, in Martinez California. Regina is closed off about her parents, her past…until she meets Jeanne Ke...

  3. Signal processing for LED lighting systems : illumination rendering and sensing

    NARCIS (Netherlands)

    Yang, H.

    2010-01-01

    Solid state lighting, employing high brightness light emitting diodes (LEDs), is becoming increasingly widely used. The advantages of LEDs include high radiative efficiency, long lifetime, limited heat generation and superior tolerance to humidity. Another important advantage of LED lighting systems

  4. Dysplasia and overgrowth. Magnetic resonance imaging of pediatric brain abnormalities secondary to alterations in the mechanistic target of rapamycin pathway

    Energy Technology Data Exchange (ETDEWEB)

    Shrot, Shai [Johns Hopkins University School of Medicine, Division of Pediatric Radiology and Pediatric Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Sheba Medical Center, Department of Diagnostic Imaging, Ramat-Gan (Israel); Hwang, Misun; Huisman, Thierry A.G.M.; Soares, Bruno P. [Johns Hopkins University School of Medicine, Division of Pediatric Radiology and Pediatric Neuroradiology, Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Stafstrom, Carl E. [Johns Hopkins University School of Medicine, Division of Pediatric Neurology, Department of Neurology, Baltimore, MD (United States)

    2018-02-15

    The current classification of malformations of cortical development is based on the type of disrupted embryological process (cell proliferation, migration, or cortical organization/post-migrational development) and the resulting morphological anomalous pattern of findings. An ideal classification would include knowledge of biological pathways. It has recently been demonstrated that alterations affecting the mechanistic target of rapamycin (mTOR) signaling pathway result in diverse abnormalities such as dysplastic megalencephaly, hemimegalencephaly, ganglioglioma, dysplastic cerebellar gangliocytoma, focal cortical dysplasia type IIb, and brain lesions associated with tuberous sclerosis. We review the neuroimaging findings in brain abnormalities related to alterations in the mTOR pathway, following the emerging trend from morphology towards genetics in the classification of malformations of cortical development. This approach improves the understanding of anomalous brain development and allows precise diagnosis and potentially targeted therapies that may regulate mTOR pathway function. (orig.)

  5. Dysplasia and overgrowth. Magnetic resonance imaging of pediatric brain abnormalities secondary to alterations in the mechanistic target of rapamycin pathway

    International Nuclear Information System (INIS)

    Shrot, Shai; Hwang, Misun; Huisman, Thierry A.G.M.; Soares, Bruno P.; Stafstrom, Carl E.

    2018-01-01

    The current classification of malformations of cortical development is based on the type of disrupted embryological process (cell proliferation, migration, or cortical organization/post-migrational development) and the resulting morphological anomalous pattern of findings. An ideal classification would include knowledge of biological pathways. It has recently been demonstrated that alterations affecting the mechanistic target of rapamycin (mTOR) signaling pathway result in diverse abnormalities such as dysplastic megalencephaly, hemimegalencephaly, ganglioglioma, dysplastic cerebellar gangliocytoma, focal cortical dysplasia type IIb, and brain lesions associated with tuberous sclerosis. We review the neuroimaging findings in brain abnormalities related to alterations in the mTOR pathway, following the emerging trend from morphology towards genetics in the classification of malformations of cortical development. This approach improves the understanding of anomalous brain development and allows precise diagnosis and potentially targeted therapies that may regulate mTOR pathway function. (orig.)

  6. Role of adenosine 5'-monophosphate-activated protein kinase subunits in skeletal muscle mammalian target of rapamycin signaling

    DEFF Research Database (Denmark)

    Deshmukh, Atul S.; Treebak, Jonas Thue; Long, Yun Chau

    2008-01-01

    AMP-activated protein kinase (AMPK) is an important energy-sensing protein in skeletal muscle. Mammalian target of rapamycin (mTOR) mediates translation initiation and protein synthesis through ribosomal S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). AMPK...... activation reduces muscle protein synthesis by down-regulating mTOR signaling, whereas insulin mediates mTOR signaling via Akt activation. We hypothesized that AMPK-mediated inhibitory effects on mTOR signaling depend on catalytic alpha2 and regulatory gamma3 subunits. Extensor digitorum longus muscle from...... (Thr37/46) (P mTOR targets, suggesting mTOR signaling is blocked by prior AMPK activation. The AICAR-induced inhibition was partly rescued...

  7. Studying Light Color using White LED Lighting

    Science.gov (United States)

    Yamagishi, Misako; Yamaba, Kazuo; Nagata, Manori; Kubo, Chiho; Nokura, Kunihiro

    Recently, white Light Emitting Diodes (LEDs) are receiving attention worldwide as new lighting devices. This study examined effects of a lighting application on performance using white LEDs. The light color—the correlated color temperature (CCT) —was assessed. It affected to psychological states and physiological conditions. Three CCT conditions were respectively set for the experiment: 2500 K, 5000 K, and 8200 K. In all, 20 younger subjects (20-30 years old), 15 middle-aged to elderly subjects (45-60 years old) and 12 elderly subjects (over 65 years-old) participated. They were presented a Numerical Verification (NV) task for performance measurement. The psychological states on performance were evaluated using the lighting assessment questionnaire. The physiological conditions were recorded using an electrocardiograph. Results show that the effects of CCT differ among age groups. Especially, the performance of younger subjects might differ from CCT conditions; elderly subjects are affected by CCT condition because of their visual acuity or response to contrast of objects.

  8. LED Context Lighting System in Residential Areas

    Directory of Open Access Journals (Sweden)

    Sook-Youn Kwon

    2014-01-01

    Full Text Available As issues of environment and energy draw keen interest around the globe due to such problems as global warming and the energy crisis, LED with high optical efficiency is brought to the fore as the next generation lighting. In addition, as the national income level gets higher and life expectancy is extended, interest in the enhancement of life quality is increasing. Accordingly, the trend of lightings is changing from mere adjustment of light intensity to system lighting in order to enhance the quality of one’s life as well as reduce energy consumption. Thus, this study aims to design LED context lighting system that automatically recognizes the location and acts of a user in residential areas and creates an appropriate lighting environment. The proposed system designed in this study includes three types of processing: first, the creation of a lighting environment index suitable for the user’s surroundings and lighting control scenarios and second, it measures and analyzes the optical characteristics that change depending on the dimming control of lighting and applies them to the index. Lastly, it adopts PIR, piezoelectric, and power sensor to grasp the location and acts of the user and create a lighting environment suitable for the current context.

  9. Rapamycin and chloroquine: the in vitro and in vivo effects of autophagy-modifying drugs show promising results in valosin containing protein multisystem proteinopathy.

    Directory of Open Access Journals (Sweden)

    Angèle Nalbandian

    Full Text Available Mutations in the valosin containing protein (VCP gene cause hereditary Inclusion body myopathy (hIBM associated with Paget disease of bone (PDB, frontotemporal dementia (FTD, more recently termed multisystem proteinopathy (MSP. Affected individuals exhibit scapular winging and die from progressive muscle weakness, and cardiac and respiratory failure, typically in their 40s to 50s. Histologically, patients show the presence of rimmed vacuoles and TAR DNA-binding protein 43 (TDP-43-positive large ubiquitinated inclusion bodies in the muscles. We have generated a VCPR155H/+ mouse model which recapitulates the disease phenotype and impaired autophagy typically observed in patients with VCP disease. Autophagy-modifying agents, such as rapamycin and chloroquine, at pharmacological doses have previously shown to alter the autophagic flux. Herein, we report results of administration of rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR signaling pathway, and chloroquine, a lysosomal inhibitor which reverses autophagy by accumulating in lysosomes, responsible for blocking autophagy in 20-month old VCPR155H/+ mice. Rapamycin-treated mice demonstrated significant improvement in muscle performance, quadriceps histological analysis, and rescue of ubiquitin, and TDP-43 pathology and defective autophagy as indicated by decreased protein expression levels of LC3-I/II, p62/SQSTM1, optineurin and inhibiting the mTORC1 substrates. Conversely, chloroquine-treated VCPR155H/+ mice revealed progressive muscle weakness, cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies and increased LC3-I/II, p62/SQSTM1, and optineurin expression levels. Our in vitro patient myoblasts studies treated with rapamycin demonstrated an overall improvement in the autophagy markers. Targeting the mTOR pathway ameliorates an increasing list of disorders, and these findings suggest that VCP disease and related neurodegenerative multisystem

  10. Inhibition of Mammalian Target of Rapamycin Complex 1 Attenuates Salt-Induced Hypertension and Kidney Injury in Dahl Salt-Sensitive Rats.

    Science.gov (United States)

    Kumar, Vikash; Wollner, Clayton; Kurth, Theresa; Bukowy, John D; Cowley, Allen W

    2017-10-01

    The goal of the present study was to explore the protective effects of mTORC1 (mammalian target of rapamycin complex 1) inhibition by rapamycin on salt-induced hypertension and kidney injury in Dahl salt-sensitive (SS) rats. We have previously demonstrated that H 2 O 2 is elevated in the kidneys of SS rats. The present study showed a significant upregulation of renal mTORC1 activity in the SS rats fed a 4.0% NaCl for 3 days. In addition, renal interstitial infusion of H 2 O 2 into salt-resistant Sprague Dawley rats for 3 days was also found to stimulate mTORC1 activity independent of a rise of arterial blood pressure. Together, these data indicate that the salt-induced increases of renal H 2 O 2 in SS rats activated the mTORC1 pathway. Daily administration of rapamycin (IP, 1.5 mg/kg per day) for 21 days reduced salt-induced hypertension from 176.0±9.0 to 153.0±12.0 mm Hg in SS rats but had no effect on blood pressure salt sensitivity in Sprague Dawley treated rats. Compared with vehicle, rapamycin reduced albumin excretion rate in SS rats from 190.0±35.0 to 37.0±5.0 mg/d and reduced the renal infiltration of T lymphocytes (CD3 + ) and macrophages (ED1 + ) in the cortex and medulla. Renal hypertrophy and cell proliferation were also reduced in rapamycin-treated SS rats. We conclude that enhancement of intrarenal H 2 O 2 with a 4.0% NaCl diet stimulates the mTORC1 pathway that is necessary for the full development of the salt-induced hypertension and kidney injury in the SS rat. © 2017 American Heart Association, Inc.

  11. Patient-led versus physician-led titration of insulin glargine in patients with uncontrolled type 2 diabetes: a randomized multinational ATLAS study.

    Science.gov (United States)

    Garg, Satish K; Admane, Karim; Freemantle, Nick; Odawara, Masato; Pan, Chang-Yu; Misra, Anoop; Jarek-Martynowa, Iwona R; Abbas-Raza, Syed; Mirasol, Roberto C; Perfetti, Riccardo

    2015-02-01

    Self-adjustment of insulin dose is commonly practiced in Western patients with type 2 diabetes but is usually not performed in Asian patients. This multinational, 24-week, randomized study compared patient-led with physician-led titration of once-daily insulin glargine in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering agents. Patient-led (n = 275) or physician-led (n = 277) subjects followed the same dose-titration algorithm guided by self-monitored fasting blood glucose (FBG; target, 110 mg/dL [6.1 mmol/L]). The primary endpoint was change in mean glycated hemoglobin (HbA1c) at week 24 in the patient-led versus physician-led titration groups. Patient-led titration resulted in a significantly higher drop in HbA1c value at 24 weeks when compared with physician-led titration (-1.40% vs. -1.25%; mean difference, -0.15; 95% confidence interval, -0.29 to 0.00; P = .043). Mean decrease in FBG was greatest in the patient-led group (-2.85 mmol/L vs. -2.48 mmol/L; P = .001). The improvements in HbA1c and FBG were consistent across countries, with similar improvements in treatment satisfaction in both groups. Mean daily insulin dose was higher in the patient-led group (28.9 units vs. 22.2 units; Ptitration achieved near-target blood glucose levels in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering drugs, demonstrating that Asian patients can self-uptitrate insulin dose effectively when guided.

  12. Developing an advanced practice nurse-led liver clinic.

    Science.gov (United States)

    McAfee, Jean L

    2012-01-01

    End-stage liver disease (ESLD) is a leading cause of digestive disease deaths in the United States and continues to increase exponentially every year. Best practice does not currently recognize or utilize a clinic practice model for ESLD management. Advanced practice registered nurses (APRNs) can impact ESLD disease management by implementing an outpatient clinic care model to focus on treatment compliance, patient education, improvement of patient outcomes, and reduction in hospital admission rates for ESLD patients. A review of 15 research articles was completed to determine the impact APRNs can make on chronic care of ESLD patients. Results from the review support APRN analysis, assessment, diagnosis, treatment, intervention, and evaluation of ESLD patients. The literature reviewed also demonstrates that ESLD patients have improved symptom management when maintained in an outpatient setting, allowing for decreased hospital and insurance expenditures. Following evaluation of the evidence, it was concluded that an APRN-led ESLD clinic merits further study.

  13. Construction of an array of LEDs coupled to a concentrator for phototherapy

    Science.gov (United States)

    Almeida, Joana; Liang, Dawei

    2011-07-01

    The use of LED devices for phototherapy has been expanding in the last decade. This technology provides a safer emission spectrum in large target tissue areas when compared to laser emissions. For enhancing the phototherapeutic effects of red light emitted by LEDs, a simple optical concentrator capable of efficient light concentration and homogenization was developed. The LEDs wavelength of 660 nm is coincident with an absorption peak of the mitochondrial photoreceptor molecule cytochrome c oxidase. The prototype was optimized by non-sequential ray-tracing software ZEMAX, attaining both excellent light uniformity and 50mW/cm2 irradiance at the concentrator output end. Heat emanated from the LEDs source is effectively dissipated by the side walls of the concentrator, ensuring a nearly constant temperature environment for tissue treatment. The prototype was tested on cutaneous hyperpigmented marks caused by cupping in two healthy volunteers. Marks were irradiated by LEDs radiations with or without the use of concentrator respectively. Equal exposure durations and light fluences were tested. The use of the concentrator-coupled LEDs source revealed an activation of blood movement immediately after LEDs exposure, an effect not attainable by the LEDs source without the concentrator even at extended exposure time. Promising futures for the treatment of inflammation, tissue repair and skin rejuvenation could be expected by adopting this simple technique.

  14. EDITORIAL: LED light sources (light for the future) LED light sources (light for the future)

    Science.gov (United States)

    Grandjean, N.

    2010-09-01

    Generating white light from electricity with maximum efficacy has been a long quest since the first incandescent lamp was invented by Edison at the end of the 19th century. Nowadays, semiconductors are making reality the holy grail of converting electrons into photons with 100% efficiency and with colours that can be mixed for white light illumination. The revolution in solid-state lighting (SSL) dates to 1994 when Nakamura reported the first high-brightness blue LED based on GaN semiconductors. Then, white light was produced by simply combining a blue dye with a yellow phosphor. After more than a decade of intensive research the performance of white LEDs is quite impressive, beating by far the luminous efficacy of compact fluorescent lamps. We are likely close to replacing our current lighting devices by SSL lamps. However, there are still technological and fabrication cost issues that could delay large market penetration of white LEDs. Interestingly, SSL may create novel ways of using light that could potentially limit electricity saving. Whatever the impact of SSL, it will be significant on our daily life. The purpose of this special cluster issue is to produce a snapshot of the current situation of SSL from different viewing angles. In an introductory paper, Tsao and co-workers from Sandia National Laboratories, present an energy-economics perspective of SSL considering societal changes and SSL technology evolution. In a second article, Narukawa et al working at Nichia Corporation—the pioneer and still the leading company in SSL—describe the state of the art of current research products. They demonstrate record performance with white LEDs exhibiting luminous efficacy of 183 lm W-1 at high-current injection. Then, a series of topical papers discuss in detail various aspects of the physics and technology of white LEDs Carrier localization in InGaN quantum wells has been considered the key to white LEDs' success despite the huge density of defects. A

  15. Are nurse-led chemotherapy clinics really nurse-led? An ethnographic study.

    Science.gov (United States)

    Farrell, Carole; Walshe, Catherine; Molassiotis, Alex

    2017-04-01

    The number of patients requiring ambulatory chemotherapy is increasing year on year, creating problems with capacity in outpatient clinics and chemotherapy units. Although nurse-led chemotherapy clinics have been set up to address this, there is a lack of evaluation of their effectiveness. Despite a rapid expansion in the development of nursing roles and responsibilities in oncology, there is little understanding of the operational aspects of nurses' roles in nurse-led clinics. To explore nurses' roles within nurse-led chemotherapy clinics. A focused ethnographic study of nurses' roles in nurse-led chemotherapy clinics, including semi-structured interviews with nurses. Four chemotherapy units/cancer centres in the UK PARTICIPANTS: Purposive sampling was used to select four cancer centres/units in different geographical areas within the UK operating nurse-led chemotherapy clinics. Participants were 13 nurses working within nurse-led chemotherapy clinics at the chosen locations. Non-participant observation of nurse-led chemotherapy clinics, semi-structured interviews with nurse participants, review of clinic protocols and associated documentation. 61 nurse-patient consultations were observed with 13 nurses; of these 13, interviews were conducted with 11 nurses. Despite similarities in clinical skills training and prescribing, there were great disparities between clinics run by chemotherapy nurses and those run by advanced nurse practitioners. This included the number of patients seen within each clinic, operational aspects, nurses' autonomy, scope of practice and clinical decision-making abilities. The differences highlighted four different levels of nurse-led chemotherapy clinics, based on nurses' autonomy and scope of clinical practice. However, this was heavily influenced by medical consultants. Several nurses perceived they were undertaking holistic assessments, however they were using medical models/consultation styles, indicating medicalization of nurses' roles

  16. Placentome Nutrient Transporters and Mammalian Target of Rapamycin Signaling Proteins Are Altered by the Methionine Supply during Late Gestation in Dairy Cows and Are Associated with Newborn Birth Weight.

    Science.gov (United States)

    Batistel, Fernanda; Alharthi, Abdulrahman Sm; Wang, Ling; Parys, Claudia; Pan, Yuan-Xiang; Cardoso, Felipe C; Loor, Juan J

    2017-09-01

    Background: To our knowledge, most research demonstrating a link between maternal nutrition and both fetal growth and offspring development after birth has been performed with nonruminants. Whether such relationships exist in large ruminants is largely unknown. Objective: We aimed to investigate whether increasing the methionine supply during late pregnancy would alter uteroplacental tissue nutrient transporters and mammalian target of rapamycin (mTOR) and their relation with newborn body weight. Methods: Multiparous Holstein cows were used in a randomized complete block design experiment. During the last 28 d of pregnancy, cows were fed a control diet or the control diet plus ethylcellulose rumen-protected methionine (0.9 g/kg dry matter intake) (Mepron; Evonik Nutrition & Care GmbH) to achieve a 2.8:1 ratio of lysine to methionine in the metabolizable protein reaching the small intestine. We collected placentome samples at parturition and used them to assess mRNA and protein expression and the phosphorylation status of mTOR pathway proteins. Results: Newborn body weight was greater in the methionine group than in the control group (44.1 kg and 41.8 kg, respectively; P ≤ 0.05). Increasing the methionine supply also resulted in greater feed intake (15.8 kg/d and 14.6 kg/d), plasma methionine (11.9 μM and 15.3 μM), and plasma insulin (1.16 μg/L and 0.81 μg/L) in cows during late pregnancy. As a result, mRNA expression of genes involved in neutral amino acid transport [solute carrier (SLC) family members SLC3A2 , SLC7A5 , SLC38A1 , and SLC38A10 ], glucose transport [ SLC2A1 , SLC2A3 , and SLC2A4 ], and the mTOR pathway [mechanistic target of rapamycin and ribosomal protein S6 kinase B1] were upregulated ( P ≤ 0.07) in methionine-supplemented cows. Among 6 proteins in the mTOR pathway, increasing the methionine supply led to greater ( P ≤ 0.09) protein expression of α serine-threonine kinase (AKT), phosphorylated (p)-AKT, p-eukaryotic elongation factor 2

  17. Assessing the colour quality of LED sources

    DEFF Research Database (Denmark)

    Jost-Boissard, S.; Avouac, P.; Fontoynont, Marc

    2015-01-01

    The CIE General Colour Rendering Index is currently the criterion used to describe and measure the colour-rendering properties of light sources. But over the past years, there has been increasing evidence of its limitations particularly its ability to predict the perceived colour quality of light...... sources and especially some LEDs. In this paper, several aspects of perceived colour quality are investigated using a side-by-side paired comparison method, and the following criteria: naturalness of fruits and vegetables, colourfulness of the Macbeth Color Checker chart, visual appreciation...... (attractiveness/ preference) and colour difference estimations for both visual scenes. Forty-five observers with normal colour vision evaluated nine light sources at 3000 K, and 36 observers evaluated eight light sources at 4000 K. Our results indicate that perceived colour differences are better dealt...

  18. LED--panacea or marketing hype?

    Science.gov (United States)

    Baillie, Jonathan

    2012-02-01

    With energy efficiency and carbon reduction, and the importance of a relaxing, therapeutic patient environment, ever more in the spotlight, LED lighting's proponents claim the technology offers healthcare estates personnel many of the answers on both fronts. However some observers believe its benefits are being over-sold, often to the detriment of other high-performing types of more 'conventional lighting', and to a sometimes uninitiated audience too easily swayed by slick sales patter. HEJ editor Jonathan Baillie spoke to one highly experienced lighting professional, Nicholas Bukorović, a former employee of Thorn, Cooper, and Thorlux Lighting, and the principal author of the last CIBSE/Society of Light and Lighting (SLL) Guide LG2 on healthcare lighting, to seek some expert illumination.

