20s proteasome a-type: Topics by WorldWideScience.org

Synergistic activity of the proteasome inhibitor PS-341 with non-myeloablative 153-Sm-EDTMP skeletally targeted radiotherapy in an orthotopic model of multiple myeloma

The ubiquitin–proteasome pathway is the principal system for extralysosomal protein degradation in eukaryotic cells, and is essential for the regulation and maintenance of basic cellular processes,...Full Text Available

2007-01-01

SAMHD1: a new insight into HIV-1 restriction in myeloid cells

Multiple myeloma is a highly radiosensitive skeletal malignancy, but bone-seeking radionuclides have not yet found their place in disease management. We previously reported that the proteasome inhibitor...Full Text Available

2006-05-15

Identification of Genes Affecting the Toxicity of Anti-Cancer Drug Bortezomib by Genome-Wide Screening in S. pombe

Human myeloid-lineage cells are refractory to HIV-1 infection. The Vpx proteins from HIV-2 and sooty mangabey SIV render these cells permissive to HIV-1 infection through proteasomal degradation of...Full Text Available

Bortezomib induces apoptosis in T lymphoma cells and natural killer lymphoma cells independent of Epstein-Barr virus infection

Bortezomib/PS-341/Velcade, a proteasome inhibitor, is widely used to treat multiple myeloma. While several mechanisms of the cytotoxicity of the drug were proposed, the actual mechanism remains elusive....Full Text Available

British Library Electronic Table of Contents (United Kingdom)

Abstract Epstein-Barr virus (EBV), which infects not only B cells, but also T cells and natural killer (NK) cells, is associated with multiple lymphoid malignancies. Recently, the proteasome inhibitor bortezomib was reported to induce apoptosis of EBV-transformed B cells. We evaluated the killing effect of this proteasome inhibitor on EBV-associated T lymphoma cells and NK lymphoma cells. First, we found that bortezomib treatment decreased the viability of multiple T and NK cell lines. No significant difference was observed between EBV-positive and EBV-negative cell lines. The decreased viability in response to bortezomib treatment was abrogated by a pan-caspase inhibitor. The induction of apoptosis was confirmed by flow cytometric assessment of annexin V staining. Additionally, cleavage o...

2011-01-01

Proteasome Inhibition in Human Breast Cancer Cells with High Catechol-O-methyltransferase Activity by Green tea polyphenol EGCG analogs

A System-Based Comparison of Gene Expression Reveals Alterations in Oxidative Stress, Disruption of Ubiquitin-Proteasome System and Altered Cell Cycle Regulation after Exposure to Cadmium and Methylmercury in Mouse Embryonic Fibroblast

A pro-drug 8 of a synthetic analog 7 is more active in its anti-proliferative activity against human breast cancer MDA-MB-231 cells possessing high Catechol-O-methyltransferase...Full Text Available

2010-02-01

A PC-Based Imaging System for the Naval Postgraduate ...

Environmental and occupational exposures to heavy metals such as methylmercury (MeHg) and cadmium (Cd) pose significant health risks to humans, including neurotoxicity. The underlying mechanisms of...Full Text Available

2010-04-01

A novel small-molecule inhibitor of NF-#kappa#B signaling

... 1 I3a TYPE OF REPORT 1 3b TIME COVERED ... Measured by this standard the system provides good results; it ... did not fully meet all the standards or ...

1989-09-01

Ligand Tuning in Asymmetric Hydrovinylation of 1,3-Dienes. A Stereoselective Route to either Steroid-C20 (S) or -C20 (R) Derivatives

The inducible transcription factor NF-#kappa#B regulates divergent signaling pathways including inflammatory response and cancer development. Selective inhibitors for NF-#kappa#B signaling are potentially useful for treatment of inflammation and cancer. NF-#kappa#B is canonically activated by preferential disposal of its inhibitory protein; I#kappa#B, which suppresses the nuclear translocation of NF-#kappa#B. I#kappa#B#alpha# (a major member of I#kappa#B family proteins) is phosphorylated with an I#kappa#B kinase (IKK) and subsequently polyubiquitylated by SCF"#beta#"T"r"C"P"1 ubiquitin-ligase in the presence of E1 and E2 prior to proteasomal degradation. Here, we describe a novel inhibitor termed GS143, which suppressed I#kappa#B#alpha# ubiquitylation, but not I#kappa#B#alpha# phosphorylation, MDM2-directed p53 ubiquitylation, and proteasome activity in vitro. GS143 markedly suppressed the destruction of I#kappa#B#alpha# stimulated by ...

