Effect of neutron irradiation on magnetic properties in the low alloy Ni-Mo steel SA508-3

NASA Astrophysics Data System (ADS)

Park, D. G.; Kim, C. G.; Kim, H. C.; Hong, J. H.; Kim, I. S.

1997-04-01

The B-H hysteresis loop and Barkhausen noise have been measured in the neutron irradiated SA508 steel of 45 μm thickness. The coercive force of B-H loop showed a slow change up to a neutron dose of 1014 n/cm2 and increased by 15.4% for a 1016 n/cm2 dose sample compared with that of the unirradiated one, related to the domain wall motion hindered by the increased defects. However, the amplitude of Barkhausen noise reflecting the wall motion decreased slowly up to 1014 n/cm2 irradiation, followed by a rapid decrease of 37.5% at 1016 n/cm2.

SYVN1, NEDD8, and FBXO2 Proteins Regulate ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Ubiquitin-mediated Proteasomal Degradation.

PubMed

Ramachandran, Shyam; Osterhaus, Samantha R; Parekh, Kalpaj R; Jacobi, Ashley M; Behlke, Mark A; McCray, Paul B

2016-12-02

We previously reported that delivery of a microRNA-138 mimic or siRNA against SIN3A to cultured cystic fibrosis (ΔF508/ΔF508) airway epithelia partially restored ΔF508-cystic fibrosis transmembrane conductance regulator (CFTR)-mediated cAMP-stimulated Cl - conductance. We hypothesized that dissecting this microRNA-138/SIN3A-regulated gene network would identify individual proteins contributing to the rescue of ΔF508-CFTR function. Among the genes in the network, we rigorously validated candidates using functional CFTR maturation and electrolyte transport assays in polarized airway epithelia. We found that depletion of the ubiquitin ligase SYVN1, the ubiquitin/proteasome system regulator NEDD8, or the F-box protein FBXO2 partially restored ΔF508-CFTR-mediated Cl - transport in primary cultures of human cystic fibrosis airway epithelia. Moreover, knockdown of SYVN1, NEDD8, or FBXO2 in combination with corrector compound 18 further potentiated rescue of ΔF508-CFTR-mediated Cl - conductance. This study provides new knowledge of the CFTR biosynthetic pathway. It suggests that SYVN1 and FBXO2 represent two distinct multiprotein complexes that may degrade ΔF508-CFTR in airway epithelia and identifies a new role for NEDD8 in regulating ΔF508-CFTR ubiquitination. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Dynamic strain aging in the high-temperature low-cycle fatigue of SA508 Cl. 3 forging steel

NASA Astrophysics Data System (ADS)

Lee, Byung Ho; Kim, In Sup

1995-10-01

The effect of dynamic strain aging on cyclic stress response and fatigue resistance of ASME SA508 Cl.3 forging steel for nuclear reactor pressure vessels has been evaluated in the temperature range of room temperature to 500°C. Total strain ranges and strain rates were varied from 0.7 to 2.0% and from 4 × 10 -4 to 1 × 10 -2 s -1, respectively. The cyclic stress response depended on the testing temperature, strain rate, and range. Generally, the initial cyclic hardening was immediately followed by cyclic softening at all strain rates. However, at 300°C, the operating temperature of nuclear reactor pressure vessels, the variation of cyclic stress amplitude showed the primary and secondary hardening stages dependent on the strain rate and strain range. Dynamic strain aging was manifested by enhanced cyclic hardening, distinguished secondary hardening, and negative strain rate sensitivity. A modified cell shutting model was described for the onset of the secondary hardening due to the dynamic strain aging and it was in good agreement with the experimental results. Fatigue life increased in strain rate at all testing temperatures. Specifically the fatigue life was longer at the dynamic strain aging temperature. Further, the dynamic strain aging was easy to initiate the crack, while crack propagation was retarded by crack branching and suppression of plastic zone, hence the dynamic strain aging caused the improvement of fatigue resistance.

Missense variations in the cystic fibrosis gene: Heteroduplex formation in the F508C mutation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Macek, M. Jr.; Ladanyi, L.; Buerger, J.

1992-11-01

Kobayashi et al. (1990) have described missense variations in the conserved region of exon 10 of the cystic fibrosis (CF) transmembrane conductance regulator gene. In their paper, two [Delta]F508/F508C compound heterozygous individuals were reported. Clinical and epithelial physiological studies in both cases were normal, suggesting that the substitution of cysteine for phenylalanine at position 508, the F508C mutation, is benign. However, Kerem et al. reported a patient with this substitution who had typical symptoms of CF. In routine [Delta]F508 mutation screening by visualization of the 3-bp deletion on a 12% polyacrylamide gel the authors detected an abnormal heteroduplex in themore » father of a CF patient of German origin. Subsequent direct sequencing of the PCR product confirmed that this clinically normal father is a compound heterozygote for the [Delta]F508/F508C mutations. This heteroduplex is slightly different from the usual heteroduplex in [Delta]F508/F508C heteroduplex was not published, it is likely that similar cases can be overseen during the widely performed [Delta]F508 mutation screening by PAGE. Detection of more cases, such as the one presented here, together with careful, standardized clinical examination of the proband, would be valuable to verify the nature of this mutation. 4 refs., 1 fig.« less

Characteristic of retained austenite decomposition during tempering and its effect on impact toughness in SA508 Gr.3 steel

NASA Astrophysics Data System (ADS)

Yan, Guanghua; Han, Lizhan; Li, Chuanwei; Luo, Xiaomeng; Gu, Jianfeng

2017-01-01

Retained austenite(RA) usually presents in the quenched Nuclear Pressure-Vessel SA508 Gr.3 steel. In the present work, the characteristic of RA decomposition and its effect on the impact toughness were investigated by microstructure observation, dilatometric experiments and Charpy impact tests. The results show that the RA transformed into martensite and bainite during tempering at 230 °C and 400 °C respectively, while mixture of long rod carbides and ferrite formed at 650 °C. The long rod carbides formed from RA decomposition decrease the critical cleavage stress for initiation of micro-cracks, and deteriorate the impact toughness of the steel. Pre-tempering at a low temperature such as 230 °C or 400 °C leading to the decomposition of RA into martensite or baintie can eliminate the deterioration of the toughness caused by direct decomposition into long rod carbides. The absorbed energy indicate that pre-tempering at 400 °C can drive dramatically improvement in the toughness of the steel.

Proinflammatory effect of sodium 4-phenylbutyrate in deltaF508-cystic fibrosis transmembrane conductance regulator lung epithelial cells: involvement of extracellular signal-regulated protein kinase 1/2 and c-Jun-NH2-terminal kinase signaling.

PubMed

Roque, Telma; Boncoeur, Emilie; Saint-Criq, Vinciane; Bonvin, Elise; Clement, Annick; Tabary, Olivier; Jacquot, Jacky

2008-09-01

Sodium 4-phenylbutyrate (4-PBA) has attracted a great deal of attention in cystic fibrosis (CF) pathology due to its capacity to traffic DeltaF508-cystic fibrosis transmembrane conductance regulator (CFTR) to the cell membrane and restore CFTR chloride function at the plasma membrane of CF lung cells in vitro and in vivo. Using two different DeltaF508-CFTR lung epithelial cell lines (CFBE41o- and IB3-1 cells, characterized with DeltaF508-homozygous and heterozygous genotype, respectively) in vitro, 4-PBA induced an increase of proinflammatory cytokine interleukin (IL)-8 production in a concentration-dependent manner. This 4-PBA-induced IL-8 production was associated with a strong reduction of proteasome and nuclear factor-kappaB transcriptional activities in the two DeltaF508-CFTR lung cells either in a resting state or after tumor necrosis factor-alpha stimulation. In contrast, a strong increase of activator protein-1 transcriptional activity was observed. The inhibition of extracellular signal-regulated protein kinase 1/2 (ERK1/2) by 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene (U0126) and 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one (PD98059) and c-Jun-NH(2)-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) by anthra[1,9-cd] pyrazol-6 (2H)-one (SP600125), respectively, was associated with a reduction (2-3.5-fold) of IL-8 production in both DeltaF508-CFTR lung cell lines treated with 4-PBA. No significant change of IL-8 production was observed after an inhibition of p38 MAPK with 4-[4-(4-fluorophenyl)-5-(4-pyridinyl)-1H-imidazol-2-yl] phenol (SB202190). Therefore, we suggest that inhibition of both ERK1/2 and JNK signaling may be a means to strongly reduce 4-PBA-induced IL-8 production in combination with 4-PBA treatment to restore CFTR Cl(-) channel function in lung epithelial cells of patients with CF.

Calculation of {alpha}/{gamma} equilibria in SA508 grade 3 steels for intercritical heat treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, B.J.; Kim, H.D.; Hong, J.H.

1998-05-01

An attempt has been made to suggest an optimum temperature for intercritical heat treatment of an SA508 grade 3 steel for nuclear pressure vessels, based on thermodynamic calculation of the {alpha}/{gamma} phase equilibria. A thermodynamic database constructed for the Fe-Mn-Ni-Mo-Cr-Si-V-Al-C-N ten-component system and an empirical criterion that the amount of reformed austenite should be around 40 pct were used for thermodynamic calculation and derivation of the optimum heat-treatment temperature, respectively. The calculated optimum temperature, 720 C, was in good agreement with an experimentally determined temperature of 725 C obtained through an independent experimental investigation of the same steel. The agreementmore » between the calculated and measured fraction of reformed austenite during the intercritical heat treatment was also confirmed. Based on the agreement between calculation and experiment, it could be concluded that thermodynamic calculations can be successfully applied to the materials and/or process design as an additive tool to the already established technology, and that the currently constructed thermodynamic database for steel systems shows an accuracy that makes such applications possible.« less

Effect of neutron irradiation on magnetic properties in the low alloy Ni-Mo steel SA508-3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, D.G.; Kim, C.G.; Kim, H.C.

1997-04-01

The B-H hysteresis loop and Barkhausen noise have been measured in the neutron irradiated SA508 steel of 45 {mu}m thickness. The coercive force of B-H loop showed a slow change up to a neutron dose of 10{sup 14} n/cm{sup 2} and increased by 15.4{percent} for a 10{sup 16} n/cm{sup 2} dose sample compared with that of the unirradiated one, related to the domain wall motion hindered by the increased defects. However, the amplitude of Barkhausen noise reflecting the wall motion decreased slowly up to 10{sup 14} n/cm{sup 2} irradiation, followed by a rapid decrease of 37.5{percent} at 10{sup 16} n/cm{supmore » 2}. {copyright} {ital 1997 American Institute of Physics.}« less

J{sub IC} evaluation of the smooth and the side-grooved CT specimen in the reactor pressure vessel steel (SA508-3)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oh, S.W.; Lim, M.B.; Kim, T.H.

1993-12-31

The elastic-plastic fracture toughness J{sub IC} of SA508-3 forging steel was investigated by using CT-type specimens. The thickness of the smooth specimen is B{sub 0} = 25.4 mm and the side groove specimen is B{sub N} = 20.4 mm and the side groove deep is S{center_dot}G = [(B{sub 0} {minus} B{sub N})/B{sub 0}] {times} 100 = 19.7% and the groove angle is 90{degree}. The J{sub IC} tests estimated according to the method proposed in the ASTM E813-81 and JSME S001-81. The side-grooved specimen have the advantage of J{sub IC} estimation, it is much easier to determine the onset of ductilemore » tearing by the R-curve method and it improved accuracy and scatter of the toughness values thus determined, provided all the size-requirements for the specimen prescribed in the JSME method were satisfied. But it is difficult to find by the ASTM method. The critical stretched zone width (SZW{sub C}) of the side-grooved specimens found to be smaller than that previously determined for the standard CT specimens without side-grooves. This was attributed to higher triaxiality produced by the side-grooves. The stretched zone width method gave slightly larger J{sub IC} values than those by the R-curve method for SA508-3, as has been observed for the standard specimen without side-groove.« less

Modeling flow stress constitutive behavior of SA508-3 steel for nuclear reactor pressure vessels

NASA Astrophysics Data System (ADS)

Sun, Mingyue; Hao, Luhan; Li, Shijian; Li, Dianzhong; Li, Yiyi

2011-11-01

Based on the measured stress-strain curves under different temperatures and strain rates, a series of flow stress constitutive equations for SA508-3 steel were firstly established through the classical theories on work hardening and softening. The comparison between the experimental and modeling results has confirmed that the established constitutive equations can correctly describe the mechanical responses and microstructural evolutions of the steel under various hot deformation conditions. We further represented a successful industrial application of this model to simulate a forging process for a large conical shell used in a nuclear steam generator, which evidences its practical and promising perspective of our model with an aim of widely promoting the hot plasticity processing for heavy nuclear components of fission reactors.

Influence of the Strength Mismatch of a Narrow Gap Welded Joint of SA508 on the Plastic η Factor

NASA Astrophysics Data System (ADS)

Koo, J. M.; Huh, Y.; Seok, C. S.

2012-11-01

In this article, the influence of the strength mismatch of a narrow gap welded joint of SA508 on the η factor was evaluated. The η factor is the principal parameter that determines the plastic portion of the J-integral. The specimens for tensile and hardness tests were collected from piping with narrow gap welding and the stress-strain curve and hardness were obtained from those. From these results, the Ramberg-Osgood (R-O) constant was obtained. Also, the finite element analysis was performed with variations in the strength mismatch and the weld width. The η factor equation considering the strength mismatch and the weld width of a narrow gap welded joint was suggested.

48 CFR 1245.508-2 - Reporting results of inventories.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Reporting results of inventories. 1245.508-2 Section 1245.508-2 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION... 1245.508-2 Reporting results of inventories. The inventory report shall also include the following: (a...

48 CFR 1245.508-2 - Reporting results of inventories.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Reporting results of inventories. 1245.508-2 Section 1245.508-2 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION... 1245.508-2 Reporting results of inventories. The inventory report shall also include the following: (a...

48 CFR 1245.508-2 - Reporting results of inventories.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Reporting results of inventories. 1245.508-2 Section 1245.508-2 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION... 1245.508-2 Reporting results of inventories. The inventory report shall also include the following: (a...

48 CFR 1245.508-2 - Reporting results of inventories.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Reporting results of inventories. 1245.508-2 Section 1245.508-2 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION... 1245.508-2 Reporting results of inventories. The inventory report shall also include the following: (a...

48 CFR 1245.508-2 - Reporting results of inventories.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Reporting results of inventories. 1245.508-2 Section 1245.508-2 Federal Acquisition Regulations System DEPARTMENT OF TRANSPORTATION... 1245.508-2 Reporting results of inventories. The inventory report shall also include the following: (a...

Computational studies of H5N1 hemagglutinin binding with SA-{alpha}-2, 3-Gal and SA-{alpha}-2, 6-Gal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li Minyong; Wang Binghe

2006-09-01

For influenza H5N1 hemagglutinin, a switch from SA-{alpha}-2, 3-Gal to SA-{alpha}-2, 6-Gal receptor specificity is a critical step leading to the conversion from avian-to-human to human-to-human infection. Therefore, the understanding of the binding modes of SA-{alpha}-2, 3-Gal and SA-{alpha}-2, 6-Gal to H5N1 hemagglutinin will be very important for the examination of possible mutations needed for going from an avian to a human flu virus. Based on the available H5N1 hemagglutinin crystal structure, the binding profiles between H5N1 hemagglutinin and two saccharide ligands, SA-{alpha}-2, 3-Gal and SA-{alpha}-2, 6-Gal, were investigated by ab initio quantum mechanics, molecular docking, molecular mechanics, and molecularmore » dynamics simulations. It was found that SA-{alpha}-2, 3-Gal has strong multiple hydrophobic and hydrogen bond interactions in its trans conformation with H5N1 hemagglutinin, whereas the SA-{alpha}-2, 6-Gal only shows weak interactions in a different conformation (cis type)« less

48 CFR 3045.508-2 - Reporting results of inventories.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Reporting results of inventories. 3045.508-2 Section 3045.508-2 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND... Management of Government Property in the Possession of Contractors 3045.508-2 Reporting results of...

48 CFR 3045.508-2 - Reporting results of inventories.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Reporting results of inventories. 3045.508-2 Section 3045.508-2 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND... Management of Government Property in the Possession of Contractors 3045.508-2 Reporting results of...

32 CFR 508.1 - Utilization of Army bands.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 3 2011-07-01 2009-07-01 true Utilization of Army bands. 508.1 Section 508.1 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY AID OF CIVIL AUTHORITIES AND... Secretary of Defense. The authority to determine whether the use of an Army band at a public gathering is...

Renal proximal tubule function is preserved in Cftrtm2camΔF508 cystic fibrosis mice

PubMed Central

Kibble, J D; Balloch, K J D; Neal, A M; Hill, C; White, S; Robson, L; Green, R; Taylor, C J

2001-01-01

Changes in proximal tubule function have been reported in cystic fibrosis patients. The aim of this study was to investigate proximal tubule function in the Cftrtm2camΔF508 cystic fibrosis (CF) mouse model. A range of techniques were used including renal clearance studies, in situ microperfusion, RT-PCR and whole-cell patch clamping. Renal Na+ clearance was similar in wild-type (1.4 ± 0.3 μl min−1, number of animals, N= 12) and CF mice (1.6 ± 0.4 μl min−1, N= 7) under control conditions. Acute extracellular volume expansion resulted in significant natriuresis in wild-type (7.0 ± 0.8 μl min−1, N= 8) and CF mice (9.3 ± 1.4 μl min−1, N= 9); no difference between genotypes was observed. In situ microperfusion revealed that fluid absorptive rate (Jv) was similar under control conditions between wild-type (2.2 ± 0.4 nl mm−1 min−1, n= 10) and CF mice (1.9 ± 0.3 nl mm−1 min−1, n= 11). Addition of a forskolin-dibutyryl cAMP (db-cAMP) cocktail to the perfusate caused no significant change in Jv in either wild-type (2.6 ± 0.7 nl mm−1 min−1, n= 10) or Cftrtm2camΔF508 mice (2.0 ± 0.5 nl mm−1 min−1, n= 10). CFTR expression was confirmed in samples of outer cortex using RT-PCR. However, no evidence for functional CFTR was obtained when outer cortical cells were stimulated with protein kinase A or forskolin-db-cAMP using whole-cell patch clamping. In conclusion, no functional deficit in proximal tubule function was found in Cftrtm2camΔF508 mice. This may be a consequence of a lack of whole-cell cAMP-dependent Cl− conductance in mouse proximal tubule cells. PMID:11306663

A chemical corrector modifies the channel function of F508del-CFTR.

PubMed

Kim Chiaw, Patrick; Wellhauser, Leigh; Huan, Ling Jun; Ramjeesingh, Mohabir; Bear, Christine E

2010-09-01

The deletion of Phe-508 (F508del) constitutes the most prevalent cystic fibrosis-causing mutation. This mutation leads to cystic fibrosis transmembrane conductance regulator (CFTR) misfolding and retention in the endoplasmic reticulum and altered channel activity in mammalian cells. This folding defect can however be partially overcome by growing cells expressing this mutant protein at low (27 degrees C) temperature. Chemical "correctors" have been identified that are also effective in rescuing the biosynthetic defect in F508del-CFTR, thereby permitting its functional expression at the cell surface. The mechanism of action of chemical correctors remains unclear, but it has been suggested that certain correctors [including 4-cyclohexyloxy-2-(1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl)-quinazoline (VRT-325)] may act to promote trafficking by interacting directly with the mutant protein. To test this hypothesis, we assessed the effect of VRT-325 addition on the channel activity of F508del-CFTR after its surface expression had been "rescued" by low temperature. It is noteworthy that short-term pretreatment with VRT-325 [but not with an inactive analog, 4-hydroxy-2-(1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl)-quinazoline (VRT-186)], caused a modest but significant inhibition of cAMP-mediated halide flux. Furthermore, VRT-325 decreased the apparent ATP affinity of purified and reconstituted F508del-CFTR in our ATPase activity assay, an effect that may account for the decrease in channel activity by temperature-rescued F508del-CFTR. These findings suggest that biosynthetic rescue mediated by VRT-325 may be conferred (at least in part) by direct modification of the structure of the mutant protein, leading to a decrease in its ATP-dependent conformational dynamics. Therefore, the challenge for therapy discovery will be the design of small molecules that bind to promote biosynthetic maturation of the major mutant without compromising its activity in

Outcomes following attempted en bloc resection of cervical chordomas in the C-1 and C-2 region versus the subaxial region: a multiinstitutional experience.

PubMed

Molina, Camilo A; Ames, Christopher P; Chou, Dean; Rhines, Laurence D; Hsieh, Patrick C; Zadnik, Patricia L; Wolinsky, Jean-Paul; Gokaslan, Ziya L; Sciubba, Daniel M

2014-09-01

Chordomas involving the mobile spine are ideally managed via en bloc resection with reconstruction to optimize local control and possibly offer cure. In the cervical spine, local anatomy poses unique challenges, limiting the feasibility of aggressive resection. The authors present a multi-institutional series of 16 cases of cervical chordomas removed en bloc. Particular attention was paid to clinical outcome, complications, and recurrence. In addition, outcomes were assessed according to position of tumor at the C1-2 level versus the subaxial (SA) spine (C3-7). The authors reviewed cases involving patients who underwent en bloc resection of cervical chordoma at 4 large spine centers. Patients were included if the lesion epicenter involved the C-1 to C-7 vertebral bodies. Demographic data and details of surgery, follow-up course, exposure to adjuvant therapy, and complications were obtained. Outcome was correlated with presence of tumor in C1-2 versus subaxial spine via a Student t-test. Sixteen patients were identified (mean age at presentation 55 ± 14 years). Seven cases (44%) cases involved C1-2, and 16 involved the subaxial spine. Median survival did not differ significantly different between the C1-2 (72 months) and SA (60 months) groups (p = 0.65). A combined (staged anteroposterior) approach was used in 81% of the cases. Use of the combined approach was significantly more common in treatment of subaxial than C1-2 tumors (100% vs 57%, p = 0.04). En bloc resection was attempted via an anterior approach in 6% of cases (C1-2: 14.3%; SA: 0%; p = 0.17) and a posterior approach in 13% of cases (C1-2: 29%; SA: 0%; p = 0.09). The most commonly reported margin classification was marginal (56% of cases), followed by violated (25%) and wide (19%). En bloc excision of subaxial tumors was significantly more likely to result in marginal margins than excision of C1-2 tumors (C1-2: 29%; SA: 78%; p = 0.03). C1-2 tumors were associated with significantly higher rates of

75 FR 70104 - Airworthiness Directives; Eurocopter France (ECF) Model SA330F, G, and J; and AS332C, L, L1, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-17

... Airworthiness Directives; Eurocopter France (ECF) Model SA330F, G, and J; and AS332C, L, L1, and L2 Helicopters... (ASB) No. 52.13 for the SA330F, G, and J helicopters, and 52.00.38 for the AS332C, C1, L, L1, and L2... authority citation for part 39 continues to read as follows: Authority: 49 U.S.C. 106(g), 40113, 44701. Sec...

Enhanced CO2 sequestration by a novel microalga: Scenedesmus obliquus SA1 isolated from bio-diversity hotspot region of Assam, India.

PubMed

Basu, Samarpita; Roy, Abhijit Sarma; Mohanty, Kaustubha; Ghoshal, Aloke K

2013-09-01

The present study aimed to isolate a high CO2 and temperature tolerant microalga capable of sequestering CO2 from flue gas. Microalga strain SA1 was isolated from a freshwater body of Assam and identified as Scenedesmus obliquus (KC733762). At 13.8±1.5% CO2 and 25 °C, maximum biomass (4.975±0.003 g L(-1)) and maximum CO2 fixation rate (252.883±0.361 mg L(-1) d(-1)) were obtained which were higher than most of the relevant studies. At elevated temperature (40 °C) and 13.8±1.5% CO2 maximum biomass (0.883±0.001 g L(-1)) was obtained. The carbohydrate, protein, lipid, and chlorophyll content of the CO2 treated SA1 were 30.87±0.64%, 9.48±1.65%, 33.04±0.46% and 6.03±0.19% respectively, which were higher than previous reports. Thus, SA1 could prove to be a potential candidate for CO2 sequestration from flue gas as well as for the production of value added substances. Copyright © 2013 Elsevier Ltd. All rights reserved.

A synonymous codon change alters the drug sensitivity of ΔF508 cystic fibrosis transmembrane conductance regulator

PubMed Central

Bali, Vedrana; Lazrak, Ahmed; Guroji, Purushotham; Fu, Lianwu; Matalon, Sadis; Bebok, Zsuzsanna

2016-01-01

Synonymous mutations, such as I507-ATC→ATT, in deletion of Phe508 in cystic fibrosis transmembrane conductance regulator (ΔF508 CFTR), the most frequent disease-associated mutant of CFTR, may affect protein biogenesis, structure, and function and contribute to an altered disease phenotype. Small-molecule drugs are being developed to correct ΔF508 CFTR. To understand correction mechanisms and the consequences of synonymous mutations, we analyzed the effect of mechanistically distinct correctors, corrector 4a (C4) and lumacaftor (VX-809), on I507-ATT and I507-ATC ΔF508 CFTR biogenesis and function. C4 stabilized I507-ATT ΔF508 CFTR band B, but without considerable biochemical and functional correction. VX-809 biochemically corrected ∼10% of both of the variants, leading to stable, forskolin+3-isobutyl-1-methylxanthine (IBMX)-activated whole-cell currents in the presence of the corrector. Omitting VX-809 during whole-cell recordings led to a spontaneous decline of the currents, suggesting posttranslational stabilization by VX-809. Treatment of cells with the C4+VX-809 combination resulted in enhanced rescue and 2-fold higher forskolin+IBMX–activated currents of both I507-ATT and I507-ATC ΔF508 CFTR, compared with VX-809 treatment alone. The lack of an effect of C4 on I507-ATC ΔF508 CFTR, but its additive effect in combination with VX-809, implies that C4 acted on VX-809–modified I507-ATC ΔF508 CFTR. Our results suggest that binding of C4 and VX-809 to ΔF508 CFTR is conformation specific and provide evidence that synonymous mutations can alter the drug sensitivity of proteins.—Bali, V., Lazrak, A., Guroji, P., Fu, L., Matalon, S., Bebok, Z. A synonymous codon change alters the drug sensitivity of ΔF508 cystic fibrosis transmembrane conductance regulator. PMID:26336913

Effects of H content on the tensile properties and fracture behavior of SA508-III steel

NASA Astrophysics Data System (ADS)

Liu, Jia-hua; Wang, Lei; Liu, Yang; Song, Xiu; Luo, Jiong; Yuan, Dan

2015-08-01

SA508-III steel was charged with different hydrogen (H) contents using a high-pressure thermal charging method to study the effects of H content on the tensile properties and evaluate the H embrittlement behavior of the steel. The results indicate that the ultimate tensile strength remains nearly unchanged with the addition of H. In contrast, the yielding strength slightly increases, and the elongation significantly decreases with increasing H content, especially at concentrations exceeding 5.6 × 10-6. On the basis of fractographic analysis, it is clear that the addition of H changes the fracture mode from microvoid coalescence to a mixture of river patterns and dimples. Carbides are strong traps for H; thus, the H atoms easily migrate in the form of Cottrell atmosphere toward the carbides following moving dislocations during tensile deformation. In addition, stress-induced H atoms accumulate at the interface between carbides and the matrix after necking under three-dimensional stress, which weakens the interfacial bonding force. Consequently, when the local H concentration reaches a critical value, microcracks occur at the interface, resulting in fracture.

Chlorpyrifos promotes colorectal adenocarcinoma H508 cell growth through the activation of EGFR/ERK1/2 signaling pathway but not cholinergic pathway.

PubMed

Suriyo, Tawit; Tachachartvanich, Phum; Visitnonthachai, Daranee; Watcharasit, Piyajit; Satayavivad, Jutamaad

2015-12-02

Aside from the effects on neuronal cholinergic system, epidemiological studies suggest an association between chlorpyrifos (CPF) exposure and cancer risk. This in vitro study examined the effects of CPF and its toxic metabolite, chlorpyrifos oxon (CPF-O), on the growth of human colorectal adenocarcinoma H508, colorectal adenocarcinoma HT-29, normal colon epithelial CCD841, liver hepatocellular carcinoma HepG2, and normal liver hepatocyte THLE-3 cells. The results showed that CPF (5-100 μM) concentration-dependently increased viability of H508 and CCD841 cells in serum-free conditions. This increasing trend was not found in HT-29, HepG2 and THLE-3 cells. In contrast, CPF-O (50-100 μM) reduced the viability of all cell lines. Cell cycle analysis showed the induction of cells in the S phase, and EdU incorporation assay revealed the induction of DNA synthesis in CPF-treated H508 cells indicating that CPF promotes cell cycle progression. Despite the observation of acetylcholinesterase activity inhibition and reactive oxygen species (ROS) generation, atropine (a non-selective muscarinic acetylcholine receptor antagonist) and N-acetylcysteine (a potent antioxidant) failed to inhibit the growth-promoting effect of CPF. CPF increased the phosphorylation of epidermal growth factor receptor (EGFR) and its downstream effector, extracellular signal regulated kinase (ERK1/2), in H508 cells. AG-1478 (a specific EGFR tyrosine kinase inhibitor) and U0126 (a specific MEK inhibitor) completely mitigated the growth promoting effect of CPF. Altogether, these results suggest that EGFR/ERK1/2 signaling pathway but not cholinergic pathway involves in CPF-induced colorectal adenocarcinoma H508 cell growth. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Master Curve and Conventional Fracture Toughness of Modified 9Cr-1Mo Steel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ji-Hyun, Yoon; Sung-Ho, Kim; Bong-Sang, Lee

2006-07-01

Modified 9Cr-1Mo steel is a primary candidate material for reactor pressure vessel of Very High Temperature Gas-Cooled Reactor (VHTR) in Korean Nuclear Hydrogen Development and Demonstration (NHDD) program. In this study, T0 reference temperature, J-R fracture resistance and Charpy impact properties were evaluated for commercial Grade 91 steel as preliminary tests for the selection of the RPV material for VHTR. The fracture toughness of the modified 9Cr-1Mo steel was compared with those of SA508-Gr.3. The objective of this study was to obtain pre-irradiation fracture toughness properties of modified 9Cr-1Mo steel as reference data for the radiation effects investigation. The resultsmore » are as follows. Charpy impact properties of the modified 9Cr-1Mo steel were similar to those of SA508-Gr.3. T0 reference temperatures were measured as -67.7 deg C and -72.4 deg C from the tests with standard PCVN (pre-cracked Charpy V-notch) and half sized PCVN specimens respectively, which were similar to results for SA508-Gr.3. The K{sub Jc} values of modified 9Cr-1Mo with test temperatures are successfully expressed with the Master Curve. The J-R fracture resistance of modified 9Cr-1Mo steel at room temperature was almost the same as that of SA508-Gr.3. On the other hand it was a little bit higher at an elevated temperature. (authors)« less

Induction of HSP70 promotes DeltaF508 CFTR trafficking.

PubMed

Choo-Kang, L R; Zeitlin, P L

2001-07-01

The DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) is a temperature-sensitive trafficking mutant that is detected as an immature 160-kDa form (band B) in gel electrophoresis. The goal of this study was to test the hypothesis that HSP70, a member of the 70-kDa heat shock protein family, promotes DeltaF508 CFTR processing to the mature 180-kDa form (band C). Both pharmacological and genetic techniques were used to induce HSP70. IB3-1 cells were treated with sodium 4-phenylbutyrate (4PBA) to promote maturation of DeltaF508 CFTR to band C. A dose-dependent increase in band C and total cellular HSP70 was observed. Under these conditions, HSP70-CFTR complexes were increased and 70-kDa heat shock cognate protein-CFTR complexes were decreased. Increased DeltaF508 CFTR maturation was also seen after transfection with an HSP70 expression plasmid and exposure to glutamine, an inducer of HSP70. With immunofluorescence techniques, the increased appearance of CFTR band C correlated with CFTR distribution beyond the perinuclear regions. These data suggest that induction of HSP70 promotes DeltaF508 CFTR maturation and trafficking.

Enhanced salt stress tolerance of rice plants expressing a vacuolar H+-ATPase subunit c1 (SaVHAc1) gene from the halophyte grass Spartina alterniflora Löisel

USDA-ARS?s Scientific Manuscript database

The physiological role of a vacuolar ATPase subunit c1 (SaVHAc1) from a halophyte grass Spartina alterniflora was studied through its expression in rice. The SaVHAc1– expressing plants showed enhanced tolerance to salt stress than the wild-type plants, mainly through adjustments in early stage and p...

Tezacaftor/Ivacaftor in Subjects with Cystic Fibrosis and F508del/F508del-CFTR or F508del/G551D-CFTR.

PubMed

Donaldson, Scott H; Pilewski, Joseph M; Griese, Matthias; Cooke, Jon; Viswanathan, Lakshmi; Tullis, Elizabeth; Davies, Jane C; Lekstrom-Himes, Julie A; Wang, Linda T

2018-01-15

Tezacaftor (formerly VX-661) is an investigational small molecule that improves processing and trafficking of the cystic fibrosis transmembrane conductance regulator (CFTR) in vitro, and improves CFTR function alone and in combination with ivacaftor. To evaluate the safety and efficacy of tezacaftor monotherapy and of tezacaftor/ivacaftor combination therapy in subjects with cystic fibrosis homozygous for F508del or compound heterozygous for F508del and G551D. This was a randomized, placebo-controlled, double-blind, multicenter, phase 2 study (NCT01531673). Subjects homozygous for F508del received tezacaftor (10 to 150 mg) every day alone or in combination with ivacaftor (150 mg every 12 h) in a dose escalation phase, as well as in a dosage regimen testing phase. Subjects compound heterozygous for F508del and G551D, taking physician-prescribed ivacaftor, received tezacaftor (100 mg every day). Primary endpoints were safety through Day 56 and change in sweat chloride from baseline through Day 28. Secondary endpoints included change in percent predicted FEV 1 (ppFEV 1 ) from baseline through Day 28 and pharmacokinetics. The incidence of adverse events was similar across treatment arms. Tezacaftor (100 mg every day)/ivacaftor (150 mg every 12 h) resulted in a 6.04 mmol/L decrease in sweat chloride and 3.75 percentage point increase in ppFEV 1 in subjects homozygous for F508del, and a 7.02 mmol/L decrease in sweat chloride and 4.60 percentage point increase in ppFEV 1 in subjects compound heterozygous for F508del and G551D from baseline through Day 28 (P < 0.05 for all). These results support continued clinical development of tezacaftor (100 mg every day) in combination with ivacaftor (150 mg every 12 h) in subjects with cystic fibrosis. Clinical trial registered with www.clinicaltrials.gov (NCT01531673).

