Evidence for concerted kinetic oxidation of progesterone by purified rat hepatic cytochrome P-450g

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

Swinney, D.C.; Ryan, D.E.; Thomas, P.E.

1988-07-26

Purified cytochrome P-450g, a male-specific rat hepatic isozyme, was observed to metabolize progesterone to two primary metabolites (6..beta..-hydroxyprogesterone and 16..cap alpha..-hydroxyprogesterone), two secondary metabolites (6..beta..,16..cap alpha..-dihydroxyprogesterone and 6-ketoprogesterone), and one tertiary metabolite (6-keto-16..cap alpha..-hydroxyprogesterone). The K/sub m,app/ for the formation of these products from progesterone was determined to be approximately 0.5 ..mu..M, while the K/sub m,app/ for metabolism of 6..beta..- and 16..cap alpha..-hydroxyprogesterone was found to be 5-10 ..mu..M. The ratio of primary to secondary metabolites did not change significantly at progesterone concentrations from 6 to 150 ..mu..M, and a lag in formation of secondary metabolites was not observed inmore » 1-min incubations. Concerted oxidation of progesterone to secondary products without the intermediate products leaving the active site was suggested by these results and confirmed by isotopic dilution experiments in which little or no dilution of metabolically formed 6..beta..,16..cap alpha..-dihydroxyprogesterone and 6-keto-16..cap alpha..-hydroxyprogesterone was observed in incubations containing a mixture of radiolabeled progesterone and unlabeled 6..beta..-hydroxyprogesterone or 16..cap alpha..-hydroxyprogesterone. Incubation of 6..beta..-hydroxyprogesterone with a reconstituted system in an atmosphere of /sup 18/I/sub 2/ resulted in > 90% incorporation of /sup 18/O in the 16..cap alpha..-position of 6..beta..,16..cap alpha..-dihydroxyprogesterone but no incorporation of /sup 18/O into 6-ketoprogesterone, even though the reaction was dependent upon enzyme and O/sub 2/, and not inhibited by mannitol, catalase, or superoxide dismutase. Factors which characterize the metabolism of progesterone by cytochrome P-450g in terms of active-site constraints and the catalytic competence of the enzyme in microsomes were also explored.« less

cap alpha. -D-Mannopyranosylmethyl-P-nitrophenyltriazene effects on the degradation and biosynthesis of N-linked oligosaccharide chains on. cap alpha. /sub 1/-acid glycoprotein by liver cells

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

Docherty, P.A.; Aronson, N.N. Jr.

1986-05-01

The effects of ..cap alpha..-D-mannopyranosylmethyl-p-nitrophenyltriazene (..cap alpha..-ManMNT) on the degradation and processing of oligosaccharide chains on ..cap alpha../sub 1/-acid glycoprotein (AGP) were studied. Addition of the triazene to a perfused liver blocked the complete degradation of endocytosed N-acetyl (/sup 14/C)glucosamine-labeled asialo-AGP and caused the accumulation of Man/sub 2/GlcNAc/sub 1/ fragments in the lysosome-enriched fraction of the liver homogenate. This compound also reduced the reincorporation of lysosomally-derived (/sup 14/C)GlcNAc into newly secreted glycoproteins. Cultured hepatocytes treated with the inhibitor synthesized and secreted fully-glycosylated AGP. However, the N-linked oligosaccharide chains on AGP secreted by the ..cap alpha..-ManMNT-treated hepatocytes remained sensitive to digestionmore » with endoglycosidase H, were resistant to neuraminidase, and consisted of Man/sub 9-7/GlcNAc/sub 2/ structures as analyzed by high resolution Bio-Gel P-4 chromatography. As measured by their resistance to cleavage by endoglycosidase H, the normal processing of all six carbohydrate chains on AGP to the complex form did not completely resume until nearly 24 h after triazene treatment. Since ManMNT is likely to irreversibly inactivate ..cap alpha..-D-mannosidases, the return of AGP to secretory forms with complex chains after 24 h probably resulted from synthesis of new processing enzymes.« less

The X-ray Crystal Structures of Human {alpha}-Phosphomannomutase 1 Reveal the Structural Basis of Congenital Disorder of Glycosylation Type 1a

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

Silvaggi,N.; Zhang, C.; Lu, Z.

2006-01-01

Carbohydrate-deficient glycoprotein syndrome type 1a (CDG-1a) is a congenital disease characterized by severe defects in nervous system development. It is caused by mutations in alpha -phosphomannomutase (of which there are two isozymes, {alpha}-PMM1 and {alpha}-PPM2). Here we report the X-ray crystal structures of human {alpha}-PMM1 in the open conformation, with and without the bound substrate, {alpha}-D-mannose 1-phosphate. {alpha}-PMM1, like most Haloalkanoic Acid Dehalogenase Superfamily (HADSF) members, consists of two domains, the cap and core, which open to bind substrate and then close to provide a solvent exclusive environment for catalysis. The substrate phosphate group is observed at a positively chargedmore » site of the cap domain, rather than at the core domain phosphoryl-transfer site defined by the D19 nucleophile and Mg{sup 2+} cofactor. This suggests that substrate binds first to the cap and then is swept into the active site upon cap closure. The orientation of the acid/base residue D21 suggests that {alpha}-PMM uses a different method of protecting the aspartylphosphate from hydrolysis than the HADSF member {beta}-phosphoglucomutase. It is hypothesized that the electrostatic repulsion of positive charges at the interface of the cap and core domains stabilizes {alpha}-PMM1 in the open conformation, and that the negatively charged substrate binds to the cap, thereby facilitating its closure over the core domain. The two isozymes {alpha}-PMM1 and {alpha}-PMM2 are shown to have a conserved active-site structure and to display similar kinetic properties. Analysis of the known mutation sites in the context of the structures reveals the genotype-phenotype relationship underlying CDG-1a.« less

Genomic organization and sequence of the Gus-s/sup a/ allele of the murine. beta. -glucuronidase gene

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

Funkenstein, B.; Leary, S.L.; Stein, J.C.

1988-03-01

The Gus-s/sup ..cap alpha../ allele of the mouse ..beta..-glucuronidase gene exhibits a high degree of inducibility by androgens due to its linkage with the Gus-r/sup ..cap alpha../ regulatory locus. The authors isolated Gus-s/sup ..cap alpha../ on a 28-kilobase pair fragment of mouse chromosome 5 and found that it contains 12 exons and 11 intervening sequences spanning 14 kilobase pairs of this genomic segment. The mRNA cap site was identified by ribonuclease protection and primer extension analyses which revealed an unusually short 5' noncoding sequence of 12 nucleotides. Proximal regulatory sequences in the 5'-flanking DNA and the complete sequence of themore » Gus-s/sup ..cap alpha../ mRNA transcript were also determined. Comparison of the amino acid sequence determined from the Gus-s/sup ..cap alpha../ nucleotide sequence with that of human ..beta..-glucuronidase indicated that the two human mRNA species differ due to alternate splicing of an exon homologous to exon 6 of the mouse gene.« less

Creatine kinase and alpha-actin mRNA levels decrease in diabetic rat hearts

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

Popovich, B.; Barrieux, A.; Dillmann, W.H.

1987-05-01

Diabetic cardiomyopathy is associated with cardiac atrophy and isoenzyme redistribution. To determine if tissue specific changes occur in mRNAs coding for ..cap alpha..-actin and creatine kinase (CK), they performed RNA blot analysis. Total ventricular RNA from control (C) and 4 wk old diabetic (D) rats were hybridized with /sup 32/P cDNA probes for ..cap alpha..-actin and CK. A tissue independent cDNA probe, CHOA was also used. Signal intensity was quantified by photodensitometry. D CK mRNA was 47 +/- 16% lower in D vs C. Insulin increases CK mRNA by 20% at 1.5 hs, and completely reverses the deficit after 4more » wks. D ..cap alpha..-actin mRNA is 66 +/- 18% lower in D vs C. Insulin normalized ..cap alpha..-actin mRNA by 5 hs. CHOA mRNA is unchanged in D vs C, but D + insulin CHOA mRNA is 30 +/- 2% lower than C. In rats with diabetic cardiomyopathy, muscle specific CK and ..cap alpha..-actin mRNAs are decreased. Insulin treatment reverses these changes.« less

Gamma-resonance investigation of the kinetics of the reduction of (. cap alpha. -benzil dioximato-1)(. cap alpha. -benzil dioximato-2)di(pyridine)iron(III)

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

Turte, K.I.; Bulgak, I.I.; Stukan, R.A.

1986-07-01

(..cap alpha..-Benzil dioximato-1)(..cap alpha..-benzil dioximato-2)di(pyridine)iron(III) in the form of the diacetone solvate (II) is spontaneously converted at room temperature into (..cap alpha..-benzil dioximato-1)(..cap alpha..-benzil dioximato-2)di(pyridine)iron(II) (III). The quantitative composition of a sample containing complexes II and III has been determined as a function of the temperature and the time by gamma-resonance spectroscopy, which made it possible to investigate the kinetics of this reaction. The changes obtained in the percentage of complex II in the sample as a function of time at a given temperature was treated with the use of the Kolmogorov-Erofeev equation for a topochemical reaction of the typemore » A/sub s/ ..-->.. B/sub s/ + C/sub g/. The rate constants of the reaction at various temperatures and the activation energy *E have been determined. In the temperature range from 293 to 304/sup 0/K *E = 25.6 kcal/mole. The possibilities of gamma-resonance spectroscopy in the investigation of topochemical reactions associated with changes in the oxidation state of iron ions have been demonstrated.« less

Reconstitution of high affinity. cap alpha. /sub 2/ adrenergic agonist binding by fusion with a pertussis toxin substrate

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

Kim, M.H.; Neubig, R.R.

1986-03-05

High affinity ..cap alpha../sub 2/ adrenergic agonist binding is thought to occur via a coupling of the ..cap alpha../sub 2/ receptor with N/sub i/, the inhibitory guanyl nucleotide binding protein. Human platelet membranes pretreated at pH 11.5 exhibit a selective inactivation of agonist binding and N/sub i/. To further study the mechanism of agonist binding, alkali treated membranes (ATM) were mixed with membranes pretreated with 10 ..mu..M phenoxybenzamine to block ..cap alpha../sub 2/ receptors (POB-M). The combined membrane pellet was incubated in 50% polyethylene glycol (PEG) to promote membrane-membrane fusion and assayed for binding to the ..cap alpha../sub 2/ agonistmore » (/sup 3/H)UK 14,304 (UK) and the antagonist (/sup 3/H) yohimbine. PEG treatment resulted in a 2-4 fold enhancement of UK binding whereas yohimbine binding was unchanged. No enhancement of UK binding was observed in the absence of PEG treatment. The reconstitution was dependent on the addition of POB-M. They found that a 1:1 ratio of POB-M:ATM was optimal. Reconstituted binding was inhibited by GppNHp. Fusion of rat C6 glioma cell membranes, which do not contain ..cap alpha../sub 2/ receptors, also enhanced agonist binding to ATM. Fusion of C6 membranes from cells treated with pertussis toxin did not enhance (/sup 3/H) UK binding. These data show that a pertussis toxin sensitive membrane component, possibly N/sub i/, can reconstitute high affinity ..cap alpha../sub 2/ agonist binding.« less

Ionization of isocitrate bound to pig hear NADP/sup +/-dependent isocitrate dehydrogenase: /sup 13/C NMR study of substrate binding

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

Ehrlich, R.S.; Colman, R.F.

1987-06-16

Isocitrate and ..cap alpha..-ketoglutarate have been synthesized with carbon-13 enrichment at specific positions. The /sup 13/C NMR spectra of these derivatives were measured as a function of pH. The magnitudes of the changes in chemical shifts with pH for free isocitrate and the magnesium-isocitrate complex suggest that the primary site of ionization at the ..beta..-carboxyl. In the presence of the enzyme NADP/sup +/-dependent isocitrate dehydrogenase and the activating metal magnesium, the carbon-13 resonances of all three carboxyls remain constant from pH 5.5 to pH 7.5. Thus, the carboxyls remain in the ionized form in the enzyme-isocitrate complex. The ..cap alpha..-hydroxylmore » carbon resonance could not be located in the enzyme-isocitrate complex, suggesting immobilization of this group. Magnesium produces a 2 ppm downfield shift of the ..beta..-carboxyl but does not change the resonances of the ..cap alpha..- and ..gamma..-carboxyls. This result is consistent with metal activation of both the dehydrogenation and decarboxylation reactions. The /sup 13/C NMR spectrum of ..cap alpha..-ketoglutarate remains unchanged in the presence of isocitrate dehydrogenase, implying the absence of alterations in geometry in the enzyme-bound form. Formation of the quaternary complex with Mg/sup 2 +/ and NADPH leads to loss of the ..cap alpha..-ketoglutarate resonances and the appearance of new resonances characteristic of ..cap alpha..-hydroxyglutarate. In addition, a broad peak ascribed to the enol form of ..cap alpha..-ketoglutarate is observed. The substantial change in the shift of the ..beta..-carboxyl of isocitrate and the lack of significant shifts in the other carboxyls of isocitrate or ..cap alpha..-ketoglutarate suggest that interaction of the ..beta..-carboxyl with the enzyme contributes to the tighter binding of isocitrate and may be significant for the oxidative decarboxylation function of isocitrate dehydrogenase.« less

Gigantic perpendicular magnetic anisotropy of heavy transition metal cappings on Fe/MgO(0 0 1)

NASA Astrophysics Data System (ADS)

Taivansaikhan, P.; Odkhuu, D.; Rhim, S. H.; Hong, S. C.

2017-11-01

Effects of capping layer by 5d transition metals (TM = Hf, Ta, W, Re, Os, Ir, Pt, and Au) on Fe/MgO(0 0 1), a typical magnetic tunneling junction, are systematically investigated using first-principles calculation for magnetism and magnetocrystalline-anisotropy (MCA). The early TMs having less than half-filled d bands favor magnetization antiparallel to Fe, whereas the late TMs having more than half-filled d bands favor parallel, which is explained in the framework of kinetic exchange energy. The Os capping, isovalent to Fe, enhances MCA significantly to gigantic energy of +11.31 meV/cell, where positive contribution is mostly from the partially filled majority d bands of magnetic quantum number of |m| = 1 along with stronger spin-orbit coupling of Os than Fe. Different TM cappings give different MCA energies as the Fermi level shifts according to the valence of TM: Re and Ir, just one valence more or less than Os, have still large PMCA but smaller than the Os. In the W and Pt cappings, valence difference by two, PMCA are further reduced; MCAs are lowered compared to Fe/MgO(0 0 1) by the cappings of the very early TMs (Hf and Ta), while the very late TM (Au) switches sign to in-plane MCA.

Lyman-alpha observations of comet Kohoutek 1973 XII with Copernicus

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

Drake, J.F.; Jenkins, E.B.; Bertaux, J.L.

1976-10-01

Comet Kohoutek 1973 XII was observed with the Princeton telescope-spectrometer on the Copernicus satellite on six occasions over a 1-month period starting on 1974 January 29. Positive detection of the cometary L..cap alpha.. emission profile was obtained on January 29 and February 2. Earlier observations of the geocoronal L..cap alpha.. emission profile allowed an instrumental intensity calibration and confirmation of the computed instrumental profile for an extended source at the L..cap alpha.. wavelength.After allowing for broadening by the instrument, we derived from the width of the L..cap alpha.. emission on January 29 a hydrogen-outflow velocity of 10.6 +- 1.8 kmmore » s/sup -1/. The intensity calibration combined with an appropriate cometary model led to cometary water-production rates with average values of 1.3 +- 0.4 x 10/sup 28/ molecules sr/sup -1/ s/sup -1/ for January 29 and 6.0 +- 2.5 x 10/sup 27/ molecules sr/sup -1/ s/sup -1/ for February 2. Only upper limits were obtained for L..cap alpha.. on and after February 14. Searches for OH and D led to negative results. (AIP)« less

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

Chan, R.K.; Otte, C.A.

Saccharomyces cerevisiae MATa cells carrying mutations in either sst1 or sst2 are supersensitive to the G1 arrest induced by ..cap alpha.. factor pheromone. When sst1 mutants were mixed with normal SST/sup +/ cells, the entire population recovered together from ..cap alpha.. factor arrest, suggesting that SST/sup +/ cells helped sst1 mutants to recover. Complementation tests and linkage analysis showed that sst1 and bar1, a mutation which eliminates the ability of MATa cells to act as a ''barrier'' to the diffusion of ..cap alpha.. factor, were lesions in the same genes. These findings suggest that sst1 mutants are defective in recoverymore » from ..cap alpha.. factor arrest because they are unable to degrade the pheromone. In contrast, recovery of sst2 mutants was not potentiated by the presence of SST/sup +/ cells in mixing experiments. When either normal MATa cells or mutant cells carrying defects in sst1 or sst2 were exposed to ..cap alpha.. factor for 1 h and then washed free of the pheromone, the sst2 cells subsequently remained arrested in the absence of ..cap alpha.. factor for a much longer time than SST/sup +/ or sst1 cells. These observations suggest that the defect in sst2 mutants is intrinsic to the cell and is involved in the mechanism of ..cap alpha.. factor action at some step after the initial interaction of the pheromone with the cell. The presence of an sst2 mutation appears to cause a growth debility, since repeated serial subculture of haploid sst2-1 strains led to the accumulation of faster-growing revertants that were pheromone resistant and were mating defective (''sterile'').« less

Isolation of human hexosaminidase. cap alpha. cDNA and expression of. cap alpha. chains in E. coli

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

Wiktorowicz, J.E.; Whitman, J.M.

1986-05-01

Pooled antisera against homogeneous, glutaraldehyde cross-linked hexosaminidase (hex) A was adsorbed with E. coli lysate insolubilized on Sepharose 4B. Aliquots of a human liver lambdagtll cDNA library (50,000-100,000 pfu) were plated on E. coli Y1090. Expression of cloned cDNA, after sufficient plaque growth at 42/sup 0/, was accomplished by induction with isopropylthiogalactoside soaked nitrocellulose filters. Identification of hex cDNA clones was performed by incubation of the filters with purified antisera. Protein A labelled with I-125 was used to develop the reactive plaques. Positive plaques, identified by autoradiography, were picked, replated at a lower density, and rescreened. This was repeated severalmore » more times until all plaques yielded positive signals. Identification of the clones as containing ..cap alpha.. or ..beta.. cDNA was accomplished by replating the purified phage and rescreening the plaques with anti-hex B antiserum preadsorbed with E. coli lysate. According to this protocol several hex ..cap alpha.. clones have been identified. While these clones generate ..beta..-galactosidase: hex ..cap alpha.. fusion proteins, these findings suggest that in the future it may be possible to obtain large quantities of unmodified hex ..cap alpha.. and ..beta.. polypeptides from E. coli for the study of the structural and enzymatic properties of these polypeptides and for diagnostic purposes in the GM2 gangliosidoses.« less

Pulse radiolysis and 77 K matrix. gamma. irradiation of dimethyl truxinates and trans-methyl cinnamate in 2-methyltetrahydrofuran

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

Takamuku, S.; Kigawa, H.; Suematsu, H.

1982-05-13

One-electron reduction of dimethyl ..mu..-truxinate (..mu..-DMT), dimethyl ..beta..-truxinate (..beta..-DMT), and dimethyl ..cap alpha..-truxillate (..cap alpha..-DMT) has been investigated by pulse radiolysis and 77 K matrix ..gamma.. irradiation of the 2-methyltetrahydrofuran solutions. Cycloreversion of the radical anions formed by an electron attachment to these cyclobutanes was observed in all cases, even at 77 K. The orientation of the cycloreversion was dependent on the stereochemistry of the cyclobutanes, and the selectivity was reasonably explained by a so-called cis effect; the best possible release of steric hindrance decides the primary step of the reaction. In 77 K matrix ..gamma.. irradiation of ..cap alpha..-DMT,more » an intense IR absorption was found after the photobleaching of trapped electrons with light > 690 nm. In other DMTs, the IR absorption band was not observed while the cycloreversion of DMT by mobile electrons occurred. Thus, the IR band in the case of ..cap alpha..-DMT was assigned to an associated dimer anion due to the interaction between the radical anion and the neutral molecule pair of trans-methyl cinnamate orginally formed by the cycloreversion of ..cap alpha..-DMT. The dimer anion was presumed to be oriented in a head-to-tail structure in a solvent cage on the basis of the original configuration of ..cap alpha..-DMT.« less

Pheromone induction of agglutination in Saccharomyces cerevisiae a cells

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

Terrance, K.; Lipke, P.N.