2008-04-18

High-mobility group box 1 release and redox regulation accompany regeneration and remodeling of skeletal muscle.

1,3-Dienes derived from steroidal D-ring C17-ketones undergo Ni(II)-catalyzed hydrovinylation to give 1,2- or 1,4-addition of ethylene. Using finely tuned phosphoramidite ligands it is possible to synthesize either the C20 (R)- or the C20 (S)-derivatives without mutual contamination. The proportion of the 1,4-adduct, which is also formed stereoselectively, can be minimized by optimizing the reaction conditions. Since the two alkenes in the resultant dienes have differing steric demands for many potential reactions, and are ideally juxtaposed for further D-ring functionalization, these intermediates could be useful for the preparation of biologically important compounds such as vitamin D analogs and various antitumor steroidal glycosides.

2008-06-21

Discovery of low-affinity preproinsulin epitopes and detection of autoreactive CD8 T-cells using combinatorial MHC multimers.

Abstract High-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) molecules, favors tissue regeneration via recruitment and activation of leukocytes and stem cells. Here we demonstrate, in a model of acute sterile muscle injury, that regeneration is accompanied by active reactive oxygen species (ROS) production counterbalanced and overcome by the generation of antioxidant moieties. Mitochondria are initially responsible for ROS formation. However, they undergo rapid disruption with almost complete disappearance. Twenty-four hours after injury, we observed a strong induction of MURF1 and atrogin-1 ubiquitin ligases, key signals in activation of the proteasome system and induction of muscle atrophy. At later time points, ROS generation is maintained by nonmitochondrial sources. The antioxidant response occurs in both regenerating fibers and leukocytes that express high levels of free thiols and antioxidant enzymes, such as superoxide dismutase ...

2011-05-09

Solar thermal cracking of methane in a particle-flow reactor for the co-production of hydrogen and carbon

Autoreactive cytotoxic CD8 T-cells (CTLs) play a key pathogenic role in the destruction of insulin-producing beta-cells resulting in type 1 diabetes. However, knowledge regarding their targets is limited, restricting the ability to monitor the course of the disease and immune interventions. In a multi-step discovery process to identify novel CTL epitopes in human preproinsulin (PPI), PPI was digested with purified human proteasomes, and resulting COOH-fragments aligned with algorithm-predicted HLA-binding peptides to yield nine potential HLA-A1, -A2, -A3 or -B7-restricted candidates. An UV-exchange method allowed the generation of a repertoire of multimers including low-affinity HLA-binding peptides. These were labeled with quantum dot-fluorochromes and encoded in a combinatorial fashion, allowing parallel and sensitive detection of specific, low-avidity T-cells. Significantly increased frequencies of T-cells against four novel PPI epitopes (PPI(4-13)/B7, ...

2011-05-31

British Library Electronic Table of Contents (United Kingdom)

An experimental investigation on the thermal decomposition of CH4 into C and H2 was carried out using a 5kW particle-flow solar chemical reactor tested in a solar furnace in the 1300-1600K range. The reactor features a continuous flow of CH4 laden with mm-sized carbon black particles, confined to a cavity receiver and directly exposed to concentrated solar irradiation of up to 1720 suns. The reactor performance was examined for varying operational parameters, namely the solar power input, seed particle volume fraction, gas volume flow rate, and CH4 molar concentration. Methane conversion and hydrogen yield exceeding 95% were obtained at residence times of less than 2.0s. A solar-to-chemical energy conversion efficiency of 16% was experimentally reached, and a maximum value of 31% was numer...

2009-01-01

Laser Photobiomodulation of Wound Healing in Diabetic and Non-Diabetic Mice: Effects in Splinted and Unsplinted Wounds

British Library Electronic Table of Contents (United Kingdom)

Abstract Objective: The aim of this investigation was to compare the healing of laser-irradiated and non-irradiated wounds covered by an occlusive dressing in mice. Background data: Many previous studies of the effects of laser irradiation of experimental wounds in mice and rats did not cover the wounds so that healing occurred mainly by contraction. Healing of covered wounds is slower and mimics more closely wound healing in humans. Materials and Methods: Forty-seven diabetic and twenty non-diabetic mice were used. A single wound (5?mm diameter) was created on the left flank of each animal and covered by Tegaderm HP dressing (Day 1). Wounds were irradiated (660?nm) for 20?s using a lower power (18?mW) or higher power (80?mW) laser starting immediately post-wounding for seven consecutive d...