  19. Switched-capacitor isolated LED driver

    Science.gov (United States)

    Sanders, Seth R.; Kline, Mitchell

    2016-03-22

    A switched-capacitor voltage converter which is particularly well-suited for receiving a line voltage from which to drive current through a series of light emitting diodes (LEDs). Input voltage is rectified in a multi-level rectifier network having switched capacitors in an ascending-bank configuration for passing voltages in uniform steps between zero volts up to full received voltage V.sub.DC. A regulator section, operating on V.sub.DC, comprises switched-capacitor stages of H-bridge switching and flying capacitors. A current controlled oscillator drives the states of the switched-capacitor stages and changes its frequency to maintain a constant current to the load. Embodiments are described for isolating the load from the mains, utilizing an LC tank circuit or a multi-primary-winding transformer.

  20. Direct illumination LED calibration for telescope photometry

    International Nuclear Information System (INIS)

    Barrelet, E.; Juramy, C.

    2008-01-01

    A calibration method for telescope photometry, based on the direct illumination of a telescope with a calibrated light source regrouping multiple LEDs, is proposed. Its purpose is to calibrate the instrument response. The main emphasis of the proposed method is the traceability of the calibration process and a continuous monitoring of the instrument in order to maintain a 0.2% accuracy over a period of years. Its specificity is to map finely the response of the telescope and its camera as a function of all light ray parameters. This feature is essential to implement a computer model of the instrument representing the variation of the overall light collection efficiency of each pixel for various filter configurations. We report on hardware developments done for SNDICE, the first application of this direct illumination calibration system which will be installed in Canada France Hawaii telescope (CFHT) for its leading supernova experiment (SNLS)

  1. Measurement of g Using a Flashing LED

    Science.gov (United States)

    Terzella, T.; Sundermier, J.; Sinacore, J.; Owen, C.; Takai, H.

    2008-10-01

    In one of the classic free-fall experiments, a small mass is attached to a strip of paper tape and both are allowed to fall through a spark timer, where sparks are generated at regular time intervals. Students analyze marks (dots) left on the tape by the timer, thereby generating distance-versus-time data, which they analyze to extract the acceleration due to gravity g with good results. The apparatus, however, is cumbersome and often frustrating for students. High-tech versions of this experiment are done with an object dropped and followed by a motion sensor connected to a computer. The sensor relies on ultrasonic ranging to record distance and time data, which may then be displayed graphically. Students inspect the graphs to determine the value of g. Although the results are excellent, the emphasis on the computer's ability to collect and analyze data leaves little analysis for the students to perform.2 Furthermore, neither technique gives an intuitive display of what is happening. The motivation for our work was to overcome these issues by developing an innovative method for measuring g. In our version of the experiment, students drop a flashing LED at a known frequency and record its trajectory using long exposure photography with a digital camera. Proper choice of flashing LED timing parameters produces an image that allows for an accurate measurement of g and at the same time helps to explain what happens during free fall. The experiment remains high-tech in the sense that students learn to use updated equipment to record data and to carry out the analysis.

  2. BiliLED low cost neonatal phototherapy, from prototype to industry

    Energy Technology Data Exchange (ETDEWEB)

    Geido, Daniel; Failache, Horacio [Instituto de Fisica de la Facultad de Ingenieria - Universidad de la Republica, Montevideo (Uruguay); Simini, Franco [Nucleo de Ingenieria Biomedica de las Facultades de Medicina e Ingenieria (Uruguay); Hospital de ClInicas. Av Italia S/N. Piso 15 sala 2, 11600 Montevideo (Uruguay)

    2007-11-15

    BiliLED is a phototherapy instrument designed to reduce bilirrubin blood rates in new born babies with jaundice. The light source is centred at 470 nm with a bandwidth of 35 nm and includes a matrix of 196 (14x14) InGaN LEDs. The optical elements are designed to maximize the light intensity useful for treatment, with a small number of LEDs in a compact and low cost unit. The optic array is such that every LED illuminates all the treatment area, which ensures redundancy and, thus, a high reliability not to be found in single-lamp instruments. Thermal dissipation and cost of BiliLED are both an order-of-magnitude smaller than conventional therapy lamps. BiliLED adjusts coetaneous irradiation with a feedback loop to compensate the loss or aging of LEDs achieving a calibrated light source for over a decade of use. A clinical trial in 20 hyperbilirrubinaemia patients shows 16% bilirrubin degradation within 24 hours of treatment, higher than most lamp phototherapy instruments. The steps from prototype to commercial model are described.

  3. BiliLED low cost neonatal phototherapy, from prototype to industry

    Science.gov (United States)

    Geido, Daniel; Failache, Horacio; Simini, Franco

    2007-11-01

    BiliLED is a phototherapy instrument designed to reduce bilirrubin blood rates in new born babies with jaundice. The light source is centred at 470 nm with a bandwidth of 35 nm and includes a matrix of 196 (14×14) InGaN LEDs. The optical elements are designed to maximize the light intensity useful for treatment, with a small number of LEDs in a compact and low cost unit. The optic array is such that every LED illuminates all the treatment area, which ensures redundancy and, thus, a high reliability not to be found in single-lamp instruments. Thermal dissipation and cost of BiliLED are both an order-of-magnitude smaller than conventional therapy lamps. BiliLED adjusts coetaneous irradiation with a feedback loop to compensate the loss or aging of LEDs achieving a calibrated light source for over a decade of use. A clinical trial in 20 hyperbilirrubinaemia patients shows 16% bilirrubin degradation within 24 hours of treatment, higher than most lamp phototherapy instruments. The steps from prototype to commercial model are described.

  4. Investigation of illumination efficiency on the LED therapy with different array types

    Science.gov (United States)

    Chen, Hsi-Chao; Liou, Cheng-Jyun

    2009-08-01

    Light-emitting diodes (LEDs) are a major discovery in twenty-one century for its advantages including small size, long lifetime, low voltage, high response and good mechanical properties. It is an environment-friendly product and maybe becomes a lighting source in future. In the other way LED lighting also is used for the lighting source of cosmetology. LED phototherapy provided medicine with a new tool capable of delivering light deep into tissues of the body, at wavelengths that are biologically optimal for pain treatment and holistic healing. The illumination efficiency is one of the key indexes for the LED phototherapy. LEDs were arranged on a disk of diameter of 100mm with different array types: a radial, a rhombus, an octagon, and a square. Then the LEDs with view angle of 120 degree were used for the lighting sources. Trace-Pro software was used for the optical simulation. The array types of radial and square were better than those of rhombus and octagon for illumination efficiency. In the mixture efficiency of a radial array was observed by different distances from 1mm to 100mm. However lighting could reach the well mixture after the treatment distance of 30mm by optical simulation. The view angle could reach +/-60 degree at the treatment distance of 50 mm for the LED phototherapy mockup.

  5. The use of light-emitting diodes (LED in commercial layer production

    Directory of Open Access Journals (Sweden)

    R Borille

    2013-06-01

    Full Text Available Artificial lighting is one of the most powerful management tools available to commercial layer producers. Artificial light allows anticipating or delaying the beginning of lay, improving egg production, and optimizing feed efficiency. This study aimed at comparing the performance of commercial layers submitted to lighting using different LED colors or conventional incandescent lamps. The study was carried out in a layer house divided in isolated environments in order to prevent any influenced from the neighboring treatments. In total, 360 Isa Brown layers, with an initial age of 56 weeks, were used. The following light sources were used: blue LED, yellow LED, green LED, red LED, white LED, and 40W incandescent light. Birds in all treatment were submitted to a 17-h continuous lighting program, and were fed a corn and soybean meal-based diet. A completely randomized experimental design with subplots was applied, with 24 treatments (six light sources and four periods of three replicates. Egg production (% was significantly different (p0.05 by light source. It was concluded that the replacement of incandescent light bulbs by white and red LEDs does not cause any negative effect on the egg production of commercial layers.

  6. BiliLED low cost neonatal phototherapy, from prototype to industry

    International Nuclear Information System (INIS)

    Geido, Daniel; Failache, Horacio; Simini, Franco

    2007-01-01

    BiliLED is a phototherapy instrument designed to reduce bilirrubin blood rates in new born babies with jaundice. The light source is centred at 470 nm with a bandwidth of 35 nm and includes a matrix of 196 (14x14) InGaN LEDs. The optical elements are designed to maximize the light intensity useful for treatment, with a small number of LEDs in a compact and low cost unit. The optic array is such that every LED illuminates all the treatment area, which ensures redundancy and, thus, a high reliability not to be found in single-lamp instruments. Thermal dissipation and cost of BiliLED are both an order-of-magnitude smaller than conventional therapy lamps. BiliLED adjusts coetaneous irradiation with a feedback loop to compensate the loss or aging of LEDs achieving a calibrated light source for over a decade of use. A clinical trial in 20 hyperbilirrubinaemia patients shows 16% bilirrubin degradation within 24 hours of treatment, higher than most lamp phototherapy instruments. The steps from prototype to commercial model are described

  7. Open LED Illuminator: A Simple and Inexpensive LED Illuminator for Fast Multicolor Particle Tracking in Neurons

    Science.gov (United States)

    Bosse, Jens B.; Tanneti, Nikhila S.; Hogue, Ian B.; Enquist, Lynn W.

    2015-01-01

    Dual-color live cell fluorescence microscopy of fast intracellular trafficking processes, such as axonal transport, requires rapid switching of illumination channels. Typical broad-spectrum sources necessitate the use of mechanical filter switching, which introduces delays between acquisition of different fluorescence channels, impeding the interpretation and quantification of highly dynamic processes. Light Emitting Diodes (LEDs), however, allow modulation of excitation light in microseconds. Here we provide a step-by-step protocol to enable any scientist to build a research-grade LED illuminator for live cell microscopy, even without prior experience with electronics or optics. We quantify and compare components, discuss our design considerations, and demonstrate the performance of our LED illuminator by imaging axonal transport of herpes virus particles with high temporal resolution. PMID:26600461

  8. Open LED Illuminator: A Simple and Inexpensive LED Illuminator for Fast Multicolor Particle Tracking in Neurons.

    Directory of Open Access Journals (Sweden)

    Jens B Bosse

    Full Text Available Dual-color live cell fluorescence microscopy of fast intracellular trafficking processes, such as axonal transport, requires rapid switching of illumination channels. Typical broad-spectrum sources necessitate the use of mechanical filter switching, which introduces delays between acquisition of different fluorescence channels, impeding the interpretation and quantification of highly dynamic processes. Light Emitting Diodes (LEDs, however, allow modulation of excitation light in microseconds. Here we provide a step-by-step protocol to enable any scientist to build a research-grade LED illuminator for live cell microscopy, even without prior experience with electronics or optics. We quantify and compare components, discuss our design considerations, and demonstrate the performance of our LED illuminator by imaging axonal transport of herpes virus particles with high temporal resolution.

  9. LED phototherapy in full-thickness burns induced by CO2 laser in rats skin.

    Science.gov (United States)

    da Silva Melo, Milene; Alves, Leandro Procópio; Fernandes, Adriana Barrinha; Carvalho, Henrique Cunha; de Lima, Carlos José; Munin, Egberto; Gomes, Mônica Fernandes; Salgado, Miguel Angel Castillo; Zângaro, Renato Amaro

    2018-04-27

    Many studies have been conducted on the treatment of burns because they are important in morbidity and mortality. These studies are mainly focused on improving care and quality of life of patients. The aim of this study was evaluate the LED phototherapy effects in rats skin full-thickness burns induced by CO 2 laser. The animals were divided in NT group that did not received any treatment and LED group that received LED irradiation at 685 nm, 220 mW, and 4.5 J/cm 2 during 40 s by burned area. Biopsies were obtained after 7, 14, and 21 days of treatment and submitted to histological and immunohistochemical analysis. The LED phototherapy shows anti-inflammatory effects, improves angiogenesis, and stimulates the migration and proliferation of fibroblasts. The T CD8+ lymphocytes were more common in burned areas compared to T CD4+ lymphocytes since statistically significant differences were observed in the LED group compared to the NT group after 7 days of treatment. These results showed that LED phototherapy performs positive influence in full-thickness burns repair from the healing process modulated by cellular immune response. The obtained results allowed inferring that burns exhibit a characteristic cell immune response and this cannot be extrapolated to other wounds such as incision and wounds induced by punch, among others.

  10. LED Virtual Simulation based on Web3D

    OpenAIRE

    Lilan Liu; Liu Han; Zhiqi Lin; Manping Li; Tao Yu

    2014-01-01

    Regarding to the high price and low market popularity of current LED indoor lighting products, a LED indoor lighting platform is proposed based on Web3D technology. The internet virtual reality technology is integrated and applied into the LED collaborative e-commerce website with Virtools. According to the characteristics of the LED indoor lighting products, this paper introduced the method to build encapsulated model and three characteristics of LED lighting: geometrical, optical and behavi...

  11. Led Astray by Hemoglobin A1c

    Directory of Open Access Journals (Sweden)

    Jean Chen MD

    2016-01-01

    Full Text Available Hemoglobin A1c (A1c is used frequently to diagnose and treat diabetes mellitus. Therefore, it is important be aware of factors that may interfere with the accuracy of A1c measurements. This is a case of a rare hemoglobin variant that falsely elevated a nondiabetic patient’s A1c level and led to a misdiagnosis of diabetes. A 67-year-old male presented to endocrine clinic for further management after he was diagnosed with diabetes based on an elevated A1c of 10.7%, which is approximately equivalent to an average blood glucose of 260 mg/dL. Multiple repeat A1c levels remained >10%, but his home fasting and random glucose monitoring ranged from 92 to 130 mg/dL. Hemoglobin electrophoresis and subsequent genetic analysis diagnosed the patient with hemoglobin Wayne, a rare hemoglobin variant. This variant falsely elevates A1c levels when A1c is measured using cation-exchange high-performance liquid chromatography. When the boronate affinity method was applied instead, the patient’s A1c level was actually 4.7%. Though hemoglobin Wayne is clinically silent, this patient was erroneously diagnosed with diabetes and started on an antiglycemic medication. Due to this misdiagnosis, the patient was at risk of escalation in his “diabetes management” and hypoglycemia. Therefore, it is important that providers are aware of factors that may result in hemoglobin A1c inaccuracy including hemoglobin variants.

  12. Review of hormone-based treatments in postmenopausal patients with advanced breast cancer focusing on aromatase inhibitors and fulvestrant

    DEFF Research Database (Denmark)

    Kümler, Iben; Knoop, Ann S; Jessing, Christina A R

    2016-01-01

    . However, overall survival was not significantly increased. CONCLUSION: Conventional treatment with an aromatase inhibitor or fulvestrant may be an adequate treatment option for most patients with hormone receptor-positive advanced breast cancer. Mammalian target of rapamycin (mTOR) inhibition and cyclin...

  13. Application of blue laser diodes and LEDs in phototherapy for neonatal jaundice

    Science.gov (United States)

    Hamza, Mostafa; Sayed El-Ahl, Mohammad H.; Hamza, Ahmad M.; Hamza, Aya M.; Hamza, Yahya M.

    2003-10-01

    The authors introduce the design of a compact phototherapy unit capable of fulfilling the recommendations of the clinical use of lasers and LEDs in phototherapy for the treatment of neonatal jaundice. The system keeps the duration of phototherapy to the minimum required for efficient treatment. Our leading clinical experience as well as the wavelength selection rules will be presented.

  14. Effect of LED irradiation on the ripening and nutritional quality of postharvest banana fruit.

    Science.gov (United States)

    Huang, Jen-Yi; Xu, Fengying; Zhou, Weibiao

    2018-04-24

    With the ability to tailor wavelengths necessary to the photosynthetically active radiation spectrum of plant pigments, light-emitting diodes (LEDs) offer vast possibilities in horticultural lighting. The influence of LED light irradiation on major postharvest features of banana was investigated. Mature green bananas were treated daily with selected blue (464-474 nm), green (515-525 nm) and red (617-627 nm) LED lights for 8 days, and compared with non-illuminated control. The positive effect of LED lighting on the acceleration of ripening in bananas was greatest for blue, followed by red and green. Under the irradiation of LED lights, faster peel de-greening and flesh softening, and increased ethylene production and respiration rate in bananas were observed during storage. Furthermore, the accumulations of ascorbic acid, total phenols, and total sugars in banana fruit were enhanced by LED light exposure. LED light treatment can induce the ripening of bananas and improve their quality and nutrition potential. These findings might provide new chemical-free strategies to shorten the time to ripen banana after harvest by using LED light source. This article is protected by copyright. All rights reserved.

  15. LED phototherapy on midpalatal suture after rapid maxilla expansion: a Raman spectroscopic study

    Science.gov (United States)

    Rosa, Cristiane B.; Habib, Fernando Antonio L.; de Araújo, Telma M.; dos Santos, Jean N.; Cangussu, Maria Cristina T.; Barbosa, Artur Felipe S.; de Castro, Isabele Cardoso V.; Soares, Luiz Guilherme P.; Pinheiro, Antonio L. B.

    2015-03-01

    A quick bone formation after maxillary expansion would reduce treatment timeand the biomodulating effects of LED light could contribute for it. The aim of this study was to analyze the effect of LED phototherapy on the acceleration of bone formation at the midpalatal suture after maxilla expansion. Thirty rats divided into 6 groups were used on the study at 2 time points - 7 days: Control; Expansion; and Expansion + LED; and 14 days: Expansion; Expansion + LED in the first week; Expansion and LED in the first and second weeks. LED irradiation occurred at every 48 h during 2 weeks. Expansion was accomplished using a spatula and maintained with a triple helicoid of 0.020" stainless steel orthodontic wire. A LED light (λ850 ± 10nm, 150mW ± 10mW, spot of 0.5cm2, t=120 sec, SAEF of 18J/cm2) was applied in one point in the midpalatal suture immediately behind the upper incisors. Near infrared Raman spectroscopic analysis of the suture region was carried and data submitted to statistical analyzes (p≤0.05). Raman spectrum analysis demonstrated that irradiation increased hydroxyapatite in the midpalatal suture after expansion. The results of this indicate that LED irradiation; have a positive biomodulation contributing to the acceleration of bone formation in the midpalatal suture after expansion procedure.

  16. Effects of LEDs on chlorophyll fluorescence and secondary metabolites in Phalaenopsis

    DEFF Research Database (Denmark)

    Ouzounis, T.; Fretté, X.; Rosenqvist, Eva

    2015-01-01

    Light emitting diodes (LEDs) are solid-state semiconductor devices that have been integrated in current greenhouse systems the last decades as they provide the opportunity to control light spectrum. Commercial production of potted orchids under LEDs has increased throughout the world the past dec...... was a little higher when compared to the control. Quantitation of secondary metabolites was performed by HPLC. The analysis showed that the treatments with additional blue light had the highest amount of flavonoids and carotenoids....

  17. Validating Community-Led Forest Biomass Assessments.

    Science.gov (United States)

    Venter, Michelle; Venter, Oscar; Edwards, Will; Bird, Michael I

    2015-01-01

    The lack of capacity to monitor forest carbon stocks in developing countries is undermining global efforts to reduce carbon emissions. Involving local people in monitoring forest carbon stocks could potentially address this capacity gap. This study conducts a complete expert remeasurement of community-led biomass inventories in remote tropical forests of Papua New Guinea. By fully remeasuring and isolating the effects of 4,481 field measurements, we demonstrate that programmes employing local people (non-experts) can produce forest monitoring data as reliable as those produced by scientists (experts). Overall, non-experts reported lower biomass estimates by an average of 9.1%, equivalent to 55.2 fewer tonnes of biomass ha(-1), which could have important financial implications for communities. However, there were no significant differences between forest biomass estimates of expert and non-expert, nor were there significant differences in some of the components used to calculate these estimates, such as tree diameter at breast height (DBH), tree counts and plot surface area, but were significant differences between tree heights. At the landscape level, the greatest biomass discrepancies resulted from height measurements (41%) and, unexpectedly, a few large missing trees contributing to a third of the overall discrepancies. We show that 85% of the biomass discrepancies at the tree level were caused by measurement taken on large trees (DBH ≥50 cm), even though they consisted of only 14% of the stems. We demonstrate that programmes that engage local people can provide high-quality forest carbon data that could help overcome barriers to reducing forest carbon emissions in developing countries. Nonetheless, community-based monitoring programmes should prioritise reducing errors in the field that lead to the most important discrepancies, notably; overcoming challenges to accurately measure large trees.

  18. High power blue LED development using different growth modes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong S.; Florescu, Doru I.; Ramer, Jeff C.; Merai, Vinod; Parekh, Aniruddh; Begarney, Michael J.; Armour, Eric A. [Veeco TurboDisc Operations, 394 Elizabeth Avenue, Somerset, NJ 08873 (United States); Lu Dong [Veeco TurboDisc Operations, 394 Elizabeth Avenue, Somerset, NJ 08873 (United States); School of Engineering, Rutgers University, Piscataway, NJ 08854 (United States)

    2004-09-01

    Blue high brightness light emitting diodes (HB-LEDs) have been developed using different growth modes in the active layers. Piezoelectric field engineering improves the optical output power in multiple quantum well (MQW) LEDs by inserting an optimized transitional superlattice (TSL) before the active MQW layers. Within single quantum well (SQW) LEDs, quasi-Quantum Dot (QD) growth for Indium localization has been realized. The SQW LED output power exceeds the strain engineered MQW LEDs. The experimental data indicates that Indium localization enhances overall quantum efficiency and results in increased output power for HB-LEDs. (copyright 2004 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  19. Big Data-Led Cancer Research, Application, and Insights.