1987-10-01

a-Agglutinin, the cell surface sexual agglutinin of yeast a cells, was assayed by its ability to bind its complementary agglutinin, ..cap alpha..-agglutinin. The specific binding of /sup 125/I-..cap alpha..-agglutinin to a cells treated with the sex pheromone ..cap alpha..-factor was 2 to 2.5 times that of binding to a cells not treated with ..cap alpha..-factor. Competition with unlabeled ..cap alpha..-agglutinin revealed that the increased binding was due to increased cell surface expression of a-agglutinin, with no apparent change in the binding constant. The increase in site number was similar to the increase in cellular agglutinability. Increased expression of a-agglutinin followedmore » the same kinetics as the increase in cellular agglutinability, with a 10-min lag followed by a 15- to 20-min response time. Induction kinetics were similar in cells in phases G1 and G2 of the cell cycle. Maximal expression levels were similar in cells treated with excess pheromone and in cells exposed to pheromone after destruction of constitutively expressed a-agglutinin.« less

Metabolism of 4-chlorobenzotrichloride in rats

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

Quistad, G.B.; Mulholland, K.M.; Skiles, G.

Special analytical methodology was developed for purification of 4-chloro(/sup 14/C)benzotrichloride, which is both volatile and hydrolytically unstable at milligram mass levels. When rats were given a single oral dose of 4-chloro(/sup 14/C)benzotrichloride at 1.5 mg/kg, within 4-6 days 87 and 9% of the applied /sup 14/C were excreted in urine and feces, respectively. The major urinary metabolite was identified as 4-chlorohippuric acid, representing 78% of the applied dose. While about two-thirds of the fecal /sup 14/C residues were unextractable with organic solvents, free 4-chlorobenzoic acid and ..cap alpha..,..cap alpha..,4,4'-tetrachlorostilbene contributed 10 and 8% of the fecal /sup 14/C. The metabolicmore » production of ..cap alpha..,..cap alpha..,4,4'-tetrachlorostilbene appears to occur by a novel metabolic pathway.« less

cap alpha. -Methylglucoside satisfies only Na/sup +/-dependent transport system of intestinal epithelium

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

Kimmich, G.A.; Randles, J.

1981-01-01

The unidirectional influx of ..cap alpha..-methylglucoside (..cap alpha..-MG) by isolated chicken intestinal epithelial cells is 98% inhibited by phlorizin. The remaining 2% of the total influx occurs in the absence of Na/sup +/, is not sensitive to phloretin, and is equal to the diffusional entry rate for 2-deoxyglucose. The glucoside is much more strongly accumulated (75-fold) than 3-O-methylglucose (3-OMG) (10-fold). Inhibitors of the serosal sugar carrier (phloretin, cytochalasin B, theophylline, and flavanoids) do not enhance ..cap alpha..-MG accumulation. It is concluded that the glycoside is not a substrate for the intestinal serosal transport system. Steady-state gradients of the sugar canmore » be represented accurately by a concentrative, phlorizin-sensitive system that is opposed by a diffusional efflux process.« less

Characterization of rat leydig cell gonadotropin receptor structure by affinity cross-linking

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

Zhang, Q.Y.; Hwang, J.; Menon, K.M.J.

1986-05-01

The gonadotropin receptor from rat leydig cell has been characterized with respect to binding kinetics and physiological regulation. The present study was intended to examine the structure of the receptor. Leydig cell suspension was prepared by either collagenase digestion or by mechanical disruption of the testis. The cells were incubated with /sup 125/I-hCG and the unreacted hCG was removed by centrifugation. The /sup 125/I-hCG was then covalently linked to the cell surface receptor using cleavable (dithiobis (succinimidyl propionate)) and non-cleavable (disuccinimidyl suberate) cross-linking reagents. The extracted cross-linked membrane proteins were resolved on SDS-polyacrylamide gels under reducing and non-reducing conditions andmore » subjected to autoradiographic analysis. Under non-reducing conditions, two labeled species with M/sub r/ = 87,000 and 120,000 were detected. However, only one labeled band was detected under reducing conditions with M/sub r/ = 64,000. The binding of /sup 125/I-hCG to the receptor was inhibited by hCG and LH, but not by a number of peptides and proteins. The data suggest that hCG receptor in leydig cell is an oligomeric complex consisting of four subunits, ..cap alpha cap alpha beta gamma... The ..beta.. and ..gamma.. subunits are each linked to an ..cap alpha.. subunit through disulfide linkage and the hormone binds to each ..cap alpha.. subunit. The two dimers formed (..cap alpha beta cap alpha gamma..) are associated by noncovalent interactions.« less

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

Yamashita, T.; Fujino, T.; Masaki, N.

The structural parameters of ..cap alpha..- and ..beta..-CdUO/sub 4/ crystals are determined by x-ray powder diffraction technique. ..cap alpha..-CdUO/sub 4/ is rhombohedral and cell parameters are a = 6.233(3) A and ..cap alpha.. = 36.12(5)/sup 0/. ..beta..-CdUO/sub 4/ crystallizes in a C-centered orthorhombic cell with a = 7.023(4), b = 6.849(3), c = 3.514(2) A. The space groups are R3m for ..cap alpha..-CdUO/sub 4/ and Cmmm for ..beta..-CdUO/sub 4/. ..cap alpha..-CdUO/sub 4/: 1U in (000), 1Cd in (1/2 1/2 1/2), 2O(1) in +-(uuu), 2O(2) in +-(vvv); u = 0.113, v= 0.350, Z = 1. ..beta..-CdUO/sub 4/: 2U in (000; 1/2more » 1/2 0), 2Cd in (1/2 0 1/2; 0 1/2 1/2), 40(1) in (0, +-y, 0; 1/2, 1/2 +-y, 0), 4O(2) in (+-x, 0, 1/2; 1/2 +-x, 1/2, 1/2); x = 0.159, y = 0.278, Z = 2. ..beta..-CdUO/sub 4/ contains collinear uranyl UO/sub 2//sup 2 +/ groups with a U-O(1) distance of 1.91 A, located either along or parallel to the c axis whereas the U-O(1) bond length in ..cap alpha..-CdUO/sub 4/ is 1.98 A which is longer than the usual uranyl bond length.« less

Variability of Lyman-alpha emission from Jupiter

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

Cochran, W.D.; Barker, E.S.

1979-12-01

The Jovian L..cap alpha.. emission line was reobserved in 1978 March using the high-resolution spectrometer of the Copernicus satellite. An intensity of 8.3 +- 2.9 kilorayleighs was measured. This value represents a significant increase in intensity over previous (1976) Copernicus observations, but is lower than the recent (1979) values obtained by Voyager 1 and IUE. The increase in intensity has been accompanied by a significant increase in line width givin strong support to the theory that the emission results from resonant scattering of the solar L..cap alpha.. line by H atoms in the upper Jovian atmosphere. The strength of Jovianmore » L..cap alpha.. emission correlates well with the level of solar activity. The solar extreme ultraviolet radiation varies with the solar cycle. This radiation causes the dissociation of H/sub 2/ and CH/sub 4/ into H atoms in the Jovian atmosphere. Therefore, in times of high solar activity, the H column density will increase, causing the observed stronger Jovian L..cap alpha.. emission.« less

A remarkable member of the polyoxometalates: the eight-nickel-capped alpha-keggin polyoxoazonickelate.

PubMed

Dong, Lanjun; Huang, Rudan; Wei, Yongge; Chu, Wei

2009-08-17

The eight-nickel-capped polyoxoazonickelate, [Ni(20)(OH)(24)(MMT)(12)(SO(4))](NO(3))(2).6H(2)O (1; MMT = 2-mercapto-5-methyl-1,3,4-thiadiazole), has been synthesized, which has an alpha-Keggin structure with eight nickel caps. In this structure, the polyatom is the late transition metal Ni(II); the central heteroatom is S, and the organic terminal ligand becomes the primary part of the Keggin structure. This is a Keplerate-type cluster, which shows a central Ni(II)(12) cuboctahedron formed by the 12 Ni(II) centers of the classical alpha-Keggin core and a Ni(II)(8) hexahedron formed by the eight nickel caps.

Glucocorticoids inhibit coordinated translation of. cap alpha. - and. beta. -globin mRNAs in Friend erythroleukemia cells

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

Papaconstantinou, J.; Stewart, J.A.; Rabek, J.P.

The dimethylsulfoxide (Me/sub 2/SO)-mediated induction of hemoglobin synthesis in Friend erythroleukemia cells is inhibited by the glucocorticoids hydrocortisone, dexamethasone, and fluocinolone acetonide; hydrocortisone, at concentrations of 10/sup -5/ to 10/sup -8/ M inhibits by 90-30% and fluocinolone acetonide at concentrations of 10/sup -8/ to 10/sup -11/ M shows a greater than 90% inhibition. At these concentrations the hormones have no effect on cell growth or viability. In this study it has been shown that there is a group of proteins, including the ..cap alpha..- and ..beta..-globins, whose regulation is associated with the induction of Friend erythroleukemia cell differentiation, and thatmore » the expression of these, in addition to ..cap alpha..- and ..beta..-globin, is affected by glucocorticoids. It is concluded that, although the translation of ..cap alpha..- and ..beta..-globin mRNA is a major site of inhibition by glucocorticoids, there is a detectable amount of ..cap alpha..- and ..beta..-globin mRNA translation which results in unequal amounts of globin synthesis and an overall more potent inhibition of hemoglobin formation.« less

X-ray fluorescence cross sections for K and L x rays of the elements

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

Krause, M.O.; Nestor, C.W. Jr.; Sparks, C.J. Jr.

1978-06-01

X-ray fluorescence cross sections are calculated for the major x rays of the K series 5 less than or equal to Z less than or equal to 101, and the three L series 12 less than or equal to Z less than or equal to 101 in the energy range 1 to 200 keV. This calculation uses Scofield's theoretical partical photoionization cross sections, Krause's evaluation of fluorescence and Coster-Kronig yields, and Scofield's theoretical radiative rates. Values are presented in table and graph format, and an estimate of their accuracy is made. The following x rays are considered: K..cap alpha../sub 1/,more » K..cap alpha../sub 1/,/sub 2/, K..beta../sub 1/, K..beta../sub 1/,/sub 3/, L..cap alpha../sub 1/, L..cap alpha../sub 1/,/sub 2/, L..beta../sub 1/, L..beta../sub 2/,/sub 15/, L..beta../sub 3/, Ll, L..gamma../sub 1/, L..gamma../sub 4/, and L/sub 1/ ..-->.. L/sub 2/,/sub 3/. For use in x-ray fluorescence analysis, K..cap alpha.. and L..cap alpha.. fluorescence cross sections are presented at specific energies: TiK identical with 4.55 keV, CrK identical with 5.46 keV, CoK identical with 7.00 keV, CuK identical with 8.13 keV, MoK..cap alpha.. identical with 17.44 keV, AgK identical with 22.5 keV, DyK identical with 47.0 keV, and /sup 241/Am identical with 59.54 keV. Supplementary material includes fluorescence and Coster--Kronig yields, fractional radiative rates, fractional fluorescence yields, total L-shell fluorescence cross sections, fluorescence and Coster-Kronig yields in condensed matter, effective fluorescence yields, average L-shell fluorescence yield, L-subshell photoionization cross section ratios, and conversion factors from barns per atom to square centimeters per gram.« less

Cross-linking of hCG to luteal receptors

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

Ji, T.H.; Ji, I.

1985-01-01

Photoaffinity labeling of the lutropin/choriogonadotropin (LH/hCG) receptor system on porcine granulosa cells has demonstrated that both the ..cap alpha.. and ..beta.. subunits of hCG directly photoaffinity label the hormone receptor. Three new bands appear on SDS-PAGE as a consequence of photoaffinity labeling by each subunit: the molecular weights of the three bands (106K, 88K, and 83K) produced by the subunit are larger by approximately 10K than those of the three bands (96K, 76K, and 73K) labeled by the ..cap alpha.. subunit. Although it could be a coincidence that the molecular weight of the ..beta.. subunit is approximately 10K larger thanmore » that of the ..cap alpha.. subunit, the similarity in these differences suggests the possibility that both the ..cap alpha.. and ..beta.. subunits have labeled the same polypeptides.« less

Differentiation to adipocytes in accompanied by an increase in the amounts of Gi- and Go-proteins in 3T3-L1 cells

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

Watkins, D.C.; Northup, J.K.; Malbon, C.C.

Treatment of cultures of 3T3-L1 cells with methylisobutyl-xanthine and dexamethasone has been shown to result in accumulation of lipid and conversion to the morphology of adipocytes in more than 90% of the cells. The status of the stimulatory (Gs), inhibitory (Gi) and Go-proteins during the course of 3T3-L1 differentiation was examined. The amount of alpha subunit of Gs (..cap alpha..Gs), assayed by radiolabeling in the presence of cholera toxin and (/sup 32/P)NAD/sup +/, increased upon differentiation as previously described by others. The amounts of ..cap alpha..Gi and ..cap alpha..Go assayed by radiolabeling in the presence of pertussis toxin and (/supmore » 32/P)NAD/sup +/ increased 3-fold upon differentiation. Immunoblots of cell membranes subjected to gel electrophoresis in sodium dodecyl sulfate were probed with two rabbit antisera raised against bovine brain ..cap alpha..Go and with one raised against the..beta..-subunit of the bovine rod-outer-segment G-protein, referred to as transducin. The immunoblotting data confirm the increase upon differentiation of ..cap alpha..Go and also demonstrate an increase in the amount of the ..beta..-subunit. Thus differentiation of 3T3-L1 cells is accompanied by dramatic changes in the complexion of G-proteins in the membranes.« less

cap alpha. /sub 2/-Adrenergic receptor-mediated sensitization of forskolin-stimulated cyclic AMP production

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

Jones, S.B.; Toews, M.L.; Turner, J.T.

1987-03-01

Preincubation of HT29 human colonic adenocarcinoma cells with ..cap alpha../sub 2/-adrenergic agonists resulted in a 10- to 20-fold increase in forskolin-stimulated cyclic AMP production as compared to cells preincubated without agonist. Similar results were obtained using either a (/sup 3/H)adenine prelabeling assay or a cyclic AMP radioimmunoassay to measure cyclic AMP levels. This phenomenon, which is termed sensitization, is ..cap alpha../sub 2/-adrenergic receptor-mediated and rapid in onset and reversal. Yohimbine, an ..cap alpha../sub 2/-adrenergic receptor-selective antagonist, blocked norepinephrine-induced sensitization, whereas prazosin (..cap alpha../sub 1/-adrenergic) and sotalol (..beta..-adrenergic) did not. The time for half-maximal sensitization was 5 min and the half-timemore » for reversal was 10 min. Only a 2-fold sensitization of cyclic AMP production stimulated by vasoactive intestinal peptide was observed, indicating that sensitization is relatively selective for forskolin. Sensitization reflects an increased production of cyclic AMP and not a decreased degradation of cyclic AMP, since incubation with a phosphodiesterase inhibitor and forskolin did not mimic sensitization. Increasing the levels of cyclic AMP during the preincubation had no effect on sensitization, indicating that sensitization is not caused by decreased cyclic AMP levels during the preincubation. This rapid and dramatic sensitization of forskolin-stimulated cyclic AMP production is a previously unreported effect that can be added to the growing list of ..cap alpha../sub 2/-adrenergic responses that are not mediated by a decrease in cyclic AMP.« less

Role of a guanine nucleotide-binding protein in. cap alpha. /sub 1/-adrenergic receptor-mediated Ca/sup 2 +/ mobilization in DDT/sub 1/ MF-2 cells

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

Cornett, L.E.; Norris, J.S.

1987-11-01

In this study the mechanisms involved in ..cap alpha../sub 1/-adrenergic receptor-mediated Ca/sup 2 +/ mobilization at the level of the plasma membrane were investigated. Stimulation of /sup 45/Ca/sup 2 +/ efflux from saponin-permeabilized DDT/sub 1/ MF-2 cells was observed with the addition of either the ..cap alpha../sub 1/-adrenergic agonist phenylephrine and guanosine-5'-triphosphate or the nonhydrolyzable guanine nucleotide guanylyl-imidodiphosphate. In the presence of (/sup 32/P) NAD, pertussis toxin was found to catalyze ADP-ribosylation of a M/sub r/ = 40,500 (n = 8) peptide in membranes prepared from DDT/sub 1/, MF-2 cells, possibly the ..cap alpha..-subunit of N/sub i/. However, stimulation ofmore » unidirectional /sup 45/Ca/sup 2 +/ efflux by phenylephrine was not affected by previous treatment of cells with 100 ng/ml pertussis toxin. These data suggest that the putative guanine nucleotide-binding protein which couples the ..cap alpha../sub 1/-adrenergic receptor to Ca/sup 2 +/ mobilization in DDT/sub 1/ MF-2 cells is not a pertussis toxin substrate and may possibly be an additional member of guanine nucleotide binding protein family.« less

E2C mechanism of elimination reactions. IX. Secondary deuterium isotope effects on rates of bimolecular reactions in alicyclic systems

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

Cook, D.

1976-06-11

Secondary ..cap alpha..-deuterium isotope effects on the rates of NBu/sub 4/OAc and NBu/sub 4/Cl promoted bimolecular reactions (E2 and SN2) of cyclohexyl tosylate and cyclohexyl bromide have been studied. The E2 reactions, previously categorized as E2C-like, show ..cap alpha..-deuterium isotope effects in the range 1.14--1.22, while the related SN2 reactions give values in the range 1.05--1.08. The discrepancy in the magnitude of the ..cap alpha..-deuterium isotope effect for the E2 and SN2 processes is consistent with the view that E2C-like reactions use ''looser'' transition states than those used in the concurrent SN2 reactions. While the reported ..cap alpha..-d isotope effectsmore » do not provide positive evidence to support the idea that the base interacts with C/sub ..cap alpha../ in the E2 transition states of the reactions studied, neither do they substantiate claims for dismissal of the concept. A comparison of the secondary ..gamma..-deuterium and ..beta..'-deuterium isotope effects arising in the reaction of cyclohexyl tosylate with NBu/sub 4/OAc in acetone indicates the two isotope effects to be of equivalent magnitude (k/sub ..beta..'-d/k/sub ..gamma..-d/ = 0.98). This observation can only be rationalized for this reaction in terms of a transition state structure in which there is extensive double bond development. It provides compelling evidence against the involvement of any transition state structure which accommodates extensive positive charge development at C/sub ..cap alpha../.« less

Alpha particle effects in burning tokamak plasmas: overview and specific examples

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

Sigmar, D.J.

1986-07-01

Using the total power balance of an ignited tokamak plasma as a guideline, a range of alpha driven effects is surveyed regarding their impact on achieving and maintaining fusion burn. Specific examples of MHD and kinetic modes and multi species transport dynamics are discussed, including the possible interaction of these categories of effects. This power balance approach rather than a straightforward enumeration of possible effects serves to reveal their non-linear dependence and the ensuing fragility of our understanding of the approach to and maintenance of ignition. Specific examples are given of the interaction between ..cap alpha..-power driven sawtoothing and idealmore » MHD stability, and direct ..cap alpha..-effects on MHD modes including kinetic corrections. Anomalous ion heat transport and central impurity peaking mechanisms and anomalous and collisional ..cap alpha..-transport including the ambipolar electric field are discussed.« less

Highly excited states in /sup 6/Li by the reaction /sup 9/Be(p,. cap alpha. )/sup 6/Li. [Width of 8. 2-MeV level

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

Delbar, T.; Gregoire, G.; Lega, J.