Creep of A508/533 Pressure Vessel Steel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richard Wright

2014-08-01

ABSTRACT Evaluation of potential Reactor Pressure Vessel (RPV) steels has been carried out as part of the pre-conceptual Very High Temperature Reactor (VHTR) design studies. These design studies have generally focused on American Society of Mechanical Engineers (ASME) Code status of the steels, temperature limits, and allowable stresses. Initially, three candidate materials were identified by this process: conventional light water reactor (LWR) RPV steels A508 and A533, 2¼Cr-1Mo in the annealed condition, and Grade 91 steel. The low strength of 2¼Cr-1Mo at elevated temperature has eliminated this steel from serious consideration as the VHTR RPV candidate material. Discussions with themore » very few vendors that can potentially produce large forgings for nuclear pressure vessels indicate a strong preference for conventional LWR steels. This preference is based in part on extensive experience with forging these steels for nuclear components. It is also based on the inability to cast large ingots of the Grade 91 steel due to segregation during ingot solidification, thus restricting the possible mass of forging components and increasing the amount of welding required for completion of the RPV. Grade 91 steel is also prone to weld cracking and must be post-weld heat treated to ensure adequate high-temperature strength. There are also questions about the ability to produce, and very importantly, verify the through thickness properties of thick sections of Grade 91 material. The availability of large components, ease of fabrication, and nuclear service experience with the A508 and A533 steels strongly favor their use in the RPV for the VHTR. Lowering the gas outlet temperature for the VHTR to 750°C from 950 to 1000°C, proposed in early concept studies, further strengthens the justification for this material selection. This steel is allowed in the ASME Boiler and Pressure Vessel Code for nuclear service up to 371°C (700°F); certain excursions above that

Fracture toughness and the master curve for modified 9Cr-1Mo steel

NASA Astrophysics Data System (ADS)

Yoon, Ji-Hyun; Yoon, Eui-Pak

2006-12-01

Modified 9Cr-1Mo steel is a primary candidate material for the reactor pressure vessel of a Very High Temperature Gas-Cooled Reactor (VHTR) in the Korean Nuclear Hydrogen Development and Demonstration (NHDD) program. In this study, the T0 reference temperature, J-R fracture resistance and Charpy impact properties were evaluated for commercial Grade 91 steel as part of the preliminary testing for a selection of the RPV material for the VHTR. The fracture toughness of the modified 9Cr-1Mo steel was compared with that of SA508-Gr.3. The objective of this study was to obtain the pre-irradiation fracture toughness properties of the modified 9Cr-1Mo steel as reference data for an investigation of radiation effects. Charpy impact properties of the modified 9Cr-1Mo steel were similar to those of SA508-Gr.3. T0 reference temperatures were measured as -67.7 and -72.4°C from the tests with standard PCVN (pre-cracked Charpy V-notch) and half-sized PCVN specimens respectively, which were similar to the results for SA508-Gr.3. The KJc values of the modified 9Cr-1Mo steel with the test temperatures are successfully expressed by the Master Curve. The J-R fracture resistance of the modified 9Cr-1Mo steel at room temperature was nearly identical to that of SA508-Gr.3; in contrast, it was slightly higher at an elevated temperature.

RNA Interference Screen to Identify Kinases That Suppress Rescue of ΔF508-CFTR.

PubMed

Trzcińska-Daneluti, Agata M; Chen, Anthony; Nguyen, Leo; Murchie, Ryan; Jiang, Chong; Moffat, Jason; Pelletier, Lawrence; Rotin, Daniela

2015-06-01

Cystic Fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene encoding the Cystic fibrosis transmembrane conductance regulator (CFTR). ΔF508-CFTR, the most common disease-causing CF mutant, exhibits folding and trafficking defects and is retained in the endoplasmic reticulum, where it is targeted for proteasomal degradation. To identify signaling pathways involved in ΔF508-CFTR rescue, we screened a library of endoribonuclease-prepared short interfering RNAs (esiRNAs) that target ∼750 different kinases and associated signaling proteins. We identified 20 novel suppressors of ΔF508-CFTR maturation, including the FGFR1. These were subsequently validated by measuring channel activity by the YFP halide-sensitive assay following shRNA-mediated knockdown, immunoblotting for the mature (band C) ΔF508-CFTR and measuring the amount of surface ΔF508-CFTR by ELISA. The role of FGFR signaling on ΔF508-CFTR trafficking was further elucidated by knocking down FGFRs and their downstream signaling proteins: Erk1/2, Akt, PLCγ-1, and FRS2. Interestingly, inhibition of FGFR1 with SU5402 administered to intestinal organoids (mini-guts) generated from the ileum of ΔF508-CFTR homozygous mice resulted in a robust ΔF508-CFTR rescue. Moreover, combination of SU5402 and VX-809 treatments in cells led to an additive enhancement of ΔF508-CFTR rescue, suggesting these compounds operate by different mechanisms. Chaperone array analysis on human bronchial epithelial cells harvested from ΔF508/ΔF508-CFTR transplant patients treated with SU5402 identified altered expression of several chaperones, an effect validated by their overexpression or knockdown experiments. We propose that FGFR signaling regulates specific chaperones that control ΔF508-CFTR maturation, and suggest that FGFRs may serve as important targets for therapeutic intervention for the treatment of CF. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

High occupancy of sigma-1 receptors in the human brain after single oral administration of fluvoxamine: a positron emission tomography study using [11C]SA4503.

PubMed

Ishikawa, Masatomo; Ishiwata, Kiichi; Ishii, Kenji; Kimura, Yuichi; Sakata, Muneyuki; Naganawa, Mika; Oda, Keiichi; Miyatake, Ryousuke; Fujisaki, Mihisa; Shimizu, Eiji; Shirayama, Yukihiko; Iyo, Masaomi; Hashimoto, Kenji

2007-10-15

Sigma-1 receptors might be implicated in the pathophysiology of psychiatric diseases, as well as in the mechanisms of action of some selective serotonin reuptake inhibitors (SSRIs). Among the several SSRIs, fluvoxamine has the highest affinity for sigma-1 receptors (Ki = 36 nM), whereas paroxetine shows low affinity (Ki = 1893 nM). The present study was undertaken to examine whether fluvoxamine binds to sigma-1 receptors in living human brain. A dynamic positron emission tomography (PET) data acquisition using the selective sigma-1 receptor ligand [(11)C]SA4503 was performed with arterial blood sampling to evaluate quantitatively the binding of [(11)C]SA4503 to sigma-1 receptors in 15 healthy male volunteers. Each subject had two PET scans before and after randomly receiving a single dose of either fluvoxamine (50, 100, 150, or 200 mg) or paroxetine (20 mg). The binding potential of [(11)C]SA4503 in 9 regions of the brain was calculated by a 2-tissue 3-compartment model. In addition, we examined the effects of functional polymorphisms of the sigma-1 receptor (SIGMAR1) gene on the binding potential of [(11)C]SA4503. Fluvoxamine bound to sigma-1 receptors in all brain regions in a dose-dependent manner, whereas paroxetine did not bind to sigma-1 receptors. However, there was no association between the SIGMAR1 gene polymorphism GC-241-240TT and binding potential. The study demonstrated that fluvoxamine bound to sigma-1 receptors in living human brain at therapeutic doses. These findings suggest that sigma-1 receptors may play an important role in the mechanism of action of fluvoxamine.

42 CFR 403.508 - Limitations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 2 2014-10-01 2014-10-01 false Limitations. 403.508 Section 403.508 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS SPECIAL PROGRAMS AND PROJECTS Beneficiary Counseling and Assistance Grants § 403.508 Limitations. (a) Use...

42 CFR 403.508 - Limitations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 2 2013-10-01 2013-10-01 false Limitations. 403.508 Section 403.508 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS SPECIAL PROGRAMS AND PROJECTS Beneficiary Counseling and Assistance Grants § 403.508 Limitations. (a) Use...

42 CFR 403.508 - Limitations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Limitations. 403.508 Section 403.508 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS SPECIAL PROGRAMS AND PROJECTS Beneficiary Counseling and Assistance Grants § 403.508 Limitations. (a) Use...

42 CFR 403.508 - Limitations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 2 2012-10-01 2012-10-01 false Limitations. 403.508 Section 403.508 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS SPECIAL PROGRAMS AND PROJECTS Beneficiary Counseling and Assistance Grants § 403.508 Limitations. (a) Use...

42 CFR 403.508 - Limitations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false Limitations. 403.508 Section 403.508 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS SPECIAL PROGRAMS AND PROJECTS Beneficiary Counseling and Assistance Grants § 403.508 Limitations. (a) Use...

45 CFR 162.508 - Enumeration System.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Enumeration System. 162.508 Section 162.508 Public... ADMINISTRATIVE REQUIREMENTS Standard Unique Health Identifier for Health Plans § 162.508 Enumeration System. The Enumeration System must do all of the following: (a) Assign a single, unique— (1) HPID to a health plan...

45 CFR 162.508 - Enumeration System.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Enumeration System. 162.508 Section 162.508 Public... ADMINISTRATIVE REQUIREMENTS Standard Unique Health Identifier for Health Plans § 162.508 Enumeration System. The Enumeration System must do all of the following: (a) Assign a single, unique— (1) HPID to a health plan...

45 CFR 162.508 - Enumeration System.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Enumeration System. 162.508 Section 162.508 Public... ADMINISTRATIVE REQUIREMENTS Standard Unique Health Identifier for Health Plans § 162.508 Enumeration System. The Enumeration System must do all of the following: (a) Assign a single, unique— (1) HPID to a health plan...

Substrate-Independent Epitaxial Growth of the Metal-Organic Framework MOF-508a.

PubMed

Wilson, M; Barrientos-Palomo, S N; Stevens, P C; Mitchell, N L; Oswald, G; Nagaraja, C M; Badyal, J P S

2018-01-31

Plasmachemical deposition is a substrate-independent method for the conformal surface functionalization of solid substrates. Structurally well-defined pulsed plasma deposited poly(1-allylimidazole) layers provide surface imidazole linker groups for the directed liquid-phase epitaxial (layer-by-layer) growth of metal-organic frameworks (MOFs) at room temperature. For the case of microporous [Zn (benzene-1,4-dicarboxylate)-(4,4'-bipyridine) 0.5 ] (MOF-508), the MOF-508a polymorph containing two interpenetrating crystal lattice frameworks undergoes orientated Volmer-Weber growth and displays CO 2 gas capture behavior at atmospheric concentrations in proportion to the number of epitaxially grown MOF-508 layers.

Increased blood glycohemoglobin A1c levels lead to overestimation of arterial oxygen saturation by pulse oximetry in patients with type 2 diabetes

PubMed Central

2012-01-01

Background Non-enzymatic glycation increases hemoglobin-oxygen affinity and reduces oxygen delivery to tissues by altering the structure and function of hemoglobin. Objectives We investigated whether an elevated blood concentration of glycosylated hemoglobin (HbA1c) could induce falsely high pulse oximeter oxygen saturation (SpO2) in type 2 diabetic patients during mechanical ventilation or oxygen therapy. Methods Arterial oxygen saturation (SaO2) and partial pressure of oxygen (PO2) were determined with simultaneous monitoring of SpO2 in 261 type 2 diabetic patients during ventilation or oxygen inhalation. Results Blood concentration of HbA1c was >7% in 114 patients and ≤ 7% in 147 patients. Both SaO2 (96.2 ± 2.9%, 95% confidence interval [CI] 95.7-96.7% vs. 95.1 ± 2.8%, 95% CI 94.7-95.6%) and SpO2 (98.0 ± 2.6%, 95% CI 97.6-98.5% vs. 95.3 ± 2.8%, 95% CI 94.9-95.8%) were significantly higher in patients with HbA1c >7% than in those with HbA1c ≤ 7% (Data are mean ± SD, all p < 0.01), but PO2 did not significantly differ between the two groups. Bland-Altman analysis demonstrated a significant bias between SpO2 and SaO2 (1.83 ±0.55%, 95% CI 1.73% -1.94%) and limits of agreement (0.76% and 2.92%) in patients with HbA1c >7%. The differences between SpO2 and SaO2 correlated closely with blood HbA1c levels (Pearson’s r = 0.307, p < 0.01). Conclusions Elevated blood HbA1c levels lead to an overestimation of SaO2 by SpO2, suggesting that arterial blood gas analysis may be needed for type 2 diabetic patients with poor glycemic control during the treatment of hypoxemia. PMID:22985301

Increased blood glycohemoglobin A1c levels lead to overestimation of arterial oxygen saturation by pulse oximetry in patients with type 2 diabetes.

PubMed

Pu, Li Jin; Shen, Ying; Lu, Lin; Zhang, Rui Yan; Zhang, Qi; Shen, Wei Feng

2012-09-17

Non-enzymatic glycation increases hemoglobin-oxygen affinity and reduces oxygen delivery to tissues by altering the structure and function of hemoglobin. We investigated whether an elevated blood concentration of glycosylated hemoglobin (HbA1c) could induce falsely high pulse oximeter oxygen saturation (SpO2) in type 2 diabetic patients during mechanical ventilation or oxygen therapy. Arterial oxygen saturation (SaO2) and partial pressure of oxygen (PO2) were determined with simultaneous monitoring of SpO2 in 261 type 2 diabetic patients during ventilation or oxygen inhalation. Blood concentration of HbA1c was >7% in 114 patients and ≤ 7% in 147 patients. Both SaO2 (96.2 ± 2.9%, 95% confidence interval [CI] 95.7-96.7% vs. 95.1 ± 2.8%, 95% CI 94.7-95.6%) and SpO2 (98.0 ± 2.6%, 95% CI 97.6-98.5% vs. 95.3 ± 2.8%, 95% CI 94.9-95.8%) were significantly higher in patients with HbA1c >7% than in those with HbA1c ≤ 7% (Data are mean ± SD, all p < 0.01), but PO2 did not significantly differ between the two groups. Bland-Altman analysis demonstrated a significant bias between SpO2 and SaO2 (1.83 ±0.55%, 95% CI 1.73% -1.94%) and limits of agreement (0.76% and 2.92%) in patients with HbA1c >7%. The differences between SpO2 and SaO2 correlated closely with blood HbA1c levels (Pearson's r = 0.307, p < 0.01). Elevated blood HbA1c levels lead to an overestimation of SaO2 by SpO2, suggesting that arterial blood gas analysis may be needed for type 2 diabetic patients with poor glycemic control during the treatment of hypoxemia.

32 CFR 508.1 - Utilization of Army bands.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PUBLIC RELATIONS COMPETITION WITH CIVILIAN BANDS § 508.1 Utilization of Army bands. (a) General... Secretary of Defense. The authority to determine whether the use of an Army band at a public gathering is... Forces, veterans, and patriotic organizations. (3) At public rallies and parades intended to stimulate...

45 CFR 50.8 - Compliance.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Compliance. 50.8 Section 50.8 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION U.S. EXCHANGE VISITOR PROGRAM-REQUEST FOR WAIVER OF THE TWO-YEAR FOREIGN RESIDENCE REQUIREMENT § 50.8 Compliance. If an alien physician acquires H...

45 CFR 50.8 - Compliance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Compliance. 50.8 Section 50.8 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION U.S. EXCHANGE VISITOR PROGRAM-REQUEST FOR WAIVER OF THE TWO-YEAR FOREIGN RESIDENCE REQUIREMENT § 50.8 Compliance. If an alien physician acquires H...

Improving the Th1 cellular efficacy of the lead Yersinia pestis rF1-V subunit vaccine using SA-4-1BBL as a novel adjuvant.

PubMed

Dinc, Gunes; Pennington, Jarrod M; Yolcu, Esma S; Lawrenz, Matthew B; Shirwan, Haval

2014-09-03

The lead candidate plague subunit vaccine is the recombinant fusion protein rF1-V adjuvanted with alum. While alum generates Th2 regulated robust humoral responses, immune protection against Yersinia pestis has been shown to also involve Th1 driven cellular responses. Therefore, the rF1-V-based subunit vaccine may benefit from an adjuvant system that generates a mixed Th1 and humoral immune response. We herein assessed the efficacy of a novel SA-4-1BBL costimulatory molecule as a Th1 adjuvant to improve cellular responses generated by the rF1-V vaccine. SA-4-1BBL as a single adjuvant had better efficacy than alum in generating CD4(+) and CD8(+) T cells producing TNFα and IFNγ, signature cytokines for Th1 responses. The combination of SA-4-1BBL with alum further increased this Th1 response as compared with the individual adjuvants. Analysis of the humoral response revealed that SA-4-1BBL as a single adjuvant did not generate a significant Ab response against rF1-V, and SA-4-1BBL in combination with alum did not improve Ab titers. However, the combined adjuvants significantly increased the ratio of Th1 regulated IgG2c in C57BL/6 mice to the Th2 regulated IgG1. Finally, a single vaccination with rF1-V adjuvanted with SA-4-1BBL+alum had better protective efficacy than vaccines containing individual adjuvants. Taken together, these results demonstrate that SA-4-1BBL improves the protective efficacy of the alum adjuvanted lead rF1-V subunit vaccine by generating a more balanced Th1 cellular and humoral immune response. As such, this adjuvant platform may prove efficacious not only for the rF1-V vaccine but also against other infections that require both cellular and humoral immune responses for protection. Copyright © 2014 Elsevier Ltd. All rights reserved.

47 CFR 54.508 - Technology plans.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Technology plans. 54.508 Section 54.508... SERVICE Universal Service Support for Schools and Libraries § 54.508 Technology plans. (a) Contents. The technology plans referred to in this subpart must include the following five elements: (1) A clear statement...

Mechanism-based corrector combination restores ΔF508-CFTR folding and function

PubMed Central

Okiyoneda, Tsukasa; Veit, Guido; Dekkers, Johanna F.; Bagdany, Miklos; Soya, Naoto; Xu, Haijin; Roldan, Ariel; Verkman, Alan S.; Kurth, Mark; Simon, Agnes; Hegedus, Tamas; Beekman, Jeffrey M.; Lukacs, Gergely L.

2013-01-01

The most common cystic fibrosis (CF) mutation, ΔF508 in the nucleotide binding domain-1 (NBD1), impairs CFTR coupled-domain folding, plasma membrane (PM) expression, function and stability. VX-809, a promising investigational corrector of ΔF508-CFTR misprocessing, has limited clinical benefit and incompletely understood mechanism, hampering drug development. Based on the effect of second site suppressor mutations, robust ΔF508-CFTR correction likely requires stabilization of NBD1 and the membrane spanning domains (MSDs)-NBD1 interface, both established primary conformational defects. Here, we elucidated the molecular targets of available correctors; class-I stabilizes the NBD1-MSD1/2 interface, class-II targets NBD2, and only chemical chaperones, surrogates of class-III correctors, stabilize the human ΔF508-NBD1. While VX-809 can correct missense mutations primarily destabilizing the NBD1-MSD1/2 interface, functional PM expression of ΔF508-CFTR also requires compounds that counteract the NBD1 and NBD2 stability defects in CF bronchial epithelial cells and intestinal organoids. Thus, structure-guided corrector combination represents an effective approach for CF therapy. PMID:23666117

A mobile diabetes management and educational system for type-2 diabetics in Saudi Arabia (SAED).

PubMed

Alotaibi, Mohammed M; Istepanian, Robert; Philip, Nada

2016-01-01

Diabetes is a chronic disease, with high prevalence across many nations, which is characterized by elevated level of blood glucose and risk of acute and chronic complication. The Kingdom of Saudi Arabia (KSA) has one of the highest levels of diabetes prevalence globally. It is well-known that the treatment of diabetes is complex process and requires both lifestyle change and clear pharmacologic treatment plan. To avoid the complication from diabetes, the effective behavioural change and extensive education and self-management is one of the key approaches to alleviate such complications. However, this process is lengthy and expensive. The recent studies on the user of smart phone technologies for diabetes self-management have proven to be an effective tool in controlling hemoglobin (HbA1c) levels especially in type-2 diabetic (T2D) patients. However, to date no reported study addressed the effectiveness of this approach in the in Saudi patients. This study investigates the impact of using mobile health technologies for the self-management of diabetes in Saudi Arabia. In this study, an intelligent mobile diabetes management system (SAED), tailored for T2D patients in KSA was developed. A pilot study of the SAED system was conducted in Saudi Arabia with 20 diabetic patients for 6 months duration. The patients were randomly categorized into a control group who did not use the SAED system and an intervention group whom used the SAED system for their diabetes management during this period. At the end of the follow-up period, the HbA1c levels in the patients in both groups were measure together with a diabetes knowledge test was also conducted to test the diabetes awareness of the patients. The results of SAED pilot study showed that the patients in the intervention group were able to significantly decrease their HbA1c levels compared to the control group. The SAED system also enhanced the diabetes awareness amongst the patients in the intervention group during the trial

Effect of microstructure on the impact toughness and temper embrittlement of SA508Gr.4N steel for advanced pressure vessel materials.

PubMed

Yang, Zhiqiang; Liu, Zhengdong; He, Xikou; Qiao, Shibin; Xie, Changsheng

2018-01-09

The effect of microstructure on the impact toughness and the temper embrittlement of a SA508Gr.4N steel was investigated. Martensitic and bainitic structures formed in this material were examined via scanning electron microscopy, electron backscatter diffraction, transmission electron microscopy, and Auger electron spectroscopy (AES) analysis. The martensitic structure had a positive effect on both the strength and toughness. Compared with the bainitic structure, this structure consisted of smaller blocks and more high-angle grain boundaries (HAGBs). Changes in the ultimate tensile strength and toughness of the martensitic structure were attributed to an increase in the crack propagation path. This increase resulted from an increased number of HAGBs and refinement of the sub-structure (block). The AES results revealed that sulfur segregation is higher in the martensitic structure than in the bainitic structure. Therefore, the martensitic structure is more susceptible to temper embrittlement than the bainitic structure.

A mouse model for the cystic fibrosis delta F508 mutation.

PubMed Central

van Doorninck, J H; French, P J; Verbeek, E; Peters, R H; Morreau, H; Bijman, J; Scholte, B J

1995-01-01

Most cystic fibrosis (CF) patients produce a mutant form (delta F508) of the cystic fibrosis transmembrane conductance regulator (CFTR), which is not properly processed in normal cells but is active as a chloride channel in several experimental systems. We used a double homologous recombination ('Hit and Run') procedure to generate a mouse model for the delta F508 mutation. Targeted embryonic stem (ES) cells (Hit clones) were found; of these either 80 or 20% of the clones had lost the delta F508 mutation, depending on the distance between the linearization site in the targeting construct and the delta F508 mutation. Correctly targeted clones underwent a second selection step resulting in ES cell clones (Run clones) heterozygous for the delta F508 mutation with an efficiency of 2-7%. Chimeric mice were generated and offspring homozygous for the delta F508 mutation showed electrophysiological abnormalities in nasal epithelium, gallbladder and in the intestine, and histological abnormalities in the intestine, typical of CF. Our data suggest that the delta F508 mice have residual delta F508 CFTR activity which would explain the mild pathology of the delta F508 mice. The delta F508 mouse may provide a useful model for the study of the processing defect of delta F508 CFTR and for the development of novel therapeutic approaches based on circumvention of the processing block. Images PMID:7556083

40 CFR 35.508 - Funding period.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Funding period. 35.508 Section 35.508... ASSISTANCE Environmental Program Grants for Tribes Preparing An Application § 35.508 Funding period. The Regional Administrator and applicant may negotiate the length of the funding period for environmental...

40 CFR 35.508 - Funding period.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Funding period. 35.508 Section 35.508... ASSISTANCE Environmental Program Grants for Tribes Preparing An Application § 35.508 Funding period. The Regional Administrator and applicant may negotiate the length of the funding period for environmental...

40 CFR 35.508 - Funding period.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Funding period. 35.508 Section 35.508... ASSISTANCE Environmental Program Grants for Tribes Preparing An Application § 35.508 Funding period. The Regional Administrator and applicant may negotiate the length of the funding period for environmental...

40 CFR 35.508 - Funding period.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Funding period. 35.508 Section 35.508... ASSISTANCE Environmental Program Grants for Tribes Preparing An Application § 35.508 Funding period. The Regional Administrator and applicant may negotiate the length of the funding period for environmental...

40 CFR 35.508 - Funding period.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Funding period. 35.508 Section 35.508... ASSISTANCE Environmental Program Grants for Tribes Preparing An Application § 35.508 Funding period. The Regional Administrator and applicant may negotiate the length of the funding period for environmental...

48 CFR 9.508 - Examples.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Examples. 9.508 Section 9... CONTRACTOR QUALIFICATIONS Organizational and Consultant Conflicts of Interest 9.508 Examples. The examples in... officer apply the general rules in 9.505 to individual contract situations. (a) Company A agrees to...

Cloning, Characterization and Expression Pattern Analysis of a Cytosolic Copper/Zinc Superoxide Dismutase (SaCSD1) in a Highly Salt Tolerant Mangrove (Sonneratia alba)

PubMed Central

Yang, Enze; Yi, Shanze; Bai, Fang; Niu, Dewei; Zhong, Junjie; Wu, Qiuhong; Chen, Shufang; Zhou, Renchao; Wang, Feng

2015-01-01

Mangroves are critical marine resources for their remarkable ability to tolerate seawater. Antioxidant enzymes play an especially significant role in eliminating reactive oxygen species and conferring abiotic stress tolerance. In this study, a cytosolic copper/zinc superoxide dismutase (SaCSD1) cDNA of Sonneratia alba, a mangrove species with high salt tolerance, was successfully cloned and then expressed in Escherichia coli Rosetta-gami (designated as SaCSD1). SaCSD1 comprised a complete open reading frame (ORF) of 459 bp which encoded a protein of 152 amino acids. Its mature protein is predicted to be 15.32 kDa and the deduced isoelectric point is 5.78. SaCSD1 has high sequence similarity (85%–90%) with the superoxide dismutase (CSD) of some other plant species. SaCSD1 was expressed with 30.6% yield regarding total protein content after being introduced into the pET-15b (Sma I) vector for expression in Rosetta-gami and being induced with IPTG. After affinity chromatography on Ni-NTA, recombinant SaCSD1 was obtained with 3.2-fold purification and a specific activity of 2200 U/mg. SaCSD1 showed good activity as well as stability in the ranges of pH between 3 and 7 and temperature between 25 and 55 °C. The activity of recombinant SaCSD1 was stable in 0.25 M NaCl, Dimethyl Sulphoxide (DMSO), glycerol, and chloroform, and was reduced to a great extent in β-mercaptoethanol, sodium dodecyl sulfate (SDS), H2O2, and phenol. Moreover, the SaCSD1 protein was very susceptive to pepsin digestion. Real-time Quantitative Polymerase Chain Reaction (PCR) assay demonstrated that SaCSD1 was expressed in leaf, stem, flower, and fruit organs, with the highest expression in fruits. Under 0.25 M and 0.5 M salt stress, the expression of SaCSD1 was down-regulated in roots, but up-regulated in leaves. PMID:26703583

Upregulation of cell proliferation via Shc and ERK1/2 MAPK signaling in SaOS-2 osteoblasts grown on magnesium alloy surface coating with tricalcium phosphate.

PubMed

Jiang, Tianlong; Guo, Lei; Ni, Shenghui; Zhao, Yuyan

2015-04-01

Magnesium (Mg) alloys have been demonstrated to be viable orthopedic implants because of mechanical and biocompatible properties similar to natural bone. In order to improve its osteogenic properties, a porous β-tricalcium phosphate (β-TCP) was coated on the Mg-3AI-1Zn alloy by alkali-heat treatment technique. The human bone-derived cells (SaOS-2) were cultured on (β-TCP)-Mg-3AI-1Zn in vitro, and the osteoblast response, the morphology and the elements on this alloy surface were investigated. Also, the regulation of key intracellular signalling proteins was investigated in the SaOS-2 cells cultured on alloy surface. The results from scanning electron microscope and immunofluorescence staining demonstrated that (β-TCP)-Mg-3AI-1Zn induced significant osteogenesis. SaOS-2 cell proliferation was improved by β-TCP coating. Moreover, the (β-TCP)-Mg-3AI-1Zn surface induced activation of key intracellular signalling proteins in SaOS-2 cells. We observed an enhanced activation of Src homology and collagen (Shc), a common point of integration between bone morphogenetic protein 2, and the Ras/mitogen-activated protein kinase (MAPK) pathway. ERK1/2 MAP kinase activation was also upregulated, suggesting a role in mediating osteoblastic cell interactions with biomaterials. The signalling pathway involving c-fos (member of the activated protein-1) was also shown to be upregulated in osteoblasts cultured on the (β-TCP)-Mg-3AI-1Zn. These results suggest that β-TCP coating may contribute to successful osteoblast function on Mg alloy surface. (β-TCP)-Mg-3AI-1Zn may upregulate cell proliferation via Shc and ERK1/2 MAPK signaling in SaOS-2 osteoblasts grown on Mg alloy surface.

27 CFR 19.508 - Consignor premises.

Code of Federal Regulations, 2010 CFR

2010-04-01

... plant or bonded wine cellar; or (ii) the consignor proprietor of an alcohol fuel plant to cover the... alcohol fuel plants qualified under 26 U.S.C. 5181. (3) The consignor proprietor may cover on one transfer... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Consignor premises. 19.508...

ImprimatinC1, a novel plant immune-priming compound, functions as a partial agonist of salicylic acid.

PubMed

Noutoshi, Yoshiteru; Jikumaru, Yusuke; Kamiya, Yuji; Shirasu, Ken

2012-01-01

Plant activators are agrochemicals that protect crops from pathogens. They confer durable resistance to a broad range of diseases by activating intrinsic immune mechanisms in plants. To obtain leads regarding useful compounds, we have screened a chemical library using an established method that allows selective identification of immune-priming compounds. Here, we report the characterisation of one of the isolated chemicals, imprimatinC1, and its structural derivative imprimatinC2. ImprimatinC1 functions as a weak analogue of salicylic acid (SA) and activates the expression of defence-related genes. However, it lacks antagonistic activity toward jasmonic acid. Structure-activity relationship analysis suggests that imprimatinC1 and C2 can be metabolised to 4-chlorobenzoic acid and 3,4-chlorobenzoic acid, respectively, to function in Arabidopsis. We also found that imprimatinC1 and C2 and their potential functional metabolites acted as partial agonists of SA. Thus, imprimatinC compounds could be useful tools for dissecting SA-dependent signal transduction pathways.

ImprimatinC1, a novel plant immune-priming compound, functions as a partial agonist of salicylic acid

PubMed Central

Noutoshi, Yoshiteru; Jikumaru, Yusuke; Kamiya, Yuji; Shirasu, Ken

2012-01-01

Plant activators are agrochemicals that protect crops from pathogens. They confer durable resistance to a broad range of diseases by activating intrinsic immune mechanisms in plants. To obtain leads regarding useful compounds, we have screened a chemical library using an established method that allows selective identification of immune-priming compounds. Here, we report the characterisation of one of the isolated chemicals, imprimatinC1, and its structural derivative imprimatinC2. ImprimatinC1 functions as a weak analogue of salicylic acid (SA) and activates the expression of defence-related genes. However, it lacks antagonistic activity toward jasmonic acid. Structure-activity relationship analysis suggests that imprimatinC1 and C2 can be metabolised to 4-chlorobenzoic acid and 3,4-chlorobenzoic acid, respectively, to function in Arabidopsis. We also found that imprimatinC1 and C2 and their potential functional metabolites acted as partial agonists of SA. Thus, imprimatinC compounds could be useful tools for dissecting SA-dependent signal transduction pathways. PMID:23050089

Screening for F508del as a first step in the molecular diagnosis of cystic fibrosis.

PubMed

Marson, Fernando Augusto de Lima; Bertuzzo, Carmen Silvia; Ribeiro, Maria Ângela Gonçalves de Oliveira; Ribeiro, Antônio Fernando; Ribeiro, José Dirceu

2013-01-01

To determine the relevance of screening for the F508del mutation of the cystic fibrosis transmembrane conductance regulator gene as a first step in the genetic diagnosis of cystic fibrosis (CF) by associating the genotype with various clinical variables. We evaluated 180 CF patients regarding the F508del mutation. The clinical data were obtained from the medical records of the patients and from interviews with their parents or legal guardians. Of the 180 patients studied, 65 (36.1%) did not carry the F508del mutation (group 0 [G0]), 67 (37.2%) were F508del heterozygous (G1), and 48 (26.7%) were F508del homozygous (G2). All three groups showed associations with the clinical variables. Homozygosis was associated with younger patients, younger age at CF diagnosis, and younger age at the first isolation of Pseudomonas aeruginosa (PA), as well as with higher prevalence of pancreatic insufficiency (PI) and non-mucoid PA (NMPA) colonization. In comparison with G1+G2 patients, G0 patients were older; first experienced clinical symptoms, digestive disease, and pulmonary disease at an older age; were older at CF diagnosis and at first PA isolation; and had a lower prevalence of PI and meconium ileus, as well as of colonization by NMPA, mucoid PA, and Burkholderia cepacia. In G1 patients, values were intermediate for age at CF diagnosis; age at first PA isolation, first pulmonary symptoms, and first clinical manifestations; MPA colonization; and OR for PI. The identification of F508del in 63.9% of the patients studied showed that this can be a useful tool as a first step in the genetic diagnosis of CF. The F508del genotype was associated with clinical severity of the disease, especially with the variables related to CF onset.

30 CFR 77.508-1 - Lightning arresters; wires entering buildings.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Lightning arresters; wires entering buildings... OF UNDERGROUND COAL MINES Electrical Equipment-General § 77.508-1 Lightning arresters; wires entering buildings. Lightning arresters protecting exposed telephone wires entering buildings shall be provided at...

30 CFR 77.508-1 - Lightning arresters; wires entering buildings.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Lightning arresters; wires entering buildings... OF UNDERGROUND COAL MINES Electrical Equipment-General § 77.508-1 Lightning arresters; wires entering buildings. Lightning arresters protecting exposed telephone wires entering buildings shall be provided at...

30 CFR 77.508-1 - Lightning arresters; wires entering buildings.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Lightning arresters; wires entering buildings... OF UNDERGROUND COAL MINES Electrical Equipment-General § 77.508-1 Lightning arresters; wires entering buildings. Lightning arresters protecting exposed telephone wires entering buildings shall be provided at...

30 CFR 77.508-1 - Lightning arresters; wires entering buildings.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Lightning arresters; wires entering buildings... OF UNDERGROUND COAL MINES Electrical Equipment-General § 77.508-1 Lightning arresters; wires entering buildings. Lightning arresters protecting exposed telephone wires entering buildings shall be provided at...

30 CFR 77.508-1 - Lightning arresters; wires entering buildings.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Lightning arresters; wires entering buildings... OF UNDERGROUND COAL MINES Electrical Equipment-General § 77.508-1 Lightning arresters; wires entering buildings. Lightning arresters protecting exposed telephone wires entering buildings shall be provided at...

77 FR 58002 - Airworthiness Directives; Turbomeca S.A. Turboshaft Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-19

... Airworthiness Directives; Turbomeca S.A. Turboshaft Engines AGENCY: Federal Aviation Administration (FAA), DOT... Turbomeca S.A. Arriel 2B and 2B1 turboshaft engines. That AD currently requires accomplishment of the TU166 modification. This new AD requires adding the Arriel 2S2 and 2C2 engines to the applicability of engines...

9 CFR 93.508 - Articles accompanying swine.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Articles accompanying swine. 93.508 Section 93.508 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Swine § 93.508 Articles accompanying swine. No litter...

9 CFR 93.508 - Articles accompanying swine.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Articles accompanying swine. 93.508 Section 93.508 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Swine § 93.508 Articles accompanying swine. No litter...

9 CFR 93.508 - Articles accompanying swine.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Articles accompanying swine. 93.508 Section 93.508 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Swine § 93.508 Articles accompanying swine. No litter...

9 CFR 93.508 - Articles accompanying swine.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Articles accompanying swine. 93.508 Section 93.508 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Swine § 93.508 Articles accompanying swine. No litter...

9 CFR 93.508 - Articles accompanying swine.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Articles accompanying swine. 93.508 Section 93.508 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... FOR MEANS OF CONVEYANCE AND SHIPPING CONTAINERS Swine § 93.508 Articles accompanying swine. No litter...

Realtime mitigation of GPS SA errors using Loran-C

NASA Technical Reports Server (NTRS)

Braasch, Soo Y.