    Science.gov (United States)

    Brown, James A L; Ni Chonghaile, Triona; Matchett, Kyle B; Lynam-Lennon, Niamh; Kiely, Patrick A

    2016-11-01

    Insights distilled from integrating multiple big-data or "omic" datasets have revealed functional hierarchies of molecular networks driving tumorigenesis and modifiers of treatment response. Identifying these novel key regulatory and dysregulated elements is now informing personalized medicine. Crucially, although there are many advantages to this approach, there are several key considerations to address. Here, we examine how this big data-led approach is impacting many diverse areas of cancer research, through review of the key presentations given at the Irish Association for Cancer Research Meeting and importantly how the results may be applied to positively affect patient outcomes. Cancer Res; 76(21); 6167-70. ©2016 AACR. ©2016 American Association for Cancer Research.

  20. Device-based local delivery of siRNA against mammalian target of rapamycin (mTOR) in a murine subcutaneous implant model to inhibit fibrous encapsulation

    OpenAIRE

    Takahashi, Hironobu; Wang, Yuwei; Grainger, David W.

    2010-01-01

    Fibrous encapsulation of surgically implant devices is associated with elevated proliferation and activation of fibroblasts in tissues surrounding these implants, frequently causing foreign body complications. Here we test the hypothesis that inhibition of the expression of mammalian target of rapamycin (mTOR) in fibroblasts can mitigate the soft tissue implant foreign body response by suppressing fibrotic responses around implants. In this study, mTOR was knocked down using small interfering...

  1. Peer-led prenatal breast-feeding education: a viable alternative to nurse-led education.

    Science.gov (United States)

    Rempel, Lynn A; Moore, Katrina C J

    2012-02-01

    To evaluate a prenatal breast-feeding class developed and facilitated by peer Breast-feeding Buddies. Non-equivalent control group quasi-experimental study comparing participants of the peer-led class (PLC) to those attending an established hospital-based breast-feeding nurse-led class (NLC). A brief questionnaire was completed immediately prior to the class, and telephone interviews were conducted approximately one week following the class, and one and six months post partum. 54 expectant mothers who registered for the community PLC and 55 expectant mothers who registered for the NLC. Breast-feeding intentions were measured at all time-points. Class evaluations, breast-feeding experiences, and breast-feeding support were measured at all post-class interviews. Both classes were considered worthwhile, but the PLC class was rated as more helpful and participants appreciated learning from the peers' personal experiences. Mothers taught by peers were more likely to access peer breast-feeding support. PLC participants initially decreased their prenatal breast-feeding duration intentions but had significantly stronger intentions to continue breast feeding at six months than did NLC mothers. A peer-led prenatal breast-feeding class is as effective as a traditional model of breast-feeding education and is a valuable tool to promote and support successful breast feeding. RECOMMENDATIONS FOR PRACTICE: Peer-led breast-feeding classes should be provided to enhance the accessibility of breast-feeding education and support for expectant mothers. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Integration of organic LEDs with inorganic LEDs for a hybrid lighting system

    Science.gov (United States)

    Kong, H. J.; Park, J. W.; Kim, Y. M.

    2013-01-01

    We demonstrate that a surface-emitting hybrid light source can be realized by a combination of organic and inorganic light-emitting devices (LEDs). To this end, a blue inorganic LED bar is deployed at one side of a transparent light guide plate (LGP), and a yellow organic LED (OLED) is in contact with the rear surface of the LGP. In such a configuration, it is found that the overall luminance is almost equivalent to the sum of the luminances measured from each light source, and the overall luminance uniformity is determined mainly by the luminance uniformity of the OLED panel at high luminances. We have achieved a white color showing the Commission Internationale d'Eclairage (CIE) chromaticity coordinates of (x = 0.34, y = 0.33), the power efficiency of 9.3 lm/W, the luminance uniformity of 63% at the luminance of 3100 cd m-2, the color rendering index as high as 89.3, and the correlated color temperature finely tunable within the range between 3000 and 8000 K. Such a system facilitates color tuning by adjusting their luminous intensities and hence the implementation of the emotional lighting system.

  3. Integration of organic LEDs with inorganic LEDs for a hybrid lighting system

    International Nuclear Information System (INIS)

    Kong, H J; Kim, Y M; Park, J W

    2013-01-01

    We demonstrate that a surface-emitting hybrid light source can be realized by a combination of organic and inorganic light-emitting devices (LEDs). To this end, a blue inorganic LED bar is deployed at one side of a transparent light guide plate (LGP), and a yellow organic LED (OLED) is in contact with the rear surface of the LGP. In such a configuration, it is found that the overall luminance is almost equivalent to the sum of the luminances measured from each light source, and the overall luminance uniformity is determined mainly by the luminance uniformity of the OLED panel at high luminances. We have achieved a white color showing the Commission Internationale d'Eclairage (CIE) chromaticity coordinates of (x = 0.34, y = 0.33), the power efficiency of 9.3 lm/W, the luminance uniformity of 63% at the luminance of 3100 cd m –2 , the color rendering index as high as 89.3, and the correlated color temperature finely tunable within the range between 3000 and 8000 K. Such a system facilitates color tuning by adjusting their luminous intensities and hence the implementation of the emotional lighting system. (paper)

  4. Is Nigerian Growth Trade-Led?

    Directory of Open Access Journals (Sweden)

    Ismail Adigun Olayemi

    2017-09-01

    Full Text Available Purpose: Nigeria is currently in recession, a situation described as induced by decreases in oil output and export, caused by the bombings of oil pipelines in its Niger Delta region, and the unanticipated decline in its value of exports and currency, resulting from the decline in oil prices. With the export value decline, somersaulting to growth, could it then be that Nigerian economic growth is trade constrained? How important is export to growth?. This study investigates these, its invention balances in its methodology. Design/methodology/approach: To achieve the above, this paper employs the Autoregressive Distributed Lag Model (ARDL and the Thirlwall's Law of balance of payment led growth, using a combination of annual (1981–2016 and quarterly (2000Q1–2016Q4 data to ensure robustness. This combination not only allows for comparison but also ensures the reflection of the current government's trade decisions and trade activities; these are missing in other studies. Findings: Using the Wald F-Statistic, Economic growth is found to be equal to export growth rate divided by income elasticity of import, the estimated income elasticity of import which is greater than 100% or elastic reflects over dependence on import both in the short and long run, implying that Nigeria imports more than it earns. Exchange rate and terms of trade are insignificant especially in the long run. The study calls for monitoring of import contents; the government needs to enforce its recent directives to stop importation of some products that are already being produced within with higher quality and adequate export promotion strategies should be formulated and enforced. Research limitations/implications: The data span is restricted by data availability, the study could as well confirm its results with monthly data for robustness and better confidence, but most of the variables are reported annually and quarterly only. Originality/value: Many studies have confirmed the

  5. Overall survival after immunotherapy, tyrosine kinase inhibitors and surgery in treatment of metastatic renal cell cancer

    DEFF Research Database (Denmark)

    de Lichtenberg, Trine Honnens; Hermann, Gregers G.; Rorth, Mikael

    2014-01-01

    Abstract Objective. The aim of this study was to evaluate overall survival (OS) after treatment of metastatic renal cell carcinoma (mRCC) following the introduction of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors. Material and methods. One-hundred and forty...

  6. HPV-16 E7 expression up-regulates phospholipase D activity and promotes rapamycin resistance in a pRB-dependent manner.

    Science.gov (United States)

    Rabachini, Tatiana; Boccardo, Enrique; Andrade, Rubiana; Perez, Katia Regina; Nonogaki, Suely; Cuccovia, Iolanda Midea; Villa, Luisa Lina

    2018-04-27

    Human Papillomavirus (HPV) infection is the main risk factor for the development and progression of cervical cancer. HPV-16 E6 and E7 expression is essential for induction and maintenance of the transformed phenotype. These oncoproteins interfere with the function of several intracellular proteins, including those controlling the PI3K/AKT/mTOR pathway in which Phospolipase D (PLD) and Phosphatidic acid (PA) play a critical role. PLD activity was measured in primary human keratinocytes transduced with retroviruses expressing HPV-16 E6, E7 or E7 mutants. The cytostatic effect of rapamycin, a well-known mTOR inhibitor with potential clinical applications, was evaluated in monolayer and organotypic cultures. HPV-16 E7 expression in primary human keratinocytes leads to an increase in PLD expression and activity. Moreover, this activation is dependent on the ability of HPV-16 E7 to induce retinoblastoma protein (pRb) degradation. We also show that cells expressing HPV-16 E7 or silenced for pRb acquire resistance to the antiproliferative effect of rapamycin. This is the first indication that HPV oncoproteins can affect PLD activity. Since PA can interfere with the ability of rapamycin to bind mTOR, the use of combined strategies to target mTOR and PLD activity might be considered to treat HPV-related malignancies.

  7. Fluoride-Induced Autophagy via the Regulation of Phosphorylation of Mammalian Targets of Rapamycin in Mice Leydig Cells.

    Science.gov (United States)

    Zhang, Jianhai; Zhu, Yuchen; Shi, Yan; Han, Yongli; Liang, Chen; Feng, Zhiyuan; Zheng, Heping; Eng, Michelle; Wang, Jundong

    2017-10-11

    Fluoride is known to impair testicular function and decrease testosterone levels, yet the underlying mechanisms remain inconclusive. The objective of this study is to investigate the roles of autophagy in fluoride-induced male reproductive toxicity using both in vivo and in vitro Leydig cell models. Using transmission electron microscopy and monodansylcadaverine staining, we observed increasing numbers of autophagosomes in testicular tissue, especially in Leydig cells of fluoride-exposed mice. Further study revealed that fluoride increased the levels of mRNA and protein expression of autophagy markers LC3, Beclin1, and Atg 5 in primary Leydig cells. Furthermore, fluoride inhibited the phosphorylation of mammalian targets of rapamycin and 4EBP1, which in turn resulted in a decrease in the levels of AKT and PI3K mRNA expression, as well as an elevation of the level of AMPK expression in both testes and primary Leydig cells. Additionally, fluoride exposure significantly changed the mRNA expression of the PDK1, TSC, and Atg13 regulator genes in primary Leydig cells but not in testicular cells. Taken together, our findings highlight the roles of autophagy in fluoride-induced testicular and Leydig cell damage and contribute to the elucidation of the underlying mechanisms of fluoride-induced male reproductive toxicity.

  8. Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Chun Yang

    2012-01-01

    Full Text Available Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST. Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

  9. Up-Regulation of the Excitatory Amino Acid Transporters EAAT1 and EAAT2 by Mammalian Target of Rapamycin

    Directory of Open Access Journals (Sweden)

    Abeer Abousaab

    2016-11-01

    Full Text Available Background: The excitatory amino-acid transporters EAAT1 and EAAT2 clear glutamate from the synaptic cleft and thus terminate neuronal excitation. The carriers are subject to regulation by various kinases. The EAAT3 isoform is regulated by mammalian target of rapamycin (mTOR. The present study thus explored whether mTOR influences transport by EAAT1 and/or EAAT2. Methods: cRNA encoding wild type EAAT1 (SLC1A3 or EAAT2 (SLC1A2 was injected into Xenopus oocytes without or with additional injection of cRNA encoding mTOR. Dual electrode voltage clamp was performed in order to determine electrogenic glutamate transport (IEAAT. EAAT2 protein abundance was determined utilizing chemiluminescence. Results: Appreciable IEAAT was observed in EAAT1 or EAAT2 expressing but not in water injected oocytes. IEAAT was significantly increased by coexpression of mTOR. Coexpression of mTOR increased significantly the maximal IEAAT in EAAT1 or EAAT2 expressing oocytes, without significantly modifying affinity of the carriers. Moreover, coexpression of mTOR increased significantly EAAT2 protein abundance in the cell membrane. Conclusions: The kinase mTOR up-regulates the excitatory amino acid transporters EAAT1 and EAAT2.

  10. Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1-Induced Parathyroid Cell Proliferation in Secondary Hyperparathyroidism.

    Science.gov (United States)

    Volovelsky, Oded; Cohen, Gili; Kenig, Ariel; Wasserman, Gilad; Dreazen, Avigail; Meyuhas, Oded; Silver, Justin; Naveh-Many, Tally

    2016-04-01

    Secondary hyperparathyroidism is characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation. However, the molecular pathways mediating the increased parathyroid cell proliferation remain undefined. Here, we found that the mTOR pathway was activated in the parathyroid of rats with secondary hyperparathyroidism induced by either chronic hypocalcemia or uremia, which was measured by increased phosphorylation of ribosomal protein S6 (rpS6), a downstream target of the mTOR pathway. This activation correlated with increased parathyroid cell proliferation. Inhibition of mTOR complex 1 by rapamycin decreased or prevented parathyroid cell proliferation in secondary hyperparathyroidism rats and in vitro in uremic rat parathyroid glands in organ culture. Knockin rpS6(p-/-) mice, in which rpS6 cannot be phosphorylated because of substitution of all five phosphorylatable serines with alanines, had impaired PTH secretion after experimental uremia- or folic acid-induced AKI. Uremic rpS6(p-/-) mice had no increase in parathyroid cell proliferation compared with a marked increase in uremic wild-type mice. These results underscore the importance of mTOR activation and rpS6 phosphorylation for the pathogenesis of secondary hyperparathyroidism and indicate that mTORC1 is a significant regulator of parathyroid cell proliferation through rpS6. Copyright © 2016 by the American Society of Nephrology.

  11. Development of thermal LED Model | Kapitonov | Journal of ...

    African Journals Online (AJOL)

    Journal of Fundamental and Applied Sciences ... operating conditions of LEDs at the design stage, taking into account a cooling system in use. ... The created models will allow to reveal unfavorable thermal operating modes for LEDs and, ...

  12. Unidirectional visible light communication and illumination with LEDs

    NARCIS (Netherlands)

    Li, S.; Pandharipande, A.; Willems, F.M.J.

    2016-01-01

    Visible light communication (VLC) with light emitting diodes (LEDs) has attracted interest for interactive and networked lighting control, and consumer infotainment applications. In this paper, we propose an LED system for jointly achieving unidirectional VLC while providing flicker-free

  13. Modelling intelligence-led policing to identify its potential

    NARCIS (Netherlands)

    Hengst-Bruggeling, M. den; Graaf, H.A.L.M. de; Scheepstal, P.G.M. van

    2014-01-01

    lntelligence-led policing is a concept of policing that has been applied throughout the world. Despite some encouraging reports, the effect of intelligence-led policing is largely unknown. This paper presents a method with which it is possible to identify intelligence-led policing's potential to

  14. High Efficiency Driving Electronics for General Illumination LED Luminaires

    Energy Technology Data Exchange (ETDEWEB)

    Upadhyay, Anand

    2012-10-31

    New generation of standalone LED driver platforms developed, which are more efficient These LED Drivers are more efficient (≥90%), smaller in size ( 0.15 in3/watt), lower in cost ( 12 cents/watt in high volumes in millions of units). And these products are very reliable having an operating life of over 50,000 hours. This technology will enable growth of LED light sources in the use. This will also help in energy saving and reducing total life cycle cost of LED units. Two topologies selected for next generation of LED drivers: 1) Value engineered single stage Flyback topology. This is suitable for low powered LED drivers up to 50W power. 2) Two stage boost power factor correction (PFC) plus LLC half bridge platform for higher powers. This topology is suitable for 40W to 300W LED drivers. Three new product platforms were developed to cover a wide range of LED drivers: 1) 120V 40W LED driver, 2) Intellivolt 75W LED driver, & 3) Intellivolt 150W LED driver. These are standalone LED drivers for rugged outdoor lighting applications. Based on these platforms number of products are developed and successfully introduced in the market place meeting key performance, size and cost goals.

  15. Design methodologies for reliability of SSL LED boards

    NARCIS (Netherlands)

    Jakovenko, J.; Formánek, J.; Perpiñà, X.; Jorda, X.; Vellvehi, M.; Werkhoven, R.J.; Husák, M.; Kunen, J.M.G.; Bancken, P.; Bolt, P.J.; Gasse, A.

    2013-01-01

    This work presents a comparison of various LED board technologies from thermal, mechanical and reliability point of view provided by an accurate 3-D modelling. LED boards are proposed as a possible technology replacement of FR4 LED boards used in 400 lumen retrofit SSL lamps. Presented design

  16. A review of passive thermal management of LED module

    NARCIS (Netherlands)

    Ye, H.; Sau, K.; Zeijl, H. van; Gielen, A.W.J.; Zhang, G.

    2011-01-01

    Recently, the high-brightness LEDs have begun to be designed for illumination application. The increased electrical currents used to drive LEDs lead to thermal issues. Thermal management for LED module is a key design parameter as high operation temperature directly affects their maximum light

  17. LED power consumption in joint illumination and communication system

    NARCIS (Netherlands)

    Deng, X.; Wu, Y.; Khalid, A.M.; Long, X.; Linnartz, J.-P.M.G.

    This paper addresses the power penalty in an illumination LED caused by visible light communication (VLC). This study models the extra power consumption of the LED by taking into account the convex relation between the dissipated electrical power versus the LED current on one hand and the concave

  18. EC-LEDS Supports the Low-Carbon Transition

    Energy Technology Data Exchange (ETDEWEB)

    2016-09-01

    EC-LEDS is a flagship U.S. government-led effort that assists countries to create and implement low emission development strategies, or LEDS -- development frameworks that promote sustainable social and economic development while reducing greenhouse gas emissions over the medium to long term.

  19. THE PHOTODYNAMIC EFFECT OF LED-MAGNETIC EXPOSURE TO PHOTOINACTIVATION OF AEROBIC PHOTOSYNTETIC BACTERIA

    Directory of Open Access Journals (Sweden)

    Suryani Dyah Astuti

    2014-01-01

    Full Text Available All photosynthetic bacteria have a major pigment of bacteriochlorophyl and accessor pigment e.g. the carotenoids, which both have an important role in photosynthesis process. This study aim to explore the exogenous organic photosensitizer from photosyntetic bacteria for photodynamic therapy application. This study is an experimental research aiming to test the potential illumination ofLED with wavelength 409, 430, 528 and 629 nm, and power optimization and time exposure LED-magnetic for optimum photo activation Rhodococcus growth. The reseach design use a factorial completely randomized design with factor ofpower and exposure time. The number ofbacterial colonies grown measure using ofTotal Plate Count (TPC methods. The result ofanova test shows that irradiation treatment with LED 409 nm, 430 nm, 528 nm and 629 nm significantly affects on bacterial colony growth. LED 409 nm exposure has the greatest potential to boost the growth ofbacterial colonies by 77%. LED exposure and the addition of1.8 mT magnetic field increases bacterial colony growth by 98%. Results of optimization of LED and magnetic fields show power 46 mW and a 40 minute (energy dose 110 J/cm2 optimum growth ofbacterial colonies increase by 184%. So LED and magnetic illumination has potentially increased the viability ofan aerob photosyntetic bacteria colonies.

  20. Target of rapamycin complex 2 signals to downstream effector yeast protein kinase 2 (Ypk2) through adheres-voraciously-to-target-of-rapamycin-2 protein 1 (Avo1) in Saccharomyces cerevisiae.

    Science.gov (United States)

    Liao, Hsien-Ching; Chen, Mei-Yu

    2012-02-24

    The conserved Ser/Thr kinase target of rapamycin (TOR) serves as a central regulator in controlling cell growth-related functions. There exist two distinct TOR complexes, TORC1 and TORC2, each coupling to specific downstream effectors and signaling pathways. In Saccharomyces cerevisiae, TORC2 is involved in regulating actin organization and maintaining cell wall integrity. Ypk2 (yeast protein kinase 2), a member of the cAMP-dependent, cGMP-dependent, and PKC (AGC) kinase family, is a TORC2 substrate known to participate in actin and cell wall regulation. Employing avo3(ts) mutants with defects in TORC2 functions that are suppressible by active Ypk2, we investigated the molecular interactions involved in mediating TORC2 signaling to Ypk2. GST pulldown assays in yeast lysates demonstrated physical interactions between Ypk2 and components of TORC2. In vitro binding assays revealed that Avo1 directly binds to Ypk2. In avo3(ts) mutants, the TORC2-Ypk2 interaction was reduced and could be restored by AVO1 overexpression, highlighting the important role of Avo1 in coupling TORC2 to Ypk2. The interaction was mapped to an internal region (amino acids 600-840) of Avo1 and a C-terminal region of Ypk2. Ypk2(334-677), a truncated form of Ypk2 containing the Avo1-interacting region, was able to interfere with Avo1-Ypk2 interaction in vitro. Overexpressing Ypk2(334-677) in yeast cells resulted in a perturbation of TORC2 functions, causing defective cell wall integrity, aberrant actin organization, and diminished TORC2-dependent Ypk2 phosphorylation evidenced by the loss of an electrophoretic mobility shift. Together, our data support the conclusion that the direct Avo1-Ypk2 interaction is crucial for TORC2 signaling to the downstream Ypk2 pathway.

  1. Treatment

    Directory of Open Access Journals (Sweden)

    Safaa M. Raghab

    2013-08-01

    The main goal of this study is to utilize a natural low cost material “as an accelerator additive to enhance the chemical treatment process using Alum coagulant and the accelerator substances were Perlite and Bentonite. The performance of the chemical treatment was enhanced using the accelerator substances with 90 mg/l Alum as a constant dose. Perlite gave better performance than the Bentonite effluent. The removal ratio for conductivity, turbidity, BOD and COD for Perlite was 86.7%, 87.4%, 89.9% and 92.8% respectively, and for Bentonite was 83.5%, 85.0%, 86.5% and 85.0% respectively at the same concentration of 40 mg/l for each.