1976-10-01

The spectra from the reaction /sup 9/Be(p, ..cap alpha..)/sup 6/Li induced by 75 and 30 MeV protons were recorded at theta/sub ..cap alpha../ = 20 and 30/sup 0/ in the laboratory frame. The region from 6 to 18 MeV excitation energy of the residual nucleus was carefully studied for possible levels. Evidence for a T = 1 level at E/sub x/ = 8.2 +- 0.2 MeV with a width GAMMA = 2.2 +- 0.2 MeV is reported. No other levels were observed in the present spectra. (AIP)

Comparisons of carcinogenicities of nickel compounds in rats

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

Sunderman, F.W. Jr.; Maenza, R.M.

This study demonstrates marked differences in the incidences of sarcomas in Fischer rats within 2 years after a single im injection of 4 insoluble nickel-containing powders amorphous nickel monosulfide (NiS), nickel subsulfide (..cap alpha..Ni/sub 3/S/sub 2/), partially converted nickel-iron sulfide matte, and metallic nickel. The powders (<2 ..mu..m median particle diameters) were administered in penicillin suspension, and each powder was tested at 2 dosages. Whereas ..cap alpha..Ni/sub 3/S/sub 2/ was highly carcinogenic, amorphous NiS did not induce any tumors. The carcinogenic potency of partially converted nickel-iron sulfide matte was less than ..cap alpha..Ni/sub 3/S/sub 2/ but greater than Ni powder.more » No sarcomas occurred at the injection site in two groups of control rats that received im injections of penicillin or Fe powder. The observed differences in carcinogenic potencies of ..cap alpha..Ni/sub 3/S/sub 2/ and amorphous NiS may provide an experimental approach to elucidate the molecular mechanisms of nickel carcinogenesis.« less

Hydrophobic interactions in complexes of antimicrobial peptides with bacterial polysaccharides.

PubMed

Kuo, Hsin H; Chan, Celine; Burrows, Lori L; Deber, Charles M

2007-06-01

Biofilms of Pseudomonas aeruginosa are responsible for chronic lung infections in cystic fibrosis patients, where they are characterized by overproduction of the exopolysaccharide alginate and are recalcitrant to treatment with conventional antibiotics. Cationic antimicrobial peptides (CAPs) are potential alternatives for the treatment of multi-drug-resistant P. aeruginosa. However, alginate in P. aeruginosa biofilms has been proposed to bind these peptides through hydrophobic interactions, consequently reducing their activity [Chan et al., J Biol Chem 2004; 279: 38749-38754]. Here we perform biophysical analyses of the interactions of alginate with a series of novel peptide antibiotics (alpha-CAPs) of prototypic sequence KK-AAAXAAAAAXAAWAAXAAA-KKKK (where X = Phe, Trp or Leu). The hydrophobic interaction interface in alginate was investigated by examining (i) the effects of polysaccharide composition with respect to D-mannuronate and L-guluronate content; (ii) glycan chain length; (iii) alpha-CAP Trp fluorescence; and (iv) 1-anilinonaphthalene-8-sulfonate fluorescence. The results show that, while M and G residues produce equivalent effects, hydrophobic interactions between alginate and alpha-CAPs require a minimal glycan chain length. Peptide interactions with alginate are deduced to be mediated by hydrophobic microdomains comprised of pyranosyl C-H groups that are inducible upon formation of alpha-CAP-alginate complexes due to charge neutralization between the two species.

Dissimilar effects of chronic treatment with aspirin, flubiprofen and indomethacin on renal prostaglandins

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

Quilley, C.P.; McGiff, J.C.; Quilley, J.

Inhibition of prostaglandin (PG) excretion is not sustained during long-term aspirin administration. The authors compared the effects of 9d treatment of SHR rats with aspirin (A), 200 mg/kg/d s.c., flubiprofen (F), 2.5 mg/kg/12h s.c., and indomethacin (I), 2.5 mg/kg/12 s.c. on excretion of radioimmunoassayable PGE/sub 2/ and PGF/sub 2..cap alpha../. Conversion of 1-(/sup 14/C) arachidonic acid (AA) by renal papillae was also examined. In vehicle-treated control rats (C) PGF/sub 2..cap alpha../ excretion varied from 32.2 +/- 6.2 (mean +/- SEM) to 41.6 +.- 7.3 ng/6h, 3-fold higher than that of PGE/sub 2/. Within 6h of administration all 3 drugs reducedmore » excretion of PGF/sub 2..cap alpha../ and PGE/sub 2/ to less than 20% and 35% of C rats. Although urinary concentrations of PGF/sub 2..cap alpha../ and PGE/sub 2/ in A-treated rats remained depressed, a 2-fold increase in urine volume resulted in excretion rates similar to C rats. In contrast, urine volume in I- and F-treated rats was unaffected while PGF/sub 2..cap alpha../ and PGE/sub 2/ excretion rates in I-treated rats were 50''% of C rats and were also lower than control in F-treated rats. Paradoxically, metabolism of AA to PGs by by renal papillae dissected on day 10, 2-4h after the last drug dose, was markedly inhibited by A (PGF/sub 2..cap alpha../ by 62% and PGE/sub 2/ by 82%), but unaffected by I and F. As the effects of cyclooxygenase inhibitors differ on in vivo and indices of PG production, their intended action should be verified by measuring PG levels in biological fluids.« less

Non-linear vacuum polarization in strong fields

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

Gyulassy, M.

1981-07-01

The Wichmann-Kroll formalism for calculating the vacuum polarization density to first order in ..cap alpha.. but to all orders in Z..cap alpha.. is derived. The most essential quantity is shown to be the electrons Green's function in these calculations. The method of constructing that Green's function in the field of finite radius nuclei is then presented.

Metabolism of. cap alpha. -C/sup 14/-histidine in the intact rat. II. Radioactive excretion products in urine

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

Wolf, G.; Wu, P.H.L.; Heck, W.W.

1956-09-01

The normal metabolic pathways in the intact rat was investigated via the radioactive urinary excretion products following administration of a physiological dose of a radioactive compound such as ..cap alpha..-C/sup 14/-DL-histidine. The major metabolites, except one, excreted in the urine 5 hours after administration of ..cap alpha..-C/sup 14/-DL-histidine were isolated and identified. Glutamic acid and urocanic acids had simlar and low activities, whereas carboxyl-labeled imidazoacetic acid was found to be the principal metabolite with a high level of activity. It was concluded that the main end-product of the catabolism of DL-histidine is imidazoleacetic acid probably formed through imidazolepyruvic acid.

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

Weinstein, L.; Droegemueller, W.; Cornette, J.

A single intra-amniotic injection of (15S)-15 methyl prostaglandin F/sub 2/..cap alpha.. (THAM) was used to induce second trimester abortion in five patients. Serial levels of (15S)-15 methyl prostaglandin F/sub 2/..cap alpha.. were subsequently measured in amniotic fluid and plasma by radioimmunoassay. The slow removal of this drug from the amniotic fluid was documented. Plasma levels of (15S)-15 methyl prostaglandin F/sub 2/..cap alpha.. increased fourfold to sevenfold after clinical rupture of the membranes in three patients, supporting the fact that prostaglandins are well absorbed from the vagina. Because this analogue of prostaglandin can cause marked peripheral bronchoconstriction when administered systemically, itmore » is best to avoid its use in patients with a history of asthma.« less

Self-modulating pressure gauge

DOEpatents

Edwards, D. Jr.; Lanni, C.P.

1979-08-07

An ion gauge is disclosed having a reduced x-ray limit and means for measuring that limit. The gauge comprises an ion gauge of the Bayard-Alpert type having a short collector and having means for varying the grid-collector voltage. The x-ray limit (i.e. the collector current resulting from x-rays striking the collector) may then be determined by the formula: I/sub x/ = ..cap alpha..I/sub l/ - I/sub h//..cap alpha.. - l where: I/sub x/ = x-ray limit, I/sub l/ and I/sub h/ = the collector current at the lower and higher grid voltage respectively; and, ..cap alpha.. = the ratio of the collector current due to positive ions at the higher voltage to that at the lower voltage.

Proteomic profiling and post-translational modifications in human keratinocytes treated with Mucuna pruriens leaf extract.

PubMed

Cortelazzo, Alessio; Lampariello, Raffaella L; Sticozzi, Claudia; Guerranti, Roberto; Mirasole, Cristiana; Zolla, Lello; Sacchetti, Gianni; Hajek, Joussef; Valacchi, Giuseppe

2014-02-03

Mucuna pruriens (Mp) is a plant belonging to the Fabaceae family, with several medicinal properties among which its potential to treat diseases where reactive oxygen species (ROS) play an important role in the pathogeneses. The aim was to investigate the effects of Mp leaf methanolic extract (MPME) on human keratinocytes protein expression and its role in preventing proteins oxidation after oxidative stress (OS) exposure. The effects of MPME on HaCaT cells protein expression were evaluated treating cells with different concentrations of MPME, with glucose oxidase (GO, source of OS) and with MPME subsequently treated with GO. The protein patterns of treated HaCaT cells are analyzed by two-dimensional gel electrophoresis (2-DE) and compared with that of untreated HaCaT. Immunoblotting was then used to evaluate the role of MPME in preventing the 4-hydroxynonenal protein adducts (4-HNE PAs) formation (marker of OS). Eighteen proteins, identified by mass spectrometry (LC-ESI-CID-MS/MS), were modulated distinctly by MPME in HaCaT. Overall, MPME counteract GO effect, reducing the GO-induced overexpression of several proteins involved in stress response (T-complex protein 1, Protein disulfide-isomerase A3, Protein DJ-1, and Stress-induced-phosphoprotein 1), in cell energy methabolism (Inorganic pyrophosphatase, Triosephosphate isomerase isoform 1, 2-phosphopyruvate-hydratase alpha-enolase, and Fructose-bisphosphate aldolase A isoform 1), in cytoskeletal organization (Cytokeratins 18, 9, 2, Cofilin-1, Annexin A2 and F-actin-capping protein subunit beta isoform 1) and in cell cycle progression (Eukaryotic translation initiation factor 5A-1 isoform B). In addition, MPME decreased the 4-HNE PAs levels, in particular on 2-phosphopyruvate-hydratase alpha-enolase and Cytokeratin 9. Our findings show that MPME might be helpful in the treatment of OS-related skin diseases by preventing protein post-translational modifications (4-HNE PAs). © 2013 Published by Elsevier Ireland Ltd.

Internode length in Pisum. Gene na may block gibberellin synthesis between ent-7. cap alpha. -hydroxykaurenoic acid and biggerellin A/sub 12/-aldehyde. [Pisum sativum

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

Ingram, T.J.; Reid, J.B.

1987-04-01

The elongation response of the gibberellin (GA) deficient genotypes na, ls, and lh of peas (Pisum sativum L.) to a range of GA-precursors was examined. Plants possessing gene na did not respond to precursors in the GA biosynthetic pathway prior to GA/sub 12/-aldehyde. In contrast, plants possessing lh and ls responded as well as wild-type plants (dwarfed with AMO-1618) to these compounds. The results suggest that GA biosynthesis is blocked prior to ent-kaurene in the lh and ls mutants and between ent-7..cap alpha..-hydroxykaurenoic acid and GA/sub 12/-aldehyde in the na mutant. Feeds of ent(/sup 3/H)kaurenoic acid and (/sup 2/H)GA/sub 12/-aldehydemore » to a range of genotypes supported the above conclusions. The na line WL1766 was shown by gas chromatography-mass spectrometry (GC-MS) to metabolize(/sup 2/H)GA/sub 12/-aldehyde to a number of (/sup 2/H)C/sub 19/-GAs including GA/sub 1/. However, there was no indication in na genotypes for the metabolism of ent-(/sup 3/H)kaurenoic acid to these GAs. In contrast, the expanding shoot tissue of all Na genotypes examined metabolized ent-(/sup 3/H)kaurenoic acid to radioactive compounds that co-chromatographed with GA/sub 1/, GA/sub 8/, GA/sub 20/, and GA/sub 29/. However, insufficient material was present for unequivocal identification of the metabolites. The radioactive profiles from HPLC of extracts of the node treated with ent-(/sup 3/H)kaurenoic acid were similar for both Na and na plants and contained ent-16..cap alpha..,17-dihydroxykaurenoic acid and ent-6..cap alpha..,7..cap alpha..,16..beta..,17-tetrahydroxykaurenoic acid (both characterized by GC-MS), suggesting that the metabolites arose from side branches of the main GA-biosynthetic pathway. Thus, both Na and na plants appear capable of ent-7..cap alpha..-hydroxylation.« less

Expression of alpha-expansin and expansin-like genes in deepwater rice.

PubMed

Lee, Yi; Kende, Hans

2002-11-01

Previously, we have studied the expression and regulation of four alpha- and 14 beta-expansin genes in deepwater rice (Oryza sativa). We now report on the structure, expression, and regulation of 22 additional alpha-expansin (Os-EXP) genes, four expansin-like (Os-EXPL) genes, and one expansin-related (Os-EXPR) gene, which have recently been identified in the expressed sequence tag and genomic databases of rice. Alpha-expansins are characterized by a series of conserved Cys residues in the N-terminal half of the protein, a histidine-phenylalanine-aspartate (HFD) motif in the central region, and a series of tryptophan residues near the carboxyl terminus. Of the 22 additional alpha-expansin genes, five are expressed in internodes and leaves, three in coleoptiles, and nine in roots, with high transcript levels in the growing regions of these organs. Transcripts of five alpha-expansin genes were found in roots only. Expression of five alpha-expansin genes was induced in the internode by treatment with gibberellin (GA) and by wounding. The wound response resulted from excising stem sections or from piercing pinholes into the stem of intact plants. EXPL proteins lack the HFD motif and have two additional Cys residues in their C- and N-terminal regions. The positions of conserved tryptophan residues at the C-terminal region are different from those of alpha- and beta-expansins. Expression of the Os-EXPL3 gene is correlated with elongation and slightly induced by applied GA. However, the expression of the Os-EXPL1 and Os-EXPL2 genes showed limited correlation with cell elongation and was not induced by GA. We found no expression of the Os-EXPR1 gene in the organs examined.

Association between bortezomib dose intensity and overall survival in mantle cell lymphoma patients on frontline VR-CAP in the phase 3 LYM-3002 study.

PubMed

Robak, Tadeusz; Huang, Huiqiang; Jin, Jie; Zhu, Jun; Liu, Ting; Samoilova, Olga; Pylypenko, Halyna; Verhoef, Gregor; Siritanaratkul, Noppadol; Osmanov, Evgenii; Pereira, Juliana; Mayer, Jiri; Hong, Xiaonan; Okamoto, Rumiko; Pei, Lixia; Rooney, Brendan; van de Velde, Helgi; Cavalli, Franco

2017-06-05

The pivotal LYM-3002 study compared frontline rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with bortezomib, rituximab, cyclophosphamide, doxorubicin and prednisone (VR-CAP) in newly diagnosed mantle cell lymphoma (MCL) patients for whom stem cell transplantation was not an option. This post hoc subanalysis of the VR-CAP data from LYM-3002 evaluated the effect of bortezomib dose intensity on OS in patients who completed ≥6 cycles of treatment. From the end of cycle 6, patients receiving ≥4.6 mg/m 2 /cycle of bortezomib had significantly longer OS (but not PFS) compared with those receiving <4.6 mg/m 2 /cycle by univariate analysis (HR 0.43 [95% CI: 0.23-0.80]; p = .0059). This association remained significant in multivariate analysis adjusting for baseline patient and disease characteristics (HR 0.40 [95% CI: 0.20-0.79]; p = .008]. Higher bortezomib dose intensity was the strongest predictor of OS in newly diagnosed MCL patients receiving VR-CAP. Clinicaltrials.gov identifier: NCT00722137.

Copernicus observations of Betelgeuse and Antares

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

Bernat, A.P.; Lambert, D.L.

1975-01-01

Copernicus observations of the M-supergiants, ..cap alpha.. Ori and ..cap alpha.. Sco, are presented. The Mg II H and K resonance lines are strongly in emission in both stars. The K line is highly asymmetric in both stars but the H line is symmetric. Upper limits for several other resonance lines are given for ..cap alpha.. Ori. The possibility is explored that the K line asymmetry is caused by overlying resonance lines of Mn I and Fe I formed in the cool circumstellar gas shells around these stars. Observations of the Mn I 4030--4033 A lines are used to showmore » that circumstellar shell absorption is too weak to explain the asymmetry. It is suggested that the absorption occurs in a cool turbulent region between the base of the circumstellar shell and the top of the chromosphere. (auth)« less

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

Walker, T.E.; Han, C.H.; Kollman, V.H.

/sup 13/C NMR of isotopically enriched metabolites has been used to study the metabolism of Microbacterium ammoniaphilum, a bacterium which excretes large quantities of L-glutamic acid into the medium. Biosynthesis from 90% (1-/sup 13/C) glucose results in relatively high specificity of the label, with (2,4-/sup 13/C/sub 2/) glutamate as the major product. The predominant biosynthetic pathway for synthesis of glutamate from glucose was determined to be the Embden Meyerhof glycolytic pathway followed by P-enolpyruvate carboxylase and the first third of the Krebs cycle. Different metabolic pathways are associated with different correlations in the enrichment of the carbons, reflected in themore » spectrum as different /sup 13/C-/sup 13/C scalar multiplet intensities. Hence, intensity and /sup 13/C-/sup 13/C multiplet analysis allows quantitation of the pathways involved. Although blockage of the Krebs cycle at the ..cap alpha..-ketoglutarate dehydrogenase step is the basis for the accumulation of glutamate, significant Krebs cycle activity was found in glucose grown cells, and extensive Krebs cycle activity in cells metabolizing (1-/sup 13/C) acetate. In addition to the observation of the expected metabolites, the disaccharide ..cap alpha..,..cap alpha..-trehalose and ..cap alpha..,..beta..-glucosylamine were identified from the /sup 13/C NMR spectra.« less

Interferon alpha adjuvant therapy in patients with high-risk melanoma: a systematic review and meta-analysis.

PubMed

Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo R; Nitti, Donato

2010-04-07

Based on previous meta-analyses of randomized controlled trials (RCTs), the use of interferon alpha (IFN-alpha) in the adjuvant setting improves disease-free survival (DFS) in patients with high-risk cutaneous melanoma. However, RCTs have yielded conflicting data on the effect of IFN-alpha on overall survival (OS). We conducted a systematic review and meta-analysis to examine the effect of IFN-alpha on DFS and OS in patients with high-risk cutaneous melanoma. The systematic review was performed by searching MEDLINE, EMBASE, Cancerlit, Cochrane, ISI Web of Science, and ASCO databases. The meta-analysis was performed using time-to-event data from which hazard ratios (HRs) and 95% confidence intervals (CIs) of DFS and OS were estimated. Subgroup and meta-regression analyses to investigate the effect of dose and treatment duration were also performed. Statistical tests were two-sided. The meta-analysis included 14 RCTs, published between 1990 and 2008, and involved 8122 patients, of which 4362 patients were allocated to the IFN-alpha arm. IFN-alpha alone was compared with observation in 12 of the 14 trials, and 17 comparisons (IFN-alpha vs comparator) were generated in total. IFN-alpha treatment was associated with a statistically significant improvement in DFS in 10 of the 17 comparisons (HR for disease recurrence = 0.82, 95% CI = 0.77 to 0.87; P < .001) and improved OS in four of the 14 comparisons (HR for death = 0.89, 95% CI = 0.83 to 0.96; P = .002). No between-study heterogeneity in either DFS or OS was observed. No optimal IFN-alpha dose and/or treatment duration or a subset of patients more responsive to adjuvant therapy was identified using subgroup analysis and meta-regression. In patients with high-risk cutaneous melanoma, IFN-alpha adjuvant treatment showed statistically significant improvement in both DFS and OS.

