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Sample records for m1a1 main battle

  1. Main: 1M2Q [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1M2Q トウモロコシ Corn Zea mays L. Casein Kinase Ii, Alpha Chain Name=Ack2; Zea Mays Mole...cule: Casein Kinase Ii, Alpha Chain; Chain: A; Fragment: Catlytic Subunit; Synonym: Ckii; Engineered: Yes Tr...ansferase 2.7.1.37 (Casein Kinase Ii, Alpha Chain) E.De Moliner, S.Sarno, S.Moro, G.Zagotto, G.Zanotti, L.A....=2-326.|PDB; 1M2Q; X-ray; A=2-328.|PDB; 1M2R; X-ray; A=2-328.|PDB; 1OM1; X-ray; A=1-332.|Mai

  2. Measurements of Gun Tube Motion and Muzzle Pointing Error of Main Battle Tanks

    Directory of Open Access Journals (Sweden)

    Peter L. McCall

    2001-01-01

    Full Text Available Beginning in 1990, the US Army Aberdeen Test Center (ATC began testing a prototype cannon mounted in a non-armored turret fitted to an M1A1 Abrams tank chassis. The cannon design incorporated a longer gun tube as a means to increase projectile velocity. A significant increase in projectile impact dispersion was measured early in the test program. Through investigative efforts, the cause of the error was linked to the increased dynamic bending or flexure of the longer tube observed while the vehicle was moving. Research and investigative work was conducted through a collaborative effort with the US Army Research Laboratory, Benet Laboratory, Project Manager – Tank Main Armament Systems, US Army Research and Engineering Center, and Cadillac Gage Textron Inc. New test methods, instrumentation, data analysis procedures, and stabilization control design resulted through this series of investigations into the dynamic tube flexure error source. Through this joint research, improvements in tank fire control design have been developed to improve delivery accuracy. This paper discusses the instrumentation implemented, methods applied, and analysis procedures used to characterize the tube flexure during dynamic tests of a main battle tank and the relationship between gun pointing error and muzzle pointing error.

  3. Musculoskeletal disorders in main battle tank personnel

    DEFF Research Database (Denmark)

    Nissen, Lars Ravnborg; Guldager, Bernadette; Gyntelberg, Finn

    2009-01-01

    PURPOSE: To compare the prevalence of musculoskeletal disorders of personnel in the main battle tank (MBT) units in the Danish army with those of personnel in other types of army units, and to investigate associations between job function in the tank, military rank, and musculoskeletal problems......, and ankle. RESULTS AND CONCLUSIONS: There were only 4 women in the MBT group; as a consequence, female personnel were excluded from the study. The participation rate was 58.0% (n = 184) in the MBT group and 56.3% (n = 333) in the reference group. The pattern of musculoskeletal disorders among personnel...

  4. Defeating Mechanisms of Armours for Main Battle Tanks

    Institute of Scientific and Technical Information of China (English)

    Manfred Held

    2005-01-01

    The fundamental protection principles of the new armours for main battle tanks against kinetic energy projectiles (KE) and chemical energy weapons (CE)--shaped charges are shortly described and their efficiency against both threats discussed. The armour topics can be split into: "perpendicular or zero-degree armours", such as rolled homogeneous armour (RHA), also with extremely high strength, ceramics, glass, liquid filled columns and explosive filled cells,"inclined armours", as spaced RHA plates with their corner effects, bulging armour, additive and integrated explosive reactive armours (ERA) and "hard kill active defence possibilities" in different defeating distances.

  5. Single-channel ground airborne radio system (SINCGARS) based remote control for the M1 Abrahms

    Science.gov (United States)

    Urda, Joseph R.

    1995-04-01

    Remote control of the Ml Abrahms Main Battle Tank through a minefield breach operation will remove the vehicle crew from the inherent hazard. A successful remote control system will provide automotive control yet not impair normal operation. This requires a minimum of physical parts, and an unobtrusive installation. Most importantly, a system failure must not impair the regular operation as a manned system. The system itself need not be complex. A minefield breach only requires simple control of automotive function and a mine plow interface. Control hardware for the Ml-Al can be reduced to two linear actuators, an electrical interface for the engine control unit, an interface for the mine plow, and the associated cables. Communication between vehicle control and operator control takes place over the vehicles organic radio (typically SINCGARS). This helps reduce the number of special purpose components for the remote control device. The device is currently awaiting an automotive safety test to prepare for its safety release. Because of the specific nature of the MDL-STD 1553-B data bus the device will not control an M1-A2 Main Battle Tank. The architecture will allow control of the M1-A2 through the 1553-B data bus however the physical hardware has not been constructed. The control scheme will not change. The communication interface will provide greater flexibility when interfacing to the vehicle tactical radio. Operational utility will be determined by U.S. Army Training and Doctrine Command personnel. The obvious benefit is that if a remote tank is lost during a minefield breach the crew is saved.

  6. 76 FR 72025 - Noise Compatibility Program Notice for W.M. Kellogg Airport, Battle Creek, MI

    Science.gov (United States)

    2011-11-21

    ... for W.M. Kellogg Airport, Battle Creek, MI AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... exposure maps submitted by the City of Battle Creek, Michigan for W.K. Kellogg Airport under the provisions... noise compatibility program that was submitted for W.K. Kellogg Airport under part 150 in conjunction...

  7. Six1 induces protein synthesis signaling expression in duck myoblasts mainly via up-regulation of mTOR

    Directory of Open Access Journals (Sweden)

    Haohan Wang

    2016-03-01

    Full Text Available Abstract As a critical transcription factor, Six1 plays an important role in the regulation of myogenesis and muscle development. However, little is known about its regulatory mechanism associated with muscular protein synthesis. The objective of this study was to investigate the effects of overexpression ofSix1 on the expression of key protein metabolism-related genes in duck myoblasts. Through an experimental model where duck myoblasts were transfected with a pEGFP-duSix1 construct, we found that overexpression of duckSix1 could enhance cell proliferation activity and increase mRNA expression levels of key genes involved in the PI3K/Akt/mTOR signaling pathway, while the expression of FOXO1, MuRF1and MAFbx was not significantly altered, indicating thatSix1 could promote protein synthesis in myoblasts through up-regulating the expression of several related genes. Additionally, in duck myoblasts treated with LY294002 and rapamycin, the specific inhibitors ofPI3K and mTOR, respectively, the overexpression of Six1 could significantly ameliorate inhibitive effects of these inhibitors on protein synthesis. Especially, the mRNA expression levels of mTOR and S6K1 were observed to undergo a visible change, and a significant increase in protein expression of S6K1 was seen. These data suggested that Six1plays an important role in protein synthesis, which may be mainly due to activation of the mTOR signaling pathway.

  8. The upstream open reading frame of cyclin-dependent kinase inhibitor 1A mRNA negatively regulates translation of the downstream main open reading frame

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyoung Mi; Cho, Hana [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Kim, Yoon Ki, E-mail: yk-kim@korea.ac.kr [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer CDKN1A mRNA is a bona fide NMD substrate. Black-Right-Pointing-Pointer The uORF of CDKN1A mRNA is efficiently translated. Black-Right-Pointing-Pointer Translation of downstream main ORF is negatively regulated by translation of uORF in CDKN1A mRNA. -- Abstract: The first round of translation occurs on mRNAs bound by nuclear cap-binding complex (CBC), which is composed of nuclear cap-binding protein 80 and 20 (CBP80/20). During this round of translation, aberrant mRNAs are recognized and downregulated in abundance by nonsense-mediated mRNA decay (NMD), which is one of the mRNA quality control mechanisms. Here, our microarray analysis reveals that the level of cyclin-dependent kinase inhibitor 1A (CDKN1A; also known as Waf1/p21) mRNAs increases in cells depleted of cellular NMD factors. Intriguingly, CDKN1A mRNA contains an upstream open reading frame (uORF), which is a NMD-inducing feature. Using chimeric reporter constructs, we find that the uORF of CDKN1A mRNA negatively modulates translation of the main downstream ORF. These findings provide biological insights into the possible role of NMD in diverse biological pathways mediated by CDKN1A.

  9. Internal (m=1, n=1) and (m=2, n=1) resistive modes in the toroidal tokamak with circular cross-section

    International Nuclear Information System (INIS)

    Bussac, M.N.; Pellat, R.; Edery, D.; Soule, J.L.

    1977-01-01

    A linear analysis is presented of the toroidal coupling between the internal resistive modes (m=1, n=1) and (m=2, n=1) in the tokamak with circular cross-section. The resistive and diamagnetic effects are included in the singular layers where the safety factor q takes respectively the values one and two. By expanding the MHD equations in powers of epsilon, the local inverse of the aspect ratio, a system of two coupled equations is obtained for the harmonic amplitudes. When the shear is finite on q=1 the toroidal coupling is negligible. In the opposite limit, one can explain (a) the experimental behaviour of the (m=1, n=1) mode before the internal disruption, and (b) the simultaneous observation of the modes (m=1, n=1) and (m=2, n=1) before the main disruption. (author)

  10. Requirements for a Device-Based Training and Testing Program for M1 Gunnery. Volume 2. Detailed Analyses and Results

    Science.gov (United States)

    1988-03-01

    ACTIVITY 11. ASSESS RESULTS OF ENCAGENENT TC GNU IDR M Alien battle dauge/c<iua1ttis Check/adJuit MRS Dtttratiw If and how crm ihould bt... UfO Of ring« lino con fco obiorvod on CRT. Kongo It not innounctd, but oppaor on CRT diti oroo. U(0 of ringt lint con bo obior»td on CRT

  11. Predicting Trainability of M1 Crewmen

    Science.gov (United States)

    1982-10-01

    Load Main Gun Clear Main Gun LOAD/UNLOAD M250 GRENADE LAUNCHER ON M1 TANK* Load Grenade Launcher Unload Grenade Launcher PREPARE GUNNER’S STATION...Clear Main Gun LOAD/UNLOAD M250 GRENADE LAUNCHER ON Ml TANK* Load Grenade Launcher Unload Grenade Lauacher PREPARE GUNNER’S STATION FOR OPERATION ON Ml

  12. A review on the gun barrel vibrations and control for a main battle tank

    Directory of Open Access Journals (Sweden)

    Tolga Dursun

    2017-10-01

    Full Text Available Achieving high hitting accuracy for a main battle tank is challenging while the tank is on the move. This can be reached by proper design of a weapon control and gun system. In order to design an effective gun system while the tank is moving, better understanding of the dynamic behavior of the gun system is required. In this study, the dynamic behaviour of a gun system is discussed in this respect. Both experimental and numerical applications for the determination of the dynamic behaviour of a tank gun system are investigated. Methods such as the use of muzzle reference system (MRS and vibration absorbers, and active vibration control technology for the control and the reduction of the muzzle tip deflections are also reviewed. For the existing gun systems without making substantial modifications, MRS could be useful in controlling the deflections of gun barrels with estimation/prediction algorithms. The vibration levels could be cut into half by the use of optimised vibration absorbers for an existing gun. A new gun system with a longer barrel can be as accurate as the one with a short barrel with the appropriate structural modifications.

  13. mTORC1 directly phosphorylates and regulates human MAF1.

    Science.gov (United States)

    Michels, Annemieke A; Robitaille, Aaron M; Buczynski-Ruchonnet, Diane; Hodroj, Wassim; Reina, Jaime H; Hall, Michael N; Hernandez, Nouria

    2010-08-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1.

  14. The Battle of Vukovar: The Battle That Saved Croatia

    National Research Council Canada - National Science Library

    Sebetovsky, Mario

    2002-01-01

    The key battle in the Croatian Homeland War that led to Croatia independence was the Battle of Vukovar Despite its importance very little has been written about this battle from a professional military perspective...

  15. La-related protein 1 (LARP1) represses terminal oligopyrimidine (TOP) mRNA translation downstream of mTOR complex 1 (mTORC1)

    DEFF Research Database (Denmark)

    Fonseca, Bruno; Zakaria, Chadi; Jia, J J

    2015-01-01

    is incompletely understood. Here, we report that LARP1 functions as a key repressor of TOP mRNA translation downstream of mTORC1. Our data show the following: (i) LARP1 associates with mTORC1 via RAPTOR; (ii) LARP1 interacts with TOP mRNAs in an mTORC1-dependent manner; (iii) LARP1 binds the 5′TOP motif...

  16. CYP1A1 m1 and m2 polymorphisms: genetic susceptibility to lung cancer

    Directory of Open Access Journals (Sweden)

    Paula Mota

    2010-01-01

    Full Text Available Lung cancer is considered an environment-related disease that develops as a consequence of exposure to mutagenic agents, namely those present in tobacco. The CYP1A1 gene codifies the phase I enzyme aryl hydrocarbon hydroxilase (AHH belonging to the cytochrome P450 system that plays a major role in the bio-activation of tobacco procarcinogenes. Two CYP1A1 polymorphisms, m1 (T6235C transition and m2 (A4889G transition, are associated with greater enzymatic activity and have been described as genetic susceptibility factors for lung cancer.The aim of this study was to verify if this association holds true in blood samples of 175 lung cancer patients and 217 non-cancer patients from Portugal's midlands region. The samples were studied by restriction fragment length polymorphism (RFLP assay.The allelic frequencies of the mutant alleles were 0.12 for allele C and 1.14 for allele G in the control population. The results were not statistically different from those alleles in the patient population. There was also no statistically significant difference in genotype distribution in lung cancer patients and controls even when combining high risk genotypes. In our control sample, as in other populations of different ethnic origin, both polymorphisms also seem to be in linkage disequilibrium. We conclude that in this sample of the Portuguese population, CYP1A1 m1 and m2 polymorphisms are too rare to be of clinical relevance, and do not seem to be associated with susceptibility to lung cancer. Resumo: O cancro do pulmão é considerado uma doença relacionada com o meio ambiente, consequência da exposição a agentes mutagénicos, nomeadamente os presentes no fumo do tabaco. O gene CYP1A1 codifica a enzima aril hidrocarboneto hidroxilase (AHH, da fase I, do sistema multienzimático do citocromo P450, que desempenha uma função preponderante na bioactivação dos procarcinogénios do tabaco. Dois polimorfismos do CYP1A1, m1 (transi

  17. Main: 1QRR [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available Molecule: Sulfolipid Biosynthesis (Sqd1) Protein; Chain: A; Engineered: Yes Isomerase A.M.Mulichak, M.J.Thei...IASIHDRISRWKALTGKSIELYVGDICDFEFLAESFKSFEPDSVVHFGEQRSAPYSMIDRSRAVYTQHNNVIGTLNVLFAIKEFGEECHLVKLGTMGEYGTPNIDIEE...LNRFCVQAAVGHPLTVYGKGGQTRGYLDIRDTVQCVEIAIANPAKAGEFRVFNQFTEQFSVNELASLVTKAGSKLGLDVKKMTVPNPRVEAEEHYYNAKHTKLMELGLEPHYLSDSLLDSLLNFAVQFKDRVDTKQIMPSVSWKKIGVKTKSMTT arabi_1QRR.jpg ...

  18. mTORC1 Directly Phosphorylates and Regulates Human MAF1

    Science.gov (United States)

    Michels, Annemieke A.; Robitaille, Aaron M.; Buczynski-Ruchonnet, Diane; Hodroj, Wassim; Reina, Jaime H.; Hall, Michael N.; Hernandez, Nouria

    2010-01-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the phosphorylations nor the kinase involved is known. We find that human MAF1 is absolutely required for pol III repression in response to serum starvation or TORC1 inhibition by rapamycin or Torin1. The protein is phosphorylated mainly on residues S60, S68, and S75, and this inhibits its pol III repression function. The responsible kinase is mTORC1, which phosphorylates MAF1 directly. Our results describe molecular mechanisms by which mTORC1 controls human MAF1, a key repressor of RNA polymerase III transcription, and add a new branch to the signal transduction cascade immediately downstream of TORC1. PMID:20516213

  19. M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Shoichi Fukui

    2018-01-01

    Full Text Available ObjectivesWe investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA.MethodsPeripheral blood mononuclear cells (PBMCs were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro.ResultsForty RA patients and 20 healthy donors were included. Twenty-two patients (55% were anticitrullinated protein antibody (ACPA positive. The median M1/M2 ratio was 0.59 (0.31–1.11, interquartile range. There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001. The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028 and significantly greater numbers of OCs in vitro (p = 0.005 than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios >1 (having relatively more M1 monocytes had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes.ConclusionM1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.

  20. THE 76-MM GUN M1A1 AND M1A2: AN ANALYSIS OF U.S. ANTI-TANK CAPABILITIES DURING WORLD WAR II

    Science.gov (United States)

    2018-01-01

    ballistic analysis is used to corroborate the battlefield history and gain an understanding of the physical and technological factors that spurred the...capabilities against the German Panther tank. Battle history indicates there was a technological capability gap against upgraded Panzer armor. This report...Engineering Technology Center Picatinny Arsenal, New Jersey UNCLASSIFIED UNCLASSIFIED The views, opinions, and/or

  1. Infinitely many N=1 dualities from m+1m=1

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Prarit; Intriligator, Kenneth; Song, Jaewon [Department of Physics, University of California,San Diego, La Jolla, CA 92093 (United States)

    2015-10-06

    We discuss two infinite classes of 4d supersymmetric theories, T{sub N}{sup (m)} and U{sub N}{sup (m)}, labelled by an arbitrary non-negative integer, m. The T{sub N}{sup (m)} theory arises from the 6d, A{sub N−1} type N=(2,0) theory reduced on a 3-punctured sphere, with normal bundle given by line bundles of degree (m+1,−m); the m=0 case is the N=2 supersymmetric T{sub N} theory. The novelty is the negative-degree line bundle. The U{sub N}{sup (m)} theories likewise arise from the 6d N=(2,0) theory on a 4-punctured sphere, and can be regarded as gluing together two (partially Higgsed) T{sub N}{sup (m)} theories. The T{sub N}{sup (m)} and U{sub N}{sup (m)} theories can be represented, in various duality frames, as quiver gauge theories, built from T{sub N} components via gauging and nilpotent Higgsing. We analyze the RG flow of the U{sub N}{sup (m)} theories, and find that, for all integer m>0, they end up at the same IR SCFT as SU(N) SQCD with 2N flavors and quartic superpotential. The U{sub N}{sup (m)} theories can thus be regarded as an infinite set of UV completions, dual to SQCD with N{sub f}=2N{sub c}. The U{sub N}{sup (m)} duals have different duality frame quiver representations, with 2m+1 gauge nodes.

  2. The MCNP Simulation of a PGNAA System at TRR-1/M1

    Science.gov (United States)

    Sangaroon, S.; Ratanatongchai, W.; Picha, R.; Khaweerat, S.; Channuie, J.

    2017-06-01

    The prompt-gamma neutron activation analysis system (PGNAA) has been installed at Thai Research Reactor-1/Modified 1 (TRR-1/M1) since 1999. The purpose of the system is for elemental and isotopic analyses. The system mainly consists of a series of the moderator and collimator, neutron and gamma-ray shielding and the HPGe detector. In this work, the condition of the system is carried out based on the Monte Carlo method using Monte Carlo N-Particle transport code and the experiment. The flux ratios (Φthermal/Φepithermal and Φthermal/Φfast) and thermal neutron flux have been obtained. The simulated prompt gamma rays of the Portland cement sample have been carried out. The simulation provides significant contribution in upgrading the PGNAA station to be available in various applications.

  3. Main: GT1CONSENSUS [PLACE

    Lifescience Database Archive (English)

    Full Text Available m of GT-1 may be achieved through direct interaction between TFIIA and GT-1; Binding of GT-1-like factors to the PR-1a promoter influ...ences the level of SA-inducible gene expression; GT-1; light; TATA; TFIIA; TBP; HR;

  4. Main: 1LR4 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1LR4 トウモロコシ Corn Zea mays L. Casein Kinase Ii, Alpha Chain Name=Ack2; Zea Mays Mole...cule: Protein Kinase Ck2; Chain: A; Synonym: Casein Kinase Ii, Alpha Chain; Engineered: Yes Transferase 2.7....ray; A=2-326.|PDB; 1M2Q; X-ray; A=2-328.|PDB; 1M2R; X-ray; A=2-328.|PDB; 1OM1; X-ray; A=1-332.|Mai

  5. Battle Management as a Basic Air Force Doctrine Operational Function

    National Research Council Canada - National Science Library

    Rhone, Jon M

    2008-01-01

    According to JP 1-02, Department of Defense Dictionary of Military and Associated Terms, battle management is "The management of activities within the operational environment, based on the commands...

  6. Influenza A Virus NS1 Protein Promotes Efficient Nuclear Export of Unspliced Viral M1 mRNA.

    Science.gov (United States)

    Pereira, Carina F; Read, Eliot K C; Wise, Helen M; Amorim, Maria J; Digard, Paul

    2017-08-01

    Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway, but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality-control checkpoints. Using fluorescent in situ hybridization to monitor segment 7 mRNA localization, we found that cytoplasmic accumulation of unspliced M1 mRNA was inefficient in the absence of NS1, both in the context of segment 7 RNPs reconstituted by plasmid transfection and in mutant virus-infected cells. This effect was independent of any major effect on steady-state levels of segment 7 mRNA or splicing but corresponded to a ∼5-fold reduction in the accumulation of M1. A similar defect in intronless hemagglutinin (HA) mRNA nuclear export was seen with an NS1 mutant virus. Efficient export of M1 mRNA required both an intact NS1 RNA-binding domain and effector domain. Furthermore, while wild-type NS1 interacted with cellular NXF1 and also increased the interaction of segment 7 mRNA with NXF1, mutant NS1 polypeptides unable to promote mRNA export did neither. Thus, we propose that NS1 facilitates late viral gene expression by acting as an adaptor between viral mRNAs and the cellular nuclear export machinery to promote their nuclear export. IMPORTANCE Influenza A virus is a major pathogen of a wide variety of mammalian and avian species that threatens public health and food security. A fuller understanding of the virus life cycle is important to aid control strategies. The virus has a small genome that encodes relatively few proteins that are often multifunctional. Here, we characterize a new function for the NS1 protein, showing that, as well as

  7. Apolipoprotein M can discriminate HNF1A-MODY from Type 1 diabetes.

    Science.gov (United States)

    Mughal, S A; Park, R; Nowak, N; Gloyn, A L; Karpe, F; Matile, H; Malecki, M T; McCarthy, M I; Stoffel, M; Owen, K R

    2013-02-01

    Missed diagnosis of maturity-onset diabetes of the young (MODY) has led to an interest in biomarkers that enable efficient prioritization of patients for definitive molecular testing. Apolipoprotein M (apoM) was suggested as a biomarker for hepatocyte nuclear factor 1 alpha (HNF1A)-MODY because of its reduced expression in Hnf1a(-/-) mice. However, subsequent human studies examining apoM as a biomarker have yielded conflicting results. We aimed to evaluate apoM as a biomarker for HNF1A-MODY using a highly specific and sensitive ELISA. ApoM concentration was measured in subjects with HNF1A-MODY (n = 69), Type 1 diabetes (n = 50), Type 2 diabetes (n = 120) and healthy control subjects (n = 100). The discriminative accuracy of apoM and of the apoM/HDL ratio for diabetes aetiology was evaluated. Mean (standard deviation) serum apoM concentration (μmol/l) was significantly lower for subjects with HNF1A-MODY [0.86 (0.29)], than for those with Type 1 diabetes [1.37 (0.26), P = 3.1 × 10(-18) ) and control subjects [1.34 (0.22), P = 7.2 × 10(-19) ). There was no significant difference in apoM concentration between subjects with HNF1A-MODY and Type 2 diabetes [0.89 (0.28), P = 0.13]. The C-statistic measure of discriminative accuracy for apoM was 0.91 for HNF1A-MODY vs. Type 1 diabetes, indicating high discriminative accuracy. The apoM/HDL ratio was significantly lower in HNF1A-MODY than other study groups. However, this ratio did not perform well in discriminating HNF1A-MODY from either Type 1 diabetes (C-statistic = 0.79) or Type 2 diabetes (C-statistic = 0.68). We confirm an earlier report that serum apoM levels are lower in HNF1A-MODY than in controls. Serum apoM provides good discrimination between HNF1A-MODY and Type 1 diabetes and warrants further investigation for clinical utility in diabetes diagnostics. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  8. Occurrence of B1 Aflatoxin in diet and M1 Aflatoxin in bovine milk

    OpenAIRE

    Adriana Frizzarin; Thiago Pereira Motta; Thamires Martins; Livia Castelani; Heloisa Solda de Azevedo; Cláudia Rodrigues Pozzi

    2012-01-01

    Ensuring food quality is one of the principles of food safety. Food for dairy cattle may be contaminated by fungi of the genus Aspergillus, which produce aflatoxins. The B1 aflatoxin, when ingested by animals, is biotransformed in liver in several other toxic metabolites, including M1 aflatoxin which is excreted in milk. M1 aflatoxin has a carcinogenic effect, which the presence in milk poses a serious risk to public health because milk and dairy products are consumed mainly by children, preg...

  9. Budget Period 1 Summary Report: Hywind Maine Project

    Energy Technology Data Exchange (ETDEWEB)

    Keiser, Meagan [Statoil, Stavanger (Norway)

    2014-02-28

    In accordance with the Statement of Project Objectives (SOPO) agreed to between the Department of Energy (“DOE”) and Statoil for the Hywind Maine project, Statoil hereby submits a Budget Period 1 Summary Report which includes accomplishments for the project. The report includes summaries of the other submitted reports (see Section 1.2-2) and progress regarding innovations leading to potential reductions in the Cost of Energy (see Section 3). The Hywind Demo project, the world’s first full-scale 2.3 megawatts (MW) floating wind turbine, installed at a water depth of 200 meter (m), 10 kilometer (km) off the coast of Norway, has proven that the Hywind floating substructure is a suitable platform for conventional multi- MW turbines. A principal goal of the Hywind Maine Project was to leverage that experience, both to demonstrate the commercial feasibility of the technology and to further develop and optimize the technology all in order to bring the costs down in a larger scale development. With the Hywind Maine Project, Statoil planned to deploy four turbines of 3 MW in approximately 140 meters water depth. Although the project in Maine will not move forward, much value was gained through the BP1 work package. Advanced modeling related to the design basis, which will have applicability beyond the Maine project, was completed. In addition, initial supply chain analyses were conducted, which will help assist with development of updated cost of energy models. Geophysical and various environmental surveys were also conducted, the results of which Statoil has committed to share publicly, and which will help build a database of information that future developers may be able to access. Finally, Statoil gained a greater understanding of the US offshore wind industry and related markets, which will assist the company as it looks for full-scale, commercial opportunities.

  10. Apolipoprotein M mediates sphingosine-1-phosphate efflux from erythrocytes

    DEFF Research Database (Denmark)

    Christensen, Pernille M.; Bosteen, Markus H.; Hajny, Stefan

    2017-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive lipid implicated in e.g. angiogenesis, lymphocyte trafficking, and endothelial barrier function. Erythrocytes are a main source of plasma S1P together with platelets and endothelial cells. Apolipoprotein M (apoM) in HDL carries 70% of plasma S1P, whereas...... 30% is carried by albumin. The current aim was to investigate the role of apoM in export of S1P from human erythrocytes. Erythrocytes exported S1P more efficiently to HDL than to albumin, particularly when apoM was present in HDL. In contrast, export of sphingosine to HDL was unaffected...... by the presence of apoM. The specific ability of apoM to promote export of S1P was independent of apoM being bound in HDL particles. Treatment with MK-571, an inhibitor of the ABCC1 transporter, effectively reduced export of S1P from human erythrocytes to apoM, whereas the export was unaffected by inhibitors...

  11. High-definition transcranial direct-current stimulation of the right M1 further facilitates left M1 excitability during crossed facilitation.

    Science.gov (United States)

    Cabibel, Vincent; Muthalib, Makii; Teo, Wei-Peng; Perrey, Stephane

    2018-04-01

    The crossed-facilitation (CF) effect refers to when motor-evoked potentials (MEPs) evoked in the relaxed muscles of one arm are facilitated by contraction of the opposite arm. The aim of this study was to determine whether high-definition transcranial direct-current stimulation (HD-tDCS) applied to the right primary motor cortex (M1) controlling the left contracting arm [50% maximum voluntary isometric contraction (MVIC)] would further facilitate CF toward the relaxed right arm. Seventeen healthy right-handed subjects participated in an anodal and cathodal or sham HD-tDCS session of the right M1 (2 mA for 20 min) separated by at least 48 h. Single-pulse transcranial magnetic stimulation (TMS) was used to elicit MEPs and cortical silent periods (CSPs) from the left M1 at baseline and 10 min into and after right M1 HD-tDCS. At baseline, compared with resting, CF (i.e., right arm resting, left arm 50% MVIC) increased left M1 MEP amplitudes (+97%) and decreased CSPs (-11%). The main novel finding was that right M1 HD-tDCS further increased left M1 excitability (+28.3%) and inhibition (+21%) from baseline levels during CF of the left M1, with no difference between anodal and cathodal HD-tDCS sessions. No modulation of CSP or MEP was observed during sham HD-tDCS sessions. Our findings suggest that CF of the left M1 combined with right M1 anodal or cathodal HD-tDCS further facilitated interhemispheric interactions during CF from the right M1 (contracting left arm) toward the left M1 (relaxed right arm), with effects on both excitatory and inhibitory processing. NEW & NOTEWORTHY This study shows modulation of the nonstimulated left M1 by right M1 HD-tDCS combined with crossed facilitation, which was probably achieved through modulation of interhemispheric interactions.

  12. Main: 1IEX [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available m Vulgare Molecule: Beta-D-Glucan Glucohydrolase Isoenzyme Exo1; Chain: A; Synonym: Beta-D-Glucan Exohydrola...Of A Plant Beta-D-Glucan Glucohydrolase Structure V. 9 1005 2001 2-Domain Fold GB:AAD23382,4566505|EMBL; AF1

  13. Islam’s First Arrow: The Battle of Badr as a Decisive Battle in Islamic History and Its Significance Today

    Science.gov (United States)

    2011-06-01

    of the Bible “eye-for-an-eye” mentality may have contributed to the political instability and rampant tribal infighting so common during this period...Khaybar (Betrayal), Battle of Karbala (Noble Sacrifice), Shaytan’s ( Satan ) Handiwork, (Ruse), Seventy-two Virgins (Noble Sacrifice), Mahdi (Deliverance...Publishing: 2004. http://www.intelcenter.com/Badr-al-Riyadh- v1-1. pdf Armstrong, Karen. Muhammad: A Prophet For Our Time. New York: Harper Collins, 2006

  14. New water guidelines developed to battle nuclear corrosion

    International Nuclear Information System (INIS)

    Strauss, S.D.

    1983-01-01

    Discusses methods of preventing degradation of nuclear steam generators due to a combination of impurities and corrosion products in the secondary system. Explains that tube and support-plate corrosion has been the main concern, manifesting itself primarily in the recirculating units used in PWR systems. Points out that the battle against corrosion is closely linked to control of ionic impurities, alkalinity, oxidants, and sludge-copper and iron corrosion products, primarily-in condensate and feedwater systems. Examines a set of secondary-water-chemistry guidelines developed by the Steam Generator Owners Group (SGOG). Presents diagram showing changes at Salem 1 to arrest corrosion, including condenser retubing, addition of condensate polisher and recirculation loop. Table indicates how preventive measures at Salem 1, affected secondary-water chemistry

  15. Waging a Battle to Promote Reading

    Science.gov (United States)

    Dix, Suzanne Liacos

    2010-01-01

    As advocates for reading, librarians cannot help but love a reading program. In this article, the author talks about the Battle of the Books, a reading enrichment program that had been in place since 1996. Battle of the Books promotes reading among middle school students by offering interesting books and a trivia-type competition. The author…

  16. Muscle Activity during Unilateral Vs. Bilateral Battle Rope Exercises

    DEFF Research Database (Denmark)

    Calatayud, J.; Martin, F.; Colado, J. C.

    2015-01-01

    Calatayud, J, Martin, F, Colado, JC, Benitez, JC, Jakobsen, MD, and Andersen, LL. Muscle activity during unilateral vs. bilateral battle rope exercises. J Strength Cond Res 29(10): 2854-2859, 2015High training intensity is important for efficient strength gains. Although battle rope training is m...

  17. Visible Battle Rhythm

    National Research Council Canada - National Science Library

    Cort, Brian; Bouchard, Alain; Gouin, Denis; Proulx, Pascale; Wright, William

    2006-01-01

    .... Visual Battle Rhythm (VBR) is a software prototype which updates the battle rhythm process with modern technology and careful information design to improve the synchronization, situational awareness and decision making ability of commanders...

  18. SOA approach to battle command: simulation interoperability

    Science.gov (United States)

    Mayott, Gregory; Self, Mid; Miller, Gordon J.; McDonnell, Joseph S.

    2010-04-01

    NVESD is developing a Sensor Data and Management Services (SDMS) Service Oriented Architecture (SOA) that provides an innovative approach to achieve seamless application functionality across simulation and battle command systems. In 2010, CERDEC will conduct a SDMS Battle Command demonstration that will highlight the SDMS SOA capability to couple simulation applications to existing Battle Command systems. The demonstration will leverage RDECOM MATREX simulation tools and TRADOC Maneuver Support Battle Laboratory Virtual Base Defense Operations Center facilities. The battle command systems are those specific to the operation of a base defense operations center in support of force protection missions. The SDMS SOA consists of four components that will be discussed. An Asset Management Service (AMS) will automatically discover the existence, state, and interface definition required to interact with a named asset (sensor or a sensor platform, a process such as level-1 fusion, or an interface to a sensor or other network endpoint). A Streaming Video Service (SVS) will automatically discover the existence, state, and interfaces required to interact with a named video stream, and abstract the consumers of the video stream from the originating device. A Task Manager Service (TMS) will be used to automatically discover the existence of a named mission task, and will interpret, translate and transmit a mission command for the blue force unit(s) described in a mission order. JC3IEDM data objects, and software development kit (SDK), will be utilized as the basic data object definition for implemented web services.

  19. GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

    Directory of Open Access Journals (Sweden)

    Senthilkumar Pitchalu Kasthurinaidu

    Full Text Available Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME. Among the XMEs, glutathione-S-transferases (GST gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs. Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs. The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

  20. Main: 1EQK [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1EQK イネ Rice Oryza sativa L. Cysteine Proteinase Inhibitor-I Oryza Sativa Molecule: Oryzacystatin-I; Chai...n: A; Engineered: Yes Hydrolase Inhibitor K.Nagata, N.Kudo, K.Abe, S.Arai, M.Tanokura ...K.Nagata, N.Kudo, K.Abe, S.Arai, M.Tanokura Three-Dimensional Solution Structure Of Oryzacystatin-I, A Cyste

  1. LARP1 functions as a molecular switch for mTORC1-mediated translation of an essential class of mRNAs.

    Science.gov (United States)

    Hong, Sungki; Freeberg, Mallory A; Han, Ting; Kamath, Avani; Yao, Yao; Fukuda, Tomoko; Suzuki, Tsukasa; Kim, John K; Inoki, Ken

    2017-06-26

    The RNA binding protein, LARP1, has been proposed to function downstream of mTORC1 to regulate the translation of 5'TOP mRNAs such as those encoding ribosome proteins (RP). However, the roles of LARP1 in the translation of 5'TOP mRNAs are controversial and its regulatory roles in mTORC1-mediated translation remain unclear. Here we show that LARP1 is a direct substrate of mTORC1 and Akt/S6K1. Deep sequencing of LARP1-bound mRNAs reveal that non-phosphorylated LARP1 interacts with both 5' and 3'UTRs of RP mRNAs and inhibits their translation. Importantly, phosphorylation of LARP1 by mTORC1 and Akt/S6K1 dissociates it from 5'UTRs and relieves its inhibitory activity on RP mRNA translation. Concomitantly, phosphorylated LARP1 scaffolds mTORC1 on the 3'UTRs of translationally-competent RP mRNAs to facilitate mTORC1-dependent induction of translation initiation. Thus, in response to cellular mTOR activity, LARP1 serves as a phosphorylation-sensitive molecular switch for turning off or on RP mRNA translation and subsequent ribosome biogenesis.

  2. Techniques used detection and quantification of aflatoxin M1 in milk

    OpenAIRE

    Adriana Frizzarin; Keila Maria Roncato Duarte

    2012-01-01

    Aflatoxin is a group of toxic substances produced by fungi, mainly Aspergillus flavus and Aspergillus parasiticus. It can be developed in agriculture products such as grains or processed food, when environment conditions of humidity and air humidity are favorable. Aflatoxins can be presented as several forms. In Milk, are called M1 and M2, resulting from aflatoxins B1 and B2 metabolism. Aflatoxin M1 (AFM1) is classified as a possible carcinogen to humans, so the occurrence of aflatoxin M1 in ...

  3. Dynamin-dependent amino acid endocytosis activates mechanistic target of rapamycin complex 1 (mTORC1).

    Science.gov (United States)

    Shibutani, Shusaku; Okazaki, Hana; Iwata, Hiroyuki

    2017-11-03

    The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of protein synthesis and potential target for modifying cellular metabolism in various conditions, including cancer and aging. mTORC1 activity is tightly regulated by the availability of extracellular amino acids, and previous studies have revealed that amino acids in the extracellular fluid are transported to the lysosomal lumen. There, amino acids induce recruitment of cytoplasmic mTORC1 to the lysosome by the Rag GTPases, followed by mTORC1 activation by the small GTPase Ras homolog enriched in brain (Rheb). However, how the extracellular amino acids reach the lysosomal lumen and activate mTORC1 remains unclear. Here, we show that amino acid uptake by dynamin-dependent endocytosis plays a critical role in mTORC1 activation. We found that mTORC1 is inactivated when endocytosis is inhibited by overexpression of a dominant-negative form of dynamin 2 or by pharmacological inhibition of dynamin or clathrin. Consistently, the recruitment of mTORC1 to the lysosome was suppressed by the dynamin inhibition. The activity and lysosomal recruitment of mTORC1 were rescued by increasing intracellular amino acids via cycloheximide exposure or by Rag overexpression, indicating that amino acid deprivation is the main cause of mTORC1 inactivation via the dynamin inhibition. We further show that endocytosis inhibition does not induce autophagy even though mTORC1 inactivation is known to strongly induce autophagy. These findings open new perspectives for the use of endocytosis inhibitors as potential agents that can effectively inhibit nutrient utilization and shut down the upstream signals that activate mTORC1. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. ApolipoproteinA1-75 G/A (M1- polymorphism and Lipoprotein(a; Anti- vs. Pro-Atherogenic properties

    Directory of Open Access Journals (Sweden)

    Ranganath L

    2007-08-01

    Full Text Available Abstract Background ApolipoproteinA1(apoA1 is the major apoprotein constituent of high-density-lipoprotein(HDL. The relationship of apoA1 -75 bp(M1- allele polymorphism with lipoprotein phenotype and cardiovascular diseae (CVD remain unclear. Overnight fasting blood samples were collected from a cohort of high-risk Omani population, 90 non-diabetic subjects and 149 type 2 diabetes mellitus (T2DM subjects for genotype and phenotype studies. Results The M1+ and M1- alleles frequencies were 0.808 and 0.192 for M1+ and M1-, respectively, comparable to the frequency of apoA1 (M1+ and M1- amongst a healthy Omani population, 0.788 and 0.212, respectively. The frequencies of the hetero- and homozygous subjects for the MspI polymorphism at -75 (M1- of the apoA1 gene were in Hardy-Weinberg equilibrium. The mean Lp(a concentration was significantly higher(P = 0.02 in subjects carrying M1- allele compared to M1+ allele of the APOA1 gene with an odd ratio of 2.3(95% CI, 1.13–14.3, irrespective of gender and the diabetic status. Conclusion ApolipoproteinA1-75 G/A (M1- polymorphism is relatively common and is positively associated with Lp(a and therefore, may confer a potential risk for cardiovascular disease (CVD.

  5. Battle of Kasserine Pass: Defeat is a Matter of Scale

    Science.gov (United States)

    2016-05-26

    a ga inst Germany in World War II ; some historians even go so far as to anticipate defeat in the first battles of all major Ameri can wars. Martin ...the battle of Kasserine Pass prove the conventional wisdom that America is doomed to defeat in its first battles? Martin Blumenson, a prominent...Much study of the battle of Kasserine Pass has been done since Martin Blumenson wrote the original history in 1966. The ULTRA and MAGIC intercepts

  6. Main: 1JH6 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available sterase; Chain: A, B; Engineered: Yes Hydrolase 3.1.4.- (Cyclic Phosphodiesterase) A.Hofmann, M.Grella, I.Bo...tos, W.Filipowicz, A.Wlodawer A.Hofmann, M.Grella, I.Botos, W.Filipowicz, A.Wloda

  7. Thermoelectric properties of p-type Ag{sub 1−x}(Pb{sub 1−y}Sn{sub y}){sub m}Sb{sub 1−z}Te{sub m+2}

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Kyunghan [Department of Chemistry, Northwestern University, Evanston, IL 60208 (United States); Center for Nanoparticle Research, Institute for Basic Science, (IBS), Seoul 151-742 (Korea, Republic of); Kong, Huijun; Uher, Ctirad [Department of Physics, University of Michigan, Ann Arbor, MI 48109 (United States); Kanatzidis, Mercouri G., E-mail: m-kanatzidis@northwestern.edu [Department of Chemistry, Northwestern University, Evanston, IL 60208 (United States)

    2016-10-15

    The thermoelectric properties of Ag{sub 1−x}(Pb{sub 1−y}Sn{sub y}){sub m}Sb{sub 1−z}Te{sub m+2} (4≤m≤16, −0.1≤x≤0.3, 1/3≤y≤2/3, 0.2≤z≤0.4; Lead Antimony Silver Tellurium Tin, LASTT-m) compositions were investigated in the temperature range of 300 to ~670 K. All samples crystallize in the average NaCl-type structure without any noticeable second phase and exhibit very narrow bandgaps of <0.1 eV. We studied a range of m values, silver concentrations (x), Pb/Sn ratios (y), and antimony concentrations (z) to determine their effects on the thermoelectric properties. The samples were investigated as melt grown polycrystalline ingots. Varying the Ag contents, the Pb/Sn ratios, and the Sb contents off-stoichiometry allowed us to control the electrical conductivity, the Seebeck coefficient, and the thermal conductivity. The electrical conductivity tends to decrease with decreasing m values. The highest ZT of ~1.1 was achieved at ~660 K for Ag{sub 0.9}Pb{sub 5}Sn{sub 5}Sb{sub 0.8}Te{sub 12} mainly due to the very low lattice thermal conductivity of ~0.4 W/(m K) around 660 K. Also, samples with charge-balanced stoichiometries, Ag(Pb{sub 1−y}Sn{sub y}){sub m}SbTe{sub m+2}, were studied and found to exhibit a lower power factor and higher lattice thermal conductivity than the Ag{sub 1−x}(Pb{sub 1−y}Sn{sub y}){sub m}Sb{sub 1−z}Te{sub m+2} compositions. - Graphical abstract: The Ag{sub 1−x}(Pb{sub 1−y}Sn{sub y}){sub m}Sb{sub 1−z}Te{sub m+2} system defines a complex and flexible class of tunable thermoelectric class of materials with high performance.

  8. Main: 1BE2 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available me=Ltp1; Synonyms=Papi; Hordeum Vulgare Molecule: Lipid Transfer Protein; Chain: Null; Synonym: Ltp Lipid Tr...ansport M.H.Lerche, F.M.Poulsen M.H.Lerche, F.M.Poulsen Two Different Binding Modes Of Palmitate In The Homologous Mai

  9. Main: 1IEW [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available m Vulgare Molecule: Beta-D-Glucan Glucohydrolase Isoenzyme Exo1; Chain: A; Synonym: Beta-D-Glucan Exohydrola...Beta-D-Glucan Glucohydrolase Structure V. 9 1005 2001 2-Domain Fold GB:AAD23382,4566505|EMBL; AF102868; AAD2

  10. Current Status of TRR-1/M1

    International Nuclear Information System (INIS)

    Sittichai, Chaiyut

    2000-01-01

    In 1961, the first Thai Research Reactor, TRR-1, having power of 1 MW was established. It was located at Office of Atomic Energy for Peace (OAEP) in Bangkok. TRR-1 was completely commissioned in June 1962. Plate typed high-enriched uranium (HEU) and U 3 O 8 -Al were used as fuel. Light water used as moderator and coolant. During 1975-1977, TRR-1 was shut down for modification. The reactor core and control system were disassembled and replaced by TRIGA Mark III. It is a circular hexagonal core typed reactor designed by General Atomics Company (GA). Afterwards, TRR-1 was officially renamed to Thai Research Reactor 1/Modification 1 (TRR-1/M1). TRR-1/M1 is a multipurpose reactor with nominal power of 2 MW. This swimming pool typed reactor uses low-enriched uranium (LEU) as fuel and light water as coolant and moderator. To date, the reactor has been operated with core No.12 that released power 1135 MWD to serve the user. The reactor has been serving for various kinds of utilization, for example, to produce radioisotope, neutron beam experiments and reactor physics experiments. This report explains in detail regarding operational experience and current status of this reactor, for example, reactor operation and reactor utilization. (author)

  11. Promiscuity of MCMV immunoevasin of NKG2D: m138/fcr-1 down-modulates RAE-1epsilon in addition to MULT-1 and H60.

    Science.gov (United States)

    Arapović, Jurica; Lenac Rovis, Tihana; Reddy, Anil Butchi; Krmpotić, Astrid; Jonjić, Stipan

    2009-11-01

    Both human and mouse cytomegalovirus (CMV) encode proteins that inhibit the activation of NK cells by down-regulating the cellular ligands for activating NK cell receptor, NKG2D. MCMV proteins m145, m152 and m155 interfere with the expression of all known NKG2D ligands, MULT-1, RAE-1 family members and H60, respectively, whereas m138 affects the expression of MULT-1 and H60. Here we show that m152 affects the maturation of newly synthesized RAE-1 molecules, but is not sufficient to prevent surface expression of RAE-1varepsilon. We have identified m138 as a main inhibitor of the surface expression of RAE-1varepsilon. In contrast to m152, m138 affects the surface-resident protein leading to its endocytosis, which can be prevented by a dynamin inhibitor. Moreover, we demonstrated that m138 does not need other viral proteins to down-modulate the expression of RAE-1varepsilon.

  12. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

    Science.gov (United States)

    Zhao, Lan-Xue; Ge, Yan-Hui; Xiong, Cai-Hong; Tang, Ling; Yan, Ying-Hui; Law, Ping-Yee; Qiu, Yu; Chen, Hong-Zhuan

    2018-03-06

    M1 muscarinic acetylcholine receptors (M1 mAChRs) are the most abundant muscarinic receptors in the hippocampus and have been shown to have procognitive effects. AMPA receptors (AMPARs), an important subtype of ionotropic glutamate receptors, are key components in neurocognitive networks. However, the role of AMPARs in procognitive effects of M1 mAChRs and how M1 mAChRs affect the function of AMPARs remain poorly understood. Here, we found that basal expression of GluA1, a subunit of AMPARs, and its phosphorylation at Ser845 were maintained by M1 mAChR activity. Activation of M1 mAChRs promoted membrane insertion of GluA1, especially to postsynaptic densities. Impairment of hippocampus-dependent learning and memory by antagonism of M1 mAChRs paralleled the reduction of GluA1 expression, and improvement of learning and memory by activation of M1 mAChRs was accompanied by the synaptic insertion of GluA1 and its increased phosphorylation at Ser845. Furthermore, abrogation of phosphorylation of Ser845 residue of GluA1 ablated M1 mAChR-mediated improvement of learning and memory. Taken together, these results show a functional correlation of M1 mAChRs and GluA1 and the essential role of GluA1 in M1 mAChR-mediated cognitive improvement.-Zhao, L.-X., Ge, Y.-H., Xiong, C.-H., Tang, L., Yan, Y.-H., Law, P.-Y., Qiu, Y., Chen, H.-Z. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

  13. Internal (m=1, n=1) and (m=2, n=1) resistive modes in the toroidal Tokomak with circular cross sections

    International Nuclear Information System (INIS)

    Bussac, M.N.; Pellat, R.; Edery, D.; Soule, J.L.

    1976-01-01

    A linear analysis is presented of the toroidal coupling between the internal resistive modes (m=1, n=1) and (m=2, n=1) in the Tokomak with circular cross sections. One includes the resistive and diamagnetic effects in the singular layers where the safety factor q takes respectively the values one and two. By expanding the MHD equations in powers of epsilon, the local inverse of the aspect ratio, one obtains a system of two coupled equations for the harmonic amplitudes. When the shear is finite on q=1, the toroidal coupling is negligible. In the opposite limit, one can explain: the experimental behaviour of the (m=1, n=1) mode before the internal disruption; the simultaneous observation of the modes (m=1, n=1) and [de

  14. Central limit theorems for sequences with m(n)-dependent main part

    NARCIS (Netherlands)

    Nieuwenhuis, G.

    1992-01-01

    Let (Xi(n); n ϵ N, 1⩽i⩽h(n)) be a double sequence of random variables with h(n)→∞ as n→∞. Suppose that the sequence can be split into two parts: an m(n)-dependent sequence (Xi,m(n); n ϵ N, 1⩽i⩽h(n)) of main terms and a sequence (Xi,m(n); n ϵ N, 1⩽i⩽h(n)) of residual terms. Here (m(n)) may be

  15. Rac1 Regulates the Activity of mTORC1 and mTORC2 and Controls Cellular Size

    Science.gov (United States)

    Saci, Abdelhafid; Cantley, Lewis C.; Carpenter, Christopher L.

    2013-01-01

    SUMMARY Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that exists in two separate complexes, mTORC1 and mTORC2, that function to control cell size and growth in response to growth factors, nutrients, and cellular energy levels. Low molecular weight GTP-binding proteins of the Rheb and Rag families are key regulators of the mTORC1 complex, but regulation of mTORC2 is poorly understood. Here, we report that Rac1, a member of the Rho family of GTPases, is a critical regulator of both mTORC1 and mTORC2 in response to growth-factor stimulation. Deletion of Rac1 in primary cells using an inducible-Cre/Lox approach inhibits basal and growth-factor activation of both mTORC1 and mTORC2. Rac1 appears to bind directly to mTOR and to mediate mTORC1 and mTORC2 localization at specific membranes. Binding of Rac1 to mTOR does not depend on the GTP-bound state of Rac1, but on the integrity of its C-terminal domain. This function of Rac1 provides a means to regulate mTORC1 and mTORC2 simultaneously. PMID:21474067

  16. Occurrence of B1 Aflatoxin in diet and M1 Aflatoxin in bovine milk

    Directory of Open Access Journals (Sweden)

    Adriana Frizzarin

    2012-12-01

    Full Text Available Ensuring food quality is one of the principles of food safety. Food for dairy cattle may be contaminated by fungi of the genus Aspergillus, which produce aflatoxins. The B1 aflatoxin, when ingested by animals, is biotransformed in liver in several other toxic metabolites, including M1 aflatoxin which is excreted in milk. M1 aflatoxin has a carcinogenic effect, which the presence in milk poses a serious risk to public health because milk and dairy products are consumed mainly by children, pregnant women and elderly. The objective of this study was to detect the presence of B1 aflatoxin in feed supplied to dairy cows and the presence of M1 aflatoxin in milk. Samples were collected from complete diet (corn silage and concentrate from a batch of 15 lactating cows from a dairy farm in the Campinas region. Two samples of diets were collected directly into the troughs in intervals of 24 hours at every 15 days, totalizing a period of 45 days. Milk samples of those cows were collected 24 hours after diet collection, directly from sample valves in the glass jars.. B1 and M1 aflatoxins were detected by the technique of High Performance Liquid Chromatography after extraction and purification on immunoaffinity columns. From the 40 samples of diets evaluated, 40% were contaminated with B1 aflatoxin, and the levels found ranged from 1.93 to 43.78μg/Kg. One sample showed result higher than the maximum recommended for grain and animal feed in Brazil (20μg/Kg. From the 75 milk samples analyzed, the presence of M1 aflatoxin was detected in 13.3% with levels ranging from 0.03 to 0.16μg/L, not exceeding the maximum permitted for marketing in the country of 0.5μg/L, however 80% of contaminated samples had values above the maximum permissible levels of 0.05μg/L, value found among countries with abundant milk production... The presence of aflatoxins highlights the importance of monitoring the production, the storage and the importance of handling food and

  17. AN M DWARF COMPANION TO AN F-TYPE STAR IN A YOUNG MAIN-SEQUENCE BINARY

    Energy Technology Data Exchange (ETDEWEB)

    Eigmüller, Ph.; Csizmadia, Sz.; Erikson, A.; Fridlund, M.; Pasternacki, Th.; Rauer, H. [Institute of Planetary Research, German Aerospace Center Rutherfordstr. 2, D-12489 Berlin (Germany); Eislöffel, J.; Lehmann, H.; Hartmann, M.; Hatzes, A. [Thüringer Landessternwarte Tautenburg Sternwarte 5, D-07778 Tautenburg (Germany); Tkachenko, A. [Instituut voor Sterrenkunde, KU Leuven Celestijnenlaan 200D, 3001 Leuven (Belgium); Voss, H., E-mail: philipp.eigmueller@dlr.de [Universitat de Barcelona, Department of Astronomy and Meteorology Martí i Franquès, 1, E-08028 Barcelona (Spain)

    2016-03-15

    Only a few well characterized very low-mass M dwarfs are known today. Our understanding of M dwarfs is vital as these are the most common stars in our solar neighborhood. We aim to characterize the properties of a rare F+dM stellar system for a better understanding of the low-mass end of the Hertzsprung–Russel diagram. We used photometric light curves and radial velocity follow-up measurements to study the binary. Spectroscopic analysis was used in combination with isochrone fitting to characterize the primary star. The primary star is an early F-type main-sequence star with a mass of (1.493 ± 0.073) M{sub ⊙} and a radius of (1.474 ± 0.040) R{sub ⊙}. The companion is an M dwarf with a mass of (0.188 ± 0.014) M{sub ⊙} and a radius of (0.234 ± 0.009) R{sub ⊙}. The orbital period is (1.35121 ± 0.00001) days. The secondary star is among the lowest-mass M dwarfs known to date. The binary has not reached a 1:1 spin–orbit synchronization. This indicates a young main-sequence binary with an age below ∼250 Myr. The mass–radius relation of both components are in agreement with this finding.

  18. Techniques used detection and quantification of aflatoxin M1 in milk

    Directory of Open Access Journals (Sweden)

    Adriana Frizzarin

    2012-02-01

    Full Text Available Aflatoxin is a group of toxic substances produced by fungi, mainly Aspergillus flavus and Aspergillus parasiticus. It can be developed in agriculture products such as grains or processed food, when environment conditions of humidity and air humidity are favorable. Aflatoxins can be presented as several forms. In Milk, are called M1 and M2, resulting from aflatoxins B1 and B2 metabolism. Aflatoxin M1 (AFM1 is classified as a possible carcinogen to humans, so the occurrence of aflatoxin M1 in milk of lactating cows is a public health issue, and because of its importance several techniques are used for its detection and quantification. These techniques include the physical-chemical as thin layer chromatography and high performance liquid chromatography and the biological techniques including immunoassays such as RIA and ELISA. This review aimed to present the techniques used to quantify aflatoxins M1 and M2 in milk and dairy products.

  19. Target-specific M1 inputs to infragranular S1 pyramidal neurons

    Science.gov (United States)

    Fanselow, Erika E.; Simons, Daniel J.

    2016-01-01

    The functional role of input from the primary motor cortex (M1) to primary somatosensory cortex (S1) is unclear; one key to understanding this pathway may lie in elucidating the cell-type specific microcircuits that connect S1 and M1. Recently, we discovered that a subset of pyramidal neurons in the infragranular layers of S1 receive especially strong input from M1 (Kinnischtzke AK, Simons DJ, Fanselow EE. Cereb Cortex 24: 2237–2248, 2014), suggesting that M1 may affect specific classes of pyramidal neurons differently. Here, using combined optogenetic and retrograde labeling approaches in the mouse, we examined the strengths of M1 inputs to five classes of infragranular S1 neurons categorized by their projections to particular cortical and subcortical targets. We found that the magnitude of M1 synaptic input to S1 pyramidal neurons varies greatly depending on the projection target of the postsynaptic neuron. Of the populations examined, M1-projecting corticocortical neurons in L6 received the strongest M1 inputs, whereas ventral posterior medial nucleus-projecting corticothalamic neurons, also located in L6, received the weakest. Each population also possessed distinct intrinsic properties. The results suggest that M1 differentially engages specific classes of S1 projection neurons, thereby regulating the motor-related influence S1 exerts over subcortical structures. PMID:27334960

  20. United States 1st Armored Division and Mission Command at the Battle of Faid Pass

    Science.gov (United States)

    2017-04-13

    MilitaryReview_20130430_ art008.pdf and John Case, “The Exigency for Mission Command: A Comparison of World War II Command Cultures ,” Small Wars Journal...Borzoi Books, 1943), 229-232. 20 Concurrent to these efforts, the US and United Kingdom continued to mass forces in England for a cross channel...and psychological . The Axis had seized the initiative; the Allies just did not know it yet.154 Preparations for the Battle of Kasserine Pass

  1. BVRI main-sequence photometry of the globular cluster M4

    International Nuclear Information System (INIS)

    Alcaino, G.; Liller, W.

    1984-01-01

    We present BV and RI photographic photometry of 1421 and 189 stars, respectively, in the intermediate metallicity globular cluster M4 (NGC 6121). This investigation includes the first results of RI main-sequence photometry of a globular cluster. The use of longer wavelengths and longer color baselines provides the potential of improved isochrone fittings and underscores the urgent need for calculations of RI synthetic isochrones to be compared with observations. The Pickering-Racine wedge was used with the ESO 3.6 m telescope, the Las Campanas 2.5 m du Pont telescope, and the CTIO 1 m Yale telescope to extend the photoelectric limit from Vroughly-equal16.1 to Vroughly-equal19.1. We have determined the position of the main-sequence turnoff to lie at V = 16.6 +- 0.2 (m.e.) and B-V = 0.80 +- 0.03 (m.e.). A comparison of our BV observations with the CCD data of Richer and Fahlman shows excellent agreement: the two fifucial main sequences agree at all points to within 0.025 mag and, on average, to 0.013 mag. For the cluster we derive a distance modulus (m-M)/sub V/ = 12.52 +- 0.2 and reddening E(B-V) = 0.44 +- 0.03, results which confirm that at a distance of 2 kpc, M4 is the closest globular clusters to the Sun. Using the isochrones of VandenBerg, we deduce an age 13 +- 2 Gyr. As noted in several other investigations, there is a striking deficiency of stars in certain parts of the color-magnitude diagram; in M4 we find a pronounced gap over approx.0.6 mag at the base of the subgiant branch

  2. Health physics aspects of the 1.5M cyclotron

    International Nuclear Information System (INIS)

    Song, W.J.; Du, H.L.; Wei, Z.Q.; Xia, X.S.; Zheng, H.Z.; Jiang, G.F.; Liu, Y.Y.

    1987-01-01

    The 1.5m cyclotron in Institute of Modern Physics, Academia Sinica had operated for about 20 years until 1984 then converted to 1.7m sector focusing cyclotron. In this period it mainly used for fast neutron physics, light ion induced nucleus reactions, radioisotope production and heavy ion reactions. The health physics performed on this cyclotron including personnel dose monitoring, area monitoring (radiation field, radioactive aerosol, surface contamination and activated components etc.), maintenance inspection, environment survey and waste disposal is presented in this paper

  3. Rates of E1, E2, M1, and M2 transitions in Ni II

    Science.gov (United States)

    Cassidy, C. M.; Hibbert, A.; Ramsbottom, C. A.

    2016-03-01

    Aims: We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d9, 3d84s, 3d74s2, 3d84p, and 3d74s4p, determined through an extensive configuration interaction calculation. Methods: The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. Results: Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. Conclusions: We believe that the present transition data are the best currently available. Full Table 4 and Tables 5-8 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/587/A107

  4. Properties of M1-M2-Si-Al-O-N glasses (M1 = La or Nd, M2 = Y or Er)

    Energy Technology Data Exchange (ETDEWEB)

    Pomeroy, M.J.; Nestor, E.; Hampshire, S. [Limerick Univ. (Ireland). Materials and Surface Science Inst.; Ramesh, R. [Littelfuse Ireland, Dundalk, Co. Louth (Ireland)

    2002-07-01

    Mixed lanthanide cation oxynitride glasses have been prepared in the M1 - M2 - Si-Al-O-N systems where M1 = La or Nd and M2 = Y or Er. The densities ({rho}), Young's moduli (E), microhardnesses (H{sub v}), glass transition temperatures (T{sub g}), dilatometric softening temperatures (T{sub dil}) and coefficients of thermal expansion (CTE) of 13 glasses were determined. The molar volume values (MV) calculated from density data, E, H{sub v}, T{sub g}, T{sub dil} and CTE values were all found to vary linearly with the effective cation field strength arising from the M1 and M2 modifier cations. Least squares intercept and slope values are presented which correlate each property to effective cation field strength together with error values which arise from glass and specimen preparation and measurement inconsistencies. These linear correlations clearly indicate that the overall glass structure remains the same for each of the thirteen glasses with only the modifier cation(s) having any influence. This influence appears to be a cross-linking effect, the strength of which increases as the effective cation field strength of the M1, M2 modifiers increases. (orig.)

  5. HAT-P-49b: a 1.7 M {sub J} planet transiting a bright 1.5 M {sub ☉} F-star

    Energy Technology Data Exchange (ETDEWEB)

    Bieryla, A.; Latham, D. W.; Buchhave, L. A.; Béky, B.; Falco, E.; Torres, G.; Noyes, R. W.; Berlind, P.; Calkins, M. C.; Esquerdo, G. A. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Hartman, J. D.; Bakos, G. Á.; Bhatti, W.; Csubry, Z.; Penev, K.; De Val-Borro, M. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Kovács, G. [Konkoly Observatory, Budapest 1121 (Hungary); Boisse, I. [Centro de Astrofísica, Universidade do Porto, Rua das Estrelas, 4150-762 Porto (Portugal); Lázár, J.; Papp, I., E-mail: abieryla@cfa.harvard.edu, E-mail: gbakos@astro.princeton.edu [Hungarian Astronomical Association (HAA), Budapest 1461 (Hungary); and others

    2014-04-01

    We report the discovery of the transiting extrasolar planet HAT-P-49b. The planet transits the bright (V = 10.3) slightly evolved F-star HD 340099 with a mass of 1.54 M {sub ☉} and a radius of 1.83 R {sub ☉}. HAT-P-49b is orbiting one of the 25 brightest stars to host a transiting planet which makes this a favorable candidate for detailed follow-up. This system is an especially strong target for Rossiter-McLaughlin follow-up due to the host star's fast rotation, 16 km s{sup –1}. The planetary companion has a period of 2.6915 days, mass of 1.73 M {sub J}, and radius of 1.41 R {sub J}. The planetary characteristics are consistent with that of a classical hot Jupiter but we note that this is the fourth most massive star to host a transiting planet with both M{sub p} and R{sub p} well determined.

  6. Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating M1/M2 macrophage polarization1

    Science.gov (United States)

    Dale, Matthew A; Xiong, Wanfen; Carson, Jeffrey S; Suh, Melissa K; Karpisek, Andrew D.; Meisinger, Trevor M.; Casale, George P.; Baxter, B. Timothy

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Damage to elastin in the ECM results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Pro-inflammatory M1 macrophages initially are recruited to sites of injury but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. AAA tissue reveals a high M1/M2 ratio where pro-inflammatory cells and their associated markers dominate. In the present study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57Bl/6 mice, antibody-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and pro-inflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2 polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a pro-inflammatory environment in aortic tissue by inducing M1 polarization and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID:27183603

  7. Nucleolin Mediates MicroRNA-directed CSF-1 mRNA Deadenylation but Increases Translation of CSF-1 mRNA*

    Science.gov (United States)

    Woo, Ho-Hyung; Baker, Terri; Laszlo, Csaba; Chambers, Setsuko K.

    2013-01-01

    CSF-1 mRNA 3′UTR contains multiple unique motifs, including a common microRNA (miRNA) target in close proximity to a noncanonical G-quadruplex and AU-rich elements (AREs). Using a luciferase reporter system fused to CSF-1 mRNA 3′UTR, disruption of the miRNA target region, G-quadruplex, and AREs together dramatically increased reporter RNA levels, suggesting important roles for these cis-acting regulatory elements in the down-regulation of CSF-1 mRNA. We find that nucleolin, which binds both G-quadruplex and AREs, enhances deadenylation of CSF-1 mRNA, promoting CSF-1 mRNA decay, while having the capacity to increase translation of CSF-1 mRNA. Through interaction with the CSF-1 3′UTR miRNA common target, we find that miR-130a and miR-301a inhibit CSF-1 expression by enhancing mRNA decay. Silencing of nucleolin prevents the miRNA-directed mRNA decay, indicating a requirement for nucleolin in miRNA activity on CSF-1 mRNA. Downstream effects followed by miR-130a and miR-301a inhibition of directed cellular motility of ovarian cancer cells were found to be dependent on nucleolin. The paradoxical effects of nucleolin on miRNA-directed CSF-1 mRNA deadenylation and on translational activation were explored further. The nucleolin protein contains four acidic stretches, four RNA recognition motifs (RRMs), and nine RGG repeats. All three domains in nucleolin regulate CSF-1 mRNA and protein levels. RRMs increase CSF-1 mRNA, whereas the acidic and RGG domains decrease CSF-1 protein levels. This suggests that nucleolin has the capacity to differentially regulate both CSF-1 RNA and protein levels. Our finding that nucleolin interacts with Ago2 indirectly via RNA and with poly(A)-binding protein C (PABPC) directly suggests a nucleolin-Ago2-PABPC complex formation on mRNA. This complex is in keeping with our suggestion that nucleolin may work with PABPC as a double-edged sword on both mRNA deadenylation and translational activation. Our findings underscore the complexity of

  8. Specificity of RSG-1.2 peptide binding to RRE-IIB RNA element of HIV-1 over Rev peptide is mainly enthalpic in origin.

    Science.gov (United States)

    Kumar, Santosh; Bose, Debojit; Suryawanshi, Hemant; Sabharwal, Harshana; Mapa, Koyeli; Maiti, Souvik

    2011-01-01

    Rev is an essential HIV-1 regulatory protein which binds to the Rev responsive element (RRE) present within the env gene of HIV-1 RNA genome. This binding facilitates the transport of the RNA to the cytoplasm, which in turn triggers the switch between viral latency and active viral replication. Essential components of this complex have been localized to a minimal arginine rich Rev peptide and stem IIB region of RRE. A synthetic peptide known as RSG-1.2 binds with high binding affinity and specificity to the RRE-IIB than the Rev peptide, however the thermodynamic basis of this specificity has not yet been addressed. The present study aims to probe the thermodynamic origin of this specificity of RSG-1.2 over Rev Peptide for RRE-IIB. The temperature dependent melting studies show that RSG-1.2 binding stabilizes the RRE structure significantly (ΔT(m) = 4.3°C), in contrast to Rev binding. Interestingly the thermodynamic signatures of the binding have also been found to be different for both the peptides. At pH 7.5, RSG-1.2 binds RRE-IIB with a K(a) = 16.2±0.6×10(7) M(-1) where enthalpic change ΔH = -13.9±0.1 kcal/mol is the main driving force with limited unfavorable contribution from entropic change TΔS = -2.8±0.1 kcal/mol. A large part of ΔH may be due to specific stacking between U72 and Arg15. In contrast binding of Rev (K(a) = 3.1±0.4×10(7) M(-1)) is driven mainly by entropy (ΔH = 0 kcal/mol and TΔS = 10.2±0.2 kcal/mol) which arises from major conformational changes in the RNA upon binding.

  9. MNK Controls mTORC1:Substrate Association through Regulation of TELO2 Binding with mTORC1

    Directory of Open Access Journals (Sweden)

    Michael C. Brown

    2017-02-01

    Full Text Available The mechanistic target of rapamycin (mTOR integrates numerous stimuli and coordinates the adaptive response of many cellular processes. To accomplish this, mTOR associates with distinct co-factors that determine its signaling output. While many of these co-factors are known, in many cases their function and regulation remain opaque. The MAPK-interacting kinase (MNK contributes to rapamycin resistance in cancer cells. Here, we demonstrate that MNK sustains mTORC1 activity following rapamycin treatment and contributes to mTORC1 signaling following T cell activation and growth stimuli in cancer cells. We determine that MNK engages with mTORC1, promotes mTORC1 association with the phosphatidyl inositol 3′ kinase-related kinase (PIKK stabilizer, TELO2, and facilitates mTORC1:substrate binding. Moreover, our data suggest that DEPTOR, the endogenous inhibitor of mTOR, opposes mTORC1:substrate association by preventing TELO2:mTORC1 binding. Thus, MNK orchestrates counterbalancing forces that regulate mTORC1 enzymatic activity.

  10. Resveratrol regulates microglia M1/M2 polarization via PGC-1α in conditions of neuroinflammatory injury.

    Science.gov (United States)

    Yang, Xiaodong; Xu, Shaoqing; Qian, Yiwei; Xiao, Qin

    2017-08-01

    Microglia are the primary cells that exert immune function in the central nervous system (CNS), and accumulating evidence suggests that microglia act as key players in the initiation of neurodegenerative diseases. It is now well recognized that microglia have functional plasticity and dual phenotypes, proinflammatory M1 and anti-inflammatory M2 phenotypes. Inhibiting the M1 phenotype while stimulating the M2 phenotype has been suggested as a potential therapeutic approach for the treatment of neuroinflammation-related diseases. Resveratrol has been demonstrated to exert anti-inflammatory effects by suppressing M1 microglia activation. However, the role of resveratrol in regulating microglia polarization and the molecular mechanisms involved have not been fully clarified. In this study, we tested whether resveratrol could suppress microglia activation by promoting microglia polarization toward the M2 phenotype via PGC-1α by measuring M1 and M2 markers in vitro and in vivo. Our study demonstrated that resveratrol reduced inflammatory damage and promoted microglia polarization to the M2 phenotype in LPS-induced neuroinflammation. In addition, resveratrol ameliorated LPS-induced sickness behavior in mice. The promoting effects of resveratrol on M2 polarization were attenuated by knocking down PGC-1α. PGC-1α not only suppressed LPS-evoked M1 marker expression by inhibition of NF-κB activity but also increased M2 marker expression by coactivation of the STAT6 and STAT3 pathways. We propose that overexpression PGC-1α by resveratrol could be a potential therapeutic approach to suppress neuroinflammation by regulating microglia polarization. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. A new series of oxycarbonate superconductors (Cu{sub 0.5}C{sub 0.5}){sub m}Ba{sub m+1}Ca{sub n-1}Cu{sub n}O{sub 2}({sub m+n})+1

    Energy Technology Data Exchange (ETDEWEB)

    Takayama-Muromachi, E.; Kawashima, T.; Matsui, Y. [National Institute for Research in Inorganic Materials, Ibaraki (Japan)

    1994-12-31

    We found a new series of oxycarbonate superconductors in the Ba-Ca-Cu-C-O system under high pressure of 5 GPa. Their ideal formula is (Cu{sub 0.5}C{sub 0.5}){sub m}Ba{sub m+1}Ca{sub n-1}Cu{sub n}O{sub 2}({sub m+n})+1 ((Cu,C)-m(m+1)(n-1)n). Thus far, n=3, 4 members of the m=1 series, (Cu,C)-1223 and (Cu,C)-1234, have been prepared in bulk while n=4, 5 members, (Cu,C)-2334 and (Cu,C)-2345, have been prepared for the m=2 series. (Cu,C)-1223 shows superconductivity below 67 K while T{sub c}`s of other compounds are above 110 K. In particular, (Cu,C)=1234 has the highest T{sub c} of 117 K.