  2. Novel Carbazole Skeleton-Based Photoinitiators for LED Polymerization and LED Projector 3D Printing

    Directory of Open Access Journals (Sweden)

    Assi Al Mousawi

    2017-12-01

    Full Text Available Radical chemistry is a very convenient way to produce polymer materials. Here, an application of a particular photoinduced radical chemistry is illustrated. Seven new carbazole derivatives Cd1–Cd7 are incorporated and proposed as high performance near-UV photoinitiators for both the free radical polymerization (FRP of (methacrylates and the cationic polymerization (CP of epoxides utilizing Light Emitting Diodes LEDs @405 nm. Excellent polymerization-initiating abilities are found and high final reactive function conversions are obtained. Interestingly, these new derivatives display much better near-UV polymerization-initiating abilities compared to a reference UV absorbing carbazole (CARET 9H-carbazole-9-ethanol demonstrating that the new substituents have good ability to red shift the absorption of the proposed photoinitiators. All the more strikingly, in combination with iodonium salt, Cd1–Cd7 are likewise preferred as cationic photoinitiators over the notable photoinitiator bis(2,4,6-trimethylbenzoylphenylphosphine oxide (BAPO for mild irradiation conditions featuring their remarkable reactivity. In particular their utilization in the preparation of new cationic resins for LED projector 3D printing is envisioned. A full picture of the included photochemical mechanisms is given.

  3. LED lighting for greenhouses. Final report; LED belysning til vaeksthuse. Slutrapport

    Energy Technology Data Exchange (ETDEWEB)

    OEstergaard, J.E. (Syddansk Univ. (SDU). Erhvervsinnovation og Teknologi, Odense (Denmark))

    2011-01-15

    The project had 3 main objectives: 1) To develop a prototype of a LED-based luminaire that can replace the existing glasshouse horticultural lighting. The project have developed a working prototype and experimentally replaced the traditional HPS luminaires in a controlled growing area. The project succeeded in producing plants of comparable quality. However, the project shows that the prototype can be improved by: x) being further integrated into the existing horticultural production technology (eg climate computers and purchase of electricity) x) adapting configuration of luminaires specifically to each plant variety x) adapting different cooling technologies to match specific customer needs x) In some cases being combined with heat input to optimize the overall economy. 2) To achieve an effective electricity savings of 50-80% - equivalent to a value of approx. DKK 5 million for a medium sized nursery. The verified electricity savings was 40%. In test setups and in well defined and controllable production areas the prototypes achieved electricity savings of > 50%. It is expected that a new generation of LEDs (Q3 2010) will allow for greater power savings. 3) To continue prototype development and initiate commercialization of the project through the company Fionia Lighting A/S. The shareholders of the company have allocated capital to the company to allow us to address the main challenges in commercializing the technology. It is expected that the company will enter a strategic alliance with a major industrial player in the beginning of 2011. (Author)

  4. Theobromine, the primary methylxanthine found in Theobroma cacao, prevents malignant glioblastoma proliferation by negatively regulating phosphodiesterase-4, extracellular signal-regulated kinase, Akt/mammalian target of rapamycin kinase, and nuclear factor-kappa B.

    Science.gov (United States)

    Sugimoto, Naotoshi; Miwa, Shinji; Hitomi, Yoshiaki; Nakamura, Hiroyuki; Tsuchiya, Hiroyuki; Yachie, Akihiro

    2014-01-01

    Theobromine, a caffeine derivative, is the primary methylxanthine produced by Theobroma cacao. We previously showed that methylxanthines, including caffeine and theophylline, have antitumor and antiinflammatory effects, which are in part mediated by their inhibition of phosphodiesterase (PDE). A member of the PDE family, PDE4, is widely expressed in and promotes the growth of glioblastoma, the most common type of brain tumor. The purpose of this study was to determine whether theobromine could exert growth inhibitory effects on U87-MG, a cell line derived from human malignant glioma. We show that theobromine treatment elevates intracellular cAMP levels and increases the activity of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, whereas it attenuates p44/42 extracellular signal-regulated kinase activity and the Akt/mammalian target of rapamycin kinase and nuclear factor-kappa B signal pathways. It also inhibits cell proliferation. These results suggest that foods and beverages containing cocoa bean extracts, including theobromine, might be extremely effective in preventing human glioblastoma.

  5. Dynamin-dependent amino acid endocytosis activates mechanistic target of rapamycin complex 1 (mTORC1).

    Science.gov (United States)

    Shibutani, Shusaku; Okazaki, Hana; Iwata, Hiroyuki

    2017-11-03

    The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of protein synthesis and potential target for modifying cellular metabolism in various conditions, including cancer and aging. mTORC1 activity is tightly regulated by the availability of extracellular amino acids, and previous studies have revealed that amino acids in the extracellular fluid are transported to the lysosomal lumen. There, amino acids induce recruitment of cytoplasmic mTORC1 to the lysosome by the Rag GTPases, followed by mTORC1 activation by the small GTPase Ras homolog enriched in brain (Rheb). However, how the extracellular amino acids reach the lysosomal lumen and activate mTORC1 remains unclear. Here, we show that amino acid uptake by dynamin-dependent endocytosis plays a critical role in mTORC1 activation. We found that mTORC1 is inactivated when endocytosis is inhibited by overexpression of a dominant-negative form of dynamin 2 or by pharmacological inhibition of dynamin or clathrin. Consistently, the recruitment of mTORC1 to the lysosome was suppressed by the dynamin inhibition. The activity and lysosomal recruitment of mTORC1 were rescued by increasing intracellular amino acids via cycloheximide exposure or by Rag overexpression, indicating that amino acid deprivation is the main cause of mTORC1 inactivation via the dynamin inhibition. We further show that endocytosis inhibition does not induce autophagy even though mTORC1 inactivation is known to strongly induce autophagy. These findings open new perspectives for the use of endocytosis inhibitors as potential agents that can effectively inhibit nutrient utilization and shut down the upstream signals that activate mTORC1. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Activation of mammalian target of rapamycin signaling promotes cell cycle progression and protects cells from apoptosis in mantle cell lymphoma.

    Science.gov (United States)

    Peponi, Evangelia; Drakos, Elias; Reyes, Guadalupe; Leventaki, Vasiliki; Rassidakis, George Z; Medeiros, L Jeffrey

    2006-12-01

    Mantle cell lymphoma (MCL) is characterized by the t(11;14) and cyclin D1 overexpression. However, additional molecular events are most likely required for oncogenesis, possibly through cell cycle and apoptosis deregulation. We hypothesized that mammalian target of rapamycin (mTOR) is activated in MCL and contributes to tumor proliferation and survival. In MCL cell lines, pharmacological inhibition of the phosphoinositide 3-kinase/AKT pathway was associated with decreased phosphorylation (activation) of mTOR and its downstream targets phosphorylated (p)-4E-BP1, p-p70S6 kinase, and p-ribosomal protein S6, resulting in apoptosis and cell cycle arrest. These changes were associated with down-regulation of cyclin D1 and the anti-apoptotic proteins cFLIP, BCL-XL, and MCL-1. Furthermore, silencing of mTOR expression using mTOR-specific short interfering RNA decreased phosphorylation of mTOR signaling proteins and induced cell cycle arrest and apoptosis. Silencing of eukaryotic initiation factor (eIF4E), a downstream effector of mTOR, recapitulated these results. We also assessed mTOR signaling in MCL tumors using immunohistochemical methods and a tissue microarray: 10 of 30 (33%) expressed Ser473p-AKT, 13 of 21 (62%) Ser2448p-mTOR, 22 of 22 (100%) p-p70S6K, and 5 of 20 (25%) p-ribosomal protein S6. Total eIF4E binding protein 1 and eukaryotic initiation factor 4E were expressed in 13 of 14 (93%) and 16 of 29 (55%) MCL tumors, respectively. These findings suggest that the mTOR signaling pathway is activated and may contribute to cell cycle progression and tumor cell survival in MCL.

  7. Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma.

    Directory of Open Access Journals (Sweden)

    Tjinta Brinkhuizen

    Full Text Available BACKGROUND: Basal cell carcinoma (BCC is the most common cancer in Caucasians. Trichoepithelioma (TE is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1 and mechanistic/mammalian target of rapamycin (mTOR are key players in these pathways. OBJECTIVES: To determine whether HIF1/mTOR signalling is involved in BCC and TE. METHODS: We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45 and TE (n = 35 samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, 80%. RESULTS: Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3, 73% and 75% (CAIX, 79% and 86% (GLUT1, 50% and 19% (HIF1α, 89% and 88% (pAKT, 55% and 61% (pS6, 15% and 25% (pMTOR, 44% and 63% (PHD2 and 44% and 49% (VEGF-A. CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included. CONCLUSIONS: HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE.

  8. Development of high-performance solar LED lighting system

    KAUST Repository

    Huang, B.J.; Wu, M.S.; Hsu, P.C.; Chen, J.W.; Chen, K.Y.

    2010-01-01

    The present study developed a high-performance charge/discharge controller for stand-alone solar LED lighting system by incorporating an nMPPO system design, a PWM battery charge control, and a PWM battery discharge control to directly drive the LED. The MPPT controller can then be removed from the stand-alone solar system and the charged capacity of the battery increases 9.7%. For LED driven by PWM current directly from battery, a reliability test for the light decay of LED lamps was performed continuously for 13,200 h. It has shown that the light decay of PWM-driven LED is the same as that of constant-current driven LED. The switching energy loss of the MOSFET in the PWM battery discharge control is less than 1%. Three solar-powered LED lighting systems (18 W, 100 W and 150 W LED) were designed and built. The long-term outdoor field test results have shown that the system performance is satisfactory with the control system developed in the present study. The loss of load probability for the 18 W solar LED system is 14.1% in winter and zero in summer. For the 100 W solar LED system, the loss of load probability is 3.6% in spring. © 2009 Elsevier Ltd. All rights reserved.

  9. Development of high-performance solar LED lighting system

    International Nuclear Information System (INIS)

    Huang, B.J.; Wu, M.S.; Hsu, P.C.; Chen, J.W.; Chen, K.Y.

    2010-01-01

    The present study developed a high-performance charge/discharge controller for stand-alone solar LED lighting system by incorporating an nMPPO system design, a PWM battery charge control, and a PWM battery discharge control to directly drive the LED. The MPPT controller can then be removed from the stand-alone solar system and the charged capacity of the battery increases 9.7%. For LED driven by PWM current directly from battery, a reliability test for the light decay of LED lamps was performed continuously for 13,200 h. It has shown that the light decay of PWM-driven LED is the same as that of constant-current driven LED. The switching energy loss of the MOSFET in the PWM battery discharge control is less than 1%. Three solar-powered LED lighting systems (18 W, 100 W and 150 W LED) were designed and built. The long-term outdoor field test results have shown that the system performance is satisfactory with the control system developed in the present study. The loss of load probability for the 18 W solar LED system is 14.1% in winter and zero in summer. For the 100 W solar LED system, the loss of load probability is 3.6% in spring.

  10. Development of high-performance solar LED lighting system

    KAUST Repository

    Huang, B.J.

    2010-08-01

    The present study developed a high-performance charge/discharge controller for stand-alone solar LED lighting system by incorporating an nMPPO system design, a PWM battery charge control, and a PWM battery discharge control to directly drive the LED. The MPPT controller can then be removed from the stand-alone solar system and the charged capacity of the battery increases 9.7%. For LED driven by PWM current directly from battery, a reliability test for the light decay of LED lamps was performed continuously for 13,200 h. It has shown that the light decay of PWM-driven LED is the same as that of constant-current driven LED. The switching energy loss of the MOSFET in the PWM battery discharge control is less than 1%. Three solar-powered LED lighting systems (18 W, 100 W and 150 W LED) were designed and built. The long-term outdoor field test results have shown that the system performance is satisfactory with the control system developed in the present study. The loss of load probability for the 18 W solar LED system is 14.1% in winter and zero in summer. For the 100 W solar LED system, the loss of load probability is 3.6% in spring. © 2009 Elsevier Ltd. All rights reserved.

  11. ZnO-nanorods: A possible white LED phosphor

    Science.gov (United States)

    Sarangi, Sachindra Nath; T., Arun; Ray, Dinseh K.; Sahoo, Pratap Kumar; Nozaki, Shinji; Sugiyama, Noriyuki; Uchida, Kazuo

    2017-05-01

    The white light-emitting diodes (LEDs) have drawn much attention to replace conventional lighting sources because of low energy consumption, high light efficiency and long lifetime. Although the most common approach to produce white light is to combine a blue LED chip and a yellow phosphor, such a white LED cannot be used for a general lighting application, which requires a broad luminescence spectrum in the visible wavelength range. We have successfully chemically synthesized the ZnO nanorods showing intense broad luminescence in the visible wavelength range and made a white LED using the ZnO nanorods as phosphor excited with a blue LED. Their lengths and diameters were 2 - 10 μm and 200 - 800 nm, respectively. The wurtzite structure was confirmed by the x-ray diffraction measurement. The PL spectrum obtained by exciting the ZnO nanorods with the He-Cd laser has two peaks, one associated with the near band-edge recombination and the other with recombination via defects. The peak intensity of the near band-edge luminescence at 388 nm is much weaker than that of the defect-related luminescence. The latter luminescence peak ranges from 450 to 850 nm and broad enough to be used as a phosphor for a white LED. A white LED has been fabricated using a blue LED with 450 nm emission and ZnO nanorod powders. The LED performances show a white light emission and the electroluminescence measurement shows a stiff increase in white light intensity with increasing blue LED current. The Commission International de1'Eclairage (CIE) chromaticity colour coordinates of 450 nm LED pumped white emission shows a coordinate of (0.31, 0.32) for white LED at 350 mA. These results indicate that ZnO nanorods provides an alternate and effective approach to achieve high-performance white LEDs and also other optoelectronic devices.

  12. Analysis of Shade Matching in Natural Dentitions Using Intraoral Digital Spectrophotometer in LED and Filtered LED Light Sources.

    Science.gov (United States)

    Chitrarsu, Vijai Krishnan; Chidambaranathan, Ahila Singaravel; Balasubramaniam, Muthukumar

    2017-10-31

    To evaluate the shade matching capabilities in natural dentitions using Vita Toothguide 3D-Master and an intraoral digital spectrophotometer (Vita Easyshade Advance 4.0) in various light sources. Participants between 20 and 40 years old with natural, unrestored right maxillary central incisors, no history of bleaching, orthodontic treatment, or malocclusion and no rotations were included. According to their shades, subjects were randomly selected and grouped into A1, A2, and A3. A total of 100 participants (50 male and 50 female) in each group were chosen for this study. Shade selection was made between 10 am and 2 pm for all light sources. The same examiner selected the shade of natural teeth with Vita Toothguide 3D-Master under natural light within 2 minutes. Once the Vita Toothguide 3D-Masterwas matched with the maxillary right central incisor, the L*, a*, and b* values, chroma, and hue were recorded with Vita Easyshade Advance 4.0 by placing it on the shade tab under the same light source. The values were statistically analyzed using one-way ANOVA and Tukey's HSD post hoc test with SPSS v22.0 software. The mean ∆E* ab values for shades A1, A2, and A3 for groups 1, 2, and 3 were statistically significantly different from each other (p spectrophotometer showed statistically significant differences in shade matching compared to Vita Toothguide 3D-Master. Incandescent light showed more accurate shade matching than the filtered LED, LED, and daylight. © 2017 by the American College of Prosthodontists.

  13. Intelligent control of dynamic LED lighting; Intelligent styring af dynamisk LED belysning. Slutrapport

    Energy Technology Data Exchange (ETDEWEB)

    Thorseth, A.; Corell, D.; Hansen, Soeren S.; Dam-Hansen, C.; Petersen, Paul Michael

    2013-01-15

    The project has resulted in a prototype of a new intelligent lighting control system. The control system enables the end user to control his or her own local lighting environment (lighting zone) according to individual preferences and needs. The report provides a description of how the developed intelligent lighting system is composed and functions. The system is designed as a work lamp that enables dynamic change of the light color scheme according to a number of light control algorithms. It is specifically designed in relation to user tests of the intelligent lighting system, which is carried out in the final part of the project. An intelligent and advanced control of LED lighting was developed, which enables optimization of the user's light conditions in a given situation. Based on a number of known parameters, the system can control lighting so that at any time optimal light conditions are created, using a minimum of electric power. (LN)

  14. Physiotherapy-led arthroplasty review clinic: a preliminary outcomes analysis.

    Science.gov (United States)

    Large, Kate E; Page, Carolyn J; Brock, Kim; Dowsey, Michelle M; Choong, Peter F M

    2014-11-01

    With the rising demand for Orthopaedics in the healthcare sector, service delivery innovations need to be explored to accommodate the increasing workload. Senior Musculoskeletal Physiotherapists have the specialised skills in the assessment of musculoskeletal conditions to determine the impact of surgery on patient outcomes. The aim of the present study was to compare outcomes between a physiotherapy-led arthroplasty review clinic (PT clinic) and the traditional model of orthopaedic surgeon review (OS clinic) after hip and knee replacement. This study was a retrospective case-controlled audit using a comprehensive database. Twenty-four patients who had a hip arthroplasty and 52 patients who had a knee arthroplasty were reviewed solely by the PT clinic at 3, 6 and 12 months after surgical reviews. These patients were matched 1:2 against patients seen only by the OS clinic. The outcome measures included International Knee Score (IKS), Harris Hip Score (HHS) and the Short Form (SF)-12. There were no significant differences in HHS or SF-12 scores for patients after hip arthroplasty. Significant differences for knee arthroplasty were observed favouring the PT clinic; IKS, PT clinic 147.6 (37.07), OS clinic 135.4 (35.68), P≤0.01, and physical component of the SF-12, PT clinic 41.98 (10.45), OS clinic 37.20 (10.44), Pphysiotherapy-led arthroplasty review clinic appears to be a safe and effective service alternative to reviews conducted by orthopaedic surgeons. WHAT IS KNOWN ABOUT THE TOPIC?: Osteoarthritis (OA) is a leading cause of musculoskeletal pain and disability and the burden of the disease is rapidly increasing. Joint arthroplasty surgery is the mainstay of treatment for people with end-stage OA; it is a high-cost, high-volume procedure that dominates surgical wait lists around Australia. Long-term follow up is encouraged by the Arthroplasty Society of Australia and endorsed by the Australian Orthopaedics Association, but it is acknowledged that it is impossible

  15. Estudo morfométrico da terapia LED de baixa potência em tendinite de ratos Morphometric study of low power LED therapy tendonitis in rats

    Directory of Open Access Journals (Sweden)

    José Mário Nunes da Silva

    2011-12-01

    Full Text Available A terapia LED de baixa potência possui efeitos analgésico e antiinflamatório. O objetivo desse estudo foi analisar a ação da terapia com LED de baixa potência na reparação tendínea por meio de histologia e histomorfometria. Foram usados 25 ratos Wistar, de 220 a 250 g, divididos em três grupos experimentais avaliados no 7º e 14º dia: A, tendinite induzida sem tratamento; B, tendinite induzida tratada com LED de baixa potência, densidade de energia 4 J/cm² por 120 segundos; e C, sem indução de tendinite. A histomorfometria mostrou-se altamente significativa (p0,05. As análises histológica e histomorfométrica demonstraram qualitativo e quantitativo aumento no número de fibroblastos aos sete dias de tratamento, e das fibras colágenas, aos 14 dias, para grupo tratado com LED de baixa potência em relação ao grupo sadio (C. O mesmo não foi percebido quando relacionado ao grupo tendinite (A14.The low power LED therapy has analgesic and anti-inflammatory effects. The objective of this study was to analyze the action of therapy with low power LED on the tendon repair, using histology and histomorphometry. Were used 25 Wistar rats, with 220 to 250 g, divided into three experimental groups (7 and 14 days: A7 and A14 induced tendonitis without treatment; B7 and B14, induced tendinitis treated with LED low power density energy 4 J /cm² for 120 seconds; and C, without induction of tendinitis. Histomorphometry was highly significant (p 0.05. Histology and histomorphometry analysis demonstrated qualitative and quantitative increase in the number of fibroblasts to seven days of treatment, and collagen fibers at 14 days for the group treated with LED low power compared to the healthy group (C. But it is unclear even when related to the tendinitis group (A14.

  16. Relationship between Quality of Life and Nurse-led Bedside Symptom Evaluations in Patients with Chemotherapy-induced Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Yang-Sook Yoo, RN, PhD

    2014-03-01

    Conclusion: Collectively, our results indicate that nurse-led bedside evaluation is a noninvasive and useful method for detecting neurotoxicity and evaluating the patient’s QOL both during and after treatment.

  17. An overview of LED applications for general illumination

    Science.gov (United States)

    Pelka, David G.; Patel, Kavita

    2003-11-01

    This paper begins by reviewing the current state of development of LEDs, their existing markets as well as their potential for energy conservation and their potential for gaining market share in the general illumination market. It discusses LED metrics such as chip size, lumens per watt, thermal resistance, and the recommended maximum current rating. The paper then goes on to consider the importance of non-imaging optics for both optically efficient and extremely compact LED lighting systems. Finally, microstructures useful for controlling the fields-of-view of LED lighting systems are considered and described in some detail. An extremely efficient and cost effective microstructure, called kinoform diffusers, is shown to have very unique properties that make this technology almost ideal for shaping the output beams of LED lighting systems. It concludes by illustrating some general illumination LED lighting systems

  18. Competing in the Global LED Industry: The Case of Taiwan

    Directory of Open Access Journals (Sweden)

    Yu-Shan Su

    2014-01-01

    Full Text Available Light-emitting diode (LED is a very essential application for energy-savings nowadays. The revenue of the Taiwan LED components industry is ranked top one in the world, followed by that of Japan and South Korea. Based on the advantage of their electronics industry, Taiwanese LED companies create a unique model to compete with the international firms. Large international LED companies achieve economies of scale by vertically integrating their operations. Taiwanese LED companies specialize and achieve an optimal efficiency by vertically disintegrating across the upstream, midstream, and downstream sectors in the value chains. Taiwanese LED companies create economies of scale and economies of scope through a complete industrial value chain.

