Androgen receptor (AR) degradation enhancer ASC-J9® in an FDA-approved formulated solution suppresses castration resistant prostate cancer cell growth.

Science.gov (United States)

Cheng, Max A; Chou, Fu-Ju; Wang, Keliang; Yang, Rachel; Ding, Jie; Zhang, Qiaoxia; Li, Gonghui; Yeh, Shuyuan; Xu, Defeng; Chang, Chawnshang

2018-03-28

ASC-J9 ® is a recently-developed androgen receptor (AR)-degradation enhancer that effectively suppresses castration resistant prostate cancer (PCa) cell proliferation and invasion. The optimal half maximum inhibitory concentrations (IC 50 ) of ASC-J9 ® at various PCa cell confluences (20%, 50%, and 100%) were assessed via both short-term MTT growth assays and long-term clonogenic proliferation assays. Our results indicate that the IC 50 values for ASC-J9 ® increased with increasing cell confluency. The IC 50 values were significantly decreased in PCa AR-positive cells compared to PCa AR-negative cells or in normal prostate cells. This suggests that ASC-J9 ® may function mainly via targeting the AR-positive PCa cells with limited unwanted side-effects to suppress the surrounding normal prostate cells. Mechanism dissection indicated that ASC-J9 ® might function via altering the apoptosis signals to suppress the PCa AR-negative PC-3 cells. Preclinical studies using multiple in vitro PCa cell lines and an in vivo mouse model with xenografted castration-resistant PCa CWR22Rv1 cells demonstrated that ASC-J9 ® has similar AR degradation effects when dissolved in FDA-approved solvents, including DMSO, PEG-400:Tween-80 (95:5), DMA:Labrasol:Tween-80 (10:45:45), and DMA:Labrasol:Tween-20 (10:45:45). Together, results from preclinical studies suggest a potential new therapy with AR-degradation enhancer ASC-J9 ® may potentially be ready to be used in human clinical trials in order to better suppress PCa at later castration resistant stages. Copyright © 2017 Elsevier B.V. All rights reserved.

Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study.

Science.gov (United States)

Porter, Danielle P; Toma, Jonathan; Tan, Yuping; Solberg, Owen; Cai, Suqin; Kulkarni, Rima; Andreatta, Kristen; Lie, Yolanda; Chuck, Susan K; Palella, Frank; Miller, Michael D; White, Kirsten L

2016-02-01

Antiretroviral regimen switching may be considered for HIV-1-infected, virologically-suppressed patients to enable treatment simplification or improve tolerability, but should be guided by knowledge of pre-existing drug resistance. The current study examined the impact of pre-existing drug resistance mutations on virologic outcomes among virologically-suppressed patients switching to Rilpivirine (RPV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). SPIRIT was a phase 3b study evaluating the safety and efficacy of switching to RPV/FTC/TDF in virologically-suppressed HIV-1-infected patients. Pre-existing drug resistance at baseline was determined by proviral DNA genotyping for 51 RPV/FTC/TDF-treated patients with known mutations by historical RNA genotype and matched controls and compared with clinical outcome at Week 48. Drug resistance mutations in protease or reverse transcriptase were detected in 62.7% of patients by historical RNA genotype and in 68.6% by proviral DNA genotyping at baseline. Proviral DNA sequencing detected 89% of occurrences of NRTI and NNRTI resistance-associated mutations reported by historical genotype. Mutations potentially affecting RPV activity, including E138A/G/K/Q, Y181C, and H221Y, were detected in isolates from 11 patients by one or both assays. None of the patients with single mutants had virologic failure through Week 48. One patient with pre-existing Y181Y/C and M184I by proviral DNA genotyping experienced virologic failure. Nineteen patients with K103N present by historical genotype were confirmed by proviral DNA sequencing and 18/19 remained virologically-suppressed. Virologic success rates were high among virologically-suppressed patients with pre-existing NRTI and NNRTI resistance-associated mutations who switched to RPV/FTC/TDF in the SPIRIT study. While plasma RNA genotyping remains preferred, proviral DNA genotyping may provide additional value in virologically-suppressed patients for whom historical resistance

TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients

Science.gov (United States)

Caceres, Gisela; McGraw, Kathy; Yip, Bon Ham; Pellagatti, Andrea; Johnson, Joseph; Zhang, Ling; Liu, Kenian; Zhang, Lan Min; Fulp, William J.; Lee, Ji-Hyun; Al Ali, Najla H.; Basiorka, Ashley; Smith, Larry J.; Daugherty, F. Joseph; Littleton, Neil; Wells, Richard A.; Sokol, Lubomir; Wei, Sheng; Komrokji, Rami S.; Boultwood, Jacqueline; List, Alan F.

2013-01-01

Stabilization of p53 in erythroid precursors in response to nucleosomal stress underlies the hypoplastic anemia in myelodysplastic syndromes (MDS) with chromosome 5q deletion [del(5q)]. We investigated whether cenersen, a clinically active 20-mer antisense oligonucleotide complementary to TP53 exon10, could suppress p53 expression and restore erythropoiesis in del(5q) MDS. Cenersen treatment of ribosomal protein S-14-deficient erythroblasts significantly reduced cellular p53 and p53-up-regulated modulator of apoptosis expression compared with controls, accompanied by a significant reduction in apoptosis and increased cell proliferation. In a two-stage erythroid differentiation assay, cenersen significantly suppressed nuclear p53 in bone marrow CD34+ cells isolated from patients with del(5q) MDS, whereas erythroid burst recovery increased proportionally to the magnitude of p53 suppression without evidence of del(5q) clonal suppression (r = −0.6; P = 0.005). To explore the effect of p53 suppression on erythropoiesis in vivo, dexamethasone, a glucocorticoid receptor-dependent p53 antagonist, was added to lenalidomide treatment in eight lower-risk, transfusion-dependent, del(5q) MDS patients with acquired drug resistance. Transfusion independence was restored in five patients accompanied by expansion of erythroid precursors and decreased cellular p53 expression. We conclude that targeted suppression of p53 could support effective erythropoiesis in lenalidomide-resistant del(5q) MDS. PMID:24043769

A Novel Two-Wire Fast Readout Approach for Suppressing Cable Crosstalk in a Tactile Resistive Sensor Array.

Science.gov (United States)

Wu, Jianfeng; Wang, Yu; Li, Jianqing; Song, Aiguo

2016-05-18

For suppressing the crosstalk problem due to wire resistances and contacted resistances of the long flexible cables in tactile sensing systems, we present a novel two-wire fast readout approach for the two-dimensional resistive sensor array in shared row-column fashion. In the approach, two wires are used for every driving electrode and every sampling electrode in the resistive sensor array. The approach with a high readout rate, though it requires a large number of wires and many sampling channels, solves the cable crosstalk problem. We also verified the approach's performance with Multisim simulations and actual experiments.

A Novel Two-Wire Fast Readout Approach for Suppressing Cable Crosstalk in a Tactile Resistive Sensor Array

Directory of Open Access Journals (Sweden)

Jianfeng Wu

2016-05-01

Full Text Available For suppressing the crosstalk problem due to wire resistances and contacted resistances of the long flexible cables in tactile sensing systems, we present a novel two-wire fast readout approach for the two-dimensional resistive sensor array in shared row-column fashion. In the approach, two wires are used for every driving electrode and every sampling electrode in the resistive sensor array. The approach with a high readout rate, though it requires a large number of wires and many sampling channels, solves the cable crosstalk problem. We also verified the approach’s performance with Multisim simulations and actual experiments.

CONFERENCE REPORT ANTIRETROVIRAL RESISTANCE

African Journals Online (AJOL)

2004-08-02

Aug 2, 2004 ... development of new agents with potential clinical utility for treating resistant ... data on the emergence of resistance among Thai women given zidovudine ... had achieved full virological suppression (viral load. < 50 copies/ml).

A role for suppressed skeletal muscle thermogenesis in pathways from weight fluctuations to the insulin resistance syndrome.

Science.gov (United States)

Dulloo, A G

2005-08-01

An impressive body of epidemiological evidence suggests that a history of large perturbations in body weight earlier in life, independently of excess weight, is a risk factor for later development of insulin-related complications, namely central obesity, type 2 diabetes and cardiovascular disease. Such an increased risk has been reported in men and women who in young adulthood experienced weight fluctuations that involved weight recovery after weight loss caused by disease, famine or voluntary 'yoyo' dieting, and is particularly strong when the weight fluctuations occurred much earlier in life and are characterized by catch-up growth after foetal and/or neonatal growth retardation. As the phase of weight recovery/catch-up growth is associated with both hyperinsulinaemia and an accelerated rate for recovering fat mass (i.e. catch-up fat), the questions arise as to whether, why and how processes that regulate catch-up fat might predispose to hyperinsulinaemia and to insulin-related diseases. In addressing these issues, this paper first reviews evidence for the existence of an adipose-specific control of thermogenesis, whose suppression contributes to the phenomenon of catch-up fat during weight recovery/catch-up growth. It subsequently concentrates upon recent findings suggesting that: (i) such suppression of thermogenesis directed at catch-up fat is accompanied by a redistribution of glucose from skeletal muscle to white adipose tissue, and (ii) substrate cycling between de novo lipogenesis and lipid oxidation can operate as a thermogenic effector in skeletal muscle in response to signalling interactions between leptin and insulin - two key 'adiposity' hormones implicated in the peripheral control of substrate metabolism. These new findings are integrated into the proposal that, in its 'evolutionary adaptive' role to spare glucose for rapid rebuilding of the fat stores, suppressed thermogenesis in skeletal muscle - via inhibition of substrate cycling between de novo

Combination of Bifunctional Alkylating Agent and Arsenic Trioxide Synergistically Suppresses the Growth of Drug-Resistant Tumor Cells

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Pei-Chih Lee

2010-05-01

Full Text Available Drug resistance is a crucial factor in the failure of cancer chemotherapy. In this study, we explored the effect of combining alkylating agents and arsenic trioxide (ATO on the suppression of tumor cells with inherited or acquired resistance to therapeutic agents. Our results showed that combining ATO and a synthetic derivative of 3a-aza-cyclopenta[a]indenes (BO-1012, a bifunctional alkylating agent causing DNA interstrand cross-links, was more effective in killing human cancer cell lines (H460, H1299, and PC3 than combining ATO and melphalan or thiotepa. We further demonstrated that the combination treatment of H460 cells with BO-1012 and ATO resulted in severe G2/M arrest and apoptosis. In a xenograft mouse model, the combination treatment with BO-1012 and ATO synergistically reduced tumor volumes in nude mice inoculated with H460 cells. Similarly, the combination of BO-1012 and ATO effectively reduced the growth of cisplatin-resistant NTUB1/P human bladder carcinoma cells. Furthermore, the repair of BO-1012-induced DNA interstrand cross-links was significantly inhibited by ATO, and consequently, γH2AX was remarkably increased and formed nuclear foci in H460 cells treated with this drug combination. In addition, Rad51 was activated by translocating and forming foci in nuclei on treatment with BO-1012, whereas its activation was significantly suppressed by ATO. We further revealed that ATO might mediate through the suppression of AKT activity to inactivate Rad51. Taken together, the present study reveals that a combination of bifunctional alkylating agents and ATO may be a rational strategy for treating cancers with inherited or acquired drug resistance.

Estradiol suppresses tissue androgens and prostate cancer growth in castration resistant prostate cancer

International Nuclear Information System (INIS)

Montgomery, Bruce; Nelson, Peter S; Vessella, Robert; Kalhorn, Tom; Hess, David; Corey, Eva

2010-01-01

Estrogens suppress tumor growth in prostate cancer which progresses despite anorchid serum androgen levels, termed castration resistant prostate cancers (CRPC), although the mechanisms are unclear. We hypothesize that estrogen inhibits CRPC in anorchid animals by suppressing tumoral androgens, an effect independent of the estrogen receptor. The human CRPC xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo, 17β-estradiol or 17β-estradiol and estrogen receptor antagonist ICI 182,780. Effects of 17β-estradiol on tumor growth were evaluated and tissue testosterone (T) and dihydrotestosterone (DHT) evaluated by mass spectrometry. Treatment of LuCaP 35V with 17β-estradiol slowed tumor growth compared to controls (tumor volume at day 21: 785 ± 81 mm 3 vs. 1195 ± 84 mm 3 , p = 0.002). Survival was also significantly improved in animals treated with 17β-estradiol (p = 0.03). The addition of the estrogen receptor antagonist ICI 182,780 did not significantly change survival or growth. 17β-estradiol in the presence and absence of ICI 182,780 suppressed tumor testosterone (T) and dihydrotestosterone (DHT) as assayed by mass spectrometry. Tissue androgens in placebo treated LuCaP 35V xenografts were; T = 0.71 ± 0.28 pg/mg and DHT = 1.73 ± 0.36 pg/mg. In 17β-estradiol treated LuCaP35V xenografts the tissue androgens were, T = 0.20 ± 0.10 pg/mg and DHT = 0.15 ± 0.15 pg/mg, (p < 0.001 vs. controls). Levels of T and DHT in control liver tissue were < 0.2 pg/mg. CRPC in anorchid animals maintains tumoral androgen levels despite castration. 17β-estradiol significantly suppressed tumor T and DHT and inhibits growth of CRPC in an estrogen receptor independent manner. The ability to manipulate tumoral androgens will be critical in the development and testing of agents targeting CRPC through tissue steroidogenesis

A Novel Crosstalk Suppression Method of the 2-D Networked Resistive Sensor Array

Directory of Open Access Journals (Sweden)

Jianfeng Wu

2014-07-01

Full Text Available The 2-D resistive sensor array in the row–column fashion suffered from the crosstalk problem for parasitic parallel paths. Firstly, we proposed an Improved Isolated Drive Feedback Circuit with Compensation (IIDFCC based on the voltage feedback method to suppress the crosstalk. In this method, a compensated resistor was specially used to reduce the crosstalk caused by the column multiplexer resistors and the adjacent row elements. Then, a mathematical equivalent resistance expression of the element being tested (EBT of this circuit was analytically derived and verified by the circuit simulations. The simulation results show that the measurement method can greatly reduce the influence on the EBT caused by parasitic parallel paths for the multiplexers’ channel resistor and the adjacent elements.

Impact damage resistance and damage suppression properties of shape memory alloys in hybrid composites—a review

International Nuclear Information System (INIS)

Angioni, S L; Meo, M; Foreman, A

2011-01-01

Composite materials are known to have a poor resistance to through-the-thickness impact loading. There are various methods for improving their impact damage tolerance, such as fiber toughening, matrix toughening, interface toughening, through-the-thickness reinforcements, and selective interlayers and hybrids. Hybrid composites with improved impact resistance are particularly useful in military and commercial civil applications. Hybridizing composites using shape memory alloys (SMA) is one solution since SMA materials can absorb the energy of the impact through superelastic deformation or recovery stress, reducing the effects of the impact on the composite structure. The SMA material may be embedded in the hybrid composites (SMAHC) in many different forms and also the characteristics of the fiber reinforcements may vary, such as SMA wires in woven laminates or SMA foils in unidirectional laminates, only to cite two examples. We will review the state of the art of SMAHC for the purpose of damage suppression. Both the active and passive damage suppression mechanisms will be considered. (topical review)

Resistance training enhances insulin suppression of endogenous glucose production in elderly women.

Science.gov (United States)

Honka, Miikka-Juhani; Bucci, Marco; Andersson, Jonathan; Huovinen, Ville; Guzzardi, Maria Angela; Sandboge, Samuel; Savisto, Nina; Salonen, Minna K; Badeau, Robert M; Parkkola, Riitta; Kullberg, Joel; Iozzo, Patricia; Eriksson, Johan G; Nuutila, Pirjo

2016-03-15

An altered prenatal environment during maternal obesity predisposes offspring to insulin resistance, obesity, and their consequent comorbidities, type 2 diabetes and cardiovascular disease. Telomere shortening and frailty are additional risk factors for these conditions. The aim of this study was to evaluate the effects of resistance training on hepatic metabolism and ectopic fat accumulation. Thirty-five frail elderly women, whose mothers' body mass index (BMI) was known, participated in a 4-mo resistance training program. Endogenous glucose production (EGP) and hepatic and visceral fat glucose uptake were measured during euglycemic hyperinsulinemia with [(18)F]fluorodeoxyglucose and positron emission tomography. Ectopic fat was measured using magnetic resonance spectroscopy and imaging. We found that the training intervention reduced EGP during insulin stimulation [from 5.4 (interquartile range 3.0, 7.0) to 3.9 (-0.4, 6.1) μmol·kg body wt(-1)·min(-1), P = 0.042] in the whole study group. Importantly, the reduction was higher among those whose EGP was more insulin resistant at baseline (higher than the median) [-5.6 (7.1) vs. 0.1 (5.4) μmol·kg body wt(-1)·min(-1), P = 0.015]. Furthermore, the decrease in EGP was associated with telomere elongation (r = -0.620, P = 0.001). The resistance training intervention did not change either hepatic or visceral fat glucose uptake or the amounts of ectopic fat. Maternal obesity did not influence the studied measures. In conclusion, resistance training improves suppression of EGP in elderly women. The finding of improved insulin sensitivity of EGP with associated telomere lengthening implies that elderly women can reduce their risk for type 2 diabetes and cardiovascular disease with resistance training. Copyright © 2016 the American Physiological Society.

Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

Directory of Open Access Journals (Sweden)

Liang Y

2016-05-01

Full Text Available Yayun Liang,1 Benford Mafuvadze,1 Johannes D Aebi,2 Salman M Hyder1 1Dalton Cardiovascular Research Center and Department of Biomedical Sciences, University of Missouri-Columbia, Columbia, MO, USA; 2Medicinal Chemistry, Roche Pharma Research and Early Development (pRED, Roche Innovation Center Basel, F Hoffmann-La Roche Ltd., Basel, Switzerland Abstract: Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration; however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4'-[6-(allylmethylaminohexyloxy]-4-bromo-2'-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071 (RO, which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway, on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the

Quinolone Resistance Reversion by Targeting the SOS Response.

Science.gov (United States)

Recacha, E; Machuca, J; Díaz de Alba, P; Ramos-Güelfo, M; Docobo-Pérez, F; Rodriguez-Beltrán, J; Blázquez, J; Pascual, A; Rodríguez-Martínez, J M

2017-10-10

Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs) and dynamic (killing curves or flow cytometry) methodologies. A peritoneal sepsis murine model was used to evaluate in vivo impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs). Killing curve assays showed a clear disadvantage for survival (Δlog 10 CFU per milliliter [CFU/ml] of 8 log units after 24 h), and the in vivo efficacy of ciprofloxacin was significantly enhanced (Δlog 10 CFU/g of 1.76 log units) in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min) of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of E. coli phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the in vivo efficacy. IMPORTANCE The rapid rise of antibiotic resistance in bacterial pathogens is now considered a major global health crisis. New strategies are needed to block the development of resistance and to extend the life of antibiotics. The SOS response is a promising target for developing therapeutics to reduce the acquisition of antibiotic resistance and enhance the bactericidal activity of antimicrobial agents such as quinolones. Significant questions remain regarding its impact as a strategy for the reversion or resensitization of antibiotic-resistant bacteria. To address this

Quercetin suppresses drug-resistant spheres via the p38 MAPK-Hsp27 apoptotic pathway in oral cancer cells.

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Su-Feng Chen

Full Text Available BACKGROUND: Treatment failure in oral squamous cell carcinoma (OSCC leading to local recurrence(s and metastases is mainly due to drug resistance. Cancer stem cells (CSCs are thought be responsible for the development of drug resistance. However, the correlations between CSCs, drug resistance, and new strategy against drug resistance in OSCC remain elusive. METHODS: A drug-resistant sphere (DRSP model was generated by using a nonadhesive culture system to induce drug-resistant cells from SCC25 oral cancer cells. A comparative analysis was performed between the parent control cells and DRSPs with a related treatment strategy focusing on the expression of epithelial-mesenchymal transition (EMT-associated markers, drug-resistance-related genes, and CSC properties in vitro, as well as tumorigenicity and the regimen for tumor regression in vivo. RESULTS: Our data show the presence of a phenomenon of EMT with gradual cellular transition from an epithelioid to mesenchymal-like spheroid morphology during induction of drug resistance. The characterization of DRSPs revealed the upregulation of the drug-resistance-related genes ABCG2 and MDR-1 and of CSC-representative markers, suggesting that DRSPs have greater resistance to cisplatin (Cis and stronger CSC properties compared with the control. Moreover, overexpression of phosphorylated heat-shock protein 27 (p-Hsp27 via the activation of p38 MAPK signaling was observed in DRSPs. Knockdown of Hsp27 decreased Cis resistance and induced apoptosis in DRSPs. Furthermore, an inhibitor of Hsp27, quercetin (Qu, suppressed p-Hsp27 expression, with alterations of the EMT signature, leading to the promotion of apoptosis in DRSPs. A xenographic study also confirmed the increase of tumorigenicity in DRSPs. The combination of Qu and Cis can reduce tumor growth and decrease drug resistance in OSCC. CONCLUSIONS: The p38 MAPK-Hsp27 axis plays an important role in CSCs-mediated drug resistance in OSCC. Targeting this axis

Development of advanced claddings for suppressing the hydrogen emission in accident conditions. Development of advanced claddings for suppressing the hydrogen emission in the accident condition

International Nuclear Information System (INIS)

Park, Jeong-Yong; KIM, Hyun-Gil; JUNG, Yang-Il; PARK, Dong-Jun; KOO, Yang-Hyun

2013-01-01

The development of accident-tolerant fuels can be a breakthrough to help solve the challenge facing nuclear fuels. One of the goals to be reached with accident-tolerant fuels is to reduce the hydrogen emission in the accident condition by improving the high-temperature oxidation resistance of claddings. KAERI launched a new project to develop the accident-tolerant fuel claddings with the primary objective to suppress the hydrogen emission even in severe accident conditions. Two concepts are now being considered as hydrogen-suppressed cladding. In concept 1, the surface modification technique was used to improve the oxidation resistance of Zr claddings. Like in concept 2, the metal-ceramic hybrid cladding which has a ceramic composite layer between the Zr inner layer and the outer surface coating is being developed. The high-temperature steam oxidation behaviour was investigated for several candidate materials for the surface modification of Zr claddings. From the oxidation tests carried out in 1 200 deg. C steam, it was found that the high-temperature steam oxidation resistance of Cr and Si was much higher than that of zircaloy-4. Al 3 Ti-based alloys also showed extremely low-oxidation rate compared to zircaloy-4. One important part in the surface modification is to develop the surface coating technology where the optimum process needs to be established depending on the surface layer materials. Several candidate materials were coated on the Zr alloy specimens by a laser beam scanning (LBS), a plasma spray (PS) and a PS followed by LBS and subject to the high-temperature steam oxidation test. It was found that Cr and Si coating layers were effective in protecting Zr-alloys from the oxidation. The corrosion behaviour of the candidate materials in normal reactor operation condition such as 360 deg. C water will be investigated after the screening test in the high-temperature steam. The metal-ceramic hybrid cladding consisted of three major parts; a Zr liner, a

A secretory protein of necrotrophic fungus Sclerotinia sclerotiorum that suppresses host resistance.

Directory of Open Access Journals (Sweden)

Wenjun Zhu

Full Text Available SSITL (SS1G_14133 of Sclerotinia sclerotiorum encodes a protein with 302 amino acid residues including a signal peptide, its secretion property was confirmed with immunolocalization and immunofluorescence techniques. SSITL was classified in the integrin alpha N-terminal domain superfamily, and its 3D structure is similar to those of human integrin α4-subunit and a fungal integrin-like protein. When S. sclerotiorum was inoculated to its host, high expression of SSITL was detected during the initial stages of infection (1.5-3.0 hpi. Targeted silencing of SSITL resulted in a significant reduction in virulence; on the other hand, inoculation of SSITL silenced transformant A10 initiated strong and rapid defense response in Arabidopsis, the highest expressions of defense genes PDF1.2 and PR-1 appeared at 3 hpi which was 9 hr earlier than that time when plants were inoculated with the wild-type strain of S. sclerotiorum. Systemic resistance induced by A10 was detected by analysis of the expression of PDF1.2 and PR-1, and confirmed following inoculation with Botrytis cinerea. A10 induced much larger lesions on Arabidopsis mutant ein2 and jar1, and slightly larger lesions on mutant pad4 and NahG in comparison with the wild-type plants. Furthermore, both transient and constitutive expression of SSITL in Arabidopsis suppressed the expression of PDF1.2 and led to be more susceptible to A10 and the wild-type strain of S. sclerotiorum and B. cinerea. Our results suggested that SSITL is an effector possibly and plays significant role in the suppression of jasmonic/ethylene (JA/ET signal pathway mediated resistance at the early stage of infection.

Feedback control for magnetic island suppression in tokamaks

NARCIS (Netherlands)

Hennen, B.A.

2011-01-01

A real-time feedback control system has been developed that finds, tracks, suppresses and/or stabilizes resistive magnetic instabilities in a nuclear fusion plasma. In a tokamak, magnetic fields confine a fusion plasma in a topology of toroidally nested magnetic surfaces. The power produced by the

Suppressing miRNA-15a/-16 expression by interleukin-6 enhances drug-resistance in myeloma cells

Directory of Open Access Journals (Sweden)

Chang Hong

2011-09-01

Full Text Available Abstract The bone marrow microenvironment facilitates the survival, differentiation, and proliferation of myeloma (MM cells. This study identified that microRNA-15a and -16 expressions tightly correlated with proliferation and drug sensitivity of MM cells. miRNA-15a/-16 expression in MM cells was significantly increased after treatment with cytotoxic agents. The interaction of bone marrow stromal cells (BMSC with MM cells resulted in decreased miRNA-15a/-16 expression and promoted the survival of the MM cells. Interleukin-6 (IL-6 produced by BMSCs suppressed the expression of miRNA-15a and 16 in a time- and dose- dependent pattern, with the suppression on miRNA-15a being more significant than on miRNA-16. miRNA-15a-transfected MM cells were found to be arrested in G1/S checkpoint, and the transfected MM cells had decreased growth and survival. In conclusion, our data suggest that via suppressing miRNA-15a and -16 expressions, IL-6 secreted by BMSCs promotes drug-resistance in myeloma cells.

Pest and disease resistance enhanced by heterologous suppression of a Nicotiana plumbaginifolia cytochrome P450 gene CYP72A2.

Science.gov (United States)

Smigocki, Ann C; Wilson, Dennis

2004-12-01

The functional role of the Nicotiana plumbaginifolia cytochrome P450 gene CYP72A2 was investigated in transgenic plants. N. tabacum plants transformed with a sense or antisense CYP72A2 construct exhibited diminished heights, branched stems, smaller leaves and deformed flowers. Western blot analysis revealed reduced levels of a 58 kDa protein corresponding to CYP72A2, suggesting that the CYP72A2 homolog was suppressed in the sense and antisense plants. Transgenic plants had increased resistance to Manduca sexta larvae that consumed about 35 to 90 less of transgenic versus control leaves. A virulent strain of Pseudomonas syringae pv. tabaci induced a disease-limiting response followed by a delayed and decreased development of disease symptoms in the transgenics. CYP72A2 gene mediated resistance suggests that the plant-pest or -pathogen interactions may have been modified by changes in bioactive metabolite pools.

MicroRNAs Suppress NB Domain Genes in Tomato That Confer Resistance to Fusarium oxysporum

Science.gov (United States)

Ouyang, Shouqiang; Park, Gyungsoon; Atamian, Hagop S.; Han, Cliff S.; Stajich, Jason E.; Kaloshian, Isgouhi; Borkovich, Katherine A.

2014-01-01

MicroRNAs (miRNAs) suppress the transcriptional and post-transcriptional expression of genes in plants. Several miRNA families target genes encoding nucleotide-binding site–leucine-rich repeat (NB-LRR) plant innate immune receptors. The fungus Fusarium oxysporum f. sp. lycopersici causes vascular wilt disease in tomato. We explored a role for miRNAs in tomato defense against F. oxysporum using comparative miRNA profiling of susceptible (Moneymaker) and resistant (Motelle) tomato cultivars. slmiR482f and slmiR5300 were repressed during infection of Motelle with F. oxysporum. Two predicted mRNA targets each of slmiR482f and slmiR5300 exhibited increased expression in Motelle and the ability of these four targets to be regulated by the miRNAs was confirmed by co-expression in Nicotiana benthamiana. Silencing of the targets in the resistant Motelle cultivar revealed a role in fungal resistance for all four genes. All four targets encode proteins with full or partial nucleotide-binding (NB) domains. One slmiR5300 target corresponds to tm-2, a susceptible allele of the Tomato Mosaic Virus resistance gene, supporting functions in immunity to a fungal pathogen. The observation that none of the targets correspond to I-2, the only known resistance (R) gene for F. oxysporum in tomato, supports roles for additional R genes in the immune response. Taken together, our findings suggest that Moneymaker is highly susceptible because its potential resistance is insufficiently expressed due to the action of miRNAs. PMID:25330340

B cells exposed to enterobacterial components suppress development of experimental colitis

DEFF Research Database (Denmark)

Schmidt, Esben Gjerløff Wedebye; Larsen, Hjalte List; Kristensen, Nanna Ny

2012-01-01

). RESULTS: We demonstrate that splenic B cells exposed to ebx produce large amounts of IL-10 in vitro and express CD1d and CD5 previously known to be associated with regulatory B cells. In SCID mice transplanted with colitogenic CD4(+) CD25(-) T cells, co-transfer of ebx-B cells significantly suppressed...... development of colitis. Suppression was dependent on B cell-derived IL-10, as co-transfer of IL-10 knockout ebx-B cells failed to suppress colitis. Ebx-B cell-mediated suppression of colitis was associated with a decrease in interferon gamma (IFN-¿)-producing T(H) 1 cells and increased frequencies of Foxp3......-expressing T cells. CONCLUSIONS: These data demonstrate that splenic B cells exposed to enterobacterial components acquire immunosuppressive functions by which they can suppress development of experimental T cell-mediated colitis in an IL-10-dependent way. (Inflamm Bowel Dis 2011;)....

Albugo-imposed changes to tryptophan-derived antimicrobial metabolite biosynthesis may contribute to suppression of non-host resistance to Phytophthora infestans in Arabidopsis thaliana

DEFF Research Database (Denmark)

Prince, David C.; Rallapalli, Ghanasyam; Xu, Deyang

2017-01-01

-derived antimicrobial compounds enables P. infestans colonization of Arabidopsis, although to a lesser extent than Albugo-infected tissue. A. laibachii also suppresses a subset of genes regulated by salicylic acid; however, salicylic acid plays only a minor role in non-host resistance to P. infestans. CONCLUSIONS......: Albugo sp. alter tryptophan-derived metabolites and suppress elements of the responses to salicylic acid in Arabidopsis. Albugo sp. imposed alterations in tryptophan-derived metabolites may play a role in Arabidopsis non-host resistance to P. infestans. Understanding the basis of non-host resistance...

Catalpol ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF-κB pathways

Energy Technology Data Exchange (ETDEWEB)

Zhou, Jun, E-mail: hustzhj@hust.edu.cn; Xu, Gang; Ma, Shuai; Li, Fen; Yuan, Miao; Xu, Huibi; Huang, Kaixun

2015-11-27

Catalpol, a bioactive component from the root of Rehmannia glutinosa, has been shown to possess hypoglycemic effects in type 2 diabetic animal models, however, the underlying mechanisms remain poorly understood. Here we investigated the effect of catalpol on high-fat diet (HFD)-induced insulin resistance and adipose tissue inflammation in mice. Oral administration of catalpol at 100 mg/kg for 4 weeks had no effect on body weight of HFD-induced obese mice, but it significantly improved fasting glucose and insulin levels, glucose tolerance and insulin tolerance. Moreover, macrophage infiltration into adipose tissue was markedly reduced by catalpol. Intriguingly, catalpol also significantly reduced mRNA expressions of M1 pro-inflammatory cytokines, but increased M2 anti-inflammatory gene expressions in adipose tissue. Concurrently, catalpol significantly suppressed the c-Jun NH2-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways in adipose tissue. Collectively, these results suggest that catalpol may ameliorate HFD-induced insulin resistance in mice by attenuating adipose tissue inflammation and suppressing the JNK and NF-κB pathways, and thus provide important new insights into the underlying mechanisms of the antidiabetic effect of catalpol. - Highlights: • Catalpol ameliorates high-fat diet (HFD)-induced insulin resistance in mice. • Catalpol reduces adipose tissue macrophage infiltration in HFD-fed mice. • Catalpol regulates M1 and M2 inflammatory gene expression in obese adipose tissue. • Catalpol suppresses the JNK and NF-κB signaling pathways in obese adipose tissue.

Catalpol ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF-κB pathways

International Nuclear Information System (INIS)

Zhou, Jun; Xu, Gang; Ma, Shuai; Li, Fen; Yuan, Miao; Xu, Huibi; Huang, Kaixun

2015-01-01

Catalpol, a bioactive component from the root of Rehmannia glutinosa, has been shown to possess hypoglycemic effects in type 2 diabetic animal models, however, the underlying mechanisms remain poorly understood. Here we investigated the effect of catalpol on high-fat diet (HFD)-induced insulin resistance and adipose tissue inflammation in mice. Oral administration of catalpol at 100 mg/kg for 4 weeks had no effect on body weight of HFD-induced obese mice, but it significantly improved fasting glucose and insulin levels, glucose tolerance and insulin tolerance. Moreover, macrophage infiltration into adipose tissue was markedly reduced by catalpol. Intriguingly, catalpol also significantly reduced mRNA expressions of M1 pro-inflammatory cytokines, but increased M2 anti-inflammatory gene expressions in adipose tissue. Concurrently, catalpol significantly suppressed the c-Jun NH2-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways in adipose tissue. Collectively, these results suggest that catalpol may ameliorate HFD-induced insulin resistance in mice by attenuating adipose tissue inflammation and suppressing the JNK and NF-κB pathways, and thus provide important new insights into the underlying mechanisms of the antidiabetic effect of catalpol. - Highlights: • Catalpol ameliorates high-fat diet (HFD)-induced insulin resistance in mice. • Catalpol reduces adipose tissue macrophage infiltration in HFD-fed mice. • Catalpol regulates M1 and M2 inflammatory gene expression in obese adipose tissue. • Catalpol suppresses the JNK and NF-κB signaling pathways in obese adipose tissue.

Double-stranded RNA uptake through topical application, mediates silencing of five CYP4 genes and suppresses insecticide resistance in Diaphorina citri.

Science.gov (United States)

Killiny, Nabil; Hajeri, Subhas; Tiwari, Siddharth; Gowda, Siddarame; Stelinski, Lukasz L

2014-01-01

Silencing of genes through RNA interference (RNAi) in insects has gained momentum during the past few years. RNAi has been used to cause insect mortality, inhibit insect growth, increase insecticide susceptibility, and prevent the development of insecticide resistance. We investigated the efficacy of topically applied dsRNA to induce RNAi for five Cytochrome P450 genes family 4 (CYP4) in Diaphorina citri. We previously reported that these CYP4 genes are associated with the development of insecticide resistance in D. citri. We targeted five CYP4 genes that share a consensus sequence with one dsRNA construct. Quantitative PCR confirmed suppressed expression of the five CYP4 genes as a result of dsRNA topically applied to the thoracic region of D. citri when compared to the expression levels in a control group. Western blot analysis indicated a reduced signal of cytochrome P450 proteins (45 kDa) in adult D. citri treated with the dsRNA. In addition, oxidase activity and insecticide resistance were reduced for D. citri treated with dsRNA that targeted specific CYP4 genes. Mortality was significantly higher in adults treated with dsRNA than in adults treated with water. Our results indicate that topically applied dsRNA can penetrate the cuticle of D. citri and induce RNAi. These results broaden the scope of RNAi as a mechanism to manage pests by targeting a broad range of genes. The results also support the application of RNAi as a viable tool to overcome insecticide resistance development in D. citri populations. However, further research is needed to develop grower-friendly delivery systems for the application of dsRNA under field conditions. Considering the high specificity of dsRNA, this tool can also be used for management of D. citri by targeting physiologically critical genes involved in growth and development.

Double-stranded RNA uptake through topical application, mediates silencing of five CYP4 genes and suppresses insecticide resistance in Diaphorina citri.

Directory of Open Access Journals (Sweden)

Nabil Killiny

Full Text Available Silencing of genes through RNA interference (RNAi in insects has gained momentum during the past few years. RNAi has been used to cause insect mortality, inhibit insect growth, increase insecticide susceptibility, and prevent the development of insecticide resistance. We investigated the efficacy of topically applied dsRNA to induce RNAi for five Cytochrome P450 genes family 4 (CYP4 in Diaphorina citri. We previously reported that these CYP4 genes are associated with the development of insecticide resistance in D. citri. We targeted five CYP4 genes that share a consensus sequence with one dsRNA construct. Quantitative PCR confirmed suppressed expression of the five CYP4 genes as a result of dsRNA topically applied to the thoracic region of D. citri when compared to the expression levels in a control group. Western blot analysis indicated a reduced signal of cytochrome P450 proteins (45 kDa in adult D. citri treated with the dsRNA. In addition, oxidase activity and insecticide resistance were reduced for D. citri treated with dsRNA that targeted specific CYP4 genes. Mortality was significantly higher in adults treated with dsRNA than in adults treated with water. Our results indicate that topically applied dsRNA can penetrate the cuticle of D. citri and induce RNAi. These results broaden the scope of RNAi as a mechanism to manage pests by targeting a broad range of genes. The results also support the application of RNAi as a viable tool to overcome insecticide resistance development in D. citri populations. However, further research is needed to develop grower-friendly delivery systems for the application of dsRNA under field conditions. Considering the high specificity of dsRNA, this tool can also be used for management of D. citri by targeting physiologically critical genes involved in growth and development.

Magnetic fusion development for global warming suppression

International Nuclear Information System (INIS)

Li Jiangang; Zhang Jie; Duan Xuru

2010-01-01

Energy shortage and environmental pollution are two critical issues for human beings in the 21st century. There is an urgent need for new sustainable energy to meet the fast growing demand for clean energy. Fusion is one of the few options which may be able to satisfy the requirement for large scale sustainable energy generation and global warming suppression and therefore must be developed as quickly as possible. Fusion research has been carried out for the past 50 years. It is too long to wait for another 50 years to generate electricity by fusion. A much more aggressive approach should be taken with international collaboration towards the early use of fusion energy to meet the urgent needs for energy and global warming suppression.

Characterization by Suppression Subtractive Hybridization of Transcripts That Are Differentially Expressed in Leaves of Anthracnose-Resistant Ramie Cultivar.

Science.gov (United States)

Xuxia, Wang; Jie, Chen; Bo, Wang; Lijun, Liu; Hui, Jiang; Diluo, Tang; Dingxiang, Peng

2012-01-01

For the purpose of screening putative anthracnose resistance-related genes of ramie ( Boehmeria nivea L. Gaud), a cDNA library was constructed by suppression subtractive hybridization using anthracnose-resistant cultivar Huazhu no. 4. The cDNAs from Huazhu no. 4, which were infected with Colletotrichum gloeosporioides , were used as the tester and cDNAs from uninfected Huazhu no. 4 as the driver. Sequencing analysis and homology searching showed that these clones represented 132 single genes, which were assigned to functional categories, including 14 putative cellular functions, according to categories established for Arabidopsis . These 132 genes included 35 disease resistance and stress tolerance-related genes including putative heat-shock protein 90, metallothionein, PR-1.2 protein, catalase gene, WRKY family genes, and proteinase inhibitor-like protein. Partial disease-related genes were further analyzed by reverse transcription PCR and RNA gel blot. These expressed sequence tags are the first anthracnose resistance-related expressed sequence tags reported in ramie.

Analysis of Tospovirus NSs Proteins in Suppression of Systemic Silencing.

Science.gov (United States)

Hedil, Marcio; Sterken, Mark G; de Ronde, Dryas; Lohuis, Dick; Kormelink, Richard

2015-01-01

RNA silencing is a sequence-specific gene regulation mechanism that in plants also acts antiviral. In order to counteract antiviral RNA silencing, viruses have evolved RNA silencing suppressors (RSS). In the case of tospoviruses, the non-structural NSs protein has been identified as the RSS. Although the tomato spotted wilt virus (TSWV) tospovirus NSs protein has been shown to exhibit affinity to long and small dsRNA molecules, its ability to suppress the non-cell autonomous part of RNA silencing has only been studied to a limited extent. Here, the NSs proteins of TSWV, groundnut ringspot virus (GRSV) and tomato yellow ring virus (TYRV), representatives for three distinct tospovirus species, have been studied on their ability and strength to suppress local and systemic silencing. A system has been developed to quantify suppression of GFP silencing in Nicotiana benthamiana 16C lines, to allow a comparison of relative RNA silencing suppressor strength. It is shown that NSs of all three tospoviruses are suppressors of local and systemic silencing. Unexpectedly, suppression of systemic RNA silencing by NSsTYRV was just as strong as those by NSsTSWV and NSsGRSV, even though NSsTYRV was expressed in lower amounts. Using the system established, a set of selected NSsTSWV gene constructs mutated in predicted RNA binding domains, as well as NSs from TSWV isolates 160 and 171 (resistance breakers of the Tsw resistance gene), were analyzed for their ability to suppress systemic GFP silencing. The results indicate another mode of RNA silencing suppression by NSs that acts further downstream the biogenesis of siRNAs and their sequestration. The findings are discussed in light of the affinity of NSs for small and long dsRNA, and recent mutant screen of NSsTSWV to map domains required for RSS activity and triggering of Tsw-governed resistance.

Development of hyper osmotic resistant CHO host cells for enhanced antibody production.

Science.gov (United States)

Kamachi, Yasuharu; Omasa, Takeshi

2018-04-01

Cell culture platform processes are generally employed to shorten the duration of new product development. A fed-batch process with continuous feeding is a conventional platform process for monoclonal antibody production using Chinese hamster ovary (CHO) cells. To establish a simplified platform process, the feeding method can be changed from continuous feed to bolus feed. However, this change induces a rapid increase of osmolality by the bolus addition of nutrients. The increased osmolality suppresses cell culture growth, and the final product concentration is decreased. In this study, osmotic resistant CHO host cells were developed to attain a high product concentration. To establish hyper osmotic resistant CHO host cells, CHO-S host cells were passaged long-term in a hyper osmotic basal medium. There were marked differences in cell growth of the original and established host cells under iso- (328 mOsm/kg) or hyper-osmolality (over 450 mOsm/kg) conditions. Cell growth of the original CHO host cells was markedly decreased by the induction of osmotic stress, whereas cell growth of the hyper osmotic resistant CHO host cells was not affected. The maximum viable cell concentration of hyper osmotic resistant CHO host cells was 132% of CHO-S host cells after the induction of osmotic stress. Moreover, the hyper osmotic resistant characteristic of established CHO host cells was maintained even after seven passages in iso-osmolality basal medium. The use of hyper osmotic resistance CHO host cells to create a monoclonal antibody production cell line might be a new approach to increase final antibody concentrations with a fed-batch process. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Gap junctions suppress electrical but not [Ca(2+)] heterogeneity in resistance arteries

DEFF Research Database (Denmark)

Hald, Bjørn Olav; Welsh, Donald G; von Holstein-Rathlou, Niels-Henrik

2014-01-01

arises, a virtual arteriole was developed that introduces variation in the activities of ion-transport proteins between cells. By varying the level of heterogeneity and subpopulations of gap junctions (GJs), the resulting simulations shows that GJs suppress electrical variation but can only reduce...

Suppression in growth hormone during overeating ameliorates the increase in insulin resistance and cardiovascular disease risk.

Science.gov (United States)

Cornford, Andrea S; Barkan, Ariel L; Hinko, Alexander; Horowitz, Jeffrey F

2012-11-15

Previously, we reported that overeating for only a few days markedly suppressed the secretion of growth hormone (GH). The purpose of the present study was to determine the role of this reduction in GH concentration on key metabolic adaptations that occur during 2 wk of overeating. Nine nonobese, healthy adults were admitted to the hospital for 2 wk, during which time they ate ∼4,000 kcal/day (70 kcal·kg fat-free mass(-1)·day(-1); 50% carbohydrate, 35% fat, and 15% protein), and their plasma GH concentration was allowed to decline naturally (control). An additional eight subjects underwent the same overeating intervention and received exogenous GH treatment (GHT) administered in four daily injections to mimic physiological GH secretion throughout the 2-wk overeating period. We measured plasma insulin and glucose concentrations in the fasting and postprandial state as well as fasting lipolytic rate, proteolytic rate, and fractional synthetic rate (FSR) using stable-isotope tracer methods. GHT prevented the fall in plasma GH concentration, maintaining plasma GH concentration at baseline levels (1.2 ± 0.2 ng/ml), which increased fasting and postprandial assessments of insulin resistance (P overeating also blunted the increase in systemic proteolysis (P overeating. In conclusion, our main findings suggest that the suppression in GH secretion that naturally occurs during the early stages of overeating may help attenuate the insulin resistance and hyperlipidemia that typically accompany overeating.

MicroRNA-128 suppresses paclitaxel-resistant lung cancer by inhibiting MUC1-C and BMI-1 in cancer stem cells.

Science.gov (United States)

Koh, Hyebin; Park, Hyeri; Chandimali, Nisansala; Huynh, Do Luong; Zhang, Jiao Jiao; Ghosh, Mrinmoy; Gera, Meeta; Kim, Nameun; Bak, Yesol; Yoon, Do-Young; Park, Yang Ho; Kwon, Taeho; Jeong, Dong Kee

2017-12-15

The existence of cancer stem cells (CSCs) is the main reason for failure of cancer treatment caused by drug resistance. Therefore, eradicating cancers by targeting CSCs remains a significant challenge. In the present study, because of the important role of BMI-1 proto-oncogene, polycomb ring finger (BMI-1) and C-terminal Mucin1 (MUC1-C) in tumor growth and maintenance of CSCs, we aimed to confirm that microRNA miR-128, as an inhibitor of BMI-1 and MUC1-C, could effectively suppress paclitaxel (PTX)-resistant lung cancer stem cells. We showed that CSCs have significantly higher expression levels of BMI-1, MUC1-C, stemness proteins, signaling factors, and higher malignancy compared with normal tumor cells. After transfection with miR-128, the BMI-1 and MUC1-C levels in CSCs were suppressed. When miR-128 was stably expressed in PTX-resistant lung cancer stem cells, the cells showed decreased proliferation, metastasis, self-renewal, migration, invasive ability, clonogenicity, and tumorigenicity in vitro and in vivo and increased apoptosis compared with miR-NC (negative control) CSCs. Furthermore, miR-128 effectively decreased the levels of β-catenin and intracellular signaling pathway-related factors in CSCs. MiR-128 also decreased the luciferase activity of MUC1 reporter constructs and reduced the levels of transmembrane MUC1-C and BMI-1. These results suggested miR-128 as an attractive therapeutic strategy for PTX-resistant lung cancer via inhibition of BMI-1 and MUC1-C.

Nonchemical, cultural management strategies to suppress phytophthora root rot in northern highbush blueberry

Science.gov (United States)

Phytophthora cinnamomi causes root rot of highbush blueberry and decreases plant growth, yield, and profitability for growers. Fungicides can suppress root rot, but cannot be used in certified organic production systems and fungicide resistance may develop. Alternative, non-chemical, cultural manag...

Suppression of Adaptive Immune Cell Activation Does Not Alter Innate Immune Adipose Inflammation or Insulin Resistance in Obesity.

Directory of Open Access Journals (Sweden)

Manikandan Subramanian

Full Text Available Obesity-induced inflammation in visceral adipose tissue (VAT is a major contributor to insulin resistance and type 2 diabetes. Whereas innate immune cells, notably macrophages, contribute to visceral adipose tissue (VAT inflammation and insulin resistance, the role of adaptive immunity is less well defined. To address this critical gap, we used a model in which endogenous activation of T cells was suppressed in obese mice by blocking MyD88-mediated maturation of CD11c+ antigen-presenting cells. VAT CD11c+ cells from Cd11cCre+Myd88fl/fl vs. control Myd88fl/fl mice were defective in activating T cells in vitro, and VAT T and B cell activation was markedly reduced in Cd11cCre+Myd88fl/fl obese mice. However, neither macrophage-mediated VAT inflammation nor systemic inflammation were altered in Cd11cCre+Myd88fl/fl mice, thereby enabling a focused analysis on adaptive immunity. Unexpectedly, fasting blood glucose, plasma insulin, and the glucose response to glucose and insulin were completely unaltered in Cd11cCre+Myd88fl/fl vs. control obese mice. Thus, CD11c+ cells activate VAT T and B cells in obese mice, but suppression of this process does not have a discernible effect on macrophage-mediated VAT inflammation or systemic glucose homeostasis.

Blunted suppression of acyl-ghrelin in response to fructose ingestion in obese adolescents: the role of insulin resistance.

Science.gov (United States)

Van Name, Michelle; Giannini, Cosimo; Santoro, Nicola; Jastreboff, Ania M; Kubat, Jessica; Li, Fangyong; Kursawe, Romy; Savoye, Mary; Duran, Elvira; Dziura, James; Sinha, Rajita; Sherwin, Robert S; Cline, Gary; Caprio, Sonia

2015-03-01

Fructose consumption has risen alongside obesity and diabetes. Gut hormones involved in hunger and satiety (ghrelin and PYY) may respond differently to fructose compared with glucose ingestion. This study evaluated the effects of glucose and fructose ingestion on ghrelin and PYY in lean and obese adolescents with differing insulin sensitivity. Adolescents were divided into lean (n = 14), obese insulin sensitive (n = 12) (OIS), and obese insulin resistant (n = 15) (OIR). In a double-blind, cross-over design, subjects drank 75 g of glucose or fructose in random order, serum was obtained every 10 minutes for 60 minutes. Baseline acyl-ghrelin was highest in lean and lowest in OIR (P = 0.02). After glucose ingestion, acyl-ghrelin decreased similarly in lean and OIS but was lower in OIR (vs. lean, P = 0.03). Suppression differences were more pronounced after fructose (lean vs. OIS, P = 0.008, lean vs. OIR, P < 0.001). OIS became significantly hungrier after fructose (P = 0.015). PYY was not significantly different at baseline, varied minimally after glucose, and rose after fructose. Compared with lean, OIS adolescents have impaired acyl-ghrelin responses to fructose but not glucose, whereas OIR adolescents have blunted responses to both. Diminished suppression of acyl-ghrelin in childhood obesity, particularly if accompanied by insulin resistance, may promote hunger and overeating. © 2015 The Obesity Society.

No choice but to find resistance to soybean aphid biotype 4

Science.gov (United States)

Host plant resistance in soybean [Glycine max (L.) Merr] utilizes its natural defenses to limit soybean aphid (Aphis glycines Matsamura, SBA) injury, reducing insecticide reliance. Specific genes called Rag or Resistance to Aphis glycines are unfavorable to SBA and may suppress their development and...

Suppressive versus augmenting effect of the same pretreatment regimen in two murine tumor systems with distinct effector mechanisms

International Nuclear Information System (INIS)

Fujiwara, Hiromi; Hamaoka, Toshiyuki; Kitagawa, Masayasu

1978-01-01

The effect of presensitization with x-irradiated tumor cells on the development of host's immune resistance against the tumor-associated transplantation antigens (TATA) was investigated in two syngeneic tumor systems with distinct effector mechanisms. When X5563 plasmacytoma, to which immune resistance was mediated exclusively by killer T lymphocytes, was intravenously inoculated into syngeneic C3H/He mice with lower number after 7000 R x-irradiation, the mice failed to exhibit any protective immunity against the subsequent challenge with viable tumor cells. Moreover, these mice lost their capability to develop any immune resistance even after an appropriate immunization procedure. The immunodepression induced by such a pretreatment regimen was specific for X5563 tumor. While no suppressor cell activity was detected in the above pretreated mice, serum factor(s) from these mice was virtually responsible for this suppression. When the serum factor mediating this tumor-specific suppression was fractionated on the Sephadex G-200 column, the suppressive activity was found in albumin-corresponding fraction, free of any immunoglobulin component. In contrast, in MM102 mammary tumor system, in which immune resistance is solely mediated by tumor-specific antibody, the pretreatment with x-irradiated MM102 cells augmented the induction of anti-tumor immunity. These results indicate that while tumor antigens given in the form of x-irradiated tumor cells suppress the induction of killer T cell-mediated immunity in one system, the same presensitization regimen of tumor antigens augments the antibody-mediated immunity in another system, thus giving a divergent effect on the distinct effector mechanisms of syngeneic tumor immunity. (author)

Quinolone Resistance Reversion by Targeting the SOS Response

Directory of Open Access Journals (Sweden)

E. Recacha

2017-10-01

Full Text Available Suppression of the SOS response has been postulated as a therapeutic strategy for potentiating antimicrobial agents. We aimed to evaluate the impact of its suppression on reversing resistance using a model of isogenic strains of Escherichia coli representing multiple levels of quinolone resistance. E. coli mutants exhibiting a spectrum of SOS activity were constructed from isogenic strains carrying quinolone resistance mechanisms with susceptible and resistant phenotypes. Changes in susceptibility were evaluated by static (MICs and dynamic (killing curves or flow cytometry methodologies. A peritoneal sepsis murine model was used to evaluate in vivo impact. Suppression of the SOS response was capable of resensitizing mutant strains with genes encoding three or four different resistance mechanisms (up to 15-fold reductions in MICs. Killing curve assays showed a clear disadvantage for survival (Δlog10 CFU per milliliter [CFU/ml] of 8 log units after 24 h, and the in vivo efficacy of ciprofloxacin was significantly enhanced (Δlog10 CFU/g of 1.76 log units in resistant strains with a suppressed SOS response. This effect was evident even after short periods (60 min of exposure. Suppression of the SOS response reverses antimicrobial resistance across a range of E. coli phenotypes from reduced susceptibility to highly resistant, playing a significant role in increasing the in vivo efficacy.

Transgenic Strategies for Enhancement of Nematode Resistance in Plants

Directory of Open Access Journals (Sweden)

Muhammad A. Ali

2017-05-01

Full Text Available Plant parasitic nematodes (PPNs are obligate biotrophic parasites causing serious damage and reduction in crop yields. Several economically important genera parasitize various crop plants. The root-knot, root lesion, and cyst nematodes are the three most economically damaging genera of PPNs on crops within the family Heteroderidae. It is very important to devise various management strategies against PPNs in economically important crop plants. Genetic engineering has proven a promising tool for the development of biotic and abiotic stress tolerance in crop plants. Additionally, the genetic engineering leading to transgenic plants harboring nematode resistance genes has demonstrated its significance in the field of plant nematology. Here, we have discussed the use of genetic engineering for the development of nematode resistance in plants. This review article also provides a detailed account of transgenic strategies for the resistance against PPNs. The strategies include natural resistance genes, cloning of proteinase inhibitor coding genes, anti-nematodal proteins and use of RNA interference to suppress nematode effectors. Furthermore, the manipulation of expression levels of genes induced and suppressed by nematodes has also been suggested as an innovative approach for inducing nematode resistance in plants. The information in this article will provide an array of possibilities to engineer resistance against PPNs in different crop plants.

Comparative Metatranscriptomics of Wheat Rhizosphere Microbiomes in Disease Suppressive and Non-suppressive Soils for Rhizoctonia solani AG8

Directory of Open Access Journals (Sweden)

Helen L. Hayden

2018-05-01

Full Text Available The soilborne fungus Rhizoctonia solani anastomosis group (AG 8 is a major pathogen of grain crops resulting in substantial production losses. In the absence of resistant cultivars of wheat or barley, a sustainable and enduring method for disease control may lie in the enhancement of biological disease suppression. Evidence of effective biological control of R. solani AG8 through disease suppression has been well documented at our study site in Avon, South Australia. A comparative metatranscriptomic approach was applied to assess the taxonomic and functional characteristics of the rhizosphere microbiome of wheat plants grown in adjacent fields which are suppressive and non-suppressive to the plant pathogen R. solani AG8. Analysis of 12 rhizosphere metatranscriptomes (six per field was undertaken using two bioinformatic approaches involving unassembled and assembled reads. Differential expression analysis showed the dominant taxa in the rhizosphere based on mRNA annotation were Arthrobacter spp. and Pseudomonas spp. for non-suppressive samples and Stenotrophomonas spp. and Buttiauxella spp. for the suppressive samples. The assembled metatranscriptome analysis identified more differentially expressed genes than the unassembled analysis in the comparison of suppressive and non-suppressive samples. Suppressive samples showed greater expression of a polyketide cyclase, a terpenoid biosynthesis backbone gene (dxs and many cold shock proteins (csp. Non-suppressive samples were characterised by greater expression of antibiotic genes such as non-heme chloroperoxidase (cpo which is involved in pyrrolnitrin synthesis, and phenazine biosynthesis family protein F (phzF and its transcriptional activator protein (phzR. A large number of genes involved in detoxifying reactive oxygen species (ROS and superoxide radicals (sod, cat, ahp, bcp, gpx1, trx were also expressed in the non-suppressive rhizosphere samples most likely in response to the infection of wheat

Parallel magnetic field suppresses dissipation in superconducting nanostrips

Energy Technology Data Exchange (ETDEWEB)

Wang, Yong-Lei; Glatz, Andreas; Kimmel, Gregory J.; Aranson, Igor S.; Thoutam, Laxman R.; Xiao, Zhi-Li; Berdiyorov, Golibjon R.; Peeters, François M.; Crabtree, George W.; Kwok, Wai-Kwong

2017-11-13

The motion of Abrikosov vortices in type-II superconductors results in a finite resistance in the presence of an applied electric current. Elimination or reduction of the resistance via immobilization of vortices is the "holy grail" of superconductivity research. Common wisdom dictates that an increase in the magnetic field escalates the loss of energy since the number of vortices increases. Here we show that this is no longer true if the magnetic field and the current are applied parallel to each other. Our experimental studies on the resistive behavior of a superconducting Mo0.79Ge0.21 nanostrip reveal the emergence of a dissipative state with increasing magnetic field, followed by a pronounced resistance drop, signifying a reentrance to the superconducting state. Large-scale simulations of the 3D time-dependent Ginzburg-Landau model indicate that the intermediate resistive state is due to an unwinding of twisted vortices. When the magnetic field increases, this instability is suppressed due to a better accommodation of the vortex lattice to the pinning configuration. Our findings show that magnetic field and geometrical confinement can suppress the dissipation induced by vortex motion and thus radically improve the performance of superconducting materials.

Parallel magnetic field suppresses dissipation in superconducting nanostrips.

Science.gov (United States)

Wang, Yong-Lei; Glatz, Andreas; Kimmel, Gregory J; Aranson, Igor S; Thoutam, Laxman R; Xiao, Zhi-Li; Berdiyorov, Golibjon R; Peeters, François M; Crabtree, George W; Kwok, Wai-Kwong

2017-11-28

The motion of Abrikosov vortices in type-II superconductors results in a finite resistance in the presence of an applied electric current. Elimination or reduction of the resistance via immobilization of vortices is the "holy grail" of superconductivity research. Common wisdom dictates that an increase in the magnetic field escalates the loss of energy since the number of vortices increases. Here we show that this is no longer true if the magnetic field and the current are applied parallel to each other. Our experimental studies on the resistive behavior of a superconducting Mo 0.79 Ge 0.21 nanostrip reveal the emergence of a dissipative state with increasing magnetic field, followed by a pronounced resistance drop, signifying a reentrance to the superconducting state. Large-scale simulations of the 3D time-dependent Ginzburg-Landau model indicate that the intermediate resistive state is due to an unwinding of twisted vortices. When the magnetic field increases, this instability is suppressed due to a better accommodation of the vortex lattice to the pinning configuration. Our findings show that magnetic field and geometrical confinement can suppress the dissipation induced by vortex motion and thus radically improve the performance of superconducting materials.

High rate of virological re-suppression among patients failing ...

African Journals Online (AJOL)

Results. Of 69 patients enrolled in the programme, 40 had at least one follow-up VL and no known drug resistance at enrolment; 27 (68%) of these re-suppressed while remaining on second-line ART following enhanced adherence support. The majority (18/27; 67%) achieved re-suppression within the first 3 months in the ...

Relationships between thought-action fusion, thought suppression and obsessive-compulsive symptoms: a structural equation modeling approach.

Science.gov (United States)

Rassin, E; Muris, P; Schmidt, H; Merckelbach, H

2000-09-01

Research has shown that there are strong similarities in content between the obsessions and compulsions that characterize obsessive-compulsive disorder and nonclinical obsessions and compulsions. However, clinical and nonclinical obsessions and compulsions do differ with respect to characteristics like frequency, intensity, discomfort and elicited resistance. Two separate concepts have been invoked to explain how normal obsessions and compulsions may develop into clinical phenomena. First, it is suggested that thought-action fusion (TAF) contributes to obsessive-compulsive symptoms. Second, thought suppression may intensify obsessive-compulsive symptoms due to its paradoxical effect on intrusive thoughts. Although both phenomena have been found to contribute to obsessive-compulsive symptoms, possible interactions between these two have never been investigated. The current study explored how TAF and thought suppression interact in the development of obsessive-compulsive symptoms. Undergraduate psychology students (N = 173) completed questionnaires pertaining to TAF, thought suppression and obsessive-compulsive symptoms. Covariances between the scores on these questionnaires were analyzed by means of structural equation modeling. Results suggest that TAF triggers thought suppression, while thought suppression, in turn, promotes obsessive-compulsive symptoms.