  12. Main: 1E1E [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available Mays Molecule: Beta-Glucosidase; Chain: A, B; Engineered: Yes Glycoside Hydrolase 3.2.1.21 (Beta-Glucosidas..., B.Henrissat, A.Esen Crystal Structure Of A Monocotyledon (Maize Zmglu1) Beta-Gl...55-566.|PDB; 1E55; X-ray; A/B=55-566.|PDB; 1E56; X-ray; A/B=55-566.|PDB; 1H49; X-ray; A/B=55-566.|PDB; 1HXJ; X-ray; A/B=60-566.|Mai...ze-2DPAGE; P49235; COLEOPTILE.|MaizeDB; 13870; -.|InterPro

  13. Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration.

    Science.gov (United States)

    Müller, Jan; von Bernstorff, Wolfram; Heidecke, Claus-Dieter; Schulze, Tobias

    2017-01-01

    Introduction . Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P 1-5 ) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. Methods . Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. Results . All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P 1 . In contrast, M1-polarized macrophages significantly downregulated S1P 4 . The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. Discussion . The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.

  14. Experimental Conditions: SE24_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available rometry with 13C‑Labeling for Chemical Assignment of Sulfur-Containing Metabolites ...SE24_S1_M1_D1 SE24 Combination of Liquid Chromatography-Fourier Transform Ion Cyclotron Resonance-Mass Spect

  15. Ire1 mediated mRNA splicing in a C-terminus deletion mutant of Drosophila Xbp1.

    Directory of Open Access Journals (Sweden)

    Dina S Coelho

    Full Text Available The Unfolded Protein Response is a homeostatic mechanism that permits eukaryotic cells to cope with Endoplasmic Reticulum (ER stress caused by excessive accumulation of misfolded proteins in the ER lumen. The more conserved branch of the UPR relies on an ER transmembrane enzyme, Ire1, which, upon ER stress, promotes the unconventional splicing of a small intron from the mRNA encoding the transcription factor Xbp1. In mammals, two specific regions (the hydrophobic region 2--HR2--and the C-terminal translational pausing site present in the Xbp1unspliced protein mediate the recruitment of the Xbp1 mRNA-ribosome-nascent chain complex to the ER membrane, so that Xbp1 mRNA can be spliced by Ire1. Here, we generated a Drosophila Xbp1 deletion mutant (Excision101 lacking both HR2 and C-terminal region, but not the Ire1 splicing site. We show that Ire1-dependent splicing of Xbp1 mRNA is reduced, but not abolished in Excision101. Our results suggest the existence of additional mechanisms for ER membrane targeting of Xbp1 mRNA that are independent of the C-terminal domain of Drosophila Xbp1unspliced.

  16. FoxM1 is a general target for proteasome inhibitors.

    Directory of Open Access Journals (Sweden)

    Uppoor G Bhat

    2009-08-01

    Full Text Available Proteasome inhibitors are currently in the clinic or in clinical trials, but the mechanism of their anticancer activity is not completely understood. The oncogenic transcription factor FoxM1 is one of the most overexpressed genes in human tumors, while its expression is usually halted in normal non-proliferating cells. Previously, we established that thiazole antibiotics Siomycin A and thiostrepton inhibit FoxM1 and induce apoptosis in human cancer cells. Here, we report that Siomycin A and thiostrepton stabilize the expression of a variety of proteins, such as p21, Mcl-1, p53 and hdm-2 and also act as proteasome inhibitors in vitro. More importantly, we also found that well-known proteasome inhibitors such as MG115, MG132 and bortezomib inhibit FoxM1 transcriptional activity and FoxM1 expression. In addition, overexpression of FoxM1 specifically protects against bortezomib-, but not doxorubicin-induced apoptosis. These data suggest that negative regulation of FoxM1 by proteasome inhibitors is a general feature of these drugs and it may contribute to their anticancer properties.

  17. Probing the electronic properties of ternary A n M3n-1B2n (n = 1: A = Ca, Sr; M = Rh, Ir and n = 3: A = Ca, Sr; M = Rh) phases: observation of superconductivity.

    Science.gov (United States)

    Takeya, Hiroyuki; ElMassalami, Mohammed; Terrazos, Luis A; Rapp, Raul E; Capaz, Rodrigo B; Fujii, Hiroki; Takano, Yoshihiko; Doerr, Mathias; Granovsky, Sergey A

    2013-06-01

    We follow the evolution of the electronic properties of the titled homologous series when n as well as the atomic type of A and M are varied where for n = 1, A = Ca, Sr and M = Rh, Ir while for n = 3, A = Ca, Sr and M = Rh. The crystal structure of n = 1 members is known to be CaRh 2 B 2 -type ( Fddd ), while that of n = 3 is Ca 3 Rh 8 B 6 -type ( Fmmm ); the latter can be visualized as a stacking of structural fragments from AM 3 B 2 ( P 6/ mmm ) and AM 2 B 2 . The metallic properties of the n = 1 and 3 members are distinctly different: on the one hand, the n = 1 members are characterized by a linear coefficient of the electronic specific heat γ ≈ 3 mJ mol -1 K -2 , a Debye temperature θ D ≈ 300 K, a normal conductivity down to 2 K and a relatively strong linear magnetoresistivity for fields up to 150 kOe. The n = 3 family, on the other hand, exhibits γ ≈ 18 mJ mol -1 K -2 , θ D ≈ 330 K, a weak linear magnetoresistivity and an onset of superconductivity (for Ca 3 Rh 8 B 6 , T c = 4.0 K and H c2 = 14.5 kOe, while for Sr 3 Rh 8 B 6 , T c = 3.4 K and H c2 ≈ 4.0 kOe). These remarkable differences are consistent with the findings of the electronic band structures and density of state (DOS) calculations. In particular, satisfactory agreement between the measured and calculated γ was obtained. Furthermore, the Fermi level, E F , of Ca 3 Rh 8 B 6 lies at almost the top of a pronounced local DOS peak, while that of CaRh 2 B 2 lies at a local valley: this is the main reason behind the differences between the, e.g., superconducting properties. Finally, although all atoms contribute to the DOS at E F , the contribution of the Rh atoms is the strongest.

  18. The September 2017 M=8.1 Chiapas and M=7.1 Puebla, Mexico, earthquakes: Chain reaction or coincidence?

    Science.gov (United States)

    Toda, S.; Stein, R. S.

    2017-12-01

    The M=8.1 and M=7.1 events struck 12 days and 600 km apart, both with an independent probability of occurrence of 0.5% per year, based on the GEAR model [Bird et al., 2015]. Are they related? First, we calculated the static stress imparted by the M=8.1 shock to the fault that ruptured in the M=7.1, and find a tiny push that would favor rupture. But the stress increase (0.2 kPa) is less than the fault would experience from the tidal stresses, and so it should be inconsequential. We next used the México Servicio Sismológico Nacional (UNAM) online catalog to look at the quakes in the month before the M=8.1 and in the 13 days since. We calculate the completeness to be M≥4.0. There are virtually no remote aftershocks from the Chiapas rupture that extend within 250 km of the M=7.1 shock during the first week after the M=8.1. So, if anything, the M=8.1 turned off for a week or more the region that ruptured in the M=7.1. Events started turning on about 2-3 days before the M=7.1, but none of those struck within 40 km of the future M=7.1 mainshock. The seismic surface waves unleashed by great earthquakes envelop the globe in just 160 minutes, and yet triggering of remote large aftershocks during these 2-3 hours is either very rare [Pollitz et al., Nature 2012] or in dispute [Fan & Shearer, 2016 vs. Yue et al., 2017]. So, the waves must trigger tiny shocks that cascade into larger shocks after some delay. Or, perhaps the stresses conveyed by the waves pump pockets of fluids that slowly diffuse into nearby fault zones, lubricating them to the point of failure [Parsons at al., 2017]. In the cases where great earthquakes are indisputably seen to trigger aftershocks at great distances or even globally, they to do so within several days, or a week at most. Since Puebla struck 12 days later, this seems to us too long a period to be explained by dynamic triggering. Even though neither quake on their own is rare, what's the chance of independent M=8.1 and M=7.1 events just 12

  19. Flavonoids with M1 Muscarinic Acetylcholine Receptor Binding Activity

    Directory of Open Access Journals (Sweden)

    Meyyammai Swaminathan

    2014-06-01

    Full Text Available Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer’s disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki = 40–110 µM, comparable to that of acetylcholine (Ki = 59 µM. Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.

  20. RAP-1a is the main rhoptry-associated-protein-1 (RAP-1) recognized during infection with Babesia sp. BQ1 (Lintan) (B. motasi-like phylogenetic group), a pathogen of sheep in China.

    Science.gov (United States)

    Niu, Qingli; Bonsergent, Claire; Rogniaux, Hélène; Guan, Guiquan; Malandrin, Laurence; Moreau, Emmanuelle

    2016-12-15

    Babesia sp. BQ1 (Lintan) is one of the parasites isolated from infected sheep in China that belongs to the B. motasi-like phylogenetic group. The rhoptry-associated-protein 1 (rap-1) locus in this group consists of a complex organization of 12 genes of three main types: 6 rap-1a variants intercalated with 5 identical copies of rap-1b and a single 3' ending rap-1c gene. In the present study, transcription analysis performed by standard RT-PCR demonstrated that the three different rap-1 gene types and the four rap-1a variants were transcribed by the parasite cultivated in vitro. Peptides, specific for each rap-1 type gene, were selected in putative linear B-epitopes and used to raise polyclonal rabbit antisera. Using these sera, the same expression pattern of RAP-1 proteins was found in parasites cultivated in vitro or collected from acute infection whereas only RAP-1a67 was detectable in merozoite extracts. However, ELISA performed with recombinant RAP-1a67, RAP-1b or RAP-1c and sera from infected sheep demonstrated that RAP-1a67 is the main RAP-1 recognized during infection, even if some infected sheep also recognized RAP-1b and/or RAP-1c. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Dilemma and quantum battle of sexes

    International Nuclear Information System (INIS)

    Nawaz, Ahmad; Toor, A H

    2004-01-01

    We analysed quantum version of the game battle of sexes using a general initial quantum state. For a particular choice of initial entangled quantum state it is shown that the classical dilemma of the battle of sexes can be resolved and a unique solution of the game can be obtained

  2. Expression of Annexin-A1 and Galectin-1 Anti-Inflammatory Proteins and mRNA in Chronic Gastritis and Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Yvana Cristina Jorge

    2013-01-01

    Full Text Available Objective. The anti-inflammatory proteins annexin-A1 and galectin-1 have been associated with tumor progression. This scenario prompted us to investigate the relationship between the gene and protein expression of annexin-A1 (ANXA1/AnxA1 and galectin-1 (LGALS1/Gal-1 in an inflammatory gastric lesion as chronic gastritis (CG and gastric adenocarcinoma (GA and its association with H. pylori infection. Methods. We analyzed 40 samples of CG, 20 of GA, and 10 of normal mucosa (C by the quantitative real-time PCR (qPCR technique and the immunohistochemistry assay. Results. High ANXA1 mRNA expression levels were observed in 90% (36/40 of CG cases (mean relative quantification RQ = 4.26 ± 2.03 and in 80% (16/20 of GA cases (mean RQ = 4.38 ± 4.77. However, LGALS1 mRNA levels were high (mean RQ = 2.44 ± 3.26 in 60% (12/20 of the GA cases, while low expression was found in CG (mean RQ = 0.43±3.13; P<0.01. Normal mucosa showed modest immunoreactivity in stroma but not in epithelium, while stroma and epithelium displayed an intense immunostaining in CG and GA for both proteins. Conclusion. These results have provided evidence that galectin-1 and mainly annexin-A1 are overexpressed in both gastritis and gastric cancer, suggesting a strong association of these proteins with chronic gastric inflammation and carcinogenesis.

  3. Pokémon Battles as a Context for Mathematical Modeling

    Science.gov (United States)

    McGuffey, William

    2017-01-01

    In this article I explore some of the underlying mathematics of Poke´mon battles and describe ways that teachers at the secondary level could explore concepts of mathematical game theory in this context. I discuss various ways of representing and analyzing a Poke´mon battle using game theory and conclude with an example of applying concepts of…

  4. Operation of TRR-1/M1 for 25 years and lessons learned in management of safety and safety culture

    International Nuclear Information System (INIS)

    Keinmeesuke, Sirichai

    2002-01-01

    The first Thai Research Reactor, TRR-1, was installed and put into operation in 1962. In 1975 the reactor was converted to a 2 MW TRIGA Mark III by replacing of the reactor core and the control system. The renamed TRR-1/M1 research reactor went critical again in November 1977. TRR-1/M1 has been operated safely for 25 years with its main utilization in research, isotope production and training. Safety management and safety culture have been implemented for 25 years both in the legislation level and the operation level. There was no nuclear incident and there were a few radiological incidents during the 25 years of operation of TRR-1/M1. The lessons learned from the incident events such as the release of N-16 and Ar-41, the release of radioactive Bromine gave valued opportunities to improve our operation procedure, safety procedure and safety culture. All type of activities with respect to safety culture such as individual awareness, commitment, motivation, supervision and responsibility have been seriously reviewed and being set as normal practices. (author)

  5. E2F1 regulates cellular growth by mTORC1 signaling.

    Directory of Open Access Journals (Sweden)

    Sebastian Real

    2011-01-01

    Full Text Available During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation.

  6. Construction of Eukaryotic Expression Vector with mBD1-mBD3 Fusion Genes and Exploring Its Activity against Influenza A Virus

    Directory of Open Access Journals (Sweden)

    Wanyi Li

    2014-03-01

    Full Text Available Influenza (flu pandemics have exhibited a great threat to human health throughout history. With the emergence of drug-resistant strains of influenza A virus (IAV, it is necessary to look for new agents for treatment and transmission prevention of the flu. Defensins are small (2–6 kDa cationic peptides known for their broad-spectrum antimicrobial activity. Beta-defensins (β-defensins are mainly produced by barrier epithelial cells and play an important role in attacking microbe invasion by epithelium. In this study, we focused on the anti-influenza A virus activity of mouse β-defensin 1 (mBD1 and β defensin-3 (mBD3 by synthesizing their fusion peptide with standard recombinant methods. The eukaryotic expression vectors pcDNA3.1(+/mBD1-mBD3 were constructed successfully by overlap-PCR and transfected into Madin-Darby canine kidney (MDCK cells. The MDCK cells transfected by pcDNA3.1(+/mBD1-mBD3 were obtained by G418 screening, and the mBD1-mBD3 stable expression pattern was confirmed in MDCK cells by RT-PCR and immunofluorescence assay. The acquired stable transfected MDCK cells were infected with IAV (A/PR/8/34, H1N1, 0.1 MOI subsequently and the virus titers in cell culture supernatants were analyzed by TCID50 72 h later. The TCID50 titer of the experimental group was clearly lower than that of the control group (p < 0.001. Furthermore, BALB/C mice were injected with liposome-encapsulated pcDNA3.1(+/mBD1-mBD3 through muscle and then challenged with the A/PR/8/34 virus. Results showed the survival rate of 100% and lung index inhibitory rate of 32.6% in pcDNA3.1(+/mBD1-mBD3group; the TCID50 titer of lung homogenates was clearly lower than that of the control group (p < 0.001. This study demonstrates that mBD1-mBD3 expressed by the recombinant plasmid pcDNA3.1(+/mBD1-mBD3 could inhibit influenza A virus replication both in vitro and in vivo. These observations suggested that the recombinant mBD1-mBD3 might be developed into an agent for

  7. Absorbed dose in the fetus of a pregnant patient when I"1"3"1 (iodide/Tc"9"9"m (pertechnetate) is administered during thyroid studies

    International Nuclear Information System (INIS)

    Vasquez A, M.; Murillo C, V.; Arbayza F, J.; Sanchez S, P.; Cabrera S, C.

    2016-10-01

    The radiation absorbed dose in the fetus of a pregnant woman during thyroid studies is estimated through the analysis of the bio-kinetics of radiopharmaceuticals containing I"1"3"1 (iodide) or Tc"9"9"m (pertechnetate). MIRD formalism and its representation Cristy-Eckerman are used. The results indicate that the absorbed dose by the fetus of a woman of 3, 6 and 9 months of gestation due to Tc"9"9"m emissions is lower than that obtained by I"1"3"1; represent 34.7%, 6% and 3.5% of the dose generate by the iodide. The auto-dose in the fetus of a pregnant woman is mainly due to the local energy deposition of the beta and gamma emissions of I"1"3"1, being greater than the one reported by the gamma emissions and conversion electrons of the Tc"9"9"m, for fetuses of 6 and 9 months. The dose incorporated to the fetus due to the organs of the maternal tissues, which are part of the bio-kinetics, are basically due to the emission of its gamma photons and correspond to 38.50% /60.52% in fetuses of 3 months, 64.71% /12.43% in fetuses of 6 months and 69.79% /10.97% in fetuses of 9 months for the radiopharmaceuticals Tc"9"9"m (pertechnetate) / I"1"3"1 (iodide). The organs of bio-kinetics that contribute to the fetus dose are mainly due to the bladder, followed by the rest, and small intestine (fetuses of 3 months); of the rest, followed by the small intestine and bladder (fetuses of 6 months); of the bladder, followed by the small intestine and stomach (fetuses of 9 months) when using I"1"3"1; while for the Tc"9"9"m the bladder and rest contribute (fetuses of 3 months); of the placenta, followed by the rest and bladder (fetuses of 6 and 9 months). (Author)

  8. Current status of the Thai Research Reactor (TRR-1/M1)

    International Nuclear Information System (INIS)

    Chueinta, Siripone; Julanan, Mongkol; Charncanchee, Decharchai

    2006-01-01

    The first Thai Research Reactor, TRR-1 went critical on 27 October 1962 at the maximum power of 1 MW. It was located at Office of Atoms for Peace (OAP) in Bangkok. Since then, TRR-1 was continuously operated and eventually shut down in 1975. Plate type, high-enriched uranium (HEU) and U 3 O 8 A1 cladding were used as the reactor fuel. Light water was used as moderator and coolant as well. In 1975, because of the problem from fuel supplier and also to supporting the Treaty of Non Proliferation of Nuclear Weapon or NPT, TRR-1 was shut down for modification. The reactor core and control system were disassembled and replaced by TRIGA Mark III. A new core was a hexagonal core shape designed by General Atomics (GA). Afterwards, TRR-1 was officially renamed to the Thai Research Reactor-1/Modification 1 (TRR-1/M1). TRR-1/M1 is a multipurpose swimming pool type reactor with nominal power of 2 MW. The TRR-1/M1 uses uranium enriched at 20% in U-235 (LEU) and ZrH alloy as fuel. Light water is also used as coolant and moderator. At present, the reactor is operating with core No.14. The reactor has been serving for various kinds of utilization namely, radioisotope production, neutron activation analysis, beam experiments and reactor physics experiments. (author)

  9. DISCOVERY OF MAIN-BELT COMET P/2006 VW{sub 139} BY Pan-STARRS1

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Henry H.; Yang Bin; Haghighipour, Nader; Kaluna, Heather M.; Denneau, Larry; Jedicke, Robert; Wainscoat, Richard J.; Armstrong, James D.; Micheli, Marco; Keane, Jacqueline V.; Urban, Laurie; Riesen, Timm; Meech, Karen J. [Institute for Astronomy, University of Hawaii, 2680 Woodlawn Drive, Honolulu, HI 96822 (United States); Fitzsimmons, Alan [Astrophysics Research Centre, Queens University Belfast, Belfast BT7 1NN (United Kingdom); Novakovic, Bojan [Department of Astronomy, Faculty of Mathematics, University of Belgrade, Studentski trg 16, 11000 Belgrade (Serbia); Duddy, Samuel R.; Lowry, Stephen C. [Centre for Astrophysics and Planetary Science, The University of Kent, Canterbury CT2 7NH (United Kingdom); Trujillo, Chadwick A. [Gemini Observatory, Northern Operations Center, 670 N. Aohoku Place, Hilo, HI 96720 (United States); Abe, Shinsuke; Cheng, Yu-Chi, E-mail: hsieh@ifa.hawaii.edu [Institute of Astronomy, National Central University, 300 Jhongda Rd, Jhongli 32001, Taiwan (China); and others

    2012-03-20

    The main-belt asteroid (300163) 2006 VW{sub 139} (later designated P/2006 VW{sub 139}) was discovered to exhibit comet-like activity by the Pan-STARRS1 (PS1) survey telescope using automated point-spread-function analyses performed by PS1's Moving Object Processing System. Deep follow-up observations show both a short ({approx}10'') antisolar dust tail and a longer ({approx}60'') dust trail aligned with the object's orbit plane, similar to the morphology observed for another main-belt comet (MBC), P/2010 R2 (La Sagra), and other well-established comets, implying the action of a long-lived, sublimation-driven emission event. Photometry showing the brightness of the near-nucleus coma remaining constant over {approx}30 days provides further evidence for this object's cometary nature, suggesting it is in fact an MBC, and not a disrupted asteroid. A spectroscopic search for CN emission was unsuccessful, though we find an upper limit CN production rate of Q{sub CN} < 1.3 Multiplication-Sign 10{sup 24} mol s{sup -1}, from which we infer a water production rate of Q{sub H{sub 2O}}<10{sup 26} mol s{sup -1}. We also find an approximately linear optical spectral slope of 7.2%/1000 A, similar to other cometary dust comae. Numerical simulations indicate that P/2006 VW{sub 139} is dynamically stable for >100 Myr, while a search for a potential asteroid family around the object reveals a cluster of 24 asteroids within a cutoff distance of 68 m s{sup -1}. At 70 m s{sup -1}, this cluster merges with the Themis family, suggesting that it could be similar to the Beagle family to which another MBC, 133P/Elst-Pizarro, belongs.

  10. Probing the electronic properties of ternary AnM3n−1B2n (n = 1: A = Ca, Sr; M = Rh, Ir and n = 3: A = Ca, Sr; M = Rh phases: observation of superconductivity

    Directory of Open Access Journals (Sweden)

    Hiroyuki Takeya, Mohammed ElMassalami, Luis A Terrazos, Raul E Rapp, Rodrigo B Capaz, Hiroki Fujii, Yoshihiko Takano, Mathias Doerr and Sergey A Granovsky

    2013-01-01

    Full Text Available We follow the evolution of the electronic properties of the titled homologous series when n as well as the atomic type of A and M are varied where for n = 1, A = Ca, Sr and M = Rh, Ir while for n = 3, A = Ca, Sr and M = Rh. The crystal structure of n = 1 members is known to be CaRh2B2-type (Fddd, while that of n = 3 is Ca3Rh8B6-type (Fmmm; the latter can be visualized as a stacking of structural fragments from AM3B2 (P6/mmm and AM2B2. The metallic properties of the n = 1 and 3 members are distinctly different: on the one hand, the n = 1 members are characterized by a linear coefficient of the electronic specific heat γ ≈ 3 mJ mol−1 K−2, a Debye temperature θD ≈ 300 K, a normal conductivity down to 2 K and a relatively strong linear magnetoresistivity for fields up to 150 kOe. The n = 3 family, on the other hand, exhibits γ ≈ 18 mJ mol−1 K−2, θD ≈ 330 K, a weak linear magnetoresistivity and an onset of superconductivity (for Ca3Rh8B6, Tc = 4.0 K and Hc2 = 14.5 kOe, while for Sr3Rh8 B6, Tc = 3.4 K and Hc2 ≈ 4.0 kOe. These remarkable differences are consistent with the findings of the electronic band structures and density of state (DOS calculations. In particular, satisfactory agreement between the measured and calculated γ was obtained. Furthermore, the Fermi level, EF, of Ca3Rh8B6 lies at almost the top of a pronounced local DOS peak, while that of CaRh2B2 lies at a local valley: this is the main reason behind the differences between the, e.g., superconducting properties. Finally, although all atoms contribute to the DOS at EF, the contribution of the Rh atoms is the strongest.

  11. Probing the electronic properties of ternary AnM3n−1B2n (n = 1: A = Ca, Sr; M = Rh, Ir and n = 3: A = Ca, Sr; M = Rh) phases: observation of superconductivity

    Science.gov (United States)

    Takeya, Hiroyuki; ElMassalami, Mohammed; Terrazos, Luis A; Rapp, Raul E; Capaz, Rodrigo B; Fujii, Hiroki; Takano, Yoshihiko; Doerr, Mathias; Granovsky, Sergey A

    2013-01-01

    We follow the evolution of the electronic properties of the titled homologous series when n as well as the atomic type of A and M are varied where for n = 1, A = Ca, Sr and M = Rh, Ir while for n = 3, A = Ca, Sr and M = Rh. The crystal structure of n = 1 members is known to be CaRh2B2-type (Fddd), while that of n = 3 is Ca3Rh8B6-type (Fmmm); the latter can be visualized as a stacking of structural fragments from AM3B2 (P6/mmm) and AM2B2. The metallic properties of the n = 1 and 3 members are distinctly different: on the one hand, the n = 1 members are characterized by a linear coefficient of the electronic specific heat γ ≈ 3 mJ mol−1 K−2, a Debye temperature θD ≈ 300 K, a normal conductivity down to 2 K and a relatively strong linear magnetoresistivity for fields up to 150 kOe. The n = 3 family, on the other hand, exhibits γ ≈ 18 mJ mol−1 K−2, θD ≈ 330 K, a weak linear magnetoresistivity and an onset of superconductivity (for Ca3Rh8B6, Tc = 4.0 K and Hc2 = 14.5 kOe, while for Sr3Rh8 B6, Tc = 3.4 K and Hc2 ≈ 4.0 kOe). These remarkable differences are consistent with the findings of the electronic band structures and density of state (DOS) calculations. In particular, satisfactory agreement between the measured and calculated γ was obtained. Furthermore, the Fermi level, EF, of Ca3Rh8B6 lies at almost the top of a pronounced local DOS peak, while that of CaRh2B2 lies at a local valley: this is the main reason behind the differences between the, e.g., superconducting properties. Finally, although all atoms contribute to the DOS at EF, the contribution of the Rh atoms is the strongest. PMID:27877576

  12. Analysis of glutathione S-transferase (M1, T1 and P1) gene ...

    African Journals Online (AJOL)

    Glutathione S-transferase enzymes are active in detoxifying a wide number of endogenous and exogenous chemical carcinogens and subsequently, are crucial in protecting the DNA. Several studies show some differences in association of glutathione S-transferase M1, T1 and P1 genetic polymorphisms with the risk of ...

  13. Estimation and Properties of a Time-Varying GQARCH(1,1-M Model

    Directory of Open Access Journals (Sweden)

    Sofia Anyfantaki

    2011-01-01

    analysis of these models computationally infeasible. This paper outlines the issues and suggests to employ a Markov chain Monte Carlo algorithm which allows the calculation of a classical estimator via the simulated EM algorithm or a simulated Bayesian solution in only ( computational operations, where is the sample size. Furthermore, the theoretical dynamic properties of a time-varying GQARCH(1,1-M are derived. We discuss them and apply the suggested Bayesian estimation to three major stock markets.

  14. m=1” coatings

    DEFF Research Database (Denmark)

    Cooper-Jensen, C.; Klinkby, Esben Bryndt; Beaucour, J.

    For neutrons the critical angle of Ni is defined as m=1. If one needs a coating with reflectivity above m=1, people have traditionally used Ni58 or Ni-based multilayers. The reason to use Ni is the high neutron scattering density and the fact that it is easy to coat Ni using magnetron sputtering....... For a neutron guide the cost of shielding around the guide is a substantial part of the total cost of the guide. We are therefore looking at other materials than Ni for m=1 coatings. Both Be and diamond have the same or higher neutron scattering density than Ni, and have a much smaller absorption cross section....... Because of the lower absorption cross section, and because of fewer emitted gamma ray photons when a neutron is absorbed, these coatings are producing much less gamma radiation and therefore reduce the shielding costs. Be is frequently used in a wide range of science and technology applications. The only...

  15. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide

    International Nuclear Information System (INIS)

    Genin, Marie; Clement, Francois; Fattaccioli, Antoine; Raes, Martine; Michiels, Carine

    2015-01-01

    Tumor associated macrophages (TAMs) are present in high density in solid tumors. TAMs share many characteristics with alternatively activated macrophages, also called M2. They have been shown to favor tumor development and a role in chemoresistance has also been suggested. Here, we investigated the effects of M2 in comparison to M1 macrophages on cancer cell sensitivity to etoposide. We set up a model of macrophage polarization, starting from THP-1 monocytes differentiated into macrophages using PMA (Phorbol 12-myristate 13-acetate). Once differentiated (M0 macrophages), they were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). To mimic the communication between cancer cells and TAMs, M0, M1 or M2 macrophages and HepG2 or A549 cancer cells were co-cultured during respectively 16 (HepG2) or 24 (A549) hours, before etoposide exposure for 24 (HepG2) or 16 (A549) hours. After the incubation, the impact of etoposide on macrophage polarization was studied and cancer cell apoptosis was assessed by western-blot for cleaved caspase-3 and cleaved PARP-1 protein, caspase activity assay and FACS analysis of Annexin V and PI staining. mRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages, which provide a new, easy and well-characterized model of polarized human macrophages. Etoposide-induced cancer cell apoptosis was markedly reduced in the presence of THP-1 M2 macrophages, while apoptosis was increased in cells co-cultured with M1 macrophages. On the other hand, etoposide did not influence M1 or M2 polarization. These results evidence for the first time a clear protective effect of M2 on the contrary to M1 macrophages on etoposide-induced cancer cell apoptosis

  16. Mouse fetal antigen 1 (mFA1), the circulating gene product of mdlk, pref-1 and SCP-1: isolation, characterization and biology

    DEFF Research Database (Denmark)

    Bachmann, E; Krogh, T N; Højrup, P

    1996-01-01

    The mouse homologue to human fetal antigen 1 (hFA1) was purified from mouse amniotic fluid by cation exchange chromatography and immunospecific affinity chromatography. Mouse FA1 (mFA1) is a single chain glycoprotein with an M(r) of 42-50 kDa (SDS-PAGE). The N-terminal amino acid sequence (39...... residues) revealed 74% identity to hFA1 and 100% identity to the translated cDNAs referred to as mouse dlk, pref-1 and SCP-1. mFA1 is the secreted processed molecule encoded by the mRNA defined by these identical mouse cDNAs. Monospecific rabbit anti-mFA1 antibodies, purified by ammonium sulfate...... precipitation and immunospecific affinity chromatography, were used for immunohistochemical and quantitative ELISA techniques. The indirect immunoperoxidase technique demonstrated mFA1 within the endocrine structures of adult mouse pancreas, whereas the exocrine tissue remained unstained. FA1-positive staining...

  17. Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption.

    Science.gov (United States)

    He, D; Kou, X; Luo, Q; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; Zeng, M; Gan, Y; Zhou, Y

    2015-01-01

    Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio. © International & American Associations for Dental Research 2014.

  18. Gamma-line intensity difference method for sup 1 sup 1 sup 7 sup m Sn at high resolution

    CERN Document Server

    Remeikis, V; Mazeika, K

    1998-01-01

    The method for detection of small differences in the gamma-spectrum line intensity for the radionuclide in different environments has been developed for measurements at high resolution. The experiments were realized with the pure germanium planar detector. Solution of the methodical problems allowed to measure the relative difference DELTA IOTA subgamma/IOTA subgamma=(3.4+-1.5)*10 sup - sup 4 of the sup 1 sup 1 sup 7 sup m Sn 156.02 keV gamma-line intensity for the radionuclide in SnO sub 2 with respect to SnS from the difference in the gamma-spectra. The error of the result is caused mainly by the statistical accuracy. It is limited by the highest counting rate at sufficiently high energy resolution and relatively short half-life of sup 1 sup 1 sup 7 sup m Sn. (author)

  19. BTB and CNC homolog 1 (Bach1) deficiency ameliorates TNBS colitis in mice: role of M2 macrophages and heme oxygenase-1.

    Science.gov (United States)

    Harusato, Akihito; Naito, Yuji; Takagi, Tomohisa; Uchiyama, Kazuhiko; Mizushima, Katsura; Hirai, Yasuko; Higashimura, Yasuki; Katada, Kazuhiro; Handa, Osamu; Ishikawa, Takeshi; Yagi, Nobuaki; Kokura, Satoshi; Ichikawa, Hiroshi; Muto, Akihiko; Igarashi, Kazuhiko; Yoshikawa, Toshikazu

    2013-01-01

    BTB and CNC homolog 1 (Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1), which plays an important role in the protection of cells and tissues against acute and chronic inflammation. However, the role of Bach1 in the gastrointestinal mucosal defense system remains little understood. HO-1 supports the suppression of experimental colitis and localizes mainly in macrophages in colonic mucosa. This study was undertaken to elucidate the Bach1/HO-1 system's effects on the pathogenesis of experimental colitis. This study used C57BL/6 (wild-type) and homozygous Bach1-deficient C57BL/6 mice in which colonic damage was induced by the administration of an enema of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Subsequently, they were evaluated macroscopically, histologically, and biochemically. Peritoneal macrophages from the respective mice were isolated and analyzed. Then, wild-type mice were injected with peritoneal macrophages from the respective mice. Acute colitis was induced similarly. TNBS-induced colitis was inhibited in Bach1-deficient mice. TNBS administration increased the expression of HO-1 messenger RNA and protein in colonic mucosa in Bach1-deficient mice. The expression of HO-1 mainly localized in F4/80-immunopositive and CD11b-immunopositive macrophages. Isolated peritoneal macrophages from Bach1-deficient mice highly expressed HO-1 and also manifested M2 macrophage markers, such as Arginase-1, Fizz-1, Ym1, and MRC1. Furthermore, TNBS-induced colitis was inhibited by the transfer of Bach1-deficient macrophages into wild-type mice. Deficiency of Bach1 ameliorated TNBS-induced colitis. Bach1-deficient macrophages played a key role in protection against colitis. Targeting of this mechanism is applicable to cell therapy for human inflammatory bowel disease.

  20. Amino Acid Activation of mTORC1 by a PB1-Domain-Driven Kinase Complex Cascade.

    Science.gov (United States)

    Linares, Juan F; Duran, Angeles; Reina-Campos, Miguel; Aza-Blanc, Pedro; Campos, Alex; Moscat, Jorge; Diaz-Meco, Maria T

    2015-08-25

    The mTORC1 complex is central to the cellular response to changes in nutrient availability. The signaling adaptor p62 contributes to mTORC1 activation in response to amino acids and interacts with TRAF6, which is required for the translocation of mTORC1 to the lysosome and the subsequent K63 polyubiquitination and activation of mTOR. However, the signal initiating these p62-driven processes was previously unknown. Here, we show that p62 is phosphorylated via a cascade that includes MEK3/6 and p38δ and is driven by the PB1-containing kinase MEKK3. This phosphorylation results in the recruitment of TRAF6 to p62, the ubiquitination and activation of mTOR, and the regulation of autophagy and cell proliferation. Genetic inactivation of MEKK3 or p38δ mimics that of p62 in that it leads to inhibited growth of PTEN-deficient prostate organoids. Analysis of human prostate cancer samples showed upregulation of these three components of the pathway, which correlated with enhanced mTORC1 activation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Amino Acid Activation of mTORC1 by a PB1-Domain-Driven Kinase Complex Cascade

    Directory of Open Access Journals (Sweden)

    Juan F. Linares

    2015-08-01

    Full Text Available The mTORC1 complex is central to the cellular response to changes in nutrient availability. The signaling adaptor p62 contributes to mTORC1 activation in response to amino acids and interacts with TRAF6, which is required for the translocation of mTORC1 to the lysosome and the subsequent K63 polyubiquitination and activation of mTOR. However, the signal initiating these p62-driven processes was previously unknown. Here, we show that p62 is phosphorylated via a cascade that includes MEK3/6 and p38δ and is driven by the PB1-containing kinase MEKK3. This phosphorylation results in the recruitment of TRAF6 to p62, the ubiquitination and activation of mTOR, and the regulation of autophagy and cell proliferation. Genetic inactivation of MEKK3 or p38δ mimics that of p62 in that it leads to inhibited growth of PTEN-deficient prostate organoids. Analysis of human prostate cancer samples showed upregulation of these three components of the pathway, which correlated with enhanced mTORC1 activation.

  2. Uncleaved ApoM signal peptide is required for formation of large ApoM/sphingosine 1-phosphate (S1P)-enriched HDL particles.

    Science.gov (United States)

    Liu, Mingxia; Allegood, Jeremy; Zhu, Xuewei; Seo, Jeongmin; Gebre, Abraham K; Boudyguina, Elena; Cheng, Dongmei; Chuang, Chia-Chi; Shelness, Gregory S; Spiegel, Sarah; Parks, John S

    2015-03-20

    Apolipoprotein M (apoM), a plasma sphingosine 1-phosphate (S1P) carrier, associates with plasma HDL via its uncleaved signal peptide. Hepatocyte-specific apoM overexpression in mice stimulates formation of both larger nascent HDL in hepatocytes and larger mature apoM/S1P-enriched HDL particles in plasma by enhancing hepatic S1P synthesis and secretion. Mutagenesis of apoM glutamine 22 to alanine (apoM(Q22A)) introduces a functional signal peptidase cleavage site. Expression of apoM(Q22A) in ABCA1-expressing HEK293 cells resulted in the formation of smaller nascent HDL particles compared with wild type apoM (apoM(WT)). When apoM(Q22A) was expressed in vivo, using recombinant adenoviruses, smaller plasma HDL particles and decreased plasma S1P and apoM were observed relative to expression of apoM(WT). Hepatocytes isolated from both apoM(WT)- and apoM(Q22A)-expressing mice displayed an equivalent increase in cellular levels of S1P, relative to LacZ controls; however, relative to apoM(WT), apoM(Q22A) hepatocytes displayed more rapid apoM and S1P secretion but minimal apoM(Q22A) bound to nascent lipoproteins. Pharmacologic inhibition of ceramide synthesis increased cellular sphingosine and S1P but not medium S1P in both apoM(WT) and apoM(Q22A) hepatocytes. We conclude that apoM secretion is rate-limiting for hepatocyte S1P secretion and that its uncleaved signal peptide delays apoM trafficking out of the cell, promoting formation of larger nascent apoM- and S1P-enriched HDL particles that are probably precursors of larger apoM/S1P-enriched plasma HDL. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Galectin-1 Is an Interactive Protein of Selenoprotein M in the Brain

    Directory of Open Access Journals (Sweden)

    Qiong Liu

    2013-11-01

    Full Text Available Selenium, an essential trace element for human health, mainly exerts its biological function through selenoproteins. Selenoprotein M (SelM is one of the highly expressed selenoproteins in the brain, but its biological effect and molecular mechanism remain unclear. Thus, the interactive protein of SelM was investigated in this paper to guide further study. In order to avoid protein translational stop, the selenocysteine-encoding UGA inside the open reading frame of SelM was site-directly changed to the cysteine-encoding UGC to generate the SelM' mutant. Meanwhile, its N terminal transmembrane signal peptide was also cut off. This truncated SelM' was used to screen a human fetal brain cDNA library by the yeast two-hybrid system. A new interactive protein of SelM' was found to be galectin-1 (Gal-1. This protein-protein interaction was further verified by the results of fluorescence resonance energy transfer techniques, glutathione S-transferase pull-down and co-immunoprecipitation assays. As Gal-1 plays important roles in preventing neurodegeneration and promoting neuroprotection in the brain, the interaction between SelM' and Gal-1 displays a new direction for studying the biological function of SelM in the human brain.

  4. Abnormal glomerular filtration rate in children, adolescents and young adults starts below 75 mL/min/1.73 m(2).

    Science.gov (United States)

    Pottel, Hans; Hoste, Liesbeth; Delanaye, Pierre

    2015-05-01

    The chronic kidney disease (CKD) classification system for children is similar to that for adults, with both mainly based on estimated glomerular filtration rate (eGFR) combined with fixed cut-off values. The main cut-off eGFR value used to define CKD is 60 mL/min/1.73 m(2), a value that is also applied for children older than 2 years of age, adolescents and young adults. Based on a literature search, we evaluated inclusion criteria for eGFR in clinical trials or research studies on CKD for children. We also collected information on direct measurements of GFR (mGFR) in children and adolescents, with the aim to estimate the normal reference range for GFR. Using serum creatinine (Scr) normal reference values and Scr-based eGFR-equations, we also evaluated the correspondence between Scr normal reference values and (e)GFR normal reference values. Based on our literature search, the inclusion of children in published CKD studies has been based on cut-off values for eGFR of >60 mL/min/1.73 m(2). The lower reference limits for mGFR far exceed this adult threshold. Using eGFR values calculated using Scr-based formulas, we found that abnormal Scr levels in children already correspond to eGFR values that are below a cut-off of 75 mL/min/1.73 m(2). Abnormal GFR in children, adolescents and young adults starts below 75 mL/min/1.73 m(2), and as abnormality is a sign of disease, we recommend referring children, adolescents and young adults with an (e)GFR of <75 mL/min/1.73 m(2) for further clinical assessment.

  5. Diversification of the vacAs1m1 and vacAs2m2 strains of Helicobacter pylori in Meriones unguiculatus

    Directory of Open Access Journals (Sweden)

    Sandra Mendoza Elizalde

    2016-11-01

    Full Text Available The bacterium Helicobacter pylori exhibits great genetic diversity, and the pathogenic roles of its virulence factors have been widely studied. However, the evolutionary dynamics of H. pylori strains during stomach colonization are not well characterized. Here, we analyzed the microevolutionary dynamics of the toxigenic strain vacAs1m1, the non-toxigenic strain vacAs2m2, and a combination of both strains in an animal model over time. Meriones unguiculatus were inoculated with the following bacteria: group 1–toxigenic strain vacAs1m1/cagA+/cagE+/babA2+; ST181, group 2–non-toxigenic strain vacAs2m2/ cagA+/ cagE+/ babA2+; ST2901, and group 3–both strains. The gerbils were euthanized at different time points (3, 6, 12 and 18 months. In group 1, genetic alterations were observed at 6 and 12 months. With the combination of both strains, group 3 also exhibited genetic alterations at 3 and 18 months; moreover, a chimera, vacA m1-m2, was detected. Additionally, four new sequence types (STs were reported in the PubMLST database for H. pylori. Synonymous and non-synonymous mutations were analyzed and associated with alterations in amino acids. Microevolutionary analysis of the STs (PHYLOViZ identified in each group revealed many mutational changes in the toxigenic (vacAs1m1 and non-toxigenic (vacAs2m2 strains. Phylogenetic assessments (eBURST did not reveal clonal complexes. Our findings indicate that the toxigenic strain, vacAs1m1, and a combination of toxigenic and non-toxigenic strains acquired genetic material by recombination. The allelic combination, vacAs2m1, displayed the best adaptation in the animal model over time, and a chimera, m1-m2, was also identified, which confirmed previous reports.

  6. [99mTc[TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent

    International Nuclear Information System (INIS)

    Kung Meiping; Stevenson, D.A.; Ploessl, K.; Meegalla, S.K.; Beckwith, A.; Essman, W.D.; Mu, M.; Lucki, I.; Kung, H.F.

    1997-01-01

    Technetium-99m is the most commonly used radionuclide in routine nuclear medicine imaging procedures. Development of 99m Tc-labeled receptor-specific imaging agents for studying the central nervous system is potentially useful for evaluation of brain function in normal and disease states. A novel 99m Tc-labeled tropane derivative, [ 99m Tc[TRODAT-1, which is useful as a potential CNS dopamine transporter imaging agent, was evaluated and characterized. After i.v. injection into rats, [ 99m Tc[TRODAT-1 displayed specific brain uptake in the rat striatal region (striatum-cerebellum/cerebellum ratio 1.8 at 60 min), where dopamine neurons are concentrated. The specific striatal uptake could be blocked by pretreating rats with a dose of competing dopamine transporter ligand, β-CIT (or RTI-55, i.v., 1 mg/kg). However, the specific striatal uptake of [ 99m Tc[TRODAT-1 was not affected by co-injection of excess free ligand (TRODAT-1, up to 200 μg per rat) or by pretreating the rats with haloperidol (i.v., 1 mg/kg). The specific uptake in striatal regions of rats that had prior 6-hydroxydopamine lesion in the substantia nigra area showed a dramatic reduction. The radioactive material recovered from the rat striatal homogenates at 60 min after i.v. injection of [ 99m Tc[TRODAT-1 showed primarily the original compound (>95%), a good indication of in vivo stability in brain tissue. Similar and comparable organ distribution patterns and brain regional uptakes of [ 99m Tc[TRODAT-1 were obtained for male and female rats. (orig./AJ). With 4 figs., 6 tabs

  7. Akt inhibition promotes ABCA1-mediated cholesterol efflux to ApoA-I through suppressing mTORC1.

    Directory of Open Access Journals (Sweden)

    Fumin Dong

    Full Text Available ATP-binding cassette transporter A1 (ABCA1 plays an essential role in mediating cholesterol efflux to apolipoprotein A-I (apoA-I, a major housekeeping mechanism for cellular cholesterol homeostasis. After initial engagement with ABCA1, apoA-I directly interacts with the plasma membrane to acquire cholesterol. This apoA-I lipidation process is also known to require cellular signaling processes, presumably to support cholesterol trafficking to the plasma membrane. We report here that one of major signaling pathways in mammalian cells, Akt, is also involved. In several cell models that express ABCA1 including macrophages, pancreatic beta cells and hepatocytes, inhibition of Akt increases cholesterol efflux to apoA-I. Importantly, Akt inhibition has little effect on cells expressing non-functional mutant of ABCA1, implicating a specific role of Akt in ABCA1 function. Furthermore, we provide evidence that mTORC1, a major downstream target of Akt, is also a negative regulator of cholesterol efflux. In cells where mTORC1 is constitutively activated due to tuberous sclerosis complex 2 deletion, cholesterol efflux to apoA-I is no longer sensitive to Akt activity. This suggests that Akt suppresses cholesterol efflux through mTORC1 activation. Indeed, inhibition of mTORC1 by rapamycin or Torin-1 promotes cholesterol efflux. On the other hand, autophagy, one of the major pathways of cholesterol trafficking, is increased upon Akt inhibition. Furthermore, Akt inhibition disrupts lipid rafts, which is known to promote cholesterol efflux to apoA-I. We therefore conclude that Akt, through its downstream targets, mTORC1 and hence autophagy, negatively regulates cholesterol efflux to apoA-I.

  8. Theoretical descriptions of novel triplet germylenes M1-Ge-M2-M3 (M1 = H, Li, Na, K; M2 = Be, Mg, Ca; M3 = H, F, Cl, Br).

    Science.gov (United States)

    Kassaee, Mohamad Zaman; Ashenagar, Samaneh

    2018-02-06

    In a quest to identify new ground-state triplet germylenes, the stabilities (singlet-triplet energy differences, ΔE S-T ) of 96 singlet (s) and triplet (t) M 1 -Ge-M 2 -M 3 species were compared and contrasted at the B3LYP/6-311++G**, QCISD(T)/6-311++G**, and CCSD(T)/6-311++G** levels of theory (M 1  = H, Li, Na, K; M 2  = Be, Mg, Ca; M 3  = H, F, Cl, Br). Interestingly, F-substituent triplet germylenes (M 3  = F) appear to be more stable and linear than the corresponding Cl- or Br-substituent triplet germylenes (M 3  = Cl or Br). Triplets with M 1  = K (i.e., the K-Ge-M 2 -M 3 series) seem to be more stable than the corresponding triplets with M 1  = H, Li, or Na. This can be attributed to the higher electropositivity of potassium. Triplet species with M 3  = Cl behave similarly to those with M 3  = Br. Conversely, triplets with M 3  = H show similar stabilities and linearities to those with M 3  = F. Singlet species of formulae K-Ge-Ca-Cl and K-Ge-Ca-Br form unexpected cyclic structures. Finally, the triplet germylenes M 1 -Ge-M 2 -M 3 become more stable as the electropositivities of the α-substituents (M 1 and M 2 ) and the electronegativity of the β-substituent (M 3 ) increase.

  9. The structural, electronic, magnetic, and mechanical properties of perovskite oxides PbM1/2Nb1/2O3 (M = Fe, Co and Ni)

    Science.gov (United States)

    Erkisi, A.; Surucu, G.; Deligoz, E.

    2018-03-01

    In this study, the structural, electronic, magnetic, and mechanical properties of perovskite oxides PbM1/2Nb1/2O3 (M = Fe, Co and Ni) are investigated. The systems are treated in ferromagnetic order. The calculations are carried out in the framework of density functional theory (DFT) within the plane-wave pseudopotential method. The exchange-correlation potential is approximated by generalized-gradient spin approach (GGA). The intra-atomic Coulomb repulsion is also taken into account in calculations (GGA + U). We have considered two generalized-gradient spin approximation functionals, which are Perdew-Burke-Ernzerhof (PBE) and PBE for solids (PBEsol) for structural parameter calculations when it included Hubbard potential. Although the spin-polarized electronic band structures of PbCo1/2Nb1/2O3 and PbNi1/2Nb1/2O3 systems exhibit metallic property in ferromagnetic phase, a bandgap is observed in spin-down states of PbFe1/2Nb1/2O3 resulting in half-metallic behavior. The main reason for this behavior is attributed to the hybridization between d-states of transition metal atoms and p-states of oxygen atoms. The stability mechanically and the calculated mechanical properties by using elastic constants show that these compounds are mechanically stable in tetragonal phase and have anisotropic character mechanically.

  10. A Shift in ApoM/S1P Between HDL-Particles in Women With Type 1 Diabetes Mellitus Is Associated With Impaired Anti-Inflammatory Effects of the ApoM/S1P Complex.

    Science.gov (United States)

    Frej, Cecilia; Mendez, Armando J; Ruiz, Mario; Castillo, Melanie; Hughes, Thomas A; Dahlbäck, Björn; Goldberg, Ronald B

    2017-06-01

    Type 1 diabetes mellitus (T1D) patients have an increased risk of cardiovascular disease despite high levels of high-density lipoproteins (HDL). Apolipoprotein M (apoM) and its ligand sphingosine 1-phospate (S1P) exert many of the anti-inflammatory effects of HDL. We investigated whether apoM and S1P are altered in T1D and whether apoM and S1P are important for HDL functionality in T1D. ApoM and S1P were quantified in plasma from 42 healthy controls and 89 T1D patients. HDL was isolated from plasma and separated into dense, medium-dense, and light HDL by ultracentrifugation. Primary human aortic endothelial cells were challenged with tumor necrosis factor-α in the presence or absence of isolated HDL. Proinflammatory adhesion molecules E-selectin and vascular cellular adhesion molecule-1 were quantified by flow cytometry. Activation of the S1P 1 - receptor was evaluated by analyzing downstream signaling targets and receptor internalization. There were no differences in plasma levels of apoM and S1P between controls and T1D patients, but the apoM/S1P complexes were shifted from dense to light HDL particles in T1D. ApoM/S1P in light HDL particles from women were less efficient in inhibiting expression of vascular cellular adhesion molecule-1 than apoM/S1P in denser particles. The light HDL particles were unable to activate Akt, whereas all HDL subfractions were equally efficient in activating Erk and receptor internalization. ApoM/S1P in light HDL particles were inefficient in inhibiting tumor necrosis factor-α-induced vascular cellular adhesion molecule-1 expression in contrast to apoM/S1P in denser HDL particles. T1D patients have a higher proportion of light particles and hence more dysfunctional HDL, which could contribute to the increased cardiovascular disease risk associated with T1D. © 2017 American Heart Association, Inc.

  11. Winter variability in the western Gulf of Maine: Part 1: Internal tides

    Science.gov (United States)

    Brown, W. S.

    2011-09-01

    During the winter 1997-1998, a field program was conducted in Wilkinson Basin-western Gulf of Maine-as part of a study of winter convective mixing. The field program consisted of (1) Wilkinson basin-scale hydrographic surveys, (2) a tight three-mooring array with ˜100 m separations measured temperature and conductivity at rates of 2-15 min and (3) a single pair of upward/downward-looking pair acoustic Doppler current profiling (ADCP) instruments measured currents with 8 m vertical resolution over the 270 m water column in north-central Wilkinson basin at a rate of 10 min. The moored array measurements below the mixed layer (˜100 m depth) between 11 January and 6 February 1998 were dominated by a combination of the relatively strong semidiurnal external (depth-independent or barotropic) tide; upon which were superposed a weaker phase-locked semidiurnal internal tide and a very weak water column mean currents of about 1 cm/s southward or approximately across the local isobaths. The harmonic analysis of a vertical average of the relatively uniform ADCP velocities in the well-mixed upper 123 m of the water column, defined the external tidal currents which were dominated by a nearly rectilinear, across-isobath (326°T) M 2 semidiurnal tidal current of about 15 cm/s. The depth-dependent residual current field, which was created by subtracting the external tidal current, consisted of (1) clockwise-rotating semidiurnal internal tidal currents of about 5 cm/s below the mixed layer; (2) clockwise-rotating inertial currents; and (3) a considerably less energetic subtidal current variability. The results from both frequency-domain empirical orthogonal function and tidal harmonic analyses of the of isotherm displacement series at each of the three moorings in the 100 m array mutually confirm an approximate east-northeastward phase propagation of the dominant M 2 semidiurnal internal tide across Wilkinson Basin. Further investigation supports the idea that this winter internal

  12. Overexpression of the polycystin-1 (PC-1) C-tail enhances sensitivity of M-1 cells to ouabain

    Science.gov (United States)

    Jansson, Kyle; Magenheimer, Brenda S.; Maser, Robin L.; Calvet, James P.; Blanco, Gustavo

    2014-01-01

    Cells derived from renal cysts of patients with autosomal dominant polycystic kidney disease (ADPKD) are abnormally sensitive to ouabain, responding to physiological ouabain concentrations with enhanced proliferation and increased forskolin-induced transepithelial fluid secretion. This requires activation of the epidermal growth factor receptor (EGFR), Src kinase, and the extracellular regulated kinases MEK and ERK. Here, we have determined if the ADPKD phenotype obtained in mouse cortical collecting duct cells by stable overexpression of the C-terminal domain of polycystin-1 (PC-1 C-tail) also elicits the ADPKD-like response to ouabain in the cells. M-1 C20 cells expressing the PC-1 C-tail, and M-1 C17 cells, lacking expression of this construct, were treated with physiological concentrations of ouabain, and cell proliferation, activation of the EGFR-Src-MEK-ERK pathway, forskolin-induced transepithelial Cl− secretion, and the sensitivity of the Na,K-ATPase to ouabain were explored. M-1 C20 cells responded to ouabain with increased cell proliferation and ERK phosphorylation. Ouabain also augmented forskolin-induced and cystic fibrosis transmembrane conductance regulator (CFTR)-mediated apical secretion of Cl− in M-1 C20 cells. These effects required activation of EGFR, Src and MEK. In contrast, ouabain had no significant effects on M-1 C17 cells. Interestingly, approximately 20 % of the Na,K-ATPase from M-1 C20 cells presented an abnormally increased sensitivity to ouabain. Overexpression of PC-1 C-tail in M-1 C20 cells is associated with a ouabain sensitive phenotype and an increased ability of the cells to proliferate and secrete anions upon ouabain stimulation. This phenotype mimics the ouabain sensitivity of ADPKD cells and may help promote their cystogenic potential. PMID:23784065

  13. hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yimeng; Zhou, Jianhong; Du, Yuchun, E-mail: ydu@uark.edu

    2014-01-20

    The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to the cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation. - Highlights: • Cellular protein hnRNP A2/B1 interacts with influenza viral protein NS1. • hnRNP A2/B1 suppresses the levels of NS1 protein, vRNA and mRNA in infected cells. • hnRNP A2/B1 protein is associated with NS1 and NS2 mRNAs. • hnRNP A2/B1 inhibits the nuclear export of NS1 mRNAs. • hnRNP A2/B1 inhibits influenza virus replication.

  14. Interaction between NBS1 and the mTOR/Rictor/SIN1 complex through specific domains.

    Directory of Open Access Journals (Sweden)

    Jian-Qiu Wang

    Full Text Available Nijmegen breakage syndrome (NBS is a chromosomal-instability syndrome. The NBS gene product, NBS1 (p95 or nibrin, is a part of the Mre11-Rad50-NBS1 complex. SIN1 is a component of the mTOR/Rictor/SIN1 complex mediating the activation of Akt. Here we show that NBS1 interacted with mTOR, Rictor, and SIN1. The specific domains of mTOR, Rictor, or SIN1 interacted with the internal domain (a.a. 221-402 of NBS1. Sucrose density gradient showed that NBS1 was located in the same fractions as the mTOR/Rictor/SIN1 complex. Knockdown of NBS1 decreased the levels of phosphorylated Akt and its downstream targets. Ionizing radiation (IR increased the NBS1 levels and activated Akt activity. These results demonstrate that NBS1 interacts with the mTOR/Rictor/SIN1 complex through the a.a. 221-402 domain and contributes to the activation of Akt activity.

  15. A M2FS Spectroscopic Study of Low-mass Young Stars in Orion OB1

    Science.gov (United States)

    Kaleida, Catherine C.; Briceno, Cesar; Calvet, Nuria; Mateo, Mario L.; Hernandez, Jesus

    2015-01-01

    Surveys of pre-main sequence stars in the ~4-10 Myr range provide a window into the decline of the accretion phase of stars and the formation of planets. Nearby star clusters and stellar associations allow for the study of these young stellar populations all the way down to the lowest mass members. One of the best examples of nearby 4-10 Myr old stellar populations is the Orion OB1 association. The CIDA Variability Survey of Orion OB1 (CVSO - Briceño et al. 2001) has used the variability properties of low-mass pre-main-sequence (PMS) stars to identify hundreds of K and M-type stellar members of the Orion OB1 association, a number of them displaying IR-excess emission and thought to be representative of more evolved disk-bearing young stars. Characterizing these young, low-mass objects using spectroscopy is integral to understanding the accretion phase in young stars. We present preliminary results of a spectroscopic survey of candidate and confirmed Orion OB1 low-mass members taken during November 2014 and February 2014 using the Michigan/Magellan Fiber Spectrograph (M2FS), a PI instrument on the Magellan Clay Telescope (PI: M. Matteo). Target fields located in the off-cloud regions of Orion were identified in the CVSO, and observed using the low and high-resolution modes of M2FS. Both low and high-resolution spectra are needed in order to confirm membership and derive masses, ages, kinematics and accretion properties. Initial analysis of these spectra reveal many new K and M-type members of the Orion OB1 association in these low extinction, off-cloud areas. These are the more evolved siblings of the youngest stars still embedded in the molecular clouds, like those in the Orion Nebula Cluster. With membership and spectroscopic indicators of accretion we are building the most comprehensive stellar census of this association, enabling us to derive a robust estimate of the fraction of young stars still accreting at a various ages, a key constraint for the end of

  16. 26 CFR 1.401(m)-2 - ACP test.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false ACP test. 1.401(m)-2 Section 1.401(m)-2 Internal... TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(m)-2 ACP test. (a) Actual contribution percentage (ACP) test—(1) In general—(i) ACP test formula. A plan satisfies the ACP test for a plan year only...

  17. Operating and support costs and affordability of a 324 ship Naval battle force

    OpenAIRE

    Antonucci, Kevin C.

    2011-01-01

    The purpose of this research was to determine both the added operating and support (OandS) costs and affordability of operating and maintaining a future naval battle force of 324 ships as proposed in the Navy's 30-year shipbuilding plan. Cost estimation including regression, 3-year moving averages, point, expert and analogous modeling was used to capture both historical and future OandS costs from FY1991 to FY2024. With an emphasis on the three main cost drivers, (manpower, fuel and maintena...

  18. Differential effects of m1 and m2 receptor antagonists in perirhinal cortex on visual recognition memory in monkeys.

    Science.gov (United States)

    Wu, Wei; Saunders, Richard C; Mishkin, Mortimer; Turchi, Janita

    2012-07-01

    Microinfusions of the nonselective muscarinic antagonist scopolamine into perirhinal cortex impairs performance on visual recognition tasks, indicating that muscarinic receptors in this region play a pivotal role in recognition memory. To assess the mnemonic effects of selective blockade in perirhinal cortex of muscarinic receptor subtypes, we locally infused either the m1-selective antagonist pirenzepine or the m2-selective antagonist methoctramine in animals performing one-trial visual recognition, and compared these scores with those following infusions of equivalent volumes of saline. Compared to these control infusions, injections of pirenzepine, but not of methoctramine, significantly impaired recognition accuracy. Further, similar doses of scopolamine and pirenzepine yielded similar deficits, suggesting that the deficits obtained earlier with scopolamine were due mainly, if not exclusively, to blockade of m1 receptors. The present findings indicate that m1 and m2 receptors have functionally dissociable roles, and that the formation of new visual memories is critically dependent on the cholinergic activation of m1 receptors located on perirhinal cells. Published by Elsevier Inc.

  19. Efficacy of magnetoacustoradiation treatment of experimental M-1, PC-1 tumors

    International Nuclear Information System (INIS)

    Chizh, D.V.; Krutilina, N.I.

    2011-01-01

    The urgency of the struggle against malignant tumors is determined by a stable growth of cancer incidence, high level of disability and morbidity, the cost and difficulty of treatment. The influence of low-frequency ultrasound and alternating magnetic field on transplanted tumors of sarcoma M-1 and alveolar liver cancer PC-1 together with radiation therapy at a SFD of 5 Gy and 20 Gy was investigated in the experiments on animals. It was established that the influence of the above physical factors inhibited sarcoma M-1 and alveolar liver cancer PC-1 growth, prolonged the life and survival of the animals of the investigated groups when compared to the intact controls, which definitely expanded the ideas about the capabilities of ultrasound and magnetic fields in cancer treatment.

  20. M1 transitions in the (sdg) boson model

    Energy Technology Data Exchange (ETDEWEB)

    Kuyucak, S.; Morrison, I.

    1988-03-03

    Using the 1/N expansion technique we derive expressions for ..beta.. -> g, ..gamma.. -> g and ..gamma.. -> ..gamma.. M1 transitions in a general boson model. The M1 matrix elements in the sdg-boson model are similar in form to those in the neutron-proton IBM. Comparisons are made to some selected M1 data exhibiting collective character.

  1. [{sup 99m}Tc]TRODAT-1: a novel technetium-99m complex as a dopamine transporter imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Meiping, Kung [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Stevenson, D A [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Ploessl, K [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Meegalla, S K [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Beckwith, A [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Essman, W D [Department of Psychiatry, University of Pennsylvania, Philadelphia (United States); Mu, M [Department of Radiology, University of Pennsylvania, Philadelphia (United States); Lucki, I [Department of Psychiatry, University of Pennsylvania, Philadelphia (United States); [Department of Pharmacology, University of Pennsylvania, Philadelphia (United States); Kung, H F [Department of Radiology, University of Pennsylvania, Philadelphia (United States); [Department of Pharmacology, University of Pennsylvania, Philadelphia (United States)

    1997-04-01

    Technetium-99m is the most commonly used radionuclide in routine nuclear medicine imaging procedures. Development of {sup 99m}Tc-labeled receptor-specific imaging agents for studying the central nervous system is potentially useful for evaluation of brain function in normal and disease states. A novel {sup 99m}Tc-labeled tropane derivative, [{sup 99m}Tc]TRODAT-1, which is useful as a potential CNS dopamine transporter imaging agent, was evaluated and characterized. After i.v. injection into rats, [{sup 99m}Tc]TRODAT-1 displayed specific brain uptake in the rat striatal region (striatum-cerebellum/cerebellum ratio 1.8 at 60 min), where dopamine neurons are concentrated. The specific striatal uptake could be blocked by pretreating rats with a dose of competing dopamine transporter ligand, {beta}-CIT (or RTI-55, i.v., 1 mg/kg). However, the specific striatal uptake of [{sup 99m}Tc]TRODAT-1 was not affected by co-injection of excess free ligand (TRODAT-1, up to 200 {mu}g per rat) or by pretreating the rats with haloperidol (i.v., 1 mg/kg). The specific uptake in striatal regions of rats that had prior 6-hydroxydopamine lesion in the substantia nigra area showed a dramatic reduction. The radioactive material recovered from the rat striatal homogenates at 60 min after i.v. injection of [{sup 99m}Tc]TRODAT-1 showed primarily the original compound (>95%), a good indication of in vivo stability in brain tissue. Similar and comparable organ distribution patterns and brain regional uptakes of [{sup 99m}Tc]TRODAT-1 were obtained for male and female rats. (orig./AJ). With 4 figs., 6 tabs.

  2. China Dimensions Data Collection: Fundamental GIS: Digital Chart of China, 1:1M, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — Fundamental GIS: Digital Chart of China, 1:1M, Version 1 consists of vector maps of China and surrounding areas. The maps include roads, railroads, drainage systems,...

  3. M1 transitions in the (sdg) boson model

    Science.gov (United States)

    Kuyucak, S.; Morrison, I.

    1988-03-01

    Using the {1}/{N} expansion technique we derive expressions for β→g, γ→g and γ→γ M1 transitions in a general boson model. The M1 matrix elements in the sdg-boson model are similar in form to those in the neutron-proton IBM. Comparisons are made to some selected M1 data exhibiting collective character.

  4. M1 transitions in the (sdg) boson model

    International Nuclear Information System (INIS)

    Kuyucak, S.; Tuebingen Univ.; Morrison, I.

    1988-01-01

    Using the 1/N expansion technique we derive expressions for β → g, γ → g and γ → γ M1 transitions in a general boson model. The M1 matrix elements in the sdg-boson model are similar in form to those in the neutron-proton IBM. Comparisons are made to some selected M1 data exhibiting collective character. (orig.)

  5. PHIBSS: MOLECULAR GAS CONTENT AND SCALING RELATIONS IN z ∼ 1-3 MASSIVE, MAIN-SEQUENCE STAR-FORMING GALAXIES

    International Nuclear Information System (INIS)

    Tacconi, L. J.; Genzel, R.; Wuyts, S.; Förster Schreiber, N. M.; Gracia-Carpio, J.; Lutz, D.; Saintonge, A.; Neri, R.; Cox, P.; Combes, F.; Bolatto, A.; Cooper, M. C.; Bournaud, F.; Burkert, A.; Comerford, J.; Davis, M.; Newman, S.; García-Burillo, S.; Naab, T.; Omont, A.

    2013-01-01

    We present PHIBSS, the IRAM Plateau de Bure high-z blue sequence CO 3-2 survey of the molecular gas properties in massive, main-sequence star-forming galaxies (SFGs) near the cosmic star formation peak. PHIBSS provides 52 CO detections in two redshift slices at z ∼ 1.2 and 2.2, with log(M * (M ☉ )) ≥ 10.4 and log(SFR(M ☉ /yr)) ≥ 1.5. Including a correction for the incomplete coverage of the M * -SFR plane, and adopting a ''Galactic'' value for the CO-H 2 conversion factor, we infer average gas fractions of ∼0.33 at z ∼ 1.2 and ∼0.47 at z ∼ 2.2. Gas fractions drop with stellar mass, in agreement with cosmological simulations including strong star formation feedback. Most of the z ∼ 1-3 SFGs are rotationally supported turbulent disks. The sizes of CO and UV/optical emission are comparable. The molecular-gas-star-formation relation for the z = 1-3 SFGs is near-linear, with a ∼0.7 Gyr gas depletion timescale; changes in depletion time are only a secondary effect. Since this timescale is much less than the Hubble time in all SFGs between z ∼ 0 and 2, fresh gas must be supplied with a fairly high duty cycle over several billion years. At given z and M * , gas fractions correlate strongly with the specific star formation rate (sSFR). The variation of sSFR between z ∼ 0 and 3 is mainly controlled by the fraction of baryonic mass that resides in cold gas.

  6. Investigation of aflatoxin M1 degradation in milk

    Directory of Open Access Journals (Sweden)

    Smajlović Ahmed

    2012-01-01

    Full Text Available Aflatoxin M1 is a highly toxic 4-hydroxylated metabolite of aflatoxins B1 and B2. It is one of the most potent hepatocarcinogens, mutagens, teratogens and immunosuppressors. Feed is often contaminated with aflatoxigenic moulds and aflatoxins with a high possibility of contaminating milk and dairy products with aflatoxin M1. Samples of artificially contaminated milk were exposed to the effects of physical conditions (temperature of -18oC and for microwaves in a microwave oven, time (during the period from 1 to 12 months and a combination of the above mentioned conditions. Following this, levels of aflatoxin M1 degradation were established by using the ELISA method. An insignificant decrease in concentration of toxin was observed which indicates that a temperature of -18°C does not significantly influence the concentration of aflatoxin M1 in the artificially contaminated milk. At the same time, treatment of milk with microwaves in a microwave oven showed an insignificant influence on the percentage of aflatoxin M1 absorbance.

  7. A comparative study, of 1 M and 8 M KOH electrolyte concentrations, used in Ni-MH batteries

    International Nuclear Information System (INIS)

    Khaldi, C.; Mathlouthi, H.; Lamloumi, J.

    2009-01-01

    One may wonder if we really should use a very high concentration of KOH electrolyte in Ni-MH batteries, to keep the thermodynamic and kinetic properties of the alloy, while this solution is very aggressive to the used alloys. In this work we present a comparative study, using different techniques of two concentrations, 1 M and 8 M KOH electrolytes. The maximum capacity values are 295 mAh g -1 and 237 mAh g -1 , the loss in capacity, after 23 cycles, are of 10% and 58%, the polarization after the activation are 110 mV and 360 mV and the thickness of the corrosion layer, on the electrode surface, are 7 nm and 42 nm, for the 1 M and 8 M KOH electrolytes, respectively. These results showed that replacing the solution 8 M with 1 M improves the performance of Ni-MH batteries and leads to better results

  8. Spontaneous transition rates for electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2) and magnetic quadrupole (M2) transitions for He-like calcium and sulfur ions

    International Nuclear Information System (INIS)

    Kingston, A.E.; Norrington, P.H.; Boone, A.W.

    2002-01-01

    The spontaneous decay rates for the electric dipole (E1), electric quadrupole (E2), magnetic dipole (M1) and magnetic quadrupole (M2) transitions between all of the 1s 2 , 1s2 l and 1s3 l states have been obtained for helium-like calcium and sulfur ions. To assess the accuracy of the calculations, the transition probabilities were calculated using two sets of configuration interaction wavefunctions. One set of wavefunctions was generated using the fully relativistic GRASP code and the other was obtained using CIV3, in which relativistic effects are introduced using the Breit-Pauli approximation. The transition rates, A values, oscillator strengths and line strengths from our two calculations are found to be similar and to compare very well with other recent results for Δn=1 or 2 transitions. For Δn=0 transitions the agreement is much less good; this is mainly due to differences in the calculated excitation energies. (author)

  9. Alterations of M1 and M4 acetylcholine receptors in the genetically dystonic (dtsz) hamster and moderate antidystonic efficacy of M1 and M4 anticholinergics.