1994-01-01

The hybrid use of Loran-C with the Global Positioning System (GPS) was shown capable of providing a sole-means of enroute air radionavigation. By allowing pilots to fly direct to their destinations, use of this system is resulting in significant time savings and therefore fuel savings as well. However, a major error source limiting the accuracy of GPS is the intentional degradation of the GPS signal known as Selective Availability (SA). SA-induced position errors are highly correlated and far exceed all other error sources (horizontal position error: 100 meters, 95 percent). Realtime mitigation of SA errors from the position solution is highly desirable. How that can be achieved is discussed. The stability of Loran-C signals is exploited to reduce SA errors. The theory behind this technique is discussed and results using bench and flight data are given.

45 CFR 73.735-508 - Other prohibitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Other prohibitions. 73.735-508 Section 73.735-508 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION STANDARDS OF CONDUCT Gifts, Entertainment, and Favors § 73.735-508 Other prohibitions. Employees shall avoid any action whether or not...

45 CFR 73.735-508 - Other prohibitions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Other prohibitions. 73.735-508 Section 73.735-508 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION STANDARDS OF CONDUCT Gifts, Entertainment, and Favors § 73.735-508 Other prohibitions. Employees shall avoid any action whether or not...

45 CFR 73.735-508 - Other prohibitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Other prohibitions. 73.735-508 Section 73.735-508 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION STANDARDS OF CONDUCT Gifts, Entertainment, and Favors § 73.735-508 Other prohibitions. Employees shall avoid any action whether or not...

Production of an extracellular thermohalophilic lipase from a moderately halophilic bacterium, Salinivibrio sp. strain SA-2.

PubMed

Amoozegar, Mohammad Ali; Salehghamari, Ensieh; Khajeh, Khosro; Kabiri, Mahbube; Naddaf, Saied

2008-06-01

Fifty strains of moderately halophilic bacteria were isolated from various salty environments in Iran. A strain designated as SA-2 was shown to be the best producer of extracellular lipase and was selected for further studies. Biochemical and physiological characterization along with 16S rDNA sequence analysis placed SA-2 in the genus Salinivibrio. The optimum salt, pH, temperature and aeration for enzyme production were 0.1 M KCl, pH 8, 35 degrees C and 150 rpm, respectively. The enzyme production was synchronized bacterial growth and reached a maximum level during the early-stationary phase in the basal medium containing 1 M NaCl. Triacylglycerols enhanced lipase production, while carbohydrates had inhibitory effects on it. The maximum lipase activity was obtained at pH 7.5, 50 degrees C and CaCl(2) concentration of 0.01 M. The enzyme was stable at pH range of 7.5-8 and retained 90% of its activity at 80 degrees C for 30 min. Different concentrations of NaNO(3), Na(2)SO(4), KCl and NaCl had no affect on lipase stability for 3 h. These results suggest that the lipase secreted by Salinivibrio sp. strain SA-2 is industrially important from the perspective of its tolerance to a broad temperature range, its moderate thermoactivity and its high tolerance to a wide range of salt concentrations (0-3 M NaCl).

46 CFR 122.508 - Wearing of life jackets.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Wearing of life jackets. 122.508 Section 122.508... Preparations for Emergencies § 122.508 Wearing of life jackets. (a) The master of a vessel shall require passengers to don life jackets when possible hazardous conditions exist, including, but not limited to: (1...

46 CFR 122.508 - Wearing of life jackets.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Wearing of life jackets. 122.508 Section 122.508... Preparations for Emergencies § 122.508 Wearing of life jackets. (a) The master of a vessel shall require passengers to don life jackets when possible hazardous conditions exist, including, but not limited to: (1...

46 CFR 122.508 - Wearing of life jackets.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Wearing of life jackets. 122.508 Section 122.508... Preparations for Emergencies § 122.508 Wearing of life jackets. (a) The master of a vessel shall require passengers to don life jackets when possible hazardous conditions exist, including, but not limited to: (1...

46 CFR 122.508 - Wearing of life jackets.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Wearing of life jackets. 122.508 Section 122.508... Preparations for Emergencies § 122.508 Wearing of life jackets. (a) The master of a vessel shall require passengers to don life jackets when possible hazardous conditions exist, including, but not limited to: (1...

46 CFR 122.508 - Wearing of life jackets.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Wearing of life jackets. 122.508 Section 122.508... Preparations for Emergencies § 122.508 Wearing of life jackets. (a) The master of a vessel shall require passengers to don life jackets when possible hazardous conditions exist, including, but not limited to: (1...

30 CFR 7.508 - Harmful gas removal components.

Code of Federal Regulations, 2012 CFR

2012-07-01

... chemical used for removal of harmful gas shall be— (1) Contained such that when stored or used it cannot... for disposal of used chemical. (c) Each harmful gas removal component shall be tested to determine its... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Harmful gas removal components. 7.508 Section 7...

30 CFR 7.508 - Harmful gas removal components.

Code of Federal Regulations, 2013 CFR

2013-07-01

... chemical used for removal of harmful gas shall be— (1) Contained such that when stored or used it cannot... for disposal of used chemical. (c) Each harmful gas removal component shall be tested to determine its... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Harmful gas removal components. 7.508 Section 7...

30 CFR 7.508 - Harmful gas removal components.

Code of Federal Regulations, 2014 CFR

2014-07-01

... chemical used for removal of harmful gas shall be— (1) Contained such that when stored or used it cannot... for disposal of used chemical. (c) Each harmful gas removal component shall be tested to determine its... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Harmful gas removal components. 7.508 Section 7...

78 FR 48824 - Airworthiness Directives; Turbomeca S.A. Turboshaft Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-12

.... Turboshaft Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking.... Arriel 1A1, 1A2, 1B, 1C, 1C1, 1C2, 1D, 1D1, 1E2, 1K1, 1S, and 1S1 turboshaft engines. This proposed AD was prompted by a ``chip illumination event'' in flight on a Turbomeca S.A. Arriel 1 engine. This...

Defective Fluid Secretion from Submucosal Glands of Nasal Turbinates from CFTR-/- and CFTRΔF508/ΔF508 Pigs

PubMed Central

Cho, Hyung-Ju; Joo, Nam Soo; Wine, Jeffrey J.

2011-01-01

Background Cystic fibrosis (CF), caused by reduced CFTR function, includes severe sinonasal disease which may predispose to lung disease. Newly developed CF pigs provide models to study the onset of CF pathophysiology. We asked if glands from pig nasal turbinates have secretory responses similar to those of tracheal glands and if CF nasal glands show reduced fluid secretion. Methodology/Principal Findings Unexpectedly, we found that nasal glands differed from tracheal glands in five ways, being smaller, more numerous (density per airway surface area), more sensitive to carbachol, more sensitive to forskolin, and nonresponsive to Substance P (a potent agonist for pig tracheal glands). Nasal gland fluid secretion from newborn piglets (12 CF and 12 controls) in response to agonists was measured using digital imaging of mucus bubbles formed under oil. Secretion rates were significantly reduced in all conditions tested. Fluid secretory rates (Controls vs. CF, in pl/min/gland) were as follows: 3 µM forskolin: 9.2±2.2 vs. 0.6±0.3; 1 µM carbachol: 143.5±35.5 vs. 52.2±10.3; 3 µM forskolin + 0.1 µM carbachol: 25.8±5.8 vs. CF 4.5±0.9. We also compared CFΔF508/ΔF508 with CFTR-/- piglets and found significantly greater forskolin-stimulated secretion rates in the ΔF508 vs. the null piglets (1.4±0.8, n = 4 vs. 0.2±0.1, n = 7). An unexpected age effect was also discovered: the ratio of secretion to 3 µM forskolin vs. 1 µM carbachol was ∼4 times greater in adult than in neonatal nasal glands. Conclusions/Significance These findings reveal differences between nasal and tracheal glands, show defective fluid secretion in nasal glands of CF pigs, reveal some spared function in the ΔF508 vs. null piglets, and show unexpected age-dependent differences. Reduced nasal gland fluid secretion may predispose to sinonasal and lung infections. PMID:21935358

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation

PubMed Central

Stefano, Daniela De; Villella, Valeria R; Esposito, Speranza; Tosco, Antonella; Sepe, Angela; Gregorio, Fabiola De; Salvadori, Laura; Grassia, Rosa; Leone, Carlo A; Rosa, Giuseppe De; Maiuri, Maria C; Pettoello-Mantovani, Massimo; Guido, Stefano; Bossi, Anna; Zolin, Anna; Venerando, Andrea; Pinna, Lorenzo A; Mehta, Anil; Bona, Gianni; Kroemer, Guido; Maiuri, Luigi; Raia, Valeria

2014-01-01

Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in CftrF508del homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation. PMID:25350163

Restoration of CFTR function in patients with cystic fibrosis carrying the F508del-CFTR mutation.

PubMed

De Stefano, Daniela; Villella, Valeria R; Esposito, Speranza; Tosco, Antonella; Sepe, Angela; De Gregorio, Fabiola; Salvadori, Laura; Grassia, Rosa; Leone, Carlo A; De Rosa, Giuseppe; Maiuri, Maria C; Pettoello-Mantovani, Massimo; Guido, Stefano; Bossi, Anna; Zolin, Anna; Venerando, Andrea; Pinna, Lorenzo A; Mehta, Anil; Bona, Gianni; Kroemer, Guido; Maiuri, Luigi; Raia, Valeria

2014-01-01

Restoration of BECN1/Beclin 1-dependent autophagy and depletion of SQSTM1/p62 by genetic manipulation or autophagy-stimulatory proteostasis regulators, such as cystamine, have positive effects on mouse models of human cystic fibrosis (CF). These measures rescue the functional expression of the most frequent pathogenic CFTR mutant, F508del, at the respiratory epithelial surface and reduce lung inflammation in Cftr(F508del) homozygous mice. Cysteamine, the reduced form of cystamine, is an FDA-approved drug. Here, we report that oral treatment with cysteamine greatly reduces the mortality rate and improves the phenotype of newborn mice bearing the F508del-CFTR mutation. Cysteamine was also able to increase the plasma membrane expression of the F508del-CFTR protein in nasal epithelial cells from F508del homozygous CF patients, and these effects persisted for 24 h after cysteamine withdrawal. Importantly, this cysteamine effect after washout was further sustained by the sequential administration of epigallocatechin gallate (EGCG), a green tea flavonoid, both in vivo, in mice, and in vitro, in primary epithelial cells from CF patients. In a pilot clinical trial involving 10 F508del-CFTR homozygous CF patients, the combination of cysteamine and EGCG restored BECN1, reduced SQSTM1 levels and improved CFTR function from nasal epithelial cells in vivo, correlating with a decrease of chloride concentrations in sweat, as well as with a reduction of the abundance of TNF/TNF-alpha (tumor necrosis factor) and CXCL8 (chemokine [C-X-C motif] ligand 8) transcripts in nasal brushing and TNF and CXCL8 protein levels in the sputum. Altogether, these results suggest that optimal schedules of cysteamine plus EGCG might be used for the treatment of CF caused by the F508del-CFTR mutation.

40 CFR 89.508 - Test procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Test procedures. 89.508 Section 89.508... Test procedures. (a)(1) For nonroad engines subject to the provisions of this subpart, the prescribed test procedures are the nonroad engine 8-mode test procedure as described in subpart E of this part...

Association between F508 deletion in CFTR and chronic pancreatitis risk.

PubMed

Zhao, Dong; Xu, Yanzhen; Li, Jiatong; Fu, Shien; Xiao, Feifan; Song, Xiaowei; Xie, Zhibin; Jiang, Min; He, Yan; Liu, Chengwu; Wen, Qiongxian; Yang, Xiaoli

2017-09-01

The cystic fibrosis transmembrane conductance regulator (CFTR) has been reported to influence individual susceptibility to chronic pancreatitis (CP), but the results of previous studies are controversial. We performed a study to demonstrate the relationship between CFTR and CP. We searched PubMed, Scopus, and Embase for studies of patients with CP. Seven studies from 1995 to 2016 were identified, and included 64,832 patients. Pooled prevalence and 95% confidence intervals (CIs) were calculated. F508 deletion in CFTR was significantly positively associated with CP risk in the overall analysis (odds ratio [OR]=3.20, 95% CI: 2.30-4.44, I 2 =31.7%). In subgroup analysis stratified by ethnicity, F508 deletion was significantly associated with CP risk in Indian populations, using a fixed effects model (ORs=5.45, 95% CI: 2.52-11.79, I 2 =0.0%), and in non-Indian populations, using a random effects model (ORs=3.59, 95% CI: 1.73-7.48, I 2 =60.9%). At the same time, we found that Indians with F508 deletion had much higher CP prevalence than non-Indians. Interestingly, F508 deletion was also associated with CP and idiopathic CP risk in subgroup analysis stratified by aeitiology, using the fixed effects model. Based on current evidence, F508 deletion is a risk factor for CP, and Indians with F508 deletion have much higher CP morbidity. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

30 CFR 75.508 - Map of electrical system.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Map of electrical system. 75.508 Section 75.508... MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Electrical Equipment-General § 75.508 Map of electrical system. [Statutory Provisions] The location and the electrical rating of all stationary electric...

30 CFR 75.508 - Map of electrical system.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Map of electrical system. 75.508 Section 75.508... MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Electrical Equipment-General § 75.508 Map of electrical system. [Statutory Provisions] The location and the electrical rating of all stationary electric...

30 CFR 75.508 - Map of electrical system.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Map of electrical system. 75.508 Section 75.508... MANDATORY SAFETY STANDARDS-UNDERGROUND COAL MINES Electrical Equipment-General § 75.508 Map of electrical system. [Statutory Provisions] The location and the electrical rating of all stationary electric...

Fractographic study of a thick wall pressure vessel failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Canonico, D.A.; Crouse, R.S.; Henson, T.J.

1979-01-01

The pressure vessel described in this paper is identified as Intermediate Test Vessel 1 (ITV-1) and was fabricated of SA508, Class 2 Steel. It was tested to failure at 54/sup 0/C (130/sup 0/F). The gross failure appeared to be a brittle fracture although accompanied by a measured strain of 0.9%. Seven regions of the fracture were examined in detail and the observed surfaces were compared to Charpy V-notch (C/sub v/) specimens of SA508, Class 2 steel broken at temperatures above and below the ductile to brittle transition temperature. Three samples from the vessel were taken in the region around themore » fatigue notch and four from areas well removed from the notch. All these were carefully examined both optically and by scanning electron microscopy (SEM). It was established that early crack extension was by ductile mode until a large flaw approximately 500 mm long 83 mm wide was developed. At this point the vessel could no longer contain the internal pressure and final rupture was by brittle fracture.« less

Identification of a Unique Ganglioside Binding Loop within Botulinum Neurotoxins C and D-SA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karalewitz, Andrew P.-A.; Kroken, Abby R.; Fu, Zhuji

2010-09-22

The botulinum neurotoxins (BoNTs) are the most potent protein toxins for humans. There are seven serotypes of BoNTs (A-G) based on a lack of cross antiserum neutralization. BoNTs utilize gangliosides as components of the host receptors for binding and entry into neurons. Members of BoNT/C and BoNT/D serotypes include mosaic toxins that are organized in D/C and C/D toxins. One D/C mosaic toxin, BoNT/D-South Africa (BoNT/D-SA), was not fully neutralized by immunization with BoNT serotype C or D, which stimulated this study. Here the crystal structures of the receptor binding domains of BoNT/C, BoNT/D, and BoNT/D-SA are presented. Biochemical andmore » cell binding studies show that BoNT/C and BoNT/D-SA possess unique mechanisms for ganglioside binding. These studies provide new information about how the BoNTs can enter host cells as well as a basis for understanding the immunological diversity of these neurotoxins.« less

12 CFR 508.8 - Default.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Default. 508.8 Section 508.8 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.8 Default. If the subject individual fails to file a petition for a...

Results of crack-arrest tests on irradiated a 508 class 3 steel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Iskander, S.K.; Milella, P.P.; Pini, M.A.

1998-02-01

Ten crack-arrest toughness values for irradiated specimens of A 508 class 3 forging steel have been obtained. The tests were performed according to the American Society for Testing and Materials (ASTM) Standard Test Method for Determining Plane-Strain Crack-Arrest Fracture Toughness, K{sub la} of Ferritic Steels, E 1221-88. None of these values are strictly valid in all five ASTM E 1221-88 validity criteria. However, they are useful when compared to unirradiated crack-arrest specimen toughness values since they show the small (averaging approximately 10{degrees}C) shifts in the mean and lower-bound crack-arrest toughness curves. This confirms that a low copper content in ASTMmore » A 508 class 3 forging material can be expected to result in small shifts of the transition toughness curve. The shifts due to neutron irradiation of the lower bound and mean toughness curves are approximately the same as the Charpy V-notch (CVN) 41-J temperature shift. The nine crack-arrest specimens were irradiated at temperatures varying from 243 to 280{degrees}C, and to a fluence varying from 1.7 to 2.7 x 10{sup 19} neutrons/cm{sup 2} (> 1 MeV). The test results were normalized to reference values that correspond to those of CVN specimens irradiated at 284{degrees}C to a fluence of 3.2 x 10{sup 19} neutrons/cm{sup 2} (> 1 MeV) in the same capsule as the crack-arrest specimens. This adjustment resulted in a shift to lower temperatures of all the data, and in particular moved two data points that appeared to lie close to or lower than the American Society of Mechanical Engineers K{sub la} curve to positions that seemed more reasonable with respect to the remaining data. A special fixture was designed, fabricated, and successfully used in the testing. For reasons explained in the text, special blocks to receive the Oak Ridge National Laboratory clip gage were designed, and greater-than-standard crack-mouth opening displacements measured were accounted for. 24 refs., 13 figs., 12 tabs.« less

General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels.

PubMed

Marcet, Brice; Becq, Frédéric; Norez, Caroline; Delmas, Patrick; Verrier, Bernard

2004-03-01

1. Cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl(-) channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl(-) channel activity of wild-type CFTR and delF508-CFTR mutant. 2. The effects of n-alkanols like octanol on CFTR activity were measured by iodide ((125)I) efflux and patch-clamp techniques on three distinct cellular models: (1). CFTR-expressing Chinese hamster ovary cells, (2). human airway Calu-3 epithelial cells and (3). human airway JME/CF15 epithelial cells which express the delF508-CFTR mutant. 3. Our data show for the first time that n-alkanols activate both wild-type CFTR and delF508-CFTR mutant. Octanol stimulated (125)I efflux in a dose-dependent manner in CFTR-expressing cells (wild-type and delF508) but not in cell lines lacking CFTR. (125)I efflux and Cl(-) currents induced by octanol were blocked by glibenclamide but insensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, as expected for a CFTR Cl(-) current. 4. CFTR activation by octanol was neither due to cell-to-cell uncoupling properties of octanol nor to an intracellular cAMP increase. CFTR activation by octanol requires phosphorylation by protein kinase-A (PKA) since it was prevented by H-89, a PKA inhibitor. 5. n-Alkanols chain length was an important determinant for channel activation, with rank order of potencies: 1-heptanol<1-octanol<2-octanol<1-decanol. Our findings may be of valuable interest for developing novel therapeutic strategies for CF.

47 CFR 54.508 - Technology plans.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Technology plans. 54.508 Section 54.508... SERVICE Universal Service Support for Schools and Libraries § 54.508 Technology plans. (a) Applicants must develop a technology plan when requesting discounts for internal connections and basic maintenance for...

The novel complex allele [A238V;F508del] of the CFTR gene: clinical phenotype and possible implications for cystic fibrosis etiological therapies.

PubMed

Diana, Anna; Polizzi, Angela Maria; Santostasi, Teresa; Ratclif, Luigi; Pantaleo, Maria Giuseppina; Leonetti, Giuseppina; Iusco, Danila Rosa; Gallo, Crescenzio; Conese, Massimo; Manca, Antonio

2016-06-01

Few mutations in cis have been annotated for F508del homozygous patients. Southern Italy patients who at a first analysis appeared homozygous for the F508del mutation (n=63) or compound heterozygous for the F508del and another mutation in the cystic fibrosis transmembrane conductance regulator gene (n=155) were searched for the A238V mutation in exon 6. The allelic frequency of the complex allele [A238V;F508del] was 0.04. When the whole data set was used (comprised also of 56 F508del/F508del and 34 F508del/other mutation controls), no differences reached the statistical significance in the clinical parameters, except chloride concentrations which were lower in [A238V;F508del]/other mutation compared with F508del/other mutation (P=0.03). The two study groups presented less complications than the control groups. Within the minimal data set (34 F508del/F508del, 27 F508del/other mutation, 4 [A238V;F508del]/F508del cases and 5 [A238V;F508del]/other mutation cases); that is, presenting all the variables in each patient, forced expiratory volume in 1 s and forced vital capacity presented a trend to lower levels in the study groups in comparison with the F508del/F508del group, and C-reactive protein approximated statistically significant higher levels in the [A238V;F508del]/other mutation as compared with F508del/F508del patients (P=0.09). The analysis of statistical dependence among the variables showed a significant anticorrelation between chloride and body mass index in the [A238V;F508del]/other mutation group. In conclusion, the complex allele [A238V;F508del] seems to be associated with less general complications than in the control groups, on the other hand possibly giving a worse pulmonary phenotype and higher systemic/local inflammatory response. These findings have implications for the correct recruitment and clinical response of F508del patients in the clinical trials testing the new etiological drugs for cystic fibrosis.

34 CFR 682.508 - Assignment of a loan.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 3 2010-07-01 2010-07-01 false Assignment of a loan. 682.508 Section 682.508 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL FAMILY EDUCATION LOAN (FFEL) PROGRAM Federal Guaranteed Student Loan Programs...

Targeting autophagy as a novel strategy for facilitating the therapeutic action of potentiators on ΔF508 cystic fibrosis transmembrane conductance regulator.

PubMed

Luciani, Alessandro; Villella, Valeria Rachela; Esposito, Speranza; Gavina, Manuela; Russo, Ilaria; Silano, Marco; Guido, Stefano; Pettoello-Mantovani, Massimo; Carnuccio, Rosa; Scholte, Bob; De Matteis, Antonella; Maiuri, Maria Chiara; Raia, Valeria; Luini, Alberto; Kroemer, Guido; Maiuri, Luigi

2012-11-01

Channel activators (potentiators) of cystic fibrosis (CF) transmembrane conductance regulator (CFTR), can be used for the treatment of the small subset of CF patients that carry plasma membrane-resident CFTR mutants. However, approximately 90% of CF patients carry the misfolded ΔF508-CFTR and are poorly responsive to potentiators, because ΔF508-CFTR is intrinsically unstable at the plasma membrane (PM) even if rescued by pharmacological correctors. We have demonstrated that human and mouse CF airways are autophagy deficient due to functional sequestration of BECN1 and that the tissue transglutaminase-2 inhibitor, cystamine, or antioxidants restore BECN1-dependent autophagy and reduce SQSTM1/p62 levels, thus favoring ΔF508-CFTR trafficking to the epithelial surface. Here, we investigated whether these treatments could facilitate the beneficial action of potentiators on ΔF508-CFTR homozygous airways. Cystamine or the superoxide dismutase (SOD)/catalase-mimetic EUK-134 stabilized ΔF508-CFTR at the plasma membrane of airway epithelial cells and sustained the expression of CFTR at the epithelial surface well beyond drug withdrawal, overexpressing BECN1 and depleting SQSTM1. This facilitates the beneficial action of potentiators in controlling inflammation in ex vivo ΔF508-CFTR homozygous human nasal biopsies and in vivo in mouse ΔF508-CFTR lungs. Direct depletion of Sqstm1 by shRNAs in vivo in ΔF508-CFTR mice synergized with potentiators in sustaining surface CFTR expression and suppressing inflammation. Cystamine pre-treatment restored ΔF508-CFTR response to the CFTR potentiators genistein, Vrx-532 or Vrx-770 in freshly isolated brushed nasal epithelial cells from ΔF508-CFTR homozygous patients. These findings delineate a novel therapeutic strategy for the treatment of CF patients with the ΔF508-CFTR mutation in which patients are first treated with cystamine and subsequently pulsed with CFTR potentiators.

12 CFR 508.11 - Relevant considerations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Relevant considerations. 508.11 Section 508.11 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.11 Relevant considerations. (a) In determining whether...

SA1 and TRF1 synergistically bind to telomeric DNA and promote DNA-DNA pairing

NASA Astrophysics Data System (ADS)

Wang, Hong; Lin, Jiangguo; Countryman, Preston; Pan, Hai; Parminder Kaur Team; Robert Riehn Team; Patricia Opresko Team; Jane Tao Team; Susan Smith Team

Impaired telomere cohesion leads to increased aneuploidy and early onset of tumorigenesis. Cohesion is thought to occur through the entrapment of two DNA strands within tripartite cohesin ring(s), along with a fourth subunit (SA1/SA2). Surprisingly, cohesion rings are not essential for telomere cohesion, which instead requires SA1 and shelterin proteins including TRF1. However, neither this unique cohesion mechanism at telomeres or DNA-binding properties of SA1 is understood. Here, using single-molecule fluorescence imaging of quantum dot-labeled proteins on DNA we discover that while SA1 diffuses across multiple telomeric and non-telomeric regions, the diffusion mediated through its N-terminal domain is slower at telomeric regions. However, addition of TRF1 traps SA1 within telomeric regions, which form longer DNA-DNA pairing tracts than with TRF1 alone, as revealed by atomic force microscopy. Together, these experimental results and coarse-grained molecular dynamics simulations suggest that TRF1 and SA1 synergistically interact with DNA to support telomere cohesion without cohesin rings.

Matrine in association with FD-2 stimulates F508del-cystic fibrosis transmembrane conductance regulator activity in the presence of corrector VX809

PubMed Central

Marengo, Barbara; Speciale, Andrea; Senatore, Lisa; Garibaldi, Silvano; Musumeci, Francesca; Nieddu, Erika; Pollarolo, Benedetta; Pronzato, Maria Adelaide; Schenone, Silvia; Mazzei, Mauro; Domenicotti, Cinzia

2017-01-01

Cystic fibrosis is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, and the predominant mutation is termed Phe508del (F508del). Therapy for F508del-CFTR patients is based on the use of Orkambi®, a combination of VX809 and VX770. However, though Orkambi leads to an improvement in the lung function of patients, a progressive reduction in its efficacy has been observed. In order to overcome this effect, the aim of the present study was to investigate the role of matrine and the in-house compound FD-2 in increasing the action of VX809 and VX770. Fischer rat thyroid cells overexpressing F508del-CFTR were treated with matrine, VX809 (corrector) and/or with a number of potentiators (VX770, FD-1 and FD-2). The results demonstrated that matrine was able to stimulate CFTR activity and, in association with FD-2, increased the functionality of the channel in the presence of VX809. Based on these results, it may be hypothesized that FD-2 may be a novel and more effective potentiator compared with VX770. PMID:29039559

Learn About Section 508

EPA Pesticide Factsheets

Find out about EPA's commitment to making its websites and other electronic and information technology (EIT) products accessible, learn what Section 508 of the Rehabilitation Act covers and why, and how to make your EIT 508 compliant.

77 FR 47106 - Manufacturer of Controlled Substances; Notice of Application; SA INTL GMBH C/O., Sigma Aldrich Co...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-07

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; SA INTL GMBH C/O., Sigma Aldrich Co. LLC Pursuant to Title 21 Code of Federal Regulations 1301.34 (a), this is notice that on May 2, 2012, SA INTL GMBH C/O., Sigma Aldrich Co. LLC., 3500...

Correlation of the thermodynamic calculation and the experimental observation of Ni-Mo-Cr low alloy steel changing Ni, Mo, and Cr contents

NASA Astrophysics Data System (ADS)

Park, Sang-Gyu; Kim, Min-Chul; Lee, Bong-Sang; Wee, Dang-Moon

2010-12-01

SA508 Gr.4N Ni-Mo-Cr low alloy steel has improved fracture toughness and strength compared to commercial low alloy steels such as SA508 Gr.3 Mn-Mo-Ni low alloy steel, which has less than 1% Ni. Higher strength and fracture toughness of low alloy steels can be achieved by increasing the Ni and Cr contents. In this study, the effects of the alloying elements of Ni and Cr on the microstructural characteristics and mechanical properties of SA508 Gr.4N Ni-Mo-Cr low alloy steel are evaluated. Changes in the stable phases of SA508 Gr.4N low alloy steel with these alloying elements were evaluated using thermodynamic calculation software. These values were then compared with the observed microstructural results. Additionally, tensile tests and Charpy impact test were carried out to evaluate the mechanical properties. The thermodynamic calculations show that Ni mainly affects the change of the matrix phase of γ and α rather than the carbide phase. Contrary to the Ni effect, Cr and Mo primarily affect the precipitation behavior of the carbide phases of Cr 23C 6, Cr 7C 3 and Mo 2C. In the microscopic observations, the lath martensitic structure becomes finer as the Ni content increases without affecting the carbides. When the Cr content decreases, the Cr carbide becomes unstable and carbide coarsening occurs. Carbide Mo 2C in the form of fine needles were observed in the high-Mo alloy. Greater strength was obtained after additions of Ni and Mo and the transition properties were improved as the Ni and Cr contents increased. These results were correlated with the thermodynamic calculation results.

General anesthetic octanol and related compounds activate wild-type and delF508 cystic fibrosis chloride channels

PubMed Central

Marcet, Brice; Becq, Frédéric; Norez, Caroline; Delmas, Patrick; Verrier, Bernard

2004-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel is defective during cystic fibrosis (CF). Activators of the CFTR Cl− channel may be useful for therapy of CF. Here, we demonstrate that a range of general anesthetics like normal-alkanols (n-alkanols) and related compounds can stimulate the Cl− channel activity of wild-type CFTR and delF508-CFTR mutant. The effects of n-alkanols like octanol on CFTR activity were measured by iodide (125I) efflux and patch-clamp techniques on three distinct cellular models: (1) CFTR-expressing Chinese hamster ovary cells, (2) human airway Calu-3 epithelial cells and (3) human airway JME/CF15 epithelial cells which express the delF508-CFTR mutant. Our data show for the first time that n-alkanols activate both wild-type CFTR and delF508-CFTR mutant. Octanol stimulated 125I efflux in a dose-dependent manner in CFTR-expressing cells (wild-type and delF508) but not in cell lines lacking CFTR. 125I efflux and Cl− currents induced by octanol were blocked by glibenclamide but insensitive to 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid, as expected for a CFTR Cl− current. CFTR activation by octanol was neither due to cell-to-cell uncoupling properties of octanol nor to an intracellular cAMP increase. CFTR activation by octanol requires phosphorylation by protein kinase-A (PKA) since it was prevented by H-89, a PKA inhibitor. n-Alkanols chain length was an important determinant for channel activation, with rank order of potencies: 1-heptanol<1-octanol<2-octanol<1-decanol. Our findings may be of valuable interest for developing novel therapeutic strategies for CF. PMID:14967738

40 CFR 90.508 - Test procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Test procedures. 90.508 Section 90.508....508 Test procedures. (a) For nonroad engines subject to the provisions of this subpart, the prescribed test procedures are the appropriate small SI engine test procedures as described in subpart E of this...

Activation of deltaF508 CFTR in a cystic fibrosis respiratory epithelial cell line by 4-phenylbutyrate, genistein and CPX.

PubMed

Andersson, C; Roomans, G M

2000-05-01

The cellular basis of cystic fibrosis (CF) is a defect in a cyclic adenosine monophosphate (cAMP)-activated chloride channel (CF transmembrane conductance regulator) in epithelial cells that leads to decreased chloride ion transport and impaired water transport across the cell membrane. This study investigated whether it was possible to activate the defective chloride channel in cystic fibrosis respiratory epithelial cells with 4-phenylbutyrate (4PBA), genistein and 8-cyclopentyl-1,3-dipropylxanthine (CPX). The CF bronchial epithelial cell line CFBE41o-, which expresses the deltaF508 mutation, was treated with these agents and loss of Cl-, indicating Cl- efflux, measured by X-ray microanalysis. 8-bromo-cAMP alone did not induce Cl- efflux in CFBE41o- cells, but after incubation with 4PBA a significant efflux of Cl- occurred. Stimulation of cells with a combination of genistein and cAMP also induced Cl- efflux, whereas a combination of pretreatment with 4PBA and a combined stimulation with genistein and cAMP induced an even larger Cl- efflux. Cl- efflux could also be stimulated by CPX, but this effect was not enhanced by 4PBA pretreatment. The deltaF508 mutation leads to impaired processing of the cystic fibrosis transmembrane conductance regulator. The increased efflux of chloride after 4-phenylbutyrate treatment can be explained by the fact that 4-phenylbutyrate allows the deltaF508 cystic fibrosis transmembrane conductance regulator to escape degradation and to be transported to the cell surface. Genistein and 8-cyclopentyl-1,3-dipropylxanthine act by stimulating chloride ion efflux by increasing the probability of the cystic fibrosis transmembrane conductance regulator being open. The combination of 4-phenylbutyrate and genistein may be useful in a potential pharmacological therapy for cystic fibrosis patients with the deltaF508 mutation.

J-R fracture characteristics of ferritic steels for RPVs and RCS piping of nuclear power plants

NASA Astrophysics Data System (ADS)

Yoon, Ji-Hyun; Lee, Bong-Sang; Hong, Jun-Hwa

2001-10-01

J-R fracture resistance tests have been performed on 3 heats of SA508-Gr.3 nuclear reactor pressure vessel (RPV) steel as well as 2 heats of SA516-Gr.70 and a heat of SA508-Gr.1a steels for nuclear reactor coolant system (RCS) piping. For the latter two steels, dynamic in addition to static J-R fracture resistances were investigated. From the test results of the SA508-Gr.3 steels, the J-R fracture resistance was superior in the following order: Si-killing steel, modified VCD steel and VCD steel. Microstructural analyses were carried out to correlate J-R fracture resistances with microstructural characteristics. According to the test results for SA508-Gr.1a and SA516-Gr.70 steels, all of the tested steels showed steep drops in fracture resistance at certain temperature and loading rate combinations. One heat of SA516-Gr.70 steel was very sensitive to dynamic strain aging and its fracture resistance was significantly low. It was concluded that microstructural and chemical factors affect the J-R fracture and DSA characteristics of SA516-Gr.70 steels.

48 CFR 3045.508 - Physical inventories.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Physical inventories. 3045.508 Section 3045.508 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Property in the Possession of Contractors 3045.508 Physical inventories. ...

48 CFR 3045.508 - Physical inventories.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Physical inventories. 3045.508 Section 3045.508 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY, HOMELAND... Property in the Possession of Contractors 3045.508 Physical inventories. ...

13 CFR 134.508 - What is the standard of review?

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false What is the standard of review? 134.508 Section 134.508 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION RULES OF... Service-Disabled Veteran Owned Small Business Concern Protests § 134.508 What is the standard of review...

5 CFR 293.508 - Type of folder to be used.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Type of folder to be used. 293.508 Section 293.508 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PERSONNEL RECORDS Employee Medical File System Records § 293.508 Type of folder to be used. Each agency must...

5 CFR 293.508 - Type of folder to be used.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Type of folder to be used. 293.508 Section 293.508 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PERSONNEL RECORDS Employee Medical File System Records § 293.508 Type of folder to be used. Each agency must...

5 CFR 293.508 - Type of folder to be used.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Type of folder to be used. 293.508 Section 293.508 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PERSONNEL RECORDS Employee Medical File System Records § 293.508 Type of folder to be used. Each agency must...

5 CFR 293.508 - Type of folder to be used.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Type of folder to be used. 293.508 Section 293.508 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PERSONNEL RECORDS Employee Medical File System Records § 293.508 Type of folder to be used. Each agency must...

5 CFR 293.508 - Type of folder to be used.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Type of folder to be used. 293.508 Section 293.508 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PERSONNEL RECORDS Employee Medical File System Records § 293.508 Type of folder to be used. Each agency must...