Midkine inhibits inducible regulatory T cell differentiation by suppressing the development of tolerogenic dendritic cells.

Science.gov (United States)

Sonobe, Yoshifumi; Li, Hua; Jin, Shijie; Kishida, Satoshi; Kadomatsu, Kenji; Takeuchi, Hideyuki; Mizuno, Tetsuya; Suzumura, Akio

2012-03-15

Midkine (MK), a heparin-binding growth factor, reportedly contributes to inflammatory diseases, including Crohn's disease and rheumatoid arthritis. We previously showed that MK aggravates experimental autoimmune encephalomyelitis (EAE) by decreasing regulatory CD4(+)CD25(+)Foxp3(+) T cells (Tregs), a population that regulates the development of autoimmune responses, although the precise mechanism remains uncertain. In this article, we show that MK produced in inflammatory conditions suppresses the development of tolerogenic dendritic cells (DCregs), which drive the development of inducible Treg. MK suppressed DCreg-mediated expansion of the CD4(+)CD25(+)Foxp3(+) Treg population. DCregs expressed significantly higher levels of CD45RB and produced significantly less IL-12 compared with conventional dendritic cells. However, MK downregulated CD45RB expression and induced IL-12 production by reducing phosphorylated STAT3 levels via src homology region 2 domain-containing phosphatase-2 in DCreg. Inhibiting MK activity with anti-MK RNA aptamers, which bind to the targeted protein to suppress the function of the protein, increased the numbers of CD11c(low)CD45RB(+) dendritic cells and Tregs in the draining lymph nodes and suppressed the severity of EAE, an animal model of multiple sclerosis. Our results also demonstrated that MK was produced by inflammatory cells, in particular, CD4(+) T cells under inflammatory conditions. Taken together, these results suggest that MK aggravates EAE by suppressing DCreg development, thereby impairing the Treg population. Thus, MK is a promising therapeutic target for various autoimmune diseases.

RAF Suppression Synergizes with MEK Inhibition in KRAS Mutant Cancer Cells

Directory of Open Access Journals (Sweden)

Simona Lamba

2014-09-01

Full Text Available KRAS is the most frequently mutated oncogene in human cancer, yet no therapies are available to treat KRAS mutant cancers. We used two independent reverse genetic approaches to identify components of the RAS-signaling pathways required for growth of KRAS mutant tumors. Small interfering RNA (siRNA screening of 37 KRAS mutant colorectal cancer cell lines showed that RAF1 suppression was synthetic lethal with MEK inhibition. An unbiased kinome short hairpin RNA (shRNA-based screen confirmed this synthetic lethal interaction in colorectal as well as in lung cancer cells bearing KRAS mutations. Compounds targeting RAF kinases can reverse resistance to the MEK inhibitor selumetinib. MEK inhibition induces RAS activation and BRAF-RAF1 dimerization and sustains MEK-ERK signaling, which is responsible for intrinsic resistance to selumetinib. Prolonged dual blockade of RAF and MEK leads to persistent ERK suppression and efficiently induces apoptosis. Our data underlie the relevance of developing combinatorial regimens of drugs targeting the RAF-MEK pathway in KRAS mutant tumors.

Suppressing Resistance to Bt Cotton with Sterile Insect Releases

Energy Technology Data Exchange (ETDEWEB)

Tabashnik, B E [Department of Entomology, University of Arizona, Tucson, AZ (United States); Sisterson, M S [USDA-ARS, San Joaquin Valley Agricultural Sciences Center, Parlier, CA (United States); Ellsworth, P C [Department of Entomology, University of Arizona, Maricopa Agricultural Center, Maricopa, AZ (United States)

2011-01-15

Genetically engineered crops that produce insecticidal toxins from Bacillus thuringiensis (Bt) are grown widely for pest control. However, insect adaptation can reduce the toxins' efficacy. The predominant strategy for delaying pest resistance to Bt crops requires refuges of non-Bt host plants to provide susceptible insects to mate with resistant insects. Variable farmer compliance is one of the limitations of this approach. Here we report the benefits of an alternative strategy where sterile insects are released to mate with resistant insects and refuges are scarce or absent. Computer simulations show that this approach works in principle against pests with recessive or dominant inheritance of resistance. During a largescale, four-year field deployment of this strategy in Arizona, resistance of pink bollworm (Pectinophora gossypiella) to Bt cotton did not increase. A multitactic eradication program that included the release of sterile moths reduced pink bollworm abundance by >99%, while eliminating insecticide sprays against this key invasive pest. (author)

Screening for suppression in young children: the Polaroid Suppression test

NARCIS (Netherlands)

Pott, J.W.R.; Oosterveen, DK; Van Hof-van Duin, J

1998-01-01

Background: Assessment of monocular visual impairment during screening of young children is often hampered by lack of cooperation. Because strabismus, amblyopia, or anisometropia may lead to monocular suppression during binocular viewing conditions, a test was developed to screen far suppression in

Attentional selection and suppression in children and adults.

Science.gov (United States)

Sun, Meirong; Wang, Encong; Huang, Jing; Zhao, Chenguang; Guo, Jialiang; Li, Dongwei; Sun, Li; Du, Boqi; Ding, Yulong; Song, Yan

2018-05-15

The fundamental role of covert spatial attention is to enhance the processing of attended items while simultaneously ignoring irrelevant items. However, relatively little is known about how brain electrophysiological activities associated with target selection and distractor suppression are involved as they develop and become fully functional. The current study aimed to identify the neurophysiological bases of the development of covert spatial attention, focusing on electroencephalographic (EEG) markers of attentional selection (N2pc) and suppression (P D ). EEG data were collected from healthy young adults and typically developing children (9-15 years old) as they searched for a shape singleton target in either the absence or the presence of a salient-but-irrelevant color singleton distractor. The ERP results showed that a lateral shape target elicited a smaller N2pc in children compared with adults regardless of whether a distractor was present or not. Moreover, the target-elicited N2pc was always followed by a similar positivity in both age groups. Counterintuitively, a lateral salient-but-irrelevant distractor elicited a large P D in children with low behavioral accuracy, whereas high-accuracy children exhibited a small and "adult-like" P D . More importantly, we found no evidence for a correlation between the target-elicited N2pc and the distractor-elicited P D in either age group. Our results provide neurophysiological evidence for the developmental differences between target selection and distractor suppression. Compared with adults, 9-15-year-old children deploy insufficient attentional selection resources to targets but use "adult-like" or even more attentional suppression resources to resist irrelevant distractors. A video abstract of this article can be viewed at: https://www.youtube.com/watch?v=NhWapx0d75I. © 2018 John Wiley & Sons Ltd.

METALLOPROTEINS DURING DEVELOPMENT OF WALKER-256 CARCINOSARCOMA RESISTANT PHENOTYPE.

Science.gov (United States)

Chekhun, V F; Lozovska, Yu V; Burlaka, A P; Ganusevich, I I; Shvets, Yu V; Lukianova, N Yu; Todor, I M; Demash, D V; Pavlova, A A; Naleskina, L A

2015-01-01

The study was focused on the detection of changes in serum and tumor metal-containing proteins in animals during development ofdoxorubicin-resistant phenotype in malignant cells after 12 courses of chemotherapy. We found that on every stage of resistance development there was a significant increase in content of ferritin and transferrin proteins (which take part in iron traffick and storage) in Walker-256 carc'inosarcoma tissue. We observed decreased serumferritin levels at the beginning stage of the resistance development and significant elevation of this protein levels in the cases withfully developed resistance phenotype. Transferrin content showed changes opposite to that offerritin. During the development of resistance phenotype the tumor tissue also exhibited increased 'free iron' concentration that putatively correlate with elevation of ROS generation and levels of MMP-2 and MMP-9 active forms. The tumor non-protein thiol content increases gradually as well. The serum of animals with early stages of resistance phenotype development showed high ceruloplasmin activity and its significant reduction after loss of tumor sensitivity to doxorubicin. Therefore, the development of resistance phenotype in Walker-256 carcinosarcoma is accompanied by both the deregulation of metal-containing proteins in serum and tumor tissue and by the changes in activity of antioxidant defense system. Thus, the results of this study allow us to determine the spectrum of metal-containing proteins that are involved in the development of resistant tumor phenotype and that may be targeted for methods for doxorubicin sensitivity correction therapy.

Role of the plant cell wall in gravity resistance.

Science.gov (United States)

Hoson, Takayuki; Wakabayashi, Kazuyuki

2015-04-01

Gravity resistance, mechanical resistance to the gravitational force, is a principal graviresponse in plants, comparable to gravitropism. The cell wall is responsible for the final step of gravity resistance. The gravity signal increases the rigidity of the cell wall via the accumulation of its constituents, polymerization of certain matrix polysaccharides due to the suppression of breakdown, stimulation of cross-link formation, and modifications to the wall environment, in a wide range of situations from microgravity in space to hypergravity. Plants thus develop a tough body to resist the gravitational force via an increase in cell wall rigidity and the modification of growth anisotropy. The development of gravity resistance mechanisms has played an important role in the acquisition of responses to various mechanical stresses and the evolution of land plants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Noise suppression and crosstalk analysis of on-chip magnetic film-type noise suppressor

Science.gov (United States)

Ma, Jingyan; Muroga, Sho; Endo, Yasushi; Hashi, Shuichiro; Naoe, Masayuki; Yokoyama, Hiroo; Hayashi, Yoshiaki; Ishiyama, Kazushi

2018-05-01

This paper discusses near field, conduction and crosstalk noise suppression of magnetic films with uniaxial anisotropy on transmission lines for a film-type noise suppressor in the GHz frequency range. The electromagnetic noise suppressions of magnetic films with different permeability and resistivity were measured and simulated with simple microstrip lines. The experimental and simulated results of Co-Zr-Nb and CoPd-CaF2 films agreed with each other. The results indicate that the higher permeability leads to a better near field shielding, and in the frequency range of 2-7 GHz, a higher conduction noise suppression. It also suggests that the higher resistivity results in a better crosstalk suppression in the frequency range below 2 GHz. These results can support the design guidelines of the magnetic film-type noise suppressor used in the next generation IC chip.

Metalloproteins during development of Walker-256 carcinosarcoma resistant phenotype

Directory of Open Access Journals (Sweden)

V. F. Chekhun

2015-04-01

Full Text Available The study was focused on the detection of changes in serum and tumor metal-containing proteins in animals during development of doxorubicin-resistant phenotype in malignant cells after 12 courses of chemotherapy. We found that on every stage of resistance development there was a significant increase in content of ferritin and transferrin proteins (which take part in iron traffick and storage in Walker-256 carcinosarcoma tissue. We observed decreased serum ferritin levels at the beginning stage of the resistance development and significant elevation of this protein levels in the cases with fully developed resistance phenotype. Transferrin content showed changes opposite to that of ferritin. During the development of resistance phenotype the tumor tissue also exhibited increased ‘free iron’ concentration that putatively correlate with elevation of ROS generation and levels of MMP-2 and MMP-9 active forms. The tumor non-protein thiol content increases gradually as well. The serum of animals with early stages of resistance phenotype development showed high ceruloplasmin activity and its significant reduction after loss of tumor sensitivity to doxorubicin. Therefore, the development of resistance phenotype in Walker-256 carcinosarcoma is accompanied by both the deregulation of metal-containing proteins in serum and tumor tissue and by the changes in activity of antioxidant defense system. Thus, the results of this study allow us to determine the spectrum of metal-containing proteins that are involved in the development of resistant tumor phenotype and that may be targeted for methods for doxorubicin sensitivity correction therapy.

Induced multiple disease resistance in wheat

International Nuclear Information System (INIS)

Borojevic, K.; Worland, A.J.

1990-01-01

Full text: The existence of genes suppressing resistance to leaf rust, stem rust and yellow rust in hexaploid wheat has been suggested. If such genes are deleted or inactivated, a more resistant variety may be obtained. In mutant lines of the wheat variety San Pastore, selected after treatment with 20,000 rad of gamma-rays, resistance to leaf rust, yellow rust, stem rust, and to some extent to Erysiphe graminis was determined. The mutants responded to infection by producing necrotic flecks in the presence of high level of disease inoculum. Similar flecks develop under stress condition. It is likely that the mother variety San Pastore carries genes for resistance which are masked by suppressor genes. Irradiation inactivates suppressors so that resistance genes which were previously masked are expressed. The first results of monosomic analysis indicate that chromosomes of groups 4 and 5 or possibly 7 may be critical for expression of resistance in the mutant lines. (author)

30 CFR 75.1107-6 - Capacity of fire suppression devices; location and direction of nozzles.

Science.gov (United States)

2010-07-01

... nozzles of each fire suppression device shall, where practicable, be located so as to take advantage of... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Capacity of fire suppression devices; location... Fire Protection Fire Suppression Devices and Fire-Resistant Hydraulic Fluids on Underground Equipment...

Molecular biology of castration-resistant prostate cancer: basis for the novel therapeutic targets.

Science.gov (United States)

Mellado, Begoña; Marin Aguilera, Mercedes; Pereira, Maria Veronica

2013-06-01

Prostate cancer cells express the androgen receptor (AR) and need the presence of androgens to survive. Androgen suppression is the gold standard first-line therapy for metastatic disease. Almost all prostate cancer patients initially respond to hormonal therapy, but most of them gradually develop castration-resistant progression. Recent evidence has shown that progression at the castration resistant prostate cancer (CRPC) stage is often mediated by AR signalling. Importantly, subsequent AR androgen inhibition, by abiraterone acetate or enzalutamide, has shown to improve patients' survival. Several mechanisms that enhance AR signalling in an androgen-depleted environment have been elucidated:(1) AR mutations that allow activation by low androgen levels or by other endogenous steroids, (2) AR amplification and/or overexpression,(3)increased local intracrine synthesis of androgens, (4) changes in AR cofactors and (5) cross-talk with cytokines and growth factors. Today, there are under development a number of novel agents targeting the AR signaling pathway. This article reviews the postulated mechanisms of AR-driven resistance to androgen suppression that have contributed to the development of new hormonal therapeutic strategies in prostate cancer.

A saponin-detoxifying enzyme mediates suppression of plant defences

Science.gov (United States)

Bouarab, K.; Melton, R.; Peart, J.; Baulcombe, D.; Osbourn, A.

2002-08-01

Plant disease resistance can be conferred by constitutive features such as structural barriers or preformed antimicrobial secondary metabolites. Additional defence mechanisms are activated in response to pathogen attack and include localized cell death (the hypersensitive response). Pathogens use different strategies to counter constitutive and induced plant defences, including degradation of preformed antimicrobial compounds and the production of molecules that suppress induced plant defences. Here we present evidence for a two-component process in which a fungal pathogen subverts the preformed antimicrobial compounds of its host and uses them to interfere with induced defence responses. Antimicrobial saponins are first hydrolysed by a fungal saponin-detoxifying enzyme. The degradation product of this hydrolysis then suppresses induced defence responses by interfering with fundamental signal transduction processes leading to disease resistance.

Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

International Nuclear Information System (INIS)

Lin, Yan-Jie; Juan, Chi-Chang; Kwok, Ching-Fai; Hsu, Yung-Pei; Shih, Kuang-Chung; Chen, Chin-Chang; Ho, Low-Tone

2015-01-01

Endothelin-1 (ET-1) is known as potent vasoconstrictor, by virtue of its mitogenic effects, and may deteriorate the process of hypertension and atherosclerosis by aggravating hyperplasia and migration in VSMCs. Our previous study demonstrated that insulin infusion caused sequential induction of hyperinsulinemia, hyperendothelinemia, insulin resistance, and then hypertension in rats. However, the underlying mechanism of ET-1 interfere insulin signaling in VSMCs remains unclear. To characterize insulin signaling during modest insulin resistant syndrome, we established and monitored rats by feeding high fructose-diet (HFD) until high blood pressure and modest insulin resistance occurred. To explore the role of ET-1/ET A R during insulin resistance, ET A R expression, ET-1 binding, and insulin signaling were investigated in the HFD-fed rats and cultured A-10 VSMCs. Results showed that high blood pressure, tunica medial wall thickening, plasma ET-1 and insulin, and accompanied with modest insulin resistance without overweight and hyperglycemia occurred in early-stage HFD-fed rats. In the endothelium-denuded aorta from HFD-fed rats, ET A R expression, but not ET B R, and ET-1 binding in aorta were increased. Moreover, decreasing of insulin-induced Akt phosphorylation and increasing of insulin-induced ERK phosphorylation were observed in aorta during modest insulin resistance. Interestingly, in ET-1 pretreated VSMCs, the increment of insulin-induced Akt phosphorylation was decreased whereas the increment of insulin-induced ERK phosphorylation was increased. In addition, insulin potentiated ET-1-induced VSMCs migration and proliferation due to increasing ET-1 binding. ETAR antagonist reversed effects of ET-1 on insulin-induced signaling and VSMCs migration and proliferation. In summary, modest insulin resistance syndrome accompanied with hyperinsulinemia leading to the potentiation on ET-1-induced actions in aortic VSMCs. ET-1 via ET A R pathway suppressed insulin

Prospects of DUV OoB suppression techniques in EUV lithography

Science.gov (United States)

Park, Chang-Min; Kim, Insung; Kim, Sang-Hyun; Kim, Dong-Wan; Hwang, Myung-Soo; Kang, Soon-Nam; Park, Cheolhong; Kim, Hyun-Woo; Yeo, Jeong-Ho; Kim, Seong-Sue

2014-04-01

Though scaling of source power is still the biggest challenge in EUV lithography (EUVL) technology era, CD and overlay controls for transistor's requirement are also precondition of adopting EUVL in mass production. Two kinds of contributors are identified as risks for CDU and Overlay: Infrared (IR) and deep ultraviolet (DUV) out of band (OOB) radiations from laser produced plasma (LPP) EUV source. IR from plasma generating CO2 laser that causes optics heating and wafer overlay error is well suppressed by introducing grating on collector to diffract IR off the optical axis and is the effect has been confirmed by operation of pre-production tool (NXE3100). EUV and DUV OOB which are reflected from mask black boarder (BB) are root causes of EUV-specific CD error at the boundaries of exposed shots which would result in the problem of CDU out of spec unless sufficiently suppressed. Therefore, control of DUV OOB reflection from the mask BB is one of the key technologies that must be developed prior to EUV mass production. In this paper, quantitative assessment on the advantage and the disadvantage of potential OOB solutions will be discussed. EUV and DUV OOB impacts on wafer CDs are measured from NXE3100 & NXE3300 experiments. Significant increase of DUV OOB impact on CD from NXE3300 compared with NXE3100 is observed. There are three ways of technology being developed to suppress DUV OOB: spectral purity filter (SPF) as a scanner solution, multi-layer etching as a solution on mask, and resist top-coating as a process solution. PROs and CONs of on-scanner, on-mask, and on-resist solution for the mass production of EUV lithography will be discussed.

Simulation of Axial Combustion Instability Development and Suppression in Solid Rocket Motors

Directory of Open Access Journals (Sweden)

David R. Greatrix

2009-03-01

Full Text Available In the design of solid-propellant rocket motors, the ability to understand and predict the expected behaviour of a given motor under unsteady conditions is important. Research towards predicting, quantifying, and ultimately suppressing undesirable strong transient axial combustion instability symptoms necessitates a comprehensive numerical model for internal ballistic simulation under dynamic flow and combustion conditions. An updated numerical model incorporating recent developments in predicting negative and positive erosive burning, and transient, frequency-dependent combustion response, in conjunction with pressure-dependent and acceleration-dependent burning, is applied to the investigation of instability-related behaviour in a small cylindrical-grain motor. Pertinent key factors, like the initial pressure disturbance magnitude and the propellant's net surface heat release, are evaluated with respect to their influence on the production of instability symptoms. Two traditional suppression techniques, axial transitions in grain geometry and inert particle loading, are in turn evaluated with respect to suppressing these axial instability symptoms.

Bacterial resistance to silver nanoparticles and how to overcome it

Science.gov (United States)

Panáček, Aleš; Kvítek, Libor; Smékalová, Monika; Večeřová, Renata; Kolář, Milan; Röderová, Magdalena; Dyčka, Filip; Šebela, Marek; Prucek, Robert; Tomanec, Ondřej; Zbořil, Radek

2018-01-01

Silver nanoparticles have already been successfully applied in various biomedical and antimicrobial technologies and products used in everyday life. Although bacterial resistance to antibiotics has been extensively discussed in the literature, the possible development of resistance to silver nanoparticles has not been fully explored. We report that the Gram-negative bacteria Escherichia coli 013, Pseudomonas aeruginosa CCM 3955 and E. coli CCM 3954 can develop resistance to silver nanoparticles after repeated exposure. The resistance stems from the production of the adhesive flagellum protein flagellin, which triggers the aggregation of the nanoparticles. This resistance evolves without any genetic changes; only phenotypic change is needed to reduce the nanoparticles' colloidal stability and thus eliminate their antibacterial activity. The resistance mechanism cannot be overcome by additional stabilization of silver nanoparticles using surfactants or polymers. It is, however, strongly suppressed by inhibiting flagellin production with pomegranate rind extract.

Evolutionary Aspects of Acaricide-Resistance Development in Spider Mites

Directory of Open Access Journals (Sweden)

Masahiro (Mh. Osakabe

2009-01-01

Full Text Available Although the development of acaricide resistance in spider mites is a long-standing issue in agricultural fields, recent problems with acaricide resistance may be characterized by the development of complex- and/or multiresistance to acaricides in distinct classes. Such complexity of resistance is not likely to be a single mechanism. Pesticide resistance involves the microevolution of arthropod pests, and population genetics underlies the evolution. In this review, we address the genetic mechanisms of acaricide resistance evolution. We discuss genetic diversity and linkage of resistance genes, relationships between mite habitat and dispersal, and the effect of dispersal on population genetic structure and the dynamics of resistance genes. Finally, we attempt to present a comprehensive view of acaricide resistance evolution and suggest risks under globalization as well as possible approaches to managing acaricide resistance evolution or emergence.

Pest control and resistance management through release of insects carrying a male-selecting transgene.

Science.gov (United States)

Harvey-Samuel, Tim; Morrison, Neil I; Walker, Adam S; Marubbi, Thea; Yao, Ju; Collins, Hilda L; Gorman, Kevin; Davies, T G Emyr; Alphey, Nina; Warner, Simon; Shelton, Anthony M; Alphey, Luke

2015-07-16

Development and evaluation of new insect pest management tools is critical for overcoming over-reliance upon, and growing resistance to, synthetic, biological and plant-expressed insecticides. For transgenic crops expressing insecticidal proteins from the bacterium Bacillus thuringiensis ('Bt crops') emergence of resistance is slowed by maintaining a proportion of the crop as non-Bt varieties, which produce pest insects unselected for resistance. While this strategy has been largely successful, multiple cases of Bt resistance have now been reported. One new approach to pest management is the use of genetically engineered insects to suppress populations of their own species. Models suggest that released insects carrying male-selecting (MS) transgenes would be effective agents of direct, species-specific pest management by preventing survival of female progeny, and simultaneously provide an alternative insecticide resistance management strategy by introgression of susceptibility alleles into target populations. We developed a MS strain of the diamondback moth, Plutella xylostella, a serious global pest of crucifers. MS-strain larvae are reared as normal with dietary tetracycline, but, when reared without tetracycline or on host plants, only males will survive to adulthood. We used this strain in glasshouse-cages to study the effect of MS male P. xylostella releases on target pest population size and spread of Bt resistance in these populations. Introductions of MS-engineered P. xylostella males into wild-type populations led to rapid pest population decline, and then elimination. In separate experiments on broccoli plants, relatively low-level releases of MS males in combination with broccoli expressing Cry1Ac (Bt broccoli) suppressed population growth and delayed the spread of Bt resistance. Higher rates of MS male releases in the absence of Bt broccoli were also able to suppress P. xylostella populations, whereas either low-level MS male releases or Bt broccoli

Development of Resistive Micromegas for Sampling Calorimetry

Science.gov (United States)

Geralis, T.; Fanourakis, G.; Kalamaris, A.; Nikas, D.; Psallidas, A.; Chefdeville, M.; Karyotakis, I.; Koletsou, I.; Titov, M.

2018-02-01

Resistive micromegas is proposed as an active element for sampling calorimetry. Future linear collider experiments or the HL-LHC experiments can profit from those developments for Particle Flow Calorimetry. Micromegas possesses remarkable properties concerning gain stability, reduced ion feedback, response linearity, adaptable sensitive element granularity, fast response and high rate capability. Recent developments on Micromegas with a protective resistive layer present excellent results, resolving the problem of discharges caused by local high charge deposition, thanks to its RC-slowed charge evacuation. Higher resistivity though, may cause loss of the response linearity at high rates. We have scanned a wide range of resistivities and performed laboratory tests with X-rays that demonstrate excellent response linearity up to rates of (a few) times 10MHz/cm2, with simultaneous mitigation of discharges. Beam test studies at SPS/CERN with hadrons have also shown a remarkable stability of the resistive Micromegas and low currents for rates up to 15MHz/cm2. We present results from the aforementioned studies confronted with MC simulation

Tcf3 and cell cycle factors contribute to butyrate resistance in colorectal cancer cells

International Nuclear Information System (INIS)

Chiaro, Christopher; Lazarova, Darina L.; Bordonaro, Michael

2012-01-01

Highlights: ► We investigate mechanisms responsible for butyrate resistance in colon cancer cells. ► Tcf3 modulates butyrate’s effects on Wnt activity and cell growth in resistant cells. ► Tcf3 modulation of butyrate’s effects differ by cell context. ► Cell cycle factors are overexpressed in the resistant cells. ► Reversal of altered gene expression can enhance the anti-cancer effects of butyrate. -- Abstract: Butyrate, a fermentation product of dietary fiber, inhibits clonal growth in colorectal cancer (CRC) cells dependent upon the fold induction of Wnt activity. We have developed a CRC cell line (HCT-R) that, unlike its parental cell line, HCT-116, does not respond to butyrate exposure with hyperactivation of Wnt signaling and suppressed clonal growth. PCR array analyses revealed Wnt pathway-related genes, the expression of which differs between butyrate-sensitive HCT-116 CRC cells and their butyrate-resistant HCT-R cell counterparts. We identified overexpression of Tcf3 as being partially responsible for the butyrate-resistant phenotype, as this DNA-binding protein suppresses the hyperinduction of Wnt activity by butyrate. Consequently, Tcf3 knockdown in HCT-R cells restores their sensitivity to the effects of butyrate on Wnt activity and clonal cell growth. Interestingly, the effects of overexpressed Tcf3 differ between HCT-116 and HCT-R cells; thus, in HCT-116 cells Tcf3 suppresses proliferation without rendering the cells resistant to butyrate. In HCT-R cells, however, the overexpression of Tcf3 inhibits Wnt activity, and the cells are still able to proliferate due to the higher expression levels of cell cycle factors, particularly those driving the G 1 to S transition. Knowledge of the molecular mechanisms determining the variable sensitivity of CRC cells to butyrate may assist in developing approaches that prevent or reverse butyrate resistance.

Development of the Military Women's Attitudes Toward Menstrual Suppression Scale: from construct definition to pilot testing.

Science.gov (United States)

Trego, Lori L

2009-01-01

The Military Women's Attitudes Toward Menstrual Suppression scale (MWATMS) was created to measure attitudes toward menstrual suppression during deployment. The human health and social ecology theories were integrated to conceptualize an instrument that accounts for military-unique aspects of the environment on attitudes toward suppression. A three-step instrument development process was followed to develop the MWATMS. The instrument was pilot tested on a convenience sample of 206 military women with deployment experience. Reliability was tested with measures of internal consistency (alpha = .97); validity was tested with principal components analysis with varimax rotation. Four components accounted for 65% of variance: Benefits/Interest, Hygiene, Convenience, and Soldier/Stress. The pilot test of the MWATMS supported its reliability and validity. Further testing is warranted for validation of this instrument.

The antagonistic regulation of abscisic acid-inhibited root growth by brassinosteroids is partially mediated via direct suppression of ABSCISIC ACID INSENSITIVE 5 expression by BRASSINAZOLE RESISTANT 1.

Science.gov (United States)

Yang, Xiaorui; Bai, Yang; Shang, Jianxiu; Xin, Ruijiao; Tang, Wenqiang

2016-09-01

Brassinosteroids (BRs) and abscisic acid (ABA) are plant hormones that antagonistically regulate many aspects of plant growth and development; however, the mechanisms that regulate the crosstalk of these two hormones are still not well understood. BRs regulate plant growth and development by activating BRASSINAZOLE RESISTANT 1 (BZR1) family transcription factors. Here we show that the crosstalk between BRs and ABA signalling is partially mediated by BZR1 regulated gene expression. bzr1-1D is a dominant mutant with enhanced BR signalling; our results showed that bzr1-1D mutant is less sensitive to ABA-inhibited primary root growth. By RNA sequencing, a subset of BZR1 regulated ABA-responsive root genes were identified. Of these genes, the expression of a major ABA signalling component ABA INSENSITIVE 5 (ABI5) was found to be suppressed by BR and by BZR1. Additional evidences showed that BZR1 could bind strongly with several G-box cis-elements in the promoter of ABI5, suppress the expression of ABI5 and make plants less sensitive to ABA. Our study demonstrated that ABI5 is a direct target gene of BZR1, and modulating the expression of ABI5 by BZR1 plays important roles in regulating the crosstalk between the BR and ABA signalling pathways. © 2016 John Wiley & Sons Ltd.

The roles of CDR1, CDR2, and MDR1 in kaempferol-induced suppression with fluconazole-resistant Candida albicans.

Science.gov (United States)

Shao, Jing; Zhang, MengXiang; Wang, TianMing; Li, Yue; Wang, ChangZhong

2016-01-01

Fungal infections caused by fluconazole-resistant Candida albicans are an intractable clinical problem, calling for new efficient antifungal drugs. Kaempferol, an active flavonoid, has been considered a potential candidate against Candida species. This work investigates the resistance reversion of kaempferol in fluconazole-resistant C. albicans and the underlying mechanism. The antifungal activities of fluconazole and/or kaempferol were assessed by a series of standard procedures including broth microdilution method, checkerboard assay and time-kill (T-K) test in nine clinical strains as well as a standard reference isolate of C. albicans. Subsequently, the morphological changes, the efflux of rhodamine 6G, and the expressions of CDR 1, CDR 2, and MDR 1 were analysed by scanning electron microscope (SEM), inverted fluorescence microscope and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in C. albicans z2003. For all the tested C. albicans strains, the minimum inhibitory concentrations (MICs) of fluconazole and kaempferol ranged 0.25-32 and 128-256 μg/mL with a range of fractional inhibitory concentration index of 0.257-0.531. In C. albicans z2003, the expression of both CDR 1 and CDR 2 were decreased after exposure to kaempferol alone with negligible rhodamine 6G accumulation, while the expression of CDR 1, CDR 2 and MDR 1 were all decreased when fluconazole and kaempferol were used concomitantly with notable fluorescence of rhodamine 6G observed. Kaempferol-induced reversion in fluconazole-resistant C. albicans might be likely due to the suppression of the expression of CDR1, CDR2 and MDR1.

Cell viability and protein turnover in nongrowing Bacillus megaterium at sporulation suppressing temperature.

Science.gov (United States)

Kucerová, H; Strnadová, M; Ludvík, J; Chaloupka, J

1999-01-01

In Bacillus megaterium, a temperature that suppresses sporulation (43 degrees C) only slightly exceeds both the optimum growth temperature and the temperature still permitting sporulation (40-41 degrees C). Here we show that, when cells grown at 35 degrees C and transferred to a sporulation medium, were subjected to shifts between 35 degrees C and the sporulation suppressing temperature (SST, 43 degrees C), their development and proteolytic activities were deeply affected. During the reversible sporulation phase that took place at 35 degrees C for 2-3 h (T2-T3), the cells developed forespores and their protein turnover was characterized by degradation of short-lived proteins and proteins made accessible to the proteolytic attack because of starvation. During the following irreversible sporulation phase refractile heat-resistant spores appeared at T4-T5. Protein turnover rate increased again after T2 and up to T8 60-70% prelabelled proteins were degraded. The SST suppressed sporulation at its beginning; at T3 no asymmetric septa were observed and the amount of heat-resistant spores at T8 was by 4-5 orders lower than at 35 degrees C. However, the cells remained viable and were able to sporulate when transferred to a lower temperature. Protein degradation was increased up to T3 but then its velocity sharply dropped and the amount of degraded protein at T8 corresponded to slightly more than one-half of that found at 35 degrees C. The cytoplasmic proteolytic activity was enhanced but the activity in the membrane fraction was decreased. When a temperature shift to SST was applied at the beginning of the irreversible sporulation phase (T2.5), the sporulation process was impaired. A portion of forespores lyzed, the others were able to complete their development but most spores were not heat-resistant and their coats showed defects. Protein degradation increased again because an effective proteolytic system was developed during the reversible sporulation phase but the

Resistance to lambda-cyhalothrin in Spanish field populations of Ceratitis capitata and metabolic resistance mediated by P450 in a resistant strain.

Science.gov (United States)

Arouri, Rabeh; Le Goff, Gaelle; Hemden, Hiethem; Navarro-Llopis, Vicente; M'saad, Mariem; Castañera, Pedro; Feyereisen, René; Hernández-Crespo, Pedro; Ortego, Félix

2015-09-01

The withdrawal of malathion in the European Union in 2009 resulted in a large increase in lambda-cyhalothrin applications for the control of the Mediterranean fruit fly, Ceratitis capitata, in Spanish citrus crops. Spanish field populations of C. capitata have developed resistance to lambda-cyhalothrin (6-14-fold), achieving LC50 values (129-287 ppm) higher than the recommended concentration for field treatments (125 ppm). These results contrast with the high susceptibility to lambda-cyhalothrin found in three Tunisian field populations. We have studied the mechanism of resistance in the laboratory-selected resistant strain W-1Kλ (205-fold resistance). Bioassays with synergists showed that resistance was almost completely suppressed by the P450 inhibitor PBO. The study of the expression of 53 P450 genes belonging to the CYP4, CYP6, CYP9 and CYP12 families in C. capitata revealed that CYP6A51 was overexpressed (13-18-fold) in the resistant strain. The W-1Kλ strain also showed high levels of cross-resistance to etofenprox (240-fold) and deltamethrin (150-fold). Field-evolved resistance to lambda-cyhalothrin has been found in C. capitata. Metabolic resistance mediated by P450 appears to be the main resistance mechanism in the resistant strain W-1Kλ. The levels of cross-resistance found may compromise the effectiveness of other pyrethroids for the control of this species. © 2014 Society of Chemical Industry. © 2014 Society of Chemical Industry.

Development of Creep-Resistant and Oxidation-Resistant Austenitic Stainless Steels for High Temperature Applications

Science.gov (United States)

Maziasz, Philip J.

2018-01-01

Austenitic stainless steels are cost-effective materials for high-temperature applications if they have the oxidation and creep resistance to withstand prolonged exposure at such conditions. Since 1990, Oak Ridge National Laboratory (ORNL) has developed advanced austenitic stainless steels with creep resistance comparable to Ni-based superalloy 617 at 800-900°C based on specially designed "engineered microstructures" utilizing a microstructure/composition database derived from about 20 years of radiation effect data on steels. The wrought high temperature-ultrafine precipitate strengthened (HT-UPS) steels with outstanding creep resistance at 700-800°C were developed for supercritical boiler and superheater tubing for fossil power plants in the early 1990s, the cast CF8C-Plus steels were developed in 1999-2001 for land-based gas turbine casing and diesel engine exhaust manifold and turbocharger applications at 700-900°C, and, in 2015-2017, new Al-modified cast stainless steels with oxidation and creep resistance capabilities up to 950-1000°C were developed for automotive exhaust manifold and turbocharger applications. This article reviews and summarizes their development and their properties and applications.

Development of botanicals to combat antibiotic resistance

Directory of Open Access Journals (Sweden)

Pooja D. Gupta

2017-10-01

Full Text Available The discovery of antibiotics in the previous century lead to reduction in mortality and morbidity due to infectious diseases but their inappropriate and irrational use has resulted in emergence of resistant microbial populations. Alteration of target sites, active efflux of drugs and enzymatic degradations are the strategies employed by the pathogenic bacteria to develop intrinsic resistance to antibiotics. This has led to an increased interest in medicinal plants since 25–50% of current pharmaceuticals are plant derived. Crude extracts of medicinal plants could serve as an alternate source of resistance modifying agents owing to the wide variety of secondary metabolites. These metabolites (alkaloids, tannins, polyphenols etc. could act as potentials for antimicrobials and resistance modifiers. Plant extracts have the ability to bind to protein domains leading to modification or inhibition protein–protein interactions. This enables the herbals to also present themselves as effective modulators of host related cellular processes viz immune response, mitosis, apoptosis and signal transduction. Thus they may exert their activity not only by killing the microorganism but by affecting key events in the pathogenic process, thereby, the bacteria, fungi and viruses may have a reduced ability to develop resistance to botanicals. The article is meant to stimulate research wherein the cidal activity of the extract is not the only parameter considered but other mechanism of action by which plants can combat drug resistant microbes are investigated. The present article emphasizes on mechanisms involved in countering multi drug resistance.

Normal pregnancy: mechanisms underlying the paradox of a ouabain-resistant state with elevated endogenous ouabain, suppressed arterial sodium calcium exchange, and low blood pressure

Science.gov (United States)

Jacobs, Brandiese E.; Liu, Yong; Pulina, Maria V.; Golovina, Vera A.

2012-01-01

Endogenous cardiotonic steroids (CTS) raise blood pressure (BP) via vascular sodium calcium exchange (NCX1.3) and transient receptor-operated channels (TRPCs). Circulating CTS are superelevated in pregnancy-induced hypertension and preeclampsia. However, their significance in normal pregnancy, where BP is low, is paradoxical. Here we test the hypothesis that vascular resistance to endogenous ouabain (EO) develops in normal pregnancy and is mediated by reduced expression of NCX1.3 and TRPCs. We determined plasma and adrenal levels of EO and the impact of exogenous ouabain in pregnancy on arterial expression of Na+ pumps, NCX1.3, TRPC3, and TRPC6 and BP. Pregnant (embryonic day 4) and nonpregnant rats received infusions of ouabain or vehicle. At 14–16 days, tissues and plasma were collected for blotting and EO assay by radioimmunoassay (RIA), liquid chromatography (LC)-RIA, and LC-multidimensional mass spectrometry (MS3). BP (−8 mmHg; P vs. nonpregnant (0.6 ± 0.08 nM; P endogenous and exogenous ouabain is mediated by suppressed NCX1.3 and reduced sensitivity of events downstream of Ca2+ entry. The mechanisms of EO resistance and the impaired fetal and placental growth due to elevated ouabain may be important in pregnancy-induced hypertension (PIH) and preeclampsia (PE). PMID:22245773

High density lipoproteins improve insulin sensitivity in high-fat diet-fed mice by suppressing hepatic inflammation[S

Science.gov (United States)

McGrath, Kristine C.; Li, Xiao Hong; Whitworth, Phillippa T.; Kasz, Robert; Tan, Joanne T.; McLennan, Susan V.; Celermajer, David S.; Barter, Philip J.; Rye, Kerry-Anne; Heather, Alison K.

2014-01-01

Obesity-induced liver inflammation can drive insulin resistance. HDL has anti-inflammatory properties, so we hypothesized that low levels of HDL would perpetuate inflammatory responses in the liver and that HDL treatment would suppress liver inflammation and insulin resistance. The aim of this study was to investigate the effects of lipid-free apoAI on hepatic inflammation and insulin resistance in mice. We also investigated apoAI as a component of reconstituted HDLs (rHDLs) in hepatocytes to confirm results we observed in vivo. To test our hypothesis, C57BL/6 mice were fed a high-fat diet (HFD) for 16 weeks and administered either saline or lipid-free apoAI. Injections of lipid-free apoAI twice a week for 2 or 4 weeks with lipid-free apoAI resulted in: i) improved insulin sensitivity associated with decreased systemic and hepatic inflammation; ii) suppression of hepatic mRNA expression for key transcriptional regulators of lipogenic gene expression; and iii) suppression of nuclear factor κB (NF-κB) activation. Human hepatoma HuH-7 cells exposed to rHDLs showed suppressed TNFα-induced NF-κB activation, correlating with decreased NF-κB target gene expression. We conclude that apoAI suppresses liver inflammation in HFD mice and improves insulin resistance via a mechanism that involves a downregulation of NF-κB activation. PMID:24347528

Endothelin-1 exacerbates development of hypertension and atherosclerosis in modest insulin resistant syndrome

Energy Technology Data Exchange (ETDEWEB)

Lin, Yan-Jie [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Juan, Chi-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Kwok, Ching-Fai [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hsu, Yung-Pei [Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China); Shih, Kuang-Chung [Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Chen, Chin-Chang [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Ho, Low-Tone, E-mail: ltho@vghtpe.gov.tw [Institute of Physiology, National Yang-Ming University, Taipei, Taiwan (China); Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan (China)

2015-05-08

suppressed insulin-induced AKT activation, whereas remained insulin-induced ERK activation. ET-1 and insulin synergistically potentiated migration and proliferation mainly through ET{sub A}R/ERK dependent pathway, which is dominant in VSMCs during modest insulin resistance syndrome. Therefore, ET-1 and ET{sub A}R are potential targets responsible for the observed synergism effect in the hypertensive atherosclerotic process through enhancement of ET-1 binding, ET-1 binding, ET{sub A}R expression, and ET-1-induced mitogenic actions in aortic VSMCs. - Highlights: • ET-1/ET{sub A}R signaling and insulin-induced pERK were high in modest insulin resistance. • ET-1 via ET{sub A}R suppressed insulin-induced pAKT but remained intact pERK in VSMCs. • Insulin potentiated ET-1-induced VSMC mitogenic action was ET{sub A}R/ERK dependent.

The retinamide VNLG-152 inhibits f-AR/AR-V7 and MNK-eIF4E signaling pathways to suppress EMT and castration-resistant prostate cancer xenograft growth.

Science.gov (United States)

Ramamurthy, Vidya P; Ramalingam, Senthilmurugan; Gediya, Lalji K; Njar, Vincent C O

2018-03-01

VNLG-152 is a novel retinamide (NR) shown to suppress growth and progression of genetically diverse prostate cancer cells via inhibition of androgen receptor signaling and eukaryotic initiation factor 4E (eIF4E) translational machinery. Herein, we report therapeutic effects of VNLG-152 on castration-resistant prostate cancer (CRPC) growth and metastatic phenotype in a CRPC tumor xenograft model. Administration of VNLG-152 significantly and dose-dependently suppressed the growth of aggressive CWR22Rv1 tumors by 63.4% and 76.3% at 10 and 20 mg·kg -1 bw, respectively (P AR)/androgen receptor splice variant-7 (AR-V7), mitogen-activated protein kinase-interacting kinases 1 and 2 (MNK1/2), phosphorylated eIF4E and their associated target proteins, including prostate-specific antigen, cyclin D1 and Bcl-2, were strongly decreased in VNLG-152-treated tumors signifying inhibition of f-AR/AR-V7 and MNK-eIF4E signaling in VNLG-152-treated CWR22Rv1 tumors as observed in vitro. VNLG-152 also suppressed the epithelial to mesenchymal transition in CWR22Rv1 tumors as evidenced by repression of N-cadherin, β-catenin, claudin, Slug, Snail, Twist, vimentin and matrix metalloproteinases (MMP-2 and MMP-9) with upsurge in E-cadherin. These results highlight the promising use of VNLG-152 in CRPC therapy and justify its further development towards clinical trials. © 2018 Federation of European Biochemical Societies.

The multi-year effects of repeatedly growing cotton with moderate resistance to Meloidogyne incognita

Science.gov (United States)

Kemerait, Robert C.

2009-01-01

Meloidogyne incognita causes more damage to cotton in the US than any other pathogen. The objective of this study was to document the cumulative effect of moderate resistance on M. incognita population density, root galling, and yield suppression in the southern United States on a moderately resistant cotton genotype grown continuously for three years. Cotton genotypes were Phytogen PH98-3196 (77% suppression of M. incognita), Acala NemX (85% suppression of M. incognita), and Delta and Pine Land DP458 B/R (susceptible standard, 0% suppression). Cotton was grown in fumigated and non-fumigated plots to measure yield loss. Each genotype and nematicide combination was planted in the same place for three years at two sites to document cumulative effects. In 2006, following three years of the different genotypes, all plots at one site were planted with susceptible cotton to document residual effects of planting resistant genotypes. Root galling and nematode population densities in the soil were significantly lower, and percentage yield suppression was numerically lower, when moderately resistant cotton was grown compared to the susceptible standard in both fields in all three years. Differences between susceptible and moderately resistant genotypes are established quickly (after only one season) and then either maintained at similar levels or slightly increased in subsequent years depending on initial nematode levels. However, when susceptible cotton was grown following three years of the moderately resistant genotypes, the nematode suppression provided by moderate resistance was undetectable by the end of the first season. Moderately resistant cotton genotypes are more beneficial than previously reported and should be pursued for nematode management. Rotation of moderately resistant and susceptible cotton could be used along with nematicides to manage root-knot nematodes in a continuous cotton cropping system and reduce selection pressure on the nematodes. PMID:22661787

Suppression of 19S proteasome subunits marks emergence of an altered cell state in diverse cancers.

Science.gov (United States)

Tsvetkov, Peter; Sokol, Ethan; Jin, Dexter; Brune, Zarina; Thiru, Prathapan; Ghandi, Mahmoud; Garraway, Levi A; Gupta, Piyush B; Santagata, Sandro; Whitesell, Luke; Lindquist, Susan

2017-01-10

The use of proteasome inhibitors to target cancer's dependence on altered protein homeostasis has been greatly limited by intrinsic and acquired resistance. Analyzing data from thousands of cancer lines and tumors, we find that those with suppressed expression of one or more 19S proteasome subunits show intrinsic proteasome inhibitor resistance. Moreover, such proteasome subunit suppression is associated with poor outcome in myeloma patients, where proteasome inhibitors are a mainstay of treatment. Beyond conferring resistance to proteasome inhibitors, proteasome subunit suppression also serves as a sentinel of a more global remodeling of the transcriptome. This remodeling produces a distinct gene signature and new vulnerabilities to the proapoptotic drug, ABT-263. This frequent, naturally arising imbalance in 19S regulatory complex composition is achieved through a variety of mechanisms, including DNA methylation, and marks the emergence of a heritably altered and therapeutically relevant state in diverse cancers.

Aedes aegypti resistance development to commonly used insecticides in Jakarta, Indonesia.

Directory of Open Access Journals (Sweden)

Penny Humaidah Hamid

Full Text Available Aedes aegypti is the primary vector of various relevant arthropod-borne viral infectious diseases worldwide. The mosquito control is still mainly performed by using insecticides but their effectiveness is increasingly questioned nowadays. We here conducted a study on Ae. aegypti resistance development towards several commonly used insecticides in the capital city of Jakarta, Indonesia. In order to achieve this goal, Ae. aegypti eggs from Jakarta were collected with ovitraps and hatched in the insectary of the Gadjah Mada University, Indonesia. The F0 generations were used for WHO resistance tests and knockdown resistance (kdr assays. Presented results clearly showed that there was resistance development of Ae. aegypti populations to the here tested pyrethroid insecticides (i. e. permethrin. Observed mortalities were less than 90% with highest resistance against 0.75% permethrin concentrations. Furthermore, a significant association of V1016G gene mutations with resistance phenotypes to 0.75% permethrin was observed. Nevertheless, the F1534C mutation did not show a significant correlation to resistance development. In conclusion, our results show that populations of Ae. aegypti mosquitoes within the city of Jakarta have developed resistance against several routinely used pyrethroid insecticides in local performed control programs. Thus, the regular verification/assessment of resistance development status will hopefully help in the future to assist local public health authorities in their mosquito control programs by recommending and managing the rotation of different routinely used insecticides with diverse effector mechanisms in order to delay Ae. aegypti resistance development.

Novel DC Bias Suppression Device Based on Adjustable Parallel Resistances

DEFF Research Database (Denmark)

Wang, Zhixun; Xie, Zhicheng; Liu, Chang

2018-01-01

resistances is designed. The mathematical model for global optimal switching of CBDs is established by field-circuit coupling method with the equivalent resistance network of ac system along with the location of substations and ground electrodes. The optimal switching scheme to minimize the global maximum dc...

Development and application of a probabilistic method for wildfire suppression cost modeling

Science.gov (United States)

Matthew P. Thompson; Jessica R. Haas; Mark A. Finney; David E. Calkin; Michael S. Hand; Mark J. Browne; Martin Halek; Karen C. Short; Isaac C. Grenfell

2015-01-01

Wildfire activity and escalating suppression costs continue to threaten the financial health of federal land management agencies. In order to minimize and effectively manage the cost of financial risk, agencies need the ability to quantify that risk. A fundamental aim of this research effort, therefore, is to develop a process for generating risk-based metrics for...

Pyrethroid resistance and cross-resistance in the German cockroach, Blattella germanica (L).

Science.gov (United States)

Wei, Y; Appel, A G; Moar, W J; Liu, N

2001-11-01

A German cockroach (Blatella germanica (L)) strain, Apyr-R, was collected from Opelika, Alabama after control failures with pyrethroid insecticides. Levels of resistance to permethrin and deltamethrin in Apyr-R (97- and 480-fold, respectively, compared with a susceptible strain, ACY) were partially or mostly suppressed by piperonyl butoxide (PBO) and S,S,S,-tributylphosphorotrithioate (DEF), suggesting that P450 monooxygenases and hydrolases are involved in resistance to these two pyrethroids in Apyr-R. However, incomplete suppression of pyrethroid resistance with PBO and DEF implies that one or more additional mechanisms are involved in resistance. Injection, compared with topical application, resulted in 43- and 48-fold increases in toxicity of permethrin in ACY and Apyr-R, respectively. Similarly, injection increased the toxicity of deltamethrin 27-fold in ACY and 28-fold in Apyr-R. These data indicate that cuticular penetration is one of the obstacles for the effectiveness of pyrethroids against German cockroaches. However, injection did not change the levels of resistance to either permethrin or deltamethrin, suggesting that a decrease in the rate of cuticular penetration may not play an important role in pyrethroid resistance in Apyr-R. Apyr-R showed cross-resistance to imidacloprid, with a resistance ratio of 10. PBO treatment resulted in no significant change in the toxicity of imidacloprid, implying that P450 monooxygenase-mediated detoxication is not the mechanism responsible for cross-resistance. Apyr-R showed no cross-resistance to spinosad, although spinosad had relatively low toxicity to German cockroaches compared with other insecticides tested in this study. This result further confirmed that the mode of action of spinosad to insects is unique. Fipronil, a relatively new insecticide, was highly toxic to German cockroaches, and the multi-resistance mechanisms in Apyr-R did not confer significant cross-resistance to this compound. Thus, we propose

Tcf3 and cell cycle factors contribute to butyrate resistance in colorectal cancer cells

Energy Technology Data Exchange (ETDEWEB)

Chiaro, Christopher, E-mail: cchiaro@tcmedc.org [Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, Scranton, PA 18509 (United States); Lazarova, Darina L., E-mail: dlazarova@tcmedc.org [Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, Scranton, PA 18509 (United States); Bordonaro, Michael, E-mail: mbordonaro@tcmedc.org [Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, Scranton, PA 18509 (United States)

2012-11-09

Highlights: Black-Right-Pointing-Pointer We investigate mechanisms responsible for butyrate resistance in colon cancer cells. Black-Right-Pointing-Pointer Tcf3 modulates butyrate's effects on Wnt activity and cell growth in resistant cells. Black-Right-Pointing-Pointer Tcf3 modulation of butyrate's effects differ by cell context. Black-Right-Pointing-Pointer Cell cycle factors are overexpressed in the resistant cells. Black-Right-Pointing-Pointer Reversal of altered gene expression can enhance the anti-cancer effects of butyrate. -- Abstract: Butyrate, a fermentation product of dietary fiber, inhibits clonal growth in colorectal cancer (CRC) cells dependent upon the fold induction of Wnt activity. We have developed a CRC cell line (HCT-R) that, unlike its parental cell line, HCT-116, does not respond to butyrate exposure with hyperactivation of Wnt signaling and suppressed clonal growth. PCR array analyses revealed Wnt pathway-related genes, the expression of which differs between butyrate-sensitive HCT-116 CRC cells and their butyrate-resistant HCT-R cell counterparts. We identified overexpression of Tcf3 as being partially responsible for the butyrate-resistant phenotype, as this DNA-binding protein suppresses the hyperinduction of Wnt activity by butyrate. Consequently, Tcf3 knockdown in HCT-R cells restores their sensitivity to the effects of butyrate on Wnt activity and clonal cell growth. Interestingly, the effects of overexpressed Tcf3 differ between HCT-116 and HCT-R cells; thus, in HCT-116 cells Tcf3 suppresses proliferation without rendering the cells resistant to butyrate. In HCT-R cells, however, the overexpression of Tcf3 inhibits Wnt activity, and the cells are still able to proliferate due to the higher expression levels of cell cycle factors, particularly those driving the G{sub 1} to S transition. Knowledge of the molecular mechanisms determining the variable sensitivity of CRC cells to butyrate may assist in developing approaches that

Development of large area resistive electrodes for ATLAS NSW Micromegas

Science.gov (United States)

Ochi, Atsuhiko

2018-02-01

Micromegas with resistive anodes will be used for the NSW upgrades of the ATLAS experiment at LHC. Resistive electrodes are used in MPGD devices to prevent sparks in high-rate operation. Large-area resistive electrodes for Micromegas have been developed using two different technologies: screen printing and carbon sputtering. The maximum resistive foil size is 45 × 220 cm with a printed pattern of 425-μm pitch strips. These technologies are also suitable for mass production. Prototypes of a production model series have been successfully produced. In this paper, we report the development, the production status, and the test results of resistive Micromegas.

Suppressed Demand and the Carbon Markets: Does development have to become dirty before it qualifies to become clean?

OpenAIRE

Gavaldão, Marina; Battye, William; Grapeloup, Mathieu; François, Yann

2012-01-01

Suppressed Demand refers to a situation where Minimum Services Levels (MSL) necessary for human development are unavailable to people or only available to an inadequate level. Numerous barriers, such as low income levels or lack of infrastructure and skills prevent access to MSLs, such as potable water, cooking energy, lighting and electrification. We investigate the concept of suppressed demand as it applies to Clean Development Mechanism (CDM) and market based incentives for GHG emission re...

Development of radiation resistant organic composites for cryogenic use

International Nuclear Information System (INIS)

Nishijima, S.

1997-01-01

The mechanism of the radiation induced degradation of the mechanical properties in composite materials have been studied and based on the mechanism the radiation resistant organic composites for fusion magnet have been developing. It was found that the degradation was brought by the change of the fracture mode from tensile (or flexural) to shear failure. Consequently the intrinsic parameter which control the degradation was concluded to be the interlaminar shear strength. To develop the radiation resistant composites, therefore, means to develop the composites showing the radiation resistant interlaminar shear strength. The mechanism was confirmed using three dimensional fabric reinforced plastics which do not have the interlaminar area. The roles of matrix in the composites were also revealed. The effects of dose quality and irradiated temperature on the radiation induced degradation were also discussed and the selection standards of the components for radiation resistant composites were proposed

Transgenic approaches for development of disease resistance in banana

International Nuclear Information System (INIS)

Shekhawat, Upendra K.S.; Ghag, Siddhesh B.; Ganapathi, Thumballi R.

2014-01-01

Banana (Musa spp.) is an important food and cash crop worldwide. Diseases and pests pose the most serious constraint to banana cultivation. Among the diseases, Fusarium wilt and Banana Bunchy Top Virus (BBTV) are the most important economically. We have explored different transgenic approaches for development of efficient resistance in banana against these two diseases. For countering Fusarium wilt, we have over expressed Petunia floral defensins using a strong constitutive promoter in transgenic banana plants. We have also tested a host induced gene silencing strategy targeting two vital fungal genes to obtain Fusarium resistant banana plants. For development of BBTV resistant banana plants also, we have used a host-induced gene silencing approach utilizing the full and partial coding sequence of the viral replication initiation protein. Successful bioassays performed in controlled greenhouse conditions have shown the efficacy of using these strategies to develop disease resistant banana plants. (author)

The contribution of thought-action fusion and thought suppression in the development of obsession-like intrusions in normal participants.

Science.gov (United States)

Rassin, E

2001-09-01

Both thought-action fusion (TAF: i.e., a cognitive bias implying an inflated sense of responsibility for one's own thoughts) and thought suppression have been claimed to contribute to the development of obsession-like intrusions. Therefore, it seems plausible that conjunction of these phenomena results in highly intense intrusions. However, possible interactions between TAF and thought suppression have not yet been investigated experimentally. In the current study, healthy volunteers were exposed to a TAF-like intrusion. They were, then, randomly assigned to a suppression (n=21) or non-suppression condition (n=19). Next, visual analogue scales (VASs) were completed measuring anxiety, feelings of responsibility and guilt, urge to neutralise and so on. Contrary to expectation, several VAS scores were lower for participants in the suppression group than for those in the non-suppression group. Hence, it is concluded that thought suppression may, at least in the short term, alleviate discomfort caused by TAF-like intrusions.

Full Viral Suppression, Low-Level Viremia, and Quantifiable Plasma HIV-RNA at the End of Pregnancy in HIV-Infected Women on Antiretroviral Treatment.

Science.gov (United States)

Baroncelli, Silvia; Pirillo, Maria F; Tamburrini, Enrica; Guaraldi, Giovanni; Pinnetti, Carmela; Degli Antoni, Anna; Galluzzo, Clementina M; Stentarelli, Chiara; Amici, Roberta; Floridia, Marco

2015-07-01

There is limited information on full viral suppression and low-level HIV-RNA viremia in HIV-infected women at the end of pregnancy. We investigated HIV-RNA levels close to delivery in women on antiretroviral treatment in order to define rates of complete suppression, low-level viremia, and quantifiable HIV-RNA, exploring as potential determinants some clinical and viroimmunological variables. Plasma samples from a national study in Italy, collected between 2003 and 2012, were used. According to plasma HIV-RNA levels, three groups were defined: full suppression (target not detected), low-level viremia (target detected but HIV-RNA (≥37 copies/ml). Multivariable logistic regression was used to define determinants of full viral suppression and of quantifiable HIV-RNA. Among 107 women evaluated at a median gestational age of 35 weeks, 90 (84.1%) had HIV-RNA HIV-RNA was 109 copies/ml (IQR 46-251), with only one case showing resistance (mutation M184V; rate: 9.1%). In multivariable analyses, women with higher baseline HIV-RNA levels and with hepatitis C virus (HCV) coinfection were significantly more likely to have quantifiable HIV-RNA in late pregnancy. Full viral suppression was significantly more likely with nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens and significantly less likely with higher HIV-RNA in early pregnancy. No cases of HIV transmission occurred. In conclusion, HIV-infected pregnant women showed a high rate of viral suppression and a low resistance rate before delivery. In most cases no target HIV-RNA was detected in plasma, suggesting a low risk of subsequent virological rebound and development of resistance. Women with high levels of HIV-RNA in early pregnancy and those who have concomitant HCV infection should be considered at higher risk of having quantifiable HIV-RNA at the end of pregnancy.

EPHA2 is a mediator of vemurafenib resistance and a novel therapeutic target in melanoma.

Science.gov (United States)

Miao, Benchun; Ji, Zhenyu; Tan, Li; Taylor, Michael; Zhang, Jianming; Choi, Hwan Geun; Frederick, Dennie T; Kumar, Raj; Wargo, Jennifer A; Flaherty, Keith T; Gray, Nathanael S; Tsao, Hensin

2015-03-01

BRAF(V600E) is the most common oncogenic lesion in melanoma and results in constitutive activation of the MAPK pathway and uncontrolled cell growth. Selective BRAF inhibitors such as vemurafenib have been shown to neutralize oncogenic signaling, restrain cellular growth, and improve patient outcome. Although several mechanisms of vemurafenib resistance have been described, directed solutions to overcome these resistance lesions are still lacking. Herein, we found that vemurafenib resistance can be (i) mediated by EPHA2, a member of the largest receptor tyrosine kinases (RTK) subfamily erythropoietin-producing hepatocellular (EPH) receptors, and (ii) associated with a greater phenotypic dependence on EPHA2. Furthermore, we developed a series of first-in-class EPHA2 inhibitors and show that these new compounds potently induce apoptosis, suppress viability, and abrogate tumorigenic growth of melanoma cells, including those that are resistant to vemurafenib. These results provide proof of concept that RTK-guided growth, and therapeutic resistance, can be prospectively defined and selectively targeted. In this study, we show that resistance to selective BRAF inhibitors can be mediated by the RTK EPHA2. Furthermore, direct targeting of EPHA2 can successfully suppress melanoma growth and mitigate therapeutic resistance. ©2014 American Association for Cancer Research.