    Science.gov (United States)

    Hamann, Melanie; Plank, Jagoda; Richter, Franziska; Bode, Christoph; Smiljanic, Sinisa; Creed, Meaghan; Nobrega, José N; Richter, Angelika

    2017-08-15

    Striatal cholinergic dysfunction has been suggested to play a critical role in the pathophysiology of dystonia. In the dt sz hamster, a phenotypic model of paroxysmal dystonia, M1 antagonists exerted moderate antidystonic efficacy after acute systemic administration. In the present study, we examined the effects of the M4 preferring antagonist tropicamid and whether long-term systemic or acute intrastriatal injections of the M1 preferring antagonist trihexyphenidyl are more effective in mutant hamsters. Furthermore, M1 and M4 receptors were analyzed by autoradiography and immunohistochemistry. Tropicamide retarded the onset of dystonic attacks, as previously observed after acute systemic administration of trihexyphenidyl. Combined systemic administration of trihexyphenidyl (30mg/kg) and tropicamide (15mg/kg) reduced the severity in acute trials and delayed the onset of dystonia during long-term treatment. In contrast, acute striatal microinjections of trihexyphenidyl, tropicamid or the positive allosteric M4 receptor modulator VU0152100 did not exert significant effects. Receptor analyses revealed changes of M1 receptors in the dorsomedial striatum, suggesting that the cholinergic system is involved in abnormal striatal plasticity in dt sz hamsters, but the pharmacological data argue against a crucial role on the phenotype in this animal model. However, antidystonic effects of tropicamide after systemic administration point to a novel therapeutic potential of M4 preferring anticholinergics for the treatment of dystonia. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Endoplasmic reticulum stress increases AT1R mRNA expression via TIA-1-dependent mechanism.

    Science.gov (United States)

    Backlund, Michael; Paukku, Kirsi; Kontula, Kimmo K; Lehtonen, Jukka Y A

    2016-04-20

    As the formation of ribonucleoprotein complexes is a major mechanism of angiotensin II type 1 receptor (AT1R) regulation, we sought to identify novel AT1R mRNA binding proteins. By affinity purification and mass spectroscopy, we identified TIA-1. This interaction was confirmed by colocalization of AT1R mRNA and TIA-1 by FISH and immunofluorescence microscopy. In immunoprecipitates of endogenous TIA- 1, reverse transcription-PCR amplified AT1R mRNA. TIA-1 has two binding sites within AT1R 3'-UTR. The binding site proximal to the coding region is glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-dependent whereas the distal binding site is not. TIA-1 functions as a part of endoplasmic reticulum (ER) stress response leading to stress granule (SG) formation and translational silencing. We and others have shown that AT1R expression is increased by ER stress-inducing factors. In unstressed cells, TIA-1 binds to AT1R mRNA and decreases AT1R protein expression. Fluorescence microscopy shows that ER stress induced by thapsigargin leads to the transfer of TIA-1 to SGs. In FISH analysis AT1R mRNA remains in the cytoplasm and no longer colocalizes with TIA-1. Thus, release of TIA-1-mediated suppression by ER stress increases AT1R protein expression. In conclusion, AT1R mRNA is regulated by TIA-1 in a ER stress-dependent manner. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Coalition Battle Management Language

    National Research Council Canada - National Science Library

    Tolk, Andreas; Galvin, Kevin; Hieb, Michael; Khimeche, Lionel

    2004-01-01

    Battle Management Language (BML) is being developed as an unambiguous language to command and control forces and equipment conducting military operations and to provide for situational awareness and a shared common operational picture...

  12. Simultaneous inhibition of mTOR-containing complex 1 (mTORC1) and MNK induces apoptosis of cutaneous T-cell lymphoma (CTCL) cells

    DEFF Research Database (Denmark)

    Marzec, Michal Tomasz; Liu, Xiaobin; Wysocka, Maria

    2011-01-01

    mTOR kinase forms the mTORC1 complex by associating with raptor and other proteins and affects a number of key cell functions. mTORC1 activates p70S6kinase 1 (p70S6K1) and inhibits 4E-binding protein 1 (4E-BP1). In turn, p70S6K1 phosphorylates a S6 protein of the 40S ribosomal subunit (S6rp) and 4E...

  13. EXTraS discovery of a 1.2-s X-ray pulsar in M31

    Science.gov (United States)

    Esposito, P.; Israel, G.; Belfiore, A.; Novara, G.; Sidoli, L.; Rodriguez Castillo, G.; De Luca, A.; Tiengo, A.; Haberl, F.; Salvaterra, R.

    2017-10-01

    A systematic search for periodic signals in the XMM-Newton's EPIC archive carried out within the EXTraS project resulted in the discovery of a 1.2-s flux modulation in 3XMM J004301.4+413017. It is the first accreting neutron star in M31 for which the spin period has been detected. Besides this distinction, 3XMM J0043 proved to be an interesting system. Doppler shifts of the spin modulation revealed an orbital motion with period of 1.27 d and the analysis of optical data shows that, while the source is likely associated to a globular cluster, a counterpart with V ˜ 22 outside the cluster cannot be excluded. The emission of the pulsar appears rather hard (most data are described by a power law with photon index <1) and, assuming the distance to M31, the 0.3-10 keV luminosity was variable, from ˜3×10^{37} to 2×10^{38} erg/s. Based on this, we discuss two main possible scenarios for 3X J0043: a peculiar low-mass X-ray binary, perhaps similar to 4U 1822-37 or 4U 1626-67, or an intermediate-mass X-ray binary akin Her X-1.

  14. Main: 1FK1 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available Molecule: Non-Specific Lipid Transfer Protein; Chain: A Lipid Transport G.W.Han, J.Y.Lee, H.K.Song, D.H.Shin....Kim, J.Choe, D.Lim, H.J.Moon, S.W.Suh Structural Basis Of Non-Specific Lipid Binding In Mai...y; @=28-120.|PDB; 1MZM; X-ray; @=28-120.|MaizeDB; 25447; -.|InterPro; IPR003612;

  15. Stochasticity and the m = 1 mode in tokamaks

    International Nuclear Information System (INIS)

    Izzo, R.; Monticello, D.A.; Stodiek, W.; Park, W.

    1986-05-01

    It has recently been proposed that stochasticity resulting from toroidal coupling could lead to a saturation of the m = 1 internal mode in tokamaks. We present results from the nonlinear evolution of the m = 1 mode with toroidal coupling that show that stochasticity is not enough to cause saturation of the m = 1 mode

  16. Some statistical features of the seismic activity related to the recent M8.2 and M7.1 earthquakes in Mexico

    Science.gov (United States)

    Guzman, L.; Baeza-Blancas, E.; Reyes, I.; Angulo Brown, F.; Rudolf Navarro, A.

    2017-12-01

    By studying the magnitude earthquake catalogs, previous studies have reported evidence that some changes in the spatial and temporal organization of earthquake activity is observedbefore and after of a main-shock. These previous studies have used different approach methods for detecting clustering behavior and distance-events density in order topoint out the asymmetric behavior of before shocks and aftershocks. Here, we present a statistical analysis of the seismic activity related to the M8.2 and M7.1 earthquakes occurredon Sept. 7th and Sept. 19th, respectively. First, we calculated the interevent time and distance for the period Sept. 7th 2016 until Oct. 20th 2017 for each seismic region ( a radius of 150 km centeredat coordinates of the M8.1 and M7.1). Next, we calculated the "velocity" of the walker as the ratio between the interevent distance and interevent time, and similarly, we also constructed the"acceleration". A slider pointer is considered to estimate some statistical features within time windows of size τ for the velocity and acceleration sequences before and after the main shocks. Specifically, we applied the fractal dimension method to detect changes in the correlation (persistence) behavior of events in the period before the main events.Our preliminary results pointed out that the fractal dimension associated to the velocity and acceleration sequences exhibits changes in the persistence behavior before the mainshock, while thescaling dimension values after the main events resemble a more uncorrelated behavior. Moreover, the relationship between the standard deviation of the velocity and the local mean velocity valuefor a given time window-size τ is described by an exponent close to 1.5, and the cumulative distribution of velocity and acceleration are well described by power law functions after the crash and stretched-exponential-like distribution before the main shock. On the other hand, we present an analysis of patterns of seismicquiescence

  17. On the formation of m = 1, n = 1 density snakes

    International Nuclear Information System (INIS)

    Sugiyama, Linda E.

    2013-01-01

    The m/n = 1/1 helical ion density “snake” located near the q = 1 magnetic surface in a toroidal, magnetically confined plasma arises naturally in resistive MHD, when the plasma density evolves separately from pressure. Nonlinear numerical simulations show that a helical density perturbation applied around q = 1 can form a quasi-steady state over q≳1 with T(tilde sign) of opposite average sign to ñ. Two principal outcomes depend on the magnitude of ñ/n and the underlying stability of the 1/1 internal kink mode. For a small q<1 central region, a moderate helical density drives a new, slowly growing type of nonlinear 1/1 internal kink inside q<1, with small ñ and ∇p(tilde sign)≃∇(nT(tilde sign)). The hot kink core moves away from, or perpendicular to, the high density region near q≃1, preserving the snake density during a sawtooth crash. The mode resembles the early stage of heavy-impurity-ion snakes in ohmic discharges, including recent observations in Alcator C-Mod. For a larger, more unstable q<1 region, the helical density perturbation drives a conventional 1/1 kink where ñ aligns with T(tilde sign), leading to a rapid sawtooth crash. The crash redistributes the density to a localized helical concentration inside q≲1, similar to experimentally observed snakes that are initiated by a sawtooth crash.

  18. The Battle of Algiers: A War of Liberation

    Science.gov (United States)

    Carter, Margaret

    1971-01-01

    The author describes the film, The Battle of Algiers," and suggests discussion ideas for a classroom analysis: emotional response; labels, e.g., enemy; responsibility; alternatives; justice; warfare and crime. Learning activities and resources are also suggested. (Author/JB)

  19. The apolipoprotein m-sphingosine-1-phosphate axis

    DEFF Research Database (Denmark)

    Arkensteijn, Bas W C; Berbée, Jimmy F P; Rensen, Patrick C N

    2013-01-01

    Apolipoprotein M (apoM) is a plasma apolipoprotein that mainly associates with high-density lipoproteins. Hence, most studies on apoM so far have investigated its effect on and association with lipid metabolism and atherosclerosis. The insight into apoM biology recently took a major turn. Apo...

  20. Evaluation on a radioimmunoassay of. alpha. /sub 1/ microglobulin (. alpha. /sub 1/-m) with simplified procedures

    Energy Technology Data Exchange (ETDEWEB)

    Matsui, Kazuyo; Moriuma, Hatsuko; Mishima, Chiho; Honda, Minoru; Tomonobu, Masahiro; Kanao, Keisuke; Fushimi, Hisako (Sumitomo Hospital, Osaka (Japan))

    1989-06-01

    A newly established double antibody radioimmunoassay (RIA) was fundamentally and clinically evaluated. Original procedures were partially modified as follows: Sample volume for serum and urine was changed to 25{mu}l, and thus 200 mg/l of {alpha}/sub 1/-m standard was prepared using 50 {mu}l of original standard solution (100 mg/l). The results were satisfactory in sensitivity (0.3 mg/l obtained from -2SD method), intraassay precision with its coefficient variation (CV) ranging from 3.0 to 7.4%, interassay precision with its CV ranging from 3.0 to 10.7%, and recovery with the mean value of 102.4% in serum and 108.2% in urine respectively. There were no changes about {alpha}/sub 1/-m value between diluted (2 times) and undiluted with high concentration samples. Normal levels of {alpha}/sub 1/-m were less than 25 mg/l is serum and less than 10 mg/l in urine. The present results indicate that the determination of {alpha}/sub 1/-m could be very simple and useful for the most sensitive screening test for the evaluation of renal function. (author).

  1. FoxM1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma by targeting Snai1

    OpenAIRE

    Yu, Chun-Peng; Yu, Shui; Shi, Lei; Wang, Song; Li, Zi-Xiang; Wang, Yan-Hua; Sun, Cheng-Jian; Liang, Jun

    2017-01-01

    Forkhead box protein M1 (FoxM1) is aberrantly expressed in several types of human malignancy, and serves an important role in tumor metastasis. Epithelial-mesenchymal transition (EMT) of cancer cells has been associated cancer metastasis; however, the implication of FoxM1 in EMT and its putative roles in the regulation of cancer metastasis remain to be elucidated. In the present study, the expression of FoxM1, Snai1 and E-cadherin in hepatocellular carcinoma (HCC) cell lines with various meta...

  2. NGTS-1b: a hot Jupiter transiting an M-dwarf

    Science.gov (United States)

    Bayliss, Daniel; Gillen, Edward; Eigmüller, Philipp; McCormac, James; Alexander, Richard D.; Armstrong, David J.; Booth, Rachel S.; Bouchy, François; Burleigh, Matthew R.; Cabrera, Juan; Casewell, Sarah L.; Chaushev, Alexander; Chazelas, Bruno; Csizmadia, Szilard; Erikson, Anders; Faedi, Francesca; Foxell, Emma; Gänsicke, Boris T.; Goad, Michael R.; Grange, Andrew; Günther, Maximilian N.; Hodgkin, Simon T.; Jackman, James; Jenkins, James S.; Lambert, Gregory; Louden, Tom; Metrailler, Lionel; Moyano, Maximiliano; Pollacco, Don; Poppenhaeger, Katja; Queloz, Didier; Raddi, Roberto; Rauer, Heike; Raynard, Liam; Smith, Alexis M. S.; Soto, Maritza; Thompson, Andrew P. G.; Titz-Weider, Ruth; Udry, Stéphane; Walker, Simon R.; Watson, Christopher A.; West, Richard G.; Wheatley, Peter J.

    2018-04-01

    We present the discovery of NGTS-1b, a hot Jupiter transiting an early M-dwarf host (Teff,* = 3916 ^{+71}_{-63} K) in a P = 2.647 d orbit discovered as part of the Next Generation Transit Survey (NGTS). The planet has a mass of 0.812 ^{+0.066}_{-0.075} MJ, making it the most massive planet ever discovered transiting an M-dwarf. The radius of the planet is 1.33 ^{+0.61}_{-0.33} RJ. Since the transit is grazing, we determine this radius by modelling the data and placing a prior on the density from the population of known gas giant planets. NGTS-1b is the third transiting giant planet found around an M-dwarf, reinforcing the notion that close-in gas giants can form and migrate similar to the known population of hot Jupiters around solar-type stars. The host star shows no signs of activity, and the kinematics hint at the star being from the thick disc population. With a deep (2.5 per cent) transit around a K = 11.9 host, NGTS-1b will be a strong candidate to probe giant planet composition around M-dwarfs via James Webb Space Telescope transmission spectroscopy.

  3. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

    Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

  4. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Science.gov (United States)

    Barros, Mário Henrique M; Hauck, Franziska; Dreyer, Johannes H; Kempkes, Bettina; Niedobitek, Gerald

    2013-01-01

    Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for

  5. Architecture of human mTOR complex 1.

    Science.gov (United States)

    Aylett, Christopher H S; Sauer, Evelyn; Imseng, Stefan; Boehringer, Daniel; Hall, Michael N; Ban, Nenad; Maier, Timm

    2016-01-01

    Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of mammalian TOR (mTOR) signaling is implicated in pathologies that include diabetes, cancer, and neurodegeneration. We resolved the architecture of human mTORC1 (mTOR with subunits Raptor and mLST8) bound to FK506 binding protein (FKBP)-rapamycin, by combining cryo-electron microscopy at 5.9 angstrom resolution with crystallographic studies of Chaetomium thermophilum Raptor at 4.3 angstrom resolution. The structure explains how FKBP-rapamycin and architectural elements of mTORC1 limit access to the recessed active site. Consistent with a role in substrate recognition and delivery, the conserved amino-terminal domain of Raptor is juxtaposed to the kinase active site. Copyright © 2016, American Association for the Advancement of Science.

  6. A universal real-time PCR assay for the quantification of group-M HIV-1 proviral load.

    Science.gov (United States)

    Malnati, Mauro S; Scarlatti, Gabriella; Gatto, Francesca; Salvatori, Francesca; Cassina, Giulia; Rutigliano, Teresa; Volpi, Rosy; Lusso, Paolo

    2008-01-01

    Quantification of human immunodeficiency virus type-1 (HIV-1) proviral DNA is increasingly used to measure the HIV-1 cellular reservoirs, a helpful marker to evaluate the efficacy of antiretroviral therapeutic regimens in HIV-1-infected individuals. Furthermore, the proviral DNA load represents a specific marker for the early diagnosis of perinatal HIV-1 infection and might be predictive of HIV-1 disease progression independently of plasma HIV-1 RNA levels and CD4(+) T-cell counts. The high degree of genetic variability of HIV-1 poses a serious challenge for the design of a universal quantitative assay capable of detecting all the genetic subtypes within the main (M) HIV-1 group with similar efficiency. Here, we describe a highly sensitive real-time PCR protocol that allows for the correct quantification of virtually all group-M HIV-1 strains with a higher degree of accuracy compared with other methods. The protocol involves three stages, namely DNA extraction/lysis, cellular DNA quantification and HIV-1 proviral load assessment. Owing to the robustness of the PCR design, this assay can be performed on crude cellular extracts, and therefore it may be suitable for the routine analysis of clinical samples even in developing countries. An accurate quantification of the HIV-1 proviral load can be achieved within 1 d from blood withdrawal.

  7. Development of mPMab-1, a Mouse-Rat Chimeric Antibody Against Mouse Podoplanin.

    Science.gov (United States)

    Yamada, Shinji; Kaneko, Mika K; Nakamura, Takuro; Ichii, Osamu; Konnai, Satoru; Kato, Yukinari

    2017-04-01

    Podoplanin (PDPN), the ligand of C-type lectin-like receptor-2, is used as a lymphatic endothelial marker. We previously established clone PMab-1 of rat IgG 2a as a specific monoclonal antibody (mAb) against mouse PDPN. PMab-1 is also very sensitive in immunohistochemical analysis; however, rat mAbs seem to be unfavorable for pathologists because anti-mouse IgG and anti-rabbit IgG are usually used as secondary antibodies in commercially available kits for immunohistochemical analysis. In this study, we develop a mouse-rat chimeric antibody, mPMab-1 of mouse IgG 2a , which was derived from rat PMab-1mAb. Immunohistochemical analysis shows that mPMab-1 detects podocytes of the kidney, lymphatic endothelial cells of the colon, and type I alveolar cells of the lung. Importantly, mPMab-1 is more sensitive than PMab-1. This conversion strategy from rat mAb to mouse mAb could be applicable to other mAbs.

  8. Mittelplate A23/A23M1. Geological and reservoir engineering concept of a dual-lateral well; Mittelplate A23/A23M1. Geologisches und lagerstaettentechnisches Konzept einer Duolateralbohrung

    Energy Technology Data Exchange (ETDEWEB)

    Osivandi, K.; Racher, D. [RWE Dea AG, Hamburg (Germany)

    2011-07-15

    The Mittelplate Oil Field is situated in the German Wadden Sea in the West Holstein Trough in the concession Heide/Buesum, about 100 km northwest of Hamburg. Operator is RWE Dea AG (50%), and the partner is Wintershall Holding GmbH (50%). Besides the reservoir layers of the Dogger Gamma, Delta, Epsilon, and Zeta, the shallow-marine/deltaic sandstone-shale-succession of the Dogger Beta (with its five oil-bearing sandstones of 1-5 m thickness each) forms the laterally widespread reservoir which was the target for Germany's and RWE Dea AG's first pressure-tight multilateral well. So far the Dogger-Beta-Reservoir has been developed with wells from the artificial island Mittelplate A using a 5-spot pattern with a successive concentric concept. In order to reduce the costs and effectively make use of the limited amount of slots, the development concept should be improved by implementing the multilateral technology. By targeting three drainage areas in total, the multilateral well Mittelplate A23/A23M1 was planned to produce oil at an initial rate of ca. 400 m{sup 3}/d. In order to achieve a horizontal interval of ca. 2640 m length, several LWD measurements including Gamma Ray- and Density- Images and Deep-Directional-Resistivity logs were necessary. The long horizontal exposure of the oil-bearing sandstone layers as well as the tangent sections for placement of the electrical submersible pump (ESP) and junction above the reservoir represented the main challenges during geological planning and realtime geosteering. A total perforation length of 1360 m was achieved, taking into account the required distances to neighboring producer wells and the laterally varying pore pressures. According to the latest production history of the well, a cumulative production of about 10% more than initially planned are expected after an initial production rate of 735 m{sup 3}/d. Thanks to the successful application of the multilateral technology and geosteering within the thin

  9. Evaluation excitation functions for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si, and "1"1"3In(n,γ)"1"1"4"mIn reactions

    International Nuclear Information System (INIS)

    Zolotarev, K.I.

    2014-10-01

    Cross section data for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions are needed for solving a wide spectrum of scientific and technical tasks. The excitation function of "2"8Si(n,p)"2"8Al reaction refers to the nuclear data involved in fusion reactor design calculations. The "2"8Si(n,p)"2"8Al reaction is interesting also as the monitor reaction for measurements at fusion facilities. Activation detectors on the basis of the 31P(n,p)31Si reaction are commonly used in the reactor dosimetry. The "1"1"3In(n,γ)"1"1"4"mIn reaction is promising regarding reactor dosimetry application for two reasons. First, due to the "1"1"4"mIn decay parameters which are rather suitable for activation measurements. Half-life of "1"1"4"mIn is equal to T_1/_2 = (49.51 ± 0.01) days and gamma spectrum accompanying decay has only one line with energy 190.27 keV and intensity (15.56 ± 0.15)%. Second, the "1"1"3In(n,γ)"1"1"4"mIn reaction rate may be measured by using one activation detector simultaneously with the "1"1"5In(n,γ)"1"1"6"mIn reaction. Preliminary analysis of existing evaluated excitation functions for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions show that new evaluations are needed for all above mentioned reactions. This report is devoted to the preparation of the new evaluations of cross sections data and related covariance matrixes of uncertainties for the "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions.

  10. Experience with S-1 in older Caucasian patients with metastatic colorectal cancer (mCRC)

    DEFF Research Database (Denmark)

    Winther, Stine Braendegaard; Zubcevic, Kanita; Qvortrup, Camilla

    2016-01-01

    BACKGROUND: An aging population will increase the number of older patients with metastatic colorectal cancer (mCRC). However, there is limited knowledge about treatment in older patients as they are under-represented in clinical trials. The oral fluoropyrimidine S-1 is associated with a lower rate...... of adverse events than capecitabine and may therefore be a suitable drug for elderly. However, data on the use of S-1 in Caucasian mCRC patients are lacking/scarce. MATERIAL AND METHODS: In the present study we evaluated safety and the efficacy of S-1 alone or in combination with oxaliplatin (SOx......) or irinotecan (IRIS) in older mCRC patients. Patients who received at least one cycle of S-1 (first-line therapy), SOx (mainly first-line therapy) or IRIS (second-line therapy) were included. RESULTS: From June 2012 to December 2014, 71 older patients received ≥1 cycle of either S-1 (n = 9), SOx (n = 44...

  11. Study of gamma-ray induced variability on F1M1-F3M3 distant tomato hybrids

    International Nuclear Information System (INIS)

    Siromeatnicov, Iulia; Cotenco, Eugenia; Ciobanu, Renata

    2013-01-01

    The outcome of the evaluation of the gamma radiation's action, the growth and development tomato plant has shown that the coefficient of variation of plant height character is on the rise with increasing doses of gamma radiation. The hybrid combination F 1 M 1 (L.hpriz.1998) irradiated with dose 150 Gy variant presented superior value a towards scrutiny for plant height of the characters, number of flowers and fruits per bunch, number of fruits per plant and fruit mass of. The character F 2 M 2 generation plant height registered diminished value compared to F 1 M 1 generation. The highest value was recorded at the hybrid combination F 2 M 2 L.hpriz.1998 200 Gy treated dose. The evaluation research has highlighted that at the doses 100 Gy, 150 Gy, 200 Gy, have confirmed an increase in characters of reproductive system: the number of flowers and fruits per bunch, number of fruits per plant, fruit mass and reduction of the characters waist and height of placing of the first inflorescences plant. Similar aspects with some differences as low as hybrid combination Lhpi1998 in relation to the radiation doses used under study were confirmed in the case F 3 M 3 . (authors)

  12. On the formation of m = 1, n = 1 density snakes

    Energy Technology Data Exchange (ETDEWEB)

    Sugiyama, Linda E. [Laboratory for Nuclear Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307 (United States)

    2013-03-15

    The m/n = 1/1 helical ion density 'snake' located near the q = 1 magnetic surface in a toroidal, magnetically confined plasma arises naturally in resistive MHD, when the plasma density evolves separately from pressure. Nonlinear numerical simulations show that a helical density perturbation applied around q = 1 can form a quasi-steady state over q Greater-Than-Or-Equivalent-To 1 with T(tilde sign) of opposite average sign to n. Two principal outcomes depend on the magnitude of n/n and the underlying stability of the 1/1 internal kink mode. For a small q<1 central region, a moderate helical density drives a new, slowly growing type of nonlinear 1/1 internal kink inside q<1, with small n and {nabla}p(tilde sign) Asymptotically-Equal-To {nabla}(nT(tilde sign)). The hot kink core moves away from, or perpendicular to, the high density region near q Asymptotically-Equal-To 1, preserving the snake density during a sawtooth crash. The mode resembles the early stage of heavy-impurity-ion snakes in ohmic discharges, including recent observations in Alcator C-Mod. For a larger, more unstable q<1 region, the helical density perturbation drives a conventional 1/1 kink where n aligns with T(tilde sign), leading to a rapid sawtooth crash. The crash redistributes the density to a localized helical concentration inside q Less-Than-Or-Equivalent-To 1, similar to experimentally observed snakes that are initiated by a sawtooth crash.

  13. mTORC1 directly phosphorylates and regulates human MAF1.

    OpenAIRE

    Michels Annemieke A; Robitaille Aaron M; Buczynski-Ruchonnet Diane; Hodroj Wassim; Reina Jaime H; Hall Michael N; Hernandez Nouria

    2010-01-01

    mTORC1 is a central regulator of growth in response to nutrient availability, but few direct targets have been identified. RNA polymerase (pol) III produces a number of essential RNA molecules involved in protein synthesis, RNA maturation, and other processes. Its activity is highly regulated, and deregulation can lead to cell transformation. The human phosphoprotein MAF1 becomes dephosphorylated and represses pol III transcription after various stresses, but neither the significance of the p...

  14. A Bayesian Decision Model for Battle Damage Assessment

    National Research Council Canada - National Science Library

    Franzen, Daniel

    1999-01-01

    Battle damage assessment (BDA) is critical to success in any air campaign. However, Desert Storm highlighted numerous deficiencies in the BDA process, and operations since Desert Storm continue to point out weaknesses...

  15. The improvement of M1 polarization in macrophages by glycopeptide derived from Ganoderma lucidum.

    Science.gov (United States)

    Sun, Li-Xin; Lin, Zhi-Bin; Lu, Jie; Li, Wei-Dong; Niu, Yan-Dong; Sun, Yu; Hu, Chen-Yang; Zhang, Guo-Qiang; Duan, Xin-Suo

    2017-06-01

    Ganoderma lucidum (Fr.) Karst (Ganodermataceae) is a medicinal mushroom that has been extensively used in China for centuries to promote longevity and improve vigor without significant adverse effects. There is continuous interest in the bioactive properties of G. lucidum in view of its newly developed popularity in other regions besides Asia, such as Europe. Glycopeptide derived from G. lucidum (Gl-PS) is one of the main effective components isolated from this mushroom. The Gl-PS has been demonstrated pleiotropic with many bioactivities including immunomodulatory and antitumor effects. Macrophages are important cells involved in innate and adaptive immunity. Classically activated macrophages (M1) and alternatively activated macrophages (M2), with their different roles, display distinct cytokine profiles: M1 preferentially produces TNF-α, IL-6, and IL-12; conversely, M2 generates more IL-10 and arginase. Gl-PS might have the potential to promote macrophage M1 polarization by lipopolysaccharide (LPS). In this study, LPS was used to induce the M1 polarization. It was shown that the level of the TNF-α, IL-6, and IL-12 were increased and the IL-10 and arginase I were decreased in the polarized M1 macrophages after application of Gl-PS compared to the control. The results indicated the potential of Gl-PS to promote M1 polarization vs M2, with the health beneficial understanding of the bioactivities of Gl-PS.

  16. Stellar evolution IV: evolution of a star of 1.5 M(S) from the main-sequence to the red-giant branch with and without overshooting from convective core

    International Nuclear Information System (INIS)

    Maeder, A.

    1975-01-01

    For a star of 1.5 M(S) with an initial composition given by X=0.70 and Z=0.03, three sets of evolutionary models are computed with different assumptions on the non-local effects characterizing the turbulent motions in the convective core. Some overshooting from the convective core may occur during Main-sequence evolution. The changes in the stellar structure, lifetimes and evolutionary tracks brought about by this process are studied. Some characteristics of the evolutionary tracks in the theoretical HR diagram have a very high sensitivity to the exact extent of the convective core, and this may provide powerful tests of events occurring in the deep stellar interior. (orig./BJ) [de

  17. Compact Nd:YAG laser operating at 1.06, 1.32, and 1.44 μm for dental caries effective disinfection

    Science.gov (United States)

    Dostálová, Tat'jana; Jelínková, Helena; Kadlecová, Martina; Němec, Michal; Å ulc, Jan; Fibrich, Martin; Nejezchleb, Karel; Kapitch, Nickalai; Å koda, Václav

    2017-02-01

    The analysis of the disinfection effect of Nd:YAG laser radiation was investigated for patients with high concentration of Streptococcus mutans in saliva (positive result in Saliva-check mutans test). For the interaction the Nd:YAG laser system generated separate switchable wavelengths with the maximum output energies 1.1, 0.6, and 0.3 J for wavelength 1.06 μm, 1.32, μm and 1.44 μm, respectively, was used. Our study proved that after the laser irradiation the Saliva-check test showed negative presence of Streptococcus mutans. The disinfection effect was confirmed for all used radiation wavelength. For 1.44 μm this effect was reached with a smallest energy density.

  18. A complex interplay between PGC-1 co-activators and mTORC1 regulates hematopoietic recovery following 5-fluorouracil treatment

    Directory of Open Access Journals (Sweden)

    Sunanda Basu

    2014-01-01

    Full Text Available In vitro stimulation of HSCs with growth factors generally leads to their depletion. Understanding the molecular mechanisms underlying expansion of HSCs in vivo following myeloablation could lead to successful expansion of HSCs ex vivo for therapeutic purposes. Current findings show that mTORC1 is activated in HSPCs following 5-fluorouracil treatment and that mTORC1 activation is dependent on mitochondrial ETC capacity of HSPCs. Moreover, expression of PGC-1 family members, proteins that regulate mitochondrial biogenesis, in HSPCs following 5-fluorouracil treatment changes; also, these proteins play a stage specific role in hematopoietic recovery. While PRC regulates HSCs' expansion during early recovery phase, PGC-1α regulates progenitor cell proliferation and recovery of hematopoiesis during later phase. During early recovery phase, PRC expression, mitochondrial activity and mTORC1 activation are relatively higher in PGC-1α−/− HSCs compared to WT HSCs, and PGC-1α−/− HSCs show greater expansion. Administration of rapamycin, but not NAC, during early recovery phase improves WT HSC numbers but decreases PGC-1α−/− HSC numbers. The current findings demonstrate that mTOR activation can increase HSC numbers provided that the energy demand created by mTOR activation is successfully met. Thus, critical tuning between mTORC1 activation and mitochondrial ETC capacity is crucial for HSC maintenance/expansion in response to mitogenic stimulation.

  19. Main: 1QNB [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available itiation Factor Tfiid-1; Chain: A, B; Synonym: Tata-Box Factor 1, Tata Sequence-Binding Protein 1, Tbp1; Eng...ineered: Yes; Molecule: Dna (5'-D(*Gp*Cp*Tp*Ap*Tp*Ap*Ap*Ap*Tp*Gp*Gp*Gp*Cp*A)-3'); Chai...n: C, E; Molecule: Dna (5'-D(*Tp*Gp*Cp*Cp*Cp*Ap*Tp*Tp*Tp*Ap*Tp*Ap*Gp*C)-3'); Chain: D, F Tata Box-Bindi

  20. Main: 1QNA [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available itiation Factor Tfiid-1; Chain: A, B; Synonym: Tata-Box Factor 1, Tata Sequence-Binding Protein 1, Tbp1; Eng...ineered: Yes; Molecule: Dna (5'-D(*Gp*Cp*Tp*Tp*Tp*Ap*Ap*Ap*Ap*Gp*Gp*Gp*Cp*A)-3'); Chai...n: C, E; Molecule: Dna (5'-D(*Tp*Gp*Cp*Cp*Cp*Tp*Tp*Tp*Tp*Ap*Ap*Ap*Gp*C)-3'); Chain: D, F Tata Box-Bindi

  1. Caenorhabditis elegans battling starvation stress: low levels of ethanol prolong lifespan in L1 larvae.

    Directory of Open Access Journals (Sweden)

    Paola V Castro

    Full Text Available The nematode Caenorhabditis elegans arrests development at the first larval stage if food is not present upon hatching. Larvae in this stage provide an excellent model for studying stress responses during development. We found that supplementing starved larvae with ethanol markedly extends their lifespan within this L1 diapause. The effects of ethanol-induced lifespan extension can be observed when the ethanol is added to the medium at any time between 0 and 10 days after hatching. The lowest ethanol concentration that extended lifespan was 1 mM (0.005%; higher concentrations to 68 mM (0.4% did not result in increased survival. In spite of their extended survival, larvae did not progress to the L2 stage. Supplementing starved cultures with n-propanol and n-butanol also extended lifespan, but methanol and isopropanol had no measurable effect. Mass spectrometry analysis of nematode fatty acids and amino acids revealed that L1 larvae can incorporate atoms from ethanol into both types of molecules. Based on these data, we suggest that ethanol supplementation may extend the lifespan of L1 larvae by either serving as a carbon and energy source and/or by inducing a stress response.

  2. A Busy period analysis for the state dependent M/M/1/K queue

    NARCIS (Netherlands)

    Al Hanbali, Ahmad; Boxma, Onno

    2010-01-01

    In this paper, we study the transient behavior of a state dependent M/M/1/K queue during the busy period. We derive in closed-form the joint transform of the length of the busy period, the number of customers served during the busy period, and the number of losses during the busy period. For two

  3. Interactions between the HIV-1 Unspliced mRNA and Host mRNA Decay Machineries

    Directory of Open Access Journals (Sweden)

    Daniela Toro-Ascuy

    2016-11-01

    Full Text Available The human immunodeficiency virus type-1 (HIV-1 unspliced transcript is used both as mRNA for the synthesis of structural proteins and as the packaged genome. Given the presence of retained introns and instability AU-rich sequences, this viral transcript is normally retained and degraded in the nucleus of host cells unless the viral protein REV is present. As such, the stability of the HIV-1 unspliced mRNA must be particularly controlled in the nucleus and the cytoplasm in order to ensure proper levels of this viral mRNA for translation and viral particle formation. During its journey, the HIV-1 unspliced mRNA assembles into highly specific messenger ribonucleoproteins (mRNPs containing many different host proteins, amongst which are well-known regulators of cytoplasmic mRNA decay pathways such as up-frameshift suppressor 1 homolog (UPF1, Staufen double-stranded RNA binding protein 1/2 (STAU1/2, or components of miRNA-induced silencing complex (miRISC and processing bodies (PBs. More recently, the HIV-1 unspliced mRNA was shown to contain N6-methyladenosine (m6A, allowing the recruitment of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2, an m6A reader host protein involved in mRNA decay. Interestingly, these host proteins involved in mRNA decay were shown to play positive roles in viral gene expression and viral particle assembly, suggesting that HIV-1 interacts with mRNA decay components to successfully accomplish viral replication. This review summarizes the state of the art in terms of the interactions between HIV-1 unspliced mRNA and components of different host mRNA decay machineries.

  4. M2-F1 in flight being towed by a C-47

    Science.gov (United States)

    1964-01-01

    The M2-F1 Lifting Body is seen here being towed behind a C-47 at the Flight Research Center (later redesignated the Dryden Flight Research Center), Edwards, California. In this rear view, the M2-F1 is flying above and to one side of the C-47. This was done to avoid wake turbulence from the towplane. Lacking wings, the M2-F1 used an unusual configuration for its control surfaces. It had two rudders on the fins, two elevons (called 'elephant ears') mounted on the outsides of the fins, and two body flaps on the upper rear fuselage. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. These initial tests produced enough flight data about the M2-F1 to proceed with flights behind the C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and

  5. Arctigenin exerts anti-colitis efficacy through inhibiting the differentiation of Th1 and Th17 cells via an mTORC1-dependent pathway.

    Science.gov (United States)

    Wu, Xin; Dou, Yannong; Yang, Yan; Bian, Difei; Luo, Jinque; Tong, Bei; Xia, Yufeng; Dai, Yue

    2015-08-15

    Arctigenin, the main effective constituent of Arctium lappa L. fruit, has previously been proven to dramatically attenuate dextran sulfate sodium (DSS)-induced colitis in mice, a frequently used animal model of inflammatory bowel disease (IBD). As Th1 and Th17 cells play a crucial role in the pathogenesis of IBD, the present study addressed whether and how arctigenin exerted anti-colitis efficacy by interfering with the differentiation and activation of Th1/Th17 cells. In vitro, arctigenin was shown to markedly inhibit the differentiation of Th17 cells from naïve T cells, and moderately inhibit the differentiation of Th1 cells, which was accompanied by lowered phosphorylation of STAT3 and STAT4, respectively. In contrast, arctigenin was lack of marked effect on the differentiation of either Th2 or regulatory T cells. Furthermore, arctigenin was shown to suppress the mammalian target of rapamycin complex 1 (mTORC1) pathway in T cells as demonstrated by down-regulated phosphorylation of the downstream target genes p70S6K and RPS6, and it functioned independent of two well-known upstream kinases PI3K/AKT and ERK. Arctigenin was also able to inhibit the activity of mTORC1 by dissociating raptor from mTOR. Interestingly, the inhibitory effect of arctigenin on T cell differentiation disappeared under a status of mTORC1 overactivation via knockdown of tuberous sclerosis complex 2 (TSC2, a negative regulator of mTORC1) or pretreatment of leucine (an agonist of mTOR). In DSS-induced mice, the inhibition of Th1/Th17 responses and anti-colitis effect of arctigenin were abrogated by leucine treatment. In conclusion, arctigenin ameliorates colitis through down-regulating the differentiation of Th1 and Th17 cells via mTORC1 pathway. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Protein phosphatase magnesium-dependent 1δ (PPM1D mRNA expression is a prognosis marker for hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Guang-Bing Li

    Full Text Available Protein phosphatase magnesium-dependent 1δ (PPM1D is an oncogene, overexpressed in many solid tumors, including ovarian cancer and breast cancer. The current study examined the expression and the prognostic value of PPM1D mRNA in human hepatocellular carcinoma (HCC.Total RNA was extracted from 86 HCC and paired non-cancerous liver tissues. PPM1D mRNA expression was determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qPCR. Immunohistochemistry assay was used to verify the expression of ppm1d protein in the HCC and non-cancerous liver tissues. HCC patients were grouped according to PPM1D mRNA expression with the average PPM1D mRNA level in non-cancerous liver tissue samples as the cut-off. Correlations between clinicopathologic variables, overall survival and PPM1D mRNA expression were analyzed.PPM1D mRNA was significantly higher in HCC than in the paired non-cancerous tissue (p<0.01. This was confirmed by ppm1d staining. 56 patients were classified as high expression group and the other 30 patients were categorized as low expression group. There were significant differences between the two groups in term of alpha-fetoprotein (α-FP level (p<0.01, tumor size (p<0.01, TNM stage (p<0.01, recurrence incidence (p<0.01 and family history of liver cancer (p<0.01. The current study failed to find significant differences between the two groups in the following clinical characteristics: age, gender, portal vein invasion, lymphnode metastasis, hepatitis B virus (HBV infection and alcohol intake. Survival time of high expression group was significantly shorter than that of low expression group (median survival, 13 months and 32 months, respectively, p<0.01.Up-regulation of PPM1D mRNA was associated with progressive pathological feature and poor prognosis in HCC patients. PPM1D mRNA may serve as a prognostic marker in HCC.

  7. The Battle between Battery and Fuel Cell Powered Electric Vehicles: A BWM Approach

    Directory of Open Access Journals (Sweden)

    Geerten van de Kaa

    2017-10-01

    Full Text Available The transition to a more sustainable personal transportation sector requires the widespread adoption of electric vehicles. However, a dominant design has not yet emerged and a standards battle is being fought between battery and hydrogen fuel cell powered electric vehicles. The aim of this paper is to analyze which factors are most likely to influence the outcome of this battle, thereby reducing the uncertainty in the industry regarding investment decisions in either of these technologies. We examine the relevant factors for standard dominance and apply a multi-criteria decision-making method, best worst method, to determine the relative importance of these factors. The results indicate that the key factors include technological superiority, compatibility, and brand reputation and credibility. Our findings show that battery powered electric vehicles have a greater chance of winning the standards battle. This study contributes to theory by providing further empirical evidence that the outcome of standards battles can be explained and predicted by applying factors for standard success. We conclude that technology dominance in the automotive industry is mostly driven by technological characteristics and characteristics of the format supporter.

  8. Improved E-ELT subsystem and component specifications, thanks to M1 test facility

    Science.gov (United States)

    Dimmler, M.; Marrero, J.; Leveque, S.; Barriga, Pablo; Sedghi, B.; Kornweibel, N.

    2014-07-01

    During the last 2 years ESO has operated the "M1 Test Facility", a test stand consisting of a representative section of the E-ELT primary mirror equipped with 4 complete prototype segment subunits including sensors, actuators and control system. The purpose of the test facility is twofold: it serves to study and get familiar with component and system aspects like calibration, alignment and handling procedures and suitable control strategies on real hardware long before the primary mirror (hereafter M1) components are commissioned. Secondly, and of major benefit to the project, it offered the possibility to evaluate component and subsystem performance and interface issues in a system context in such detail, that issues could be identified early enough to feed back into the subsystem and component specifications. This considerably reduces risk and cost of the production units and allows refocusing the project team on important issues for the follow-up of the production contracts. Experiences are presented in which areas the results of the M1 Test Facility particularly helped to improve subsystem specifications and areas, where additional tests were adopted independent of the main test facility. Presented are the key experiences of the M1 Test Facility which lead to improved specifications or identified the need for additional testing outside of the M1 Test Facility.

  9. Los Alamos National Laboratory DOE M441.1-1 implementation

    International Nuclear Information System (INIS)

    Worl, Laura A.; Veirs, D. Kirk; Smith, Paul H.; Yarbro, Tresa F.; Stone, Timothy A.

    2010-01-01

    Loss of containment of nuclear material stored in containers such as food-pack cans, paint cans, or taped slip lid cans has generated concern about packaging requirements for interim storage of nuclear materials in working facilities such as the plutonium facility at Los Alamos National Laboratory (LANL). The Department of Energy (DOE) issued DOE M 441.1-1, Nuclear Materials Packaging Manual on March 7, 2008 in response to the Defense Nuclear Facilities Safety Board Recommendation 2005-1. The Manual directs DOE facilities to follow detailed packaging requirements to protect workers from exposure to nuclear materials stored outside of approved engineered-contamination barriers. Los Alamos National Laboratory has identified the activities that will be performed to bring LANL into compliance with DOE M 441.1-1. These include design, qualification and procurement of new containers, repackaging based on a risk-ranking methodology, surveillance and maintenance of containers, and database requirements. The primary purpose is to replace the out-dated nuclear material storage containers with more robust containers that meet present day safety and quality standards. The repackaging campaign is supported by an integrated risk reduction methodology to prioritize the limited resources to the highest risk containers. This methodology is systematically revised and updated based on the collection of package integrity data. A set of seven nested packages with built-in filters have been designed. These range in size from 1 qt. to 10 gallon. Progress of the testing to meet Manual requirements will be given. Due to the number of packages at LANL, repackaging to achieve full compliance will take five to seven years.

  10. β-adrenergic-stimulated macrophages: Comprehensive localization in the M1M2 spectrum

    Science.gov (United States)

    Lamkin, Donald M.; Ho, Hsin-Yun; Ong, Tiffany H.; Kawanishi, Carly K.; Stoffers, Victoria L.; Ahlawat, Nivedita; Ma, Jeffrey C.Y.; Arevalo, Jesusa M. G.; Cole, Steve W.; Sloan, Erica K.

    2016-01-01

    β-adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one predefined category of the M1M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages. PMID:27485040

  11. Development of high field superconducting Tokamak 'TRIAM-1M'

    International Nuclear Information System (INIS)

    Ito, Satoshi; Suzuki, Takao; Suzuki, Shohei; Nishi, Masatsugu; Kawasaki, Takahide.

    1984-01-01

    The tokamak nuclear fusion apparatus ''TRIAM-1M'' which is constructed in the Research Institute for Applied Mechanics, Kyushu University, has a number of distinctive features as compared with other tokamak projects, that is, the toroidal field coils are made of superconductors for the first time in Japan, and the apparatus is small and has strong magnetic field. Hitachi Ltd. designed and has forwarded the manufacture of the TRIAM-1M. In this paper, the total constitution of the apparatus and the design and manufacture of the plasma vacuum vessel, superconducting toroidal coils and others are reported. The objectives of research are the containment of strong field tokamak plasma and the establishment of the law of proportion, the development of turbulent flow heating method, the adoption of mixed wave current driving method and the practical use of Nb 3 Sn superconducting coils. The apparatus is composed of the vacuum vessel containing plasma, toroidal field coils, poloidal field coils, current transformer coils and turbulent flow heating coils for plasma heating, heat insulating vacuum vessel and supporting structures. The evacuating facility, helium liquefying refrigerator and cooling water facility are installed around the main body. (Kako, I.)

  12. What caused the rise of water level in the battle of Luermen bay in 1661? Tsunami, Storm surge, or Tide?

    Science.gov (United States)

    Wu, Tso-Ren; Wu, Han; Tsai, Yu-Lin

    2016-04-01

    In 1661, Chinese navy led by General Zheng Chenggong at the end of Ming Dynasty had a naval battle against Netherlands. This battle was not only the first official sea warfare that China confronted the Western world, but also the only naval battle won by Chinese Navy so far. This event was important because it changed the fate of Taiwan until today. One of the critical points that General Zheng won the battle was entering Luermen bay unexpected. Luermen bay was and is an extreme shallow bay with a 2.1m maximum water depth during the high tide, which was not possible for a fleet of 20,000 marines to across. Therefore, no defense was deployed from the Netherlands side. However, plenty of historical literatures mentioned a strange phenomenon that helped Chinese warships entered the Luermen bay, the rise of water level. In this study, we will discuss the possible causes that might rise the water level, e.g. Tsunami, storm surge, and high tide. We analyzed it based on the knowledge of hydrodynamics. We performed the newly developed Impact Intensify Analysis (IIA) for finding the potential tsunami sources, and the COMCOT tsunami model was adopted for the nonlinear scenario simulations, associated with the high resolution bathymetry data. Both earthquake and mudslide tsunamis were inspected. Other than that, we also collected the information of tide and weather for identifying the effects form high tide and storm surge. After the thorough study, a scenario that satisfy most of the descriptions in the historical literatures will be presented. The results will explain the cause of mysterious event that changed the destiny of Taiwan.

  13. The KEK 1 m hydrogen bubble chamber

    International Nuclear Information System (INIS)

    Doi, Yoshikuni; Araoka, Osamu; Hayashi, Kohei; Hayashi, Yoshio; Hirabayashi, Hiromi.

    1978-03-01

    A medium size hydrogen bubble chamber has been constructed at the National Laboratory for High Energy Physics, KEK. The bubble chamber has been designed to be operated with a maximum rate of three times per half a second in every two second repetition time of the accelerator, by utilizing a hydraulic expansion system. The bubble chamber has a one meter diameter and a visible volume of about 280 l. A three-view stereo camera system is used for taking photographic pictures of the chamber. A 2 MW bubble chamber magnet is constructed. The main part of the bubble chamber vessel is supported by the magnet yoke. The magnet gives a maximum field of 18.4 kG at the centre of the fiducial volume of the chamber. The overall system of the KEK 1 m hydrogen bubble chamber facility is described in some detail. Some operational characteristics of the facility are also reported. (auth.)

  14. China Dimensions Data Collection: China Administrative Regions GIS Data: 1:1M, County Level, 1 July 1990

    Data.gov (United States)

    National Aeronautics and Space Administration — China Administrative Regions GIS Data: 1:1M, County Level, 1 July 1990 consists of geographic boundary data for the administrative regions of China as of 1 July...

  15. Main: 1UVB [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available ativa Molecule: Nonspecific Lipid Transfer Protein; Synonym: Ltp 1, Pap 1; Chain: A; Other_details: Complexe...NMR; @=26-116.|PDB; 1RZL; X-ray; @=26-116.|Gramene; P23096; -.|InterPro; IPR003612; AAI....|InterPro; IPR000528; Plant_LTP.|Pfam; PF00234; Tryp_alpha_amyl; 1.|PRINTS; PR00382; LIPIDTRNSFER.|SMART; SM00499; AAI... 0.224, R-Free: 0.265 Length: 116 AA, Molecular weight: 11364 Da MARAQLVLVALVAALLLAAPHAAVAI

  16. Theoretical analyses of a 1.617-μm laser with a MOPA configuration

    Science.gov (United States)

    Cai, He; Han, Juhong; Wang, You; Rong, Kepeng; Yu, Hang; Wang, Shunyan; An, Guofei; Zhang, Wei; Wu, Peng; Yu, Qiang; Wang, Hongyuan

    2018-01-01

    In the recent years, lasers around 1.6 μm are attracted much attention since their wavelengths fit the atmospheric transmission window and can be used for applications in a range of fields including laser radar, gas sensing, and free-space communications. As one of the lasing wavelengths of an Er:YAG medium is just located in the 1.6 μm region, such a laser has been gaining more and more extensive applications in the near infrared. Until now, rare literatures have been found in the MOPA (Master Oscillator Power Amplifier) study of a 1.617 μm Er:YAG laser because the effect of upconversion will become greater while a higher doping concentration is adopted. In this study, we theoretically analyze the amplification features of a 1.617 μm Er:YAG seed laser by using a multiple MOPA configuration. In the simulation, a kinetic model is established to investigate how the doping concentration, crystal length, and pump power affect the amplification efficiency of a seed laser. The results would be helpful to construct a feasible 1.617 μm laser system.

  17. M1-transitions in the MIT bag model

    International Nuclear Information System (INIS)

    Hackman, R.H.; Deshpande, N.G.; Dicus, D.A.; Teplitz, V.L.

    1977-03-01

    In the MIT bag model, the M1-transitions of low lying hadrons are investigated. The following calculations are performed: 32 hadron masses are recomputed with a choice of bag parameters designed to give the correct values for the proton magnetic moment, μ/sub p/, and several masses, M/sub rho/ M/sub ω/ M/sub Δ/ M/sub Ω/, and M/sub D/; (2) eta, eta', eta/sub c/ mixing is computed in an untrustworthy approximation; and the widths for 38 M1-transitions are computed

  18. Quaternary Pt{sub 2}Ru{sub 1}Fe{sub 1}M{sub 1}/C (M=Ni, Mo, or W) catalysts for methanol electro-oxidation reaction

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Min Ku; Lee, Ki Rak; Kang, Kweon Ho; Park, Geun Il [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Jeon, Hyung Joon [Kyoto University, Kyoto (Japan); McGinn, Paul J. [University of Notre Dame, Indiana (United States)

    2015-02-15

    Quaternary Pt{sub 2}Ru{sub 1}Fe{sub 1}M{sub 1}/C (M=Ni, Mo, or W) catalysts were investigated for the methanol electro-oxidation reaction (MOR). Electrocatalytic activities of the quaternary catalysts for CO electro-oxidation were studied via CO stripping experiments, and the Pt{sub 2}Ru{sub 1}Fe{sub 1}Ni{sub 1}/C and Pt{sub 2}Ru{sub 1}Fe{sub 1}W{sub 1}/C catalysts exhibited lowered on-set potential compared to that of a commercial PtRu/C catalyst. MOR activities of the quaternary catalysts were determined by linear sweep voltammetry (LSV) experiments, and the Pt{sub 2}Ru{sub 1}Fe{sub 1}W{sub 1}/C catalyst outperformed the commercial PtRu/C catalyst by 170 and 150% for the mass and specific activities, respectively. X-ray photoelectron spectroscopy (XPS) was employed to analyze surface oxidation states of constituent atoms, and it was identified that the structure of the synthesized catalysts are close to a nano-composite of Pt and constituent metal hydroxides and oxides. In addition, the XPS results suggested that the bi-functional mechanism accounts for the improved performance of the Pt{sub 2}Ru{sub 1}Fe{sub 1}Ni{sub 1}/C and Pt{sub 2}Ru{sub 1} Fe{sub 1}W{sub 1}/C catalysts.

  19. Battle Experience; Solomon Islands Actions Information. Bulletin Number 4

    Science.gov (United States)

    1942-11-01

    IS SECONDARY TO TOR- PEDOES . THE FOUR DESTROYERS IN THE REAR COULD HAVE BEEN MORE EFFECTIVELY EMPLOYED IN THE VAN CONCENTRATED WITH THE OTHER...PROPERLY. THEY SHOULD BE USED OFFENSIVELY. THEIR TOR­ PEDOES ARE THEIR PRIMARY WEAPONS AND SHOULD BE USED PROPERLY AT EVERY OPPORTUNITY. Shortly after...is out in guns #4 and #5 but they still have power and battle lighting. All safety links on the torpedoes failed. Three torpedoes slid out of #1

  20. DNase Sda1 allows invasive M1T1 Group A Streptococcus to prevent TLR9-dependent recognition.

    Directory of Open Access Journals (Sweden)

    Satoshi Uchiyama

    Full Text Available Group A Streptococcus (GAS has developed a broad arsenal of virulence factors that serve to circumvent host defense mechanisms. The virulence factor DNase Sda1 of the hyperinvasive M1T1 GAS clone degrades DNA-based neutrophil extracellular traps allowing GAS to escape extracellular killing. TLR9 is activated by unmethylated CpG-rich bacterial DNA and enhances innate immune resistance. We hypothesized that Sda1 degradation of bacterial DNA could alter TLR9-mediated recognition of GAS by host innate immune cells. We tested this hypothesis using a dual approach: loss and gain of function of DNase in isogenic GAS strains and presence and absence of TLR9 in the host. Either DNA degradation by Sda1 or host deficiency of TLR9 prevented GAS induced IFN-α and TNF-α secretion from murine macrophages and contributed to bacterial survival. Similarly, in a murine necrotizing fasciitis model, IFN-α and TNF-α levels were significantly decreased in wild type mice infected with GAS expressing Sda1, whereas no such Sda1-dependent effect was seen in a TLR9-deficient background. Thus GAS Sda1 suppressed both the TLR9-mediated innate immune response and macrophage bactericidal activity. Our results demonstrate a novel mechanism of bacterial innate immune evasion based on autodegradation of CpG-rich DNA by a bacterial DNase.

  1. Radial Color Gradient in a Globular Cluster 1. M68

    Directory of Open Access Journals (Sweden)

    Sukyoung Yi

    1990-12-01

    Full Text Available Stars in M68 from the observed color-magnitude diagrams with CCD were integrated to find any radial gradient. The result shows that M68 has a slightly bluer core. The main cause of these calculated radial color variations seems to come from the random distribution of giants.

  2. Austrian Moderate Altitude Studies (AMAS): benefits of exposure to moderate altitudes (1,500-2,500 m).

    Science.gov (United States)

    Schobersberger, Wolfgang; Leichtfried, Veronika; Mueck-Weymann, Michael; Humpeler, Egon

    2010-09-01

    A considerable part of the millions of Alpine tourists suffer from pre-existing diseases (e.g., metabolic syndrome) and high daily stress levels. The main goal of the Austrian Moderate Altitude Study (AMAS) was to investigate (a) the consequences of an active vacation at moderate altitude on the key parameters of the metabolic syndrome (AMAS I) and (b) the effects of a short active vacation on adult progenitor cells, bio-psychological parameters, and heart rate variability (HRV). During the AMAS I pilot study (n = 22; 1,700 m a.s.l.) and AMAS I main study (n = 71; 1,700 m a.s.l. and 200 m a.s.l.), the volunteers simulated 3-week coached hiking vacations. For AMAS II, healthy volunteers (n = 13) participated in a 1-week active holiday at 1,700 m. There were significant improvements of obesity, hypertension, dyslipidemia, and insulin resistance of AMAS I patients after the vacation. In AMAS II participants, we found an increase in circulating endothelial progenitor cells as well as improvements in bio-psychological and HRV parameters. Active vacations at moderate altitude are associated with a variety of positive health effects in persons with metabolic syndrome and in healthy subjects.

  3. Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up-regulation of HO-1 in murine macrophages.

    Science.gov (United States)

    Xu, Xiaolong; Guo, Yuhong; Zhao, Jingxia; He, Shasha; Wang, Yan; Lin, Yan; Wang, Ning; Liu, Qingquan

    2017-09-01

    Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC 50 value of 1.04μM. Results from NPOI further showed that the K on and K off of PUN-PTP1B complex were 3.38e2M -1 s -1 and 4.13e-3s -1 , respectively. The active site Arg24 of PTP1B was identified as a key binding site of PUN by computation simulation and point mutation. Moreover, inhibition of PTP1B by PUN promoted an M2c-like macrophage polarization and enhanced anti-inflammatory cytokines expression, including IL-10 and M-CSF. Based on gene expression profile, we elucidated that PUN treatment significantly up-regulated 275 genes and down-regulated 1059 genes. M1-like macrophage marker genes, such as Tlr4, Irf1/2, Hmgb1, and Stat1 were down-regulated, while M2 marker genes, including Tmem171, Gpr35, Csf1, Il1rn, Cebpb, Fos, Vegfα, Slc11a1, and Bhlhe40 were up-regulated in PUN-treated macrophages. Hmox-1, a gene encoding HO-1 protein, was preferentially expressed with 16-fold change. Inhibition of HO-1 obviously restored PUN-induced M2 polarization and IL-10 secretion. In addition, phosphorylation of both Akt and STAT3 contributed to PUN-induced HO-1 expression. This study provided new insights into the mechanisms of PUN-mediated anti-inflammatory and anti-oxidant activities and provided new therapeutic strategies for inflammatory diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. A new and efficient culture method for porcine bone marrow-derived M1- and M2-polarized macrophages.

    Science.gov (United States)

    Gao, Jiye; Scheenstra, Maaike R; van Dijk, Albert; Veldhuizen, Edwin J A; Haagsman, Henk P

    2018-06-01

    Macrophages play an important role in the innate immune system as part of the mononuclear phagocyte system (MPS). They have a pro-inflammatory signature (M1-polarized macrophages) or anti-inflammatory signature (M2-polarized macrophages) based on expression of surface receptors and secretion of cytokines. However, very little is known about the culture of macrophages from pigs and more specific about the M1 and M2 polarization in vitro. Porcine monocytes or mononuclear bone marrow cells were used to culture M1- and M2-polarized macrophages in the presence of GM-CSF and M-CSF, respectively. Surface receptor expression was measured with flow cytometry and ELISA was used to quantify cytokine secretion in response to LPS and PAM 3 CSK 4 stimulation. Human monocyte-derived macrophages were used as control. Porcine M1- and M2-polarized macrophages were cultured best using porcine GM-CSF and murine M-CSF, respectively. Cultures from bone marrow cells resulted in a higher yield M1- and M2-polarized macrophages which were better comparable to human monocyte-derived macrophages than cultures from porcine monocytes. Porcine M1-polarized macrophages displayed the characteristic fried egg shape morphology, lower CD163 expression and low IL-10 production. Porcine M2-polarized macrophages contained the spindle-like morphology, higher CD163 expression and high IL-10 production. Porcine M1- and M2-polarized macrophages can be most efficiently cultured from mononuclear bone marrow cells using porcine GM-CSF and murine M-CSF. The new culture method facilitates more refined studies of porcine macrophages in vitro, important for both porcine and human health since pigs are increasingly used as model for translational research. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Hsp70 cochaperones HspBP1 and BAG-1M differentially regulate steroid hormone receptor function.

    Directory of Open Access Journals (Sweden)

    Regina T Knapp

    Full Text Available Hsp70 binding protein 1 (HspBP1 and Bcl2-associated athanogene 1 (BAG-1, the functional orthologous nucleotide exchange factors of the heat shock protein 70 kilodalton (Hsc70/Hsp70 chaperones, catalyze the release of ADP from Hsp70 while inducing different conformational changes of the ATPase domain of Hsp70. An appropriate exchange rate of ADP/ATP is crucial for chaperone-dependent protein folding processes. Among Hsp70 client proteins are steroid receptors such as the glucocorticoid receptor (GR, the mineralocorticoid receptor (MR, and the androgen receptor (AR. BAG-1 diversely affects steroid receptor activity, while to date the influence of HspBP1 on steroid receptor function is mostly unknown. Here, we compared the influence of HspBP1 and BAG-1M on Hsp70-mediated steroid receptor folding complexes and steroid receptor activity. Coimmunoprecipitation studies indicated preferential binding of Hsp40 and the steroid receptors to BAG-1M as compared to HspBP1. Furthermore, Hsp70 binding to the ligand-binding domain of GR was reduced in the presence of HspBP1 but not in the presence of BAG-1M as shown by pull-down assays. Reporter gene experiments revealed an inhibitory effect on GR, MR, and AR at a wide range of HspBP1 protein levels and at hormone concentrations at or approaching saturation. BAG-1M exhibited a transition from stimulatory effects at low BAG-1M levels to inhibitory effects at higher BAG-1M levels. Overall, BAG-1M and HspBP1 had differential impacts on the dynamic composition of steroid receptor folding complexes and on receptor function with important implications for steroid receptor physiology.

  6. Induction of CYP1A1, CYP1A2, and CYP1B1 mRNAs by nitropolycyclic aromatic hydrocarbons in various human tissue-derived cells: chemical-, cytochrome P450 isoform-, and cell-specific differences

    Energy Technology Data Exchange (ETDEWEB)

    Iwanari, M.; Nakajima, M.; Yokoi, T. [Div. of Drug Metabolism, Kanazawa Univ., Kanazawa (Japan); Kizu, R.; Hayakawa, K. [Lab. of Hygienic Chemistry, Kanazawa Univ., Kanazawa (Japan)

    2002-06-01

    Nitropolycyclic aromatic hydrocarbons (NPAHs) are found in diesel exhaust and ambient air. NPAHs as well as polycyclic aromatic hydrocarbons (PAHs) are known to have mutagenicity, carcinogenicity, and endocrine-disruptive effects. In the present study, the inducibility of the human cytochrome P450-1 (CYP1) family by NPAHs was compared with those produced by their parent PAHs and some reductive metabolites, amino-PAHs. Furthermore, to investigate the differences in the inducibility of the CYP1 family in human tissues, various human tissue-derived cell lines, namely HepG2 (hepatocellular carcinoma), ACHN (renal carcinoma), A549 (lung carcinoma), MCF-7 (breast carcinoma), LS-180 (colon carcinoma), HT-1197 (bladder carcinoma), HeLa (cervix of uterus adenocarcinoma), OMC-3 (ovarian carcinoma), and NEC14 (testis embryonal carcinoma), were treated with NPAHs, PAHs, or amino-PAHs. The mRNA levels of CYP1A1, CYP1A2, and CYP1B1 were determined with reverse transcription-polymerase chain reaction (RT-PCR). The cell lines were classified into two groups: CYP1 inducible cell lines, comprising HepG2, MCF-7, LS-180, and OMC-3 cells, and CYP1 non-inducible cell lines, comprising ACHN, A549, HT-1197, HeLa, and NEC14 cells. In inducible cell lines, the induction profile of chemical specificity was similar for CYP1A1, CYP1A2, and CYP1B1, although the extent of induction differed among the cell lines and for the CYP isoforms. Pyrene, 1-nitropyrene, 1-aminopyrene, 1,3-, 1,6-, and 1,8-dinitropyrenes slightly induced CYP1 mRNAs, but 1,3-dinitropyrene produced a 6-fold induction of CYP1A1 mRNA in MCF-7 cells. 2-Nitrofluoranthene and 3-nitrofluoranthene exhibited stronger inducibility than fluoranthene in the inducible cell lines. 6-Nitrochrysene induced CYP1 mRNAs to the same extent or more potently than chrysene. The induction potencies of 6-nitrobenzo[a]pyrene and 7-nitrobenz[a]anthracene were weaker than those of their parents benzo[a]pyrene and benz[a]anthracene, respectively. This

  7. Mission hazard assessment for STARS Mission 1 (M1) in the Marshall Islands area

    Energy Technology Data Exchange (ETDEWEB)

    Outka, D.E.; LaFarge, R.A.

    1993-07-01

    A mission hazard assessment has been performed for the Strategic Target System Mission 1 (known as STARS M1) for hazards due to potential debris impact in the Marshall Islands area. The work was performed at Sandia National Laboratories as a result of discussion with Kwajalein Missile Range (KMR) safety officers. The STARS M1 rocket will be launched from the Kauai Test Facility (KTF), Hawaii, and deliver two payloads to within the viewing range of sensors located on the Kwajalein Atoll. The purpose of this work has been to estimate upper bounds for expected casualty rates and impact probability or the Marshall Islands areas which adjoin the STARS M1 instantaneous impact point (IIP) trace. This report documents the methodology and results of the analysis.

  8. The Ukraine Crisis: The Battle of Superpowers

    OpenAIRE

    Elmquist-Clausen, Caroline

    2016-01-01

    This project concerns the Ukraine crisis, and how the crisis can be explained as a battle between Russia and the West. The project takes it departure in neoclassical realism, and uses this theory to understand how the actors in the crisis balance each other. This project concerns the Ukraine crisis, and how the crisis can be explained as a battle between Russia and the West. The project takes it departure in neoclassical realism, and uses this theory to understand how the actors in the cri...

  9. Airland Battle Doctrine

    Science.gov (United States)

    1988-09-01

    Professional Paper 463 / September 1988 OTIC - EL cOPY V 0- 00 00 N Airland Battle Doctrine DTIC S ELECTE DEC 2 81988D Douglas W. Skinner Dcb A...missiles to ground targets. Initial deployment will be on the Army’s OV-i Bronco and the Air Force’s TR-l and C-18. This is another outgrowth of the

  10. Regulation of Human Macrophage M1M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1

    Directory of Open Access Journals (Sweden)

    Federica Raggi

    2017-09-01

    Full Text Available Macrophages (Mf are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1 and alternatively activated (anti-inflammatory M2 subsets. We present data showing that hypoxia hinders Mf polarization toward the M1 phenotype by decreasing the expression of T cell costimulatory molecules and chemokine homing receptors and the production of proinflammatory, Th1-priming cytokines typical of classical activation, while promoting their acquisition of phenotypic and secretory features of alternative activation. Furthermore, we identify the triggering receptor expressed on myeloid cells (TREM-1, a member of the Ig-like immunoregulatory receptor family, as a hypoxia-inducible gene in Mf and demonstrate that its engagement by an agonist Ab reverses the M2-polarizing effect of hypoxia imparting a M1-skewed phenotype to Mf. Finally, we provide evidence that Mf infiltrating the inflamed hypoxic joints of children affected by oligoarticular juvenile idiopatic arthritis express high surface levels of TREM-1 associated with predominant M1 polarization and suggest the potential of this molecule in driving M1 proinflammatory reprogramming in the hypoxic synovial environment.

  11. Regulation of Human Macrophage M1M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1

    Science.gov (United States)

    Raggi, Federica; Pelassa, Simone; Pierobon, Daniele; Penco, Federica; Gattorno, Marco; Novelli, Francesco; Eva, Alessandra; Varesio, Luigi; Giovarelli, Mirella; Bosco, Maria Carla

    2017-01-01

    Macrophages (Mf) are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1) and alternatively activated (anti-inflammatory M2) subsets. We present data showing that hypoxia hinders Mf polarization toward the M1 phenotype by decreasing the expression of T cell costimulatory molecules and chemokine homing receptors and the production of proinflammatory, Th1-priming cytokines typical of classical activation, while promoting their acquisition of phenotypic and secretory features of alternative activation. Furthermore, we identify the triggering receptor expressed on myeloid cells (TREM)-1, a member of the Ig-like immunoregulatory receptor family, as a hypoxia-inducible gene in Mf and demonstrate that its engagement by an agonist Ab reverses the M2-polarizing effect of hypoxia imparting a M1-skewed phenotype to Mf. Finally, we provide evidence that Mf infiltrating the inflamed hypoxic joints of children affected by oligoarticular juvenile idiopatic arthritis express high surface levels of TREM-1 associated with predominant M1 polarization and suggest the potential of this molecule in driving M1 proinflammatory reprogramming in the hypoxic synovial environment. PMID:28936211

  12. Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.

    Science.gov (United States)

    Farias, L H S; Rodrigues, A P D; Coêlho, E C; Santos, M F; Sampaio, S C; Silva, E O

    2017-09-01

    American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions. Thus, the main objective of this study was to evaluate whether CTX has a role in macrophage M1 polarization during Leishmania infection murine macrophages, Leishmania amazonensis promastigotes and L. amazonensis-infected macrophages were challenged with CTX. MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide] toxicity assays were performed on murine macrophages, and no damage was observed in these cells. Promastigotes, however, were affected by treatment with CTX (IC50 = 22·86 µg mL-1) as were intracellular amastigotes. Macrophages treated with CTX also demonstrated increased reactive oxygen species production. After they were infected with Leishmania, macrophages exhibited an increase in nitric oxide production that converged into an M1 activation profile, as suggested by their elevated production of the cytokines interleukin-6 and tumour necrosis factor-α and changes in their morphology. CTX was able to reverse the L. amazonensis-mediated inhibition of macrophage immune responses and is capable of polarizing macrophages to the M1 profile, which is associated with a better prognosis for cutaneous leishmaniasis treatment.