  19. 'No blue' LED solution for photolithography room illumination

    DEFF Research Database (Denmark)

    Ou, Haiyan; Corell, Dennis Dan; Dam-Hansen, Carsten

    2010-01-01

    This paper explored the feasibility of using a LED-based bulb as the illumination light source for photolithography room. A no-blue LED was designed, and the prototype was fabricated. The spectral power distribution of both the LED bulb and the yellow fluorescent tube was measured. Based on that...... color rendering ability than the YFT. Furthermore, LED solution has design flexibility to improve it further. The prototype has been tested with photoresist SU8-2005. Even after 15 days of illumination, no effect was observed. So this LED-based solution was demonstrated to be a very promising light......, colorimetric values were calculated and compared on terms of chromatic coordinates, correlated color temperature, color rendering index, and chromatic deviation. Gretagmacbeth color charts were used as a more visional way to compare the two light sources, which shows that our no-blue LED bulb has much better...

  20. Effects of light emitting diode (LED) therapy and cold water immersion therapy on exercise-induced muscle damage in rats.

    Science.gov (United States)

    Camargo, Mariana Zingari; Siqueira, Cláudia Patrícia Cardoso Martins; Preti, Maria Carla Perozim; Nakamura, Fábio Yuzo; de Lima, Franciele Mendes; Dias, Ivan Frederico Lupiano; Toginho Filho, Dari de Oliveira; Ramos, Solange de Paula

    2012-09-01

    The aim of this work is to analyze the effects of LED therapy at 940 nm or cold water immersion therapy (CWI) after an acute bout of exercise on markers of muscle damage and inflammation. Thirty-two male Wistar rats were allocated into four groups: animals kept at rest (control), exercised animals (E), exercised + CWI (CWI), and exercised + LED therapy (LED). The animals swam for 100 min, after which blood samples were collected for lactate analysis. Animals in the E group were returned to their cages without treatment, the CWI group was placed in cold water (10°C) for 10 min and the LED group received LED irradiation on both gastrocnemius muscles (4 J/cm(2) each). After 24 h, the animals were killed and the soleus muscles were submitted to histological analysis. Blood samples were used for hematological and CK analyses. The results demonstrated that the LED group presented fewer areas of muscle damage and inflammatory cell infiltration and lower levels of CK activity than the E group. Fewer areas of damaged muscle fiber were observed in the LED group than in CWI. CWI and LED did not reduce edema areas. Hematological analysis showed no significant effect of either treatment on leukocyte counts. The results suggest that LED therapy is more efficient than CWI in preventing muscle damage and local inflammation after exercise.

  1. Interior LED Lighting Technology. Navy Energy Technology Validation (Techval) Program

    Science.gov (United States)

    2015-09-01

    usually on most of the time. • Consider replacing existing CFL, high-intensity discharge (HID), or halogen lamp light fixtures/ lamps with LED fixtures... lamps . What is the Technology? An LED is a semiconductor-diode that emits light when power is applied. A driver is used, much as a ballast, to...available in integrated luminaires that can be used to replace existing luminaires. LEDs are also available as direct replacement lamps for many

  2. UV-LED Curing Efficiency of Wood Coatings

    OpenAIRE

    Véronic Landry; Pierre Blanchet; Gabrielle Boivin; Jean-François Bouffard; Mirela Vlad

    2015-01-01

    Ultraviolet light emitting diodes (UV-LEDs) have attracted great interest in recent years. They can be used to polymerize coatings, such as those used for prefinished wood flooring. In this project, two lamps were compared for their suitability to be used on a wood flooring finishing line: a UV-microwave and a UV-LED lamp. Low heat emission was found for the UV-LED lamp compared to the UV-microwave one. This study also reveals that the 4 W/cm2 UV-LED lamp used is not powerf...

  3. A synthetic method of solar spectrum based on LED

    Science.gov (United States)

    Wang, Ji-qiang; Su, Shi; Zhang, Guo-yu; Zhang, Jian

    2017-10-01

    A synthetic method of solar spectrum which based on the spectral characteristics of the solar spectrum and LED, and the principle of arbitrary spectral synthesis was studied by using 14 kinds of LED with different central wavelengths.The LED and solar spectrum data were selected by Origin Software firstly, then calculated the total number of LED for each center band by the transformation relation between brightness and illumination and Least Squares Curve Fit in Matlab.Finally, the spectrum curve of AM1.5 standard solar spectrum was obtained. The results met the technical indexes of the solar spectrum matching with ±20% and the solar constant with >0.5.

  4. PV power system using hybrid converter for LED indictor applications

    International Nuclear Information System (INIS)

    Tseng, Sheng-Yu; Wang, Hung-Yuan; Chen, Chien-Chih

    2013-01-01

    Highlights: • This paper presents a LED indictor driving circuit with a PV arrays as its power source. • The perturb-and-observe method is adopted to extract the maximum power of PV arrays. • The proposed circuit structure has a less component counts and higher conversion efficiency. • A prototype of LED indictor driving circuit has been implemented to verify its feasibility. • The proposed hybrid converter is suitable for LED inductor applications. - Abstract: This paper presents a LED indictor driving circuit with a PV arrays as its power source. The LED indictor driving circuit includes battery charger and discharger (LED driving circuit). In this research, buck converter is used as a charger, and forward converter with active clamp circuit is adopted as a discharger to drive the LED indictor. Their circuit structures use switch integration technique to simplify them and to form the proposed hybrid converter, which has a less component counts, lighter weight, smaller size, and higher conversion efficiency. Moreover, the proposed hybrid converter uses a perturb-and-observe method to extract the maximum power from PV arrays. Finally, a prototype of an LED indictor driving circuit with output voltage of 10 V and output power of 20 W has been implemented to verify its feasibility. It is suitable for the LED inductor applications

  5. Improving “color rendering” of LED lighting for the growth of lettuce

    Science.gov (United States)

    Han, Tao; Vaganov, Vitaliy; Cao, Shixiu; Li, Qiang; Ling, Lili; Cheng, Xiaoyao; Peng, Lingling; Zhang, Congzhi; Yakovlev, Alexey N.; Zhong, Yang; Tu, Mingjing

    2017-04-01

    Light plays a vital role on the growth and development of plant. On the base of white light with high color rendering to the benefit of human survival and life, we proposed to improve “color rendering” of LED lighting for accelerating the growth of lettuce. Seven spectral LED lights were adopted to irradiate the lettuces under 150 μmol·m-2·s-1 for a 16 hd-1 photoperiod. The leaf area and number profiles, plant biomass, and photosynthetic rate under the as-prepared LED light treatments were investigated. We let the absorption spectrum of fresh leaf be the emission spectrum of ideal light and then evaluate the “color rendering” of as-prepared LED lights by the Pearson product-moment correlation coefficient and CIE chromaticity coordinates. Under the irradiation of red-yellow-blue light with high correlation coefficient of 0.587, the dry weights and leaf growth rate are 2-3 times as high as the sharp red-blue light. The optimized LED light for lettuce growth can be presumed to be limited to the angle (about 75°) between the vectors passed through the ideal light in the CIE chromaticity coordinates. These findings open up a new idea to assess and find the optimized LED light for plant growth.

  6. Effect of LED light on seeds of Capsicum annuum L. var. serrano

    Directory of Open Access Journals (Sweden)

    Alejandra María Moreno-Jiménez

    2017-11-01

    Full Text Available Serrano pepper (Capsicum annuum L. is a crop of economic, nutritional and medicinal importance; so it is necessary to increase its production and improve its characteristics. The objective of this research was to evaluate the stimulatory effect of light emitting diodes (LEDs on serrano pepper seedlings. Germination percentage, stem length, leaf width, leaf length, number of leaves, total chlorophyll content and carotenoid content were analyzed. The seeds were exposed to white, blue and red LED light, using fluorescent light as a control and a photoperiod of 11/13 hours. Once germinated, the seedlings continued with exposure to light for 30 days. After the laboratory conditions, the seedlings were transferred to a greenhouse for 60 days. The results show that there were no significant differences between LED light treatments on seed germination. The variables stem length, leaf width and leaf length, were favored with red light. Blue and red LEDs highlighted by increasing the number of leaves. Seedlings treated with blue light showed the highest content of photosynthetic pigments (chlorophyll= 0.84 mg g-1, carotenoid= 0.12 mg g-1. In conclusion, the red LED light is effective for the growth of serrano pepper seedlings, while the production of photosynthetic pigments was favored by blue LED light.   Keywords: peppers, light-emitting diodes, germination, growth, photosynthetic pigments

  7. Raman study of the effect of LED light on grafted bone defects

    Science.gov (United States)

    Soares, Luiz G. G. P.; Aciole, Jouber M. S.; Aciole, Gilbeth T. S.; Barbosa, Artur F. S.; Silveira-Júnior, Landulfo; Pinheiro, Antônio L. B.

    2013-03-01

    Benefits of the isolated or combined use light and biomaterials on bone healing have been suggested. Our group has used several models to assess the effects of laser on bone. A Raman spectral analysis on surgical bone defects grafted or not with Hydroxyapatite (HA), treated or not with LED was carried out. 40 rats were divided into 4 groups. On Group I the defect was filled with the clot. On Group II, the defect was filled with the HA. On groups III the defect was filled with Clot and further irradiated with LED and on group IV the defects was filled with the HA and further irradiated with LED. LED (λ850 +/- 10nm, 150mW, A= 0.5cm2, 68s, 20 J/cm2 per session, 140 J/cm2 per treatment) was applied at 48 h intervals during 15 days. Specimens were taken after 15 and 30 days after surgery and kept on liquid nitrogen, and underwent Raman analysis. For this, the peak of hydroxyapatite (~960 cm-1) was used as marker of bone mineralization. Significant difference was observed at both times (p<0.05). When the biomaterial was used higher peaks were observed. Association with LED further improved the intensity. Conclusion: It is concluded that LED light improved the effect of the HA.

  8. Mammalian target of rapamycin complex 1 activation is required for the stimulation of human skeletal muscle protein synthesis by essential amino acids.

    Science.gov (United States)

    Dickinson, Jared M; Fry, Christopher S; Drummond, Micah J; Gundermann, David M; Walker, Dillon K; Glynn, Erin L; Timmerman, Kyle L; Dhanani, Shaheen; Volpi, Elena; Rasmussen, Blake B

    2011-05-01

    The relationship between mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis during instances of amino acid surplus in humans is based solely on correlational data. Therefore, the goal of this study was to use a mechanistic approach specifically designed to determine whether increased mTORC1 activation is requisite for the stimulation of muscle protein synthesis following L-essential amino acid (EAA) ingestion in humans. Examination of muscle protein synthesis and signaling were performed on vastus lateralis muscle biopsies obtained from 8 young (25 ± 2 y) individuals who were studied prior to and following ingestion of 10 g of EAA during 2 separate trials in a randomized, counterbalanced design. The trials were identical except during 1 trial, participants were administered a single oral dose of a potent mTORC1 inhibitor (rapamycin) prior to EAA ingestion. In response to EAA ingestion, an ~60% increase in muscle protein synthesis was observed during the control trial, concomitant with increased phosphorylation of mTOR (Ser(2448)), ribosomal S6 kinase 1 (Thr(389)), and eukaryotic initiation factor 4E binding protein 1 (Thr(37/46)). In contrast, prior administration of rapamycin completely blocked the increase in muscle protein synthesis and blocked or attenuated activation of mTORC1-signaling proteins. The inhibition of muscle protein synthesis and signaling was not due to differences in either extracellular or intracellular amino acid availability, because these variables were similar between trials. These data support a fundamental role for mTORC1 activation as a key regulator of human muscle protein synthesis in response to increased EAA availability. This information will be useful in the development of evidence-based nutritional therapies targeting mTORC1 to counteract muscle wasting associated with numerous clinical conditions.

  9. Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin.

    Science.gov (United States)

    Bhagwat, Shripad V; Gokhale, Prafulla C; Crew, Andrew P; Cooke, Andy; Yao, Yan; Mantis, Christine; Kahler, Jennifer; Workman, Jennifer; Bittner, Mark; Dudkin, Lorina; Epstein, David M; Gibson, Neil W; Wild, Robert; Arnold, Lee D; Houghton, Peter J; Pachter, Jonathan A

    2011-08-01

    The phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway is frequently activated in human cancers, and mTOR is a clinically validated target. mTOR forms two distinct multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, metabolism, proliferation, and survival. Rapamycin and its analogues partially inhibit mTOR through allosteric binding to mTORC1, but not mTORC2, and have shown clinical utility in certain cancers. Here, we report the preclinical characterization of OSI-027, a selective and potent dual inhibitor of mTORC1 and mTORC2 with biochemical IC(50) values of 22 nmol/L and 65 nmol/L, respectively. OSI-027 shows more than 100-fold selectivity for mTOR relative to PI3Kα, PI3Kβ, PI3Kγ, and DNA-PK. OSI-027 inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo. OSI-027 and OXA-01 (close analogue of OSI-027) potently inhibit proliferation of several rapamycin-sensitive and -insensitive nonengineered and engineered cancer cell lines and also, induce cell death in tumor cell lines with activated PI3K-AKT signaling. OSI-027 shows concentration-dependent pharmacodynamic effects on phosphorylation of 4E-BP1 and AKT in tumor tissue with resulting tumor growth inhibition. OSI-027 shows robust antitumor activity in several different human xenograft models representing various histologies. Furthermore, in COLO 205 and GEO colon cancer xenograft models, OSI-027 shows superior efficacy compared with rapamycin. Our results further support the important role of mTOR as a driver of tumor growth and establish OSI-027 as a potent anticancer agent. OSI-027 is currently in phase I clinical trials in cancer patients. ©2011 AACR

  10. Assessment of community led total sanitation uptake in rural Kenya ...

    African Journals Online (AJOL)

    Background: Community Led Total Sanitation (CLTS) is an innovative community led drive to set up pit latrines in rural Kenya with an aim of promoting sustainable sanitation through behaviour change. It's a behaviour change approach based on social capital that triggers households to build pit latrines without subsidy.

  11. High Output LED-Based Profile Lighting Fixture

    DEFF Research Database (Denmark)

    Török, Lajos; Beczkowski, Szymon; Munk-Nielsen, Stig

    2011-01-01

    Recent developments in power light emitting diode (LED) industry have made LEDs suitable for being efficiently used in high intensity lighting fixtures instead of the commonly used high intensity discharge (HID) lamps. A high output LEDbased profile-light fixture is presented in this paper...

  12. Thermo-mechanical model optimization of HB-LED packaging

    NARCIS (Netherlands)

    Yuan, C.A.; Erinc, M.; Gielen, A.W.J.; Waal, A. van der; Driel, W. van; Zhang, K.

    2011-01-01

    Lighting is an advancing phenomenon both on the technology and on the market level due to the rapid development of the solid state lighting technology. The efforts in improving the efficacy of high brightness LED's (HB-LED) have concentrated on the packaging architecture. Packaging plays a

  13. The Lifetime Prediction of LED Drivers and Lamps

    NARCIS (Netherlands)

    Sun, B.

    2017-01-01

    Light-Emitting Diodes (LEDs) have become a very promising alternative lighting source with the main advantages of a longer lifetime and a higher efficiency than traditional ones. However, the LED lamp’s lifetime is compromised by its driver’s reliability. Although extensive studies have been made on

  14. Flicker Reduction in LED-LCDs with Local Backlight

    DEFF Research Database (Denmark)

    Nadernejad, Ehsan; Mantel, Claire; Burini, Nino

    2013-01-01

    Local backlight dimming of LCD with LED backlight can reduce power consumption and improve quality of displayed images and videos. However, important variations of LED over time produce a visually annoying artifact called flickering. In this work, we propose a new algorithm to reduce flickering w...

  15. On-off switching patterns for smart LED lighting

    NARCIS (Netherlands)

    Linnartz, J.P.M.G.; Schenk, T.C.W.; Feri, L.; Yang, Hongming; Tjalkens, T.J.; Willems, F.M.J.

    2009-01-01

    This paper formulates a new communication problem for smart LED lighting sys tems designed for light effect control. It introduces the key requirements imposed on the design of the LED driving sequences, which include multiple access, arbi trary duty cycle and no disturbance caused on the normal

  16. The WIMSE-E module W-LED

    International Nuclear Information System (INIS)

    Roth, M.J.

    1992-06-01

    This report describes the WIMS-E edit module W-LED. W-LED sets up a library of cross section and other nuclear data for a set of materials for subsequent use in a whole reactor program such as PANTHER. (author)

  17. Improved power quality based high brightness LED lamp driver

    African Journals Online (AJOL)

    user

    consists of a PFC Cuk DC-DC converter which operates in continuous conduction mode (CCM) to improve the ... In proposed LED driver as shown in Figure 1, a Cuk buck boost AC-DC converter ... Design and Analysis of Proposed LED Driver.

  18. Spectral Design Flexibility of LED Brings Better life

    DEFF Research Database (Denmark)

    Ou, Haiyan; Corell, Dennis Dan; Ou, Yiyu

    2012-01-01

    Light-emitting diodes (LEDs) are penetrating into the huge market of general lighting because they are energy saving and environmentally friendly. The big advantage of LED light sources, compared to traditional incandescent lamps and fluorescent light tubes, is the flexible spectral design to make...

  19. An inverse method for color uniformity in white LED spotlights

    NARCIS (Netherlands)

    Prins, C.R.; Thije Boonkkamp, ten J.H.M.; Tukker, T.W.; IJzerman, W.L.

    2013-01-01

    Color over Angle (CoA) variation in the light output of white phosphor-converted LEDs is a common problem in LED lighting technology. In this article we propose an inverse method to design an optical element that eliminates the color variation for a point light source. The method in this article is

  20. Tuning the color point of a white LED

    NARCIS (Netherlands)

    Adhikary, Manashee; Meretska, Maryna; Ladovrechis, K.; Fokkema, Wouter K.; Vissenberg, Gilles; Lagendijk, Ad; Ijzerman, W.L.; Vos, Willem L.

    2018-01-01

    White light is conveniently characterized by a color point that is represented on the color space. Color point of white LED is fixed by the design parameters (e.g. Phosphor type and concentration). When the design parameters are chosen, the color point of the white LED cannot be changed. Here, we

  1. An inverse method for color uniformity in white LED spotlights

    NARCIS (Netherlands)

    Prins, C.R.; Thije Boonkkamp, ten J.H.M.; Tukker, T.W.; IJzerman, W.L.

    2014-01-01

    Color over Angle (CoA) variation in the light output of white phosphor-converted LEDs is a common problem in LED lighting technology. In this article we propose an inverse method to design an optical element that eliminates the color variation for a point light source. The method in this article is

  2. Design of LED lamps | Ashryatov | Journal of Fundamental and ...

    African Journals Online (AJOL)

    Design of LED lamps. ... In this paper, we study the effect of LED high brightness on the brightness of a luminaire. The nomenclature of diffusers used in the production of ... The variant of the lighting system energy efficiency increase with luminaires and linear fluorescent lamps is considered. In the proposed variant, the ...

  3. Éalonnage de sources lumineuses de type LED

    DEFF Research Database (Denmark)

    Durix, Bastien; Quéau, Yvain; Lucas, Tom

    We describe three calibration methods of a LED (light-emitting diode), in order to apply photometric stereo to a scene illuminated by LEDs. The most accurate of these methods will allow us to obtain very realistic 3D models. Nevertheless, the scene must remain still during the whole shooting sequ...

  4. Low Cost Lithography Tool for High Brightness LED Manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Andrew Hawryluk; Emily True

    2012-06-30

    The objective of this activity was to address the need for improved manufacturing tools for LEDs. Improvements include lower cost (both capital equipment cost reductions and cost-ofownership reductions), better automation and better yields. To meet the DOE objective of $1- 2/kilolumen, it will be necessary to develop these highly automated manufacturing tools. Lithography is used extensively in the fabrication of high-brightness LEDs, but the tools used to date are not scalable to high-volume manufacturing. This activity addressed the LED lithography process. During R&D and low volume manufacturing, most LED companies use contact-printers. However, several industries have shown that these printers are incompatible with high volume manufacturing and the LED industry needs to evolve to projection steppers. The need for projection lithography tools for LED manufacturing is identified in the Solid State Lighting Manufacturing Roadmap Draft, June 2009. The Roadmap states that Projection tools are needed by 2011. This work will modify a stepper, originally designed for semiconductor manufacturing, for use in LED manufacturing. This work addresses improvements to yield, material handling, automation and throughput for LED manufacturing while reducing the capital equipment cost.

  5. Issues and solutions: opportunities for European LED manufacturers

    Science.gov (United States)

    Pearsall, T. P.

    2007-09-01

    Marketing studies by EPIC show significant revenue opportunities by 2012 for UHB-LEDs in the automotive, LCD backlighting, and architectural lighting sectors. The goal of this workshop on manufacturing issues is to consider five key issues for UHB-LED manufacturing and to propose solutions that will pave the way to full exploitation of the opportunities.

  6. Luminaries-level structure improvement of LEDs for heat dissipation ...

    Indian Academy of Sciences (India)

    the natural convection heat transfer process of LED luminaries is simulated by compu- ... Heat dissipation has become one of the key problems limiting the large ... micro channel heat radiator, are able to reject heat efficiently, they may make LED ... convection heat transfer coefficient, for example, adopting finned surface to ...

  7. Luminous flux and colour maintenance investigation of integrated LED lamps

    DEFF Research Database (Denmark)

    Corell, Dennis Dan; Thorseth, Anders; Dam-Hansen, Carsten

    2014-01-01

    This article will present an investigation of the luminous flux and colour maintenance of white LED based retrofit lamps. The study includes 23 different types of integrated LED lamps, covering 18 directional and 5 non-directional. Luminous flux and colour data for operation up to 20000 h has been...

  8. Two-way visible light communication and illumination with LEDs

    NARCIS (Netherlands)

    Li, S.; Pandharipande, A.; Willems, F.M.J.