DEAD ZONE IN THE POLAR-CAP ACCELERATOR OF PULSARS

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

Chen, Alexander Y.; Beloborodov, Andrei M.

We study plasma flows above pulsar polar caps using time-dependent simulations of plasma particles in the self-consistent electric field. The flow behavior is controlled by the dimensionless parameter {alpha} = j/c{rho}{sub GJ}, where j is the electric current density and {rho}{sub GJ} is the Goldreich-Julian charge density. The region of the polar cap where 0 < {alpha} < 1 is a {sup d}ead zone{sup -}in this zone, particle acceleration is inefficient and pair creation is not expected even for young, rapidly rotating pulsars. Pulsars with polar caps near the rotation axis are predicted to have a hollow-cone structure of radiomore » emission, as the dead zone occupies the central part of the polar cap. Our results apply to charge-separated flows of electrons (j < 0) or ions (j > 0). In the latter case, we consider the possibility of a mixed flow consisting of different ion species, and observe the development of two-stream instability. The dead zone at the polar cap is essential for the development of an outer gap near the null surface {rho}{sub GJ} = 0.« less

Breakup processes in heavy-ion induced reactions

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

Udagawa, T.; Tamura, T.; Shimoda, T.

1979-11-01

Cross sections for breakup of /sup 20/Ne into /sup 16/O and ..cap alpha.. during scattering from /sup 40/Ca were calculated in terms of the distorted-wave Born approximation. The inclusive /sup 16/O cross section observed in the /sup 40/Ca(/sup 20/Ne,/sup 16/O) reaction was then found to be fitted very well by the sum of this breakup contribution and that of the ..cap alpha..-transfer reaction calculated in our previous work.

Dielectronic satellite spectra of hydrogen-like titanium (Ti XXII)

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

Bitter, M.; von Goeler, S.; Cohen, S.

High resolution spectra of the Ly ..cap alpha../sub 1/ and Ly ..cap alpha../sub 2/ lines of hydrogenlike titanium, TiXXII, and the associated dielectronic satellites which are due to transitions 1snl-2pnl with n greater than or equal to 2, have been observed from tokamak discharges with auxiliary ion cyclotron heating (ICRH) with central electron temperatures of 2 keV and central electron densities of 8 x 10/sup 13/ cm/sup -3/ on the Princeton Large Torus (PLT). The data have been used for a detailed comparison with theoretical predictions based on the Z - expansion method and Hartree - Fock calculations. The resultsmore » obtained with the Z - expansion method are in excellent agreement with the observed spectral data except for minor discrepancies between the theoretical and experimental wavelengths of 0.0003 A for the n = 2 satellites and of 0.0001 A for the separation of the Ly ..cap alpha../sub 1/ and Ly ..cap alpha../sub 2/ lines. Very good agreement with the experimental data is also obtained for the results from the Hartree - Fock calculations though somewhat larger discrepancies (approx. = 0.0009 A) exist between experimental and theoretical wavelengths which are systematically too small. The observed spectra are used for diagnosis of the central ion and electron temperatures of the PLT discharges and for a measurement of the dielectronic recombination rate coefficient of TiXXII.« less

Oxidative stress in immunocompetent patients with severe community-acquired pneumonia. A pilot study.

PubMed

Trefler, S; Rodríguez, A; Martín-Loeches, I; Sanchez, V; Marín, J; Llauradó, M; Romeu, M; Díaz, E; Nogués, R; Giralt, M

2014-03-01

A comparison was made of the oxidative stress (OS) levels of patients with either viral or bacterial severe community-acquired pneumonia (sCAP) and of patients without infection (healthy volunteers (HV) and patients with acute myocardial infarction (AMI)). A prospective observational study was made. Critically ill patients with sCAP. The TBARS level was measured as an index of oxidative injury. SOD, CAT and redox glutathione system (GSH, GSSG, GR, GPx) activities were measured as reflecting antioxidant capacity. Severity of illness was assessed by the APACHE II, SOFA and SIRS scores. Thirty-seven subjects were included: 15 patients with CAP (12 of bacterial origin [BCAP] and 3 due to 2009 A/H1N1 virus [VCAP]), 10 HV and 12 AMI patients. Intensive care CAP mortality was 26.7% (n=4). Plasmatic TBARS levels were higher in CAP patients than in HV, but similar to those recorded in AMI patients. In contrast, VCAP was associated with lower TBARS levels, and some components of the glutathione redox system were higher in BCAP patients and HV. The OS levels did not differ between survivors and non-survivors. Our results suggest the occurrence of higher OS in sCAP patients compared with HV. In contrast, lower TBARS levels were observed in VCAP patients, suggesting an increase of antioxidant activity related to the redox glutathione system. However, further research involving a larger cohort is needed in order to confirm these findings. Copyright © 2012 Elsevier España, S.L. and SEMICYUC. All rights reserved.

Isolation of tungsten and tantalum isotopes without supports from. cap alpha. -particle-irradiated hafnium targets

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

Gasita, S.M.; Iota, B.Z.; Malachkov, A.G.

1985-11-01

An extraction procedure has been developed for successive isolation of tungsten (/sup 178/W and /sup 181/W) and tantalum (/sup 179/Ta and /sup 182/Ta) isotopes without supports from ..cap alpha..particle-irradiated hafnium targets. The target, irradiated on a cyclotron, is dissolved in hydrofluoric acid. Tantalum isotopes are extracted with tributyl phosphate (TBP) from 1-5 M HF and are then reextracted with a 1:1 ammonia solution, and hydrofluoric acid is removed by heating. Tungsten isotopes are extracted with a chloroform solution or N-benzoyl-N-phenylhydroxylamine (BPHA) from 11-12 M H/sub 2/SO/sub 4/ or ..cap alpha..-benzoin oxime from 4.5-5.5 M H/sub 2/SO/sub 4/ and are thenmore » reextracted with a l:l ammonia solution. The yield of tungsten isotopes is not less than 95%, and the content of radioactive impurities of other isotopes is not more than 0.1%.« less

Selective inhibition by chloramphenicol of pregnenolone-16. cap alpha. -carbonitrile-inducible rat liver cytochrome P-450 isozymes

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

Graves, P.E.; Kaminsky, L.S.; Halpert, J.

Pregnenolone-16 ..cap alpha..-carbonitrile (PCN) has been shown to induce, in male rats, cytochrome P-450 isozymes responsible for the formation of R-10-hydroxywarfarin and R-dehydrowarfarin. Antibodies to the major PCN-inducible isozyme (PB/PCN-E) inhibit both activities in microsomal preparations. Recently the authors have shown that PCN treatment of female rats also induces the formation of both R-warfarin metabolites. However, in both sexes chloramphenicol (CAP) treatment selectively inhibits only the rate of formation of the R-dehydrowarfarin. A decrease in microsomal P-450 content occurs after in vivo administration of CAP to PCN-treated rats of both sexes. This is in contrast to the lack of effectmore » of CAP on P-450 levels in phenobarbital-treated rats. Covalent binding of /sup 14/C-CAP to microsomal protein in vitro was increased 3 to 4-fold following PCN treatment. Chromatographic evidences suggests the presence of at least two PCN-induced isozymes of similar molecular weights in both male and female rat liver microsomes. These data are consistent with the multiplicity of PCN-inducible P-450 in rat liver.« less

Chromosomal aberrations and delays in cell progression induced by x-rays in Tradescantia clone 02 meristems

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

Geard, C.R.

1983-01-01

In root meristems of Tradescantia clone 02 (developed by Sparrow and his colleagues for mutation studies), X-rays interfere with the progression of cells through the cell cycle and induce chromosomal aberrations in a dose-dependent manner consistent with linear-quadratic kinetics. Sequential mitotic cell accumulations after irradiation indicate that sensitivity to aberration induction is probably greatest in cells from late S to early G2, with chromatid interchanges the most frequent aberration type and all aberrations consistent with initiation from the interaction between two lesions. The ratio of the coefficients in the linear (..cap alpha..) and the quadratic (..beta..) terms (..cap alpha../..beta..) ismore » equal to the dose average of specific energy produced by individual particles in the site where interaction takes place. The ratio ..cap alpha../..beta.. for chromosomal aberrations is similar to that previously found for X-ray-induced mutation in Tradescantia stamen hairs, supporting the proposal that radiation-induced mutational events are due to chromosomal aberrations with interaction distances of about 1..mu..m. Abrahamson and co-workers have noted that both ..cap alpha../..beta.. ratios appear to be related to nuclear target size and are similar for chromosomal and mutational endpoints in the same organism. These findings support this concept; however, it is apparent that any situation which diminishes yield at high doses (e.g., mitotic delay) will probably affect the ..beta.. component. 23 references, 5 figures, 2 tables.« less

Chromosomal aberrations and delays in cell progression induced by x-rays in Tradescantia clone 02 meristems

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

Geard, C.R.

1983-01-01

In root meristems of Tradescantia clone 02 (developed by Sparrow and his colleagues for mutation studies), X-rays interfere with the progression of cells through the cell cycle and induce chromosomal aberrations in a dose-dependent manner consistent with linear-quadratic kinetics. Sequential mitotic cell accumulations after irradiation indicate that sensitivity to aberrration induction is probably greatest in cells from late S to early G2, with chromatid interchanges the most frequent aberration type and all aberrations consistent with intiation from the interaction between two lesions. The ratio of the coefficients in the linear (..cap alpha..) and the quadratic (..beta..) terms (..cap alpha../..beta..) ismore » equal to the dose average of specific energy produced by individual particles in the site where interaction takes place. The ratio ..cap alpha../..beta.. for chromosomal aberrations is similar to that previously found for X-ray-induced mutation in Tradescantia stamen hairs, supporting the proposal that radiation-induced mutational events are due to chromosomal aberrations with interaction distances of about 1 ..mu..m. Abrahmson and co-workers have noted that both ..cap alpha../..beta.. ratios appear to be related to nuclear target size and are similar for chromosomal and mutational endpoints in the same organism. These findings support this concept; however, it is apparent that any situation which diminishes yield at high doses (e.g., mitotic delay) will primarily affect the ..beta.. component, resulting in low assessments of interaction site diameters.« less

Exact near-onset analysis of the spin-density-wave instability in ferromagnetic superconductors: The linearly polarized state

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

Hu, C.

1984-09-01

Using an approach similar to Abvikosov's theory of the vortex state near H/sub c/2, we have performed an exact, near-onset analysis of a spin-density-wave instability leading to the ''linearly polarized state'' of Greenside et al. in ferromagnetic superconductors. The approach is based on a generalized Ginzburg-Landau theory for such materials, as formulated by Blount and Varma. Two models have been considered. In the (..cap alpha..,..beta..) model, where the bulk magnetic energy is taken to be (1/2)..cap alpha../sub m/M/sup 2/+(1/4)..beta../sub m/M/sup 4/, we find the transition to be second order, and obtain explicit formulas for various physical quantities to leading ordermore » in the deviation from onset. We have also rigorously analyzed the most favored spatial structure just below onset, among all possibilities allowed by the instability, and have concluded that a plane-wave-like structure is favored in a physical limit considered. In the (..cap alpha..,..gamma..) model, where the bulk magnetic energy is taken to be (1/2)..cap alpha../sub m/M/sup 2/+(1/6)..gamma../sub m/M/sup 6/ as is supported by recent experiments for ErRh/sub 4/B/sub 4/, we find the transition to be first order. This approach is then confined to an unphysical branch, which does not permit us to calculate various physical quantities on the physical branch.« less

Drosophila Casein Kinase I Alpha Regulates Homolog Pairing and Genome Organization by Modulating Condensin II Subunit Cap-H2 Levels

PubMed Central

Nguyen, Huy Q.; Nye, Jonathan; Buster, Daniel W.; Klebba, Joseph E.; Rogers, Gregory C.; Bosco, Giovanni

2015-01-01

The spatial organization of chromosomes within interphase nuclei is important for gene expression and epigenetic inheritance. Although the extent of physical interaction between chromosomes and their degree of compaction varies during development and between different cell-types, it is unclear how regulation of chromosome interactions and compaction relate to spatial organization of genomes. Drosophila is an excellent model system for studying chromosomal interactions including homolog pairing. Recent work has shown that condensin II governs both interphase chromosome compaction and homolog pairing and condensin II activity is controlled by the turnover of its regulatory subunit Cap-H2. Specifically, Cap-H2 is a target of the SCFSlimb E3 ubiquitin-ligase which down-regulates Cap-H2 in order to maintain homologous chromosome pairing, chromosome length and proper nuclear organization. Here, we identify Casein Kinase I alpha (CK1α) as an additional negative-regulator of Cap-H2. CK1α-depletion stabilizes Cap-H2 protein and results in an accumulation of Cap-H2 on chromosomes. Similar to Slimb mutation, CK1α depletion in cultured cells, larval salivary gland, and nurse cells results in several condensin II-dependent phenotypes including dispersal of centromeres, interphase chromosome compaction, and chromosome unpairing. Moreover, CK1α loss-of-function mutations dominantly suppress condensin II mutant phenotypes in vivo. Thus, CK1α facilitates Cap-H2 destruction and modulates nuclear organization by attenuating chromatin localized Cap-H2 protein. PMID:25723539

Antisymmetrization effects and the form factor of the real part of the. cap alpha. -nucleus potential

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

Majka, Z.; Budzanowski, A.; Grotowski, K.

1978-07-01

Antisymmetrization effects in the ..cap alpha..-nucleus interaction are investigated on the basis of a microscopic model in an one nucleon exchange approximation. It influences the form factor, increasing the halfway radius and decreasing the diffuseness as compared with the direct term of the potential only. Antisymmetrization preserves the shape of the potential which can be parametrized by a Woods-Saxon squared form. The phenomenological potential with the energy independent form factor of the above shape fits experimental data in a wide energy region.

Cross sections and differential spectra for reactions of 2-20 MeV neutrons of /sup 27/Al

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

Blann, M.; Komoto, T.T.

1988-01-01

This report summarizes product yields, secondary n,p and ..cap alpha.. spectra, and ..gamma..-ray spectra calculated for incident neutrons of 2-20 MeV on /sup 27/Al targets. Results are all from the code ALICE, using the version ALISO which does weighting of results for targets which are a mix of isotopes. Where natural isotopic targets are involved, yields and n,p,..cap alpha.. spectra will be reported weighted over isotopic yields. Gamma-ray spectra, however, will be reported for the most abundant isotope.

Separation of anionic oligosaccharides by high-performance liquid chromatography

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

Green, E.D.; Baenziger, J.U.

1986-10-01

The authors have developed methods for rapid fractionation of anionic oligosaccharides containing sulfate and/or sialic acid moieties by high-performance liquid chromatography (HPLC). Ion-exchange HPLC on amine-bearing columns (Micropak AX-10 and AX-5) at pH 4.0 is utilized to separate anionic oligosaccharides bearing zero, one, two, three, or four charges, independent of the identity of the anionic moieties (sulfate and/or sialic acid). Ion-exchange HPLC at pH 1.7 allows separation of neutral, mono-, di-, and tetrasialylated, monosulfated, and disulfated oligosaccharides. Oligosaccharides containing three sialic acid residues and those bearing one each of sulfate and sialic acid, however, coelute at pH 1.7. Since themore » latter two oligosaccharide species separate at pH 4.0, analysis at pH 4.0 followed by analysis at pH 1.7 can be utilized to completely fractionate complex mixtures of sulfated and sialylated oligosaccharides. Ion-suppression amine adsorption HPLC has previously been shown to separate anionic oligosaccharides on the basis of net carbohydrate content (size). In this study they demonstrate the utility of ion-suppression amine adsorption HPLC for resolving sialylated oligosaccharide isomers which differ only in the linkages of sialic acid residues (..cap alpha..2,3 vs ..cap alpha..2,6) and/or location of ..cap alpha..2,3- and ..cap alpha..2,6-linked sialic acid moieties on the peripheral branches of oligosaccharides. These two methods can be used in tandem to separate oligosaccharides, both analytically and preparatively, based on their number, types, and linkages of anionic moieties.« less

South Polar Cap

NASA Technical Reports Server (NTRS)

2005-01-01

8 December 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows landforms created by sublimation processes on the south polar residual cap of Mars. The bulk of the ice in the south polar residual cap is frozen carbon dioxide.

Location near: 86.6oS, 342.2oW Image width: width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Summer

Tubulin chaperone E binds microtubules and proteasomes and protects against misfolded protein stress.

PubMed

Voloshin, Olga; Gocheva, Yana; Gutnick, Marina; Movshovich, Natalia; Bakhrat, Anya; Baranes-Bachar, Keren; Bar-Zvi, Dudy; Parvari, Ruti; Gheber, Larisa; Raveh, Dina

2010-06-01

Mutation of tubulin chaperone E (TBCE) underlies hypoparathyroidism, retardation, and dysmorphism (HRD) syndrome with defective microtubule (MT) cytoskeleton. TBCE/yeast Pac2 comprises CAP-Gly, LRR (leucine-rich region), and UbL (ubiquitin-like) domains. TBCE folds alpha-tubulin and promotes alpha/beta dimerization. We show that Pac2 functions in MT dynamics: the CAP-Gly domain binds alpha-tubulin and MTs, and functions in suppression of benomyl sensitivity of pac2Delta mutants. Pac2 binds proteasomes: the LRR binds Rpn1, and the UbL binds Rpn10; the latter interaction mediates Pac2 turnover. The UbL also binds the Skp1-Cdc53-F-box (SCF) ubiquitin ligase complex; these competing interactions for the UbL may impact on MT dynamics. pac2Delta mutants are sensitive to misfolded protein stress. This is suppressed by ectopic PAC2 with both the CAP-Gly and UbL domains being essential. We propose a novel role for Pac2 in the misfolded protein stress response based on its ability to interact with both the MT cytoskeleton and the proteasomes.

Calculated half-lives and kinetic energies for spontaneous emission of heavy ions from nuclei

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

Poenaru, D.N.; Greiner, W.; Depta, K.

The most probable decays by spontaneous emission of heavy ions are listed for nuclides with Z = 47--106 and total half-lives>1 ..mu..sec. Partial half-lives, branching ratios relative to ..cap alpha.. decay, kinetic energies, and Q values are estimated by using the analytical superasymmetric fission model, a semiempirical formula for those ..cap alpha..-decay lifetimes which have not been measured, and the new Wapstra--Audi mass tables. Numerous ''stable'' nuclides with Z>40 are found to be metastable with respect to the new decay modes. The current experimental status is briefly reviewed.

Algal succession and chronosequences on abandoned mine spoils

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

Shubert, L.E.; Starks, T.L.

1978-06-01

Soils were collected from spoil material aged 0 to 45 years. The soils were analyzed for the presence of algal species, chlorophyll ..cap alpha.., major cations, anions and trace elements. There was a gradual increase in the number of algal species and chlorophyll ..cap alpha.. from 1 year old spoils to adjacent unmined natural sites. A total of 41 algal species were identified from all sites. Several species were only found at the unmined sites and they may represent a stable algal community. Results of a statistical analysis on the litho- and chronosequence of the soils will be discussed.

Biosynthesis of ketomycin. (II) biomimetic model for beta-lactamase catalysis: host-guest interactions in cyclodextrin-penicillin inclusion complex

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

Mak, H.W.