2010-01-01

Magnetic properties of some Au_3R compounds

Differential expression of fatty acid uptake in 3T3-L1 cells

The magnetization of a series of intermetallic compounds Au_3R, where R is Gd through Yb, was investigated at 2.5 to 300"0K in applied fields up to 26 kOe. All the compounds studied exhibited the orthorhombic TiCu_3--Do/sub a/ type structure. For high temperatures, the temperature dependence of the inverse susceptibility followed a Curie--Weiss law, yielding effective paramagnetic moments in good agreement with the values calculated for free tripositive rare earth ions. At low temperatures, deviations from Curie--Weiss behavior were observed in all cases. These deviations are ascribed to the influence of crystal-field and exchange interactions. (auth).

1974-12-03

Effects of microwaves on the colony-forming capacity of haemopoietic stem cells in mice

Cultured 3T3-L1 cells have been used as a model system to investigate the mechanism of fatty acid uptake by adipose tissue. Using a 1:1 molar ratio of /sup 14/C-oleate and defatted bovine serum albumin (BSA), fatty acid (FA) uptake was quantitated at 4/sup 0/ and 37/sup 0/ as cell associated radioactivity. The profile of FA uptake in preadipocytes and adipocytes was biphasic; an initial rapid phase (1-20s) followed by a second slower phase (60-480s). At 37/sup 0/ the initial rate of FA accumulation in preadipocytes was identical to that in adipocytes, whereas the rate of accumulation during the second phase increased 7-fold (100 ..mu..M total FA) as a consequence of adipose conversion. When uptake measurements were made at 4/sup 0/ in adipocytes, the initial rate was identical to that at 37/sup 0/, however the rate of second phase decreased 5-fold. Incubation of /sup 14/C-BSA and nonradiolabeled FA with adipocyte monolayers (100 ..mu..M total ...

1987-05-01

A transient enhanced diffusion model of lattice restoration during rapid thermal annealing (RTA)

A suspension of bone marrow cells from femurs of female (CBA . C57B1)F1 mice was exposed to 2450 MHz CW microwaves in a specially designed waveguide exposure system. The temperature of the suspension rose, during exposure to microwaves, from 20/sup 0/C to 45/sup 0/C, and at an interval within 20/sup 0/C to 45/sup 0/C the number of haemopoietic stem cells (CFUs) was determined by the spleen exocolony method. The time of exposure of bone marrow cells to each temperature studied was 20 s. Control suspensions of bone marrow cells were exposed to a water bath temperature. There were no significant effects of the CFUs with the water bath temperature, while after exposure to microwaves the number of spleen colonies was elevated with a nadir at the temperature of 37/sup 0/C. With a microwave-induced increase of the temperature above 41/sup 0/C the number of CFUs in the bone marrow suspension decreased. The increase in the number of colonies was related ...

1987-01-01

Regular frequency patterns in the classical delta Scuti star HD 144277 observed by the MOST satellite

A transient-enhanced diffusion has been observed during the furnace or rapid thermal annealing of As-implanted Si. The relations of the enhanced diffusion to residual defects and lattice restoration have been studied in detail. The As concentration profiles and residual defects are measured. It is found from the data that the lattice has been restored when the implanted sample is annealed at 1150 deg C (or 1050 deg C) for 1s. The defect density decreases rapidly with increase of annealing time (from 1 to 12s). The enhanced diffusion coefficient maximum appears in the annealing time ranging from 1 to 5s. Allmost a 'complete' annealing of displacemet damage is obtained and the diffusion coefficient is less than that in above-mentioned conditions when the implanted samples are annealed at 1150 deg C in the time ranging from 12 to 20s. the mechanism of lattice restoration and enhanced diffusion in annealing process have been discussed.

CERN Document Server

We present high-precision time-series photometry of the classical delta Scuti star HD 144277 obtained with the MOST (Microvariability and Oscillations of STars) satellite in two consecutive years. The observed regular frequency patterns are investigated asteroseismologically. HD 144277 is a hot A-type star that is located on the blue border of the classical instability strip. While we mostly observe low radial order modes in classical delta Scuti stars, HD 144277 presents a different case. Its high observed frequencies, i.e., between 59.9c/d (693.9 microHz) and 71.1c/d (822.8microHz), suggest higher radial orders. We examine the progression of the regular frequency spacings from the low radial order to the asymptotic frequency region. Frequency analysis was performed using Period04 and SigSpec. The results from the MOST observing runs in 2009 and 2010 were compared to each other. The resulting frequencies were submitted to asteroseismic analysis. HD 144277 was ...