  13. mTORC1 is a critical mediator of oncogenic Semaphorin3A signaling

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Daisuke; Kawahara, Kohichi; Maeda, Takehiko, E-mail: maeda@nupals.ac.jp

    2016-08-05

    Aberration of signaling pathways by genetic mutations or alterations in the surrounding tissue environments can result in tumor development or metastasis. However, signaling molecules responsible for these processes have not been completely elucidated. Here, we used mouse Lewis lung carcinoma cells (LLC) to explore the mechanism by which the oncogenic activity of Semaphorin3A (Sema3A) signaling is regulated. Sema3A knockdown by shRNA did not affect apoptosis, but decreased cell proliferation in LLCs; both the mammalian target of rapamycin complex 1 (mTORC1) level and glycolytic activity were also decreased. In addition, Sema3A knockdown sensitized cells to inhibition of oxidative phosphorylation by oligomycin, but conferred resistance to decreased cell viability induced by glucose starvation. Furthermore, recombinant SEMA3A rescued the attenuation of cell proliferation and glycolytic activity in LLCs after Sema3A knockdown, whereas mTORC1 inhibition by rapamycin completely counteracted this effect. These results demonstrate that Sema3A signaling exerts its oncogenic effect by promoting an mTORC1-mediated metabolic shift from oxidative phosphorylation to aerobic glycolysis. -- Highlights: •Sema3A knockdown decreased proliferation of Lewis lung carcinoma cells (LLCs). •Sema3A knockdown decreased mTORC1 levels and glycolytic activity in LLCs. •Sema3A knockdown sensitized cells to inhibition of oxidative phosphorylation. •Sema3A promotes shift from oxidative phosphorylation to aerobic glycolysis via mTORC1.

  14. Main: AS1CAMV [PLACE

    Lifescience Database Archive (English)

    Full Text Available MV 35S promoter; from -85 to -58 (subdomain AI); Binding with ASF-1 (activation sequence factor 1) from pea ...and tobacco; Expression in root and leaf; CaMV 35S promoter; ASF-1; leaf; root; as-1; Cauliflower mosaic virus; CaMV; CCACTGACGTAAGGGATGACGCACAATCC ...

  15. Radiative rates for E1, E2, M1 and M2 transitions in Fe X

    International Nuclear Information System (INIS)

    Aggarwal, K.M.; Keenan, F.P.

    2004-01-01

    Energies of the 54 levels belonging to the (1s 2 2s 2 2p 6 ) 3s 2 3p 5 , 3s3p 6 , 3s 2 3p 4 3d and 3s3p 5 3d configurations of Fe X have been calculated using the GRASP code of Dyall and colleagues (1989). Additionally, radiative rates, oscillator strengths, and line strengths are calculated for all electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2), and magnetic quadrupole (M2) transitions among these levels. Comparisons are made with results available in the literature, and the accuracy of the data is assessed. Our energy levels are estimated to be accurate to better than 3%, whereas results for other parameters are probably accurate to better than 20% . Additionally, the agreement between measured and calculated lifetimes is better than 10%. (authors)

  16. Modification of barley powdery mildew resistance controlled by the gene M1-a212

    International Nuclear Information System (INIS)

    Torp, J.; Joergensen, J.H.

    1989-01-01

    Full text: The barley line Sultan 5 carries resistance gene M1-a12. Seeds were treated with EMS or NaN 3 . Among 10381 M 1 -spike progenies inoculated with M1-a12 a-virulent isolates of Erysiphe graminis, 25 segregated for less resistant infection type. Among 10 mutants analyzed, 9 had mutant allels of M1-a12 and one had a recessive mutant gene in a different locus acting as a ''suppressor'' of M1-a12. (author)

  17. Infrared (1.4-4.1μm) spectra of Wolf-Rayet stars

    International Nuclear Information System (INIS)

    Williams, P.M.

    1982-01-01

    The spectra of a variety of Wolf-Rayet stars have been observed with approximately 1% spectral resolution in the 1.4-4.1μm region using UKIRT. Strong lines due to ions of helium and carbon are observed and their relative strengths discussed. The He I singlet at 2.058μm is anomalously strong relative to other He I lines in WC stars and is responsible for the difference in the (H-K) colours of WN and WC stars. Emission line corrections to H, K and L magnitudes of different types are discussed. The Sanduleak O VI star ST 3 shows very strong C IV lines like the WC5 stars but not the strong He I. (Auth.)

  18. NFBD1/MDC1 participates in the regulation of G2/M transition in mammalian cells

    International Nuclear Information System (INIS)

    Bu, Youquan; Suenaga, Yusuke; Okoshi, Rintaro; Sang, Meixiang; Kubo, Natsumi; Song, Fangzhou; Nakagawara, Akira; Ozaki, Toshinori

    2010-01-01

    NFBD1/MDC1 is a large nuclear protein involved in the early cellular response to DNA damage. Upon DNA damage, NFBD1 has an ability to facilitate the efficient DNA repair. In the present study, we have found that, in addition to DNA damage response, NFBD1 plays a critical role in the regulation of G2/M transition. Expression study using synchronized HeLa cells demonstrated that, like the mitotic kinase Plk1, NFBD1 expression level is maximal in G2/M-phase of the cell cycle. siRNA-mediated knockdown of NFBD1 resulted in G2/M arrest as well as simultaneous apoptosis in association with a significant increase in the amounts of γH2AX and pro-apoptotic p73. Since a remarkable down-regulation of mitotic phospho-histone H3 was detectable in NFBD1-knocked down cells, it is likely that knocking down of NFBD1 inhibits G2/M transition. Taken together, our present findings suggest that NFBD1 has a pivotal role in the regulation of proper mitotic entry.

  19. Up-regulation of A1M1-microglobulin in skin by heme and reactive oxygen species gives protection from oxidative damage.

    Science.gov (United States)

    Olsson, Magnus G; Allhorn, Maria; Larsson, Jörgen; Cederlund, Martin; Lundqvist, Katarina; Schmidtchen, Artur; Sørensen, Ole E; Mörgelin, Matthias; Akerström, Bo

    2011-01-01

    During bleeding the skin is subjected to oxidative insults from free heme and radicals, generated from extracellular hemoglobin. The lipocalin α(1)-microglobulin (A1M) was recently shown to have reductase properties, reducing heme-proteins and other substrates, and to scavenge heme and radicals. We investigated the expression and localization of A1M in skin and the possible role of A1M in the protection of skin tissue from damage induced by heme and reactive oxygen species. Skin explants, keratinocyte cultures and purified collagen I were exposed to heme, reactive oxygen species, and/or A1M and investigated by biochemical methods and electron microscopy. The results demonstrate that A1M is localized ubiquitously in the dermal and epidermal layers, and that the A1M-gene is expressed in keratinocytes and up-regulated after exposure to heme and reactive oxygen species. A1M inhibited the heme- and reactive oxygen species-induced ultrastructural damage, up-regulation of antioxidation and cell cycle regulatory genes, and protein carbonyl formation in skin and keratinocytes. Finally, A1M bound to purified collagen I (K(d) = 0.96×10(-6) M) and could inhibit and repair the destruction of collagen fibrils by heme and reactive oxygen species. The results suggest that A1M may have a physiological role in protection of skin cells and matrix against oxidative damage following bleeding.

  20. mTOR complex 1: a key player in neuroadaptations induced by drugs of abuse.

    Science.gov (United States)

    Neasta, Jeremie; Barak, Segev; Hamida, Sami Ben; Ron, Dorit

    2014-07-01

    The mammalian (or mechanistic) target of rapamycin (mTOR) complex 1 (mTORC1) is a serine and threonine kinase that regulates cell growth, survival, and proliferation. mTORC1 is a master controller of the translation of a subset of mRNAs. In the central nervous system mTORC1 plays a crucial role in mechanisms underlying learning and memory by controlling synaptic protein synthesis. Here, we review recent evidence suggesting that the mTORC1 signaling pathway promotes neuroadaptations following exposure to a diverse group of drugs of abuse including stimulants, cannabinoids, opiates, and alcohol. We further describe potential molecular mechanisms by which drug-induced mTORC1 activation may alter brain functions. Finally, we propose that mTORC1 is a focal point shared by drugs of abuse to mediate drug-related behaviors such as reward seeking and excessive drug intake, and offer future directions to decipher the contribution of the kinase to mechanisms underlying addiction. Recent studies suggesting that exposure to diverse classes of drugs of abuse as well as exposure to drug-associated memories lead to mTORC1 kinase activation in the limbic system. In turn, mTORC1 controls the onset and the maintenance of pathological neuroadaptions that underlie several features of drug addiction such as drug seeking and relapse. Therefore, we propose that targeting mTORC1 and its effectors is a promising strategy to treat drug disorders. © 2014 International Society for Neurochemistry.

  1. Forbidden Raman scattering processes. I. General considerations and E1--M1 scattering

    International Nuclear Information System (INIS)

    Harney, R.C.

    1979-01-01

    The generalized theory of forbidden Raman scattering processes is developed in terms of the multipole expansion of the electromagnetic interaction Hamiltonian. Using the general expressions, the theory of electric dipole--magnetic dipole (E1--M1) Raman scattering is derived in detail. The 1 S 0 → 3 P 1 E1--M1 Raman scattering cross section in atomic magnesium is calculated for two applicable laser wavelengths using published f-value data. Since resonantly enhanced cross sections larger than 10 -29 cm 2 /sr are predicted it should be possible to experimentally observe this scattering phenomenon. In addition, by measuring the frequency dependence of the cross section near resonance, it may be possible to directly determine the relative magnitudes of the Axp and AxA contributions to the scattering cross section. Finally, possible applications of the effect in atomic and molecular physics are discussed

  2. Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.

    Science.gov (United States)

    Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klüter, Harald; Gratchev, Alexei; Harmsen, Martin C; Kzhyshkowska, Julia

    2017-10-01

    Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications. Copyright © 2016 Elsevier GmbH. All rights reserved.

  3. The WA105-3x1x1 m3 dual phase LAr-TPC demonstrator

    CERN Document Server

    Murphy, Sebastien

    2016-11-15

    The dual phase Liquid Argon Time Projection Chamber (LAr TPC) is the state-of-art technology for neutrino detection thanks to its superb 3D tracking and calorimetry performance. Its main feature is the charge amplification in gas argon which provides excellent signal-to-noise ratio. Electrons produced in the liquid argon are extracted in the gas phase. Here, a readout plane based on Large Electron Multiplier detectors provides amplification of the charges before its collection onto an anode with strip readout. The charge amplification enables constructing fully homoge- nous giant LAr-TPCs with tuneable gain, excellent charge imaging performance and increased sensitivity to low energy events. Following a staged approach the WA105 collaboration is con- structing a dual phase LAr-TPC with an active volume of 3x1x1m3 that will soon be tested with cosmic rays. Its construction and operation aims to test scalable solutions for the crucial aspects of this technology: ultra high argon purity in non-evacuable tank, la...

  4. Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation

    Science.gov (United States)

    Melnik, Bodo C.

    2015-01-01

    Based on own translational research of the biochemical and hormonal effects of cow’s milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. Milk is sufficient to activate mTORC1, the crucial regulator of protein, lipid, and nucleotide synthesis orchestrating anabolism, cell growth and proliferation. To fulfill its mTORC1-activating function, milk delivers four key metabolic messengers: (1) essential branched-chain amino acids (BCAAs); (2) glutamine; (3) palmitic acid; and (4) bioactive exosomal microRNAs, which in a synergistical fashion promote mTORC1-dependent translation. In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER) stress and drives an aimless quasi-program, which promotes aging and age-related diseases. PMID:26225961

  5. Milk—A Nutrient System of Mammalian Evolution Promoting mTORC1-Dependent Translation

    Directory of Open Access Journals (Sweden)

    Bodo C. Melnik

    2015-07-01

    Full Text Available Based on own translational research of the biochemical and hormonal effects of cow’s milk consumption in humans, this review presents milk as a signaling system of mammalian evolution that activates the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1, the pivotal regulator of translation. Milk, a mammary gland-derived secretory product, is required for species-specific gene-nutrient interactions that promote appropriate growth and development of the newborn mammal. This signaling system is highly conserved and tightly controlled by the lactation genome. Milk is sufficient to activate mTORC1, the crucial regulator of protein, lipid, and nucleotide synthesis orchestrating anabolism, cell growth and proliferation. To fulfill its mTORC1-activating function, milk delivers four key metabolic messengers: (1 essential branched-chain amino acids (BCAAs; (2 glutamine; (3 palmitic acid; and (4 bioactive exosomal microRNAs, which in a synergistical fashion promote mTORC1-dependent translation. In all mammals except Neolithic humans, postnatal activation of mTORC1 by milk intake is restricted to the postnatal lactation period. It is of critical concern that persistent hyperactivation of mTORC1 is associated with aging and the development of age-related disorders such as obesity, type 2 diabetes mellitus, cancer, and neurodegenerative diseases. Persistent mTORC1 activation promotes endoplasmic reticulum (ER stress and drives an aimless quasi-program, which promotes aging and age-related diseases.

  6. Characterization of a major late herpes simplex virus type 1 mRNA.

    Science.gov (United States)

    Costa, R H; Devi, B G; Anderson, K P; Gaylord, B H; Wagner, E K

    1981-05-01

    A major, late 6-kilobase (6-kb) mRNa mapping in the large unique region of herpes simplex virus type 1 (HSV-1) was characterized by using two recombinant DNA clones, one containing EcoRI fragment G (0.190 to 0.30 map units) in lambda. WES.B (L. Enquist, M. Madden, P. Schiop-Stansly, and G. Vandl Woude, Science 203:541-544, 1979) and one containing HindIII fragment J (0.181 to 0.259 map units) in pBR322. This 6-kb mRNA had its 3' end to the left of 0.231 on the prototypical arrangement of the HSV-1 genome and was transcribed from right to left. It was bounded on both sides by regions containing a large number of distinct mRNA species, and its 3' end was partially colinear with a 1.5-kb mRNA which encoded a 35,000-dalton polypeptide. The 6-kb mRNA encoded a 155,000-dalton polypeptide which was shown to be the only one of this size detectable by hybrid-arrested translation encoded by late polyadenylated polyribosomal RNA. The S1 nuclease mapping experiments indicated that there were no introns in the coding sequence for this mRNA and that its 3' end mapped approximately 800 nucleotides to the left of the BglII site at 0.231, whereas its 5' end extended very close to the BamHI site at 0.266.

  7. N,N'-di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1) suppresses the proliferation of PANC-1 pancreatic cancer cells via apoptosis and G2/M cell cycle arrest.

    Science.gov (United States)

    Chen, Su-Feng; Xia, Jun; Lv, Ya-Ping; Liu, Jin-Lin; Li, Wan-Xiang; Yu, Xi-Ping; Hu, Wei-Xiao; Zhou, Yong-Lie

    2015-04-01

    Pancreatic cancer is one of the human gastrointestinal malignancies with a high mortality and poor prognosis. Approximately eighty percent of patients are diagnosed with unresectable or metastatic disease. Thus, development of novel chemicals in the treatment of pancreatic cancer is imperative. This study aimed to investigate the anticancer effects of N,N'-di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1), a new tetrazine derivative, on the PANC-1 pancreatic cancer cell line and clarify the underlying molecular mechanism. Using an MTT assay, we found that ZGDHu-1 significantly suppressed the proliferation of PANC-1 cells in a time- and dose-dependent manner. Moreover, according to the morphological and flow cytometric analysis, the results indicated that ZGDHu-1 induced PANC-1 cell apoptosis and G2/M cell cycle arrest in a dose-dependent manner. In the western blot analysis, expression of the pro-apoptotic Bax gene was upregulated while the anti-apoptotic Bcl-2 gene was downregulated following treatment with ZGDHu-1. ZGDHu-1 also activated pro-caspase-3 and PARP and increased the expression of NF-κB inhibitor IκB. Furthermore, the expression levels of G2/M regulatory molecules such as cyclin B1 and cdc2 were decreased while that of Chk1 was increased. These results suggested that ZGDHu-1 suppressed the proliferation of pancreatic cancer cells, rendering it a potential therapeutic drug for the treatment of pancreatic cancer.

  8. Fabrication of 1m x 1m readout strips panel and quality verification of new set of SFS dielectric material

    International Nuclear Information System (INIS)

    Kumar, A.; Pandey, A.; Sogarwal, Hariom; Marimuthu, N.; Singh, V.; Subrahmanyam, V.S.

    2016-01-01

    India based Neutrino Observatory (INO) is going to use ∼ 30,000 Resistive Plate Chamber (RPC) as an active detector. Resistive Plate chambers are parallel plate fast gaseous detector made up of high resistivity (10"1"2 ohm) of glass or bakelite. Glass plates work as electrodes of positive and negative potential. When a charged particle passes through chamber it ionizes the gas and charge move towards opposite electrodes. The pick-up panels pick these signals. Signals are sent to front end electronics. The characteristic impedance of the strips of the panels should be matched with front end electronics which helps in minimizing the reflected signal. Since INO is an underground laboratory, all material used in it must be fireproof. Since ∼ 60,000 pick-up panels are going to be used in INO hence it should be cheaper also. We recently received a new set of Silicon Fiber Sheets - a dielectric material, of 25 pieces of 1m x 0.5m having thickness 05 mm. We fabricated a set of readout strips panel of dimension 1m x 1m. We will present this work in detail

  9. Combined glutathione S transferase M1/T1 null genotypes is associated with type 2 diabetes mellitus

    Science.gov (United States)

    POROJAN, MIHAI D.; BALA, CORNELIA; ILIES, ROXANA; CATANA, ANDREEA; POPP, RADU A.; DUMITRASCU, DAN L.

    2015-01-01

    Background Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population. Methods We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons. Results Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852–2.447; p=0.647, OR=0.854, CI=0.436–1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149–0.655) Conclusions The main finding of our study is that the combined, double GSTM1/GSTT1 null genotypes are to be considered among the polymorphic genetic risk factors for type 2 DM. PMID:26528065

  10. Symbiotic nature of the object M1-77

    International Nuclear Information System (INIS)

    Kondrt'eva, L.N.

    2004-01-01

    Many year spectral observations show, that the object M1-77 is the symbiotic system, which consists of a M-giant and a B-star. An emission spectra arises from an envelope, which was formed from a giant's extended atmosphere, and now is ionized by the hotter component. Some spectral changes were registered in M1-77: the forbidden lines intensities increase relatively to that of Hα. It is connected with the decrease of hydrogen emission. (author)

  11. A novel link between Sus1 and the cytoplasmic mRNA decay machinery suggests a broad role in mRNA metabolism

    Directory of Open Access Journals (Sweden)

    Llopis Ana

    2010-03-01

    Full Text Available Abstract Background Gene expression is achieved by the coordinated action of multiple factors to ensure a perfect synchrony from chromatin epigenetic regulation through to mRNA export. Sus1 is a conserved mRNA export/transcription factor and is a key player in coupling transcription initiation, elongation and mRNA export. In the nucleus, Sus1 is associated to the transcriptional co-activator SAGA and to the NPC associated complex termed TREX2/THSC. Through these associations, Sus1 mediates the nuclear dynamics of different gene loci and facilitate the export of the new transcripts. Results In this study, we have investigated whether the yeast Sus1 protein is linked to factors involved in mRNA degradation pathways. We provide evidence for genetic interactions between SUS1 and genes coding for components of P-bodies such as PAT1, LSM1, LSM6 and DHH1. We demonstrate that SUS1 deletion is synthetic lethal with 5'→3' decay machinery components LSM1 and PAT1 and has a strong genetic interaction with LSM6 and DHH1. Interestingly, Sus1 overexpression led to an accumulation of Sus1 in cytoplasmic granules, which can co-localise with components of P-bodies and stress granules. In addition, we have identified novel physical interactions between Sus1 and factors associated to P-bodies/stress granules. Finally, absence of LSM1 and PAT1 slightly promotes the Sus1-TREX2 association. Conclusions In this study, we found genetic and biochemical association between Sus1 and components responsible for cytoplasmic mRNA metabolism. Moreover, Sus1 accumulates in discrete cytoplasmic granules, which partially co-localise with P-bodies and stress granules under specific conditions. These interactions suggest a role for Sus1 in gene expression during cytoplasmic mRNA metabolism in addition to its nuclear function.

  12. Quadrupole decay strength of the M1 scissors mode of {sup 156}Gd

    Energy Technology Data Exchange (ETDEWEB)

    Beck, T.; Beller, J.; Gayer, U.; Mertes, L.; Pai, H.; Pietralla, N.; Ries, P.; Romig, C.; Werner, V.; Zweidinger, M. [IKP, TU Darmstadt (Germany); Derya, V. [IKP, Universitaet zu Koeln (Germany); Isaak, J.; Loeher, B.; Savran, D. [EMMI, GSI, Darmstadt (Germany); FIAS, Frankfurt (Germany); Scheck, M. [IKP, TU Darmstadt (Germany); School of Engineering, UWS, Paisley (United Kingdom); SUPA, Glasgow (United Kingdom); Tornow, W.; Weller, H.R. [Duke University, Durham (United States)

    2015-07-01

    The isovector low-lying J{sup π}{sub K}=1{sup +}{sub 1} scissors mode of deformed nuclei has been studied extensively in (e,e{sup '}) and (γ,γ{sup '}) experiments over the last 30 years with the main focus on strong M1 transitions to the ground state band. In the framework of the semiclassical two-rotor-model it has its origin in quadrupole deformation. A considerable E2 matrix element between the rotational band of the scissors mode and the ground band is predicted which has not been addressed experimentally. A photon-scattering experiment with linearly-polarized quasi monoenergetic vector (γ)-rays has been performed at the High Intensity vector (γ)-ray Source (HIvector (γ)S) at Duke University, Durham, NC, exploiting the γ{sup 3} setup. We have measured an E2/M1-multipole mixing ratio for the 1{sup +}{sub sc}→2{sup +}{sub 1} transition for the first time. The Alaga rule is applicable and delivers a first estimate of the transition strength B(E2:2{sup +}{sub sc}→0{sup +}{sub 1}). A candidate for a 2{sup +}{sub sc}→2{sup +}{sub 1} transition is discussed.

  13. Controlled 1.1-1.6 μm luminescence in gold-free multi-stacked InAs/InP heterostructure nanowires.

    Science.gov (United States)

    Zhang, Guoqiang; Tateno, Kouta; Birowosuto, Muhammad Danang; Notomi, Masaya; Sogawa, Tetsuomi; Gotoh, Hideki

    2015-03-20

    We report controlled 1.1-1.6 μm luminescence in gold-free multi-stacked InAs/InP heterostructure nanowires (NWs). We realized the NWs by using an indium-particle-assisted vapor-liquid-solid synthesis approach. The growth temperature, as low as 320 °C, enables the formation of an atomically abrupt InP/InAs interface by supressing the diffusion and weakening the reservoir effect in the indium droplet. The low growth temperature also enables us to grow multi-stacked InAs/InP NWs in the axial direction without any growth on the NW side face. The high controllability of the growth technology ensures that the luminescence can be tailored by the thickness of InAs segment in InP NWs and cover the 1.3-1.5 μm telecommunication window range. By using the nanoscale-spatial-resolution technology combing cathodoluminescence with scanning electron microscopy, we directly correlated the site of different-thickness InAs segments with its luminescence property in a single NW and demonstrate the InAs-thickness-controlled energy of optical emission in 1.1-1.6 μm.

  14. The Battle for Okinawa: A Direct Approach for Direct Defeat

    National Research Council Canada - National Science Library

    Robling, Terry

    1995-01-01

    Throughout the fall of 1944 and early spring of 1945, the Japanese defenders of Okinawa prepared a defensive battle strategy that resulted in Japanese defeat and the most casualties for both forces...

  15. Impaired endothelial barrier function in apolipoprotein M-deficient mice is dependent on sphingosine-1-phosphate receptor 1

    DEFF Research Database (Denmark)

    Christensen, Pernille M; Liu, Catherine H; Swendeman, Steven L

    2016-01-01

    Apolipoprotein M (ApoM) transports sphingosine-1-phosphate (S1P) in plasma, and ApoM-deficient mice (Apom(-/-)) have ∼50% reduced plasma S1P levels. There are 5 known S1P receptors, and S1P induces adherens junction formation between endothelial cells through the S1P1 receptor, which in turn...... suppresses vascular leak. Increased vascular permeability is a hallmark of inflammation. The purpose of this study was to explore the relationships between vascular leakage in ApoM deficiency and S1P1 function in normal physiology and in inflammation. Vascular permeability in the lungs was assessed...... by accumulation of dextran molecules (70 kDa) and was increased ∼40% in Apom(-/-) mice compared to WT (C57Bl6/j) mice. Reconstitution of plasma ApoM/S1P or treatment with an S1P1 receptor agonist (SEW2871) rapidly reversed the vascular leakage to a level similar to that in WT mice, suggesting that it is caused...

  16. Main: 1HXJ [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available Mays Molecule: Beta-Glucosidase; Chain: A, B; Synonym: Gentiobiase, Cellobiase, Beta-D-Glucoside Glucohydro...nctional Architecture Of The Catalytic Center Of A Maize Beta-Glucosidase Zm-P60.1 Plant Physiol. V. 127 973...|PDB; 1HXJ; X-ray; A/B=60-566.|Maize-2DPAGE; P49235; COLEOPTILE.|MaizeDB; 13870;

  17. Main: 1UHT [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 85c Name=Dl3285c; Synonyms=At4g14490, At4g14490; Arabidopsis Thaliana Molecule: Expressed Protein; Chain: A;... Fragment: Forkhead Associated Domain, Fha Domain; Synonym: Hypothetical Protein; Engineered: Yes Structural..., T.Terada, T.Yabuki, M.Aoki, T.Matsuda, E.Seki, H.Hirota, M.Yoshida, A.Tanaka, T.Osanai, K.Shinozaki, M.Sek....Matsuda, E.Seki, H.Hirota, M.Yoshida, A.Tanaka, T.Osanai, K.Shinozaki, M.Seki, T....Kigawa, S.Yokoyama Solution Structure Of The Fha Domain Of Arabidopsis Thaliana Hypothetical Protein To Be Published Fha Domai

  18. Main sequence of the metal-poor globular cluster M30 (NGC 7099)

    International Nuclear Information System (INIS)

    Alcaino, G.; Liller, W.

    1980-01-01

    We present photographic photometry for 673 stars in the metal-poor globular cluster M30 (NGC 7099). The Racine wedge was used with the CTIO 1-m Yale telescope (Δm=3/sup m/.60), the CTIO 4-m telescope (Δm=6/sup m/.83), and the ESO 3.6-m telescope (Δm=4/sup m/.12) to extend the photoelectric limit from Vapprox. =16.3 to Vapprox. =20.4. For the main-sequence turn-off, we have determined its position to lie at V=18.4 +- 0.1 (m.e.) and B-V=0.49 +- 0.03 (m.e.). From these values, we calculate the intrinsic values M/sub v/ =3.87 and (B-V) 0 =0.47. For the cluster as a whole, we derive a distance modulus (m-M)/sub V/=14.53 +- 0.15 and reddening E(B-V)=0.02 +- 0.02. Using the models of Iben and Rood [Astrophys. J. 159, 605 (1970)] and the isochrones of Demarque and McClure [(1977), in Evolution of Galaxies and Stellar Populations, edited by B. Tinsley and R. B. Larson (Yale University Observatory, New Haven), p. 199], we deduce the cluster's age to be 14.5( +- 4.0) x 10 9 yr. The large uncertainty in this value emphasizes the dire need for more work on cluster evolution

  19. Optimisation of 1.3 μm strained-layer semiconductor lasers

    International Nuclear Information System (INIS)

    Pacey, C.

    1999-03-01

    -wells to the device length. The experimental study confirms the conclusions drawn in the theoretical investigation that the optimum structure for a 1.3 μm InGaAsP laser for low threshold current, high efficiency and high characteristic temperature operation consists of six 1% compressively strained 50 A quantum-wells in a device of medium length (approx. 450 μm). The inclusion of a high reflection coating on one facet provides further improvement in the device performance, but increases the production cost dramatically. Also investigated in the experimental section is the effect of changing the device material from InGaAsP to InGaAlAs. The results discussed do not offer firm evidence of any improvement in the device characteristics in switching from a P-based to an Al-based structure. This is mainly due to the added complication of switching to a RWG structure from a BH structure. Another explanation for the relatively poor performance of InGaAsP 1.3 μm lasers has been examined. That is leakage of the carriers out of the well region. Evidence of a leakage current has been seen primarily in devices with a low number of quantum-wells. A novel measurement technique has been demonstrated, which should prove useful for obtaining a numerical value for the leakage current in semiconductor lasers. The results presented suggest that leakage current is not significant for a 9 well device until operating at temperatures above around 373 K. This is supported by evidence supplied by the spontaneous emission spectra. (author)

  20. The mutual dependence of M1 fertility and M2 mutations in rice

    International Nuclear Information System (INIS)

    Gopinathan Nair, V.

    1982-01-01

    The mutual dependence of M 1 fertility and M 2 mutations in rice was studied after treatment with gamma rays and EMS. The frequency of chlorophyll mutations increased with decrease in seed fertility when M 1 ears were selected at random. However, at the lowest fertility class the mutation frequency was low. This reduction is attributed to the elimination of mutants in the high sterility class. The mutation yield can therefore be significantly enhanced by selecting M 1 ears of low fertility. The segregation ratio of mutants increased as fertility decreased. Mutation spectrum was however not influenced by M 1 fertility. This makes selection for fertility quite ineffective in altering the mutation spectrum. (author)

  1. The Intrinsic Characteristics of Galaxies on the SFR–M ∗ Plane at 1.2 < z < 4: I. The Correlation between Stellar Age, Central Density, and Position Relative to the Main Sequence

    Science.gov (United States)

    Lee, Bomee; Giavalisco, Mauro; Whitaker, Katherine; Williams, Christina C.; Ferguson, Henry C.; Acquaviva, Viviana; Koekemoer, Anton M.; Straughn, Amber N.; Guo, Yicheng; Kartaltepe, Jeyhan S.; Lotz, Jennifer; Pacifici, Camilla; Croton, Darren J.; Somerville, Rachel S.; Lu, Yu

    2018-02-01

    We use the deep CANDELS observations in the GOODS North and South fields to revisit the correlations between stellar mass (M *), star formation rate (SFR) and morphology, and to introduce a fourth dimension, the mass-weighted stellar age, in galaxies at 1.2history for each galaxy. Like others, we find that the slope of the main sequence (MS) of star formation in the ({M}* ;{SFR}) plane bends at high mass. We observe clear morphological differences among galaxies across the MS, which also correlate with stellar age. At all redshifts, galaxies that are quenching or quenched, and thus old, have high {{{Σ }}}1 (the projected density within the central 1 kpc), while younger, star-forming galaxies span a much broader range of {{{Σ }}}1, which includes the high values observed for quenched galaxies, but also extends to much lower values. As galaxies age and quench, the stellar age and the dispersion of {{{Σ }}}1 for fixed values of M * shows two different regimes: one at the low-mass end, where quenching might be driven by causes external to the galaxies; the other at the high-mass end, where quenching is driven by internal causes, very likely the mass given the low scatter of {{{Σ }}}1 (mass quenching). We suggest that the monotonic increase of central density as galaxies grow is one manifestation of a more general phenomenon of structural transformation that galaxies undergo as they evolve.

  2. Influence of extracellular zinc on M1 microglial activation.

    Science.gov (United States)

    Higashi, Youichirou; Aratake, Takaaki; Shimizu, Shogo; Shimizu, Takahiro; Nakamura, Kumiko; Tsuda, Masayuki; Yawata, Toshio; Ueba, Tetuya; Saito, Motoaki

    2017-02-27

    Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia. Pre-treatment of microglia with 30-60 μM ZnCl 2 resulted in dose-dependent increases in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNFα) secretion when M1 activation was induced by lipopolysaccharide administration. In contrast, the cell-permeable zinc chelator TPEN, the radical scavenger Trolox, and the P2X7 receptor antagonist A438079 suppressed the effects of zinc pre-treatment on microglia. Furthermore, endogenous zinc release was induced by cerebral ischaemia-reperfusion, resulting in increased expression of IL-1β, IL-6, TNFα, and the microglial M1 surface marker CD16/32, without hippocampal neuronal cell loss, in addition to impairments in object recognition memory. However, these effects were suppressed by the zinc chelator CaEDTA. These findings suggest that extracellular zinc may prime microglia to enhance production of pro-inflammatory cytokines via P2X7 receptor activation followed by reactive oxygen species generation in response to stimuli that trigger M1 activation, and that these inflammatory processes may result in deficits in object recognition memory.

  3. mPGES-1-derived PGE2 mediates dehydration natriuresis

    Science.gov (United States)

    Jia, Zhanjun; Liu, Gang; Sun, Ying; Kakizoe, Yutaka; Guan, Guangju; Zhang, Aihua; Zhou, Shu-Feng

    2013-01-01

    PGE2 is a natriuretic factor whose production is elevated after water deprivation (WD) but its role in dehydration natriuresis is not well-defined. The goal of the present study was to investigate the role of microsomal prostaglandin E synthase-1 (mPGES-1) in dehydration natriuresis. After 24-h WD, wild-type (WT) mice exhibited a significant increase in 24-h urinary Na+ excretion accompanied with normal plasma Na+ concentration and osmolality. In contrast, WD-induced elevation of urinary Na+ excretion was completely abolished in mPGES-1 knockout (KO) mice in parallel with increased plasma Na+ concentration and a trend increase in plasma osmolality. WD induced a 1.8-fold increase in urinary PGE2 output and a 1.6-fold increase in PGE2 content in the renal medulla of WT mice, both of which were completely abolished by mPGES-1 deletion. Similar patterns of changes were observed for urinary nitrate/nitrite and cGMP. The natriuresis in dehydrated WT mice was associated with a significant downregulation of renal medullary epithelial Na channel-α mRNA and protein, contrasting to unaltered expressions in dehydrated KO mice. By quantitative RT-PCR, WD increased the endothelial nitric oxide synthase (eNOS), inducible NOS, and neuronal NOS expressions in the renal medulla of WT mice by 3.9-, 1.48-, and 2.6-fold, respectively, all of which were significantly blocked in mPGES-1 KO mice. The regulation of eNOS expression was further confirmed by immunoblotting. Taken together, our results suggest that mPGES-1-derived PGE2 contributes to dehydration natriuresis likely via NO/cGMP. PMID:23171554

  4. The search for main-belt comets: The Pan-STARRS1 perspective

    Science.gov (United States)

    Hsieh, H.; Denneau, L.; Wainscoat, R.; Jedicke, R.; Schorghofer, N.; Micheli, M.; Veres, P.; Kleyna, J.; Bolin, B.

    2014-07-01

    In recent years, an increasing number of objects have been discovered in the main asteroid belt that exhibit comet-like activity. Some instances of activity are believed to result from sublimation of volatile sub-surface ice, and the objects exhibiting this type of activity have come to be known as main-belt comets (MBCs; Hsieh & Jewitt 2006). For most MBCs, the presence of gas is only inferred from visible dust emission, although water vapor outgassing has recently been directly detected from (1) Ceres (Kuppers et al. 2014), indicating that water sublimation on MBCs could also be possible. In other instances, comet-like dust emission has been found to result from impacts onto otherwise inert objects, rotational disruption, or a combination of effects (cf., Jewitt 2012). In these cases, the objects can be referred to as disrupted asteroids. Collectively, MBCs and disrupted asteroids are known as active asteroids. MBCs have attracted interest in astrobiology due to theoretical studies indicating that material from the asteroid belt region could have been a significant primordial source of the water and other volatiles on the Earth. Icy asteroids also contain some of the least altered material from the inner protosolar disk still in existence today, presenting us with opportunities to learn about the earliest stages of our solar system's formation. The added bonus of the MBCs' relatively close proximity in the asteroid belt means that in situ spacecraft studies are entirely feasible using present-day technology. Pan-STARRS1 (PS1) is a wide-field synoptic survey telescope located on Halekala in Hawaii. It employs a 3.2×3.2 deg 1.4 gigapixel camera and uses an SDSS-like filter system. As of 2014 March 31, the Pan-STARRS1 survey has discovered three MBCs --- P/2006 VW139, P/2012 T1 (PANSTARRS), and P/2013 R3 (Catalina-PANSTARRS) --- as well as one disrupted asteroid (P/2013 P5 (PANSTARRS)), two active Centaurs, 33 Jupiter-family comets, and 17 long-period comets. For

  5. Douglas Haig and the Battle of the Somme

    Science.gov (United States)

    1984-03-01

    4J "insights into tomorrow" AA A A tDSTRIBUTON STATEMENT A Approved fta public rlow800 Diasibution Unlimited 84 0 , 0 DISCLAIMER The views and...Israeli Wars, p. 348. 16 John Keegan, The Face of Battle (New York: Penguin Books, 1976), p. 303. 5 17. has said this is characteristically the American way...Random House, 1982. Keegan, John. The Face of Battle. New York: Penguin Books, 1976. Mao Tse-tung. On the Protracted War. Peking: Foreign Languages

  6. Differential regulation by agonist and phorbol ester of cloned m1 and m2 muscarinic acetylcholine receptors in mouse Y1 adrenal cells and in Y1 cells deficient in cAMP-dependent protein kinase

    International Nuclear Information System (INIS)

    Scherer, N.M.; Nathanson, N.M.

    1990-01-01

    Cloned muscarinic acetylcholine m1 and m2 receptors were expressed in stably transfected mouse Y1 adrenal cells and in a variant Y1 line, Kin-8, which is deficient in cAMP-dependent protein kinase activity (PKA - ). m1 and m2 receptors were rapidly internalized following exposure of transfected PKA + or PKA - cells to the muscarinic agonist carbachol. Thus, agonist-dependent internalization of m1 and m2 did not require PKA activity. A differential effect of PKA on regulation by agonist of the m2 receptor, but not the m1 receptor, was unmasked in PKA - cells. These data indicate that the basal activity of PKA may modulate the agonist-dependent internalization of the m2 receptor, but not the m1 receptor. The internalization of the m1 and m2 receptors in both PKA + and PKA - cells was accompanied by desensitization of functional responses. Exposure of PKA + cells to 10 -7 M phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, resulted in a 30 ± 9% decrease in the number of m1 receptors on the cell surface. The m2 receptor was not internalized following treatment of either PKA + or PKA - cells with PMA. Thus, the m1 and m2 receptors show differential sensitivity to internalization by PMA. Agonist-dependent internalization of the m1 receptor appeared to be independent of activation of PKC because (1) agonist-dependent internalization of m1 was not attenuated in PKA - cells, (2) the rate and extent of internalization of m1 in cells exposed to PMA were less than those in cells exposed to agonist, and (3) treatment of cells with concanavalin A selectivity blocked internalization of m1 in cells exposed to PMA, but not to agonist. The effects of agonist and PMA on receptor internalization were not additive. Exposure of PKA + or PKA - cells to PMA reduced the magnitude of pilocarpine-stimulated PI hydrolysis by about 25%

  7. M2-F1 lifting body and Paresev 1B on ramp

    Science.gov (United States)

    1963-01-01

    In this photo of the M2-F1 lifting body and the Paresev 1B on the ramp, the viewer sees two vehicles representing different approaches to building a research craft to simulate a spacecraft able to land on the ground instead of splashing down in the ocean as the Mercury capsules did. The M2-F1 was a lifting body, a shape able to re-enter from orbit and land. The Paresev (Paraglider Research Vehicle) used a Rogallo wing that could be (but never was) used to replace a conventional parachute for landing a capsule-type spacecraft, allowing it to make a controlled landing on the ground. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop

  8. Nicotine can skew the characterization of the macrophage type-1 (M{Phi}1) phenotype differentiated with granulocyte-macrophage colony-stimulating factor to the M{Phi}2 phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Yanagita, Manabu; Kobayashi, Ryohei [Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka 565-0871 (Japan); Murakami, Shinya, E-mail: ipshinya@dent.osaka-u.ac.jp [Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka 565-0871 (Japan)

    2009-10-09

    Macrophages (M{Phi}s) exhibit functional heterogeneity and plasticity in the local microenvironment. Recently, it was reported that M{Phi}s can be divided into proinflammatory M{Phi}s (M{Phi}1) and anti-inflammatory M{Phi}s (M{Phi}2) based on their polarized functional properties. Here, we report that nicotine, the major ingredient of cigarette smoke, can modulate the characteristics of M{Phi}1. Granulocyte-macrophage colony-stimulating factor-driven M{Phi}1 with nicotine (Ni-M{Phi}1) showed the phenotypic characteristics of M{Phi}2. Like M{Phi}2, Ni-M{Phi}1 exhibited antigen-uptake activities. Ni-M{Phi}1 suppressed IL-12, but maintained IL-10 and produced high amounts of MCP-1 upon lipopolysaccharide stimulation compared with M{Phi}1. Moreover, we observed strong proliferative responses of T cells to lipopolysaccharide-stimulated M{Phi}1, whereas Ni-M{Phi}1 reduced T cell proliferation and inhibited IFN-{gamma} production by T cells. These results suggest that nicotine can change the functional characteristics of M{Phi} and skew the M{Phi}1 phenotype to M{Phi}2. We propose that nicotine is a potent regulator that modulates immune responses in microenvironments.

  9. Ethics control of vertebrate animals experiments in biosatellite BION-M1 project

    Science.gov (United States)

    Ilyin, Eugene

    During April 19-May 19, 2013 it was realized 30-days flight of Russian biosatellite Bion-M1. The main goal of this flight was to study effects of microgravity upon behavior and structural-functional state of different physiological systems of vertebrates. The folloving species were accommodated aboard of biosatellite: 45 mice C57bl/6, 8 Mongolian gerbils Meriones unguiculatus, 15 lizards, i.e. geckos Chondrodctylus turneri Gray, and fish Oreochromis mossambicus. The selection and traing of mice for the flight and ground-based control experiments was carried out at the Research Institute of Mitoengineering by Moscow State University. The protocols for animals care and reserch were revised and adopted by Bioethics Commission of above mentioned institute (decision on November 01, 2013, N35). The final version of Bion-M1 Scientific Reseach Program and protocols for separate experiments were discussed and adopted by Biomedical Ethics Commission of Institute of Biomedical Problems (decision on April 4, 2014, N317). The IMBP Commission has a status of Physiological Section of Russian Bioethics Committee by Russian Commision for UNESCO affairs and follows the Russian Bioethical Guidelines for Experiments in Aerospace and Naval Medicine and other national and international rules including COSPAR International Policy and Guidelines for Animal Care and Use in Space-born Research. Because US-scientists were the main partners in mice investigations the decision of IMBP Biomedical Commission related to Bion-M1 project was sended for information to Institutional Animal Care and Use Committee of NASA Ames Research Center. Postflight estimation of mice was done by Russian veterinary with the participation of NASA Chief veterinary.

  10. Anticonvulsant activity of a mGlu(4alpha) receptor selective agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid.

    Science.gov (United States)

    Chapman, A G; Talebi, A; Yip, P K; Meldrum, B S

    2001-07-20

    The metabotropic Group III agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid (ACPT-1), selective for the mGlu(4alpha) receptor, suppresses sound-induced seizures in DBA/2 mice following its intracerebroventricular (i.c.v.) administration (ED(50) 5.6 [2.9-10.7], nmol i.c.v., 15 min, clonic phase) and in genetically epilepsy-prone (GEP) rats following focal administration into the inferior colliculus (ED(50) 0.08 [0.01-0.50], nmol, 60 min, clonic phase). ACPT-1 also protects against clonic seizures induced in DBA/2 mice by the Group I agonist, (RS)-3,5-dihydroxyphenylglycine (3,5-DHPG) (ED(50) 0.60 [0.29-1.2], nmol i.c.v.) and by the Group III antagonist, (RS)-alpha-methylserine-O-phosphate (MSOP) (ED(50) 49.3 [37.9-64.1], nmol i.c.v.). Another Group III agonist, (RS)-4-phosphonophenyl-glycine (PPG), preferentially activating the mGlu(8) receptor, previously shown to protect against sound-induced seizures in DBA/2 mice and GEP rats, also protects against seizures induced in DBA/2 by 3,5-DHPG (ED(50) 3.7 [2.4-5.7], nmol i.c.v.) and by the Group III antagonist, MSOP (ED(50) 40.2 [21.0-77.0], nmol i.c.v.). At very high doses (500 nmol i.c.v. and above), Group III antagonists have pro-convulsant and convulsant activity. The anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(4) receptor agonist ACPT-1, is partially reversed by the co-administration of the Group III antagonists, MSOP, (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4), in the 20-50 nmol dose range. At doses of 50-200 nmol, MPPG and MAP4 cause further reversal of the ACPT-1 anticonvulsant protection, while the MSOP effect on ACPT-1 protection is abolished at higher doses. In contrast, the anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(8) receptor agonist PPG, is not

  11. Thai Research Reactor (TRR-1/M1) Neutron Beam Measurements

    International Nuclear Information System (INIS)

    Ratanatongchai, Wichian

    2009-07-01

    Full text: Neutron beam tube of neutron radiography facility at Thai Research Reactor (TRR-1/M1) Thailand Institute of Nuclear Technology (public organization) is a divergent beam. The rectangular open-end of the beam tube is 16 cm x 17 cm while the inner-end is closed to the reactor core. The neutron beam size was measured using 20 cm x 40 cm neutron imaging plate. The measurement at the position 100 cm from the end of the collimator has shown that the beam size was 18.2 cm x 19.0 cm. Gamma ray in neutron the beam was also measured by the identical position using industrial X ray film. The area of gamma ray was 27.8 cm x 31.1 cm with the highest intensity found to be along the neutron beam circumference

  12. Battle of Narratives

    Science.gov (United States)

    2012-06-01

    NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS Approved for public release; distribution is unlimited BATTLE OF NARRATIVES...from the NAVAL POSTGRADUATE SCHOOL June 2012 Author: Lars Ruth Approved by: Prof. Sean F. Everton Thesis Advisor Dr. Hy...are more important than are others. For example, for some, social security and taxes are very important while gun control and LGBT are not. For

  13. Dual mTORC1/C2 inhibitors suppress cellular geroconversion (a senescence program).

    Science.gov (United States)

    Leontieva, Olga V; Demidenko, Zoya N; Blagosklonny, Mikhail V

    2015-09-15

    In proliferating cells, mTOR is active and promotes cell growth. When the cell cycle is arrested, then mTOR converts reversible arrest to senescence (geroconversion). Rapamycin and other rapalogs suppress geroconversion, maintaining quiescence instead. Here we showed that ATP-competitive kinase inhibitors (Torin1 and PP242), which inhibit both mTORC1 and TORC2, also suppressed geroconversion. Despite inhibition of proliferation (in proliferating cells), mTOR inhibitors preserved re-proliferative potential (RP) in arrested cells. In p21-arrested cells, Torin 1 and PP242 detectably suppressed geroconversion at concentrations as low as 1-3 nM and 10-30 nM, reaching maximal gerosuppression at 30 nM and 300 nM, respectively. Near-maximal gerosuppression coincided with inhibition of p-S6K(T389) and p-S6(S235/236). Dual mTOR inhibitors prevented senescent morphology and hypertrophy. Our study warrants investigation into whether low doses of dual mTOR inhibitors will prolong animal life span and delay age-related diseases. A new class of potential anti-aging drugs can be envisioned.

  14. Analytic theory of the nonlinear M = 1 tearing mode

    International Nuclear Information System (INIS)

    Hazeltine, R.D.; Meiss, J.D.; Morrison, P.J.

    1985-09-01

    Numerical studies show that the m = 1 tearing mode continues to grow exponentially well into the nonlinear regime, in contrast with the slow, ''Rutherford,'' growth of m > 1 modes. We present a single helicity calculation which generalizes that of Rutherford to the case when the constant-psi approximation is invalid. As in that theory, the parallel current becomes an approximate flux function when the island size, W, exceeds the linear tearing layer width. However for the m = 1 mode, W becomes proportional to deltaB, rather than (deltaB)/sup 1/2/ above this critical amplitude. This implies that the convective nonlinearity in Ohm's law, which couples the m = 0 component to the m = 1 component, dominates the resistive diffusion term. The balance between the inductive electric field and this convective nonlinearity results in exponential growth. Assuming the form of the perturbed fields to be like that of the linear mode, we find that the growth occurs at 71% of the linear rate

  15. Comparison of methods by TLC and HPTLC for determination of aflatoxin M1 in milk and B1 in eggs Comparação de metodologia para análise de aflatoxina M1 em leite e aflatoxina B1 em ovos por CCD e CCDAE

    Directory of Open Access Journals (Sweden)

    V. M. Scussel

    2003-12-01

    Full Text Available Milk and egg matrixes were assayed for aflatoxin M1 (AFM1 and B1 (AFB1 respectively, by AOAC official and modified methods with detection and quantification by thin layer chromatography (TLC and high performance thin layer chromatography (HPTLC. The modified methods: Blanc followed by Romer, showed to be most appropriate for AFM1 analysis in milk. Both methods reduced emulsion formation, produced cleaner extracts, no streaking spots, precision and accuracy improved, especially when quantification was performed by HPTLC. The use of ternary mixture in the Blanc Method was advantageous as the solvent could extract AFM1 directly from the first stage (extraction, leaving other compounds in the binary mixture layer, avoiding emulsion formation, thus reducing toxin loss. The relative standard deviation (RSD% values were low, 16 and 7% when TLC and HPTLC were used, with a mean recovery of 94 and 97%, respectively. As far as egg matrix and final extract are concerned, both methods evaluated for AFB1 need further studies. Although that matrix leads to emulsion with consequent loss of toxin, the Romer modified presented a reasonable clean extract (mean recovery of 92 and 96% for TLC and HPTLC, respectively. Most of the methods studied did not performed as expected mainly due to the matrixes high content of triglicerides (rich on saturated fatty acids, cholesterol, carotene and proteins. Although nowadays most methodology for AFM1 is based on HPLC, TLC determination (Blanc and Romer modified for AFM1 and AFB1 is particularly recommended to those, inexperienced in food and feed mycotoxins analysis and especially who cannot afford to purchase sophisticated (HPLC,HPTLC instrumentation.Aflatoxinas M1 (AFM1 e B1 (AFB1 foram analisadas em leite e ovos respectivamente, por diferentes métodos oficiais da AOAC e modificações usando detecção por cromatografia em camada delgada (CCD e CCD de alta eficiência (CCDAE. Os métodos modificados: Blanc e Romer

  16. RuO4-mediated oxidation of secondary amines: Part 1. Are hydroxylamines main intermediates?

    Directory of Open Access Journals (Sweden)

    Florea Cristina A.

    2016-01-01

    Full Text Available The RuO4-catalyzed oxidation of secondary amines Bn-NH-CH2R (1a-b; R=H, Me gave mainly amides, but minute amounts of nitrones PhCH=N(O-CH2R (9a-b and traces of Bn-N(OH-CH2R (R=H, 4a were also detected. In the presence of cyanide, up to 22 reaction products were identified, but mainly α-aminonitriles. Comparison of the oxidation products of 1a-b with those of 4a-b, 9a-b, and Bn-N(O=CHR (10a-b showed that 4a-b cannot be main reaction intermediates formed from 1a-b.

  17. Philostorgius’ Account of the Battle at Mursa

    Directory of Open Access Journals (Sweden)

    Alenka Cedilnik

    2014-07-01

    Full Text Available On September 28, 351 AD, Emperor Constantius II defeated the usurper Magnentius in the battle at Mursa. While the battle is described in several ancient sources, the present study focuses on the account given by Philostorgius. Philostorgius is the first known author to have included in his description of the battle the appearance of a cross in the sky, drawing on the writings of an unknown Arian historian. But for all its seemingly miraculous connotations, Philostorgius’ story is no mere figment of the imagination. It is based on a perfectly natural meteorological phenomenon, the parhelia or phantom suns, which had been observed on May 7, 351, in the sky above Jerusalem. They were interpreted at the time as the sign of Christ’s cross, and the contemporary Jerusalem bishop, Cyril, provided a detailed description in a letter to Emperor Constantius. But while the Bishop already saw this phenomenon as a sign of God’s favour to Constantius, the appearance of the cross above Jerusalem was not immediately associated with the slightly later conflict at Mursa. This connection was only established by Arian historians, who used the story of the vision before the Mursa battle to glorify Emperor Constantius, a supporter of Arianism. The earliest source known today is an anonymous Arian historian writing in the late 4th century: his work provided the basis for Philostorgius’ account of the Mursa battle. Still, the association of the visions above Jerusalem and Mursa is perhaps not to be attributed merely to the Arian authors’ partiality to Emperor Constantius. It may have been prompted by two natural but hardly everyday celestial phenomena as well: on May 28, 355, the Balkans, including Mursa, witnessed a total solar eclipse, while August 8, 351, brought a partial eclipse to an area of the Balkans (but not to Mursa. The two eclipses may have influenced Philostorgius’ account of the Mursa battle. While neither the eclipse nor the parhelia visible

  18. Recent Advances in the Medicinal Chemistry of the Metabotropic Glutamate Receptor 1 (mGlu1)

    Science.gov (United States)

    2011-01-01

    This Review summarizes the medicinal chemistry found in publications on both orthosteric and allosteric modulators of the metabotropic glutamate receptor 1 (mGlu1) from 2005 to the present. The time period covered by the scope of this current review has been particularly rich in mGlu1-related publications with numbers quadrupling when compared to the preceding five year period of 2000−2005. Publications in the field peaked in 2007 with over 35 articles appearing in the peer reviewed literature in the course of that year. Given that glutamate is one of the primary excitatory neurotransmitters in the mammalian central nervous system (CNS), it is unsurprising that it acts upon several receptors that are considered to be of potential therapeutic interest for many indications. Orthosteric and allosteric modulation of the receptor is possible, with a logical extrapolation to the chemotypes used for each strategy. The last five years of publications have yielded many mGlu1 selective antagonist chemotypyes, most of which have shown efficacy in pain in vivo models. However, the primary impact of these compounds has been to highlight the mechanistic safety risks of mGlu1 antagonism, independent of chemotype. As a review in medicinal chemistry, the primary focus of this paper will be on the design and, to a lesser degree, synthetic strategies for the delivery of subtype selective, CNS penetrant, druglike compounds through a “medchem” program, targeting modulators of the mGlu1 receptor. PMID:22860168

  19. Hecamede: Homeric nurse of the battle-wounded in the Trojan War.

    Science.gov (United States)

    Balanika, Alexia P; Baltas, Christos S

    2014-02-01

    The Homeric epics present the 10-year lasting Trojan War, offering the description of battle wounds and medical care of injuries. Hecamede is referred by the Homer as a battlefield nurse who had knowledge of the treatment of bleeding battle wounds.

  20. Main: 1LR5 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available Aux311; Zea Mays Molecule: Auxin Binding Protein 1; Chain: A, B, C, D; Engineered: Yes; Mutation: Yes Protei...-.|EMBL; L08425; AAA33430.1; -.|PIR; S16262; S16262.|PDB; 1LR5; X-ray; A/B/C/D=39-201.|PDB; 1LRH; X-ray; A/B/C/D=39-201.|Mai

  1. Effect of PCB 126 on aryl hydrocarbon receptor 1 (AHR1) and AHR1 nuclear translocator 1 (ARNT1) mRNA expression and CYP1 monooxygenase activity in chicken (Gallus domesticus) ovarian follicles.

    Science.gov (United States)

    Wójcik, Dagmara; Antos, Piotr A; Katarzyńska, Dorota; Hrabia, Anna; Sechman, Andrzej

    2015-12-03

    The aim of the experiment was to study the in vitro effect of 3,3',4,4',5-pentachlorobiphenyl (PCB 126; a coplanar PCB congener) on aryl hydrocarbon receptor (AHR1) and AHR1 nuclear translocator (ARNT1) mRNA expression and the activity of CYP1 family monooxygenases in chicken ovarian follicles. White (1-4 mm) and yellowish (4-8 mm) prehierarchical follicles as well as fragments of the theca and granulosa layers of the 3 largest preovulatory follicles (F3-F1) were incubated in a medium supplemented with 0 (control group), 1, 10 or 100 nM PCB 126. The incubation was carried out for 6 h or 24 h for determination of mRNA expression of AHR1 and ARNT1 genes (real-time qPCR) and CYP1 monooxygenase activity (EROD and MROD fluorometric assays), respectively. It was found that chicken ovarian follicles express mRNA of AHR1 and ARNT1 genes. A modulatory effect of PCB 126 on AHR1 and ARNT1 expression depended not only on the biphenyl concentration but also on the follicular layer and the maturational state of the follicle. EROD and MROD activities appeared predominantly in the granulosa layer of the yellow preovulatory follicles. PCB 126 induced these activities in a dose-dependent manner in all ovarian follicles. The obtained results suggest that ovarian follicles, especially the granulosa layer, are involved in the detoxification process of PCBs in the laying hen. Taking this finding into consideration it can be suggested that the granulosa layer of the yellow hierarchical follicles plays a key role in the protective mechanism which reduces the amount of transferred dioxin-like compounds into the yolk of the oocyte. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. E1 and M1 strength functions at low energy

    Science.gov (United States)

    Schwengner, Ronald; Massarczyk, Ralph; Bemmerer, Daniel; Beyer, Roland; Junghans, Arnd R.; Kögler, Toni; Rusev, Gencho; Tonchev, Anton P.; Tornow, Werner; Wagner, Andreas

    2017-09-01

    We report photon-scattering experiments using bremsstrahlung at the γELBE facility of Helmholtz-Zentrum Dresden-Rossendorf and using quasi-monoenergetic, polarized γ beams at the HIγS facility of the Triangle Universities Nuclear Laboratory in Durham. To deduce the photoabsorption cross sections at high excitation energy and high level density, unresolved strength in the quasicontinuum of nuclear states has been taken into account. In the analysis of the spectra measured by using bremsstrahlung at γELBE, we perform simulations of statistical γ-ray cascades using the code γDEX to estimate intensities of inelastic transitions to low-lying excited states. Simulated average branching ratios are compared with model-independent branching ratios obtained from spectra measured by using monoenergetic γ beams at HIγS. E1 strength in the energy region of the pygmy dipole resonance is discussed in nuclei around mass 90 and in xenon isotopes. M1 strength in the region of the spin-flip resonance is also considered for xenon isotopes. The dipole strength function of 74Ge deduced from γELBE experiments is compared with the one obtained from experiments at the Oslo Cyclotron Laboratory. The low-energy upbend seen in the Oslo data is interpreted as M1 strength on the basis of shell-model calculations.

  3. E1 and M1 strength functions at low energy

    Directory of Open Access Journals (Sweden)

    Schwengner Ronald

    2017-01-01

    Full Text Available We report photon-scattering experiments using bremsstrahlung at the γELBE facility of Helmholtz-Zentrum Dresden-Rossendorf and using quasi-monoenergetic, polarized γ beams at the HIγS facility of the Triangle Universities Nuclear Laboratory in Durham. To deduce the photoabsorption cross sections at high excitation energy and high level density, unresolved strength in the quasicontinuum of nuclear states has been taken into account. In the analysis of the spectra measured by using bremsstrahlung at γELBE, we perform simulations of statistical γ-ray cascades using the code γDEX to estimate intensities of inelastic transitions to low-lying excited states. Simulated average branching ratios are compared with model-independent branching ratios obtained from spectra measured by using monoenergetic γ beams at HIγS. E1 strength in the energy region of the pygmy dipole resonance is discussed in nuclei around mass 90 and in xenon isotopes. M1 strength in the region of the spin-flip resonance is also considered for xenon isotopes. The dipole strength function of 74Ge deduced from γELBE experiments is compared with the one obtained from experiments at the Oslo Cyclotron Laboratory. The low-energy upbend seen in the Oslo data is interpreted as M1 strength on the basis of shell-model calculations.

  4. Forkhead Box M1 Is Regulated by Heat Shock Factor 1 and Promotes Glioma Cells Survival under Heat Shock Stress*

    Science.gov (United States)

    Dai, Bingbing; Gong, Aihua; Jing, Zhitao; Aldape, Kenneth D.; Kang, Shin-Hyuk; Sawaya, Raymond; Huang, Suyun

    2013-01-01

    The forkhead box M1 (FoxM1) is a key transcription factor regulating multiple aspects of cell biology. Prior studies have shown that FoxM1 is overexpressed in a variety of human tumors, including brain tumor, and plays a critical role in cancer development and progression. In this study we found that FoxM1 was up-regulated by heat shock factor 1 (HSF1) under heat shock stress condition in multiple cell lines. Knockdown of HSF1 with HSF1 siRNA or inhibition of HSF1 with a HSF1 inhibitor abrogated heat shock-induced expression of FoxM1. Genetic deletion of HSF1 in mouse embryo fibroblast cells also abolished heat shock stress-induced FoxM1 expression. Moreover, we showed that HSF1 directly bound to FoxM1 promoter and increased FoxM1 promoter activity. Furthermore, we demonstrated that FoxM1 was required for the G2-M phase progression through regulating Cdc2, Cdc20, and Cdc25B under a mild heat shock stress but enhanced cell survival under lethal heat shock stress condition. Finally, in human glioblastoma specimens, FoxM1 overexpression correlated with elevated HSF1 expression. Our results indicate that FoxM1 is regulated by HSF1 and is critical for HSF1-mediated heat shock response. We demonstrated a novel mechanism of stress resistance controlled by HSF1 and a new HSF-FoxM1 connection that mediates cellular thermotolerance. PMID:23192351

  5. book and video reviews battles in britain and their political

    African Journals Online (AJOL)

    Illustrated, maps. ISBN I 85326 672 8. R61-00 ... battles fought on British soil from the Norse invasion under King Harold. Hardrada (September ... but also sets each battle against the political and historical background of the time. Seymour ...

  6. Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages.

    Science.gov (United States)

    Soldano, Stefano; Pizzorni, Carmen; Paolino, Sabrina; Trombetta, Amelia Chiara; Montagna, Paola; Brizzolara, Renata; Ruaro, Barbara; Sulli, Alberto; Cutolo, Maurizio

    2016-01-01

    Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing pro-fibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its pro-fibrotic effects through the interaction with its receptors (ETA and ETB). The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells. Cultured human monocytes (THP-1 cell line) were activated into macrophages (M0 macrophages) with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls) or treated with either ET-1 (100nM) or interleukin-4 (IL-4, 10ng/mL, M2 inducer) for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM)-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells) or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M) for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Gene expression of interleukin(IL)-10 and macrophage derived chemokine (CCL-22) was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography. ET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBM-derived macrophages compared to M0-controls and untreated cells. In cultured PBM-derived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1-mediated effects were

  7. Status of prompt gamma neutron activation analysis (PGAA) at TRR-1/M1 (Thai Research Reactor-1/Modified 1)

    Energy Technology Data Exchange (ETDEWEB)

    Asvavijnijkulchai, Chanchai; Dharmavanij, Wanchai; Siangsanan, Pariwat; Ratanathongchai, Wichian; Chongkum, Somporn [Physics Division, Office of Atomic Energy for Peace, Vibhavadi Rangsit Road, Chatuchak, Bangkok (Thailand)

    1999-08-01

    The first prompt gamma activation analysis (PGAA) was designed, constructed and installed at a 6 inch diameter neutron beam port of the Thai Research Reactor-1/Modified 1 (TRR-1/M1) since 1989. Beam characteristic were made by Gd foil irradiation, X-ray film exposing and densitometry scanning consequently. The thermal neutron flux at sample position was measured by Au foil activation, and was about 1 x 10{sup 7} n.cm{sup 2}.sec{sup -1} at 700 kW operating power. The experiments have been conducted successfully. In 1998, the PGAA facility has been developed for the reactor operating power at 1.2 MW. The new PGAA system, e.g., beam shutter, gamma collimator and biological shields have been designed to reduce the leakage of neutrons and gamma radiation to the acceptance levels in accordance with the International Commission on Radiation Protection Publication 60 (ICRP 60). The construction and installation will be completed in April 1999. (author)

  8. Status of prompt gamma neutron activation analysis (PGAA) at TRR-1/M1 (Thai Research Reactor-1/Modified 1)

    International Nuclear Information System (INIS)

    Asvavijnijkulchai, Chanchai; Dharmavanij, Wanchai; Siangsanan, Pariwat; Ratanathongchai, Wichian; Chongkum, Somporn

    1999-01-01

    The first prompt gamma activation analysis (PGAA) was designed, constructed and installed at a 6 inch diameter neutron beam port of the Thai Research Reactor-1/Modified 1 (TRR-1/M1) since 1989. Beam characteristic were made by Gd foil irradiation, X-ray film exposing and densitometry scanning consequently. The thermal neutron flux at sample position was measured by Au foil activation, and was about 1 x 10 7 n.cm 2 .sec -1 at 700 kW operating power. The experiments have been conducted successfully. In 1998, the PGAA facility has been developed for the reactor operating power at 1.2 MW. The new PGAA system, e.g., beam shutter, gamma collimator and biological shields have been designed to reduce the leakage of neutrons and gamma radiation to the acceptance levels in accordance with the International Commission on Radiation Protection Publication 60 (ICRP 60). The construction and installation will be completed in April 1999. (author)

  9. Cervical Cancer Cell Supernatants Induce a Phenotypic Switch from U937-Derived Macrophage-Activated M1 State into M2-Like Suppressor Phenotype with Change in Toll-Like Receptor Profile

    Directory of Open Access Journals (Sweden)

    Karina Sánchez-Reyes

    2014-01-01

    Full Text Available Cervical cancer (CC is the second most common cancer among women worldwide. Infection with human papillomavirus (HPV is the main risk factor for developing CC. Macrophages are important immune effector cells; they can be differentiated into two phenotypes, identified as M1 (classically activated and M2 (alternatively activated. Macrophage polarization exerts profound effects on the Toll-like receptor (TLR profile. In this study, we evaluated whether the supernatant of human CC cells HeLa, SiHa, and C-33A induces a shift of M1 macrophage toward M2 macrophage in U937-derived macrophages. Results. The results showed that soluble factors secreted by CC cells induce a change in the immunophenotype of macrophages from macrophage M1 into macrophage M2. U937-derived macrophages M1 released proinflammatory cytokines and nitric oxide; however, when these cells were treated with the supernatant of CC cell lines, we observed a turnover of M1 toward M2. These cells increased CD163 and IL-10 expression. The expression of TLR-3, -7, and -9 is increased when the macrophages were treated with the supernatant of CC cells. Conclusions. Our result strongly suggests that CC cells may, through the secretion of soluble factors, induce a change of immunophenotype M1 into M2 macrophages.

  10. VU6010608, a Novel mGlu7 NAM from a Series of N-(2-(1H-1,2,4-Triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamides.

    Science.gov (United States)

    Reed, Carson W; McGowan, Kevin M; Spearing, Paul K; Stansley, Branden J; Roenfanz, Hanna F; Engers, Darren W; Rodriguez, Alice L; Engelberg, Eileen M; Luscombe, Vincent B; Loch, Matthew T; Remke, Daniel H; Rook, Jerri M; Blobaum, Anna L; Conn, P Jeffrey; Niswender, Colleen M; Lindsley, Craig W

    2017-12-14

    Herein, we report the structure-activity relationships within a series of mGlu 7 NAMs based on an N -(2-(1 H -1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)benzamide core with excellent CNS penetration ( K p 1.9-5.8 and K p,uu 0.4-1.4). Analogues in this series displayed steep SAR. Of these, VU6010608 ( 11a ) emerged with robust efficacy in blocking high frequency stimulated long-term potentiation in electrophysiology studies.

  11. Waiting time distribution in M/D/1 queueing systems

    DEFF Research Database (Denmark)

    Iversen, Villy Bæk; Staalhagen, Lars

    1999-01-01

    The well-known formula for the waiting time distribution of M/D/1 queueing systems is numerically unsuitable when the load is close to 1.0 and/or the results for a large waiting time are required. An algorithm for any load and waiting time is presented, based on the state probabilities of M/D/1...

  12. USPIO-labeling in M1 and M2-polarized macrophages: An in vitro study using a clinical magnetic resonance scanner.

    Science.gov (United States)

    Zini, Chiara; Venneri, Mary A; Miglietta, Selenia; Caruso, Damiano; Porta, Natale; Isidori, Andrea M; Fiore, Daniela; Gianfrilli, Daniele; Petrozza, Vincenzo; Laghi, Andrea

    2018-08-01

    Aim of the study was to evaluate USPIO labeling in different macrophage populations using a clinical 3.0T MR unit with optical and electron microscopy as the gold standard. Human monocytic cell line THP-1 cells were differentiated into macrophages. Afterwards, M0 macrophages were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). These groups were incubated with USPIO-MR contrast agent (P904) for 36 hr; M0, M0 + P904, M1 +  P904, and M2 + P904 were analyzed in gel phantoms with a 3.0T MR scanner. m-RNA of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages. M2 + P904 showed a much higher T1 signal (p <  0.0001), a significantly lower (p < 0.0001) T2* signal, and significantly higher R* (p < 0.0001) compared to the other populations. Hystological analysis confirmed higher iron content in the M2-polarized population compared to both M1-polarized (p = 0.04) and M0-P904 (p = 0.003). Ultrastructure analysis demonstrated ubiquitous localization of P904 within the cellular compartments. Our results demonstrate that a selective USPIO-labeling of different macrophage populations can be detected in vitro using the 3.0T clinical scanner. © 2017 Wiley Periodicals, Inc.

  13. Vukovar 1991 Battle and Cultural Memory

    Directory of Open Access Journals (Sweden)

    Sandra Cvikić

    2014-03-01

    Full Text Available In this paper it is argued that Vukovar 1991 Battle traumatic memory wearing away process is a social issue and cannot be simply amputated by modernist narratives from accumulated traces of the past. Instead, those traumatic memories are constantly reconstructed, repressed, or transformed in some way or another under the pressure of manipulative power politics and competing ideologies in contemporary Croatian society.  Therefore, the question this paper asks is whether war crimes and atrocities committed in Vukovar 1991 have its meaningful place in the Croatian cultural memory and whether  social research techniques into contemporary cultural memory in Croatia can afford to avoid testimonial narrations of the Vukovar 1991 Battle and war experiences since they are an integral part of the collective memory?

  14. Role of mTORC1 Controlling Proteostasis after Brain Ischemia

    Directory of Open Access Journals (Sweden)

    Maria J. Perez-Alvarez

    2018-02-01

    Full Text Available Intense efforts are being undertaken to understand the pathophysiological mechanisms triggered after brain ischemia and to develop effective pharmacological treatments. However, the underlying molecular mechanisms are complex and not completely understood. One of the main problems is the fact that the ischemic damage is time-dependent and ranges from negligible to massive, involving different cell types such as neurons, astrocytes, microglia, endothelial cells, and some blood-derived cells (neutrophils, lymphocytes, etc.. Thus, approaching such a complicated cellular response generates a more complex combination of molecular mechanisms, in which cell death, cellular damage, stress and repair are intermixed. For this reason, animal and cellular model systems are needed in order to dissect and clarify which molecular mechanisms have to be promoted and/or blocked. Brain ischemia may be analyzed from two different perspectives: that of oxygen deprivation (hypoxic damage per se and that of deprivation of glucose/serum factors. For investigations of ischemic stroke, middle cerebral artery occlusion (MCAO is the preferred in vivo model, and uses two different approaches: transient (tMCAO, where reperfusion is permitted; or permanent (pMCAO. As a complement to this model, many laboratories expose different primary cortical neuron or neuronal cell lines to oxygen-glucose deprivation (OGD. This ex vivo model permits the analysis of the impact of hypoxic damage and the specific response of different cell types implicated in vivo, such as neurons, glia or endothelial cells. Using in vivo and neuronal OGD models, it was recently established that mTORC1 (mammalian Target of Rapamycin Complex-1, a protein complex downstream of PI3K-Akt pathway, is one of the players deregulated after ischemia and OGD. In addition, neuroprotective intervention either by estradiol or by specific AT2R agonists shows an important regulatory role for the mTORC1 activity, for

  15. Aflatoxin M1 Contamination in Ice-Cream

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-06-01

    Full Text Available Aflatoxin M1 (AFM1 is the hydroxylated metabolite of aflatoxin B1 (AFB1 that it can be found in milk and dairy products. In this study, ELISA (Enzyme Linked Immunosorbent Assay technique was used for detection of AFM1 in ice-cream in Guilan province (Northern Iran. A total of 90 ice-cream samples was randomly obtained from different supermarkets. In 62 of the 90 ice-cream samples examined (68.88%, the presence of AFM1 was detected in concentrations between 8.4 -147.7 ng/l. The mean level of AFM1 in positive samples was 40.36 ng/l. AFM1 levels in 11 samples (12.22% were higher than the maximum tolerance limit (50 ng/l accepted by ISIRI, European Community and Codex Alimentarius.