    2017-01-01

    Visible light communications (VLC) with light-emitting diodes (LEDs) has attracted applications, such as data communications, lighting control, and light interaction. In this paper, we propose a system by which two LED devices are used for two-way VLC while also providing illumination. We consider

  9. Antitumor efficacy profile of PKI-402, a dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor.

    Science.gov (United States)

    Mallon, Robert; Hollander, Irwin; Feldberg, Larry; Lucas, Judy; Soloveva, Veronica; Venkatesan, Aranapakam; Dehnhardt, Christoph; Delos Santos, Efren; Chen, Zecheng; Dos Santos, Osvaldo; Ayral-Kaloustian, Semiramis; Gibbons, Jay

    2010-04-01

    PKI-402 is a selective, reversible, ATP-competitive, equipotent inhibitor of class I phosphatidylinositol 3-kinases (PI3K), including PI3K-alpha mutants, and mammalian target of rapamycin (mTOR; IC(50) versus PI3K-alpha = 2 nmol/L). PKI-402 inhibited growth of human tumor cell lines derived from breast, brain (glioma), pancreas, and non-small cell lung cancer tissue and suppressed phosphorylation of PI3K and mTOR effector proteins (e.g., Akt at T308) at concentrations that matched those that inhibited cell growth. In MDA-MB-361 [breast: Her2(+) and PIK3CA mutant (E545K)], 30 nmol/L PKI-402 induced cleaved poly(ADP-ribose) polymerase (PARP), a marker for apoptosis. In vivo, PKI-402 inhibited tumor growth in MDA-MB-361, glioma (U87MG), and lung (A549) xenograft models. In MDA-MB-361, PKI-402 at 100 mg/kg (daily for 5 days, one round) reduced initial tumor volume of 260 mm(3) to 129 mm(3) and prevented tumor regrowth for 70 days. In MDA-MB-361 tumors, PKI-402 (100 mg/kg, single dose) suppressed Akt phosphorylation (at T308) and induced cleaved PARP. Suppression of phosphorylated Akt (p-Akt) was complete at 8 hours and still evident at 24 hours. Cleaved PARP was evident at 8 and 24 hours. In normal tissue (heart and lung), PKI-402 (100 mg/kg) had minimal effect on p-Akt, with no detectable cleaved PARP. Preferential accumulation of PKI-402 in tumor tissue was observed. Complete, sustained suppression of Akt phosphorylation may cause tumor regression in MDA-MB-361 and other xenograft models. We are testing whether dual PI3K/mTOR inhibitors can durably suppress p-Akt, induce cleaved PARP, and cause tumor regression in a diverse set of human tumor xenograft models. Mol Cancer Ther; 9(4); 976-84. (c)2010 AACR.

  10. Expression status and prognostic significance of mammalian target of rapamycin pathway members in urothelial carcinoma of urinary bladder after cystectomy.

    Science.gov (United States)

    Schultz, Luciana; Albadine, Roula; Hicks, Jessica; Jadallah, Sana; DeMarzo, Angelo M; Chen, Ying-Bei; Nielsen, Matthew E; Neilsen, Matthew E; Gonzalgo, Mark L; Sidransky, David; Schoenberg, Mark; Netto, George J

    2010-12-01

    Bladder urothelial carcinoma has high rates of mortality and morbidity. Identifying novel molecular prognostic factors and targets of therapy is crucial. Mammalian target of rapamycin (mTOR) pathway plays a pivotal role in establishing cell shape, migration, and proliferation. Tissue microarrays were constructed from 132 cystectomies (1994-2002). Immunohistochemistry was performed for Pten, c-myc, p27, phosphorylated (phos)Akt, phosS6, and 4E-BP1. Markers were evaluated for pattern, percentage, and intensity of staining. Mean length of follow-up was 62.6 months (range, 1-182 months). Disease progression, overall survival (OS), and disease-specific survival (DSS) rates were 42%, 60%, and 68%, respectively. Pten showed loss of expression in 35% of bladder urothelial carcinoma. All markers showed lower expression in invasive bladder urothelial carcinoma compared with benign urothelium with the exception of 4E-BP1. Pten, p27, phosAkt, phosS6, and 4E-BP1 expression correlated with pathologic stage (pathological stage; P<.03). Pten, 4E-BP1, and phosAkt expression correlated with divergent aggressive histology and invasion. phosS6 expression inversely predicted OS (P=.01), DSS (P=.001), and progression (P=.05). c-myc expression inversely predicted progression (P=.01). In a multivariate analysis model that included TNM stage grouping, divergent aggressive histology, concomitant carcinoma in situ, phosS6, and c-myc expression, phosS6 was an independent predictor of DSS (P=.03; hazard ratio [HR], -0.19), whereas c-myc was an independent predictor of progression (P=.02; HR, -0.38). In a second model substituting organ-confined disease and lymph node status for TNM stage grouping, phosS6 and c-myc remained independent predictors of DSS (P=.03; HR, -0.21) and progression (P=.03; HR, -0.34), respectively. We found an overall down-regulation of mTOR pathway in bladder urothelial carcinoma. phosS6 independently predicted DSS, and c-myc independently predicted progression

  11. Meeting the challenges of developing LED-based projection displays

    Science.gov (United States)

    Geißler, Enrico

    2006-04-01

    The main challenge in developing a LED-based projection system is to meet the brightness requirements of the market. Therefore a balanced combination of optical, electrical and thermal parameters must be reached to achieve these performance and cost targets. This paper describes the system design methodology for a digital micromirror display (DMD) based optical engine using LEDs as the light source, starting at the basic physical and geometrical parameters of the DMD and other optical elements through characterization of the LEDs to optimizing the system performance by determining optimal driving conditions. LEDs have a luminous flux density which is just at the threshold of acceptance in projection systems and thus only a fully optimized optical system with a matched set of LEDs can be used. This work resulted in two projection engines, one for a compact pocket projector and the other for a rear projection television, both of which are currently in commercialization.

  12. Determination of LEDs degradation with entropy generation rate

    Science.gov (United States)

    Cuadras, Angel; Yao, Jiaqiang; Quilez, Marcos

    2017-10-01

    We propose a method to assess the degradation and aging of light emitting diodes (LEDs) based on irreversible entropy generation rate. We degraded several LEDs and monitored their entropy generation rate ( S ˙ ) in accelerated tests. We compared the thermoelectrical results with the optical light emission evolution during degradation. We find a good relationship between aging and S ˙ (t), because S ˙ is both related to device parameters and optical performance. We propose a threshold of S ˙ (t) as a reliable damage indicator of LED end-of-life that can avoid the need to perform optical measurements to assess optical aging. The method lays beyond the typical statistical laws for lifetime prediction provided by manufacturers. We tested different LED colors and electrical stresses to validate the electrical LED model and we analyzed the degradation mechanisms of the devices.

  13. The LED monitoring system of the PHOENICS experiment

    International Nuclear Information System (INIS)

    Urban, D.

    1991-07-01

    The PHOENICS experiment at ELSA uses a LED monitoring system to control pulse height and time measurement with scintillation counters. A green LED is mounted at the light guide of each of the 304 involved photomultiplier tubes. The LEDs are driven by fast voltage pulses of 5 ns FWHM width and about 20 V amplitude. Simulation of single events is possible by computer controlled switching of individual LEDs. In order to correct for the temperature dependence of the LED intensity an automatic temperature recording system was coupled to the computer. This monitor system allows to control the pulse height and time measurement with an accuracy of about 2% and 100 ps respectively. (orig.) [de

  14. Progress in extremely high brightness LED-based light sources

    Science.gov (United States)

    Hoelen, Christoph; Antonis, Piet; de Boer, Dick; Koole, Rolf; Kadijk, Simon; Li, Yun; Vanbroekhoven, Vincent; Van De Voorde, Patrick

    2017-09-01

    Although the maximum brightness of LEDs has been increasing continuously during the past decade, their luminance is still far from what is required for multiple applications that still rely on the high brightness of discharge lamps. In particular for high brightness applications with limited étendue, e.g. front projection, only very modest luminance values in the beam can be achieved with LEDs compared to systems based on discharge lamps or lasers. With dedicated architectures, phosphor-converted green LEDs for projection may achieve luminance values up to 200-300 Mnit. In this paper we report on the progress made in the development of light engines based on an elongated luminescent concentrator pumped by blue LEDs. This concept has recently been introduced to the market as ColorSpark High Lumen Density LED technology. These sources outperform the maximum brightness of LEDs by multiple factors. In LED front projection, green LEDs are the main limiting factor. With our green modules, we now have achieved peak luminance values of 2 Gnit, enabling LED-based projection systems with over 4000 ANSI lm. Extension of this concept to yellow and red light sources is presented. The light source efficiency has been increased considerably, reaching 45-60 lm/W for green under practical application conditions. The module architecture, beam shaping, and performance characteristics are reviewed, as well as system aspects. The performance increase, spectral range extensions, beam-shaping flexibility, and cost reductions realized with the new module architecture enable a breakthrough in LED-based projection systems and in a wide variety of other high brightness applications.

  15. Designing low cost LED display for the billboard

    Science.gov (United States)

    Hong, Yi-Jian; Uang, Chii-Maw; Wang, Ping-Chieh; Ho, Zu-Sheng

    2011-10-01

    With quickly advance of the computer, microelectronics and photonics technologies, LED display panel becomes a new electronic advertising media. It can be used to show any information whatever characters or graphics. Most LED display panels are built of many Light-Emitting Diodes arranged in a matrix form. The display has many advantages such as low power, low cost, long life and high definition. Because the display panel is asked to show rich color, the LED display panel's driving system becomes very complex. The design methodology of LED display panel's driver becomes more and more important to meet the market requirements. Cost is always the most important issue in public market domain. In this paper, we report a design methodology of LED display panel's driver based on the microprocessor control unit (MCU) system and LED display controller IC, HT1632C, to control three colors, RGB, color LED display panel and the modular panel size is 24*16 in matrix form. The HT1632C is a memory mapping LED display controller, it can be used on many applications, such as digital clock, thermometer, counter, voltmeter or other instrumentation readouts. Three pieces of HT1632C are used to drive a 24*16 RGB LED display panel, in our design case. Each HT163C chip is used to control one of the R, G and B color. As the drive mode is driven in DC mode, the RGB display panel can create and totally of seven colors under the control of MCU. The MCU generates the control signal to drive HT1632C. In this study, the software design methodology is adopted with dynamic display principle. When the scan frequency is 60Hz, LED display panel will get the clear picture and be able to display seven colors.

  16. Vision communications based on LED array and imaging sensor

    Science.gov (United States)

    Yoo, Jong-Ho; Jung, Sung-Yoon

    2012-11-01

    In this paper, we propose a brand new communication concept, called as "vision communication" based on LED array and image sensor. This system consists of LED array as a transmitter and digital device which include image sensor such as CCD and CMOS as receiver. In order to transmit data, the proposed communication scheme simultaneously uses the digital image processing and optical wireless communication scheme. Therefore, the cognitive communication scheme is possible with the help of recognition techniques used in vision system. By increasing data rate, our scheme can use LED array consisting of several multi-spectral LEDs. Because arranged each LED can emit multi-spectral optical signal such as visible, infrared and ultraviolet light, the increase of data rate is possible similar to WDM and MIMO skills used in traditional optical and wireless communications. In addition, this multi-spectral capability also makes it possible to avoid the optical noises in communication environment. In our vision communication scheme, the data packet is composed of Sync. data and information data. Sync. data is used to detect the transmitter area and calibrate the distorted image snapshots obtained by image sensor. By making the optical rate of LED array be same with the frame rate (frames per second) of image sensor, we can decode the information data included in each image snapshot based on image processing and optical wireless communication techniques. Through experiment based on practical test bed system, we confirm the feasibility of the proposed vision communications based on LED array and image sensor.

  17. Reliability test and failure analysis of high power LED packages

    International Nuclear Information System (INIS)

    Chen Zhaohui; Zhang Qin; Wang Kai; Luo Xiaobing; Liu Sheng

    2011-01-01

    A new type application specific light emitting diode (LED) package (ASLP) with freeform polycarbonate lens for street lighting is developed, whose manufacturing processes are compatible with a typical LED packaging process. The reliability test methods and failure criterions from different vendors are reviewed and compared. It is found that test methods and failure criterions are quite different. The rapid reliability assessment standards are urgently needed for the LED industry. 85 0 C/85 RH with 700 mA is used to test our LED modules with three other vendors for 1000 h, showing no visible degradation in optical performance for our modules, with two other vendors showing significant degradation. Some failure analysis methods such as C-SAM, Nano X-ray CT and optical microscope are used for LED packages. Some failure mechanisms such as delaminations and cracks are detected in the LED packages after the accelerated reliability testing. The finite element simulation method is helpful for the failure analysis and design of the reliability of the LED packaging. One example is used to show one currently used module in industry is vulnerable and may not easily pass the harsh thermal cycle testing. (semiconductor devices)

  18. Dome diagnostics system of optical parameters and characteristics of LEDs

    Science.gov (United States)

    Peretyagin, Vladimir S.; Pavlenko, Nikita A.

    2017-09-01

    Scientific and technological progress of recent years in the production of the light emitting diodes (LEDs) has led to the expansion of areas of their application from the simplest systems to high precision lighting devices used in various fields of human activity. However, development and production (especially mass production) of LED lighting devices are impossible without a thorough analysis of its parameters and characteristics. There are many ways and devices for analysis the spatial, energy and colorimetric parameters of LEDs. The most methods are intended for definition only one parameter (for example, luminous flux) or one characteristic (for example, the angular distribution of energy or the spectral characteristics). Besides, devices used these methods are intended for measuring parameters in only one point or plane. This problem can be solved by using a dome diagnostics system of optical parameters and characteristics of LEDs, developed by specialists of the department OEDS chair of ITMO University in Russia. The paper presents the theoretical aspects of the analysis of LED's spatial (angular), energy and color parameters by using mentioned of diagnostics system. The article also presents the results of spatial), energy and color parameters measurements of some LEDs brands.

  19. Spectral design flexibility of LED brings better life

    Science.gov (United States)

    Ou, Haiyan; Corell, Dennis; Ou, Yiyu; Poulsen, Peter B.; Dam-Hansen, Carsten; Petersen, Paul-Michael

    2012-03-01

    Light-emitting diodes (LEDs) are penetrating into the huge market of general lighting because they are energy saving and environmentally friendly. The big advantage of LED light sources, compared to traditional incandescent lamps and fluorescent light tubes, is the flexible spectral design to make white light using different color mixing schemes. The spectral design flexibility of white LED light sources will promote them for novel applications to improve the life quality of human beings. As an initial exploration to make use of the spectral design flexibility, we present an example: 'no blue' white LED light source for sufferers of disease Porphyria. An LED light source prototype, made of high brightness commercial LEDs applying an optical filter, was tested by a patient suffering from Porphyria. Preliminary results have shown that the sufferer could withstand the light source for much longer time than the standard light source. At last future perspectives on spectral design flexibility of LED light sources improving human being's life will be discussed, with focus on the light and health. The good health is ensured by the spectrum optimized so that vital hormones (melatonin and serotonin) are produced during times when they support human daily rhythm.

  20. [Study on the safety of blue light leak of LED].

    Science.gov (United States)

    Shen, Chong-Yu; Xu, Zheng; Zhao, Su-Ling; Huang, Qing-Yu

    2014-02-01

    In this paper, the blue light properties of LED illumination devices have been investigated. Against the status quo of China's LED lighting, we measured the spectrum component of LED lamps and analyzed the photobiological safety under the current domestic and international standards GB/T 20145-2006/CIE S009/E: 2002 and IEC62471: 2006 standards as well as CTL-0744_2009-laser resolution, which provides the reference to the manufacture of LED lighting lamps as well as related safety standards and laws. If the radiance intensity of blue light in LED is lower than 100 W x m(-2) x Sr(-1), there is no harm to human eyes. LEDs will not cause harm to human eyes under normal use, but we should pay attention to the protection of special populations (children), and make sure that they avoid looking at a light source for a long time. The research has found that the blue-rich lamps can affect the human rule of work and rest, and therefore, the LED lamps with color temperature below 4 000 K and color rendering index of 80 are suitable for indoor use. At the same time, the lamps with different parameters should be selected according to the different distances.

  1. Visual color matching system based on RGB LED light source

    Science.gov (United States)

    Sun, Lei; Huang, Qingmei; Feng, Chen; Li, Wei; Wang, Chaofeng

    2018-01-01

    In order to study the property and performance of LED as RGB primary color light sources on color mixture in visual psychophysical experiments, and to find out the difference between LED light source and traditional light source, a visual color matching experiment system based on LED light sources as RGB primary colors has been built. By simulating traditional experiment of metameric color matching in CIE 1931 RGB color system, it can be used for visual color matching experiments to obtain a set of the spectral tristimulus values which we often call color-matching functions (CMFs). This system consists of three parts: a monochromatic light part using blazed grating, a light mixing part where the summation of 3 LED illuminations are to be visually matched with a monochromatic illumination, and a visual observation part. The three narrow band LEDs used have dominant wavelengths of 640 nm (red), 522 nm (green) and 458 nm (blue) respectively and their intensities can be controlled independently. After the calibration of wavelength and luminance of LED sources with a spectrophotometer, a series of visual color matching experiments have been carried out by 5 observers. The results are compared with those from CIE 1931 RGB color system, and have been used to compute an average locus for the spectral colors in the color triangle, with white at the center. It has been shown that the use of LED is feasible and has the advantages of easy control, good stability and low cost.

  2. Design of a cylindrical LED substrate without radiator

    Science.gov (United States)

    Tang, Fan; Guo, Zhenning

    2017-12-01

    To reduce the weight and production costs of light-emitting diode (LED) lamps, we applied the principle of the chimney effect to design a cylindrical LED substrate without a radiator. We built a 3D model by using Solidworks software and applied the flow simulation plug-in to conduct model simulation, thereby optimizing the heat source distribution and substrate thickness. The results indicate that the design achieved optimal cooling with a substrate with an upper extension length of 35 mm, a lower extension length of 8 mm, and a thickness of 1 mm. For a substrate of those dimensions, the highest LED chip temperature was 64.78 °C, the weight of the substrate was 35.09 g, and R jb = 7.00 K/W. If the substrate is powered at 8, 10, and 12 W, its temperature meets LED safety requirements. In physical tests, the highest temperature for a physical 8 W cylindrical LED substrate was 66 °C, which differed by only 1.22 °C from the simulation results, verifying the validity of the simulation. The designed cylindrical LED substrate can be used in high-power LED lamps that do not require radiators. This design is not only excellent for heat dissipation, but also for its low weight, low cost, and simplicity of manufacture.

  3. Involvement of the VDE homing endonuclease and rapamycin in regulation of the Saccharomyces cerevisiae GSH11 gene encoding the high affinity glutathione transporter.

    Science.gov (United States)

    Miyake, Tsuyoshi; Hiraishi, Hiroyuki; Sammoto, Hiroyuki; Ono, Bun-Ichiro

    2003-10-10

    The Saccharomyces cerevisiae gene HGT1/GSH11 encodes the high affinity glutathione transporter and is repressed by cysteine added to the culture medium. It has been found previously that a 5'-upstream cis-element, CCGCCACAC, is responsible for regulating GSH11 expression and that several proteins bind to this element (Miyake, T., Kanayama, M., Sammoto, H., and Ono, B. (2002) Mol. Genet. Genomics 266, 1004-1011). In this report we present evidence that the most prominent of these proteins is VDE, known previously as the homing endonuclease encoded by VMA1. We show also that GSH11 is not expressed in a VDE-deleted strain and that inability to express the GSH11 of this strain is overcome by introduction of the coding region of VDE or the entire VMA1 gene. It is also found that VDE does not cut DNA in the vicinity of the GSH11 cis-element. Rapamycin, an inhibitor of the target of rapamycin (TOR) signal-transduction system, is found to enhance expression of GSH11 in a VDE-dependent manner under conditions of sulfur starvation. These results indicate that GSH11 is regulated by a system sensitive to sulfur starvation (presumably via cysteine depletion) and a more general system involving the nutritional starvation signal mediated by the TOR system. Both systems need to be operational (inhibition of TOR and sulfur starvation) for full expression of GSH11.