48 CFR 1845.508 - Physical inventories.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Physical inventories. 1845.508 Section 1845.508 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND SPACE... Contractors 1845.508 Physical inventories. NASA contractors shall reconcile inventories with the official...

50 CFR 600.508 - Fishing operations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Fishing operations. 600.508 Section 600.508 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MAGNUSON-STEVENS ACT PROVISIONS Foreign Fishing § 600.508 Fishing...

Probing Conformational Rescue Induced by a Chemical Corrector of F508del-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Mutant*

PubMed Central

Yu, Wilson; Chiaw, Patrick Kim; Bear, Christine E.

2011-01-01

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that cause loss of function of the CFTR channel on the apical surface of epithelial cells. The major CF-causing mutation, F508del-CFTR, is misfolded, retained in the endoplasmic reticulum, and degraded. Small molecule corrector compounds have been identified using high throughput screens, which partially rescue the trafficking defect of F508del-CFTR, allowing a fraction of the mutant protein to escape endoplasmic reticulum retention and traffic to the plasma membrane, where it exhibits partial function as a cAMP-regulated chloride channel. A subset of such corrector compounds binds directly to the mutant protein, prompting the hypothesis that they rescue the biosynthetic defect by inducing improved protein conformation. We tested this hypothesis directly by evaluating the consequences of a corrector compound on the conformation of each nucleotide binding domain (NBD) in the context of the full-length mutant protein in limited proteolytic digest studies. Interestingly, we found that VRT-325 was capable of partially restoring compactness in NBD1. However, VRT-325 had no detectable effect on the conformation of the second half of the molecule. In comparison, ablation of the di-arginine sequence, R553XR555 (F508del-KXK-CFTR), modified protease susceptibility of NBD1, NBD2, and the full-length protein. Singly, each intervention led to a partial correction of the processing defect. Together, these interventions restored processing of F508del-CFTR to near wild type. Importantly, however, a defect in NBD1 conformation persisted, as did a defect in channel activation after the combined interventions. Importantly, this defect in channel activation can be fully corrected by the addition of the potentiator, VX-770. PMID:21602569

Targeting autophagy as a novel strategy for facilitating the therapeutic action of potentiators on ΔF508 cystic fibrosis transmembrane conductance regulator

PubMed Central

Luciani, Alessandro; Villella, Valeria Rachela; Esposito, Speranza; Gavina, Manuela; Russo, Ilaria; Silano, Marco; Guido, Stefano; Pettoello-Mantovani, Massimo; Carnuccio, Rosa; Scholte, Bob; De Matteis, Antonella; Maiuri, Maria Chiara; Raia, Valeria; Luini, Alberto; Kroemer, Guido; Maiuri, Luigi

2012-01-01

Channel activators (potentiators) of cystic fibrosis (CF) transmembrane conductance regulator (CFTR), can be used for the treatment of the small subset of CF patients that carry plasma membrane-resident CFTR mutants. However, approximately 90% of CF patients carry the misfolded ΔF508-CFTR and are poorly responsive to potentiators, because ΔF508-CFTR is intrinsically unstable at the plasma membrane (PM) even if rescued by pharmacological correctors. We have demonstrated that human and mouse CF airways are autophagy deficient due to functional sequestration of BECN1 and that the tissue transglutaminase-2 inhibitor, cystamine, or antioxidants restore BECN1-dependent autophagy and reduce SQSTM1/p62 levels, thus favoring ΔF508-CFTR trafficking to the epithelial surface. Here, we investigated whether these treatments could facilitate the beneficial action of potentiators on ΔF508-CFTR homozygous airways. Cystamine or the superoxide dismutase (SOD)/catalase-mimetic EUK-134 stabilized ΔF508-CFTR at the plasma membrane of airway epithelial cells and sustained the expression of CFTR at the epithelial surface well beyond drug withdrawal, overexpressing BECN1 and depleting SQSTM1. This facilitates the beneficial action of potentiators in controlling inflammation in ex vivo ΔF508-CFTR homozygous human nasal biopsies and in vivo in mouse ΔF508-CFTR lungs. Direct depletion of Sqstm1 by shRNAs in vivo in ΔF508-CFTR mice synergized with potentiators in sustaining surface CFTR expression and suppressing inflammation. Cystamine pre-treatment restored ΔF508-CFTR response to the CFTR potentiators genistein, Vrx-532 or Vrx-770 in freshly isolated brushed nasal epithelial cells from ΔF508-CFTR homozygous patients. These findings delineate a novel therapeutic strategy for the treatment of CF patients with the ΔF508-CFTR mutation in which patients are first treated with cystamine and subsequently pulsed with CFTR potentiators. PMID:22874563

Towards a Science of Command and Control (C2)

DTIC Science & Technology

2005-06-01

Topic: C4ISR/C2 Architecture Associate Professor David H Cropley Systems Engineering & Evaluation Centre, University of South Australia Mawson ...Lakes Campus, Mawson Lakes, SA 5095, Australia Tel: (+618) 8302 3301 Fax: (+618) 8302 5344 Email: david.cropley@unisa.edu.au Report...ADDRESS(ES) Systems Engineering & Evaluation Centre,University of South Australia, Mawson Lakes Campus, Mawson Lakes, SA 5095, Australia, , 8

24 CFR 965.508 - Individual relief.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Individual relief. 965.508 Section 965.508 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... PHA-OWNED OR LEASED PROJECTS-GENERAL PROVISIONS Resident Allowances for Utilities § 965.508 Individual...

Application of positron annihilation lineshape analysis to fatigue damage and thermal embrittlement for nuclear plant materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uchida, M.; Ohta, Y.; Nakamura, N.

1995-08-01

Positron annihilation (PA) lineshape analysis is sensitive to detect microstructural defects such as vacancies and dislocations. The authors are developing a portable system and applying this technique to nuclear power plant material evaluations; fatigue damage in type 316 stainless steel and SA508 low alloy steel, and thermal embrittlement in duplex stainless steel. The PA technique was found to be sensitive in the early fatigue life (up to 10%), but showed a little sensitivity for later stages of the fatigue life in both type 316 stainless steel and SA508 ferritic steel. Type 316 steel showed a higher PA sensitivity than SA508more » since the initial SA508 microstructure already contained a high dislocation density in the as-received state. The PA parameter increased as a fraction of aging time in CF8M samples aged at 350 C and 400 C, but didn`t change much in CF8 samples.« less

7 CFR 1207.508 - USDA costs.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 10 2011-01-01 2011-01-01 false USDA costs. 1207.508 Section 1207.508 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Rules and Regulations General § 1207.508 USDA costs. Pursuant to § 1207.341 of the Plan the Board shall...

7 CFR 1207.508 - USDA costs.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 10 2013-01-01 2013-01-01 false USDA costs. 1207.508 Section 1207.508 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Rules and Regulations General § 1207.508 USDA costs. Pursuant to § 1207.341 of the Plan the Board shall...

7 CFR 1207.508 - USDA costs.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 10 2014-01-01 2014-01-01 false USDA costs. 1207.508 Section 1207.508 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Rules and Regulations General § 1207.508 USDA costs. Pursuant to § 1207.341 of the Plan the Board shall...

7 CFR 1207.508 - USDA costs.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false USDA costs. 1207.508 Section 1207.508 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Rules and Regulations General § 1207.508 USDA costs. Pursuant to § 1207.341 of the Plan the Board shall...

7 CFR 1207.508 - USDA costs.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 10 2012-01-01 2012-01-01 false USDA costs. 1207.508 Section 1207.508 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... Rules and Regulations General § 1207.508 USDA costs. Pursuant to § 1207.341 of the Plan the Board shall...

78 FR 19015 - Importer of Controlled Substances; Notice of Application; SA INTL GMBH C/O., Sigma Aldrich Co. LLC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer of Controlled Substances; Notice of Application; SA INTL GMBH C/O., Sigma Aldrich Co. LLC Pursuant to Title 21 Code of Federal Regulations 1301.34 (a), this is notice that on February 1, 2013, SA INTL GMBH C/O., Sigma Aldrich Co. LLC., 3500 Dekalb...

45 CFR 160.508 - Authority of the ALJ.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Authority of the ALJ. 160.508 Section 160.508 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES ADMINISTRATIVE DATA STANDARDS AND RELATED... scope and timing of documentary discovery as permitted by this subpart; (8) Regulate the course of the...

12 CFR 508.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... meaning of section 2(4) of the Home Owners' Loan Act of 1933, as amended, 12 U.S.C. 1462(4) (“HOLA”), an... 10(a)(1)(D) of the HOLA, 12 U.S.C. 1467a(a)(1)(D) and a subsidiary of a savings and loan holding...

12 CFR 508.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... meaning of section 2(4) of the Home Owners' Loan Act of 1933, as amended, 12 U.S.C. 1462(4) (“HOLA”), an... 10(a)(1)(D) of the HOLA, 12 U.S.C. 1467a(a)(1)(D) and a subsidiary of a savings and loan holding...

The role of cystic fibrosis transmembrane conductance regulator phenylalanine 508 side chain in ion channel gating

PubMed Central

Cui, Liying; Aleksandrov, Luba; Hou, Yue-Xian; Gentzsch, Martina; Chen, Jey-Hsin; Riordan, John R; Aleksandrov, Andrei A

2006-01-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel employing the ABC transporter structural motif. Deletion of a single residue (Phe508) in the first nucleotide-binding domain (NBD1), which occurs in most patients with cystic fibrosis, impairs both maturation and function of the protein. However, substitution of the Phe508 with small uncharged amino acids, including cysteine, is permissive for maturation. To explore the possible role of the phenylalanine aromatic side chain in channel gating we introduced a cysteine at this position in cysless CFTR, enabling its selective chemical modification by sulfhydryl reagents. Both cysless and wild-type CFTR ion channels have identical mean open times when activated by different nucleotide ligands. Moreover, both channels could be locked in an open state by introducing an ATPase inhibiting mutation (E1371S). However, the introduction of a single cysteine (F508C) prevented the cysless E1371S channel from maintaining the permanently open state, allowing closing to occur. Chemical modification of cysless E1371S/F508C by sulfhydryl reagents was used to probe the role of the side chain in ion channel function. Specifically, benzyl-methanethiosulphonate modification of this variant restored the gating behaviour to that of cysless E1371S containing the wild-type phenylalanine at position 508. This provides the first direct evidence that a specific interaction of the Phe508 aromatic side chain plays a role in determining the residency time in the closed state. Thus, despite the fact that this aromatic side chain is not essential for CFTR folding, it is important in the ion channel function. PMID:16484308

33 CFR 165.508 - Security Zone; Georgetown Channel, Potomac River, Washington, DC.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., Potomac River, Washington, DC. 165.508 Section 165.508 Navigation and Navigable Waters COAST GUARD... § 165.508 Security Zone; Georgetown Channel, Potomac River, Washington, DC. (a) Definitions. (1) The... zone: All waters of the Georgetown Channel of the Potomac River, from the surface to the bottom, 75...

33 CFR 165.508 - Security Zone; Georgetown Channel, Potomac River, Washington, DC.

Code of Federal Regulations, 2014 CFR

2014-07-01

..., Potomac River, Washington, DC. 165.508 Section 165.508 Navigation and Navigable Waters COAST GUARD... § 165.508 Security Zone; Georgetown Channel, Potomac River, Washington, DC. (a) Definitions. (1) The... zone: All waters of the Georgetown Channel of the Potomac River, from the surface to the bottom, 75...

33 CFR 165.508 - Security Zone; Georgetown Channel, Potomac River, Washington, DC.

Code of Federal Regulations, 2012 CFR

2012-07-01

..., Potomac River, Washington, DC. 165.508 Section 165.508 Navigation and Navigable Waters COAST GUARD... § 165.508 Security Zone; Georgetown Channel, Potomac River, Washington, DC. (a) Definitions. (1) The... zone: All waters of the Georgetown Channel of the Potomac River, from the surface to the bottom, 75...

33 CFR 165.508 - Security Zone; Georgetown Channel, Potomac River, Washington, DC.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., Potomac River, Washington, DC. 165.508 Section 165.508 Navigation and Navigable Waters COAST GUARD... § 165.508 Security Zone; Georgetown Channel, Potomac River, Washington, DC. (a) Definitions. (1) The... zone: All waters of the Georgetown Channel of the Potomac River, from the surface to the bottom, 75...

33 CFR 165.508 - Security Zone; Georgetown Channel, Potomac River, Washington, DC.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., Potomac River, Washington, DC. 165.508 Section 165.508 Navigation and Navigable Waters COAST GUARD... § 165.508 Security Zone; Georgetown Channel, Potomac River, Washington, DC. (a) Definitions. (1) The... zone: All waters of the Georgetown Channel of the Potomac River, from the surface to the bottom, 75...

12 CFR 508.7 - Conduct of hearings.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Conduct of hearings. 508.7 Section 508.7 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.7 Conduct of hearings. (a) Hearings provided by this...

12 CFR 508.5 - Petition for hearing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Petition for hearing. 508.5 Section 508.5 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.5 Petition for hearing. (a) To obtain a hearing, the...

12 CFR 508.6 - Initiation of hearing.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Initiation of hearing. 508.6 Section 508.6 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.6 Initiation of hearing. (a) Within 10 days of the filing...

12 CFR 508.9 - Rules of evidence.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Rules of evidence. 508.9 Section 508.9 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.9 Rules of evidence. (a) Formal rules of evidence shall...

41 CFR 101-26.508-3 - Consolidation of requisitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Consolidation of requisitions. 101-26.508-3 Section 101-26.508-3 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS SUPPLY AND PROCUREMENT 26-PROCUREMENT...

12 CFR 508.10 - Burden of persuasion.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 5 2011-01-01 2011-01-01 false Burden of persuasion. 508.10 Section 508.10 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.10 Burden of persuasion. The petitioner has the burden of...

12 CFR 508.10 - Burden of persuasion.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 Banks and Banking 6 2014-01-01 2012-01-01 true Burden of persuasion. 508.10 Section 508.10 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.10 Burden of persuasion. The petitioner has the burden of...

12 CFR 508.10 - Burden of persuasion.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 Banks and Banking 6 2013-01-01 2012-01-01 true Burden of persuasion. 508.10 Section 508.10 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.10 Burden of persuasion. The petitioner has the burden of...

12 CFR 508.10 - Burden of persuasion.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 Banks and Banking 6 2012-01-01 2012-01-01 false Burden of persuasion. 508.10 Section 508.10 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.10 Burden of persuasion. The petitioner has the burden of...

12 CFR 508.10 - Burden of persuasion.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Burden of persuasion. 508.10 Section 508.10 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.10 Burden of persuasion. The petitioner has the burden of...

ETC 408/508: Technical Editing

ERIC Educational Resources Information Center

Charlton, Michael

2013-01-01

ETC 408/508: Technical Editing is a cross-listed undergraduate and graduate course at Missouri Western State University, an open admissions public university with approximately 6,000 students. 508 is an elective course for students in the Master of Applied Arts in Written Communication degree and highly recommended for those in the Technical…

Biomechanical comparison of four C1 to C2 rigid fixative techniques: anterior transarticular, posterior transarticular, C1 to C2 pedicle, and C1 to C2 intralaminar screws.

PubMed

Lapsiwala, Samir B; Anderson, Paul A; Oza, Ashish; Resnick, Daniel K

2006-03-01

We performed a biomechanical comparison of several C1 to C2 fixation techniques including crossed laminar (intralaminar) screw fixation, anterior C1 to C2 transarticular screw fixation, C1 to 2 pedicle screw fixation, and posterior C1 to C2 transarticular screw fixation. Eight cadaveric cervical spines were tested intact and after dens fracture. Four different C1 to C2 screw fixation techniques were tested. Posterior transarticular and pedicle screw constructs were tested twice, once with supplemental sublaminar cables and once without cables. The specimens were tested in three modes of loading: flexion-extension, lateral bending, and axial rotation. All tests were performed in load and torque control. Pure bending moments of 2 nm were applied in flexion-extension and lateral bending, whereas a 1 nm moment was applied in axial rotation. Linear displacements were recorded from extensometers rigidly affixed to the C1 and C2 vertebrae. Linear displacements were reduced to angular displacements using trigonometry. Adding cable fixation results in a stiffer construct for posterior transarticular screws. The addition of cables did not affect the stiffness of C1 to C2 pedicle screw constructs. There were no significant differences in stiffness between anterior and posterior transarticular screw techniques, unless cable fixation was added to the posterior construct. All three posterior screw constructs with supplemental cable fixation provide equal stiffness with regard to flexion-extension and axial rotation. C1 lateral mass-C2 intralaminar screw fixation restored resistance to lateral bending but not to the same degree as the other screw fixation techniques. All four screw fixation techniques limit motion at the C1 to 2 articulation. The addition of cable fixation improves resistance to flexion and extension for posterior transarticular screw fixation.

In vitro cytotoxicity evaluation of a 50.8% NiTi single crystal.

PubMed

Manceur, Aziza; Chellat, Fatiha; Merhi, Yahye; Chumlyakov, Yuriy; Yahia, L'Hocine

2003-11-01

To our knowledge, the biocompatibility of nickel-titanium (NiTi) single crystals has not been reported. Yet certain orientations of single crystals present several advantages over the polycrystalline form in terms of maximal strain, fatigue resistance, and temperature range of superelasticity. Therefore we tested the in vitro biocompatibility of 50.8% NiTi single crystals in the orientation <001> after four different heat treatments in a helium atmosphere followed by mechanical polishing. The study was performed on the material extracts after immersion of the specimens in cell culture medium (DMEM) for 7 days at 37 degrees C. Cytotoxicity studies were performed on L-929 mouse fibroblasts using the MTT assay. J-774 macrophages were used to assess the potential inflammatory effect of the extracts by IL1-beta and TNF-alpha dosages (sandwich ELISA method). Exposure of L-929 to material extracts did not affect cell viability. In addition, IL1-beta and TNF-alpha secretion was not stimulated after incubation with NiTi extracts compared to the negative controls. These results were predictable since atomic absorption spectroscopy did not detect nickel ions in the extracts with a resolution of 1 ppm. Within the limits of in vitro testing, our results demonstrate that the TiNi(50.8%) single crystals do not trigger a cytotoxic reaction. Copyright 2003 Wiley Periodicals, Inc.

78 FR 77614 - Airworthiness Directives; Turbomeca S.A. Turboshaft Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-24

.... Turboshaft Engines AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking... Turbomeca S.A. Arriel 2B1 turboshaft engines that do not have modification TU157 incorporated. AD 2007-19... the compliance interval; and include the power turbine (C2) cycle consumption rate when determining...

Salinity/temperature ranges for application of seawater SA-T-P models

NASA Astrophysics Data System (ADS)

Marion, G. M.; Millero, F. J.; Feistel, R.

2009-01-01

At the present time, little is known about how broad salinity and temperature ranges are for seawater thermodynamic models that are functions of absolute salinity (SA), temperature (T) and pressure (P). Such models rely on fixed compositional ratios of the major components (e.g. Na/Cl, Mg/Cl, Ca/Cl, SO4/Cl, etc.). As seawater evaporates or freezes, solid phases (e.g. CaCO3(s) or CaSO42H2O(s)) will eventually precipitate. This will change the compositional ratios, and these salinity models will no longer be applicable. A future complicating factor is the lowering of seawater pH as the atmospheric concentrations of CO2 increase. A geochemical model (FREZCHEM) was used to quantify the SA-T boundaries at P=0.1 MPa and the range of these boundaries for future atmospheric CO2 increases. An omega supersaturation model for CaCO3 minerals based on homogeneous nucleation was extended from 25-40°C to 3°C. CaCO3 minerals were the boundary defining minerals (first to precipitate) between 3°C (at SA=104 g kg-1 and 40°C (at SA=66 g kg-1. At 2.82°C, calcite(CaCO3) transitioned to ikaite(CaCO36H2O) as the dominant boundary defining mineral for colder temperatures, which culminated in a low temperature boundary of -4.93°C. Increasing atmospheric CO2 from 385 μatm (in Year 2008) to 550 μatm (in Year 2100) would increase the SA and t boundaries as much as 11 g kg-1 and 0.66°C, respectively. The model-calculated calcite-ikaite transition temperature of 2.82°C is in excellent agreement with ikaite formation in natural environments that occurs at temperatures of 3°C or lower. Furthermore, these results provide a quantitative theoretical explanation (FREZCHEM model calculations) for why ikaite is the solid phase CaCO3 mineral that precipitates during seawater freezing.

Cohesin-SA1 deficiency drives aneuploidy and tumourigenesis in mice due to impaired replication of telomeres

PubMed Central

Remeseiro, Silvia; Cuadrado, Ana; Carretero, María; Martínez, Paula; Drosopoulos, William C; Cañamero, Marta; Schildkraut, Carl L; Blasco, María A; Losada, Ana

2012-01-01

Cohesin is a protein complex originally identified for its role in sister chromatid cohesion, although increasing evidence portrays it also as a major organizer of interphase chromatin. Vertebrate cohesin consists of Smc1, Smc3, Rad21/Scc1 and either stromal antigen 1 (SA1) or SA2. To explore the functional specificity of these two versions of cohesin and their relevance for embryonic development and cancer, we generated a mouse model deficient for SA1. Complete ablation of SA1 results in embryonic lethality, while heterozygous animals have shorter lifespan and earlier onset of tumourigenesis. SA1-null mouse embryonic fibroblasts show decreased proliferation and increased aneuploidy as a result of chromosome segregation defects. These defects are not caused by impaired centromeric cohesion, which depends on cohesin-SA2. Instead, they arise from defective telomere replication, which requires cohesion mediated specifically by cohesin-SA1. We propose a novel mechanism for aneuploidy generation that involves impaired telomere replication upon loss of cohesin-SA1, with clear implications in tumourigenesis. PMID:22415365

Genome-Wide Supported Risk Variants in MIR137, CACNA1C, CSMD1, DRD2, and GRM3 Contribute to Schizophrenia Susceptibility in Pakistani Population.

PubMed

Fatima, Ambrin; Farooq, Muhammad; Abdullah, Uzma; Tariq, Muhammad; Mustafa, Tanveer; Iqbal, Muhammad; Tommerup, Niels; Mahmood Baig, Shahid

2017-09-01

Schizophrenia is a chronic neuropsychiatric disease afflicting around 1.1% of the population worldwide. Recently, MIR137 , CACNA1C , CSMD1 , DRD2 , and GRM3 have been reported as the most robustly emerging candidates involved in the etiology of schizophrenia. In this case control study, we performed an association analysis of rs1625579 ( MIR137 ), rs1006737, rs4765905 ( CACNA1C ), rs10503253 ( CSMD1 ), rs1076560 ( DRD2 ), rs12704290, rs6465084, and rs148754219 ( GRM3 ) in Pakistani population. Schizophrenia was diagnosed on the basis of the Diagnostic and Statistical Manual of Mental Disorders 4th ed (DSM-IV). Detailed clinical information, family history of all patients and healthy controls were collected. RFLP based case control association study was performed in a Pakistani cohort of 508 schizophrenia patients and 300 healthy control subjects. Alleles and genotype frequencies were calculated using SPSS. A significant difference in the genotype and allele frequencies for rs4765905, rs1076560 and rs6465084 were found between the patients and controls (p=0.000). This study provides substantial evidence supporting the role of CACNA1C , GRM3 and DRD2 as schizophrenia susceptibility genes in Pakistani population.

An unexpected effect of TNF-α on F508del-CFTR maturation and function

PubMed Central

Bitam, Sara; Urbach, Valérie; Sermet-Gaudelus, Isabelle; Hinzpeter, Alexandre; Edelman, Aleksander

2015-01-01

Cystic fibrosis (CF) is a multifactorial disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene ( CFTR), which encodes a cAMP-dependent Cl - channel. The most frequent mutation, F508del, leads to the synthesis of a prematurely degraded, otherwise partially functional protein. CFTR is expressed in many epithelia, with major consequences in the airways of patients with CF, characterized by both fluid transport abnormalities and persistent inflammatory responses. The relationship between the acute phase of inflammation and the expression of wild type (WT) CFTR or F508del-CFTR is poorly understood. The aim of the present study was to investigate this effect. The results show that 10 min exposure to TNF-alpha (0.5-50ng/ml) of F508del-CFTR-transfected HeLa cells and human bronchial cells expressing F508del-CFTR in primary culture (HBE) leads to the maturation of F508del-CFTR and induces CFTR chloride currents. The enhanced CFTR expression and function upon TNFα is sustained, in HBE cells, for at least 24 h. The underlying mechanism of action involves a protein kinase C (PKC) signaling pathway, and occurs through insertion of vesicles containing F508del-CFTR to the plasma membrane, with TNFα behaving as a corrector molecule. In conclusion, a novel and unexpected action of TNFα has been discovered and points to the importance of systematic studies on the roles of inflammatory mediators in the maturation of abnormally folded proteins in general and in the context of CF in particular. PMID:26594334

18 CFR 50.8 - Acceptance/rejection of applications.

Code of Federal Regulations, 2010 CFR

2010-04-01

... applications. 50.8 Section 50.8 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT APPLICATIONS FOR PERMITS TO SITE INTERSTATE ELECTRIC TRANSMISSION FACILITIES § 50.8 Acceptance/rejection of applications. (a) Applications will be...

Word Frequency Analysis. MOS: 11C. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

EU .I~~k St.AAIWS6PPUTO.6 115 6 %CRRWi A SicURILY . ;u IPS ’.’’ 65pS - g* " ks - - (. S SIGAL 0S0LNT M Sirt STAKES * g1Pptl 6STRA ESIB S...a9. PMl 26 M0AY @,... oPC "N 409 6..TKING I C.LEgMSPTSP ..... ,,,.p5~IeM S.t MAS.,...AS.EI.....NUJOI So....~1.ap 1o MAY 10R.pClI AoS 0..7.T1, PI

46 CFR 185.508 - Wearing of life jackets.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Wearing of life jackets. 185.508 Section 185.508... TONS) OPERATIONS Preparations for Emergencies § 185.508 Wearing of life jackets. (a) The master of a vessel shall require passengers to don life jackets when possible hazardous conditions exist, including...

46 CFR 185.508 - Wearing of life jackets.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Wearing of life jackets. 185.508 Section 185.508... TONS) OPERATIONS Preparations for Emergencies § 185.508 Wearing of life jackets. (a) The master of a vessel shall require passengers to don life jackets when possible hazardous conditions exist, including...

46 CFR 185.508 - Wearing of life jackets.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false Wearing of life jackets. 185.508 Section 185.508... TONS) OPERATIONS Preparations for Emergencies § 185.508 Wearing of life jackets. (a) The master of a vessel shall require passengers to don life jackets when possible hazardous conditions exist, including...

46 CFR 185.508 - Wearing of life jackets.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false Wearing of life jackets. 185.508 Section 185.508... TONS) OPERATIONS Preparations for Emergencies § 185.508 Wearing of life jackets. (a) The master of a vessel shall require passengers to don life jackets when possible hazardous conditions exist, including...

46 CFR 185.508 - Wearing of life jackets.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false Wearing of life jackets. 185.508 Section 185.508... TONS) OPERATIONS Preparations for Emergencies § 185.508 Wearing of life jackets. (a) The master of a vessel shall require passengers to don life jackets when possible hazardous conditions exist, including...

22 CFR 50.8 - Certification of Report of Birth Abroad of a United States Citizen.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Certification of Report of Birth Abroad of a United States Citizen. 50.8 Section 50.8 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS... payment of the required fee, the Department of State's Passport Office may issue to the citizen, the...

22 CFR 50.8 - Certification of Report of Birth Abroad of a United States Citizen.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Certification of Report of Birth Abroad of a United States Citizen. 50.8 Section 50.8 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS... payment of the required fee, the Department of State's Passport Office may issue to the citizen, the...

22 CFR 50.8 - Certification of Report of Birth Abroad of a United States Citizen.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Certification of Report of Birth Abroad of a United States Citizen. 50.8 Section 50.8 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS... payment of the required fee, the Department of State's Passport Office may issue to the citizen, the...

22 CFR 50.8 - Certification of Report of Birth Abroad of a United States Citizen.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Certification of Report of Birth Abroad of a United States Citizen. 50.8 Section 50.8 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS... payment of the required fee, the Department of State's Passport Office may issue to the citizen, the...

22 CFR 50.8 - Certification of Report of Birth Abroad of a United States Citizen.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Certification of Report of Birth Abroad of a United States Citizen. 50.8 Section 50.8 Foreign Relations DEPARTMENT OF STATE NATIONALITY AND PASSPORTS... payment of the required fee, the Department of State's Passport Office may issue to the citizen, the...

Closed-loop control of SaO2 in the neonate.

PubMed

Morozoff, P E; Evans, R W

1992-01-01

A microprocessor-based device has been designed to control oxygen saturation (SaO2) in neonates by adjusting the inspired air-oxygen mixture (FiO2) delivered by a mechanical blender. The user sets a target SaO2, which the controller attempts to maintain. Alarms are actuated if the neonate's SaO2 is outside predefined limits. SaO2 levels are extracted from a commercial pulse oximeter and analyzed by an eight-bit microprocessing unit (MPU). Delivered percentages of FiO2 are adjusted by a motorized air-oxygen blender. The controller has a menu-driven user interface and can graphically present four-hour trends of the SaO2, FiO2, or blender setting. Sixteen hours of collected data can be stored and later downloaded to a personal computer. A real-time multitasking operating system forms the nucleus of the controller's software. Major tasks that share MPU time are control, filtering, user display, data collection, data archiving, alarm monitoring, and user input. Analog SaO2 levels are read and converted to digital values, which are then filtered to extract noise. A differential control algorithm is used to determine the required FiO2 blender setting. The blender is then adjusted to the new setting, after which the controller waits to repeat the process of sampling SaO2 and adjusting FiO2. System response time and blender increments are adjustable to allow a user to tune the controller to the patient's needs. Alarm conditions of concern within the device are SaO2 and FiO2 sensor disconnection, blender disconnection, and SaO2 limiting errors. In preliminary trials, for a target of 92.0% SaO2, a prototype controller maintained an average of 91.6% with a standard deviation of 5.0% over a one-hour period.(ABSTRACT TRUNCATED AT 250 WORDS)

14 CFR 1204.508 - Delegation of authority of certain civil rights functions to Department of Health, Education, and...

Code of Federal Regulations, 2012 CFR

2012-01-01

... rights functions to Department of Health, Education, and Welfare. 1204.508 Section 1204.508 Aeronautics... Delegations and Designations § 1204.508 Delegation of authority of certain civil rights functions to... responsible NASA official under Title VI, Civil Rights Act of 1964 (78 Stat. 252) (42 U.S.C. 2000d), with...

14 CFR 1204.508 - Delegation of authority of certain civil rights functions to Department of Health, Education, and...

Code of Federal Regulations, 2011 CFR

2011-01-01

... rights functions to Department of Health, Education, and Welfare. 1204.508 Section 1204.508 Aeronautics... Delegations and Designations § 1204.508 Delegation of authority of certain civil rights functions to... responsible NASA official under Title VI, Civil Rights Act of 1964 (78 Stat. 252) (42 U.S.C. 2000d), with...

14 CFR 1204.508 - Delegation of authority of certain civil rights functions to Department of Health, Education, and...

Code of Federal Regulations, 2010 CFR

2010-01-01

... rights functions to Department of Health, Education, and Welfare. 1204.508 Section 1204.508 Aeronautics... Delegations and Designations § 1204.508 Delegation of authority of certain civil rights functions to... responsible NASA official under Title VI, Civil Rights Act of 1964 (78 Stat. 252) (42 U.S.C. 2000d), with...

14 CFR 1204.508 - Delegation of authority of certain civil rights functions to Department of Health, Education, and...

Code of Federal Regulations, 2013 CFR

2013-01-01

... rights functions to Department of Health, Education, and Welfare. 1204.508 Section 1204.508 Aeronautics... Delegations and Designations § 1204.508 Delegation of authority of certain civil rights functions to... responsible NASA official under Title VI, Civil Rights Act of 1964 (78 Stat. 252) (42 U.S.C. 2000d), with...

A small-molecule modulator interacts directly with deltaPhe508-CFTR to modify its ATPase activity and conformational stability.

PubMed

Wellhauser, Leigh; Kim Chiaw, Patrick; Pasyk, Stan; Li, Canhui; Ramjeesingh, Mohabir; Bear, Christine E

2009-06-01

The deletion of Phe-508 (DeltaPhe508) constitutes the most prevalent of a number of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) that cause cystic fibrosis (CF). This mutation leads to CFTR misfolding and retention in the endoplasmic reticulum, as well as impaired channel activity. The biosynthetic defect can be partially overcome by small-molecule "correctors"; once at the cell surface, small-molecule "potentiators" enhance the channel activity of DeltaPhe508-CFTR. Certain compounds, such as VRT-532, exhibit both corrector and potentiator functions. In the current studies, we confirmed that the inherent chloride channel activity of DeltaPhe508-CFTR (after biosynthetic rescue) is potentiated in studies of intact cells and membrane vesicles. It is noteworthy that we showed that the ATPase activity of the purified and reconstituted mutant protein is directly modulated by binding of VRT-532 [4-methyl-2-(5-phenyl-1H-pyrazol-3-yl)-phenol] ATP turnover by reconstituted DeltaPhe508-CFTR is decreased by VRT-532 treatment, an effect that may account for the increase in channel open time induced by this compound. To determine whether the modification of DeltaPhe508-CFTR function caused by direct VRT-532 binding is associated with structural changes, we evaluated the effect of VRT-532 binding on the protease susceptibility of the major mutant. We found that binding of VRT-532 to DeltaPhe508-CFTR led to a minor but significant decrease in the trypsin susceptibility of the full-length mutant protein and a fragment encompassing the second half of the protein. These findings suggest that direct binding of this small molecule induces and/or stabilizes a structure that promotes the channel open state and may underlie its efficacy as a corrector of DeltaPhe508-CFTR.

Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population.

PubMed

Estrada, Karol; Aukrust, Ingvild; Bjørkhaug, Lise; Burtt, Noël P; Mercader, Josep M; García-Ortiz, Humberto; Huerta-Chagoya, Alicia; Moreno-Macías, Hortensia; Walford, Geoffrey; Flannick, Jason; Williams, Amy L; Gómez-Vázquez, María J; Fernandez-Lopez, Juan C; Martínez-Hernández, Angélica; Jiménez-Morales, Silvia; Centeno-Cruz, Federico; Mendoza-Caamal, Elvia; Revilla-Monsalve, Cristina; Islas-Andrade, Sergio; Córdova, Emilio J; Soberón, Xavier; González-Villalpando, María E; Henderson, E; Wilkens, Lynne R; Le Marchand, Loic; Arellano-Campos, Olimpia; Ordóñez-Sánchez, Maria L; Rodríguez-Torres, Maribel; Rodríguez-Guillén, Rosario; Riba, Laura; Najmi, Laeya A; Jacobs, Suzanne B R; Fennell, Timothy; Gabriel, Stacey; Fontanillas, Pierre; Hanis, Craig L; Lehman, Donna M; Jenkinson, Christopher P; Abboud, Hanna E; Bell, Graeme I; Cortes, Maria L; Boehnke, Michael; González-Villalpando, Clicerio; Orozco, Lorena; Haiman, Christopher A; Tusié-Luna, Teresa; Aguilar-Salinas, Carlos A; Altshuler, David; Njølstad, Pål R; Florez, Jose C; MacArthur, Daniel G

2014-06-11

Latino populations have one of the highest prevalences of type 2 diabetes worldwide. To investigate the association between rare protein-coding genetic variants and prevalence of type 2 diabetes in a large Latino population and to explore potential molecular and physiological mechanisms for the observed relationships. Whole-exome sequencing was performed on DNA samples from 3756 Mexican and US Latino individuals (1794 with type 2 diabetes and 1962 without diabetes) recruited from 1993 to 2013. One variant was further tested for allele frequency and association with type 2 diabetes in large multiethnic data sets of 14,276 participants and characterized in experimental assays. Prevalence of type 2 diabetes. Secondary outcomes included age of onset, body mass index, and effect on protein function. A single rare missense variant (c.1522G>A [p.E508K]) was associated with type 2 diabetes prevalence (odds ratio [OR], 5.48; 95% CI, 2.83-10.61; P = 4.4 × 10(-7)) in hepatocyte nuclear factor 1-α (HNF1A), the gene responsible for maturity onset diabetes of the young type 3 (MODY3). This variant was observed in 0.36% of participants without type 2 diabetes and 2.1% of participants with it. In multiethnic replication data sets, the p.E508K variant was seen only in Latino patients (n = 1443 with type 2 diabetes and 1673 without it) and was associated with type 2 diabetes (OR, 4.16; 95% CI, 1.75-9.92; P = .0013). In experimental assays, HNF-1A protein encoding the p.E508K mutant demonstrated reduced transactivation activity of its target promoter compared with a wild-type protein. In our data, carriers and noncarriers of the p.E508K mutation with type 2 diabetes had no significant differences in compared clinical characteristics, including age at onset. The mean (SD) age for carriers was 45.3 years (11.2) vs 47.5 years (11.5) for noncarriers (P = .49) and the mean (SD) BMI for carriers was 28.2 (5.5) vs 29.3 (5.3) for noncarriers (P = .19). Using whole-exome sequencing

Rescue of murine F508del CFTR activity in native intestine by low temperature and proteasome inhibitors.