  16. Expression of aryl hydrocarbon receptor 1 (AHR1), AHR1 nuclear translocator 1 (ARNT1) and CYP1 family monooxygenase mRNAs and their activity in chicken ovarian follicles following in vitro exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

    Science.gov (United States)

    Antos, Piotr A; Błachuta, Małgorzata; Hrabia, Anna; Grzegorzewska, Agnieszka K; Sechman, Andrzej

    2015-09-02

    The aim of this in vitro study was to determine the effect of TCDD and luteinizing hormone (LH) on mRNA expression of aryl hydrocarbon receptor 1 (AHR1), AHR1 nuclear translocator 1 (ARNT1), and the CYP1 family monooxygenases (CYP1A4, CYP1A5, CYP1B1), and to assess the basal and TCDD-induced activity of these enzymes in chicken ovarian follicles. White (WF) and yellowish (YF) prehierarchical follicles and fragments of the theca (TL) and granulosa (GL) layers of the 3 largest preovulatory follicles (F3-F1) were exposed to TCDD (10nM), ovine LH (oLH; 10ng/mL) or a combination of TCDD (10nM) and oLH (10ng/mL), and increasing doses of TCDD (0.01-100nM). AHR1 and ARNT1 mRNA transcripts were found in all examined follicles. The effect of TCDD and oLH on AHR1 and ARNT1 mRNA expression depended on the maturational state of the follicle. CYP1A4 was predominantly expressed in the GL of the F3-F1 follicles; in comparison with the WF, a higher level of CYP1A5 mRNA was found both in the GL and TL of F3-F1 follicles. Alternatively, the highest level of CYP1B1 mRNA was noticed in the WF follicles. In different developmental stages of the follicle TCDD and oLH induced a different CYP1 isoform. TCDD increased EROD and MROD activities in all the investigated ovarian follicles. In conclusion, AHR1 and ARNT1 mRNA expression indicate that the chicken ovary is a target tissue for dioxin and dioxin-like compounds. The expression of CYP1-family genes and TCDD-inducible EROD and MROD activities in ovarian follicles suggest the possibility of xenobiotic detoxification in the chicken ovary. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Main: 1QN6 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available itiation Factor Tfiid-1; Chain: A, B; Synonym: Tata-Box Factor 1, Tata Sequence-Binding Protein 1, Tbp1; Eng...ineered: Yes; Molecule: Dna (5'-D(*Gp*Cp*Tp*Ap*Tp*Ap*Ap*Tp*Ap*Gp*Gp*Gp*Cp*A)-3'); Chai...n: C, E; Molecule: Dna (5'-D(*Tp*Gp*Cp*Cp*Cp*Tp*Ap*Tp*Tp*Ap*Tp*Ap*Gp*C)-3'); Chain: D, F Tata Box-Bindi

  18. Main: 1QN5 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available itiation Factor Tfiid-1; Chain: A, B; Synonym: Tata-Box Factor 1, Tata Sequence-Binding Protein 1, Tbp1; Eng...ineered: Yes; Molecule: Dna (5'-D(*Gp*Cp*Tp*Ap*Tp*Ap*Ap*Gp*Ap*Gp*Gp*Gp*Cp*A)-3'); Chai...n: C, E; Molecule: Dna (5'-D(*Tp*Gp*Cp*Cp*Cp*Tp*Cp*Tp*Tp*Ap*Tp*Ap*Gp*C)-3'); Chain: D, F Tata Box-Bindi

  19. Inner nuclear envelope protein SUN1 plays a prominent role in mammalian mRNA export.

    Science.gov (United States)

    Li, Ping; Noegel, Angelika A

    2015-11-16

    Nuclear export of messenger ribonucleoproteins (mRNPs) through the nuclear pore complex (NPC) can be roughly classified into two forms: bulk and specific export, involving an nuclear RNA export factor 1 (NXF1)-dependent pathway and chromosome region maintenance 1 (CRM1)-dependent pathway, respectively. SUN proteins constitute the inner nuclear envelope component of the l I: nker of N: ucleoskeleton and C: ytoskeleton (LINC) complex. Here, we show that mammalian cells require SUN1 for efficient nuclear mRNP export. The results indicate that both SUN1 and SUN2 interact with heterogeneous nuclear ribonucleoprotein (hnRNP) F/H and hnRNP K/J. SUN1 depletion inhibits the mRNP export, with accumulations of both hnRNPs and poly(A)+RNA in the nucleus. Leptomycin B treatment indicates that SUN1 functions in mammalian mRNA export involving the NXF1-dependent pathway. SUN1 mediates mRNA export through its association with mRNP complexes via a direct interaction with NXF1. Additionally, SUN1 associates with the NPC through a direct interaction with Nup153, a nuclear pore component involved in mRNA export. Taken together, our results reveal that the inner nuclear envelope protein SUN1 has additional functions aside from being a central component of the LINC complex and that it is an integral component of the mammalian mRNA export pathway suggesting a model whereby SUN1 recruits NXF1-containing mRNP onto the nuclear envelope and hands it over to Nup153. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. Mitochondrial lineage M1 traces an early human backflow to Africa.

    Science.gov (United States)

    González, Ana M; Larruga, José M; Abu-Amero, Khaled K; Shi, Yufei; Pestano, José; Cabrera, Vicente M

    2007-07-09

    The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA) sequences and 261 partial sequences belonging to haplogroup M1 was carried out. The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance.

  1. Mitochondrial lineage M1 traces an early human backflow to Africa

    Directory of Open Access Journals (Sweden)

    Pestano José

    2007-07-01

    Full Text Available Abstract Background The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA sequences and 261 partial sequences belonging to haplogroup M1 was carried out. Results The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. Conclusion This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance.

  2. Transient analysis of an M/M/1 queue with multiple vacations

    Directory of Open Access Journals (Sweden)

    Kaliappan Kalidass

    2014-05-01

    Full Text Available In this paper, we have obtained explicit expressions for the time dependent probabilities of the M/M/1  queue with server vacations under a multiple vacation scheme. The corresponding steady state probabilities have been obtained. We also obtain the time dependent performance measures of the systems

  3. Genetic analysis of rice semidwarf mutant Tad-M-1

    International Nuclear Information System (INIS)

    Wang Naiyuan; Yang Rencui

    1995-01-01

    This paper dealed with the inheritance of the rice semidwarf of Tad-M-,a mutant line bred from traditional indica rice Variety Tadukan by radiation. The results indicated that semidwarf of Tad-M-1 was controlled by one pair of recessive gene, which was nonallelic to sd-1 gene of variety Aijiaonante and sd-g gene of variety Xinguiai and allelic to the semidwarf gene of Yunnan japonica variety Xueheaizao and Sichuan indica variety Yizila.The possible uses of Tad-M-1 in rice breeding was also discussed

  4. Low-level Battle Management Language

    NARCIS (Netherlands)

    Alstad, A.; Mevassvik, O.M.; Nielsen, M.N.; Løvlid, R.A.; Henderson, H.C.; Jansen, R.E.J.; Reus, N.M. de

    2013-01-01

    TNO (The Netherlands) and FFI (Norway) are cooperating in extending a COTS Computer Generated Forces (CGF) tool with a Coalition Battle Management Language (C-BML) interface for executing C-BML orders and issuing reports. Due to the lack of satisfactory models for command and control (C2)/combat

  5. Selective mGAT2 (BGT-1) GABA Uptake Inhibitor

    DEFF Research Database (Denmark)

    Vogensen, Stine Byskov; Jørgensen, Lars; Madsen, Karsten Kirkegaard

    2013-01-01

    β-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1−4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compou...... 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors....

  6. Technique for measuring the accumulation of /sup 99/Tcsup(m) stannous-ethane-1-hydroxy-1, 1-diphosphonate in the canine tibia

    Energy Technology Data Exchange (ETDEWEB)

    Khan, R A [Royal Postgraduate Medical School, London (UK); Best, J K; Lavender, J P

    1978-01-01

    An experimental technique is described to measure the accumulation of /sup 99/Tcsup(m)-stannous-ethane-1-hydroxy-1, 1-diphosphonate (/sup 99/Tcsup(m)-EHDP) in the canine tibia. The method involves infusion at a constant rate of known amounts of /sup 99/Tcsup(m)-EHDP into the nutrient artery supplying the tibial bone. The accumulation of the diphosphonate in bone was measured by an external sodium iodide, NaI(Tl), scintillation detector. Results are presented showing that for small amounts of /sup 99/Tcsup(m)-EHDP (0.004 to 0.300 mg per hour) the accumulation is a nearly linear function with time for 60 minutes, after which the uptake may become variable with either a plateau formation or considerable fluctuation of activity.

  7. Chronic innate immune activation of TBK1 suppresses mTORC1 activity and dysregulates cellular metabolism.

    Science.gov (United States)

    Hasan, Maroof; Gonugunta, Vijay K; Dobbs, Nicole; Ali, Aktar; Palchik, Guillermo; Calvaruso, Maria A; DeBerardinis, Ralph J; Yan, Nan

    2017-01-24

    Three-prime repair exonuclease 1 knockout (Trex1 -/- ) mice suffer from systemic inflammation caused largely by chronic activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-TANK-binding kinase-interferon regulatory factor 3 (cGAS-STING-TBK1-IRF3) signaling pathway. We showed previously that Trex1-deficient cells have reduced mammalian target of rapamycin complex 1 (mTORC1) activity, although the underlying mechanism is unclear. Here, we performed detailed metabolic analysis in Trex1 -/- mice and cells that revealed both cellular and systemic metabolic defects, including reduced mitochondrial respiration and increased glycolysis, energy expenditure, and fat metabolism. We also genetically separated the inflammatory and metabolic phenotypes by showing that Sting deficiency rescued both inflammatory and metabolic phenotypes, whereas Irf3 deficiency only rescued inflammation on the Trex1 -/- background, and many metabolic defects persist in Trex1 -/- Irf3 -/- cells and mice. We also showed that Leptin deficiency (ob/ob) increased lipogenesis and prolonged survival of Trex1 -/- mice without dampening inflammation. Mechanistically, we identified TBK1 as a key regulator of mTORC1 activity in Trex1 -/- cells. Together, our data demonstrate that chronic innate immune activation of TBK1 suppresses mTORC1 activity, leading to dysregulated cellular metabolism.

  8. Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo.

    Directory of Open Access Journals (Sweden)

    Shweta Joshi

    Full Text Available Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis.

  9. Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Obinata, Hideru; Kumaraswamy, Sunil B

    2011-01-01

    Protection of the endothelium is provided by circulating sphingosine-1-phosphate (S1P), which maintains vascular integrity. We show that HDL-associated S1P is bound specifically to both human and murine apolipoprotein M (apoM). Thus, isolated human ApoM(+) HDL contained S1P, whereas ApoM(-) HDL did...... not. Moreover, HDL in Apom(-/-) mice contains no S1P, whereas HDL in transgenic mice overexpressing human apoM has an increased S1P content. The 1.7-Å structure of the S1P-human apoM complex reveals that S1P interacts specifically with an amphiphilic pocket in the lipocalin fold of apoM. Human ApoM......(+) HDL induced S1P(1) receptor internalization, downstream MAPK and Akt activation, endothelial cell migration, and formation of endothelial adherens junctions, whereas apoM(-) HDL did not. Importantly, lack of S1P in the HDL fraction of Apom(-/-) mice decreased basal endothelial barrier function in lung...

  10. Sestrin2 inhibits mTORC1 through modulation of GATOR complexes

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Sig; Ro, Seung-Hyun; Kim, Myungjin; Park, Hwan-Woo; Semple, Ian A.; Park, Haeli; Cho, Uhn-Soo; Wang, Wei; Guan, Kun-Liang; Karin, Michael; Lee, Jun Hee (Michigan); (UCSD)

    2015-03-30

    Sestrins are stress-inducible metabolic regulators that suppress a wide range of age- and obesity-associated pathologies, many of which are due to mTORC1 overactivation. Upon various stresses, the Sestrins inhibit mTORC1 activity through an indirect mechanism that is still unclear. GATORs are recently identified protein complexes that regulate the activity of RagB, a small GTPase essential for mTORC1 activation. GATOR1 is a GTPase activating protein (GAP) for RagB whereas GATOR2 functions as an inhibitor of GATOR1. However, how the GATORs are physiologically regulated is unknown. Here we show that Sestrin2 binds to GATOR2, and liberates GATOR1 from GATOR2-mediated inhibition. Released GATOR1 subsequently binds to and inactivates RagB, ultimately resulting in mTORC1 suppression. Consistent with this biochemical mechanism, genetic ablation of GATOR1 nullifies the mTORC1-inhibiting effect of Sestrin2 in both cell culture and Drosophila models. Collectively, we elucidate a new signaling cascade composed of Sestrin2-GATOR2-GATOR1-RagB that mediates stress-dependent suppression of mTORC1 activity.

  11. Identification of the GST-T1 and GST-M1 null genotypes using high resolution melting analysis.

    Science.gov (United States)

    Drobná, Zuzana; Del Razo, Luz Maria; Garcia-Vargas, Gonzalo; Sánchez-Ramírez, Blanca; González-Horta, Carmen; Ballinas-Casarrubias, Lourdes; Loomis, Dana; Stýblo, Miroslav

    2012-01-13

    Glutathione S-transferases, including GST-T1 and GST-M1, are known to be involved in the phase II detoxification pathways for xenobiotics as well as in the metabolism of endogenous compounds. Polymorphisms in these genes have been linked to an increased susceptibility to carcinogenesis and associated with risk factors that predispose to certain inflammatory diseases. In addition, GST-T1 and GST-M1 null genotypes have been shown to be responsible for interindividual variations in the metabolism of arsenic, a known human carcinogen. To assess the specific GST genotypes in the Mexican population chronically exposed to arsenic, we have developed a multiplex High Resolution Melting PCR (HRM-PCR) analysis using a LightCycler480 instrument. This method is based on analysis of the PCR product melting curve that discriminates PCR products according to their lengths and base sequences. Three pairs of primers that specifically recognize GST-T1, GST-M1, and β-globin, an internal control, to produce amplicons of different length were designed and combined with LightCycler480 High Resolution Melting Master Mix containing ResoLight, a completely saturating DNA dye. Data collected from melting curve analysis were evaluated using LightCycler480 software to determine specific melting temperatures of individual melting curves representing target genes. Using this newly developed multiplex HRM-PCR analysis, we evaluated GST-T1 and GST-M1 genotypes in 504 DNA samples isolated from the blood of individuals residing in Zimapan, Lagunera, and Chihuahua regions in Mexico. We found that the Zimapan and Lagunera populations have similar GST-T1 and GST-M1 genotype frequencies which differ from those of the Chihuahua population. In addition, 14 individuals have been identified as carriers of the double null genotype, i.e., null genotypes in both GST-T1 and GST-M1 genes. Although this procedure does not distinguish between biallelic (+/+) and monoallelic (+/-) genotypes, it can be used in an

  12. Collider baseline parameters: Milestone M1.5

    CERN Document Server

    Schulte, Daniel

    2016-01-01

    The deliverable D1.1 provided a preliminary specification of the layout and target operation parameters for the FCC-hh hadron collider concept. It serves as the basis for the studies in all work packages. Tis milestone summarises the outcome of the first studies of this design. The goal of the FCC hadron collider is to provide proton-proton collisions at a centre-of-mass energy of 100 TeV. The machine is compatible with ion beam operation. Assuming a nominal dipole field of 16 T, such a machine is based on a perimeter of 100 km. The machine is designed to accommodate two main proton experiments that are operated simultaneously. The machine delivers a peak luminosity of 5-30 x 1034 cm-2s-1. The layout allows for two additional special-purpose experiments.

  13. The Physical Driver of the Optical Eigenvector 1 in Quasar Main Sequence

    Energy Technology Data Exchange (ETDEWEB)

    Panda, Swayamtrupta; Czerny, Bożena [Center for Theoretical Physics, Polish Academy of Sciences, Warsaw (Poland); Nicolaus Copernicus Astronomical Center, Polish Academy of Sciences, Warsaw (Poland); Wildy, Conor, E-mail: panda@cft.edu.pl [Center for Theoretical Physics, Polish Academy of Sciences, Warsaw (Poland)

    2017-11-07

    Quasars are complex sources, characterized by broad band spectra from radio through optical to X-ray band, with numerous emission and absorption features. This complexity leads to rich diagnostics. However, Boroson and Green (1992) used Principal Component Analysis (PCA), and with this analysis they were able to show significant correlations between the measured parameters. The leading component, related to Eigenvector 1 (EV1) was dominated by the anticorrelation between the FeII optical emission and [OIII] line and EV1 alone contained 30% of the total variance. It opened a way in defining a quasar main sequence, in close analogy to the stellar main sequence on the Hertzsprung-Russel (HR) diagram (Sulentic et al., 2001). The question still remains which of the basic theoretically motivated parameters of an active nucleus (Eddington ratio, black hole mass, accretion rate, spin, and viewing angle) is the main driver behind the EV1. Here we limit ourselves to the optical waveband, and concentrate on theoretical modeling the FeII to Hβ ratio, and we test the hypothesis that the physical driver of EV1 is the maximum of the accretion disk temperature, reflected in the shape of the spectral energy distribution (SED). We performed computations of the Hβ and optical FeII for a broad range of SED peak position using CLOUDY photoionisation code. We assumed that both Hβ and FeII emission come from the Broad Line Region represented as a constant density cloud in a plane-parallel geometry. We expected that a hotter disk continuum will lead to more efficient production of FeII but our computations show that the FeII to Hβ ratio actually drops with the rise of the disk temperature. Thus either hypothesis is incorrect, or approximations used in our paper for the description of the line emissivity is inadequate.

  14. The Physical Driver of the Optical Eigenvector 1 in Quasar Main Sequence

    Directory of Open Access Journals (Sweden)

    Swayamtrupta Panda

    2017-11-01

    Full Text Available Quasars are complex sources, characterized by broad band spectra from radio through optical to X-ray band, with numerous emission and absorption features. This complexity leads to rich diagnostics. However, Boroson and Green (1992 used Principal Component Analysis (PCA, and with this analysis they were able to show significant correlations between the measured parameters. The leading component, related to Eigenvector 1 (EV1 was dominated by the anticorrelation between the FeII optical emission and [OIII] line and EV1 alone contained 30% of the total variance. It opened a way in defining a quasar main sequence, in close analogy to the stellar main sequence on the Hertzsprung-Russel (HR diagram (Sulentic et al., 2001. The question still remains which of the basic theoretically motivated parameters of an active nucleus (Eddington ratio, black hole mass, accretion rate, spin, and viewing angle is the main driver behind the EV1. Here we limit ourselves to the optical waveband, and concentrate on theoretical modeling the FeII to Hβ ratio, and we test the hypothesis that the physical driver of EV1 is the maximum of the accretion disk temperature, reflected in the shape of the spectral energy distribution (SED. We performed computations of the Hβ and optical FeII for a broad range of SED peak position using CLOUDY photoionisation code. We assumed that both Hβ and FeII emission come from the Broad Line Region represented as a constant density cloud in a plane-parallel geometry. We expected that a hotter disk continuum will lead to more efficient production of FeII but our computations show that the FeII to Hβ ratio actually drops with the rise of the disk temperature. Thus either hypothesis is incorrect, or approximations used in our paper for the description of the line emissivity is inadequate.

  15. Calculation of parity violating effects in the 62P/sub 1/2/-72P/sub 1/2/ forbidden M1 transition in thallium

    International Nuclear Information System (INIS)

    Neuffer, D.B.

    1977-05-01

    Calculations are presented of the E1 amplitude expected in forbidden M1 transitions of Tl and Cs if parity is violated in the neutral weak e-N interaction, as proposed in a number of gauge models, including that of Weinberg and Salam. Valence electron wave functions are generated as numerical solutions to the Dirac equation in a modified Tietz central potential. These wave functions are used to calculate allowed E1 transition rates, hfs splittings, and Stark E1 transition ampitudes. These results are compared with experiment and the agreement is generally good. The relativistic Tl 6 2 P/sub 1/2/-7 2 P/sub 1/2/ M1 transition amplitude M is also calculated, and corrections due to interconfiguration interaction, Breit interaction, and hfs mixing are included. The parity violating E1 amplitude E/sub PV/ is calculated and a value for the circular dichroism in the Weinberg model delta = -2.6 x 10 -3 is obtained. Parity violating effects in other Tl transitions are discussed. Contributions to the M1 amplitude for the forbidden Cs 6 2 S/sub 1/2/-7 2 S/sub 1/2/ and 6 2 S/sub 1/2/-8 2 S/sub 1/2/ transitions and to the Cs 6 2 S/sub 1/2/ g-factor anomaly from relativistic effects, Breit interaction, interconfiguration interaction, and hfs mixing are calculated, and it is found that this current theoretical description is not entirely adequate. The parity violating E1 amplitude E/sub PV/ for the 6S/sub 1/2/-7 2 S/sub 1/2/ and 6S/sub 1/2/-8 2 S/sub 1/2/ transitions is evaluated. With a measured value M/sub expt/ and the Weinberg value Q/sub W/ = -99, a circular dichroism delta = 1.64 x 10 -4 for the 6 2 S/sub 1/2/-7 2 S/sub 1/2/ transition is found

  16. The development of 99mTc-d, 1-HM-PAO

    International Nuclear Information System (INIS)

    Bai Lanqin; Huang Jinjie; Fan Li; Bai Suzhen; Li Guoli; Jing Hui; Xiao Lun

    1991-12-01

    The 99m Tc-d,1-HM-PAO is an ideal radiopharmaceutical for regional cerebral blood perfusion imaging. The improvement of synthesis and separation of diastereoisomers leads to obtain high purity (>99%) of d, 1-HM-PAO and meso-HM-PAO. During separation H NMR spectroscopy was used to monitor the relative composition of these two diastereoisomers that can ensure the purity of pligand of d,1-HM-PAO. The intravenous injection of 99m Tc-d,1-HM-PAO was formed by adding fresh 99m Tc washing liquor into a sterile. Pyrogen-free and freeze-dried vial. The radiochemical purity (RCP) of 99m Tc-d,1-HM-PAO was greater than 80%. From the experiments of 99m Tc-d,1-HM-PAO in mice, after two minutes of intravenously (I>V>) administration about 2.24% of injected dose (I.D.)appeared in the brain, and after 24 hours about 72% of radioactivity of injected dose still left in the brain. But for the 99m Tc-meso-HM-PAO after two minutes of i.v. administration, about 1.93% of I.D. appeared in the brain, and 24 hours later, 25% of radioactivity of I.D. was in the brain. This result shows that in the brain the radioactivity of 99m Tc-meso-HM-PAO declines faster than that of 99m Td-d,1-HM-PAO

  17. Growth suppression of colorectal cancer by plant-derived multiple mAb CO17-1A × BR55 via inhibition of ERK1/2 phosphorylation.

    Science.gov (United States)

    Kwak, Dong Hoon; Moussavou, Ghislain; Lee, Ju Hyoung; Heo, Sung Youn; Ko, Kisung; Hwang, Kyung-A; Jekal, Seung-Joo; Choo, Young-Kug

    2014-11-14

    We have generated the transgenic Tabaco plants expressing multiple monoclonal antibody (mAb) CO7-1A × BR55 by cross-pollinating with mAb CO17-1A and mAb BR55. We have demonstrated the anti-cancer effect of plant-derived multiple mAb CO17-1A × BR55. We find that co-treatment of colorectal mAbs (anti-epithelial cellular adhesion molecule (EpCAM), plant-derived monoclonal antibody (mAb(P)) CO17-1A and mAb(P) CO17-1A × BR55) with RAW264.7 cells significantly inhibited the cell growth in SW620 cancer cells. In particular, multi mAb(P) CO17-1A × BR55 significantly and efficiently suppressed the growth of SW620 cancer cells compared to another mAbs. Apoptotic death-positive cells were significantly increased in the mAb(P) CO17-1A × BR55-treated. The mAb(P) CO17-1A × BR55 treatment significantly decreased the expression of B-Cell lymphoma-2 (BCl-2), but the expression of Bcl-2-associated X protein (Bax), and cleaved caspase-3 were markedly increased. In vivo, the mAb(P) CO17-1A × BR55 significantly and efficiently inhibited the growth of colon tumors compared to another mAbs. The apoptotic cell death and inhibition of pro-apoptotic proteins expression were highest by treatment with mAb(P) CO17-1A × BR55. In addition, the mAb(P) CO17-1A × BR55 significantly inhibited the extracellular signal-regulated kinase 1 and 2 (ERK1/2) phosphorylation in cancer cells and tumors. Therefore, this study results suggest that multiple mAb(P) CO17-1A × BR55 has a significant effect on apoptosis-mediated anticancer by suppression of ERK1/2 phosphorylation in colon cancer compared to another mAbs. In light of these results, further clinical investigation should be conducted on mAb(P) CO17-1A × BR55 to determine its possible chemopreventive and/or therapeutic efficacy against human colon cancer.

  18. Production and characterization of a murine monoclonal IgM antibody to human C1q receptor (C1qR)

    International Nuclear Information System (INIS)

    Ghebrehiwet, B.

    1986-01-01

    A hybridoma cell line that produces a monoclonal antibody (MAb) to cell surface C1q receptor (C1qr) has been produced by fusion of the P3 x 63-Ag8.653 mouse myeloma cell line with the spleen cells of a CD-1 mouse that had been hyperimmunized with viable Raji cell suspensions (5 x 10 7 cells/inoculum). This MAb, designated II1/D1, is an IgM antibody with lambda-light chain specificity. Radiolabeled or unlabeled, highly purified II1/D1 was used to determine that: a) this antibody competes for C1q binding sites on C1qR-bearing cells; b) the molecule recognized by this MAb is the C1qR; and c) cells that are known to bind C1q also bind II1/D1 in a specific manner. Western blot analysis of solubilized Raji, or U937 cell membranes, showed that the 125 I-MAb detected a major protein band of approximately 85000 m.w. in its unreduced state, indicating that the C1qR is similar, if not identical, in both types of cells. Analyses of 125 I-II/D1 binding experiments revealed that the antibody bound to Raji cells or u937 cells in a specific manner. Uptake of the antibody was saturable, with equilibrium virtually attained within 35 min. Scatchard analysis of the binding data using the intact MAb suggests that the affinity constant K/sub D/ is 2.9 x 10 -10 M, and at apparent saturation, 24.6 ng of the antibody were bound per 2 x 10 6 cells, giving an estimated 7.8 x 10 3 antibody molecules bound per cell. That the II1/D1 antibody is specifically directed to the C1q was further evidenced by an ELISA in which the ability of C1qR-bearing cells to bind the MAb was abrogated by c-C1q in a specific dose-dependent manner

  19. Half-lives of isomeric levels of sup 1 sup 0 sup 7 sup m Ag, sup 1 sup 0 sup 9 sup m Ag and sup 1 sup 0 sup 3 sup m Rh photoactivated by sup 6 sup 0 Co gamma-ray irradiation

    CERN Document Server

    Yoshida, E; Kojima, Y; Shizuma, K

    2000-01-01

    Photoactivation by gamma-rays from sup 6 sup 0 Co of 10 kCi has been performed for isomers of sup 1 sup 0 sup 7 sup m Ag, sup 1 sup 0 sup 9 sup m Ag and sup 1 sup 0 sup 3 sup m Rh and half-lives of these isomers were determined. Gamma-rays emitted from sup 1 sup 0 sup 7 sup m Ag and sup 1 sup 0 sup 9 sup m Ag were measured with a low-background Ge detector and internal conversion electrons from sup 1 sup 0 sup 3 sup m Rh were measured with a 2 pi gas flow counter. The half-lives obtained are: sup 1 sup 0 sup 7 sup m Ag: 44.5+-0.8 s, sup 1 sup 0 sup 9 sup m Ag: 38.0+-1.2 s and sup 1 sup 0 sup 3 sup m Rh: 54.8+-3.8 min. The results are in agreement with previous values obtained by different excitation methods.

  20. Behavior of 14C aflatoxin M1 during camembert cheese making.

    Science.gov (United States)

    Fremy, J M; Roiland, J C; Gaymard, A

    1990-01-01

    Camembert cheeses are made from raw milk spiked with aflatoxin M1. Three aflatoxin M1 levels (7.5 micrograms/L, 3 micrograms/L, and 0.3 micrograms/L) are used. In curds 35.6, 47.1, and 57.7% of aflatoxin M1, respectively, are recovered, and in wheys 64.4, 52.9, and 42.3%, respectively, are recovered. During the first 15 days of storage, the aflatoxin M1 content of different cheeses decreases 25, 55, and 75%, respectively. A similar experiment is made with milk contaminated with 14C labeled aflatoxin M1. The same results are obtained, except for the behavior of aflatoxin M1 in cheese; the same 14C activity is recovered during storage for 30 days.

  1. Main: 1FHF [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available oat Peroxidase; Glycine Max Molecule: Seed Coat Peroxidase; Chain: A, B, C; Engineered: Yes Oxidoreductase 1...LFPIVFGVIFDASFTDPRIGASLMRLHFHDCFVQGCDGSVLLNNTDTIESEQDALPNINSIRGLDVVNDIKTAVENSCPDTVSCADILAI

  2. [Appearance of aflatoxin M1 during the manufacture of Camembert cheese].

    Science.gov (United States)

    Frémy, J M; Roiland, J C

    1979-01-01

    Several classic cheese making of camembert are made from raw milk spiked with Aflatoxin M1. Three Aflatoxin levels 7.5 microgram/l, 3 microgram/l are used. In respective curds 35.6, 47.1 and 57.7% of Aflatoxin M1 are recovered and 64.4, 52.9 and 42.3% in respective whey. During the first 15 days of storage the Aflatoxin M1 content of different cheeses decrease respectively 25, 55, 75%. A similar experience is made with a milk contamined in Aflatoxin M1 C14 labelled. Same results are recovered, except about behaviour of Aflatoxin M1 in cheese: a same C14 activity is recovered during storage for 30 days.

  3. Small suitability of the DLEC1, MLH1 and TUSC4 mRNA expression ...

    Indian Academy of Sciences (India)

    JACEK KORDIAK

    2017-06-18

    Jun 18, 2017 ... The DLEC1, TUSC4 and MLH1 expression was analysed in lung tumour tissue samples obtained from ... among men, however, the incidence is also rising in women ... rate of lung cancer patients is still poor, mainly because .... Up to 30 PYs. 18 ..... study performed by our group, high percentage (78%).

  4. Main: 1DU5 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1DU5 トウモロコシ Corn Zea mays L. Zeamatin Precursor. Name=Zlp; Zea Mays Molecule: Zeamatin; Chai...eta Sandwich SWS:ZEAM_MAIZE,P33679|EMBL; U06831; AAA92882.1; -.|PIR; T02075; T02075.|PDB; 1DU5; X-ray; A/B=22-227.|Mai

  5. Probing the central engine and environment of AGN using ARIES 1.3-m and 3.6-m telescopes

    Science.gov (United States)

    Chand, Hum; Rakshit, Suvendu; Jalan, Priyanka; Ojha, Vineet; Srianand, Raghunathan; Vivek, Mariappan; Mishra, Sapna; Omar, Amitesh; Kumar, Parveen; Joshi, Ravi; Gopal-Krishna; Kumar, Rathna

    2018-04-01

    We discuss three long term observational programmes to probe the central engine and environment of active galactic nuclei (AGN) using the recently installed ARIES 1.3-m and 3.6-m telescopes. The first programme is on the photometric reverberation mapping of low luminosity AGN by mainly using the ARIES 1.3-m telescope. The major impact of this programme other than to estimate the black hole mass will be to extend the broad line region (BLR) radius-luminosity (RBLR-LAGN) relation to the unexplored low luminosity regime, and to constrain the AGN broad line region geometry. The second programme is to use long slit spectroscopy on the ARIES 3.6-m telescope to discover new high redshift quasar pairs with angular separation less than 1-arcmin. Here, the background QSOs sight-line will be used to probe the environment of the foreground QSOs at kpc-Mpc scales. The major impact of this programme will be on the discovery of new pairs which have been missed in the SDSS survey due to fiber collision below 1-arcmin separation, and use them to understand about any excess overdensity around the QSO, any anisotropic emission of QSOs, and/or any episodic activity of QSOs. The third programme is related to spectral variability studies of the C IV broad absorption line (BAL) QSOs, based on low resolution spectroscopy using the ARIES 3.6-m telescope. Here, those most interesting cases will be monitored, where the BAL flow emerges afresh or disappears completely in the C IV trough of BAL QSOs sample as seen in SDSS multi-epoch observations. Continuous monitoring of such a sample will be important for our understanding of the nature and origin of the flow, along with their stability and dynamical evolution.

  6. Binding of DEAD-box helicase Dhh1 to the 5'-untranslated region of ASH1 mRNA represses localized translation of ASH1 in yeast cells.

    Science.gov (United States)

    Zhang, Qianjun; Meng, Xiuhua; Li, Delin; Chen, Shaoyin; Luo, Jianmin; Zhu, Linjie; Singer, Robert H; Gu, Wei

    2017-06-09

    Local translation of specific mRNAs is regulated by dynamic changes in their subcellular localization, and these changes are due to complex mechanisms controlling cytoplasmic mRNA transport. The budding yeast Saccharomyces cerevisiae is well suited to studying these mechanisms because many of its transcripts are transported from the mother cell to the budding daughter cell. Here, we investigated the translational control of ASH1 mRNA after transport and localization. We show that although ASH1 transcripts were translated after they reached the bud tip, some mRNAs were bound by the RNA-binding protein Puf6 and were non-polysomal. We also found that the DEAD-box helicase Dhh1 complexed with the untranslated ASH1 mRNA and Puf6. Loss of Dhh1 affected local translation of ASH1 mRNA and resulted in delocalization of ASH1 transcript in the bud. Forcibly shifting the non-polysomal ASH1 mRNA into polysomes was associated with Dhh1 dissociation. We further demonstrated that Dhh1 is not recruited to ASH1 mRNA co-transcriptionally, suggesting that it could bind to ASH1 mRNA within the cytoplasm. Of note, Dhh1 bound to the 5'-UTR of ASH1 mRNA and inhibited its translation in vitro These results suggest that after localization to the bud tip, a portion of the localized ASH1 mRNA becomes translationally inactive because of binding of Dhh1 and Puf6 to the 5'- and 3'-UTRs of ASH1 mRNA. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Does occupational exposure to solvents and pesticides in association with glutathione S-transferase A1, M1, P1, and T1 polymorphisms increase the risk of bladder cancer? The Belgrade case-control study.

    Directory of Open Access Journals (Sweden)

    Marija G Matic

    Full Text Available OBJECTIVE: We investigated the role of the glutathione S-transferase A1, M1, P1 and T1 gene polymorphisms and potential effect modification by occupational exposure to different chemicals in Serbian bladder cancer male patients. PATIENTS AND METHODS: A hospital-based case-control study of bladder cancer in men comprised 143 histologically confirmed cases and 114 age-matched male controls. Deletion polymorphism of glutathione S-transferase M1 and T1 was identified by polymerase chain reaction method. Single nucleotide polymorphism of glutathione S-transferase A1 and P1 was identified by restriction fragment length polymorphism method. As a measure of effect size, odds ratio (OR with corresponding 95% confidence interval (95%CI was calculated. RESULTS: The glutathione S-transferase A1, T1 and P1 genotypes did not contribute independently toward the risk of bladder cancer, while the glutathione S-transferase M1-null genotype was overrepresented among cases (OR = 2.1, 95% CI = 1.1-4.2, p = 0.032. The most pronounced effect regarding occupational exposure to solvents and glutathione S-transferase genotype on bladder cancer risk was observed for the low activity glutathione S-transferase A1 genotype (OR = 9.2, 95% CI = 2.4-34.7, p = 0.001. The glutathione S-transferase M1-null genotype also enhanced the risk of bladder cancer among subjects exposed to solvents (OR = 6,5, 95% CI = 2.1-19.7, p = 0.001. The risk of bladder cancer development was 5.3-fold elevated among glutathione S-transferase T1-active patients exposed to solvents in comparison with glutathione S-transferase T1-active unexposed patients (95% CI = 1.9-15.1, p = 0.002. Moreover, men with glutathione S-transferase T1-active genotype exposed to pesticides exhibited 4.5 times higher risk in comparison with unexposed glutathione S-transferase T1-active subjects (95% CI = 0.9-22.5, p = 0.067. CONCLUSION: Null or low-activity genotypes of the

  8. The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

    Energy Technology Data Exchange (ETDEWEB)

    Terrier, Olivier; Moules, Vincent; Carron, Coralie; Cartet, Gaeelle [Equipe VirCell, Laboratoire de Virologie et Pathologie Humaine, VirPath EMR 4610, Universite de Lyon, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, Faculte de medecine RTH Laennec, rue Guillaume Paradin, F-69008 Lyon (France); Frobert, Emilie [Laboratoire de Virologie, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, 59 boulevard Pinel, F-69677 Bron Cedex, Lyon (France); Yver, Matthieu; Traversier, Aurelien [Equipe VirCell, Laboratoire de Virologie et Pathologie Humaine, VirPath EMR 4610, Universite de Lyon, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, Faculte de medecine RTH Laennec, rue Guillaume Paradin, F-69008 Lyon (France); Wolff, Thorsten [Division of Influenza/Respiratory Viruses, Robert Koch Institute, Nordufer 20, D-13353 Berlin (Germany); Riteau, Beatrice [Laboratoire de Virologie et Pathologie Humaine, VirPath EMR 4610, Universite de Lyon, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, Faculte de medecine RTH Laennec, rue Guillaume Paradin, F-69008 Lyon (France); Naffakh, Nadia [Institut Pasteur, Unite de Genetique Moleculaire des Virus Respiratoires, URA CNRS 3015, EA302 Universite Paris Diderot, Paris (France); and others

    2012-10-10

    Influenza A are nuclear replicating viruses which hijack host machineries in order to achieve optimal infection. Numerous functional virus-host interactions have now been characterized, but little information has been gathered concerning their link to the virally induced remodeling of the host cellular architecture. In this study, we infected cells with several human and avian influenza viruses and we have analyzed their ultrastructural modifications by using electron and confocal microscopy. We discovered that infections lead to a major and systematic disruption of nucleoli and the formation of a large number of diverse viral structures showing specificity that depended on the subtype origin and genomic composition of viruses. We identified NS1 and M1 proteins as the main actors in the remodeling of the host ultra-structure and our results suggest that each influenza A virus strain could be associated with a specific cellular fingerprint, possibly correlated to the functional properties of their viral components.

  9. The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

    International Nuclear Information System (INIS)

    Terrier, Olivier; Moules, Vincent; Carron, Coralie; Cartet, Gaëlle; Frobert, Emilie; Yver, Matthieu; Traversier, Aurelien; Wolff, Thorsten; Riteau, Beatrice; Naffakh, Nadia

    2012-01-01

    Influenza A are nuclear replicating viruses which hijack host machineries in order to achieve optimal infection. Numerous functional virus–host interactions have now been characterized, but little information has been gathered concerning their link to the virally induced remodeling of the host cellular architecture. In this study, we infected cells with several human and avian influenza viruses and we have analyzed their ultrastructural modifications by using electron and confocal microscopy. We discovered that infections lead to a major and systematic disruption of nucleoli and the formation of a large number of diverse viral structures showing specificity that depended on the subtype origin and genomic composition of viruses. We identified NS1 and M1 proteins as the main actors in the remodeling of the host ultra-structure and our results suggest that each influenza A virus strain could be associated with a specific cellular fingerprint, possibly correlated to the functional properties of their viral components.

  10. Stability of a1 mg/mL oral solution zidovudine

    International Nuclear Information System (INIS)

    Garcia Penna, Caridad Margarita; Morales Lacarrere, Ivan; Martinez Espinosa, Vivian

    2011-01-01

    The carrying out of a high-performance liquid chromatography analytical method was assessed; applicable to stability study of oral solution zidovudine (1 mg/mL) was made. The analytical method was linear, precise, specific and exact in the study concentrations. The stability study of oral solution zidovudine (1 mg/mL) was conducted determining expiring date. The shelf life study was conducted over 24 months at room temperature; whereas that of accelerated stability was conducted with the product under wet and temperature conditions; analysis was carried out over three months. Formula met quality specifications described in Pharmacopeia. Results from the shelf life study demonstrated that product keeps the parameters determining its quality during that time and in accelerated studies there was not significant product degradation. Under above mentioned conditions two years were established as expiring date

  11. PARP-1 modulation of mTOR signaling in response to a DNA alkylating agent.

    Directory of Open Access Journals (Sweden)

    Chantal Ethier

    Full Text Available Poly(ADP-ribose polymerase-1 (PARP-1 is widely involved in cell death responses. Depending on the degree of injury and on cell type, PARP activation may lead to autophagy, apoptosis or necrosis. In HEK293 cells exposed to the alkylating agent N-methyl-N'-nitro-N'-nitrosoguanine (MNNG, we show that PARP-1 activation triggers a necrotic cell death response. The massive poly(ADP-ribose (PAR synthesis following PARP-1 activation leads to the modulation of mTORC1 pathway. Shortly after MNNG exposure, NAD⁺ and ATP levels decrease, while AMP levels drastically increase. We characterized at the molecular level the consequences of these altered nucleotide levels. First, AMP-activated protein kinase (AMPK is activated and the mTORC1 pathway is inhibited by the phosphorylation of Raptor, in an attempt to preserve cellular energy. Phosphorylation of the mTORC1 target S6 is decreased as well as the phosphorylation of the mTORC2 component Rictor on Thr1135. Finally, Akt phosphorylation on Ser473 is lost and then, cell death by necrosis occurs. Inhibition of PARP-1 with the potent PARP inhibitor AG14361 prevents all of these events. Moreover, the antioxidant N-acetyl-L-cysteine (NAC can also abrogate all the signaling events caused by MNNG exposure suggesting that reactive oxygen species (ROS production is involved in PARP-1 activation and modulation of mTOR signaling. In this study, we show that PARP-1 activation and PAR synthesis affect the energetic status of cells, inhibit the mTORC1 signaling pathway and possibly modulate the mTORC2 complex affecting cell fate. These results provide new evidence that cell death by necrosis is orchestrated by the balance between several signaling pathways, and that PARP-1 and PAR take part in these events.

  12. M-shell ionization of heavy elements by 0.1-1.0 MeV/amu 1,2H and 3,4He ions

    International Nuclear Information System (INIS)

    Pajek, M.; Banas, D.; Braziewicz, J.; Czarnota, M.; Bienkowski, A.; Jaskola, M.; Korman, A.; Trautmann, D.; Lapicki, G.

    2006-01-01

    The M-shell ionization in high-Z atoms by low-energy light 1 1 H, 1 2 H, 2 3 He, and 2 4 He ions have been studied systematically in the energy range 0.1-1.0 MeV/amu in order to verify the available theoretical approaches describing the M-shell ionization by charged particles in asymmetric collisions. The present low-energy data, combined with our earlier results reported for M-shell ionization by hydrogen and helium ions for higher energies, form a systematic experimental basis to test the theoretical predictions of M-shell ionization based on the plane-wave Born approximation (PWBA), the semiclassical approximation (SCA), and the binary-encounter approximation (BEA). In the PWBA based approaches the energy loss (E), Coulomb deflection (C), perturbed stationary state (PSS), and relativistic (R) effects were considered within the ECPSSR theory and its recent modification, called the ECUSAR theory, in which a description of the PSS effect was corrected to account for the united- and separated-atom (USA) electron binding energy limits. In the SCA calculations with relativistic wave functions the binding effect was included only in the limiting cases of separated-atom and united-atom limits. Possible contribution of the electron capture, multiple ionization, and recoil ionization to the M-shell vacancy production, which is dominated for light ions impact by direct single ionization process, are also discussed. The universal scaling of measured M-shell x-ray production and ionization cross sections was investigated in detail. Using the present data the isotopic effect has been studied by comparing the measured M-shell ionization cross-section ratios for equal-velocity hydrogen 1 1 H and 1 2 H as well as helium 2 3 He and 2 4 He isotopes. In addition, the ratios of measured ionization cross sections for 1 2 H and 2 4 He were used to investigate the role of the binding effect. The present results are of practical importance for the application of particle-induced x

  13. Predicting Battle Outcomes with Classification Trees

    National Research Council Canada - National Science Library

    Coban, Muzaffer

    2001-01-01

    ... from the actual battlefield, The models built by using classification trees reveal that the objective variables alone cannot explain the outcome of battles, Relative factors, such as leadership, have deep...

  14. A 3 GHz transimpedance OEIC receiver for 1.3-1.55 μm fiber-optic systems

    International Nuclear Information System (INIS)

    Chang, G.K.; Hong, W.P.; Gimlett, J.L.; Bhat, R.; Nguyen, C.K.; Sasaki, G.; Young, J.C.

    1990-01-01

    This paper reports a high-performance, MSM-HEMT transimpedance photoreceiver fabricated using OMCVD grown InAlAs/InGaAs heterostructures on an InP substrate. This is the first demonstration of a monolithically integrated receiver amplifier that incorporates a cascode amplifier stage and a Schottky diode level-shifting stage implemented on InP-based OEIC photoreceivers. The transimpedance amplifier has an open loop gain of 5.7 and a bandwidth of 3.0 GHz which represent the highest gain and the highest speed performance reported for 1.3--1.55 μm wavelength OEIC receivers

  15. Transient solution of an M/M/1 vacation queue with a waiting server and impatient customers

    Directory of Open Access Journals (Sweden)

    Sherif I. Ammar

    2017-07-01

    Full Text Available Recently, Ammar [1] has discussed the transient behavior of a multiple vacations queue with impatient customers. In this paper, a similar technique is used to derive a new elegant explicit solution for an M/M/1 vacation queue with impatient customers and a waiting server, where the server is allowed to take a vacation whenever the system is empty after waiting for a random period of time. If the server does not return from the vacation before the expiry of the customer impatience time, the customer abandons the system forever. Moreover, the formulas of mean and variance expressed in terms of the obtained possibilities for this model.

  16. Th1/M1 conversion to Th2/M2 responses in models of inflammation lacking cell death stimulates maturation of monocyte precursors to fibroblasts

    Directory of Open Access Journals (Sweden)

    JoAnn eTrial

    2013-09-01

    Full Text Available We have demonstrated that cardiac fibrosis arises from the differentiation of monocyte-derived fibroblasts. We present here evidence that this process requires sequential Th1 and Th2 induction promoting analogous M1 (classically activated and M2 (alternatively activated macrophage polarity. Our models are 1 mice subjected to daily repetitive ischemia reperfusion (I/R without infarction and 2 the in vitro transmigration of human mononuclear leukocytes through human cardiac microvascular endothelium. In the mouse heart, leukocytes entered after I/R in response to monocyte chemoattractant protein-1 (MCP-1 which is the major cytokine induced by this protocol. Monocytes within the heart then differentiated into fibroblasts making collagen while bearing the markers of M2 macrophages. T cells were seen in these hearts as well as in the human heart with cardiomyopathy. In the in vitro model, transmigration of the leukocytes was likewise induced by MCP-1 and some monocytes matured into fibroblasts bearing M2 markers. In this model, the MCP-1 stimulus induced a transient Th1 and M1 response that developed into a predominately Th2 and M2 response. An increase in the Th2 product IL-13 was present in both the human and the mouse models, consistent with its known role in fibrosis. In these simplified models, in which there is no cell death to stimulate an anti-inflammatory response, there is nonetheless a resolution of inflammation enabling a profibrotic environment. This induces the maturation of monocyte precursors into fibroblasts.

  17. The cannabinoid CB1 receptor and mTORC1 signalling pathways interact to modulate glucose homeostasis in mice

    Directory of Open Access Journals (Sweden)

    Francisco J. Bermudez-Silva

    2016-01-01

    Full Text Available The endocannabinoid system (ECS is an intercellular signalling mechanism that is present in the islets of Langerhans and plays a role in the modulation of insulin secretion and expansion of the β-cell mass. The downstream signalling pathways mediating these effects are poorly understood. Mammalian target of rapamycin complex 1 (mTORC1 signalling is a key intracellular pathway involved in energy homeostasis and is known to importantly affect the physiology of pancreatic islets. We investigated the possible relationship between cannabinoid type 1 (CB1 receptor signalling and the mTORC1 pathway in the endocrine pancreas of mice by using pharmacological analysis as well as mice genetically lacking the CB1 receptor or the downstream target of mTORC1, the kinase p70S6K1. In vitro static secretion experiments on islets, western blotting, and in vivo glucose and insulin tolerance tests were performed. The CB1 receptor antagonist rimonabant decreased glucose-stimulated insulin secretion (GSIS at 0.1 µM while increasing phosphorylation of p70S6K1 and ribosomal protein S6 (rpS6 within the islets. Specific pharmacological blockade of mTORC1 by 3 nM rapamycin, as well as genetic deletion of p70S6K1, impaired the CB1-antagonist-mediated decrease in GSIS. In vivo experiments showed that 3 mg/kg body weight rimonabant decreased insulin levels and induced glucose intolerance in lean mice without altering peripheral insulin sensitivity; this effect was prevented by peripheral administration of low doses of rapamycin (0.1 mg/kg body weight, which increased insulin sensitivity. These findings suggest a functional interaction between the ECS and the mTORC1 pathway within the endocrine pancreas and at the whole-organism level, which could have implications for the development of new therapeutic approaches for pancreatic β-cell diseases.

  18. MicroRNA-214 Reduces Insulin-like Growth Factor-1 (IGF-1) Receptor Expression and Downstream mTORC1 Signaling in Renal Carcinoma Cells*

    Science.gov (United States)

    Das, Falguni; Dey, Nirmalya; Bera, Amit; Kasinath, Balakuntalam S.; Ghosh-Choudhury, Nandini; Choudhury, Goutam Ghosh

    2016-01-01

    Elevated IGF-1/insulin-like growth factor-1 receptor (IGF-1R) autocrine/paracrine signaling in patients with renal cell carcinoma is associated with poor prognosis of the disease independent of their von Hippel-Lindau (VHL) status. Increased expression of IGF-1R in renal cancer cells correlates with their potency of tumor development and progression. The mechanism by which expression of IGF-1R is increased in renal carcinoma is not known. We report that VHL-deficient and VHL-positive renal cancer cells possess significantly decreased levels of mature, pre-, and pri-miR-214 than normal proximal tubular epithelial cells. We identified an miR-214 recognition element in the 3′UTR of IGF-1R mRNA and confirmed its responsiveness to miR-214. Overexpression of miR-214 decreased the IGF-1R protein levels, resulting in the inhibition of Akt kinase activity in both types of renal cancer cells. IGF-1 provoked phosphorylation and inactivation of PRAS40 in an Akt-dependent manner, leading to the activation of mTORC1 signal transduction to increase phosphorylation of S6 kinase and 4EBP-1. Phosphorylation-deficient mutants of PRAS40 and 4EBP-1 significantly inhibited IGF-1R-driven proliferation of renal cancer cells. Expression of miR-214 suppressed IGF-1R-induced phosphorylation of PRAS40, S6 kinase, and 4EBP-1, indicating inhibition of mTORC1 activity. Finally, miR-214 significantly blocked IGF-1R-forced renal cancer cell proliferation, which was reversed by expression of 3′UTR-less IGF-1R and constitutively active mTORC1. Together, our results identify a reciprocal regulation of IGF-1R levels and miR-214 expression in renal cancer cells independent of VHL status. Our data provide evidence for a novel mechanism for IGF-1R-driven renal cancer cell proliferation involving miR-214 and mTORC1. PMID:27226530

  19. Emergence and oscillation of cosmic space by joining M1-branes

    Energy Technology Data Exchange (ETDEWEB)

    Sepehri, Alireza [Shahid Bahonar University, Faculty of Physics, Kerman (Iran, Islamic Republic of); Research Institute for Astronomy and Astrophysics of Maragha (RIAAM), Maragha (Iran, Islamic Republic of); Rahaman, Farook [Jadavpur University, Department of Mathematics, Kolkata, West Bengal (India); Capozziello, Salvatore [Universita di Napoli Federico II, Dipartimento di Fisica ' ' E. Pancini' ' , Naples (Italy); Gran Sasso Science Institute (INFN), L' Aquila (Italy); Tomsk State Pedagogical University, Tomsk (Russian Federation); INFN Sezione di Napoli, Naples (Italy); Ali, Ahmed Farag [Benha University, Department of Physics, Faculty of Science, Benha (Egypt); Pradhan, Anirudh [G L A University, Department of Mathematics, Institute of Applied Sciences and Humanities, Mathura, Uttar Pradesh (India)

    2016-05-15

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti-M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of M1 and the bulk leading to an expansion of M1-branes. When M1-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To remove these states, M1-branes become compact, the sign of compacted gravity changes, causing anti-gravity to arise: in this case, branes get away from each other. By articulating M1-BIons, an M3-brane and an anti-M3-brane are created and connected by three wormholes forming an M3-BIon. This new system behaves like the initial system and by closing branes to each other, they become compact and, by getting away from each other, they open. Our universe is located on one of these M3-branes and, by compactifying the M3-brane, it contracts and, by opening it, it expands. (orig.)

  20. Emergence and oscillation of cosmic space by joining M1-branes

    International Nuclear Information System (INIS)

    Sepehri, Alireza; Rahaman, Farook; Capozziello, Salvatore; Ali, Ahmed Farag; Pradhan, Anirudh

    2016-01-01

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti-M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of M1 and the bulk leading to an expansion of M1-branes. When M1-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To remove these states, M1-branes become compact, the sign of compacted gravity changes, causing anti-gravity to arise: in this case, branes get away from each other. By articulating M1-BIons, an M3-brane and an anti-M3-brane are created and connected by three wormholes forming an M3-BIon. This new system behaves like the initial system and by closing branes to each other, they become compact and, by getting away from each other, they open. Our universe is located on one of these M3-branes and, by compactifying the M3-brane, it contracts and, by opening it, it expands. (orig.)

  1. ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original biochemistry and cell biological properties.

    Science.gov (United States)

    Wang, Fang; Liang, Yong-Ju; Wu, Xing-Ping; Su, Xiao-Dong; Fu, Li-Wu

    2012-03-01

    S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo. Our results showed that the proliferation, cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells). Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan, but remained sensitive to the non-ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks. Thus, this model could serve as a good system for further investigation of ABCG2-mediated MDR.

  2. PpNAC1, a main regulator of phenylalanine biosynthesis and utilization in maritime pine.

    Science.gov (United States)

    Pascual, María Belén; Llebrés, María-Teresa; Craven-Bartle, Blanca; Cañas, Rafael A; Cánovas, Francisco M; Ávila, Concepción

    2018-05-01

    The transcriptional regulation of phenylalanine metabolism is particularly important in conifers, long-lived species that use large amounts of carbon in wood. Here, we show that the Pinus pinaster transcription factor, PpNAC1, is a main regulator of phenylalanine biosynthesis and utilization. A phylogenetic analysis classified PpNAC1 in the NST proteins group and was selected for functional characterization. PpNAC1 is predominantly expressed in the secondary xylem and compression wood of adult trees. Silencing of PpNAC1 in P. pinaster results in the alteration of stem vascular radial patterning and the down-regulation of several genes associated with cell wall biogenesis and secondary metabolism. Furthermore, transactivation and EMSA analyses showed that PpNAC1 is able to activate its own expression and PpMyb4 promoter, while PpMyb4 is able to activate PpMyb8, a transcriptional regulator of phenylalanine and lignin biosynthesis in maritime pine. Together, these results suggest that PpNAC1 is a functional ortholog of the ArabidopsisSND1 and NST1 genes and support the idea that key regulators governing secondary cell wall formation could be conserved between gymnosperms and angiosperms. Understanding the molecular switches controlling wood formation is of paramount importance for fundamental tree biology and paves the way for applications in conifer biotechnology. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  3. Clinical significance of serum circulating insulin-like growth factor-1 (IGF-1) mRNA in hepatocellular carcinoma.

    Science.gov (United States)

    Karabulut, S; Duranyıldız, D; Tas, F; Gezer, U; Akyüz, F; Serilmez, M; Ozgür, E; Yasasever, C T; Vatansever, S; Aykan, N F

    2014-03-01

    The principal aim of our study was to investigate the usefulness of serum protein and circulating mRNA of insulin-like growth factor-1 (IGF-1) as a diagnostic and prognostic tool in hepatocellular carcinoma (HCC). Fifty-four HCC patients and age- and sex-matched 20 healthy controls were enrolled into this study. Pretreatment serum IGF-1 and IGF-1 mRNA were determined by the solid-phase sandwich ELISA and quantitative RT-PCR method, respectively. The median age at diagnosis was 60 years, range 36-77 years; where majority of group were male (n = 48, 88.8%). All patients had cirrhotic history. Forty-six percent (n = 25) of patients had Child-Pugh score A, 30% (n = 16) had score B or C. All of the patients were treated with local therapies and none of them received sorafenib. The baseline serum IGF-1 mRNA levels were significantly higher in HCC patients than in the control group (p = 0.04), whereas no significant difference was observed for IGF-1 protein levels between the two group (p = 0.18). Patients with history of HBV infection, who were not treated, and who received multiple palliative treatment for HCC had higher serum IGF-1 mRNA levels (p = 0.03, 0.03, and 0.05, respectively). Poor performance status (p IGF-1 nor serum IGF-1 mRNA had significantly adverse effect on survival (p = 0.53 and 0.42, respectively).

  4. Expression of annexin-A1 and galectin-1 anti-inflammatory proteins and mRNA in chronic gastritis and gastric cancer.

    Science.gov (United States)

    Jorge, Yvana Cristina; Mataruco, Mayra Mioto; Araújo, Leandro Pires; Rossi, Ana Flávia Teixeira; de Oliveira, Juliana Garcia; Valsechi, Marina Curado; Caetano, Alaor; Miyazaki, Kenji; Fazzio, Célia Sebastiana de Jesus; Thomé, Jorge Alberto; Rahal, Paula; Oliani, Sonia Maria; Silva, Ana Elizabete

    2013-01-01

    The anti-inflammatory proteins annexin-A1 and galectin-1 have been associated with tumor progression. This scenario prompted us to investigate the relationship between the gene and protein expression of annexin-A1 (ANXA1/AnxA1) and galectin-1 (LGALS1/Gal-1) in an inflammatory gastric lesion as chronic gastritis (CG) and gastric adenocarcinoma (GA) and its association with H. pylori infection. We analyzed 40 samples of CG, 20 of GA, and 10 of normal mucosa (C) by the quantitative real-time PCR (qPCR) technique and the immunohistochemistry assay. High ANXA1 mRNA expression levels were observed in 90% (36/40) of CG cases (mean relative quantification RQ = 4.26  ±  2.03) and in 80% (16/20) of GA cases (mean RQ = 4.38  ±  4.77). However, LGALS1 mRNA levels were high (mean RQ = 2.44  ±  3.26) in 60% (12/20) of the GA cases, while low expression was found in CG (mean RQ = 0.43 ± 3.13; P gastritis and gastric cancer, suggesting a strong association of these proteins with chronic gastric inflammation and carcinogenesis.

  5. Analysis of Select Herpes Simplex Virus 1 (HSV-1) Proteins for Restriction of Human Immunodeficiency Virus Type 1 (HIV-1): HSV-1 gM Protein Potently Restricts HIV-1 by Preventing Intracellular Transport and Processing of Env gp160.

    Science.gov (United States)

    Polpitiya Arachchige, Sachith; Henke, Wyatt; Pramanik, Ankita; Kalamvoki, Maria; Stephens, Edward B

    2018-01-15

    Virus-encoded proteins that impair or shut down specific host cell functions during replication can be used as probes to identify potential proteins/pathways used in the replication of viruses from other families. We screened nine proteins from herpes simplex virus 1 (HSV-1) for the ability to enhance or restrict human immunodeficiency virus type 1 (HIV-1) replication. We show that several HSV-1 proteins (glycoprotein M [gM], US3, and UL24) potently restricted the replication of HIV-1. Unlike UL24 and US3, which reduced viral protein synthesis, we observed that gM restriction of HIV-1 occurred through interference with the processing and transport of gp160, resulting in a significantly reduced level of mature gp120/gp41 released from cells. Finally, we show that an HSV-1 gM mutant lacking the majority of the C-terminal domain (HA-gM[Δ345-473]) restricted neither gp160 processing nor the release of infectious virus. These studies identify proteins from heterologous viruses that can restrict viruses through novel pathways. IMPORTANCE HIV-1 infection of humans results in AIDS, characterized by the loss of CD4 + T cells and increased susceptibility to opportunistic infections. Both HIV-1 and HSV-1 can infect astrocytes and microglia of the central nervous system (CNS). Thus, the identification of HSV-1 proteins that directly restrict HIV-1 or interfere with pathways required for HIV-1 replication could lead to novel antiretroviral strategies. The results of this study show that select viral proteins from HSV-1 can potently restrict HIV-1. Further, our results indicate that the gM protein of HSV-1 restricts HIV-1 through a novel pathway by interfering with the processing of gp160 and its incorporation into virus maturing from the cell. Copyright © 2018 American Society for Microbiology.

  6. Cytosolic Pellino-1-Mediated K63-Linked Ubiquitination of IRF5 in M1 Macrophages Regulates Glucose Intolerance in Obesity

    Directory of Open Access Journals (Sweden)

    Donghyun Kim

    2017-07-01

    Full Text Available IRF5 is a signature transcription factor that induces M1 macrophage polarization. However, little is known regarding cytosolic proteins that induce IRF5 activation for M1 polarization. Here, we report the interaction between ubiquitin E3 ligase Pellino-1 and IRF5 in the cytoplasm, which increased nuclear translocation of IRF5 by K63-linked ubiquitination in human and mouse M1 macrophages. LPS and/or IFN-γ increased Pellino-1 expression, and M1 polarization was attenuated in Pellino-1-deficient macrophages in vitro and in vivo. Defective M1 polarization in Pellino-1-deficient macrophages improved glucose intolerance in mice fed a high-fat diet. Furthermore, macrophages in adipose tissues from obese humans exhibited increased Pellino-1 expression and IRF5 nuclear translocation compared with nonobese subjects, and these changes are associated with insulin resistance index. This study demonstrates that cytosolic Pellino-1-mediated K63-linked ubiquitination of IRF5 in M1 macrophages regulates glucose intolerance in obesity, suggesting a cytosolic mediator function of Pellino-1 in TLR4/IFN-γ receptor-IRF5 axis during M1 polarization.

  7. Interaction of CPCCOEt with a chimeric mGlu1b and calcium sensing receptor

    DEFF Research Database (Denmark)

    Bräuner-Osborne, H; Jensen, Anders A.; Krogsgaard-Larsen, P

    1999-01-01

    7-Hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt) has previously been shown to be a selective non-competitive antagonist at the metabotropic glutamate (mGlu) receptor subtype 1. In this study we have tested the effect of CPCCOEt on mGlu1b, the calcium sensing receptor (...

  8. RASSF1A hypermethylation is associated with ASXL1 mutation and indicates an adverse outcome in non-M3 acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Liu F

    2017-08-01

    Full Text Available Fang Liu,1,* Ming Gong,2,* Li Gao,2,* Xiaoping Cai,3 Hui Zhang,2 Yigai Ma2 1Department of Oncology, Chinese PLA General Hospital, 2Department of Hematology, China-Japan Friendship Hospital, 3Department of Geriatric Medicine, Army General Hospital, Beijing, People’s Republic of China *These authors contributed equally to this work Objective: The purpose of this study was to evaluate the frequency of RASSF1A hypermethylation in patients with acute myeloid leukemia (AML, in an attempt to modify the current molecular model for disease prognosis.Materials and methods: Aberrant RASSF1A promoter methylation levels were assessed in 226 newly diagnosed non-M3 AML patients and 30 apparently healthy controls, by quantitative methylation-specific polymerase chain reaction. Meanwhile, RASSF1A mRNA levels were detected by real-time quantitative polymerase chain reaction. Furthermore, hematological characteristics, cytogenetic abnormalities, and genetic aberrations were assessed. Finally, associations of RASSF1A hypermethylation with clinical outcomes were evaluated.Results: RASSF1A hypermethylation was observed in 23.0% of patients with non-M3 AML (52/226, but not in controls. Meanwhile, hypermethylation of the RASSF1A promoter was significantly associated with ASXL1 mutation. Furthermore, the log-rank test revealed that RASSF1A hypermethylation indicated decreased relapse-free survival (RFS and overall survival (OS in patients with non-M3 AML (P=0.012 and P=0.014, respectively. In multivariate analysis, RASSF1A hypermethylation was an independent prognostic factor for RFS (P=0.040, but not for OS (P=0.060.Conclusion: Hypermethylation of the RASSF1A promoter is associated with ASXL1 mutation in non-M3 AML patients, likely indicating poor outcome. These findings provide a molecular basis for stratified diagnosis and prognostic evaluation. Keywords: RASSF1A, hypermethylation, acute myeloid leukemia, clinical outcome, survival

  9. Renal imaging with a new agent sup(99m)Tc-d1-DMS

    International Nuclear Information System (INIS)

    Tanaka, A.

    1980-01-01

    By using sup(99m)-Tc-d1 DMS labeled with 99 m-Tc using stannous chloride and prepared with freeze-dried d1-DMS containing a 3:1 molar ratio of DMS and Sn +2 the effect of stereochemical factor of DMS on kidney affinity, renal images, blood clearance, urinary excretion was studied in experimental animals and two normal volunteers and 75 patients. The comparation revealed a quite similar formation of complex II from d1-DMS to that from the meso-form, judge from its absorption spectra and absorption behavior into the gel. The stereochemical difference of DMS is not a critical factor for the formation of the sup(99m)-Tc-DMS complex with high affinity for the kidney, although it is believed that the renal accumulation of Tc-complex will depend greatly on chemical configuration of the complex. (APR)

  10. 2008 - Color & Infrared (4 band) - Statewide NAIP (1m)

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) The NAIP_1M_CLRIR_2008 dataset is a 1:40000 scale (1 meter) truecolor and infrared (4 band) NAIP imagery product acquired during the summer of...

  11. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2014-05-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  12. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-11-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  13. Main: 1WEW [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 60420. Name=At5g60420; Arabidopsis Thaliana Molecule: Dna-Binding Family Protein; Chain: A; Fragment: Phd Domai...F.He, Y.Muto, M.Inoue, T.Kigawa, M.Shirouzu, T.Terada, S.Yokoyama Solution Structure Of Phd Domai...n In Dna-Binding Family Protein Aam98074 To Be Published Nmr, Structural Genomics, Phd Domai

  14. Final report on COOMET Vickers PTB/VNIIFTRI key comparison (COOMET.M.H-K1.b and COOMET.M.H-K1.c)

    Science.gov (United States)

    Aslanyan, E.; Herrmann, K.

    2013-01-01

    This report describes a COOMET key comparison on Vickers hardness scales of two National Metrology Institutes—PTB and VNIIFTRI. The pilot laboratory was PTB, which was the linking institute with the key comparison reference values of CCM.H-K1. In the key comparison two sets of hardness reference blocks for the Vickers hardness scales HV1 and HV30, each consisting of three hardness reference blocks with the hardness levels 240 HV, 540 HV and 840 HV, are used. The same hardness reference blocks were used previously in the key comparison CCM.H-K1. The measurement results and uncertainty assessments, announced by VNIIFTRI, are in good agreement with the key comparison reference values of CCM.H-K1. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  15. The Р60-S6K1 isoform of ribosomal protein S6 kinase 1 is a product of alternative mRNA translation

    Directory of Open Access Journals (Sweden)

    I. V. Zaiets

    2018-07-01

    Full Text Available Ribosomal protein S6 kinase 1 (S6K1 is a well-known downstream effector of mTORC1 (mechanistic target of rapamycin complex 1 participating primarily in the regulation of cell growth and metabolism. Deregulation of mTOR/S6K1 signaling can promote numerous human pathologies, including cancer, neurodegeneration, cardiovascular disease, and metabolic disorders. As existing data suggest, the S6K1 gene encodes several protein isoforms, including p85-S6K1, p70-S6K1, and p60-S6K1. The two of these isoforms, p85-S6K1 and p70-S6K1, were extensively studied to date. The origin and functional significance of the p60-S6K1 isoform remains a mystery, however, it was suggested that the isoform could be a product of alternative S6K1 mRNA translation. Herein we report the generation of HEK-293 cells exclusively expressing p60-S6K1 as a result of CRISPR/Cas9-mediated inactivation of p85/p70-S6K1 translation. Moreover, the generated modified cells displayed the elevated level of p60-S6K1 expression compared to that in wild-type HEK-293 cells. Our data confirm an assumption that p60-S6K1 is alternatively translated, most probably, from the common for both p70- and p85-S6K1 mRNA transcript and reveal a link between p60-S6K1 expression and such cellular processes as cell proliferation and motility. In addition, our findings indicate that the p60-S6K1 isoform of S6K1 may undergo a mode of regulation distinct from p70- and p85-S6K1 due to the absence of mTOR-regulated p60-S6K1 phosphorylation at T389 that is important for S6K1 activation.

  16. A WEB-based integrated data processing system for the TRIAM-1M

    International Nuclear Information System (INIS)

    Hasegawa, M.; Higashijima, A.; Nakamura, K.; Hanada, K.; Sato, K.N.; Sakamoto, M.; Idei, H.; Kawasaki, S.; Nakashima, H.