The antibiotic ketomycin is formed from shikimic acid via chorismic acid and prephenic acid. Phenylalanine and 2',5'-dihydrophenylalanine derived from shikimic acid are not intermediates in the biosynthesis. Degradation of ketomycin derived from (1,6-/sup 14/C)shikimic acid showed that prephenic acid is converted into ketomycin with stereospecific discrimination between the two enantiotopic edges of the ring, the pro-S-R edge giving rise to the C-2', C-3' side of the cyclohexane ring of ketomycin. The resistance of pathogenic bacteria to the action of ..beta..-lactam antibiotics is mainly ascribed to their ability to produce ..beta..-lactamase to cleave the ..beta..-lactam ring. It is essential to understandmore » the molecular nature of ..beta..-lactamase-penicillin recognition for designing and formulating more effective ..beta..-lactam antibiotics. A biomimetic study of ..beta..-lactamase is therefore initiated. To meet the requirements of hydrophobic and serine protease characteristics of ..beta..-lactamase, ..cap alpha..-cyclodextrin is chosen as a biomimetic model for ..beta..-lactamase. The structural specificity and the chemical dynamics of ..cap alpha..-cyclodextrin-phenoxymethyl penicillin inclusion complex in solid state and in solution have been determined by IR and NMR spectroscopy. The spectral results strongly indicate that the phenyl portion of the phenoxymethyl penicillin forms a stable inclusion complex with the hydrophobic cavity of ..cap alpha..-cyclodextrin in solution as well as in the solid state. Kinetic studies followed by /sup 1/HNMR and HPLC analyses under alkaline condition have shown that the ..cap alpha..-cyclodextrin mimics the catalytic function of serine of ..beta..-lactamase in the stereospecific hydrolysis of the ..beta..-lactam ring of phenoxymethyl penicillin.« less

South Polar Cap

NASA Technical Reports Server (NTRS)

2005-01-01

17 March 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows mesas and pits formed by sublimation of carbon dioxide of the south polar cap.

Location near: 85.8oS, 351.5oW Image width: 2 km (1.2 mi) Illumination from: upper left Season: Southern Summer

[Cytokine changes in community-acquired pneumonia in elderly and intervention of traditional Chinese medicine].

PubMed

Ye, Shanghe; Gong, Guolang; Zheng, Haiwen; Hu, Guohua; Xia, Tao

2010-06-01

To make a study of the cytokine changes in community-acquired pneumonia (CAP) in the elderly and the intervention of traditional Chinese medicine that can clear away the lung-heat and dissipate blood stasis (Qingfeihuayu soup). The 82 cases with CAP in the elderly were divided at random into two treatment group and control group. Based on heteropathy, the treatment group was given Qingfeihuayu soup two times a day. The control group was given Rocephin 2 g once daily for 7 days. The clinical effect and the changes in TNF-alpha, IL-6 and IL-10 were observed before and after the treatment. A healthy group was also set up. Before treatment, IL-6 and TNF-alpha in both groups were higher than the healthy group (P < 0.01) and IL-10 lower than the healthy group (P < 0.01). After treatment, IL-6 and TNF-alpha in both groups decreased (P < 0.01) while IL-10 in treatment group increased. There existed a great difference compared with the control group (P < 0.01). The total effective rate in the treatment group is 92.50% while the control group is 85.71%. thus have a great difference (P < 0.05). During the process of the development of CAP in the elderly, there existed the phenomenon of the excessive release of TNF-alpha, IL-6 and the too much inhibition of IL-10. The unbalance of TNF-alpha, IL-6, IL-10 can be a monitoring index reflecting the severity of the disease. The Chinese medicine Qingfeihuayu soup has obviously have regulating and clinical effect.

Results from the Crystal Ball at DORIS II

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

Gaiser, J.E.

1983-10-01

Results are presented from studies of the inclusive photon spectra in hadronic decays of the UPSILON' and UPSILON and the exclusive channel UPSILON' ..-->.. ..gamma gamma..UPSILON ..-->.. ..cap alpha cap alpha..l/sup +/l/sup -/, by the Crystal Ball detector at DORIS II. We measure two signals in the UPSILON' ..-->.. ..gamma.. + anything inclusive channel at E(..gamma..) == 108.3 +- 0.9 +- 3.0 MeV and at E(..gamma..) == 127.5 +- 1.2 +- 4.0 MeV. Branching ratios obtained for these signals are: BR(UPSILON' ..-->.. ..gamma..(108) + anything) == (6.3 +- 1.3 +- 1.4)% BR(UPSILON' ..-->.. ..gamma..(128) + anything) == (6.0 +- 1.3more » +- 1.4)%.« less

MFTF-. cap alpha. + T progress report

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

Nelson, W.D.

1985-04-01

Early in FY 1983, several upgrades of the Mirror Fusion Test Facility (MFTF-B) at Lawrence Livermore National Laboratory (LLNL) were proposed to the fusion community. The one most favorably received was designated MFTF-..cap alpha..+T. The engineering design of this device, guided by LLNL, has been a principal activity of the Fusion Engineering Design Center during FY 1983. This interim progress report represents a snapshot of the device design, which was begun in FY 1983 and will continue for several years. The report is organized as a complete design description. Because it is an interim report, some parts are incomplete; theymore » will be supplied as the design study proceeds. As described in this report, MFTF-..cap alpha..+T uses existing facilities, many MFTF-B components, and a number of innovations to improve on the physics parameters of MFTF-B. It burns deuterium-tritium and has a central-cell Q of 2, a wall loading GAMMA/sub n/ of 2 MW/m/sup 2/ (with a central-cell insert module), and an availability of 10%. The machine is fully shielded, allows hands-on maintenance of components outside the vacuum vessel 24 h after shutdown, and has provisions for repair of all operating components.« less

Muscarinic cholinergic and alpha/sub 1/ adrenergic receptors in murine atria: phosphatidylinositol breakdown and receptor interaction

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

Scherer, R.W.

Upon stimulation of muscarinic cholinergic receptors, there is a decrease in the force of contraction rate of firing in heart, while stimulation of ..cap alpha.. adrenergic receptors causes an increase in the force of contraction with no change in the heart rate. Yet both receptors stimulate the breakdown of phosphatidylinositol (PI). Therefore, the breakdown of PI was examined to determine how the process differed between the two receptor systems. Murine atria, prelabelled with (/sup 3/H)inositol, were stimulated with the muscarinic cholinergic agonists, carbamylcholine (CARB), and oxotremorine (OXO); and with the ..cap alpha.. adrenergic agonists, norepinephrine (NE) and phenylephrine (PE); eithermore » singly or in combination. Breakdown of PI was assessed by measurement of individual inositol phosphates by anion exchange chromatography. Binding of CARB to atrial muscarinic receptors was measured by competition with (/sup 3/H)quinuclidinyl benzilate.« less

Structural and biological characterization of a capsular polysaccharide produced by Staphylococcus haemolyticus.

PubMed

Flahaut, Sigrid; Vinogradov, Evgeny; Kelley, Kathryn A; Brennan, Shannon; Hiramatsu, Keiichi; Lee, Jean C

2008-03-01

The DNA sequence of the genome of Staphylococcus haemolyticus JCSC1435 revealed a putative capsule operon composed of 13 genes in tandem. The first seven genes (capABCDEFG(Sh)) showed > or = 57% similarity with the Staphylococcus aureus cap5 or cap8 locus. However, the capHIJKLM(Sh) genes are unique to S. haemolyticus and include genes encoding a putative flippase, an aminotransferase, two glycosyltransferases, and a transcriptional regulator. Capsule-like material was readily apparent by immunoelectron microscopy on bacteria harvested in the postexponential phase of growth. Electron micrographs of a JCSC1435 mutant with a deleted cap region lacked the capsule-like material. Both strains produced small amounts of surface-associated material that reacted with antibodies to polyglutamic acid. S. haemolyticus cap genes were amplified from four of seven clinical isolates of S. haemolyticus from humans, and three of these strains produced a serologically cross-reactive capsular polysaccharide. In vitro assays demonstrated that the acapsular mutant strain showed greater biofilm formation but was more susceptible to complement-mediated opsonophagocytic killing than the parent strain. Structural characterization of capsule purified from S. haemolyticus strain JCSC1435 showed a trisaccharide repeating unit: -3-alpha-L-FucNAc-3-(2-NAc-4-N-Asp-2,4,6-trideoxy-beta-D-Glc)-4-alpha-D-GlcNAc-. This structure is unique among staphylococcal polysaccharides in that its composition includes a trideoxy sugar residue with aspartic acid as an N-acyl substituent.

Absolute configuration of a chiral CHD group via neutron diffraction: confirmation of the absolute stereochemistry of the enzymatic formation of malic acid

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

Bau, R.; Brewer, I.; Chiang, M.Y.

Neutron diffraction has been used to monitor the absolute stereochemistry of an enzymatic reaction. (-)(2S)malic-3-d acid was prepared by the action of fumarase on fumaric acid in D/sub 2/O. After a large number of cations were screened, it was found that (+)(R)..cap alpha..-phenylethylamine forms the large crystals necessary for a neutron diffraction analysis. The subsequent structure determination showed that (+)(R)..cap alpha..-phenylethylammonium (-)(2S)malate-3-d has an absolute configuration of R at the CHD site. This result confirms the absolute stereochemistry of fumarate-to-malate transformation as catalyzed by the enzyme fumarase.

Role of carotenoids in the phototropic response of corn seedings

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

Vierstra, R.D.; Poff, K.L.

1981-10-01

The herbicide 4 chloro-5-(methylamino)-2-..cap alpha..,..cap alpha..,..cap alpha..,-trifluoro-m-tolyl)-3(2H)- pyridazinone (SAN 9789), which blocks the synthesis in higher plants of colored carotenoids but not of flavins, was used to examine the involvement of carotenoids in corn seeding phototropism. It was concluded that ''bulk'' carotenoids are not the photoreceptor pigment based on the results that increasing concentrations of SAN 9789 (up to 100 micromolar) did not alter the phototropic sensitivity to 380 nanometers light (using geotropism as a control) and did not increase the threshold intensities of fluence response curves for both 380 and 450 nanometers light even though carotenoid content was reducedmore » to 1 to 2% of normal. SAN 9789 treatment, however, did reduce seedling sensitivity toward 450 nanometers light indicating that carotenoids are involved in phototropism. Carotenoids, which are located mainly in the primary leaves, may act in phototropism as an internal screen, enhancing the light intensity gradient across the seedling and thus contributing to the ability of the seedling to perceive light direction. These results, indicate that the action spectra for phototropic responses can be significantly affected by the absorbance of screening pigments in vivo thus altering its shape from the in vitro absorption spectrum of the photoreceptor pigment.« less

Secondary. cap alpha. -deuterium kinetic isotope effects in solvolyses of ferrocenylmethyl acetate and benzoate in ethanol

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

Sutic, D.; Asperger, S.; Borcic, S.

1982-12-17

Secondary ..cap alpha..-deuterium kinetic isotope effects (KIE) in solvolyses of ferrocenyldideuteriomethyl acetate and benzoate were determined in 96% (v/v) ethanol, at 25/sup 0/C, as k/sub H//k/sub D/ = 1.24 and 1.26, respectively. The KIEs were also determined in the presence of 0.1 mol dm/sup -3/ lithium perchlorate: the k/sub H//k/ sub D/ values were 1.23 and 1.22 for acetate and benzoate complexes, respectively. The maximum KIE for the C-O bond cleavage of a primary substrate is as large as, or larger than, that of secondary derivatives, which is estimated to be 1.23 per deuterium. The measured KIE of about 12%more » per D therefore represents a strongly reduced effect relative to its maximum. The solvolyses exhibit ''a special salt effect''. This effect indicates the presence of solvent-separated ion pairs and the return to tight pairs. As the maximum KIE is expected in solvolyses involving transformation of one type of ion pair into another, the strongly reduced ..cap alpha..-D KIE supports the structure involving direct participation of electrons that in the ground state are localized at the iron atom. The alkyl-oxygen cleavage is accompanied by 10-15% acyl-oxygen cleavage.« less

Hydrogen transport and hydrogen embrittlement in stainless steels

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

Perng, T.P.

1985-01-01

In order to understand the kinetics of gaseous hydrogen-induced slow crack growth (SCG) in metastable austenitic stainless steels, hydrogen permeation and/or cracking velocity were measured and compared for three types of stainless steels. These included austenitic, ferritic, and duplex (..gamma../..cap alpha..) alloys. Deformation in AISI 301 resulted in various amounts of ..cap alpha..' martensite, which enhanced the effective hydrogen diffusivity and permeability. No phase transformation was observed in deformed AISI 310. The effective hydrogen diffusivity in this alloy was slightly reduced after plastic deformation, presumably by dislocation trapping. In either the dynamic or static tensile test, AISI 301 exhibited themore » greatest hydrogen embrittlement and therefore the highest SCG velocity among all the alloys tested in this work. The SCG velocity was believed to be controlled by the rate of accumulation of hydrogen in the embrittlement region ahead of the crack tip and therefore could be explained with the hydrogen transport parameters measured from the permeation experiments. The relatively high SCG velocity in AISI 301 was probably due to the fast transport of hydrogen through the primarily stress-induced ..cap alpha..' phase around the crack. No SCG was observed in AISI 310. The presence of H/sub 2/O vapor was found to reduce both the hydrogen permeation and SCG velocity.« less

Vacuum energy density near static distorted black holes

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

Frolov, V.P.; Sanchez, N.

1986-03-15

We investigate the contribution of massless fields of spins 0, 1/2, and 1 to the vacuum polarization near the event horizon of static Ricci-flat space-times. We do not assume any particular spatial symmetry. Within the Page-Brown ''ansatz'' we calculate /sup ren/ and /sup ren/ near static distorted black holes, for both the Hartle-Hawking (Vertical Bar>/sub H/) and Boulware (Vertical Bar>/sub B/) vacua. Using Israel's description of static space-times, we express these quantities in an invariant geometric way. We obtain that /sub H//sup ren/ and /sub H//sup ren/ near the horizon depend only on the two-dimensional geometry of the horizon surface.more » We find /sub H//sup ren/ = (1/48..pi../sup 2/ )K/sub 0/, /sub H//sup ren/ = (7..cap alpha..+12..beta.. )K/sub 0/ /sup 2/-..cap alpha../sup(/sup 2/)..delta..K/sub 0/. $K sub 0: is the Gaussian curvature of the horizon, and ..cap alpha.. and ..beta.. are numerical coefficients depending on the spin of a field. The term in /sup(/sup 2/)..delta..K/sub 0/ is characteristic of the distortion of the black hole. When the event horizon is not distorted, K/sub 0/ is a constant and this term disappears.« less

The upregulation of receptor activator NF-kappaB ligand expression by interleukin-1alpha and Porphyromonas endodontalis in human osteoblastic cells.

PubMed

Chen, S-C; Huang, F-M; Lee, S-S; Li, M-Z; Chang, Y-C

2009-04-01

To investigate the receptor activator of nuclear factor-kappa B (NF-kappaB) ligand (RANKL) in osteoblastic cells stimulated with inflammatory mediators. The expression of RANKL in human osteoblastic cell line U2OS stimulated by pro-inflammatory cytokine interleukin (IL)-1alpha and black-pigmented bacteria Porphyromonas endodontalis was investigated by Western blot and enzyme-linked immunosorbent assay (ELISA). The significance of the results obtained from control and treated groups was statistically analysed by the paired Student's t-test. IL-1alpha was found to upregulate RANKL production in U2OS cells (P < 0.05). Investigations of the time dependence of RANKL expression in IL-1alpha-treated cells revealed a rapid accumulation of RANKL protein after 1 h of exposure; it remained elevated throughout the 24-h incubation period shown by Western blot and ELISA. In addition, P. endodontalis also increased RANKL expression in U2OS cells after 4-h incubation period demonstrated by Western blot and ELISA (P < 0.05). IL-1alpha and P. endodontalis may be involved in developing apical periodontitis through the stimulation of RANKL production.

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

Calva-Tellez, E.; Yennie, D.R.

The Coulomb corrections of relative order Z..cap alpha.. to inelastic electron and muon scattering are examined. Although individual terms are large, the net result is too small to be experimentally significant.

South Polar Scarps

NASA Technical Reports Server (NTRS)

2003-01-01

MGS MOC Release No. MOC2-438, 31 July 2003

The terrain of the south polar residual ice cap, made up mostly of frozen carbon dioxide, has come to be known by many as 'swiss cheese terrain,' because many areas of the cap resemble slices of swiss cheese. However, not all of the south polar cap looks like a tasty lunch food. This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a series of curving scarps formed by erosion and sublimation of carbon dioxide from the south polar cap. This area is located near 86.3oS, 51.2oW. The image is illuminated by sunlight from the upper left; the area is about 1.5 km (0.9 mi) wide.

Neutrophil-derived alpha defensins control inflammation by inhibiting macrophage mRNA translation

PubMed Central

Tomlinson, Gareth H.; Miles, Katherine; Smith, Richard W. P.; Rossi, Adriano G.; Hiemstra, Pieter S.; van ’t Wout, Emily F. A.; Dean, Jonathan L. E.; Gray, Nicola K.; Lu, Wuyuan; Gray, Mohini

2016-01-01

Neutrophils are the first and most numerous cells to arrive at the site of an inflammatory insult and are among the first to die. We previously reported that alpha defensins, released from apoptotic human neutrophils, augmented the antimicrobial capacity of macrophages while also inhibiting the biosynthesis of proinflammatory cytokines. In vivo, alpha defensin administration protected mice from inflammation, induced by thioglychollate-induced peritonitis or following infection with Salmonella enterica serovar Typhimurium. We have now dissected the antiinflammatory mechanism of action of the most abundant neutrophil alpha defensin, Human Neutrophil Peptide 1 (HNP1). Herein we show that HNP1 enters macrophages and inhibits protein translation without inducing the unfolded-protein response or affecting mRNA stability. In a cell-free in vitro translation system, HNP1 powerfully inhibited both cap-dependent and cap-independent mRNA translation while maintaining mRNA polysomal association. This is, to our knowledge, the first demonstration of a peptide released from one cell type (neutrophils) directly regulating mRNA translation in another (macrophages). By preventing protein translation, HNP1 functions as a “molecular brake” on macrophage-driven inflammation, ensuring both pathogen clearance and the resolution of inflammation with minimal bystander tissue damage. PMID:27044108

Assessment of posttraumatic stress disorder in Cambodian refugees using the Clinician-Administered PTSD Scale: psychometric properties and symptom severity.

PubMed

Hinton, Devon E; Chhean, Dara; Pich, Vuth; Pollack, M H; Orr, Scott P; Pitman, Roger K

2006-06-01

Posttraumatic stress disorder (PTSD) symptoms were assessed by using the Clinician-Administered PTSD Scale (CAPS) in a consecutive sample of Cambodian refugees attending a psychiatric clinic in the United States. Psychometric properties of the translated CAPS and severity of PTSD-related symptoms were examined. The CAPS demonstrated adequate psychometric properties, including coefficient alpha (.92) and item-total correlations (.48-.85). Of the sample 56% (101/179) met Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for current PTSD. Those patients who met criteria for current PTSD had significantly higher CAPS total scores (M = 65.3, SD = 18.1) than those who did not meet the criteria (M = 13.9, SD = 16.7).

Effects of preventing O-glycosylation on the secretion of human chorionic gonadotropin in Chinese hamster ovary cells

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

Matzuk, M.M.; Krieger, M.; Corless, C.L.

1987-09-01

Human chorionic gonadotropin (hCG) is a member of a family of heterodimeric glycoprotein hormones that have a common ..cap alpha.. subunit but differ in their hormone-specific ..beta..-subunits. The ..beta.. subunit of hCG (hCG..beta..) is unique among the ..beta.. subunits in that it contains four mucin-like O-linked oligosaccharides attached to a carboxyl-terminal extension. To study the effects of O-glycosylation on the secretion and assembly of hCG, expression vectors containing either hCG..beta.. gene alone or together with the hCG..cap alpha.. gene were transfected into a mutant Chinese hamster ovary cell line, 1d1D, which exhibits a reversible defect in O-glycosylation. The results revealmore » that hCG..beta.. can be secreted normally in the absence of its O-linked oligosaccharides. hCG..beta.. devoid of O-linked carbohydrate can also combine efficiently with hCG..cap alpha.. and be secreted as an intact dimer. The authors conclude that in Chinese hamster ovary cells, the hCG..beta.. O-linked chains play no role in the assembly and secretion of hCG. The normal and O-linked oligosaccharide-deficient forms of hCG secreted by these cells should prove useful in examining the role of O-linked chains on the biological function of hCG.« less

Hormonal regulation of hepatic glycogenolysis in the carp, Cyprinus carpio

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

Janssens, P.A.; Lowrey, P.