Population suppression in support of the sterile insect technique

International Nuclear Information System (INIS)

Mangan, R.L.

2005-01-01

Suppression or eradication of insect pest populations by the release of sterile insects is often dependent on supplementary methods of pest reduction to levels where the target pest population can be overflooded with sterile insects. Population suppression activities take place in advance of, or coincide with, the production of sterile insects. Supplementary methods to remove breeding opportunities, or management methods that prevent access of pests to the hosts, may reduce the population or prevent damage. Insecticides have been used widely in direct applications or applied as baits, in traps, or on specific sites where the pest makes contact or reproduces. As sterile insect release does not kill the pest, adult biting pests or fertile mated females of the pests will continue to attack hosts after the release of sterile insects. Thus supplementary pest suppression programmes and quarantine measures are essential to prevent damage or the spread of disease. Eradication or effective pest management requires that the entire population of the pest be treated, or that the programme apply immigration barriers. When supplementary pest control activities benefit the human population in areas being treated, such as in mosquito or screwworm eradication programmes, these activities are usually acceptable to the public, but when the public receives no direct benefit from supplementary control activities such as in fruit fly programmes, social resistance may develop. (author)

Development of fire resistant, nontoxic aircraft interior materials

Science.gov (United States)

Haley, G.; Silverman, B.; Tajima, Y.

1976-01-01

All available newly developed nonmetallic polymers were examined for possible usage in developing fire resistant, nontoxic nonmetallic parts or assemblies for aircraft interiors. Specifically, feasibility for the development of clear films for new decorative laminates, compression moldings, injection molded parts, thermoformed plastic parts, and flexible foams were given primary considerations. Preliminary data on the flame resistant characteristics of the materials were obtained. Preliminary toxicity data were generated from samples of materials submitted from the contractor. Preliminary data on the physical characteristics of various thermoplastic materials to be considered for either compression molded, injection molded, or thermoformed parts were obtained.

Development of radiation-resisting high molecular-weight materials

International Nuclear Information System (INIS)

Nakagawa, Tsutomu

1976-01-01

The excellent radiation-resisting polyvinyl chloride developed at the opportunity of the research on the relationships between the protection of living body and the polymer-technological protection from radiation is reviewed. The report is divided into four main parts, namely 1) the change in the molecular arrangement of market-available, high molecular-weight materials by gamma-ray irradiation, 2) the protection of high molecular-weight materials from radiation, 3) the relationships between the biological radiation-protective substances and the change to radiation-resisting property of synthesized high molecular-weight substances, and 4) the development of the radiation-resisting high molecular-weight materials as metal-collecting agents. Attention is paid to the polyvinyl chloride having N-methyl-dithio-carbamate radical (PMD), synthesized by the author et. al., that has excellent radiation-resisting property. PMD has some possibility to form thiol- and amino-radicals necessary to protect living things from radiation. It is believed that the protection effects of N-methyl-dithio-carbamate radical are caused by the relatively stable S radical produced by the energy transfer. PMD film is suitable for the irradiation of foods, because it hardly changes the permeability of oxygen and carbon dioxide. PMD produces mercaptide or chelate. A new metal-collecting agent (PSDC) having reactivity with the metallic ions with radiation-resisting property was developed, which is derived from polyvinyl chloride and sodium N-methyl-N-carboxy-methyl-dithio-carbamate. (Iwakiri, K.)

Xylitol prevents NEFA-induced insulin resistance in rats

Science.gov (United States)

Kishore, P.; Kehlenbrink, S.; Hu, M.; Zhang, K.; Gutierrez-Juarez, R.; Koppaka, S.; El-Maghrabi, M. R.

2013-01-01

Aims/hypothesis Increased NEFA levels, characteristic of type 2 diabetes mellitus, contribute to skeletal muscle insulin resistance. While NEFA-induced insulin resistance was formerly attributed to decreased glycolysis, it is likely that glucose transport is the rate-limiting defect. Recently, the plant-derived sugar alcohol xylitol has been shown to have favourable metabolic effects in various animal models. Furthermore, its derivative xylulose 5-phosphate may prevent NEFA-induced suppression of glycolysis. We therefore examined whether and how xylitol might prevent NEFA-induced insulin resistance. Methods We examined the ability of xylitol to prevent NEFA-induced insulin resistance. Sustained ~1.5-fold elevations in NEFA levels were induced with Intralipid/heparin infusions during 5 h euglycaemic–hyperinsulinaemic clamp studies in 24 conscious non-diabetic Sprague-Dawley rats, with or without infusion of xylitol. Results Intralipid infusion reduced peripheral glucose uptake by ~25%, predominantly through suppression of glycogen synthesis. Co-infusion of xylitol prevented the NEFA-induced decreases in both glucose uptake and glycogen synthesis. Although glycolysis was increased by xylitol infusion alone, there was minimal NEFA-induced suppression of glycolysis, which was not affected by co-infusion of xylitol. Conclusions/interpretation We conclude that xylitol prevented NEFA-induced insulin resistance, with favourable effects on glycogen synthesis accompanying the improved insulin-mediated glucose uptake. This suggests that this pentose sweetener has beneficial insulin-sensitising effects. PMID:22460760

Insecticide Rotation Programs with Entomopathogenic Organisms for Suppression of Western Flower Thrips (Thysanoptera: Thripidae) Adult Populations under Greenhouse Conditions.

Science.gov (United States)

Kivett, Jessica M; Cloyd, Raymond A; Bello, Nora M

2015-08-01

Western flower thrips, Frankliniella occidentalis (Pergande), is one of the most destructive insect pests of greenhouse production systems with the ability to develop resistance to a wide variety of insecticides. A common resistance management strategy is rotating insecticides with different modes of action. By incorporating entomopathogenic organisms (fungi and bacteria), which have discrete modes of action compared to standard insecticides, greenhouse producers may preserve the effectiveness of insecticides used for suppression of western flower thrips populations. The objective of this study was to determine how different rotation programs that include entomopathogenic organisms (Beauveria bassiana, Isaria fumosoroseus, Metarhizium anisopliae, and Chromobacterium subtsugae) and commonly used standard insecticides (spinosad, chlorfenapyr, abamectin, and pyridalyl) may impact the population dynamics of western flower thrips adult populations by means of suppression. Eight-week rotation programs were applied to chrysanthemum, Dendranthema x morifolium plants and weekly counts of western flower thrips adults captured on yellow sticky cards were recorded as a means to evaluate the impact of the rotation programs. A final quality assessment of damage caused by western flower thrips feeding on foliage and flowers was also recorded. Furthermore, a cost comparison of each rotation program was conducted. Overall, insecticide rotation programs that incorporated entomopathogenic organisms were not significantly different than the standard insecticide rotation programs without entomopathogenic organisms in suppressing western flower thrips adult populations. However, there were no significant differences among any of the rotation programs compared to the water control. Moreover, there was no differential effect of the rotation programs on foliage and flower quality. Cost savings of up to 34% (in US dollars) are possible when including entomopathogenic organisms in the

17β-estradiol exerts anticancer effects in anoikis-resistant hepatocellular carcinoma cell lines by targeting IL-6/STAT3 signaling

Energy Technology Data Exchange (ETDEWEB)

Lee, Seulki, E-mail: sl10f@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Minjong, E-mail: minjonglee2@naver.com [Division of Gastroenterology, Department of Internal Medicine, Kangwon National University Hospital, 156 Baengnyeong-ro, Chuncheon-si, Gangwon-do (Korea, Republic of); Kim, Jong Bin, E-mail: kkimjp@hanmail.net [Hormel Institute, University of Minnesota, 801 16th Ave NE, Austin, MN, 55912 (United States); Jo, Ara, E-mail: loveara0315@naver.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Cho, Eun Ju, E-mail: creatioex@gmail.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yu, Su Jong, E-mail: ydoctor2@hanmail.net [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Lee, Jeong-Hoon, E-mail: pindra@empal.com [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Yoon, Jung-Hwan, E-mail: yoonjh@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of); Kim, Yoon Jun, E-mail: yoonjun@snu.ac.kr [Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799 (Korea, Republic of)

2016-05-13

17β-Estradiol (E2) has been proven to exert protective effects against HCC; however, its mechanism on HCC proliferation and suppression of invasion remains to be further explored. Because HCC up-regulates serum Interleukin-6 (IL-6) levels and Signal Transducer and Activator of Transcription 3 (STAT3), molecular agents that attenuate IL-6/STAT3 signaling can potentially suppress HCC development. In this study, we examined involvement of E2 in anoikis resistance that induces invasion capacities and chemo-resistance. Huh-BAT and HepG2 cells grown under anchorage-independent condition were selected. The anoikis-resistant (AR) cells showed stronger chemo-resistance against sorafenib, doxorubicin, 5-fluorouracil and cisplatin compared to adherent HCC cells. AR HCC cells exhibited decreased expression of E-cadherin and increased expression of the N-cadherin and vimentin compared to adherent HCC cells. We then demonstrated that E2 suppressed cell proliferation in AR HCC cells. IL-6 treatment enhanced invasive characteristics, and E2 reversed it. Regarding mechanism of E2, it decreased in the phosphorylation of STAT3 that overexpressed on AR HCC cells. The inhibitory effect of E2 on cell growth was accompanied with cell cycle arrest at G2/M phase and caspase-3/9/PARP activation through c-Jun N-terminal Kinase (JNK) phosphorylation. Taken together, these findings suggested that E2 inhibited the proliferation of AR HCC cells through down-regulation of IL-6/STAT3 signaling. Thus, E2 can be a potential therapeutic drug for treatment of metastatic or chemo-resistant HCC. -- Highlights: •Anoikis-resistant HCC cells characterized chemo-resistant and metastatic potentials. •17β-Estradiol down-regulated IL-6/STAT3 signaling in anoikis-resistant HCC cells. •17β-Estradiol suppressed cell proliferation by inducing G2/M phase arrest and apoptosis though JNK phosphorylation.

Suppression of Ghrelin Exacerbates HFCS-Induced Adiposity and Insulin Resistance.

Science.gov (United States)

Ma, Xiaojun; Lin, Ligen; Yue, Jing; Wu, Chia-Shan; Guo, Cathy A; Wang, Ruitao; Yu, Kai-Jiang; Devaraj, Sridevi; Murano, Peter; Chen, Zheng; Sun, Yuxiang

2017-06-19

High fructose corn syrup (HFCS) is widely used as sweetener in processed foods and soft drinks in the United States, largely substituting sucrose (SUC). The orexigenic hormone ghrelin promotes obesity and insulin resistance; ghrelin responds differently to HFCS and SUC ingestion. Here we investigated the roles of ghrelin in HFCS- and SUC-induced adiposity and insulin resistance. To mimic soft drinks, 10-week-old male wild-type (WT) and ghrelin knockout ( Ghrelin -/- ) mice were subjected to ad lib. regular chow diet supplemented with either water (RD), 8% HFCS (HFCS), or 10% sucrose (SUC). We found that SUC-feeding induced more robust increases in body weight and body fat than HFCS-feeding. Comparing to SUC-fed mice, HFCS-fed mice showed lower body weight but higher circulating glucose and insulin levels. Interestingly, we also found that ghrelin deletion exacerbates HFCS-induced adiposity and inflammation in adipose tissues, as well as whole-body insulin resistance. Our findings suggest that HFCS and SUC have differential effects on lipid metabolism: while sucrose promotes obesogenesis, HFCS primarily enhances inflammation and insulin resistance, and ghrelin confers protective effects for these metabolic dysfunctions.

Suppression of Ghrelin Exacerbates HFCS-Induced Adiposity and Insulin Resistance

Directory of Open Access Journals (Sweden)

Xiaojun Ma

2017-06-01

Full Text Available High fructose corn syrup (HFCS is widely used as sweetener in processed foods and soft drinks in the United States, largely substituting sucrose (SUC. The orexigenic hormone ghrelin promotes obesity and insulin resistance; ghrelin responds differently to HFCS and SUC ingestion. Here we investigated the roles of ghrelin in HFCS- and SUC-induced adiposity and insulin resistance. To mimic soft drinks, 10-week-old male wild-type (WT and ghrelin knockout (Ghrelin−/− mice were subjected to ad lib. regular chow diet supplemented with either water (RD, 8% HFCS (HFCS, or 10% sucrose (SUC. We found that SUC-feeding induced more robust increases in body weight and body fat than HFCS-feeding. Comparing to SUC-fed mice, HFCS-fed mice showed lower body weight but higher circulating glucose and insulin levels. Interestingly, we also found that ghrelin deletion exacerbates HFCS-induced adiposity and inflammation in adipose tissues, as well as whole-body insulin resistance. Our findings suggest that HFCS and SUC have differential effects on lipid metabolism: while sucrose promotes obesogenesis, HFCS primarily enhances inflammation and insulin resistance, and ghrelin confers protective effects for these metabolic dysfunctions.

Mechanism of Innate Resistance to Viral Encephalitis.

Science.gov (United States)

1976-12-01

development of immunity (20). Although serum antibody was not detected in recipients of immune SC unless they were challenged wih virus, it is reasonable to...inununo- suppression, cytotoxicity 21. ASSIRACr m(nm -oel ab w noomeao aid Momlw by block nmbu) Factors that influence the phenotypic expression of...both strains of mice withstood IP challenge with virus. In contrast, only resistant mice (C3H/RV) were able to withstand IC challenge . Similarly, C3H

Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway.

Science.gov (United States)

Dong, Guang-Zhi; Jeong, Ji Hye; Lee, Yu-Ih; Lee, So Yoon; Zhao, Hui-Yuan; Jeon, Raok; Lee, Hwa Jin; Ryu, Jae-Ha

2017-04-01

Pancreatic cancer is one of the leading causes of cancer, and it has the lowest 5-year survival rates. It is necessary to develop more potent anti-pancreatic cancer drugs to overcome the fast metastasis and resistance to surgery, radiotherapy, chemotherapy, and combinations of these. We have identified several diarylheptanoids as anti-pancreatic cancer agents from Alpinia officinarum (lesser galangal) and Alnus japonica. These diarylheptanoids suppressed cell proliferation and induced the cell cycle arrest of pancreatic cancer cells (PANC-1). Among them, the most potent compounds 1 and 7 inhibited the shh-Gli-FoxM1 pathway and their target gene expression in PANC-1 cells. Furthermore, they suppressed the expression of the cell cycle associated genes that were rescued by the overexpression of exogenous FoxM1. Taken together, (E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (1) from Alpinia officinarum (lesser galangal) and platyphyllenone (7) from Alnus japonica inhibit PANC-1 cell proliferation by suppressing the shh-Gli-FoxM1 pathway, and they can be potential candidates for anti-pancreatic cancer drug development.

Simulation of Axial Combustion Instability Development and Suppression in Solid Rocket Motors

OpenAIRE

David R. Greatrix

2009-01-01

In the design of solid-propellant rocket motors, the ability to understand and predict the expected behaviour of a given motor under unsteady conditions is important. Research towards predicting, quantifying, and ultimately suppressing undesirable strong transient axial combustion instability symptoms necessitates a comprehensive numerical model for internal ballistic simulation under dynamic flow and combustion conditions. An updated numerical model incorporating recent developments in predi...

Economics of wildfire management the development and application of suppression expenditure models

CERN Document Server

Hand, Michael S; Liang, Jingjing; Thompson, Matthew P

2014-01-01

In this age of climatic and financial uncertainty, it becomes increasingly important to balance the cost, benefits and risk of wildfire management. In the United States, increased wildland fire activity over the last 15 years has resulted in drastic damage and loss of life. An associated rapid increase in fire management costs has consumed higher portions of budgets of public entities involved in wildfire management, challenging their ability to fulfill other responsibilities. Increased public scrutiny highlights the need to improve wildland fire management for cost effectiveness. This book closely examines the development of basic wildfire suppression cost models for the United States and their application to a wide range of settings from informing incident decision making to programmatic review. The book also explores emerging trends in suppression costs and introduces new spatially explicit cost models to account for characteristics of the burned landscape. Finally, it discusses how emerging risk assessmen...

An electromagnetic inerter-based vibration suppression device

International Nuclear Information System (INIS)

Gonzalez-Buelga, A; Clare, L R; Neild, S A; Jiang, J Z; Inman, D J

2015-01-01

This paper describes how an inerter-based device for structural vibration suppression can be realized using an electromagnetic transducer such as a linear motor. When the motor shaft moves, a difference of voltage is generated across the transducer coil. The voltage difference is proportional to the relative velocity between its two terminals. The electromagnetic transducer will exert a force proportional to current following the Lorentz principle if the circuit is closed around the transducer coil. If an electronic circuit consisting of a capacitor, an inductance and a resistance with the appropriate configuration is connected, the resulting force reflected back into the mechanical domain is equivalent to that achieved by a mechanical inerter-based device. The proposed configuration is easy to implement and very versatile, provided a high quality conversion system with negligible losses. With the use of electromagnetic devices, a new generation of vibration absorbers can be realized, for example in the electrical domain it would be relatively uncomplicated to synthesize multi-frequency or real time tunable vibration absorbers by adding electrical components in parallel. In addition by using resistance emulators in the electrical circuits, part of the absorbed vibration energy can be converted into usable power. Here an electromagnetic tuned inerter damper (E-TID) is tested experimentally using real time dynamic substructuring. A voltage compensation unit was developed in order to compensate for coil losses. This voltage compensation unit requires power, which is acquired through harvesting from the vibration energy using a resistance emulator. A power balance analysis was developed in order to ensure the device can be self sufficient. Promising experimental results, using this approach, have been obtained and are presented in this paper. The ultimate goal of this research is the development of autonomous electromagnetic vibration absorbers, able to harvest energy

Discordant CSF/plasma HIV-1 RNA in individuals on virologically suppressive antiretroviral therapy in Western India.

Science.gov (United States)

Dravid, Ameet N; Natrajan, Kartik; Kulkarni, Milind M; Saraf, Chinmay K; Mahajan, Uma S; Kore, Sachin D; Rathod, Niranjan M; Mahajan, Umakant S; Wadia, Rustom S

2018-02-01

Aim of this study was to estimate the prevalence of cerebrospinal fluid (CSF)/Plasma HIV-1 RNA discordance in virologically suppressed individuals presenting with incident neurologic symptoms.In this retrospective cohort study conducted between March 1, 2009, and March 1, 2017, HIV-1 infected adults exposed to atleast 12 months of antiretroviral therapy (ART) and having plasma viral load (VL) CSF/Plasma HIV-1 RNA discordance by measuring HIV-1 RNA in collected plasma and CSF samples. CSF/plasma HIV-1 RNA discordance was defined as either detectable CSF HIV-1 RNA (VL > 20 copies/mL) with an undetectable plasma RNA (complete viral suppression, VL ≤20 copies/mL) or CSF HIV-1 RNA ≥ 0.5 log10 higher than plasma RNA when plasma VL was between 20 and 1000 copies/mL (low-level viremia, LLV).Out of 1584 virologically suppressed patients, 71 (4.4%) presented with incident neurologic symptoms. Twenty out of 71 (28.2%) patients were diagnosed with CSF/Plasma HIV-1 discordance. Median plasma and CSF VL in patients with discordance was 120 [interquartile range (IQR): CSF HIV-1 genotypic resistance testing was done showed mutations that would compromise efficacy of prescribed ART regimen. Prevalence of CSF/plasma HIV-1 RNA discordance was higher among neurologically symptomatic patients with plasma LLV as compared with those with complete viral suppression (70% vs 11.8%, P CSF/plasma HIV-1 RNA discordance indicates replication of HIV-1 that has adapted to the CNS or has developed antiretroviral drug resistance. Larger studies should be performed to study incidence of discordance in India. This will help in managing patients presenting with neurologic symptoms on suppressive ART with appropriate neuroeffective therapy.

Transcriptome Analysis of Chlorantraniliprole Resistance Development in the Diamondback Moth Plutella xylostella

Science.gov (United States)

Hu, Zhendi; Chen, Huanyu; Yin, Fei; Li, Zhenyu; Dong, Xiaolin; Zhang, Deyong; Ren, Shunxiang; Feng, Xia

2013-01-01

Background The diamondback moth Plutella xyllostella has developed a high level of resistance to the latest insecticide chlorantraniliprole. A better understanding of P. xylostella’s resistance mechanism to chlorantraniliprole is needed to develop effective approaches for insecticide resistance management. Principal Findings To provide a comprehensive insight into the resistance mechanisms of P. xylostella to chlorantraniliprole, transcriptome assembly and tag-based digital gene expression (DGE) system were performed using Illumina HiSeq™ 2000. The transcriptome analysis of the susceptible strain (SS) provided 45,231 unigenes (with the size ranging from 200 bp to 13,799 bp), which would be efficient for analyzing the differences in different chlorantraniliprole-resistant P. xylostella stains. DGE analysis indicated that a total of 1215 genes (189 up-regulated and 1026 down-regulated) were gradient differentially expressed among the susceptible strain (SS) and different chlorantraniliprole-resistant P. xylostella strains, including low-level resistance (GXA), moderate resistance (LZA) and high resistance strains (HZA). A detailed analysis of gradient differentially expressed genes elucidated the existence of a phase-dependent divergence of biological investment at the molecular level. The genes related to insecticide resistance, such as P450, GST, the ryanodine receptor, and connectin, had different expression profiles in the different chlorantraniliprole-resistant DGE libraries, suggesting that the genes related to insecticide resistance are involved in P. xylostella resistance development against chlorantraniliprole. To confirm the results from the DGE, the expressional profiles of 4 genes related to insecticide resistance were further validated by qRT-PCR analysis. Conclusions The obtained transcriptome information provides large gene resources available for further studying the resistance development of P. xylostella to pesticides. The DGE data provide

Transcriptome analysis of chlorantraniliprole resistance development in the diamondback moth Plutella xylostella.

Directory of Open Access Journals (Sweden)

Qingsheng Lin

Full Text Available BACKGROUND: The diamondback moth Plutella xyllostella has developed a high level of resistance to the latest insecticide chlorantraniliprole. A better understanding of P. xylostella's resistance mechanism to chlorantraniliprole is needed to develop effective approaches for insecticide resistance management. PRINCIPAL FINDINGS: To provide a comprehensive insight into the resistance mechanisms of P. xylostella to chlorantraniliprole, transcriptome assembly and tag-based digital gene expression (DGE system were performed using Illumina HiSeq™ 2000. The transcriptome analysis of the susceptible strain (SS provided 45,231 unigenes (with the size ranging from 200 bp to 13,799 bp, which would be efficient for analyzing the differences in different chlorantraniliprole-resistant P. xylostella stains. DGE analysis indicated that a total of 1215 genes (189 up-regulated and 1026 down-regulated were gradient differentially expressed among the susceptible strain (SS and different chlorantraniliprole-resistant P. xylostella strains, including low-level resistance (GXA, moderate resistance (LZA and high resistance strains (HZA. A detailed analysis of gradient differentially expressed genes elucidated the existence of a phase-dependent divergence of biological investment at the molecular level. The genes related to insecticide resistance, such as P450, GST, the ryanodine receptor, and connectin, had different expression profiles in the different chlorantraniliprole-resistant DGE libraries, suggesting that the genes related to insecticide resistance are involved in P. xylostella resistance development against chlorantraniliprole. To confirm the results from the DGE, the expressional profiles of 4 genes related to insecticide resistance were further validated by qRT-PCR analysis. CONCLUSIONS: The obtained transcriptome information provides large gene resources available for further studying the resistance development of P. xylostella to pesticides. The DGE data

Suppression of radiation mutagenesis by dactinomycin in Chinese hamster cells

International Nuclear Information System (INIS)

Tokita, N.; Capenter, S.G.; Chen, D.J.; MacInnes, M.A.; Raju, M.R.

1985-01-01

Dactinomycin (AMD) suppression of radiation mutagenesis was investigated using an in vitro mutation assay (6-thioguanine resistance) in Chinese hamster ovary cells. Cells were exposed to acute single doses of x rays followed by 1 hr-treatment with 0.1 or 1 μg/ml AMD. The cell survival curves plotted as a function of x-ray doses were similar for radiation alone and radiation plus AMD. The results suggest that AMD treatment was only slightly mutagenic, however, when given immediately after irradiation, it suppressed radiatiion mutagenesis at higher x-ray dose regions (below 10% survival levels). Higher AMD concentrations appeared more suppressive than lower concentrations. Dose-response data analyzed based on Poisson distribution models suggest the stochastic dependence of x-ray mutagenesis and AMD cytotoxity

Development of Magnetorheological Resistive Exercise Device for Rowing Machine

Directory of Open Access Journals (Sweden)

Vytautas Grigas

2016-01-01

Full Text Available Training equipment used by professional sportsmen has a great impact on their sport performance. Most universal exercisers may help only to improve the general physical condition due to the specific kinematics and peculiar resistance generated by their loading units. Training of effective techniques and learning of psychomotor skills are possible only when exercisers conform to the movements and resistance typical for particular sports kinematically and dynamically. Methodology of developing a magnetorheological resistive exercise device for generating the desired law of passive resistance force and its application in a lever-type rowing machine are described in the paper. The structural parameters of a controllable hydraulic cylinder type device were found by means of the computational fluid dynamics simulation performed by ANSYS CFX software. Parameters describing the magnetorheological fluid as non-Newtonian were determined by combining numerical and experimental research of the resistance force generated by the original magnetorheological damper. A structural scheme of the device control system was developed and the variation of the strength of magnetic field that affects the magnetorheological fluid circulating in the device was determined, ensuring a variation of the resistance force on the oar handle adequate for the resistance that occurs during a real boat rowing stroke.

Nicotine suppresses the neurotoxicity by MPP+/MPTP through activating α7nAChR/PI3K/Trx-1 and suppressing ER stress.

Science.gov (United States)

Cai, Yanxue; Zhang, Xianwen; Zhou, Xiaoshuang; Wu, Xiaoli; Li, Yanhui; Yao, Jianhua; Bai, Jie

2017-03-01

Parkinson's disease (PD) is a neurodegenerative disease. Nicotine has been reported to have the role in preventing Parkinson's disease. However, its mechanism is still unclear. In present study we found that nicotine suppressed 1-methyl-4-phenylpyridinium ion(MPP + ) toxicity in PC12 cells by MTT assay. The expression of thioredoxin-1(Trx-1) was decreased by MPP + , which was restored by nicotine. The nicotine suppressed expressions of Glucose-regulated protein 78(GRP78/Bip) and C/EBP homologous protein (CHOP) induced by MPP + . The methyllycaconitine (MLA), the inhibitor of α7nAChR and LY294002, the inhibitor of phosphatidylinositol 3-kinase (PI3K) blocked the suppressions of above molecules, respectively. Consistently, pretreatment with nicotine ameliorated the motor ability, restored the declines of Trx-1 and tyrosine hydroxylase (TH), and suppressed the expressions of Bip and CHOP induced by 1-Methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. Our results suggest that nicotine plays role in resisting MPP + /MPTP neurotoxicity through activating the α7nAChR/PI3K/Trx-1 pathway and suppressing ER stress. Copyright © 2017 Elsevier B.V. All rights reserved.

[Role of oral cavity colonization resistance in dental caries development].

Science.gov (United States)

Petrushanko, T A; Chereda, V V; Loban', G A

2013-01-01

Colonization resistance is one of local immunity mechanisms determined by a combination of factors that inhibit the adhesion and growth of mucous membrane bacteria. We examined patients with different levels of caries intensity assessing oral mucosa colonization resistance by our own method. Caries development resulted in changes of colonization resistance with the increased rate of inhibition of the oral mucosa colonization resistance barrier.

NF-κB RelA renders tumor-associated macrophages resistant to and capable of directly suppressing CD8+ T cells for tumor promotion.

Science.gov (United States)

Li, Liwen; Han, Lei; Sun, Fan; Zhou, Jingjiao; Ohaegbulam, Kim C; Tang, Xudong; Zang, Xingxing; Steinbrecher, Kris A; Qu, Zhaoxia; Xiao, Gutian

2018-01-01

Activation of the inflammatory transcription factor NF-κB in tumor-associated macrophages (TAMs) is assumed to contribute to tumor promotion. However, whether and how NF-κB drives the antitumor macrophages to become pro-tumorigenic have not been determined in any cancer type yet. Similarly, how TAMs repress CD8 + cytotoxic T lymphocytes (CTLs) remains largely unknown, although their importance in regulatory T (Treg) cell regulation and tumor promotion has been well appreciated. Here, using an endogenous lung cancer model we uncover a direct crosstalk between TAMs and CTLs. TAMs suppress CTLs through the T-cell inhibitory molecule B7x (B7-H4/B7S1) in a cell-cell contact manner, whereas CTLs kill TAMs in a tumor antigen-specific manner. Remarkably, TAMs secrete the known T-cell suppressive cytokine interleukin-10 (IL-10) to activate, but not to repress, CTLs. Notably, one major role of cell-intrinsic NF-κB RelA is to drive TAMs to suppress CTLs for tumor promotion. It induces B7x expression in TAMs directly, and restricts IL-10 expression indirectly by repressing expression of the NF-κB cofactor Bcl3 and subsequent Bcl3/NF-κB1-mediated transcription of IL-10. It also renders TAMs resistant to CTLs by up-regulating anti-apoptotic genes. These studies help understand how immunity is shaped in lung tumorigenesis, and suggest a RelA-targeted immunotherapy for this deadliest cancer.

Novel genetic factors involved in resistance to Bacillus thuringiensis in Plutella xylostella.

Science.gov (United States)

Ayra-Pardo, C; Raymond, B; Gulzar, A; Rodríguez-Cabrera, L; Morán-Bertot, I; Crickmore, N; Wright, D J

2015-12-01

The widespread and sustainable exploitation of the entomopathogen Bacillus thuringiensis (Bt) in pest control is threatened by the evolution of resistance. Although resistance is often associated with loss of binding of the Bt toxins to the insect midgut cells, other factors have been implicated. Here we used suppressive subtractive hybridization and gene expression suppression to identify additional molecular components involved in Bt-resistance in Plutella xylostella. We isolated transcripts from genes that were differentially expressed in the midgut of larvae from a resistant population, following ingestion of a Bt kurstaki HD1 strain-based commercial formulation (DiPel), and compared with a genetically similar susceptible population. Quantitative real-time polymerase-chain reaction (RT-PCR) analysis confirmed the differential basal expression of a subset of these genes. Gene expression suppression of three of these genes (P. xylostella cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1, stromal cell-derived factor 2-like 1 and hatching enzyme-like 1) significantly increased the pathogenicity of HD1 to the resistant population. In an attempt to link the multitude of factors reportedly influencing resistance to Bt with the well-characterized loss of toxin binding, we also considered Bt-resistance models in P. xylostella and other insects. © 2015 The Royal Entomological Society.

Chemical suppressors of mlo-mediated powdery mildew resistance

Science.gov (United States)

Wu, Hongpo; Kwaaitaal, Mark; Strugala, Roxana; Schaffrath, Ulrich; Bednarek, Paweł

2017-01-01

Loss-of-function of barley mildew locus o (Mlo) confers durable broad-spectrum penetration resistance to the barley powdery mildew pathogen, Blumeria graminis f. sp. hordei (Bgh). Given the importance of mlo mutants in agriculture, surprisingly few molecular components have been identified to be required for this type of resistance in barley. With the aim to identify novel cellular factors contributing to mlo-based resistance, we devised a pharmacological inhibitor screen. Of the 41 rationally chosen compounds tested, five caused a partial suppression of mlo resistance in barley, indicated by increased levels of Bgh host cell entry. These chemicals comprise brefeldin A (BFA), 2′,3′-dideoxyadenosine (DDA), 2-deoxy-d-glucose, spermidine, and 1-aminobenzotriazole. Further inhibitor analysis corroborated a key role for both anterograde and retrograde endomembrane trafficking in mlo resistance. In addition, all four ribonucleosides, some ribonucleoside derivatives, two of the five nucleobases (guanine and uracil), some guanine derivatives as well as various polyamines partially suppress mlo resistance in barley via yet unknown mechanisms. Most of the chemicals identified to be effective in partially relieving mlo resistance in barley also to some extent compromised powdery mildew resistance in an Arabidopsis mlo2 mlo6 double mutant. In summary, our study identified novel suppressors of mlo resistance that may serve as valuable probes to unravel further the molecular processes underlying this unusual type of disease resistance. PMID:29127104

miR-612 suppresses the stemness of liver cancer via Wnt/β-catenin signaling

Energy Technology Data Exchange (ETDEWEB)

Tang, Jun [Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032 (China); Tao, Zhong-Hua [Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai 200032 (China); Wen, Duo; Wan, Jin-Liang; Liu, Dong-Li; Zhang, Shu; Cui, Jie-Feng; Sun, Hui-Chuan; Wang, Lu [Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032 (China); Zhou, Jian; Fan, Jia [Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032 (China); Institute of Biomedical Sciences of Fudan University, Shanghai 200032 (China); Wu, Wei-Zhong, E-mail: wu.weizhong@zs-hospital.sh.cn [Liver Cancer Institute and Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032 (China)

2014-04-25

Highlights: • miR-612 suppresses tumorsphere and clone formation of HCC cells. • miR-612 reduces drug resistance of HCC cells. • miR-612 suppresses tumorigenesis of HCC in NOD/SCID mice. • miR-612 inhibits an invasive frontier of HCC xenografts. • miR-612 suppresses Wnt/β-catenin signaling. - Abstract: Previous research showed that microRNA-612 (miR-612) has inhibitory effects on cell proliferation, migration, invasion, and metastasis of hepatocellular carcinoma (HCC). AKT2 was confirmed to be a direct target of miR-612, through which the epithelial–mesenchymal transition (EMT) and metastasis of HCC were inhibited. Our present findings reveal that miR-612 is able to suppress the stemness of HCC by reducing the number and size of tumorspheres as well as clone formation in soft agar, and to relieve drug resistance to cisplatin and 5-fluorouracil. In addition, miR-612 hampered the capacity of tumorigenesis in NOD/SCID mice and redistributed the tumor invasive frontier of miR-612-modulating cells. Finally, our findings suggest that Wnt/β-catenin signaling is required in the regulation of EMT-associated stem cell-like traits by miR-612.

17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression.

Science.gov (United States)

Xiao, Y; Guan, J

2015-01-01

Flavopiridol, a cyclin-dependent kinase inhibitor (CDKI), shows promising anti-tumor activity in hematologic malignancies. However, Flavopiridol-induced protective autophagy may lead to drug resistance. Here we found that Hsp90 inhibitor 17-AAG can sensitize mantle cell lymphoma (MCL) cells to flavopiridol by suppressing flavopiridol-triggered protective autophagy. The suppressing effect of 17-AAG on autophgy was mediated by Beclin1 degradation and ERK inactivation. Furthermore, 17-AAG enhanced flavopiridol-induced apoptosis and growth suppression in MCL cells. Our study may provide some insights into CDKI -targeted chemotherapies.

Sodium fire suppression

International Nuclear Information System (INIS)

Malet, J.C.

1979-01-01

Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

Sodium fire suppression

Energy Technology Data Exchange (ETDEWEB)

Malet, J C [DSN/SESTR, Centre de Cadarache, Saint-Paul-lez-Durance (France)

1979-03-01

Ignition and combustion studies have provided valuable data and guidelines for sodium fire suppression research. The primary necessity is to isolate the oxidant from the fuel, rather than to attempt to cool the sodium below its ignition temperature. Work along these lines has led to the development of smothering tank systems and a dry extinguishing powder. Based on the results obtained, the implementation of these techniques is discussed with regard to sodium fire suppression in the Super-Phenix reactor. (author)

Development of flame retardant, radiation resistant insulating materials

Energy Technology Data Exchange (ETDEWEB)

Hagiwara, M.

1984-01-01

On the cables used for nuclear power stations, in particular those ranked as IE class, flame retardation test, simulated LOCA environment test, radiation resistance test and so on are imposed. The results of the evaluation of performance by these tests largely depend on the insulating materials mainly made of polymers. Ethylene propylene copolymer rubber has been widely used as cable insulator because of its electrical characteristics, workability, economy and relatively good radiation resistance, but it is combustible, therefore, in the practical use, it is necessary to make it fire resistant. The author et al. have advanced the research on the molecular design of new fire retarding materials, and successfully developed acenaphthylene bromide condensate, which is not only fire resistant but also effective for improving radiation resistance. The condition of flame retardant, radiation resistant auxiliary agents is explained, and there are additive type and reaction type in fire retarding materials. The synthesis of acenaphthylene bromide condensate and its effect of giving flame retardant and radiation resistant properties are reported. The characteristics of the cables insulated with the flame retardant ethylene propylene rubber containing acenaphthylene bromide condensate were tested, and the results are shown. (Kako, I.).

Development of large area resistive electrodes for ATLAS NSW MicroMEGAS

CERN Document Server

Ochi, Atsuhiko; The ATLAS collaboration

2015-01-01

MicroMegas with resistive anode will be used for the NSW upgrade of the ATLAS experiment at LHC. The resistive electrode is one of key technology for MPGDs to prevent sparks. Large area resistive electrodes for the MM have been developed using two different technology; screen printing and carbon sputtering. Maximum size of each resistive foil is 45cm x 220cm with printed pattern of 425 micron pitch strips. Those technologies are also suitable to mass production. The prototypes of series production model have been produced successfully. We will report the development and production status and test results of the resistive MicroMegas.

WILDFIRE IGNITION RESISTANCE ESTIMATOR WIZARD SOFTWARE DEVELOPMENT REPORT

Energy Technology Data Exchange (ETDEWEB)

Phillips, M.; Robinson, C.; Gupta, N.; Werth, D.

2012-10-10

This report describes the development of a software tool, entitled “WildFire Ignition Resistance Estimator Wizard” (WildFIRE Wizard, Version 2.10). This software was developed within the Wildfire Ignition Resistant Home Design (WIRHD) program, sponsored by the U. S. Department of Homeland Security, Science and Technology Directorate, Infrastructure Protection & Disaster Management Division. WildFIRE Wizard is a tool that enables homeowners to take preventive actions that will reduce their home’s vulnerability to wildfire ignition sources (i.e., embers, radiant heat, and direct flame impingement) well in advance of a wildfire event. This report describes the development of the software, its operation, its technical basis and calculations, and steps taken to verify its performance.

Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum.

Science.gov (United States)

Ellis, Giovanina M; Huang, Sharon; Hitti, Jane; Frenkel, Lisa M

2011-11-01

Compare the risk of HIV drug resistance in women stopping suppressive nelfinavir (NFV)-based or Nevirapine (NVP)-based antiretroviral therapy (ART) after pregnancy. Specimens collected after stopping ART were tested for drug resistance by an oligonucleotide ligation assay and consensus sequencing. When postpartum drug resistance was detected, specimens obtained at study entry and during ART were evaluated. Sixteen of 38 women with ART-induced suppression of viral replication suspended ART postpartum. Resistance mutations were detected in 75% who stopped NFV-ART and in 50% who stopped NVP-ART. M184V, associated with Lamivudine resistance, was more frequent among those randomized to NFV-ART compared with NVP-ART (6 of 8 versus 1 of 8; P = 0.04), and nonnucleoside reverse transcriptase inhibitor resistance was detected in 4 of 8 stopping NVP-ART. HIV drug resistance was frequently observed among women who stopped suppressive NVP-ART or NFV-ART postpartum. This suggests that NFV-ART may have suboptimal potency, that staggering discontinuation of NVP-ART may be warranted, and/or ART adherence may be lax in women who choose to stop ART postpartum.

Endoplasmic reticulum stress regulates inflammation and insulin resistance in skeletal muscle from pregnant women.

Science.gov (United States)

Liong, Stella; Lappas, Martha

2016-04-15

Sterile inflammation and infection are key mediators of inflammation and peripheral insulin resistance associated with gestational diabetes mellitus (GDM). Studies have shown endoplasmic reticulum (ER) stress to induce inflammation and insulin resistance associated with obesity and type 2 diabetes, however is paucity of studies investigating the effects of ER stress in skeletal muscle on inflammation and insulin resistance associated with GDM. ER stress proteins IRE1α, GRP78 and XBP-1s were upregulated in skeletal muscle of obese pregnant women, whereas IRE1α was increased in GDM women. Suppression of ER stress, using ER stress inhibitor tauroursodeoxycholic acid (TUDCA) or siRNA knockdown of IRE1α and GRP78, significantly downregulated LPS-, poly(I:C)- or IL-1β-induced production of IL-6, IL-8, IL-1β and MCP-1. Furthermore, LPS-, poly(I:C)- or TNF-α-induced insulin resistance was improved following suppression of ER stress, by increasing insulin-stimulated phosphorylation of IR-β, IRS-1, GLUT-4 expression and glucose uptake. In summary, our inducible obesity and GDM-like models suggests that the development of GDM may be involved in activating ER stress-induced inflammation and insulin resistance in human skeletal muscle. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Baicalein suppresses the androgen receptor (AR)-mediated prostate cancer progression via inhibiting the AR N-C dimerization and AR-coactivators interaction.

Science.gov (United States)

Xu, Defeng; Chen, Qiulu; Liu, Yalin; Wen, Xingqiao

2017-12-01

Androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and progression. Androgen deprivation therapy with antiandrogens to reduce androgen biosynthesis or prevent androgens from binding to AR are widely used to suppress AR-mediated PCa growth. However, most of ADT may eventually fail with development of the castration resistance after 12-24 months. Here we found that a natural product baicalein can effectively suppress the PCa progression via targeting the androgen-induced AR transactivation with little effect to AR protein expression. PCa cells including LNCaP, CWR22Rv1, C4-2, PC-3, and DU145, were treated with baicalein and luciferase assay was used to evaluate their effect on the AR transactivation. Cell growth and IC 50 were determined by MTT assay after 48 hrs treatment. RT-PCR was used to evaluate the mRNA levels of AR target genes including PSA, TMPRSS2, and TMEPA1. Western blot was used to determine AR and PSA protein expression. The natural product of baicalein can selectively inhibit AR transactivation with little effect on the other nuclear receptors, including ERα, and GR. At a low concentration, 2.5 μM of baicalein effectively suppresses the growth of AR-positive PCa cells, and has little effect on AR-negative PCa cells. Mechanism dissection suggest that baicalein can suppress AR target genes (PSA, TMPRSS2, and TMEPA1) expression in both androgen responsive LNCaP cells and castration resistant CWR22Rv1 cells, that may involve the inhibiting the AR N/C dimerization and AR-coactivators interaction. Baicalein may be developed as an effective anti-AR therapy via its ability to inhibit AR transactivation and AR-mediated PCa cell growth.

Methods for quantifying adipose tissue insulin resistance in overweight/obese humans.

Science.gov (United States)

Ter Horst, K W; van Galen, K A; Gilijamse, P W; Hartstra, A V; de Groot, P F; van der Valk, F M; Ackermans, M T; Nieuwdorp, M; Romijn, J A; Serlie, M J

2017-08-01

Insulin resistance of adipose tissue is an important feature of obesity-related metabolic disease. However, assessment of lipolysis in humans requires labor-intensive and expensive methods, and there is limited validation of simplified measurement methods. We aimed to validate simplified methods for the quantification of adipose tissue insulin resistance against the assessment of insulin sensitivity of lipolysis suppression during hyperinsulinemic-euglycemic clamp studies. We assessed the insulin-mediated suppression of lipolysis by tracer-dilution of [1,1,2,3,3- 2 H 5 ]glycerol during hyperinsulinemic-euglycemic clamp studies in 125 overweight or obese adults (85 men, 40 women; age 50±11 years; body mass index 38±7 kg m -2 ). Seven indices of adipose tissue insulin resistance were validated against the reference measurement method. Low-dose insulin infusion resulted in suppression of the glycerol rate of appearance ranging from 4% (most resistant) to 85% (most sensitive), indicating a good range of adipose tissue insulin sensitivity in the study population. The reference method correlated with (1) insulin-mediated suppression of plasma glycerol concentrations (r=0.960, PInsulin Resistance (Adipo-IR) index (fasting plasma insulin-NEFA product; r=-0.526, Pinsulin-glycerol product (r=-0.467, PInsulin Resistance Index (fasting plasma insulin-basal lipolysis product; r=0.460, PInsulin Sensitivity Check Index (QUICKI)-NEFA index (r=0.621, Pinsulin resistance (area under the curve ⩾0.801, Pinsulin sensitivity (that is, the antilipolytic action of insulin) can be reliably quantified in overweight and obese humans by simplified index methods. The sensitivity and specificity of the Adipo-IR index and the fasting plasma insulin-glycerol product, combined with their simplicity and acceptable agreement, suggest that these may be most useful in clinical practice.

Resistance monitoring and cross-resistance role of CYP6CW1 between buprofezin and pymetrozine in field populations of Laodelphax striatellus (Fallén).

Science.gov (United States)

Zhang, Yueliang; Han, Yangchun; Liu, Baosheng; Yang, Qiong; Guo, Huifang; Liu, Zewen; Wang, Lihua; Fang, Jichao

2017-11-07

Monitoring resistance and investigating insecticide resistance mechanisms are necessary for controlling the small brown planthopper, Laodelphax striatellus. The susceptibility to four common insecticides of L. striatellus collected from Jiangsu, Anhui, Zhejiang and Jilin provinces of China in 2015 was monitored. The results showed that all field populations remained susceptible to chlorpyrifos and thiamethoxam with resistance ratios (RRs) of 2.3- to 9.5 and 1.6- to 3.3, respectively, while the insects had developed moderate pymetrozine resistance with RRs of 18.7 to 34.5. Resistance against buprofezin had developed to an alarmingly high level in three southeastern provinces of China with RRs of 108.8 to 156.1, but in Jilin it had an RR of only 26.6. Moreover, in line with both the buprofezin and pymetrozine resistance levels, we found LsCYP6CW1 to be over-expressed in all field L. striatellus populations, which indicated that it might be important for cross-resistance between buprofezin and pymetrozine. RNA interference (RNAi) ingestion resulted in the effective suppression of LsCYP6CW1 expression, and significantly increased susceptibility to both buprofezin and pymetrozine compared with the control, which further confirmed that overexpression of LsCYP6CW1 was involved in the cross-resistance to buprofezin and pymetrozine in field L. Striatellus populations.

Development of a novel severe triple allergen asthma model in mice which is resistant to dexamethasone and partially resistant to TLR7 and TLR9 agonist treatment.

Directory of Open Access Journals (Sweden)

Matthias J Duechs

Full Text Available Severe asthma is characterised by persistent inflammation, hyperreactivity and remodeling of the airways. No efficient treatment is available, this is particularly the case for steroid resistant phenotypes. Our aim therefore was to develop a preclinical model showing characteristics of severe human asthma including steroid insensitivity. Mice were first sensitized with ovalbumin, extracts of cockroach or house dust mite followed by a challenge period of seven weeks. Further to this, an additional group of mice was sensitized with all three allergens and then challenged with allergen alternating weekly between allergens. All three allergens applied separately to the mice induced comparably strong Th2-type airway inflammation, airway hyperreactivity and airway remodeling, which was characterised by fibrosis and increased smooth muscle thickness. In contrast, application of all three allergens together resulted in a greater Th2 response and increased airway hyperreactivity and a stronger albeit not significant remodeling phenotype compared to using HDM or CRA. In this triple allergen model dexamethasone application, during the last 4 weeks of challenge, showed no suppressive effects on any of these parameters in this model. In contrast, both TLR7 agonist resiquimod and TLR9 agonist CpG-ODN reduced allergen-specific IgE, eosinophils, and collagen I in the lungs. The TLR9 agonist also reduced IL-4 and IL-5 whilst increasing IFN-γ and strongly IL-10 levels in the lungs, effects not seen with the TLR7 agonist. However, neither TLR agonist had any effect on airway hyperreactivity and airway smooth muscle mass. In conclusion we have developed a severe asthma model, which is steroid resistant and only partially sensitive to TLR7 and TLR9 agonist treatment. This model may be particular useful to test new potential therapeutics aiming at treating steroid resistant asthma in humans and investigating the underlying mechanisms responsible for steroid

Hyperleptinemia is required for the development of leptin resistance.

Directory of Open Access Journals (Sweden)

Zachary A Knight

2010-06-01

Full Text Available Leptin regulates body weight by signaling to the brain the availability of energy stored as fat. This negative feedback loop becomes disrupted in most obese individuals, resulting in a state known as leptin resistance. The physiological causes of leptin resistance remain poorly understood. Here we test the hypothesis that hyperleptinemia is required for the development of leptin resistance in diet-induced obese mice. We show that mice whose plasma leptin has been clamped to lean levels develop obesity in response to a high-fat diet, and the magnitude of this obesity is indistinguishable from wild-type controls. Yet these obese animals with constant low levels of plasma leptin remain highly sensitive to exogenous leptin even after long-term exposure to a high fat diet. This shows that dietary fats alone are insufficient to block the response to leptin. The data also suggest that hyperleptinemia itself can contribute to leptin resistance by downregulating cellular response to leptin as has been shown for other hormones.

Targeting Pin1 by inhibitor API-1 regulates microRNA biogenesis and suppresses hepatocellular carcinoma development.

Science.gov (United States)

Pu, Wenchen; Li, Jiao; Zheng, Yuanyuan; Shen, Xianyan; Fan, Xin; Zhou, Jian-Kang; He, Juan; Deng, Yulan; Liu, Xuesha; Wang, Chun; Yang, Shengyong; Chen, Qiang; Liu, Lunxu; Zhang, Guolin; Wei, Yu-Quan; Peng, Yong

2018-01-30

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, but there are few effective treatments. Aberrant microRNA (miRNA) biogenesis is correlated with HCC development. We previously demonstrated that peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) participates in miRNA biogenesis and is a potential HCC treatment target. However, how Pin1 modulates miRNA biogenesis remains obscure. Here, we present in vivo evidence that Pin1 overexpression is directly linked to the development of HCC. Administration with the Pin1 inhibitor (API-1), a specific small molecule targeting Pin1 peptidyl-prolyl isomerase domain and inhibiting Pin1 cis-trans isomerizing activity, suppresses in vitro cell proliferation and migration of HCC cells. But API-1-induced Pin1 inhibition is insensitive to HCC cells with low Pin1 expression and/or low exportin-5 (XPO5) phosphorylation. Mechanistically, Pin1 recognizes and isomerizes the phosphorylated serine-proline motif of phosphorylated XPO5 and passivates phosphorylated XPO5. Pin1 inhibition by API-1 maintains the active conformation of phosphorylated XPO5 and restores XPO5-driven precursor miRNA nuclear-to-cytoplasm export, activating anticancer miRNA biogenesis and leading to both in vitro HCC suppression and HCC suppression in xenograft mice. Experimental evidence suggests that Pin1 inhibition by API-1 up-regulates miRNA biogenesis by retaining active XPO5 conformation and suppresses HCC development, revealing the mechanism of Pin1-mediated miRNA biogenesis and unequivocally supporting API-1 as a drug candidate for HCC therapy, especially for Pin1-overexpressing, extracellular signal-regulated kinase-activated HCC. (Hepatology 2018). © 2018 by the American Association for the Study of Liver Diseases.

Ideal and conventional feedback systems for RWM suppression

International Nuclear Information System (INIS)

Pustovitov, V.D.

2002-01-01

Feedback suppression of resistive wall modes (RWM) is studied analytically using a model based on a standard cylindrical approximation. Two feedback systems are compared: 'ideal', creating only the field necessary for RMW suppression, and 'conventional', like that used in the DIII-D tokamak and considered as a candidate for ITER. The widespread opinion that the feedback with poloidal sensors is better than that with radial sensors is discussed. It is shown that the 'conventional' feedback with radial sensors can be effective only in a limited range, while using the input signal from internal poloidal sensors allows easy fulfilment of the stability criterion. This is a property of the 'conventional' feedback, but the 'ideal' feedback would stabilise RWM in both cases. (author)

Effect of oxygen defects on transport properties and Tc of YBa2Cu3O6+x: Displacement energy for plane and chain oxygen and implications for irradiation-induced resistivity and Tc suppression

International Nuclear Information System (INIS)

Tolpygo, S.K.; Lin, J.; Gurvitch, M.; Hou, S.Y.; Phillips, J.M.

1996-01-01

The effect of electron irradiation with energy from 20 to 120 keV on the resistivity, Hall coefficient, and superconducting critical temperature T c of YBa 2 Cu 3 O 6+x thin films has been studied. The threshold energy of incident electrons for T c suppression has been found, and the displacement energy for oxygen in CuO 2 planes has been evaluated as 8.4 eV for irradiation along the c axis. The kinetics of production of the in-plane oxygen vacancies has been studied and found to be governed by athermal recombination of vacancy-interstitial pairs. The evaluated recombination volume constitutes about 21 unit cells. The increase in the T-linear resistivity slope and Hall coefficient at unchanged T c was observed in irradiations with subthreshold incident energies and was ascribed to the effect of chain oxygen displacements. The upper limit on the displacement energy for chain oxygen has been estimated as 2.8 eV. In x=0.9 samples the T c suppression by in-plane oxygen defects and increase in residual resistivity have been found to be, respectively, -280 K and 1.5 mΩcm per defect in the unit cell. It is shown that T c suppression by in-plane oxygen defects is a universal function of the transport impurity scattering rate and can be described qualitatively by pair-breaking theory for d-wave superconductors with nonmagnetic potential scatterers. Evaluation of scattering and pair-breaking rates as well as the scattering cross section and potential is given. A comparison of the influence of in-plane oxygen defects on transport properties with that of other in-plane defects, such as Zn and Ni substitutions for Cu, is also made. copyright 1996 The American Physical Society

Alpha-1 Antitrypsin Prevents the Development of Preeclampsia Through Suppression of Oxidative Stress.

Science.gov (United States)

Feng, Yaling; Xu, Jianjuan; Zhou, Qin; Wang, Rong; Liu, Nin; Wu, Yanqun; Yuan, Hua; Che, Haisha

2016-01-01

Preeclampsia (PE) and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT) played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS, and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

Alpha-1 antitrypsin prevents the development of preeclampsia through suppression of oxidative stress

Directory of Open Access Journals (Sweden)

Yaling eFeng

2016-05-01

Full Text Available Preeclampsia (PE and its complications have become the leading cause of maternal and fetal morbidity and mortality in the world. And the development of PE is still barely predictable and thus challenging to prevent and manage clinically. Oxidative stress contributes to the development of the disease. Our previous study demonstrated that exogenous Alpha-1 antitrypsin (AAT played a cytoprotective role in vascular endothelial cell by suppressing oxidative stress. In this study, we aim to investigate whether AAT contributes to the development of PE, and to identify the mechanism behind these effects. We found that AAT levels were significantly decreased in placenta tissues from women with PE compared that of healthy women. Notably, we demonstrate that AAT injection is able to relieve the high blood pressure and reduce urine protein levels in a dose-dependent manner in PE mice. In addition, our results showed that AAT injection exhibited an anti-oxidative stress role by significantly reducing PE mediated-upregulation of ROS, MMP9 and MDA, and increasing the levels of SOD, eNOS and GPx with increased dosage of AAT. Furthermore, we found that AAT injection inactivated PE mediated activation of PAK/STAT1/p38 signaling. These findings were confirmed in human samples. In conclusion, our study suggests that exogenous AAT injection increases the antioxidants and suppresses oxidative stress, and subsequent prevention of PE development through inactivation of STAT1/p38 signaling. Thus, AAT would become a potential strategy for PE therapy.

Development of heat-resistant magnetic sensor

International Nuclear Information System (INIS)

Takaya, Shigeru; Arakawa, Hisashi; Keyakida, Satoshi

2013-01-01

A heat-resistant flux gate magnetic sensor has been developed. Permendur, which has high Curie point, is employed as the magnetic core material and the detection method of the external magnetic field is modified. The characteristics of the developed magnetic sensor up to 500degC were evaluated. The sensor output increased linearly with the external magnetic field in the range of ±5 G and the standard deviation at 500degC was about 0.85G. (author)

Overcoming cetuximab resistance in Ewing's sarcoma by inhibiting lactate dehydrogenase-A.

Science.gov (United States)

Fu, Jiaxin; Jiang, Han; Wu, Chenxuan; Jiang, Yi; Xiao, Lianping; Tian, Yonggang

2016-07-01

Ewing's sarcoma, the second most common type of malignant bone tumor, generally occurs in children and young adults. The current treatment of Ewing's sarcoma comprises systemic anti‑cancer chemotherapy with complete surgical resection. However, the majority of patients with Ewing's sarcoma develop resistance to chemotherapy. The present study revealed an oncogenic role of lactate dehydrogenase‑A (LDHA) in the resistance of Ewing's sarcoma to cetuximab. LDHA was shown to be upregulated at the protein and mRNA level in cetuximab‑resistant Ewing's sarcoma tissues and a cell line. In addition, a link between LDHA‑induced glycolysis and cetuximab resistance in Ewing's sarcoma cells was revealed. Of note, inhibition of LDHA by either small interfering RNA or LDHA inhibitor oxamate significantly re‑sensitized cetuximab‑resistant cells to cetuximab. Combined treatment with LDHA inhibitor and cetuximab synergistically reduced the viability of cetuximab-resistant cells through the suppression of LDHA. The present study revealed a novel mechanism of cetuximab resistance from the perspective of cancer‑cell metabolism and provided a sensitization approach, which may aid in the development of anti-chemoresistance strategies for the treatment of cetuximab-resistant Ewing's sarcoma.

Distinguishing among potential mechanisms of singleton suppression.

Science.gov (United States)

Gaspelin, Nicholas; Luck, Steven J

2018-04-01

Previous research has revealed that people can suppress salient stimuli that might otherwise capture visual attention. The present study tests between 3 possible mechanisms of visual suppression. According to first-order feature suppression models , items are suppressed on the basis of simple feature values. According to second-order feature suppression models , items are suppressed on the basis of local discontinuities within a given feature dimension. According to global-salience suppression models , items are suppressed on the basis of their dimension-independent salience levels. The current study distinguished among these models by varying the predictability of the singleton color value. If items are suppressed by virtue of salience alone, then it should not matter whether the singleton color is predictable. However, evidence from probe processing and eye movements indicated that suppression is possible only when the color values are predictable. Moreover, the ability to suppress salient items developed gradually as participants gained experience with the feature that defined the salient distractor. These results are consistent with first-order feature suppression models, and are inconsistent with the other models of suppression. In other words, people primarily suppress salient distractors on the basis of their simple features and not on the basis of salience per se. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Suppression of the auxin response pathway enhances susceptibility to Phytophthora cinnamomi while phosphite-mediated resistance stimulates the auxin signalling pathway

Science.gov (United States)

2014-01-01

Background Phytophthora cinnamomi is a devastating pathogen worldwide and phosphite (Phi), an analogue of phosphate (Pi) is highly effective in the control of this pathogen. Phi also interferes with Pi starvation responses (PSR), of which auxin signalling is an integral component. In the current study, the involvement of Pi and the auxin signalling pathways in host and Phi-mediated resistance to P. cinnamomi was investigated by screening the Arabidopsis thaliana ecotype Col-0 and several mutants defective in PSR and the auxin response pathway for their susceptibility to this pathogen. The response to Phi treatment was also studied by monitoring its effect on Pi- and the auxin response pathways. Results Here we demonstrate that phr1-1 (phosphate starvation response 1), a mutant defective in response to Pi starvation was highly susceptible to P. cinnamomi compared to the parental background Col-0. Furthermore, the analysis of the Arabidopsis tir1-1 (transport inhibitor response 1) mutant, deficient in the auxin-stimulated SCF (Skp1 − Cullin − F-Box) ubiquitination pathway was also highly susceptible to P. cinnamomi and the susceptibility of the mutants rpn10 and pbe1 further supported a role for the 26S proteasome in resistance to P. cinnamomi. The role of auxin was also supported by a significant (P < 0.001) increase in susceptibility of blue lupin (Lupinus angustifolius) to P. cinnamomi following treatment with the inhibitor of auxin transport, TIBA (2,3,5-triiodobenzoic acid). Given the apparent involvement of auxin and PSR signalling in the resistance to P. cinnamomi, the possible involvement of these pathways in Phi mediated resistance was also investigated. Phi (especially at high concentrations) attenuates the response of some Pi starvation inducible genes such as AT4, AtACP5 and AtPT2 in Pi starved plants. However, Phi enhanced the transcript levels of PHR1 and the auxin responsive genes (AUX1, AXR1and AXR2), suppressed the primary root

Managing for soil health can suppress pests

Directory of Open Access Journals (Sweden)

Amanda Hodson

2016-08-01

Full Text Available A “healthy” soil can be thought of as one that functions well, both agronomically and ecologically, and one in which soil biodiversity and crop management work in synergy to suppress pests and diseases. UC researchers have pioneered many ways of managing soil biology for pest management, including strategies such as soil solarization, steam treatment and anaerobic soil disinfestation, as well as improvements on traditional methods, such as reducing tillage, amending soil with organic materials, and cover cropping. As managing for soil health becomes more of an explicit focus due to restrictions on the use of soil fumigants, integrated soil health tests will be needed that are validated for use in California. Other research needs include breeding crops for disease resistance and pest suppressive microbial communities as well as knowledge of how beneficial organisms influence plant health.