    2008-01-01

    In TRIAM-1M, plasma discharge can be sustained for over five hours [H. Zushi, et al., Steady-state tokamak operation, ITB transition and sustainment and ECCD experiments in TRIAM-1M, Nucl. Fusion 45 (2005) S142-S156]. In order to avoid sitting in front of one console for the purpose of monitoring the plasma discharge, it is recommended that the experimental information be accessible from any location at any time. In addition, simple services to access experimental information are required in order to promote the participation of multiple researchers in the TRIAM-1M experiment. Thus, A WEB-based integrated data processing system that provides management for experiment planning, an experimental log, numerical data, and plasma supervision has been installed in the TRIAM-1M. These services are composed primarily of an Apache WEB server, a Tomcat JSP/Servlet container, and a MySQL relational database. This system is constructed using the object-oriented Java language, which is easy to maintain and develop because of the intrinsic characteristics of the Java language. When participating in experiments, researchers are required only to prepare a WEB browser on any platform and are no longer required to memorize complex operations because all services are provided with a uniform user interface through a WEB browser. Furthermore, with the integration of these services, the required information and numerical data can be provided promptly by tracing HTML links that are created dynamically by server applications

  17. A WEB-based integrated data processing system for the TRIAM-1M

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, M. [Advanced Fusion Research Center, Research Institute for Applied Mechanics, Kyushu University, Fukuoka 816-8580 (Japan)], E-mail: hasegawa@triam.kyushu-u.ac.jp; Higashijima, A; Nakamura, K; Hanada, K; Sato, K N; Sakamoto, M; Idei, H; Kawasaki, S; Nakashima, H [Advanced Fusion Research Center, Research Institute for Applied Mechanics, Kyushu University, Fukuoka 816-8580 (Japan)

    2008-05-15

    In TRIAM-1M, plasma discharge can be sustained for over five hours [H. Zushi, et al., Steady-state tokamak operation, ITB transition and sustainment and ECCD experiments in TRIAM-1M, Nucl. Fusion 45 (2005) S142-S156]. In order to avoid sitting in front of one console for the purpose of monitoring the plasma discharge, it is recommended that the experimental information be accessible from any location at any time. In addition, simple services to access experimental information are required in order to promote the participation of multiple researchers in the TRIAM-1M experiment. Thus, A WEB-based integrated data processing system that provides management for experiment planning, an experimental log, numerical data, and plasma supervision has been installed in the TRIAM-1M. These services are composed primarily of an Apache WEB server, a Tomcat JSP/Servlet container, and a MySQL relational database. This system is constructed using the object-oriented Java language, which is easy to maintain and develop because of the intrinsic characteristics of the Java language. When participating in experiments, researchers are required only to prepare a WEB browser on any platform and are no longer required to memorize complex operations because all services are provided with a uniform user interface through a WEB browser. Furthermore, with the integration of these services, the required information and numerical data can be provided promptly by tracing HTML links that are created dynamically by server applications.

  18. Vite et bien 1 A1/A2 : méthode rapide pour adultes

    CERN Document Server

    Miquel, Claire

    2009-01-01

    Vite et bien s'adresse à des adultes pressés et impatients de communiquer avec succès en français ! Le vocabulaire est simple et usuel et les thèmes, variés, pour faire face, efficacement, à toutes les situations de la vie quotidienne et professionnelle. Livre + CD audio et corrigés inclus. La méthode rapide Vite et bien 1 permet à la fois d'apprendre le français et de découvrir la réalité de la vie en France, les différences culturelles, le langage de la vie quotidienne, le tout en un temps record. En effet, le premier volume couvre, en vingt unités, les niveaux A1 et A2 du Cadre Européen de référence (CECR). Ainsi, en 100 à 120 heures de cours selon les publics, il sera possible d'acquérir une bonne base de grammaire et de vocabulaire, claire, simple, fonctionnelle, et de se sentir à l'aise dans la communication orale et écrite. L'ouvrage s'adresse aux vrais et et aux faux débutants, constituant donc un outil d'apprentissage et/ou de rafraîchissement des connaissances. Chacune des v...

  19. Addendum to 'Half coalescence of the m=1, n=1 magnetic island in tokamaks'

    International Nuclear Information System (INIS)

    Bussac, M.N.; Pellat, R.

    1985-01-01

    As an addendum to our previous work concerning the half-coalescence instability of an m=1, n=1 magnetic island in tokamaks, the potential energy is given for an arbitrary shape of the separatrix. (orig.)

  20. Charge Transfer Effects in Naturally Occurring van der Waals Heterostructures (PbSe )1.16(TiSe2 )m (m =1 , 2)

    Science.gov (United States)

    Yao, Q.; Shen, D. W.; Wen, C. H. P.; Hua, C. Q.; Zhang, L. Q.; Wang, N. Z.; Niu, X. H.; Chen, Q. Y.; Dudin, P.; Lu, Y. H.; Zheng, Y.; Chen, X. H.; Wan, X. G.; Feng, D. L.

    2018-03-01

    van der Waals heterostructures (VDWHs) exhibit rich properties and thus has potential for applications, and charge transfer between different layers in a heterostructure often dominates its properties and device performance. It is thus critical to reveal and understand the charge transfer effects in VDWHs, for which electronic structure measurements have proven to be effective. Using angle-resolved photoemission spectroscopy, we studied the electronic structures of (PbSe )1.16(TiSe2 )m (m =1 , 2), which are naturally occurring VDWHs, and discovered several striking charge transfer effects. When the thickness of the TiSe2 layers is halved from m =2 to m =1 , the amount of charge transferred increases unexpectedly by more than 250%. This is accompanied by a dramatic drop in the electron-phonon interaction strength far beyond the prediction by first-principles calculations and, consequently, superconductivity only exists in the m =2 compound with strong electron-phonon interaction, albeit with lower carrier density. Furthermore, we found that the amount of charge transferred in both compounds is nearly halved when warmed from below 10 K to room temperature, due to the different thermal expansion coefficients of the constituent layers of these misfit compounds. These unprecedentedly large charge transfer effects might widely exist in VDWHs composed of metal-semiconductor contacts; thus, our results provide important insights for further understanding and applications of VDWHs.

  1. 99mTc complexes of 1,3-propanedithiol derivatives

    International Nuclear Information System (INIS)

    Alagui, A.; Apparu, M.; Vidal, M.; Mathieu, J.P.

    1987-01-01

    The labelling of 1,3-n alkylpropanedithiols and of 15-(1,3-dimercapto 2-propyl)pentadecanoic acid by 99m Tc was performed by an exchange reaction with the hexachlorotechnetate ion 99m TcCl 6 2- and by reduction of 99m TcO 4 - with Sn(II) in the presence of the ligand. The biological distribution of the exotechnetium complexes obtained by the latter method in mouse does not reveal a high tropism of these labelling compounds in relation to a particular tissue. (author) 14 refs.; 2 tabs

  2. Theory of the m=1 kink mode in toroidal plasmas

    International Nuclear Information System (INIS)

    Blank, J.H. de.

    1990-01-01

    The work in this thesis addresses the stability problems arising in tokamak experiments. In part I of this thesis the internal m=1 kink instability in tokamak plasmas is considered within the confines of ideal magnetohydrodynamics (ideal MHD), in which model the pressure is considered to be isotropic, while state is assumed. Because irreversible processes are disregarded, there is an energy principle. By extremizing the energy associated with infinitesimal perturbations of the plasma, a normal mode is obtained. The m=n=1 mode is resonant at the q=1 surface, and therefore, equilibria with a broad region where q#approx = # 1 are expected to be particularly unstable. The m=1 instability is computed for these q profiles. In Part II of this thesis, the internal m=1 kink instability is considered in a stationary rotating tokamak plasma, in which the particle velocity distribution is allowed to be non-thermal. In a tokamak plasma that is intensely heated by neutron beams or radiofrequent waves, these features, which cannot be described with ideal MHD, may become important, especially in the cases with high m=1 growth rates found in Part I. The energy principle of a generalized fluid theory is applied in these cases, without specifying the equation of state of the plasma. Therefore the resulting energy functional for the m=1 mode is incomplete and not direct applicable, however, the result makes clear that a kinetic description of the plasma is required only to a first approximation, and can therefore be applied analytically. The guiding center approximation is applied, which neglects finite gyroradius effects and collisions. Application of the dispersion relation, that is obtained from kinetic theory, shows that compared to the ideal MHD case, growth rates are strongly reduced due to Landau damping while the stability boundaries are not changed. (author). 72 refs.; 11 figs

  3. Preparing high performance of LiFe{sub (1−x)}M{sub x}PO{sub 4} by using Fe{sub (1−x)}M{sub x}C{sub 2}O{sub 4} as raw material precipitated from ferrochrome alloy leaching solution

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Guo-rong, E-mail: hgrhsj@263.net; Liu, Ji-jun; Du, Ke; Peng, Zhong-dong; Cao, Yan-bing; Wang, Wei-gang; Duan, Jian-guo

    2014-08-01

    To separate ferrum from chromium in the leaching sulfate solution of ferrochrome alloy, the oxalic acid was employed to precipitate the ferrum as the form of FeC{sub 2}O{sub 4} and Cr was left in the solution. In this route, small amount of nickel, cobalt and manganese exited in ferrochrome alloy were also precipitated simultaneously together with ferrous oxalate. Analysis from ICP shows that the molar percent of Fe in oxalic precipitate is 97.9% and the main doped elements are Ni (1.1%) and Mn (0.4%).The mixed metal oxalate Fe{sub (1−x)}M{sub x}C{sub 2}O{sub 4} was used as a raw material to prepare doped LiFePO{sub 4} cathode material of lithium ion batteries. The obtained LiFe{sub (1−x)}M{sub x}PO{sub 4}/C was a single olivine-type phase with higher crystallinity and presents the well-distributed fine particles. It shows an outstanding electrochemical performance with a discharge capacity of 162 mAh/g at the rate of 0.1 C, 136 mAh/g at 1 C and 103 mAh/g at 5 C. When cycled at 1 C for 50 times, the capacity retention is 98.2%.

  4. Deficiency in mTORC1-controlled C/EBP beta-mRNA translation improves metabolic health in mice

    NARCIS (Netherlands)

    Zidek, Laura M.; Ackermann, Tobias; Hartleben, Goetz; Eichwald, Sabrina; Kortman, Gertrud; Kiehntopf, Michael; Leutz, Achim; Sonenberg, Nahum; Wang, Zhao-Qi; von Maltzahn, Julia; Mueller, Christine; Calkhoven, Cornelis F.

    The mammalian target of rapamycin complex 1 (mTORC1) is a central regulator of physiological adaptations in response to changes in nutrient supply. Major downstream targets of mTORC1 signalling are the mRNA translation regulators p70 ribosomal protein S6 kinase 1 (S6K1p70) and the 4E-binding

  5. The Confusion of the Battlefield. A New Perspective on the Tapestries of the Battle of Pavia (c. 1525-1531

    Directory of Open Access Journals (Sweden)

    Paredes, Cecilia

    2014-12-01

    Full Text Available This contribution is devoted to the tapestry cycle of the Battle of Pavia conserved at the Museo Capodimonte in Naples. Seven tapestries compose this prestigious tapestry set that commemorates the first military success of Charles V: the battle held in Pavia on 24 February 1525. Up to now the tapestries have been interpreted as independent panels representing different episodes of the battle. In this contribution we will show that the seven panels actually originated in one single design, which we rediscovered by assembling them in a different sequence. In fact, the panels provide a description of the battle in a fabulous and unique panoramic landscape: the most monumental siege city view ever conceived in the sixteenth century. This discovery not only changes our lecture of the tapestries, but also raises numerous questions that should be addressed in future studies.

  6. PGE2-induced colon cancer growth is mediated by mTORC1

    International Nuclear Information System (INIS)

    Dufour, Marc; Faes, Seraina; Dormond-Meuwly, Anne; Demartines, Nicolas; Dormond, Olivier

    2014-01-01

    Highlights: • PGE 2 activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE 2 induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE 2 induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E 2 (PGE 2 ) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE 2 directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE 2 -induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE 2 increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE 2 EP 4 receptor was responsible for transducing the signal to mTORC1. Moreover, PGE 2 increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE 2 -induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE 2 increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE 2 mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth

  7. Adhesion and fracture toughness at α-Ti(0 0 0 1)/TiC(1 1 1): A first-principles investigation

    International Nuclear Information System (INIS)

    Li, Jian; Yang, Yanqing; Feng, Guanghai; Luo, Xian; Sun, Qing; Jin, Na

    2013-01-01

    The interfacial properties of α-Ti(0 0 0 1)/TiC(1 1 1) interface, such as adhesion, interface energy, interfacial fracture toughness, bonding nature, are investigated using first-principles calculations. Six interface models with different TiC(1 1 1) termination and stacking sites are investigated to clarify their influence on the interfacial stability and adhesion strength. C-terminated-hollow-site and Ti-terminated-center-site models exhibit identical epitaxial stacking style after fully relaxation, and can be regarded as the Ti and TiC sides of the most stable and strongest interface. The possible negative interface energy indicates the interfacial diffusion, and even new phase formation, is likely to happen across the interface. The largest interfacial fracture toughness is estimated about 4.8 MPa m 1/2 . The valence electron density and partial density of states (PDOS) indicate that its interfacial bonding is mainly contributed from C-Ti covalent bonds and Ti-Ti metallic interaction.

  8. Synthesis of Poly(m-pyridylene-1,2-diphenylvinylene

    Directory of Open Access Journals (Sweden)

    Rosana S. Montani

    2000-03-01

    Full Text Available The synthesis by dehalogenating polycondensation and characterization of a new soluble conjugated polymer, poly(m-pyridylene-1,2-diphenylvinylene, DP-PPyV, is reported here. It shows good mechanical properties and a λmax = 330 nm. The maximum intensity peak of MALDI-TOF corresponds to 1.800 Da.

  9. Precision hfs of 126Cs(T1/2=1.63 m) by ABMR

    International Nuclear Information System (INIS)

    Pinard, J.; Duong, H.T.; Marescaux, D.; Stroke, H.H.; Redi, O.; Gustafsson, M.; Nilsson, T.; Matsuki, S.; Kishimoto, Y.; Kominato, K.; Ogawa, I.; Shibata, M.; Tada, M.; Persson, J.R.; Nojiri, Y.; Momota, S.; Inamura, T.T.; Wakasugi, M.; Juncar, P.; Murayama, T.; Nomura, T.; Koizumi, M.

    2005-01-01

    The hfs separation Δν of 126 Cs(T1/2=1.63 m) in the 6s S1/22 ground state was obtained in a precision measurement near zero magnetic field by means of atomic beam magnetic resonance with laser optical pumping on-line with the CERN-PSB-ISOLDE mass separator. The result, Δν=3629.514 (0.001) MHz, corrects significantly a previous published value from a high-field experiment. With our result, the precision of the nuclear magnetic moment, μ(Cs126)∼0.776μN, is now limited by the influence of extended nuclear structure on the hfs (the Bohr-Weisskopf effect)

  10. The MAP, M/G1,G2/1 queue with preemptive priority

    Directory of Open Access Journals (Sweden)

    Bong Dae Choi

    1997-01-01

    Full Text Available We consider the MAP, M/G1,G2/1 queue with preemptive resume priority, where low priority customers arrive to the system according to a Markovian arrival process (MAP and high priority customers according to a Poisson process. The service time density function of low (respectively: high priority customers is g1(x (respectively: g2(x. We use the supplementary variable method with Extended Laplace Transforms to obtain the joint transform of the number of customers in each priority queue, as well as the remaining service time for the customer in service in the steady state. We also derive the probability generating function for the number of customers of low (respectively, high priority in the system just after the service completion epochs for customers of low (respectively, high priority.

  11. Dynamics of mTORC1 activation in response to amino acids

    Science.gov (United States)

    Manifava, Maria; Smith, Matthew; Rotondo, Sergio; Walker, Simon; Niewczas, Izabella; Zoncu, Roberto; Clark, Jonathan; Ktistakis, Nicholas T

    2016-01-01

    Amino acids are essential activators of mTORC1 via a complex containing RAG GTPases, RAGULATOR and the vacuolar ATPase. Sensing of amino acids causes translocation of mTORC1 to lysosomes, an obligate step for activation. To examine the spatial and temporal dynamics of this translocation, we used live imaging of the mTORC1 component RAPTOR and a cell permeant fluorescent analogue of di-leucine methyl ester. Translocation to lysosomes is a transient event, occurring within 2 min of aa addition and peaking within 5 min. It is temporally coupled with fluorescent leucine appearance in lysosomes and is sustained in comparison to aa stimulation. Sestrin2 and the vacuolar ATPase are negative and positive regulators of mTORC1 activity in our experimental system. Of note, phosphorylation of canonical mTORC1 targets is delayed compared to lysosomal translocation suggesting a dynamic and transient passage of mTORC1 from the lysosomal surface before targetting its substrates elsewhere. DOI: http://dx.doi.org/10.7554/eLife.19960.001 PMID:27725083

  12. PI3K-Akt-mTORC1-S6K1/2 Axis Controls Th17 Differentiation by Regulating Gfi1 Expression and Nuclear Translocation of RORγ

    Directory of Open Access Journals (Sweden)

    Yutaka Kurebayashi

    2012-04-01

    Full Text Available The PI3K-Akt-mTORC1 axis contributes to the activation, survival, and proliferation of CD4+ T cells upon stimulation through TCR and CD28. Here, we demonstrate that the suppression of this axis by deletion of p85α or PI3K/mTORC1 inhibitors as well as T cell-specific deletion of raptor, an essential component of mTORC1, impairs Th17 differentiation in vitro and in vivo in a S6K1/2-dependent fashion. Inhibition of PI3K-Akt-mTORC1-S6K1 axis impairs the downregulation of Gfi1, a negative regulator of Th17 differentiation. Furthermore, we demonstrate that S6K2, a nuclear counterpart of S6K1, is induced by the PI3K-Akt-mTORC1 axis, binds RORγ, and carries RORγ to the nucleus. These results point toward a pivotal role of PI3K-Akt-mTORC1-S6K1/2 axis in Th17 differentiation.

  13. Geniposide activates GSH S-transferase by the induction of GST M1 and GST M2 subunits involving the transcription and phosphorylation of MEK-1 signaling in rat hepatocytes

    International Nuclear Information System (INIS)

    Kuo, W.-H.; Chou, F.-P.; Young, S.-C.; Chang, Y.-C.; Wang, C.-J.

    2005-01-01

    Geniposide, an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis, has biological capabilities of detoxication, antioxidation, and anticarcinogenesis. We have recently found that geniposide possesses a potential for detoxication by inducing GST activity and the expression of GST M1 and GST M2 subunits. In this study, the signaling pathway of geniposide leading to the activation of GSH S-transferase (GST) was investigated. Primary cultured rat hepatocytes were treated with geniposide in the presence or absence of mitogen-activated protein kinase (MAPK) inhibitors and examined for GST activity, expression of GST M1 and M2 subunits, and protein levels of MAPK signaling proteins. Western blotting data demonstrated that geniposide induced increased protein levels of GST M1 and GST M2 (∼1.76- and 1.50-fold of control, respectively). The effect of geniposide on the increased protein levels of GST M1 and GST M2 was inhibited by the MEK-1 inhibitor PD98059, but not by other MAPK inhibitors. The GST M1 and GST M2 transcripts as determined by RT-PCR and GST activity were also inhibited concurrently by the MEK-1 inhibitor PD98059. The protein levels of up- and down-stream effectors of the MEK-1, including Ras, Raf, and Erk1/2, and the phosphorylation state of Erk1/2 were found to be induced by geniposide, indicating a two-phase influence of geniposide. The results suggest that geniposide induced GST activity and the expression of GST M1 and GST M2 acting through MEK-1 pathway by activating and increasing expression of Ras/Raf/MEK-1 signaling mediators

  14. Studies of monoclonal antibodies IOR-CEA-1 and IOR-EGF/R3 labelled with {sup 99m}Tc; Estudo de marcacao dos anticorpos monoclonais IOR-CEA-1 e IOR-EGF/R3 com {sup 99m}Tc

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta de Barros Rodrigues

    2005-07-01

    Nuclear Medicine is a speciality that uses radioisotopes for the diagnosis or treatment of diseases and it is considered one of the best tools among the diagnostic modalities for detection of cancer. {sup 99m}Tc is one of the main isotopes for labelling antibodies and in Nuclear Medicine in general, due to its adequate physical properties, availability and low cost. Labelled monoclonal antibodies have shown promising results for diagnosis and therapy of cancer and their use has brought great experimental and clinical advances in the field of oncology. The main clinical applications of immunoscintigraphy with monoclonal antibodies are staging and evaluation of tumoral reappearance. The antibodies employed in this work were: OIR-CEA-1, a murine monoclonal antibody that acts directly against CEA expressed in several neoplasia in particular those from the gastrointestinal tract (colorectal cancer) and IOR-EGF/R3, a murine monoclonal antibody that binds to the external domain of EGF-R and it has been used in the diagnosis of tumors of epithelial origin. The objectives of this work were the development and optimization of the reduction and purification processes, the radiolabelling techniques and quality control procedures (radiochemical, immunoreactivity and cystein challenge) and imaging studies of monoclonal antibodies OIR-CEA-1 and IOR-EGF/R3, using the simple, fast and efficient method of direct labelling of the antibody with {sup 99m}Tc. The final results was the definition of the best conditions for the preparation of lyophilized reactive kits of OIR-CEA-1 and IOR- EGF/R3 for an efficient diagnostic application in Nuclear Medicine. The most adequate conditions for the labelling of the antibodies were: 1.0 mg Ab, 29 {mu}L MDP, 3.0 {mu}g Sn{sup 2+}, 1 mL of {sup 99m}Tc and 30 min. reaction time. With these conditions the labelling yield was always higher than 95% and the maximum activity of {sup 99m}Tc was about 2220 MBq (60 mCi). The evidences of the efficiency and

  15. HQET at order 1/m. Pt. 1. Non-perturbative parameters in the quenched approximation

    International Nuclear Information System (INIS)

    Blossier, Benoit; Della Morte, Michele; Garron, Nicolas; Edinburgh Univ.; Sommer, Rainer

    2010-01-01

    We determine non-perturbatively the parameters of the lattice HQET Lagrangian and those of heavy-light axial-vector and vector currents in the quenched approximation. The HQET expansion includes terms of order 1/m b . Our results allow to compute, for example, the heavy-light spectrum and B-meson decay constants in the static approximation and to order 1/m b in HQET. The determination of the parameters is separated into universal and non-universal parts. The universal results can be used to determine the parameters for various discretizations. The computation reported in this paper uses the plaquette gauge action and the ''HYP1/2'' action for the b-quark described by HQET. The parameters of the currents also depend on the light-quark action, for which we choose non-perturbatively O(a)-improved Wilson fermions. (orig.)

  16. HQET at order 1/m. Pt. 1. Non-perturbative parameters in the quenched approximation

    Energy Technology Data Exchange (ETDEWEB)

    Blossier, Benoit [Paris XI Univ., 91 - Orsay (France). Lab. de Physique Theorique; Della Morte, Michele [Mainz Univ. (Germany). Inst. fuer Kernphysik; Garron, Nicolas [Universidad Autonoma de Madrid (Spain). Dept. Fisica Teorica y Inst. de Fisica Teorica UAM/CSIC; Edinburgh Univ. (United Kingdom). School of Physics and Astronomy - SUPA; Sommer, Rainer [Deutsches Elektronen-Synchrotron (DESY), Zeuthen (Germany). John von Neumann-Inst. fuer Computing NIC

    2010-01-15

    We determine non-perturbatively the parameters of the lattice HQET Lagrangian and those of heavy-light axial-vector and vector currents in the quenched approximation. The HQET expansion includes terms of order 1/m{sub b}. Our results allow to compute, for example, the heavy-light spectrum and B-meson decay constants in the static approximation and to order 1/m{sub b} in HQET. The determination of the parameters is separated into universal and non-universal parts. The universal results can be used to determine the parameters for various discretizations. The computation reported in this paper uses the plaquette gauge action and the ''HYP1/2'' action for the b-quark described by HQET. The parameters of the currents also depend on the light-quark action, for which we choose non-perturbatively O(a)-improved Wilson fermions. (orig.)

  17. Nutrient-induced stimulation of protein synthesis in mouse skeletal muscle is limited by the mTORC1 repressor REDD1.

    Science.gov (United States)

    Gordon, Bradley S; Williamson, David L; Lang, Charles H; Jefferson, Leonard S; Kimball, Scot R

    2015-04-01

    In skeletal muscle, the nutrient-induced stimulation of protein synthesis requires signaling through the mechanistic target of rapamycin complex 1 (mTORC1). Expression of the repressor of mTORC1 signaling, regulated in development and DNA damage 1 (REDD1), is elevated in muscle during various atrophic conditions and diminished under hypertrophic conditions. The question arises as to what extent REDD1 limits the nutrient-induced stimulation of protein synthesis. The objective was to examine the role of REDD1 in limiting the response of muscle protein synthesis and mTORC1 signaling to a nutrient stimulus. Wild type REDD1 gene (REDD1(+/+)) and disruption in the REDD1 gene (REDD1(-/-)) mice were feed deprived for 16 h and randomized to remain feed deprived or refed for 15 or 60 min. The tibialis anterior was then removed for analysis of protein synthesis and mTORC1 signaling. In feed-deprived mice, protein synthesis and mTORC1 signaling were significantly lower in REDD1(+/+) than in REDD1(-/-) mice. Thirty minutes after the start of refeeding, protein synthesis in REDD1(+/+) mice was stimulated by 28%, reaching a value similar to that observed in feed-deprived REDD1(-/-) mice, and was accompanied by increased phosphorylation of mTOR (Ser2448), p70S6K1 (Thr389), and 4E-BP1 (Ser65) by 81%, 167%, and 207%, respectively. In refed REDD1(-/-) mice, phosphorylation of mTOR (Ser2448), p70S6K1 (Thr389), and 4E-BP1 (Ser65) were significantly augmented above the values observed in refed REDD1(+/+) mice by 258%, 405%, and 401%, respectively, although protein synthesis was not coordinately increased. Seventy-five minutes after refeeding, REDD1 expression in REDD1(+/+) mice was reduced (∼15% of feed-deprived REDD1(+/+) values), and protein synthesis and mTORC1 signaling were not different between refed REDD1(+/+) mice and REDD1(-/-) mice. The results show that REDD1 expression limits protein synthesis in mouse skeletal muscle by inhibiting mTORC1 signaling during periods of feed

  18. Development of a 1-m plasma source for heavy ion beam charge neutralization

    Science.gov (United States)

    Efthimion, Philip C.; Gilson, Erik P.; Grisham, Larry; Davidson, Ronald C.; Yu, Simon; Waldron, William; Grant Logan, B.

    2005-05-01

    Highly ionized plasmas are being employed as a medium for charge neutralizing heavy ion beams in order to focus to a small spot size. Calculations suggest that plasma at a density of 1-100 times the ion beam density and at a length ˜0.1-1 m would be suitable for achieving a high level of charge neutralization. A radio frequency (RF) source was constructed at the Princeton Plasma Physics Laboratory (PPPL) in support of the joint Neutralized Transport Experiment (NTX) at the Lawrence Berkeley National Laboratory (LBNL) to study ion beam neutralization. Pulsing the source enabled operation at pressures ˜10 -6 Torr with plasma densities of 10 11 cm -3. Near 100% ionization was achieved. The plasma was 10 cm in length, but future experiments require a source 1 m long. The RF source does not easily scale to the length. Consequently, large-volume plasma sources based upon ferroelectric ceramics are being considered. These sources have the advantage of being able to increase the length of the plasma and operate at low neutral pressures. The source will utilize the ferroelectric ceramic BaTiO 3 to form metal plasma. A 1 m long section of the drift tube inner surface of NTX will be covered with ceramic. A high voltage (˜1-5 kV) is applied between the drift tube and the front surface of the ceramic by placing a wire grid on the front surface. Plasma densities of 10 12 cm -3 and neutral pressures ˜10 -6 Torr are expected. A test stand to produce 20 cm long plasma is being constructed and will be tested before a 1 m long source is developed.

  19. Development of a 1-m plasma source for heavy ion beam charge neutralization

    International Nuclear Information System (INIS)

    Efthimion, Philip C.; Gilson, Erik P.; Grisham, Larry; Davidson, Ronald C.; Yu, Simon; Waldron, William; Grant Logan, B.

    2005-01-01

    Highly ionized plasmas are being employed as a medium for charge neutralizing heavy ion beams in order to focus to a small spot size. Calculations suggest that plasma at a density of 1-100 times the ion beam density and at a length ∼0.1-1 m would be suitable for achieving a high level of charge neutralization. A radio frequency (RF) source was constructed at the Princeton Plasma Physics Laboratory (PPPL) in support of the joint Neutralized Transport Experiment (NTX) at the Lawrence Berkeley National Laboratory (LBNL) to study ion beam neutralization. Pulsing the source enabled operation at pressures ∼10 -6 Torr with plasma densities of 10 11 cm -3 . Near 100% ionization was achieved. The plasma was 10 cm in length, but future experiments require a source 1 m long. The RF source does not easily scale to the length. Consequently, large-volume plasma sources based upon ferroelectric ceramics are being considered. These sources have the advantage of being able to increase the length of the plasma and operate at low neutral pressures. The source will utilize the ferroelectric ceramic BaTiO 3 to form metal plasma. A 1 m long section of the drift tube inner surface of NTX will be covered with ceramic. A high voltage (∼1-5 kV) is applied between the drift tube and the front surface of the ceramic by placing a wire grid on the front surface. Plasma densities of 10 12 cm -3 and neutral pressures ∼10 -6 Torr are expected. A test stand to produce 20 cm long plasma is being constructed and will be tested before a 1 m long source is developed

  20. HTLV-1 Tax plugs and freezes UPF1 helicase leading to nonsense-mediated mRNA decay inhibition.

    Science.gov (United States)

    Fiorini, Francesca; Robin, Jean-Philippe; Kanaan, Joanne; Borowiak, Malgorzata; Croquette, Vincent; Le Hir, Hervé; Jalinot, Pierre; Mocquet, Vincent

    2018-01-30

    Up-Frameshift Suppressor 1 Homolog (UPF1) is a key factor for nonsense-mediated mRNA decay (NMD), a cellular process that can actively degrade mRNAs. Here, we study NMD inhibition during infection by human T-cell lymphotropic virus type I (HTLV-1) and characterise the influence of the retroviral Tax factor on UPF1 activity. Tax interacts with the central helicase core domain of UPF1 and might plug the RNA channel of UPF1, reducing its affinity for nucleic acids. Furthermore, using a single-molecule approach, we show that the sequential interaction of Tax with a RNA-bound UPF1 freezes UPF1: this latter is less sensitive to the presence of ATP and shows translocation defects, highlighting the importance of this feature for NMD. These mechanistic insights reveal how HTLV-1 hijacks the central component of NMD to ensure expression of its own genome.

  1. N=1 field theory duality from M theory

    International Nuclear Information System (INIS)

    Schmaltz, M.; Sundrum, R.

    1998-01-01

    We investigate Seiberg close-quote s N=1 field theory duality for four-dimensional supersymmetric QCD with the M-theory 5-brane. We find that the M-theory configuration for the magnetic dual theory arises via a smooth deformation of the M-theory configuration for the electric theory. The creation of Dirichlet 4-branes as Neveu-Schwarz 5-branes are passed through each other in type IIA string theory is given an elegant derivation from M theory. copyright 1998 The American Physical Society

  2. Data of evolutionary structure change: 1M3DI-1T60W [Confc[Archive

    Lifescience Database Archive (English)

    Full Text Available tryIDChain>1M3DI APLPM--MPVAE ...> -- EEE> ATOM 14546 CA ALA I 86 32.542 22.976 78.017 1.00...ain>1T60W EPMPMSMAPITG > EEE> IECHG-RGTCN >EEEE - EEEE.../entryIDChain> IECNGARGTCH >EEEEGGGEEEE>

  3. M2 macrophages coexist with a Th1-driven profile in periapical cysts.

    Science.gov (United States)

    Ribeiro, C M; de Carli, M L; Nonogaki, S; Nogueira, D A; Pereira, A A C; Sperandio, F F; Hanemann, J A C

    2018-02-01

    To evaluate the participation of both Th1 and Th2 responses in periapical cysts by assessing the presence of M2 macrophages, as well as acute IL-1 β, TNF-α and IL-6 cytokines. Twenty-four cases of periapical cysts were selected. Immuno-expressions of IL-1 β, IL-6, TNF-α and CD163 were analysed in the cystic capsules in both superficial and deeper regions. Data were analysed with paired Wilcoxon test and Spearman correlation coefficient (P ≤ 0.05). There was a higher expression of IL-1β, IL-6, TNF-α and M2 macrophages in the superficial region (P periapical cysts and correlated with the expression of certain acute Th1-related cytokines. This illustrates the coexistence of an acute and chronic Th2-driven immune response in these lesions. Although M2 macrophages favour the healing process, their presence is not sufficient for periapical cyst regression, once an acute active response has occurred due to an infectious stimuli. © 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.

  4. Genetic and epigenetic inactivation of SESTRIN1 controls mTORC1 and response to EZH2 inhibition in follicular lymphoma.

    Science.gov (United States)

    Oricchio, Elisa; Katanayeva, Natalya; Donaldson, Maria Christine; Sungalee, Stephanie; Pasion, Joyce P; Béguelin, Wendy; Battistello, Elena; Sanghvi, Viraj R; Jiang, Man; Jiang, Yanwen; Teater, Matt; Parmigiani, Anita; Budanov, Andrei V; Chan, Fong Chun; Shah, Sohrab P; Kridel, Robert; Melnick, Ari M; Ciriello, Giovanni; Wendel, Hans-Guido

    2017-06-28

    Follicular lymphoma (FL) is an incurable form of B cell lymphoma. Genomic studies have cataloged common genetic lesions in FL such as translocation t(14;18), frequent losses of chromosome 6q, and mutations in epigenetic regulators such as EZH2 Using a focused genetic screen, we identified SESTRIN1 as a relevant target of the 6q deletion and demonstrate tumor suppression by SESTRIN1 in vivo. Moreover, SESTRIN1 is a direct target of the lymphoma-specific EZH2 gain-of-function mutation ( EZH2 Y641X ). SESTRIN1 inactivation disrupts p53-mediated control of mammalian target of rapamycin complex 1 (mTORC1) and enables mRNA translation under genotoxic stress. SESTRIN1 loss represents an alternative to RRAGC mutations that maintain mTORC1 activity under nutrient starvation. The antitumor efficacy of pharmacological EZH2 inhibition depends on SESTRIN1, indicating that mTORC1 control is a critical function of EZH2 in lymphoma. Conversely, EZH2 Y641X mutant lymphomas show increased sensitivity to RapaLink-1, a bifunctional mTOR inhibitor. Hence, SESTRIN1 contributes to the genetic and epigenetic control of mTORC1 in lymphoma and influences responses to targeted therapies. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  5. Battling Obesity in K-12 Learners from an Exercise Physiology Perspective

    Science.gov (United States)

    Rattigan, Peter; Biren, Greg

    2007-01-01

    Physical education practitioners and programs have the opportunity and obligation to help children become physically educated, healthy, and active adults. This article discusses the battle against obesity in K-12 learners from an exercise physiology perspective and focuses on the fact that practitioners have all the tools they need to battle this…

  6. Hydrogeologic Setting of A/M Area: Framework for Groundwater Transport. Book 1

    Energy Technology Data Exchange (ETDEWEB)

    Van Pelt, R.; Lewis, S.E.; Aadland, R.K.

    1994-03-11

    This document includes a brief summary of the regional geology within a 200--mile radius of the A/M Area, a summary of stratigraphy and hydrostratigraphic nomenclature as it applies to the A/M Area, and a summary of stratigraphy and hydrostratigraphy specific to the A/M Area. Five different stratigraphic cross sections show site-specific geology of the Tertiary section of the Upper Atlantic Coastal Plain geologic province within the A/M Area. The Cretaceous section lacks detail because the deepest wells penetrate only the uppermost part of the Upper Cretaceous sediments. Most of the wells are confined to the Tertiary section. The A/M Area is located in the northwestern corner of the Savannah River Site (SRS). The area serves as a main administrative hub for the site. Between 1958 and 1985, approximately 2,000,000 pounds of volatile organic solvents (metal degreasers, primarily trichloroethylene and tetrachloroethylene) were routed to the M Area Settling Basin. Between 1954 and 1958, effluent also was discharged to Tim`s Branch via the A014 Outfall. In the main M Area Solvent Handling/Storage Area, a significant amount of leakage occurred from drums stored during this time period. Extensive quantities of solvents were transported, via the Process Sewer Line, to the M Area Settling Basin, and leaks occurred along this line as well. A smaller source area has been identified and is centered around the Savannah River Laboratory (SRL) (now called the Savannah River Technology Center [SRTC]) Complex. All of these source areas are represented by solvent contamination in the groundwater system. (Abstract Truncated)

  7. The computer code Eurdyn - 1 M. (Release 1) Part 2: User's Manual

    International Nuclear Information System (INIS)

    Donea, J.; Giuliani, S.

    1979-01-01

    This report is the user's manual for the computer code Eurdyn-1 M developed at the J.R.C. Ispra for use in containment and fuel subassembly analyses for fast reactor safety studies. The input data are defined and a test problem is presented to illustrate both the input and the output of results

  8. Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin.

    Science.gov (United States)

    Bhagwat, Shripad V; Gokhale, Prafulla C; Crew, Andrew P; Cooke, Andy; Yao, Yan; Mantis, Christine; Kahler, Jennifer; Workman, Jennifer; Bittner, Mark; Dudkin, Lorina; Epstein, David M; Gibson, Neil W; Wild, Robert; Arnold, Lee D; Houghton, Peter J; Pachter, Jonathan A

    2011-08-01

    The phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway is frequently activated in human cancers, and mTOR is a clinically validated target. mTOR forms two distinct multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, metabolism, proliferation, and survival. Rapamycin and its analogues partially inhibit mTOR through allosteric binding to mTORC1, but not mTORC2, and have shown clinical utility in certain cancers. Here, we report the preclinical characterization of OSI-027, a selective and potent dual inhibitor of mTORC1 and mTORC2 with biochemical IC(50) values of 22 nmol/L and 65 nmol/L, respectively. OSI-027 shows more than 100-fold selectivity for mTOR relative to PI3Kα, PI3Kβ, PI3Kγ, and DNA-PK. OSI-027 inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo. OSI-027 and OXA-01 (close analogue of OSI-027) potently inhibit proliferation of several rapamycin-sensitive and -insensitive nonengineered and engineered cancer cell lines and also, induce cell death in tumor cell lines with activated PI3K-AKT signaling. OSI-027 shows concentration-dependent pharmacodynamic effects on phosphorylation of 4E-BP1 and AKT in tumor tissue with resulting tumor growth inhibition. OSI-027 shows robust antitumor activity in several different human xenograft models representing various histologies. Furthermore, in COLO 205 and GEO colon cancer xenograft models, OSI-027 shows superior efficacy compared with rapamycin. Our results further support the important role of mTOR as a driver of tumor growth and establish OSI-027 as a potent anticancer agent. OSI-027 is currently in phase I clinical trials in cancer patients. ©2011 AACR

  9. Presynaptic mGlu1 and mGlu5 autoreceptors facilitate glutamate exocytosis from mouse cortical nerve endings.

    Science.gov (United States)

    Musante, Veronica; Neri, Elisa; Feligioni, Marco; Puliti, Aldamaria; Pedrazzi, Marco; Conti, Valerio; Usai, Cesare; Diaspro, Alberto; Ravazzolo, Roberto; Henley, Jeremy M; Battaglia, Giuseppe; Pittaluga, Anna

    2008-09-01

    The effects of mGlu1 and mGlu5 receptor activation on the depolarization-evoked release of [3H]d-aspartate ([3H]D-ASP) from mouse cortical synaptosomes were investigated. The mGlu1/5 receptor agonist 3,5-DHPG (0.1-100microM) potentiated the K+(12mM)-evoked [3H]D-ASP overflow. The potentiation occurred in a concentration-dependent manner showing a biphasic pattern. The agonist potentiated [3H]D-ASP exocytosis when applied at 0.3microM; the efficacy of 3,5-DHPG then rapidly declined and reappeared at 30-100microM. The fall of efficacy of agonist at intermediate concentration may be consistent with 3,5-DHPG-induced receptor desensitization. Facilitation of [3H]D-ASP exocytosis caused by 0.3microM 3,5-DHPG was prevented by the selective mGlu5 receptor antagonist MPEP, but was insensitive to the selective mGlu1 receptor antagonist CPCCOEt. In contrast, CPCCOEt prevented the potentiation by 50microM 3,5-DHPG, while MPEP had minimal effect. Unexpectedly, LY 367385 antagonized both the 3,5-DHPG-induced effects. A total of 0.3microM 3,5-DHPG failed to facilitate the K+-evoked [3H]D-ASP overflow from mGlu5 receptor knockout (mGlu5-/-) cortical synaptosomes, but not from nerve terminals prepared from the cortex of animals lacking the mGlu1 receptors, the crv4/crv4 mice. On the contrary, 50microM 3,5-DHPG failed to affect the [3H]D-ASP exocytosis from cortical synaptosomes obtained from crv4/crv4 and mGlu5-/-mice. Western blot analyses in subsynaptic fractions support the existence of both mGlu1 and mGlu5 autoreceptors located presynaptically, while immunocytochemistry revealed their presence at glutamatergic terminals. We propose that mGlu1 and mGlu5 autoreceptors exist on mouse glutamatergic cortical terminals; mGlu5 receptors may represent the "high affinity" binding sites for 3,5-DHPG, while mGlu1 autoreceptors represent the "low affinity" binding sites.

  10. The Battle of Savo Island August 9th, 1942. Strategical and Tactical Analysis. Part I

    Science.gov (United States)

    1950-01-01

    Department publIcation SSC-677, Survey of the Bolcmon Islands. March 16, 1943, Confidential. *OCTW 62 personal latter to Captain RC. Parker, USN(Ret...cakiral Jellicu had si&Unalled Ad- miral Oqattr "Wh•re !e the anek-q’s battles Fleet?" and Lsirl Beatty •had repliid la a most v& omnic kid inoomplete m

  11. Energy-conscious building automation. Phase 1 - pilot study. Main report; Energirigtig bygningsautomation. Fase 1 - Forundersoegelse. Hovedrapport

    Energy Technology Data Exchange (ETDEWEB)

    Hummelshoej, R.M.; Kaarup Olsen, P. (COWI A/S, Kgs. Lyngby (Denmark)); Brohus, H. (Aalborg Univ. (AAU), Inst. for Byggeri og Anlaeg, Aalborg (Denmark)); Olesen, Bjarne W. (Danmarks Tekniske Univ., DTU Byg. Institut for Byggeri og Anlaeg, ICIEE, Kgs. Lyngby (Denmark)); Bang Skjoedt, A.; Giliamsen, P. (TAC A/S, Herlev (Denmark))

    2009-09-15

    Building Automation is a significant and sometimes overlooked element of low-energy buildings to ensure large energy savings by e.g. demand control and to ensure optimised operation of ventilation system, cooling and heating system etc. in both new buildings and in modernisation of existing buildings. In the building design including installation, automation makes up a large part of the total construction costs. A rough figure is 3-500 DKK/m{sup 2}. It is estimated that energy-efficient building automation can reduce buildings' energy demand by about 15 kWh/m{sup 2} (electricity and heating) on average. Based on this possible reduction of building energy demand, the project deals with optimisation of control/adjustment of building installations for lighting, heating, cooling and ventilation systems. An investigated key parameter is how much it will be okay for the room temperature to 'glide' (change) during the occupied hours in a heavy and a light office building, and how this will influence the energy demand and the sensation of the indoor climate. The project shows that it is possible to save about 15 kWh/m{sup 2} primary energy by letting the temperature 'glide' +2,5 deg. C during the daily occupied hours instead of +1 deg. C. With this operation philosophy, the building constructions' thermo-active capacity can be utilised better, and there will be less requirements for automation and operation of the climate system. In the project is assessed how large a zone area can be covered by typical sensors in order to maintain a satisfactory indoor climate and the corresponding energy demand. The electricity consumption for building automation may account for up to 6 kWh/m{sup 2} per year. The project has made a preliminary basis for indicating a good practice for 1) automation of buildings with a view to good indoor climate and a low energy demand and 2) necessary equipping with meters to be able to document energy savings and energy

  12. 99mTc Labeled Glucagon-Like Peptide-1-Analogue (99mTc-GLP1) Scintigraphy in the Management of Patients with Occult Insulinoma

    Science.gov (United States)

    Sowa-Staszczak, Anna; Trofimiuk-Müldner, Małgorzata; Stefańska, Agnieszka; Tomaszuk, Monika; Buziak-Bereza, Monika; Gilis-Januszewska, Aleksandra; Jabrocka-Hybel, Agata; Głowa, Bogusław; Małecki, Maciej; Bednarczuk, Tomasz; Kamiński, Grzegorz; Kowalska, Aldona; Mikołajczak, Renata; Janota, Barbara; Hubalewska-Dydejczyk, Alicja

    2016-01-01

    Introduction The aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma. Materials and Methods Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions. Results Positive results of GLP-1 scintigraphy were observed in 28 patients. In 18 patients postsurgical histopathological examination confirmed diagnosis of insulinoma. Two patients had contraindications to the surgery, one patient did not want to be operated. One patient, who presented with postprandial hypoglycemia, with positive result of GLP-1 imaging was not qualified for surgery and is in the observational group. Eight patients were lost for follow up, among them 6 patients with positive GLP-1 scintigraphy result. One patient with negative scintigraphy was diagnosed with malignant insulinoma. In two patients with negative scintigraphy Munchausen syndrome was diagnosed (patients were taking insulin). Other seven patients with negative results of 99mTcGLP-1 scintigraphy and postprandial hypoglycemia with C-peptide and insulin levels within the limits of normal ranges are in the observational group. We would like to mention that 99mTc-GLP1-SPECT/CT was also performed in 3 pts with nesidioblastosis (revealing diffuse tracer uptake in two and a focal lesion in one case) and in two patients with malignant insulinoma (with the a focal uptake in the localization of a removed pancreatic headin one case and negative GLP-1 1 scintigraphy in the other patient). Conclusions 99mTc-GLP1-SPECT/CT could be helpful examination in the management of patients with hypoglycemia enabling proper localization of the pancreatic lesion and effective

  13. BMAL1-dependent regulation of the mTOR signaling pathway delays aging.

    Science.gov (United States)

    Khapre, Rohini V; Kondratova, Anna A; Patel, Sonal; Dubrovsky, Yuliya; Wrobel, Michelle; Antoch, Marina P; Kondratov, Roman V

    2014-01-01

    The circadian clock, an internal time-keeping system, has been linked with control of aging, but molecular mechanisms of regulation are not known. BMAL1 is a transcriptional factor and core component of the circadian clock; BMAL1 deficiency is associated with premature aging and reduced lifespan. Here we report that activity of mammalian Target of Rapamycin Complex 1 (mTORC1) is increased upon BMAL1 deficiency both in vivo and in cell culture. Increased mTOR signaling is associated with accelerated aging; in accordance with that, treatment with the mTORC1 inhibitor rapamycin increased lifespan of Bmal1-/- mice by 50%. Our data suggest that BMAL1 is a negative regulator of mTORC1 signaling. We propose that the circadian clock controls the activity of the mTOR pathway through BMAL1-dependent mechanisms and this regulation is important for control of aging and metabolism.

  14. Electric conductivity of double fluorides in the systems M1F-Th(U)F4(M1=K, Tl) and M2F2-ThF4(M2=Ca, Sr, Ba)

    International Nuclear Information System (INIS)

    Murin, I.V.; Andreev, A.M.; Amelin, Yu.V.

    1982-01-01

    The temperature dependence of electric conductivity of some double fluorides formed in the systems M 1 F-Th(U)F 4 (M 1 =K, Tl) and M 2 F 2 -ThF 4 (M 2 =Ca, Sr, Ba) as well as UF 3 in a wide temperature range is studied. It is shown that the values of electric conductivity and activation energy of these fluorides depend on the compound structure and cation nature. The temperature electric conductivity dependence for double fluorides with the tysonite structure is close to the lanthanum fluoride dependence. Taking into account low electron electric conductivity component the conclusion is drawn that the investigated compounds can be used as solid electrolytes

  15. Molybdenum emission from impurity-induced m= 1 snake-modes on the Alcator C-Mod tokamak

    Energy Technology Data Exchange (ETDEWEB)

    Delgado-Aparicio, L. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08540 (United States); MIT - Plasma Science and Fusion Center, Cambridge, Massachusetts 02139 (United States); Bitter, M.; Gates, D.; Hill, K.; Pablant, N. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08540 (United States); Granetz, R.; Reinke, M.; Podpaly, Y.; Rice, J. [MIT - Plasma Science and Fusion Center, Cambridge, Massachusetts 02139 (United States); Beiersdorfer, P. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); Sugiyama, L. [MIT - Laboratory for Nuclear Science, Cambridge, Massachusetts 02139 (United States)

    2012-10-15

    A suite of novel high-resolution spectroscopic imaging diagnostics has facilitated the identification and localization of molybdenum impurities as the main species during the formation and lifetime of m= 1 impurity-induced snake-modes on Alcator C-Mod. Such measurements made it possible to infer, for the first time, the perturbed radiated power density profiles from which the impurity density can be deduced.

  16. Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2.

    Directory of Open Access Journals (Sweden)

    Cécile Pierre-Eugene

    Full Text Available BACKGROUND: In diabetic patients, the pharmacokinetics of injected human insulin does not permit optimal control of glycemia. Fast and slow acting insulin analogues have been developed, but they may have adverse properties, such as increased mitogenic or anti-apoptotic signaling. Insulin/IGF1 hybrid receptors (IR/IGF1R, present in most tissues, have been proposed to transmit biological effects close to those of IGF1R. However, the study of hybrid receptors is difficult because of the presence of IR and IGF1R homodimers. Our objective was to perform the first study on the pharmacological properties of the five marketed insulin analogues towards IR/IGF1R hybrids. METHODOLOGY: To study the effect of insulin analogues on IR/IGF1R hybrids, we used our previously developed Bioluminescence Resonance Energy Transfer (BRET assay that permits specific analysis of the pharmacological properties of hybrid receptors. Moreover, we have developed a new, highly sensitive BRET-based assay to monitor phophatidylinositol-3 phosphate (PIP(3 production in living cells. Using this assay, we performed a detailed pharmacological analysis of PIP(3 production induced by IGF1, insulin and insulin analogues in living breast cancer-derived MCF-7 and MDA-MB231 cells. RESULTS: Among the five insulin analogues tested, only glargine stimulated IR/IGF1R hybrids with an EC50 that was significantly lower than insulin and close to that of IGF1. Glargine more efficiently stimulated PIP(3 production in MCF-7 cells but not in MDA-MB231 cells as compared to insulin. In contrast, glargine metabolites M1 and M2 showed lower potency for hybrid receptors stimulation, PIP(3 production, Akt and Erk1/2 phosphorylation and DNA synthesis in MCF-7 cells, compared to insulin. CONCLUSION: Glargine, possibly acting through IR/IGF1R hybrids, displays higher potency, whereas its metabolites M1 and M2 display lower potency than insulin for the stimulation of proliferative/anti-apoptotic pathways in

  17. Geometry and bonding in the ground and lowest triplet state of D{sub 6h} symmetric crenellated edged C{sub 6[3m(m-1)+1]}H{sub 6(2m-1)} (m = 2,..., 6) graphene hydrocarbon molecules

    Energy Technology Data Exchange (ETDEWEB)

    Philpott, Michael R., E-mail: philpott@imr.edu [Center for Computational Materials Science, Institute of Materials Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, 980-8577 Sendai (Japan); Kawazoe, Yoshiyuki [Center for Computational Materials Science, Institute of Materials Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, 980-8577 Sendai (Japan)

    2009-03-30

    Ab initio plane wave all valence electron based DFT calculations were used to explore the dichotomy of perimeter vs. interior in the electronic and geometric structure of the D{sub 6h} singlet ground state and D{sub 2h} lowest triplet state of planar graphene hydrocarbon molecules with crenellated (arm chair) edges and the general formula C{sub 6[3m(m-1)+1]} H{sub 6(2m-1)} where m = 2,...,6. The largest molecule C{sub 546}H{sub 66} was 4.78 nm across and contained 2250 valence electrons. These molecules are nominally 'fully benzenoid hydrocarbons'. However with increasing size, the core of central atoms abandoned any fully benzenoid geometry they had in small systems and organized into single layer graphite (graphene) structure. The perimeter atoms of the crenellation adopted a conjugated geometry with unequal bonds and between core and perimeter there were some C{sub 6} rings retaining remnants of aromatic sextet-type properties. Compared to a zigzag edge the crenellated edge conferred stability in all the systems studied as measured by the singlet homo-lumo level gap BG{sub 0} and the singlet-lowest triplet energy gap {Delta}E{sub ST}. For the largest crenellated system (m = 6) BG{sub 0} and {Delta}E{sub ST} were approximately 0.7 eV, larger in value than for similarly sized hexagonal graphenes with zigzag edges. Triplet states were identified for all the molecules in the series and in the case of the m = 2 molecule hexabenzocoronene C{sub 42}H{sub 18}, two conformations with D{sub 2h} symmetry were identified and compared to features on the triplet state potential energy surface of benzene.

  18. Super Phenix 1: in Service inspection of main and safety tanks weldments

    International Nuclear Information System (INIS)

    Asty, Michel; Vertut, Jean; Argous, J.P.

    1980-05-01

    In service inspection of the main tank of the Super Phenix 1 reactor is a new demand as compared to Phenix: the authorities have asked that surface and internal defects could be detected and their evolution monitored in the future. The presence of thermal baffles inside the main tank precludes the access on that side: the distance between the main and safety tanks takes into account the room needed for an In Service Inspection module. An inspection vehicle is presently under development, which includes ultrasonic examination (focussed probes) and visual examination (TV cameras) capabilities. We briefly describe the techniques that have been selected for ultrasonic testing and also for the vehicle and its guidance between the tanks

  19. Super Phenix 1: In-service inspection of main and safety tanks weldments

    Energy Technology Data Exchange (ETDEWEB)

    Asty, M [DTech/STA, Centre d' Etudes Nucleaires de Saclay (France); Vertut, J [DPR/STEP, Centre d' Etudes Nucleaires de Saclay (France); Argous, J P [DRNR/STRS, Centre d' Etudes Nucleaires de Cadarache (France)

    1980-11-01

    In Service Inspection of the main tank of the Super Phenix 1 reactor is a new demand compared to Phenix: the authorities have asked that surface and internal defects be detected and their evolution monitored in the future. The presence of thermal baffles inside the main tank precludes the access on that side: the distance between the main and safety tanks takes into account the room needed for an In Service Inspection module. An inspection vehicle is presently under development, which includes ultrasonic examination (focussed probes) and visual examination (TV cameras) capabilities. We briefly describe the techniques that have been selected for ultrasonic testing and also for the vehicle and its guidance between the tanks. (author)

  20. Super Phenix 1: In-service inspection of main and safety tanks weldments

    International Nuclear Information System (INIS)

    Asty, M.; Vertut, J.; Argous, J.P.

    1980-01-01

    In Service Inspection of the main tank of the Super Phenix 1 reactor is a new demand compared to Phenix: the authorities have asked that surface and internal defects be detected and their evolution monitored in the future. The presence of thermal baffles inside the main tank precludes the access on that side: the distance between the main and safety tanks takes into account the room needed for an In Service Inspection module. An inspection vehicle is presently under development, which includes ultrasonic examination (focussed probes) and visual examination (TV cameras) capabilities. We briefly describe the techniques that have been selected for ultrasonic testing and also for the vehicle and its guidance between the tanks. (author)

  1. Caenorhabditis elegans ATPase inhibitor factor 1 (IF1 MAI-2 preserves the mitochondrial membrane potential (Δψm and is important to induce germ cell apoptosis.

    Directory of Open Access Journals (Sweden)

    L P Fernández-Cárdenas

    Full Text Available When the electrochemical proton gradient is disrupted in the mitochondria, IF1 (Inhibitor Factor-1 inhibits the reverse hydrolytic activity of the F1Fo-ATP synthase, thereby allowing cells to conserve ATP at the expense of losing the mitochondrial membrane potential (Δψm. The function of IF1 has been studied mainly in different cell lines, but these studies have generated contrasting results, which have not been helpful to understand the real role of this protein in a whole organism. In this work, we studied IF1 function in Caenorhabditis elegans to understand IF1´s role in vivo. C. elegans has two inhibitor proteins of the F1Fo-ATPase, MAI-1 and MAI-2. To determine their protein localization in C. elegans, we generated translational reporters and found that MAI-2 is expressed ubiquitously in the mitochondria; conversely, MAI-1 was found in the cytoplasm and nuclei of certain tissues. By CRISPR/Cas9 genome editing, we generated mai-2 mutant alleles. Here, we showed that mai-2 mutant animals have normal progeny, embryonic development and lifespan. Contrasting with the results previously obtained in cell lines, we found no evident defects in the mitochondrial network, dimer/monomer ATP synthase ratio, ATP concentration or respiration. Our results suggest that some of the roles previously attributed to IF1 in cell lines could not reflect the function of this protein in a whole organism and could be attributed to specific cell lines or methods used to silence, knockout or overexpress this protein. However, we did observe that animals lacking IF1 had an enhanced Δψm and lower physiological germ cell apoptosis. Importantly, we found that mai-2 mutant animals must be under stress to observe the role of IF1. Accordingly, we observed that mai-2 mutant animals were more sensitive to heat shock, oxidative stress and electron transport chain blockade. Furthermore, we observed that IF1 is important to induce germ cell apoptosis under certain types of

  2. Crosstalk between mTORC1 and cAMP Signaling

    Science.gov (United States)

    2016-09-01

    whether bidirectional inhibition of trafficking be- tween the endoplasmic reticulum (ER) and Golgi would affect Gln-induced activation of mTORC1 (23). We...Shimizu N, Matsumoto K, Itoh M, Ishitani T. 2012. NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor...L, Pan D, Edgar BA. 2003. Rheb promotes cell growth as a component of the insulin/ TOR signalling network . Nat Cell Biol 5: 566–571. Sengupta S

  3. The Armys M-1 Abrams, M-2/M-3 Bradley, and M-1126 Stryker: Background and Issues for Congress

    Science.gov (United States)

    2016-04-05

    the Army John McHugh , urging instead the limited production of 70 M-1A2SEPv2 tanks per year from FY2013 to FY2017. 32 Congress subsequently decided...House Members sent a letter to Secretary of the Army McHugh expressing concern over the Army’s failure to fund production of the M-1A2. Congress...John McHugh by Rep. Sander Levin and Rep. Mike Rogers, May 6, 2011. 33 See CRS Reports: CRS Report R43323, Defense: FY2014 Authorization and

  4. IQGAP1 is important for activation of caspase-1 in macrophages and is targeted by Yersinia pestis type III effector YopM.

    Science.gov (United States)

    Chung, Lawton K; Philip, Naomi H; Schmidt, Valentina A; Koller, Antonius; Strowig, Till; Flavell, Richard A; Brodsky, Igor E; Bliska, James B

    2014-07-01

    YopM is a leucine-rich repeat (LRR)-containing effector in several Yersinia species, including Yersinia pestis and Y. pseudotuberculosis. Different Yersinia strains encode distinct YopM isoforms with variable numbers of LRRs but conserved C-terminal tails. A 15-LRR isoform in Y. pseudotuberculosis YPIII was recently shown to bind and inhibit caspase-1 via a YLTD motif in LRR 10, and attenuation of YopM(-) YPIII was reversed in mice lacking caspase-1, indicating that caspase-1 inhibition is a major virulence function of YopM(YPIII). To determine if other YopM proteins inhibit caspase-1, we utilized Y. pseudotuberculosis strains natively expressing a 21-LRR isoform lacking the YLTD motif (YopM(32777)) or ectopically expressing a Y. pestis 15-LRR version with a functional (YopM(KIM)) or inactivated (YopM(KIM) D271A) YLTD motif. Results of mouse and macrophage infections with these strains showed that YopM(32777), YopM(KIM), and YopM(KIM) D271A inhibit caspase-1 activation, indicating that the YLTD motif is dispensable for this activity. Analysis of YopM(KIM) deletion variants revealed that LRRs 6 to 15 and the C-terminal tail are required to inhibit caspase-1 activation. YopM(32777), YopM(KIM), and YopM(KIM) deletion variants were purified, and binding partners in macrophage lysates were identified. Caspase-1 bound to YopM(KIM) but not YopM(32777). Additionally, YopM(KIM) bound IQGAP1 and the use of Iqgap1(-/-) macrophages revealed that this scaffolding protein is important for caspase-1 activation upon infection with YopM(-) Y. pseudotuberculosis. Thus, while multiple YopM isoforms inhibit caspase-1 activation, their variable LRR domains bind different host proteins to perform this function and the LRRs of YopM(KIM) target IQGAP1, a novel regulator of caspase-1, in macrophages. Importance: Activation of caspase-1, mediated by macromolecular complexes termed inflammasomes, is important for innate immune defense against pathogens. Pathogens can, in turn, subvert

  5. Global comparison of warring groups in 2002-2007: fatalities from targeting civilians vs. fighting battles.

    Science.gov (United States)

    Hicks, Madelyn Hsiao-Rei; Lee, Uih Ran; Sundberg, Ralph; Spagat, Michael

    2011-01-01

    Warring groups that compete to dominate a civilian population confront contending behavioral options: target civilians or battle the enemy. We aimed to describe degrees to which combatant groups concentrated lethal behavior into intentionally targeting civilians as opposed to engaging in battle with opponents in contemporary armed conflict. We identified all 226 formally organized state and non-state groups (i.e. actors) that engaged in lethal armed conflict during 2002-2007: 43 state and 183 non-state. We summed civilians killed by an actor's intentional targeting with civilians and combatants killed in battles in which the actor was involved for total fatalities associated with each actor, indicating overall scale of armed conflict. We used a Civilian Targeting Index (CTI), defined as the proportion of total fatalities caused by intentional targeting of civilians, to measure the concentration of lethal behavior into civilian targeting. We report actor-specific findings and four significant trends: 1.) 61% of all 226 actors (95% CI 55% to 67%) refrained from targeting civilians. 2.) Logistic regression showed actors were more likely to have targeted civilians if conflict duration was three or more years rather than one year. 3.) In the 88 actors that targeted civilians, multiple regressions showed an inverse correlation between CTI values and the total number of fatalities. Conflict duration of three or more years was associated with lower CTI values than conflict duration of one year. 4.) When conflict scale and duration were accounted for, state and non-state actors did not differ. We describe civilian targeting by actors in prolonged conflict. We discuss comparable patterns found in nature and interdisciplinary research. Most warring groups in 2002-2007 did not target civilians. Warring groups that targeted civilians in small-scale, brief conflict concentrated more lethal behavior into targeting civilians, and less into battles, than groups in larger

  6. Fitting Lanchester Equations to the Battles of Kursk and Ardennes

    OpenAIRE

    Lucas, Thomas W.; Turkes, Turker

    2004-01-01

    The article of record as published may be found at http://dx.doi.org/10.1002/nav.10101 Lanchester equations and their extensions are widely used to calculate attrition in models of warfare. This paper examines how Lanchester models fit detailed daily data on the battles of Kursk and Ardennes. The data on Kursk, often called the greatest tank battle in history, was only recently made available. A new approach is used to find the optimal parameter values and gain an understanding...

  7. The Battle of Moscow - Turning Point of World War II

    Directory of Open Access Journals (Sweden)

    V M Falin

    2015-12-01

    Full Text Available The article is dedicated to the Battle of Moscow in October- December, 1941. Author analyzes the causes of the failure of German army, who tries to encircle and capture Moscow, the events taking place on the outskirts of Moscow, German troops attempts to encircle Moscow. The author presents data on the speech by Adolf Hitler in Berlin on October 5, 1941, in which he acknowledged the failure of the Blitzkrieg and the Battle for Moscow and its suburbs. The researcher uses the documents of the Wehrmacht High Command, which stated that after the Battle of Moscow, German troops could not on any further stage of the war to restore the quality and morale of the armed forces, with whom Reich rushed to a campaign for world domination. The author, a prominent public and political figure of the USSR, also relies on personal recollections, interviews with prominent generals of World War II, including I. Konev.

  8. PODAAC-DYNTO-1D1M1

    Data.gov (United States)

    National Aeronautics and Space Administration — The absolute dynamic topography data (similar to sea level but with respect to the geoid) are on monthly 1 degree grids. These data were generated to help support...

  9. 2014 - Color & Infrared (4 band) - Statewide NAIP (1m)

    Data.gov (United States)

    Vermont Center for Geographic Information — (Link to Metadata) The NAIP_1M_CLRIR_2014 dataset is a (1 meter) truecolor and infrared (4 band) NAIP imagery product acquired during the summer of 2014 by the...

  10. Main: 1JB9 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1JB9 トウモロコシ Corn Zea mays L. Ferredoxin-Nadp Reductase Precursor Zea Mays Molecule:...SLLYDEEFTSYLKQYPDNFRYDKALSREQKNRSGGKMYVQDKIEEYSDEIFKLLDGGAHIYFCGLKGMMPGIQDTLKKVAERRGESWDQKLAQLKKNKQWHVEVY corn_1JB9.jpg ...

  11. M2-F1 in flight over lakebed on tow line

    Science.gov (United States)

    1963-01-01

    After initial ground-tow flights of the M2-F1 using the Pontiac as a tow vehicle, the way was clear to make air tows behind a C-47. The first air tow took place on 16 August 1963. Pilot Milt Thompson found that the M2-F1 flew well, with good control. This first flight lasted less than two minutes from tow-line release to touchdown. The descent rate was 4,000 feet per minute. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got

  12. assessing aflatoxin m1 levels among lactating mothers' in damaturu ...

    African Journals Online (AJOL)

    userpc

    1Department of Microbiology Ahmadu Bello University Zaria, Kaduna State. ... Aflatoxin M1 (AFM1) is a biomarker of aflatoxin B1 exposure in breast milk, a possible risk factor for infant early ..... Mycotoxins in food and feed: present status and ...

  13. Distribution of radiative strength with excitation energy: the E1 and M1 giant resonances

    International Nuclear Information System (INIS)

    Brown, G.E.; Speth, J.

    1979-01-01

    Calculations of the giant dipole resonance in the particle-hole model, employing empirical values for the unperturbed particle and hole energies, have been unsuccessful in pushing the dipole state to a sufficiently high energy. it is argued that unperturbed levels correspondign to an effective mass of m*/m approx. 0.6 to 0.7 should be employed. The couplings of particles and holes to vibrations are the crucial ingredients in these considerations. More generally, it is argued that the effective mass relevant to excitations near the Fermi surface is that corresponding to empirical single-particle levels, m*/m greater than or equal to 1.0. For particle-hole excitations above the Fermi surface, it is a decreasing function of excitation energy, reaching the above values 0.6 to 0.7 for E greater than or equal to 2 dirac constant/b omega, dirac constant/sub omega/ being the shell spacing. This has the consequence of spreading out the M1 strength. A new interpretation of experimental strengths is proposed

  14. Dale Reed with model in front of M2-F1

    Science.gov (United States)

    1967-01-01

    during the initial auto tows. Auto tows were done using a 1000 foot rope fastened to the NASA Pontiac. Rogers Dry Lake provided miles of unobstructed motoring. On April 5, 1963, Thompson lifted the M2-F1's nose off of the ground for the first time on tow. Speed was 86 miles per hour. The little craft seemed to bounce uncontrollably back and forth on the main landing gear, and stopped when he lowered the nose to the ground. He tried again, but each time with the same results. He felt it was a landing gear problem that could have caused the aircraft to roll on its back if he had lifting the main gear off of the ground. Looking at movies of the tests, engineers decided that the bouncing was probably caused by unwanted rudder movements. Flight control system number two was replaced in favor of number one, and it never bounced again. Speeds on tow inched up to 110 miles per hour, which allowed Thompson to climb to about 20 feet, then glide for about 20 seconds after releasing the line. That was the most that could be expected during an auto tow. In the spring of 1963 the M2-F1 was shipped to Ames Research Center, where it was mounted on twenty-foot poles inside the 40-foot by 80-foot wind tunnel. For two weeks, Thompson and engineers Ed Browne and Dick Eldredge took turns 'flying' it as air blasted by at a 135 miles per hour. They learned more about its flying qualities, and accumulated important data for the upcoming aero tows. A NASA C-47 was used for all of the aero tows. The first was on August 16, 1963. The M2-F1 had recently been equipped with an ejection seat, small rockets in the tail to extend the landing flare for about 5 seconds (if needed), and Thompson prepared for the flight with a few more tows behind the Pontiac. Forward visibility in the M2-F1 was very limited on tow, requiring Thompson to fly about 20 feet higher than the C-47 so he could see the plane through the nose window. Towing speed was about 100 miles per hour. Tow release was at 12,000 feet. The

  15. Main: FEB1 [TP Atlas

    Lifescience Database Archive (English)

    Full Text Available y in urban areas - Male peptide pheromone ESP1 regulates female reproductive behavior...male tear fluids Various social behaviors in mice are regulated by chemical signals called pheromones that a... and neural mechanisms that are involved in the decoding of ESP family signals in the vomeronasal system, which leads to behavior

  16. 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.

  17. Main: 1UT7 [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1UT7 シロイヌナズナ Arabidopsis Arabidopsis thaliana (L.) Heynh. Nac-Domain Containing Pro... Meristem Protein; Synonym: Nam, Anac, Abscisic Acid Responsive Nac, Dicyanoaurate Derivative; Chain: A, B; ...Fragment: Dna-Binding Nac Domain, Residues 1-168; Engineered: Yes; Other_details:...A.Ernst, A.N.Olsen, K.Skriver, S.Larsen, L.Lo Leggio Structure Of The Conserved Domain Of Anac, A Member Of ... Transcription Factor, Dna Binding, Abscisic Acid Response, Arabidopsis Thaliana, Crystal Structure, Nac Domai

  18. Main: 1L6H [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available cule: Non-Specific Lipid Transfer Protein; Chain: A; Synonym: Ltp2 Lipid Transport D.Samuel, P.-C.Lyu D.Samu... SWS:P83210,P83210|PDB; 1L6H; NMR; A=1-69.|Gramene; P83210; -.|InterPro; IPR003612; AAI.|Pfam; PF00234; Tryp..._alpha_amyl; 1.|SMART; SM00499; AAI; 1. Nmr, Minimized Average Structure Length: 69 AA, Molecular weight: 7009 Da AGCNAGQLTVCTGAI

  19. 1,25 dihydroxyvitamin D3 (1,25) regulation of c-myc mRNA in HL-60 leukemia cells

    International Nuclear Information System (INIS)

    Simpson, R.U.; Bresnick, E.H.; Begley, D.A.