1987-04-01

Carp (Cyprinus carpio) liver maintained normal glycogen content and enzyme complement for several days in organ culture. Epinephrine-stimulated glycogenolysis, phosphorylase activation, and cyclic AMP (cAMP) accumulation in a concentration-dependent manner with EC/sub 50/s of 100, 100, and 500 nM, respectively. These actions were blocked by the ..beta..-adrenergic antagonist, propranolol, but not by the ..cap alpha..-adrenergic antagonist phentolamine. Glycogenolysis and tissue cAMP were uninfluenced by 10/sup -6/ M arginine vasotocin, arginine vasopressin, lysine vasotocin, lysine vasopressin, mesotocin, or oxytocin, but were slightly increased by 10/sup -5/ M isotocin and slightly decreased by 10/sup -6/ M angiotensin II. (/sup 125/I)-iodocyanopindolol (ICP), amore » ..beta..-adrenergic ligand, bound to isolated carp liver membranes with a K/sub D/ of 83 pM. Maximum binding of 45 fmol/mg protein was at 600 pM. Propranolol, isoprenaline, epinephrine, phenylephrine, norepinephrine, and phenoxybenzamine displaced ICP with K/sub D/s of 100 nM, 2, 20, 20, 60, and 200 ..mu..M, respectively. The ..cap alpha..-adrenergic antagonists, yohimbine and prazosin, showed no specific binding. These data provide evidence that catecholamines act via ..beta..-adrenergic receptors in carp liver and that ..cap alpha..-adrenergic receptors are not present. Vasoactive peptides play no significant role in regulation of carp liver glycogenolysis.« less

Hydrogen and deuterium in the local interstellar medium

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

Murthy, J.N.

1987-01-01

This work reports on the results of a series of IUE observations of interstellar HI and DI Ly..cap alpha.. absorption against the chromospheric Ly..cap alpha.. emission of the nearby late-type stars ..cap alpha.. Cen B(1.3 pc), epsilon Eri (3.3 pc), Procyon (3.5 pc), Altair (5.1 pc), Capella (13.2 pc), and HR 1099 (33 pc). The density, velocity dispersion, and bulk velocity of the neutral hydrogen along the line of sight to each of these stars was derived. Lower limits were placed on the deuterium-to-hydrogen (D/H) ratio towards the same stars. These IUE results are generally consistent with previous observations ofmore » the same stars with the Copernicus satellite showing that this modeling procedure is independent of stellar variations over a period of several years. The HI absorption profile towards Altair shows a broad saturated core and steep line wings, consistent with a multicomponent interstellar medium in that direction. The bulk velocities towards the other stars are consistent with a bulk flow from the approximate direction of the galactic center but do show local variations from a uniform flow, possibly indicating a complicated velocity structure even in the solar neighborhood. Interstellar deuterium is detected towards every star except Altair and the derived values for the D/H ratio are consistent with those previously found with Copernicus.« less

Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: distributions of sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

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

Green, E.D.; Baenziger, J.U.

1988-01-05

The asparagine-linked oligosaccharides on the pituitary glycoprotein hormones lutropin (LH), follitropin (FSH), and thyrotropin (TSH) consist of a heterogeneous array of neutral, sulfated, sialylated, and sulfated/sialylated structures. In this study, the authors determined the relative quantities of the various asparagine-linked oligosaccharides on LH, FSH, and TSH from these three animal species. The proportions of sulfated versus sialylated oligosaccharides varied markedly among the different hormones. Both hormone- and animal species-specific differences in the types and distributions of sulfated, sialylated, and sulfated/sialylated structures were evident. In particular, LH and FSH, which are synthesized in the same pituitary cell and bear ..cap alpha..-subunitsmore » with the identical amino acid sequence, contained significantly different distributions of sulfated and sialylated oligosaccharides. For all three animal species, the ratio of sialylated to sulfated oligosaccharides differed by >10-fold for LH and FSH, with sulfated structures dominating on LH and sialylated structures on FSH. Sialylated oligosaccharides were also heterogeneous with respect to sialic acid linkage (..cap alpha..2,3 versus ..cap alpha..2,6). The differences in oligosaccharide structures among the various pituitary glycoprotein hormones as well as among the various glycosylation sites within a single hormone support the hypothesis that glycosylation may serve important functional roles in the expression and/or regulation of hormone bioactivity.« less

Effects of dietary saw palmetto on the prostate of transgenic adenocarcinoma of the mouse prostate model (TRAMP).

PubMed

Wadsworth, Teri L; Worstell, Teresa R; Greenberg, Norman M; Roselli, Charles E

2007-05-01

Several of the proposed mechanisms for the actions of the liposterolic extract of saw palmetto (SPE) are exerted on known risk factors for prostate cancer (CaP). This study investigated whether SPE could prevent the progression of CaP in a transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Two different doses of SPE designed to deliver 50 mg/kg/day SPE and 300 mg/kg/day SPE were administered in a custom diet to TRAMP mice for 12 or 24 weeks. Body and organ weights were used to evaluate toxicity, and radioimmunoassay was used to measure plasma and tissue androgen levels to monitor effects of SPE on 5alpha reductase activity. Prostate tissues were evaluated histologically to determine the effect of treatment on tumor grade, cell proliferation, and apoptosis. Treatment with 300 mg/kg/day SPE from 4 to 24 weeks of age significantly reduced the concentration of 5alpha-dihydrotestosterone (DHT) in the prostate and resulted in a significant increase in apoptosis and significant decrease in pathological tumor grade and frank tumor incidence. Dietary supplementation with SPE may be effective in controlling CaP tumorigenesis. SPE suppression of prostatic DHT levels lends support to the hypothesis that inhibition of the enzyme 5alpha-reductase is a mechanism of action of this substance. (c) 2007 Wiley-Liss, Inc.

Expanded turn conformations: characterization and sequence-structure correspondence in alpha-turns with implications in helix folding.

PubMed

Dasgupta, Bhaskar; Pal, Lipika; Basu, Gautam; Chakrabarti, Pinak

2004-05-01

Like the beta-turns, which are characterized by a limiting distance between residues two positions apart (i, i+3), a distance criterion (involving residues at positions i and i+4) is used here to identify alpha-turns from a database of known protein structures. At least 15 classes of alpha-turns have been enumerated based on the location in the phi,psi space of the three central residues (i+1 to i+3)-one of the major being the class AAA, where the residues occupy the conventional helical backbone torsion angles. However, moving towards the C-terminal end of the turn, there is a shift in the phi,psi angles towards more negative phi, such that the electrostatic repulsion between two consecutive carbonyl oxygen atoms is reduced. Except for the last position (i+4), there is not much similarity in residue composition at different positions of hydrogen and non-hydrogen bonded AAA turns. The presence or absence of Pro at i+1 position of alpha- and beta-turns has a bearing on whether the turn is hydrogen-bonded or without a hydrogen bond. In the tertiary structure, alpha-turns are more likely to be found in beta-hairpin loops. The residue composition at the beginning of the hydrogen bonded AAA alpha-turn has similarity with type I beta-turn and N-terminal positions of helices, but the last position matches with the C-terminal capping position of helices, suggesting that the existence of a "helix cap signal" at i+4 position prevents alpha-turns from growing into helices. Our results also provide new insights into alpha-helix nucleation and folding. Copyright 2004 Wiley-Liss, Inc.

A capacitive, biocompatible and adhesive electrode for long-term and cap-free monitoring of EEG signals.

PubMed

Lee, Seung Min; Kim, Jeong Hun; Byeon, Hang Jin; Choi, Yoon Young; Park, Kwang Suk; Lee, Sang-Hoon

2013-06-01

Long-term electroencephalogram (EEG) monitoring broadens EEG applications to various areas, but it requires cap-free recording of EEG signals. Our objective here is to develop a capacitive, small-sized, adhesive and biocompatible electrode for the cap-free and long-term EEG monitoring. We have developed an electrode made of polydimethylsiloxane (PDMS) and adhesive PDMS for EEG monitoring. This electrode can be attached to a hairy scalp and be completely hidden by the hair. We tested its electrical and mechanical (adhesive) properties by measuring voltage gain to frequency and adhesive force using 30 repeat cycles of the attachment and detachment test. Electrode performance on EEG was evaluated by alpha rhythm detection and measuring steady state visually evoked potential and N100 auditory evoked potential. We observed the successful recording of alpha rhythm and evoked signals to diverse stimuli with high signal quality. The biocompatibility of the electrode was verified and a survey found that the electrode was comfortable and convenient to wear. These results indicate that the proposed EEG electrode is suitable and convenient for long term EEG monitoring.

Cryopyrin-associated periodic syndromes: development of a patient-reported outcomes instrument to assess the pattern and severity of clinical disease activity.

PubMed

Hoffman, Hal M; Wolfe, Frederick; Belomestnov, Pavel; Mellis, Scott J

2008-09-01

Development of an instrument for characterization of symptom patterns and severity in patients with cryopyrin-associated periodic syndromes (CAPS). Two generations of daily health assessment forms (DHAFs) were evaluated in this study. The first-generation DHAF queried 11 symptoms. Analyses of results obtained with that instrument identified five symptoms included in a revised second-generation DHAF that was tested for internal consistency and test-retest reliability. This DHAF was also assessed during the initial portion of a phase 3 clinical study of CAPS treatment. Forty-eight CAPS patients provided data for the first-generation DHAFs. Five symptoms (rash, fever, joint pain, eye redness/pain, and fatigue) were included in the revised second-generation DHAF. Symptom severity was highly variable during all study phases with as many as 89% of patients reporting at least one symptom flare, and percentages of days with flares reaching 58% during evaluation of the second-generation instrument. Mean composite key symptom scores (KSSs) computed during evaluation of the second-generation DHAF correlated well with Physician's Global Assessment of Disease Activity (r=0.91, p<0.0001) and patient reports of limitations of daily activities (r=0.68, p<0.0001). Test-retest reliability and Cronbach's alpha's were high (0.93 and 0.94, respectively) for the second-generation DHAF. Further evaluation of this DHAF during a baseline period and placebo treatment in a phase 3 clinical study of CAPS patients indicated strong correlations between baseline KSS and Physician's Global Assessment of Disease Activity. Cronbach's alpha's at baseline and test-retest reliability were also high. Potentially important study limitations include small sample size, the lack of a standard tool for CAPS symptom assessment against which to validate the DHAF, and no assessment of the instrument's responsivity to CAPS therapy. The DHAF is a new instrument that may be useful for capturing symptom patterns and severity in CAPS patients and monitoring responses to therapies for these conditions.

Preparation of alpha-cyclodextrin-terminated polyrotaxane consisting of beta-cyclodextrins and pluronic as a building block of a biodegradable network.

PubMed

Ooya, Tooru; Ito, Akihiro; Yui, Nobuhiko

2005-05-23

A beta-CD-based biodegradable polyrotaxane was prepared by capping both terminals of polypseudorotaxane consisting of hydrazide-terminated PEG-block-PPG-block-PEG (Pluronic P-105) and beta-CD-succinates with mono-aldehyde alpha-CDs. By decreasing pH, the fluorescent intensity of TNS was increased with time, indicating cleavage of the terminal hydrazone bonds followed by beta-CD-succinate release. The terminal alpha-CD moieties of the polyrotaxane are useful for self-assembled formation with some guest molecules. [Diagram: see text

Solubilization of cyclohexane in aqueous solutions of sodium. cap alpha. -alkyl alkanoates

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

Sagitani, H.; Suzuki, T.; Nagai, M.

1982-01-01

The effect of branched alkyl chain length and the position of the COONa group on the solubilizing power of n-alkane sodium carboxylates was studied. The lipophilic property and the amount of solubilized cyclohexane increased with the branched chain length of branched soaps, and with the change of the position of the -COONa group from 3 to 7 in the alkyl chain of pentadecane -3, -5, and -7 sodium carboxylates. Alpha-branched soaps having proper branched alkyl chains were better solubilizers for cyclohexane than straight chain compounds. The amount of cyclohexane solublized by C/sub 10/ H/sub 21/ CH(C/sub 6/H/sub 13/) COONa wasmore » about three times greater than the amount solubilized by C/sub 17/ H/sub 35/ COONa. There was a marked increase in the solubilization of cyclohexane replacing ..cap alpha..-branched fatty acid soaps with optimum amount of cosurfactants such as C/sub 8/H/sub 17/ (OCH/sub 2/CH/sub 2/)/sub 2/OH. Namely, solubilization increased markedly at the optimum hydrophile-lipophile balance of mixed surfactant. 21 references.« less

South Polar Variety

NASA Technical Reports Server (NTRS)

2005-01-01

28 July 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a view of linear troughs and mesas formed in the frozen carbon dioxide of the martian south polar residual cap. This image, obtained in May 2005, is a reminder that not all of the south polar cap landscapes resemble 'swiss cheese.'

Location near: 86.7oS, 24.8oW Image width: width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Spring

Waning Cap

NASA Technical Reports Server (NTRS)

2006-01-01

14 June 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows the outer edge of the south polar residual cap of Mars. During summer, the scarps that delineate the sides of the mesas, retreat (on average) by about 3 meters (10 feet) owing to the sublimation of solid carbon dioxide.

Location near: 85.6oS, 349.8oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Summer

Inhibition of radioemesis by disruption of catecholamines in dogs

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

Luthra, Y.K.; Mattsson, J.L.; Yochmowitz, M.G.

1981-03-01

Dogs were treated 30 min to 1 h before x irradiation with ..cap alpha..-methyl-p-tyrosine or 6-hydroxydopamine. A third group of dogs was given a known antiradioemetic drug, haloperidol to verify the sensitivity of the procedure. Irradiated but untreated controls were also used. Light methoxyflurane anesthesia was used for restraint during the exposure. Exposure dose was 800 rad kerma delivered at 50 rad/min to a 10 x 10-cm area covering the abdominal area from xiphoid to pubis. Haloperidol and 6-hydroxydopamine significantly reduced the number of emetic episodes and delayed the onset time to the first episode, ..cap alpha..-Methyl-p-tyrosine caused no significantmore » changes. The effectiveness of 6-hydroxydopamine indicates that catecholaminergic neurons are involved in radioemesis, whereas haloperidol and phenothiazine-derivative tranquilizers inhibit radiomesis by blocking catecholamine receptor neurons.« less

ADP-ribosylation of membrane components by pertussis and cholera toxin

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

Ribeiro-Neto, F.A.P.; Mattera, F.; Hildebrandt, J.D.

1985-01-01

Pertussis and cholera toxins are important tools to investigate functional and structural aspects of the stimulatory (N/sub s/) and inhibitory (N/sub i/) regulatory components of adenylyl cyclase. Cholera toxin acts on N/sub s/ by ADP-ribosylating its ..cap alpha../sub s/ subunit; pertussis toxin acts on N/sub i/ by ADP-ribosylating its ..cap alpha..; subunit. By using (/sup 32/P)NAD/sup +/ and determining the transfer of its (/sup 32/P)ADP-ribose moiety to membrane components, it is possible to obtain information on N/sub s/ and N/sub i/. A set of protocols is presented that can be used to study simultaneously and comparatively the susceptibility of N/submore » s/ and N/sub i/ to be ADP-ribosylated by cholera and pertussis toxin.« less

/sup 45/Ca efflux for myometrial cells: comparison of the effects of prostaglandin F/sub 2/. cap alpha. (PGF/sub 2/), oxytocin (OT) and arachidonate (A)

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

Katona, G.; Molnar, M.; Toth, M.

1986-03-01

The aim of this study was to measure PGF/sub 2..cap alpha../-induced Ca/sup 2 +/ release from uterine cells and to compare this to the actions of OT and A. Smooth muscle cells isolated from the uterus (shell gland) of laying hens were cultured for 7 days in M199 plus 10% fetal calf serum. The cells were treated with digitonin (20..mu..M) and preloaded with /sup 45/Ca for 40 min. Addition of PGF/sub 2..cap alpha../ caused a biphasic /sup 45/Ca-efflux. There was a small but significant /sup 45/Ca-release within 30 sec (rapid phase) followed by a larger one within 7 min (slowmore » phase). In comparison, both OT and A stimulated /sup 45/Ca efflux during a single, slow phase. The maximal effect of A was observed at < 7 min, whereas that of OT was slower, peaking after 7 min. Mepacrin, an inhibitor of A release, attenuated the action of OT without having any effect on A promoted /sup 45/Ca-efflux. Indomethacin, an inhibitor of PG synthase, failed to suppress the Ca-releasing effect of A suggesting the A itself or a lipoxygenase product may have been responsible for the observed effects. Moreover, these results provide suggestive evidence that A release is an important step in the action of various uterotonic agents converging on the mobilization of intracellular Ca.« less

Frozen Frozen CO2

NASA Technical Reports Server (NTRS)

2005-01-01

2 October 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a view of frozen carbon dioxide in the south polar residual cap of Mars. Much of the south polar residual cap exhibits terrain that resembles stacks of sliced Swiss cheese, but this portion of the cap lacks the typical, circular depressions that characterize much of the region. Carbon dioxide on Mars freezes at a temperature of around 148 Kelvins, which is -125oC or about -193oF.