Ethanol, vinegar and Origanum vulgare oil vapour suppress the development of anthracnose rot in tomato fruit.

Science.gov (United States)

Tzortzakis, Nikos G

2010-08-15

Anthracnose rot (Colletotrichum coccodes) development in vitro or in tomato (Lycopersicon esculentum L.) fruit was evaluated after treatment with absolute ethyl alcohol (AEA), vinegar (VIN), chlorine (CHL) or origanum oil (ORI) and storage at 12 degrees C and 95% relative humidity during or following exposure to the volatiles. Fruit treated with vapours reduced fungal spore germination/production, but in the case of AEA- and VIN-treated fruits, fungal mycelium development was accelerated. Fruit lesion development was suppressed after fruit exposure to pure (100% v/v) AEA or ORI vapours which were accompanied by increased fruit cracking. Exposure to pure VIN-, CHL- and ORI vapours reduced (up to 92%) spore germination in vitro, but no differences were observed in the AEA treatment. The benefits associated with volatiles-enrichment were maintained in fruit pre-exposed to vapours, resulting in suppression in spore germination and spore production. However, studies performed on fungi grown on Potato Dextrose Agar revealed fewer direct effects of volatiles on fungal colony development and spore germination per se, implying that suppression of pathogen development was due in a large part to the impact of volatiles on fruit-pathogen interactions and/or 'memory' effects on fruit tissue. Work is currently focussing on the mechanisms underlying the impacts of volatiles on fruit quality related attributes. The results of this study indicate that volatiles may be considered as an alternative to the traditional postharvest sanitizing techniques. Each commodity needs to be individually assessed, and the volatile concentration and sanitising technique optimised, before the volatile treatment is used commercially. Copyright 2010 Elsevier B.V. All rights reserved.

MiR-22 Suppresses BMP7 in the Development of Cirrhosis

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Dong Ji

2015-06-01

Full Text Available Background/Aims: New strategies for the prevention and treatment of cirrhosis are urgently needed for improving therapeutic outcome. A role of microRNAs (miRNAs in the pathogenesis of cirrhosis has been recently acknowledged, whereas the exact involved miRNAs as well as the associated molecular signaling pathways have not been determined. Specifically, the studies on the relationship between miR-22 and bone morphogenic protein 7 (BMP7 in the development of cirrhosis are lacking. Methods: We examined the correlation of the levels of miR-22 and bone morphogenic protein 7 (BMP7 in the liver biopsies from patients with cirrhosis. We examined overexpression or suppression of miR-22 on BMP7 in hepatocytes. We examined the binding of miR-22 to the 3'-UTR of BMP7 mRNA. Finally, in a carbon tetrachloride (CCl4-induced cirrhosis model in mice, we gave mice adeno-associated viruses carrying antisense of miR-22, and examined its effects on BMP7 levels and the hallmarks of cirrhosis. Results: The levels of miR-22 and BMP7 in the liver biopsies from patients were strongly and inversely correlated. MiR-22 inhibited BMP7 expression in hepatocytes, through directly binding the 3'-UTR of BMP7 mRNA. Expression of antisense miR-22 significantly attenuated the levels of liver fibrosis, portal hypertension and sodium retention caused by CCl4, possibly through upregulation of BMP7. Conclusions: MiR-22 promotes the development of cirrhosis through BMP7 suppression.

Development of noise-suppressed detector for single ion hit system

Energy Technology Data Exchange (ETDEWEB)

Sakai, Takuro; Hamano, Tsuyoshi; Suda, Tamotsu; Hirao, Toshio; Kamiya, Tomihiro [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment

1997-03-01

A noise-suppressed detector for single ion detection has been developed, and combined with the heavy ion microbeam apparatus. This detector consists of a pair of micro channel plates (MCP`s) and a very thin carbon foil. The detection signal is formed by the coincidence of the signals from these MCP`s, so that this detector and the coincidence measurement unit can reduce miscounting in the circuit. The detection efficiency for 15 MeV heavy ions was evaluated to be comparable to that of a silicon surface-barrier detector (SSD) and the miscounting rate was 4 orders lower than the noise rate of a single MCP. The rise time of the detection signal was also estimated. (author)

Bacillus cereus AR156 primes induced systemic resistance by suppressing miR825/825* and activating defense-related genes in Arabidopsis.

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Niu, Dongdong; Xia, Jing; Jiang, Chunhao; Qi, Beibei; Ling, Xiaoyu; Lin, Siyuan; Zhang, Weixiong; Guo, Jianhua; Jin, Hailing; Zhao, Hongwei

2016-04-01

Small RNAs play an important role in plant immune responses. However, their regulatory function in induced systemic resistance (ISR) is nascent. Bacillus cereus AR156 is a plant growth-promoting rhizobacterium that induces ISR in Arabidopsis against bacterial infection. Here, by comparing small RNA profiles of Pseudomonas syringae pv. tomato (Pst) DC3000-infected Arabidopsis with and without AR156 pretreatment, we identified a group of Arabidopsis microRNAs (miRNAs) that are differentially regulated by AR156 pretreatment. miR825 and miR825* are two miRNA generated from a single miRNA gene. Northern blot analysis indicated that they were significantly downregulated in Pst DC3000-infected plants pretreated with AR156, in contrast to the plants without AR156 pretreatment. miR825 targets two ubiquitin-protein ligases, while miR825* targets toll-interleukin-like receptor (TIR)-nucleotide binding site (NBS) and leucine-rich repeat (LRR) type resistance (R) genes. The expression of these target genes negatively correlated with the expression of miR825 and miR825*. Moreover, transgenic plants showing reduced expression of miR825 and miR825* displayed enhanced resistance to Pst DC3000 infection, whereas transgenic plants overexpressing miR825 and miR825* were more susceptible. Taken together, our data indicates that Bacillus cereus AR156 pretreatment primes ISR to Pst infection by suppressing miR825 and miR825* and activating the defense related genes they targeted. © 2015 Institute of Botany, Chinese Academy of Sciences.

Developing Inset Resistant Maize Varieties for Food Security in Kenya

International Nuclear Information System (INIS)

Mugo, S.

2002-01-01

The Insect Resistant Maize for Africa (IRMA) project aims at increasing maize production and food security through development and deployment of stem borer resistant maize germplasm developed using conventional and through biotechnology methods such as Bt maize. Bt maize offers farmers an effective and practical option for controlling stem borers. It was recognized that the development and routine use of Bt maize will require addressing relevant bio-safety, environmental, and community concerns and research and information gathering activities are in place to address these concerns and research and information gathering activities are in place to address these concerns. Suitable Bt gene have been acquired or synthesized and back-crossed into elite maize germplasm at CIMMYT-Mexico, and the effective Cry-proteins against the major maize stem borers in Kenya were identified to better target pests. Stem borer resistant maize germplasm is being developed through conventional breeding, using locally adapted and exotic germplasm. for safe and effective deployment of Bt maize,studies on its impacts on target and non-target arthropods as well as studies on the effects of Bt maize on key non-target arthropods as well as studies on gene flow are underway. Insect resistance management strategies are being developed through quantifying the effectiveness, ???. Socioeconomic impact studies are revealing factors in the society that may influence the adoption of Bt maize in Kenya. Also, baseline data, essential for the monitoring and evaluation of the Bt maize technology in Kenya, has been established. Technology transfer and capacity building, creating awareness and communications have received attention in the project. This paper describes the major research activities as they relate to development of the stem bore resistant maize germplasm

Swelling and swelling resistance possibilities of austenitic stainless steels in fusion reactors

International Nuclear Information System (INIS)

Maziasz, P.J.

1983-01-01

Fusion reactor helium generation rates in stainless steels are intermediate to those found in EBR-II and HFIR, and swelling in fusion reactors may differ from the fission swelling behavior. Advanced titanium-modified austenitic stainless steels exhibit much better void swelling resistance than AISI 316 under EBR-II (up to approx. 120 dpa) and HFIR (up to approx. 44 dpa) irradiations. The stability of fine titanium carbide (MC) precipitates plays an important role in void swelling resistance for the cold-worked titanium-modified steels irradiated in EBR-II. Futhermore, increased helium generation in these steels can (a) suppress void conversion, (b) suppress radiation-induced solute segregation (RIS), and (c) stabilize fine MC particles, if sufficient bubble nucleation occurs early in the irradation. The combined effects of helium-enhanced MC stability and helium-suppressed RIS suggest better void swelling resistance in these steels for fusion service than under EBR-II irradiation

RNA interference of three up-regulated transcripts associated with insecticide resistance in an imidacloprid resistant population of Leptinotarsa decemlineata.

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Clements, Justin; Schoville, Sean; Peterson, Nathan; Huseth, Anders S; Lan, Que; Groves, Russell L

2017-01-01

The Colorado potato beetle, Leptinotarsa decemlineata (Say), is a major agricultural pest of potatoes in the Central Sands production region of Wisconsin. Previous studies have shown that populations of L. decemlineata have become resistant to many classes of insecticides, including the neonicotinoid insecticide, imidacloprid. Furthermore, L. decemlineata has multiple mechanisms of resistance to deal with a pesticide insult, including enhanced metabolic detoxification by cytochrome p450s and glutathione S-transferases. With recent advances in the transcriptomic analysis of imidacloprid susceptible and resistant L. decemlineata populations, it is possible to investigate the role of candidate genes involved in imidacloprid resistance. A recently annotated transcriptome analysis of L. decemlineata was obtained from select populations of L. decemlineata collected in the Central Sands potato production region, which revealed a subset of mRNA transcripts constitutively up-regulated in resistant populations. We hypothesize that a portion of the up-regulated transcripts encoding for genes within the resistant populations also encode for pesticide resistance and can be suppressed to re-establish a susceptible phenotype. In this study, a discrete set of three up-regulated targets were selected for RNA interference experiments using a resistant L. decemlineata population. Following the successful suppression of transcripts encoding for a cytochrome p450, a cuticular protein, and a glutathione synthetase protein in a select L. decemlineata population, we observed reductions in measured resistance to imidacloprid that strongly suggest these genes control essential steps in imidacloprid metabolism in these field populations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Elisa development for detection of glyphosat resistant gm soybean

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Владислав Геннадійович Спиридонов

2015-11-01

Full Text Available During research we have utilized recombinant enzyme 5-enolpyruvylshikimate-3-phosphate synthase (CP4 EPSPS, conferring resistance to glyphosate for GM soybean, for the hen immunization and obtaining specific yolk antibodies IgY. Stages of ELISA development that can detect at least 0,1 % of GM-soybean resistant to glyphosate were present

Development and applications of the contact electric resistance technique

Energy Technology Data Exchange (ETDEWEB)

Saario, T.

1995-12-31

At the moment both the scientific understanding of corrosion processes and the engineering practices of corrosion control in power plants can benefit considerably from the development of in situ on-line instruments for characterisation of the surface films on construction materials. In this work a new in situ Contact Electric Resistance (CER) technique has been developed for measurement of electric resistance of surface films on metals. The CER technique was applied in this work in several different research areas. These include e.g. localized corrosion of stainless steel in paper mill wet end environment, investigation of the effect of inhibitors in steam generator crevice environments, passivation of GaAs single crystals by sulphate treatment and monitoring of the kinetics of oxide growth on zirconium metals in high temperature water. The CER technique has a measurement capacity ranging from 10-9 {omega} to 105 {omega}. The lowest range of resistance is typical for metallic layers deposited on the surface in electrodeposition processes. The highest range of resistance is found for insulator type of films e.g. on zirconium metals. (author)

Androgens as double-edged swords: Induction and suppression of follicular development.

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Pan, Jie-Xue; Zhang, Jun-Yu; Ke, Zhang-Hong; Wang, Fang-Fang; Barry, John A; Hardiman, Paul J; Qu, Fan

2015-01-01

Androgens, which are mediated via the androgen receptor (AR), play important roles in normal follicular development and female fertility. However, just like a double-edged sword, besides the positive effects of androgen on follicular development, abnormal androgen levels, especially as in hyperandrogenism, seriously suppress normal follicular development. A crucial balance exists between the importance of androgens in follicular development and their negative effects when in excess. As the first meiotic division and epigenetic reprogramming are two critical events in oogenesis, abnormal androgen levels or deficiency in androgen/AR signaling in the ovary may affect these vital events. Oocytes have a tendency to develop genomic instability, thus resulting in an increasing incidence of unpredictable adult diseases. Although many studies have explored the effects of androgens and AR on follicular development, the conclusions are controversial and there has been no thorough review of this topic. This review focuses on the roles of androgens in the physiological process of follicular development, summarizes new insights into the roles of androgens in the arrested development of follicles, and discusses the potential risk of adult diseases originating from abnormal follicular androgen levels or androgen receptor signals, which may determine areas for future studies.

The overexpression and nuclear translocation of Trx-1 during hypoxia confers on HepG2 cells resistance to DDP, and GL-V9 reverses the resistance by suppressing the Trx-1/Ref-1 axis.

Science.gov (United States)

Zhao, Li; Li, Wei; Zhou, Yuxin; Zhang, Yi; Huang, Shaoliang; Xu, Xuefen; Li, Zhiyu; Guo, Qinglong

2015-05-01

Microenvironmental hypoxia gives many tumor cells the capacity for drug resistance. Thioredoxin family members play critical roles in the regulation of cellular redox homeostasis in a stressed environment. In this study, we established a hypoxia-drug resistance (hypoxia-DR) model using HepG2 cells and discovered that the overexpression and nuclear translocation of thioredoxin-1 (Trx-1) are closely associated with this resistance through the regulation of the metabolism by the oxidative stress response to glycolysis. Intranuclear Trx-1 enhances the DNA-binding activity of HIF-1α via its interaction with and reducing action on Ref-1, resulting in increased expression of glycolysis-related proteins (PDHK1, HKII, and LDHA), glucose uptake, and lactate generation under hypoxia. Meanwhile, we found that GL-V9, a newly synthesized flavonoid derivative, shows an ability to reverse the hypoxia-DR and has low toxicity both in vivo and in vitro. GL-V9 could inhibit the expression and nuclear translocation of Trx-1 and then suppress HIF-1α DNA-binding activity by inhibiting the Trx-1/Ref-1 axis. As a result, glycolysis is weakened and oxidative phosphorylation is enhanced. Thus, GL-V9 leads to an increment in intracellular ROS generation and consequently intensified apoptosis induced by DDP. Copyright © 2015 Elsevier Inc. All rights reserved.

Environmental factors influencing the development and spread of antibiotic resistance.

Science.gov (United States)

Bengtsson-Palme, Johan; Kristiansson, Erik; Larsson, D G Joakim

2018-01-01

Antibiotic resistance and its wider implications present us with a growing healthcare crisis. Recent research points to the environment as an important component for the transmission of resistant bacteria and in the emergence of resistant pathogens. However, a deeper understanding of the evolutionary and ecological processes that lead to clinical appearance of resistance genes is still lacking, as is knowledge of environmental dispersal barriers. This calls for better models of how resistance genes evolve, are mobilized, transferred and disseminated in the environment. Here, we attempt to define the ecological and evolutionary environmental factors that contribute to resistance development and transmission. Although mobilization of resistance genes likely occurs continuously, the great majority of such genetic events do not lead to the establishment of novel resistance factors in bacterial populations, unless there is a selection pressure for maintaining them or their fitness costs are negligible. To enable preventative measures it is therefore critical to investigate under what conditions and to what extent environmental selection for resistance takes place. In addition, understanding dispersal barriers is not only key to evaluate risks, but also to prevent resistant pathogens, as well as novel resistance genes, from reaching humans. © FEMS 2017.

Superoxide anion radicals induce IGF-1 resistance through concomitant activation of PTP1B and PTEN

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Singh, Karmveer; Maity, Pallab; Krug, Linda; Meyer, Patrick; Treiber, Nicolai; Lucas, Tanja; Basu, Abhijit; Kochanek, Stefan; Wlaschek, Meinhard; Geiger, Hartmut; Scharffetter-Kochanek, Karin

2015-01-01

The evolutionarily conserved IGF-1 signalling pathway is associated with longevity, metabolism, tissue homeostasis, and cancer progression. Its regulation relies on the delicate balance between activating kinases and suppressing phosphatases and is still not very well understood. We report here that IGF-1 signalling in vitro and in a murine ageing model in vivo is suppressed in response to accumulation of superoxide anions () in mitochondria, either by chemical inhibition of complex I or by genetic silencing of -dismutating mitochondrial Sod2. The -dependent suppression of IGF-1 signalling resulted in decreased proliferation of murine dermal fibroblasts, affected translation initiation factors and suppressed the expression of α1(I), α1(III), and α2(I) collagen, the hallmarks of skin ageing. Enhanced led to activation of the phosphatases PTP1B and PTEN, which via dephosphorylation of the IGF-1 receptor and phosphatidylinositol 3,4,5-triphosphate dampened IGF-1 signalling. Genetic and pharmacologic inhibition of PTP1B and PTEN abrogated -induced IGF-1 resistance and rescued the ageing skin phenotype. We thus identify previously unreported signature events with , PTP1B, and PTEN as promising targets for drug development to prevent IGF-1 resistance-related pathologies. PMID:25520316

Ideal and conventional feedback systems for RWM suppression

Energy Technology Data Exchange (ETDEWEB)

Pustovitov, V.D.

2002-01-01

Feedback suppression of resistive wall modes (RWM) is studied analytically using a model based on a standard cylindrical approximation. Two feedback systems are compared: 'ideal', creating only the field necessary for RMW suppression, and 'conventional', like that used in the DIII-D tokamak and considered as a candidate for ITER. The widespread opinion that the feedback with poloidal sensors is better than that with radial sensors is discussed. It is shown that the 'conventional' feedback with radial sensors can be effective only in a limited range, while using the input signal from internal poloidal sensors allows easy fulfilment of the stability criterion. This is a property of the 'conventional' feedback, but the 'ideal' feedback would stabilise RWM in both cases. (author)

Mechanisms and ecological consequences of plant defence induction and suppression in herbivore communities

Science.gov (United States)

Kant, M. R.; Jonckheere, W.; Knegt, B.; Lemos, F.; Liu, J.; Schimmel, B. C. J.; Villarroel, C. A.; Ataide, L. M. S.; Dermauw, W.; Glas, J. J.; Egas, M.; Janssen, A.; Van Leeuwen, T.; Schuurink, R. C.; Sabelis, M. W.; Alba, J. M.

2015-01-01

Background Plants are hotbeds for parasites such as arthropod herbivores, which acquire nutrients and energy from their hosts in order to grow and reproduce. Hence plants are selected to evolve resistance, which in turn selects for herbivores that can cope with this resistance. To preserve their fitness when attacked by herbivores, plants can employ complex strategies that include reallocation of resources and the production of defensive metabolites and structures. Plant defences can be either prefabricated or be produced only upon attack. Those that are ready-made are referred to as constitutive defences. Some constitutive defences are operational at any time while others require activation. Defences produced only when herbivores are present are referred to as induced defences. These can be established via de novo biosynthesis of defensive substances or via modifications of prefabricated substances and consequently these are active only when needed. Inducibility of defence may serve to save energy and to prevent self-intoxication but also implies that there is a delay in these defences becoming operational. Induced defences can be characterized by alterations in plant morphology and molecular chemistry and are associated with a decrease in herbivore performance. These alterations are set in motion by signals generated by herbivores. Finally, a subset of induced metabolites are released into the air as volatiles and function as a beacon for foraging natural enemies searching for prey, and this is referred to as induced indirect defence. Scope The objective of this review is to evaluate (1) which strategies plants have evolved to cope with herbivores and (2) which traits herbivores have evolved that enable them to counter these defences. The primary focus is on the induction and suppression of plant defences and the review outlines how the palette of traits that determine induction/suppression of, and resistance/susceptibility of herbivores to, plant defences can

Metabolic changes during development of Walker-256 carcinosarcoma resistance to doxorubicin.

Science.gov (United States)

Todor, I N; Lukyanova, N Yu; Shvets, Yu V; Lozovska, Yu V; Chekhun, V F

2015-03-01

To study indices of energy metabolism, content of K(+) and Mg(++) both in peripheral blood and in Walker-256 carcinosarcoma during development of resistance to doxorubicin. Resistance of Walker-256 carcinosarcoma to doxorubicin has been developed through 12 subsequent transplantations of tumor after the chemotherapy. Parental strain was inhibited by drug by 65%, while transitional resistant substrains - by 30% and 2%, respectively. Determination of biochemical indices in blood serum and homogenates of tumor tissue, level of potassium, magnesium, lactate, glucose, activities of lactate dehydrogenase and glucose-6-phosphate dehydrogenase was performed with the help of biochemical and immune-enzyme analyzer GBG ChemWell 2990 (USA) using standard kits. Polarography was used to determine indices of mitochondrial oxidative phosphorylation. Study of mitochondrial membrane potential was carried out on flow cytometer Beckman Coulter Epics XL using dye JC-1. It has been determined that development of drug resistance causes the decrease of K(+), Mg(++), glucose content in blood serum and increase of these indices in tumor tissue. At the same time, gradual tumor's loss of sensitivity is characterized by decrease of glycolysis activity in it and activation of mitochondrial oxidative phosphorylation and pentose phosphate pathway of glucose degradation, which causes more intensive formation of NADPH. Development of drug resistance of tumor causes certain metabolic changes in organism and tumor. Further study of such changes will make possible to determine tumor and extratumor markers of resistance.

A reassessment of the risk of rust fungi developing resistance to fungicides.

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Oliver, Richard P

2014-11-01

Rust fungi are major pathogens of many annual and perennial crops. Crop protection is largely based on genetic and chemical control. Fungicide resistance is a significant issue that has affected many crop pathogens. Some pathogens have rapidly developed resistance and hence are regarded as high-risk species. Rust fungi have been classified as being low risk, in spite of sharing many relevant features with high-risk pathogens. An examination of the evidence suggests that rust fungi may be wrongly classified as low risk. Of the nine classes of fungicide to which resistance has developed, six are inactive against rusts. The three remaining classes are quinone outside inhibitors (QoIs), demethylation inhibitors (DMIs) and succinate dehydrogenase inhibitors (SDHIs). QoIs have been protected by a recently discovered intron that renders resistant mutants unviable. Low levels of resistance have developed to DMIs, but with limited field significance. Older SDHI fungicides were inactive against rusts. Some of the SDHIs introduced since 2003 are active against rusts, so it may be that insufficient time has elapsed for resistance to develop, especially as SDHIs are generally sold in mixtures with other actives. It would therefore seem prudent to increase the level of vigilance for possible cases of resistance to established and new fungicides in rusts. © 2014 Society of Chemical Industry.

Suppressing propylene carbonate decomposition by coating graphite electrode foil with silver

International Nuclear Information System (INIS)

Gao, J.; Zhang, H.P.; Fu, L.J.; Zhang, T.; Wu, Y.P.; Takamura, T.; Wu, H.Q.; Holze, R.

2007-01-01

A method has been developed to suppress the decomposition of propylene carbonate (PC) by coating graphite electrode foil with a layer of silver. Results from electrochemical impedance measurements show that the Ag-coated graphite electrode presents lower charge transfer resistance and faster diffusion of lithium ions in comparison with the virginal one. Cyclic voltammograms and discharge-charge measurements suggest that the decomposition of propylene carbonate and co-intercalation of solvated lithium ions are prevented, and lithium ions can reversibly intercalate into and deintercalate from the Ag-coated graphite electrode. These results indicate that Ag-coating is a good way to improve the electrochemical performance of graphitic carbon in PC-based electrolyte solutions

Baicalin and its metabolites suppresses gluconeogenesis through activation of AMPK or AKT in insulin resistant HepG-2 cells.

Science.gov (United States)

Wang, Tao; Jiang, Hongmei; Cao, Shijie; Chen, Qian; Cui, Mingyuan; Wang, Zhijie; Li, Dandan; Zhou, Jing; Wang, Tao; Qiu, Feng; Kang, Ning

2017-12-01

Scutellaria baicalensis Georgi (S. baicalensis), as a traditional Chinese herbal medicine, is an important component of several famous Chinese medicinal formulas for treating patients with diabetes mellitus. Baicalin (BG), a main bioactive component of S. baicalensis, has been reported to have antidiabetic effects. However, pharmacokinetic studies have indicated that BG has poor oral bioavailability. Therefore, it is hard to explain the pharmacological effects of BG in vivo. Interestingly, several reports show that BG is extensively metabolized in rats and humans. Therefore, we speculate that the BG metabolites might be responsible for the pharmacological effects. In this study, BG and its three metabolites (M1-M3) were examined their effects on glucose consumption in insulin resistant HepG-2 cells with a commercial glucose assay kit. Real-time PCR and western blot assay were used to confirm genes and proteins of interest, respectively. The results demonstrate that BG and its metabolites (except for M3) enhanced the glucose consumption which might be associated with inhibiting the expression of the key gluconeogenic genes, including glucose-6-phosphatase (G6Pase), phosphoenolypyruvate carboxykinase (PEPCK) and glucose transporter 2 (GLUT2). Further study found that BG and M1 could suppress hepatic gluconeogenesis via activation of the AMPK pathway, while M2 could suppress hepatic gluconeogenesis via activation of the PI3K/AKT signaling pathway. Taken together, our findings suggest that both BG and its metabolites have antihyperglycemic activities, and might be the active forms of oral doses of BG in vivo. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Understanding plant defence responses against herbivore attacks: an essential first step towards the development of sustainable resistance against pests.

Science.gov (United States)

Santamaria, M Estrella; Martínez, Manuel; Cambra, Inés; Grbic, Vojislava; Diaz, Isabel

2013-08-01

Plant-herbivore relationships are complex interactions encompassing elaborate networks of molecules, signals and strategies used to overcome defences developed by each other. Herbivores use multiple feeding strategies to obtain nutrients from host plants. In turn, plants respond by triggering defence mechanisms to inhibit, block or modify the metabolism of the pest. As part of these defences, herbivore-challenged plants emit volatiles to attract natural enemies and warn neighbouring plants of the imminent threat. In response, herbivores develop a variety of strategies to suppress plant-induced protection. Our understanding of the plant-herbivore interphase is limited, although recent molecular approaches have revealed the participation of a battery of genes, proteins and volatile metabolites in attack-defence processes. This review describes the intricate and dynamic defence systems governing plant-herbivore interactions by examining the diverse strategies plants employ to deny phytophagous arthropods the ability to breach newly developed mechanisms of plant resistance. A cornerstone of this understanding is the use of transgenic tools to unravel the complex networks that control these interactions.

The invasive plant Alternanthera philoxeroides was suppressed more intensively than its native congener by a native generalist: implications for the biotic resistance hypothesis.

Directory of Open Access Journals (Sweden)

Shufeng Fan

Full Text Available Prior studies on preferences of native herbivores for native or exotic plants have tested both the enemy release hypothesis and the biotic resistance hypothesis and have reported inconsistent results. The different levels of resistance of native and exotic plants to native herbivores could resolve this controversy, but little attention has been paid to this issue. In this study, we investigated population performance, photosynthesis, leaf nitrogen concentration, and the constitutive and induced resistances of the successful invasive plant, Alternanthera philoxeroides, and its native congener, Alternanthera sessilis, in the presence of three population densities of the grasshopper, Atractomorpha sinensis. When the grasshopper was absent, leaf biomass, total biomass, photosynthesis, and leaf nitrogen concentration of A. philoxeroides were higher than those of A. sessilis. However, the morphological and physiological performances of A. philoxeroides were all decreased more intensively than A. sessilis after herbivory by grasshoppers. Especially as the concentrations of constitutive lignin and cellulose in leaf of A. philoxeroides were higher than A. sessilis, A. philoxeroides exhibited increased leaf lignin concentration to reduce its palatability only at severe herbivore load, whereas, leaf lignin, cellulose, and polyphenolic concentrations of A. sessilis all increased with increasing herbivory pressure, and cellulose and polyphenolic concentrations were higher in A. sessilis than in A. philoxeroides after herbivory. Our study indicated that the capability of the invasive plant to respond to native insect damage was lower than the native plant, and the invasive plant was suppressed more intensively than its native congener by the native insect. Our results support the biotic resistance hypothesis and suggest that native herbivores can constrain the abundance and reduce the adverse effects of invasive species.

Can microbial cells develop resistance to oxidative stress in antimicrobial photodynamic inactivation?

Science.gov (United States)

Kashef, Nasim; Hamblin, Michael R

2017-03-01

Infections have been a major cause of disease throughout the history of humans on earth. With the introduction of antibiotics, it was thought that infections had been conquered. However, bacteria have been able to develop resistance to antibiotics at an exponentially increasing rate. The growing threat from multi-drug resistant organisms calls for intensive action to prevent the emergence of totally resistant and untreatable infections. Novel, non-invasive, non-antibiotic strategies are needed that act more efficiently and faster than current antibiotics. One promising alternative is antimicrobial photodynamic inactivation (APDI), an approach that produces reactive oxygen species when dyes and light are combined. So far, it has been questionable if bacteria can develop resistance against APDI. This review paper gives an overview of recent studies concerning the susceptibility of bacteria towards oxidative stress, and suggests possible mechanisms of the development of APDI-resistance that should at least be addressed. Some ways to potentiate APDI and also to overcome future resistance are suggested. Copyright © 2017 Elsevier Ltd. All rights reserved.

Is hormesis an underestimated factor in the development of herbicide resistance?

Directory of Open Access Journals (Sweden)

Belz, Regina G.

2014-02-01

Full Text Available The growing impact of herbicide resistant weeds increasingly affects weed management and the delay of resistance evolution has become a major task of chemical weed control. Hormesis and, thus, the phenomenon that low doses of herbicides can boost weed growth could be of importance in this regard since the recommended field rate may represent a low dose for weeds that have evolved resistance to the applied herbicide and, thus, a potential hormetic dose. Applying the field rate may thus not only directly select resistant biotypes, it may also indirectly promote the success and spread of resistant biotypes via hormesis. Nevertheless, hormetic effects in resistant weeds are hitherto merely randomly observed and, thus, a clear quantitative basis to judge the significance of hormesis for resistance evolution is lacking. Therefore, this study aimed at quantifying the degree and frequency of herbicide hormesis in sensitive and resistant weed species in order to provide a first indication of whether the phenomenon deserves consideration as a potential factor contributing to the development of herbicide resistance. In germination assays complete dose-response experiments were conducted with sensitive and resistant biotypes of Matricaria inodora (ALS-target-site resistant; treated with iodosulfuron-methyl-sodium/mesosulfuron-methyl, Eleusine indica (glyphosateresistant; treated with glyphosate, and Chenopodium album (triazine/triazinone-target-site resistant; treated with terbuthylazine. After 10 days of cultivation under controlled conditions plant growth was analyzed by measuring shoot/root length and mass. Results indicated that herbicide hormesis occurred on average with a total frequency of 29% in sensitive/resistant biotypes with an average growth increase of 53% occurring typically within a dose zone exceeding 350fold. Hormetic effects occurred, however, very variable and only for specific endpoints and not plant growth in general. If such a

Status of Methodology Development for the Evaluation of Proliferation Resistance

International Nuclear Information System (INIS)

Lee, Yong Deok; Ko, Won Il; Lee, Jung Won

2010-01-01

Concerning the increasing energy demand and green house effect, nuclear energy is now the most feasible option. Therefore, recently, oil countries even have a plan to build the nuclear power plant for energy production. If nuclear systems are to make a major and sustainable contribution to the worlds energy supply, future nuclear energy systems must meet specific requirements. One of the requirements is to satisfy the proliferation resistance condition in an entire nuclear system. Therefore, from the beginning of future nuclear energy system development, it is important to consider a proliferation resistance to prevent the diversion of nuclear materials. The misuse of a nuclear system must be considered as well. Moreover, in the import and export of nuclear system, the evaluation of the proliferation resistance on the nuclear system becomes a key factor The INPRO (International Project on Innovative Nuclear Reactors and Fuel Cycles) program initiated by the IAEA proposed proliferation resistance (PR) as a key component of a future innovative nuclear system (INS) with a sustainability, economics, safety of nuclear installation and waste management. The technical goal for Generation IV (Gen IV) nuclear energy systems (NESs) highlights a Proliferation Resistance and Physical Protection (PR and PP), sustainability, safety, reliability and economics as well. Based on INPRO and Gen IV study, the methodology development for the evaluation of proliferation resistance has been carried out in KAERI. Finally, the systematic procedure for methodology was setup and the indicators for the procedure were decided. The methodology involves the evaluation from total nuclear system to individual process. Therefore, in this study, the detailed procedure for the evaluation of proliferation resistance and the newly proposed additional indicators are described and several conditions are proposed to increase the proliferation resistance in the future nuclear system. The assessment of PR

Benchmark enclosure fire suppression experiments - phase 1 test report.

Energy Technology Data Exchange (ETDEWEB)

Figueroa, Victor G.; Nichols, Robert Thomas; Blanchat, Thomas K.

2007-06-01

A series of fire benchmark water suppression tests were performed that may provide guidance for dispersal systems for the protection of high value assets. The test results provide boundary and temporal data necessary for water spray suppression model development and validation. A review of fire suppression in presented for both gaseous suppression and water mist fire suppression. The experimental setup and procedure for gathering water suppression performance data are shown. Characteristics of the nozzles used in the testing are presented. Results of the experiments are discussed.

Development of Methods for Genetic Assessment of Antibiotic Resistance In Animal Herds

DEFF Research Database (Denmark)

Schmidt, Gunilla Veslemøy

with a parallel selection for resistant bacteria. Since the hazards related to antibiotic resistance development have been recognized, the prudent use of antibiotics has been in focus, especially concerning their use in animal production. For many years antibiotics have been, and still are, recklessly used...... in the animal production especially in the form of growth promoters. Due to the associated risks of resistant zoonotic bacteria transmission from animals to humans, it is of interest to keep antibiotic use and antibiotic resistance under strict surveillance.This PhD study was based on the development of real......-time PCR (qPCR) assays that supply an easy and rapid method for quantifying antibiotic resistance levels in animal herds. The pig production is accountable for a large portion of the antibiotics used for food producing animals in Denmark. Therefore, the antibiotic resistance genes included in this study...

Development of application technology of radiation-resistant microorganism

International Nuclear Information System (INIS)

Kim, Dong Ho; Lim, Sang Yong; Joe, Min Ho; Jung, Jin Woo; Jung, Sun Wook; Song, Du Sup; Choi, Young Ji

2009-02-01

The scope of the project is divided into of three parts; (i) to define the survival strategy of radiation-resistant microbes, especially Deinococcus (ii) acquisition of gene resources encoding the novel protein and related with the production of functional materials (iii) development of control technology against radiation-resistant microbes. To this aim, first, the whole transcriptional response of the D. radiodurans strain haboring pprI mutation, which plays an important role in radiation resistance, was analyzed by cDNA microarray. The anti-oxidant activity of the major carotenoid of D. radiodurans, deinoxanthin, was analyzed and the strain was constructed, in which the gene necessary for bio- synthesis of deinoxanthin is deleted. The response to cadmium of D. radiodurans was also investigated through cDNA microarray analysis. Radiogenic therapy, one of the cancer treatments, is designed to use radiation-inducible gene for the treatment. To develop the gene-transfer vehicle for radiogenic therapy, we have investigated the virulence mechanism of Salmonella, which is tumor-targeting bacteria and studied the synergistic effect of some anti-cancer agents on radiation treatment for cancer. Finally, we confirmed that irradiation could decompose a fungus toxin, patulin, into various harmless by-products

Development of application technology of radiation-resistant microorganism

Energy Technology Data Exchange (ETDEWEB)

Kim, Dong Ho; Lim, Sang Yong; Joe, Min Ho; Jung, Jin Woo; Jung, Sun Wook; Song, Du Sup; Choi, Young Ji [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2009-02-15

The scope of the project is divided into of three parts; (i) to define the survival strategy of radiation-resistant microbes, especially Deinococcus (ii) acquisition of gene resources encoding the novel protein and related with the production of functional materials (iii) development of control technology against radiation-resistant microbes. To this aim, first, the whole transcriptional response of the D. radiodurans strain haboring pprI mutation, which plays an important role in radiation resistance, was analyzed by cDNA microarray. The anti-oxidant activity of the major carotenoid of D. radiodurans, deinoxanthin, was analyzed and the strain was constructed, in which the gene necessary for bio- synthesis of deinoxanthin is deleted. The response to cadmium of D. radiodurans was also investigated through cDNA microarray analysis. Radiogenic therapy, one of the cancer treatments, is designed to use radiation-inducible gene for the treatment. To develop the gene-transfer vehicle for radiogenic therapy, we have investigated the virulence mechanism of Salmonella, which is tumor-targeting bacteria and studied the synergistic effect of some anti-cancer agents on radiation treatment for cancer. Finally, we confirmed that irradiation could decompose a fungus toxin, patulin, into various harmless by-products.

Antibiotic Resistance in the Food Chain: A Developing Country-Perspective.

Science.gov (United States)

Founou, Luria Leslie; Founou, Raspail Carrel; Essack, Sabiha Yusuf

2016-01-01

Antibiotics are now "endangered species" facing extinction due to the worldwide emergence of antibiotic resistance (ABR). Food animals are considered as key reservoirs of antibiotic-resistant bacteria with the use of antibiotics in the food production industry having contributed to the actual global challenge of ABR. There are no geographic boundaries to impede the worldwide spread of ABR. If preventive and containment measures are not applied locally, nationally and regionally, the limited interventions in one country, continent and for instance, in the developing world, could compromise the efficacy and endanger ABR containment policies implemented in other parts of the world, the best-managed high-resource countries included. Multifaceted, comprehensive, and integrated measures complying with the One Health approach are imperative to ensure food safety and security, effectively combat infectious diseases, curb the emergence and spread of ABR, and preserve the efficacy of antibiotics for future generations. Countries should follow the World Health Organization, World Organization for Animal Health, and the Food and Agriculture Organization of the United Nations recommendations to implement national action plans encompassing human, (food) animal, and environmental sectors to improve policies, interventions and activities that address the prevention and containment of ABR from farm-to-fork. This review covers (i) the origin of antibiotic resistance, (ii) pathways by which bacteria spread to humans from farm-to-fork, (iii) differences in levels of antibiotic resistance between developed and developing countries, and (iv) prevention and containment measures of antibiotic resistance in the food chain.

Correlates of HIV-1 viral suppression in a cohort of HIV-positive drug users receiving antiretroviral therapy in Hanoi, Vietnam

Science.gov (United States)

Jordan, Michael R; La, Hanh; Nguyen, Hien Duc; Sheehan, Heidi; Lien, Trinh Thi Minh; Van Dang, Duong; Hellinger, James; Wanke, Christine; Tang, Alice M

2009-01-01

Summary Injection drug users bear the burden of HIV in Vietnam and are a focus of national treatment programs. To date, determinants of successful therapy in this population are unknown. Substance use and clinical correlates of viral suppression were studied in 100 HIV-1 infected drug users receiving antiretroviral therapy (ART) for at least 6 months in Hanoi, Vietnam. Mean age of the cohort was 29.9 + 4.9 years; all were men. A majority of patients (73%) achieved viral suppression (HIV-RNA 95% adherence (p<0.01) and current use of trimethoprim/sulfamethoxazole (p<0.01); current or ever diagnosed with tuberculosis was associated with viral non-suppression (p=0.006). Tobacco use was prevalent (84%), and surprisingly 48% of patients reported active drug use; neither was associated with viral non-suppression. This is the first study to document successful ART treatment in a population of Vietnamese drug users; rates of viral suppression are comparable to other international populations. The 28% of patients without HIV-1 suppression highlights the need for adherence promotion, risk reduction programs, and population based surveillance strategies for assessing the emergence of HIV drug resistance in settings where access to viral load and drug resistance testing is limited. PMID:19451329

Development of debris resistant bottom end piece

International Nuclear Information System (INIS)

Lee, Jae Kyung; Sohn, Dong Seong; Yim, Jeong Sik; Hwang, Dae Hyun; Song, Kee Nam; Oh, Dong Seok; Rhu, Ho Sik; Lee, Chang Woo; Kim, Seong Soo; Oh, Jong Myung

1993-12-01

Debris-related fuel failures have been identified as one of the major causes of fuel failures. In order to reduce the possibility of debris-related fuel failures, it is necessary to develop Debris-Resistant Bottom End Piece. For this development, mechanical strength test and pressure drop test were performed, and the test results were analyzed. And the laser cutting, laser welding and electron beam welding technology, which were the core manufacturing technology of DRBEP, were developed. Final design were performed, and the final drawing and specifications were prepared. The prototype of DRBEP was manufactured according to the developed munufacturing procedure. (Author)

The EPED pedestal model and edge localized mode-suppressed regimes: Studies of quiescent H-mode and development of a model for edge localized mode suppression via resonant magnetic perturbations

Energy Technology Data Exchange (ETDEWEB)

Snyder, P. B.; Osborne, T. H.; Burrell, K. H.; Groebner, R. J.; Leonard, A. W.; Wade, M. R. [General Atomics, P.O. Box 85608, San Diego, California 92186-5608 (United States); Nazikian, R. [Princeton Plasma Physics Laboratory, Princeton, New Jersey (United States); Orlov, D. M. [University of California-San Diego, San Diego, California 92093 (United States); Schmitz, O. [Institut fuer Plasmaphysik, Forschungszentrum Juelich GmbH, Association FZJ-EURATOM, Juelich (Germany); Wilson, H. R. [York Plasma Institute, Department of Physics, University of York, Heslington, York YO10 5DD (United Kingdom)

2012-05-15

The EPED model predicts the H-mode pedestal height and width based upon two fundamental and calculable constraints: (1) onset of non-local peeling-ballooning modes at low to intermediate mode number, (2) onset of nearly local kinetic ballooning modes at high mode number. We present detailed tests of the EPED model in discharges with edge localized modes (ELMs), employing new high resolution measurements, and finding good quantitative agreement across a range of parameters. The EPED model is then applied for the first time to quiescent H-mode (QH), finding a similar level of agreement between predicted and observed pedestal height and width, and suggesting that the model can be used to predict the critical density for QH-mode operation. Finally, the model is applied toward understanding the suppression of ELMs with 3D resonant magnetic perturbations (RMP). Combining EPED with plasma response physics, a new working model for RMP ELM suppression is developed. We propose that ELMs are suppressed when a 'wall' associated with the RMP blocks the inward penetration of the edge transport barrier. A calculation of the required location of this 'wall' with EPED is consistent with observed profile changes during RMP ELM suppression and offers an explanation for the observed dependence on safety factor (q{sub 95}).

Protectin DX suppresses hepatic gluconeogenesis through AMPK-HO-1-mediated inhibition of ER stress.

Science.gov (United States)

Jung, Tae Woo; Kim, Hyung-Chun; Abd El-Aty, A M; Jeong, Ji Hoon

2017-06-01

Several studies have shown that protectins, which are ω-3 fatty acid-derived proresolution mediators, may improve insulin resistance. Recently, protectin DX (PDX) was documented to attenuate insulin resistance by stimulating IL-6 expression in skeletal muscle, thereby regulating hepatic gluconeogenesis. These findings made us investigate the direct effects of PDX on hepatic glucose metabolism in the context of diabetes. In the current study, we show that PDX regulates hepatic gluconeogenesis in a manner distinct from its indirect glucoregulatory activity via IL-6. We found that PDX stimulated AMP-activated protein kinase (AMPK) phosphorylation, thereby inducing heme oxygenase 1 (HO-1) expression. This induction blocked hepatic gluconeogenesis by suppressing endoplasmic reticulum (ER) stress in hepatocytes under hyperlipidemic conditions. These effects were significantly dampened by silencing AMPK or HO-1 expression with small interfering RNA (siRNA). We also demonstrated that administration of PDX to high fat diet (HFD)-fed mice resulted in increased hepatic AMPK phosphorylation and HO-1 expression, whereas hepatic ER stress was substantially attenuated. Furthermore, PDX treatment suppressed the expression of gluconeogenic genes, thereby decreasing blood glucose levels in HFD-fed mice. In conclusion, our findings suggest that PDX inhibits hepatic gluconeogenesis via AMPK-HO-1-dependent suppression of ER stress. Thus, PDX may be an effective therapeutic target for the treatment of insulin resistance and type 2 diabetes through the regulation of hepatic gluconeogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

The consequences of suppressing affective displays in romantic relationships: A challenge and threat perspective.

Science.gov (United States)

Peters, Brett J; Jamieson, Jeremy P

2016-10-01

Emotion suppression is one of the most studied topics in emotion regulation. However, little is known about how response-focused regulation strategies unfold in romantic relationships from the perspectives of both emotion regulators and their interaction partners. Using the biopsychosocial (BPS) model of challenge and threat as an organizing framework, 2 experiments examined effects of expressive suppression (vs. expression) on affective, cognitive, physiological, and behavioral processes in regulators and their romantic partners. In Experiment 1 a crowd-sourced sample of individuals currently in a romantic relationship simulated scenarios in which the self or partner engaged in response-focused emotion regulation (expression or suppression of affective displays). Suppressors expected worse outcomes compared with expressers. However, individuals on the receiving end of suppression (suppression targets) did not differ from expression targets. Experiment 2 then examined romantic couples' responses to suppression/expression in vivo. Regulators were randomly assigned to suppress/express affective displays and partners (targets) were unaware of the manipulation. Suppressors and suppression targets exhibited more malignant physiological responses (increased vascular resistance and elevated cortisol reactivity) during an emotional conversation and reduced intimacy behavior as measured with a novel touch task. Consequences for relationship processes are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Study on dissolution behavior of polymer-bound and polymer-blended photo-acid generator (PAG) resists

Science.gov (United States)

Yamamoto, Hiroki; Kozawa, Takahiro; Tagawa, Seiichi

2013-03-01

The requirements for the next generation resist materials are so challenging that it is indispensable for feasibility of EUV lithography to grasp basic chemistry of resist matrices in all stage of resist processes. Under such circumstances, it is very important to know dissolution characteristics of the resist film into alkaline developer though the dissolution of exposed area of resist films in alkaline developer to form a pattern is a complex reactive process. In this study, the influence of EUV and KrF exposure on the dissolution behavior of polymer bound PAG and polymer blended PAG was studied in detail using quartz crystal microbalance (QCM) methods. The difference in swelling formation between KrF and EUV exposure was observed. It is likely that difference of reaction mechanism induces the difference of these swelling. Also, it is observed that the swelling of polymer-bound PAG is less than that of polymer blended PAG in both KrF and EUV exposure. This result indicates that polymer-bound PAG suppresses swelling very well and showed an excellent performance. Actually, the developed polymer bound-PAG resist showed an excellent performance (half pitch 50 nm line and space pattern). Thus, polymer bound PAG is one of the promising candidate for 16 nm EUV resist.

Polymyxin resistance of Pseudomonas aeruginosa phoQ mutants is dependent on additional two-component regulatory systems

DEFF Research Database (Denmark)

Gutu, Alina D; Sgambati, Nicole; Strasbourger, Pnina

2013-01-01

Pseudomonas aeruginosa can develop resistance to polymyxin as a consequence of mutations in the PhoPQ regulatory system, mediated by covalent lipid A modification. Transposon mutagenesis of a polymyxin-resistant phoQ mutant defined 41 novel loci required for resistance, including two regulatory s......, indicate that addition of 4-amino-L-arabinose to lipid A is not the only PhoPQ-regulated biochemical mechanism required for resistance, and demonstrate that colRS and cprS mutations can contribute to high-level clinical resistance....... with the known role of this modification in polymyxin resistance. Surprisingly, tandem deletion of colRS or cprRS in the ΔphoQ mutant or individual deletion of cprR or cprS failed to suppress 4-amino-L-arabinose addition to lipid A, indicating that this modification alone is not sufficient for Pho...

In situ analysis of negative-tone resist pattern formation using organic-solvent-based developer process

Science.gov (United States)

Santillan, Julius Joseph; Yamada, Keisaku; Itani, Toshiro

2014-01-01

In situ resist “pattern formation” analysis during the development process using high-speed atomic force microscopy has been improved for application not only for conventional aqueous 0.26 N tetramethylammonium hydroxide (aq. TMAH), but also organic solvent n-butyl acetate (nBA) developers. Comparative investigations of resist dissolution in these developers, using the same resist material (hybrid of polyhydroxystyrene and methacrylate), showed a grainlike, uniform dissolution of the “unexposed resist film” in nBA development and uneven dissolution of the “exposed resist film” in aq. TMAH development. These results suggest the importance of dissolution uniformity in further improving the resulting pattern line width roughness.

Suppression of ERβ signaling via ERβ knockout or antagonist protects against bladder cancer development.

Science.gov (United States)

Hsu, Iawen; Chuang, Kun-Lung; Slavin, Spencer; Da, Jun; Lim, Wei-Xun; Pang, See-Tong; O'Brien, Jeanne H; Yeh, Shuyuan

2014-03-01

Epidemiological studies showed that women have a lower bladder cancer (BCa) incidence, yet higher muscle-invasive rates than men, suggesting that estrogen and the estrogen receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), may play critical roles in BCa progression. Using in vitro cell lines and an in vivo carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced mouse BCa model, we found that ERβ plays a positive role in promoting BCa progression. Knockdown of ERβ with ERβ-shRNA in ERβ-positive human BCa J82, 647v and T24 cell lines led to suppressed cell growth and invasion. Mice lacking ERβ have less cancer incidence with reduced expression of the proliferation marker Ki67 in BBN-induced BCa. Consistently, our results show that non-malignant urothelial cells with ERβ knockdown are more resistant to carcinogen-induced malignant transformation. Mechanism dissection found that targeting ERβ suppressed the expression of minichromosome maintenance complex component 5 (MCM5), a DNA replication licensing factor that is involved in tumor cell growth. Restoring MCM5 expression can partially reverse ERβ knockdown-mediated growth reduction. Supportively, treating cells with the ERβ-specific antagonist, 4-[2-Phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP), reduced BCa cell growth and invasion, as well as MCM5 expression. Furthermore, we provide the first evidence that BCa burden and mortality can be controlled by PHTPP treatment in the carcinogen-induced BCa model. Together, these results demonstrate that ERβ could play positive roles in promoting BCa progression via MCM5 regulation. Targeting ERβ through ERβ-shRNA, PHTPP or via downstream targets, such as MCM5, could serve as potential therapeutic approaches to battle BCa.

Mechanisms and ecological consequences of plant defence induction and suppression in herbivore communities.

Science.gov (United States)

Kant, M R; Jonckheere, W; Knegt, B; Lemos, F; Liu, J; Schimmel, B C J; Villarroel, C A; Ataide, L M S; Dermauw, W; Glas, J J; Egas, M; Janssen, A; Van Leeuwen, T; Schuurink, R C; Sabelis, M W; Alba, J M

2015-06-01

Plants are hotbeds for parasites such as arthropod herbivores, which acquire nutrients and energy from their hosts in order to grow and reproduce. Hence plants are selected to evolve resistance, which in turn selects for herbivores that can cope with this resistance. To preserve their fitness when attacked by herbivores, plants can employ complex strategies that include reallocation of resources and the production of defensive metabolites and structures. Plant defences can be either prefabricated or be produced only upon attack. Those that are ready-made are referred to as constitutive defences. Some constitutive defences are operational at any time while others require activation. Defences produced only when herbivores are present are referred to as induced defences. These can be established via de novo biosynthesis of defensive substances or via modifications of prefabricated substances and consequently these are active only when needed. Inducibility of defence may serve to save energy and to prevent self-intoxication but also implies that there is a delay in these defences becoming operational. Induced defences can be characterized by alterations in plant morphology and molecular chemistry and are associated with a decrease in herbivore performance. These alterations are set in motion by signals generated by herbivores. Finally, a subset of induced metabolites are released into the air as volatiles and function as a beacon for foraging natural enemies searching for prey, and this is referred to as induced indirect defence. The objective of this review is to evaluate (1) which strategies plants have evolved to cope with herbivores and (2) which traits herbivores have evolved that enable them to counter these defences. The primary focus is on the induction and suppression of plant defences and the review outlines how the palette of traits that determine induction/suppression of, and resistance/susceptibility of herbivores to, plant defences can give rise to

Development of ceftazidime resistance in an acute Burkholderia pseudomallei infection

Directory of Open Access Journals (Sweden)

Sarovich DS

2012-08-01

Full Text Available Derek S Sarovich,1,2,* Erin P Price,1,2,* Direk Limmathurotsakul,3 James M Cook,1 Alex T Von Schulze,1 Spenser R Wolken,1 Paul Keim,1 Sharon J Peacock,3,4 Talima Pearson1 1Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, AZ, USA; 2Tropical and Emerging Infectious Diseases Division, Menzies School of Health Research, Darwin, Australia; 3Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 4Department of Medicine, University of Cambridge, Cambridge, United Kingdom*These authors contributed equally to this workAbstract: Burkholderia pseudomallei, a bacterium that causes the disease melioidosis, is intrinsically resistant to many antibiotics. First-line antibiotic therapy for treating melioidosis is usually the synthetic β-lactam, ceftazidime (CAZ, as almost all B. pseudomallei strains are susceptible to this drug. However, acquired CAZ resistance can develop in vivo during treatment with CAZ, which can lead to mortality if therapy is not switched to a different drug in a timely manner. Serial B. pseudomallei isolates obtained from an acute Thai melioidosis patient infected by a CAZ susceptible strain, who ultimately succumbed to infection despite being on CAZ therapy for the duration of their infection, were analyzed. Isolates that developed CAZ resistance due to a proline to serine change at position 167 in the β-lactamase PenA were identified. Importantly, these CAZ resistant isolates remained sensitive to the alternative melioidosis treatments; namely, amoxicillin-clavulanate, imipenem, and meropenem. Lastly, real-time polymerase chain reaction-based assays capable of rapidly identifying CAZ resistance in B. pseudomallei isolates at the position 167 mutation site were developed. The ability to rapidly identify the emergence of CAZ resistant B. pseudomallei populations in melioidosis patients will allow timely alterations in treatment strategies

Development of herbicide resistance in black-grass (Alopecurus myosuroides in Bavaria

Directory of Open Access Journals (Sweden)

Gehring, Klaus

2016-02-01

Full Text Available Black-grass (Alopecurus myosuroides is one of the most important grass weeds in Bavaria. Chemical weed control with high efficacy is very important in crops like winter cereals, oilseed rape and maize. Crop rotations with more winter cereals, reduced soil cultivation and e.g. contract harvesting enhanced distribution of blackgrass in arable farming regions. Effects of herbicide resistance were observed since the last 20 years. The blackgrass herbicide resistance is well observed by the official plant protection service of Bavaria. A wide experience of resistance tests shows the development of resistant black-grass and provides an opportunity for future prospects in resistance dynamics.

5 Development of a resistance management.cdr

African Journals Online (AJOL)

user

the rotaional use of the acaricidal products in ways that reduces the selection pressure of active ingredients of same chemistry on the target-site in tick populations and as a result retard resistance development. acaricidal products on the market was based on mode of action of the active ingredients. The strategy requires.

The modification of siRNA with 3' cholesterol to increase nuclease protection and suppression of native mRNA by select siRNA polyplexes.

Science.gov (United States)

Ambardekar, Vishakha V; Han, Huai-Yun; Varney, Michelle L; Vinogradov, Serguei V; Singh, Rakesh K; Vetro, Joseph A

2011-02-01

Polymer-siRNA complexes (siRNA polyplexes) are being actively developed to improve the therapeutic application of siRNA. A major limitation for many siRNA polyplexes, however, is insufficient mRNA suppression. Given that modifying the sense strand of siRNA with 3' cholesterol (chol-siRNA) increases the activity of free nuclease-resistant siRNA in vitro and in vivo, we hypothesized that complexation of chol-siRNA can increase mRNA suppression by siRNA polyplexes. In this study, the characteristics and siRNA activity of self assembled polyplexes formed with chol-siRNA or unmodified siRNA were compared using three types of conventional, positively charged polymers: (i) biodegradable, cross-linked nanogels (BDNG) (ii) graft copolymers (PEI-PEG), and (iii) linear block copolymers (PLL10-PEG, and PLL50-PEG). Chol-siRNA did not alter complex formation or the resistance of polyplexes to siRNA displacement by heparin but increased nuclease protection by BDNG, PLL10-PEG, and PLL50-PEG polyplexes over polyplexes with unmodified siRNA. Chol-CYPB siRNA increased suppression of native CYPB mRNA in mammary microvascular endothelial cells (MVEC) by BDNG polyplexes (35%) and PLL10-PEG polyplexes (69%) over comparable CYPB siRNA polyplexes but had no effect on PEI-PEG or PLL50-PEG polyplexes. Overall, these results indicate that complexation of chol-siRNA increases nuclease protection and mRNA suppression by select siRNA polyplexes. These results also suggest that polycationic block length is an important factor in increasing mRNA suppression by PLL-PEG chol-siRNA polyplexes in mammary MVEC. Copyright © 2010 Elsevier Ltd. All rights reserved.

Compton suppression gamma ray spectrometry

International Nuclear Information System (INIS)

Landsberger, S.; Iskander, F.Y.; Niset, M.; Heydorn, K.

2002-01-01

In the past decade there have been many studies to use Compton suppression methods in routine neutron activation analysis as well as in the traditional role of low level gamma ray counting of environmental samples. On a separate path there have been many new PC based software packages that have been developed to enhance photopeak fitting. Although the newer PC based algorithms have had significant improvements, they still suffer from being effectively used in weak gamma ray lines in natural samples or in neutron activated samples that have very high Compton backgrounds. We have completed a series of experiments to show the usefulness of Compton suppression. As well we have shown the pitfalls when using Compton suppression methods for high counting deadtimes as in the case of neutron activated samples. We have also investigated if counting statistics are the same both suppressed and normal modes. Results are presented in four separate experiments. (author)

Suppression of turbulent resistivity in turbulent Couette flow

Science.gov (United States)

Si, Jiahe; Colgate, Stirling A.; Sonnenfeld, Richard G.; Nornberg, Mark D.; Li, Hui; Colgate, Arthur S.; Westpfahl, David J.; Romero, Van D.; Martinic, Joe

2015-07-01

Turbulent transport in rapidly rotating shear flow very efficiently transports angular momentum, a critical feature of instabilities responsible both for the dynamics of accretion disks and the turbulent power dissipation in a centrifuge. Turbulent mixing can efficiently transport other quantities like heat and even magnetic flux by enhanced diffusion. This enhancement is particularly evident in homogeneous, isotropic turbulent flows of liquid metals. In the New Mexico dynamo experiment, the effective resistivity is measured using both differential rotation and pulsed magnetic field decay to demonstrate that at very high Reynolds number rotating shear flow can be described entirely by mean flow induction with very little contribution from correlated velocity fluctuations.

Suppression of turbulent resistivity in turbulent Couette flow

Energy Technology Data Exchange (ETDEWEB)

Si, Jiahe, E-mail: jsi@nmt.edu; Sonnenfeld, Richard G.; Colgate, Arthur S.; Westpfahl, David J.; Romero, Van D.; Martinic, Joe [New Mexico Institute of Mining and Technology, Socorro, New Mexico 87801 (United States); Colgate, Stirling A.; Li, Hui [Los Alamos National Laboratory, Los Alamos, New Mexico 87544 (United States); Nornberg, Mark D. [University of Wisconsin-Madison, Madison, Wisconsin 53706 (United States)

2015-07-15

Turbulent transport in rapidly rotating shear flow very efficiently transports angular momentum, a critical feature of instabilities responsible both for the dynamics of accretion disks and the turbulent power dissipation in a centrifuge. Turbulent mixing can efficiently transport other quantities like heat and even magnetic flux by enhanced diffusion. This enhancement is particularly evident in homogeneous, isotropic turbulent flows of liquid metals. In the New Mexico dynamo experiment, the effective resistivity is measured using both differential rotation and pulsed magnetic field decay to demonstrate that at very high Reynolds number rotating shear flow can be described entirely by mean flow induction with very little contribution from correlated velocity fluctuations.

Suppression of turbulent resistivity in turbulent Couette flow

International Nuclear Information System (INIS)

Si, Jiahe; Sonnenfeld, Richard G.; Colgate, Arthur S.; Westpfahl, David J.; Romero, Van D.; Martinic, Joe; Colgate, Stirling A.; Li, Hui; Nornberg, Mark D.