PubMed

Wilke, Martina; Bot, Alice; Jorna, Huub; Scholte, Bob J; de Jonge, Hugo R

2012-01-01

Most patients with Cystic Fibrosis (CF) carry at least one allele with the F508del mutation, resulting in a CFTR chloride channel protein with a processing, gating and stability defect, but with substantial residual activity when correctly sorted to the apical membranes of epithelial cells. New therapies are therefore aimed at improving the folding and trafficking of F508del CFTR, (CFTR correctors) or at enhancing the open probability of the CFTR chloride channel (CFTR potentiators). Preventing premature breakdown of F508del CFTR is an alternative or additional strategy, which is investigated in this study. We established an ex vivo assay for murine F508del CFTR rescue in native intestinal epithelium that can be used as a pre-clinical test for candidate therapeutics. Overnight incubation of muscle stripped ileum in modified William's E medium at low temperature (26°C), and 4 h or 6 h incubation at 37°C with different proteasome inhibitors (PI: ALLN, MG-132, epoxomicin, PS341/bortezomib) resulted in fifty to hundred percent respectively of the wild type CFTR mediated chloride secretion (forskolin induced short-circuit current). The functional rescue was accompanied by enhanced expression of the murine F508del CFTR protein at the apical surface of intestinal crypts and a gain in the amount of complex-glycosylated CFTR (band C) up to 20% of WT levels. Sustained rescue in the presence of brefeldin A shows the involvement of a post-Golgi compartment in murine F508del CFTR degradation, as was shown earlier for its human counterpart. Our data show that proteasome inhibitors are promising candidate compounds for improving rescue of human F508del CFTR function, in combination with available correctors and potentiators.

Sodium 4-phenylbutyrate downregulates Hsc70: implications for intracellular trafficking of DeltaF508-CFTR.

PubMed

Rubenstein, R C; Zeitlin, P L

2000-02-01

The most common mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), DeltaF508, is a trafficking mutant that has prolonged associations with molecular chaperones and is rapidly degraded, at least in part by the ubiquitin-proteasome system. Sodium 4-phenylbutyrate (4PBA) improves DeltaF508-CFTR trafficking and function in vitro in cystic fibrosis epithelial cells and in vivo. To further understand the mechanism of action of 4PBA, we tested the hypothesis that 4PBA modulates the targeting of DeltaF508-CFTR for ubiquitination and degradation by reducing the expression of Hsc70 in cystic fibrosis epithelial cells. IB3-1 cells (genotype DeltaF508/W1282X) that were treated with 0.05-5 mM 4PBA for 2 days in culture demonstrated a dose-dependent reduction in Hsc70 protein immunoreactivity and mRNA levels. Immunoprecipitation with Hsc70-specific antiserum demonstrated that Hsc70 and CFTR associated under control conditions and that treatment with 4PBA reduced these complexes. Levels of immunoreactive Hsp40, Hdj2, Hsp70, Hsp90, and calnexin were unaffected by 4PBA treatment. These data suggest that 4PBA may improve DeltaF508-CFTR trafficking by allowing a greater proportion of mutant CFTR to escape association with Hsc70.

12 CFR 508.13 - Decision of the Office.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Decision of the Office. 508.13 Section 508.13 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.13 Decision of the Office. (a) Within 30 days after the recommended decision has been certifie...

47 CFR 54.508 - Technology plans.

Code of Federal Regulations, 2011 CFR

2011-10-01

... SERVICE Universal Service Support for Schools and Libraries § 54.508 Technology plans. (a) Applicants must... for using telecommunications and information technology to improve education or library services; (2... technologies to improve education or library services; (3) An assessment of the telecommunication services...

47 CFR 54.508 - Technology plans.

Code of Federal Regulations, 2012 CFR

2012-10-01

... SERVICE Universal Service Support for Schools and Libraries § 54.508 Technology plans. (a) Applicants must... for using telecommunications and information technology to improve education or library services; (2... technologies to improve education or library services; (3) An assessment of the telecommunication services...

Acoustic performance of a 50.8-cm (20-inch) diameter variable-pitch fan and inlet. Volume 2: Acoustic data

NASA Technical Reports Server (NTRS)

Bilwakesh, K. R.; Clemons, A.; Stimpert, D. L.

1979-01-01

Results from acoustic tests on a 50.8 cm (20 inch) QCSEE Under-the-Wing (UTW) engine, variable pitch fan and inlet simulator are tabulated. Tests were run in both forward and reverse thrust mdoes with a bellmouth inlet, five accelerating inlets (one hardwall and four treated), and four low Mach number inlets (one hardwall and three treated). The 1/3 octave-band acoustic data are presented for the model size on the measured 5.2 m (17.0 ft) arc and also data scaled to full QCSEE size 71:20 on a 152.4 m (500 ft) sideline.

40 CFR 50.8 - National primary ambient air quality standards for carbon monoxide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 2 2010-07-01 2010-07-01 false National primary ambient air quality standards for carbon monoxide. 50.8 Section 50.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS NATIONAL PRIMARY AND SECONDARY AMBIENT AIR QUALITY STANDARDS § 50.8 National primary ambient air quality standards for...

40 CFR 50.8 - National primary ambient air quality standards for carbon monoxide.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 2 2014-07-01 2014-07-01 false National primary ambient air quality standards for carbon monoxide. 50.8 Section 50.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS NATIONAL PRIMARY AND SECONDARY AMBIENT AIR QUALITY STANDARDS § 50.8 National primary ambient air quality standards for...

40 CFR 50.8 - National primary ambient air quality standards for carbon monoxide.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 2 2012-07-01 2012-07-01 false National primary ambient air quality standards for carbon monoxide. 50.8 Section 50.8 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS NATIONAL PRIMARY AND SECONDARY AMBIENT AIR QUALITY STANDARDS § 50.8 National primary ambient air quality standards for...

Synergy-based small-molecule screen using a human lung epithelial cell line yields ΔF508-CFTR correctors that augment VX-809 maximal efficacy.

PubMed

Phuan, Puay-Wah; Veit, Guido; Tan, Joseph; Roldan, Ariel; Finkbeiner, Walter E; Lukacs, Gergely L; Verkman, A S

2014-07-01

The most prevalent cystic fibrosis transmembrane conductance regulator (CFTR) mutation causing cystic fibrosis, ΔF508, impairs folding of nucleotide binding domain (NBD) 1 and stability of the interface between NBD1 and the membrane-spanning domains. The interfacial stability defect can be partially corrected by the investigational drug VX-809 (3-[6-[[[1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl]amino]-3-methyl-2-pyridinyl]-benzoic acid) or the R1070W mutation. Second-generation ΔF508-CFTR correctors are needed to improve on the modest efficacy of existing cystic fibrosis correctors. We postulated that a second corrector targeting a distinct folding/interfacial defect might act in synergy with VX-809 or the R1070W suppressor mutation. A biochemical screen for ΔF508-CFTR cell surface expression was developed in a human lung epithelium-derived cell line (CFBE41o(-)) by expressing chimeric CFTRs with a horseradish peroxidase (HRP) in the fourth exofacial loop in either the presence or absence of R1070W. Using a luminescence readout of HRP activity, screening of approximately 110,000 small molecules produced nine novel corrector scaffolds that increased cell surface ∆F508-CFTR expression by up to 200% in the presence versus absence of maximal VX-809. Further screening of 1006 analogs of compounds identified from the primary screen produced 15 correctors with an EC50 < 5 µM. Eight chemical scaffolds showed synergy with VX-809 in restoring chloride permeability in ∆F508-expressing A549 cells. An aminothiazole increased chloride conductance in human bronchial epithelial cells from a ΔF508 homozygous subject beyond that of maximal VX-809. Mechanistic studies suggested that NBD2 is required for the aminothiazole rescue. Our results provide proof of concept for synergy screening to identify second-generation correctors, which, when used in combination, may overcome the "therapeutic ceiling" of first-generation correctors. Copyright © 2014 by The

Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells

PubMed Central

Stanton, Bruce A.; Coutermarsh, Bonita; Barnaby, Roxanna; Hogan, Deborah

2015-01-01

Background P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770. Methods and Results F508del-CFBE cells and primary cultures of CF-HBE cells (F508del/F508del) were exposed to VX-809 alone or a combination of VX-809 + VX-770 for 48 hours and the effect of P. aeruginosa on F508del-CFTR Cl secretion was measured in Ussing chambers. The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. PAO1, PA14, PAK and 6 clinical isolates of P. aeruginosa (3 mucoid and 3 non-mucoid) significantly reduced drug stimulated F508del-CFTR Cl secretion, and plasma membrane F508del-CFTR. Conclusion The observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials. PMID:26018799

Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells.

PubMed

Stanton, Bruce A; Coutermarsh, Bonita; Barnaby, Roxanna; Hogan, Deborah

2015-01-01

P. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770. F508del-CFBE cells and primary cultures of CF-HBE cells (F508del/F508del) were exposed to VX-809 alone or a combination of VX-809 + VX-770 for 48 hours and the effect of P. aeruginosa on F508del-CFTR Cl secretion was measured in Ussing chambers. The effect of VX-809 on F508del-CFTR abundance was measured by cell surface biotinylation and western blot analysis. PAO1, PA14, PAK and 6 clinical isolates of P. aeruginosa (3 mucoid and 3 non-mucoid) significantly reduced drug stimulated F508del-CFTR Cl secretion, and plasma membrane F508del-CFTR. The observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials.

Study on Material Selection of Reactor Pressure Vessel of SCWR

NASA Astrophysics Data System (ADS)

Ma, Shuli; Luo, Ying; Yin, Qinwei; Li, Changxiang; Xie, Guofu

This paper first analyzes the feasibility of SA-508 Grade 3 Class 1 Steel as an alternative material for Supercritical Water-Cooled Reactor (SCWR) Reactor Pressure Vessel (RPV). This kind of steel is limited to be applied in SCWR RPV due to its quenching property, though large forging could be accomplished by domestic manufacturers in forging aspect. Therefore, steels with higher strength and better quenching property are needed for SWCR RPV. The chemical component of SA-508 Gr.3 Cl.2 steel is similar to that of SA-508 Gr.3 Cl.1 steel, and more appropriate matching of strength and toughness could be achieved by the adjusting the elements contents, as well as proper control of tempering temperature and time. In light of the fact that Cl.2 steel has been successfully applied to steam generator, it could be an alternative material for SWCR RPV. SA-508 Gr.4N steel with high strength and good toughness is another alternative material for SCWR RPV. But large amount of research work before application is still needed for the lack of data on welding and irradiation etc.

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression

PubMed Central

Veit, Guido; Avramescu, Radu G.; Perdomo, Doranda; Phuan, Puay-Wah; Bagdany, Miklos; Apaja, Pirjo M.; Borot, Florence; Szollosi, Daniel; Wu, Yu-Sheng; Finkbeiner, Walter E.; Hegedus, Tamas; Verkman, Alan S.; Lukacs, Gergely L.

2015-01-01

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770–induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)–NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF. PMID:25101887

14 CFR § 1204.508 - Delegation of authority of certain civil rights functions to Department of Health, Education, and...

Code of Federal Regulations, 2014 CFR

2014-01-01

... rights functions to Department of Health, Education, and Welfare. § 1204.508 Section § 1204.508... Delegations and Designations § 1204.508 Delegation of authority of certain civil rights functions to... responsible NASA official under Title VI, Civil Rights Act of 1964 (78 Stat. 252) (42 U.S.C. 2000d), with...

50 CFR 600.508 - Fishing operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Fishing operations. 600.508 Section 600... ADMINISTRATION, DEPARTMENT OF COMMERCE MAGNUSON-STEVENS ACT PROVISIONS Foreign Fishing § 600.508 Fishing.... fishing vessels. These joint venture operations with U.S. fishing vessels may be conducted throughout the...

50 CFR 600.508 - Fishing operations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Fishing operations. 600.508 Section 600... ADMINISTRATION, DEPARTMENT OF COMMERCE MAGNUSON-STEVENS ACT PROVISIONS Foreign Fishing § 600.508 Fishing.... fishing vessels. These joint venture operations with U.S. fishing vessels may be conducted throughout the...

50 CFR 600.508 - Fishing operations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 12 2014-10-01 2014-10-01 false Fishing operations. 600.508 Section 600... ADMINISTRATION, DEPARTMENT OF COMMERCE MAGNUSON-STEVENS ACT PROVISIONS Foreign Fishing § 600.508 Fishing.... fishing vessels. These joint venture operations with U.S. fishing vessels may be conducted throughout the...

50 CFR 600.508 - Fishing operations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Fishing operations. 600.508 Section 600... ADMINISTRATION, DEPARTMENT OF COMMERCE MAGNUSON-STEVENS ACT PROVISIONS Foreign Fishing § 600.508 Fishing.... fishing vessels. These joint venture operations with U.S. fishing vessels may be conducted throughout the...

Stabilization of Giant Fullerenes C2(41)-C90, D3(85)-C92, C1(132)-C94, C2(157)-C96, and C1(175)-C98 by Encapsulation of a Large La2C2 Cluster: The Importance of Cluster-Cage Matching.

PubMed

Zhao, Shasha; Zhao, Pei; Cai, Wenting; Bao, Lipiao; Chen, Muqing; Xie, Yunpeng; Zhao, Xiang; Lu, Xing

2017-04-05

Successful isolation and unambiguous crystallographic assignment of a series of higher carbide cluster metallofullerenes present new insights into the molecular structures and cluster-cage interactions of endohedral metallofullerenes. These new species are identified as La 2 C 2 @C 2 (41)-C 90 , La 2 C 2 @D 3 (85)-C 92 , La 2 C 2 @C 1 (132)-C 94 , La 2 C 2 @C 2 (157)-C 96 , and La 2 C 2 @C 1 (175)-C 98 . This is the first report for these new cage structures except for D 3 (85)-C 92 . Our experimental and theoretical results demonstrate that La 2 C 92-106 are more inclined to exist stably in the carbide form La 2 C 2 @C 90-104 rather than as the dimetallofullerenes La 2 @C 92-106 , which are rationalized by considering a synergistic effect of inserting a C 2 unit into the cage, which ensures strong metal-cage interactions by partially neutralizing the charges from the metal ions and by fulfilling the coordination requirement of the La 3+ ions as much as possible.

Chromomycin SA analogs from a marine-derived Streptomyces sp.

PubMed Central

Hu, Youcai; Espindola, Ana Paula D. M; Stewart, Nathan A.; Wei, Shuguang; Posner, Bruce A.; MacMillan, John B.

2011-01-01

Two chromomycin SA analogs, chromomycin SA3 and chromomycin SA2, along with deacetylchromomycin A3 and five previously reported chromomycin analogs were isolated from a marine-derived Streptomyces sp. The structures of the new compounds were determined by spectroscopic methods including 1D and 2D NMR techniques, HRMS and chemical methods. Chromomycin SA3 and chromomycin SA2 are the first naturally occuring chromomycin analogs with truncated side-chains. Biological evaluation of chromomycin analogs for cytotoxicity against two non-small cell lung cancer (NSCLC) cell-lines, A549 and HCC44, demonstrated a decrease in cytotoxicity for the truncated sides chain chromomycin analogs. PMID:21807523

Non-native Conformers of Cystic Fibrosis Transmembrane Conductance Regulator NBD1 Are Recognized by Hsp27 and Conjugated to SUMO-2 for Degradation.

PubMed

Gong, Xiaoyan; Ahner, Annette; Roldan, Ariel; Lukacs, Gergely L; Thibodeau, Patrick H; Frizzell, Raymond A

2016-01-22

A newly identified pathway for selective degradation of the common mutant of the cystic fibrosis transmembrane conductance regulator (CFTR), F508del, is initiated by binding of the small heat shock protein, Hsp27. Hsp27 collaborates with Ubc9, the E2 enzyme for protein SUMOylation, to selectively degrade F508del CFTR via the SUMO-targeted ubiquitin E3 ligase, RNF4 (RING finger protein 4) (1). Here, we ask what properties of CFTR are sensed by the Hsp27-Ubc9 pathway by examining the ability of NBD1 (locus of the F508del mutation) to mimic the disposal of full-length (FL) CFTR. Similar to FL CFTR, F508del NBD1 expression was reduced 50-60% by Hsp27; it interacted preferentially with the mutant and was modified primarily by SUMO-2. Mutation of the consensus SUMOylation site, Lys(447), obviated Hsp27-mediated F508del NBD1 SUMOylation and degradation. As for FL CFTR and NBD1 in vivo, SUMO modification using purified components in vitro was greater for F508del NBD1 versus WT and for the SUMO-2 paralog. Several findings indicated that Hsp27-Ubc9 targets the SUMOylation of a transitional, non-native conformation of F508del NBD1: (a) its modification decreased as [ATP] increased, reflecting stabilization of the nucleotide-binding domain by ligand binding; (b) a temperature-induced increase in intrinsic fluorescence, which reflects formation of a transitional NBD1 conformation, was followed by its SUMO modification; and (c) introduction of solubilizing or revertant mutations to stabilize F508del NBD1 reduced its SUMO modification. These findings indicate that the Hsp27-Ubc9 pathway recognizes a non-native conformation of mutant NBD1, which leads to its SUMO-2 conjugation and degradation by the ubiquitin-proteasome system. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

41 CFR 105-72.508 - Contract provisions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... instances in which a contractor violates or breaches the contract terms, and provide for such remedial... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Contract provisions. 105-72.508 Section 105-72.508 Public Contracts and Property Management Federal Property Management...

Ether modifications to 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine (SA4503): effects on binding affinity and selectivity for sigma receptors and monoamine transporters.

PubMed

Xu, Rong; Lord, Sarah A; Peterson, Ryan M; Fergason-Cantrell, Emily A; Lever, John R; Lever, Susan Z

2015-01-01

Two series of novel ether analogs of the sigma (σ) receptor ligand 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazine (SA4503) have been prepared. In one series, the alkyl portion of the 4-methoxy group was replaced with allyl, propyl, bromoethyl, benzyl, phenethyl, and phenylpropyl moieties. In the second series, the 3,4-dimethoxy was replaced with cyclic methylenedioxy, ethylenedioxy and propylenedioxy groups. These ligands, along with 4-O-des-methyl SA4503, were evaluated for σ1 and σ2 receptor affinity, and compared to SA4503 and several known ether analogs. SA4503 and a subset of ether analogs were also evaluated for dopamine transporter (DAT) and serotonin transporter (SERT) affinity. The highest σ1 receptor affinities, Ki values of 1.75-4.63 nM, were observed for 4-O-des-methyl SA4503, SA4503 and the methylenedioxy analog. As steric bulk increased, σ1 receptor affinity decreased, but only to a point. Allyl, propyl and bromoethyl substitutions gave σ1 receptor Ki values in the 20-30 nM range, while bulkier analogs having phenylalkyl, and Z- and E-iodoallyl, ether substitutions showed higher σ1 affinities, with Ki values in the 13-21 nM range. Most ligands studied exhibited comparable σ1 and σ2 affinities, resulting in little to no subtype selectivity. SA4503, the fluoroethyl analog and the methylenedioxy congener showed modest six- to fourteen-fold selectivity for σ1 sites. DAT and SERT interactions proved much more sensitive than σ receptor interactions to these structural modifications. For example, the benzyl congener (σ1Ki=20.8 nM; σ2Ki=16.4 nM) showed over 100-fold higher DAT affinity (Ki=121 nM) and 6-fold higher SERT affinity (Ki=128nM) than the parent SA4503 (DAT Ki=12650 nM; SERT Ki=760 nM). Thus, ether modifications to the SA4503 scaffold can provide polyfunctional ligands having a broader spectrum of possible pharmacological actions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Manipulating proteostasis to repair the F508del-CFTR defect in cystic fibrosis.

PubMed

Esposito, Speranza; Tosco, Antonella; Villella, Valeria R; Raia, Valeria; Kroemer, Guido; Maiuri, Luigi

2016-12-01

Cystic fibrosis (CF) is a lethal monogenic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that entails the (diagnostic) increase in sweat electrolyte concentrations, progressive lung disease with chronic inflammation and recurrent bacterial infections, pancreatic insufficiency, and male infertility. Therapies aimed at restoring the CFTR defect have emerged. Thus, a small molecule which facilitates chloride channel opening, the potentiator Ivacaftor, has been approved for the treatment of CF patients bearing a particular class of rare CFTR mutations. However, small molecules that directly target the most common misfolded CFTR mutant, F508del, and improve its intracellular trafficking in vitro, have been less effective than expected when tested in CF patients, even in combination with Ivacaftor. Thus, new strategies are required to circumvent the F508del-CFTR defect. Airway and intestinal epithelial cells from CF patients bearing the F508del-CFTR mutation exhibit an impressive derangement of cellular proteostasis, with oxidative stress, overactivation of the tissue transglutaminase (TG2), and disabled autophagy. Proteostasis regulators such as cysteamine can rescue and stabilize a functional F508del-CFTR protein through suppressing TG2 activation and restoring autophagy in vivo in F508del-CFTR homozygous mice, in vitro in CF patient-derived cell lines, ex vivo in freshly collected primary patient's nasal cells, as well as in a pilot clinical trial involving homozygous F508del-CFTR patients. Here, we discuss how the therapeutic normalization of defective proteostasis can be harnessed for the treatment of CF patients with the F508del-CFTR mutation.

Small molecule correctors of F508del-CFTR discovered by structure-based virtual screening

NASA Astrophysics Data System (ADS)

Kalid, Ori; Mense, Martin; Fischman, Sharon; Shitrit, Alina; Bihler, Hermann; Ben-Zeev, Efrat; Schutz, Nili; Pedemonte, Nicoletta; Thomas, Philip J.; Bridges, Robert J.; Wetmore, Diana R.; Marantz, Yael; Senderowitz, Hanoch

2010-12-01

Folding correctors of F508del-CFTR were discovered by in silico structure-based screening utilizing homology models of CFTR. The intracellular segment of CFTR was modeled and three cavities were identified at inter-domain interfaces: (1) Interface between the two Nucleotide Binding Domains (NBDs); (2) Interface between NBD1 and Intracellular Loop (ICL) 4, in the region of the F508 deletion; (3) multi-domain interface between NBD1:2:ICL1:2:4. We hypothesized that compounds binding at these interfaces may improve the stability of the protein, potentially affecting the folding yield or surface stability. In silico structure-based screening was performed at the putative binding-sites and a total of 496 candidate compounds from all three sites were tested in functional assays. A total of 15 compounds, representing diverse chemotypes, were identified as F508del folding correctors. This corresponds to a 3% hit rate, tenfold higher than hit rates obtained in corresponding high-throughput screening campaigns. The same binding sites also yielded potentiators and, most notably, compounds with a dual corrector-potentiator activity (dual-acting). Compounds harboring both activity types may prove to be better leads for the development of CF therapeutics than either pure correctors or pure potentiators. To the best of our knowledge this is the first report of structure-based discovery of CFTR modulators.

Installation Restoration Program. Phase 2. Confirmation/Quantification. Stage 1. Air Force Plant 4, Fort Worth, Texas. Volume 5. Appendix A-2.

DTIC Science & Technology

1987-12-01

Limit Spiked Samale Samole ISailced C" auod R sIus’lt (SSR) esult. (SR) A-dded ( .SA) Iels: I. I 1. A.luminum 75-125 - I Z. Antimony - 3. Arsenic " I...UntKtarix *s %Control Limit Spiked Samale Sample SieiCm.,ound _ _R R esult (SSR) Re t,.- (SR) Added (SA) Z,10 1. AUlunu m 7 I I I 2. Antimonyj ____ 3...No. DATE Lab Sample) ;S4 No Katrix waot, " . n ...Central L imi Spiked Samale Samale Spiked Comnpound M Rsult: (SSR) Result (SR) jAdded (SA) XR

Curcumin/poly(2-methyl-2-oxazoline-b-tetrahydrofuran-b-2-methyl-2-oxazoline) formulation: An improved penetration and biological effect of curcumin in F508del-CFTR cell lines.

PubMed

Gonçalves, Cristine; Gomez, Jean-Pierre; Même, William; Rasolonjatovo, Bazoly; Gosset, David; Nedellec, Steven; Hulin, Philippe; Huin, Cécile; Le Gall, Tony; Montier, Tristan; Lehn, Pierre; Pichon, Chantal; Guégan, Philippe; Cheradame, Hervé; Midoux, Patrick

2017-08-01

Neutral amphiphilic triblock ABA copolymers are of great interest to solubilize hydrophobic drugs. We reported that a triblock ABA copolymer consisting of methyl-2-oxazoline (MeOx) and tetrahydrofuran (THF) (MeOx 6 -THF 19 -MeOx 6 ) (TBCP2) can solubilize curcumin (Cur) a very hydrophobic molecule exhibiting multiple therapeutic effects but whose insolubility and low stability in water is a major drawback for clinical applications. Here, we provide evidences by flow cytometry and confocal microscopy that Cur penetration in normal and ΔF508-CFTR human airway epithelial cell lines is facilitated by TBCP2. When used on ΔF508-CFTR cell lines, the Cur/TBCP2 formulation promotes the restoration of the expression of the CFTR protein in the plasma membrane. Furthermore, patch-clamp and MQAE fluorescence experiments show that this effect is associated with a correction of a Cl - selective current at the membrane surface of F508del-CFTR cells. The results show the great potential of the neutral amphiphilic triblock copolymer MeOx 6 -THF 19 -MeOx 6 as carrier for curcumin in a Cystic Fibrosis context. We anticipate that other MeOx n -THF m -MeOx n copolymers could have similar behaviours for other highly insoluble therapeutic drugs or cosmetic active ingredients. Copyright © 2017 Elsevier B.V. All rights reserved.

Four Novel p.N385K, p.V36A, c.1033–1034insT and c.1417–1418delCT Mutations in the Sphingomyelin Phosphodiesterase 1 (SMPD1) Gene in Patients with Types A and B Niemann-Pick Disease (NPD)

PubMed Central

Manshadi, Masoumeh Dehghan; Kamalidehghan, Behnam; Keshavarzi, Fatemeh; Aryani, Omid; Dadgar, Sepideh; Arastehkani, Ahoora; Tondar, Mahdi; Ahmadipour, Fatemeh; Meng, Goh Yong; Houshmand, Massoud

2015-01-01

Background: Types A and B Niemann-Pick disease (NPD) are autosomal-recessive lysosomal storage disorders caused by the deficient activity of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene. Methods: In order to determine the prevalence and distribution of SMPD1 gene mutations, the genomic DNA of 15 unrelated Iranian patients with types A and B NPD was examined using PCR, DNA sequencing and bioinformatics analysis. Results: Of 8 patients with the p.G508R mutation, 5 patients were homozygous, while the other 3 were heterozygous. One patient was heterozygous for both the p.N385K and p.G508R mutations. Another patient was heterozygous for both the p.A487V and p.G508R mutations. Two patients (one homozygous and one heterozygous) showed the p.V36A mutation. One patient was homozygous for the c.1033–1034insT mutation. One patient was homozygous for the c.573delT mutation, and 1 patient was homozygous for the c.1417–1418delCT mutation. Additionally, bioinformatics analysis indicated that two new p.V36A and p.N385K mutations decreased the acid sphingomyelinase (ASM) protein stability, which might be evidence to suggest the pathogenicity of these mutations. Conclusion: with detection of these new mutations, the genotypic spectrum of types A and B NPD is extended, facilitating the definition of disease-related mutations. However, more research is essential to confirm the pathogenic effect of these mutations. PMID:25811928

Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression.

PubMed

Veit, Guido; Avramescu, Radu G; Perdomo, Doranda; Phuan, Puay-Wah; Bagdany, Miklos; Apaja, Pirjo M; Borot, Florence; Szollosi, Daniel; Wu, Yu-Sheng; Finkbeiner, Walter E; Hegedus, Tamas; Verkman, Alan S; Lukacs, Gergely L

2014-07-23

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770-induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)-NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF. Copyright © 2014, American Association for the Advancement of Science.

[Pseudo-Bartter syndrome as manifestation of cystic fibrosis with DF508 mutation].

PubMed

Galaviz-Ballesteros, María de Jesús; Acosta-Rodríguez-Bueno, Carlos Patricio; Consuelo-Sánchez, Alejandra; Franco-Álvarez, Isidro; Olalla-Mora, Odilo Iván; Vázquez-Frias, Rodrigo

Pseudo Bartter syndrome (PBS) is defined as hypokalaemic hypochloraemic metabolic alkalosis in the absence of renal tubular pathology. Children with cystic fibrosis (CF) are at risk of developing electrolyte abnormalities and even PBS may occur. 5 months old female infant with a history of two events of dehydration with vomit, refusal to eat, chronic cough, polyuria, malnutrition, metabolic alkalosis, hypokalemia, hyponatremia, hypochloremia and acute renal failure. Chronic cough study was performed, discarding pulmonary tuberculosis, gastroesophageal reflux disease and impaired swallowing. PBS was diagnosed due to hypokalaemic hypochloraemic metabolic alkalosis in the absence of renal tubular pathology. CF was corroborated by electrolytes in sweat and through molecular analysis of the delta F508 mutation. This is one of the few reported cases linking PBS and this mutation. In patients with hyponatremic dehydration episodes with hypokalaemic hypochloraemic metabolic alkalosis, PBS should be considered as differential diagnosis. CF could be presented as PBS, mainly in patients younger than 2 years. Copyright © 2016 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

High resolution spectroscopy of jet cooled phenyl radical: The ν1 and ν2 a1 symmetry C-H stretching modes

NASA Astrophysics Data System (ADS)

Chang, Chih-Hsuan; Nesbitt, David J.

2016-07-01

A series of CH stretch modes in phenyl radical (C6H5) has been investigated via high resolution infrared spectroscopy at sub-Doppler resolution (˜60 MHz) in a supersonic discharge slit jet expansion. Two fundamental vibrations of a1 symmetry, ν1 and ν2, are observed and rotationally analyzed for the first time, corresponding to in-phase and out-of-phase symmetric CH stretch excitation at the ortho/meta/para and ortho/para C atoms with respect to the radical center. The ν1 and ν2 band origins are determined to be 3073.968 50(8) cm-1 and 3062.264 80(7) cm-1, respectively, which both agree within 5 cm-1 with theoretical anharmonic scaling predictions based on density functional B3LYP/6-311g++(3df,3dp) calculations. Integrated band strengths for each of the CH stretch bands are analyzed, with the relative intensities agreeing remarkably well with theoretical predictions. Frequency comparison with previous low resolution Ar-matrix spectroscopy [A. V. Friderichsen et al., J. Am. Chem. Soc. 123, 1977 (2001)] reveals a nearly uniform Δν ≈ + 10-12 cm-1 blue shift between gas phase and Ar matrix values for ν1 and ν2. This differs substantially from the much smaller red shift (Δν ≈ - 1 cm-1) reported for the ν19 mode, and suggests a simple physical model in terms of vibrational mode symmetry and crowding due to the matrix environment. Finally, the infrared phenyl spectra are well described by a simple asymmetric rigid rotor Hamiltonian and show no evidence for spectral congestion due to intramolecular vibrational coupling, which bodes well for high resolution studies of other ring radicals and polycyclic aromatic hydrocarbons. In summary, the combination of slit jet discharge methods with high resolution infrared lasers enables spectroscopic investigation of even highly reactive combustion and interstellar radical intermediates under gas phase, jet-cooled (Trot ≈ 11 K) conditions.

Purification and characterization of native and recombinant SaPIN2a, a plant sieve element-localized proteinase inhibitor.

PubMed

Wang, Zhen-Yu; Ding, Ling-Wen; Ge, Zhi-Juan; Wang, Zhaoyu; Wang, Fanghai; Li, Ning; Xu, Zeng-Fu

2007-01-01

SaPIN2a encodes a proteinase inhibitor in nightshade (Solanum americanum), which is specifically localized to the enucleate sieve elements. It has been proposed to play an important role in phloem development by regulating proteolysis in sieve elements. In this study, we purified and characterized native SaPIN2a from nightshade stems and recombinant SaPIN2a expressed in Escherichia coli. Purified native SaPIN2a was found as a charge isomer family of homodimers, and was weakly glycosylated. Native SaPIN2a significantly inhibited serine proteinases such as trypsin, chymotrypsin, and subtilisin, with the most potent inhibitory activity on subtilisin. It did not inhibit cysteine proteinase papain and aspartic proteinase cathepsin D. Recombinant SaPIN2a had a strong inhibitory effect on chymotrypsin, but its inhibitory activities toward trypsin and especially toward subtilisin were greatly reduced. In addition, native SaPIN2a can effectively inhibit midgut trypsin-like activities from Trichoplusia ni and Spodoptera litura larvae, suggesting a potential for the production of insect-resistant transgenic plants.

Assembly and misassembly of cystic fibrosis transmembrane conductance regulator: folding defects caused by deletion of F508 occur before and after the calnexin-dependent association of membrane spanning domain (MSD) 1 and MSD2.

PubMed

Rosser, Meredith F N; Grove, Diane E; Chen, Liling; Cyr, Douglas M

2008-11-01

Cystic fibrosis transmembrane conductance regulator (CFTR) is a polytopic membrane protein that functions as a Cl(-) channel and consists of two membrane spanning domains (MSDs), two cytosolic nucleotide binding domains (NBDs), and a cytosolic regulatory domain. Cytosolic 70-kDa heat shock protein (Hsp70), and endoplasmic reticulum-localized calnexin are chaperones that facilitate CFTR biogenesis. Hsp70 functions in both the cotranslational folding and posttranslational degradation of CFTR. Yet, the mechanism for calnexin action in folding and quality control of CFTR is not clear. Investigation of this question revealed that calnexin is not essential for CFTR or CFTRDeltaF508 degradation. We identified a dependence on calnexin for proper assembly of CFTR's membrane spanning domains. Interestingly, efficient folding of NBD2 was also found to be dependent upon calnexin binding to CFTR. Furthermore, we identified folding defects caused by deletion of F508 that occurred before and after the calnexin-dependent association of MSD1 and MSD2. Early folding defects are evident upon translation of the NBD1 and R-domain and are sensed by the RMA-1 ubiquitin ligase complex.