Location near: 87.2oS, 28.4oW Image width: width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Spring

Congenital Muscle Disease Study of Patient and Family Reported Medical Information

ClinicalTrials.gov

2017-05-05

Congenital Muscular Dystrophy (Including Unspecified/Undiagnosed); Dystroglycanopathy; Congenital Fiber Type Disproportion; Rigid Spine Muscular Dystrophy; Congenital Myopathy (Including Unspecified/Undiagnosed); Collagen VI CMD (Ullrich CMD, Intermediate, Bethlem Myopathy); Laminin Alpha 2 Related Congenital Muscular Dystrophy; LAMA2-CMD/Merosin Deficient/MDC1A; Walker-Warburg Syndrome; Muscle-Eye-Brain Disease; Fukuyama/Fukutin Related Muscular Dystrophy; Integrin Alpha 7 Deficiency; Integrin Alpha 9 Deficiency; LMNA-CMD/Lamin A/C/Laminopathy; SEPN1-Related Myopathy; Bethlem Myopathy; Actin Aggregation Myopathy; Cap Disease; Central Core Disease; Centronuclear Myopathy; Core Rod Myopathy; Hyaline Body Myopathy; Multiminicore Myopathy; Myotubular Myopathy; Nemaline Myopathy; Tubular Aggregate Myopathy; Zebra Body Myopathy; Reducing Body Myopathy; Spheroid Body Myopathy; LGMD1B (LMNA); LGMD1E (DES); LGMD2G (TCAP); LGMD2H (TRIM32); LGMD2I (FKRP); LGMD2J (TTN); LGMD2K (POMT1); LGMD2M (FKTN); LGMD2N (POMT2); LGMD2O (POMGnT1); LGMD2P (DAG1); LGMD2Q (PLEC1); LGMD2R (DES); LGMD2S (TRAPPC11); LGMD2T (GMPPB); LGMD2U (ISPD); LGMD2V (GAA); Ullrich Congenital Muscular Dystrophy; Titinopathy; Choline Kinase B Receptor; Emery-Dreifuss Muscular Dystrophy; RYR1 Related Myopathy; SYNE1/Nesprin Related Muscular Dystrophy; Telethonin Related Muscular Dystrophy (TCAP/Titin-Cap); Congenital Myasthenic Syndrome; Escobar Syndrome; Myofibrillar Myopathy; Malignant Hyperthermia; Alpha-Dystroglycan Related Muscular Dystrophy (DAG1, DPM1, DPM2, DPM3, FKRP, FKTN); Alpha-Dystroglycan Related Muscular Dystrophy (GAA, ISPD, LARGE, POMT1, POMT2, POMGnT1); Alpha-Dystroglycan Related Muscular Dystrophy (Unspecified/Undiagnosed/Other)

The relationship between red meat allergy and sensitization to gelatin and galactose-alpha-1,3-galactose

PubMed Central

Mullins, Raymond James; James, Hayley; Platts-Mills, Thomas A.E.; Commins, Scott

2012-01-01

Background We have observed patients clinically allergic to red meat and meat-derived gelatin. Objective We describe a prospective evaluation of the clinical significance of gelatin sensitization, the predictive value of a positive test and an examination of the relationship between allergic reactions to red meat and sensitization to gelatin and alpha-Gal. Methods Adult patients evaluated 1997-2011 for suspected allergy/anaphylaxis to medication, insect venom or food were skin tested with gelatin colloid. In vitro (ImmunoCap) testing was undertaken where possible. Results Positive gelatin tests were observed in 40/1335 individuals; 30/40 patients with red meat allergy (12 also clinically allergic to gelatin); 2/2 with gelatin colloid anaphylaxis; 4/172 with idiopathic anaphylaxis (all responded to intravenous gelatin challenge of 0.02 to 0.4g); 4/368 with drug allergy. Testing was negative in all patients with venom allergy (n=241), non-meat food allergy (n=222), and miscellaneous disorders (n=290). ImmunoCap was positive to alpha-Gal in 20/24 meat allergics and in 20/22 with positive gelatin skin tests. The results of gelatin skin testing and anti-alpha-Gal IgE were strongly correlated (r=0.46; P<0.01). Alpha-Gal was detected in bovine gelatin colloids at concentrations of ~ 0.44 to 0.52ug/gm gelatin by inhibition radioimmunoassay. Conclusion Most patients allergic to red meat were sensitized to gelatin and a subset was clinically allergic to both. The detection of alpha-Gal in gelatin and correlation between the results of alpha-Gal and gelatin testing raises the possibility that alpha-Gal IgE may be the target of reactivity to gelatin. The pathogenic relationship between tick bites and sensitization to red meat, alpha-Gal and gelatin (with or without clinical reactivity) remains uncertain. PMID:22480538

Reconfiguring the AR-TIF2 Protein–Protein Interaction HCS Assay in Prostate Cancer Cells and Characterizing the Hits from a LOPAC Screen

PubMed Central

Fancher, Ashley T.; Hua, Yun; Camarco, Daniel P.; Close, David A.; Strock, Christopher J.

2016-01-01

Abstract The continued activation of androgen receptor (AR) transcription and elevated expression of AR and transcriptional intermediary factor 2 (TIF2) coactivator observed in prostate cancer (CaP) recurrence and the development of castration-resistant CaP (CRPC) support a screening strategy for small-molecule inhibitors of AR-TIF2 protein–protein interactions (PPIs) to find new drug candidates. Small molecules can elicit tissue selective effects, because the cells of distinct tissues express different levels and cohorts of coregulatory proteins. We reconfigured the AR-TIF2 PPI biosensor (PPIB) assay in the PC-3 CaP cell line to determine whether AR modulators and hits from an AR-TIF2 PPIB screen conducted in U-2 OS cells would behave differently in the CaP cell background. Although we did not observe any significant differences in the compound responses between the assay performed in osteosarcoma and CaP cells, the U-2 OS AR-TIF2 PPIB assay would be more amenable to screening, because both the virus and cell culture demands are lower. We implemented a testing paradigm of counter-screens and secondary hit characterization assays that allowed us to identify and deprioritize hits that inhibited/disrupted AR-TIF2 PPIs and AR transcriptional activation (AR-TA) through antagonism of AR ligand binding or by non-specifically blocking nuclear receptor trafficking. Since AR-TIF2 PPI inhibitor/disruptor molecules act distally to AR ligand binding, they have the potential to modulate AR-TA in a cell-specific manner that is distinct from existing anti-androgen drugs, and to overcome the development of resistance to AR antagonism. We anticipate that the application of this testing paradigm to characterize the hits from an AR-TIF2 PPI high-content screening campaign will enable us to prioritize the AR-TIF2 PPI inhibitor/disruptor leads that have potential to be developed into novel therapeutics for CaP and CRPC. PMID:27606620

Crystal structure of Bacillus anthracis transpeptidase enzyme CapD.

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

Wu, R.; Richter, S.; Zhang, R.

2009-09-04

Bacillus anthracis elaborates a poly-{gamma}-d-glutamic acid capsule that protects bacilli from phagocytic killing during infection. The enzyme CapD generates amide bonds with peptidoglycan cross-bridges to anchor capsular material within the cell wall envelope of B. anthracis. The capsular biosynthetic pathway is essential for virulence during anthrax infections and can be targeted for anti-infective inhibition with small molecules. Here, we present the crystal structures of the {gamma}-glutamyltranspeptidase CapD with and without {alpha}-l-Glu-l-Glu dipeptide, a non-hydrolyzable analog of poly-{gamma}-d-glutamic acid, in the active site. Purified CapD displays transpeptidation activity in vitro, and its structure reveals an active site broadly accessible for poly-{gamma}-glutamatemore » binding and processing. Using structural and biochemical information, we derive a mechanistic model for CapD catalysis whereby Pro{sup 427}, Gly{sup 428}, and Gly{sup 429} activate the catalytic residue of the enzyme, Thr{sup 352}, and stabilize an oxyanion hole via main chain amide hydrogen bonds.« less

Outcomes after radical prostatectomy for patients with clinical stages T1-T2 prostate cancer with pathologically positive lymph nodes in the prostate-specific antigen era.

PubMed

Dorin, Ryan P; Lieskovsky, Gary; Fairey, Adrian S; Cai, Jie; Daneshmand, Siamak

2013-11-01

To evaluate the outcomes of radical prostatectomy (RP) and pelvic lymph node dissection (PLND) for clinically organ confined prostate cancer (CaP) with regional lymph node metastases (pN1) treated in the era of prostate-specific antigen (PSA) screening. A single institution cohort of 2,487 men with cT1-T2 CaP treated with open radical prostatectomy and pelvic lymph node dissection between 1988 and 2008 were analyzed. Kaplan-Meier and Cox proportional regression models were used to analyze overall survival (OS), clinical recurrence-free survival (cRFS), and biochemical recurrence-free survival (bRFS). Overall, 150 out of 2,487 patients (6%) had pN1 disease, with a median follow-up of 10.4 years. The predicted 10-year OS, cRFS, and bRFS rates for patients with pN0 and pN1 were 86% and 74% (Log rank P < 0.001), 97% and 84% (Log rank P < 0.001), and 88% and 57% (Log rank P < 0.001), respectively. In the subset of pN1 patients treated with surgery only (n = 49), the predicted 10-year OS, cRFS, and bRFS rates were 81%, 80%, and 59%, respectively. Exploratory univariate regression analysis showed that age (P = 0.003), total number of lymph nodes identified (P = 0.040), and total number of positive lymph nodes identified (P = 0.004) were associated with OS. Total number of positive lymph nodes (LNs) identified was also significantly associated with cRFS (P = 0.05). The incidence of pN1 in patients with cT1-T2 CaP treated with surgery in the era of PSA screening was low. RP and PLND demonstrated therapeutic efficacy in a subset of pN1 patients treated with surgery alone. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of growth retardants and fumigations with ozone and sulfur dioxide on growth and flowering of Euphorbia pulcherrima Willd

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

Cathey, H.M.; Heggestad, H.E.

1973-01-01

Eight cultivars of poinsettia, Euphorbia pulcherrima Willd., were evaluated for sensitivity to ..cap alpha..-cyclopropyl-..cap alpha.. (4-methoxyphenyl)-5-pyrimidine methanol (ancymidol) and protection from ozone and sulfur dioxide injury afforded by applications of ancymidol and (2-chloroethyl) trimethyl ammonium chloride (chlormequat). Foliar sprays of ancymidol were at least 80 to 500 times and the soil drench 1000 times more active than chlormequat in retarding stem elongation. The diam of the bracts was reduced, but branching increased more on plants treated with ancymidol than on untreated plants. The cv. Annette Hegg (AH) was more sensitive to ozone fumigations than was Eckespoint C-1' (C-1). Sulfur dioxidemore » also caused more injury to AH than to C-1. Ancymidol and chlormequat reduced visible injury induced by ozone and sulfur dioxide.« less

Copernicus observational searches for OH and H/sub 2/O in diffuse clouds

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

Smith, W.H.; Snow, T.P. Jr.

1979-03-01

An intensive search for OH and H/sub 2/O in the directions of sigma Sco, ..cap alpha.. Cam, and omicron Per was undertaken with the Copernicus satellite. Multiple scans were carried out over the wavelength region for the expected absorption features due to the OH D--X and H/sub 2/O C--X transitions. The feature due to OH was possibly detected toward sigma Sco, and only an upper limit can be given toward ..cap alpha.. Cam. H/sub 2/O was not detected in any of the stars at the signal level accumulated. The OH abundance toward sigma Sco and the respective lower limits formore » the OH/H/sub 2/O ratios are discussed with regard to the extant models for the steady-state abundances of OH and H/sub 2/O, and shown not to be inconsistent with ion-molecule schemes.« less

Tumor initiating activities of various derivatives of benz(a)anthracene and 7, 12-dimethyl-benz(a)anthracene in mouse skin

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

Slaga, T.J.; Gleason, G.L.; DiGiovanni, J.

Current information indicates that polycyclic aromatic hydrocarbons (PAH) exert their toxic, mutagenic, and carcinogenic activities after they have been metabolically activated by target cells to reactive epoxides. The results obtained from IN VIVO and IN VITRO binding, mutagenicity, metabolism, and carcinogenicity studies have led to the conclusion that BP-7, 8-diol is a proximate carcinogenic metabolite of BP, and the BP-diol-epoxide is an ultimate carcinogenic metabolite of BP. Recent results concerning the strong carcinogenicity of BP-7..beta.., 8..cap alpha..-diol-9..cap alpha..,10..cap alpha..-epoxide in newborn mice and in mouse skin strongly indicate that it is the ultimate carcinogenic metabolite of BP. Since diol-epoxides maymore » be responsible for the carcinogenicity of PAH other than BP, diols and diol-epoxides as well as other derivatives of PAH were tested for skin tumor-initiation in a two-stage system of tumorigenesis. In addition, since activation of methylated PAH may involve the side-chain methyl group, the skin tumor-initiating activity of various side-chain derivatives of methylated PA were determined. In this report, the skin tumor initiation of various derivatives of a nonmethylated PAH, BA as well as a methylated PAH, DMBA are compared. The data suggest that bay region diol-epoxides may be important in BA and DMBA carcinogenicity in mice which is supportive of the theory proposed by Jerina and co-workers which predicts that diol-epoxides in the bay region are the major determinants of PAH carcinogenicity.« less

Assignments of /sup 1/H nuclear magnetic resonances of the cystyl, asparaginyl, and aromatic residues of arginine vasopressin in D/sub 2/O. A comparison with lysine vasopressin and oxytocin in terms of solution conformation

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

Wyssbrod, H.R.; Fischman, A.J.; Live, D.H.

1979-07-18

The resonances of the C/sup ..cap alpha../ and C/sup ..beta../ protons of the cystyl, asparaginyl, and aromatic residues of (8-arginine)vasopressin (AVP) in D/sub 2/O at pD 3.8 and 20/sup 0/C were assigned in a rigorous manner by the use of isotopic isomers of AVP that contain specific replacements of protons by deuterons and by comparison of /sup 1/H NMR characteristics of AVP to those of (8-lysine)vasopressin (LVP) and oxytocin (OT). Although there is extensive overlap of resonances of C/sup ..beta../ protons even at 360 MHz, all of the chemical shifts of these protons and most of the couplings between themmore » and their vicinal C/sup ..cap alpha../ protons could be determined, at least to a first approximation. It was concluded that the cyclic moieties (residues 1-6) of AVP, LVP, and OT possess essentially the same overall backbone conformation, and that the side-chain conformation - or rotamer populations - about the C/sup ..cap alpha../-C/sup ..beta../ bonds of the cystyl residue (positions 1 and 6), the tyrosyl residue (position 2), and the asparaginyl residue (position 5) are similar. This study indicates that selective replacements of C/sup ..beta../ protons by deuterons are necessary to improve the accuracy of coupling constants extracted from 360-MHz spectra of a AVP for use in conformational analysis.« less

Polar Cap Retreat

NASA Technical Reports Server (NTRS)

2004-01-01

13 August 2004 This red wide angle Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a view of the retreating seasonal south polar cap in the most recent spring in late 2003. Bright areas are covered with frost, dark areas are those from which the solid carbon dioxide has sublimed away. The center of this image is located near 76.5oS, 28.2oW. The scene is large; it covers an area about 250 km (155 mi) across. The scene is illuminated by sunlight from the upper left.

Long-term treatment with calcium-alpha-ketoglutarate corrects secondary hyperparathyroidism.

PubMed

Zimmermann, E; Wassmer, S; Steudle, V

1996-01-01

Calcium-alpha-ketoglutarate (Ca-ket) is known as a highly effective phosphate (P) binder in hemodialysis (HD) patients. In addition, alpha-ketoglutarate has been shown to improve metabolic alterations. We investigated the effect of long-term P-binding therapy with Ca-ket to determine whether P accumulation is the main reason of secondary hyperparathyroidism (HPT) in HD patients or not. Ca-ket was prescribed to 14 HD patients as a soluble preparation in a mean dosage of 4.5 g/day (0.975 g elemental Ca) for a period of 36 months. Serum P continuously dropped from prestudy 2.6 +/- 0.1 (mean +/- SEM) to 1.9 +/- 0.07 mmol/l (p < 0.001), whereas serum Ca increased from 2.2 +/- 0.1 to 2.47 +/- 0.08 mmol/l (p < 0.05). Thus, Ca/P ratio in serum converted significantly from 0.91 +/- 0.02 (prestudy) to 1.28 +/- 0.01 (p < 0.001). Intact parathyroid hormone (iPTH) continuously normalized in all patients from 29 +/- 5 to 8 +/- 2 pmol/l (p < 0.001). The present data show that long-term treatment with Ca-ket normalizes secondary HPT by simultaneously P binding and correcting Ca/P ratio in serum without vitamin D treatment.

Validation of a Proposed Tumor Regression Grading Scheme for Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy as a Prognostic Indicator for Survival.

PubMed

Lee, Sun Mi; Katz, Matthew H G; Liu, Li; Sundar, Manonmani; Wang, Hua; Varadhachary, Gauri R; Wolff, Robert A; Lee, Jeffrey E; Maitra, Anirban; Fleming, Jason B; Rashid, Asif; Wang, Huamin

2016-12-01

Neoadjuvant therapy has been increasingly used to treat patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC). Although the College of American Pathologists (CAP) grading scheme for tumor response in posttherapy specimens has been used, its clinical significance has not been validated. Previously, we proposed a 3-tier histologic tumor regression grading (HTRG) scheme (HTRG 0, no viable tumor; HTRG 1, <5% viable tumor cells; HTRG 2, ≥5% viable tumor cells) and showed that the 3-tier HTRG scheme correlated with prognosis. In this study, we sought to validate our proposed HTRG scheme in a new cohort of 167 consecutive PDAC patients who completed neoadjuvant therapy and pancreaticoduodenectomy. We found that patients with HTRG 0 or 1 were associated with a lower frequency of lymph node metastasis (P=0.004) and recurrence (P=0.01), lower ypT (P<0.001) and AJCC stage (P<0.001), longer disease-free survival (DFS, P=0.004) and overall survival (OS, P=0.02) than those with HTRG 2. However, there was no difference in either DFS or OS between the groups with CAP grade 2 and those with CAP grade 3 (P>0.05). In multivariate analysis, HTRG grade 0 or 1 was an independent prognostic factor for better DFS (P=0.03), but not OS. Therefore we validated the proposed HTRG scheme from our previous study. The proposed HTRG scheme is simple and easy to apply in practice by pathologists and might be used as a successful surrogate for longer DFS in patients with potentially resectable PDAC who completed neoadjuvant therapy and surgery.

Alpha-catenin-dependent recruitment of the centrosomal protein CAP350 to adherens junctions allows epithelial cells to acquire a columnar shape.

PubMed

Gavilan, Maria P; Arjona, Marina; Zurbano, Angel; Formstecher, Etienne; Martinez-Morales, Juan R; Bornens, Michel; Rios, Rosa M

2015-03-01

Epithelial morphogenesis involves a dramatic reorganisation of the microtubule cytoskeleton. How this complex process is controlled at the molecular level is still largely unknown. Here, we report that the centrosomal microtubule (MT)-binding protein CAP350 localises at adherens junctions in epithelial cells. By two-hybrid screening, we identified a direct interaction of CAP350 with the adhesion protein α-catenin that was further confirmed by co-immunoprecipitation experiments. Block of epithelial cadherin (E-cadherin)-mediated cell-cell adhesion or α-catenin depletion prevented CAP350 localisation at cell-cell junctions. Knocking down junction-located CAP350 inhibited the establishment of an apico-basal array of microtubules and impaired the acquisition of columnar shape in Madin-Darby canine kidney II (MDCKII) cells grown as polarised epithelia. Furthermore, MDCKII cystogenesis was also defective in junctional CAP350-depleted cells. CAP350-depleted MDCKII cysts were smaller and contained either multiple lumens or no lumen. Membrane polarity was not affected, but cortical microtubule bundles did not properly form. Our results indicate that CAP350 may act as an adaptor between adherens junctions and microtubules, thus regulating epithelial differentiation and contributing to the definition of cell architecture. We also uncover a central role of α-catenin in global cytoskeleton remodelling, in which it acts not only on actin but also on MT reorganisation during epithelial morphogenesis.

Alpha-catenin-Dependent Recruitment of the Centrosomal Protein CAP350 to Adherens Junctions Allows Epithelial Cells to Acquire a Columnar Shape

PubMed Central

Zurbano, Angel; Formstecher, Etienne; Martinez-Morales, Juan R.; Bornens, Michel; Rios, Rosa M.

2015-01-01

Epithelial morphogenesis involves a dramatic reorganisation of the microtubule cytoskeleton. How this complex process is controlled at the molecular level is still largely unknown. Here, we report that the centrosomal microtubule (MT)-binding protein CAP350 localises at adherens junctions in epithelial cells. By two-hybrid screening, we identified a direct interaction of CAP350 with the adhesion protein α-catenin that was further confirmed by co-immunoprecipitation experiments. Block of epithelial cadherin (E-cadherin)-mediated cell-cell adhesion or α-catenin depletion prevented CAP350 localisation at cell-cell junctions. Knocking down junction-located CAP350 inhibited the establishment of an apico-basal array of microtubules and impaired the acquisition of columnar shape in Madin-Darby canine kidney II (MDCKII) cells grown as polarised epithelia. Furthermore, MDCKII cystogenesis was also defective in junctional CAP350-depleted cells. CAP350-depleted MDCKII cysts were smaller and contained either multiple lumens or no lumen. Membrane polarity was not affected, but cortical microtubule bundles did not properly form. Our results indicate that CAP350 may act as an adaptor between adherens junctions and microtubules, thus regulating epithelial differentiation and contributing to the definition of cell architecture. We also uncover a central role of α-catenin in global cytoskeleton remodelling, in which it acts not only on actin but also on MT reorganisation during epithelial morphogenesis. PMID:25764135

Live Dynamics of 53BP1 Foci Following Simultaneous Induction of Clustered and Dispersed DNA Damage in U2OS Cells

PubMed Central

Sollazzo, Alice; Brzozowska, Beata; Cheng, Lei; Lundholm, Lovisa; Scherthan, Harry

2018-01-01

Cells react differently to clustered and dispersed DNA double strand breaks (DSB). Little is known about the initial reaction to simultaneous induction of DSBs with different complexities. Here, we used live cell microscopy to analyse the behaviour of 53BP1-GFP (green fluorescence protein) foci formation at DSBs induced in U2OS cells by alpha particles, X-rays or mixed beams over a 75 min period post irradiation. X-ray-induced foci rapidly increased and declined over the observation interval. After an initial increase, mixed beam-induced foci remained at a constant level over the observation interval, similarly as alpha-induced foci. The average areas of radiation-induced foci were similar for mixed beams and X-rays, being significantly smaller than those induced by alpha particles. Pixel intensities were highest for mixed beam-induced foci and showed the lowest level of variability over time as compared to foci induced by alphas and X-rays alone. Finally, mixed beam-exposed foci showed the lowest level of mobility as compared to alpha and X-ray exposure. The results suggest paralysation of chromatin around foci containing clustered DNA damage. PMID:29419809

Magnesium Induced Nucleophile Activation in the Guanylyltransferase mRNA Capping Enzyme

PubMed Central

Swift, Robert V.; Ong, Chau D.; Amaro, Rommie E.