2015-01-01

Turbulent transport in rapidly rotating shear flow very efficiently transports angular momentum, a critical feature of instabilities responsible both for the dynamics of accretion disks and the turbulent power dissipation in a centrifuge. Turbulent mixing can efficiently transport other quantities like heat and even magnetic flux by enhanced diffusion. This enhancement is particularly evident in homogeneous, isotropic turbulent flows of liquid metals. In the New Mexico dynamo experiment, the effective resistivity is measured using both differential rotation and pulsed magnetic field decay to demonstrate that at very high Reynolds number rotating shear flow can be described entirely by mean flow induction with very little contribution from correlated velocity fluctuations

Antibiotic resistance in the food chain: A developing country-perspective

Directory of Open Access Journals (Sweden)

Luria Leslie Founou

2016-11-01

Full Text Available Antibiotics are now endangered species facing extinction due to the worldwide emergence of antibiotic resistance (ABR. Food animals are considered as key reservoirs of antibiotic-resistant bacteria with the use of antibiotics in the food production industry having contributed to the actual global challenge of ABR. There are no geographic boundaries to impede the worldwide spread of ABR. If preventive and containment measures are not applied locally, nationally and regionally, the limited interventions in one country, continent and for instance, in the developing world, could compromise the efficacy and endanger ABR containment policies implemented in other parts of the world, the best-managed high-resource countries included. Multifaceted, comprehensive and integrated measures complying with the One Health approach are imperative to ensure food safety and security, effectively combat infectious diseases, curb the emergence and spread of ABR, and preserve the efficacy of antibiotics for future generations. Countries should follow the World Health Organization, World Organization for Animal Health, and the Food and Agriculture Organization of the United Nations recommendations to implement national action plans encompassing human, (food animal, and environmental sectors to improve policies, interventions and activities that address the prevention and containment of ABR from farm-to-fork. This review covers (i the origin of antibiotic resistance, (ii pathways by which bacteria spread to humans from farm-to-fork, (iii differences in levels of antibiotic resistance between developed and developing countries, and (iv prevention and containment measures of antibiotic resistance in the food chain.

Transcriptional Network Analysis Reveals Drought Resistance Mechanisms of AP2/ERF Transgenic Rice

Directory of Open Access Journals (Sweden)

Hongryul Ahn

2017-06-01

Full Text Available This study was designed to investigate at the molecular level how a transgenic version of rice “Nipponbare” obtained a drought-resistant phenotype. Using multi-omics sequencing data, we compared wild-type rice (WT and a transgenic version (erf71 that had obtained a drought-resistant phenotype by overexpressing OsERF71, a member of the AP2/ERF transcription factor (TF family. A comprehensive bioinformatics analysis pipeline, including TF networks and a cascade tree, was developed for the analysis of multi-omics data. The results of the analysis showed that the presence of OsERF71 at the source of the network controlled global gene expression levels in a specific manner to make erf71 survive longer than WT. Our analysis of the time-series transcriptome data suggests that erf71 diverted more energy to survival-critical mechanisms related to translation, oxidative response, and DNA replication, while further suppressing energy-consuming mechanisms, such as photosynthesis. To support this hypothesis further, we measured the net photosynthesis level under physiological conditions, which confirmed the further suppression of photosynthesis in erf71. In summary, our work presents a comprehensive snapshot of transcriptional modification in transgenic rice and shows how this induced the plants to acquire a drought-resistant phenotype.

Rolling Resistance Measurement and Model Development

DEFF Research Database (Denmark)

Andersen, Lasse Grinderslev; Larsen, Jesper; Fraser, Elsje Sophia

2015-01-01

There is an increased focus worldwide on understanding and modeling rolling resistance because reducing the rolling resistance by just a few percent will lead to substantial energy savings. This paper reviews the state of the art of rolling resistance research, focusing on measuring techniques, s......, surface and texture modeling, contact models, tire models, and macro-modeling of rolling resistance...

Human health risk assessment (HHRA) for environmental development and transfer of antibiotic resistance

DEFF Research Database (Denmark)

Ashbolt, Nicholas J.; Amézquita, Alejandro; Backhaus, Thomas

2013-01-01

to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens. Methods: The authors participated in a workshop held 4-8 March 2012 in Québec, Canada, to define the scope and objectives...... of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development "hot spots," exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options. Discussion: Various...... novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b...

Transgenic strategies for improving rice disease resistance

African Journals Online (AJOL)

STORAGESEVER

2009-05-04

May 4, 2009 ... practice. However, the useful life-span of many resistant cultivars is only a few years, due to the breakdown of the .... Thus, suppression of insect feeding by transgenic .... different types of defense-responsive genes were found.

DEVELOPMENT OF RESISTANCE IN BACTERIA AGAINST ANTI - MICROBIAL AGENTS: REASONS, THREATS AND ONGOING ENCOUNTER

OpenAIRE

Shibabrata Pattanayak

2011-01-01

Development of Multi Druug Resistant bacteria is creating a very severe problem in anti-microbial chemotherapy. Many recently developed antibiotics are found incapable to control resistant organisms.The reasons of development of resistance gene in the bacterial plasmid and their quick spread among various related and unrelated bacteria are analysed in this article along with discussion of world wide ongoing research to combat the problem.

A human model of dietary saturated fatty acid induced insulin resistance.

Science.gov (United States)

Koska, Juraj; Ozias, Marlies K; Deer, James; Kurtz, Julie; Salbe, Arline D; Harman, S Mitchell; Reaven, Peter D

2016-11-01

Increased consumption of high-fat diets is associated with the development of insulin resistance and type 2 diabetes. Current models to study the mechanisms of high-fat diet-induced IR in humans are limited by their long duration or low efficacy. In the present study we developed and characterized an acute dietary model of saturated fatty acid-enriched diet induced insulin resistance. High caloric diets enriched with saturated fatty acids (SFA) or carbohydrates (CARB) were evaluated in subjects with normal and impaired glucose tolerance (NGT or IGT). Both diets were compared to a standard eucaloric American Heart Association (AHA) control diet in a series of crossover studies. Whole body insulin resistance was estimated as steady state plasma glucose (SSPG) concentrations during the last 30min of a 3-h insulin suppression test. SSPG was increased after a 24-h SFA diet (by 83±74% vs. control, n=38) in the entire cohort, which was comprised of participants with NGT (92±82%, n=22) or IGT (65±55%, n=16) (all pinsulin resistance in both NGT and IGT subjects. Insulin resistance persisted overnight after the last SFA meal and was attenuated by one day of a healthy diet. This model offers opportunities for identifying early mechanisms and potential treatments of dietary saturated fat induced insulin resistance. Published by Elsevier Inc.

Exposure characteristics of positive tone electron beam resist containing p-chloro-α-methylstyrene

Science.gov (United States)

Ochiai, Shunsuke; Takayama, Tomohiro; Kishimura, Yukiko; Asada, Hironori; Sonoda, Manae; Iwakuma, Minako; Hoshino, Ryoichi

2017-07-01

The positive tone resist consisted of methyl-α-chloroacrylate (ACM) and α-methylstyrene (MS) has higher sensitivity and higher dry etching resistance than poly (methylmethacrylate) (PMMA) due to the presence of a chlorine atom and a phenyl group. Copolymers consisted of ACM and p-chloro-α-methylstyrene (PCMS), where the additional chlorine atom is introduced in phenyl group compared with ACM-MS resist are synthesized and their exposure characteristics are investigated. ACM-PCMS resist with the ACM:PCMS composition ratio of 49:51 indicates the high solubility for amyl acetate developer. As the ACM composition ratio increases, the solubility of ACM-PCMS resist is suppressed. In both ACM-PCMS and ACM-MS resists, the sensitivity decreases while the contrast increases with increasing ACM ratio. When the composition ratio of ACM:PCMS is 69:31, 100/100 nm line and space pattern having a good shape is obtained at 120 μC/cm2 which is comparable to the required exposure dose for conventional ACM-MS resist with ACM:MS=50:50. Dry etching resistance of ACM:PCMS resists for Ar gas is also presented.

Susceptibility of hepatitis B virus to lamivudine restored by resistance to adefovir

NARCIS (Netherlands)

Zaaijer, H. L.; Takkenberg, R. B.; Weegink, C. J.; Rebers, S. P. H.; Menting, S.; Reesink, H. W.; Schinkel, J.; Molenkamp, R.

2009-01-01

Serial monotherapy and add-on regimes for treatment of chronic hepatitis B virus (HBV) infection may induce the accumulation of viral resistance mutations in patients, reducing the options for ongoing viral suppression. The induction of antiviral resistance by serial application of polymerase

Development of high-performance concrete having high resistance to chloride penetration

International Nuclear Information System (INIS)

Oh, Byung Hwan; Cha, Soo Won; Jang, Bong Seok; Jang, Seung Yup

2002-01-01

The resistance to chloride penetration is one of the simplest measures to determine the durability of concrete, e.g. resistance to freezing and thawing, corrosion of steel in concrete and other chemical attacks. Thus, high-performance concrete may be defined as the concrete having high resistance to chloride penetration as well as high strength. The purpose of this paper is to investigate the resistance to chloride penetration of different types of concrete and to develop high-performance concrete that has very high resistance to chloride penetration, and thus, can guarantee high durability. A large number of concrete specimens have been tested by the rapid chloride permeability test method as designated in AASHTO T 277 and ASTM C 1202. The major test variables include water-to-binder ratios, type of cement, type and amount of mineral admixtures (silica fume, fly ash and blast-furnace slag), maximum size of aggregates and air-entrainment. Test results show that concrete containing optimal amount of silica fume shows very high resistance to chloride penetration, and high-performance concrete developed in this study can be efficiently employed to enhance the durability of concrete structures in severe environments such as nuclear power plants, water-retaining structures and other offshore structures

SCREENING FOR DEVELOPMENT OF HOST PLANT RESISTANCE ...

African Journals Online (AJOL)

Tangaza

losses of cowpea yields and if not controlled, they limit the yields to less than 300kg/ha (Singh et al., 1990). A considerable progress has been made during the past decade in cowpea breeding and a range of varieties have been developed with resistance to several diseases, insect pests and parasitic weeds. Much time ...

Antimicrobial resistance 1979-2009 at Karolinska hospital, Sweden: normalized resistance interpretation during a 30-year follow-up on Staphylococcus aureus and Escherichia coli resistance development.

Science.gov (United States)

Kronvall, Göran

2010-09-01

To utilize a material of inhibition zone diameter measurements from disc diffusion susceptibility tests between 1979 and 2009, an objective setting of epidemiological breakpoints was necessary because of methodological changes. Normalized resistance interpretation (NRI) met this need and was applied to zone diameter histograms for Staphylococcus aureus and Escherichia coli isolates. The results confirmed a slow resistance development as seen in Northern countries. The S. aureus resistance levels for erythromycin, clindamycin and fusidic acid in 2009 were 3.2%, 1.8% and 1.4% with denominator correction. A rise in resistance to four antimicrobials in 1983 was probably because of a spread of resistant Methicillin Susceptible Staphylococcus Aureus (MSSA). For E. coli, the denominator-corrected resistance levels in 2009 were 27% for ampicillin, around 3% for third-generation cephalosporins, 0.1% for imipenem, 2.5% for gentamicin, 19% for trimethoprim, 4.5% for co-trimoxazole, 1.2% for nitrofurantoin and 9% for ciprofloxacin. The temporal trends showed a rise in fluoroquinolone resistance from 1993, a parallel increase in gentamicin resistance, a substantial increase in trimethoprim and sulphonamide resistance in spite of decreased consumption, and a steady rise in ampicillin resistance from a constant level before 1989. A short review of global resistance surveillance studies is included.

HDAC Inhibitors Disrupt Programmed Resistance to Apoptosis During Drosophila Development

Directory of Open Access Journals (Sweden)

Yunsik Kang

2017-06-01

Full Text Available We have previously shown that the ability to respond to apoptotic triggers is regulated during Drosophila development, effectively dividing the fly life cycle into stages that are either sensitive or resistant to apoptosis. Here, we show that the developmentally programmed resistance to apoptosis involves transcriptional repression of critical proapoptotic genes by histone deacetylases (HDACs. Administration of HDAC inhibitors (HDACi, like trichostatin A or suberoylanilide hydroxamic acid, increases expression of proapoptotic genes and is sufficient to sensitize otherwise resistant stages. Conversely, reducing levels of proapoptotic genes confers resistance to otherwise sensitive stages. Given that resistance to apoptosis is a hallmark of cancer cells, and that HDACi have been recently added to the repertoire of FDA-approved agents for cancer therapy, our results provide new insights for how HDACi help kill malignant cells and also raise concerns for their potential unintended effects on healthy cells.

DEVELOPMENT OF RESISTANCE IN BACTERIA AGAINST ANTI - MICROBIAL AGENTS: REASONS, THREATS AND ONGOING ENCOUNTER

Directory of Open Access Journals (Sweden)

Shibabrata Pattanayak

2011-07-01

Full Text Available Development of Multi Druug Resistant bacteria is creating a very severe problem in anti-microbial chemotherapy. Many recently developed antibiotics are found incapable to control resistant organisms.The reasons of development of resistance gene in the bacterial plasmid and their quick spread among various related and unrelated bacteria are analysed in this article along with discussion of world wide ongoing research to combat the problem.

Development of proliferation resistance assessment methodology based on international standard

International Nuclear Information System (INIS)

Ko, W. I.; Chang, H. L.; Lee, Y. D.; Lee, J. W.; Park, J. H.; Kim, Y. I.; Ryu, J. S.; Ko, H. S.; Lee, K. W.

2012-04-01

Nonproliferation is one of the main requirements to be satisfied by the advanced future nuclear energy systems that have been developed in the Generation IV and INPRO studies. The methodologies to evaluate proliferation resistance has been developed since 1980s, however, the systematic evaluation approach has begun from around 2000. Domestically a study to develop national method to evaluate proliferation resistance (PR) of advanced future nuclear energy systems has started in 2007 as one of the long-term nuclear R and D subjects in order to promote export and international credibility and transparency of national nuclear energy systems and nuclear fuel cycle technology development program. In the first phase (2007-2010) development and improvement of intrinsic evaluation parameters for the evaluation of proliferation resistance, quantification of evaluation parameters, development of evaluation models, and development of permissible ranges of evaluation parameters have been carried out. In the second phase (2010-2012) generic principle of to evaluate PR was established, and techincal guidelines, nuclear material diversion pathway analysis method, and a method to integrate evaluation parameters have been developed. which were applied to 5 alternative nuclear fuel cycles to estimate their appicability and objectivity. In addition, measures to enhance PR of advanced future nuclear energy systems and technical guidelines of PR assessment using intrinsic PR evaluation parameters were developed. Lastly, requlatory requirements to secure nonproliferation requirements of nuclear energy systems from the early design stage, operation and to decommissioning which will support the export of newly developed advanced future nuclear energy system

The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development.

Science.gov (United States)

Miyazaki, Masaki; Miyazaki, Kazuko; Chen, Kenian; Jin, Yi; Turner, Jacob; Moore, Amanda J; Saito, Rintaro; Yoshida, Kenichi; Ogawa, Seishi; Rodewald, Hans-Reimer; Lin, Yin C; Kawamoto, Hiroshi; Murre, Cornelis

2017-05-16

Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire, including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On the basis of these and previous observations, we propose that the E-Id protein axis specifies innate and adaptive lymphoid cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

Proton beam micromachining on strippable aqueous base developable negative resist

International Nuclear Information System (INIS)

Rajta, I.; Uzonyi, I.; Baradacs, E.; Chatzichristidi, M.; Raptis, I.; Valamontes, E.S.

2004-01-01

Complete text of publication follows. Proton Beam Micromachining (PBM, also known as P-beam writing), a novel direct- write process for the production of 3D microstructures, can be used to make multilevel structures in a single layer of resist by varying the ion energy. The interaction between the bombarding ions and the target material is mainly ionization, and very few ions suffer high angle nuclear collisions, therefore structures made with PBM have smooth near vertical side walls. The most commony applied resists in PBM are the positive, conventional, polymethyl methacrylate (PMMA); and the negative, chemically amplified, SU-8 (Micro Chem Corp). SU-8 is an epoxy based resist suitable also for LIGA and UV-LIGA processes, it offers good sensitivity, good process latitude, very high aspect ratio and therefore it dominates in the high aspect ratio micromachining applications. SU-8 requires 30 nC/mm 2 fluence for PBM irradiations at 2 MeV protons. Its crosslinking chemistry is based on the eight epoxy rings in the polymer chain, which provide a very dense three dimensional network in the presence of suitably activated photo acid generators (PAGs) which is very difficult to be stripped away after development. Thus, stripping has to be assisted with plasma processes or with special liquid removers. Moreover, the SU-8 developer is organic, propylene glycol methyl ether acetate (PGMEA), and thus environmentally non-friendly. To overcome the SU-8 stripping limitations, design of a negative resist system where solubility change is not based solely on cross- linking but also on the differentiation of hydrophilicity between exposed and non-exposed areas is desirable. A new resist formulation, fulfilling the above specifications has been developed recently [1]. This formulation is based on a specific grade epoxy novolac (EP) polymer, a partially hydrogenated poly-4-hydroxy styrene (PHS) polymer, and an onium salt as photoacid generator (PAG), and has been successfully

H19 mediates methotrexate resistance in colorectal cancer through activating Wnt/β-catenin pathway

International Nuclear Information System (INIS)

Wu, Ke-feng; Liang, Wei-Cheng; Feng, Lu; Pang, Jian-xin; Waye, Mary Miu-Yee; Zhang, Jin-Fang; Fu, Wei-Ming

2017-01-01

Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. As one of the earliest cytotoxic drugs, methotrexate (MTX) serves as an anti-metabolite and anti-folate chemotherapy for various cancers. Unfortunately, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the therapeutic efficacy of MTX in clinics. Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years. More and more emerging evidences have demonstrated that they play important regulatory roles in various biological activities and disease progression including drug resistance. In the present study, a MTX-resistant colorectal cell line HT-29 (HT-29-R) was developed, which displayed the active proliferation and shortened cell cycle. LncRNA H19 was found to be significantly upregulated in this resistant cell line. Further investigation showed that H19 knockdown sensitized the MTX resistance in HT-29-R cells while its overexpression improved the MTX resistance in the parental cells, suggesting that H19 mediate MTX resistance. The Wnt/β-catenin signaling was activated in HT-29-R cells, and H19 knockdown suppressed this signaling in the parental cells. In conclusion, H19 mediated MTX resistance via activating Wnt/β-catenin signaling, which help to develop H19 as a promising therapeutic target for MTX resistant CRC. - Highlights: • A methotrexate (MTX) -resistant colorectal cancer cell line HT-29 (HT-29-R) has been developed. • H19 was upregulated in HT-29-R cells. • H19 mediated MTX resistance in colorectal cancer (CRC). • Wnt/β-catenin pathway was involved in the H19-mediated MTX resistance in CRC cells.

H19 mediates methotrexate resistance in colorectal cancer through activating Wnt/β-catenin pathway

Energy Technology Data Exchange (ETDEWEB)

Wu, Ke-feng [Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical University, Zhanjiang, Guangdong (China); Liang, Wei-Cheng [School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong (China); Feng, Lu [Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong (China); Pang, Jian-xin [School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 (China); Waye, Mary Miu-Yee [School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong (China); Zhang, Jin-Fang [Department of Orthopaedics & Traumatology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong (China); Fu, Wei-Ming, E-mail: fuweiming76@smu.edu.cn [School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515 (China)

2017-01-15

Colorectal cancer (CRC) is a common malignancy, most of which remain unresponsive to chemotherapy. As one of the earliest cytotoxic drugs, methotrexate (MTX) serves as an anti-metabolite and anti-folate chemotherapy for various cancers. Unfortunately, MTX resistance prevents its clinical application in cancer therapy. Thereby, overcoming the drug resistance is an alternative strategy to maximize the therapeutic efficacy of MTX in clinics. Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years. More and more emerging evidences have demonstrated that they play important regulatory roles in various biological activities and disease progression including drug resistance. In the present study, a MTX-resistant colorectal cell line HT-29 (HT-29-R) was developed, which displayed the active proliferation and shortened cell cycle. LncRNA H19 was found to be significantly upregulated in this resistant cell line. Further investigation showed that H19 knockdown sensitized the MTX resistance in HT-29-R cells while its overexpression improved the MTX resistance in the parental cells, suggesting that H19 mediate MTX resistance. The Wnt/β-catenin signaling was activated in HT-29-R cells, and H19 knockdown suppressed this signaling in the parental cells. In conclusion, H19 mediated MTX resistance via activating Wnt/β-catenin signaling, which help to develop H19 as a promising therapeutic target for MTX resistant CRC. - Highlights: • A methotrexate (MTX) -resistant colorectal cancer cell line HT-29 (HT-29-R) has been developed. • H19 was upregulated in HT-29-R cells. • H19 mediated MTX resistance in colorectal cancer (CRC). • Wnt/β-catenin pathway was involved in the H19-mediated MTX resistance in CRC cells.

The Modification of siRNA with 3′ Cholesterol to Increase Nuclease Protection and Suppression of Native mRNA by Select siRNA Polyplexes

Science.gov (United States)

Ambardekar, Vishakha V.; Han, Huai-Yun; Varney, Michelle L.; Vinogradov, Serguei V.; Singh, Rakesh K.; Vetro, Joseph A.

2010-01-01

Polymer-siRNA complexes (siRNA polyplexes) are being actively developed to improve the therapeutic application of siRNA. A major limitation for many siRNA polyplexes, however, is insufficient mRNA suppression. Given that modifying the sense strand of siRNA with 3′ cholesterol (chol-siRNA) increases the activity of free nuclease-resistant siRNA in vitro and in vivo, we hypothesized that complexation of chol-siRNA can increase mRNA suppression by siRNA polyplexes. In this study, the characteristics and siRNA activity of self assembled polyplexes formed with chol-siRNA or unmodified siRNA were compared using three types of conventional, positively charged polymers: (i) biodegradable, cross-linked nanogels (BDNG) (ii) graft copolymers (PEI-PEG), and (iii) linear block copolymers (PLL10-PEG, and PLL50-PEG). Chol-siRNA did not alter complex formation or the resistance of polyplexes to siRNA displacement by heparin but increased nuclease protection by BDNG, PLL10-PEG, and PLL50-PEG polyplexes over polyplexes with unmodified siRNA. Chol-CYPB siRNA increased suppression of native CYPB mRNA in mammary microvascular endothelial cells (MVEC) by BDNG polyplexes (35%) and PLL10-PEG polyplexes (69%) over comparable CYPB siRNA polyplexes but had no effect on PEI-PEG or PLL50-PEG polyplexes. Overall, these results indicate that complexation of chol-siRNA increases nuclease protection and mRNA suppression by select siRNA polyplexes. These results also suggest that polycationic block length is an important factor in increasing mRNA suppression by PLL-PEG chol-siRNA polyplexes in mammary MVEC. PMID:21047680

Zinc and copper in animal feed - development of resistance and co-resistance to antimicrobial agents in bacteria of animal origin

OpenAIRE

Yazdankhah, Siamak; Rudi, Knut; Bernhoft, Aksel

2014-01-01

Farmed animals such as pig and poultry receive additional Zn and Cu in their diets due to supplementing elements in compound feed as well as medical remedies. Enteral bacteria in farmed animals are shown to develop resistance to trace elements such as Zn and Cu. Resistance to Zn is often linked with resistance to methicillin in staphylococci, and Zn supplementation to animal feed may increase the proportion of multiresistant E. coli in the gut. Resistance to Cu in bacteria, in particular ente...

Antibiosis in Soybean Genotypes and the Resistance Levels to Spodoptera eridania (Cramer) (Lepidoptera: Noctuidae).

Science.gov (United States)

Souza, B H S; Silva, A G; Janini, J C; Boica Júnior, A L

2014-12-01

The southern armyworm (SAW) Spodoptera eridania (Cramer) is one of the most common armyworm species defoliating soybeans. Preliminary screening trials have indicated that some soybean genotypes exhibit resistance to SAW. Therefore, in this study, we evaluated the development of SAW larvae fed on ten soybean genotypes in order to identify genotypes with antibiosis-type resistance. Neonate SAW larvae were daily fed with young leaves collected from plants at the vegetative growth stages V4-V5. Larval development and survival were recorded. Genotypes PI 227687 and PI 227682 delayed larval, pupal, and larva-adult development and yielded larvae with the lowest weight and survival and pupae with the lowest weight. Genotypes IAC 100 and DM 339 also negatively affected larval and pupal development and larval survival but at a lower level. Based on our results, the soybean lines PI 227687 and PI 227682 could be used as sources of genes for soybean breeding programs aiming to develop high yield, SAW-resistant cultivars. Moreover, further trials must be carried out under field conditions to validate if the commercial cultivars IAC 100 and DM 339, which expressed moderate levels of antibiosis-type resistance in the laboratory, are effective in suppressing SAW larvae populations.

Using and development of multi adversity resistance system in cotton

Directory of Open Access Journals (Sweden)

Metin Durmuş ÇETİN

2014-12-01

Full Text Available The basic approach in plant breeding, make it possible to show the full genetic potential of plant. This methods also protect the health of plant growth over the period, by increasing resistance to diseases and pests is expected to provide. For this purpose, by Bird in 1963, with the name of multi adversity resistance has been initiated in cotton breeding and for many years as a result of the work carried out important varieties and germplasm have been developed. Nowadays, those using for varieties resistant to stress factors such as heat and drought are evaluated. And successful results are obtained.

Development of power MOSFET (150 W class)

Science.gov (United States)

Kuboyama, Satoshi; Tamura, Takashi; Uesugi, Masato; Kanno, Tooru

1992-08-01

An overview of the power Metal Oxide Semiconductor (MOS) Field Effect Transistor (FET) is presented. Development was being conducted to upgrade radiation resistance without impairing electrical characteristics and to improve chip process design for decreasing on resistance by trading off with switching speed (device capacity) and small package design. Chip design were conducted to decrease the process temperature for increasing total dose resistance, suppress parasitic transistor behavior for augmenting single event resistance, and optimize FET cell structure and dimension for decreasing on resistance. Evaluation test of the trial produced samples was conducted. Package materials were selected and their assembly technologies were established. Evaluation test was conducted especially focusing on the effects of bonding and sealing property, and lead forming. The possibility to provide the engineering model to the JEM (Japanese Experiment Module) project was obtained.

Harms caused by China's 1906-17 opium suppression intervention.

Science.gov (United States)

Windle, James

2013-09-01

Between 1906 and 1917 China (under the Imperial and then Republican regimes) enacted a highly effective intervention to suppress the production of opium. Evidence from British Foreign Office records suggest that the intervention was centred, in many areas, upon a highly repressive incarnation of law enforcement in which rural populations had their property destroyed, their land confiscated and/or were publically tortured, humiliated and executed. Crops were forcefully eradicated and resistance was often brutally suppressed by the military. As few farmers received compensation or support for alternative livelihood creation the intervention pushed many deeper into poverty. Importantly, the repressive nature of the opium ban appears to have been a contributing factor to the fragmentation of China, highlighting the counter-productivity of repressive interventions to reduce drug crop production. Copyright © 2013 Elsevier B.V. All rights reserved.

Development of heat resistant ion exchange resin. First Report

International Nuclear Information System (INIS)

Onozuka, Teruo; Shindo, Manabu

1995-01-01

In nuclear power stations, as a means of maintaining the soundness of nuclear reactors, the cleaning of reactor cooling water has been carried out. But as for the ion exchange resin which is used as the cleaning agent in the filtrating and desalting facility in reactor water cleaning system, since the heat resistance is low, high temperature reactor water is cooled once and cleaned, therefore large heat loss occurs. If the cleaning can be done at higher temperature, the reduction of heat loss and compact cleaning facilities become possible. In this study, a new ion exchange resin having superior heat resistance has been developed, and the results of the test of evaluating the performance of the developed ion exchange resin are reported. The heat loss in reactor water cleaning system, the heat deterioration of conventional ion exchange resin, and the development of the anion exchange resin of alkyl spacer type are described. The outline of the performance evaluation test, the experimental method, and the results of the heat resistance, ion exchange characteristics and so on of C4 resin are reported. The with standable temperature of the developed anion exchange resin was estimated as 80 - 90degC. The ion exchange performance at 95degC of this resin did not change from that at low temperature in chloride ions and silica, and was equivalent to that of existing anion exchange resin. (K.I.)

Development of heat resistant ion exchange resin. First Report

Energy Technology Data Exchange (ETDEWEB)

Onozuka, Teruo; Shindo, Manabu [Tohoku Electric Power Co., Inc., Sendai (Japan)

1995-01-01

In nuclear power stations, as a means of maintaining the soundness of nuclear reactors, the cleaning of reactor cooling water has been carried out. But as for the ion exchange resin which is used as the cleaning agent in the filtrating and desalting facility in reactor water cleaning system, since the heat resistance is low, high temperature reactor water is cooled once and cleaned, therefore large heat loss occurs. If the cleaning can be done at higher temperature, the reduction of heat loss and compact cleaning facilities become possible. In this study, a new ion exchange resin having superior heat resistance has been developed, and the results of the test of evaluating the performance of the developed ion exchange resin are reported. The heat loss in reactor water cleaning system, the heat deterioration of conventional ion exchange resin, and the development of the anion exchange resin of alkyl spacer type are described. The outline of the performance evaluation test, the experimental method, and the results of the heat resistance, ion exchange characteristics and so on of C4 resin are reported. The with standable temperature of the developed anion exchange resin was estimated as 80 - 90degC. The ion exchange performance at 95degC of this resin did not change from that at low temperature in chloride ions and silica, and was equivalent to that of existing anion exchange resin. (K.I.).

Nematode suppression and growth stimulation in corn plants (Zea mays L.) irrigated with domestic effluent.

Science.gov (United States)

Barros, Kenia Kelly; do Nascimento, Clístenes Williams Araújo; Florencio, Lourdinha

2012-01-01

Treated wastewater has great potential for agricultural use due to its concentrations of nutrients and organic matter, which are capable of improving soil characteristics. Additionally, effluents can induce suppression of plant diseases caused by soil pathogens. This study evaluates the effect of irrigation with effluent in a UASB reactor on maize (Zea mays L.) development and on suppression of the diseases caused by nematodes of the genus Meloidogyne. Twelve lysimeters of 1 m(3) each were arranged in a completely randomized design, with four treatments and three replicates. The following treatments were used: T1 (W+I), irrigation with water and infestation with nematodes; T2 (W+I+NPK), irrigation with water, infestation with nematodes and fertilization with nitrogen (N), phosphorus (P) and potassium (K); T3 (E+I), irrigation with effluent and infestation with nematodes; and T4 (E+I+P), irrigation with effluent, infestation with nematodes and fertilization with phosphorus. The plants irrigated with the effluent plus the phosphorus fertilizer had better growth and productivity and were more resistant to the disease symptoms caused by the nematodes. The suppression levels may have been due to the higher levels of Zn and NO(3)(-) found in the leaf tissue of the plants irrigated with the effluent and phosphorus fertilizer.

Development of debris-resistant bottom end piece

International Nuclear Information System (INIS)

Sohn, Dong Seong; Lee, Jae Kyung; Hwang, Dae Hyun; Yim, Jung Sik; Song, Kee Nam; Oh, Dong Seok; Im, Hyun Tae

1993-01-01

Debris-related fuel failures has been identified to be one of the major causes of fuel failures recently occured in nuclear power plants. In order to reduce the possibility of debris-related fuel failures, it is necessary to prevent the debris from reaching to fuel rods. In this regard, it is important to develop Debris-Resistant Bottom End Piece. (Author)

Application of Composite Materials in the Fire Explosion Suppression System

Institute of Scientific and Technical Information of China (English)

REN Shah

2012-01-01

In order to lighten the weight of the special vehicles and improve their mobility and flexibility, the weight of all subsystems of the whole vehicle must be reduced in the general planning. A fire explosion suppression system is an important subsystem for the self-protection of vehicle, protection of crews and safety of a vehicle. The performances of the special vehicles determine their survival ability and combat capability. The composite bottle is made of aluminum alloy with externally wrapped carbon fiber ; it has been proven by a large number of tests that the new type explosion suppression fire distinguisher made of such composite materials applied in the special vehicle has reliable performance, each of its technical indexes is higher or equal to that of a steel distinguisher, and the composites can also optimize the assembly structure of the bottle, and improve the reliability and corrosion resistance. Most important is that the composite materials can effectively lighten the weight of the fire explosion suppression system to reach the target of weight reduction of the subsystem in general planning.

Curcumin Modulates the Radiosensitivity of Colorectal Cancer Cells by Suppressing Constitutive and Inducible NF-κB Activity

International Nuclear Information System (INIS)

Sandur, Santosh K.; Deorukhkar, Amit; Pandey, Manoj K.; Pabon, Ana Maria B.S.; Shentu, Shujun; Guha, Sushovan; Aggarwal, Bharat B.; Krishnan, Sunil

2009-01-01

Purpose: Radiation therapy is an integral part of the preoperative treatment of rectal cancers. However, only a minority of patients achieve a complete pathologic response to therapy because of resistance of these tumors to radiation therapy. This resistance may be mediated by constitutively active pro-survival signaling pathways or by inducible/acquired mechanisms in response to radiation therapy. Simultaneous inhibition of these pathways can sensitize these tumors to radiation therapy. Methods and Materials: Human colorectal cancer cells were exposed to clinically relevant doses of gamma rays, and the mechanism of their radioresistance was investigated. We characterized the transcription factor nuclear factor-κB (NF-κB) activation as a mechanism of inducible radioresistance in colorectal cancer and used curcumin, the active ingredient in the yellow spice turmeric, to overcome this resistance. Results: Curcumin inhibited the proliferation and the post-irradiation clonogenic survival of multiple colorectal cancer cell lines. Radiation stimulated NF-κB activity in a dose- and time-dependent manner, whereas curcumin suppressed this radiation-induced NF-κB activation via inhibition of radiation-induced phosphorylation and degradation of inhibitor of κB alpha, inhibition of inhibitor of κB kinase activity, and inhibition of Akt phosphorylation. Curcumin also suppressed NF-κB-regulated gene products (Bcl-2, Bcl-x L , inhibitor of apoptosis protein-2, cyclooxygenase-2, and cyclin D1). Conclusions: Our results suggest that transient inducible NF-κB activation provides a prosurvival response to radiation that may account for development of radioresistance. Curcumin blocks this signaling pathway and potentiates the antitumor effects of radiation therapy.

Herbivory enhances the resistance of mangrove forest to cordgrass invasion.

Science.gov (United States)

Zhang, Yihui; Meng, Hanyu; Wang, Yi; He, Qiang

2018-06-01

The biotic resistance hypothesis proposes that biotic interactions, such as competition and herbivory, resist the establishment and spread of non-native species. The relative and interactive role of competition and herbivory in resisting plant invasions, however, remains poorly understood. We investigated the interactive role of competition and herbivory (by the native rodent Rattus losea) in resisting Spartina alterniflora (cordgrass) invasions into mangrove forests. In southern China, although exotic cordgrass numerically dominates intertidal mudflats and open gaps in mangrove forests, intact forests appear to be highly resistant to cordgrass invasion. A field transplant and rodent exclusion experiment showed that while the impact of rodent grazing on cordgrass was weak on mangrove forest edges and open mudflats, rodent grazing strongly suppressed cordgrass in mangrove understory habitats. A greenhouse experiment confirmed a synergistic interaction between grazing and light availability (a proxy for mangrove shading and light competition) in suppressing cordgrass establishment, with the strongest impacts of grazing in low light conditions that likely weakened cordgrass to survive and resprout. When both were present, as in mangrove understory habitats, grazing and low light acted in concert to eliminate cordgrass establishment, resulting in resistance of mangrove forests to cordgrass invasion. Our results reveal that grazing by native herbivores can enhance the resistance of mangrove forests to cordgrass invasion in southern China, and suggest that investigating multifactor interactions may be critical to understanding community resistance to exotic invasions. © 2018 by the Ecological Society of America.

Human Health Risk Assessment (HHRA) for Environmental Development and Transfer of Antibiotic Resistance

Science.gov (United States)

Amézquita, Alejandro; Backhaus, Thomas; Borriello, Peter; Brandt, Kristian K.; Collignon, Peter; Coors, Anja; Finley, Rita; Gaze, William H.; Heberer, Thomas; Lawrence, John R.; Larsson, D.G. Joakim; McEwen, Scott A.; Ryan, James J.; Schönfeld, Jens; Silley, Peter; Snape, Jason R.; Van den Eede, Christel; Topp, Edward

2013-01-01

Background: Only recently has the environment been clearly implicated in the risk of antibiotic resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks. Objective: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of antibiotic treatment caused by antibiotic-resistant pathogens. Methods: The authors participated in a workshop held 4–8 March 2012 in Québec, Canada, to define the scope and objectives of an environmental assessment of antibiotic-resistance risks to human health. We focused on key elements of environmental-resistance-development “hot spots,” exposure assessment (unrelated to food), and dose response to characterize risks that may improve antibiotic-resistance management options. Discussion: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental antibiotic resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental “hot spot” compartments; and c) modifying traditional dose–response approaches to address doses of ARB for various health outcomes and pathways. Conclusions: We propose that environmental aspects of antibiotic-resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental antibiotic resistance that informs risk managers. Citation: Ashbolt NJ, Amézquita A, Backhaus T, Borriello P, Brandt KK, Collignon P, Coors A, Finley R, Gaze WH, Heberer T, Lawrence JR, Larsson DG, McEwen SA, Ryan JJ, Schönfeld J, Silley P, Snape JR

Rifampin Resistance rpoB Alleles or Multicopy Thioredoxin/Thioredoxin Reductase Suppresses the Lethality of Disruption of the Global Stress Regulator spx in Staphylococcus aureus

DEFF Research Database (Denmark)

Villanueva, Maite; Jousselin, Ambre; Baek, Kristoffer T

2016-01-01

is a thiol/oxidative stress sensor that interacts with the C-terminal domain of the RNA polymerase RpoA subunit, leading to changes in gene expression that help sustain viability under various conditions. Using genetic and deep-sequencing methods, we show that spx is essential in S. aureus...... discovered that Spx, an RNA polymerase-interacting stress regulator implicated in many stress responses in S. aureus, including responses to oxidative and cell wall antibiotics, is essential. We describe two mechanisms that suppress the lethality of spx disruption. One mechanism highlights how only certain...... rifampin resistance-encoding alleles of RpoB confer new properties on RNA polymerase, with important mechanistic implications. We describe additional stress conditions where the loss of spx is deleterious, thereby highlighting Spx as a multifaceted regulator and attractive drug discovery target....

Induced mutations to develop sources of resistance to rice blast, Pyricularia grisea Sacc

International Nuclear Information System (INIS)

Correa-Victoria, F.J.

2001-01-01

Rice blast caused by Pyricularia grisea is the most important disease limiting yields worldwide. The pathogen has many virulent forms or pathotypes, hence durable blast resistance is lacking. Studies on strategy to develop durable blast resistance based on defining the genetic structure of the population, using DNA-fingerprinting, and virulence diversity are described. This strategy is leading to the identification of resistance genes/sources against all isolates within a genetic family of the pathogen. Combinations of genes showing complementary resistance to different genetic families of the fungus exclude any compatible interaction with a blast isolate. Identification of complementary resistance genes is based on detecting those virulence factors whose combinations in individual isolates within the pathogen population have a frequency near zero. Identifying and combining resistance genes to which combinations of corresponding virulence genes are absent in the pathogen population should confer more durable resistance than that previously obtained. The use of induced mutations in the development of resistance was limited, since in most cases single gene changes were responsible for the induced resistance against all the pathogen population. The main objective here is to develop many mutants, each with a gene resistant to just one or a few families of the blast pathogen; and crossing them can accumulate the different resistance genes. A total of 201 Latin American commercial cultivars, including Cuban, Brazilian and Venezuelan were analyzed with different genetic families of the blast pathogen to identify potential sources of resistance to blast and identify complementary resistance sources. Characterization of the resistance of 37 mutants of the Colombian rice cultivar Oryzica 1 was conducted in collaboration with the INEA in Colombia. Results suggested that mutations for resistance to genetic families to which Oryzica 1 is susceptible were induced, although one

Laboratory investigation into the development of resistance of Daphnia manga (straus) to environmental pollutants

Energy Technology Data Exchange (ETDEWEB)

LeBlanc, G.A.

1982-04-01

The purpose of this study was to determine the ability of Daphnia magna (Straus) to develop resistance to selected environmental pollutants through physiological adaptation or the selection of genetically fit organisms. The results of the study demonstrated that daphnids pre-exposed to copper, lead or zinc for 20 h had become significantly resistant to the toxic effects of these metals. Similar tests performed with sodium lauryl sulfate, however, resulted in no increased resistance. Exposure of successive generations of daphnids to copper resulted in the development of significant resistance to copper. However, this resistance was determined to be the result of physiological adaptation and was not due to the selection of genetically fit organisms. Multigeneration exposures to sodium lauryl sulfate failed to produce any increased resistance to the toxic effects of this compound.Exposure of successive generations to sodium lauryl sulfate increased each generation's sensitivity to the toxicity of this compound. To determine if resistance to one pollutant might confer resistance to others, the resistance, to zinc and lead, of daphnids pre-exposed to copper was assessed. Copper-resistant daphnids demonstrated no increased resistance to the toxic effects of zinc or lead.

Experience with IBS-suppression lattice in RHIC

International Nuclear Information System (INIS)

Litvinenko, V.N.; Luo, Y.; Ptitsyn, V.; Satogata, T.; Tepikian, S.; Bai, M.; Bruno, D.; Cameron, P.; Connolly, R.; Della Penna, A.; Drees, A.; Fedotov, A.; Ganetis, G.; Hoff, L.; Louie, W.; Malitsky, N.; Marr, G.; Marusic, A.; Montag, C.; Pilat, F.; Roser, T.; Trbojevic, D.; Tsoupas, N.

2008-01-01

An intra-beam scattering (IBS) is the limiting factor of the luminosity lifetime for RHIC operating with heavy ions. In order to suppress the IBS we designed and implemented new lattice with higher betatron tunes. This lattice had been developed during last three years and had been used for gold ions in yellow ring of the RHIC during d-Au part of the RHIC Run-8. The use of this lattice allowed both significant increases in the luminosity lifetime and the luminosity levels via reduction of beta-stars in the IPS. In this paper we report on the development, the tests and the performance of IBS-suppression lattice in RHIC, including the resulting increases in the peak and the average luminosity. We also report on our plans for future steps with the IBS suppression

Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity

DEFF Research Database (Denmark)

Nellemann, B.; Vendelbo, M.H.; Nielsen, Thomas Svava

2014-01-01

Insulin resistance induced by growth hormone (GH) is linked to promotion of lipolysis by unknown mechanisms. We hypothesized that suppression of the activity of pyruvate dehydrogenase in the active form (PDHa) underlies GH-induced insulin resistance similar to what is observed during fasting....

Deconstructing Interocular Suppression: Attention and Divisive Normalization.

Directory of Open Access Journals (Sweden)

Hsin-Hung Li

2015-10-01

Full Text Available In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression, the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature and divisive normalization contribute to interocular suppression.

Deconstructing Interocular Suppression: Attention and Divisive Normalization.

Science.gov (United States)

Li, Hsin-Hung; Carrasco, Marisa; Heeger, David J

2015-10-01

In interocular suppression, a suprathreshold monocular target can be rendered invisible by a salient competitor stimulus presented in the other eye. Despite decades of research on interocular suppression and related phenomena (e.g., binocular rivalry, flash suppression, continuous flash suppression), the neural processing underlying interocular suppression is still unknown. We developed and tested a computational model of interocular suppression. The model included two processes that contributed to the strength of interocular suppression: divisive normalization and attentional modulation. According to the model, the salient competitor induced a stimulus-driven attentional modulation selective for the location and orientation of the competitor, thereby increasing the gain of neural responses to the competitor and reducing the gain of neural responses to the target. Additional suppression was induced by divisive normalization in the model, similar to other forms of visual masking. To test the model, we conducted psychophysics experiments in which both the size and the eye-of-origin of the competitor were manipulated. For small and medium competitors, behavioral performance was consonant with a change in the response gain of neurons that responded to the target. But large competitors induced a contrast-gain change, even when the competitor was split between the two eyes. The model correctly predicted these results and outperformed an alternative model in which the attentional modulation was eye specific. We conclude that both stimulus-driven attention (selective for location and feature) and divisive normalization contribute to interocular suppression.

High doses of corticosteroid suppress resistance to Ichthyophonus in starry flounder

Science.gov (United States)

Perry, J.A.; Kocan, R.M.; Winton, J.R.; Hershberger, P.K.

2004-01-01

Application of pharmacological doses of the corticosteroid dexamethasone phosphate to starry flounder Platichthys stellatus resulted in a predisposition to clinical ichthyophoniasis and a progression from latent Ichthyophonus infections to patent, histologically identifiable infections. Among Ichthyophonus-challenged starry flounder, the prevalences of clinical infections and histologically identifiable infections were significantly greater in two groups that received dexamethasone (100% and 31%, respectively) than in the respective control groups (8% and 0%). Proliferation of Ichthyophonus infections in corticosteroid-treated groups may have resulted from suppression of the cellular immune response that typically follows corticosteroid application; however, further studies are needed to determine whether these effects occur at lower, physiological concentrations of corticosteroids.

Imidacloprid Exposure Suppresses Neural Crest Cells Generation during Early Chick Embryo Development.

Science.gov (United States)

Wang, Chao-Jie; Wang, Guang; Wang, Xiao-Yu; Liu, Meng; Chuai, Manli; Lee, Kenneth Ka Ho; He, Xiao-Song; Lu, Da-Xiang; Yang, Xuesong

2016-06-15

Imidacloprid is a neonicotinoid pesticide that is widely used in the control pests found on crops and fleas on pets. However, it is still unclear whether imidacloprid exposure could affect early embryo development-despite some studies having been conducted on the gametes. In this study, we demonstrated that imidacloprid exposure could lead to abnormal craniofacial osteogenesis in the developing chick embryo. Cranial neural crest cells (NCCs) are the progenitor cells of the chick cranial skull. We found that the imidacloprid exposure retards the development of gastrulating chick embryos. HNK-1, PAX7, and Ap-2α immunohistological stainings indicated that cranial NCCs generation was inhibited after imidacloprid exposure. Double immunofluorescent staining (Ap-2α and PHIS3 or PAX7 and c-Caspase3) revealed that imidacloprid exposure inhibited both NCC proliferation and apoptosis. In addition, it inhibited NCCs production by repressing Msx1 and BMP4 expression in the developing neural tube and by altering expression of EMT-related adhesion molecules (Cad6B, E-Cadherin, and N-cadherin) in the developing neural crests. We also determined that imidacloprid exposure suppressed cranial NCCs migration and their ability to differentiate. In sum, we have provided experimental evidence that imidacloprid exposure during embryogenesis disrupts NCCs development, which in turn causes defective cranial bone development.

Corrosion-resistant coating development

Energy Technology Data Exchange (ETDEWEB)

Stinton, D.P.; Kupp, D.M.; Martin, R.L. [Oak Ridge National Lab., TN (United States)

1997-12-01

SiC-based heat exchangers have been identified as the prime candidate material for use as heat exchangers in advanced combined cycle power plants. Unfortunately, hot corrosion of the SiC-based materials created by alkali metal salts present in the combustion gases dictates the need for corrosion-resistant coatings. The well-documented corrosion resistance of CS-50 combined with its low (and tailorable) coefficient of thermal expansion and low modulus makes CS-50 an ideal candidate for this application. Coatings produced by gelcasting and traditional particulate processing have been evaluated.

Composts containing fluorescent pseudomonads suppress fusarium root and stem rot development on greenhouse cucumber.

Science.gov (United States)

Bradley, Geoffrey G; Punja, Zamir K

2010-11-01

Three composts (Ball, dairy, and greenhouse) were tested for the ability to suppress the development of Fusarium root and stem rot (caused by Fusarium oxysporum f. sp. radicis-cucumerinum) on greenhouse cucumber. Dairy and greenhouse composts significantly reduced disease severity (P = 0.05), while Ball compost had no effect. Assessment of total culturable microbes in the composts showed a positive relationship between disease suppressive ability and total population levels of pseudomonads. In vitro antagonism assays between compost-isolated bacterial strains and the pathogen showed that strains of Pseudomonas aeruginosa exhibited the greatest antagonism. In growth room trials, strains of P. aeruginosa and nonantagonistic Pseudomonas maculicola, plus 2 biocontrol strains of Pseudomonas fluorescens, were tested for their ability to reduce (i) survival of F. oxysporum, (ii) colonization of plants by the pathogen, and (iii) disease severity. Cucumber seedlings grown in compost receiving P. aeruginosa and P. fluorescens had reduced disease severity index scores after 8 weeks compared with control plants without bacteria. Internal stem colonization by F. oxysporum was significantly reduced by P. aeruginosa. The bacteria colonized plant roots at 1.9 × 10(6) ± 0.73 × 10(6) CFU·(g root tissue)-1 and survival was >107 CFU·(g compost)-1 after 6 weeks. The locus for 2,4-diacetylphloroglucinol production was detected by Southern blot analysis and confirmed by PCR. The production of the antibiotic 2,4-diacetylphloroglucinol in liquid culture by P. aeruginosa was confirmed by thin layer chromatography. These results demonstrate that composts containing antibiotic-producing P. aeruginosa have the potential to suppress diseases caused by Fusarium species.

Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy.

Science.gov (United States)

Tenney, Daniel J; Rose, Ronald E; Baldick, Carl J; Pokornowski, Kevin A; Eggers, Betsy J; Fang, Jie; Wichroski, Michael J; Xu, Dong; Yang, Joanna; Wilber, Richard B; Colonno, Richard J

2009-05-01

Patients with chronic hepatitis B virus (HBV) infection who develop antiviral resistance lose benefits of therapy and may be predisposed to further resistance. Entecavir (ETV) resistance (ETVr) results from HBV reverse transcriptase substitutions at positions T184, S202, or M250, which emerge in the presence of lamivudine (LVD) resistance substitutions M204I/V +/- L180M. Here, we summarize results from comprehensive resistance monitoring of patients with HBV who were continuously treated with ETV for up to 5 years. Monitoring included genotypic analysis of isolates from all patients at baseline and when HBV DNA was detectable by polymerase chain reaction (> or = 300 copies/mL) from Years 1 through 5. In addition, genotyping was performed on isolates from patients experiencing virologic breakthrough (> or = 1 log(10) rise in HBV DNA). In vitro phenotypic ETV susceptibility was determined for virologic breakthrough isolates, and for HBV containing novel substitutions emerging during treatment. The results over 5 years of therapy showed that in nucleoside-naïve patients, the cumulative probability of genotypic ETVr and genotypic ETVr associated with virologic breakthrough was 1.2% and 0.8%, respectively. In contrast, a reduced barrier to resistance was observed in LVD-refractory patients, as the LVD resistance substitutions, a partial requirement for ETVr, preexist, resulting in a 5-year cumulative probability of genotypic ETVr and genotypic ETVr associated with breakthrough of 51% and 43%, respectively. Importantly, only four patients who achieved < 300 copies/mL HBV DNA subsequently developed ETVr. Long-term monitoring showed low rates of resistance in nucleoside-naïve patients during 5 years of ETV therapy, corresponding with potent viral suppression and a high genetic barrier to resistance. These findings support ETV as a primary therapy that enables prolonged treatment with potent viral suppression and minimal resistance.

Regularized Adaptive Notch Filters for Acoustic Howling Suppression

DEFF Research Database (Denmark)

Gil-Cacho, Pepe; van Waterschoot, Toon; Moonen, Marc

2009-01-01

In this paper, a method for the suppression of acoustic howling is developed, based on adaptive notch filters (ANF) with regularization (RANF). The method features three RANFs working in parallel to achieve frequency tracking, howling detection and suppression. The ANF-based approach to howling...

Long-lived cancer-resistant rodents as new model species for cancer research

Directory of Open Access Journals (Sweden)

Jorge eAzpurua

2013-01-01

Full Text Available Most rodents are small and short-lived, but several lineages have independently evolved long lifespans without a concomitant increase in body mass. Most notably, the two subterranean species naked mole rat (NMR and blind mole rat (BMR which have maximum lifespans of 32 and 21 years respectively. The longevity of these species has sparked interest in the tumor suppression strategies that may have also evolved, because for many rodent species (including mice, rats, guinea pigs, gerbils and hamsters tumors are major source of late-life mortality. Here, we review the recent literature on anticancer mechanisms in long-lived rodents. Both NMR and BMR seem to have developed tumor defenses that rely on extra-cellular signals. However, while the NMR relies on a form of contact inhibition to suppress growth, the BMR evolved a mechanism mediated by the release of interferon and rapid necrotic cell death. Although both organisms ultimately rely on canonical downstream tumor suppressors (pRB and p53 the studies reveal species can evolve different strategies to achieve tumor-resistance. Importantly, studies of these cancer-resistant rodents may benefit human health if such mechanisms can be activated in human cells.

Performance of μ-RWELL detector vs resistivity of the resistive stage

Science.gov (United States)

Bencivenni, G.; De Oliveira, R.; Felici, G.; Gatta, M.; Morello, G.; Ochi, A.; Lener, M. Poli; Tskhadadze, E.

2018-04-01

The μ-RWELL is a compact spark-protected single amplification stage Micro-Pattern-Gaseous-Detector (MPGD). The detector amplification stage is realized with a polyimide structure, micro-patterned with a dense matrix of blind-holes, integrated into the readout structure. The anode is formed by a thin Diamond Like Carbon (DLC) resistive layer separated by an insulating glue layer from the readout strips. The introduction of the resistive layer strongly suppressing the transition from streamer to spark gives the possibility to achieve large gains (> 104), without significantly affecting the capability to be efficiently operated in high particle fluxes. In this work we present the results of a systematic study of the μ-RWELL performance as a function of the DLC resistivity. The tests have been performed either with collimated 5.9 keV X-rays or with pion and muon beams at the SPS Secondary Beamline H4 and H8 at CERN.

Highly corrosion resistant zirconium based alloy for reactor structural material

International Nuclear Information System (INIS)

Ito, Yoichi.

1996-01-01

The alloy of the present invention is a zirconium based alloy comprising tin (Sn), chromium (Cr), nickel (Ni) and iron (Fe) in zirconium (Zr). The amount of silicon (Si) as an impurity is not more than 60ppm. It is preferred that Sn is from 0.9 to 1.5wt%, that of Cr is from 0.05 to 0.15wt%, and (Fe + Ni) is from 0.17 to 0.5wt%. If not less than 0.12wt% of Fe is added, resistance against nodular corrosion is improved. The upper limit of Fe is preferably 0.40wt% from a view point of uniform suppression for the corrosion. The nodular corrosion can be suppressed by reducing the amount of Si-rich deposition product in the zirconium based alloy. Accordingly, a highly corrosion resistant zirconium based alloy improved for the corrosion resistance of zircaloy-2 and usable for a fuel cladding tube of a BWR type reactor can be obtained. (I.N.)

Interconnection between flowering time control and activation of systemic acquired resistance

Directory of Open Access Journals (Sweden)

Zeeshan Zahoor Banday

2015-03-01

Full Text Available The ability to avoid or neutralize pathogens is inherent to all higher organisms including plants. Plants recognize pathogens through receptors, and mount resistance against the intruders, with the help of well-elaborated defense arsenal. In response to some local infections, plants develop systemic acquired resistance (SAR, which provides heightened resistance during subsequent infections. Infected tissues generate mobile signalling molecules that travel to the systemic tissues, where they epigenetically modify expression of a set of genes to initiate the manifestation of SAR in distant tissues. Immune responses are largely regulated at transcriptional level. Flowering is a developmental transition that occurs as a result of the coordinated action of large numbers of transcription factors that respond to intrinsic signals and environmental conditions. The plant hormone salicylic acid (SA which is required for SAR activation positively regulates flowering. Certain components of chromatin remodelling complexes that are recruited for suppression of precocious flowering are also involved in suppression of SAR in healthy plants. FLOWERING LOCUS D (FLD, a putative histone demethylase positively regulates SAR manifestation and flowering transition in Arabidopsis. Similarly, incorporation of histone variant H2A.Z in nucleosomes mediated by PHOTOPERIOD-INDEPENDENT EARLY FLOWERING 1 (PIE1, an orthologue of yeast chromatin remodelling complex SWR1, concomitantly influences SAR and flowering time. SUMO conjugation and deconjugation mechanisms also similarly affect SAR and flowering in an SA-dependent manner. The evidences suggest a common underlying regulatory mechanism for activation of SAR and flowering in plants.

Older Adults Can Suppress Unwanted Memories When Given an Appropriate Strategy

Science.gov (United States)

2015-01-01

Memory suppression refers to the ability to exclude distracting memories from conscious awareness, and this ability can be assessed with the think/no-think paradigm. Recent research with older adults has provided evidence suggesting both intact and deficient memory suppression. The present studies seek to understand the conditions contributing to older adults’ ability to suppress memories voluntarily. We report 2 experiments indicating that the specificity of the think/no-think task instructions contributes to older adults’ suppression success: When older adults receive open-ended instructions that require them to develop a retrieval suppression strategy on their own, they show diminished memory suppression compared with younger adults. Conversely, when older adults receive focused instructions directing them to a strategy thought to better isolate inhibitory control, they show suppression-induced forgetting similar to that exhibited by younger adults. Younger adults demonstrate memory suppression regardless of the specificity of the instructions given, suggesting that the ability to select a successful suppression strategy spontaneously may be compromised in older adults. If so, this deficit may be associated with diminished control over unwanted memories in naturalistic settings if impeded strategy development reduces the successful deployment of inhibitory control. PMID:25602491

Development of a CB Resistant Durable, Flexible Hydration System

National Research Council Canada - National Science Library

Hall, Peyton W; Zeller, Frank T; Bulluck, John W; Dingus, Michael L

2002-01-01

A durable, flexible hydration system resistant to contamination by contact with VX, GD, and HD chemical agents, as well as damage by the decontaminants sodium hypochlorite and DS-2 is being developed for aviator use...

The fitness of drug-resistant malaria parasites in a rodent model: multiplicity of infection

OpenAIRE

Huijben, Silvie; Sim, Derek G.; Nelson, William, A.; Read, Andrew F.

2011-01-01

Malaria infections normally consist of more than one clonally-replicating lineage. Within-host interactions between sensitive and resistant parasites can have profound effects on the evolution of drug resistance. Here, using the Plasmodium chabaudi mouse malaria model, we ask whether the costs and benefits of resistance are affected by the number of co-infecting strains competing with a resistant clone. We found strong competitive suppression of resistant parasites in untreated infections and...

Postnatal development of resistance to short-term high-dose toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in TCDD-resistant and -semiresistant rats

International Nuclear Information System (INIS)

Simanainen, Ulla; Tuomisto, Jouni T.; Pohjanvirta, Raimo; Syrjaelae, Paula; Tuomisto, Jouko; Viluksela, Matti

2004-01-01

Despite great interspecies differences in adult 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) sensitivity, the toxic potency of TCDD is similar across species in fetal mortality. Han/Wistar (Kuopio; H/W) rats are exceptionally resistant to acute toxicity of TCDD, but show sensitivity to embryotoxicity and teratogenicity. The resistance of adult H/W rats to acute TCDD toxicity is based on a point mutation in the transactivation domain of the aryl hydrocarbon receptor (AHR) and to an unknown gene ''B''. This study investigated the time course of postnatal development of resistance to TCDD and the significance of genotypic variation in resistance development. H/W, line A (a new line with the H/W-type mutated AHR), and line B rats (a line with normal AHR but moderately resistant because of gene ''B'') were exposed to a single dose of TCDD 2-56 days after birth. H/W and line A rats received 1000 μg/kg; male and female B rats received 200 and 100 μg/kg, respectively. Survival was monitored for 42 days. Interestingly, although TCDD ceased growth and weight gain in all TCDD groups, the younger dosed animals did not seem to reach the body weight of the older dosed animals even in 100 days. The survival results after 42 days showed that line A rats are fairly resistant to TCDD immediately after birth, and their full TCDD resistance develops during the first week of life. The moderate resistance of line B rats develops approximately at the time of weaning. This difference in the time course of resistance development suggests that there are basic differences in pathways mediating resistance in lines A and B rats

Suppression of irradiation effects in gold-doped silicon detectors

International Nuclear Information System (INIS)

McPherson, M.; Sloan, T.; Jones, B.K.

1997-01-01

Two sets of silicon detectors were irradiated with 1 MeV neutrons to different fluences and then characterized. The first batch were ordinary p-i-n photodiodes fabricated from high-resistivity (400 Ω cm) silicon, while the second batch were gold-doped powder diodes fabricated from silicon material initially of low resistivity (20 Ω cm). The increase in reverse leakage current after irradiation was found to be more in the former case than in the latter. The fluence dependence of the capacitance was much more pronounced in the p-i-n diodes than in the gold-doped diodes. Furthermore, photo current generation by optical means was less in the gold doped devices. All these results suggest that gold doping in silicon somewhat suppresses the effects of neutron irradiation. (author)

Purulent pericarditis in a dog administered immune-suppressing drugs

International Nuclear Information System (INIS)

Mohri, T.; Takashima, K.; Yamane, T.; Sato, H.; Yamane, Y.