40 CFR 94.508 - Calculation and reporting of test results.

Code of Federal Regulations, 2012 CFR

2012-07-01

... results. 94.508 Section 94.508 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Line Testing Programs § 94.508 Calculation and reporting of test results. (a) Manufacturers shall calculate initial test results using the applicable test procedure specified in § 94.506(a). These results...

40 CFR 94.508 - Calculation and reporting of test results.

Code of Federal Regulations, 2013 CFR

2013-07-01

... results. 94.508 Section 94.508 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Line Testing Programs § 94.508 Calculation and reporting of test results. (a) Manufacturers shall calculate initial test results using the applicable test procedure specified in § 94.506(a). These results...

Preliminary treatment of bovine mastitis caused by Staphylococcus aureus, with trx-SA1, recombinant endolysin of S. aureus bacteriophage IME-SA1.

PubMed

Fan, Jindai; Zeng, Zhiliang; Mai, Kaijie; Yang, Yu; Feng, Jiaqi; Bai, Yang; Sun, Baoli; Xie, Qingmei; Tong, Yigang; Ma, Jingyun

2016-08-15

Methicillin-resistant Staphylococcus aureus (MRSA) has become a great threat to human and animal health and there is an urgent need to develop novel antibacterial agents to control this pathogen. The objective of this study was to obtain an active recombinant endolysin from the novel bacteriophage (IME-SA1), and conduct an efficacy trial of its effectiveness against bovine mastitis. We isolated a phage that was virulent and specific for S. aureus with an optimal multiplicity of infection of 0.01. Electron microscopy revealed that IME-SA1 was a member of the family Myoviridae, with an isometric head (98nm) and a long contractile tail (200nm). Experimental lysis experiments indicated the phage had an incubation period of 20min with a burst size of 80. When host bacteria were in early exponential growth stages, a multiplicity of infection of 0.01 resulted in a complete bacterial lysis after 9h. The endolysin gene (804bp) was cloned into the pET-32a bacterial expression vector and recombinant endolysin Trx-SA1 was successfully obtained with molecular size of about 47kDa. Preliminary results of therapeutic trials in cow udders showed that Trx-SA1 could effectively control mild clinical mastitis caused by S. aureus. The endolysin Trx-SA1 might be an alternative treatment strategy for infections caused by S. aureus, including MRSA. Copyright © 2016 Elsevier B.V. All rights reserved.

78 FR 39339 - Importer of Controlled Substances; Notice of Registration; SA INTL GMBH C/O., Sigma Aldrich Co., LLC

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-01

... Registration; SA INTL GMBH C/O., Sigma Aldrich Co., LLC By Notice dated March 20, 2013, and published in the Federal Register on March 28, 2013, 78 FR 19015, SA INTL GMBH C/O., Sigma Aldrich Co. LLC., 3500 Dekalb... registration of SA INTL GMBH C/O., Sigma Aldrich Co. LLC., to import the basic classes of controlled substances...

40 CFR 92.508 - Calculation and reporting of test results.

Code of Federal Regulations, 2012 CFR

2012-07-01

... results. 92.508 Section 92.508 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Remanufacturer Production Line Testing and Audit Programs § 92.508 Calculation and reporting of test results. (a) Manufacturers and remanufacturers shall calculate initial test results using the applicable test procedure...

40 CFR 92.508 - Calculation and reporting of test results.

Code of Federal Regulations, 2013 CFR

2013-07-01

... results. 92.508 Section 92.508 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Remanufacturer Production Line Testing and Audit Programs § 92.508 Calculation and reporting of test results. (a) Manufacturers and remanufacturers shall calculate initial test results using the applicable test procedure...

48 CFR 3045.508-3 - Quantitative and monetary control.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Quantitative and monetary control. 3045.508-3 Section 3045.508-3 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND... Management of Government Property in the Possession of Contractors 3045.508-3 Quantitative and monetary...

48 CFR 3045.508-3 - Quantitative and monetary control.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 7 2011-10-01 2011-10-01 false Quantitative and monetary control. 3045.508-3 Section 3045.508-3 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND... Management of Government Property in the Possession of Contractors 3045.508-3 Quantitative and monetary...

Increasing the Endoplasmic Reticulum Pool of the F508del Allele of the Cystic Fibrosis Transmembrane Conductance Regulator Leads to Greater Folding Correction by Small Molecule Therapeutics.

PubMed

Chung, W Joon; Goeckeler-Fried, Jennifer L; Havasi, Viktoria; Chiang, Annette; Rowe, Steven M; Plyler, Zackery E; Hong, Jeong S; Mazur, Marina; Piazza, Gary A; Keeton, Adam B; White, E Lucile; Rasmussen, Lynn; Weissman, Allan M; Denny, R Aldrin; Brodsky, Jeffrey L; Sorscher, Eric J

2016-01-01

Small molecules that correct the folding defects and enhance surface localization of the F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) comprise an important therapeutic strategy for cystic fibrosis lung disease. However, compounds that rescue the F508del mutant protein to wild type (WT) levels have not been identified. In this report, we consider obstacles to obtaining robust and therapeutically relevant levels of F508del CFTR. For example, markedly diminished steady state amounts of F508del CFTR compared to WT CFTR are present in recombinant bronchial epithelial cell lines, even when much higher levels of mutant transcript are present. In human primary airway cells, the paucity of Band B F508del is even more pronounced, although F508del and WT mRNA concentrations are comparable. Therefore, to augment levels of "repairable" F508del CFTR and identify small molecules that then correct this pool, we developed compound library screening protocols based on automated protein detection. First, cell-based imaging measurements were used to semi-quantitatively estimate distribution of F508del CFTR by high content analysis of two-dimensional images. We evaluated ~2,000 known bioactive compounds from the NIH Roadmap Molecular Libraries Small Molecule Repository in a pilot screen and identified agents that increase the F508del protein pool. Second, we analyzed ~10,000 compounds representing diverse chemical scaffolds for effects on total CFTR expression using a multi-plate fluorescence protocol and describe compounds that promote F508del maturation. Together, our findings demonstrate proof of principle that agents identified in this fashion can augment the level of endoplasmic reticulum (ER) resident "Band B" F508del CFTR suitable for pharmacologic correction. As further evidence in support of this strategy, PYR-41-a compound that inhibits the E1 ubiquitin activating enzyme-was shown to synergistically enhance F508del rescue by C18, a small

Saturn 1B launch vehicle flight evaluation report, SA-206, Skylab-2

NASA Technical Reports Server (NTRS)

1973-01-01

The performance evaluation of the SA-206 launch vehicle for the Skylab 2 launch is presented. Flight problems are identified, the causes are determined, and recommendations are made for appropriate corrective action. Summaries of launch operations and spacecraft performance are included. The significant events, failures, and anomalies are tabulated.

Generation of ΔF508-CFTR T84 cell lines by CRISPR/Cas9-mediated genome editing.

PubMed

Chung, Woo Young; Song, Myungjae; Park, Jinhong; Namkung, Wan; Lee, Jinu; Kim, Hyongbum; Lee, Min Goo; Kim, Joo Young

2016-12-01

To provide a simple method to make a stable ΔF508-CFTR-expressing T84 cell line that can be used as an efficient screening model system for ΔF508-CFTR rescue. CFTR knockout cell lines were generated by Cas9 with a single-guide RNA (sgRNA) targeting exon 1 of the CFTR genome, which produced indels that abolished CFTR protein expressions. Next, stable ΔF508-CFTR expression was achieved by genome integration of ΔF508-CFTR via the lentivirus infection system. Finally, we showed functional rescue of ΔF508-CFTR not only by growing the cells at a low temperature, but also incubating with VX-809, a ΔF508-CFTR corrector, in the established T84 cells expressing ΔF508-CFTR. This cell system provides an appropriate screening platform for rescue of ΔF508-CFTR, especially related to protein folding, escaped from endoplasmic-reticulum-associated protein degradation, and membrane transport.

20 CFR 663.508 - What is a “program of training services”?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false What is a âprogram of training servicesâ? 663.508 Section 663.508 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR ADULT AND DISLOCATED WORKER ACTIVITIES UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT Eligible Training...

20 CFR 663.508 - What is a “program of training services”?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false What is a âprogram of training servicesâ? 663.508 Section 663.508 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR ADULT AND DISLOCATED WORKER ACTIVITIES UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT Eligible Training...

∆F508 CFTR interactome remodelling promotes rescue of cystic fibrosis.

PubMed

Pankow, Sandra; Bamberger, Casimir; Calzolari, Diego; Martínez-Bartolomé, Salvador; Lavallée-Adam, Mathieu; Balch, William E; Yates, John R

2015-12-24

Deletion of phenylalanine 508 of the cystic fibrosis transmembrane conductance regulator (∆F508 CFTR) is the major cause of cystic fibrosis, one of the most common inherited childhood diseases. The mutated CFTR anion channel is not fully glycosylated and shows minimal activity in bronchial epithelial cells of patients with cystic fibrosis. Low temperature or inhibition of histone deacetylases can partly rescue ∆F508 CFTR cellular processing defects and function. A favourable change of ∆F508 CFTR protein-protein interactions was proposed as a mechanism of rescue; however, CFTR interactome dynamics during temperature shift and inhibition of histone deacetylases are unknown. Here we report the first comprehensive analysis of the CFTR and ∆F508 CFTR interactome and its dynamics during temperature shift and inhibition of histone deacetylases. By using a novel deep proteomic analysis method, we identify 638 individual high-confidence CFTR interactors and discover a ∆F508 deletion-specific interactome, which is extensively remodelled upon rescue. Detailed analysis of the interactome remodelling identifies key novel interactors, whose loss promote ∆F508 CFTR channel function in primary cystic fibrosis epithelia or which are critical for CFTR biogenesis. Our results demonstrate that global remodelling of ∆F508 CFTR interactions is crucial for rescue, and provide comprehensive insight into the molecular disease mechanisms of cystic fibrosis caused by deletion of F508.

20 CFR 638.508 - Sale of services or objects.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Sale of services or objects. 638.508 Section 638.508 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR JOB CORPS PROGRAM UNDER TITLE IV-B OF THE JOB TRAINING PARTNERSHIP ACT Center Operations § 638.508 Sale of services...

Command and Control Rapid Prototyping Continuum (C2RPC): The Framework for Achieving a New C2 Strategy

DTIC Science & Technology

2011-06-01

Sync Matrix Assessing J/ADOCS (Fires) TBMCS (ATO) Executing Monitoring (SA) C2 Strategy Objectives • Provide Expanded Mission Management...Computers, and Intelligence T&E Test and Evaluation PMW150 Program Warfare Office Command and Control TBMCS Theater Battle Management Core System POR

The Ricor K508 cryocooler operational experience on Mars

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Dean L.; Lysek, Mark J.; Morookian, John Michael

The Mars Science Laboratory (Curiosity) landed successfully on Mars on August 5, 2012, eight months after launch. The chosen landing site of Gale Crater, located at 4.5 degrees south latitude, 137.4 degrees east longitude, has provided a much more benign environment than was originally planned for during the critical design and integration phases of the MSL Project when all possible landing sites were still being considered. The expected near-surface atmospheric temperatures at the Gale Crater landing site during Curiosity's primary mission (1 Martian year or 687 Earth days) are from −90°C to 0°C. However, enclosed within Curiosity's thermal control fluidmore » loops the Chemistry and Mineralogy (CheMin) instrument is maintained at approximately +20°C. The CheMin instrument uses X-ray diffraction spectroscopy to make precise measurements of mineral constituents of Mars rocks and soil. The instrument incorporated the commercially available Ricor K508 Stirling cycle cryocooler to cool the CCD detector. After several months of brushing itself off, stretching and testing out its subsystems, Curiosity began the exploration of the Mars surface in October 2012. The CheMin instrument on the Mars Science Laboratory (MSL) received its first soil sample from Curiosity on October 24, and successfully analyzed its first soil sample. After a brief review of the rigorous Ricor K508 cooler qualification tests and life tests based on the original MSL environmental requirements this paper presents final pre-launch instrument integration and testing results, and details the operational data of the CheMin cryocooler, providing a snapshot of the resulting CheMin instrument analytical data.« less

A Molecularly Cloned, Live-Attenuated Japanese Encephalitis Vaccine SA14-14-2 Virus: A Conserved Single Amino Acid in the ij Hairpin of the Viral E Glycoprotein Determines Neurovirulence in Mice

PubMed Central

Kim, Jin-Kyoung; Yun, Gil-Nam; Lee, Eun-Young; Li, Long; Kuhn, Richard J.; Rossmann, Michael G.; Morrey, John D.; Lee, Young-Min

2014-01-01

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that causes fatal neurological disease in humans, is one of the most important emerging pathogens of public health significance. JEV represents the JE serogroup, which also includes West Nile, Murray Valley encephalitis, and St. Louis encephalitis viruses. Within this serogroup, JEV is a vaccine-preventable pathogen, but the molecular basis of its neurovirulence remains unknown. Here, we constructed an infectious cDNA of the most widely used live-attenuated JE vaccine, SA14-14-2, and rescued from the cDNA a molecularly cloned virus, SA14-14-2MCV, which displayed in vitro growth properties and in vivo attenuation phenotypes identical to those of its parent, SA14-14-2. To elucidate the molecular mechanism of neurovirulence, we selected three independent, highly neurovirulent variants (LD50, <1.5 PFU) from SA14-14-2MCV (LD50, >1.5×105 PFU) by serial intracerebral passage in mice. Complete genome sequence comparison revealed a total of eight point mutations, with a common single G1708→A substitution replacing a Gly with Glu at position 244 of the viral E glycoprotein. Using our infectious SA14-14-2 cDNA technology, we showed that this single Gly-to-Glu change at E-244 is sufficient to confer lethal neurovirulence in mice, including rapid development of viral spread and tissue inflammation in the central nervous system. Comprehensive site-directed mutagenesis of E-244, coupled with homology-based structure modeling, demonstrated a novel essential regulatory role in JEV neurovirulence for E-244, within the ij hairpin of the E dimerization domain. In both mouse and human neuronal cells, we further showed that the E-244 mutation altered JEV infectivity in vitro, in direct correlation with the level of neurovirulence in vivo, but had no significant impact on viral RNA replication. Our results provide a crucial step toward developing novel therapeutic and preventive strategies against JEV and possibly other

Evidence against Resveratrol as a viable therapy for the rescue of defective ΔF508 CFTR

PubMed Central

Jai, Ying; Shah, Kalpit; Bridges, Robert J.; Bradbury, Neil A.

2015-01-01

BACKGROUND Resveratrol, a natural phenolic compound, has been reported to rescue mutant ΔF508 CFTR in expression systems and primary epithelial cells. Although this implies a therapeutic benefit to patients with CF, investigations were performed using resveratrol concentrations greatly in excess of those achievable in plasma. We evaluated the efficacy of resveratrol as a CFTR corrector in relevant primary airway cells, using physiologically achievable resveratrol concentrations. METHODS Cells expressing wt or ΔF508 CFTR were exposed to chronic or acute resveratrol. CFTR mRNA and protein expression were monitored. The effects of resveratrol on primary ΔF508 human airway cells were evaluated by equivalent current analysis using modified Ussing chambers. RESULTS Consistent with previously published data in heterologous expression systems, high doses of resveratrol increased CFTR expression; however physiologically relevant concentrations were without effect. In contrast to heterologous expression systems, resveratrol was unable to increase mutant CFTR channel activity in primary airway cells. Elevated amiloride-sensitive currents, indicative of sodium transport and characteristically elevated in CF airway cells, were also unaffected by resveratrol CONCLUSIONS High concentrations of resveratrol can increase CFTR mRNA and protein in some cell types. In addition, acute resveratrol exposure can stimulate CFTR mediated chloride secretion, probably by increasing cellular cAMP levels. Resveratrol at physiologically achievable levels yielded no benefit in primary ΔF508 airway cells, either in terms of amiloride-sensitive currents of CFTR currents. PMID:26342647

In vitro effect of important herbal active constituents on human cytochrome P450 1A2 (CYP1A2) activity.

PubMed

Pan, Yan; Tiong, Kai Hung; Abd-Rashid, Badrul Amini; Ismail, Zakiah; Ismail, Rusli; Mak, Joon Wah; Ong, Chin Eng

2014-10-15

This study was designed to investigate eight herbal active constituents (andrographolide, asiaticoside, asiatic acid, madecassic acid, eupatorin, sinensetin, caffeic acid, and rosmarinic acid) on their potential inhibitory effects on human cytochrome P450 1A2 (CYP1A2) activity. A fluorescence-based enzyme assay was performed by co-incubating human cDNA-expressed CYP1A2 with its selective probe substrate, 3-cyano-7-ethoxycoumarin (CEC), in the absence or presence of various concentrations of herbal active constituents. The metabolite (cyano-hydroxycoumarin) formed was subsequently measured in order to obtain IC50 values. The results indicated that only eupatorin and sinensetin moderately inhibited CYP1A2 with IC50 values of 50.8 and 40.2 μM, while the other active compounds did not significantly affect CYP1A2 activity with IC50 values more than 100 μM. Ki values further determined for eupatorin and sinensetin were 46.4 and 35.2 μM, respectively. Our data indicated that most of the investigated herbal constituents have negligible CYP1A2 inhibitory effect. In vivo studies however may be warranted to ascertain the inhibitory effect of eupatorin and sinensetin on CYP1A2 activity in clinical situations. Copyright © 2014 Elsevier GmbH. All rights reserved.

saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription.

PubMed

Portnoy, Victoria; Lin, Szu Hua Sharon; Li, Kathy H; Burlingame, Alma; Hu, Zheng-Hui; Li, Hao; Li, Long-Cheng

2016-03-01

Small activating RNAs (saRNAs) targeting specific promoter regions are able to stimulate gene expression at the transcriptional level, a phenomenon known as RNA activation (RNAa). It is known that RNAa depends on Ago2 and is associated with epigenetic changes at the target promoters. However, the precise molecular mechanism of RNAa remains elusive. Using human CDKN1A (p21) as a model gene, we characterized the molecular nature of RNAa. We show that saRNAs guide Ago2 to and associate with target promoters. saRNA-loaded Ago2 facilitates the assembly of an RNA-induced transcriptional activation (RITA) complex, which, in addition to saRNA-Ago2 complex, includes RHA and CTR9, the latter being a component of the PAF1 complex. RITA interacts with RNA polymerase II to stimulate transcription initiation and productive elongation, accompanied by monoubiquitination of histone 2B. Our results establish the existence of a cellular RNA-guided genome-targeting and transcriptional activation mechanism and provide important new mechanistic insights into the RNAa process.

1α,25(OH)2-Vitamin D3 Inhibits C2C12 Cell Differentiation by Activating c-Src and ERK1/2.

PubMed

Wang, Zhonghua; Jiang, Aijun; Mei, Jingwei; Zhang, Xinyan

2018-05-01

The steroid hormone 1α,25(OH)2-vitamin D3 (1,25-D3) induced some biological responses through activation of MAPK cascades in various cell types. It seems that 1,25-D3 plays different roles at different stages of proliferating, differentiating, and differentiated C2C12 cells. We wanted to detect the effect of 1,25-D3 on myogenic differentiation and the role of ERK1/2 in differentiating stage induced by 2% horse serum with 1,25-D3. In this study, cells were induced to differentiate with 2% horse serum until the 7th day (with addition of 1,25-D3 every two days). The protein level of MHC (myosin heavy chain) and phosphorylation level of Src and ERK1/2 were determined with western blot. U0126 (MEK inhibitor) and PP2 (Src specific inhibitor) were used to confirm the relationship between 1,25-D3, MHC, Src, and ERK1/2. 1,25-D3 inhibited differentiation of C2C12 cells and fusion of myotubes by phosphorylating and activating Src and ERK1/2. Phosphorylation of ERK1/2 was inhibited, not only by U0126 but also by PP2 (a Src specific inhibitor) which led to the promotion of differentiation of C2C12 cells; however, U0126 did not inhibit Src phosphorylation. These results suggested that 1,25-D3 possibly inhibited C2C12 differentiation through Src and ERK1/2, and Src played an upstream role in this signaling pathway.

In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR.

PubMed Central

Rubenstein, R C; Egan, M E; Zeitlin, P L

1997-01-01

The most common cystic fibrosis transmembrane conductance regulator mutation, delta F508-CFTR, is a partially functional chloride channel that is retained in the endoplasmic reticulum and degraded. We hypothesize that a known transcriptional regulator, sodium 4-phenylbutyrate (4PBA), will enable a greater fraction of delta F508-CFTR to escape degradation and appear at the cell surface. Primary cultures of nasal polyp epithelia from CF patients (delta F508 homozygous or heterozygous), or the CF bronchial epithelial cell line IB3-1 (delta F508/W1282X) were exposed to 4PBA for up to 7 d in culture. 4PBA treatment at concentrations of 0.1 and 2 mM resulted in the restoration of forskolin-activated chloride secretion. Protein kinase A-activated, linear, 10 pS chloride channels appeared at the plasma membrane of IB3-1 cells at the tested concentration of 2.5 mM. Treatment of IB3-1 cells with 0.1-1 mM 4PBA and primary nasal epithelia with 5 mM 4PBA also resulted in the appearance of higher molecular mass forms of CFTR consistent with addition and modification of oligosaccharides in the Golgi apparatus, as detected by immunoblotting of whole cell lysates with anti-CFTR antisera. Immunocytochemistry in CF epithelial cells treated with 4PBA was consistent with increasing amounts of delta F508-CFTR. These data indicate that 4PBA is a promising pharmacologic agent for inducing correction of the CF phenotype in CF patients carrying the delta F508 mutation. PMID:9366560

In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing delta F508-CFTR.

PubMed

Rubenstein, R C; Egan, M E; Zeitlin, P L

1997-11-15

The most common cystic fibrosis transmembrane conductance regulator mutation, delta F508-CFTR, is a partially functional chloride channel that is retained in the endoplasmic reticulum and degraded. We hypothesize that a known transcriptional regulator, sodium 4-phenylbutyrate (4PBA), will enable a greater fraction of delta F508-CFTR to escape degradation and appear at the cell surface. Primary cultures of nasal polyp epithelia from CF patients (delta F508 homozygous or heterozygous), or the CF bronchial epithelial cell line IB3-1 (delta F508/W1282X) were exposed to 4PBA for up to 7 d in culture. 4PBA treatment at concentrations of 0.1 and 2 mM resulted in the restoration of forskolin-activated chloride secretion. Protein kinase A-activated, linear, 10 pS chloride channels appeared at the plasma membrane of IB3-1 cells at the tested concentration of 2.5 mM. Treatment of IB3-1 cells with 0.1-1 mM 4PBA and primary nasal epithelia with 5 mM 4PBA also resulted in the appearance of higher molecular mass forms of CFTR consistent with addition and modification of oligosaccharides in the Golgi apparatus, as detected by immunoblotting of whole cell lysates with anti-CFTR antisera. Immunocytochemistry in CF epithelial cells treated with 4PBA was consistent with increasing amounts of delta F508-CFTR. These data indicate that 4PBA is a promising pharmacologic agent for inducing correction of the CF phenotype in CF patients carrying the delta F508 mutation.

Chandra Observations of the Field Containing HESS J1616-508

NASA Astrophysics Data System (ADS)

Hare, Jeremy; Kargaltsev, Oleg; Pavlov, George G.; Rangelov, Blagoy; Volkov, Igor

2017-06-01

We report the results of three Chandra observations covering most of the extent of the TeV γ-ray source HESS J1616-508 and a search for a lower-energy counterpart to this source. We detect 56 X-ray sources, 37 of which have counterparts at lower frequencies, including a young massive star cluster, but none of them appear to be a particularly promising counterpart to the TeV source. The brightest X-ray source, CXOU J161423.4-505738, with a flux F 0.5-7 keV ≈ 5 × 10-13 erg cm-2 s-1, has a hard spectrum that is well fit by a power-law model with a photon index Γ = 0.2 ± 0.3 and is a likely intermediate polar CV candidate. No counterparts of this source were detected at other wavelengths. CVs are not known to produce extended TeV emission, and the source is also largely offset (19‧) from HESS J1616-508, making them unlikely to be associated. We have also set an upper limit on the X-ray flux of PSR J1614-5048 in the 0.5-8 keV band (F 0.5-8 keV < 5 × 10-15 erg cm-2 s-1 at a 90% confidence level). This makes PSR J1614-5048 one of the least X-ray-efficient pulsars known, with an X-ray efficiency {η }0.5{--8{keV}}={L}0.5{--8{keV}}/\\dot{E}< 2× {10}-5. We find no evidence supporting the association between the pulsar and the TeV source. We rule out a number of X-ray sources as possible counterparts to the TeV emission and do not find a plausible counterpart among the other sources. Lastly, we discuss the possible relation of PSR J1617-5055 to HESS J1616-508 in light of the new observations.

Integration of C1 and C2 Metabolism in Trees

PubMed Central

Jardine, Kolby J.; Higuchi, Niro; Bill, Markus; Porras, Rachel; Chambers, Jeffrey Q.

2017-01-01

C1 metabolism in plants is known to be involved in photorespiration, nitrogen and amino acid metabolism, as well as methylation and biosynthesis of metabolites and biopolymers. Although the flux of carbon through the C1 pathway is thought to be large, its intermediates are difficult to measure and relatively little is known about this potentially ubiquitous pathway. In this study, we evaluated the C1 pathway and its integration with the central metabolism using aqueous solutions of 13C-labeled C1 and C2 intermediates delivered to branches of the tropical species Inga edulis via the transpiration stream. Delivery of [13C]methanol and [13C]formaldehyde rapidly stimulated leaf emissions of [13C]methanol, [13C]formaldehyde, [13C]formic acid, and 13CO2, confirming the existence of the C1 pathway and rapid interconversion between methanol and formaldehyde. However, while [13C]formate solutions stimulated emissions of 13CO2, emissions of [13C]methanol or [13C]formaldehyde were not detected, suggesting that once oxidation to formate occurs it is rapidly oxidized to CO2 within chloroplasts. 13C-labeling of isoprene, a known photosynthetic product, was linearly related to 13CO2 across C1 and C2 ([13C2]acetate and [2-13C]glycine) substrates, consistent with reassimilation of C1, respiratory, and photorespiratory CO2. Moreover, [13C]methanol and [13C]formaldehyde induced a quantitative labeling of both carbon atoms of acetic acid emissions, possibly through the rapid turnover of the chloroplastic acetyl-CoA pool via glycolate oxidation. The results support a role of the C1 pathway to provide an alternative carbon source for glycine methylation in photorespiration, enhance CO2 concentrations within chloroplasts, and produce key C2 intermediates (e.g., acetyl-CoA) central to anabolic and catabolic metabolism. PMID:28946627

Integration of C 1 and C 2 Metabolism in Trees

DOE PAGES

Jardine, Kolby J.; Fernandes de Souza, Vinicius; Oikawa, Patty; ...

2017-09-23

C 1 metabolism in plants is known to be involved in photorespiration, nitrogen and amino acid metabolism, as well as methylation and biosynthesis of metabolites and biopolymers. Although the flux of carbon through the C 1 pathway is thought to be large, its intermediates are difficult to measure and relatively little is known about this potentially ubiquitous pathway. In this study, we evaluated the C 1 pathway and its integration with the central metabolism using aqueous solutions of 13C-labeled C 1 and C 2 intermediates delivered to branches of the tropical species Inga edulis via the transpiration stream. Delivery ofmore » [ 13C]methanol and [ 13C]formaldehyde rapidly stimulated leaf emissions of [ 13C]methanol, [ 13C]formaldehyde, [ 13C]formic acid, and 13CO 2, confirming the existence of the C 1 pathway and rapid interconversion between methanol and formaldehyde. However, while [ 13C]formate solutions stimulated emissions of 13CO 2, emissions of [ 13C]methanol or [ 13C]formaldehyde were not detected, suggesting that once oxidation to formate occurs it is rapidly oxidized to CO 2 within chloroplasts. 13C-labeling of isoprene, a known photosynthetic product, was linearly related to 13CO 2 across C 1 and C 2 ([ 13C 2]acetate and [2- 13C]glycine) substrates, consistent with reassimilation of C 1, respiratory, and photorespiratory CO 2. Moreover, [ 13C]methanol and [ 13C]formaldehyde induced a quantitative labeling of both carbon atoms of acetic acid emissions, possibly through the rapid turnover of the chloroplastic acetyl-CoA pool via glycolate oxidation. The results support a role of the C 1 pathway to provide an alternative carbon source for glycine methylation in photorespiration, enhance CO 2 concentrations within chloroplasts, and produce key C 2 intermediates (e.g., acetyl-CoA) central to anabolic and catabolic metabolism.« less

Integration of C 1 and C 2 Metabolism in Trees

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jardine, Kolby J.; Fernandes de Souza, Vinicius; Oikawa, Patty

C 1 metabolism in plants is known to be involved in photorespiration, nitrogen and amino acid metabolism, as well as methylation and biosynthesis of metabolites and biopolymers. Although the flux of carbon through the C 1 pathway is thought to be large, its intermediates are difficult to measure and relatively little is known about this potentially ubiquitous pathway. In this study, we evaluated the C 1 pathway and its integration with the central metabolism using aqueous solutions of 13C-labeled C 1 and C 2 intermediates delivered to branches of the tropical species Inga edulis via the transpiration stream. Delivery ofmore » [ 13C]methanol and [ 13C]formaldehyde rapidly stimulated leaf emissions of [ 13C]methanol, [ 13C]formaldehyde, [ 13C]formic acid, and 13CO 2, confirming the existence of the C 1 pathway and rapid interconversion between methanol and formaldehyde. However, while [ 13C]formate solutions stimulated emissions of 13CO 2, emissions of [ 13C]methanol or [ 13C]formaldehyde were not detected, suggesting that once oxidation to formate occurs it is rapidly oxidized to CO 2 within chloroplasts. 13C-labeling of isoprene, a known photosynthetic product, was linearly related to 13CO 2 across C 1 and C 2 ([ 13C 2]acetate and [2- 13C]glycine) substrates, consistent with reassimilation of C 1, respiratory, and photorespiratory CO 2. Moreover, [ 13C]methanol and [ 13C]formaldehyde induced a quantitative labeling of both carbon atoms of acetic acid emissions, possibly through the rapid turnover of the chloroplastic acetyl-CoA pool via glycolate oxidation. The results support a role of the C 1 pathway to provide an alternative carbon source for glycine methylation in photorespiration, enhance CO 2 concentrations within chloroplasts, and produce key C 2 intermediates (e.g., acetyl-CoA) central to anabolic and catabolic metabolism.« less

High temperature, low-cycle fatigue of copper-base alloys in argon. Part 1: Preliminary results for 12 alloys at 1000 F (538 C)

NASA Technical Reports Server (NTRS)

Conway, J. B.; Stentz, R. H.; Berling, J. T.

1973-01-01

Short-term tensile evaluations at room temperature and 538 C and low-cycle fatigue evaluations at 538 C are presented for the following materials: Zirconium copper-annealed, Zirconium copper-1/4 hard, Zirconium copper-1/2 hard, Tellurium copper-1/2 hard, Chromium copper-SA and aged, OFHC copper-hard, OFHC copper-1/4 hard, OFHC copper-annealed, Silver-as drawn, Zr-Cr-Mg copper-SA, CW and aged, Electroformed copper-30-35 ksi, and Co-Be-Zr- copper-SA, aged. A total of 50 tensile tests and 76 low-cycle fatigue tests were performed using a strain rate of 0.2 percent per second.

Synthesis of N1-tritylethane-1,1,2,2-d4-1,2-diamine: a novel mono-protected C-deuterated ethylenediamine synthon

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Jun; Hong, Kunlun; Bonnesen, Peter V

2012-01-01

A convenient and high-yield synthesis for N1-tritylethane-1,1,2,2-d4-1,2-diamine, a novel mono-protected ethylenediamine-C-d4, is reported. N1-tritylethane-1,1,2,2-d4-1,2-diamine was prepared in three steps from ethylene oxide-d4 in a combined yield in the range 68-76%. Also reported is a synthesis of ethylenediamine-C-d4 in two steps from 1,2-dibromoethane-d4 in a combined yield in the range 61-65%.

7 CFR 1755.508 - Customer access location protection.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 11 2014-01-01 2014-01-01 false Customer access location protection. 1755.508 Section 1755.508 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE TELECOMMUNICATIONS POLICIES ON SPECIFICATIONS, ACCEPTABLE MATERIALS, AND STANDARD...

7 CFR 1755.508 - Customer access location protection.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 11 2012-01-01 2012-01-01 false Customer access location protection. 1755.508 Section 1755.508 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE TELECOMMUNICATIONS POLICIES ON SPECIFICATIONS, ACCEPTABLE MATERIALS, AND STANDARD...

7 CFR 1755.508 - Customer access location protection.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 11 2013-01-01 2013-01-01 false Customer access location protection. 1755.508 Section 1755.508 Agriculture Regulations of the Department of Agriculture (Continued) RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE TELECOMMUNICATIONS POLICIES ON SPECIFICATIONS, ACCEPTABLE MATERIALS, AND STANDARD...

76 FR 35346 - Airworthiness Directives; Eurocopter France Model SA-365C, SA-365C1, SA-365C2, SA-365N, SA-365N1...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-17

... Eurocopter France (Eurocopter) helicopters. This action requires visually inspecting the adhesive bead between the bushing and the Starflex star (Starflex) arm for a crack, a gap, or loss of the adhesive bead... inspecting the adhesive bead between the bushing and the Starflex arm for a crack, a gap, or loss of the...

Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma

PubMed Central

Lewis, Michael J; Wiebe, John P; Heathcote, J Godfrey

2004-01-01

Background Recent evidence suggests that progesterone metabolites play important roles in regulating breast cancer. Previous studies have shown that tumorous tissues have higher 5α-reductase (5αR) and lower 3α-hydroxysteroid oxidoreductase (3α-HSO) and 20α-HSO activities. The resulting higher levels of 5α-reduced progesterone metabolites such as 5α-pregnane-3,20-dione (5αP) in tumorous tissue promote cell proliferation and detachment, whereas the 4-pregnene metabolites, 4-pregnen-3α-ol-20-one (3αHP) and 4-pregnen-20α-ol-3-one (20αDHP), more prominent in normal tissue, have the opposite (anti-cancer-like) effects. The aim of this study was to determine if the differences in enzyme activities between tumorous and nontumorous breast tissues are associated with differences in progesterone metabolizing enzyme gene expression. Methods Semi-quantitative RT-PCR was used to compare relative expression (as a ratio of 18S rRNA) of 5αR type 1 (SRD5A1), 5αR type 2 (SRD5A2), 3α-HSO type 2 (AKR1C3), 3α-HSO type 3 (AKR1C2) and 20α-HSO (AKR1C1) mRNAs in paired (tumorous and nontumorous) breast tissues from 11 patients, and unpaired tumor tissues from 17 patients and normal tissues from 10 reduction mammoplasty samples. Results Expression of 5αR1 and 5αR2 in 11/11 patients was higher (mean of 4.9- and 3.5-fold, respectively; p < 0.001) in the tumor as compared to the paired normal tissues. Conversely, expression of 3α-HSO2, 3α-HSO3 and 20α-HSO was higher (2.8-, 3.9- and 4.4-fold, respectively; p < 0.001) in normal than in tumor sample. The mean tumor:normal expression ratios for 5αR1 and 5αR2 were about 35–85-fold higher than the tumor:normal expression ratios for the HSOs. Similarly, in the unmatched samples, the tumor:normal ratios for 5αR were significantly higher than the ratios for the HSOs. Conclusions The study shows changes in progesterone metabolizing enzyme gene expression in human breast carcinoma. Expression of SRD5A1 (5αR1) and SRD5A2 (5αR2

Expression of progesterone metabolizing enzyme genes (AKR1C1, AKR1C2, AKR1C3, SRD5A1, SRD5A2) is altered in human breast carcinoma.