2011-01-01

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Development of non-phosphate detergent with zeolite and. alpha. -olefin sulfonate. Zeolite-AOS ni yoru senzai no murinka

Alteration of installation of reactors (alteration of No. 1 and No. 2 reactor facilities) in the Sendai Nuclear Power Station, Kyushu Electric Power Co. , Inc

Development was explained of non-phosphate detergent with zeolite (Z) and alpha-olefin sulfonate (AOS). 4A type Z was taken notice of as a builder to replace phosphate. In calcium ion trapping power, conventional sodium tripolyphosphate (STP) and Z are 158mgCaO/g and 150mg/g, respectively. However, because Z by the conventional method is large in crystal diameter, coagulates and adheres to matter to be washed, was newly developed fine Z, 0.9 {mu} m in primary grain diameter, which does not give abrasion nor occlusion to the washing machine, nor precipitate in the river. Because linear alkylbenzene sulfonate, combined with Z, is poorer in washing power than that, done with STP, was developed AOS, new non-phoshate use interfacial active detergent, which is excellent in all washing power, biodegradation speed and physical powder property. Improvement was variously made also in powdery detergent production technology. Though the non-phosphate ...

1990-07-01

Thermal fatigue of HIPed W/Cr-bronze divertor small scale mock-ups

The Nuclear Safety Commission presented the report to the Minister of International Trade and Industry on April 5, 1984, after the careful investigation and deliberation on the alteration of installation of No.1 and No.2 reactor facilities in the Sendai Nuclear Power Station. The technical capability of Kyushu Electric Power Co., Inc., was recognized to be adequate. It was judged that the safety after this alteration of installation of the reactor facilities can be ensured. The main items of examination were as follows. The mechanical, nuclear and thermo-hydraulic designs of 17 x 17 B-type fuel assemblies were regarded as adequate. The coexistence of A-type and B-type fuel assemblies does not cause any problem about the safety. The safety at the time of abnormal transient change and accident in the mixed fuel assembly core was confirmed. In No.2 reactor, the degree of enrichment of the fuel for replacement and the number of fuel assemblies to be replaced are ...

1984-08-01

Development and use of localized arc filament plasma actuators for high-speed flow control

Thermal fatigue is one of the key factors governing the lifetime of the divertor plate. Tungsten is a promising candidate to cover the surface of the divertor plate in the design of the international thermonuclear experimental reactor (ITER). The W/Cr-bronze divertor small scale mock-ups were manufactured by hot isostatic pressing (HIPing) technique. Thermal fatigue tests of W/Cr-bronze divertor mock-ups have been carried out by an electron beam facility. The mock-ups were tested under a cyclic surface heat flux of 9 MW m"-"2 for 1000 cycles. The electron beam was loaded on the mock-up surface for 20 s and unloaded for 20 s, alternately. The flow rate of water coolant was 0.1 L s"-"1. The 0.3 mm diameter NiCr-NiSi thermocouples were used to monitor the temperature distribution of the mock-up. It was found that the maximum temperature of the tungsten surface was about 400 degree sign C. The saturated temperature at the joint of tungsten and ...

2004-11-15

Beta and gamma decay heat measurements between 0.1s - 50,000s for neturon fission of {sup 235}U, {sup 238}U and {sup 239}Pu. Progress report, June 1, 1992--December 31, 1994

The paper discusses recent results on the development of localized arc filament plasma actuators and their use in controlling high-speed and high Reynolds number jet flows. Multiple plasma actuators (up to 8) are controlled using a custom-built 8-channel high-voltage pulsed plasma generator. The plasma generator independently controls pulse repetition rate (0-200 kHz), duty cycle and phase for each individual actuator. Current and voltage measurements demonstrated the power consumption of each actuator to be quite low (20 W at 20% duty cycle). Emission spectroscopy temperature measurements in the pulsed arc filament showed rapid temperature increase over the first 10-20 ?s of arc operation, from below 1000 deg. C to up to about 2000 deg. C. At longer discharge pulse durations, 20-100 ?s, the plasma temperature levels off at approximately 2000 deg. C. Modelling calculations using an unsteady, quasi-one-dimensional arc filament model showed that ...

2007-02-07

Technology base research on zinc/air battery systems: Final report

In the investigations reported here, a helium-jet/tape-transport system was used for the rapid transfer of fission products to a low-background environment where their aggregate beta and gamma-ray spectra were measured as a function of delay time after neutron induced fission of {sup 235}U, {sup 238}U and {sup 239}Pu. Beta and gamma-ray energy distributions have been deduced for delay times as short as 0.2 s and extending out to 100,000s. Instrumentation development during the initial phase of the project included: (1) assembly and characterization of a NaI(Tl) spectrometer for determining aggregate gamma-ray energy distributions, (2) development and characterization of a beta spectrometer (having excellent gamma-ray rejection) for measuring aggregate beta-particle energy distributions, (3) assembly and characterization of a Compton-suppressed HPGe spectrometer for determining gamma-ray intensities of individual fission products to deduce fission-product yields. Spectral decomposition ...