2009-01-01

A 5-year-old castrated mongrel dog was brought to our hospital with anorexia and vomiting. Laboratory testing revealed immune-mediated hemolytic anemia (IMHA), and so treatment was initiated with multiple immune-suppressing drugs, achieving partial remission from IMHA. However, cardiac tamponade due to purulent pericarditis was identified as a secondary disease. Culture of pericardial fluid yielded numerous Candida albicans and multidrug-resistant Acinetobacter sp. Pericardiocentesis was performed, and the condition of the dog improved. However, the dog died the next day

ABA suppresses Botrytis cinerea elicited NO production in tomato to influence H2O2 generation and increase host susceptibility

Directory of Open Access Journals (Sweden)

Anushen eSivakumaran

2016-05-01

Full Text Available Abscisic acid (ABA production has emerged a susceptibility factor in plant-pathogen interactions. This work examined the interaction of ABA with NO in tomato following challenge with the ABA-synthesising pathogen, Botrytis cinerea. Trace gas detection using a quantum cascade laser detected NO production within minutes of challenge with B. cinerea whilst photoacoustic laser detection detected ethylene production – an established mediator of defence against this pathogen - occurring after 6 h. Application of the NO generation inhibitor N-Nitro-L-arginine methyl ester (L-NAME suppressed both NO and ethylene production and resistance against B. cinerea. The tomato mutant sitiens fails to accumulate ABA (abscisic acid, shows increased resistance to B. cinerea and we noted exhibited elevated NO and ethylene production. Exogenous application of L-NAME or ABA reduced NO production in sitiens and reduced resistance to B. cinerea. Increased resistance to B. cinerea in sitiens have previously been linked to increased reactive oxygen species (ROS generation but this was reduced in both L-NAME and ABA treated sitiens. Taken together, our data suggests that ABA can decreases resistance to B. cinerea via reduction of NO production which also suppresses both ROS and ethylene production.

Burst suppression probability algorithms: state-space methods for tracking EEG burst suppression

Science.gov (United States)

Chemali, Jessica; Ching, ShiNung; Purdon, Patrick L.; Solt, Ken; Brown, Emery N.

2013-10-01

Objective. Burst suppression is an electroencephalogram pattern in which bursts of electrical activity alternate with an isoelectric state. This pattern is commonly seen in states of severely reduced brain activity such as profound general anesthesia, anoxic brain injuries, hypothermia and certain developmental disorders. Devising accurate, reliable ways to quantify burst suppression is an important clinical and research problem. Although thresholding and segmentation algorithms readily identify burst suppression periods, analysis algorithms require long intervals of data to characterize burst suppression at a given time and provide no framework for statistical inference. Approach. We introduce the concept of the burst suppression probability (BSP) to define the brain's instantaneous propensity of being in the suppressed state. To conduct dynamic analyses of burst suppression we propose a state-space model in which the observation process is a binomial model and the state equation is a Gaussian random walk. We estimate the model using an approximate expectation maximization algorithm and illustrate its application in the analysis of rodent burst suppression recordings under general anesthesia and a patient during induction of controlled hypothermia. Main result. The BSP algorithms track burst suppression on a second-to-second time scale, and make possible formal statistical comparisons of burst suppression at different times. Significance. The state-space approach suggests a principled and informative way to analyze burst suppression that can be used to monitor, and eventually to control, the brain states of patients in the operating room and in the intensive care unit.

TIGRESS: TRIUMF-ISAC gamma-ray escape-suppressed spectrometer

Science.gov (United States)

Svensson, C. E.; Amaudruz, P.; Andreoiu, C.; Andreyev, A.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Boston, A. J.; Chakrawarthy, R. S.; Chen, A. A.; Churchman, R.; Drake, T. E.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Hackman, G.; Hyland, B.; Jones, B.; Kanungo, R.; Maharaj, R.; Martin, J. P.; Morris, D.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Ressler, J. J.; Roy, R.; Sarazin, F.; Schumaker, M. A.; Scraggs, H. C.; Smith, M. B.; Starinsky, N.; Valiente-Dobón, J. J.; Waddington, J. C.; Watters, L. M.

2005-10-01

The TRIUMF-ISAC gamma-ray escape-suppressed spectrometer (TIGRESS) is a new γ-ray detector array being developed for use at TRIUMF's Isotope Separator and Accelerator (ISAC) radioactive ion beam facility. TIGRESS will comprise 12 32-fold segmented clover-type HPGe detectors coupled with 20-fold segmented modular Compton suppression shields and custom digital signal processing electronics. This paper provides an overview of the TIGRESS project and progress in its development to date.

Activity of Simulated Human Dosage Regimens of Meropenem and Vaborbactam against Carbapenem-Resistant Enterobacteriaceae in an In Vitro Hollow-Fiber Model.

Science.gov (United States)

Sabet, Mojgan; Tarazi, Ziad; Rubio-Aparicio, Debora; Nolan, Thomas G; Parkinson, Jonathan; Lomovskaya, Olga; Dudley, Michael N; Griffith, David C

2018-02-01

The objective of these studies was to evaluate the exposures of meropenem and vaborbactam that would produce antibacterial activity and prevent resistance development in carbapenem-resistant Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae strains when tested at an inoculum of 10 8 CFU/ml. Thirteen K. pneumoniae isolates, three Enterobacter cloacae isolates, and one Escherichia coli isolate were examined in an in vitro hollow-fiber model over 32 h. Simulated dosage regimens of 1 to 2 g of meropenem with 1 to 2 g of vaborbactam, with meropenem administered every 8 h by a 3-h infusion based on phase 1 or phase 3 patient pharmacokinetic data, were studied in the model. A dosage of 2 g of meropenem in combination with 2 g of vaborbactam was bactericidal against K. pneumoniae , E. cloacae , and E. coli strains, with meropenem-vaborbactam MICs of up to 8 mg/liter. When the vaborbactam exposure was adjusted to the levels observed in patients enrolled in phase 3 trials (24-h free AUC, ∼550 mg · h/liter, versus 320 mg · h/liter in the phase 1 studies), 2 g of meropenem with 2 g of vaborbactam was also bactericidal against strains with meropenem-vaborbactam MICs of 16 mg/liter. In addition, this level of vaborbactam also suppressed the development of resistance observed using phase 1 exposures. In this pharmacodynamic model, exposures similar to 2 g of meropenem in combination with 2 g of vaborbactam administered every 8 h by a 3-h infusion in phase 3 trials produced antibacterial activity and suppressed the development of resistance against carbapenem-resistant KPC-producing strains of Enterobacteriaceae . Copyright © 2018 American Society for Microbiology.

Development of radiation resistant PEEK insulation cable

International Nuclear Information System (INIS)

Mio, Keigo; Ogiwara, Norio; Hikichi, Yusuke; Furukori, Hisayoshi; Arai, Hideyuki; Nishizawa, Daiji; Nishidono, Toshiro

2009-04-01

Material characterization and development has been carried out for cable insulation suitable for use in the J-PARC 3-GeV RCS radiation environment. In spite of its high cost, PEEK (polyether-ether-ketone) has emerged as the leading candidate satisfying requirements of being non-halogen based, highly incombustible and with radiation resistant at least 10 MGy, along with the usual mechanical characteristics such as good elongation at break, which are needed in a cable insulation. Gamma-ray irradiation tests have been done in order to study radiation resistance of PEEK cable. Further, mechanical, electrical and fire retardant characteristics of a complete cable such as would be used at the J-PARC RCS were investigated. As a result, PEEK cables were shown to be not degraded by radiation up to at least 10 MGy, and thus could be expected to operate stably under the 3-GeV RCS radiation environment. (author)

Zinc and copper in animal feed – development of resistance and co-resistance to antimicrobial agents in bacteria of animal origin

Directory of Open Access Journals (Sweden)

Siamak Yazdankhah

2014-09-01

Full Text Available Farmed animals such as pig and poultry receive additional Zn and Cu in their diets due to supplementing elements in compound feed as well as medical remedies. Enteral bacteria in farmed animals are shown to develop resistance to trace elements such as Zn and Cu. Resistance to Zn is often linked with resistance to methicillin in staphylococci, and Zn supplementation to animal feed may increase the proportion of multiresistant E. coli in the gut. Resistance to Cu in bacteria, in particular enterococci, is often associated with resistance to antimicrobial drugs like macrolides and glycopeptides (e.g. vancomycin. Such resistant bacteria may be transferred from the food-producing animals to humans (farmers, veterinarians, and consumers. Data on dose-response relation for Zn/Cu exposure and resistance are lacking; however, it seems more likely that a resistance-driven effect occurs at high trace element exposure than at more basal exposure levels. There is also lack of data which could demonstrate whether Zn/Cu-resistant bacteria may acquire antibiotic resistance genes/become antibiotics resistant, or if antibiotics-resistant bacteria are more capable to become Zn/Cu resistant than antibiotics-susceptible bacteria. Further research is needed to elucidate the link between Zn/Cu and antibiotic resistance in bacteria.

Wireless Inductive Power Device Suppresses Blade Vibrations

Science.gov (United States)

Morrison, Carlos R.; Provenza, Andrew J.; Choi, Benjamin B.; Bakhle, Milind A.; Min, James B.; Stefko, George L.; Duffy, Kirsten P.; Fougers, Alan J.

2011-01-01

Vibration in turbomachinery can cause blade failures and leads to the use of heavier, thicker blades that result in lower aerodynamic efficiency and increased noise. Metal and/or composite fatigue in the blades of jet engines has resulted in blade destruction and loss of lives. Techniques for suppressing low-frequency blade vibration, such as gtuned circuit resistive dissipation of vibratory energy, h or simply "passive damping," can require electronics incorporating coils of unwieldy dimensions and adding unwanted weight to the rotor. Other approaches, using vibration-dampening devices or damping material, could add undesirable weight to the blades or hub, making them less efficient. A wireless inductive power device (WIPD) was designed, fabricated, and developed for use in the NASA Glenn's "Dynamic Spin Rig" (DSR) facility. The DSR is used to simulate the functionality of turbomachinery. The relatively small and lightweight device [10 lb (approx.=4.5 kg)] replaces the existing venerable and bulky slip-ring. The goal is the eventual integration of this technology into actual turbomachinery such as jet engines or electric power generators, wherein the device will facilitate the suppression of potentially destructive vibrations in fan blades. This technology obviates slip rings, which require cooling and can prove unreliable or be problematic over time. The WIPD consists of two parts: a remote element, which is positioned on the rotor and provides up to 100 W of electrical power to thin, lightweight piezoelectric patches strategically placed on/in fan blades; and a stationary base unit that wirelessly communicates with the remote unit. The base unit supplies inductive power, and also acts as an input and output corridor for wireless measurement, and active control command to the remote unit. Efficient engine operation necessitates minimal disturbance to the gas flow across the turbine blades in any effort to moderate blade vibration. This innovation makes it

Development of Efficient Screening Methods for Resistant Cucumber Plants to Meloidogyne incognita

Directory of Open Access Journals (Sweden)

Sung Min Hwang

2014-06-01

Full Text Available Root-knot nematodes represent a significant problem in cucumber, causing reduction in yield and quality. To develop screening methods for resistance of cucumber to root-knot nematode Meloidogyne incognita, development of root-knot nematode of four cucumber cultivars (‘Dragonsamchuk’, ‘Asiastrike’, ‘Nebakja’ and ‘Hanelbakdadaki’ according to several conditions such as inoculum concentration, plant growth stage and transplanting period was investigated by the number of galls and egg masses produced in each seedling 45 days after inoculation. There was no difference in galls and egg masses according to the tested condition except for inoculum concentration. Reproduction of the nematode on all the tested cultivars according to inoculum concentration increased in a dose-dependent manner. On the basis of the result, the optimum conditions for root-knot development on the cultivars is to transplant period of 1 week, inoculum concentration of 5,000 eggs/plant and plant growth stage of 3-week-old in a greenhouse (25 ± 5°C. In addition, under optimum conditions, resistance of 45 commercial cucumber cultivars was evaluated. One rootstock cultivar, Union was moderately resistant to the root-knot nematode. However, no significant difference was in the resistance of the others cultivar. According to the result, we suggest an efficient screening method for new resistant cucumber to the root-knot nematode, M. incognita.

Enhanced Transmission of Drug-Resistant Parasites to Mosquitoes following Drug Treatment in Rodent Malaria

OpenAIRE

Bell, Andrew S.; Huijben, Silvie; Paaijmans, Krijn P.; Sim, Derek G.; Chan, Brian H. K.; Nelson, William A.; Read, Andrew F.

2012-01-01

The evolution of drug resistant Plasmodium parasites is a major challenge to effective malaria control. In theory, competitive interactions between sensitive parasites and resistant parasites within infections are a major determinant of the rate at which parasite evolution undermines drug efficacy. Competitive suppression of resistant parasites in untreated hosts slows the spread of resistance; competitive release following treatment enhances it. Here we report that for the murine model Plasm...

[Resistance risk, cross-resistance and biochemical resistance mechanism of Laodelphax striatellus to buprofezin].

Science.gov (United States)

Mao, Xu-lian; Liu, Jin; Li, Xu-ke; Chi, Jia-jia; Liu, Yong-jie

2016-01-01

In order to investigate the resistance development law and biochemical resistance mechanism of Laodelphax striatellus to buprofezin, spraying rice seedlings was used to continuously screen resistant strains of L. striatellus and dipping rice seedlings was applied to determine the toxicity and cross-resistance of L. striatellus to insecticides. After 32-generation screening with buprofezin, L. striatellus developed 168.49 folds resistance and its reality heritability (h2) was 0.11. If the killing rate was 80%-90%, L. striatellus was expected to develop 10-fold resistance to buprofezin only after 5 to 6 generations breeding. Because the actual reality heritability of field populations was usually lower than that of the resistant strains, the production of field populations increasing with 10-fold resistance would need much longer time. The results of cross-resistance showed that resistant strain had high level cross-resistance with thiamethoxam and imidacloprid, low level cross-resistance with acetamiprid, and no cross-resistance with pymetrozine and chlorpyrifos. The activity of detoxification enzymes of different strains and the syergism of synergist were measured. The results showed that cytochrome P450 monooxygenase played a major role in the resistance of L. striatellus to buprofezin, the esterase played a minor role and the GSH-S-transferase had no effect. Therefore, L. striatellus would have high risk to develop resistance to buprofezin when used in the field and might be delayed by using pymetrozine and chlorpyrifos.

Adoptively transferred immune T cells eradicate established tumors in spite of cancer-induced immune suppression

Science.gov (United States)

Arina, Ainhoa; Schreiber, Karin; Binder, David C.; Karrison, Theodore; Liu, Rebecca B.; Schreiber, Hans

2014-01-01

Myeloid-derived CD11b+Gr1+ suppressor cells (MDSC) and tumor-associated macrophages (TAM) are considered a major obstacle for effective adoptive T cell therapy. Myeloid cells suppress naive T cell proliferation ex vivo and can prevent the generation of T cell responses in vivo. We find, however, that immune T cells adoptively transferred eradicate well-established tumors in the presence of MDSC and TAM which are strongly immunosuppressive ex vivo. These MDSC and TAM were comparable in levels and immunosuppression among different tumor models. Longitudinal microscopy of tumors in vivo revealed that after T cell transfer tumor vasculature and cancer cells disappeared simultaneously. During T-cell mediated tumor destruction, the tumor stroma contained abundant myeloid cells (mainly TAM) that retained their suppressive properties. Preimmunized but not naive mice resisted immune suppression caused by an unrelated tumor-burden supporting the idea that in vivo, myeloid immunosuppressive cells can suppress naive but not memory T cell responses. PMID:24367029

A Comparison of Urge Intensity and the Probability of Tic Completion During Tic Freely and Tic Suppression Conditions.

Science.gov (United States)

Specht, Matt W; Nicotra, Cassandra M; Kelly, Laura M; Woods, Douglas W; Ricketts, Emily J; Perry-Parrish, Carisa; Reynolds, Elizabeth; Hankinson, Jessica; Grados, Marco A; Ostrander, Rick S; Walkup, John T

2014-03-01

Tic-suppression-based treatments (TSBTs) represent a safe and effective treatment option for Chronic Tic Disorders (CTDs). Prior research has demonstrated that treatment naive youths with CTDs have the capacity to safely and effectively suppress tics for prolonged periods. It remains unclear how tic suppression is achieved. The current study principally examines how effective suppression is achieved and preliminary correlates of the ability to suppress tics. Twelve youths, ages 10 to 17 years, with moderate-to-marked CTDs participated in an alternating sequence of tic freely and reinforced tic suppression conditions during which urge intensity and tic frequency were frequently assessed. Probability of tics occurring was half as likely following high-intensity urges during tic suppression (31%) in contrast to low-intensity urges during tic freely conditions (60%). Age was not associated with ability to suppress. Intelligence indices were associated with or trended toward greater ability to suppress tics. Attention difficulties were not associated with ability to suppress but were associated with tic severity. In contrast to our "selective suppression" hypothesis, we found participants equally capable of suppressing their tics regardless of urge intensity during reinforced tic suppression. Tic suppression was achieved with an "across-the-board" effort to resist urges. Preliminary data suggest that ability to suppress may be associated with general cognitive variables rather than age, tic severity, urge severity, and attention. Treatment naive youths appear to possess a capacity for robust tic suppression. TSBTs may bolster these capacities and/or enable their broader implementation, resulting in symptom improvement. © The Author(s) 2014.

Development of gamma-ray-suppression type of small-sized neutron detector based on a 6Li-glass scintillator

International Nuclear Information System (INIS)

Matsumoto, T.; Harano, H.; Shimoyama, T.; Kudo, K.; Uritani, A.

2005-01-01

A small-sized thermal neutron detector based on a 6 Li-glass scintillator and a plastic optical fiber was developed for measurement of a dose distribution of thermal neutrons in a thermal neutron standard field. A contribution of gamma rays can not be neglected in the neutron measurement with this detector, although the 6 Li-glass scintillator can be distinguishable for the neutrons and the gamma rays by difference of each pulse height. Moreover, to reduce an uncertainty of neutron counts caused by the gamma ray background around a discrimination level, we suggested a gamma-ray-suppression type of small-sized thermal neutron detector with a 6 Li-glass scintillator, a hollow CsI(Tl) scintillator and plastic optical fibers. The detector can reject signals due to the gamma rays with an anti-coincidence method. In the present paper, we evaluated an ability of a gamma-ray suppression of the detector using the EGS4 electron-photon transport Monte-Carlo code with the PRESTA routine. As the results, the sufficient gamma-ray suppression effect was shown. (author)

Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway

International Nuclear Information System (INIS)

Mi, Shanwei; Xiang, Gang; Yuwen, Daolu; Gao, Jian; Guo, Wenjie; Wu, Xuefeng; Wu, Xudong; Sun, Yang; Su, Yongqian; Shen, Yan; Xu, Qiang

2016-01-01

Resistance to cisplatin is a major obstacle for the success of non-small cell lung cancer therapy. The mechanisms underlying cisplatin resistance are not fully understood. In this study, we found that the increase of basal auotophagy accompanied the development of cisplatin resistance. Meanwhile the blockade of the Akt/mTOR pathway occurred in the process. Inhibition of this pathway was induced by cisplatin treatment in the resistant non-small cell lung carcinoma cells. Andrographolide, a natural diterpenoid, promoted the activation of the Akt/mTOR signaling by downregulating PTEN and suppressed autophagy, which subsequently resensitized the resistant cells to cisplatin-mediated apoptosis. Cisplatin treatment in combination with andrographolide significantly prevented the growth of the resistant cells in vivo. These results highlight the involvement of autophagy in cisplatin-resistance development and suggest that inhibition of autophagy via tuning the Akt/mTOR signaling could be a promising strategy in the therapy for cisplatin-resistant non-small cell lung cancer. - Highlights: • The increase of basal auotophagy accompanied the development of cisplatin resistance in NSCLC cells. • Cisplatin induced the blockade of the Akt/mTOR pathway. • Andrographolide promoted the activation of the Akt/mTOR signaling. • Andrographolide downregulated PTEN expression. • Cisplatin treatment in combination with andrographolide resensitized the resistant cells to cisplatin.

Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway

Energy Technology Data Exchange (ETDEWEB)

Mi, Shanwei; Xiang, Gang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Yuwen, Daolu [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Gao, Jian; Guo, Wenjie; Wu, Xuefeng; Wu, Xudong; Sun, Yang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Su, Yongqian [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Shen, Yan, E-mail: shenyan@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

2016-11-01

Resistance to cisplatin is a major obstacle for the success of non-small cell lung cancer therapy. The mechanisms underlying cisplatin resistance are not fully understood. In this study, we found that the increase of basal auotophagy accompanied the development of cisplatin resistance. Meanwhile the blockade of the Akt/mTOR pathway occurred in the process. Inhibition of this pathway was induced by cisplatin treatment in the resistant non-small cell lung carcinoma cells. Andrographolide, a natural diterpenoid, promoted the activation of the Akt/mTOR signaling by downregulating PTEN and suppressed autophagy, which subsequently resensitized the resistant cells to cisplatin-mediated apoptosis. Cisplatin treatment in combination with andrographolide significantly prevented the growth of the resistant cells in vivo. These results highlight the involvement of autophagy in cisplatin-resistance development and suggest that inhibition of autophagy via tuning the Akt/mTOR signaling could be a promising strategy in the therapy for cisplatin-resistant non-small cell lung cancer. - Highlights: • The increase of basal auotophagy accompanied the development of cisplatin resistance in NSCLC cells. • Cisplatin induced the blockade of the Akt/mTOR pathway. • Andrographolide promoted the activation of the Akt/mTOR signaling. • Andrographolide downregulated PTEN expression. • Cisplatin treatment in combination with andrographolide resensitized the resistant cells to cisplatin.

Development of Bait Stations for Fruit Fly Suppression in Support of SIT. Working Material

International Nuclear Information System (INIS)

2009-01-01

A more economic and practical fruit fly suppression tool is needed to replace conventional aerial and ground bait sprays applications over human settlements, protected natural areas, and difficult to access areas where fruit fly hosts exist. This has been a major request from area-wide integrated pest management action programmes using the Sterile Insect Technique (SIT) as a component. In recent years, especially in Europe, most conventional insecticides used to control fruit pests have been banned (e.g. malathion, dichlorvos and other organophosphates), therefore areas producing fruits and vegetables for markets that request low insecticide residues or even fruit and vegetable organic farming is seeking for a more economic fruit fly control option to the spinosad-based bait sprays and to the use of mass trapping. To address these requests, bait stations can be one of the most suitable alternatives. The development of these devices needs to take into consideration cost-effectiveness, and long lasting attractants and killing agents, and should target female fruit flies. Recent developments of synthetic food attractants and long-lasting formulations open the possibility to improve the existent baits stations or develop new ones. With this objective the Insect Pest Control Subprogramme of the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture organized a Consultants Meeting ('Development of Bait Stations for Fruit Fly Suppression in Support of SIT'), held in Mazatlan, Mexico, from 30 October to 1 November 2008, with the participation of 14 scientists from the Instituto Nacional de Tecnologia Agropecuaria, Argentina; Department of Primary Industries and Fisheries, Australia; North American Plant Protection Organization, Canada; African Insect Science for Food and Health, Kenya; Universidad Politecnica de Valencia, Spain; Institut de Recerca i Tecnologia Agroalimentaries, Spain, Secretaria de Agricultura, Ganaderia, Desarrollo Rural, Pesca y

Quantum-mechanical suppression of bremsstrahlung

Energy Technology Data Exchange (ETDEWEB)

Becker-Szendy, R.; Keller, L.; Niemi, G.; Perl, M.; Rochester, L. [Stanford Univ., CA (United States); Anthony, P. [Stanford Univ., CA (United States)]|[Lawrence Livermore National Lab., CA (United States); Bosted, P. [American Univ., Washington, DC (United States); Cavalli-Sforza, M.; Kelley, L.; Klein, S. [Univ. of California, Santa Cruz, CA (United States)] [and others

1994-12-01

The authors have studied quantum-mechanical suppression of bremsstrahlung of low-energy 1-500 MeV photons from high-energy 25 GeV electrons. They have measured the LPM effect, where multiple scattering of the radiating electron destroys coherence required for the emission of low-energy photons, and the dielectric effect, where the emitted photon traveling in the radiator medium interferes with itself. For the experiment, the collaboration developed a novel method of extracting a parasitic low-intensity high-energy electron beam into the fixed target area during normal SLC operation of the accelerator. The results agree quantitatively with Migdal`s calculation of the LPM effect. Surface effects, for which there is no satisfactory theoretical prediction, are visible at low photon energies. For very thin targets, the suppression disappears, as expected. Preliminary results on dielectric suppression of bremsstrahlung are in qualitative agreement with the expectation.

Effects of intranasal insulin on endogenous glucose production in insulin-resistant men.

Science.gov (United States)

Xiao, Changting; Dash, Satya; Stahel, Priska; Lewis, Gary F

2018-03-14

The effects of intranasal insulin on the regulation of endogenous glucose production (EGP) in individuals with insulin resistance were assessed in a single-blind, crossover study. Overweight or obese insulin-resistant men (n = 7; body mass index 35.4 ± 4.4 kg/m 2 , homeostatic model assessment of insulin resistance 5.6 ± 1.6) received intranasal spray of either 40 IU insulin lispro or placebo in 2 randomized visits. Acute systemic spillover of intranasal insulin into the circulation was matched with a 30-minute intravenous infusion of insulin lispro in the nasal placebo arm. EGP was assessed under conditions of a pancreatic clamp with a primed, constant infusion of glucose tracer. Under these experimental conditions, compared with placebo, intranasal administration of insulin did not significantly affect plasma glucose concentrations, EGP or glucose disposal in overweight/obese, insulin-resistant men, in contrast to our previous study, in which an equivalent dose of intranasal insulin significantly suppressed EGP in lean, insulin-sensitive men. Insulin resistance is probably associated with impairment in centrally mediated insulin suppression of EGP. © 2018 John Wiley & Sons Ltd.

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

Recombination suppression at the dominant Rhg1/Rfs2 locus underlying soybean resistance to the cyst nematode.

Science.gov (United States)

Afzal, Ahmed J; Srour, Ali; Saini, Navinder; Hemmati, Naghmeh; El Shemy, Hany A; Lightfoot, David A

2012-04-01

Host resistance to "yellow dwarf" or "moonlight" disease cause by any population (Hg type) of Heterodera glycines I., the soybean cyst nematode (SCN), requires a functional allele at rhg1. The host resistance encoded appears to mimic an apoptotic response in the giant cells formed at the nematode feeding site about 24-48 h after nematode feeding commences. Little is known about how the host response to infection is mediated but a linked set of 3 genes has been identified within the rhg1 locus. This study aimed to identify the role of the genes within the locus that includes a receptor-like kinase (RLK), a laccase and an ion antiporter. Used were near isogeneic lines (NILs) that contrasted at their rhg1 alleles, gene-based markers, and a new Hg type 0 and new recombination events. A syntenic gene cluster on Lg B1 was found. The effectiveness of SNP probes from the RLK for distinguishing homolog sequence variants on LgB1 from alleles at the rhg1 locus on LgG was shown. The resistant allele of the rhg1 locus was shown to be dominant in NILs. None of the recombination events were within the cluster of the three candidate genes. Finally, rhg1 was shown to reduce the plant root development. A model for rhg1 as a dominant multi-gene resistance locus based on the developmental control was inferred.

Development of LP turbine rotor steels resistant to stress corrosion cracking

International Nuclear Information System (INIS)

Nakayama, Takenori; Sugie, Kiyoshi; Fujiwara, Kazuo; Takano, Masayoshi; Kinoshita, Shushi

1988-01-01

The effect of various alloying elements on caustic SCC of 3.5 NiCrMoV steel for turbine rotor forgings was studied. From the results, low P (≤ 0.005 %) steel and low P (≤ 0.005 %) - Nb (0.02/0.03 %) steel has been developed as a rotor material, resistant to SCC. It is confirmed that the developed steel has a higher resistance to SCC and to temper embrittlement, and has equivalent other mechanical properties to those of conventional rotor steel. In addition, the role of P and Nb in SCC was also discussed. (author)

Small-molecule inhibition of HIV pre-mRNA splicing as a novel antiretroviral therapy to overcome drug resistance.

Directory of Open Access Journals (Sweden)

Nadia Bakkour

2007-10-01

Full Text Available The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for antiretroviral therapy and to develop new drugs. Here, we show that an indole derivative (IDC16 that interferes with exonic splicing enhancer activity of the SR protein splicing factor SF2/ASF suppresses the production of key viral proteins, thereby compromising subsequent synthesis of full-length HIV-1 pre-mRNA and assembly of infectious particles. IDC16 inhibits replication of macrophage- and T cell-tropic laboratory strains, clinical isolates, and strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Importantly, drug treatment of primary blood cells did not alter splicing profiles of endogenous genes involved in cell cycle transition and apoptosis. Thus, human splicing factors represent novel and promising drug targets for the development of antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.

Neuroendocrine prostate cancer (NEPCa) increased the neighboring PCa chemo-resistance via altering the PTHrP/p38/Hsp27/androgen receptor (AR)/p21 signals

Science.gov (United States)

Cui, Yun; Sun, Yin; Hu, Shuai; Luo, Jie; Li, Lei; Li, Xin; Yeh, Shuyuan; Jin, Jie; Chang, Chawnshang

2016-01-01

Prostatic neuroendocrine cells (NE) are an integral part of prostate cancer (PCa) that are associated with PCa progression. As the current androgen-deprivation therapy (ADT) with anti-androgens may promote the neuroendocrine PCa (NEPCa) development, and few therapies can effectively suppress NEPCa, understanding the impact of NEPCa on PCa progression may help us to develop better therapies to battle PCa. Here we found NEPCa cells could increase the docetaxel-resistance of their neighboring PCa cells. Mechanism dissection revealed that through secretion of PTHrP, NEPCa cells could alter the p38/MAPK/Hsp27 signals in their neighboring PCa cells that resulted in increased androgen receptor (AR) activity via promoting AR nuclear translocation. The consequences of increased AR function might then increase docetaxel-resistance via increasing p21 expression. In vivo xenograft mice experiments also confirmed NEPCa could increase the docetaxel-resistance of neighboring PCa, and targeting this newly identified PTHrP/p38/Hsp27/AR/p21 signaling pathway with either p38 inhibitor (SB203580) or sh-PTHrP may result in improving/restoring the docetaxel sensitivity to better suppress PCa. PMID:27375022

Development of a parallel plate proportional counter TRD with suppressed sensitivity to ionization

International Nuclear Information System (INIS)

Solomey, N.; Krolak, P.; Graham, G.

1995-01-01

The development of a Parallel Plate Proportional Counter which has a highly suppressed sensitivity to ionization but retains a good X-ray signal to noise ratio is presented. Details of the laboratory development and actual beam tests showing the e/π rejection are described. Because of its insensitivity to ionization this type of detector can be useful in an environment where the number of minimum ionizing particles are high, but uninteresting; however, the detector is very sensitive to the highly localized electron cloud from converted X-rays making it ideal as a transition radiation X-ray detector. Thus, this detector only gives a signal for charged particles above TR threshold; all other particles below this threshold produce no TR X-rays giving only a pedestal-like signal. The system's potential performance for π/p separation in the intended neutral Hyperon experiment is evaluated

Consumer innovation resistance as routines: is it an obstacle to development and well-being?

Directory of Open Access Journals (Sweden)

Ryzhkova Marina

2016-01-01

Full Text Available In this article we define the role of innovation in the economy of knowledge and in providing social and economic wellbeing to the population. The innovation resistance is defined as a complex phenomenon and as a result of agent-object relationships. Then the article is focused on consumer innovation resistance as a main obstacle to development of knowledge-based economy. Two types of consumer innovation resistance are revealed. The source of active consumer innovation resistance is the result of non-compliance of consumer expectations and characteristics of a new product. Passive consumer innovation resistance comes from the lack of desire to change stable behavior patterns and from unwillingness to learn. Also we classify the deterministic factors of consumer innovation resistance as exogenous indirect and direct factors and as endogenous factors, what can help to work out a general approach to overcoming the innovation resistance. Innovations can be considered as habits and routines to changes, which can be developed and distributed both to the young population and to the elderly. Some insights in this direction are offered.

Utilization of SRNL-developed radiation-resistant polymer in high radiation environments

Energy Technology Data Exchange (ETDEWEB)

Skibo, A. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

2017-09-27

The radiation-resistant polymer developed by the Savannah River National Laboratory is adaptable for multiple applications to enhance polymer endurance and effectiveness in radiation environments. SRNL offers to collaborate with TEPCO in evaluation, testing, and utilization of SRNL’s radiation-resistant polymer in the D&D of the Fukushima Daiichi NPS. Refinement of the scope and associated costs will be conducted in consultation with TECPO.

Risk assessment of UVB effects on resistance to infectious diseases

International Nuclear Information System (INIS)

Garssen, J.; Goettsch, W.; Slob, W.; Loveren, H. van; de Gruijl, F.

1996-01-01

The aim of this study was to develop a quantitative risk assessment of lowered resistance to infections in humans due to (solar) ultraviolet B (UVB) exposure. We followed the steps for risk assessment as defined by the U.S. National Academy of Sciences: (1) hazard identification, (2) dose-response assessment, (3) exposure assessment, and (4) risk characterization. For step 1, the suppressory effects of UVB radiation on the immune system has been reviewed, supplemented with new data, and analyzed. Experiments on UV-induced immunosuppression cannot be performed with humans for ethical reasons, but herpes simplex virus infection appears to be the human paradigm. Thus, UVB radiation appears to be a potential hazard to immunologic functions. Step 2 is crucial, but dose-response relationships for infections have never been measured in humans. We used our earlier dose-response rat data for suppression of lymphocyte stimulation and computed that the UVB dose resulting in a 50% reduction of lymphocyte stimulation by Listeria monocytogenes is 6.800 J/m 2 . Using mixed skin lymphocyte response assays we found that humans are 3.8 times less sensitive than rats (interspecies variation [IEV]). To account for the 2.5 percentile of most susceptible individuals in a population, an additional factor (intraspecies variation [IAV]) was introduced (0.5 for humans). Using these data, we computed that 13.100 J/m 2 of UVB radiation emitted by FS40 lamps would suppress 50% of the proliferative response of lymphocytes to L. monocytogenes in most sensitive skin type 2 humans. In step 3, we assumed the action spectrum for the responses analyzed by us as identical to an action spectrum for suppression of contact hypersensitivity that is available in the literature. In step 4, we calculated that approximately 100 min of solar exposure at around noon in Italy or Spain would suppress the resistance to infections by L. monocytogenes in the most sensitive humans. (author)

Risk assessment of UVB effects on resistance to infectious diseases

Energy Technology Data Exchange (ETDEWEB)

Garssen, J.; Goettsch, W.; Slob, W.; Loveren, H. van [National Institute of Public Health and Environment, Bilthoven (Netherlands); de Gruijl, F. [Rijksuniversiteit Utrecht (Netherlands)

1996-08-01

The aim of this study was to develop a quantitative risk assessment of lowered resistance to infections in humans due to (solar) ultraviolet B (UVB) exposure. We followed the steps for risk assessment as defined by the U.S. National Academy of Sciences: (1) hazard identification, (2) dose-response assessment, (3) exposure assessment, and (4) risk characterization. For step 1, the suppressory effects of UVB radiation on the immune system has been reviewed, supplemented with new data, and analyzed. Experiments on UV-induced immunosuppression cannot be performed with humans for ethical reasons, but herpes simplex virus infection appears to be the human paradigm. Thus, UVB radiation appears to be a potential hazard to immunologic functions. Step 2 is crucial, but dose-response relationships for infections have never been measured in humans. We used our earlier dose-response rat data for suppression of lymphocyte stimulation and computed that the UVB dose resulting in a 50% reduction of lymphocyte stimulation by Listeria monocytogenes is 6.800 J/m{sup 2}. Using mixed skin lymphocyte response assays we found that humans are 3.8 times less sensitive than rats (interspecies variation [IEV]). To account for the 2.5 percentile of most susceptible individuals in a population, an additional factor (intraspecies variation [IAV]) was introduced (0.5 for humans). Using these data, we computed that 13.100 J/m{sup 2} of UVB radiation emitted by FS40 lamps would suppress 50% of the proliferative response of lymphocytes to L. monocytogenes in most sensitive skin type 2 humans. In step 3, we assumed the action spectrum for the responses analyzed by us as identical to an action spectrum for suppression of contact hypersensitivity that is available in the literature. In step 4, we calculated that approximately 100 min of solar exposure at around noon in Italy or Spain would suppress the resistance to infections by L. monocytogenes in the most sensitive humans. (author).

Advances in surface ion suppression from RILIS: Towards the Time-of-Flight Laser Ion Source (ToF-LIS)

CERN Document Server

Rothe, S; Crepieux, B; Day Goodacre, T; Fedosseev, V N; Giles, T; Marsh, B A; Ramos, J P; Rossel, R E

2016-01-01

We present results from the development towards the Time-of-Flight Laser Ion Source (ToF-LIS) aiming for the suppression of isobaric contaminants through fast beam gating. The capability to characterize high resistance ion sources has been successfully demonstrated. A ninefold selectivity gain has been achieved through suppression of surface ionized potassium, while maintaining >90% transmission for laser-ionized gallium using a thin wall graphite ionizer cavity combined with a fast beam gate. Initial results from the investigation of glassy carbon as a potential hot cavity ion source are presented. Power-cycle tests of a newly designed mount for fragile ion source cavities indicates its capability to survive the thermal stress expected during operation in an ISOLDE target unit. Finally, we introduce fast ion beam switching at a rate of 10 kHz using the ISOLDE ion beam switchyard as a new concept for ion beam distribution and conclude by highlighting the potential applications of this ion beam multiplexing te...

Expressive suppression and neural responsiveness to nonverbal affective cues.

Science.gov (United States)

Petrican, Raluca; Rosenbaum, R Shayna; Grady, Cheryl

2015-10-01

Optimal social functioning occasionally requires concealment of one's emotions in order to meet one's immediate goals and environmental demands. However, because emotions serve an important communicative function, their habitual suppression disrupts the flow of social exchanges and, thus, incurs significant interpersonal costs. Evidence is accruing that the disruption in social interactions, linked to habitual expressive suppression use, stems not only from intrapersonal, but also from interpersonal causes, since the suppressors' restricted affective displays reportedly inhibit their interlocutors' emotionally expressive behaviors. However, expressive suppression use is not known to lead to clinically significant social impairments. One explanation may be that over the lifespan, individuals who habitually suppress their emotions come to compensate for their interlocutors' restrained expressive behaviors by developing an increased sensitivity to nonverbal affective cues. To probe this issue, the present study used functional magnetic resonance imaging (fMRI) to scan healthy older women while they viewed silent videos of a male social target displaying nonverbal emotional behavior, together with a brief verbal description of the accompanying context, and then judged the target's affect. As predicted, perceivers who reported greater habitual use of expressive suppression showed increased neural processing of nonverbal affective cues. This effect appeared to be coordinated in a top-down manner via cognitive control. Greater neural processing of nonverbal cues among perceivers who habitually suppress their emotions was linked to increased ventral striatum activity, suggestive of increased reward value/personal relevance ascribed to emotionally expressive nonverbal behaviors. These findings thus provide neural evidence broadly consistent with the hypothesized link between habitual use of expressive suppression and compensatory development of increased responsiveness to

Research and development in dust and silicosis suppression

Energy Technology Data Exchange (ETDEWEB)

Breuer, H

1975-08-21

MAK values of 4 mg/m/sup 3/ for respirable dust containing quartz and 0.15 mg/m/sup 3/ for respirable quartz dust have been established for 5 years' exposure in West German hard coal mines. Routine gravimetric measurements were introduced in 1974 and these are supplemented by the digital Tyndallometer which indicates short-term variations. Gravimetric measurements have indicated the main sources of dust and improved dust suppression measures have considerably reduced respirable dust concentrations in some cases, e.g., by seam infusion, by spraying of the face machine path and at crushers, and by dedusters on heading machines.

Area-wide population suppression of codling moth

International Nuclear Information System (INIS)

Calkins, C.O.; Knight, A.L.; Richardson, G.; Bloem, K.A.

2000-01-01

The area-wide pest population control concept began with E.F. Knipling (1979) in the 1970s. Control of a pest population on individual fields does little to control the overall pest population because only a portion of the population is being affected. Expanding control tactics beyond individual farms tends to suppress the population on a wider scale and frequently results in suppression of the population for more than one year. The Agriculture Research Service (ARS) believes that this concept has not been addressed with the focus and support that it deserves. The ARS Administration made a conscious decision in 1994 to create a series of area-wide programmes funded out of ARS-based funds that had previously been used for pilot tests. These programmes involve a coordinated effort among ARS and university scientists, growers, and fieldmen for agriculture supply centres and fruit packing houses. The first area-wide programme supported by ARS was the codling moth (CM), Cydia pomonella L. (Lepidoptera: Tortricidae) suppression programme. The codling moth is the key pest of pome fruit throughout the western United States (Beers et al. 1993). About half of the insecticides applied on these crops are directed toward this pest. A non-insecticidal control technique, mating disruption (MD), is available to replace the organophosphates. Removal of the hard pesticides directed against this pest would do the most to allow natural enemies to survive and reproduce in the orchards, which in turn would have the effect of reducing secondary pests. Elimination of the pesticides would also remove much of the health risks to workers and would minimise buildup of pesticide resistance. The objectives of the Codling Moth Area-wide Program are to enhance the efficacy of the non-pesticide approach, to demonstrate that mating disruption will work if conducted properly, to develop biological technology to lower costs of control that complement mating disruption, to implement effective

Development of Elite BPH-Resistant Wide-Spectrum Restorer Lines for Three and Two Line Hybrid Rice.

Science.gov (United States)

Fan, Fengfeng; Li, Nengwu; Chen, Yunping; Liu, Xingdan; Sun, Heng; Wang, Jie; He, Guangcun; Zhu, Yingguo; Li, Shaoqing

2017-01-01

Hybrid rice has contributed significantly to the world food security. Breeding of elite high-yield, strong-resistant broad-spectrum restorer line is an important strategy for hybrid rice in commercial breeding programs. Here, we developed three elite brown planthopper (BPH)-resistant wide-spectrum restorer lines by pyramiding big-panicle gene Gn8.1 , BPH-resistant genes Bph6 and Bph9 , fertility restorer genes Rf3, Rf4, Rf5 , and Rf6 through molecular marker assisted selection. Resistance analysis revealed that the newly developed restorer lines showed stronger BPH-resistance than any of the single-gene donor parent Luoyang-6 and Luoyang-9. Moreover, the three new restorer lines had broad spectrum recovery capabilities for Honglian CMS, Wild abortive CMS and two-line GMS sterile lines, and higher grain yields than that of the recurrent parent 9,311 under nature field conditions. Importantly, the hybrid crosses also showed good performance for grain yield and BPH-resistance. Thus, the development of elite BPH-resistant wide-spectrum restorer lines has a promising future for breeding of broad spectrum BPH-resistant high-yield varieties.

Resistance to cycloxaprid in Laodelphax striatellus is associated with altered expression of nicotinic acetylcholine receptor subunits.

Science.gov (United States)

Zhang, Yueliang; Han, Yangchun; Yang, Qiong; Wang, Lihua; He, Peng; Liu, Zewen; Li, Zhong; Guo, Huifang; Fang, Jichao

2018-04-01

Cycloxaprid is a new oxabridged cis-configuration neonicotinoid insecticide, the resistance development potential and underlying resistance mechanism of which were investigated in the small brown planthopper, Laodelphax striatellus (Fallén), an important agricultural pest of rice. A cycloxaprid-resistant strain (YN-CPD) only achieved 10-fold higher resistance, in contrast to 106-fold higher resistance to buprofezin and 332-fold higher resistance to chlorpyrifos achieved after exposure to similar selection pressure, and the cycloxaprid selected line showed no cross-resistance to the buprofezin and chlorpyrifos-selected resistance strains. Moreover, we identified 10 nicotinic acetylcholine receptor (nAChR) subunits from the transcriptome of L. striatellus, and six segments had open reading frames (ORFs). While we did not find mutations in the nAChR genes of L. striatellus, subunits Lsα1 and Lsβ1 exhibited, respectively, 9.60-fold and 3.36-fold higher expression in the resistant strain, while Lsα8 exhibited 0.44-fold lower expression. Suppression of Lsα1 through ingestion of dsLsα1 led to an increase in susceptibility to cycloxaprid. The findings indicate that resistance to cycloxaprid develops slowly compared with resistance to other chemicals and without cross-resistance to chlorpyrifos or buprofezin; over-expressed Lsα1 is associated with low cycloxaprid resistance levels, but the importance of over-expressed Lsβ1 and reduced expression of Lsα8 could not be excluded. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Social hierarchy and depression: the role of emotion suppression.

Science.gov (United States)

Langner, Carrie A; Epel, Elissa S; Matthews, Karen A; Moskowitz, Judith T; Adler, Nancy E

2012-01-01

Position in the social hierarchy is a major determinant of health outcomes. We examined the associations between aspects of social hierarchy and depressive symptoms with a specific focus on one potential psychological mechanism: emotion suppression. Suppressing negative emotion has mental health costs, but individuals with low social power and low social status may use these strategies to avoid conflict. Study 1 assessed perceived social power, tendency to suppress negative emotion, and depressive symptoms in a community sample of women. Low social power was related to greater depressive symptoms, and this relationship was partially mediated by emotion suppression. Study 2 examined education as a proxy for social hierarchy position, anger suppression, and depressive symptoms in a national, longitudinal cohort study (The coronary artery risk development in young adults [CARDIA] study; Cutter et al., 1991). Much as in study 1, low education levels were correlated with greater depressive symptoms, and this relationship was partially mediated by anger suppression. Further, suppression mediated the relationship between low education and subsequent depression up to 15 years later. These findings support the theory that social hierarchy affects mental health in part through a process of emotion suppression.

Physical model of lean suppression pressure oscillation phenomena: steam condensation in the light water reactor pressure suppression system (PSS)

International Nuclear Information System (INIS)

McCauley, E.W.; Holman, G.S.; Aust, E.; Schwan, H.; Vollbrandt, J.

1980-01-01

Using the results of large scale multivent tests conducted by GKSS, a physical model of chugging is developed. The unique combination of accurate digital data and cinematic data has provided the derivation of a detailed, quantified correlation between the dynamic physical variables and the associated two-phase thermo-hydraulic phenomena occurring during lean suppression (chugging) phases of the loss-of-coolant accident in a boiling water reactor pressure suppression system

Interplay between lipids and branched-chain amino acids in development of insulin resistance

Science.gov (United States)

Newgard, Christopher B.

2013-01-01

Summary Fatty acids (FA) and FA-derived metabolites have long been implicated in the development of insulin resistance and type 2 diabetes. Surprisingly, application of metabolomics technologies has revealed that branched-chain amino acids (BCAA) and related metabolites are more strongly associated with insulin resistance than many common lipid species. Moreover, the BCAA-related signature is predictive of incident diabetes and intervention outcomes, and uniquely responsive to therapeutic interventions. Nevertheless, in animal feeding studies, BCAA supplementation requires the background of a high-fat diet to promote insulin resistance. This article develops a model to explain how lipids and BCAA may synergize to promote metabolic diseases. PMID:22560213

Development of Convenient Screening Method for Resistant Radish to Plasmodiophora brassicae

Directory of Open Access Journals (Sweden)

Su-Jung Jo

2011-08-01

Full Text Available To establish simple and reliable screening method for resistant radish to Plasmodiophora brassicae Woron. using soil-drenching inoculation, the development of clubroot on radish seedlings inoculated with P. brassicae GN-1 isolate according to several conditions such as inoculum concentration, plant growth stage and incubation period after inoculation was studied. To select resistant radish against clubroot, 10-day-old seedlings were inoculated with P. brassicae by drenching the roots with the spore suspension of the pathogen to give 1×10(9 spores/pot. The inoculated seedlings were incubated in a growth chamber at 20℃ for 3 days then cultivated in a greenhouse (20±5℃ for 6 weeks. Under the optimum conditions, 46 commercial cultivars of radish were tested for resistance to YC-1 (infecting 15 clubroot-resistant cultivars of Chinese cabbage and GN-1 (wild type isolates of P. brassicae. Among them, thirty-five cultivars showed resistance to both isolates and one cultivar represented susceptible response to the pathogens. On the other hand, the other cultivars showed different responses against the tested P. brassicae pathogens. The results suggest that this method is an efficient system for screening radish with resistance to clubroot.

Characterization of a disease susceptibility locus for exploring an efficient way to improve rice resistance against bacterial blight

Institute of Scientific and Technical Information of China (English)

Qi Cheng; Weihua Mao; Wenya Xie; Qinsong Liu; Jianbo Cao; Meng Yuan; Qinglu Zhang; Xianghua Li; Shiping Wang

2017-01-01

Bacterial blight caused by Xanthomonas oryzae pv.oryzae (Xoo) is the most harmful bacterial disease of rice worldwide.Previously,we characterized major disease resistance (MR) gene xa25,which confers race-specific resistance to Xoo strain PXO339.The xa25 is a recessive allele of the SWEET13 locus,but SWEET13's interaction with PXO339 and how efficiently using this locus for rice breeding still need to be defined.Here we show that the SWEET13 allele from rice Zhenshan 97 is a susceptibility gene to PXO339.Using this allele's promoter to regulate xa25 resulted in disease,suggesting that the promoter is a key determinant in SWEET13 caused disease in Zhanshan 97 after PXO339 infection.PXO339 transcriptionally induces SWEET13 to cause disease.Partial suppressing SWEET13 expression leads to a high level of resistance to PXO339.Thus,the transcriptionally suppressed SWEET13 functions as xa25 in resistance to PXO339.Hybrid rice is widely grown in many countries.However,recessive MR genes have not been efficiently used for disease resistance breeding in hybrid rice production for both parents of the hybrid have to carry the same recessive gene.However,the suppressed SWEET13 functions dominantly,which will have advantage to improve the resistance of hybrid rice to xa25-incomptible Xoo.

Anthelmintic resistance in equine nematodes

Directory of Open Access Journals (Sweden)

Jacqueline B. Matthews

2014-12-01

Full Text Available Anthelmintics have been applied indiscriminately to control horse nematodes for over 40 years. Three broad-spectrum anthelmintic classes are currently registered for nematode control in horses: benzimidazoles (fenbendazole, oxibendazole, tetrahydropyrimidines (pyrantel and macrocyclic lactones (ivermectin, moxidectin. Generally, control strategies have focused on nematode egg suppression regimens that involve the frequent application of anthelmintics to all horses at intervals based on strongyle egg reappearance periods after treatment. The widespread use of such programmes has substantially reduced clinical disease, especially that associated with large strongyle species; however, high treatment frequency has led to considerable selection pressure for anthelmintic resistance, particularly in cyathostomin species. Field studies published over the last decade indicate that benzimidazole resistance is widespread globally in cyathostomins and there are also many reports of resistance to pyrantel in these worms. Cyathostomin resistance to macrocyclic lactone compounds is emerging, principally measured as a reduction in strongyle egg reappearance time observed after treatment. Ivermectin resistance is a further concern in the small intestinal nematode, Parascaris equorum, an important pathogen of foals. These issues indicate that horse nematodes must now be controlled using methods less dependent on anthelmintic use and more reliant on management practices designed to reduce the force of infection in the environment. Such strategies include improved grazing management integrated with targeted anthelmintic administration involving faecal egg count (FEC-directed treatments. The latter require that the supporting diagnostic tests available are robust and practically applicable. Recent research has focused on maximising the value of FEC analysis in horses and on optimizing protocols for anthelmintic efficacy testing. Other studies have sought to develop

Suppressed Belief

Directory of Open Access Journals (Sweden)

Komarine Romdenh-Romluc

2009-12-01

Full Text Available Moran’s revised conception of conscious belief requires us to reconceptualise suppressed belief. The work of Merleau-Ponty offers a way to do this. His account of motor-skills allows us to understand suppressed beliefs as pre-reflective ways of dealing with the world.

Consequences of stereotype suppression and internal suppression motivation : A self-regulation approach

NARCIS (Netherlands)

Gordijn, Ernestine H; Hindriks, Inge; Koomen, W; Dijksterhuis, Ap; van Knipppenberg, A.

The present research studied the effects of suppression of stereotypes on subsequent stereotyping. Moreover, the moderating influence of motivation to suppress stereotypes was examined. The first three experiments showed that suppression of stereotypes leads to the experience of engaging in

Development of Magneto-Resistive Angular Position Sensors for Space Applications

Science.gov (United States)

Hahn, Robert; Langendorf, Sven; Seifart, Klaus; Slatter, Rolf; Olberts, Bastian; Romera, Fernando

2015-09-01

Magnetic microsystems in the form of magneto- resistive (MR) sensors are firmly established in automobiles and industrial applications. They measure path, angle, electrical current, or magnetic fields. MR technology opens up new sensor possibilities in space applications and can be an enabling technology for optimal performance, high robustness and long lifetime at reasonable costs. In a recent assessment study performed by HTS GmbH and Sensitec GmbH under ESA Contract a market survey has confirmed that space industry has a very high interest in novel, contactless position sensors based on MR technology. Now, a detailed development stage is pursued, to advance the sensor design up to Engineering Qualification Model (EQM) level and to perform qualification testing for a representative pilot space application.The paper briefly reviews the basics of magneto- resistive effects and possible sensor applications and describes the key benefits of MR angular sensors with reference to currently operational industrial and space applications. The results of the assessment study are presented and potential applications and uses of contactless magneto-resistive angular sensors for spacecraft are identified. The baseline mechanical and electrical sensor design will be discussed. An outlook on the EQM development and qualification tests is provided.

Military women's attitudes toward menstruation and menstrual suppression in relation to the deployed environment: development and testing of the MWATMS-9 (short form).

Science.gov (United States)

Trego, Lori L; Jordan, Patricia J

2010-01-01

To determine military women's attitudes toward menstruation and menstrual suppression with oral contraceptives in the deployed environment. A cross-sectional descriptive design with the administration of the Menstrual Attitude Questionnaire (MAQ) and the 55-item Military Women's Attitudes Towards Menstrual Suppression Scale (MWATMS) to a convenience sample (n = 278) of women in the U.S. Army with deployment experience. The MAQ's five subscales' mean scores ranged from 3.4 (+/-1.11) to 5.1 (+/-1.06), indicating neutral to moderate attitudes toward menstruation. Measurement development on the MWATMS produced a nine-item scale with three components: stress effects, benefits to self, and environmental barriers. Menstrual attitudes were generally neutral in this sample; however, military women favor menstrual suppression during deployment owing to the effects of stress during deployment, benefits that suppression would provide, and the barriers to menstrual hygiene in the deployed environment. Women who perceived menstruation as bothersome and debilitating had positive attitudes toward menstrual suppression. These findings can contribute to appropriate predeployment women's health care and improve the readiness for deployment in female soldiers. Providers should educate women on the risks and benefits of menstrual suppression methods and provide guidance on impact that the deployed environment can have on their menstrual experiences.

The role of efflux pumps in Bacteroides fragilis resistance to antibiotics.

Science.gov (United States)

Ghotaslou, Reza; Yekani, Mina; Memar, Mohammad Yousef

2018-05-01

The resistance of Bacteroides fragilis to the most antimicrobial agents has been reported in the world. Identification of the microbial resistance mechanisms can play an important role in controlling these resistances. Currently, B. fragilis is resistant to most antibiotics. The multi-drug efflux pumps have been shown to underlie the antimicrobial resistance in B. fragilis strains. Two types of these efflux pumps including RND and MATE can be regarded as main structures responsible for antibiotic resistance. Therefore, the strategy for suppressing of this efflux system may be useful in the treatment and control of the multidrug-resistant B. fragilis. The purpose of this study is to review the B. fragilis efflux pumps and their functions in the resistance to antibiotics. Copyright © 2018 Elsevier GmbH. All rights reserved.

Xenopus Zic3 controls notochord and organizer development through suppression of the Wnt/β-catenin signaling pathway.

Science.gov (United States)

Fujimi, Takahiko J; Hatayama, Minoru; Aruga, Jun

2012-01-15

Zic3 controls neuroectodermal differentiation and left-right patterning in Xenopus laevis embryos. Here we demonstrate that Zic3 can suppress Wnt/β-catenin signaling and control development of the notochord and Spemann's organizer. When we overexpressed Zic3 by injecting its RNA into the dorsal marginal zone of 2-cell-stage embryos, the embryos lost mesodermal dorsal midline structures and showed reduced expression of organizer markers (Siamois and Goosecoid) and a notochord marker (Xnot). Co-injection of Siamois RNA partially rescued the reduction of Xnot expression caused by Zic3 overexpression. Because the expression of Siamois in the organizer region is controlled by Wnt/β-catenin signaling, we subsequently examined the functional interaction between Zic3 and Wnt signaling. Co-injection of Xenopus Zic RNAs and β-catenin RNA with a reporter responsive to the Wnt/β-catenin cascade indicated that Zic1, Zic2, Zic3, Zic4, and Zic5 can all suppress β-catenin-mediated transcriptional activation. In addition, co-injection of Zic3 RNA inhibited the secondary axis formation caused by ventral-side injection of β-catenin RNA in Xenopus embryos. Zic3-mediated Wnt/β-catenin signal suppression required the nuclear localization of Zic3, and involved the reduction of β-catenin nuclear transport and enhancement of β-catenin degradation. Furthermore, Zic3 co-precipitated with Tcf1 (a β-catenin co-factor) and XIC (I-mfa domain containing factor required for dorsoanterior development). The findings in this report produce a novel system for fine-tuning of Wnt/β-catenin signaling. Copyright © 2011. Published by Elsevier Inc.

Development of a suppression method for deposition of radioactive cobalt after chemical decontamination: Confirmation of the Suppression Mechanism with Preoxidized Ferrite Film for Deposition of Radioactive Cobalt

International Nuclear Information System (INIS)

Ito, Tsuyoshi; Hosokawa, Hideyuki; Nagase, Makoto; Aizawa, Motohiro; Fuse, Motomasa

2012-09-01

Recently, chemical decontamination at the beginning of a periodical inspection is applied to many Japanese boiling water reactor (BWR) plants in order to reduce radiation exposure. In the chemical decontamination, the oxides that have incorporated 60 Co are dissolved using reductive and oxidative chemical reagents. Some of the piping stainless steel (SS) base metal is exposed to the reactor water after this decontamination. The oxide film growth rate of the piping during plant operation just after the decontamination is higher than that just before it. Therefore, there is a possibility that the deposition amount of 60 Co on the piping just after decontamination is higher than that just before the chemical decontamination. The Hi-F Coat (Hitachi ferrite coating) process has been developed to lower recontamination after the chemical decontamination. In this process, a fine Fe 3 O 4 coating film is formed on the piping SS base metal in aqueous solution at 363 K using three chemical reagents: ferrous ion, oxidant, and pH adjuster. The growth rate of the corrosion oxide film that incorporated 60 Co on the piping during plant operation is suppressed by the fine ferrite film that blocks both diffusion of oxidant in the reactor water to the SS base metal and metal ions in the oxide film to the reactor water. As a result, the amount of 60 Co deposition is suppressed by the Hi-F coating film. In a previous report, we found that the Hi-F Coat process lowered the amount of 60 Co to 1/3 that for non-coated specimens. To improve the suppression of 60 Co deposition further, we combined the Hi-F Coat process with a pre-oxidation step which we named the pre-oxidized Hi-F Coat process. In laboratory experiments, using the pre-oxidized Hi-F Coat process we found the deposited amount of 60 Co was 1/10 that for non-coated specimens. By combining the Hi-F Coat process with the pre-oxidation step, the suppression effect of 60 Co deposition was three times higher than that of the Hi

Development of antibiotic marker-free creeping bentgrass resistance against herbicides.

Science.gov (United States)

Lee, Ki-Won; Kim, Ki-Yong; Kim, Kyung-Hee; Lee, Byung-Hyun; Kim, Jin-Seog; Lee, Sang-Hoon

2011-01-01

Herbicide-resistant creeping bentgrass plants (Agrostis stolonifera L.) without antibiotic-resistant markers were produced by Agrobacterium-mediated transformation. Embryogenic callus tissues were infected with Agrobacterium tumefaciens EHA105, harboring the bar and the CP4-EPSPS genes for bialaphos and glyphosate resistance. Phosphinothricin-resistant calli and plants were selected. Soil-grown plants were obtained at 14-16 weeks after transformation. Genetic transformation of the selected, regenerated plants was validated by PCR. Southern blot analysis revealed that at least one copy of the transgene was integrated into the genome of the transgenic plants. Transgene expression was confirmed by Northern blot. CP4-EPSPS protein was detected by ELISA. Transgenic plants remained green and healthy when sprayed with Basta, containing 0.5% glufosinate ammonium or glyphosate. The optimized Agrobacterium-mediated transformation method resulted in an average of 9.4% transgenic plants. The results of the present study suggest that the optimized marker-free technique could be used as an effective and reliable method for routine transformation, which may facilitate the development of varieties of new antibiotic-free grass species.

ST37 Klebsiella pneumoniae: development of carbapenem resistance in vivo during antimicrobial therapy in neonates.