PubMed

Lewis, Michael J; Wiebe, John P; Heathcote, J Godfrey

2004-06-22

Recent evidence suggests that progesterone metabolites play important roles in regulating breast cancer. Previous studies have shown that tumorous tissues have higher 5alpha-reductase (5alphaR) and lower 3alpha-hydroxysteroid oxidoreductase (3alpha-HSO) and 20alpha-HSO activities. The resulting higher levels of 5alpha-reduced progesterone metabolites such as 5alpha-pregnane-3,20-dione (5alphaP) in tumorous tissue promote cell proliferation and detachment, whereas the 4-pregnene metabolites, 4-pregnen-3alpha-ol-20-one (3alphaHP) and 4-pregnen-20alpha-ol-3-one (20alphaDHP), more prominent in normal tissue, have the opposite (anti-cancer-like) effects. The aim of this study was to determine if the differences in enzyme activities between tumorous and nontumorous breast tissues are associated with differences in progesterone metabolizing enzyme gene expression. Semi-quantitative RT-PCR was used to compare relative expression (as a ratio of 18S rRNA) of 5alphaR type 1 (SRD5A1), 5alphaR type 2 (SRD5A2), 3alpha-HSO type 2 (AKR1C3), 3alpha-HSO type 3 (AKR1C2) and 20alpha-HSO (AKR1C1) mRNAs in paired (tumorous and nontumorous) breast tissues from 11 patients, and unpaired tumor tissues from 17 patients and normal tissues from 10 reduction mammoplasty samples. Expression of 5alphaR1 and 5alphaR2 in 11/11 patients was higher (mean of 4.9- and 3.5-fold, respectively; p < 0.001) in the tumor as compared to the paired normal tissues. Conversely, expression of 3alpha-HSO2, 3alpha-HSO3 and 20alpha-HSO was higher (2.8-, 3.9- and 4.4-fold, respectively; p < 0.001) in normal than in tumor sample. The mean tumor:normal expression ratios for 5alphaR1 and 5alphaR2 were about 35-85-fold higher than the tumor:normal expression ratios for the HSOs. Similarly, in the unmatched samples, the tumor:normal ratios for 5alphaR were significantly higher than the ratios for the HSOs. The study shows changes in progesterone metabolizing enzyme gene expression in human breast carcinoma. Expression of

46 CFR 308.508 - Issuance of an Open Cargo Policy.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 8 2013-10-01 2013-10-01 false Issuance of an Open Cargo Policy. 308.508 Section 308.508 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION EMERGENCY OPERATIONS WAR RISK INSURANCE War Risk Cargo Insurance Ii-Open Policy War Risk Cargo Insurance § 308.508 Issuance of an Open...

46 CFR 308.508 - Issuance of an Open Cargo Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

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46 CFR 308.508 - Issuance of an Open Cargo Policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

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46 CFR 308.508 - Issuance of an Open Cargo Policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

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46 CFR 308.508 - Issuance of an Open Cargo Policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

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χ_{c1} and χ_{c2} Resonance Parameters with the Decays χ_{c1,c2}→J/ψμ^{+}μ^{-}.

PubMed

Aaij, R; Adeva, B; Adinolfi, M; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Alfonso Albero, A; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Andreassi, G; Andreotti, M; Andrews, J E; Appleby, R B; Archilli, F; d'Argent, P; Arnau Romeu, J; Artamonov, A; Artuso, M; Aslanides, E; Atzeni, M; Auriemma, G; Baalouch, M; Babuschkin, I; Bachmann, S; Back, J J; Badalov, A; Baesso, C; Baker, S; Balagura, V; Baldini, W; Baranov, A; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Baryshnikov, F; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Beiter, A; Bel, L J; Beliy, N; Bellee, V; Belloli, N; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Beranek, S; Berezhnoy, A; Bernet, R; Berninghoff, D; Bertholet, E; Bertolin, A; Betancourt, C; Betti, F; Bettler, M-O; van Beuzekom, M; Bezshyiko, Ia; Bifani, S; Billoir, P; Birnkraut, A; Bizzeti, A; Bjørn, M; Blake, T; Blanc, F; Blusk, S; Bocci, V; Boettcher, T; Bondar, A; Bondar, N; Bordyuzhin, I; Borghi, S; Borisyak, M; Borsato, M; Bossu, F; Boubdir, M; Bowcock, T J V; Bowen, E; Bozzi, C; Braun, S; Britton, T; Brodzicka, J; Brundu, D; Buchanan, E; Burr, C; Bursche, A; Buytaert, J; Byczynski, W; Cadeddu, S; Cai, H; Calabrese, R; Calladine, R; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Campora Perez, D H; Capriotti, L; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carniti, P; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Cattaneo, M; Cavallero, G; Cenci, R; Chamont, D; Chapman, M G; Charles, M; Charpentier, Ph; Chatzikonstantinidis, G; Chefdeville, M; Chen, S; Cheung, S F; Chitic, S-G; Chobanova, V; Chrzaszcz, M; Chubykin, A; Ciambrone, P; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Cogan, J; Cogneras, E; Cogoni, V; Cojocariu, L; Collins, P; Colombo, T; Comerma-Montells, A; Contu, A; Cook, A; Coombs, G; Coquereau, S; Corti, G; Corvo, M; Costa Sobral, C M; Couturier, B; Cowan, G A; Craik, D C; Crocombe, A; Cruz Torres, M; Currie, R; D'Ambrosio, C; Da Cunha Marinho, F; Dall'Occo, E; Dalseno, J; Davis, A; De Aguiar Francisco, O; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Serio, M; De Simone, P; Dean, C T; Decamp, D; Del Buono, L; Dembinski, H-P; Demmer, M; Dendek, A; Derkach, D; Deschamps, O; Dettori, F; Dey, B; Di Canto, A; Di Nezza, P; Dijkstra, H; Dordei, F; Dorigo, M; Dosil Suárez, A; Douglas, L; Dovbnya, A; Dreimanis, K; Dufour, L; Dujany, G; Durante, P; Dzhelyadin, R; Dziewiecki, M; Dziurda, A; Dzyuba, A; Easo, S; Ebert, M; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; Ely, S; Esen, S; Evans, H M; Evans, T; Falabella, A; Farley, N; Farry, S; Fazzini, D; Federici, L; Ferguson, D; Fernandez, G; Fernandez Declara, P; Fernandez Prieto, A; Ferrari, F; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fini, R A; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fleuret, F; Fohl, K; Fontana, M; Fontanelli, F; Forshaw, D C; Forty, R; Franco Lima, V; Frank, M; Frei, C; Fu, J; Funk, W; Furfaro, E; Färber, C; Gabriel, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; Garcia Martin, L M; García Pardiñas, J; Garra Tico, J; Garrido, L; Garsed, P J; Gascon, D; Gaspar, C; Gavardi, L; Gazzoni, G; Gerick, D; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gianì, S; Gibson, V; Girard, O G; Giubega, L; Gizdov, K; Gligorov, V V; Golubkov, D; Golutvin, A; Gomes, A; Gorelov, I V; Gotti, C; Govorkova, E; Grabowski, J P; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graverini, E; Graziani, G; Grecu, A; Greim, R; Griffith, P; Grillo, L; Gruber, L; Gruberg Cazon, B R; Grünberg, O; Gushchin, E; Guz, Yu; Gys, T; Göbel, C; Hadavizadeh, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hamilton, B; Han, X; Hancock, T H; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Hasse, C; Hatch, M; He, J; Hecker, M; Heinicke, K; Heister, A; Hennessy, K; Henrard, P; Henry, L; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hombach, C; Hopchev, P H; Hu, W; Huard, Z C; Hulsbergen, W; Humair, T; Hushchyn, M; Hutchcroft, D; Ibis, P; Idzik, M; Ilten, P; Jacobsson, R; Jalocha, J; Jans, E; Jawahery, A; Jiang, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kandybei, S; Karacson, M; Kariuki, J M; Karodia, S; Kazeev, N; Kecke, M; Keizer, F; Kelsey, M; Kenzie, M; Ketel, T; Khairullin, E; Khanji, B; Khurewathanakul, C; Kirn, T; Klaver, S; Klimaszewski, K; Klimkovich, T; Koliiev, S; Kolpin, M; Kopecna, R; Koppenburg, P; Kosmyntseva, A; Kotriakhova, S; Kozeiha, M; Kravchuk, L; Kreps, M; Kress, F; Krokovny, P; Kruse, F; Krzemien, W; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kuonen, A K; Kvaratskheliya, T; Lacarrere, D; Lafferty, G; Lai, A; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; Leflat, A; Lefrançois, J; Lefèvre, R; Lemaitre, F; Lemos Cid, E; Leroy, O; Lesiak, T; Leverington, B; Li, P-R; Li, T; Li, Y; Li, Z; Likhomanenko, T; Lindner, R; Lionetto, F; Lisovskyi, V; Liu, X; Loh, D; Loi, A; Longstaff, I; Lopes, J H; Lucchesi, D; Luchinsky, A; Lucio Martinez, M; Luo, H; Lupato, A; Luppi, E; Lupton, O; Lusiani, A; Lyu, X; Machefert, F; Maciuc, F; Macko, V; Mackowiak, P; Maddrell-Mander, S; Maev, O; Maguire, K; Maisuzenko, D; Majewski, M W; Malde, S; Malecki, B; Malinin, A; Maltsev, T; Manca, G; Mancinelli, G; Marangotto, D; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marinangeli, M; Marino, P; Marks, J; Martellotti, G; Martin, M; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Massacrier, L M; Massafferri, A; Matev, R; Mathad, A; Mathe, Z; Matteuzzi, C; Mauri, A; Maurice, E; Maurin, B; Mazurov, A; McCann, M; McNab, A; McNulty, R; Mead, J V; Meadows, B; Meaux, C; Meier, F; Meinert, N; Melnychuk, D; Merk, M; Merli, A; Michielin, E; Milanes, D A; Millard, E; Minard, M-N; Minzoni, L; Mitzel, D S; Mogini, A; Molina Rodriguez, J; Mombächer, T; Monroy, I A; Monteil, S; Morandin, M; Morello, M J; Morgunova, O; Moron, J; Morris, A B; Mountain, R; Muheim, F; Mulder, M; Müller, D; Müller, J; Müller, K; Müller, V; Naik, P; Nakada, T; Nandakumar, R; Nandi, A; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, T D; Nguyen-Mau, C; Nieswand, S; Niet, R; Nikitin, N; Nikodem, T; Nogay, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Ogilvy, S; Oldeman, R; Onderwater, C J G; Ossowska, A; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pais, P R; Palano, A; Palutan, M; Papanestis, A; Pappagallo, M; Pappalardo, L L; Parker, W; Parkes, C; Passaleva, G; Pastore, A; Patel, M; Patrignani, C; Pearce, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perret, P; Pescatore, L; Petridis, K; Petrolini, A; Petrov, A; Petruzzo, M; Picatoste Olloqui, E; Pietrzyk, B; Pikies, M; Pinci, D; Pisani, F; Pistone, A; Piucci, A; Placinta, V; Playfer, S; Plo Casasus, M; Polci, F; Poli Lener, M; Poluektov, A; Polyakov, I; Polycarpo, E; Pomery, G J; Ponce, S; Popov, A; Popov, D; Poslavskii, S; Potterat, C; Price, E; Prisciandaro, J; Prouve, C; Pugatch, V; Puig Navarro, A; Pullen, H; Punzi, G; Qian, W; Quagliani, R; Quintana, B; Rachwal, B; Rademacker, J H; Rama, M; Ramos Pernas, M; Rangel, M S; Raniuk, I; Ratnikov, F; Raven, G; Ravonel Salzgeber, M; Reboud, M; Redi, F; Reichert, S; Dos Reis, A C; Remon Alepuz, C; Renaudin, V; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Robbe, P; Robert, A; Rodrigues, A B; Rodrigues, E; Rodriguez Lopez, J A; Rogozhnikov, A; Roiser, S; Rollings, A; Romanovskiy, V; Romero Vidal, A; Ronayne, J W; Rotondo, M; Rudolph, M S; Ruf, T; Ruiz Valls, P; Ruiz Vidal, J; Saborido Silva, J J; Sadykhov, E; Sagidova, N; Saitta, B; Salustino Guimaraes, V; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santimaria, M; Santovetti, E; Sarpis, G; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrina, D; Schael, S; Schellenberg, M; Schiller, M; Schindler, H; Schmelling, M; Schmelzer, T; Schmidt, B; Schneider, O; Schopper, A; Schreiner, H F; Schubiger, M; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Semennikov, A; Sepulveda, E S; Sergi, A; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Siddi, B G; Silva Coutinho, R; Silva de Oliveira, L; Simi, G; Simone, S; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, E; Smith, I T; Smith, J; Smith, M; Soares Lavra, L; Sokoloff, M D; Soler, F J P; Souza De Paula, B; Spaan, B; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Stefko, P; Stefkova, S; Steinkamp, O; Stemmle, S; Stenyakin, O; Stepanova, M; Stevens, H; Stone, S; Storaci, B; Stracka, S; Stramaglia, M E; Straticiuc, M; Straumann, U; Sun, J; Sun, L; Sutcliffe, W; Swientek, K; Syropoulos, V; Szumlak, T; Szymanski, M; T'Jampens, S; Tayduganov, A; Tekampe, T; Tellarini, G; Teubert, F; Thomas, E; van Tilburg, J; Tilley, M J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Tonelli, D; Toriello, F; Tourinho Jadallah Aoude, R; Tournefier, E; Traill, M; Tran, M T; Tresch, M; Trisovic, A; Tsaregorodtsev, A; Tsopelas, P; Tully, A; Tuning, N; Ukleja, A; Usachov, A; Ustyuzhanin, A; Uwer, U; Vacca, C; Vagner, A; Vagnoni, V; Valassi, A; Valat, S; Valenti, G; Vazquez Gomez, R; Vazquez Regueiro, P; Vecchi, S; van Veghel, M; Velthuis, J J; Veltri, M; Veneziano, G; Venkateswaran, A; Verlage, T A; Vernet, M; Vesterinen, M; Viana Barbosa, J V; Viaud, B; Vieira, D; Vieites Diaz, M; Viemann, H; Vilasis-Cardona, X; Vitti, M; Volkov, V; Vollhardt, A; Voneki, B; Vorobyev, A; Vorobyev, V; Voß, C; de Vries, J A; Vázquez Sierra, C; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wang, J; Ward, D R; Wark, H M; Watson, N K; Websdale, D; Weiden, A; Weisser, C; Whitehead, M; Wicht, J; Wilkinson, G; Wilkinson, M; Williams, M; Williams, M P; Williams, M; Williams, T; Wilson, F F; Wimberley, J; Winn, M; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wraight, K; Wyllie, K; Xie, Y; Xu, M; Xu, Z; Yang, Z; Yang, Z; Yao, Y; Yin, H; Yu, J; Yuan, X; Yushchenko, O; Zarebski, K A; Zavertyaev, M; Zhang, L; Zhang, Y; Zhelezov, A; Zheng, Y; Zhu, X; Zhukov, V; Zonneveld, J B; Zucchelli, S

2017-12-01

The decays χ_{c1}→J/ψμ^{+}μ^{-} and χ_{c2}→J/ψμ^{+}μ^{-} are observed and used to study the resonance parameters of the χ_{c1} and χ_{c2} mesons. The masses of these states are measured to be m(χ_{c1})=3510.71±0.04(stat)±0.09(syst)  MeV and m(χ_{c2})=3556.10±0.06(stat)±0.11(syst)  MeV, where the knowledge of the momentum scale for charged particles dominates the systematic uncertainty. The momentum-scale uncertainties largely cancel in the mass difference m(χ_{c2})-m(χ_{c1})=45.39±0.07(stat)±0.03(syst)  MeV. The natural width of the χ_{c2} meson is measured to be Γ(χ_{c2})=2.10±0.20(stat)±0.02(syst)  MeV. These results are in good agreement with and have comparable precision to the current world averages.

χc 1 and χc 2 Resonance Parameters with the Decays χc 1 ,c 2→J /ψ μ+μ-

NASA Astrophysics Data System (ADS)

Aaij, R.; Adeva, B.; Adinolfi, M.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Alfonso Albero, A.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Archilli, F.; d'Argent, P.; Arnau Romeu, J.; Artamonov, A.; Artuso, M.; Aslanides, E.; Atzeni, M.; Auriemma, G.; Baalouch, M.; Babuschkin, I.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baker, S.; Balagura, V.; Baldini, W.; Baranov, A.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Baryshnikov, F.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Beiter, A.; Bel, L. J.; Beliy, N.; Bellee, V.; Belloli, N.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Beranek, S.; Berezhnoy, A.; Bernet, R.; Berninghoff, D.; Bertholet, E.; Bertolin, A.; Betancourt, C.; Betti, F.; Bettler, M.-O.; van Beuzekom, M.; Bezshyiko, Ia.; Bifani, S.; Billoir, P.; Birnkraut, A.; Bizzeti, A.; Bjørn, M.; Blake, T.; Blanc, F.; Blusk, S.; Bocci, V.; Boettcher, T.; Bondar, A.; Bondar, N.; Bordyuzhin, I.; Borghi, S.; Borisyak, M.; Borsato, M.; Bossu, F.; Boubdir, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Britton, T.; Brodzicka, J.; Brundu, D.; Buchanan, E.; Burr, C.; Bursche, A.; Buytaert, J.; Byczynski, W.; Cadeddu, S.; Cai, H.; Calabrese, R.; Calladine, R.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Campora Perez, D. H.; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Cattaneo, M.; Cavallero, G.; Cenci, R.; Chamont, D.; Chapman, M. G.; Charles, M.; Charpentier, Ph.; Chatzikonstantinidis, G.; Chefdeville, M.; Chen, S.; Cheung, S. F.; Chitic, S.-G.; Chobanova, V.; Chrzaszcz, M.; Chubykin, A.; Ciambrone, P.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collins, P.; Colombo, T.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombs, G.; Coquereau, S.; Corti, G.; Corvo, M.; Costa Sobral, C. M.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Cruz Torres, M.; Currie, R.; D'Ambrosio, C.; Da Cunha Marinho, F.; Dall'Occo, E.; Dalseno, J.; Davis, A.; De Aguiar Francisco, O.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Serio, M.; De Simone, P.; Dean, C. T.; Decamp, D.; Del Buono, L.; Dembinski, H.-P.; Demmer, M.; Dendek, A.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Nezza, P.; Dijkstra, H.; Dordei, F.; Dorigo, M.; Dosil Suárez, A.; Douglas, L.; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Durante, P.; Dzhelyadin, R.; Dziewiecki, M.; Dziurda, A.; Dzyuba, A.; Easo, S.; Ebert, M.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Farley, N.; Farry, S.; Fazzini, D.; Federici, L.; Ferguson, D.; Fernandez, G.; Fernandez Declara, P.; Fernandez Prieto, A.; Ferrari, F.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fini, R. A.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fleuret, F.; Fohl, K.; Fontana, M.; Fontanelli, F.; Forshaw, D. C.; Forty, R.; Franco Lima, V.; Frank, M.; Frei, C.; Fu, J.; Funk, W.; Furfaro, E.; Färber, C.; Gabriel, E.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Garcia Martin, L. M.; García Pardiñas, J.; Garra Tico, J.; Garrido, L.; Garsed, P. J.; Gascon, D.; Gaspar, C.; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianı, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gizdov, K.; Gligorov, V. V.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gorelov, I. V.; Gotti, C.; Govorkova, E.; Grabowski, J. P.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greim, R.; Griffith, P.; Grillo, L.; Gruber, L.; Gruberg Cazon, B. R.; Grünberg, O.; Gushchin, E.; Guz, Yu.; Gys, T.; Göbel, C.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hamilton, B.; Han, X.; Hancock, T. H.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Hasse, C.; Hatch, M.; He, J.; Hecker, M.; Heinicke, K.; Heister, A.; Hennessy, K.; Henrard, P.; Henry, L.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hombach, C.; Hopchev, P. H.; Hu, W.; Huard, Z. C.; Hulsbergen, W.; Humair, T.; Hushchyn, M.; Hutchcroft, D.; Ibis, P.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jalocha, J.; Jans, E.; Jawahery, A.; Jiang, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Karacson, M.; Kariuki, J. M.; Karodia, S.; Kazeev, N.; Kecke, M.; Keizer, F.; Kelsey, M.; Kenzie, M.; Ketel, T.; Khairullin, E.; Khanji, B.; Khurewathanakul, C.; Kirn, T.; Klaver, S.; Klimaszewski, K.; Klimkovich, T.; Koliiev, S.; Kolpin, M.; Kopecna, R.; Koppenburg, P.; Kosmyntseva, A.; Kotriakhova, S.; Kozeiha, M.; Kravchuk, L.; Kreps, M.; Kress, F.; Krokovny, P.; Kruse, F.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; Leflat, A.; Lefrançois, J.; Lefèvre, R.; Lemaitre, F.; Lemos Cid, E.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, P.-R.; Li, T.; Li, Y.; Li, Z.; Likhomanenko, T.; Lindner, R.; Lionetto, F.; Lisovskyi, V.; Liu, X.; Loh, D.; Loi, A.; Longstaff, I.; Lopes, J. H.; Lucchesi, D.; Luchinsky, A.; Lucio Martinez, M.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Lusiani, A.; Lyu, X.; Machefert, F.; Maciuc, F.; Macko, V.; Mackowiak, P.; Maddrell-Mander, S.; Maev, O.; Maguire, K.; Maisuzenko, D.; Majewski, M. W.; Malde, S.; Malecki, B.; Malinin, A.; Maltsev, T.; Manca, G.; Mancinelli, G.; Marangotto, D.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marinangeli, M.; Marino, P.; Marks, J.; Martellotti, G.; Martin, M.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Massacrier, L. M.; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurice, E.; Maurin, B.; Mazurov, A.; McCann, M.; McNab, A.; McNulty, R.; Mead, J. V.; Meadows, B.; Meaux, C.; Meier, F.; Meinert, N.; Melnychuk, D.; Merk, M.; Merli, A.; Michielin, E.; Milanes, D. A.; Millard, E.; Minard, M.-N.; Minzoni, L.; Mitzel, D. S.; Mogini, A.; Molina Rodriguez, J.; Mombächer, T.; Monroy, I. A.; Monteil, S.; Morandin, M.; Morello, M. J.; Morgunova, O.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Mulder, M.; Müller, D.; Müller, J.; Müller, K.; Müller, V.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, T. D.; Nguyen-Mau, C.; Nieswand, S.; Niet, R.; Nikitin, N.; Nikodem, T.; Nogay, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Oldeman, R.; Onderwater, C. J. G.; Ossowska, A.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pais, P. R.; Palano, A.; Palutan, M.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Parker, W.; Parkes, C.; Passaleva, G.; Pastore, A.; Patel, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petrov, A.; Petruzzo, M.; Picatoste Olloqui, E.; Pietrzyk, B.; Pikies, M.; Pinci, D.; Pisani, F.; Pistone, A.; Piucci, A.; Placinta, V.; Playfer, S.; Plo Casasus, M.; Polci, F.; Poli Lener, M.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Pomery, G. J.; Ponce, S.; Popov, A.; Popov, D.; Poslavskii, S.; Potterat, C.; Price, E.; Prisciandaro, J.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Pullen, H.; Punzi, G.; Qian, W.; Quagliani, R.; Quintana, B.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Ramos Pernas, M.; Rangel, M. S.; Raniuk, I.; Ratnikov, F.; Raven, G.; Ravonel Salzgeber, M.; Reboud, M.; Redi, F.; Reichert, S.; dos Reis, A. C.; Remon Alepuz, C.; Renaudin, V.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Robbe, P.; Robert, A.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Lopez, J. A.; Rogozhnikov, A.; Roiser, S.; Rollings, A.; Romanovskiy, V.; Romero Vidal, A.; Ronayne, J. W.; Rotondo, M.; Rudolph, M. S.; Ruf, T.; Ruiz Valls, P.; Ruiz Vidal, J.; Saborido Silva, J. J.; Sadykhov, E.; Sagidova, N.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santimaria, M.; Santovetti, E.; Sarpis, G.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schael, S.; Schellenberg, M.; Schiller, M.; Schindler, H.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schreiner, H. F.; Schubiger, M.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Sepulveda, E. S.; Sergi, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Siddi, B. G.; Silva Coutinho, R.; Silva de Oliveira, L.; Simi, G.; Simone, S.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, E.; Smith, I. T.; Smith, J.; Smith, M.; Soares Lavra, l.; Sokoloff, M. D.; Soler, F. J. P.; Souza De Paula, B.; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Stefko, P.; Stefkova, S.; Steinkamp, O.; Stemmle, S.; Stenyakin, O.; Stepanova, M.; Stevens, H.; Stone, S.; Storaci, B.; Stracka, S.; Stramaglia, M. E.; Straticiuc, M.; Straumann, U.; Sun, J.; Sun, L.; Sutcliffe, W.; Swientek, K.; Syropoulos, V.; Szumlak, T.; Szymanski, M.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Tellarini, G.; Teubert, F.; Thomas, E.; van Tilburg, J.; Tilley, M. J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Toriello, F.; Tourinho Jadallah Aoude, R.; Tournefier, E.; Traill, M.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tully, A.; Tuning, N.; Ukleja, A.; Usachov, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagner, A.; Vagnoni, V.; Valassi, A.; Valat, S.; Valenti, G.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vecchi, S.; van Veghel, M.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Venkateswaran, A.; Verlage, T. A.; Vernet, M.; Vesterinen, M.; Viana Barbosa, J. V.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Viemann, H.; Vilasis-Cardona, X.; Vitti, M.; Volkov, V.; Vollhardt, A.; Voneki, B.; Vorobyev, A.; Vorobyev, V.; Voß, C.; de Vries, J. A.; Vázquez Sierra, C.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wang, J.; Ward, D. R.; Wark, H. M.; Watson, N. K.; Websdale, D.; Weiden, A.; Weisser, C.; Whitehead, M.; Wicht, J.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M. P.; Williams, M.; Williams, T.; Wilson, F. F.; Wimberley, J.; Winn, M.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wraight, K.; Wyllie, K.; Xie, Y.; Xu, M.; Xu, Z.; Yang, Z.; Yang, Z.; Yao, Y.; Yin, H.; Yu, J.; Yuan, X.; Yushchenko, O.; Zarebski, K. A.; Zavertyaev, M.; Zhang, L.; Zhang, Y.; Zhelezov, A.; Zheng, Y.; Zhu, X.; Zhukov, V.; Zonneveld, J. B.; Zucchelli, S.; LHCb Collaboration

2017-12-01

The decays χc 1→J /ψ μ+μ- and χc 2→J /ψ μ+μ- are observed and used to study the resonance parameters of the χc 1 and χc 2 mesons. The masses of these states are measured to be m (χc 1)=3510.71 ±0.04 (stat ) ±0.09 (syst ) MeV and m (χc 2)=3556.10 ±0.06 (stat ) ±0.11 (syst ) MeV , where the knowledge of the momentum scale for charged particles dominates the systematic uncertainty. The momentum-scale uncertainties largely cancel in the mass difference m (χc 2)-m (χc 1)=45.39 ±0.07 (stat ) ±0.03 (syst ) MeV . The natural width of the χc 2 meson is measured to be Γ (χc 2)=2.10 ±0.20 (stat ) ±0.02 (syst ) MeV . These results are in good agreement with and have comparable precision to the current world averages.

12 CFR 508.12 - Proposed findings and conclusions and recommended decision.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Proposed findings and conclusions and recommended decision. 508.12 Section 508.12 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY REMOVALS, SUSPENSIONS, AND PROHIBITIONS WHERE A CRIME IS CHARGED OR PROVEN § 508.12 Proposed...

Functional genomic responses to cystic fibrosis transmembrane conductance regulator (CFTR) and CFTR(delta508) in the lung.

PubMed

Xu, Yan; Liu, Cong; Clark, Jean C; Whitsett, Jeffrey A

2006-04-21

Cystic fibrosis (CF), a common lethal pulmonary disorder in Caucasians, is caused by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR) that disturbs fluid homeostasis and host defense in target organs. The effects of CFTR and delta508-CFTR were assessed in transgenic mice that 1) lack CFTR expression (Cftr-/-); 2) express the human delta508 CFTR (CFTR(delta508)); 3) overexpress the normal human CFTR (CFTR(tg)) in respiratory epithelial cells. Genes were selected from Affymetrix Murine Gene-Chips analysis and subjected to functional classification, k-means clustering, promoter cis-elements/modules searching, literature mining, and pathway exploring. Genomic responses to Cftr-/- were not corrected by expression of CFTR(delta508). Genes regulating host defense, inflammation, fluid and electrolyte transport were similarly altered in Cftr-/- and CFTR(delta508) mice. CFTR(delta508) induced a primary disturbance in expression of genes regulating redox and antioxidant systems. Genomic responses to CFTR(tg) were modest and were not associated with lung pathology. CFTR(tg) and CFTR(delta508) induced genes encoding heat shock proteins and other chaperones but did not activate the endoplasmic reticulum-associated degradation pathway. RNAs encoding proteins that directly interact with CFTR were identified in each of the CFTR mouse models, supporting the hypothesis that CFTR functions within a multiprotein complex whose members interact at the level of protein-protein interactions and gene expression. Promoters of genes influenced by CFTR shared common regulatory elements, suggesting that their co-expression may be mediated by shared regulatory mechanisms. Genes and pathways involved in the response to CFTR may be of interest as modifiers of CF.

Saturable Absorption in 2D Ti3 C2 MXene Thin Films for Passive Photonic Diodes.

PubMed

Dong, Yongchang; Chertopalov, Sergii; Maleski, Kathleen; Anasori, Babak; Hu, Longyu; Bhattacharya, Sriparna; Rao, Apparao M; Gogotsi, Yury; Mochalin, Vadym N; Podila, Ramakrishna

2018-03-01

MXenes comprise a new class of 2D transition metal carbides, nitrides, and carbonitrides that exhibit unique light-matter interactions. Recently, 2D Ti 3 CNT x (T x represents functional groups such as OH and F) was found to exhibit nonlinear saturable absorption (SA) or increased transmittance at higher light fluences, which is useful for mode locking in fiber-based femtosecond lasers. However, the fundamental origin and thickness dependence of SA behavior in MXenes remain to be understood. 2D Ti 3 C 2 T x thin films of different thicknesses are fabricated using an interfacial film formation technique to systematically study their nonlinear optical properties. Using the open aperture Z-scan method, it is found that the SA behavior in Ti 3 C 2 T x MXene arises from plasmon-induced increase in the ground state absorption at photon energies above the threshold for free carrier oscillations. The saturation fluence and modulation depth of Ti 3 C 2 T x MXene is observed to be dependent on the film thickness. Unlike other 2D materials, Ti 3 C 2 T x is found to show higher threshold for light-induced damage with up to 50% increase in nonlinear transmittance. Lastly, building on the SA behavior of Ti 3 C 2 T x MXenes, a Ti 3 C 2 T x MXene-based photonic diode that breaks time-reversal symmetry to achieve nonreciprocal transmission of nanosecond laser pulses is demonstrated. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

47 CFR 73.508 - Standards of good engineering practice.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 4 2010-10-01 2010-10-01 false Standards of good engineering practice. 73.508 Section 73.508 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES... engineering practice. (a) All noncommercial educational stations and LPFM stations operating with more than 10...

47 CFR 73.508 - Standards of good engineering practice.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 4 2014-10-01 2014-10-01 false Standards of good engineering practice. 73.508 Section 73.508 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES... engineering practice. (a) All noncommercial educational stations and LPFM stations operating with more than 10...

47 CFR 73.508 - Standards of good engineering practice.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 4 2012-10-01 2012-10-01 false Standards of good engineering practice. 73.508 Section 73.508 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES... engineering practice. (a) All noncommercial educational stations and LPFM stations operating with more than 10...

47 CFR 73.508 - Standards of good engineering practice.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 4 2013-10-01 2013-10-01 false Standards of good engineering practice. 73.508 Section 73.508 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES... engineering practice. (a) All noncommercial educational stations and LPFM stations operating with more than 10...

47 CFR 73.508 - Standards of good engineering practice.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 4 2011-10-01 2011-10-01 false Standards of good engineering practice. 73.508 Section 73.508 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES... engineering practice. (a) All noncommercial educational stations and LPFM stations operating with more than 10...

77 FR 71491 - Airworthiness Directives; Turbomeca S.A. Turboshaft Engines

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-03

... Airworthiness Directives; Turbomeca S.A. Turboshaft Engines AGENCY: Federal Aviation Administration (FAA), DOT... Turbomeca S.A. Arriel 1E2, 1S, and 1S1 turboshaft engines. That AD currently requires a one-time inspection... 74 45 15. You may view this service information at the FAA, Engine & Propeller Directorate, 12 New...

Section 508 Standards Resources

EPA Pesticide Factsheets

Learn which software applications, operating systems, web-based applications, and other electronic and information technology (EIT) products are covered by Section 508 of the Rehabilitation Act; and resources for making sure your EIT products are compliant

Processing and fractional utilization of lignocellulosic substrates by "pure" and "natural and defined mixed" culture C.TM1, C.SA IV and rumen mixed culture consortia CD.

PubMed

Sankar, M; Chandra, T S

2003-01-01

A detailed analysis was made of chemical fractions of common agro-residues before and after pretreatment (alkali and hydrogen peroxide), and the selective utilization of components such as WSS, EBS, TSS, lignin, cellulose and hemicellulose by pure and mixed cultures of cellulolytic and xylanolytic Clostridia was monitored and correlated with the organisms' enzyme activity. For all cultures pretreatment gave higher utilization of hemicellulose and cellulose fractions; hydrogen peroxide pretreatment was more effective than NaOH treatment. Lignin utilization was not very significant even on pretreatment. C.TM1 and C.SA IV utilized hemicellulose and cellulose better than mixed cultures in selected substrates. These results help to determine the substrate composition, pretreatment conditions and enzyme system of the organism needed when designing an inoculum for agricultural waste treatment processes such as composting or biogas generation.

Collisions of slow ions C3Hn+ and C3Dn+ (n = 2-8) with room temperature carbon surfaces: mass spectra of product ions and the ion survival probability.

PubMed

Pysanenko, Andriy; Zabka, Jan; Feketeová, Linda; Märk, Tilmann D; Herman, Zdenek

2008-01-01

Collisions of C3Hn+ (n = 2-8) ions and some of their per- deuterated analogs with room temperature carbon (HOPG) surfaces (hydrocarbon-covered) were investigated over the incident energy range 13-45 eV in beam scattering experiments. The mass spectra of product ions were measured and main fragmentation paths of the incident projectile ions, energized in the surface collision, were determined. The extent of fragmentation increased with increasing incident energy. Mass spectra of even-electron ions C3H7+ and C3H5+ showed only fragmentations, mass spectra of radical cations C3H8*+ and C3H6*+ showed both simple fragmentations of the projectile ion and formation of products of its surface chemical reaction (H-atom transfer between the projectile ion and hydrocarbons on the surface). No carbon-chain build-up reaction (formation of C4 hydrocarbons) was detected. The survival probability of the incident ions, S(a), was usually found to be about 1-2% for the radical cation projectile ions C3H8*+, C3H6*+, C3H4*+ and C3H2*+ and several percent up to about 20% for the even-electron projectile ions C3H7+, C3H5+, C3H3+. A plot of S(a) values of C1, C2, C3, some C7 hydrocarbon ions, Ar+ and CO2+ on hydrocarbon-covered carbon surfaces as a function of the ionization energies (IE) of the projectile species showed a drop from about 10% to about 1% and less at IE 8.5-9.5 eV and further decrease with increasing IE. A strong correlation was found between log S(a) and IE, a linear decrease over the entire range of IE investigated (7-16 eV), described by log S(a) = (3.9 +/- 0.5)-(0.39 +/- 0.04) IE.