1997-05-01

Successful treatment of skin infiltration in childhood hematological malignancies with total skin electron beam therapy. A report of two cases

The capacity extension of additives was tested in a 200 cm/sup 2/bi-cell and a Zn powder moving-bed slurry. It was found that for the Type A additives in 12 M KOH, 25 g/l of silicate provided higher capacity than stannate, titanate and aluminate additives. The optimum concentration of sorbitol (a Type B additive that stabilizes polymeric chains involving ZnO) was found to be 15 g/l in 12 M KOH. A silicate and sorbitol combination added to Zn powder slurry in 12 M KOH provided a 20% increase in discharge capacity (195 Ah/l at 200 A/cm/sup 2/) compared to the maximum capacity obtained with silicate alone. A much lower capacity (74 Ah/l) was realized with silicate as Type C additive (precipitation of ZnO away from the Zn surface, for low KOH concentrations). The mechanisms of passivation and capacity extension were discussed and a model presented. The cell voltage and power densities were determined for the discharge process as a function of (a) ...

1987-09-01

Natriuretic peptides in vascular physiology and pathology.

Two children with cutaneous lymphoma and leukemia who were treated with total skin electron beam therapy (TSEB) are described here. Patient 1. A 7-year-old boy was admitted because of a mass over the bilateral parotis and anemia. The white blood cell count on admission was 5,000/ul. Bone marrow examination revealed 70 per cent monoblasts (M5a type by FAB classification). Complete remission was obtained following the regimen of daunomycin, cytosine arabinoside, 6-mercaptopurine and prednisolone. He was again admitted because of a skin nodule on the left thigh 19 months after initial diagnosis. A biopsy of the skin nodule demonstrated monoblastic infiltration. He received 20 Grays (Gy) to the left thigh and this led to resolution of the skin nodule. At that time, other skin nodules appeared on the right upper and lower extremities. He was treated with TSEB. Daily doses of 1 Gy were given twice a week with a 4 MeV electron beam and a total dose of ...

1988-07-01

Genomic analysis of the symbiotic marine crenarchaeon, Cenarchaeumsymbiosum

Four major natriuretic peptides have been isolated: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Dendroaspis-type natriuretic peptide (DNP). Natriuretic peptides play an important role in the regulation of cardiovascular homeostasis maintaining blood pressure and extracellular fluid volume. The classical endocrine effects of natriuretic peptides to modulate fluid and electrolyte balance and vascular smooth muscle tone are complemented by autocrine and paracrine actions that include regulation of coronary blood flow and, therefore, myocardial perfusion; modulation of proliferative responses during myocardial and vascular remodeling; and cytoprotective anti-ischemic effects. The actions of natriuretic peptides are mediated by the specific binding of these peptides to three cell surface receptors: type A natriuretic peptide receptor (NPR-A), type B natriuretic peptide receptor (NPR-B), ...

2008-01-01

Geological evolution of the center-southern portion of the Guyana shield based on the geochemical, geochronological and isotopic studies of paleoproterozoic granitoids from southeastern Roraima, Brazil; Evolucao geologica da porcao centro-sul do escudo das Guianas com base no estudo geoquimico, geocronologico e isotopico dos granitoides paleoproterozoicos do sudeste de Roraima, Brasil

Crenarchaea are ubiquitous and abundant microbial constituents of soils, sediments, lakes and ocean waters, yet relatively little is known about their fundamental evolutionary, ecological, and physiological properties. To better describe the ubiquitous nonthermophilic Crenarchaea, we analyzed the genome sequence of one representative, the uncultivated sponge symbiont, Cenarchaeum symbiosum. C. symbiosum genotypes coinhabiting the same host partitioned into two dominant populations, corresponding to previously described a- and b-type ribosomal RNA variants. Although synthetic, overlapping a- and b-type ribotypes harbored significant genetic variability. A single tiling path comprising the dominant a-type genotype was assembled, and used to explore the biological properties of C. symbiosum and its planktonic relatives. Out of a total of 2,066 predicted open reading frames, 36% were more highly conserved with other Archaea. The remainder partitioned between bacteria ...

2006-06-24