    1986-01-01

    Recently, 1,25 was shown to induce differentiation and decrease c-myc levels in HL-60 cells. The authors have confirmed these observations by RNA dot blot analysis. Cells treated with 50 nM 1,25 for 4, 24 and 48 hr showed c-myc mRNA levels of 26, 17 and 15% of control respectively. β-Actin mRNA levels were not altered. To ascertain whether 1, 25 regulated c-myc transcriptionally, an HL-60 nuclear RNA runoff assay was developed. Assay of total nuclei transcriptional activity revealed that 50% of RNA elongation was α-amanitin (0.8 μg/ml) sensitive and was linear with nuclei concentration (0.1-1 x 10 7 nuclei). 1,25 (50 nM) treated (45-96 hr) cells had decreased (approx.40%) total transcription rate relative to control. Decreased total RNA synthesis occurred concomitant with NBT reducing activity. 32 P-RNA runoff transcripts from HL-60 nuclei were hybridized to excess (5 μg DNA was excess) Pst I linearized c-myc and β-actin clones (in pBR322) immobilized on nitrocellulose filter. 32 P-RNA input from 2 x 10 6 to 2 x 10 7 cpm yielded linear hybridization signal. Analysis of blot dot intensity revealed no difference in transcription of c-myc in nuclei from 1,25 dosed or control cells. (myc/actin ratios: 1,25 (50 nM, 72 hr) =1.1 +/- 0.3 and control (72 hr) = 1.0, N=3 or 2 or 3 dots ea). These preliminary data suggest 1,25 does not affect c-myc transcription in HL-60 nuclei and may regulate c-myc mRNA post-transcriptionally

  20. Cyclic AMP is a key regulator of M1 to M2a phenotypic conversion of microglia in the presence of Th2 cytokines.

    Science.gov (United States)

    Ghosh, Mousumi; Xu, Yong; Pearse, Damien D

    2016-01-13

    Microglia and macrophages play a central role in neuroinflammation. Pro-inflammatory cytokines trigger their conversion to a classically activated (M1) phenotype, sustaining inflammation and producing a cytotoxic environment. Conversely, anti-inflammatory cytokines polarize the cells towards an alternatively activated (M2), tissue reparative phenotype. Elucidation of the signal transduction pathways involved in M1 to M2 phenotypic conversion may provide insight into how the innate immune response can be harnessed during distinct phases of disease or injury to mediate neuroprotection and neurorepair. Microglial cells (cell line and primary) were subjected to combined cyclic adenosine monophosphate (cyclic AMP) and IL-4, or either alone, in the presence of pro-inflammatory mediators, lipopolysaccharide (LPS), or tumor necrosis factor-α (TNF-α). Their effects on the expression of characteristic markers for M1 and M2 microglia were assessed. Similarly, the M1 and M2 phenotypes of microglia and macrophages within the lesion site were then evaluated following a contusive spinal cord injury (SCI) to the thoracic (T8) spinal cord of rats and mice when the agents were administered systemically. It was demonstrated that cyclic AMP functions synergistically with IL-4 to promote M1 to M2 conversion of microglia in culture. The combination of cyclic AMP and IL-4, but neither alone, induced an Arg-1(+)/iNOS(-)cell phenotype with concomitant expression of other M2-specific markers including TG2 and RELM-α. M2-converted microglia showed ameliorated production of pro-inflammatory cytokines (TNF-α and IP-10) and reactive oxygen species, with no alteration in phagocytic properties. M2a conversion required protein kinase A (PKA), but not the exchange protein directly activated by cyclic AMP (EPAC). Systemic delivery of cyclic AMP and IL-4 after experimental SCI also promoted a significant M1 to M2a phenotypic change in microglia and macrophage population dynamics in the lesion

  1. Lysosomal Regulation of mTORC1 by Amino Acids in Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Yao Yao

    2017-07-01

    Full Text Available The mechanistic target of rapamycin complex 1 (mTORC1 is a master regulator of cell growth in eukaryotic cells. The active mTORC1 promotes cellular anabolic processes including protein, pyrimidine, and lipid biosynthesis, and inhibits catabolic processes such as autophagy. Consistent with its growth-promoting functions, hyper-activation of mTORC1 signaling is one of the important pathomechanisms underlying major human health problems including diabetes, neurodegenerative disorders, and cancer. The mTORC1 receives multiple upstream signals such as an abundance of amino acids and growth factors, thus it regulates a wide range of downstream events relevant to cell growth and proliferation control. The regulation of mTORC1 by amino acids is a fast-evolving field with its detailed mechanisms currently being revealed as the precise picture emerges. In this review, we summarize recent progress with respect to biochemical and biological findings in the regulation of mTORC1 signaling on the lysosomal membrane by amino acids.

  2. Hydrogen retention properties of co-deposition under high-density plasmas in TRIAM-1M

    International Nuclear Information System (INIS)

    Tokitani, M.; Miyamoto, M.; Tokunaga, K.; Fujiwara, T.; Yoshida, N.; Sakamoto, M.; Zushi, H.; Hanada, K.; TRIAM Group,; Nagata, S.; Tsuchiya, B.

    2007-01-01

    Retention of hydrogen in co-deposits formed under high-density plasma discharge in TRIAM-1M was studied. In order to quantify the retained hydrogen, material probe experiments were performed under the high-density (n at e ∼10 19 m -3 ) discharges. After the exposure to the plasma, the quantitative analysis of deposition, hydrogen retention, and microscopic modification of specimens were performed by means of ion beam analysis and transmission electron microscopy. The co-deposits mainly consisted of Mo. The deposition rate of Mo was about ten times higher than that of the low-density discharge case. The hydrogen concentrations (H/Mo) retained in the co-deposits were 0.06-0.17, which was much higher than that in bulk-Mo and almost equal to the low-density case. These results indicate that as long as the co-deposition layers are continuously formed, strong wall pumping in TRIAM-1M is maintained during the discharges

  3. Amino Acids Regulate mTORC1 by an Obligate Two-step Mechanism*

    Science.gov (United States)

    Dyachok, Julia; Earnest, Svetlana; Iturraran, Erica N.; Cobb, Melanie H.

    2016-01-01

    The mechanistic target of rapamycin complex 1 (mTORC1) coordinates cell growth with its nutritional, hormonal, energy, and stress status. Amino acids are critical regulators of mTORC1 that permit other inputs to mTORC1 activity. However, the roles of individual amino acids and their interactions in mTORC1 activation are not well understood. Here we demonstrate that activation of mTORC1 by amino acids includes two discrete and separable steps: priming and activation. Sensitizing mTORC1 activation by priming amino acids is a prerequisite for subsequent stimulation of mTORC1 by activating amino acids. Priming is achieved by a group of amino acids that includes l-asparagine, l-glutamine, l-threonine, l-arginine, l-glycine, l-proline, l-serine, l-alanine, and l-glutamic acid. The group of activating amino acids is dominated by l-leucine but also includes l-methionine, l-isoleucine, and l-valine. l-Cysteine predominantly inhibits priming but not the activating step. Priming and activating steps differ in their requirements for amino acid concentration and duration of treatment. Priming and activating amino acids use mechanisms that are distinct both from each other and from growth factor signaling. Neither step requires intact tuberous sclerosis complex of proteins to activate mTORC1. Concerted action of priming and activating amino acids is required to localize mTORC1 to lysosomes and achieve its activation. PMID:27587390

  4. Effect of recycling in the HL-1M tokamak

    International Nuclear Information System (INIS)

    Zheng Yongzhen

    2004-01-01

    Tokamak plasma discharge disruption at high density is investigated. The instability analysis on model indicates that the disruption is resulted from the energy loss arising from hydrogen recycling on the edge of the plasma. This energy loss could lead to a contraction of the current channel and the production of a disruptively unstable configuration. Using a simple model we shall investigate the implications of recycling for disruptions. The critical high-density n≤1.6 x 10 20 m -3 is reached in HL-1M. (author)

  5. KBE009: An antimalarial bestatin-like inhibitor of the Plasmodium falciparum M1 aminopeptidase discovered in an Ugi multicomponent reaction-derived peptidomimetic library.

    Science.gov (United States)

    González-Bacerio, Jorge; Maluf, Sarah El Chamy; Méndez, Yanira; Pascual, Isel; Florent, Isabelle; Melo, Pollyana M S; Budu, Alexandre; Ferreira, Juliana C; Moreno, Ernesto; Carmona, Adriana K; Rivera, Daniel G; Alonso Del Rivero, Maday; Gazarini, Marcos L

    2017-09-01

    Malaria is a global human parasitic disease mainly caused by the protozoon Plasmodium falciparum. Increased parasite resistance to current drugs determines the relevance of finding new treatments against new targets. A novel target is the M1 alanyl-aminopeptidase from P. falciparum (PfA-M1), which is essential for parasite development in human erythrocytes and is inhibited by the pseudo-peptide bestatin. In this work, we used a combinatorial multicomponent approach to produce a library of peptidomimetics and screened it for the inhibition of recombinant PfA-M1 (rPfA-M1) and the in vitro growth of P. falciparum erythrocytic stages (3D7 and FcB1 strains). Dose-response studies with selected compounds allowed identifying the bestatin-based peptidomimetic KBE009 as a submicromolar rPfA-M1 inhibitor (K i =0.4μM) and an in vitro antimalarial compound as potent as bestatin (IC 50 =18μM; without promoting erythrocyte lysis). At therapeutic-relevant concentrations, KBE009 is selective for rPfA-M1 over porcine APN (a model of these enzymes from mammals), and is not cytotoxic against HUVEC cells. Docking simulations indicate that this compound binds PfA-M1 without Zn 2+ coordination, establishing mainly hydrophobic interactions and showing a remarkable shape complementarity with the active site of the enzyme. Moreover, KBE009 inhibits the M1-type aminopeptidase activity (Ala-7-amido-4-methylcoumarin substrate) in isolated live parasites with a potency similar to that of the antimalarial activity (IC 50 =82μM), strongly suggesting that the antimalarial effect is directly related to the inhibition of the endogenous PfA-M1. These results support the value of this multicomponent strategy to identify PfA-M1 inhibitors, and make KBE009 a promising hit for drug development against malaria. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Comparative study of A-site order in the lead-free bismuth titanates M1/2Bi1/2TiO3 (M=Li, Na, K, Rb, Cs, Ag, Tl) from first-principles

    International Nuclear Information System (INIS)

    Gröting, Melanie; Albe, Karsten

    2014-01-01

    We investigate the possibility of enhancing chemical order in the relaxor ferroelectric Na 1/2 Bi 1/2 TiO 3 upon substitution of Na + by other monovalent cations M + using total energy calculations based on density functional theory. All chemically available monovalent cations M + , which are Li, Na, Ag, K, Tl, Rb and Cs, are considered and an analysis of the structurally relaxed structures in terms of symmetry-adapted distortion modes is given in order to quantify the chemically induced structural distortions. We demonstrate that the replacement of Na + by other monovalent cations can hardly alter the tendency of chemical order with respect to Na 1/2 Bi 1/2 TiO 3 . Only Tl 1/2 Bi 1/2 TiO 3 and Ag 1/2 Bi 1/2 TiO 3 show enhanced tendency for chemical ordering. Both heavy metals behave similar to the light alkali metals in terms of structural relaxations and relative stabilities of the ordered configurations. Although a comparison of the Goldschmidt factors of components (M TiO 3 ) − reveals for Tl a value above the upper stability limit for perovskites, the additional lone-pair effect of Tl + stabilizes the ordered structure. - Graphical abstract: Amplitudes of chemically induced distortion modes in different ordered perovskites M 1/2 Bi 1/2 TiO 3 and visualisation of atomic displacements associated with distortion mode X + 1 in the 001-ordered compounds Li 1/2 Bi 1/2 TiO 3 and Cs 1/2 Bi 1/2 TiO 3 . Due to a substantial size mismatch between bismuth (green) and caesium (dark blue), incorporation of the latter leads to enhanced displacements of oxygen atoms (red) and suppresses displacements of titanium (silver) as compared to lithium (light blue) or other smaller monovalent cations. - Highlights: • Lead-free A-site mixed bismuth titanates M 1/2 Bi 1/2 TiO 3 are studied by first-principles calculations. • Investigation of chemical ordering tendency for M=Li, Na, K, Rb, Cs, Ag, and Tl. • Group theoretical analysis of different ordered structures. • Ag and Tl

  7. Main: 1U3C [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available olecule: Cryptochrome 1 Apoprotein; Chain: A; Fragment: Phr Domain, Residues 1-509; Synonym: Blue Light Phot....Machius, J.Deisenhofer Structure Of The Photolyase-Like Domain Of Cryptochrome 1 From Arabidopsis Thaliana.

  8. Main: 1U3D [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available olecule: Cryptochrome 1 Apoprotein; Chain: A; Fragment: Phr Domain, Residues 1-509; Synonym: Blue Light Phot....Machius, J.Deisenhofer Structure Of The Photolyase-Like Domain Of Cryptochrome 1 From Arabidopsis Thaliana.

  9. Main: 1PXY [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available bidopsis Thaliana Molecule: Fimbrin-Like Protein; Chain: A, B; Fragment: Actin-Crosslinking Core, Residues 1...al, Y.Tseng, D.Wirtz, D.R.Kovar, C.J.Staiger, S.C.Almo Structure Of The Actin-Crosslinking Core Of Fimbrin S...tructure V. 12 999 2004 Calponin Homology, F-Actin-Binding Domain (Abd), F-Actin-Crosslinking, Structural Ge

  10. China Dimensions Data Collection: China Administrative Regions GIS Data: 1:1M, County Level, 1990

    Data.gov (United States)

    National Aeronautics and Space Administration — China Administrative Regions GIS Data: 1:1M, County Level, 1990 consists of geographic boundary data for the administrative regions of China as of 31 December 1990....

  11. PICK1 uncoupling from mGluR7a causes absence-like seizures

    OpenAIRE

    Bertaso, Federica; Zhang, Chuansheng; Scheschonka, Astrid; de Bock, Frédéric; Fontanaud, Pierre; Marin, Philippe; Huganir, Richard L; Betz, Heinrich; Bockaert, Joël; Fagni, Laurent; Lerner-Natoli, Mireille

    2008-01-01

    Absence epilepsy is a neurological disorder that causes a recurrent loss of consciousness and generalized spike-and-wave discharges on an electroencephalogram (EEG). The role of metabotropic glutamate receptors (mGluRs) and associated scaffolding proteins in absence epilepsy has been unclear to date. We investigated a possible role for these proteins in absence epilepsy, focusing on the mGluR7a receptor and its PDZ-interacting protein, protein interacting with C kinase 1 (PICK1), in rats and ...

  12. SAD-A kinase controls islet β-cell size and function as a mediator of mTORC1 signaling.

    Science.gov (United States)

    Nie, Jia; Liu, Xiaolei; Lilley, Brendan N; Zhang, Hai; Pan, Y Albert; Kimball, Scot R; Zhang, Jun; Zhang, Weiping; Wang, Li; Jefferson, Leonard S; Sanes, Joshua R; Han, Xiao; Shi, Yuguang

    2013-08-20

    The mammalian target of rapamycin (mTOR) plays an important role in controlling islet β-cell function. However, the underlying molecular mechanisms remain poorly elucidated. Synapses of amphids defective kinase-A (SAD-A) is a 5' adenosine monophosphate-activated protein kinase-related protein kinase that is exclusively expressed in pancreas and brain. In this study, we investigated a role of the kinase in regulating pancreatic β-cell morphology and function as a mediator of mTOR complex 1 (mTORC1) signaling. We show that global SAD-A deletion leads to defective glucose-stimulated insulin secretion and petite islets, which are reminiscent of the defects in mice with global deletion of ribosomal protein S6 kinase 1, a downstream target of mTORC1. Consistent with these findings, selective deletion of SAD-A in pancreas decreased islet β-cell size, whereas SAD-A overexpression significantly increased the size of mouse insulinomas cell lines β-cells. In direct support of SAD-A as a unique mediator of mTORC1 signaling in islet β-cells, we demonstrate that glucose dramatically stimulated SAD-A protein translation in isolated mouse islets, which was potently inhibited by rapamycin, an inhibitor of mTORC1. Moreover, the 5'-untranslated region of SAD-A mRNA is highly structured and requires mTORC1 signaling for its translation initiation. Together, these findings identified SAD-A as a unique pancreas-specific effector protein of mTORC1 signaling.

  13. Note: A 1-m Foucault pendulum rolling on a ball

    Science.gov (United States)

    Salva, H. R.; Benavides, R. E.; Venturino, J. A.; Cuscueta, D. J.; Ghilarducci, A. A.

    2013-10-01

    We have built a short Foucault pendulum of 1-m length. The aim of this work was to increase the sensitivity to elliptical trajectories from other longer pendula. The design was a semi-rigid pendulum that rolls over a small ball. The measurements of the movements (azimuth and elliptical trajectory) were done by an optical method. The resulting pendulum works in a medium satisfactory way due to problems of the correct choice of the mass of the bob together with the diameter of the supporting ball. It is also important to keep the rolling surface very clean.

  14. 77 FR 29918 - Proposed Amendment of Class E Airspace; Battle Creek, MI

    Science.gov (United States)

    2012-05-21

    ... airspace is necessary to accommodate new Standard Instrument Approach Procedures (SIAP) at W. K. Kellogg.... Kellogg Airport, Battle Creek, MI. Controlled airspace is needed for the safety and management of IFR... controlled airspace at W.K. Kellogg Airport, Battle Creek, MI. Environmental Review This proposal will be...

  15. Conductivity ageing studies on 1M10ScSZ (M4+=Ce, Hf)

    DEFF Research Database (Denmark)

    Omar, Shobit; Bin Najib, Waqas; Bonanos, Nikolaos

    2011-01-01

    The long-term conductivity stability is tested on zirconia based electrolyte materials for solid oxide fuel cell applications. The ageing studies have been performed on the samples of ZrO2 co-doped with 10mol% of Sc2O3 and 1mol% MO2, where M = Ce or Hf (denoted respectively 1Ce10ScSZ and 1Hf10Sc......SZ) in oxidising and reducing atmospheres, at 600°C for 3000h. At 600°C, these compositions show initial conductivity of around 9–12mS∙cm−1 in air. After 3000h of ageing, no phase transitions are observed in any of the samples. For the first 1000h, the degradation rate is higher than in the subsequent 2000h......; thereafter, conductivity degrades linearly with time for all samples. In air, the loss in the conductivity is lower than in reducing conditions. The 1Ce10ScSZ shows the highest degradation rate of 3.8%/1000h in wet H2/N2 after the first 1000h of ageing. A colour change of the 1Ce10ScSZ sample from white...

  16. Mice lacking mPGES-1 are resistant to lithium-induced polyuria.

    Science.gov (United States)

    Jia, Zhanjun; Wang, Haiping; Yang, Tianxin

    2009-12-01

    Cyclooxygenase-2 activity is required for the development of lithium-induced polyuria. However, the involvement of a specific, terminal prostaglandin (PG) isomerase has not been evaluated. The present study was undertaken to assess lithium-induced polyuria in mice deficient in microsomal prostaglandin E synthase-1 (mPGES-1). A 2-wk administration of LiCl (4 mmol.kg(-1).day(-1) ip) in mPGES-1 +/+ mice led to a marked polyuria with hyposmotic urine. This was associated with elevated renal mPGES-1 protein expression and increased urine PGE(2) excretion. In contrast, mPGES-1 -/- mice were largely resistant to lithium-induced polyuria and a urine concentrating defect, accompanied by nearly complete blockade of high urine PGE(2) and cAMP output. Immunoblotting, immunohistochemistry, and quantitative (q) RT-PCR consistently detected a significant decrease in aquaporin-2 (AQP2) protein expression in both the renal cortex and medulla of lithium-treated +/+ mice. This decrease was significantly attenuated in the -/- mice. qRT-PCR detected similar patterns of changes in AQP2 mRNA in the medulla but not in the cortex. Similarly, the total protein abundance of the Na-K-2Cl cotransporter (NKCC2) in the medulla but not in the cortex of the +/+ mice was significantly reduced by lithium treatment. In contrast, the dowregulation of renal medullary NKCC2 expression was significantly attenuated in the -/- mice. We conclude that mPGES-1-derived PGE(2) mediates lithium-induced polyuria likely via inhibition of AQP2 and NKCC2 expression.

  17. Synthesis of Ethane-1-Hydroxy-1,1-diphosphonic acid (EHDP) and preparation of labeled kits by 99mTc for bone studies

    International Nuclear Information System (INIS)

    Yassin, T.; Assaad, T.; Ghanem, E.; Ajaia, R.; Karajoli, N.

    2013-08-01

    Ethane-1-Hydroxy-1,1-diphosphonic acid monohydrate (EHDP) is very important precursor in radiopharmaceutical applications for bone diagnosis after labeling with 99mTc, was synthesized in high yield and purity. The compound was characterized by spectroscopic method. EHDP kit for bone imaging after labeling with technetium 99m was prepared according to an optimum conditions, Each vial contains 15 mg of EHDP and 25 mg of stannous chloride SnCl2. The prepared kit showed high quality satisfying the requirements of international pharmacopeias from of physical, chemical and radiochemical properties. The labeling yield exceeded 95% with an average value 99.6%. Biodistribution study of 99mTc-EHDP showed better clearance after three hours of injection in comparison with 99mTc-MDP kit (author).

  18. Main: 1WEO [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available tic Subunit Name=Irx3; Synonyms=T10b6_80; Arabidopsis Thaliana Molecule: Cellulose Synthase, Catalytic Subunit (Irx3); Chai...GDKEHLMSEMNFEKTFGQSSIFVTSTLMEEGGVPPSSSPAVLLKEAIHVISCGYEDKTEWGTELGWIYGSITEDILTGFKMHCRGWRSIYCMPKRPAFKGSAPINLSD...RLNQVLRWALGSVEIFFSRHSPLWYGYKGGKLKWLERFAYANTTIYPFTSIPLLAYCILPAICLLTDKFIMPPISTFASLFFISLFMSIIVTGILELRWSGVSIEEWW...RNEQFWVIGGISAHLFAVVQGLLKILAGIDTNFTVTSKATDDDDFGELYAFKWTTLLIPPTTVLIINIVGVVAGISDAINNGYQSWGPLFGKLFFSFWVIVHLYPFLKGLMGRQNRTPTIVVIWSVLLASIFSLLWVRIDPFVLKTKGPDTSKCGINC arabi_1WEO.jpg ...

  19. Fine structure of the giant M1 resonance in 90Zr.

    Science.gov (United States)

    Rusev, G; Tsoneva, N; Dönau, F; Frauendorf, S; Schwengner, R; Tonchev, A P; Adekola, A S; Hammond, S L; Kelley, J H; Kwan, E; Lenske, H; Tornow, W; Wagner, A

    2013-01-11

    The M1 excitations in the nuclide 90Zr have been studied in a photon-scattering experiment with monoenergetic and linearly polarized beams from 7 to 11 MeV. More than 40 J(π)=1+ states have been identified from observed ground-state transitions, revealing the fine structure of the giant M1 resonance with a centroid energy of 9 MeV and a sum strength of 4.17(56) μ(N)(2). The result for the total M1 strength and its fragmentation are discussed in the framework of the three-phonon quasiparticle-phonon model.

  20. Outrunning Asthma: Football Player Rashad Jennings Battled Childhood Asthma with Exercise and Determination

    Science.gov (United States)

    ... us Outrunning Asthma Football player Rashad Jennings battled childhood asthma with exercise and determination Photo: ABC National Football ... Dancing with the Stars” champion Rashad Jennings battled childhood asthma with grit and determination. He has partnered with ...

  1. Nanometre-accurate form measurement machine for E-ELT M1 segments

    NARCIS (Netherlands)

    Bos, A.; Henselmans, R.; Rosielle, P.C.J.N.; Steinbuch, M.

    2015-01-01

    To enable important scientific discoveries, ESO has defined a new ground-based telescope: the European Extremely Large Telescope (E-ELT). The baseline design features a telescope with a 39-m-class primary mirror (M1), making it the largest and most powerful telescope in the world. The M1 consists of

  2. Converting a Manned LCU into an Unmanned Surface Vehicle (USV): An Open Systems Architecture (OSA) Case Study

    Science.gov (United States)

    2014-09-01

    Better Buying Power BCA business case analysis BDA battle damage assessment BII Business Innovation Initiative BSA battle space awareness C&C command...developed and used USVs for purposes such as minesweeping and battle damage assessment ( BDA ) (James 2012). At the same time, the U.S. Navy developed...rint’ Corps mot1Vt1 media by Lat)’"~,: Cpl. Juancnnqw Combat Camera/Released) Monnes and SailorS asstaned 10 1he 261h M:mnc: E~pc.:ditionary Unil

  3. Key mediators of intracellular amino acids signaling to mTORC1 activation.

    Science.gov (United States)

    Duan, Yehui; Li, Fengna; Tan, Kunrong; Liu, Hongnan; Li, Yinghui; Liu, Yingying; Kong, Xiangfeng; Tang, Yulong; Wu, Guoyao; Yin, Yulong

    2015-05-01

    Mammalian target of rapamycin complex 1 (mTORC1) is activated by amino acids to promote cell growth via protein synthesis. Specifically, Ras-related guanosine triphosphatases (Rag GTPases) are activated by amino acids, and then translocate mTORC1 to the surface of late endosomes and lysosomes. Ras homolog enriched in brain (Rheb) resides on this surface and directly activates mTORC1. Apart from the presence of intracellular amino acids, Rag GTPases and Rheb, other mediators involved in intracellular amino acid signaling to mTORC1 activation include human vacuolar sorting protein-34 (hVps34) and mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3). Those molecular links between mTORC1 and its mediators form a complicate signaling network that controls cellular growth, proliferation, and metabolism. Moreover, it is speculated that amino acid signaling to mTORC1 may start from the lysosomal lumen. In this review, we discussed the function of these mediators in mTORC1 pathway and how these mediators are regulated by amino acids in details.

  4. Glucocorticoids selectively inhibit the transcription of the interleukin 1β gene and decrease the stability of interleukin 1β mRNA

    International Nuclear Information System (INIS)

    Lee, S.W.; Tsou, A.P.; Chan, H.; Thomas, J.; Petrie, K.; Eugui, E.M.; Allison, A.C.

    1988-01-01

    Transcription of the interleukin 1β (IL-1β) gene was studied by mRNA hybridization with a cDNA probe in the human promonocytic cell line U-937. Phorbol ester and lipopolysaccharide increased the steady-state level of Il-1β mRNA. Glucocorticoids markedly decreased IL-1β mRNA levels by two mechanisms. Transcription of the IL-1 gene was inhibited, as shown by in vitro transcription assays with nuclei isolated from glucocorticoid-treated cells. Moreover, kinetic analyses and pulse-labeling of mRNAs showed that glucocorticoids selectively decrease the stability of IL-1β mRNA, without affecting the stability of β-actin and FOS mRNAs. Inhibition of the formation and effects IL-1 is a mechanism by which glucocorticoids can exert antiinflammatory and immunosuppressive effects

  5. [RTEL1 (regulator of telomere elongation helicase 1), a DNA helicase essential for genome stability].

    Science.gov (United States)

    Le Guen, Tangui; Jullien, Laurent; Schertzer, Mike; Lefebvre, Axelle; Kermasson, Laetitia; de Villartay, Jean-Pierre; Londoño-Vallejo, Arturo; Revy, Patrick

    2013-12-01

    RTEL1 (regulator of telomere length helicase 1) is a DNA helicase that has been identified more than 10 years ago. Many works since, mainly in the nematode Caenorhabditis elegans and the mouse, have highlighted its role in chromosomal stability, maintenance of telomere length, and DNA repair. Recently, four laboratories have characterized RTEL1 mutations in patients with dyskeratosis congenita (DC) and Hoyeraal-Hreidarsson (HH) syndrome, a rare and severe variant of DC. We here summarize the current knowledge on RTEL1 and discuss the possible other functions that RTEL1 could play. © 2013 médecine/sciences – Inserm.

  6. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    International Nuclear Information System (INIS)

    Zhirnov, O.P.; Manykin, A.A.; Rossman, J.S.; Klenk, H.D.

    2016-01-01

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  7. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    Energy Technology Data Exchange (ETDEWEB)

    Zhirnov, O.P., E-mail: zhirnov@inbox.ru [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Manykin, A.A. [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Rossman, J.S. [School of Biosciences, University of Kent, Canterbury CT27NJ (United Kingdom); Klenk, H.D. [Institute of Virology, Philipps University, Marburg 35037 (Germany)

    2016-05-15

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  8. Acidic tumor microenvironment abrogates the efficacy of mTORC1 inhibitors.

    Science.gov (United States)

    Faes, Seraina; Duval, Adrian P; Planche, Anne; Uldry, Emilie; Santoro, Tania; Pythoud, Catherine; Stehle, Jean-Christophe; Horlbeck, Janine; Letovanec, Igor; Riggi, Nicolo; Demartines, Nicolas; Dormond, Olivier

    2016-12-05

    Blocking the mechanistic target of rapamycin complex-1 (mTORC1) with chemical inhibitors such as rapamycin has shown limited clinical efficacy in cancer. The tumor microenvironment is characterized by an acidic pH which interferes with cancer therapies. The consequences of acidity on the anti-cancer efficacy of mTORC1 inhibitors have not been characterized and are thus the focus of our study. Cancer cell lines were treated with rapamycin in acidic or physiological conditions and cell proliferation was investigated. The effect of acidity on mTORC1 activity was determined by Western blot. The anticancer efficacy of rapamycin in combination with sodium bicarbonate to increase the intratumoral pH was tested in two different mouse models and compared to rapamycin treatment alone. Histological analysis was performed on tumor samples to evaluate proliferation, apoptosis and necrosis. Exposing cancer cells to acidic pH in vitro significantly reduced the anti-proliferative effect of rapamycin. At the molecular level, acidity significantly decreased mTORC1 activity, suggesting that cancer cell proliferation is independent of mTORC1 in acidic conditions. In contrast, the activation of mitogen-activated protein kinase (MAPK) or AKT were not affected by acidity, and blocking MAPK or AKT with a chemical inhibitor maintained an anti-proliferative effect at low pH. In tumor mouse models, the use of sodium bicarbonate increased mTORC1 activity in cancer cells and potentiated the anti-cancer efficacy of rapamycin. Combining sodium bicarbonate with rapamycin resulted in increased tumor necrosis, increased cancer cell apoptosis and decreased cancer cell proliferation as compared to single treatment. Taken together, these results emphasize the inefficacy of mTORC1 inhibitors in acidic conditions. They further highlight the potential of combining sodium bicarbonate with mTORC1 inhibitors to improve their anti-tumoral efficacy.

  9. The Gaugamela Battle Eclipse: An Archaeoastronomical Analysis

    Science.gov (United States)

    Polcaro, V. F.; Valsecchi, G. B.; Verderame, L.

    A total lunar eclipse occurred during the night preceding the decisive Battle of Gaugamela (20th September 331 BCE), when the Macedonian army, led by Alexander the Great, finally defeated the Persian king Darius and his army. This astronomical event, well known to historians, had a relevant role on the battle outcome. The eclipse was described in detail by Babylonian astronomers, though, unfortunately, the text of their report has only partially been preserved. We have reconstructed the evolution of the phenomenon as it appeared to the observer in Babylonia, by using the positional astronomy code "Planetario V2.0". On the base of this reconstruction we suggest a number of integrations to the lost part of the text, allowing a finer astrological interpretation of the eclipse and of its influence on the mood of the armies that set against each other on the following morning.

  10. Crystal structures of the 2:2 complex of 1,1′-(1,2-phenylenebis(3-m-tolylurea and tetrabutylammonium chloride or bromide

    Directory of Open Access Journals (Sweden)

    Chao Huang

    2017-09-01

    Full Text Available The title compounds, tetrabutylammonium chloride–1,1′-(1,2-phenylenebis(3-m-tolylurea (1/1, C16H36N+·Cl−·C22H22N4O2 or [(n-Bu4N+·Cl−(C22H22N4O2] (I and tetrabutylammonium bromide–1,1′-(1,2-phenylenebis(3-m-tolylurea (1/1, C16H36N+·Br−·C22H22N4O2 or [(n-Bu4N+·Br−(C22H22N4O2] (II, both comprise a tetrabutylammonium cation, a halide anion and an ortho-phenylene bis-urea molecule. Each halide ion shows four N—H...X (X = Cl or Br interactions with two urea receptor sites of different bis-urea moieties. A crystallographic inversion centre leads to the formation of a 2:2 arrangement of two halide anions and two bis-urea molecules. In the crystals, the dihedral angle between the two urea groups of the bis-urea molecule in (I [defined by the four N atoms, 165.4 (2°] is slightly smaller than that in (II [167.4 (2°], which is probably due to the smaller ionic radius of chloride compared to bromide.

  11. Dissociation of SERPINE1 mRNA from the translational repressor proteins Ago2 and TIA-1 upon platelet activation.

    Science.gov (United States)

    Corduan, Aurélie; Plé, Hélène; Laffont, Benoit; Wallon, Thérèse; Plante, Isabelle; Landry, Patricia; Provost, Patrick

    2015-05-01

    Platelets play an important role in haemostasis, as well as in thrombosis and coagulation processes. They harbour a wide variety of messenger RNAs (mRNAs), that can template de novo protein synthesis, and an abundant array of microRNAs, which are known to mediate mRNA translational repression through proteins of the Argonaute (Ago) family. The relationship between platelet microRNAs and proteins capable of mediating translational repression, however, remains unclear. Here, we report that half of platelet microRNAs is associated to mRNA-regulatory Ago2 protein complexes, in various proportions. Associated to these Ago2 complexes are platelet mRNAs known to support de novo protein synthesis. Reporter gene activity assays confirmed the capacity of the platelet microRNAs, found to be associated to Ago2 complexes, to regulate translation of these platelet mRNAs through their 3'UTR. Neither the microRNA repertoire nor the microRNA composition of Ago2 complexes of human platelets changed upon activation with thrombin. However, under conditions favoring de novo synthesis of Plasminogen Activator Inhibitor-1 (PAI-1) protein, we documented a rapid dissociation of the encoding platelet SERPINE1 mRNA from Ago2 protein complexes as well as from the translational repressor protein T-cell-restricted intracellular antigen-1 (TIA-1). These findings are consistent with a scenario by which lifting of the repressive effects of Ago2 and TIA-1 protein complexes, involving a rearrangement of proteinmRNA complexes rather than disassembly of Ago2microRNA complexes, would allow translation of SERPINE1 mRNA into PAI-1 in response to platelet activation.

  12. B-1 Aircraft Main Hydraulic Pump Tests With MIL-H-87257 Hydraulic Fluid

    National Research Council Canada - National Science Library

    Sharma, Shashi

    1998-01-01

    In an effort to convert the B-1 aircraft from MIL-H-5606 to M1-H-87257, the Air Force sponsored a study conducted by Rockwell International from April 1991 through June 1992, under contract F34601-89-C-0401...

  13. Holmium-doped fluorotellurite microstructured fibers for 2.1 μm lasing.

    Science.gov (United States)

    Yao, Chuanfei; He, Chunfeng; Jia, Zhixu; Wang, Shunbin; Qin, Guanshi; Ohishi, Yasutake; Qin, Weiping

    2015-10-15

    Holmium (Ho3+)-doped fluorotellurite microstructured fibers based on TeO2-BaF2-Y2O3 glasses are fabricated by using a rod-in-tube method. By using a 1.992 μm fiber laser as the pump source, lasing at 2.077 μm is obtained from a 27 cm long Ho3+-doped fluorotellurite microstructured fiber. The maximum unsaturated power is about 161 mW and the corresponding slope efficiency is up to 67.4%. The influence of fiber length on lasing at 2.1 μm is also investigated. Our results show that Ho3+-doped fluorotellurite microstructured fibers are promising gain media for 2.1 μm laser applications.

  14. Studies of monoclonal antibodies IOR-CEA-1 and IOR-EGF/R3 labelled with 99mTc

    International Nuclear Information System (INIS)

    Dias, Carla Roberta de Barros Rodrigues

    2005-01-01

    Nuclear Medicine is a speciality that uses radioisotopes for the diagnosis or treatment of diseases and it is considered one of the best tools among the diagnostic modalities for detection of cancer. 99m Tc is one of the main isotopes for labelling antibodies and in Nuclear Medicine in general, due to its adequate physical properties, availability and low cost. Labelled monoclonal antibodies have shown promising results for diagnosis and therapy of cancer and their use has brought great experimental and clinical advances in the field of oncology. The main clinical applications of immunoscintigraphy with monoclonal antibodies are staging and evaluation of tumoral reappearance. The antibodies employed in this work were: OIR-CEA-1, a murine monoclonal antibody that acts directly against CEA expressed in several neoplasia in particular those from the gastrointestinal tract (colorectal cancer) and IOR-EGF/R3, a murine monoclonal antibody that binds to the external domain of EGF-R and it has been used in the diagnosis of tumors of epithelial origin. The objectives of this work were the development and optimization of the reduction and purification processes, the radiolabelling techniques and quality control procedures (radiochemical, immunoreactivity and cystein challenge) and imaging studies of monoclonal antibodies OIR-CEA-1 and IOR-EGF/R3, using the simple, fast and efficient method of direct labelling of the antibody with 99m Tc. The final results was the definition of the best conditions for the preparation of lyophilized reactive kits of OIR-CEA-1 and IOR- EGF/R3 for an efficient diagnostic application in Nuclear Medicine. The most adequate conditions for the labelling of the antibodies were: 1.0 mg Ab, 29 μL MDP, 3.0 μg Sn 2+ , 1 mL of 99m Tc and 30 min. reaction time. With these conditions the labelling yield was always higher than 95% and the maximum activity of 99m Tc was about 2220 MBq (60 mCi). The evidences of the efficiency and quality of the methods here

  15. M2-F1 in flight during low-speed car tow

    Science.gov (United States)

    1963-01-01

    The M2-F1 shown in flight during a low-speed car tow runs across the lakebed. Such tests allowed about two minutes to test the vehicle's handling in flight. NASA Flight Research Center (later redesignated the Dryden Flight Research Center) personnel conducted as many as 8 to 14 ground-tow flights in a single day either to test the vehicle in preparation for air tows or to train pilots to fly the vehicle before they undertook air tows. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30

  16. Production of HIV-1 vif mRNA Is Modulated by Natural Nucleotide Variations and SLSA1 RNA Structure in SA1D2prox Genomic Region

    Directory of Open Access Journals (Sweden)

    Masako Nomaguchi

    2017-12-01

    Full Text Available Genomic RNA of HIV-1 contains localized structures critical for viral replication. Its structural analysis has demonstrated a stem-loop structure, SLSA1, in a nearby region of HIV-1 genomic splicing acceptor 1 (SA1. We have previously shown that the expression level of vif mRNA is considerably altered by some natural single-nucleotide variations (nSNVs clustering in SLSA1 structure. In this study, besides eleven nSNVs previously identified by us, we totally found nine new nSNVs in the SLSA1-containing sequence from SA1, splicing donor 2, and through to the start codon of Vif that significantly affect the vif mRNA level, and designated the sequence SA1D2prox (142 nucleotides for HIV-1 NL4-3. We then examined by extensive variant and mutagenesis analyses how SA1D2prox sequence and SLSA1 secondary structure are related to vif mRNA level. While the secondary structure and stability of SLSA1 was largely changed by nSNVs and artificial mutations introduced to restore the original NL4-3 form from altered ones by nSNVs, no clear association of the two SLSA1 properties with vif mRNA level was observed. In contrast, when naturally occurring SA1D2prox sequences that contain multiple nSNVs were examined, we attained significant inverse correlation between the vif level and SLSA1 stability. These results may suggest that SA1D2prox sequence adapts over time, and also that the altered SA1D2prox sequence, SLSA1 stability, and vif level are mutually related. In total, we show here that the entire SA1D2prox sequence and SLSA1 stability critically contribute to the modulation of vif mRNA level.

  17. Random comparison study of the clinical response to 153Sm-EDTMP 1.0 mCi/kg and 1.5 mCi/kg

    International Nuclear Information System (INIS)

    Pan, Z.; Zhu, S.

    2001-01-01

    Sixty-seven patient with painful bone metastases were randomized to two groups. Group 1 (n=34) received 1.0 mCi/kg of 153 Sm-EDTMP and group II (n=33) received 1.5 mCi/kg. All of them met inclusion criteria and there was no significantly difference between the basic conditions of two groups. After receiving 153 Sm-EDTMP intravenously, all patients were kept in close follow-up weekly with blood counting, physician visiting and collecting patient's self-filling-in diary including pain score, Karnofsky performance scale and analgesic consumption. The follow-up duration was six weeks. The final overall condition assessed by physician were graded into no change (including worse), slight relief, significant relief and complete relief. Only significant relief and complete relief were considered as effectiveness for pain relief. Haematological toxicity grade was evaluated based on the nadir of WBC ad PLT counts. The results indicated that the higher dosage group had a higher effectiveness rate (75.76%) compared to the lower dosage group (67.65%), but without statistic significance (x 2 =0.5365, 0.25 153 Sm-EDTMP could be used for those patients with better haematological function and 1.0 mCi/kg used for those patients with poorer haematological function. (author)

  18. M1 transitions between superdeformed states in 195Tl

    International Nuclear Information System (INIS)

    Zheng Xing; Xingqu Chen; Xiaochun Wang

    1996-01-01

    Using a triaxial-particle-rotor model, the quadrupole and dipole transition energies, kinematic and dynamic moments of inertia, electromagnetic transition probabilities and the relative intensity of the E2 γ-transitions are calculated for superdeformed bands in 195 Tl. A strong perturbation effect of rotation on transition energies and M1 and E2 transitions of superdeformed states is investigated. The total M1 transitions, enhanced by internal conversion, are expected to compete strongly with the E2 γ-ray at low spins in the superdeformed 195 Tl nucleus. (author)

  19. Calculation of M1-excitations in the 42Ca, 44Ca and 54Fe with allowance for the 1p 1h * phonon configurations

    International Nuclear Information System (INIS)

    Kamerdzhiev, S.P.; Tkachev, V.N.

    1988-01-01

    The microscopic model of account of 1p1hx phonon configurations is used to describe M1-excitations in 42 Ca, 44 Ca and 54 Fe 1f 7/2 -shell. The most low-lying and more collectivized electrical phonons are taken into account. The Boron-Mottelson collective model with parameters obtained in the experiment is used to describe them. The calculation results are compared with calculations on other models. A set of all data allows to make the supposition that the deficient part of M1-resonance force in nuclei of 1f 7/2 -shell should be distributed on low-intensive 1 + -levels in the wide range of the nucleon binding energy

  20. Main: 1UHN [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available ineered: Yes Metal Binding Protein M.Nagae, A.Nozawa, N.Koizumi, H.Sano, H.Hashimot...n 2 Name=Cbl2; Arabidopsis Thaliana Molecule: Calcineurin B-Like Protein 2; Chain: A; Fragment: Residues 32-220; Synonym: Atcbl2; Eng

  1. Screening the Medicines for Malaria Venture "Malaria Box" against the Plasmodium falciparum aminopeptidases, M1, M17 and M18.

    Directory of Open Access Journals (Sweden)

    Alessandro Paiardini

    Full Text Available Malaria is a parasitic disease that remains a global health burden. The ability of the parasite to rapidly develop resistance to therapeutics drives an urgent need for the delivery of new drugs. The Medicines for Malaria Venture have compounds known for their antimalarial activity, but not necessarily the molecular targets. In this study, we assess the ability of the "MMV 400" compounds to inhibit the activity of three metalloaminopeptidases from Plasmodium falciparum, PfA-M1, PfA-M17 and PfM18 AAP. We have developed a multiplex assay system to allow rapid primary screening of compounds against all three metalloaminopeptidases, followed by detailed analysis of promising compounds. Our results show that there were no PfM18AAP inhibitors, whereas two moderate inhibitors of the neutral aminopeptidases PfA-M1 and PfA-M17 were identified. Further investigation through structure-activity relationship studies and molecular docking suggest that these compounds are competitive inhibitors with novel binding mechanisms, acting through either non-classical zinc coordination or independently of zinc binding altogether. Although it is unlikely that inhibition of PfA-M1 and/or PfA-M17 is the primary mechanism responsible for the antiplasmodial activity reported for these compounds, their detailed characterization, as presented in this work, pave the way for their further optimization as a novel class of dual PfA-M1/PfA-M17 inhibitors utilising non-classical zinc binding groups.

  2. Quantitative mapping of precursory seismic quiescence before the 1989, M 7.1off-Sanriku earthquake, Japan

    Directory of Open Access Journals (Sweden)

    N. Umino

    1999-06-01

    Full Text Available The first main shock of the off-Sanriku earthquake sequence (02/11/89, M 7.1; 18/07/92, M 6.9; 28/12/94, M 7.5 was preceded by a precursory seismic quiescence lasting 2.5 ± 1 year and up to this main shock. The detailed properties of this quiescence were mapped as a function of time and space by a gridding technique using the ZMAP computer code, and the statistical significance was estimated by generating a synthetic catalog based on the microearthquake catalog of Tohoku University, which was the data set used. The statistically most significant expression of this precursory quiescence has a probability of 0.1% to have occurred at random and was located in the eastern part of the 1989 aftershock area, at a point to which the 1994 aftershocks extended also. If we define the dimensions of the quiescence anomaly by a vertical cylinder with the depth of the entire seismogenic layer, centered at the point of most significant quiescence and showing a rate decrease of 75%, then we find its radius is 25 ± 9 km. If we allow other shapes, such as the simplified aftershock volume of 1989, or other simple geometric figures, to define the rate decrease we find dimensions of 80 by 80 km. The characteristics of the quiescence anomaly do not depend strongly on the choice of free parameters within the following ranges: 100 ? number of events ? 400, 2.0 ? Mmin £ 3.0, 1 ? time window ? 3 years. With our method, a thorough analysis of the period before the 1994 main shock is not possible because of the interference of the extended aftershock sequence of 1989. Nevertheless, we identified a quiescence of nearly zero earthquakes located near the center of the 1994 aftershock area that lasted for one year up to that main shock. However, this quiescence period ranked only 46th in significance, behind other quiescences of equal duration and similar dimensions distributed in time and space through the data set. Because of the ubiquitous existence of periods of near

  3. Aflatoxin B1 and M1: Biological Properties and Their Involvement in Cancer Development

    Directory of Open Access Journals (Sweden)

    Silvia Marchese

    2018-05-01

    Full Text Available Aflatoxins are fungal metabolites found in feeds and foods. When the ruminants eat feedstuffs containing Aflatoxin B1 (AFB1, this toxin is metabolized and Aflatoxin M1 (AFM1 is excreted in milk. International Agency for Research on Cancer (IARC classified AFB1 and AFM1 as human carcinogens belonging to Group 1 and Group 2B, respectively, with the formation of DNA adducts. In the last years, some epidemiological studies were conducted on cancer patients aimed to evaluate the effects of AFB1 and AFM1 exposure on cancer cells in order to verify the correlation between toxin exposure and cancer cell proliferation and invasion. In this review, we summarize the activation pathways of AFB1 and AFM1 and the data already reported in literature about their correlation with cancer development and progression. Moreover, considering that few data are still reported about what genes/proteins/miRNAs can be used as damage markers due to AFB1 and AFM1 exposure, we performed a bioinformatic analysis based on interaction network and miRNA predictions to identify a panel of genes/proteins/miRNAs that can be used as targets in further studies for evaluating the effects of the damages induced by AFB1 and AFM1 and their capacity to induce cancer initiation.

  4. Occupational Toluene Exposure Induces Cytochrome P450 2E1 mRNA Expression in Peripheral Lymphocytes

    Science.gov (United States)

    Mendoza-Cantú, Ania; Castorena-Torres, Fabiola; de León, Mario Bermúdez; Cisneros, Bulmaro; López-Carrillo, Lizbeth; Rojas-García, Aurora E.; Aguilar-Salinas, Alberto; Manno, Maurizio; Albores, Arnulfo

    2006-01-01

    Print workers are exposed to organic solvents, of which the systemic toxicant toluene is a main component. Toluene induces expression of cytochrome P450 2E1 (CYP2E1), an enzyme involved in its own metabolism and that of other protoxicants, including some procarcinogens. Therefore, we investigated the association between toluene exposure and the CYP2E1 response, as assessed by mRNA content in peripheral lymphocytes or the 6-hydroxychlorzoxazone (6OH-CHZ)/chlorzoxazone (CHZ) quotient (known as CHZ metabolic ratio) in plasma, and the role of genotype (5′-flanking region RsaI/PstI polymorphic sites) in 97 male print workers. The geometric mean (GM) of toluene concentration in the air was 52.80 ppm (10–760 ppm); 54% of the study participants were exposed to toluene concentrations that exceeded the maximum permissible exposure level (MPEL). The GM of urinary hippuric acid at the end of a work shift (0.041 g/g creatinine) was elevated relative to that before the shift (0.027 g/g creatinine; p < 0.05). The GM of the CHZ metabolic ratio was 0.33 (0–9.3), with 40% of the subjects having ratios below the GM. However, the average CYP2E1 mRNA level in peripheral lymphocytes was 1.07 (0.30–3.08), and CYP2E1 mRNA levels within subjects correlated with the toluene exposure ratio (environmental toluene concentration:urinary hippuric acid concentration) (p = 0.014). Genotype did not alter the association between the toluene exposure ratio and mRNA content. In summary, with further validation, CYP2E1 mRNA content in peripheral lymphocytes could be a sensitive and noninvasive biomarker for the continuous monitoring of toluene effects in exposed persons. PMID:16581535

  5. Glutathione S-transferase M1 and T1, CYP1A2-2467T/delT ...

    African Journals Online (AJOL)

    The present study investigated the impact of metabolic gene polymorphisms in modulating lung cancer risk susceptibility. Gene polymorphisms encoding Cytochrome 1A2 (CYP1A2) and Glutathione-S-transferases (GSTT1 and GSTM1) are involved in the bioactivation and detoxification of tobacco carcinogens and may ...

  6. mTORC1-independent reduction of retinal protein synthesis in type 1 diabetes.

    Science.gov (United States)

    Fort, Patrice E; Losiewicz, Mandy K; Pennathur, Subramaniam; Jefferson, Leonard S; Kimball, Scot R; Abcouwer, Steven F; Gardner, Thomas W

    2014-09-01

    Poorly controlled diabetes has long been known as a catabolic disorder with profound loss of muscle and fat body mass resulting from a simultaneous reduction in protein synthesis and enhanced protein degradation. By contrast, retinal structure is largely maintained during diabetes despite reduced Akt activity and increased rate of cell death. Therefore, we hypothesized that retinal protein turnover is regulated differently than in other insulin-sensitive tissues, such as skeletal muscle. Ins2(Akita) diabetic mice and streptozotocin-induced diabetic rats exhibited marked reductions in retinal protein synthesis matched by a concomitant reduction in retinal protein degradation associated with preserved retinal mass and protein content. The reduction in protein synthesis depended on both hyperglycemia and insulin deficiency, but protein degradation was only reversed by normalization of hyperglycemia. The reduction in protein synthesis was associated with diminished protein translation efficiency but, surprisingly, not with reduced activity of the mTORC1/S6K1/4E-BP1 pathway. Instead, diabetes induced a specific reduction of mTORC2 complex activity. These findings reveal distinctive responses of diabetes-induced retinal protein turnover compared with muscle and liver that may provide a new means to ameliorate diabetic retinopathy. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  7. Fock representations of the superalgebra sl(n+1 vertical bar m), its quantum analogue Uq[sl(n+1 vertical bar m)] and related quantum statistics

    International Nuclear Information System (INIS)

    Palev, T.D.; Stoilova, N.I.; Jeugt, J. van der

    1999-12-01

    Fock space representations of the Lie superalgebra sl(n + 1 vertical bar m) and of its quantum analogue U q [sl(n + 1 vertical bar m)] are written down. The results are based on a description of these superalgebras via creation and annihilation operators. The properties of the underlying statistics are briefly discussed. (author)

  8. Radiation-induced conduction under high electric field (1 x 106 to 1 x 108 V/m) in polyethylene-terephthalate

    International Nuclear Information System (INIS)

    Maeda, H.; Kurashige, M.; Ito, D.; Nakakita, T.

    1978-01-01

    Radiation-induced conduction in polyethylene-terephthalate (PET) has been measured under high electric field (1.0 x 10 6 to 1.6 x 10 8 V/m). In a 6-μm-thick PET film, saturation of the radiation-induced current occurs at field strengths above 1.2 x 10 8 V/m. This has been demonstrated by the thickness and dose rate dependence of the induced current. Radiation-induced conductivity increases monotonically with field strength, then shows a saturation tendency. This may be explained by geminate recombination. Above 1 x 10 8 V/m, slowly increasing radiation-induced current appears. This may be caused by electron injection from the cathode, enhanced by the accumulation of the hetero space charges near it

  9. Divorcing the Late Upper Palaeolithic demographic histories of mtDNA haplogroups M1 and U6 in Africa

    Directory of Open Access Journals (Sweden)

    Pennarun Erwan

    2012-12-01

    Full Text Available Abstract Background A Southwest Asian origin and dispersal to North Africa in the Early Upper Palaeolithic era has been inferred in previous studies for mtDNA haplogroups M1 and U6. Both haplogroups have been proposed to show similar geographic patterns and shared demographic histories. Results We report here 24 M1 and 33 U6 new complete mtDNA sequences that allow us to refine the existing phylogeny of these haplogroups. The resulting phylogenetic information was used to genotype a further 131 M1 and 91 U6 samples to determine the geographic spread of their sub-clades. No southwest Asian specific clades for M1 or U6 were discovered. U6 and M1 frequencies in North Africa, the Middle East and Europe do not follow similar patterns, and their sub-clade divisions do not appear to be compatible with their shared history reaching back to the Early Upper Palaeolithic. The Bayesian Skyline Plots testify to non-overlapping phases of expansion, and the haplogroups’ phylogenies suggest that there are U6 sub-clades that expanded earlier than those in M1. Some M1 and U6 sub-clades could be linked with certain events. For example, U6a1 and M1b, with their coalescent ages of ~20,000–22,000 years ago and earliest inferred expansion in northwest Africa, could coincide with the flourishing of the Iberomaurusian industry, whilst U6b and M1b1 appeared at the time of the Capsian culture. Conclusions Our high-resolution phylogenetic dissection of both haplogroups and coalescent time assessments suggest that the extant main branching pattern of both haplogroups arose and diversified in the mid-later Upper Palaeolithic, with some sub-clades concomitantly with the expansion of the Iberomaurusian industry. Carriers of these maternal lineages have been later absorbed into and diversified further during the spread of Afro-Asiatic languages in North and East Africa.

  10. Remaining Sites Verification Package for the 100-F-26:12, 1.8-m (72-in.) Main Process Sewer Pipeline. Attachment to Waste Site Reclassification Form 2007-034

    International Nuclear Information System (INIS)

    Capron, J.M.

    2008-01-01

    The 100-F-26:12 waste site was an approximately 308-m-long, 1.8-m-diameter east-west-trending reinforced concrete pipe that joined the North Process Sewer Pipelines (100-F-26:1) and the South Process Pipelines (100-F-26:4) with the 1.8-m reactor cooling water effluent pipeline (100-F-19). In accordance with this evaluation, the verification sampling results support a reclassification of this site to Interim Closed Out. The results of verification sampling show that residual contaminant concentrations do not preclude any future uses and allow for unrestricted use of shallow zone soils. The results also demonstrate that residual contaminant concentrations are protective of groundwater and the Columbia River

  11. β-Secretase BACE1 regulates hippocampal and reconstituted M-currents in a β-subunit-like fashion.

    Science.gov (United States)

    Hessler, Sabine; Zheng, Fang; Hartmann, Stephanie; Rittger, Andrea; Lehnert, Sandra; Völkel, Meike; Nissen, Matthias; Edelmann, Elke; Saftig, Paul; Schwake, Michael; Huth, Tobias; Alzheimer, Christian

    2015-02-25

    The β-secretase BACE1 is widely known for its pivotal role in the amyloidogenic pathway leading to Alzheimer's disease, but how its action on transmembrane proteins other than the amyloid precursor protein affects the nervous system is only beginning to be understood. We report here that BACE1 regulates neuronal excitability through an unorthodox, nonenzymatic interaction with members of the KCNQ (Kv7) family that give rise to the M-current, a noninactivating potassium current with slow kinetics. In hippocampal neurons from BACE1(-/-) mice, loss of M-current enhanced neuronal excitability. We relate the diminished M-current to the previously reported epileptic phenotype of BACE1-deficient mice. In HEK293T cells, BACE1 amplified reconstituted M-currents, altered their voltage dependence, accelerated activation, and slowed deactivation. Biochemical evidence strongly suggested that BACE1 physically associates with channel proteins in a β-subunit-like fashion. Our results establish BACE1 as a physiologically essential constituent of regular M-current function and elucidate a striking new feature of how BACE1 impacts on neuronal activity in the intact and diseased brain. Copyright © 2015 the authors 0270-6474/15/353298-14$15.00/0.

  12. Enhancing the biophysical properties of mRFP1 through incorporation of fluoroproline

    Energy Technology Data Exchange (ETDEWEB)

    Deepankumar, Kanagavel; Nadarajan, Saravanan Prabhu; Ayyadurai, Niraikulam; Yun, Hyungdon, E-mail: hyungdon@ynu.ac.kr

    2013-11-01

    Graphical abstract: Enhancing the biophysical properties of mRFP1 through incorporation of (2S, 4R)-4-fluoroproline at proline residues after mutating non-permissive site Pro63 into Ala. -- Highlights: •We incorporate (4S)-FP into mRFP1 led to insoluble protein. •Whereas, incorporation of (4R)-FP resulted in soluble but lost its fluorescence. •mRFP1-P63A mutant accommodate (4R)-FP and gave soluble protein with fluorescence. •Moreover mRFP1-P63A[(4R)-FP] showed enhanced biophysical properties of protein. -- Abstract: Here we enhanced the stability and biophysical properties of mRFP1 through a combination of canonical and non-canonical amino acid mutagenesis. The global replacement of proline residue with (2S, 4R)-4-fluoroproline [(4R)-FP] into mRFP1 led to soluble protein but lost its fluorescence, whereas (2S, 4S)-4-fluoroproline [(4S)-FP] incorporation resulted in insoluble protein. The bioinformatics analysis revealed that (4R)-FP incorporation at Pro63 caused fluorescence loss due to the steric hindrance of fluorine atom of (4R)-FP with the chromophore. Therefore, Pro63 residue was mutated with the smallest amino acid Ala to maintain non coplanar conformation of the chromophore and helps to retain its fluorescence with (4R)-FP incorporation. The incorporation of (4R)-FP into mRFP1-P63A showed about 2–3-fold enhancement in thermal and chemical stability. The rate of maturation is also greatly accelerated over the presence of (4R)-FP into mRFP1-P63A. Our study showed that a successful enhancement in the biophysical property of mRFP1-P63A[(4R)-FP] using non-canonical amino acid mutagenesis after mutating non-permissive site Pro63 into Ala.

  13. Enhancing the biophysical properties of mRFP1 through incorporation of fluoroproline

    International Nuclear Information System (INIS)

    Deepankumar, Kanagavel; Nadarajan, Saravanan Prabhu; Ayyadurai, Niraikulam; Yun, Hyungdon

    2013-01-01

    Graphical abstract: Enhancing the biophysical properties of mRFP1 through incorporation of (2S, 4R)-4-fluoroproline at proline residues after mutating non-permissive site Pro63 into Ala. -- Highlights: •We incorporate (4S)-FP into mRFP1 led to insoluble protein. •Whereas, incorporation of (4R)-FP resulted in soluble but lost its fluorescence. •mRFP1-P63A mutant accommodate (4R)-FP and gave soluble protein with fluorescence. •Moreover mRFP1-P63A[(4R)-FP] showed enhanced biophysical properties of protein. -- Abstract: Here we enhanced the stability and biophysical properties of mRFP1 through a combination of canonical and non-canonical amino acid mutagenesis. The global replacement of proline residue with (2S, 4R)-4-fluoroproline [(4R)-FP] into mRFP1 led to soluble protein but lost its fluorescence, whereas (2S, 4S)-4-fluoroproline [(4S)-FP] incorporation resulted in insoluble protein. The bioinformatics analysis revealed that (4R)-FP incorporation at Pro63 caused fluorescence loss due to the steric hindrance of fluorine atom of (4R)-FP with the chromophore. Therefore, Pro63 residue was mutated with the smallest amino acid Ala to maintain non coplanar conformation of the chromophore and helps to retain its fluorescence with (4R)-FP incorporation. The incorporation of (4R)-FP into mRFP1-P63A showed about 2–3-fold enhancement in thermal and chemical stability. The rate of maturation is also greatly accelerated over the presence of (4R)-FP into mRFP1-P63A. Our study showed that a successful enhancement in the biophysical property of mRFP1-P63A[(4R)-FP] using non-canonical amino acid mutagenesis after mutating non-permissive site Pro63 into Ala

  14. Main modelling features of the ASTEC V2.1 major version

    International Nuclear Information System (INIS)

    Chatelard, P.; Belon, S.; Bosland, L.; Carénini, L.; Coindreau, O.; Cousin, F.; Marchetto, C.; Nowack, H.; Piar, L.; Chailan, L.

    2016-01-01

    Highlights: • Recent modelling improvements of the ASTEC European severe accident code are outlined. • Key new physical models now available in the ASTEC V2.1 major version are described. • ASTEC progress towards a multi-design reactor code is illustrated for BWR and PHWR. • ASTEC strong link with the on-going EC CESAM FP7 project is emphasized. • Main remaining modelling issues (on which IRSN efforts are now directing) are given. - Abstract: A new major version of the European severe accident integral code ASTEC, developed by IRSN with some GRS support, was delivered in November 2015 to the ASTEC worldwide community. Main modelling features of this V2.1 version are summarised in this paper. In particular, the in-vessel coupling technique between the reactor coolant system thermal-hydraulics module and the core degradation module has been strongly re-engineered to remove some well-known weaknesses of the former V2.0 series. The V2.1 version also includes new core degradation models specifically addressing BWR and PHWR reactor types, as well as several other physical modelling improvements, notably on reflooding of severely damaged cores, Zircaloy oxidation under air atmosphere, corium coolability during corium concrete interaction and source term evaluation. Moreover, this V2.1 version constitutes the back-bone of the CESAM FP7 project, which final objective is to further improve ASTEC for use in Severe Accident Management analysis of the Gen.II–III nuclear power plants presently under operation or foreseen in near future in Europe. As part of this European project, IRSN efforts to continuously improve both code numerical robustness and computing performances at plant scale as well as users’ tools are being intensified. Besides, ASTEC will continue capitalising the whole knowledge on severe accidents phenomenology by progressively keeping physical models at the state of the art through a regular feed-back from the interpretation of the current and

  15. Methylated Glutathione S-transferase 1 (mGSTP1) is a potential plasma free DNA epigenetic marker of prognosis and response to chemotherapy in castrate-resistant prostate cancer.

    Science.gov (United States)

    Mahon, K L; Qu, W; Devaney, J; Paul, C; Castillo, L; Wykes, R J; Chatfield, M D; Boyer, M J; Stockler, M R; Marx, G; Gurney, H; Mallesara, G; Molloy, P L; Horvath, L G; Clark, S J

    2014-10-28

    Glutathione S-transferase 1 (GSTP1) inactivation is associated with CpG island promoter hypermethylation in the majority of prostate cancers (PCs). This study assessed whether the level of circulating methylated GSTP1 (mGSTP1) in plasma DNA is associated with chemotherapy response and overall survival (OS). Plasma samples were collected prospectively from a Phase I exploratory cohort of 75 men with castrate-resistant PC (CRPC) and a Phase II independent validation cohort (n=51). mGSTP1 levels in free DNA were measured using a sensitive methylation-specific PCR assay. The Phase I cohort identified that detectable baseline mGSTP1 DNA was associated with poorer OS (HR, 4.2 95% CI 2.1-8.2; P<0.0001). A decrease in mGSTP1 DNA levels after cycle 1 was associated with a PSA response (P=0.008). In the Phase II cohort, baseline mGSTP1 DNA was a stronger predictor of OS than PSA change after 3 months (P=0.02). Undetectable plasma mGSTP1 after one cycle of chemotherapy was associated with PSA response (P=0.007). We identified plasma mGSTP1 DNA as a potential prognostic marker in men with CRPC as well as a potential surrogate therapeutic efficacy marker for chemotherapy and corroborated these findings in an independent Phase II cohort. Prospective Phase III assessment of mGSTP1 levels in plasma DNA is now warranted.

  16. Specificity in endoplasmic reticulum-stress signaling in yeast entails a step-wise engagement of HAC1 mRNA to clusters of the stress sensor Ire1.

    Science.gov (United States)

    van Anken, Eelco; Pincus, David; Coyle, Scott; Aragón, Tomás; Osman, Christof; Lari, Federica; Gómez Puerta, Silvia; Korennykh, Alexei V; Walter, Peter

    2014-12-30

    Insufficient protein-folding capacity in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR). In the ER lumen, accumulation of unfolded proteins activates the transmembrane ER-stress sensor Ire1 and drives its oligomerization. In the cytosol, Ire1 recruits HAC1 mRNA, mediating its non-conventional splicing. The spliced mRNA is translated into Hac1, the key transcription activator of UPR target genes that mitigate ER-stress. In this study, we report that oligomeric assembly of the ER-lumenal domain is sufficient to drive Ire1 clustering. Clustering facilitates Ire1's cytosolic oligomeric assembly and HAC1 mRNA docking onto a positively charged motif in Ire1's cytosolic linker domain that tethers the kinase/RNase to the transmembrane domain. By the use of a synthetic bypass, we demonstrate that mRNA docking per se is a pre-requisite for initiating Ire1's RNase activity and, hence, splicing. We posit that such step-wise engagement between Ire1 and its mRNA substrate contributes to selectivity and efficiency in UPR signaling.

  17. The computer code EURDYN-1M (release 2). User's manual

    International Nuclear Information System (INIS)

    1982-01-01

    EURDYN-1M is a finite element computer code developed at J.R.C. Ispra to compute the response of two-dimensional coupled fluid-structure configurations to transient dynamic loading for reactor safety studies. This report gives instructions for preparing input data to EURDYN-1M, release 2, and describes a test problem in order to illustrate both the input and the output of the code

  18. Identification and Validation of a Potent Dual Inhibitor of the P. falciparum M1 and M17 Aminopeptidases Using Virtual Screening.

    Directory of Open Access Journals (Sweden)

    Chiara Ruggeri

    Full Text Available The Plasmodium falciparum PfA-M1 and PfA-M17 metalloaminopeptidases are validated drug targets for the discovery of antimalarial agents. In order to identify dual inhibitors of both proteins, we developed a hierarchical virtual screening approach, followed by in vitro evaluation of the highest scoring hits. Starting from the ZINC database of purchasable compounds, sequential 3D-pharmacophore and molecular docking steps were applied to filter the virtual 'hits'. At the end of virtual screening, 12 compounds were chosen and tested against the in vitro aminopeptidase activity of both PfA-M1 and PfA-M17. Two molecules showed significant inhibitory activity (low micromolar/nanomolar range against both proteins. Finally, the crystal structure of the most potent compound in complex with both PfA-M1 and PfA-M17 was solved, revealing the binding mode and validating our computational approach.

  19. Strategies for a centralized single product multiclass M/G/1 make-to-stock queue

    OpenAIRE

    Abouee-Mehrizi, Hossein; Balcıoğlu, Ahmet Barış; Balcioglu, Ahmet Baris; Baron, Opher

    2012-01-01

    Make-to-stock queues are typically investigated in the M/M/1 settings. For centralized single-item systems with backlogs, the multilevel rationing (MR) policy is established as optimal and the strict priority (SP) policy is a practical compromise, balancing cost and ease of implementation. However, the optimal policy is unknown when service time is general, i.e., for M/G/1 queues. Dynamic programming, the tool commonly used to investigate the MR policy in make-to-stock queues, is less practic...

  20. Analysis of experimental air-detritiation data using TSOAK-M1

    International Nuclear Information System (INIS)

    Land, R.H.; Maroni, V.A.; Minkoff, M.

    1980-01-01

    A computer code (TSOAK-M1) has been developed which permits the determination of tritium reaction (T 2 to HTO)/adsorption/release and instrument correction parameters from enclosure (building) detritiation test data. The code is based on a simplified model which treats each parameter as a normalized time-independent constant throughout the data-unfolding steps. TSOAK-M1 was used to analyze existing small-cubicle test data with good success, and the resulting normalized parameters were employed to evaluate hypothetical reactor-building detritiation scenarios. It was concluded from the latter evaluation that the complications associated with moisture formation, adsorption, and release, particularly in terms of extended cleanup times, may not be as great as was previously thought. It is recommended that the validity of the TSOAK-M1 model be tested using data from detritiation tests conducted on large experimental enclosures (5 to 10 m 3 ) and, if possible, actual facility buildings

  1. Glycosylation analysis and protein structure determination of murine fetal antigen 1 (mFA1)--the circulating gene product of the delta-like protein (dlk), preadipocyte factor 1 (Pref-1) and stromal-cell-derived protein 1 (SCP-1) cDNAs

    DEFF Research Database (Denmark)

    Krogh, T N; Bachmann, E; Teisner, B

    1997-01-01

    By means of sequence analysis, murine fetal antigen 1 (mFA1) isolated from Mus musculus amniotic fluid was shown to be the circulating protein of the delta-like protein, stromal-cell-derived protein 1 (SCP-1) and preadipocyte factor 1 (Pref-1) gene products. The protein contains 36 cysteine...... residues arranged in six epidermal-growth-factor-like domains. The purification of several C-terminal peptides of varying lengths showed mFA1 to be C-terminal heterogeneous. O-linked glycosylations of the NeuNAc alpha2-3Gal beta1-3(NeuNAc alpha2-6)GalNAc type were present on all C-terminal peptides...... at residues Thr235, Thr244 and Thr248, although glycosylation on Thr244 was only partial. Three N-linked glycosylations were localized in mFA1 (Asn77, Asn142 and Asn151), two of which (Asn142 and Asn151) were in the unusual Asn-Xaa-Cys motif. Fucosylated biantennary complex-type and small amounts (less than 5...

  2. Design, fabrication and testing of a 56 mm bore twin-aperture 1 m long dipole magnet made with SSC type cable

    Energy Technology Data Exchange (ETDEWEB)

    Ostler, J.; Perini, D.; Russenschuck, S.; Siegel, N.; Siemko, A.; Trinquart, G.; Walckiers, L.; Weterings, W. [CERN, Geneva (Switzerland)

    1996-07-01

    In the framework of the LHC superconducting dipole magnet model program, a 56 mm bore, twin-aperture dipole model 1 m long, using existing cables of the standard SSC type, was launched to initiate studies of lower field magnets with smaller strand size cables for a 7 TeV collider. This model was designed, built, assembled and tested at CERN and reached a peak field of 9.7 T at 1.8 K. The paper reviews the main design principles, presents the fabrication and assembly procedures and finally discusses the overall test results.

  3. Design, fabrication and testing of a 56 mm bore twin-aperture 1 m long dipole magnet made with SSC type cable

    International Nuclear Information System (INIS)

    Ostler, J.; Perini, D.; Russenschuck, S.; Siegel, N.; Siemko, A.; Trinquart, G.; Walckiers, L.; Weterings, W.

    1996-01-01

    In the framework of the LHC superconducting dipole magnet model program, a 56 mm bore, twin-aperture dipole model 1 m long, using existing cables of the standard SSC type, was launched to initiate studies of lower field magnets with smaller strand size cables for a 7 TeV collider. This model was designed, built, assembled and tested at CERN and reached a peak field of 9.7 T at 1.8 K. The paper reviews the main design principles, presents the fabrication and assembly procedures and finally discusses the overall test results

  4. Modes in a non-neutral plasma of finite length, m=0,1

    International Nuclear Information System (INIS)

    Rasband, S. Neil; Spencer, Ross L.