Science.gov (United States)

Li, Pengling; Wang, Min; Li, Xianping; Hu, Feihu; Yang, Min; Xie, Yixin; Cao, Wei; Xia, Xiaomeng; Zheng, Rong; Tian, Jingjing; Zhang, Kan; Chen, Fang; Tang, Aiguo

2017-08-01

To investigate the mechanism leading to in vivo carbapenem resistance development in Klebsiella pneumoniae. Carbapenemase was detected using the modified carbapenem inactivation method. β-lactamases resistant genes were identified by PCR and sequencing. Clonal relatedness was evaluated by random amplified polymorphic DNA and multiple locus sequence typing. The relationship between sequence typing and resistant genes was analyzed by using the chi-squared test. All ST37 carbapenem-resistant isolates were bla OXA-1 positive and all ST37 carbapenem-sensitive isolates were bla OXA-1 negative at Stage I. A significant relationship between carbapenem resistance and bla OXA-1 was observed. The bla OXA-1 -positive rate was significantly higher in ST37 K. pneumoniae than others. This is the first study about the development of carbapenem resistance in vivo potentially mediated by bla OXA-1 in ST37 K. pneumoniae among neonates.

Diagnostic and therapeutic progress of multi-drug resistance with anti-HBV nucleos(t)ide analogues

Institute of Scientific and Technical Information of China (English)

Zhuo-Lun Song; Yu-Jun Cui; Wei-Ping Zheng; Da-Hong Teng; Hong Zheng

2012-01-01

Nucleos(t)ide analogues (NA) are a breakthrough in the treatment and management of chronic hepatitis B.NA could suppress the replication of hepatitis B virus (HBV) and control the progression of the disease.However,drug resistance caused by their long-term use becomes a practical problem,which influences the long-term outcomes in patients.Liver transplantation is the only choice for patients with HBV-related end-stage liver disease.But,the recurrence of HBV after transplantation often caused by the development of drug resistance leads to unfavorable outcomes for the recipients.Recentiy,the multi-drug resistance (MDR) has become a common issue raised due to the development and clinical application of a variety of NA.This may complicate the antiviral therapy and bring poorly prognostic outcomes.Although clinical evidence has suggested that combination therapy with different NA could effectively reduce the viral load in patients with MDR,the advent of new antiviral agents with high potency and high genetic barrier to resistance brings hope to antiviral therapy.The future of HBV researches relies on how to prevent the MDR occurrence and develop reasonable and effective treatment strategies.This review focuses on the diagnostic and therapeutic progress in MDR caused by the anti-HBV NA and describes some new research progress in this field.

miR-216b suppresses breast cancer growth and metastasis by targeting SDCBP

International Nuclear Information System (INIS)

Jana, Samir; Sengupta, Suman; Biswas, Subir; Chatterjee, Annesha; Roy, Himansu; Bhattacharyya, Arindam

2017-01-01

Breast cancer is the most deadly cancer among women and the second leading cause of cancer death worldwide. Treatment effectiveness is complicated with tumor invasiveness/drug resistance. To tailor treatments more effectively to individual patients, it is important to define tumor growth and metastasis at molecular levels. SDCBP is highly overexpressed and associated with a strikingly poor prognosis in breast cancer. However the post transcriptional regulation of SDCBP overexpression remains to be an unexplored area. Our study reveals that miR-216b directly regulates SDCBP expression by binding to its 3′UTR region. miR-216b is a tumor suppressive miRNA and it is underexpressed during metastatic breast cancer. Consequently, overexpression of miR-216b resulted in decreased proliferation, migration and invasion in BC cell lines by modulating the expression of SDCBP. Inhibition of miR-216b divergent the tumor suppressive role by inducing the growth proliferation, migration and invasion in vitro. There is therefore a negative correlation between the expression of miR-216b and its target gene SDCBP in the BC tissue samples as well as cell lines. Simultaneous expression of miR-216b and SDCBP rescued the growth, migration and invasion effect suggesting that tumor suppressive action of miR-216b may be directly mediated by SDCBP. In summary, the study identifies miR-216b as a regulator of SDCBP expression in breast cancer which can potentially be targeted for developing newer therapies for the effective treatment of this killer disease.

Macrolides and lincosamides in cattle and pigs: use and development of antimicrobial resistance.

Science.gov (United States)

Pyörälä, Satu; Baptiste, Keith Edward; Catry, Boudewijn; van Duijkeren, Engeline; Greko, Christina; Moreno, Miguel A; Pomba, M Constança Matias Ferreira; Rantala, Merja; Ružauskas, Modestas; Sanders, Pascal; Threlfall, E John; Torren-Edo, Jordi; Törneke, Karolina

2014-05-01

Macrolides and lincosamides are important antibacterials for the treatment of many common infections in cattle and pigs. Products for in-feed medication with these compounds in combination with other antimicrobials are commonly used in Europe. Most recently approved injectable macrolides have very long elimination half-lives in both pigs and cattle, which allows once-only dosing regimens. Both in-feed medication and use of long-acting injections result in low concentrations of the active substance for prolonged periods, which causes concerns related to development of antimicrobial resistance. Acquired resistance to macrolides and lincosamides among food animal pathogens, including some zoonotic bacteria, has now emerged. A comparison of studies on the prevalence of resistance is difficult, since for many micro-organisms no agreed standards for susceptibility testing are available. With animal pathogens, the most dramatic increase in resistance has been seen in the genus Brachyspira. Resistance towards macrolides and lincosamides has also been detected in staphylococci isolated from pigs and streptococci from cattle. This article reviews the use of macrolides and lincosamides in cattle and pigs, as well as the development of resistance in target and some zoonotic pathogens. The focus of the review is on European conditions. Copyright © 2014. Published by Elsevier Ltd.

Direct Evidence that Myocardial Insulin Resistance following Myocardial Ischemia Contributes to Post-Ischemic Heart Failure

Science.gov (United States)

Fu, Feng; Zhao, Kun; Li, Jia; Xu, Jie; Zhang, Yuan; Liu, Chengfeng; Yang, Weidong; Gao, Chao; Li, Jun; Zhang, Haifeng; Li, Yan; Cui, Qin; Wang, Haichang; Tao, Ling; Wang, Jing; Quon, Michael J; Gao, Feng

2015-01-01

A close link between heart failure (HF) and systemic insulin resistance has been well documented, whereas myocardial insulin resistance and its association with HF are inadequately investigated. This study aims to determine the role of myocardial insulin resistance in ischemic HF and its underlying mechanisms. Male Sprague-Dawley rats subjected to myocardial infarction (MI) developed progressive left ventricular dilation with dysfunction and HF at 4 wk post-MI. Of note, myocardial insulin sensitivity was decreased as early as 1 wk after MI, which was accompanied by increased production of myocardial TNF-α. Overexpression of TNF-α in heart mimicked impaired insulin signaling and cardiac dysfunction leading to HF observed after MI. Treatment of rats with a specific TNF-α inhibitor improved myocardial insulin signaling post-MI. Insulin treatment given immediately following MI suppressed myocardial TNF-α production and improved cardiac insulin sensitivity and opposed cardiac dysfunction/remodeling. Moreover, tamoxifen-induced cardiomyocyte-specific insulin receptor knockout mice exhibited aggravated post-ischemic ventricular remodeling and dysfunction compared with controls. In conclusion, MI induces myocardial insulin resistance (without systemic insulin resistance) mediated partly by ischemia-induced myocardial TNF-α overproduction and promotes the development of HF. Our findings underscore the direct and essential role of myocardial insulin signaling in protection against post-ischemic HF. PMID:26659007

Candida Biofilms: Development, Architecture, and Resistance

Science.gov (United States)

CHANDRA, JYOTSNA; MUKHERJEE, PRANAB K.

2015-01-01

Intravascular device–related infections are often associated with biofilms (microbial communities encased within a polysaccharide-rich extracellular matrix) formed by pathogens on the surfaces of these devices. Candida species are the most common fungi isolated from catheter-, denture-, and voice prosthesis–associated infections and also are commonly isolated from contact lens–related infections (e.g., fungal keratitis). These biofilms exhibit decreased susceptibility to most antimicrobial agents, which contributes to the persistence of infection. Recent technological advances have facilitated the development of novel approaches to investigate the formation of biofilms and identify specific markers for biofilms. These studies have provided extensive knowledge of the effect of different variables, including growth time, nutrients, and physiological conditions, on biofilm formation, morphology, and architecture. In this article, we will focus on fungal biofilms (mainly Candida biofilms) and provide an update on the development, architecture, and resistance mechanisms of biofilms. PMID:26350306

Disease Suppressive Soils: New Insights from the Soil Microbiome.

Science.gov (United States)

Schlatter, Daniel; Kinkel, Linda; Thomashow, Linda; Weller, David; Paulitz, Timothy

2017-11-01

Soils suppressive to soilborne pathogens have been identified worldwide for almost 60 years and attributed mainly to suppressive or antagonistic microorganisms. Rather than identifying, testing and applying potential biocontrol agents in an inundative fashion, research into suppressive soils has attempted to understand how indigenous microbiomes can reduce disease, even in the presence of the pathogen, susceptible host, and favorable environment. Recent advances in next-generation sequencing of microbiomes have provided new tools to reexamine and further characterize the nature of these soils. Two general types of suppression have been described: specific and general suppression, and theories have been developed around these two models. In this review, we will present three examples of currently-studied model systems with features representative of specific and general suppressiveness: suppression to take-all (Gaeumannomyces graminis var. tritici), Rhizoctonia bare patch of wheat (Rhizoctonia solani AG-8), and Streptomyces. To compare and contrast the two models of general versus specific suppression, we propose a number of hypotheses about the nature and ecology of microbial populations and communities of suppressive soils. We outline the potential and limitations of new molecular techniques that can provide novel ways of testing these hypotheses. Finally, we consider how this greater understanding of the phytobiome can facilitate sustainable disease management in agriculture by harnessing the potential of indigenous soil microbes.

Energy balance in a Z pinch with suppressed Rayleigh-Taylor instability

Science.gov (United States)

Baksht, R. B.; Oreshkin, V. I.; Rousskikh, A. G.; Zhigalin, A. S.

2018-03-01

At present Z-pinch has evolved into a powerful plasma source of soft x-ray. This paper considers the energy balance in a radiating metallic gas-puff Z pinch. In this type of Z pinch, a power-law density distribution is realized, promoting suppression of Rayleigh-Taylor (RT) instabilities that occur in the pinch plasma during compression. The energy coupled into the pinch plasma, is determined as the difference between the total energy delivered to the load from the generator and the magnetic energy of the load inductance. A calibrated voltage divider and a Rogowski coil were used to determine the coupled energy and the load inductance. Time-gated optical imaging of the pinch plasma showed its stable compression up to the stagnation phase. The pinch implosion was simulated using a 1D two-temperature radiative magnetohydrodynamic code. Comparison of the experimental and simulation results has shown that the simulation adequately describes the pinch dynamics for conditions in which RT instability is suppressed. It has been found that the proportion of the Ohmic heating in the energy balance of a Z pinch with suppressed RT instability is determined by Spitzer resistance and makes no more than ten percent.

Symbiotic immuno-suppression: is disease susceptibility the price of bleaching resistance?

Science.gov (United States)

Merselis, Daniel G; Lirman, Diego; Rodriguez-Lanetty, Mauricio

2018-01-01

Accelerating anthropogenic climate change threatens to destroy coral reefs worldwide through the processes of bleaching and disease. These major contributors to coral mortality are both closely linked with thermal stress intensified by anthropogenic climate change. Disease outbreaks typically follow bleaching events, but a direct positive linkage between bleaching and disease has been debated. By tracking 152 individual coral ramets through the 2014 mass bleaching in a South Florida coral restoration nursery, we revealed a highly significant negative correlation between bleaching and disease in the Caribbean staghorn coral, Acropora cervicornis . To explain these results, we propose a mechanism for transient immunological protection through coral bleaching: removal of Symbiodinium during bleaching may also temporarily eliminate suppressive symbiont modulation of host immunological function. We contextualize this hypothesis within an ecological perspective in order to generate testable predictions for future investigation.

Glechoma hederacea Suppresses RANKL-mediated Osteoclastogenesis.

Science.gov (United States)

Hwang, J K; Erkhembaatar, M; Gu, D R; Lee, S H; Lee, C H; Shin, D M; Lee, Y R; Kim, M S

2014-07-01

Glechoma hederacea (GH), commonly known as ground-ivy or gill-over-the-ground, has been extensively used in folk remedies for relieving symptoms of inflammatory disorders. However, the molecular mechanisms underlying the therapeutic action of GH are poorly understood. Here, we demonstrate that GH constituents inhibit osteoclastogenesis by abrogating receptor activator of nuclear κ-B ligand (RANKL)-induced free cytosolic Ca(2+) ([Ca(2+)]i) oscillations. To evaluate the effect of GH on osteoclastogenesis, we assessed the formation of multi-nucleated cells (MNCs), enzymatic activity of tartrate-resistant acidic phosphatase (TRAP), expression of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), and [Ca(2+)]i alterations in response to treatment with GH ethanol extract (GHE) in primarily cultured bone marrow-derived macrophages (BMMs). Treatment of RANKL-stimulated or non-stimulated BMMs with GHE markedly suppressed MNC formation, TRAP activity, and NFATc1 expression in a dose-dependent manner. Additionally, GHE treatment induced a large transient elevation in [Ca(2+)]i while suppressing RANKL-induced [Ca(2+)]i oscillations, which are essential for NFATc1 activation. GHE-evoked increase in [Ca(2+)]i was dependent on extracellular Ca(2+) and was inhibited by 1,4-dihydropyridine (DHP), inhibitor of voltage-gated Ca(2+) channels (VGCCs), but was independent of store-operated Ca(2+) channels. Notably, after transient [Ca(2+)] elevation, treatment with GHE desensitized the VGCCs, resulting in an abrogation of RANKL-induced [Ca(2+)]i oscillations and MNC formation. These findings demonstrate that treatment of BMMs with GHE suppresses RANKL-mediated osteoclastogenesis by activating and then desensitizing DHP-sensitive VGCCs, suggesting potential applications of GH in the treatment of bone disorders, such as periodontitis, osteoporosis, and rheumatoid arthritis. © International & American Associations for Dental Research.

Nematode parasites of animals are more prone to develop xenobiotic resistance than nematode parasites of plants

Directory of Open Access Journals (Sweden)

Silvestre A.

2004-06-01

Full Text Available In this paper, we concentrate on a comparison of plant and animal-parasitic nematodes, to gain insight into the factors that influence the acquisition of the drug resistance by nematodes. Comparing nematode parasite of domestic animals and cultivated plants, it appears that drug resistance threatens only domestic animal production. Does the paucity of report on nematicide field resistance reflect reality or, is nematicide resistance bypassed by other management practices, specific to cultivated plants (i.e. agricultural control ? First, it seems that selection pressure by treatments in plants is not as efficient as selection pressure in ruminants. Agronomic practices (i.e. sanitation, early planting, usage of nematodes resistant cultivar and crop rotation are frequently used to control parasitic-plant nematodes. Although the efficiency of such measures is generally moderate to high, integrated approaches are developing successfully in parasitic-plant nematode models. Secondly, the majority of anthelmintic resistance cases recorded in animal-parasitic nematodes concern drug families that are not used in plant-parasitic nematodes control (i.e. benzimidazoles, avermectines and levamisole. Thirdly, particular life traits of parasitic-plant nematodes (low to moderate fecundity and reproductive strategy are expected to reduce probability of appearance and transmission of drug resistance genes. It has been demonstrated that, for a large number of nematodes such as Meloidogyne spp., the mode of reproduction by mitotic parthenogenesis reduced genetic diversity of populations which may prevent a rapid drug resistance development. In conclusion, anthelmintic resistance develops in nematode parasite of animals as a consequence of an efficient selection pressure. Early detection of anthelmintic resistance is then crucial : it is not possible to avoid it, but only to delay its development in farm animal industry.

Deconstructing continuous flash suppression.

Science.gov (United States)

Yang, Eunice; Blake, Randolph

2012-03-08

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in contrast detection thresholds) as a function of the visual features of the stimulus being suppressed and the stimulus evoking suppression, namely, the popular "Mondrian" CFS stimulus (N. Tsuchiya & C. Koch, 2005). First, we found that CFS differentially suppresses the spatial components of the suppressed stimulus: Observers' sensitivity for stimuli of relatively low spatial frequency or cardinally oriented features was more strongly impaired in comparison to high spatial frequency or obliquely oriented stimuli. Second, we discovered that this feature-selective bias primarily arises from the spatiotemporal structure of the CFS stimulus, particularly within information residing in the low spatial frequency range and within the smooth rather than abrupt luminance changes over time. These results imply that this CFS stimulus operates by selectively attenuating certain classes of low-level signals while leaving others to be potentially encoded during suppression. These findings underscore the importance of considering the contribution of low-level features in stimulus-driven effects that are reported under CFS.

Top-coatless 193nm positive-tone development immersion resist for logic application

Science.gov (United States)

Liu, Lian Cong; Yeh, Tsung Ju; Lin, Yeh-Sheng; Huang, Yu Chin; Kuo, Chien Wen; Huang, Wen Liang; Lin, Chia Hung; Yu, Chun Chi; Hsu, Ray; Wan, I.-Yuan; Lin, Jeff; Im, Kwang-Hwyi; Lim, Hae Jin; Jeon, Hyun K.; Suzuki, Yasuhiro; Xu, Cheng Bai

2015-03-01

In this paper, we summarize our development efforts for a top-coatless 193nm immersion positive tone development (PTD) contact hole (C/H) resist with improved litho and defect performances for logic application specifically with an advance node. The ultimate performance goal was to improve the depth of focus (DoF) margin, mask error enhancement factor (MEEF), critical dimension uniformity (CDU), contact edge roughness (CER), and defect performance. Also, the through pitch CD difference was supposed to be comparable to the previous control resist. Effects of polymer and PAG properties have been evaluated for this purpose. The material properties focused in the evaluation study were polymer activation energy (Ea), polymer solubility differentiated by polymerization process types, and diffusion length (DL) and acidity (pKa) of photoacid generator (PAG). Additionally, the impact of post exposure bake (PEB) temperature was investigated for process condition optimization. As a result of this study, a new resist formulation to satisfy all litho and defect performance was developed and production yield was further improved.

Dexamethasone suppression test

Science.gov (United States)

DST; ACTH suppression test; Cortisol suppression test ... During this test, you will receive dexamethasone. This is a strong man-made (synthetic) glucocorticoid medicine. Afterward, your blood is drawn ...

Differential expression of miR-1, a putative tumor suppressing microRNA, in cancer resistant and cancer susceptible mice

Directory of Open Access Journals (Sweden)

Jessica L. Fleming

2013-04-01

Full Text Available Mus spretus mice are highly resistant to several types of cancer compared to Mus musculus mice. To determine whether differences in microRNA (miRNA expression account for some of the differences in observed skin cancer susceptibility between the strains, we performed miRNA expression profiling of skin RNA for over 300 miRNAs. Five miRNAs, miR-1, miR-124a-3, miR-133a, miR-134, miR-206, were differentially expressed by array and/or qPCR. miR-1 was previously shown to have tumor suppressing abilities in multiple tumor types. We found miR-1 expression to be lower in mouse cutaneous squamous cell carcinomas (cSCCs compared to normal skin. Based on the literature and our expression data, we performed detailed studies on predicted miR-1 targets and evaluated the effect of miR-1 expression on two murine cSCC cell lines, A5 and B9. Following transfection of miR-1, we found decreased mRNA expression of three validated miR-1 targets, Met, Twf1 and Ets1 and one novel target Bag4. Decreased expression of Ets1 was confirmed by Western analysis and by 3’ reporter luciferase assays containing wildtype and mutated Ets1 3’UTR. We evaluated the effect of miR-1 on multiple tumor phenotypes including apoptosis, proliferation, cell cycle and migration. In A5 cells, expression of miR-1 led to decreased proliferation compared to a control miR. miR-1 expression also led to increased apoptosis at later time points (72 and 96 h and to a decrease in cells in S-phase. In summary, we identified five miRNAs with differential expression between cancer resistant and cancer susceptible mice and found that miR-1, a candidate tumor suppressor, has targets with defined roles in tumorigenesis.

Clinical evidence on the magnitude of change in growth pathway activity in relation to Tamoxifen resistance is required.

Science.gov (United States)

Mansouri, Sepideh; Farahmand, Leila; Teymourzadeh, Azin; Majidzadeh-A, Keivan

2017-08-08

Despite prolonged disease-free survival and overall survival rates in estrogen receptor (ER)-positive patients undergoing adjuvant treatment, Tamoxifen therapy tends to fail due to eventual acquisition of resistance. Although numerous studies have emphasized the role of receptor tyrosine kinases (RTKs) in the development of Tamoxifen resistance, inadequate clinical evidence is available regarding the alteration of biomarker expression during acquired resistance, thus undermining the validity of the findings. Results of two meta-analyses investigating the effect of HER2 status on the prognosis of Tamoxifen-receiving patients have demonstrated that despite HER2-negative patients having longer disease-free survival; there is no difference in overhaul survival between the two groups. Furthermore, due to the intricate molecular interactions among estrogen receptors including ERα36, ERα66, and also RTKs, it is not surprising that RTK suppression does not restore Tamoxifen sensitivity. In considering such a complex network, we speculate that by the time HER2/EGFR is suppressed via targeted therapies, activation of ERα66 and ERα36 initiate molecular signaling pathways downstream of RTKs, thereby enhancing cell proliferation even in the presence of both Tamoxifen and RTK inhibitors. Although clinical findings regarding the molecular pathways downstream of RTKs have been thoroughly discussed in this review, further clinical studies are required in determining a consistency between preclinical and clinical findings. Discovering the best targets in preventing tumor progression requires thorough comprehension of estrogen-dependent and estrogen-independent pathways during Tamoxifen resistance development. Indeed, exploring additional clinically-proven targets would allow for better characterized treatments being available for breast cancer patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Development of weldable, corrosion-resistant iron-aluminide alloys

Energy Technology Data Exchange (ETDEWEB)

Maziasz, P.J.; Goodwin, G.M.; Wang, X.L. [Oak Ridge National Laboratory, TN (United States)

1995-05-01

Corrosion-resistant, weldable FeAl alloys have been developed with improved high-temperature strength industrial applications. Previous processing difficulties with these alloys led to their evaluation as weld-overlay claddings on conventional structural steels to take advantage of their good properties now. Simplified and better processing methods for monolithic FeAl components are also currently being developed so that components for industrial testing can be made. Other avenues for producing FeAl coatings are currently being explored. Neutron scattering experiments residual stress distributions in the FeAl weld-overlay cladding began in FY 1993 and continued this year.

Deconstructing continuous flash suppression

OpenAIRE

Yang, Eunice; Blake, Randolph

2012-01-01

In this paper, we asked to what extent the depth of interocular suppression engendered by continuous flash suppression (CFS) varies depending on spatiotemporal properties of the suppressed stimulus and CFS suppressor. An answer to this question could have implications for interpreting the results in which CFS influences the processing of different categories of stimuli to different extents. In a series of experiments, we measured the selectivity and depth of suppression (i.e., elevation in co...

Estimation of interface resistivity in bonded Si for the development of high performance radiation detectors

International Nuclear Information System (INIS)

Kanno, Ikuo; Yamashita, Makoto; Nomiya, Seiichiro; Onabe, Hideaki

2007-01-01

For the development of high performance radiation detectors, direct bonding of Si wafers would be an useful method. Previously, p-n bonded Si were fabricated and they showed diode characteristics. The interface resistivity was, however, not investigated in detail. For the study of interface resistivity, n-type Si wafers with different resistivities were bonded. The resistivity of bonded Si wafers were measured and the interface resistivity was estimated by comparing with the results of model calculations. (author)

Eco-friendly electron beam lithography using water-developable resist material derived from biomass

Science.gov (United States)

Takei, Satoshi; Oshima, Akihiro; Wakabayashi, Takanori; Kozawa, Takahiro; Tagawa, Seiichi

2012-07-01

We investigated the eco-friendly electron beam (EB) lithography using a high-sensitive negative type of water-developable resist material derived from biomass on hardmask layer for tri-layer processes. A water developable, non-chemically amplified, high sensitive, and negative tone resist material in EB lithography was developed for environmental affair, safety, easiness of handling, and health of the working people, instead of the common developable process of trimethylphenylammonium hydroxide. The images of 200 nm line and 800 nm space pattern with exposure dose of 7.0 μC/cm2 and CF4 etching selectivity of 2.2 with hardmask layer were provided by specific process conditions.

Plum pox virus capsid protein suppresses plant pathogen-associated molecular pattern (PAMP)-triggered immunity.

Science.gov (United States)

Nicaise, Valerie; Candresse, Thierry

2017-08-01

The perception of pathogen-associated molecular patterns (PAMPs) by immune receptors launches defence mechanisms referred to as PAMP-triggered immunity (PTI). Successful pathogens must suppress PTI pathways via the action of effectors to efficiently colonize their hosts. So far, plant PTI has been reported to be active against most classes of pathogens, except viruses, although this defence layer has been hypothesized recently as an active part of antiviral immunity which needs to be suppressed by viruses for infection success. Here, we report that Arabidopsis PTI genes are regulated upon infection by viruses and contribute to plant resistance to Plum pox virus (PPV). Our experiments further show that PPV suppresses two early PTI responses, the oxidative burst and marker gene expression, during Arabidopsis infection. In planta expression of PPV capsid protein (CP) was found to strongly impair these responses in Nicotiana benthamiana and Arabidopsis, revealing its PTI suppressor activity. In summary, we provide the first clear evidence that plant viruses acquired the ability to suppress PTI mechanisms via the action of effectors, highlighting a novel strategy employed by viruses to escape plant defences. © 2016 BSPP AND JOHN WILEY & SONS LTD.

Identification and Reconstruction of Prostate Tumor-Suppressing Exosomes for Therapeutic Applications

Science.gov (United States)

2016-03-01

to the altered contents of exosomes , those from prostate cancer cells (tumor exosomes ) no longer have tumor suppressive functions. If this... cancer . To develop this concept, exosomes will be isolated from normal prostate epithelial cells by differential centrifugations or affinity...purifications and evaluated for tumor suppressing activities against various prostate cancer cells (Aim 1). Then the components of the tumor suppressing exosomes

A Double-Resistive Active Power Filter System to Attenuate Harmonic Voltages of a Radial Power Distribution Feeder

DEFF Research Database (Denmark)

Sun, Xiaofeng; Han, Ruijing; Shen, Hong

2016-01-01

voltages. This paper proposes a double-resistive active power filter (D-RAPF) system consisting of a terminal-RAPF and an attenuation-RAPF for each individual harmonic. The terminal-RAPF operating as the characteristic impedance of the feeder is installed at the end bus to suppress harmonic propagation......Harmonic propagation between power-factor correction capacitors and system inductors seriously deteriorates power quality in a radial power distribution feeder. Installation of a resistive active power filter (RAPF) at the end bus only suppresses harmonic propagation, not attenuates harmonic...... at all harmonic frequencies. The attenuation-RAPF, whose control gain can be set according to the requirements of the harmonic voltage distortion limit, is installed at a specific position for each individual harmonic to attenuate the corresponding harmonic voltages. The D-RAPF system not only suppresses...

The tobacco smoke component acrolein induces glucocorticoid resistant gene expression via inhibition of histone deacetylase.

Science.gov (United States)

Randall, Matthew J; Haenen, Guido R M M; Bouwman, Freek G; van der Vliet, Albert; Bast, Aalt

2016-01-05

Chronic obstructive pulmonary disease (COPD) is the leading cause of cigarette smoke-related death worldwide. Acrolein, a crucial reactive electrophile found in cigarette smoke mimics many of the toxic effects of cigarette smoke-exposure in the lung. In macrophages, cigarette smoke is known to hinder histone deacetylases (HDACs), glucocorticoid-regulated enzymes that play an important role in the pathogenesis of glucocorticoid resistant inflammation, a common feature of COPD. Thus, we hypothesize that acrolein plays a role in COPD-associated glucocorticoid resistance. To examine the role of acrolein on glucocorticoid resistance, U937 monocytes, differentiated with PMA to macrophage-like cells were treated with acrolein for 0.5h followed by stimulation with hydrocortisone for 8h, or treated simultaneously with LPS and hydrocortisone for 8h without acrolein. GSH and nuclear HDAC activity were measured, or gene expression was analyzed by qPCR. Acrolein-mediated TNFα gene expression was not suppressed by hydrocortisone whereas LPS-induced TNFα expression was suppressed. Acrolein also significantly inhibited nuclear HDAC activity in macrophage-like cells. Incubation of recombinant HDAC2 with acrolein led to the formation of an HDAC2-acrolein adduct identified by mass spectrometry. Therefore, these results suggest that acrolein-induced inflammatory gene expression is resistant to suppression by the endogenous glucocorticoid, hydrocortisone. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Furanodiene Induces Extrinsic and Intrinsic Apoptosis in Doxorubicin-Resistant MCF-7 Breast Cancer Cells via NF-κB-Independent Mechanism.

Science.gov (United States)

Zhong, Zhang-Feng; Yu, Hai-Bing; Wang, Chun-Ming; Qiang, Wen-An; Wang, Sheng-Peng; Zhang, Jin-Ming; Yu, Hua; Cui, Liao; Wu, Tie; Li, De-Qiang; Wang, Yi-Tao

2017-01-01

Chemotherapy is used as a primary approach in cancer treatment after routine surgery. However, chemo-resistance tends to occur when chemotherapy is used clinically, resulting in poor prognosis and recurrence. Currently, Chinese medicine may provide insight into the design of new therapies to overcome chemo-resistance. Furanodiene, as a heat-sensitive sesquiterpene, is isolated from the essential oil of Rhizoma Curcumae . Even though mounting evidence claiming that furanodiene possesses anti-cancer activities in various types of cancers, the underlying mechanisms against chemo-resistant cancer are not fully clear. Our study found that furanodiene could display anti-cancer effects by inhibiting cell viability, inducing cell cytotoxicity, and suppressing cell proliferation in doxorubicin-resistant MCF-7 breast cancer cells. Furthermore, furanodiene preferentially causes apoptosis by interfering with intrinsic/extrinsic-dependent and NF-κB-independent pathways in doxorubicin-resistant MCF-7 cells. These observations also prompt that furanodiene may be developed as a promising natural product for multidrug-resistant cancer therapy in the future.

DEVELOPMENT OF ATTRITION RESISTANT IRON-BASED FISCHER-TROPSCH CATALYSTS

International Nuclear Information System (INIS)

Adeyinka A. Adeyiga

2001-01-01

The Fischer-Tropsch (F-T) reaction provides a way of converting coal-derived synthesis gas (CO+H 2 ) to liquid fuels. Since the reaction is highly exothermic, one of the major problems in control of the reaction is heat removal. Recent work has shown that the use of slurry bubble column reactors (SBCRs) can largely solve this problem. The use of iron-based catalysts is attractive not only due to their low cost and ready availability, but also due to their high water-gas shift activity which makes it possible to use these catalysts with low H 2 /CO ratios. However, a serious problem with use of Fe catalysts in a SBCR is their tendency to undergo attrition. This can cause fouling/plugging of downstream filters and equipment, makes the separation of catalyst from the oil/wax product very difficult if not impossible, and results in a steady loss of catalyst from the reactor. Recently, fundamental understanding of physical attrition is being addressed by incorporating suitable binders into the catalyst recipe. This has resulted in the preparation of a spray dried Fe-based catalyst having aps of 70 mm with high attrition resistance. This Fe-based attrition resistant, active and selective catalyst gave 95% CO conversion through 125 hours of testing in a fixed-bed at 270 C, 1.48 MPa, H 2 /CO=0.67 and 2.0 NL/g-cat/h with C 5 + selectivity of >78% and methane selectivity of <5%. However, further development of the catalyst is needed to address the chemical attrition due to phase changes that any Fe-catalyst goes through potentially causing internal stresses within the particle and resulting in weakening, spalling or cracking. The objective of this research is to develop robust iron-based Fischer-Tropsch catalysts that have suitable activity, selectivity and stability to be used in the slurry bubble column reactor. Specifically we aim to develop to: (i) improve the performance and preparation procedure of the high activity, high attrition resistant, high alpha iron

Development of a resistance management strategy for ixodid ticks ...

African Journals Online (AJOL)

The strategy developed for managing resistance in ticks with the acaricidal products on the market was based on mode of action of the active ingredients. The strategy requires the rotaional use of the acaricidal products in ways that reduces the selection pressure of active ingredients of same chemistry on the target-site in ...

Study and development of a spectrometer with Compton suppression and gamma coincidence counting

International Nuclear Information System (INIS)

Masse, D.

1990-10-01

This paper presents the characteristics of a spectrometer consisting of a Ge detector surrounded by a NaI(T1) detector that can operate in Compton-suppression and gamma-gamma coincidence modes. The criteria that led to this measurement configuration are discussed and the spectrometer performances are shown for 60 Co and 137 Cs gamma-ray sources. The results for the measurement of 189 Ir (Compton suppression) and for the measurement of 101 Rh (gamma-gamma coincidence) in the presence of other radioisotopes are given. 83 Rb and 105 Ag isotopes are also measured with this spectrometer [fr

Developing artemisinin based drug combinations for the treatment of drug resistant falciparum malaria: A review

Directory of Open Access Journals (Sweden)

Olliaro P

2004-01-01

Full Text Available The emergence and spread of drug resistant malaria represents a considerable challenge to controlling malaria. To date, malaria control has relied heavily on a comparatively small number of chemically related drugs, belonging to either the quinoline or the antifolate groups. Only recently have the artemisinin derivatives been used but mostly in south east Asia. Experience has shown that resistance eventually curtails the life-span of antimalarial drugs. Controlling resistance is key to ensuring that the investment put into developing new antimalarial drugs is not wasted. Current efforts focus on research into new compounds with novel mechanisms of action, and on measures to prevent or delay resistance when drugs are introduced. Drug discovery and development are long, risky and costly ventures. Antimalarial drug development has traditionally been slow but now various private and public institutions are at work to discover and develop new compounds. Today, the antimalarial development pipeline is looking reasonably healthy. Most development relies on the quinoline, antifolate and artemisinin compounds. There is a pressing need to have effective, easy to use, affordable drugs that will last a long time. Drug combinations that have independent modes of action are seen as a way of enhancing efficacy while ensuring mutual protection against resistance. Most research work has focused on the use of artesunate combined with currently used standard drugs, namely, mefloquine, amodiaquine, sulfadoxine/pyrimethamine, and chloroquine. There is clear evidence that combinations improve efficacy without increasing toxicity. However, the absolute cure rates that are achieved by combinations vary widely and depend on the level of resistance of the standard drug. From these studies, further work is underway to produce fixed dose combinations that will be packaged in blister packs. This review will summarise current antimalarial drug developments and outline recent

Development of superior radiation resistant materials and cables. 2

Energy Technology Data Exchange (ETDEWEB)

Ikehara, Junichiro; Kanemitsuya, Kazuhiko; Ohara, Hideo; Araki, Syogo; Hamachi, Katsuhiko [Mitsubishi Cable Industries Ltd., Tokyo (Japan)

1996-01-01

Many nuclear power plants have been constructed in Japan and electric power generation is now highly dependent on this technology. Therefore, the needs for facilities that will enrich and reprocess nuclear fuel from nuclear power stations will be high. As there are areas with high levels of radiation, the cables which can be used in these environments are needed. We have developed a superior radiation-resistant cable which uses halogen flame-retardant materials. This radiation-resistant cable consists of Ethylene-propylene rubber (EPDM) insulation and Chlorosulfonated polyethylene (CSM) sheath can be safely used in areas with high levels of radiation. We developed this product to aid in disaster prevention. Non-halogen, flame-retardant EPDM is used for the insulation, and low-halogen, flame-retardant CSM and new non-halogen, flame-retardant materials are used for the sheath. These cables have superior flame-retardant properties and generate little smoke on corrosive gas. This products can hence reduce the danger of a secondary disaster in a fire. We expect that these cables will find application in areas with high levels of radiation. (author).

Development of superior radiation resistant materials and cables. 2

International Nuclear Information System (INIS)

Ikehara, Junichiro; Kanemitsuya, Kazuhiko; Ohara, Hideo; Araki, Syogo; Hamachi, Katsuhiko

1996-01-01

Many nuclear power plants have been constructed in Japan and electric power generation is now highly dependent on this technology. Therefore, the needs for facilities that will enrich and reprocess nuclear fuel from nuclear power stations will be high. As there are areas with high levels of radiation, the cables which can be used in these environments are needed. We have developed a superior radiation-resistant cable which uses halogen flame-retardant materials. This radiation-resistant cable consists of Ethylene-propylene rubber (EPDM) insulation and Chlorosulfonated polyethylene (CSM) sheath can be safely used in areas with high levels of radiation. We developed this product to aid in disaster prevention. Non-halogen, flame-retardant EPDM is used for the insulation, and low-halogen, flame-retardant CSM and new non-halogen, flame-retardant materials are used for the sheath. These cables have superior flame-retardant properties and generate little smoke on corrosive gas. This products can hence reduce the danger of a secondary disaster in a fire. We expect that these cables will find application in areas with high levels of radiation. (author)

FAO/IAEA Consultants Group Meeting on The Potential for Tsetse Flies to Develop Resistance to Insecticides

International Nuclear Information System (INIS)

1993-01-01

Chemical insecticides are playing an increasingly important role in control of tsetse flies (Glossina spp), vectors of human and animal trypanosomiasis in large regions of Africa. Although insecticide resistance has not yet been reported in tsetse, there is no cause for complacency regarding its occurrence in the future. As new reports of insecticide resistance in other disease vectors and agronomic pests continue to accumulate at a rapid rate, it is increasingly clear that no comprehensive approach to tsetse control can afford to ignore the potential resistance problem, as the loss of insecticides from the limited set of options for control would be disastrous. it is likely that one or more of the pyrethroid resistance mechanisms already known from several other species of Diptera will manifest itself in tsetse, in response to the increased selection engendered by the wider adoption of deltamethrin-treated targets in tsetse control at the local level and in eradication efforts. Also, selection for behavioural avoidance of traps and targets could result in decreased control efficiency, although the mechanisms that might cause such behavioural resistance are poorly understood at present. There is thus an increasingly urgent need for information on the potential for resistance development in tsetse, on accurate and feasible methods for detection, monitoring, and characterization of resistance, on properties of resistant strains, and on appropriate tactics for resistance prevention and management. Because of the extraordinary difficulties in rearing posed by tsetse life history, it is essential that these research efforts get underway immediately. The Consultants Group on the Possibility of Development of Insecticide Resistance in Tsetse has accordingly prepared this report with a consideration of the present state of knowledge, a discussion of the essential elements of a resistance research program, and specific recommendations. A summary of the recommendations in

FAO/IAEA Consultants Group Meeting on The Potential for Tsetse Flies to Develop Resistance to Insecticides

Energy Technology Data Exchange (ETDEWEB)

NONE

1993-07-01

Chemical insecticides are playing an increasingly important role in control of tsetse flies (Glossina spp), vectors of human and animal trypanosomiasis in large regions of Africa. Although insecticide resistance has not yet been reported in tsetse, there is no cause for complacency regarding its occurrence in the future. As new reports of insecticide resistance in other disease vectors and agronomic pests continue to accumulate at a rapid rate, it is increasingly clear that no comprehensive approach to tsetse control can afford to ignore the potential resistance problem, as the loss of insecticides from the limited set of options for control would be disastrous. it is likely that one or more of the pyrethroid resistance mechanisms already known from several other species of Diptera will manifest itself in tsetse, in response to the increased selection engendered by the wider adoption of deltamethrin-treated targets in tsetse control at the local level and in eradication efforts. Also, selection for behavioural avoidance of traps and targets could result in decreased control efficiency, although the mechanisms that might cause such behavioural resistance are poorly understood at present. There is thus an increasingly urgent need for information on the potential for resistance development in tsetse, on accurate and feasible methods for detection, monitoring, and characterization of resistance, on properties of resistant strains, and on appropriate tactics for resistance prevention and management. Because of the extraordinary difficulties in rearing posed by tsetse life history, it is essential that these research efforts get underway immediately. The Consultants Group on the Possibility of Development of Insecticide Resistance in Tsetse has accordingly prepared this report with a consideration of the present state of knowledge, a discussion of the essential elements of a resistance research program, and specific recommendations. A summary of the recommendations in

Model development for quantitative evaluation of proliferation resistance of nuclear fuel cycles

Energy Technology Data Exchange (ETDEWEB)

Ko, Won Il; Kim, Ho Dong; Yang, Myung Seung

2000-07-01

This study addresses the quantitative evaluation of the proliferation resistance which is important factor of the alternative nuclear fuel cycle system. In this study, model was developed to quantitatively evaluate the proliferation resistance of the nuclear fuel cycles. The proposed models were then applied to Korean environment as a sample study to provide better references for the determination of future nuclear fuel cycle system in Korea. In order to quantify the proliferation resistance of the nuclear fuel cycle, the proliferation resistance index was defined in imitation of an electrical circuit with an electromotive force and various electrical resistance components. The analysis on the proliferation resistance of nuclear fuel cycles has shown that the resistance index as defined herein can be used as an international measure of the relative risk of the nuclear proliferation if the motivation index is appropriately defined. It has also shown that the proposed model can include political issues as well as technical ones relevant to the proliferation resistance, and consider all facilities and activities in a specific nuclear fuel cycle (from mining to disposal). In addition, sensitivity analyses on the sample study indicate that the direct disposal option in a country with high nuclear propensity may give rise to a high risk of the nuclear proliferation than the reprocessing option in a country with low nuclear propensity.

Model development for quantitative evaluation of proliferation resistance of nuclear fuel cycles

International Nuclear Information System (INIS)

Ko, Won Il; Kim, Ho Dong; Yang, Myung Seung

2000-07-01

This study addresses the quantitative evaluation of the proliferation resistance which is important factor of the alternative nuclear fuel cycle system. In this study, model was developed to quantitatively evaluate the proliferation resistance of the nuclear fuel cycles. The proposed models were then applied to Korean environment as a sample study to provide better references for the determination of future nuclear fuel cycle system in Korea. In order to quantify the proliferation resistance of the nuclear fuel cycle, the proliferation resistance index was defined in imitation of an electrical circuit with an electromotive force and various electrical resistance components. The analysis on the proliferation resistance of nuclear fuel cycles has shown that the resistance index as defined herein can be used as an international measure of the relative risk of the nuclear proliferation if the motivation index is appropriately defined. It has also shown that the proposed model can include political issues as well as technical ones relevant to the proliferation resistance, and consider all facilities and activities in a specific nuclear fuel cycle (from mining to disposal). In addition, sensitivity analyses on the sample study indicate that the direct disposal option in a country with high nuclear propensity may give rise to a high risk of the nuclear proliferation than the reprocessing option in a country with low nuclear propensity

Suppression sours sacrifice: emotional and relational costs of suppressing emotions in romantic relationships.

Science.gov (United States)

Impett, Emily A; Kogan, Aleksandr; English, Tammy; John, Oliver; Oveis, Christopher; Gordon, Amie M; Keltner, Dacher

2012-06-01

What happens when people suppress their emotions when they sacrifice for a romantic partner? This multimethod study investigates how suppressing emotions during sacrifice shapes affective and relationship outcomes. In Part 1, dating couples came into the laboratory to discuss important romantic relationship sacrifices. Suppressing emotions was associated with emotional costs for the partner discussing his or her sacrifice. In Part 2, couples participated in a 14-day daily experience study. Within-person increases in emotional suppression during daily sacrifice were associated with decreases in emotional well-being and relationship quality as reported by both members of romantic dyads. In Part 3, suppression predicted decreases in relationship satisfaction and increases in thoughts about breaking up with a romantic partner 3 months later. In the first two parts of the study, authenticity mediated the costly effects of suppression. Implications for research on close relationships and emotion regulation are discussed.

Climate change, transgenic corn adoption and field-evolved resistance in corn earworm.

Science.gov (United States)

Venugopal, P Dilip; Dively, Galen P

2017-06-01

Increased temperature anomaly during the twenty-first century coincides with the proliferation of transgenic crops containing the bacterium Bacillus thuringiensis (Berliner) (Bt) to express insecticidal Cry proteins. Increasing temperatures profoundly affect insect life histories and agricultural pest management. However, the implications of climate change on Bt crop-pest interactions and insect resistance to Bt crops remains unexamined. We analysed the relationship of temperature anomaly and Bt adoption with field-evolved resistance to Cry1Ab Bt sweet corn in a major pest, Helicoverpa zea (Boddie). Increased Bt adoption during 1996-2016 suppressed H. zea populations, but increased temperature anomaly buffers population reduction. Temperature anomaly and its interaction with elevated selection pressure from high Bt acreage probably accelerated the Bt-resistance development. Helicoverpa zea damage to corn ears, kernel area consumed, mean instars and proportion of late instars in Bt varieties increased with Bt adoption and temperature anomaly, through additive or interactive effects. Risk of Bt-resistant H. zea spreading is high given extensive Bt adoption, and the expected increase in overwintering and migration. Our study highlights the challenges posed by climate change for Bt biotechnology-based agricultural pest management, and the need to incorporate evolutionary processes affected by climate change into Bt-resistance management programmes.

Pressure-induced suppression of ferromagnetic phase and conduction in CaMn1-xRuxO3

International Nuclear Information System (INIS)

Markovich, V.; Fita, I.; Puzniak, R.; Rozenberg, E.; Martin, C.; Wisniewski, A.; Maignan, A.; Raveau, B.; Yuzhelevskii, Y.; Gorodetsky, G.

2005-01-01

Magnetic and transport properties of polycrystalline CaMn 1-x Ru x O 3 (x=0-0.4) perovskites were investigated under pressures up to 12kbar. It was found that an applied pressure suppresses ferromagnetism and increases resistivity. The results are discussed in the context of phase separation and valence effects

Suppressing magnetic island growth by resonant magnetic perturbation

Science.gov (United States)

Yu, Q.; Günter, S.; Lackner, K.

2018-05-01

The effect of externally applied resonant magnetic perturbations (RMPs) on the growth of magnetic islands is investigated based on two-fluid equations. It is found that if the local bi-normal electron fluid velocity at the resonant surface is sufficiently large, static RMPs of the same helicity and of moderate amplitude can suppress the growth of magnetic islands in high-temperature plasmas. These islands will otherwise grow, driven by an unfavorable plasma current density profile and bootstrap current perturbation. These results indicate that the error field can stabilize island growth, if the error field amplitude is not too large and the local bi-normal electron fluid velocity is not too low. They also indicate that applied rotating RMPs with an appropriate frequency can be utilized to suppress island growth in high-temperature plasmas, even for a low bi-normal electron fluid velocity. A significant change in the local equilibrium plasma current density gradient by small amplitude RMPs is found for realistic plasma parameters, which are important for the island stability and are expected to be more important for fusion reactors with low plasma resistivity.

Curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway.

Science.gov (United States)

Tian, Binqiang; Zhao, Yingmei; Liang, Tao; Ye, Xuxiao; Li, Zuowei; Yan, Dongliang; Fu, Qiang; Li, Yonghui

2017-08-01

We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells and N-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin. Moreover, introduction of constitutively active AKT1 abolished the inhibitory effect of curcumin on cell proliferation, migration, and restored the phosphorylation levels of 4E-BP1 and S6K1, suggesting that curcumin functions via suppressing IGF2-mediated AKT/mTOR signaling pathway. In summary, our results reveal that suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway is one of the mechanisms of action of curcumin. Our findings suggest a new therapeutic strategy against human bladder cancer caused by aberrant activation of IGF2, which are useful for translational application of curcumin.

Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis.

Science.gov (United States)

Wang, Ying; Rishi, Arun K; Wu, Wenjuan; Polin, Lisa; Sharma, Sunita; Levi, Edi; Albelda, Steven; Pass, Harvey I; Wali, Anil

2011-11-01

Malignant pleural mesothelioma (MPM) is an aggressive, asbestos-related malignancy of the thoracic pleura. Although, platinum-based agents are the first line of therapy, there is an urgent need for second-line therapies to treat the drug-resistant MPM. Cell cycle as well as apoptosis pathways are frequently altered in MPM and thus remain attractive targets for intervention strategies. Curcumin, the major component in the spice turmeric, alone or in combination with other chemotherapeutics has been under investigation for a number of cancers. In this study, we investigated the biological and molecular responses of MPM cells to curcumin treatments and the mechanisms involved. Flow-cytometric analyses coupled with western immunoblotting and gene-array analyses were conducted to determine mechanisms of curcumin-dependent growth suppression of human (H2373, H2452, H2461, and H226) and murine (AB12) MPM cells. Curcumin inhibited MPM cell growth in a dose- and time-dependent manner while pretreatment of MPM cells with curcumin enhanced cisplatin efficacy. Curcumin activated the stress-activated p38 kinase, caspases 9 and 3, caused elevated levels of proapoptotic proteins Bax, stimulated PARP cleavage, and apoptosis. In addition, curcumin treatments stimulated expression of novel transducers of cell growth suppression such as CARP-1, XAF1, and SULF1 proteins. Oral administration of curcumin inhibited growth of murine MPM cell-derived tumors in vivo in part by stimulating apoptosis. Thus, curcumin targets cell cycle and promotes apoptosis to suppress MPM growth in vitro and in vivo. Our studies provide a proof-of-principle rationale for further in-depth analysis of MPM growth suppression mechanisms and their future exploitation in effective management of resistant MPM.

Distinct apoptotic blocks mediate resistance to panHER inhibitors in HER2+ breast cancer cells.

Science.gov (United States)

Karakas, Bahriye; Ozmay, Yeliz; Basaga, Huveyda; Gul, Ozgur; Kutuk, Ozgur

2018-05-04

Despite the development of novel targeted therapies, de novo or acquired chemoresistance remains a significant factor for treatment failure in breast cancer therapeutics. Neratinib and dacomitinib are irreversible panHER inhibitors, which block their autophosphorylation and downstream signaling. Moreover, neratinib and dacomitinib have been shown to activate cell death in HER2-overexpressing cell lines. Here we showed that increased MCL1 and decreased BIM and PUMA mediated resistance to neratinib in ZR-75-30 and SKBR3 cells while increased BCL-XL and BCL-2 and decreased BIM and PUMA promoted neratinib resistance in BT474 cells. Cells were also cross-resistant to dacomitinib. BH3 profiles of HER2+ breast cancer cells efficiently predicted antiapoptotic protein dependence and development of resistance to panHER inhibitors. Reactivation of ERK1/2 was primarily responsible for acquired resistance in SKBR3 and ZR-75-30 cells. Adding specific ERK1/2 inhibitor SCH772984 to neratinib or dacomitinib led to increased apoptotic response in neratinib-resistant SKBR3 and ZR-75-30 cells, but we did not detect a similar response in neratinib-resistant BT474 cells. Accordingly, suppression of BCL-2/BCL-XL by ABT-737 was required in addition to ERK1/2 inhibition for neratinib- or dacomitinib-induced apoptosis in neratinib-resistant BT474 cells. Our results showed that different mitochondrial apoptotic blocks mediated acquired panHER inhibitor resistance in HER2+ breast cancer cell lines as well as highlighted the potential of BH3 profiling assay in prediction of panHER inhibitor resistance in breast cancer cells. Copyright © 2018 Elsevier B.V. All rights reserved.

High Concentration of Melatonin Regulates Leaf Development by Suppressing Cell Proliferation and Endoreduplication in Arabidopsis.

Science.gov (United States)

Wang, Qiannan; An, Bang; Shi, Haitao; Luo, Hongli; He, Chaozu

2017-05-05

N -acetyl-5-methoxytryptamine (Melatonin), as a crucial messenger in plants, functions in adjusting biological rhythms, stress tolerance, plant growth and development. Several studies have shown the retardation effect of exogenous melatonin treatment on plant growth and development. However, the in vivo role of melatonin in regulating plant leaf growth and the underlying mechanism are still unclear. In this study, we found that high concentration of melatonin suppressed leaf growth in Arabidopsis by reducing both cell size and cell number. Further kinetic analysis of the fifth leaves showed that melatonin remarkably inhibited cell division rate. Additionally, flow cytometic analysis indicated that melatonin negatively regulated endoreduplication during leaf development. Consistently, the expression analysis revealed that melatonin regulated the transcriptional levels of key genes of cell cycle and ribosome. Taken together, this study suggests that high concentration of melatonin negatively regulated the leaf growth and development in Arabidopsis , through modulation of endoreduplication and the transcripts of cell cycle and ribosomal key genes.

An EAR-motif-containing ERF transcription factor affects herbivore-induced signaling, defense and resistance in rice.

Science.gov (United States)

Lu, Jing; Ju, Hongping; Zhou, Guoxin; Zhu, Chuanshu; Erb, Matthias; Wang, Xiaopeng; Wang, Peng; Lou, Yonggen

2011-11-01

Ethylene responsive factors (ERFs) are a large family of plant-specific transcription factors that are involved in the regulation of plant development and stress responses. However, little to nothing is known about their role in herbivore-induced defense. We discovered a nucleus-localized ERF gene in rice (Oryza sativa), OsERF3, that was rapidly up-regulated in response to feeding by the rice striped stem borer (SSB) Chilo suppressalis. Antisense and over-expression of OsERF3 revealed that it positively affects transcript levels of two mitogen-activated protein kinases (MAPKs) and two WRKY genes as well as concentrations of jasmonate (JA), salicylate (SA) and the activity of trypsin protease inhibitors (TrypPIs). OsERF3 was also found to mediate the resistance of rice to SSB. On the other hand, OsERF3 was slightly suppressed by the rice brown planthopper (BPH) Nilaparvata lugens (Stål) and increased susceptibility to this piercing sucking insect, possibly by suppressing H(2)O(2) biosynthesis. We propose that OsERF3 affects early components of herbivore-induced defense responses by suppressing MAPK repressors and modulating JA, SA, ethylene and H(2)O(2) pathways as well as plant resistance. Our results also illustrate that OsERF3 acts as a central switch that gears the plant's metabolism towards an appropriate response to chewing or piercing/sucking insects. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

Targeting androgen receptor to suppress macrophage-induced EMT and benign prostatic hyperplasia (BPH) development.

Science.gov (United States)

Lu, Tianjing; Lin, Wen-Jye; Izumi, Kouji; Wang, Xiaohai; Xu, Defeng; Fang, Lei-Ya; Li, Lei; Jiang, Qi; Jin, Jie; Chang, Chawnshang

2012-10-01

Early studies suggested macrophages might play roles in inflammation-associated benign prostatic hyperplasia (BPH) development, yet the underlying mechanisms remain unclear. Here we first showed that CD68(+) macrophages were identified in both epithelium and the stromal area of human BPH tissues. We then established an in vitro co-culture model with prostate epithelial and macrophage cell lines to study the potential impacts of infiltrating macrophages in the BPH development and found that co-culturing prostate epithelial cells with macrophages promoted migration of macrophages. In a three-dimensional culture system, the sphere diameter of BPH-1 prostate cells was significantly increased during coculture with THP-1 macrophage cells. Mechanism dissection suggested that expression levels of epithelial-mesenchymal transition (EMT) markers, such as N-cadherin, Snail, and TGF-β2, were increased, and administration of anti-TGF-β2 neutralizing antibody during co-culture suppressed the EMT and THP-1-mediated growth of BPH-1 cells, suggesting THP-1 might go through EMT to influence the BPH development and progression. Importantly, we found that modulation of androgen receptor (AR) in BPH-1 and mPrE cells significantly increased THP-1 and RAW264.7 cell migration, respectively, and enhanced expression levels of EMT markers, suggesting that AR in prostate epithelial cells might play a role in promoting macrophage-mediated EMT in prostate epithelial cells. Silencing AR function via an AR degradation enhancer, ASC-J9, decreased the macrophage migration to BPH-1 cells and suppressed EMT marker expression. Together, these results provide the first evidence to demonstrate that prostate epithelial AR function is important for macrophage-mediated EMT and proliferation of prostate epithelial cells, which represents a previously unrecognized role of AR in the cross-talk between macrophages and prostate epithelial cells. These results may provide new insights for a new therapeutic

BCL2-BH4 antagonist BDA-366 suppresses human myeloma growth.

Science.gov (United States)

Deng, Jiusheng; Park, Dongkyoo; Wang, Mengchang; Nooka, Ajay; Deng, Qiaoya; Matulis, Shannon; Kaufman, Jonathan; Lonial, Sagar; Boise, Lawrence H; Galipeau, Jacques; Deng, Xingming

2016-05-10

Multiple myeloma (MM) is a heterogeneous plasma cell malignancy and remains incurable. B-cell lymphoma-2 (BCL2) protein correlates with the survival and the drug resistance of myeloma cells. BH3 mimetics have been developed to disrupt the binding between BCL2 and its pro-apoptotic BCL2 family partners for the treatment of MM, but with limited therapeutic efficacy. We recently identified a small molecule BDA-366 as a BCL2 BH4 domain antagonist, converting it from an anti-apoptotic into a pro-apoptotic molecule. In this study, we demonstrated that BDA-366 induces robust apoptosis in MM cell lines and primary MM cells by inducing BCL2 conformational change. Delivery of BDA-366 substantially suppressed the growth of human MM xenografts in NOD-scid/IL2Rγnull mice, without significant cytotoxic effects on normal hematopoietic cells or body weight. Thus, BDA-366 functions as a novel BH4-based BCL2 inhibitor and offers an entirely new tool for MM therapy.

Enhanced sensitivity of A549 cells to the cytotoxic action of anticancer drugs via suppression of Nrf2 by procyanidins from Cinnamomi Cortex extract

Energy Technology Data Exchange (ETDEWEB)

Ohnuma, Tomokazu; Matsumoto, Takashi; Itoi, Ayano; Kawana, Ayako; Nishiyama, Takahito; Ogura, Kenichiro [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan); Hiratsuka, Akira, E-mail: hiratuka@toyaku.ac.jp [Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392 (Japan)

2011-10-07

Highlights: {yields} We found a novel inhibitor of Nrf2 known as a chemoresistance factor. {yields} Overexpressed Nrf2 in lung cancer cells was suppressed by Cinnamomi Cortex extract. {yields} Cytotoxic action of anticancer drugs in cells treated with the extract was enhanced. {yields} Procyanidin tetramers and pentamers were active components in suppressing Nrf2. -- Abstract: Nuclear factor-E2-related factor 2 (Nrf2) is an important cytoprotective transcription factor because Nrf2-regulated enzymes play a key role in antioxidant and detoxification processes. Recent studies have reported that lung cancer cells overexpressing Nrf2 exhibit increased resistance to chemotherapy. Suppression of overexpressed Nrf2 is needed for a new therapeutic approach against lung cancers. In the present study, we found that Cinnamomi Cortex extract (CCE) has an ability to suppress Nrf2-regulated enzyme activity and Nrf2 expression in human lung cancer A549 cells with high Nrf2 activity. Moreover, we demonstrated that CCE significantly enhances sensitivity of A549 cells to the cytotoxic action of doxorubicin and etoposide as well as increasing the intracellular accumulation of both drugs. These results suggest that CCE might be an effective concomitant agent to reduce anticancer drug resistance derived from Nrf2 overexpression. Bioactivity-guided fractionation revealed that procyanidin tetramers and pentamers contained in CCE were active components in suppressing Nrf2.

Mechanisms of insulin resistance in obesity

Science.gov (United States)

Ye, Jianping

2014-01-01

Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

How glyphosate affects plant disease development: it is more than enhanced susceptibility.

Science.gov (United States)

Hammerschmidt, Ray

2018-05-01

Glyphosate has been shown to affect the development of plant disease in several ways. Plants utilize phenolic and other shikimic acid pathway-derived compounds as part of their defense against pathogens, and glyphosate inhibits the biosynthesis of these compounds via its mode of action. Several studies have shown a correlation between enhanced disease and suppression of phenolic compound production after glyphosate. Glyphosate-resistant crop plants have also been studied for changes in resistance as a result of carrying the glyphosate resistance trait. The evidence indicates that neither the resistance trait nor application of glyphosate to glyphosate-resistant plants increases susceptibility to disease. The only exceptions to this are cases where glyphosate has been shown to reduce rust diseases on glyphosate-resistant crops, supporting a fungicidal role for this chemical. Finally, glyphosate treatment of weeds or volunteer crops can cause a temporary increase in soil-borne pathogens that may result in disease development if crops are planted too soon after glyphosate application. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Development of a novel zirconia dental post resistant to hydrothermal degradation

International Nuclear Information System (INIS)

Camposilvan, E; Marro, F G; Mestra, A; Anglada, M J

2012-01-01

Tetragonal Zirconia Polycrystals stabilized with 3% mol. content of yttria (3Y-TZP) has excellent properties in terms of strength and fracture toughness. These properties are mostly imputable to the transformation toughening mechanism, by which the doped metastable tetragonal phase of zirconia transforms to monoclinic under applied stress ahead of a crack. This phenomenon is accompanied by a volume expansion of 5%, and increases the resistance to crack growth, thus leading to higher toughness and strength. An important drawback of this material is represented by the Low Temperature Degradation (LTD or aging), which consists in the progressive tetragonal-to-monoclinic phase transformation by the influence of water. This work focuses on the improvement of 3Y-TZP aging behavior in order to develop a novel dental post, by means of the addition of ceria from the surface. This was achieved through the impregnation of the pre-sintered samples with a solution containing Cerium, followed by sintering. Various pre-sintering temperatures were studied in terms of microstructure, mechanical properties and aging resistance. The novel zirconia dental posts developed in this work are much more resistant to LTD as compared to the base material with no loss in mechanical properties.

ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal

Directory of Open Access Journals (Sweden)

Choi Cheol-Hee

2005-10-01

Full Text Available Abstract One of the major problems related with anticancer chemotherapy is resistance against anticancer drugs. The ATP-binding cassette (ABC transporters are a family of transporter proteins that are responsible for drug resistance and a low bioavailability of drugs by pumping a variety of drugs out cells at the expense of ATP hydrolysis. One strategy for reversal of the resistance of tumor cells expressing ABC transporters is combined use of anticancer drugs with chemosensitizers. In this review, the physiological functions and structures of ABC transporters, and the development of chemosensitizers are described focusing on well-known proteins including P-glycoprotein, multidrug resistance associated protein, and breast cancer resistance protein.

Diphlorethohydroxycarmalol from Ishige okamurae Suppresses Osteoclast Differentiation by Downregulating the NF-κB Signaling Pathway

Directory of Open Access Journals (Sweden)

Hye Jung Ihn

2017-12-01

Full Text Available Marine algae possess a variety of beneficial effects on human health. In this study, we investigated whether diphlorethohydroxycarmalol (DPHC, isolated from Ishige okamurae, a brown alga, suppresses receptor activator of nuclear factor-κB ligand (RANKL-induced osteoclast differentiation. DPHC significantly suppressed RANKL-induced osteoclast differentiation and macrophage-colony stimulating factor (M-CSF expression in a dose-dependent manner. In addition, it significantly inhibited actin ring formation, the expression of osteoclast marker genes, such as tartrate-resistant acid phosphatase (TRAP, nuclear factor of activated T-cells cytoplasmic 1 (Nfatc1, cathepsin K (Ctsk, and dendritic cell-specific transmembrane protein (Dcstamp, and osteoclast-induced bone resorption. Analysis of the RANKL-mediated signaling pathway showed that the phosphorylation of both IκB and p65 was specifically inhibited by DPHC. These results suggest that DPHC substantially suppresses osteoclastogenesis by downregulating the RANK-NF-κB signaling pathway. Thus, it holds significant potential for the treatment of skeletal diseases associated with an enhanced osteoclast activity.

Epigenetic suppression of EGFR signaling in G-CIMP+ glioblastomas.

Science.gov (United States)

Li, Jie; Taich, Zachary J; Goyal, Amit; Gonda, David; Akers, Johnny; Adhikari, Bandita; Patel, Kunal; Vandenberg, Scott; Yan, Wei; Bao, Zhaoshi; Carter, Bob S; Wang, Renzhi; Mao, Ying; Jiang, Tao; Chen, Clark C

2014-09-15

The intrinsic signaling cascades and cell states associated with the Glioma CpG Island Methylator Phenotype (G-CIMP) remain poorly understood. Using published mRNA signatures associated with EGFR activation, we demonstrate that G-CIMP+ tumors harbor decreased EGFR signaling using three independent datasets, including the Chinese Glioma Genome Atlas(CGGA; n=155), the REMBRANDT dataset (n=288), and The Cancer Genome Atlas (TCGA; n=406). Additionally, an independent collection of 25 fresh-frozen glioblastomas confirmed lowered pERK levels in G-CIMP+ specimens (pCIMP+ glioblastomas harbored lowered mRNA levels for EGFR and H-Ras. Induction of G-CIMP+ state by exogenous expression of a mutated isocitrate dehydrogenase 1, IDH1-R132H, suppressed EGFR and H-Ras protein expression as well as pERK accumulation in independent glioblastoma models. These suppressions were associated with increased deposition of the repressive histone markers, H3K9me3 and H3K27me3, in the EGFR and H-Ras promoter regions. The IDH1-R132H expression-induced pERK suppression can be reversed by exogenous expression of H-RasG12V. Finally, the G-CIMP+ Ink4a-Arf-/- EGFRvIII glioblastoma line was more resistant to the EGFR inhibitor, Gefitinib, relative to its isogenic G-CIMP- counterpart. These results suggest that G-CIMP epigenetically regulates EGFR signaling and serves as a predictive biomarker for EGFR inhibitors in glioblastoma patients.

Suppression of gastric acid increases the risk of developing immunoglobulin E-mediated drug hypersensitivity: human diclofenac sensitization and a murine sensitization model.

Science.gov (United States)

Riemer, A B; Gruber, S; Pali-Schöll, I; Kinaciyan, T; Untersmayr, E; Jensen-Jarolim, E

2010-03-01

Hypersensitivity reactions towards non-steroidal anti-inflammatory drugs (NSAID) are common, although true allergies are detectable only in a subgroup of patients. The current study was prompted by a case observation, where a patient experienced generalized urticaria following his second course of diclofenac and proton pump inhibitor medication, and was found to have diclofenac-specific IgE. During recent years, our group has been investigating the importance of gastric digestion in the development of food allergies, demonstrating anti-acid medication as a risk factor for sensitization against food proteins. Here, we aimed to investigate whether the mechanism of food allergy induction described can also be causative in NSAID allergy, using diclofenac as a paradigm. We subjected BALB/c mice to several oral immunization regimens modelled after the patient's medication intake. Diclofenac was applied with or without gastric acid suppression, in various doses, alone or covalently coupled to albumin, a protein abundant in gastric juices. Immune responses were assessed on the antibody level, and functionally examined by in vitro and in vivo crosslinking assays. Only mice receiving albumin-coupled diclofenac under gastric acid suppression developed anti-diclofenac IgG1 and IgE, whereas no immune responses were induced by the drug alone or without gastric acid suppression. Antibody induction was dose dependent with the group receiving the higher dose of the drug showing sustained anti-diclofenac titres. The antibodies induced triggered basophil degranulation in vitro and positive skin tests in vivo. Gastric acid suppression was found to be a causative mechanism in the induction of IgE-mediated diclofenac allergy.

CX4945 suppresses the growth of castration-resistant prostate cancer cells by reducing AR-V7 expression.

Science.gov (United States)

Deng, Chuangzhong; Chen, Jieping; Guo, Shengjie; Wang, Yanjun; Zhou, Qianghua; Li, Zaishang; Yang, Xingping; Yu, Xingsu; Zhang, Zhenfeng; Zhou, Fangjian; Han, Hui; Yao, Kai

2017-08-01

The aberrant expression of casein kinase 2 (CK2) has been reported to be involved in the tumorigenesis and progression of prostate cancer. The inhibition of CK2 activity represses androgen-dependent prostate cancer cells by attenuating the androgen receptor (AR) signaling pathway. In this study, we examined the effect of CK2 inhibition in castration-resistant prostate cancer (CRPC) cells, in which AR variants (ARVs) play a predominant role. A newly synthetic CK2 selective inhibitor CX4945 was utilized to study the effect of CK2 inhibition in CRPC cells by CCK8 assay and colony formation assay. Protein and mRNA levels of full-length AR (AR-FL) and AR-V7 were determined by qPCR and western blot, respectively. The nuclear translocation of p50 and p65 was assessed to reflect the activity of the NF-κB pathway. CX4945 reduced the proliferation of CRPC cells in a dose-dependent and time-dependent manner. AR-V7 rather than AR-FL was downregulated by CX4945 in both the mRNA and protein level. Furthermore, CX4945 could restore the sensitivity of CRPC cells to bicalutamide. The analysis of possible mechanisms demonstrated that the inhibition of CK2 diminished the phosphorylation of p65 at ser529 and thus attenuated the activity of the NF-κB pathway. The inhibition of CK2 by CX4945 can repress the viability of CRPC cells and restore their sensitivity to anti-androgen therapy by suppressing AR-V7. This finding presents a potential option for the treatment of prostate cancer, especially CRPC.

Pilot testing and protocol development of giant applesnail suppression at Mandalay National Wildlife Refuge, Louisiana—July–October 2017

Science.gov (United States)

Carter, Jacoby; Merino, Sergio

2018-03-19

This report provides an overview of the pilot study and description of the techniques developed for a future mitigation study of Pomacea maculata (giant applesnail) at the U.S. Fish and Wildlife Service Mandalay National Wildlife Refuge, Louisiana (MNWR). Egg mass suppression is a potential strategy for the mitigation of the invasive giant applesnail. In previous studies at Langan Municipal Park in Mobile, Alabama (LMP), and National Park Service Jean Lafitte National Park-Barataria Unit, Louisiana (JLNP), we determined that spraying food-grade oil (coconut oil or Pam™ spray) on egg masses significantly reduced egg hatching. At JLNP we also developed methods to estimate snail population size. The purpose of this pilot study was to adapt techniques developed for previous studies to the circumstances of MNWR in preparation for a larger experiment whereby we will test the effectiveness of egg mass suppression as an applesnail mitigation tool. We selected four canals that will be used as treatment and control sites for the experiment (two each). We established that an efficient way to destroy egg masses is to knock them down with a high-velocity stream of water pumped directly from the canal. The traps used at JLNP had to be modified to accommodate the greater range of water-level fluctuation at MNWR. One of the three marking methods used at JLNP was selected for use at MNWR.

Involvement of microRNA miR-2b-3p in regulation of metabolic resistance to insecticides in Plutella xylostella.

Science.gov (United States)

Etebari, K; Afrad, M H; Tang, B; Silva, R; Furlong, M J; Asgari, S

2018-03-24

The diamondback moth, Plutella xylostella, has developed extremely high levels of resistance to chlorantraniliprole and other classes of insecticides in the field. As microRNAs (miRNAs) play important roles in various biological processes through gene regulation, we examined the miRNA profile of P. xylostella in response to chlorantraniliprole exposure. RNA sequencing analysis showed that insecticide treatment caused significant changes in the abundance of some miRNAs. Increasing exposure time and insecticide concentration induced more dysregulated miRNAs in P. xylostella larvae. We also screened potential target genes for some of the differentially expressed miRNAs (such as miR-2b-3p, miR-14b-5p and let-7-5p), which may play important roles in insecticide resistance development. Exposure of P. xylostella larvae to chlorantraniliprole caused considerable overexpression in the transcript levels of potential target genes cytochrome P450 9f2 (CYP9F2) and 307a1 (CYP307a1). Application of miR-2b-3p and miR-14b-5p mimics significantly suppressed the relative transcript levels of CYP9F2 and CYP307a1, respectively, in a P. xylostella cell line. Furthermore, enrichment of P. xylostella diet with miR-2b-3p mimics significantly increased mortality in deltamethrin-resistant larvae when exposed to deltamethrin. The results suggest that miR-2b-3p may suppress CYP9F2 transcript levels in P. xylostella and consequently inhibit larval detoxification pathways. The findings provide an insight into possible role of miRNAs in regulation of metabolic resistance of insects to insecticides. © 2018 The Royal Entomological Society.

Survey of pollution-resistant plants and their cultivating techniques; Osen busshitsu taisei shokubutsu to sono shokusai gijutsu ni kansuru chosa

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-03-01

The reduction of forests due to environmental pollution has been surveyed, to investigate the pollution-resistant plants and solid microorganisms. In Japan, the blight of needle-leaf trees (pine and momi fir) and of Japanese oak has occurred, and blight of some other trees, such as wild cherry trees, Japanese apricot trees, birch, Japanese cedar, cypress and bamboo, has been reported from various regions. In this article, plants reported to be resistant to pollutants are listed, and the physiological features of these plants are described. Furthermore, to develop pollution-resistant plants, reports relating to clarification of the mechanism of resistance development and the genes involved are reviewed. Microorganisms which symbioses for roots support these root functions. They also suppress the activity of pathogenic microorganisms and improve the environment around the roots, thus helping plants to grow normally. The roles played by symbiotic microorganisms and how to utilize these organisms are discussed. Their functions in coping with acid rain and heavy metal pollution, and how to utilize such functions are also discussed. 707 refs., 13 figs., 13 tabs.

Histone deacetylase inhibitor trichostatin A resensitizes gemcitabine resistant urothelial carcinoma cells via suppression of TG-interacting factor

Energy Technology Data Exchange (ETDEWEB)

Yeh, Bi-Wen [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Li, Wei-Ming [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Li, Ching-Chia [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Kang, Wan-Yi [Department of Pathology, Kuo General Hospital, Tainan 701, Taiwan (China); Huang, Chun-Nung [Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Hour, Tzyh-Chyuan [Institute of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Liu, Zi-Miao [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); and others

2016-01-01

Gemcitabine and cisplatin (GC) has been widely used for advanced and metastatic urothelial carcinoma (UC). However, resistance to this remedy has been noticed. We have demonstrated that increase of TG-interacting factor (TGIF) in specimens is associated with worse prognosis of upper tract UC (UTUC) patients. The roles of TGIF in the gemcitabine resistance of UC were explored. Specimens of 23 locally advanced/advanced stage UTUC patients who received GC systemic chemotherapy after radical nephroureterectomy were collected to evaluate the alterations of TGIF in the resistance to the remedy by using immunohistochemistry. In vitro characterizations of mechanisms mediating TGIF in gemcitabine resistance were conducted by analyzing NTUB1 cells and their gemcitabine-resistant subline, NGR cells. Our results show that increased TGIF is significantly associated with chemo-resistance, poor progression-free survival, and higher cancer-related deaths of UTUC patients. Higher increases of TGIF, p-AKT{sup Ser473} and invasive ability were demonstrated in NGR cells. Overexpression of TGIF in NTUB1 cells upregulated p-AKT{sup Ser473} activation, enhanced migration ability, and attenuated cellular sensitivity to gemcitabine. Knockdown of TGIF in NGR cells downregulated p-AKT{sup Ser473} activation, declined migration ability, and enhanced cellular sensitivity to gemcitabine. In addition, histone deacetylases inhibitor trichostatin A (TSA) inhibited TGIF, p-AKT{sup Ser473} expression and migration ability. Synergistic effects of gemcitabine and TSA on NGR cells were also demonstrated. Collectively, TGIF contributes to the gemcitabine resistance of UC via AKT activation. Combined treatment with gemcitabine and TSA might be a promising therapeutic remedy to improve the gemcitabine resistance of UC. - Highlights: • TGIF expression in UC cells is associated with chemoresistance to gemcitabine. • TGIF-regulated AKT activation contributes to the gemcitabine resistance. • Increased

Histone deacetylase inhibitor trichostatin A resensitizes gemcitabine resistant urothelial carcinoma cells via suppression of TG-interacting factor

International Nuclear Information System (INIS)

Yeh, Bi-Wen; Li, Wei-Ming; Li, Ching-Chia; Kang, Wan-Yi; Huang, Chun-Nung; Hour, Tzyh-Chyuan; Liu, Zi-Miao

2016-01-01

Gemcitabine and cisplatin (GC) has been widely used for advanced and metastatic urothelial carcinoma (UC). However, resistance to this remedy has been noticed. We have demonstrated that increase of TG-interacting factor (TGIF) in specimens is associated with worse prognosis of upper tract UC (UTUC) patients. The roles of TGIF in the gemcitabine resistance of UC were explored. Specimens of 23 locally advanced/advanced stage UTUC patients who received GC systemic chemotherapy after radical nephroureterectomy were collected to evaluate the alterations of TGIF in the resistance to the remedy by using immunohistochemistry. In vitro characterizations of mechanisms mediating TGIF in gemcitabine resistance were conducted by analyzing NTUB1 cells and their gemcitabine-resistant subline, NGR cells. Our results show that increased TGIF is significantly associated with chemo-resistance, poor progression-free survival, and higher cancer-related deaths of UTUC patients. Higher increases of TGIF, p-AKT Ser473 and invasive ability were demonstrated in NGR cells. Overexpression of TGIF in NTUB1 cells upregulated p-AKT Ser473 activation, enhanced migration ability, and attenuated cellular sensitivity to gemcitabine. Knockdown of TGIF in NGR cells downregulated p-AKT Ser473 activation, declined migration ability, and enhanced cellular sensitivity to gemcitabine. In addition, histone deacetylases inhibitor trichostatin A (TSA) inhibited TGIF, p-AKT Ser473 expression and migration ability. Synergistic effects of gemcitabine and TSA on NGR cells were also demonstrated. Collectively, TGIF contributes to the gemcitabine resistance of UC via AKT activation. Combined treatment with gemcitabine and TSA might be a promising therapeutic remedy to improve the gemcitabine resistance of UC. - Highlights: • TGIF expression in UC cells is associated with chemoresistance to gemcitabine. • TGIF-regulated AKT activation contributes to the gemcitabine resistance. • Increased TGIF is significantly

Aging and repeated thought suppression success.

Directory of Open Access Journals (Sweden)

Ann E Lambert

Full Text Available Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility.

Resistance to cyclosporin A derives from mutations in hepatitis C virus nonstructural proteins.

Science.gov (United States)

Arai, Masaaki; Tsukiyama-Kohara, Kyoko; Takagi, Asako; Tobita, Yoshimi; Inoue, Kazuaki; Kohara, Michinori

2014-05-23

Cyclosporine A (CsA) is an immunosuppressive drug that targets cyclophilins, cellular cofactors that regulate the immune system. Replication of hepatitis C virus (HCV) is suppressed by CsA, but the molecular basis of this suppression is still not fully understood. To investigate this suppression, we cultured HCV replicon cells (Con1, HCV genotype 1b, FLR-N cell) in the presence of CsA and obtained nine CsA-resistant FLR-N cell lines. We determined full-length HCV sequences for all nine clones, and chose two (clones #6 and #7) of the nine clones that have high replication activity in the presence of CsA for further analysis. Both clones showed two consensus mutations, one in NS3 (T1280V) and the other in NS5A (D2292E). Characterization of various mutants indicated that the D2292E mutation conferred resistance to high concentrations of CsA (up to 2 μM). In addition, the missense mutation T1280V contributed to the recovery of colony formation activity. The effects of these mutations are also evident in two established HCV replicon cell lines-HCV-RMT ([1], genotype 1a) and JFH1 (genotype 2a). Moreover, three other missense mutations in NS5A-D2303H, S2362G, and E2414K-enhanced the resistance to CsA conferred by D2292E; these double or all quadruple mutants could resist approximately 8- to 25-fold higher concentrations of CsA than could wild-type Con1. These four mutations, either as single or combinations, also made Con1 strain resistant to two other cyclophilin inhibitors, N-methyl-4-isoleucine-cyclosporin (NIM811) or Debio-025. Interestingly, the changes in IC50 values that resulted from each of these mutations were the lowest in the Debio-025-treated cells, indicating its highest resistant activity against the adaptive mutation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Pleotropic effects of leptin to reverse insulin resistance and diabetic ketoacidosis

DEFF Research Database (Denmark)

Perry, Rachel J; Petersen, Kitt Falk; Shulman, Gerald I.

2016-01-01

In this review we discuss the mechanisms for the pleotropic effects of leptin replacement therapy to reverse liver and muscle insulin resistance in lipodystrophic individuals, as well as insulin-independent effects of leptin replacement therapy to suppress white adipose tissue lipolysis, hepatic...

Aldo-keto reductase 1B10 promotes development of cisplatin resistance in gastrointestinal cancer cells through down-regulating peroxisome proliferator-activated receptor-γ-dependent mechanism.

Science.gov (United States)

Matsunaga, Toshiyuki; Suzuki, Ayaka; Kezuka, Chihiro; Okumura, Naoko; Iguchi, Kazuhiro; Inoue, Ikuo; Soda, Midori; Endo, Satoshi; El-Kabbani, Ossama; Hara, Akira; Ikari, Akira

2016-08-25

Cisplatin (cis-diamminedichloroplatinum, CDDP) is one of the most effective chemotherapeutic drugs that are used for treatment of patients with gastrointestinal cancer cells, but its continuous administration often evokes the development of chemoresistance. In this study, we investigated alterations in antioxidant molecules and functions using a newly established CDDP-resistant variant of gastric cancer MKN45 cells, and found that aldo-keto reductase 1B10 (AKR1B10) is significantly up-regulated with acquisition of the CDDP resistance. In the nonresistant MKN45 cells, the sensitivity to cytotoxic effect of CDDP was decreased and increased by overexpression and silencing of AKR1B10, respectively. In addition, the AKR1B10 overexpression markedly suppressed accumulation and cytotoxicity of 4-hydroxy-2-nonenal that is produced during lipid peroxidation by CDDP treatment, suggesting that the enzyme acts as a crucial factor for facilitation of the CDDP resistance through inhibiting induction of oxidative stress by the drug. Transient exposure to CDDP and induction of the CDDP resistance decreased expression of peroxisome proliferator-activated receptor-γ (PPARγ) in MKN45 and colon cancer LoVo cells. Additionally, overexpression of PPARγ in the cells elevated the sensitivity to the CDDP toxicity, which was further augmented by concomitant treatment with a PPARγ ligand rosiglitazone. Intriguingly, overexpression of AKR1B10 in the cells resulted in a decrease in PPARγ expression, which was recovered by addition of an AKR1B10 inhibitor oleanolic acid, inferring that PPARγ is a downstream target of AKR1B10-dependent mechanism underlying the CDDP resistance. Combined treatment with the AKR1B10 inhibitor and PPARγ ligand elevated the CDDP sensitivity, which was almost the same level as that in the parental cells. These results suggest that combined treatment with the AKR1B10 inhibitor and PPARγ ligand is an effective adjuvant therapy for overcoming CDDP resistance of

The halo effect: suppression of pink bollworm on non-Bt cotton by Bt cotton in China.

Directory of Open Access Journals (Sweden)

Peng Wan

Full Text Available In some previously reported cases, transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt have suppressed insect pests not only in fields planted with such crops, but also regionally on host plants that do not produce Bt toxins. Here we used 16 years of field data to determine if Bt cotton caused this "halo effect" against pink bollworm (Pectinophora gossypiella in six provinces of the Yangtze River Valley of China. In this region, the percentage of cotton hectares planted with Bt cotton increased from 9% in 2000 to 94% in 2009 and 2010. We found that Bt cotton significantly decreased the population density of pink bollworm on non-Bt cotton, with net decreases of 91% for eggs and 95% for larvae on non-Bt cotton after 11 years of Bt cotton use. Insecticide sprays targeting pink bollworm and cotton bollworm (Helicoverpa armigera decreased by 69%. Previously reported evidence of the early stages of evolution of pink bollworm resistance to Bt cotton in China has raised concerns that if unchecked, such resistance could eventually diminish or eliminate the benefits of Bt cotton. The results reported here suggest that it might be possible to find a percentage of Bt cotton lower than the current level that causes sufficient regional pest suppression and reduces the risk of resistance.

Suppression of PCD-related genes affects salt tolerance in Arabidopsis.

Science.gov (United States)

Bahieldin, Ahmed; Alqarni, Dhafer A M; Atef, Ahmed; Gadalla, Nour O; Al-matary, Mohammed; Edris, Sherif; Al-Kordy, Magdy A; Makki, Rania M; Al-Doss, Abdullah A; Sabir, Jamal S M; Mutwakil, Mohammed H Z; El-Domyati, Fotouh M

2016-01-01

This work aims at examining a natural exciting phenomenon suggesting that suppression of genes inducing programmed cell death (PCD) might confer tolerance against abiotic stresses in plants. PCD-related genes were induced in tobacco under oxalic acid (OA) treatment (20 mM), and plant cells were characterized to confirm the incidence of PCD. The results indicated that PCD was triggered 24 h after the exposure to OA. Then, RNAs were extracted from tobacco cells 0, 2, 6, 12 and 24 h after treatment for deep sequencing. RNA-Seq analyses were done with a special emphasis to clusters whose PCD-related genes were upregulated after 2 h of OA exposure. Accordingly, 23 tobacco PCD-related genes were knocked down via virus-induced gene silencing (VIGS), whereas our results indicated the influence of five of them on inducing or suppressing PCD. Knockout T-DNA insertion mutants of these five genes in Arabidopsis were tested under salt stress (0, 100, 150, and 200 mM NaCl), and the results indicated that a mutant of an antiapoptotic gene, namely Bax Inhibitor-1 (BI-1), whose VIGS induced PCD in tobacco, was salt sensitive, while a mutant of an apoptotic gene, namely mildew resistance locus O (Mlo), whose VIGS suppressed PCD, was salt tolerant as compared to the WT (Col) control. These data support our hypothesis that retarding PCD-inducing genes can result in higher levels of salt tolerance, while retarding PCD-suppressing genes can result in lower levels of salt tolerance in plants. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

Self-administered nicotine differentially impacts body weight gain in obesity-prone and obesity-resistant rats.

Science.gov (United States)

Rupprecht, Laura E; Smith, Tracy T; Donny, Eric C; Sved, Alan F

2017-07-01

Obesity and tobacco smoking represent the largest challenges to public health, but the causal relationship between nicotine and obesity is poorly understood. Nicotine suppresses body weight gain, a factor impacting smoking initiation and the failure to quit, particularly among obese smokers. The impact of nicotine on body weight regulation in obesity-prone and obesity-resistant populations consuming densely caloric diets is unknown. In the current experiment, body weight gain of adult male rats maintained on a high energy diet (31.8% kcal from fat) distributed into obesity-prone (OP), obesity-resistant (OR) and an intermediate group, which was placed on standard rodent chow (Chow). These rats were surgically implanted with intravenous catheters and allowed to self-administer nicotine (0 or 60μg/kg/infusion, a standard self-administration dose) in 1-h sessions for 20 consecutive days. Self-administered nicotine significantly suppressed body weight gain but not food intake in OP and Chow rats. Self-administered nicotine had no effect on body weight gain in OR rats. These data suggest that: 1) OR rats are also resistant to nicotine-induced suppression of body weight gain; and 2) nicotine may reduce levels of obesity in a subset of smokers prone to obesity. Copyright © 2017 Elsevier Inc. All rights reserved.

Development and first tests of GEM-like detectors with resistive electrodes

CERN Document Server

Peskov, Vladimir; Centro, Sandro; Di Mauro, A; Lund-Jensen, B; Martinengo, P; Nappi, E; Oliveira, R; Pietropaolo, F; Picchi, P; Periale, L; Rodionov, I; Ventura, Sandro

2007-01-01

We have developed and tested several prototypes of GEM-like detectors with electrodes coated with resistive layers or completely made of resistive materials. These detectors can operate stably at gains close to 105. The resistive layers limit the energy of discharges appearing at higher gains thus making the detectors very robust. We demonstrated that the cathodes of some of these detectors could be coated by CsI or SbCs layers to enhance the detection efficiency for the UV and visible photons. We also discovered that such detectors can operate stably in the cascade mode and high overall gains ($~10^{6}$) are reachable. Applications in several areas, for example in RICH or in noble liquid TPCs are therefore possible. The first results from the detection of UV photons at room and cryogenic temperatures will be given.

Take-all of Wheat and Natural Disease Suppression: A Review

Directory of Open Access Journals (Sweden)

Youn-Sig Kwak

2013-06-01

Full Text Available In agro-ecosystems worldwide, some of the most important and devastating diseases are caused by soil-borne necrotrophic fungal pathogens, against which crop plants generally lack genetic resistance. However, plants have evolved approaches to protect themselves against pathogens by stimulating and supporting specific groups of beneficial microorganisms that have the ability to protect either by direct inhibition of the pathogen or by inducing resistance mechanisms in the plant. One of the best examples of protection of plant roots by antagonistic microbes occurs in soils that are suppressive to take-all disease of wheat. Take-all, caused by Gaeumannomyces graminis var. tritici, is the most economically important root disease of wheat worldwide. Take-all decline (TAD is the spontaneous decline in incidence and severity of disease after a severe outbreak of take-all during continuous wheat or barley monoculture. TAD occurs worldwide, and in the United States and The Netherlands it results from a build-up of populations of 2,4-diacetylphloroglucinol (2,4-DAPG-producing fluorescent Pseudomonas spp. during wheat monoculture. The antibiotic 2,4-DAPG has a broad spectrum of activity and is especially active against the take-all pathogen. Based on genotype analysis by repetitive sequence-based-PCR analysis and restriction fragment length polymorphism of phlD, a key 2,4-DAPG biosynthesis gene, at least 22 genotypes of 2,4-DAPG producing fluorescent Pseudomonas spp. have been described worldwide. In this review, we provide an overview of G. graminis var. tritici, the take-all disease, Pseudomonas biocontrol agents, and mechanism of disease suppression.

Corrosion resistance improvement of ferritic steels through hydrogen additions to the BWR coolant

International Nuclear Information System (INIS)

Gordon, B.M.; Jewett, C.W.; Pickett, A.E.; Indig, M.E.

1984-01-01

Motivated by the success of oxygen suppression for mitigation of intergranular stress corrosion cracking (IGSCC) in weld sensitized austenitic materials used in Boiling Water Reactors (BWRs), oxygen suppression, through hydrogen additions to the feedwater was investigated to determine its affect on the corrosion resistance of ferritic and martensitic BWR structural materials. The results of these investigations are presented in this paper, where particular emphasis is placed on the corrosion performance of BWR pressure vessel low alloy steels, carbon steel piping materials and martensitic pump materials. It is important to note that the corrosion resistance of these materials in the BWR environment is excellent. Consequently this investigation was also motivated to determine whether there were any detrimental effects of hydrogen additions, as well as to identify any additional margin in ferritic/martensitic materials corrosion performance

A study on heat resistance of high temperature resistant coating

Energy Technology Data Exchange (ETDEWEB)

Zhang, Liping; Wang, Xueying; Zhang, Qibin; Qin, Yanlong; Lin, Zhu [Research Institute of Engineering Technology of CNPC, Tianjin (China)

2005-04-15

A high temperature resistant coating has been developed, which is mainly for heavy oil production pipes deserved the serious corrosion. The coating has excellent physical and mechanical performance and corrosion resistance at room and high temperature. In order to simulate the underground working condition of heavy oil pipes,the heat resistance of the high temperature resistant coating has been studied. The development and a study on the heat resistance of the DHT high temperature resistance coating have been introduced in this paper

A study on heat resistance of high temperature resistant coating

International Nuclear Information System (INIS)

Zhang, Liping; Wang, Xueying; Zhang, Qibin; Qin, Yanlong; Lin, Zhu

2005-01-01

A high temperature resistant coating has been developed, which is mainly for heavy oil production pipes deserved the serious corrosion. The coating has excellent physical and mechanical performance and corrosion resistance at room and high temperature. In order to simulate the underground working condition of heavy oil pipes,the heat resistance of the high temperature resistant coating has been studied. The development and a study on the heat resistance of the DHT high temperature resistance coating have been introduced in this paper

Investigation and development of the suppression methods of the {sup 42}K background in LArGe

Energy Technology Data Exchange (ETDEWEB)

Lubashevskiy, Alexey [Max-Planck-Institut fuer Kernphysik, Saupfercheckweg 1, D-69117 Heidelberg (Germany); Collaboration: GERDA-Collaboration

2013-07-01

GERDA is an ultra-low background experiment aimed for the neutrinoless double beta decay search. The search is performed using HPGe detectors operated in liquid argon (LAr). One of the most dangerous backgrounds in GERDA is the background from {sup 42}K which is a daughter isotope of cosmogenically produced {sup 42}Ar. {sup 42}K ions are collected towards to the detector by the electric field of the detector. Estimation of the background contribution and development of the suppression methods were performed in the low background test facility LArGe. For this purpose encapsulated HPGe and bare BEGe detectors were operated in 1m{sup 3} of LAr in the LArGe setup. It is equipped with scintillation veto, so particles which deposit part of their energy in LAr can be detected by 9 PMTs. In order to better understand background and to increase statistics the LAr of LArGe was spiked with specially produced {sup 42}Ar. All these investigations allowed us to estimate background contribution from {sup 42}K and demonstrate the possibility to suppress it in future measurements in GERDA Phase II.

MITF Modulates Therapeutic Resistance through EGFR Signaling.

Science.gov (United States)

Ji, Zhenyu; Erin Chen, Yiyin; Kumar, Raj; Taylor, Michael; Jenny Njauw, Ching-Ni; Miao, Benchun; Frederick, Dennie T; Wargo, Jennifer A; Flaherty, Keith T; Jönsson, Göran; Tsao, Hensin

2015-07-01

Response to targeted therapies varies significantly despite shared oncogenic mutations. Nowhere is this more apparent than in BRAF (V600E)-mutated melanomas where initial drug response can be striking and yet relapse is commonplace. Resistance to BRAF inhibitors have been attributed to the activation of various receptor tyrosine kinases (RTKs), although the underlying mechanisms have been largely uncharacterized. Here, we found that EGFR-induced vemurafenib resistance is ligand dependent. We employed whole-genome expression analysis and discovered that vemurafenib resistance correlated with the loss of microphthalmia-associated transcription factor (MITF), along with its melanocyte lineage program, and with the activation of EGFR signaling. An inverse relationship between MITF, vemurafenib resistance, and EGFR was then observed in patient samples of recurrent melanoma and was conserved across melanoma cell lines and patients' tumor specimens. Functional studies revealed that MITF depletion activated EGFR signaling and consequently recapitulated the resistance phenotype. In contrast, forced expression of MITF in melanoma and colon cancer cells inhibited EGFR and conferred sensitivity to BRAF/MEK inhibitors. These findings indicate that an "autocrine drug resistance loop" is suppressed by melanocyte lineage signal(s), such as MITF. This resistance loop modulates drug response and could explain the unique sensitivity of melanomas to BRAF inhibition.

Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

International Nuclear Information System (INIS)

Watanabe, Tomoyuki; Saotome, Masao; Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi; Funaki, Makoto; Hayashi, Hideharu

2014-01-01

Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ m ) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H 2 O 2 ), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ m depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H 2 O 2 -induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ m depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin-resistance. • Inhibition of DRP or ROS

Roles of mitochondrial fragmentation and reactive oxygen species in mitochondrial dysfunction and myocardial insulin resistance

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Tomoyuki [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Saotome, Masao, E-mail: msaotome@hama-med.ac.jp [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Nobuhara, Mamoru; Sakamoto, Atsushi; Urushida, Tsuyoshi; Katoh, Hideki; Satoh, Hiroshi [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan); Funaki, Makoto [Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503 (Japan); Hayashi, Hideharu [Internal Medicine III, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192 (Japan)

2014-05-01

Purpose: Evidence suggests an association between aberrant mitochondrial dynamics and cardiac diseases. Because myocardial metabolic deficiency caused by insulin resistance plays a crucial role in heart disease, we investigated the role of dynamin-related protein-1 (DRP1; a mitochondrial fission protein) in the pathogenesis of myocardial insulin resistance. Methods and Results: DRP1-expressing H9c2 myocytes, which had fragmented mitochondria with mitochondrial membrane potential (ΔΨ{sub m}) depolarization, exhibited attenuated insulin signaling and 2-deoxy-D-glucose (2-DG) uptake, indicating insulin resistance. Treatment of the DRP1-expressing myocytes with Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (TMPyP) significantly improved insulin resistance and mitochondrial dysfunction. When myocytes were exposed to hydrogen peroxide (H{sub 2}O{sub 2}), they increased DRP1 expression and mitochondrial fragmentation, resulting in ΔΨ{sub m} depolarization and insulin resistance. When DRP1 was suppressed by siRNA, H{sub 2}O{sub 2}-induced mitochondrial dysfunction and insulin resistance were restored. Our results suggest that a mutual enhancement between DRP1 and reactive oxygen species could induce mitochondrial dysfunction and myocardial insulin resistance. In palmitate-induced insulin-resistant myocytes, neither DRP1-suppression nor TMPyP restored the ΔΨ{sub m} depolarization and impaired 2-DG uptake, however they improved insulin signaling. Conclusions: A mutual enhancement between DRP1 and ROS could promote mitochondrial dysfunction and inhibition of insulin signal transduction. However, other mechanisms, including lipid metabolite-induced mitochondrial dysfunction, may be involved in palmitate-induced insulin resistance. - Highlights: • DRP1 promotes mitochondrial fragmentation and insulin-resistance. • A mutual enhancement between DRP1 and ROS ipromotes insulin-resistance. • Palmitate increases DRP1 expression and induces insulin-resistance

Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

DEFF Research Database (Denmark)

Højlund, Kurt

2014-01-01

. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance....... Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin...

Resistive switching properties and low resistance state relaxation in Al/Pr0.7Ca0.3MnO3/Pt junctions

International Nuclear Information System (INIS)

Li Songlin; Liao, Z L; Li, J; Gang, J L; Zheng, D N

2009-01-01

Metal/insulator/metal structures composed of active Al top electrodes (TEs) and oxygen-deficient Pr 0.7 Ca 0.3 MnO 3 (PCMO) insulator layers are prepared on platinized silicon substrates. The junction resistance exhibits an obvious negative differential resistance region in the first bias sweep and an irreversible increase from 2 to 100 MΩ in repeated ±4 V sweeps. The pulse duration needed to fully switch the junctions is found to be on the order of milliseconds. When 100-500 μs negative pulses are used, the junctions show an incomplete switch to the low resistance state (LRS) which exhibits fluctuating resistances. The fluctuation in the LRS is suppressed and the high-to-low resistance ratio increases gradually when the negative pulse duration is increased from 100 to 500 μs. For relaxed junctions, pulse switching experiments reveal that the LRS undergoes a dynamically stable process at the beginning and then reaches a lower and metastable resistance value. Resistance retention tests also indicate that the high resistance state is very stable, while the metastable LRS gradually relaxes to higher resistance values. The experimental results are discussed with the formation and dissociation of an interfacial AlO x layer at the interface between Al TEs and PCMO layers.

Breaking continuous flash suppression: A new measure of unconscious processing during interocular suppression?

Directory of Open Access Journals (Sweden)

Timo eStein

2011-12-01

Full Text Available Until recently, it has been thought that under interocular suppression high-level visual processing is strongly inhibited if not abolished. With the development of continuous flash suppression (CFS, a variant of binocular rivalry, this notion has now been challenged by a number of reports showing that even high-level aspects of visual stimuli, such as familiarity, affect the time stimuli need to overcome CFS and emerge into awareness. In this breaking CFS (b-CFS paradigm, differential unconscious processing during suppression is inferred when (a speeded detection responses to initially invisible stimuli differ, and (b no comparable differences are found in non-rivalrous control conditions supposed to measure general threshold differences between stimuli. To critically evaluate these assumptions was the aim of the present study. In six experiments we compared the time upright and inverted faces needed to be detected. We found that not only under CFS, but also in control conditions upright faces were detected faster and more accurately than inverted faces, although the effect was larger during CFS. However, reaction time (RT distributions indicated critical differences between the CFS and the control condition. When RT distributions were matched, similar effect sizes were obtained in both conditions. Moreover, subjective ratings revealed that CFS and control conditions are not perceptually comparable. These findings cast doubt on the usefulness of non-rivalrous control conditions to rule out mere detection threshold differences as a cause of shorter detection latencies during CFS. In conclusion, we acknowledge that the b-CFS paradigm can be fruitfully applied as a highly sensitive device to probe differences between stimuli in their potency to gain access to awareness. However, our current findings suggest that such differences can not unequivocally be attributed to differential unconscious processing under interocular suppression.

Accretion and ejection in resistive GR-MHD

Energy Technology Data Exchange (ETDEWEB)

Qian, Qian

2017-05-10

In this thesis, the accretion and ejection processes from a black hole accretion system is investigated by means of resistive general relativistic magnetohydrodynamic simulations. As a supplement to the results from prior research with non-relativistic simulations, my results confirm that the winds and outflows originated from thin accretion disks can also be observed in general relativistic simulations. In the first part, the execution of the implementation of resistivity, namely magnetic diffusivity, into the existing non-resistive general relativistic magnetohydrodynamic code HARM is illustrated. The test simulations of the new code rHARM include the comparison with analytical solution of the diffusion equation and a classic shock tube test. rHARM shows reliable performances in these tests. In the second part, rHARM is applied to investigate the evolution of magnetized tori. The results show that the existence of resistivity leads to inefficient accretions of matter from tori onto black holes by weakening the magnetorotational instability inside the tori. An indication for a critical magnetic diffusivity in this simulation setup is found beyond which no magnetorotational instability develops in the linear regime. In the third part, as the main purpose of this PhD project, rHARM is used to perform simulations of magnetically diffusive thin accretion disks that are threaded by a large-scale poloidal magnetic field around non-rotating and rotating black holes. These long-term simulations last 3000 code time units, which are about 195 rotation periods at the disk inner boundary, correspondingly. Their computational domains extend from black hole horizon to 80 Schwarzschild radii. Outflows driven from the accretion disk are clearly seen. These outflows have the typical radial velocity of 0.1 speed of light. In my analyses, I argue that these outflows are driven by the magnetic pressure gradient from the toroidal magnetic field generated by the rotation of the disk

Thyroid profiles in a patient with resistance to thyroid hormone and episodes of thyrotoxicosis, including repeated painless thyroiditis.

Science.gov (United States)

Taniyama, Matsuo; Otsuka, Fumiko; Tozaki, Teruaki; Ban, Yoshiyuki

2013-07-01

Thyrotoxic disease can be difficult to recognize in patients with resistance to thyroid hormone (RTH) because the clinical symptoms of thyrotoxicosis cannot be observed, and thyrotropin (TSH) may not be suppressed because of hormone resistance. Painless thyroiditis is a relatively common cause of thyrotoxicosis, but its occurrence in RTH has not been reported. We assessed the thyroid profile in a patient with RTH and episodes of thyrotoxicosis who experienced repeated painless thyroiditis. A 44-year-old Japanese woman with RTH, which was confirmed by the presence of a P453A mutation in the thyroid hormone receptor β (TRβ) gene, showed a slight elevation of the basal levels of thyroid hormones, which indicated that her pituitary RTH was mild. She experienced a slight exacerbation of hyperthyroxinemia concomitant with TSH suppression. A diagnosis of painless thyroiditis was made because of the absence of TSH receptor antibodies, low Tc-99m pertechnetate uptake by the thyroid gland, and transient suppression followed by a slight elevation of TSH following the elevation of thyroid hormones. The patient's complaints of general malaise and occasional palpitations did not change throughout the course of painless thyroiditis. Three years later, painless thyroiditis occurred again without any deterioration of the clinical manifestations. Mild pituitary RTH can be overcome by slight exacerbation of hyperthyroxinemia during mild thyrotoxicosis. When pituitary resistance is severe and TSH is not suppressed, thyrotoxicosis may be overlooked.

Refusing Relevance: School Administrator Resistance to Offering Professional Development Addressing LGBTQ Issues in Schools

Science.gov (United States)

Payne, Elizabethe C.; Smith, Melissa J.

2018-01-01

Purpose: The purpose of this article is to provide insight to the multiple ways that school leaders resist, avoid, or block LGBTQ (lesbian, gay, bisexual, and transgender, queer, and questioning) professional development for their staff and, thus, resist the conversations around school responsibility to these students and families. Research…

Analytic modeling of the feedback stabilization of resistive wall modes

International Nuclear Information System (INIS)

Pustovitov, Vladimir D.

2003-01-01

Feedback suppression of resistive wall modes (RWM) is studied analytically using a model based on a standard cylindrical approximation. Optimal choice of the input signal for the feedback, effects related to the geometry of the feedback active coils, RWM suppression in a configuration with ITER-like double wall, are considered here. The widespread opinion that the feedback with poloidal sensors is better than that with radial sensors is discussed. It is shown that for an ideal feedback system the best input signal would be a combination of radial and poloidal perturbations measured inside the vessel. (author)

Infection of inbred rat strains with Rift Valley fever virus: development of a congenic resistant strain and observations on age-dependence of resistance.

Science.gov (United States)

Anderson, G W; Rosebrock, J A; Johnson, A J; Jennings, G B; Peters, C J

1991-05-01

A congenic rat strain (WF.LEW) was derived from the susceptible Wistar-Furth (WF) (background strain) and the resistant LEW (donor strain) inbred strains and was used to evaluate the phenotypic expression of a dominant Mendelian gene that confers resistance to fatal hepatic disease caused by the ZH501 strain of Rift Valley fever virus (RVFV). Resistance to hepatic disease developed gradually with age, with full expression at approximately 10 weeks in the WF.LEW and LEW rat strains. The ZH501 strain caused fatal hepatitis in WF rats regardless of age. However, resistance to the SA75 RVFV strain (relatively non-pathogenic for adult rats), was age- and dose-dependent in both WF and LEW rats. The resistance gene transferred to the newly derived WF.LEW congenic rat strain appears to amplify age-dependent resistance of adult rats, resulting in protection against fatal hepatic disease caused by the virulent ZH501 strain. The congenic rat strain will be a valuable asset in elucidating the mechanism of resistance to Rift Valley fever virus governed by the dominant Mendelian gene.

Control of fire blight (Erwinia amylovora on apple trees with trunk-injected plant resistance inducers and antibiotics and assessment of induction of pathogenesis-related protein genes

Directory of Open Access Journals (Sweden)

Srđan G. Aćimović

2015-02-01

Full Text Available Management of fire blight is complicated by limitations on use of antibiotics in agriculture, antibiotic resistance development, and limited efficacy of alternative control agents. Even though successful in control, preventive antibiotic sprays also affect non-target bacteria, aiding the selection for resistance which could ultimately be transferred to the pathogen Erwinia amylovora. Trunk injection is a target-precise pesticide delivery method that utilizes tree xylem to distribute injected compounds. Trunk injection could decrease antibiotic usage in the open environment and increase the effectiveness of compounds in fire blight control. In field experiments, after 1-2 apple tree injections of either streptomycin, potassium phosphites (PH or acibenzolar-S-methyl (ASM, significant reduction of blossom and shoot blight symptoms was observed compared to water- or non-injected control trees. Overall disease suppression with streptomycin was lower than typically observed following spray applications to flowers. Trunk injection of oxytetracycline resulted in excellent control of shoot blight severity, suggesting that injection is a superior delivery method for this antibiotic. Injection of both ASM and PH resulted in the significant induction of PR-1, PR-2 and PR-8 protein genes in apple leaves indicating induction of systemic acquired resistance (SAR under field conditions. The time separating SAR induction and fire blight symptom suppression indicated that various defensive compounds within the SAR response were synthesized and accumulated in the canopy. ASM and PH suppressed fire blight even after cessation of induced gene expression. With the development of injectable formulations and optimization of doses and injection schedules, the injection of protective compounds could serve as an effective option for fire blight control.

Roux-en-Y gastric bypass surgery suppresses hypothalamic PTP1B protein level and alleviates leptin resistance in obese rats.

Science.gov (United States)

Liu, Jia-Yu; Mu, Song; Zhang, Shu-Ping; Guo, Wei; Li, Qi-Fu; Xiao, Xiao-Qiu; Zhang, Jun; Wang, Zhi-Hong

2017-09-01

The present study aimed to explore the effect of Roux-en-Y gastric bypass (RYGB) surgery on protein tyrosine phosphatase 1B (PTP1B) expression levels and leptin activity in hypothalami of obese rats. Obese rats induced by a high-fat diet (HFD) that underwent RYGB (n=11) or sham operation (SO, n=9), as well as an obese control cohort (Obese, n=10) and an additional normal-diet group (ND, n=10) were used. Food efficiency was measured at 8 weeks post-operation. Plasma leptin levels were evaluated and hypothalamic protein tyrosine phosphatase 1B (PTP1B) levels and leptin signaling activity were examined at the genetic and protein levels. The results indicated that food efficiency was typically lower in RYGB rats compared with that in the Obese and SO rats. In the RYGB group, leptin receptor expression and proopiomelanocortin was significantly higher, while Neuropeptide Y levels were lower than those in the Obese and SO groups. Furthermore, the gene and protein expression levels of PTP1B in the RYGB group were lower, while levels of phosphorylated signal transducer and activator of transcription 3 protein were much higher compared with those in the Obese and SO groups. In conclusion, RYGB surgery significantly suppressed hypothalamic PTP1B protein expression. PTP1B regulation may partially alleviate leptin resistance.

Rehabilitation of Understocked Loblolly-Shortleaf Pine Stands - II. Development of Intermediate and Suppressed Trees Following Release in Natural Stands

Science.gov (United States)

James B. Baker; Michael G. Shelton

1998-01-01

Development of 86 intermediate and suppressed loblolly pine (Pinus taeda L.) trees, that had been recently released from overtopping pines and hardwoods, was monitored over a 15 year period. The trees were growing in natural stands on good sites (site index = 90 ft at 50 years) that had been recently cut to stocking levels ranging from 10 to 50 percent. At time of...

Skin effect suppression for Cu/CoZrNb multilayered inductor

Science.gov (United States)

Sato, Noriyuki; Endo, Yasushi; Yamaguchi, Masahiro

2012-04-01

The Cu/Co85Zr3Nb12 multilayer is studied as a conductor of a spiral inductor to suppress the skin effect at the 5 GHz range (matches IEEE 802.11 a standard) using negative-permeability in CoZrNb films beyond the ferromagnetic resonance frequency. The skin effect suppression becomes remarkable when the thickness of Cu in each period of the multilayer, tCu, is less than the skin depth of Cu at the targeting frequency. For the 5 GHz operation, tCu ≤ 750 nm. The resistance of the Cu/CoZrNb multilayered spiral inductor decreases as much as 8.7%, while keeping the same inductance of 1.1 nH as that of a similar air core. Accordingly, Q = 16. Therefore, the proposed method can contribute to realize a high-Q spiral inductor. We also study the potentially applicable frequency of this method. Given a soft magnetic material with Ms = 105 emu/cc and Hk = 5 Oe, the method can be applied at 700 MHz, the lowermost carrier frequency band for the 4th generation cellular phone system.

In vitro development of resistance to enrofloxacin, erythromycin, tylosin, tiamulin and oxytetracycline in Mycoplasma gallisepticum, Mycoplasma iowae and Mycoplasma synoviae.

Science.gov (United States)

Gautier-Bouchardon, A V; Reinhardt, A K; Kobisch, M; Kempf, I

2002-08-02

The in vitro emergence of resistance to enrofloxacin, erythromycin, tylosin, tiamulin, and oxytetracycline in three avian Mycoplasma species, Mycoplasma gallisepticum, Mycoplasma synoviae and Mycoplasma iowae was studied. Mutants were selected stepwise and their MICs were determined after 10 passages in subinhibitory concentrations of antibiotic. High-level resistance to erythromycin and tylosin developed within 2-6 passages in the three Mycoplasma species. Resistance to enrofloxacin developed more gradually. No resistance to tiamulin or oxytetracycline could be evidenced in M. gallisepticum or M. synoviae after 10 passages whereas, resistant mutants were obtained with M. iowae. Cross-sensitivity tests performed on mutants demonstrated that mycoplasmas made resistant to tylosin were also resistant to erythromycin, whereas mutants made resistant to erythromycin were not always resistant to tylosin. Some M. iowae tiamulin-resistant mutants were also resistant to both macrolide antibiotics. Enrofloxacin and oxytetracycline did not induce any cross-resistance to the other antibiotics tested. These results show that Mycoplasma resistance to macrolides can be quickly selected in vitro, and thus, providing that similar results could be obtained under field conditions, that development of resistance to these antibiotics in vivo might also be a relatively frequent event.

Development of Acid Resistance Velocity Sensor for Analyzing Acidic Fluid Flow Characteristics

Energy Technology Data Exchange (ETDEWEB)

Choi, Gyujin; Yoon, Jinwon; Yu, Sangseok [Chungnam Nat’l Univ., Daejeon (Korea, Republic of)

2016-10-15

This study presents the development of an acid resistance velocity sensor that is used for measuring velocity inside a copper sulfate plating bath. First, researchers investigated the acid resistance coating to confirm the suitability of the anti-acid sensor in a very corrosive environment. Then, researchers applied signal processing methods to reduce noise and amplify the signal. Next, researchers applied a pressure-resistive sensor with an operation amplifier (Op Amp) and low-pass filter with high impedance to match the output voltage of a commercial flowmeter. Lastly, this study compared three low-pass filters (Bessel, Butterworth and Chebyshev) to select the appropriate signal process circuit. The results show 0.0128, 0.0023, and 5.06% of the mean square error, respectively. The Butterworth filter yielded more precise results when compared to a commercial flowmeter. The acid resistive sensor is capable of measuring velocities ranging from 2 to 6 m/s with a 2.7% margin of error.

HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

Science.gov (United States)

Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick CK; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher KC; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

2014-01-01

Introduction First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥2 TAMs; and 32 with M184V+≥1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤200 cells/µL at genotyping (OR=4.43, 95% CI [1.59–12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. Conclusions Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving

Insulin resistance in obesity can be reliably identified from fasting plasma insulin.

Science.gov (United States)

ter Horst, K W; Gilijamse, P W; Koopman, K E; de Weijer, B A; Brands, M; Kootte, R S; Romijn, J A; Ackermans, M T; Nieuwdorp, M; Soeters, M R; Serlie, M J

2015-12-01

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), Pobese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

Susceptibility to neonicotinoids and risk of resistance development in the brown planthopper, Nilaparvata lugens (Stål) (Homoptera: Delphacidae).

Science.gov (United States)

Wang, Yanhua; Chen, Jin; Zhu, Yu Cheng; Ma, Chongyong; Huang, Yue; Shen, Jinliang

2008-12-01

In recent years, outbreaks of the brown planthopper, Nilaparvata lugens (Stål), have occurred more frequently in China. The objective of this study was to determine the susceptibility of N. lugens to neonicotinoids and other insecticides in major rice production areas in China. Results indicated that substantial variations in the susceptibility to different insecticides existed in N. lugens. Field populations had developed variable resistance levels to neonicotinoids, with a high resistance level to imidacloprid (RR: 135.3-301.3-fold), a medium resistance level to imidaclothiz (RR: 35-41.2-fold), a low resistance level to thiamethoxam (up to 9.9-fold) and no resistance to dinotefuran, nitenpyram and thiacloprid (RR buprofezin. In addition, N. lugens had been able to develop 1424-fold resistance to imidacloprid in the laboratory after the insect was selected with imidacloprid for 26 generations. Long-term use of imidacloprid in a wide range of rice-growing areas might be associated with high levels of resistance in N. lugens. Therefore, insecticide resistance management strategies must be developed to prevent further increase in resistance.

Signal mediators at induction of heat resistance of wheat plantlets by short-term heating

Directory of Open Access Journals (Sweden)

Yu. V. Karpets

2015-12-01

Full Text Available The effects of functional interplay of calcium ions, reactive oxygen species (ROS and nitric oxide (NO in the cells of wheat plantlets roots (Triticum aestivum L. at the induction of their heat resistance by a short-term influence of hyperthermia (heating at the temperature of 42 °С during 1 minute have been investigated. The transitional increase of NO and H2O2 content, invoked by heating, was suppressed by the treatment of plantlets with the antagonists of calcium EGTA (chelator of exocellular calcium, lanthanum chloride (blocker of calcium channels of various types and neomycin (inhibitor of phosphatidylinositol-dependent phospholipase C. The rise of hydrogen peroxide content, caused by hardening, was partially suppressed by the action of inhibitors of nitrate reductase (sodium wolframate and NO-synthase (NG-nitro-L-arginine methyl ester – L-NAME, and the increasing of nitric oxide content was suppressed by the treatment of plants with the antioxidant ionol and with the scavenger of hydrogen peroxide (dimethylthiourea. These compounds and antagonists of calcium also partially removed the effect of the rise of plantlets’ heat resistance, invoked by hardening heating. The conclusion on calcium’s role in the activation of enzymatic systems, generating reactive oxygen species and nitric oxide, and on the functional interplay of these signal mediators at the induction of heat resistance of plantlets by hardening heating is made.

The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer.

Science.gov (United States)

Belotte, Jimmy; Fletcher, Nicole M; Awonuga, Awoniyi O; Alexis, Mitchell; Abu-Soud, Husam M; Saed, Mohammed G; Diamond, Michael P; Saed, Ghassan M

2014-04-01

To investigate the role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer (EOC). Two parent EOC cell lines (MDAH-2774 and SKOV-3) and their chemoresistant counterparts (cisplatin, 50 µmol/L) were used. Total RNA was extracted and subjected to real-time reverse transcriptase polymerase chain reaction to evaluate the expression of glutathione reductase (GSR) and inducible nitric oxide synthase (iNOS), as well as nitrate/nitrite levels. Analysis of variance was used for main effects and Tukey for post hoc analysis at P nitrate/nitrite levels were significantly higher in SKOV-3 cisplatin resistant cells while iNOS mRNA levels were significantly higher in MDAH-2774 cisplatin resistant cells (P < .05). Our data suggest that the development of cisplatin resistance tilts the balance toward a pro-oxidant state in EOC.

Semi-insulating Sn-Zr-O: Tunable resistance buffer layers

Energy Technology Data Exchange (ETDEWEB)

Barnes, Teresa M.; Burst, James M.; Reese, Matthew O.; Perkins, Craig L. [National Renewable Energy Laboratory, Golden, Colorado 80401 (United States)

2015-03-02

Highly resistive and transparent (HRT) buffer layers are critical components of solar cells and other opto-electronic devices. HRT layers are often undoped transparent conducting oxides. However, these oxides can be too conductive to form an optimal HRT. Here, we present a method to produce HRT layers with tunable electrical resistivity, despite the presence of high concentrations of unintentionally or intentionally added dopants in the film. This method relies on alloying wide-bandgap, high-k dielectric materials (e.g., ZrO{sub 2}) into the host oxide to tune the resistivity. We demonstrate Sn{sub x}Zr{sub 1−x}O{sub 2}:F films with tunable resistivities varying from 0.001 to 10 Ω cm, which are controlled by the Zr mole fraction in the films. Increasing Zr suppresses carriers by expanding the bandgap almost entirely by shifting the valence-band position, which allows the HRT layers to maintain good conduction-band alignment for a low-resistance front contact.

In Vitro Development of Ciprofloxacin Resistance of Salmonella enterica Serovars Typhimurium, Enteritidis, and Indiana Isolates from Food Animals.

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Zhang, Wen-Hui; Zhang, Chuan-Zhen; Liu, Zhi-Jie; Gu, Xi-Xi; Li, Wan; Yang, Ling; Liu, Ya-Hong; Zeng, Zhen-Ling; Jiang, Hong-Xia

2017-09-01

Difference in the development of resistance may be associated with the epidemiological spread and drug resistance of different Salmonella enterica serovar strains. In the present study, three susceptible S. enterica serovars, Typhimurium (ST), Enteritidis (SE), and Indiana (SI) strains, were subjected to stepwise selection with increasing ciprofloxacin concentrations. The results indicated that the mutation frequencies of the SI group were 10 1 -10 4 higher and developed resistance to ciprofloxacin more rapidly compared with the ST and SE groups. Ciprofloxacin accumulation in the SI strain was also higher than the other two strains in the presence of an efflux pump inhibitor. The development of ciprofloxacin resistance was quite different among the three serovar strains. In SI, increasing AcrAB-TolC efflux pump expression and single or double mutations in gyrA with or without a single parC mutation (T57S) were found in the development of ciprofloxacin resistance. In SE, an increase in the AcrAB-TolC efflux pump regulatory gene ramA gradually decreased as resistant bacteria developed; then resistance resulted from gyrA D87G and gyrB E466D mutations and/or in other active efflux pumps besides AcrAB-TolC. For ST, ramA expression increased rapidly along with gyrA D87 N and/or gyrB S464F mutations. In conclusion, persistent use of ciprofloxacin may aggravate the resistance of different S. enterica serovars and prudent use of the fluoroquinolones is needed. The quicker resistance and higher mutation frequency of the SI isolates present a potential public health threat.

Development of Antibiotic Resistance Against Ureaplasma urealyticum Strains Isolated from Urogenital Samples

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Musa Saraçoğlu

2018-04-01

Full Text Available Objective: To assess any change in the antibiotic sensitivity of Ureaplasma urealyticum strains isolated from urogenital samples in the course of time. Materials and Methods: Hospital records were retrospectively examined and cases with growth of U. urealyticum in urogenital samples in the years 2008 and 2013 were identified. Furthermore, the change in the course of time was examined by taking into consideration the cases we reported in 2001. Results: Higher rates of sensitivity against tetracycline and doxycycline were observed in 60 patients with isolated U. urealyticum. Higher rates of resistance against ofloxacin and ciprofloxacin were observed. A significant difference was found in resistance against antibiotics when the records of 2008 and 2013 were compared. A statistically significant increase was found in resistance against ofloxacin and ciprofloxacin when the records of 2001 were compared with the records of 2008 and 2013 (p<0.0005. Conclusion: U. urealyticum strains demonstrated high levels of resistance to quinolones. Resistance development is increasing in the course of time. Sensitivity against tetracycline and doxycycline has continued at high rates. It would be beneficial to consider these results during empirical treatment to be applied in cases ineligible for culturing.