  4. Characterization of the cloned full-length and a truncated human target of rapamycin: Activity, specificity, and enzyme inhibition as studied by a high capacity assay

    International Nuclear Information System (INIS)

    Toral-Barza, Lourdes; Zhang Weiguo; Lamison, Craig; LaRocque, James; Gibbons, James; Yu, Ker

    2005-01-01

    The mammalian target of rapamycin (mTOR/TOR) is implicated in cancer and other human disorders and thus an important target for therapeutic intervention. To study human TOR in vitro, we have produced in large scale both the full-length TOR (289 kDa) and a truncated TOR (132 kDa) from HEK293 cells. Both enzymes demonstrated a robust and specific catalytic activity towards the physiological substrate proteins, p70 S6 ribosomal protein kinase 1 (p70S6K1) and eIF4E binding protein 1 (4EBP1), as measured by phosphor-specific antibodies in Western blotting. We developed a high capacity dissociation-enhanced lanthanide fluorescence immunoassay (DELFIA) for analysis of kinetic parameters. The Michaelis constant (K m ) values of TOR for ATP and the His6-S6K substrate were shown to be 50 and 0.8 μM, respectively. Dose-response and inhibition mechanisms of several known inhibitors, the rapamycin-FKBP12 complex, wortmannin and LY294002, were also studied in DELFIA. Our data indicate that TOR exhibits kinetic features of those shared by traditional serine/threonine kinases and demonstrate the feasibility for TOR enzyme screen in searching for new inhibitors

  5. Evaluating UV-C LED disinfection performance and ...

    Science.gov (United States)

    This study evaluated ultraviolet (UV) light emitting diodes (LEDs) emitting at 260 nm, 280 nm, and the combination of 260|280 nm together for their efficacy at inactivating Escherichia. coli, MS2 coliphage, human adenovirus type 2 (HAdV2), and Bacillus pumilus spores; research included an evaluation of genomic damage. Inactivation by the LEDs was compared with the efficacy of conventional UV sources, the low-pressure (LP) and medium-pressure (MP) mercury vapor lamps. The work also calculated the electrical energy per order of reduction of the microorganisms by the five UV sources.For E. coli, all five UV sources yielded similar inactivation rates. For MS2 coliphage, the 260 nm LED was most effective. For HAdV2 and B. pumilus, the MP UV lamp was significantly more effective than the LP UV and UVC LED sources. When considering electrical energy per order of reduction, the LP UV lamp was the most efficient for E. coli and MS2, and the MPUV and LPUV were equally efficient for HAdV2 and B. pumilus spores. Among the UVC LEDs, the 280 nm LED unit required the least energy per log reduction of E. coli and HAdV2. The 280 nm and 260|280 nm LED units were equally efficient per log reduction of B. pumilus spores, and the 260 nm LED unit required the lowest energy per order of reduction of MS2 coliphage. The combination of the 260 nm and 280 nm UV LED wavelengths was also evaluated for potential synergistic effects. No dual-wavelength synergy was detected for inactivation of

  6. University of Nevada Las Vegas LED Display Engineering

    Energy Technology Data Exchange (ETDEWEB)

    None

    2010-08-31

    The primary objective of this part of the project is to develop and implement a method that compensates for the inefficiency of the green LED. The proposed engineering solution which will be the backbone of this project will be to use RGBW combination in every pixel to save energy. Two different RGBW geometrical pixel configurations will be implemented and compared against traditional LED configurations. These configurations will be analyzed for energy efficiency while keeping the quality of the display the same. Cost of the addition of white LEDs to displays along with energy cost savings will be presented and analyzed.

  7. Energy efficient LED layout optimization for near-uniform illumination

    Science.gov (United States)

    Ali, Ramy E.; Elgala, Hany

    2016-09-01

    In this paper, we consider the problem of designing energy efficient light emitting diodes (LEDs) layout while satisfying the illumination constraints. Towards this objective, we present a simple approach to the illumination design problem based on the concept of the virtual LED. We formulate a constrained optimization problem for minimizing the power consumption while maintaining a near-uniform illumination throughout the room. By solving the resulting constrained linear program, we obtain the number of required LEDs and the optimal output luminous intensities that achieve the desired illumination constraints.

  8. Iluminación LED. Un arma de doble filo

    OpenAIRE

    Sánchez de Miguel, Alejandro

    2004-01-01

    La iluminación LED es el futuro de la iluminación. Sin embargo, como toda tecnología, puede usarse de manera correcta o incorrecta. En el caso de los LED, el abaratamiento de la producción de luz podría provocar un aumento descontrolado de la Contaminación lumínica. Por otro, el uso correcto de los LED podría ser la solución al mismo mal por su capacidad de encendido casi instantáneo.

  9. The possible ocular hazards of LED dental illumination applications.

    Science.gov (United States)

    Stamatacos, Catherine; Harrison, Janet L

    2013-01-01

    The use of high-intensity illumination via Light-Emitting Diode (LED) headlamps is gaining in popularity with dentists and student dentists. Practitioners are using LED headlamps together with magnifying loupes, overhead LED illumination and fiber-optic dental handpieces for long periods of time. Although most manufacturers of these LED illuminators advertise that their devices emit "white" light, these still consist of two spectral bands--the blue spectral band, with its peak at 445 nm, and the green with its peak at 555 nm. While manufacturers suggest that their devices emit "white" light, spectral components of LED lights from different companies are significantly different. Dental headlamp manufacturers strive to create a white LED, and they advertise that this type of light emitted from their product offers bright white-light illumination. However, the manufacturing of a white LED light is done through selection of a white LED-type based on the peak blue strength in combination with the green peak strength and thus creating a beam-forming optic, which determines the beam quality. Some LED illuminators have a strong blue-light component versus the green-light component. Blue-light is highly energized and is close in the color spectrum to ultraviolet-light. The hazards of retinal damage with the use of high-intensity blue-lights has been well-documented. There is limited research regarding the possible ocular hazards of usage of high-intensity illuminating LED devices. Furthermore, the authors have found little research, standards, or guidelines examining the possible safety issues regarding the unique dental practice setting consisting of the combined use of LED illumination systems. Another unexamined component is the effect of high-intensity light reflective glare and magnification back to the practitioner's eyes due to the use of water during dental procedures. Based on the result of Dr. Janet Harrison's observations of beginning dental students in a

  10. Design of High Efficiency Illumination for LED Lighting

    Directory of Open Access Journals (Sweden)

    Yong-Nong Chang

    2013-01-01

    Full Text Available A high efficiency illumination for LED street lighting is proposed. For energy saving, this paper uses Class-E resonant inverter as main electric circuit to improve efficiency. In addition, single dimming control has the best efficiency, simplest control scheme and lowest circuit cost among other types of dimming techniques. Multiple serial-connected transformers used to drive the LED strings as they can provide galvanic isolation and have the advantage of good current distribution against device difference. Finally, a prototype circuit for driving 112 W LEDs in total was built and tested to verify the theoretical analysis.

  11. Three consecutive days of application of LED therapy is necessary to inhibit experimentally induced root resorption in rats: a microtomographic study.

    Science.gov (United States)

    Higashi, Dayla Thyeme; Andrello, Avacir Casanova; Tondelli, Pedro Marcelo; de Oliveira Toginho Filho, Dari; de Paula Ramos, Solange

    2017-01-01

    Previous studies have suggested that phototherapy may modulate orthodontic tooth movement and the incidence of root resorption. We aimed to identify a minimal dose-response relationship to LED therapy with regard to orthodontic tooth movement (OTM) and root resorption in rats. Forty-eight male Wistar rats were divided into six groups with equal and random distribution: control (C) no intervention; three daily LED irradiation (CLED); submitted only to OTM (RR); OTM and LED irradiation on the first day (LED1); OTM and two LED irradiation on the first and second days (LED2); and OTM and three LED irradiation on the first, second, and third days (LED3). Orthodontic appliance was installed in groups RR, LED1, LED2, and LED3 to promote OTM. Animals from groups CLED, LED1, LED2, and LED3 received LED therapy (940 nm, 4 J, 4 J/cm2) according to each group of treatment. After 7 days, all the animals were sacrificed. The jaws were fixed and scanned with microtomography (micro-CT). The micro-CT images were reconstructed on 2D and 3D models. These models were used to identify and measure root resorption number and dimensions (diameter, depth, and volume). The distance between the first and second molars was used to verify tooth displacement. The results showed that LED3 group had significantly lower number of root resorption. The root resorption dimensions (diameter and depth) had no significant differences among the experimental groups. LED3 group had significant tooth displacement in relation to C and CLED groups. In conclusion, three daily LED therapy doses are required to inhibit root resorption after appliance of orthodontic forces.

  12. A Lifetime Prediction Method for LEDs Considering Real Mission Profiles

    DEFF Research Database (Denmark)

    Qu, Xiaohui; Wang, Huai; Zhan, Xiaoqing

    2017-01-01

    operations due to the varying operational and environmental conditions during the entire service time (i.e., mission profiles). To overcome the challenge, this paper proposes an advanced lifetime prediction method, which takes into account the field operation mission profiles and also the statistical......The Light-Emitting Diode (LED) has become a very promising alternative lighting source with the advantages of longer lifetime and higher efficiency than traditional ones. The lifetime prediction of LEDs is important to guide the LED system designers to fulfill the design specifications...... properties of the life data available from accelerated degradation testing. The electrical and thermal characteristics of LEDs are measured by a T3Ster system, used for the electro-thermal modeling. It also identifies key variables (e.g., heat sink parameters) that can be designed to achieve a specified...

  13. Microbial raw data for UV-C LED disinfection study

    Data.gov (United States)

    U.S. Environmental Protection Agency — This study evaluated ultraviolet (UV) light emitting diodes (LEDs) emitting at 260 nm, 280 nm, and the combination of 260|280 nm together for their efficacy at...

  14. Integrated parabolic nanolenses on MicroLED color pixels

    Science.gov (United States)

    Demory, Brandon; Chung, Kunook; Katcher, Adam; Sui, Jingyang; Deng, Hui; Ku, Pei-Cheng

    2018-04-01

    A parabolic nanolens array coupled to the emission of a nanopillar micro-light emitting diode (LED) color pixel is shown to reduce the far field divergence. For a blue wavelength LED, the total emission is 95% collimated within a 0.5 numerical aperture zone, a 3.5x improvement over the same LED without a lens structure. This corresponds to a half-width at half-maximum (HWHM) line width reduction of 2.85 times. Using a resist reflow and etchback procedure, the nanolens array dimensions and parabolic shape are formed. Experimental measurement of the far field emission shows a HWHM linewidth reduction by a factor of 2x, reducing the divergence over the original LED.

  15. Light Emitting Diode (LED) circular traffic signal lifetime management system.

    Science.gov (United States)

    2011-02-01

    The objective of this research is to build lifetime curves for red, yellow, and green LED circular traffic signals through 20,000-hr. accelerated stress testing of samples operating under Louisianas environmental conditions.

  16. Laboratory Evaluation of LED T8 Replacement Lamp Products

    Energy Technology Data Exchange (ETDEWEB)

    Richman, Eric E.; Kinzey, Bruce R.; Miller, Naomi J.

    2011-05-23

    A report on a lab setting analysis involving LED lamps intended to directly replace T8 fluorescent lamps (4') showing light output, power, and economic comparisons with other fluorescent options.

  17. LED Retrofit Kits, TLEDs, and Lighting Controls: An Application Guide

    Energy Technology Data Exchange (ETDEWEB)

    None

    2017-03-01

    This document provides guidance for retrofitting existing fluorescent troffers including the LED and associated control options available, the pro/cons and costs/benefits of each option, and agency specific requirements (where applicable).

  18. Assessment of community led total sanitation uptake in rural Kenya

    African Journals Online (AJOL)

    K. N. Ogendo, Bsc, MPH, Living goods Nairobi, Kenya,Ministry of Health, Environmental Health ... led drive to set up pit latrines in rural kenya with an aim of promoting sustainable ... Development and Sustainable Development goals lay.

  19. Flat-panel video resolution LED display system

    Science.gov (United States)

    Wareberg, P. G.; Kennedy, D. I.

    The system consists of a 128 x 128 element X-Y addressable LED array fabricated from green-emitting gallium phosphide. The LED array is interfaced with a 128 x 128 matrix TV camera. Associated electronics provides for seven levels of grey scale above zero with a grey scale ratio of square root of 2. Picture elements are on 0.008 inch centers resulting in a resolution of 125 lines-per-inch and a display area of approximately 1 sq. in. The LED array concept lends itself to modular construction, permitting assembly of a flat panel screen of any desired size from 1 x 1 inch building blocks without loss of resolution. A wide range of prospective aerospace applications exist extending from helmet-mounted systems involving small dedicated arrays to multimode cockpit displays constructed as modular screens. High-resolution LED arrays are already used as CRT replacements in military film-marking reconnaissance applications.

  20. Comparative clinical study using laser and LED-therapy for orofacial pain relief: dentin hypersensitivity and cervicogenic headache

    Science.gov (United States)

    Lizarelli, Rosane F. Z.; Pizzo, Renata C. A.; Florez, Fernando L. E.; Grecco, Clovis; Speciali, Jose G.; Bagnato, Vanderlei S.

    2015-06-01

    Considering several clinical situations, low intensity laser therapy has been widely applied in pain relief or analgesia mechanism. With the advent of new LED-based (light emitting diode) light sources, the need of further clinical experiments aiming to compare the effectiveness among them is paramount. The LED system therapeutic use can be denominated as LEDT - Light Emitting Diode Therapy. This study proposed two clinical evaluations of pain relief effect: to dentin hypersensitivity and to cervicogenic headache using different sources of lasers (low and high intensity) and light emitting diodes (LEDs), one emitting at the spectral band of red (630+/- 5nm) and the other one at infrared band (880+/- 5nm). Two different clinical studies were performed and presented interesting results. Considering dentin hypersensitivity, red and infrared led were so effective than the control group (high intensity laser system); by the other side, considering cervicogenic headache, control group (infrared laser) was the best treatment in comparison to red and infrared led system.

  1. Comparative Study of Lettuce and Radish Grown Under Red and Blue LEDs and White Fluorescent Lamps

    Science.gov (United States)

    Mickens, Matthew A.; Massa, Gioia; Newsham, Gerard; Wheeler, Raymond; Birmele, Michele

    2016-01-01

    Growing vegetable crops in space will be an essential part of sustaining astronauts during long-range missions. To drive photosynthesis, red and blue light-emitting diodes (LEDs) have attracted attention because of their efficiency, longevity, small size, and safety. In efforts to optimize crop yield, there is also recent interest in analyzing the subtle effects of additional wavelengths on plant growth. For instance, since plants often look purplish gray under red and blue LEDs, the addition of green light allows easy recognition of disease and the assessment of plant health status. However, it is important to know if wavelengths outside the traditional red and blue wavebands have a direct effect on enhancing or hindering the mechanisms involved in plant growth. In this experiment, a comparative study was performed on two short cycle crops of red romaine lettuce (Lactuca sativa cv. "Outredgeous") and radish (Raphanus sativa cv. 'Cherry Bomb'), which were grown under two light treatments. The first treatment being red (630 nm) and blue (450 nm) LEDs alone, while the second treatment consisted of daylight tri-phosphor fluorescent lamps (CCT approximately 5000 K) at equal photosynthetic photon flux (PPF). The treatment effects were evaluated by measuring the fresh biomass produced, plant morphology and leaf dimensions, leaf chlorophyll content, and adenosine triphosphate (ATP) within plant leaf/storage root tissues.

  2. EVALUATION OF ADOPTION OF LED LIGHTING TECHNOLOGY IN MALAYSIA

    OpenAIRE

    Khorasanizadeh, Hasti

    2017-01-01

    Electrical energy consumption in Malaysia is rapidly increasing with illumination being the second largest contributor to this increment. Light Emitting Diode (LED) could be a viable option to reduce the illumination based energy consumption. LEDs are energy efficient and easier to recycle compared to traditional lighting sources such as incandescent and fluorescent lamps. They also have longer life time and lower failure rate. In this thesis, the feasibility of replacing...

  3. Biological Research in Canisters (BRIC) - Light Emitting Diode (LED)

    Science.gov (United States)

    Levine, Howard G.; Caron, Allison

    2016-01-01

    The Biological Research in Canisters - LED (BRIC-LED) is a biological research system that is being designed to complement the capabilities of the existing BRIC-Petri Dish Fixation Unit (PDFU) for the Space Life and Physical Sciences (SLPS) Program. A diverse range of organisms can be supported, including plant seedlings, callus cultures, Caenorhabditis elegans, microbes, and others. In the event of a launch scrub, the entire assembly can be replaced with an identical back-up unit containing freshly loaded specimens.

  4. LEDs Illuminate Bulbs for Better Sleep, Wake Cycles

    Science.gov (United States)

    2015-01-01

    Life on the International Space Station (ISS) wreaks havoc on an astronaut’s biological rhythms, and one way NASA mitigates the problem is through the use of LED lighting to alternately stimulate energy and focus and induce relaxation. Satellite Beach, Florida-based Lighting Science partnered with Kennedy Space Center to commercialize an LED system designed for the ISS, resulting in its DefinityDigital product line of light bulbs now used in numerous homes, hotel chains, and resorts.

  5. Control and Driving Methods for LED Based Intelligent Light Sources

    OpenAIRE

    Beczkowski, Szymon

    2012-01-01

    High power light-emitting diodes allow the creation of luminaires capable of generating saturated colour light at very high efficacies. Contrary to traditional light sources like incandescent and high-intensity discharge lamps, where colour is generated using filters, LEDs use additive light mixing, where the intensity of each primary colour diode has to be adjusted to the needed intensity to generate specified colour. The function of LED driver is to supply the diode with power needed to ach...

  6. Testing high brightness LEDs relative to application environment

    Science.gov (United States)

    Singer, Jeffrey; Mangum, Scott; Lundberg, John

    2006-08-01

    Application of light emitting diodes is expanding as the luminous output and efficiencies of these devices improve. At the same time, the number of LED package types is increasing, making it challenging to determine the appropriate device for use in lighting product designs. A range of factors should be considered when selecting a LED for an application including color coordinates, luminous efficacy, cost, lumen maintenance, application life, packaging and manufacturability. Additional complexities can be introduced as LED packages become obsolete and replacement parts must be selected. The replacement LED characteristics must be understood and assessed against the parameters of the original device, in order to determine if the change will be relatively simple or will force other end-product changes. While some characteristics are readily measured and compared, other factors, such as lumen maintenance, are difficult to verify. This paper will discuss the characteristics of a LED that should be considered during the design process as well as methods to validate these characteristics, particularly those which are not typically on data sheets or, are critical to the design and warrant additional validation. Particular attention will be given to LED lumen maintenance. While published manufacturer data typically provides temperature versus performance curves, the data may not be useful depending upon the application's operating environment. Models must be created to estimate the LED's junction temperature and degradation curve at the applied temperature in order to develop a more precise life estimate. This paper presents one approach to a LED device life and performance study designed with application environments in mind.

  7. Design of High Efficiency Illumination for LED Lighting

    OpenAIRE

    Chang, Yong-Nong; Cheng, Hung-Liang; Kuo, Chih-Ming

    2013-01-01

    A high efficiency illumination for LED street lighting is proposed. For energy saving, this paper uses Class-E resonant inverter as main electric circuit to improve efficiency. In addition, single dimming control has the best efficiency, simplest control scheme and lowest circuit cost among other types of dimming techniques. Multiple serial-connected transformers used to drive the LED strings as they can provide galvanic isolation and have the advantage of good current distribution against de...

  8. A new LED light source for display cases

    DEFF Research Database (Denmark)

    Dam-Hansen, Carsten; Petersen, Paul Michael

    Abstract: We report a new LED light source suitable for illumination of gold objects. It has a variable correlated color temperature from 2760 K to 2200 K with a high color rendering index up to 97.......Abstract: We report a new LED light source suitable for illumination of gold objects. It has a variable correlated color temperature from 2760 K to 2200 K with a high color rendering index up to 97....

  9. LED Street Lighting Solutions: Flagstaff, Arizona as a Case Study

    Science.gov (United States)

    Hall, Jeffrey C.

    2018-01-01

    Dark-sky protection in Flagstaff, Arizona extends back to 1958, with the first ordinance in the City banning advertising floodlights. The current ordinance, adopted in 1989, is comprehensive and has played a critical role in maintaining the quality of the night sky for astronomy, tourism, public enjoyment, and other purposes. Flagstaff, like many communities around the world, is now working on a transition from legacy bulb-based technology to LED for its outdoor lighting. The City, Lowell Observatory, the U. S. Naval Observatory, and the Flagstaff Dark Skies Coalition have been working intensively for two years to identify an LED-based street lighting solution that will preserve the City's dark skies while meeting municipal needs. We will soon be installing test fixtures for an innovative solution incorporating narrow-band amber LED and modest amounts of low-CCT white LED. In this talk, I will review the types of LEDs available for outdoor lighting and discuss the plans for Flagstaff's street lighting in the LED era, which we hope will be a model for communities worldwide.

  10. UV-LEDs Efficiently Inactivate DNA and RNA Coliphages

    Directory of Open Access Journals (Sweden)

    Alyaa M. Zyara

    2017-01-01

    Full Text Available UV-LEDs are a new method of disinfecting drinking water. Some viruses are very resistant to UV and the efficiency of UV-LEDs to disinfect them needs to be studied. Drinking water was disinfected with UV-LEDs after spiking the water with MS2 and four UV- and/or Cl-resistant coliphages belonging to RNA or DNA coliphages isolated from municipal wastewater. UV-LEDs operating at a wavelength of 270 nm for 2 min with 120 mW of irradiation caused 0.93–2.73 Log10-reductions of coliphages tested in a reactor of a 5.2 L volume. Irradiation time of 10 min in the same system increased the Log10-reductions to 4.30–5.16. Traditional mercury UV (Hg-UV lamp at a 254 nm wavelength caused 0.67–4.08 Log10-reductions in 2 min and 4.56–7.21 Log10-reductions in 10 min in 10 mL of water. All coliphages tested except MS2 achieved 4 Log10-reductions with UV-LEDs at a dose that corresponded to 70 mWs/cm2 using Hg-UV. Thus, UV-LEDs are a promising method of disinfecting UV- and/or Cl-resistant viruses.

  11. Optimal colour quality of LED clusters based on memory colours.

    Science.gov (United States)

    Smet, Kevin; Ryckaert, Wouter R; Pointer, Michael R; Deconinck, Geert; Hanselaer, Peter

    2011-03-28

    The spectral power distributions of tri- and tetrachromatic clusters of Light-Emitting-Diodes, composed of simulated and commercially available LEDs, were optimized with a genetic algorithm to maximize the luminous efficacy of radiation and the colour quality as assessed by the memory colour quality metric developed by the authors. The trade-off of the colour quality as assessed by the memory colour metric and the luminous efficacy of radiation was investigated by calculating the Pareto optimal front using the NSGA-II genetic algorithm. Optimal peak wavelengths and spectral widths of the LEDs were derived, and over half of them were found to be close to Thornton's prime colours. The Pareto optimal fronts of real LED clusters were always found to be smaller than those of the simulated clusters. The effect of binning on designing a real LED cluster was investigated and was found to be quite large. Finally, a real LED cluster of commercially available AlGaInP, InGaN and phosphor white LEDs was optimized to obtain a higher score on memory colour quality scale than its corresponding CIE reference illuminant.