    2003-01-01

    For realistic, cold equilibria of finite length representing a pure electron plasma confined in a cylindrical Malmberg-Penning trap, the mode spectrum for Trivelpiece-Gould, m=0, and for diocotron, m=1, modes is calculated numerically. A novel method involving finite elements is used to successfully compute eigenfrequencies and eigenfunctions for plasma equilibria shaped like pancakes, cigars, long cylinders, and all things in between. Mostly sharp-boundary density configurations are considered but also included in this study are diffuse density profiles including ones with peaks off axis leading to instabilities. In all cases the focus has been on elucidating the role of finite length in determining mode frequencies and shapes. For m=0 accurate eigenfrequencies are tabulated and their dependence on mode number and aspect ratio is computed. For m=1 it is found that the eigenfrequencies are 2% to 3% higher than given by the Fine-Driscoll formula [Phys. Plasmas 5, 601 (1998)]. The 'new modes' of Hilsabeck and O'Neil [Phys. Plasmas 8, 407 (2001)] are identified as Dubin modes. For hollow profiles finite length in cold-fluid can account for up to ∼70% of the theoretical instability growth rate

  5. Some observations on the synthesis and electrolytic properties of (Ba1-xCax (M0.9Y0.1O3, M = Ce, Zr-based samples modified with calcium

    Directory of Open Access Journals (Sweden)

    Dudek Magdalena

    2016-03-01

    Full Text Available In this paper, the impact of partial substitution of calcium for barium in (Ba1-xCax (M0.9Y0.1 O3, M = Ce, Zr on physicochemical properties of the powders and sintered samples was investigated. The powders, with various contents of calcium (x = 0, 0.02, 0.05, 0.1, were prepared by means of thermal decomposition of organometallic precursors containing EDTA. All of the BaCeO3-based powders synthesised at 1100 °C were monophasic with a rhombohedral structure, however, completely cubic BaZrO3-based solid solutions were obtained at 1200 °C. A study of the sinterability of BaZr0.9Y0.1O3 and BaCe0.9Y0.1O3-based pellets was performed under non-isothermal conditions within a temperature range of 25 to 1200 °C. The partial substitution of barium for calcium in the (Ba1-xCax (M0.9Y0.1 O3, M = Ce, Zr solid solution improved the sinterability of the samples in comparison to the initial BaCe0.9Y0.1O3 or BaZr0.9Y0.1O3. The relative density of calcium-modified BaCe0.9Y0.1O3-based samples reached approximately 95 to 97 % after sintering at 1500 °C for 2 h in air. The same level of relative density was achieved after sintering calcium-modified BaZr0.9Y0.1O3 at 1600 °C for 2 h. Analysis of the electrical conductivity from both series of investigated materials showed that the highest ionic conductivity, in air and wet 5 % H2 in Ar, was attained for the compositions of x = 0.02 to 0.05 (Ba1-xCax(M0.9Y0.1O3, M = Zr, Ce. The oxygen reduction reaction on the interface Pt│BaM0.9Y0.1O3, M = Ce, Zr was investigated using Pt microelectrodes. Selected samples of (Ba1-xCax (M0.9Y0.1O3, M = Zr, Ce were tested as ceramic electrolytes in hydrogen-oxygen solid oxide fuel cells operating at temperatures of 700 to 850 °C.

  6. Sample Scripts for Illumina 1M-Duo [

    Lifescience Database Archive (English)

    Full Text Available load_data.txt 4. Importing the result of typing data of the illumina 1M-Duo This script helps you to create ...the result table of all typing data. Example of script: create_table_tbl_fr_recluster.sql CREATE TABLE `tbl_

  7. Main: 1FWO [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1FWO イネ Rice Oryza sativa L. Oryzain Beta Chain Precursor Oryza Sativa Molecule: Oryzain Beta Chain; Chai...eered: Yes; Mutation: Yes Hydrolase 3.4.22.- (Oryzain Beta Chain) D.Tolkatchev, P.Xu, F.Ni D.Tolkatchev, P.X...olds Into A Stack Of Two Beta-Hairpins, A Scaffold Present In The Emerging Family Of Granulin-Like Growth Fa...ctors J.Pept.Res. V. 57 227 2001 Beta-Hairpin Stack Fold, Granulin/Epithelin-Like Protein Repeats SWS:ORYB_O

  8. The DAG project, a 4m class telescope: the telescope main structure performances

    Science.gov (United States)

    Marchiori, G.; Busatta, A.; Ghedin, L.; Marcuzzi, E.; Manfrin, C.; Battistel, C.; Pirnay, O.; Flebus, Carlo; Yeşilyaprak, C.; Keskin, O.; Yerli, S.

    2016-07-01

    Dogu Anatolu Gözlemevi (DAG-Eastern Anatolia Observatory) Project is a 4m class optical, near-infrared Telescope and suitable enclosure which will be located at an altitude of 3.170m in Erzurum, Turkey. The DAG telescope is a project fully funded by Turkish Ministry of Development and the Atatürk University of Astrophysics Research Telescope - ATASAM. The Project is being developed by the Belgian company AMOS (project leader), which is also the optics supplier and EIE GROUP, the Telescope Main Structure supplier and responsible for the final site integration. The design of the Telescope Main Structure fits in the EIE TBO Program which aims at developing a Dome/Telescope systemic optimization process for both performances and competitive costs based on previous project commitments like NTT, VLT, VST and ASTRI. The optical Configuration of the DAG Telescope is a Ritchey-Chretien with two Nasmyth foci and a 4m primary thin mirror controlled in shape and position by an Active Optic System. The main characteristics of the Telescope Main Structure are an Altitude-Azimuth light and rigid structure system with Direct Drive Systems for both axis, AZ Hydrostatic Bearing System and Altitude standard bearing system; both axes are equipped with Tape Encoder System. An innovative Control System characterizes the telescope performance.

  9. The battle for meaning: A cross-national film reception analysis of The Battle Cry of Peace in Switzerland and the Netherlands during World War I

    NARCIS (Netherlands)

    de Zwaan, K.; gerber, adrian

    2016-01-01

    This article offers a cross-national analysis of the historical reception of the American war film The Battle Cry of Peace (J. Stuart Blackton and Wilfred North/Vitagraph, 1915) in the neutral countries of the Netherlands and Switzerland during World War I. Treating propaganda as a mode de lecture,

  10. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

    Science.gov (United States)

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-08-26

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

  11. Comparison of the Abbott m2000 HIV-1 Real-Time and Roche AMPLICOR Monitor v1.5 HIV-1 assays on plasma specimens from Rakai, Uganda.

    Science.gov (United States)

    Ssebugenyi, I; Kizza, A; Mpoza, B; Aluma, G; Boaz, I; Newell, K; Laeyendecker, O; Shott, J P; Serwadda, D; Reynolds, S J

    2011-07-01

    The need for viral load (VL) monitoring of HIV patients receiving antiretroviral therapy (ART) in resource-limited settings (RLS) has become apparent with studies showing the limitations of immunological monitoring. We compared the Abbott m2000 Real-Time (Abbott) HIV-1 assay with the Roche AMPLICOR Monitor v1.5 (Roche) HIV-1 assay over a range of VL concentrations. Three hundred and eleven plasma samples were tested, including 164 samples from patients on ART ≥ six months and 147 from ART-naïve patients. The Roche assay detected ≥400 copies/mL in 158 (50.8%) samples. Of these, Abbott produced 145 (91.8%) detectable results ≥400 copies/mL; 13 (8.2%) samples produced discrepant results. Concordance between the assays for detecting HIV-1 RNA ≥400 copies/mL was 95.8% (298/311). The sensitivity, specificity, positive predictive value and negative predictive value of Abbott to detect HIV-1 RNA ≥400 copies/mL were 91.8%, 100%, 100% and 92.2%, respectively. For the 151 samples with HIV-1 RNA ≥400 copies/mL for both assays, a good linear correlation was found (r = 0.81, P Abbott assay performed well in our setting, offering an alternative methodology for HIV-1 VL for laboratories with realtime polymerase chain reaction (PCR) capacity.

  12. Cerebrospinal fluid melanin-concentrating hormone (MCH and hypocretin-1 (HCRT-1, orexin-A in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Frank M Schmidt

    Full Text Available Ancillary to decline in cognitive abilities, patients with Alzheimer's disease (AD frequently suffer from behavioural and psychological symptoms of dementia (BPSD. Hypothalamic polypeptides such as melanin-concentrating hormone (MCH and hypocretin-1 (HCRT-1, orexin-A are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF levels were measured in 33 patients with AD and 33 healthy subjects (HS using a fluorescence immunoassay (FIA. A significant main effect of diagnosis (F(1,62 = 8.490, p<0.01 on MCH levels was found between AD (93.76±13.47 pg/mL and HS (84.65±11.40 pg/mL. MCH correlated with T-tau (r = 0.47; p<0.01 and P-tau (r = 0.404; p<0.05 in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r = -0.362, p<0.05 and was increased in more severely affected patients (MMSE≤20 compared to HS (p<0.001 and BPSD-positive patients compared to HS (p<0.05. In CSF-HCRT-1, a significant main effect of sex (F(1,31 = 4.400, p<0.05 with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD.

  13. Magnetic ordering of quasi-1 D S=1/2 Heisenberg antiferromagnet Cu benzoate at sub-mK temperatures

    International Nuclear Information System (INIS)

    Karaki, Y.; Masutomi, R.; Kubota, M.; Ishimoto, H.; Asano, T.; Ajiro, Y.

    2003-01-01

    We have measured the AC susceptibility of quasi-1D S=1/2 Heisenberg antiferromagnet Cu benzoate at temperatures down to 0.2 mK. A sharp susceptibility peak is observed at 0.8 mK under an earth field. This fact indicates a 3D ordering of linear chains coupled by a weak magnetic interaction between chains

  14. Inflammation induced mTORC2-Akt-mTORC1 signaling promotes macrophage foam cell formation.

    Science.gov (United States)

    Banerjee, Dipanjan; Sinha, Archana; Saikia, Sudeshna; Gogoi, Bhaskarjyoti; Rathore, Arvind K; Das, Anindhya Sundar; Pal, Durba; Buragohain, Alak K; Dasgupta, Suman

    2018-06-05

    The transformation of macrophages into lipid loaded foam cells is a critical and early event in the pathogenesis of atherosclerosis. Several recent reports highlighted that induction of TLR4 signaling promotes macrophage foam cell formation; however, the underlying molecular mechanisms have not been clearly elucidated. Here, we found that the TLR4 mediated inflammatory signaling communicated with mTORC2-Akt-mTORC1 metabolic cascade in macrophage and thereby promoting lipid uptake and foam cell formation. Mechanistically, LPS treatment markedly upregulates TLR4 mediated inflammatory pathway which by activating mTORC2 induces Akt phosphorylation at serine 473 and that aggravate mTORC1 dependent scavenger receptors expression and consequent lipid accumulation in THP-1 macrophages. Inhibition of mTORC2 either by silencing Rictor expression or inhibiting its association with mTOR notably prevents LPS induced Akt activation, scavenger receptors expression and macrophage lipid accumulation. Although suppression of mTORC1 expression by genetic knockdown of Raptor did not produce any significant change in Akt S473 phosphorylation, however, incubation with Akt activator in Rictor silenced cells failed to promote scavenger receptors expression and macrophage foam cell formation. Thus, present research explored the signaling pathway involved in inflammation induced macrophage foam cells formation and therefore, targeting this pathway might be useful for preventing macrophage foam cell formation. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  15. Energetic M1 transitions as a probe of nuclear collectivity at high temperatures

    International Nuclear Information System (INIS)

    Baktash, C.

    1987-01-01

    At ORNL, we have recently utilized the Spin Spectrometer setup to investigate the differential effects of increasing spin and excitation energy on nuclear shape and collectivity in 158 Yb. Along the yrast line of this and other N = 88 nuclei, weakly prolate shapes gradually give way to triaxial, and then finally to non-collective oblate shapes as the spin approaches 40 h-bar. However, above the yrast line, large deformation and collectivity once again sets in. This is evidenced by the emergence of a broad quadrupole structure (E/sub γ/ ≅ 1.2 MeV) in the continuum gamma-ray spectra that grows with increasing temperature. The short (sub ps) lifetimes of these transitions attest to the collective nature of these structures. The emergence and growth of the quadrupole structure at high excitation energies is closely correlated with the appearance of energetic (E/sub γ/ ≅ 2.5 MeV), fast M1 transitions which form another broad structure in the continuum spectra. From the centroid of the M1 bump, a quadrupole deformation parameter of 0.35 is inferred. Because of this sensitivity, these energetic M1 transitions provide a unique probe of nuclear shape in the excitation energy range of ≅ 3 to 10 MeV. 6 refs., 2 figs

  16. Stress relaxation damage in K9 glass plate irradiated by 1.06μm CW laser

    International Nuclear Information System (INIS)

    Luo Fu; Sun Chengwei

    2001-01-01

    Based on the stress relaxation model in 1D planar geometry and the visco-elastic constitutive equation, the temperature and stress histories in the K9 glass samples irradiated by CW laser beams (λ = 1.06 μm) have been calculated. The results indicate that the residual tensile stress due to the stress relaxation effect during cooling after the laser radiation may be greater than the tensile fracture strength of samples, while the maximum compression stress during the laser heating is less than the requirement for compression damage. For a K9 glass window of 3 mm thickness, its damage due to the stress relaxation may be induced by a laser radiation of 0.946 MW/cm 2 for 0.2s . Therefore, the stress relaxation should be regarded as the main mechanism of damage in K9 glass windows while a CW laser beam (λ = 1.06 μm) irradiates it with large spot

  17. The cysteine 34 residue of A1M1-microglobulin is essential for protection of irradiated cell cultures and reduction of carbonyl groups.

    Science.gov (United States)

    Rutardottir, S; Nilsson, E J C; Pallon, J; Gram, M; Åkerström, B

    2013-07-01

    α1-microglobulin (A1M) is a 26 kDa plasma and a tissue protein belonging to the lipocalin family. The reductase and free radical scavenger A1M has been shown to protect cells and extracellular matrix against oxidative and irradiation-induced damage. The reductase activity was previously shown to depend upon an unpaired cysteinyl side-chain, C34, and three lysyl side-chains, K92, 118, and 130, located around the open end of the lipocalin pocket. The aim of this work was to investigate whether the cell and matrix protection by A1M is a result of its reductase activity by using A1M-variants with site-directed mutations of the C34, K92, K118, and K130 positions. The results show that the C34 side-chain is an absolute requirement for protection of HepG2 cell cultures against alpha-particle irradiation-induced cell death, upregulation of stress response and cell cycle regulation genes. Mutation of C34 also resulted in loss of the reduction capacity toward heme- and hydrogen peroxide-oxidized collagen, and the radical species 2,2´-azino-bis (3-ethyl-benzo-thiazoline-6-sulphonic acid) (ABTS). Furthermore, mutation of C34 significantly suppressed the cell-uptake of A1M. The K92, K118, and K130 side-chains were of minor importance in cell protection and reduction of oxidized collagen but strongly influenced the reduction of the ABTS-radical. It is concluded that antioxidative protection of cells and collagen by A1M is totally dependent on its C34 amino acid residue. A model of the cell protection mechanism of A1M should be based on the redox activity of the free thiolyl group of the C34 side-chain and a regulatory role of the K92, K118, and K130 residues.

  18. Evaluation of bisphenol A glucuronidation according to UGT1A1*28 polymorphism by a new LC–MS/MS assay

    International Nuclear Information System (INIS)

    Trdan Lušin, Tina; Roškar, Robert; Mrhar, Aleš

    2012-01-01

    The endocrine disruptor bisphenol A (BPA) is a frequently used chemical in the manufacture of consumer products. In humans, BPA is extensively metabolized to BPA glucuronide (BPAG) by different UDP-glucuronosyltransferase (UGT) isoforms. The study has been performed with the intention to improve the accuracy of published physiologically based pharmacokinetic models and to improve regulatory risk assessments of BPA. In order to gain insight into intestine, kidney, liver, and lung glucuronidation of BPA, human microsomes of all tested organs were used. BPAG formation followed Michaelis–Menten kinetics in the intestine and kidney, but followed substrate inhibition kinetics in the liver. Human lung microsomes did not show glucuronidation activity towards BPA. While the liver intrinsic clearance was very high (857 mL min −1 kg body weight −1 ), the tissue intrinsic clearances for the kidney and intestine were less than 1% of liver intrinsic clearance. Since BPA is a UGT1A1 substrate, we postulated that the common UGT1A1*28 polymorphism influences BPA glucuronidation, and consequently, BPA detoxification. Hepatic tissue intrinsic clearances for UGT1A1*1/*1, UGT1A1*1/*28, and UGT1A1*28/*28 microsomes were 1113, 1075, and 284 mL min −1 kg body weight −1 , respectively. Prior to microsomal experiments, the bioproduction of BPAG and stable isotope-labeled BPAG (BPAG d16 ) was performed for the purpose of the reliable and accurate quantification of BPAG. In addition, a sensitive LC–MS/MS analytical method for the simultaneous determination of BPA and BPAG based on two stable isotope-labeled internal standards was developed and validated. In conclusion, our in vitro results show that the liver is the main site of BPA glucuronidation (K m 8.9 μM, V max 8.5 nmol min −1 mg −1 ) and BPA metabolism may be significantly influenced by a person's genotype (K m 10.0–13.1 μM, V max 3.4–16.2 nmol min −1 mg −1 ). This discovery may be an important fact for the

  19. PGE{sub 2}-induced colon cancer growth is mediated by mTORC1

    Energy Technology Data Exchange (ETDEWEB)

    Dufour, Marc, E-mail: Marc.dufour@chuv.ch; Faes, Seraina, E-mail: Seraina.faes@chuv.ch; Dormond-Meuwly, Anne, E-mail: Anne.meuwly-Dormond@chuv.ch; Demartines, Nicolas, E-mail: Demartines@chuv.ch; Dormond, Olivier, E-mail: Olivier.dormond@chuv.ch

    2014-09-05

    Highlights: • PGE{sub 2} activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE{sub 2} induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE{sub 2} induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E{sub 2} (PGE{sub 2}) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE{sub 2} directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE{sub 2}-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE{sub 2} increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE{sub 2} EP{sub 4} receptor was responsible for transducing the signal to mTORC1. Moreover, PGE{sub 2} increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE{sub 2}-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE{sub 2} increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE{sub 2} mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth.

  20. vacA s1m1 genotype and cagA EPIYA-ABC pattern are predominant among Helicobacter pylori strains isolated from Mexican patients with chronic gastritis.

    Science.gov (United States)

    Atrisco-Morales, Josefina; Martínez-Santos, Verónica I; Román-Román, Adolfo; Alarcón-Millán, Judit; De Sampedro-Reyes, José; Cruz-Del Carmen, Iván; Martínez-Carrillo, Dinorah N; Fernández-Tilapa, Gloria

    2018-03-01

    Virulent genotypes of Helicobacter pylori vacA s1m1/cagA + /babA2 + have been associated with severe gastric diseases. VacA, CagA and BabA are polymorphic proteins, and their association with the disease is allele-dependent. The aims of this work were: (i) to determine the prevalence of H. pylori by type of chronic gastritis; (ii) to describe the frequency of cagA, babA2 and vacA genotypes in strains from patients with different types of chronic gastritis; (iii) to characterize the variable region of cagA alleles. A total of 164 patients with chronic gastritis were studied. Altogether, 50 H. pylori strains were isolated, and the status of cagA, babA2 and vacA genotypes was examined by PCR. cagA EPIYA segment identification was performed using PCR and sequencing of cagA fragments of six randomly selected strains.Results/Key findings. The overall prevalence of H. pylori was 30.5 %. Eighty percent of the isolated strains were vacA s1m1, and the cagA and babA2 genes were detected in 74 and 32 % of the strains, respectively. The most frequent genotypes were vacA s1m1/cagA + /babA2 - and vacA s1m1/cagA + /babA2 + , with 40 % (20/50) and 28 % (14/50), respectively. In cagA + , the most frequent EPIYA motif was -ABC (78.4 %), and EPIYA-ABCC and -ABCCC motifs were found in 10.8 % of the strains. A modified EPIYT-B motif was found in 66.6 % of the sequenced strains. H. pylori strains carrying vacA s1m1, cagA + and babA2 - genotypes were the most prevalent in patients with chronic gastritis from the south of Mexico. In the cagA + strains, the EPIYA-ABC motif was the most common.

  1. Dual inhibition of mTORC1 and mTORC2 perturbs cytoskeletal organization and impairs endothelial cell elongation.

    Science.gov (United States)

    Tsuji-Tamura, Kiyomi; Ogawa, Minetaro

    2018-02-26

    Elongation of endothelial cells is an important process in vascular formation and is expected to be a therapeutic target for inhibiting tumor angiogenesis. We have previously demonstrated that inhibition of mTORC1 and mTORC2 impaired endothelial cell elongation, although the mechanism has not been well defined. In this study, we analyzed the effects of the mTORC1-specific inhibitor everolimus and the mTORC1/mTORC2 dual inhibitor KU0063794 on the cytoskeletal organization and morphology of endothelial cell lines. While both inhibitors equally inhibited cell proliferation, KU0063794 specifically caused abnormal accumulation of F-actin and disordered distribution of microtubules, thereby markedly impairing endothelial cell elongation and tube formation. The effects of KU0063794 were phenocopied by paclitaxel treatment, suggesting that KU0063794 might impair endothelial cell morphology through over-stabilization of microtubules. Although mTORC1 is a key signaling molecule in cell proliferation and has been considered a target for preventing angiogenesis, mTORC1 inhibitors have not been sufficient to suppress angiogenesis. Our results suggest that mTORC1/mTORC2 dual inhibition is more effective for anti-angiogenic therapy, as it impairs not only endothelial cell proliferation, but also endothelial cell elongation. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Fabrication and testing of main sodium pumps of Superphenix 1

    International Nuclear Information System (INIS)

    Noel, H.; Pasqualini, G.

    1985-01-01

    The complexity of the loads involved and the extremely fine analysis required necessitates extensive design calculations for the Superphenix 1 primary and secondary pumps and associated expansion tanks, aiming toward detailed design validation, after slight adjustments, mainly to the secondary pumps and expansion tanks. The component parts to be built were far larger than those for the previous pumps (Rapsodie, Phenix), with very low manufacturing tolerances, which led to precision machining and welding operations, together with numerous dimensional inspections and materials characterization tests to achieve the required quality standards

  3. Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Ronald S. Duman

    2018-05-01

    Full Text Available Therapeutic medications for the treatment of depression have serious limitations, particularly delayed onset and low rates of efficacy. However, the discovery that a single subanesthetic dose of ketamine, a glutamate NMDA receptor channel blocker, can produce a rapid (within hours antidepressant response that is sustained (about 1 week, even in patients considered treatment-resistant, has invigorated the field. In addition to these remarkable actions, ketamine has proven effective for the treatment of suicidal ideation. Efforts are under way to develop ketamine-like drugs with fewer side effects as well as agents that act at other sites within the glutamate neurotransmitter system. This includes ketamine metabolites and stereoisomers, drugs that act as NMDA allosteric modulators or that block mGluR2/3 autoreceptors. In addition, targets that enhance glutamate neurotransmission or synaptic function (or both, which are essential for the rapid and sustained antidepressant actions of ketamine in rodent models, are being investigated; examples are the muscarinic cholinergic antagonist scopolamine and activators of mechanistic target of rapamycin complex 1 (mTORC1 signaling, which is required for the actions of ketamine. The discovery of ketamine and its unique mechanisms heralds a new era with tremendous promise for the development of novel, rapid, and efficacious antidepressant medications.

  4. TSOAK-M1: an examination of its model and methods

    International Nuclear Information System (INIS)

    Edgell, D.H.

    1983-05-01

    Fusion facilities will contain a sizable inventory of tritium fuel that will be vulnerable to release. Once released, molecular tritium begins converting into tritiated water which is 10000 times more hazardous and tends to adsorb onto surfaces. The rate of conversion and adsorption/desorption must be accurately known to estimate cleanup times and radiation hazards realistically. Argonne National Laboratory developed a computer code, TSOAK-M1, to determine the conversion/ adsorption/desorption parameters and to model cleanups. The Canadian Fusion Fuels Technology Project examined the program for reliability and potential applications. TSOAK-M1 assumes a pseudo second order radiolytic conversion where a first order surface reaction seems more appropriate. This difference in order should be investigated to accurately determine the reaction law. TSOAK-M1 determines the model parameters from experimental data using an optimization routine. However the data used is judged insufficient. More data is needed where the conversion of molecular tritium to tritiated water has a significant effect due to adsorption/desorption. SOAKER, an improved version of the TSOAK-M1 model, which combines first and second order reactions has been implemented in Wang BASIC. Once the reaction law and the parameters have been accurately determined the program could be a useful tool in the study and design of decontamination systems

  5. LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation.

    Science.gov (United States)

    Milkereit, Ruth; Persaud, Avinash; Vanoaica, Liviu; Guetg, Adriano; Verrey, Francois; Rotin, Daniela

    2015-05-22

    Mammalian target of rapamycin 1 (mTORC1), a master regulator of cellular growth, is activated downstream of growth factors, energy signalling and intracellular essential amino acids (EAAs) such as Leu. mTORC1 activation occurs at the lysosomal membrane, and involves V-ATPase stimulation by intra-lysosomal EAA (inside-out activation), leading to activation of the Ragulator, RagA/B-GTP and mTORC1 via Rheb-GTP. How Leu enters the lysosomes is unknown. Here we identified the lysosomal protein LAPTM4b as a binding partner for the Leu transporter, LAT1-4F2hc (SLC7A5-SLAC3A2). We show that LAPTM4b recruits LAT1-4F2hc to lysosomes, leading to uptake of Leu into lysosomes, and is required for mTORC1 activation via V-ATPase following EAA or Leu stimulation. These results demonstrate a functional Leu transporter at the lysosome, and help explain the inside-out lysosomal activation of mTORC1 by Leu/EAA.

  6. Achievements and Prospects in Electrochemical-Based Biosensing Platforms for Aflatoxin M1 Detection in Milk and Dairy Products

    Directory of Open Access Journals (Sweden)

    Ana-Maria Gurban

    2017-12-01

    Full Text Available Aflatoxins, which are mainly produced by Aspergillus flavus and parasiticus growing on plants and products stored under inappropriate conditions, represent the most studied group of mycotoxins. Contamination of human and animal milk with aflatoxin M1, the hydroxylated metabolite of aflatoxin B1, is an important health risk factor due to its carcinogenicity and mutagenicity. Due to the low concentration of this aflatoxin in milk and milk products, the analytical methods used for its quantification have to be highly sensitive, specific and simple. This paper presents an overview of the analytical methods, especially of the electrochemical immunosensors and aptasensors, used for determination of aflatoxin M1.

  7. A Belief Network Decision Support Method Applied to Aerospace Surveillance and Battle Management Projects

    National Research Council Canada - National Science Library

    Staker, R

    2003-01-01

    This report demonstrates the application of a Bayesian Belief Network decision support method for Force Level Systems Engineering to a collection of projects related to Aerospace Surveillance and Battle Management...

  8. Expression, purification, and characterization of the Necator americanus aspartic protease-1 (Na-APR-1 (M74)) antigen, a component of the bivalent human hookworm vaccine.

    Science.gov (United States)

    Seid, Christopher A; Curti, Elena; Jones, R Mark; Hudspeth, Elissa; Rezende, Wanderson; Pollet, Jeroen; Center, Lori; Versteeg, Leroy; Pritchard, Sonya; Musiychuk, Konstantin; Yusibov, Vidadi; Hotez, Peter J; Bottazzi, Maria Elena

    2015-01-01

    Over 400 million people living in the world's poorest developing nations are infected with hookworms, mostly of the genus Necator americanus. A bivalent human hookworm vaccine composed of the Necator americanus Glutathione S-Transferase-1 (Na-GST-1) and the Necator americanus Aspartic Protease-1 (Na-APR-1 (M74)) is currently under development by the Sabin Vaccine Institute Product Development Partnership (Sabin PDP). Both monovalent vaccines are currently in Phase 1 trials. Both Na-GST-1 and Na-APR-1 antigens are expressed as recombinant proteins. While Na-GST-1 was found to express with high yields in Pichia pastoris, the level of expression of Na-APR-1 in this host was too low to be suitable for a manufacturing process. When the tobacco plant Nicotiana benthamiana was evaluated as an expression system, acceptable levels of solubility, yield, and stability were attained. Observed expression levels of Na-APR-1 (M74) using this system are ∼300 mg/kg. Here we describe the achievements and obstacles encountered during process development as well as characterization and stability of the purified Na-APR-1 (M74) protein and formulated vaccine. The expression, purification and analysis of purified Na-APR-1 (M74) protein obtained from representative 5 kg reproducibility runs performed to qualify the Na-APR-1 (M74) production process is also presented. This process has been successfully transferred to a pilot plant and a 50 kg scale manufacturing campaign under current Good Manufacturing Practice (cGMP) has been performed. The 50 kg run has provided a sufficient amount of protein to support the ongoing hookworm vaccine development program of the Sabin PDP.

  9. The face of war: Trauma analysis of a mass grave from the Battle of Lützen (1632.

    Directory of Open Access Journals (Sweden)

    Nicole Nicklisch

    Full Text Available Contemporary accounts of battles are often incomplete or even erroneous because they reflect the-often biased-viewpoints of the authors. Battlefield archaeology faces the task of compiling an historical analysis of a battle and of gathering all the available facts. Besides cultural historical evidence and artefacts, the human remains of those who have fallen in battle also provide invaluable information. In studying mass graves from a military context, the injury types and patterns are significant. They allow us to reconstruct the circumstances surrounding the soldiers' deaths and provide information on the hostilities that occurred on the battlefield. One such mass grave was discovered in 2011 at Lützen, Saxony-Anhalt (Germany. Based on its geographical location and on the results obtained from archaeological examinations carried out in the area, the grave could be dated to the Thirty Years War (1618-1648. Further archaeological research confirmed that the dead had been soldiers from the Battle of Lützen (1632. The mass grave was block-lifted and then comprehensively examined at the State Museum of Prehistory in Halle (Saale. As well as osteological examinations to determine age, sex, height, state of health, i.e. diseases or injuries, imaging methods were also employed and histological and isotopic analyses carried out. The focus of this study was on the injuries sustained by the soldiers both prior to and during the battle. The results revealed that the 47 deceased had been between the ages of 15 and 50 when they died. Numerous healed injuries showed that the men had often been involved in violent encounters. Approximately three in every four soldiers had injuries that could have been fatal. Wounds inflicted by handguns, particularly to the skull, were predominant. The integrative analysis of the archaeological and anthropological data allowed us to conclude that the majority had been killed during a cavalry attack.

  10. Development of Neutron Imaging System for Neutron Tomography at Thai Research Reactor TRR-1/M1

    Science.gov (United States)

    Wonglee, S.; Khaweerat, S.; Channuie, J.; Picha, R.; Liamsuwan, T.; Ratanatongchai, W.

    2017-09-01

    The neutron imaging is a powerful non-destructive technique to investigate the internal structure and provides the information which is different from the conventional X-ray/Gamma radiography. By reconstruction of the obtained 2-dimentional (2D) images from the taken different angle around the specimen, the tomographic image can be obtained and it can provide the information in more detail. The neutron imaging system at Thai Research Reactor TRR-1/M1 of Thailand Institute of Nuclear Technology (Public Organization) has been developed to conduct the neutron tomography since 2014. The primary goal of this work is to serve the investigation of archeological samples, however, this technique can also be applied to various fields, such as investigation of industrial specimen and others. This research paper presents the performance study of a compact neutron camera manufactured by Neutron Optics such as speed and sensitivity. Furthermore, the 3-dimentional (3D) neutron image was successfully reconstructed at the developed neutron imaging system of TRR-1/M1.

  11. An Approach to Quantifying Pokemon's Entertainment Impact with focus on Battle

    OpenAIRE

    Panumate, Chetprayoon; Xiong, Shuo; Iida, Hiroyuki

    2015-01-01

    This paper explores the attractiveness of Pokemon which is a turn-based Role Playing Game (RPG) and has been very popular for the decades. In this study we focus on Pokemon battle which is the most important component in Pokemon. The game refinement theory is used as a tool to assess the degree of sophistication of Pokemon battle. For this purpose we apply two approaches of game progress modeling to derive game refinement measure, i.e., score limit sports approach and board game approach. We ...

  12. Magnetic probe measurement of MHD behaviors in the TRIAM-1M tokamak

    International Nuclear Information System (INIS)

    Yanagisawa, Michihiko; Kawasaki, Shoji; Moriyama, Shin-ichi; Nagao, Akihiro; Nakamura, Kazuo; Hiraki, Naoji; Nakamura, Yukio; Itoh, Satoshi; Jotaki, Eriko.

    1988-01-01

    MHD behavior and following disruption were observed at low-q discharge and high-density discharge in TRIAM-1A. It was observed by magnetic probe, that interaction between m=3/n=2 and m=2/n=1 modes in low-q discharge, and growth of m=2/n=1 in high discharge drive to disruption. (J.P.N)

  13. Effect of Cocoa Polyphenolic Extract on Macrophage Polarization from Proinflammatory M1 to Anti-Inflammatory M2 State

    Directory of Open Access Journals (Sweden)

    Laura Dugo

    2017-01-01

    Full Text Available Polyphenols-rich cocoa has many beneficial effects on human health, such as anti-inflammatory effects. Macrophages function as control switches of the immune system, maintaining the balance between pro- and anti-inflammatory activities. We investigated the hypothesis that cocoa polyphenol extract may affect macrophage proinflammatory phenotype M1 by favoring an alternative M2 anti-inflammatory state on macrophages deriving from THP-1 cells. Chemical composition, total phenolic content, and antioxidant capacity of cocoa polyphenols extracted from roasted cocoa beans were determined. THP-1 cells were activated with both lipopolysaccharides and interferon-γ for M1 or with IL-4 for M2 switch, and specific cytokines were quantified. Cellular metabolism, through mitochondrial oxygen consumption, and ATP levels were evaluated. Here, we will show that cocoa polyphenolic extract attenuated in vitro inflammation decreasing M1 macrophage response as demonstrated by a significantly lowered secretion of proinflammatory cytokines. Moreover, treatment of M1 macrophages with cocoa polyphenols influences macrophage metabolism by promoting oxidative pathways, thus leading to a significant increase in O2 consumption by mitochondrial complexes as well as a higher production of ATP through oxidative phosphorylation. In conclusion, cocoa polyphenolic extract suppresses inflammation mediated by M1 phenotype and influences macrophage metabolism by promoting oxidative pathways and M2 polarization of active macrophages.

  14. mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes

    Directory of Open Access Journals (Sweden)

    Annabel Y. Minard

    2016-09-01

    Full Text Available FGF21 improves the metabolic profile of obese animals through its actions on adipocytes. To elucidate the signaling network responsible for mediating these effects, we quantified dynamic changes in the adipocyte phosphoproteome following acute exposure to FGF21. FGF21 regulated a network of 821 phosphosites on 542 proteins. A major FGF21-regulated signaling node was mTORC1/S6K. In contrast to insulin, FGF21 activated mTORC1 via MAPK rather than through the canonical PI3K/AKT pathway. Activation of mTORC1/S6K by FGF21 was surprising because this is thought to contribute to deleterious metabolic effects such as obesity and insulin resistance. Rather, mTORC1 mediated many of the beneficial actions of FGF21 in vitro, including UCP1 and FGF21 induction, increased adiponectin secretion, and enhanced glucose uptake without any adverse effects on insulin action. This study provides a global view of FGF21 signaling and suggests that mTORC1 may act to facilitate FGF21-mediated health benefits in vivo.

  15. Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression

    DEFF Research Database (Denmark)

    Bisgaard, Line S; Mogensen, Christina K; Rosendahl, Alexander

    2016-01-01

    Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE-/- mice, their M1/M2 phenotype,......, ACSL1, SRB1, DGAT1, and cpt1a) was decreased in advanced versus early lesions. In conclusion, PEMs and BMDMs are phenotypically distinct and differ from macrophages in lesions with respect to expression of M1/M2 markers and lipid metabolism genes....

  16. 1.06 μm reflectivity measurements of metal optics

    International Nuclear Information System (INIS)

    Saito, T.T.

    1975-01-01

    The equipment and technique for the measurement of 1.06 μm reflectivity of diamond turned, diamond turned/polished, and polished metal mirrors is presented. From an analysis of repeatability and systematic errors it is concluded the precision of the measurements is 0.003 and the accuracy is 0.005. Diamond turned mirrors compete well with the best 1 μm reflectivity values reported and are superior to polished surfaces studied in this work. (U.S.)

  17. Different expression of FoxM1 in human benign and malignant pleural effusion.

    Science.gov (United States)

    Tang, Zhonghao; Li, Hongqing; Zhu, Huili; Bai, Chunxue

    2015-01-01

    The aims of this study were as follows: to analyze the forkhead box M1 (FoxM1) expression in benign and malignant pleural effusion by reverse transcription-polymerase chain reaction assay (RT-PCR); to explore the role of FoxM1 in formation and progress in malignant pleural effusion, and whether there is significant difference in expression level of FoxM1 between benign and malignant pleural effusion; to seek a gene marker diagnostically useful to identify benign and malignant pleural effusion in diagnosis and treatment of pleural effusion; and to collect expression level data of FoxM1 in 23 malignant pleural effusion samples (17 adenocarcinoma samples, four squamous carcinoma samples and two small cell lung carcinoma samples) and 15 benign pleural effusion samples (11 inflammatory pleural effusions, two transudates, two tuberculous pleural effusions) by RT-PCR. Among all 38 samples, average FoxM1 expression level of benign pleural effusions is (235.09 ± 59.99), while malignant pleural effusions (828.77 ± 109.76). Among 23 malignant samples, average FoxM1 expression level is (529.27 ± 75.85) in samples without cytological diagnostic evidence, while (1,218.12 ± 167.21) in samples with cytological diagnostic evidence. Differences of FoxM1 expression level between benign pleural effusions and malignant ones have statistical significance. There is an area of 0.881 under the receiver-operating characteristic curve, which verifies the accuracy of using FoxM1 expression level as diagnostic index to identify benign and malignant pleural effusions. According to our study, diagnostic sensitivity and specificity for FoxM1 expression level at 418.1 were 82.6 and 86.7 %, respectively, while 47.8 and 100 %, respectively, at 768.7. FoxM1 expression level in malignant pleural effusions is significantly higher than in benign ones. This study provides a new approach in clinical diagnosis, with FoxM1 as a specific molecule marker to identify benign and malignant pleural

  18. The C5a/C5aR1 axis controls the development of experimental allergic asthma independent of LysM-expressing pulmonary immune cells.

    Directory of Open Access Journals (Sweden)

    Anna V Wiese

    Full Text Available C5a regulates the development of maladaptive immune responses in allergic asthma mainly through the activation of C5a receptor 1 (C5aR1. Yet, the cell types and the mechanisms underlying this regulation are ill-defined. Recently, we described increased C5aR1 expression in lung tissue eosinophils but decreased expression in airway and pulmonary macrophages as well as in pulmonary CD11b+ conventional dendritic cells (cDCs and monocyte-derived DCs (moDCs during the allergic effector phase using a floxed green fluorescent protein (GFP-C5aR1 knock-in mouse. Here, we determined the role of C5aR1 signaling in neutrophils, moDCs and macrophages for the pulmonary recruitment of such cells and the importance of C5aR1-mediated activation of LysM-expressing cells for the development of allergic asthma. We used LysM-C5aR1 KO mice with a specific deletion of C5aR1 in LysMCre-expressing cells and confirmed the specific deletion of C5aR1 in neutrophils, macrophages and moDCs in the airways and/or the lung tissue. We found that alveolar macrophage numbers were significantly increased in LysM-C5aR1 KO mice. Induction of ovalbumin (OVA-driven experimental allergic asthma in GFP-C5aR1fl/fl and LysM-C5aR1 KO mice resulted in strong but similar airway resistance, mucus production and Th2/Th17 cytokine production. In contrast, the number of airway but not of pulmonary neutrophils was lower in LysM-C5aR1 KO as compared with GFP-C5aR1fl/fl mice. The recruitment of macrophages, cDCs, moDCs, T cells and type 2 innate lymphoid cells was not altered in LysM-C5aR1 KO mice. Our findings demonstrate that C5aR1 is critical for steady state control of alveolar macrophage numbers and the transition of neutrophils from the lung into the airways in OVA-driven allergic asthma. However, C5aR1 activation of LysM-expressing cells plays a surprisingly minor role in the recruitment and activation of such cells and the development of the allergic phenotype in OVA-driven experimental

  19. MiR-520b suppresses proliferation of hepatoma cells through targeting ten-eleven translocation 1 (TET1) mRNA

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Weiying; Lu, Zhanping; Gao, Yuen [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin (China); Ye, Lihong [State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin (China); Song, Tianqiang, E-mail: tjchi@hotmai.com [Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin (China); Zhang, Xiaodong, E-mail: zhangxd@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin (China)

    2015-05-08

    Accumulating evidence indicates that microRNAs are able to act as oncogenes or tumor suppressor genes in human cancer. We previously reported that miR-520b was down-regulated in hepatocellular carcinoma (HCC) and its deregulation was involved in hepatocarcinogenesis. In the present study, we report that miR-520b suppresses cell proliferation in HCC through targeting the ten-eleven translocation 1 (TET1) mRNA. Notably, we identified that miR-520b was able to target 3′-untranslated region (3′UTR) of TET1 mRNA by luciferase reporter gene assays. Then, we revealed that miR-520b was able to reduce the expression of TET1 at the levels of mRNA and protein using reverse transcription-polymerase chain reaction and Western blotting analysis. In terms of function, 5-ethynyl-2-deoxyuridine (EdU) incorporation and colony formation assays demonstrated that the forced miR-520b expression remarkably inhibited proliferation of hepatoma cells, but TET1 overexpression could rescue the inhibition of cell proliferation mediated by miR-520b. Furthermore, anti-miR-520b enhanced proliferation of hepatoma cells, whereas silencing of TET1 abolished anti-miR-520b-induced acceleration of cell proliferation. Then, we validated that the expression levels of miR-520b were negatively related to those of TET1 mRNA in clinical HCC tissues. Thus, we conclude that miR-520b depresses proliferation of liver cancer cells through targeting 3′UTR of TET1 mRNA. Our finding provides new insights into the mechanism of hepatocarcinogenesis. - Highlights: • TET1 is a novel target gene of miR-520b. • TET1 is upregulated in clinical HCC tissues. • MiR-520b is negatively correlated with TET1 in clinical HCC tissues. • MiR-520b depresses the proliferation of HCC cells through targeting TET1 mRNA.

  20. Phospholipase C-{delta}{sub 1} regulates interleukin-1{beta} and tumor necrosis factor-{alpha} mRNA expression

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Eric; Jakinovich, Paul; Bae, Aekyung [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States); Rebecchi, Mario, E-mail: Mario.rebecchi@SBUmed.org [Department of Anesthesiology, Health Sciences Center L4 Rm 081, Stony Brook University, Stony Brook, NY 11794 (United States)

    2012-10-01

    Phospholipase C-{delta}{sub 1} (PLC{delta}{sub 1}) is a widely expressed highly active PLC isoform, modulated by Ca{sup 2+} that appears to operate downstream from receptor signaling and has been linked to regulation of cytokine production. Here we investigated whether PLC{delta}{sub 1} modulated expression of the pro-inflammatory cytokines interleukin-1{beta} (IL-1{beta}), tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6) in rat C6 glioma cells. Expression of PLC{delta}{sub 1} was specifically suppressed by small interfering RNA (siRNA) and the effects on cytokine mRNA expression, stimulated by the Toll-like receptor (TLR) agonist, lipopolysaccharide (LPS), were examined. Real-time polymerase chain reaction (RT-PCR) results showed that PLC{delta}{sub 1} knockdown enhanced expression IL-1{beta} and tumor necrosis factor-{alpha} (TNF-{alpha}) mRNA by at least 100 fold after 4 h of LPS stimulation compared to control siRNA treatment. PLC{delta}{sub 1} knock down caused persistently high Nf{kappa}b levels at 4 h of LPS stimulation compared to control siRNA-treated cells. PLC{delta}{sub 1} knockdown was also associated with elevated nuclear levels of c-Jun after 30 min of LPS stimulation, but did not affect LPS-stimulated p38 or p42/44 MAPK phosphorylation, normally associated with TLR activation of cytokine gene expression; rather, enhanced protein kinase C (PKC) phosphorylation of cellular proteins was observed in the absence of LPS stimulation. An inhibitor of PKC, bisindolylmaleimide II (BIM), reversed phosphorylation, prevented elevation of nuclear c-Jun levels, and inhibited LPS-induced increases of IL-1{beta} and TNF-{alpha} mRNA's induced by PLC{delta}{sub 1} knockdown. Our results show that loss of PLC{delta}{sub 1} enhances PKC/c-Jun signaling and up-modulates pro-inflammatory cytokine gene transcription in concert with the TLR-stimulated p38MAPK/Nf{kappa}b pathway. Our findings are consistent with the idea that PLC{delta}{sub 1} is a

  1. Cryo-EM Structure of a KCNQ1/CaM Complex Reveals Insights into Congenital Long QT Syndrome.

    Science.gov (United States)

    Sun, Ji; MacKinnon, Roderick

    2017-06-01

    KCNQ1 is the pore-forming subunit of cardiac slow-delayed rectifier potassium (I Ks ) channels. Mutations in the kcnq1 gene are the leading cause of congenital long QT syndrome (LQTS). Here, we present the cryoelectron microscopy (cryo-EM) structure of a KCNQ1/calmodulin (CaM) complex. The conformation corresponds to an "uncoupled," PIP 2 -free state of KCNQ1, with activated voltage sensors and a closed pore. Unique structural features within the S4-S5 linker permit uncoupling of the voltage sensor from the pore in the absence of PIP 2 . CaM contacts the KCNQ1 voltage sensor through a specific interface involving a residue on CaM that is mutated in a form of inherited LQTS. Using an electrophysiological assay, we find that this mutation on CaM shifts the KCNQ1 voltage-activation curve. This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP 2 , and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. In Vivo Measurements in Mice in the Bion-M 1 Mission

    Science.gov (United States)

    Andreev-Andrievskiy, Alexander; Custaud, Marc-Antoine; Popova, Anfisa; Borovik, Anatoliy; Dolgov, Oleg; Anokhin, Konstantin; Tsvirkun, Daria; Vinogradova, Olga

    The main aim of BION-M 1 mission was to reveal morphological, biochemical and molecular mechanisms of adaptation to prolonged exposure in microgravity. Besides that functional state and behavior were assessed in vivo using test battery, home cage observations and implantable telemetry in space-flown mice (SF), control mice from the ground replica of the flight experiment (GC) and in mice kept in vivarium (SFV and GCV). Blood pressure and heart rate were monitored continuously in a subgroup of mice using implantable telemetry throughout the flight as well as before and after it. After 30-days flight aboard BION-M 1 biosatellite SF mice have gained more weight than GC, SFV or GCV mice (11%). SF mice displayed pronounced motor impairment upon examination shortly after landing. 1 day after the flight mice were less active and more anxious in the open-field test, less coordinated in the Rotarod and aerial drop test and had less grip force compared to both control and pre-flight values. Exercise performance was greatly reduced after 30-days flight and recovered by day 7 post-flight. Before the flight mice were trained to perform a simple task using positively reinforced free operant conditioning approach. After the flight performance in the same task was preserved, however learning ability was impaired. Mice displayed drastic reduction of heart rate during launch and reentry acceleration periods. Heart rate (by 8-10%) and, to a lesser extent blood pressure (by 5%) were elevated during the 30-days flight. After return heart rate in SF mice remained elevated throughout the 7-days observation period with no apparent recovery. In summary, mice display pronounced disadaptation to 1g after 30-days exposure in microgravity with different physiological systems having different recovery dynamics. Of particular interest, hemodynamic reactions in mice closely resemble reactions in larger organisms, implying that factors that govern the cardiovascular system adaptation to

  3. The battle of "nano" paclitaxel.

    Science.gov (United States)

    Sofias, Alexandros Marios; Dunne, Michael; Storm, Gert; Allen, Christine

    2017-12-01

    Paclitaxel (PTX) is one of the three most widely used chemotherapeutic agents, together with doxorubicin and cisplatin, and is first or second line treatment for several types of cancers. In 2000, Taxol, the conventional formulation of PTX, became the best-selling cancer drug of all time with annual sales of 1.6 billion. In 2005, the introduction of the albumin-based formulation of PTX, known as Abraxane, ended Taxol's monopoly of the PTX market. Abraxane's ability to push the Taxol innovator and generic formulations aside attracted fierce competition amongst competitors worldwide to develop their own unique, new and improved formulation of PTX. At this time there are at least 18 companies focused on pre-clinical and/or clinical development of nano-formulations of PTX. These pharmaceutical companies are investing substantial capital to capture a share of the lucrative global PTX market. It is hoped that any formulation that dominates the market will result in tangible benefits to patients in terms of both survival and quality of life. Given all of this activity, here we address the question: Who is going to win the battle of "nano" paclitaxel? Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Thermally induced A'-A site exchange in novel layered perovskites Ag2[Ca1.5M3O10] (M = Nb, Ta).

    Science.gov (United States)

    Bhuvanesh, Nattamai S P; Woodward, Patrick M

    2002-12-04

    We have synthesized and characterized new layered perovskites Ag2[A1.5M3O10] (A = Ca, M = Nb, Ta), from their lithium analogues, by soft-chemical ion exchange. These oxides show topotactic irreversible thermally induced A'-A site exchange, resulting in Ag1.1Ca0.9[Ca0.6Ag0.9M3O10], conferred from our high-temperature X-ray and ionic conductivity studies. The latter phases are the first compounds where Ag+ ions reside in both A' and A sites in layered perovskites. The absence of similar phase transition for A = Sr suggests that these transitions strongly depend on the size, charge, and the coordination preference of A' and A cations. This result provides a new synthetic tool for modifying the occupation of the 12-coordinate A site of layered perovskites using soft chemical routes.

  5. Corneal tissue ablation using 6.1 μm quantum cascade laser

    Science.gov (United States)

    Huang, Yong; Kang, Jin U.

    2012-03-01

    High absorption property of tissues in the IR range (λ> 2 μm) results in effective tissue ablation, especially near 3 μm. In the mid-infrared range, wavelengths of 6.1 μm and 6.45 μm fall into the absorption bands of the amide protein groups Amide-I and Amide-II, respectively. They also coincide with the deformation mode of water, which has an absorption peak at 6.1 μm. This coincidence makes 6.1 μm laser a better ablation tool that has promising effectiveness and minimum collateral damages than 3 μm lasers. In this work, we performed bovine corneal ablation test in-vitro using high-power 6.1μm quantum cascade laser (QCL) operated at pulse mode. Quantum cascade laser has the advantages of low cost, compact size and tunable wavelength, which makes it great alternative Mid-IR light source to conventional tunable free-electron lasers (FEL) for medical applications. Preliminary results show that effective corneal stroma craters were achieved with much less collateral damage in corneal tissue that contains less water. Future study will focus on optimizing the control parameters of QCL to attain neat and precise ablation of corneal tissue and development of high peak power QCL.

  6. The 1 × 1 m hypersonic wind tunnel Kochel/Tullahoma 1940-1960

    Science.gov (United States)

    Eckardt, Dietrich

    2015-03-01

    Peenemünde and Cape Canaveral mark cornerstones of space history. Kochel in Southern Germany and Tullahoma in Tennessee, USA also belong in this category. The technically unique Kochel wind tunnel was part of the German long-distance missile development strategy, planned and prepared in secret before the beginning of World War II. A 57 MW closed-circuit wind tunnel facility with 1 × 1 m measuring section was planned for continuous-flow simulation at high Mach numbers Ma 7-10. In the early 1940 s a site beside the Walchensee Power Station at Kochel am See in Upper Bavaria, Germany was chosen to provide the required altitude difference of 200 m for the hydraulic turbine drives. The preparatory activities for the erection of this impressive hypersonic wind tunnel facility were pushed ahead until an enforced temporary pause in September 1944. In early May 1945 US troops occupied the area and, in due course, scientists of General Arnold's Scientific Advisory Group, the `von Kármán team', ordered the transfer to the USA of available equipment, design materials and other paperwork. Here, at the Arnold Engineering Development Center (AEDC) Tullahoma, TN this `Tunnel A' was built to begin operation around 1957. The testing was conducted on the Mach 7 experimental aircraft X-15, space shuttle developments and still secret investigations on unmanned hypersonic vehicles.

  7. PAI-1 mRNA expression and plasma level in rheumatoid arthritis: relationship with 4G/5G PAI-1 polymorphism.

    Science.gov (United States)

    Muñoz-Valle, José Francisco; Ruiz-Quezada, Sandra Luz; Oregón-Romero, Edith; Navarro-Hernández, Rosa Elena; Castañeda-Saucedo, Eduardo; De la Cruz-Mosso, Ulises; Illades-Aguiar, Berenice; Leyva-Vázquez, Marco Antonio; Castro-Alarcón, Natividad; Parra-Rojas, Isela

    2012-12-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, cartilage and bone. PAI-1 is a key regulator of the fibrinolytic system through which plasminogen is converted to plasmin. The plasmin activates the matrix metalloproteinase system, which is closely related with the joint damage and bone destruction in RA. The aim of this study was to investigate the relationship between 4G/5G PAI-1 polymorphism with mRNA expression and PAI-1 plasma protein levels in RA patients. 113 RA patients and 123 healthy subjects (HS) were included in the study. The 4G/5G PAI-1 polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism method; the PAI-1 mRNA expression was determined by real-time PCR; and the soluble PAI-1 (sPAI-1) levels were quantified using an ELISA kit. No significant differences in the genotype and allele frequencies of 4G/5G PAI-1 polymorphism were found between RA patients and HS. However, the 5G/5G genotype was the most frequent in both studied groups: RA (42%) and HS (44%). PAI-1 mRNA expression was slightly increased (0.67 fold) in RA patients with respect to HS (P = 0.0001). In addition, in RA patients, the 4G/4G genotype carriers showed increased PAI-1 mRNA expression (3.82 fold) versus 4G/5G and 5G/5G genotypes (P = 0.0001), whereas the sPAI-1 plasma levels did not show significant differences. Our results indicate that the 4G/5G PAI-1 polymorphism is not a marker of susceptibility in the Western Mexico. However, the 4G/4G genotype is associated with high PAI-1 mRNA expression but not with the sPAI-1 levels in RA patients.

  8. Oiling and cleanup issues in wetlands, M/T Julie N spill, Portland, Maine

    International Nuclear Information System (INIS)

    Michel, J.; Lehmann, S.M.; Henry, C.B.Jr.

    1998-01-01

    The clean up and environmental assessment techniques which were used following the September 1996 oil spill from the M/T Julie N in Portland Harbor, Maine were reviewed and documented. The spill resulted in heavy oiling of wetland. Aerial photography, ground-truth surveys, transects and chemical sampling were conducted to try to assess the impact to wetlands and to decide on appropriate cleanup options. A range of cleanup methods were attempted including low-pressure flushing, shoreline cleaning agents, vegetation cutting, and natural recovery. 9 refs., 3 tabs., 1 fig

  9. Support for the Confederate Battle Flag in the Southern United States: Racism or Southern Pride?

    Directory of Open Access Journals (Sweden)

    Joshua D. Wright

    2017-05-01

    Full Text Available Supporters of the Confederate battle flag often argue that their support is driven by pride in the South, not negative racial attitudes. Opponents of the Confederate battle flag often argue that the flag represents racism, and that support for the flag is an expression of racism and an attempt to maintain oppression of Blacks in the Southern United States. We evaluate these two competing views in explaining attitudes toward the Confederate battle flag in the Southern United States through a survey of 526 Southerners. In the aggregate, our latent variable model suggests that White support for the flag is driven by Southern pride, political conservatism, and blatant negative racial attitudes toward Blacks. Using cluster-analysis we were able to distinguish four distinct sub-groups of White Southerners: Cosmopolitans, New Southerners, Traditionalists, and Supremacists. The greatest support for the Confederate battle flag is seen among Traditionalists and Supremacists; however, Traditionalists do not display blatant negative racial attitudes toward Blacks, while Supremacists do. Traditionalists make up the majority of Confederate battle flag supporters in our sample, weakening the claim that supporters of the flag are generally being driven by negative racial attitudes toward Blacks.

  10. EDF-1 downregulates the CaM/Cn/NFAT signaling pathway during adipogenesis

    International Nuclear Information System (INIS)

    López-Victorio, Carlos J.; Velez-delValle, Cristina; Beltrán-Langarica, Alicia; Kuri-Harcuch, Walid

    2013-01-01

    Highlights: ► EDF-1 participates early adipogenesis in 3T3F442A cells induced with Staurosporine/Dexamethasone. ► EDF-1 associates with CaM and Cn, most likely inactivating Cn. ► EDF-1/CaM complex seems to prevent NFATc1 activation by Cn. ► EDF-1 regulates the Cn/CaM/NFATc1 pathway during adipogenesis. ► EDF-1 may regulate the activation of Cn through a complex formation with CaM. - Abstract: The endothelial differentiation factor-1 (EDF-1) is a calmodulin binding protein that regulates calmodulin-dependent enzymes. In endothelial cells, this factor can form a protein complex with calmodulin. We analyzed the relationship between this factor and the members of calmodulin/calcineurin/nuclear factor of activated T-cells (NFAT) signaling pathway during adipogenesis of 3T3-F442A cells. We found that the expression of edf1 is upregulated during early adipogenesis, whereas that of calcineurin gene is lowered, suggesting that this pathway should be downregulated to allow for adipogenesis to occur. We also found that EDF-1 associates with calmodulin and calcineurin, most likely inactivating calcineurin. Our results showed that EDF-1 inactivates the calmodulin/calcineurin/NFAT pathway via sequestration of calmodulin, during early adipogenesis, and we propose a mechanism that negatively regulates the activation of calcineurin through a complex formation between EDF-1 and calmodulin. This finding raises the possibility that modulating this pathway might offer some alternatives to regulate adipose biology

  11. EDF-1 downregulates the CaM/Cn/NFAT signaling pathway during adipogenesis

    Energy Technology Data Exchange (ETDEWEB)

    López-Victorio, Carlos J.; Velez-delValle, Cristina; Beltrán-Langarica, Alicia [Department of Cell Biology, Center for Research and Advanced Studies-IPN, Apdo. Postal 14-740, México City 07000 (Mexico); Kuri-Harcuch, Walid, E-mail: walidkuri@gmail.com [Department of Cell Biology, Center for Research and Advanced Studies-IPN, Apdo. Postal 14-740, México City 07000 (Mexico)

    2013-03-01

    Highlights: ► EDF-1 participates early adipogenesis in 3T3F442A cells induced with Staurosporine/Dexamethasone. ► EDF-1 associates with CaM and Cn, most likely inactivating Cn. ► EDF-1/CaM complex seems to prevent NFATc1 activation by Cn. ► EDF-1 regulates the Cn/CaM/NFATc1 pathway during adipogenesis. ► EDF-1 may regulate the activation of Cn through a complex formation with CaM. - Abstract: The endothelial differentiation factor-1 (EDF-1) is a calmodulin binding protein that regulates calmodulin-dependent enzymes. In endothelial cells, this factor can form a protein complex with calmodulin. We analyzed the relationship between this factor and the members of calmodulin/calcineurin/nuclear factor of activated T-cells (NFAT) signaling pathway during adipogenesis of 3T3-F442A cells. We found that the expression of edf1 is upregulated during early adipogenesis, whereas that of calcineurin gene is lowered, suggesting that this pathway should be downregulated to allow for adipogenesis to occur. We also found that EDF-1 associates with calmodulin and calcineurin, most likely inactivating calcineurin. Our results showed that EDF-1 inactivates the calmodulin/calcineurin/NFAT pathway via sequestration of calmodulin, during early adipogenesis, and we propose a mechanism that negatively regulates the activation of calcineurin through a complex formation between EDF-1 and calmodulin. This finding raises the possibility that modulating this pathway might offer some alternatives to regulate adipose biology.

  12. Nonlinear ω*-stabilization of the m = 1 mode in tokamaks

    International Nuclear Information System (INIS)

    Rogers, B.; Zakharov, L.

    1995-08-01

    Earlier studies of sawtooth oscillations in Tokamak Fusion Test Reactor supershots (Levinton et al, Phys. Rev. Lett. 72, 2895 (1994); Zakharov, et al, Plasma Phys. and Contr. Nucl. Fus. Res., Proc. 15th Int. Conf., Seville 1994, Vienna) have found an apparent contradiction between conventional linear theory and experiment: even in sawtooth-free discharges, the theory typically predicts instability due to a nearly ideal m = 1 mode. Here, the nonlinear evolution of such mode is analyzed using numerical simulations of a two-fluid magnetohydrodynamic (MHD) model. We find the mode saturates nonlinearly at a small amplitude provided the ion and electron drift-frequencies ω* i,e are somewhat above the linear stability threshold of the collisionless m = 1 reconnecting mode. The comparison of the simulation results to m = 1 mode activity in TFTR suggests additional, stabilizing effects outside the present model are also important

  13. The battle of the dumps continues

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Although East Rand Gold and Uranium Company is about to start exploitation of the old slimes dams to produce gold, uranium and sulphuric acid, the battle to suppress dust and establish vegetation on the old dumps continues. The physical problems, planning, co-ordination and legal aspects of mine dump reclamation are outlined

  14. Design of the 1.8 Tesla wiggler for the DAΦNE Main Rings

    International Nuclear Information System (INIS)

    Sanelli, C.; Hsieh, H.

    1992-01-01

    The electromagnetic and mechanical design of the eight wiggler magnets for DAΦNE Main Rings is described. The wigglers have a large 1.8 Tesla flat top magnetic field, 64 cm period and 4 cm gap. The magnetic 3-D calculations, the electromagnetic design and the adopted mechanical solutions, with particular attention to the vacuum chamber problems are described. A full scale prototype (5 full poles and two half pole) will be constructed in order to verify the accuracy of magnetic calculations, the end pole design and the multipole content. (author) 4 figs.; 1 tab

  15. Evaluation of CYP1A1 and CYP2B1/2 m-RNA induction in rat liver slices using the NanoString technology: a novel tool for drug discovery lead optimization.

    Science.gov (United States)

    Palamanda, Jairam R; Kumari, Pramila; Murgolo, Nicholas; Benbow, Larry; Lin, Xinjie; Nomeir, Amin A

    2009-08-01

    Cytochrome P450 (CYP) induction in rodents and humans is considered a liability for new chemical entities (NCEs) in drug discovery. In particular, CYP1A1 and CYP2B1/2 have been associated with the induction of liver tumors in oncogenicity studies during safety evaluation studies of potential drugs. In our laboratory, real time PCR (Taqman) has been used to quantify the induction of rat hepatic CYP1A1 and CYP2B1/2 in precision -cut rat liver slices. A novel technology that does not require m-RNA isolation or RT-PCR, (developed by NanoString Technologies) has been investigated to quantify CYP1A1 and CYP2B1/2 induction in rat liver slices. Seventeen commercially available compounds were evaluated using both Taqman and NanoString technologies. Precision-cut rat liver slices were incubated with individual compounds for 24 hr at 37 degrees C in a humidified CO(2) incubator and CYP1A1 and CYP2B1/2 m-RNA were quantified. The results from the NanoString technology were similar to those of the Taqman(R) with a high degree of correlation for both CYP isoforms (r(2)>0.85). Therefore, NanoString provides an additional new technology to evaluate the induction of CYP1A1 and 2B1/2, as well as potentially other enzymes or transporters in rat liver slices.

  16. Global comparison of warring groups in 2002-2007: fatalities from targeting civilians vs. fighting battles.

    Directory of Open Access Journals (Sweden)

    Madelyn Hsiao-Rei Hicks

    Full Text Available BACKGROUND: Warring groups that compete to dominate a civilian population confront contending behavioral options: target civilians or battle the enemy. We aimed to describe degrees to which combatant groups concentrated lethal behavior into intentionally targeting civilians as opposed to engaging in battle with opponents in contemporary armed conflict. METHODOLOGY/PRINCIPAL FINDINGS: We identified all 226 formally organized state and non-state groups (i.e. actors that engaged in lethal armed conflict during 2002-2007: 43 state and 183 non-state. We summed civilians killed by an actor's intentional targeting with civilians and combatants killed in battles in which the actor was involved for total fatalities associated with each actor, indicating overall scale of armed conflict. We used a Civilian Targeting Index (CTI, defined as the proportion of total fatalities caused by intentional targeting of civilians, to measure the concentration of lethal behavior into civilian targeting. We report actor-specific findings and four significant trends: 1. 61% of all 226 actors (95% CI 55% to 67% refrained from targeting civilians. 2. Logistic regression showed actors were more likely to have targeted civilians if conflict duration was three or more years rather than one year. 3. In the 88 actors that targeted civilians, multiple regressions showed an inverse correlation between CTI values and the total number of fatalities. Conflict duration of three or more years was associated with lower CTI values than conflict duration of one year. 4. When conflict scale and duration were accounted for, state and non-state actors did not differ. We describe civilian targeting by actors in prolonged conflict. We discuss comparable patterns found in nature and interdisciplinary research. CONCLUSIONS/SIGNIFICANCE: Most warring groups in 2002-2007 did not target civilians. Warring groups that targeted civilians in small-scale, brief conflict concentrated more lethal

  17. M-theory solutions invariant under D(2,1; γ) + D(2,1;γ)

    International Nuclear Information System (INIS)

    Bachas, C.; D'Hoker, E.; Estes, J.; Krym, D.

    2014-01-01

    We simplify and extend the construction of half-BPS solutions to 11-dimensional supergravity, with isometry superalgebra D(2,1;γ) + D(2,1;γ). Their space-time has the form AdS 3 x S 3 x S 3 warped over a Riemann surface Σ. It describes near-horizon geometries of M2 branes ending on, or intersecting with, M5 branes along a common string. The general solution to the BPS equations is specified by a reduced set of data (γ, h, G), where γ is the real parameter of the isometry superalgebra, and h and G are functions on Σ whose differential equations and regularity conditions depend only on the sign of γ. The magnitude of γ enters only through the map of h,G onto the supergravity fields, thereby promoting all solutions into families parametrized by vertical stroke γ vertical stroke. By analyzing the regularity conditions for the supergravity fields, we prove two general theorems: (i) that the only solution with a 2-dimensional CFT dual is AdS 3 x S 3 x S 3 x R 2 , modulo discrete identifications of the flat R 2 , and (ii) that solutions with γ 4 /Z 2 or AdS 7 ' regions; highly-curved M5-branes; and a coordinate singularity called the ''cap''. By putting these ''Lego'' pieces together we recover all known global regular solutions with the above symmetry, including the self-dual strings on M5 for γ 0, but now promoted to families parametrized by vertical stroke γ vertical stroke. We also construct exactly new regular solutions which are asymptotic to AdS 4 /Z 2 for γ 0 solutions with highly curved M5-brane regions, which are the formal continuation of the self-dual string solutions across the decompactification point at γ = 0. (Copyright copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  18. Presence of moulds and aflatoxin M1 in milk

    Directory of Open Access Journals (Sweden)

    Janković Vesna V.

    2009-01-01

    Full Text Available Aflatoxin M1 (AFM1 appears in milk or dairy products as a direct result of the cattle's ingestion of feed contaminated with aflatoxin B1 (AFB1. This study comprises mycological and mycotoxicological investigations of 23 milk samples (raw, infant food, pasteurized, whey and yoghurt. The mycological testing showed dominant presence of genus Geotrichum. G. candidum was found in 9 samples, with the highest contamination in the raw milk samples. The contamination level of AM1 is defined by using direct competitive enzyme- -linked immunosorbent assay (ELISA. AFM1 was found in 9 samples. AFM1 levels were lower than the recommended limits. However, as AFM1 is considered a probable human carcinogen (2B type, it is necessary to achieve a low level of AFM1 in milk. Therefore, cows' feed samples from various cowsheds are supposed to be evaluated routinely for aflatoxin, and kept away from fungal contamination as much as possible.

  19. Main: 1V3H [RPSD[Archive

    Lifescience Database Archive (English)

    Full Text Available 1V3H 大豆 Soybean Glycine max (L.) Merrill Beta-Amylase Name=Bmy1; Glycine Max Molecule: Beta-Amylase; Chai... 495 AA, Molecular weight: 56011 Da ATSDSNMLLNYVPVYVMLPLGVVNVDNVFEDPDGLKEQLLQLRAAGVDGVMVDVWWGIIELKGPKQYDWRAYRSLFQLVQECGLTLQAI...MSFHQCGGNVGDIVNIPIPQWVLDIGESNHDIFYTNRSGTRNKEYLTVGVDNEPIFHGRTAIEIYSDYMKSFRENMSDFLESGLIIDIEVG...FLTWYSNKLLNHGDQILDEANKAFLGCKVKLAIKVSGIHWWYKVENHAAELTAGYYNLNDRDGYRPIARMLSRHHAILNFTCLEMRDSEQPSDAKSGPQELVQQVLSG...GWREDIRVAGENALPRYDATAYNQIILNAKPQGVNNNGPPKLSMFGVTYLRLSDDLLQKSNFNIFKKFVLKMHADQDYCANPQKYNHAITPLKPSAPKIPIEVLLEATKPTLPFPWLPETDMKVDG soybean_1V3H.jpg ...

  20. SIRT1 and FOXO1 mRNA expression in PBMC correlates to physical activity in COPD patients

    Directory of Open Access Journals (Sweden)

    Taka C

    2017-11-01

    Full Text Available Chihiro Taka, Ryuji Hayashi, Kazuki Shimokawa, Kotaro Tokui, Seisuke Okazawa, Kenta Kambara, Minehiko Inomata, Toru Yamada, Shoko Matsui, Kazuyuki Tobe First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Sugitani, Toyama, Toyama, Japan Background: Physical activity (PA is considered as one of the most important prognostic predictors in chronic obstructive pulmonary disease (COPD patients. Longevity gene, SIRT1, is reported to be involved in the pathogenesis of COPD by regulating the signaling pathways of oxidative stress, inflammation, and aging. We hypothesize that SIRT1 and related genes are also associated with the benefits of PA in COPD patients.Methods: Eighteen COPD outpatients were enrolled in this study, and their PA level was assessed with an accelerometer. We assessed the SIRT1 and related genes mRNA expression levels in the peripheral blood mononuclear cells (PBMCs of the subjects. We carried out respiratory function testing, blood gas analysis, the 6-minute walk test, and measurement of the cross-sectional area of the erector spinae muscles (ESMCSA by chest computed tomography. We analyzed the association of PA with the results of each of the examinations.Results: The mean age was 72±9 years, and the mean forced expiratory volume in 1 second was 1.4±0.56 L (52%±19% predicted. Our findings revealed a correlation between the daily PA and ESMCSA. The SIRT1 and Forkhead box O (FOXO1 mRNA expression levels in PBMCs were positively correlated with moderate-PA time (r=0.60, p=0.008 for SIRT1 and r=0.59, p=0.01 for FOXO1. Keywords: COPD, accelerometer, mRNA, walking, sedentary, moderate