30 CFR 285.508 - What rent payments must I pay on ROW grants or RUE grants associated with renewable energy projects?

Code of Federal Regulations, 2011 CFR

2011-07-01

... RUE grants associated with renewable energy projects? 285.508 Section 285.508 Mineral Resources BUREAU... RENEWABLE ENERGY ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF Payments and Financial... associated with renewable energy projects? (a) For each ROW grant MMS approves under subpart C of this part...

The effects of temperature and aeration on the corrosion of A508III low alloy steel in boric acid solutions at 25-95 °C

NASA Astrophysics Data System (ADS)

Xiao, Qian; Lu, Zhanpeng; Chen, Junjie; Yao, Meiyi; Chen, Zhen; Ejaz, Ahsan

2016-11-01

The effects of temperature, solution composition and dissolved oxygen on the corrosion rate and electrochemical behavior of an A508III low alloy steel in boric acid solution with lithium hydroxide at 25-95 °C are investigated. In aerated solutions, increasing the boric acid concentration increases the corrosion rate and the anodic current density. The corrosion rate in deaerated solutions increases with increasing temperature. A corrosion rate peak value is found at approximately 75 °C in aerated solutions. Increasing temperature increases the oxygen diffusion coefficient, decreases the dissolved oxygen concentration, accelerates the hydrogen evolution reaction, and accelerates both the active dissolution and the film forming reactions. Increasing dissolved oxygen concentration does not significantly affect the corrosion rate at 50 and 60 °C, increases the corrosion rate at 70 and 80 °C, and decreases the corrosion rate at 87.5 and 95 °C in a high concentration boric acid solution with lithium hydroxide.

Allosteric modulation balances thermodynamic stability and restores function of ΔF508 CFTR

PubMed Central

Aleksandrov, Andrei A.; Kota, Pradeep; Cui, Liying; Jensen, Tim; Alekseev, Alexey E.; Reyes, Santiago; He, Lihua; Gentzsch, Martina; Aleksandrov, Luba A.; Dokholyan, Nikolay V.; Riordan, John R.

2013-01-01

Most cystic fibrosis is caused by a deletion of a single residue (F508) in CFTR that disrupts the folding and biosynthetic maturation of the ion channel protein. Progress towards understanding the underlying mechanisms and overcoming the defect remain incomplete. Here we show that the thermal instability of human ΔF508 CFTR channel activity evident in both cell-attached membrane patches and planar phospholipid bilayers is not observed in corresponding mutant CFTRs of several non-mammalian species. These more stable orthologs are distinguished from their mammalian counterparts by the substitution of proline residues at several key dynamic locations in the first nucleotide domain (NBD1), including the structurally diverse region (SDR), the gamma phosphate switch loop and the Regulatory Insertion (RI). Molecular Dynamic analyses revealed that addition of the prolines could reduce flexibility at these locations and increase the temperatures of unfolding transitions of ΔF508 NBD1 to that of the wild-type. Introduction of these prolines experimentally into full-length human ΔF508 CFTR together with the already recognized I539T suppressor mutation, also in the SDR, restored channel function and thermodynamic stability as well as its trafficking to and lifetime at the cell surface. Thus, while cellular manipulations that circumvent its culling by quality control systems leave ΔF508 CFTR dysfunctional at physiological temperature, restoration of the delicate balance between the dynamic protein’s inherent stability and channel activity returns a near-normal state. PMID:22406676

Advanced Environmental Barrier Coating and SA Tyrannohex SiC Composites Integration for Improved Thermomechanical and Environmental Durability

NASA Technical Reports Server (NTRS)

Zhu, Dongming; Halbig, Michael; Singh, Mrityunjay

2018-01-01

The development of 2700 degF capable environmental barrier coating (EBC) systems, particularly, the Rare Earth "Hafnium" Silicon bond coat systems, have significantly improved the temperature capability and environmental stability of SiC/SiC Ceramic Matrix Composite Systems. We have specifically developed the advanced 2700 degF EBC systems, integrating the EBC to the high temperature SA Tyrannohex SiC fiber composites, for comprehensive performance and durability evaluations for potential turbine engine airfoil component applications. The fundamental mechanical properties, environmental stability and thermal gradient cyclic durability performance of the EBC - SA Tyrannohex composites were investigated. The paper will particularly emphasize the high pressure combustion rig recession, cyclic thermal stress resistance and thermomechanical low cycle fatigue testing of uncoated and environmental barrier coated Tyrannohex SiC SA composites in these simulated turbine engine combustion water vapor, thermal gradients, and mechanical loading conditions. We have also investigated high heat flux and flexural fatigue degradation mechanisms, determined the upper limits of operating temperature conditions for the coated SA composite material systems in thermomechanical fatigue conditions. Recent progress has also been made by using the self-healing rare earth-silicon based EBCs, thus enhancing the SA composite hexagonal fiber columns bonding for improved thermomechanical and environmental durability in turbine engine operation environments. More advanced EBC- composite systems based on the new EBC-Fiber Interphases will also be discussed.

A New Protein Phosphatase 2C (FsPP2C1) Induced by Abscisic Acid Is Specifically Expressed in Dormant Beechnut Seeds1

PubMed Central

Lorenzo, Oscar; Rodríguez, Dolores; Nicolás, Gregorio; Rodríguez, Pedro L.; Nicolás, Carlos

2001-01-01

An abscisic acid (ABA)-induced cDNA fragment encoding a putative protein phosphatase 2C (PP2C) was obtained by means of differential reverse transcriptase-polymerase chain reaction approach. The full-length clone was isolated from a cDNA library constructed using mRNA from ABA-treated beechnut (Fagus sylvatica) seeds. This clone presents all the features of plant type PP2C and exhibits homology to members of this family such as AthPP2CA (61%), ABI1 (48%), or ABI2 (47%), therefore it was named FsPP2C1. The expression of FsPP2C1 is detected in dormant seeds and increases after ABA treatment, when seeds are maintained dormant, but it decreases and tends to disappear when dormancy is being released by stratification or under gibberellic acid treatment. Moreover, drought stress seems to have no effect on FsPP2C1 transcript accumulation. The FsPP2C1 transcript expression is tissue specific and was found to accumulate in ABA-treated seeds rather than in other ABA-treated vegetative tissues examined. These results suggest that the corresponding protein could be related to ABA-induced seed dormancy. By expressing FsPP2C1 in Escherichia coli as a histidine tag fusion protein, we have obtained direct biochemical evidence supporting Mg2+-dependent phosphatase activity of this protein. PMID:11299374

23 CFR 636.508 - Can price or cost be an issue in discussions?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Can price or cost be an issue in discussions? 636.508 Section 636.508 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND... Can price or cost be an issue in discussions? You may inform an offeror that its price is considered...

23 CFR 636.508 - Can price or cost be an issue in discussions?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 23 Highways 1 2012-04-01 2012-04-01 false Can price or cost be an issue in discussions? 636.508 Section 636.508 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND... Can price or cost be an issue in discussions? You may inform an offeror that its price is considered...

23 CFR 636.508 - Can price or cost be an issue in discussions?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Can price or cost be an issue in discussions? 636.508 Section 636.508 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND... Can price or cost be an issue in discussions? You may inform an offeror that its price is considered...

23 CFR 636.508 - Can price or cost be an issue in discussions?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Can price or cost be an issue in discussions? 636.508 Section 636.508 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND... Can price or cost be an issue in discussions? You may inform an offeror that its price is considered...

Nuclear Countermeasure Activity of TP508 Linked to Restoration of Endothelial Function and Acceleration of DNA Repair

PubMed Central

Olszewska-Pazdrak, Barbara; McVicar, Scott D.; Rayavara, Kempaiah; Moya, Stephanie M.; Kantara, Carla; Gammarano, Chris; Olszewska, Paulina; Fuller, Gerald M.; Sower, Laurie E.; Carney, Darrell H.

2016-01-01

There is increasing evidence that radiation-induced damage to endothelial cells and loss of endothelial function may contribute to both acute radiation syndromes and long-term effects of whole-body nuclear irradiation. Therefore, several drugs are being developed to mitigate the effects of nuclear radiation, most of these drugs will target and protect or regenerate leukocytes and platelets. Our laboratory has demonstrated that TP508, a 23-amino acid thrombin peptide, activates endothelial cells and stem cells to revascularize and regenerate tissues. We now show that TP508 can mitigate radiation-induced damage to endothelial cells in vitro and in vivo. Our in vitro results demonstrate that human endothelial cells irradiation attenuates nitric oxide (NO) signaling, disrupts tube formation and induces DNA double-strand breaks (DSB). TP508 treatment reverses radiation effects on NO signaling, restores tube formation and accelerates the repair of radiation-induced DSB. The radiation-mitigating effects of TP508 on endothelial cells were also seen in CD-1 mice where systemic injection of TP508 stimulated endothelial cell sprouting from aortic explants after 8 Gy irradiation. Systemic doses of TP508 that mitigated radiation-induced endothelial cell damage, also significantly increased survival of CD-1 mice when injected 24 h after 8.5 Gy exposure. These data suggest that increased survival observed with TP508 treatment may be due to its effects on vascular and microvascular endothelial cells. Our study supports the usage of a regenerative drug such as TP508 to activate endothelial cells as a countermeasure for mitigating the effects of nuclear radiation. PMID:27388041

38 CFR 17.508 - Access to quality assurance records and documents within the agency.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2014-07-01 2014-07-01 false Access to quality assurance records and documents within the agency. 17.508 Section 17.508 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Confidentiality of Healthcare Quality Assurance Review...

38 CFR 17.508 - Access to quality assurance records and documents within the agency.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Access to quality assurance records and documents within the agency. 17.508 Section 17.508 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Confidentiality of Healthcare Quality Assurance Review...

38 CFR 17.508 - Access to quality assurance records and documents within the agency.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Access to quality assurance records and documents within the agency. 17.508 Section 17.508 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Confidentiality of Healthcare Quality Assurance Review...

38 CFR 17.508 - Access to quality assurance records and documents within the agency.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2012-07-01 2012-07-01 false Access to quality assurance records and documents within the agency. 17.508 Section 17.508 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Confidentiality of Healthcare Quality Assurance Review...

38 CFR 17.508 - Access to quality assurance records and documents within the agency.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 38 Pensions, Bonuses, and Veterans' Relief 1 2013-07-01 2013-07-01 false Access to quality assurance records and documents within the agency. 17.508 Section 17.508 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS MEDICAL Confidentiality of Healthcare Quality Assurance Review...

Corrosion inhibition of steam generator tubesheet by Alloy 690 cladding in secondary side environments

NASA Astrophysics Data System (ADS)

Hur, Do Haeng; Choi, Myung Sik; Lee, Deok Hyun; Han, Jung Ho; Shim, Hee Sang

2013-11-01

Denting is a phenomenon that a steam generator tube is distorted by a volume expansion of corrosion products of the tube support and tubesheet materials adjacent to the tube. Although denting has been mitigated by a modification of the design and material of the tube support structures, it has been an inevitable concern in the crevice region of the top of tubesheet. This paper provides a new technology to prevent denting by cladding the secondary surface of the tubesheet with a corrosion resistant material. In this study, Alloy 690 material was cladded onto the surface of an SA508 tubesheet to a thickness of about 9 mm. The corrosion rates of the original SA508 tubesheet and the Alloy 690 clad material were measured in acidic and alkaline simulated environments. Using Alloy 690 cladding, the corrosion rate of the tubesheet within a magnetite sludge pile decreased by a factor of 680 in 0.1 M NiCl2 solution at 300 °C, and by a factor of 58 in 2 M NaOH solution at 315 °C. This means that denting can drastically be prevented by cladding the secondary tubesheet surface with corrosion resistant materials.

23 CFR 636.508 - Can price or cost be an issue in discussions?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Can price or cost be an issue in discussions? 636.508... TRAFFIC OPERATIONS DESIGN-BUILD CONTRACTING Discussions, Proposal Revisions and Source Selection § 636.508 Can price or cost be an issue in discussions? You may inform an offeror that its price is considered...

F508del-CFTR rescue: a matter of cell stress response.

PubMed

Nieddu, Erika; Pollarolo, Benedetta; Merello, Luisa; Schenone, Silvia; Mazzei, Mauro

2013-01-01

Cystic fibrosis (CF) is a common inherited fatal disease affecting 70,000 people worldwide, with a median predicted age of survival of approximately 38 years. The deletion of Phenylalanine in position 508 of the Cystic Fibrosis Transmembrane conductance Regulator (F508del-CFTR) is the most common mutation in CF patients: the deleted protein, not properly folded, is degraded. To date no commercial drugs are available. Low temperature, some osmolytes and conditions able to induce heat shock protein 70 (Hsp70) expression and heat shock cognate 70 (Hsc70) inhibition result in F508del-CFTR rescue, hence restoring its physiological function: this review sheds light on the correlation between these several evidences. Interestingly, all these approaches have a role in the cell stress response (CSR), a set of cell reactions to stress. In addition, unpredictably, F508del-CFTR rescue has to be considered in the frame of CSR: entities that induce - or are induced during - the CSR are, in general, also able to correct trafficking defect of CFTR. Specifically, the low temperature induces, by definition, a CSR; osmolytes, such as glycerol and trimethylamine N-oxide (TMAO), are products of the CSR; pharmacological correctors, such as Matrine and 4-phenylbutirric acid (4PBA), down-regulate the constitutive Hsc70 in favor of an up-regulation of the inducible chaperone Hsp70, another component of the CSR. The identification of a common mechanism of action for different types of correctors could drive the discovery of new active molecules in CF, overcoming methods clinically inapplicable, such as the low temperature.

The CFTR trafficking mutation F508del inhibits the constitutive activity of SLC26A9.

PubMed

Bertrand, Carol A; Mitra, Shalini; Mishra, Sanjay K; Wang, Xiaohui; Zhao, Yu; Pilewski, Joseph M; Madden, Dean R; Frizzell, Raymond A

2017-06-01

Several members of the SLC26A family of anion transporters associate with CFTR, forming complexes in which CFTR and SLC26A functions are reciprocally regulated. These associations are thought to be facilitated by PDZ scaffolding interactions. CFTR has been shown to be positively regulated by NHERF-1, and negatively regulated by CAL in airway epithelia. However, it is unclear which PDZ-domain protein(s) interact with SLC26A9, a SLC26A family member found in airway epithelia. We have previously shown that primary, human bronchial epithelia (HBE) from non-CF donors exhibit constitutive anion secretion attributable to SLC26A9. However, constitutive anion secretion is absent in HBE from CF donors. We examined whether changes in SLC26A9 constitutive activity could be attributed to a loss of CFTR trafficking, and what role PDZ interactions played. HEK293 coexpressing SLC26A9 with the trafficking mutant F508del CFTR exhibited a significant reduction in constitutive current compared with cells coexpressing SLC26A9 and wt CFTR. We found that SLC26A9 exhibits complex glycosylation when coexpressed with F508del CFTR, but its expression at the plasma membrane is decreased. SLC26A9 interacted with both NHERF-1 and CAL, and its interaction with both significantly increased with coexpression of wt CFTR. However, coexpression with F508del CFTR only increased SLC26A9's interaction with CAL. Mutation of SLC26A9's PDZ motif decreased this association with CAL, and restored its constitutive activity. Correcting aberrant F508del CFTR trafficking in CF HBE with corrector VX-809 also restored SLC26A9 activity. We conclude that when SLC26A9 is coexpressed with F508del CFTR, its trafficking defect leads to a PDZ motif-sensitive intracellular retention of SLC26A9. Copyright © 2017 the American Physiological Society.

24 CFR 3280.508 - Heat loss, heat gain and cooling load calculations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Thermal Protection § 3280.508 Heat loss, heat gain and cooling load calculations. (a) Information, values... Loads—Manufactured Homes—February 1992-PNL 8006, HUD User No. 0005945. (c) Areas where the insulation... 24 Housing and Urban Development 5 2013-04-01 2013-04-01 false Heat loss, heat gain and cooling...

24 CFR 3280.508 - Heat loss, heat gain and cooling load calculations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Thermal Protection § 3280.508 Heat loss, heat gain and cooling load calculations. (a) Information, values... Loads—Manufactured Homes—February 1992-PNL 8006, HUD User No. 0005945. (c) Areas where the insulation... 24 Housing and Urban Development 5 2010-04-01 2010-04-01 false Heat loss, heat gain and cooling...

24 CFR 3280.508 - Heat loss, heat gain and cooling load calculations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Thermal Protection § 3280.508 Heat loss, heat gain and cooling load calculations. (a) Information, values... Loads—Manufactured Homes—February 1992-PNL 8006, HUD User No. 0005945. (c) Areas where the insulation... 24 Housing and Urban Development 5 2011-04-01 2011-04-01 false Heat loss, heat gain and cooling...

24 CFR 3280.508 - Heat loss, heat gain and cooling load calculations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Thermal Protection § 3280.508 Heat loss, heat gain and cooling load calculations. (a) Information, values... Loads—Manufactured Homes—February 1992-PNL 8006, HUD User No. 0005945. (c) Areas where the insulation... 24 Housing and Urban Development 5 2012-04-01 2012-04-01 false Heat loss, heat gain and cooling...

24 CFR 3280.508 - Heat loss, heat gain and cooling load calculations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Thermal Protection § 3280.508 Heat loss, heat gain and cooling load calculations. (a) Information, values... Loads—Manufactured Homes—February 1992-PNL 8006, HUD User No. 0005945. (c) Areas where the insulation... 24 Housing and Urban Development 5 2014-04-01 2014-04-01 false Heat loss, heat gain and cooling...

26 CFR 1.412(c)(1)-2 - Shortfall method.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Shortfall method. 1.412(c)(1)-2 Section 1.412(c... (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.412(c)(1)-2 Shortfall method. (a) In general—(1) Shortfall method. The shortfall method is a funding method that adapts a plan's...

Genetic determinants restricting the reassortment of heterologous NSP2 genes into the simian rotavirus SA11 genome.

PubMed

Mingo, Rebecca; Zhang, Shu; Long, Courtney P; LaConte, Leslie E W; McDonald, Sarah M

2017-08-24

Rotaviruses (RVs) can evolve through the process of reassortment, whereby the 11 double-stranded RNA genome segments are exchanged among strains during co-infection. However, reassortment is limited in cases where the genes or encoded proteins of co-infecting strains are functionally incompatible. In this study, we employed a helper virus-based reverse genetics system to identify NSP2 gene regions that correlate with restricted reassortment into simian RV strain SA11. We show that SA11 reassortants with NSP2 genes from human RV strains Wa or DS-1 were efficiently rescued and exhibit no detectable replication defects. However, we could not rescue an SA11 reassortant with a human RV strain AU-1 NSP2 gene, which differs from that of SA11 by 186 nucleotides (36 amino acids). To map restriction determinants, we engineered viruses to contain chimeric NSP2 genes in which specific regions of AU-1 sequence were substituted with SA11 sequence. We show that a region spanning AU-1 NSP2 gene nucleotides 784-820 is critical for the observed restriction; yet additional determinants reside in other gene regions. In silico and in vitro analyses were used to predict how the 784-820 region may impact NSP2 gene/protein function, thereby informing an understanding of the reassortment restriction mechanism.

Identification of high-risk Listeria monocytogenes serotypes in lineage I (serotype 1/2a, 1/2c, 3a and 3c) using multiplex PCR

USDA-ARS?s Scientific Manuscript database

Aims: Using molecular subtyping techniques, Listeria monocytogenes is divided into three major phylogenetic lineages, and a multiplex PCR method can differentiate five L. monocytogenes subgroups: 1/2a-3a, 1/2c-3c, 1/2b-3b-7, 4b-4d-4e, and 4a-4c. In the current study, we conducted genome comparison...

Aldo-keto reductases AKR1C1, AKR1C2 and AKR1C3 may enhance progesterone metabolism in ovarian endometriosis.

PubMed

Hevir, N; Vouk, K; Sinkovec, J; Ribič-Pucelj, M; Rižner, T Lanišnik

2011-05-30

Endometriosis is a very common disease that is characterized by increased formation of estradiol and disturbed progesterone action. This latter is usually explained by a lack of progesterone receptor B (PR-B) expression, while the role of pre-receptor metabolism of progesterone is not yet fully understood. In normal endometrium, progesterone is metabolized by reductive 20α-hydroxysteroid dehydrogenases (20α-HSDs), 3α/β-HSDs and 5α/β-reductases. The aldo-keto reductases 1C1 and 1C3 (AKR1C1 and AKR1C3) are the major reductive 20α-HSDs, while the oxidative reaction is catalyzed by 17β-HSD type 2 (HSD17B2). Also, 3α-HSD and 3β-HSD activities have been associated with the AKR1C isozymes. Additionally, 5α-reductase types 1 and 2 (SRD5A1, SRD5A2) and 5β-reductase (AKR1D1) are responsible for the formation of 5α- and 5β-reduced pregnanes. In this study, we examined the expression of PR-AB and the progesterone metabolizing enzymes in 31 specimens of ovarian endometriosis and 28 specimens of normal endometrium. Real-time PCR analysis revealed significantly decreased mRNA levels of PR-AB, HSD17B2 and SRD5A2, significantly increased mRNA levels of AKR1C1, AKR1C2, AKR1C3 and SRD5A1, and negligible mRNA levels of AKR1D1. Immunohistochemistry staining of endometriotic tissue compared to control endometrium showed significantly lower PR-B levels in epithelial cells and no significant differences in stromal cells, there were no significant differences in the expression of AKR1C3 and significantly higher AKR1C2 levels were seen only in stromal cells. Our expression analysis data at the mRNA level and partially at the cellular level thus suggest enhanced metabolism of progesterone by SRD5A1 and the 20α-HSD and 3α/β-HSD activities of AKR1C1, AKR1C2 and AKR1C3. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Diabetic subjects diagnosed through the Diabetes Prevention Trial-Type 1 (DPT-1) are often asymptomatic with normal A1C at diabetes onset.

PubMed

Triolo, Taylor M; Chase, H Peter; Barker, Jennifer M

2009-05-01

Upon diagnosis of type 1 diabetes, patients are usually symptomatic, and many have ketoacidosis. Screening for islet autoantibodies (IAs) has been shown to decrease A1C level and rate of hospitalization at diabetes onset. Metabolic tests and the presence of symptoms were described at diabetes onset during the Diabetes Prevention Trial-Type 1 (DPT-1). The DPT-1 screened relatives of patients with type 1 diabetes for islet cell autoantiobodies (ICAs). Those with positive ICAs had intravenous and oral glucose tolerance tests (IVGTTs and OGTTs) and were randomized into one of two prevention trials. Throughout the DPT-1 parenteral and oral insulin study, 246 people were diagnosed with type 1 diabetes. Of the 246 subjects diagnosed with diabetes, 218 had data regarding the presence of symptoms, and 138 (63.3%) reported no symptoms suggestive of diabetes. Eight subjects (3.67%) presented with ketosis. Subjects presented with a mean +/- SD A1C of 6.41 +/- 1.15%. At diagnosis, 90 subjects (50.8%) had A1C in the normal range (<6.2%). OGTT data at the time of diagnosis indicate that 35.4% had a glucose result of <100 mg/dl at 0 min. The majority of subjects diagnosed with type 1 diabetes through the DPT-1 were asymptomatic at onset and had normal fasting glucose and A1C levels. This suggests that intermittent screening (IA followed by OGTT) may allow diagnosis of diabetes before severe metabolic decompensation. Screening with A1C will miss identifying many of the subjects with newly diagnosed type 1 diabetes in this cohort.

31 CFR 594.508 - Transactions related to telecommunications authorized.

Code of Federal Regulations, 2012 CFR

2012-07-01

... telecommunications authorized. 594.508 Section 594.508 Money and Finance: Treasury Regulations Relating to Money and... related to telecommunications authorized. All transactions ordinarily incident to the receipt or transmission of telecommunications involving persons whose property or interests in property are blocked...

31 CFR 594.508 - Transactions related to telecommunications authorized.

Code of Federal Regulations, 2014 CFR

2014-07-01

... telecommunications authorized. 594.508 Section 594.508 Money and Finance: Treasury Regulations Relating to Money and... related to telecommunications authorized. All transactions ordinarily incident to the receipt or transmission of telecommunications involving persons whose property or interests in property are blocked...

31 CFR 594.508 - Transactions related to telecommunications authorized.

Code of Federal Regulations, 2013 CFR

2013-07-01

... telecommunications authorized. 594.508 Section 594.508 Money and Finance: Treasury Regulations Relating to Money and... related to telecommunications authorized. All transactions ordinarily incident to the receipt or transmission of telecommunications involving persons whose property or interests in property are blocked...

31 CFR 594.508 - Transactions related to telecommunications authorized.

Code of Federal Regulations, 2010 CFR

2010-07-01

... telecommunications authorized. 594.508 Section 594.508 Money and Finance: Treasury Regulations Relating to Money and... related to telecommunications authorized. All transactions ordinarily incident to the receipt or transmission of telecommunications involving persons whose property or interests in property are blocked...

31 CFR 545.508 - Transactions related to telecommunications authorized.

Code of Federal Regulations, 2010 CFR

2010-07-01

... telecommunications authorized. 545.508 Section 545.508 Money and Finance: Treasury Regulations Relating to Money and... related to telecommunications authorized. All transactions ordinarily incident to the receipt or transmission of telecommunications involving the territory of Afghanistan controlled by the Taliban are...

31 CFR 594.508 - Transactions related to telecommunications authorized.

Code of Federal Regulations, 2011 CFR

2011-07-01

... telecommunications authorized. 594.508 Section 594.508 Money and Finance: Treasury Regulations Relating to Money and... related to telecommunications authorized. All transactions ordinarily incident to the receipt or transmission of telecommunications involving persons whose property or interests in property are blocked...

AME survey-003 A2: on the attractiveness of an medicine career in current China with a survey of 7,508 medical professionals and 443 non-medical professionals

PubMed Central

Li, Yáo T.

2016-01-01

This is a part of the study of AME survey-003, aiming to understand the motivation and attractiveness of a career in medicine in China. The surveys were conducted on DXY platform with 3,564 medical professionals during October 26 to November 20; on Sojump platform with 1,587 medical professionals during October 28 to December 14, and 443 non-medical professionals during November 15 to December, all in 2015. Similar to our previous result, the not regretted participants vs. regretted participants (N/Y) ratio was 1.1 (P<0.01), and there was no significant difference in N/Y ratio between male and female medical professionals. Medical professionals working in class-IIIA hospitals, small township hospitals, or primary care clinics had a relatively higher job satisfaction than those in hospitals of other classes, while lecturer-level attending doctors (zhuzhi yishi) had a relatively lower job satisfaction than doctors of other grades. A large portion of respondents who replied they regretted entered medical profession said they would still like to be in this profession if they could be in their preferred hospital class and specialty. Public health and basic science research staff, anesthesiologists, oncologists had a relatively higher job satisfaction, while accident and emergency physicians, nurses, and pediatricians had a relatively lower job satisfaction. Medical professionals in Yunnan and Gansu ranked consistently high in job satisfaction than other provinces; despite they were not in the economically advanced regions in China. Similar to our previous result, the majority of the participants favored China to open up medical market to qualified foreign medical organizations to take part in fair competition, as well as favor the government to support regulated private hospitals. Pooled data of 7,508 medical professionals with data from AME survey-003 A1 included showed medicine was the top career choice among medical professionals’ children (104/508, 20

AME survey-003 A2: on the attractiveness of an medicine career in current China with a survey of 7,508 medical professionals and 443 non-medical professionals.

PubMed

Wáng, Yì Xiáng J; Li, Yáo T

2016-02-01

This is a part of the study of AME survey-003, aiming to understand the motivation and attractiveness of a career in medicine in China. The surveys were conducted on DXY platform with 3,564 medical professionals during October 26 to November 20; on Sojump platform with 1,587 medical professionals during October 28 to December 14, and 443 non-medical professionals during November 15 to December, all in 2015. Similar to our previous result, the not regretted participants vs. regretted participants (N/Y) ratio was 1.1 (P<0.01), and there was no significant difference in N/Y ratio between male and female medical professionals. Medical professionals working in class-IIIA hospitals, small township hospitals, or primary care clinics had a relatively higher job satisfaction than those in hospitals of other classes, while lecturer-level attending doctors (zhuzhi yishi) had a relatively lower job satisfaction than doctors of other grades. A large portion of respondents who replied they regretted entered medical profession said they would still like to be in this profession if they could be in their preferred hospital class and specialty. Public health and basic science research staff, anesthesiologists, oncologists had a relatively higher job satisfaction, while accident and emergency physicians, nurses, and pediatricians had a relatively lower job satisfaction. Medical professionals in Yunnan and Gansu ranked consistently high in job satisfaction than other provinces; despite they were not in the economically advanced regions in China. Similar to our previous result, the majority of the participants favored China to open up medical market to qualified foreign medical organizations to take part in fair competition, as well as favor the government to support regulated private hospitals. Pooled data of 7,508 medical professionals with data from AME survey-003 A1 included showed medicine was the top career choice among medical professionals' children (104/508, 20.5%), followed

Measurement of HbA1c and HbA2 by Capillarys 2 Flex Piercing HbA1c programme for simultaneous management of diabetes and screening for thalassemia

PubMed Central

Ke, Peifeng; Liu, Jiawei; Chao, Yan; Wu, Xiaobin; Xiong, Yujuan; Lin, Li; Wan, Zemin; Wu, Xinzhong; Xu, Jianhua; Zhuang, Junhua; Huang, Xianzhang

2017-01-01

Introduction Thalassemia could interfere with some assays for haemoglobin A1c (HbA1c) measurement, therefore, it is useful to be able to screen for thalassemia while measuring HbA1c. We used Capillarys 2 Flex Piercing (Capillarys 2FP) HbA1c programme to simultaneously measure HbA1c and screen for thalassemia. Materials and methods Samples from 498 normal controls and 175 thalassemia patients were analysed by Capillarys 2FP HbA1c programme (Sebia, France). For method comparison, HbA1c was quantified by Premier Hb9210 (Trinity Biotech, Ireland) in 98 thalassaemia patients samples. For verification, HbA1c from eight thalassaemia patients was confirmed by IFCC reference method. Results Among 98 thalassaemia samples, Capillarys 2FP did not provide an HbA1c result in three samples with HbH due to the overlapping of HbBart’s with HbA1c fraction; for the remaining 95 thalassaemia samples, Bland-Altman plot showed 0.00 ± 0.35% absolute bias between two systems, and a significant positive bias above 7% was observed only in two HbH samples. The HbA1c values obtained by Capillarys 2FP were consistent with the IFCC targets (relative bias below ± 6%) in all of the eight samples tested by both methods. For screening samples with alpha (α-) thalassaemia silent/trait or beta (β-) thalassemia trait, the optimal HbA2 cut-off values were ≤ 2.2% and > 2.8%, respectively. Conclusions Our results demonstrated the Capillarys 2FP HbA1c system could report an accurate HbA1c value in thalassemia silent/trait, and HbA2 value (≤ 2.2% for α-thalassaemia silent/trait and > 2.8% for β-thalassemia trait) and abnormal bands (HbH and/or HbBart’s for HbH disease, HbF for β-thalassemia) may provide valuable information for screening. PMID:28900367

Measurement of HbA1c and HbA2 by Capillarys 2 Flex Piercing HbA1c programme for simultaneous management of diabetes and screening for thalassemia.

PubMed

Ke, Peifeng; Liu, Jiawei; Chao, Yan; Wu, Xiaobin; Xiong, Yujuan; Lin, Li; Wan, Zemin; Wu, Xinzhong; Xu, Jianhua; Zhuang, Junhua; Huang, Xianzhang

2017-10-01

Thalassemia could interfere with some assays for haemoglobin A 1c (HbA 1c ) measurement, therefore, it is useful to be able to screen for thalassemia while measuring HbA 1c . We used Capillarys 2 Flex Piercing (Capillarys 2FP) HbA 1c programme to simultaneously measure HbA 1c and screen for thalassemia. Samples from 498 normal controls and 175 thalassemia patients were analysed by Capillarys 2FP HbA 1c programme (Sebia, France). For method comparison, HbA 1c was quantified by Premier Hb9210 (Trinity Biotech, Ireland) in 98 thalassaemia patients samples. For verification, HbA 1c from eight thalassaemia patients was confirmed by IFCC reference method. Among 98 thalassaemia samples, Capillarys 2FP did not provide an HbA 1c result in three samples with HbH due to the overlapping of HbBart's with HbA 1c fraction; for the remaining 95 thalassaemia samples, Bland-Altman plot showed 0.00 ± 0.35% absolute bias between two systems, and a significant positive bias above 7% was observed only in two HbH samples. The HbA 1c values obtained by Capillarys 2FP were consistent with the IFCC targets (relative bias below ± 6%) in all of the eight samples tested by both methods. For screening samples with alpha (α-) thalassaemia silent/trait or beta (β-) thalassemia trait, the optimal HbA 2 cut-off values were ≤ 2.2% and > 2.8%, respectively. Our results demonstrated the Capillarys 2FP HbA 1c system could report an accurate HbA 1c value in thalassemia silent/trait, and HbA 2 value (≤ 2.2% for α-thalassaemia silent/trait and > 2.8% for β-thalassemia trait) and abnormal bands (HbH and/or HbBart's for HbH disease, HbF for β-thalassemia) may provide valuable information for screening.

Anchored PDE4 regulates chloride conductance in wild-type and ΔF508-CFTR human airway epithelia

PubMed Central

Blanchard, Elise; Zlock, Lorna; Lao, Anna; Mika, Delphine; Namkung, Wan; Xie, Moses; Scheitrum, Colleen; Gruenert, Dieter C.; Verkman, Alan S.; Finkbeiner, Walter E.; Conti, Marco; Richter, Wito

2014-01-01

Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that impair its expression and/or chloride channel function. Here, we provide evidence that type 4 cyclic nucleotide phosphodiesterases (PDE4s) are critical regulators of the cAMP/PKA-dependent activation of CFTR in primary human bronchial epithelial cells. In non-CF cells, PDE4 inhibition increased CFTR activity under basal conditions (ΔISC 7.1 μA/cm2) and after isoproterenol stimulation (increased ΔISC from 13.9 to 21.0 μA/cm2) and slowed the return of stimulated CFTR activity to basal levels by >3-fold. In cells homozygous for ΔF508-CFTR, the most common mutation found in CF, PDE4 inhibition alone produced minimal channel activation. However, PDE4 inhibition strongly amplified the effects of CFTR correctors, drugs that increase expression and membrane localization of CFTR, and/or CFTR potentiators, drugs that increase channel gating, to reach ∼25% of the chloride conductance observed in non-CF cells. Biochemical studies indicate that PDE4s are anchored to CFTR and mediate a local regulation of channel function. Taken together, our results implicate PDE4 as an important determinant of CFTR activity in airway epithelia, and support the use of PDE4 inhibitors to potentiate the therapeutic benefits of CFTR correctors and potentiators.—Blanchard, E., Zlock, L., Lao, A., Mika, D., Namkung, W., Xie, M., Scheitrum, C., Gruenert, D.C., Verkman, A.S., Finkbeiner, W.E., Conti, M., Richter, W. Anchored PDE4 regulates chloride conductance in wild type and ΔF508-CFTR human airway epithelia. PMID:24200884