  12. Pharmacist-Led Self-management Interventions to Improve Diabetes Outcomes. A Systematic Literature Review and Meta-Analysis

    NARCIS (Netherlands)

    van Eikenhorst, Linda; Taxis, Katja; van Dijk, Liset; de Gier, Han

    2017-01-01

    Background: Treatment of diabetes requires a strict treatment scheme which demands patient self-management. Pharmacists are in a good position to provide self-management support. This review examines whether pharmacist-led interventions to support self-management in diabetes patients improve

  13. Pharmacist-led self-management interventions to improve diabetes outcomes. A systematic literature review and meta-analysis.

    NARCIS (Netherlands)

    Eikenhorst, L. van; Dijk, L. van; Taxis, K; Gier, H. de

    2017-01-01

    Background Treatment of diabetes requires a strict treatment scheme which demands patient self-management. Pharmacists are in a good position to provide self-management support. This review examines whether pharmacist-led interventions to support self-management in diabetes patients improve clinical

  14. Long-lived visible luminescence of UV LEDs and impact on LED excited time-resolved fluorescence applications

    International Nuclear Information System (INIS)

    Jin, D; Connally, R; Piper, J

    2006-01-01

    We report the results of a detailed study of the spectral and temporal properties of visible emission from three different GaN-based ultraviolet (UV) light emitting diodes (UV LEDs). The primary UV emission in the 360-380 nm band decays rapidly (less than 1 μs) following switch-off; however, visible luminescence (470-750 nm) with a decay lifetime of tens of microseconds was observed at approximately 10 -4 of the UV intensity. For applications of UV LEDs in time-resolved fluorescence (TRF) employing lanthanide chelates, the visible luminescence from the LEDs competes with the target Eu 3+ or Tb 3+ fluorescence in both spectral and temporal domains. A UV band-pass filter (Schott UG11 glass) was therefore used to reduce the visible luminescence of the UV LEDs by three orders of magnitude relative to UV output to yield a practical excitation source for TRF

  15. Influence of laser and LED irradiation on mast cells of cutaneous wounds of rats with iron deficiency anemia

    Science.gov (United States)

    Becher Rosa, Cristiane; Oliveira Sampaio, Susana C. P.; Monteiro, Juliana S. C.; Ferreira, Maria F. L.; Zanini, Fátima A. A.; Santos, Jean N.; Cangussú, Maria Cristina T.; Pinheiro, Antonio L. B.

    2011-03-01

    This work aimed to study histologically the effect of Laser or LED phototherapy on mast cells on cutaneous wounds of rats with iron deficiency. 18 rats were used and fed with special peleted iron-free diet. An excisional wound was created on the dorsum of each animal which were divided into: Group I - Control with anemia + no treatment; Group II - Anemia + Laser; Group III - Anemia + LED; Group IV - Healthy + no treatment; Group V - Healthy + Laser; Group VI - Healthy + LED. Irradiation was performed using a diode Laser (λ660nm, 40mW, CW, total dose of 10J/cm2, 4X2.5J/cm2) or a RED-LED ( λ700nm, 15mW, CW, total dose of 10J/cm2). Histological specimens were routinely processed, cut and stained with toluidine blue and mast cell counts performed. No significant statistic difference was found between groups as to the number of degranulated, non-degradulated or total mast cells. Greater mean values were found for degranulated mast cells in the Anemia + LED. LED irradiation on healthy specimens resulted in a smaller number of degranulated mast cells. Our results leads to conclude that there are no significant differences in the number of mast cells seven days after irradiation following Laser or LED phototherapy.

  16. Efficacy of embedded nurse-led versus conventional physician-led follow-up in rheumatoid arthritis

    DEFF Research Database (Denmark)

    de Thurah, Annette; Esbensen, Bente Appel; Roelsgaard, Ida Kristiane

    2017-01-01

    difference (SMD) -0.17 (95 % CI -1.0 to 0.67), whereas a statistical significant difference in favour of nurse-led follow-up was seen after 2 years (SMD: 0.6 (95% CI -0.00 to 1.20)). CONCLUSION: After 1 year no difference in disease activity, indicated by DAS-28, were found between embedded nurse-led follow...

  17. A hexane fraction of guava Leaves (Psidium guajava L.) induces anticancer activity by suppressing AKT/mammalian target of rapamycin/ribosomal p70 S6 kinase in human prostate cancer cells.

    Science.gov (United States)

    Ryu, Nae Hyung; Park, Kyung-Ran; Kim, Sung-Moo; Yun, Hyung-Mun; Nam, Dongwoo; Lee, Seok-Geun; Jang, Hyeung-Jin; Ahn, Kyoo Seok; Kim, Sung-Hoon; Shim, Bum Sang; Choi, Seung-Hoon; Mosaddik, Ashik; Cho, Somi K; Ahn, Kwang Seok

    2012-03-01

    This study was carried out to evaluate the anticancer effects of guava leaf extracts and its fractions. The chemical compositions of the active extracts were also determined. In the present study, we set out to determine whether the anticancer effects of guava leaves are linked with their ability to suppress constitutive AKT/mammalian target of rapamycin (mTOR)/ribosomal p70 S6 kinase (S6K1) and mitogen-activated protein kinase (MAPK) activation pathways in human prostate cancer cells. We found that guava leaf hexane fraction (GHF) was the most potent inducer of cytotoxic and apoptotic effects in PC-3 cells. The molecular mechanism or mechanisms of GHF apoptotic potential were correlated with the suppression of AKT/mTOR/S6K1 and MAPK signaling pathways. This effect of GHF correlated with down-regulation of various proteins that mediate cell proliferation, cell survival, metastasis, and angiogenesis. Analysis of GHF by gas chromatography and gas chromatography-mass spectrometry tentatively identified 60 compounds, including β-eudesmol (11.98%), α-copaene (7.97%), phytol (7.95%), α-patchoulene (3.76%), β-caryophyllene oxide (CPO) (3.63%), caryophylla-3(15),7(14)-dien-6-ol (2.68%), (E)-methyl isoeugenol (1.90%), α-terpineol (1.76%), and octadecane (1.23%). Besides GHF, CPO, but not phytol, also inhibited the AKT/mTOR/S6K1 signaling pathway and induced apoptosis in prostate cancer cells. Overall, these findings suggest that guava leaves can interfere with multiple signaling cascades linked with tumorigenesis and provide a source of potential therapeutic compounds for both the prevention and treatment of cancer.

  18. Verbaalne soolo Jaanus Nõgistolt : Led R-ist, Narva Linna Sümfooniaorkestrist ja Led Zeppelinist / Jaanus Nõgisto ; interv. Margo Pajuste

    Index Scriptorium Estoniae

    Nõgisto, Jaanus, 1956-

    2007-01-01

    Rockansambli Led Zeppelini muusikast, ansamblist Led R ja heliplaadist "Led the R Out" räägib kitarrist Jaanus Nõgisto. Led R ja Narva Linna Sümfooniaorkestri kontserdid: 22. juunil Pärnus ja 14. juulil Haapsalu lossihoovis, ansambli Led R kontsert koos Havana Blackiga 3. aug. Sõru sadamas Hiiumaal

  19. Characteristics of patients with erectile dysfunction in a family physician-led erectile dysfunction clinic: Retrospective case series

    OpenAIRE

    Lap Kin Chiang; Cheuk-Wai Kam; Kin-Chung Michael Yau; Lorna Ng

    2017-01-01

    Objectives: 1. To examine the characteristics of patients with erectile dysfunction in a family physician led erectile dysfunction clinic; 2. To review association of chronic disease spectrum and erectile dysfunction; 3. To review initial treatment pattern and outcome. Design: Retrospective case series review. Subjects: All consecutive patients seen in a regional hospital family physician led erectile dysfunction clinic from April 2014 to March 2015. Main outcome measures: 1. The severity of ...

  20. Modulation of translation-initiation in CHO-K1 cells by rapamycin-induced heterodimerization of engineered eIF4G fusion proteins.

    Science.gov (United States)

    Schlatter, Stefan; Senn, Claudia; Fussenegger, Martin

    2003-07-20

    Translation-initiation is a predominant checkpoint in mammalian cells which controls protein synthesis and fine-tunes the flow of information from gene to protein. In eukaryotes, translation-initiation is typically initiated at a 7-methyl-guanylic acid cap posttranscriptionally linked to the 5' end of mRNAs. Alternative cap-independent translation-initiation involves 5' untranslated regions (UTR) known as internal ribosome entry sites, which adopt a particular secondary structure. Translation-initiating ribosome assembly at cap or IRES elements is mediated by a multiprotein complex of which the initiation factor 4F (eIF4F) consisting of eIF4A (helicase), eIF4E (cap-binding protein), and eIF4G is a major constituent. eIF4G is a key target of picornaviral protease 2A, which cleaves this initiation factor into eIF4G(Delta) and (Delta)eIF4G to redirect the cellular translation machinery exclusively to its own IRES-containing transcripts. We have designed a novel translation control system (TCS) for conditional as well as adjustable translation of cap- and IRES-dependent transgene mRNAs in mammalian cells. eIF4G(Delta) and (Delta)eIF4G were fused C- and N-terminally to the FK506-binding protein (FKBP) and the FKBP-rapamycin-binding domain (FRB) of the human FKBP-rapamycin-associated protein (FRAP), respectively. Rapamycin-induced heterodimerization of eIF4G(Delta)-FKBP and FRB-(Delta)eIF4G fusion proteins reconstituted a functional chimeric elongation factor 4G in a dose-dependent manner. Rigorous quantitative expression analysis of cap- and IRES-dependent SEAP- (human placental secreted alkaline phosphatase) and luc- (Photinus pyralis luciferase) encoding reporter constructs confirmed adjustable translation control and revealed increased production of desired proteins in response to dimerization-induced heterologous eIF4G in Chinese hamster ovary (CHO-K1) cells. Copyright 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 83: 210-225, 2003.

  1. Kinetic modelling of in vitro data of PI3K, mTOR1, PTEN enzymes and on-target inhibitors Rapamycin, BEZ235, and LY294002.

    Science.gov (United States)

    Goltsov, Alexey; Tashkandi, Ghassan; Langdon, Simon P; Harrison, David J; Bown, James L

    2017-01-15

    The phosphatidylinositide 3-kinases (PI3K) and mammalian target of rapamycin-1 (mTOR1) are two key targets for anti-cancer therapy. Predicting the response of the PI3K/AKT/mTOR1 signalling pathway to targeted therapy is made difficult because of network complexities. Systems biology models can help explore those complexities but the value of such models is dependent on accurate parameterisation. Motivated by a need to increase accuracy in kinetic parameter estimation, and therefore the predictive power of the model, we present a framework to integrate kinetic data from enzyme assays into a unified enzyme kinetic model. We present exemplar kinetic models of PI3K and mTOR1, calibrated on in vitro enzyme data and founded on Michaelis-Menten (MM) approximation. We describe the effects of an allosteric mTOR1 inhibitor (Rapamycin) and ATP-competitive inhibitors (BEZ235 and LY294002) that show dual inhibition of mTOR1 and PI3K. We also model the kinetics of phosphatase and tensin homolog (PTEN), which modulates sensitivity of the PI3K/AKT/mTOR1 pathway to these drugs. Model validation with independent data sets allows investigation of enzyme function and drug dose dependencies in a wide range of experimental conditions. Modelling of the mTOR1 kinetics showed that Rapamycin has an IC 50 independent of ATP concentration and that it is a selective inhibitor of mTOR1 substrates S6K1 and 4EBP1: it retains 40% of mTOR1 activity relative to 4EBP1 phosphorylation and inhibits completely S6K1 activity. For the dual ATP-competitive inhibitors of mTOR1 and PI3K, LY294002 and BEZ235, we derived the dependence of the IC 50 on ATP concentration that allows prediction of the IC 50 at different ATP concentrations in enzyme and cellular assays. Comparison of drug effectiveness in enzyme and cellular assays showed that some features of these drugs arise from signalling modulation beyond the on-target action and MM approximation and require a systems-level consideration of the whole PI3K

  2. Monochromic radiation through light-emitting diode (LED positively augments in vitro shoot regeneration in Orchid (Dendrobium sonia

    Directory of Open Access Journals (Sweden)

    Vandita Billore

    2017-07-01

    Full Text Available Monochromatic lights emitted by light-emitting diodes (LEDs have generated great interest for efficient and controlled growth in vitro, especially of plants which are endangered or require specific intensity and wavelength of light. In the present study, we have evaluated the effect of monochromatic LEDs on in vitro morphogenesis: growth, proliferation of shoot cultures, and rooting of Dendrobium sonia. Different light sources viz. white LEDs (W, blue LEDs (B, yellow LEDs (Y and red LEDs (R were tested under photoperiod of 16 h of exposure and 8 h of dark. The frequency of morphogenesis depended on the wavelength of the applied monochromatic light. Higher wavelength monochromatic light (yellow light was observed to induce higher shoot proliferation (98%, early PLB (protocorm-like bodies formation, differentiation into green buds and shoot initiation as compared to red, blue and white light treatments. Yellow light also yielded higher number of shoots per explants (29 shoots/explant than red, blue and white light treatments. The results suggest that the monochromatic light sources stimulate morphogenic effects on in vitro culture of Dendrobium sonia, and that yellow light treatment can be used to enhance the efficiency of micropropagation.

  3. UV-LED Curing Efficiency of Wood Coatings

    Directory of Open Access Journals (Sweden)

    Véronic Landry

    2015-12-01

    Full Text Available Ultraviolet light emitting diodes (UV-LEDs have attracted great interest in recent years. They can be used to polymerize coatings, such as those used for prefinished wood flooring. In this project, two lamps were compared for their suitability to be used on a wood flooring finishing line: a UV-microwave and a UV-LED lamp. Low heat emission was found for the UV-LED lamp compared to the UV-microwave one. This study also reveals that the 4 W/cm2 UV-LED lamp used is not powerful enough to cure UV high solids acrylate coatings while satisfactory results can be obtained for UV water-based formulations. In fact, conversion percentages were found to be low for the high solids coatings, leaving the coatings tacky. Higher conversion percentages were obtained for the UV water-based formulations. As a result, mass loss, hardness, and scratch resistance found for the samples cured by UV-LED were closed to the ones found for the samples cured using the UV microwave lamp.

  4. Blue laser diode (LD) and light emitting diode (LED) applications

    International Nuclear Information System (INIS)

    Bergh, Arpad A.

    2004-01-01

    The family of blue LEDs, edge emitting and surface emitting lasers, enable a number of applications. Blue lasers are used in digital applications such as optical storage in high density DVDs. The resolution of the spot size and hence the storage density is diffraction limited and is inversely proportional to the square of the wavelength of the laser. Other applications include printing, optical scanners, and high-resolution photo-lithography. As light emitters, blue LEDs are used for signaling and in direct view large area emissive displays. They are also making inroads into signage and LCD back-lighting, mobile platforms, and decorative accent lighting in curtains, furniture, etc. Blue LEDs produce white light either with phosphor wavelength converters or in combination with red and green LEDs. The full potential of LED light sources will require three devices to enable complete control over color and intensity. Sensing and medical/bio applications have a major impact on home security, on monitoring the environment, and on health care. New emerging diagnostic and therapeutic applications will improve the quality and reduce the cost of health care. (copyright 2004 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  5. Blue laser diode (LD) and light emitting diode (LED) applications

    Energy Technology Data Exchange (ETDEWEB)

    Bergh, Arpad A [Optoelectronics Industry Development Association (OIDA), 1133 Connecticut Avenue, NW, Suite 600, Washington, DC 20036-4329 (United States)

    2004-09-01

    The family of blue LEDs, edge emitting and surface emitting lasers, enable a number of applications. Blue lasers are used in digital applications such as optical storage in high density DVDs. The resolution of the spot size and hence the storage density is diffraction limited and is inversely proportional to the square of the wavelength of the laser. Other applications include printing, optical scanners, and high-resolution photo-lithography. As light emitters, blue LEDs are used for signaling and in direct view large area emissive displays. They are also making inroads into signage and LCD back-lighting, mobile platforms, and decorative accent lighting in curtains, furniture, etc. Blue LEDs produce white light either with phosphor wavelength converters or in combination with red and green LEDs. The full potential of LED light sources will require three devices to enable complete control over color and intensity. Sensing and medical/bio applications have a major impact on home security, on monitoring the environment, and on health care. New emerging diagnostic and therapeutic applications will improve the quality and reduce the cost of health care. (copyright 2004 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  6. Aerial LED signage by use of crossed-mirror array

    Science.gov (United States)

    Yamamoto, Hirotsugu; Kujime, Ryousuke; Bando, Hiroki; Suyama, Shiro

    2013-03-01

    3D representation of digital signage improves its significance and rapid notification of important points. Real 3D display techniques such as volumetric 3D displays are effective for use of 3D for public signs because it provides not only binocular disparity but also motion parallax and other cues, which will give 3D impression even people with abnormal binocular vision. Our goal is to realize aerial 3D LED signs. We have specially designed and fabricated a reflective optical device to form an aerial image of LEDs with a wide field angle. The developed reflective optical device composed of crossed-mirror array (CMA). CMA contains dihedral corner reflectors at each aperture. After double reflection, light rays emitted from an LED will converge into the corresponding image point. The depth between LED lamps is represented in the same depth in the floating 3D image. Floating image of LEDs was formed in wide range of incident angle with a peak reflectance at 35 deg. The image size of focused beam (point spread function) agreed to the apparent aperture size.

  7. Colorimetry and efficiency of white LEDs: Spectral width dependence

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Elaine; Edwards, Paul R.; Martin, Robert W. [Department of Physics, SUPA, Strathclyde University, Glasgow (United Kingdom)

    2012-03-15

    The potential colour rendering capability and efficiency of white LEDs constructed by a combination of individual red, green and blue (RGB) LEDs are analysed. The conventional measurement of colour rendering quality, the colour rendering index (CRI), is used as well as a recently proposed colour quality scale (CQS), designed to overcome some of the limitations of CRI when narrow-band emitters are being studied. The colour rendering performance is maximised by variation of the peak emission wavelength and relative intensity of the component LEDs, with the constraint that the spectral widths follow those measured in actual devices. The highest CRI achieved is 89.5, corresponding to a CQS value of 79, colour temperature of 3800 K and a luminous efficacy of radiation (LER) of 365 lm/W. By allowing the spectral width of the green LED to vary the CRI can be raised to 90.9, giving values of 82.5 and 370 lm/W for the CQS and LER, respectively. The significance of these values are discussed in terms of optimising the possible performance of RGB LEDs. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. Materials and Designs for High-Efficacy LED Light Engines

    Energy Technology Data Exchange (ETDEWEB)

    Ibbetson, James [Cree, Inc., Durham, NC (United States); Gresback, Ryan [Cree, Inc., Durham, NC (United States)

    2017-09-28

    Cree, Inc. conducted a narrow-band downconverter (NBD) materials development and implementation program which will lead to warm-white LED light engines with enhanced efficacy via improved spectral efficiency with respect to the human eye response. New red (600-630nm) NBD materials could result in as much as a 20% improvement in warm-white efficacy at high color quality relative to conventional phosphor-based light sources. Key program innovations included: high quantum yield; narrow peak width; minimized component-level losses due to “cross-talk” and light scattering among red and yellow-green downconverters; and improved reliability to reach parity with conventional phosphors. NBD-enabled downconversion efficiency gains relative to conventional phosphors yielded an end-of-project LED light engine efficacy of >160 lm/W at room temperature and 35 A/cm2, with a correlated color temperature (CCT) of ~3500K and >90 CRI (Color Rending Index). NBD-LED light engines exhibited equivalent luminous flux and color point maintenance at >1,000 hrs. of highly accelerated reliability testing as conventional phosphor LEDs. A demonstration luminaire utilizing an NBD-based LED light engine had a steady-state system efficacy of >150 lm/W at ~3500K and >90 CRI, which exceeded the 2014 DOE R&D Plan luminaire milestone for FY17 of >150 lm/W at just 80 CRI.

  9. Understanding and controlling chromaticity shift in LED devices

    Energy Technology Data Exchange (ETDEWEB)

    Davis, Lynn; Mills, Karmann; Lamvik, Michael; Perkins, Curtis; Bobashev, Georgiy; Young, Joseph; Yaga, Robert; Johnson, Cortina

    2017-05-30

    Chromaticity shift in light-emitting diode (LED) devices arises from multiple mechanisms, and at least five different chromaticity shift modes (CSMs) have been identified to date. This paper focuses on the impacts of irreversible phosphor degradation as a cause of chromaticity shifts in LED devices. The nitride phosphors used to produce warm white LEDs are especially vulnerable to degradation due to thermal and chemical effects such as reactions with oxygen and water. As a result, LED devices utilizing these phosphors were found to undergo either a green shift or, less commonly, a red shift depending on the phosphor mix in the LED devices. These types of chromaticity shifts are classified as CSM-2 (green shift) and CSM-5 (red shift). This paper provides an overview of the kinetic processes responsible for green and red chromaticity shifts along with examples from accelerated stress testing of 6” downlights. Both CSMs appear to proceed through analogous mechanisms that are initiated at the surface of the phosphor. A green shift is produced by the surface oxidation of the nitride phosphor that changes the emission profile to lower wavelengths. As the surface oxidation reaction proceeds, reactant limitations slow the rate and bulk oxidation processes become more prevalent. We found that a red chromaticity shift arises from quenching of the green phosphor, also possibly due to surface reactions of oxygen, which shift the emission chromaticity in the red direction. In conclusion, we discuss the implications of these findings on projecting chromaticity.