2012-01-01

The messenger RNA guanylyltransferase, or mRNA capping enzyme, co-transcriptionally caps the 5′-end of nascent mRNA with GMP during the second in a set of three enzymatic reactions that result in the formation of an N7-methyl guanosine cap during mRNA maturation. The mRNA capping enzyme is characterized, in part, by a conserved lysine nucleophile that attacks the alpha-phosphorous atom of GTP, forming a lysine-GMP intermediate. Experiments have firmly established that magnesium is required for efficient intermediate formation, but have provided little insight into the requirement’s molecular origins. Using empirical and thermodynamic integration pKa estimates, along with conventional MD simulations, we show that magnesium binding likely activates the lysine nucleophile by increasing its acidity and by biasing the deprotonated nucleophile into conformations conducive to intermediate formation. These results provide additional functional understanding of an important enzyme in the mRNA transcript life cycle and allow functional analogies to be drawn that affect our understanding of the metal dependence of related superfamily members. PMID:23205906

An expedient procedure for the oxidative cleavage of olefinic bonds with PhI(OAc)2, NMO, and catalytic OsO4.

PubMed

Nicolaou, K C; Adsool, Vikrant A; Hale, Christopher R H

2010-04-02

PhI(OAc)(2) in the presence of OsO(4) (cat.) and 2,6-lutidine cleaves olefinic bonds to yield the corresponding carbonyl compounds, albeit, in some cases, with alpha-hydroxy ketones as byproduct. A more practical and clean protocol to effect oxidative cleavage of olefinic bonds involves NMO, OsO(4) (cat.), 2,6-lutidine, and PhI(OAc)(2).

Clinical audit project in undergraduate medical education curriculum: an assessment validation study

PubMed Central

Steketee, Carole; Mak, Donna

2016-01-01

Objectives To evaluate the merit of the Clinical Audit Project (CAP) in an assessment program for undergraduate medical education using a systematic assessment validation framework. Methods A cross-sectional assessment validation study at one medical school in Western Australia, with retrospective qualitative analysis of the design, development, implementation and outcomes of the CAP, and quantitative analysis of assessment data from four cohorts of medical students (2011- 2014). Results The CAP is fit for purpose with clear external and internal alignment to expected medical graduate outcomes.  Substantive validity in students’ and examiners’ response processes is ensured through relevant methodological and cognitive processes. Multiple validity features are built-in to the design, planning and implementation process of the CAP.  There is evidence of high internal consistency reliability of CAP scores (Cronbach’s alpha > 0.8) and inter-examiner consistency reliability (intra-class correlation>0.7). Aggregation of CAP scores is psychometrically sound, with high internal consistency indicating one common underlying construct.  Significant but moderate correlations between CAP scores and scores from other assessment modalities indicate validity of extrapolation and alignment between the CAP and the overall target outcomes of medical graduates.  Standard setting, score equating and fair decision rules justify consequential validity of CAP scores interpretation and use. Conclusions This study provides evidence demonstrating that the CAP is a meaningful and valid component in the assessment program. This systematic framework of validation can be adopted for all levels of assessment in medical education, from individual assessment modality, to the validation of an assessment program as a whole.  PMID:27716612

Clinical audit project in undergraduate medical education curriculum: an assessment validation study.

PubMed

Tor, Elina; Steketee, Carole; Mak, Donna

2016-09-24

To evaluate the merit of the Clinical Audit Project (CAP) in an assessment program for undergraduate medical education using a systematic assessment validation framework. A cross-sectional assessment validation study at one medical school in Western Australia, with retrospective qualitative analysis of the design, development, implementation and outcomes of the CAP, and quantitative analysis of assessment data from four cohorts of medical students (2011- 2014). The CAP is fit for purpose with clear external and internal alignment to expected medical graduate outcomes.  Substantive validity in students' and examiners' response processes is ensured through relevant methodological and cognitive processes. Multiple validity features are built-in to the design, planning and implementation process of the CAP.  There is evidence of high internal consistency reliability of CAP scores (Cronbach's alpha > 0.8) and inter-examiner consistency reliability (intra-class correlation>0.7). Aggregation of CAP scores is psychometrically sound, with high internal consistency indicating one common underlying construct.  Significant but moderate correlations between CAP scores and scores from other assessment modalities indicate validity of extrapolation and alignment between the CAP and the overall target outcomes of medical graduates.  Standard setting, score equating and fair decision rules justify consequential validity of CAP scores interpretation and use. This study provides evidence demonstrating that the CAP is a meaningful and valid component in the assessment program. This systematic framework of validation can be adopted for all levels of assessment in medical education, from individual assessment modality, to the validation of an assessment program as a whole.

Guanosine 5'-triphosphate binding protein (G/sub i/) and two additional pertussis toxin substrates associated with muscarinic receptors in rat heart myocytes: characterization and age dependency

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

Moscona-Amir, E.; Henis, Y.I.; Sokolovsky, M.

1988-07-12

The coupling of muscarinic receptors with G-proteins was investigated in cultured myocytes prepared from the hearts of newborn rats. The coupling was investigated in both young (5 days after plating) and aged (14 days after plating) cultures, in view of the completely different effects of 5'-guanylyl imidodiphosphate (Gpp(NH)p) on muscarinic agonist binding to homogenates from young vs aged cultures. Pretreatment of cultures from both ages by Bordetella pertussis toxin (IAP) was found to eliminate any Gpp(NH)p effect on carbamylcholine binding. IAP by itself induced a rightward shift in the carbamylcholine competition curve in homogenates from aged cultures, but no suchmore » effect was observed in homogenates from young cultures. IAP-catalyzed (/sup 32/P)ADP-ribosylation of membrane preparations from young and aged cultures revealed major differences between them. Young cultures exhibited a major IAP substrate at 40 kDa, which was also recognized by anti-..cap alpha../sub i/ antibodies, and two novel IAP substrates at 28 and 42 kDa, which were weakly ADP-ribosylated by the toxin and were not recognized with either anti-..cap alpha../sub i/ or anti-..cap alpha../sub 0/ antibodies. In aged cultures, only the 40-kDa band (ribosylated to a lower degree) was detected. The parallel age-dependent changes in the three IAP substrates (28, 40, and 42 kDa) and in the interactions of the G-protein(s) with the muscarinic receptors strongly suggest close association between the two phenomena. All of these age-dependent changes in the G-protein related parameters were prevented by phosphatidylcholine-liposome treatment of the aged cultures. The role of the membrane lipid composition in these phenomena is discussed.« less

Host-pathogen interactions. XXIX. Oligogalacturonides released from sodium polypectate by endopolygalacturonic acid lyase are elicitors of phytoalexins in soybean. [Glycine max L

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

Davis, K.R.; Darvill, A.G.; Albersheim, P.

1986-02-01

Recent studies have demonstrated that an apparently homogeneous preparation of an ..cap alpha..-1,4-D-endopolygalacturonic acid lyase (EC 4.2,2.2) isolated from the phytopathogenic bacterium Erwinia carotovora induced phytoalexin accumulation in cotyledons of soybean (Glycine max (L.) Merr. cv Wayne) and that this pectin-degrading enzyme released heat-stable elicitors of phytoalexins from soybean cell walls, citrus pectin, and sodium polypectate. The present paper reports the purification, by anion-exchange chromatography on QAE-Sephadex columns followed by gel-permeation chromatography on a Bio-Gel P-6 column, of the two fractions with highest specific elicitor activity present in a crude elicitor-preparation obtained by lyase treatment of sodium polypectate. Structural analysismore » of the fraction with highest specific elicitor activity indicated that the major, if not only, component was a decasaccharide of ..cap alpha..-1,4-D-galactosyluronic acid that contained the expected product of lyase cleavage, 4-deoxy-..beta..-L-5-threo-hexopyranos-4-enyluronic acid (4,5-unsaturated galactosyluronic acid), at the nonreducing terminus. This modified decagalacturonide fraction exhibited half-maximum and maximum elicitor activity at 1 microgram/cotyledon (6 micromolar) and 5 micrograms/cotyledon (32 micromolar) galactosyluronic acid equivalents, respectively. Reducing 90 to 95% of the carboxyl groups of the galactosyluronic acid residues abolished the elicitor activity of the decagalacturonide fraction. The second most elicitor-active fraction contained mostly undeca-..cap alpha..-1,4-D-galactosyluronic acid that contained 4,5-unsaturated galactosyluronic acid at the nonreducing termini. This fraction exhibited half-maximum and maximum elicitor activity at approximately 3 micrograms/cotyledon (17 micromolar) and 6 micrograms/cotyledon (34 micromolar) galactosyluronic acid equivalents, respectively.« less

Inhibition of metabolism and DNA binding of polycyclic aromatic hydrocarbons (PAHs) by plant phenols in epidermis of SENCAR mice

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

Das, M.; Bik, D.P.; Bickers, D.R.

1986-03-05

Naturally occurring plant phenols such as tannic acid (TA), quercetin (QT), myricetin (MY) and anthraflavic acid (AA) have been shown to inhibit the mutagenicity of several bay-region diolepoxides of PAHs. Since skin is a target for PAH carcinogenesis, they investigated the effect of these plant phenols on epidermal aryl hydrocarbon hydroxylase (AHH) activity and the binding of PAHs to DNA in SENCAR mice. Each of the plant phenols tested was found to be an in vitro and in vivo inhibitor of epidermal AHH activity with I/sub 50/ values ranging from 4.4 x 10/sup -5/ - 12.4 x 10/sup -5/M inmore » control and 3-methylcholanthrene (MCA) pretreated skin. On an equimolar basis TA was the most potent inhibitor with a Ki of 81 ..mu..M. Incubation of TA, QT, MY and AA with epidermal microsomes resulted in varying degrees of inhibition of enzyme mediated covalent binding of benzo(a)pyrene (BP) to calf thymus DNA. TA (25 ..mu..M) showed maximum inhibition (64%). A single topical application (12 ..mu..mol) of TA, QT, MY and AA resulted in significant decrease in the binding of BP, BP-7,8-diol and 7,12-dimethylbenz(a)anthracene to epidermal DNA. The formation of (+)-7..beta..,8..cap alpha..-dihydroxy-9..cap alpha..,10..cap alpha..-epoxy-7,8,9,10-tetrahydro-BP-deoxyguanine adduct in epidermis was significantly reduced (62-86%) following topical application of the plant phenols. Their results suggest that some of these plant phenols have substantial though variable potential to modify the risk of PAHs induced skin carcinogenicity.« less

Bonding in the first-row diatomic molecules within the local spin-density approximation

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

Painter, G.S.; Averill, F.W.

1982-08-15

The Hohenberg-Kohn-Sham density-functional equations in the local spin-density approximation (LSDA) have been solved with essentially no loss of accuracy for dimers of the first row of the Periodic Table with the use of a fully-self-consistent spin-polarized Gaussian-orbital approach. Spectroscopic constants (binding energies, equilibrium separations, and ground-state vibrational frequencies) have been derived from the calculated potential-energy curves. Intercomparison of results obtained using the exchange-correlation functionals of Slater (scaled exchange or X..cap alpha..), Gunnarsson and Lundqvist (GL), and Vosko, Wilk, and Nusair (VWN) permits assessment of the relative merits of each and serves to identify general shortcomings in the LSDA. Basic trendsmore » are similar for each functional, but the treatment of the spin dependence of the exchange-correlation energy in the GL and VWN functionals yields a variation of the binding energy across the series which is more systematic than that in the X..cap alpha.. approximation. Agreement between the present results and those of Dunlap, Connolly, and Sabin in the X..cap alpha.., approximation confirms the accuracy of the variational charge-density-fit procedure used in the latter work. The refinements in correlation treatment within the VWN functional are reflected in improvements in binding energies which are only slight for most dimers in the series. This behavior is attributed to the error remaining in the exchange channel within the LSDA and demonstrates the necessity for self-interaction corrections for more accurate binding-energy determinations. Within the current LSDA, absolute accuracies of the VWN functional for the first-row dimers are within 2.3 eV for binding energies, 0.07 a.u. for bond lengths, and approx.200 cm/sup -1/ for vibrational frequencies.« less

ESR study of electron reactions with esters and triglycerides

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

Sevilla, M.D.; Morehouse, K.M.; Swarts, S.

1981-04-02

Reactions which occurred after electron attachment at 77K to a number of small carboxylic acid esters and triglycerides in an aqueous glass are reported. Most ester anions are found to decay on warming to form alkyl radicals by ..beta.. scission: RC(O/sup -/)OR' ..-->.. RCO/sub 2//sup -/ + R'.. The alkyl radical (R'.) produced by annealing is found to abstract hydrogen from the parent ester at an ..cap alpha..-carbon site, R'.+ R''CH/sub 2/CO/sub 2/R' ..-->.. R''CHCO/sub 2/R', or in the case of ethyl formate from the formate hydrogen, CH/sub 3/CH/sub 2/.+ HCO/sub 2/C/sub 2/H/sub 5/ ..-->.. C/sub 2/H/sub 6/ +.CO/sub 2/C/submore » 2/H/sub 5/. Results found for the methyl formate anion suggest hydrogen abstraction by the anion itself may compete with alkyl radical formation. The anion of the triglyceride triacetin is found to undergo an analogous mechanism to the ester anions producing the propane diol diester radical, .CH/sub 2/CH(Ac)CH/sub 2/(Ac), Ac = acetate. This species subsequently abstracts hydrogen from the parent compound to produce the ..cap alpha..-carbon radical, .CH/sub 2/CO/sub 2/R. Results found after annealing the tripropionin radical anion give evidence for abstraction from the ..cap alpha.. carbon in the propionate side groups producing CH/sub 3/CHCO/sub 2/R. Studies of a ..gamma..-irradiated ester (ethyl myristate) and two triglycerides (tripalmitin and tristearin) yield results which suggest that the mechanism of ester anion decay found in aqueous glasses applies to ..gamma..-irradiated neat long-chain esters and triglycerides. Results found in this work are compared to the results of product analysis.« less

Structural elucidation of the Brucella melitensis M antigen by high-resolution NMR at 500 MHz

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

Bundle, D.R.; Cherwonogrodzky, J.W.; Perry, M.B.

The Brucella M antigen from the species type strain Brucella melitensis 16M has been identified as a component of the cell wall lipopolysaccharide (LPS). O polysaccharide liberated from this LPS by mild acid hydrolysis exhibited M activity in serological tests and was shown to be a homopolymer of 4-formamido-4,6-dideoxy-..cap alpha..-D-mannopyranosyl residues arranged in an oligosaccharide repeating unit as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the native lipopolysaccharide. Structural analysis of the O polysaccharide by NMR methods was difficult due to apparent microheterogeneity of the repeating unit, which was in fact caused by the presence of rotational isomers ofmore » the N-formyl moiety. This problem was resolved by chemical modification of the polysaccharide to its amino and N-acetyl derivatives, the 500-MHz /sup 1/H and 125-MHz /sup 13/C NMR spectra of which could be analyzed in terms of a unique structure through application of pH-dependent ..beta..-shifts and two-dimensional techniques that included COSY, relayed COSY, and NOESY experiments together with heteronuclear C/H shift correlation spectroscopy. On the basis of these experiments and supported by methylation and periodate oxidation data, the structure of the M polysaccharide was determined as a linear polymer of unbranched pentasaccharide repeating units consisting of four 1,2-linked and one 1,3-lined 4,6-dideoxy-4-formamido-..cap alpha..-D-mannopyranosyl residues. The marked structural similarity of the M antigen and the A antigen, which is known to be a 1,2-linked homopolysaccharide of 4,6-dideoxy-4-formamido-..cap alpha..-D-mannopyranosyl units, accounts for cross-serological reactions of the two and the long-standing confusion surrounding the nature of their antigenic determinants.« less

Increased helix and protein stability through the introduction of a new tertiary hydrogen bond.

PubMed

Peterson, R W; Nicholson, E M; Thapar, R; Klevit, R E; Scholtz, J M

1999-03-12

In an effort to quantify the importance of hydrogen bonding and alpha-helix formation to protein stability, a capping box motif was introduced into the small phosphocarrier protein HPr. Previous studies had confirmed that Ser46, at the N-cap position of the short helix-B in HPr, serves as an N-cap in solution. Thus, only a single-site mutation was required to produce a canonical S-X-X-E capping box: Lys49 at the N3 position was substituted with a glutamic acid residue. Thermal and chemical denaturation studies on the resulting K49E HPr show that the designed variant is approximately 2 kcal mol-1 more stable than the wild-type protein. However, NMR studies indicate that the side-chain of Glu49 does not participate in the expected capping H-bond interaction, but instead forms a new tertiary H-bond that links helix-B to the four-stranded beta-sheet of HPr. Here, we demonstrate that a strategy in which new non-native H-bonds are introduced can generate proteins with increased stability. We discuss why the original capping box design failed, and compare the energetic consequences of the new tertiary side-chain to main-chain H-bond with a local (helix-capping) side-chain to main-chain H-bond on the protein's global stability. Copyright 1999 Academic Press.

Supramolecular Inclusion in Cyclodextrins: A Pictorial Spectroscopic Demonstration

ERIC Educational Resources Information Center

Haldar, Basudeb; Mallick, Arabinda; Chattopadhyay, Nitin

2008-01-01

A spectroscopic experiment is presented that reveals that the hydrophobically end-modified water-soluble polymeric fluorophore, pyrene end-capped poly(ethylene oxide) (PYPY), interacts differently with [alpha], [beta], and [gamma]-cyclodextrins (CD) to form supramolecular inclusion complexes. The emission spectrum of PYPY in aqueous solution shows…

Disc valve for sampling erosive process streams

DOEpatents

Mrochek, J.E.; Dinsmore, S.R.; Chandler, E.W.

1984-08-16

This is a patent for a disc-type, four-port sampling valve for service with erosive high temperature process streams. Inserts and liners of ..cap alpha..-silicon carbide respectively, in the faceplates and in the sampling cavities, limit erosion while providing lubricity for a smooth and precise operation. 1 fig.

South Polar Ice Cap

NASA Technical Reports Server (NTRS)

2003-01-01

MGS MOC Release No. MOC2-337, 21 April 2003

This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows the 'swiss cheese' pattern of frozen carbon dioxide on the south polar residual cap. Observation of these materials over two Mars years has revealed that the scarps that bound the mesas and small buttes are retreating-the carbon dioxide ice is subliming away-at a rate of about 3 meters (3 yards) per Mars year in some places. The picture covers an area about 900 m (about 900 yards) wide near 87.1oS, 93.7oW. Sunlight illuminates the scene from the upper left.

Intracellular compartmentalization and degradation of free polymannose oligosaccharides released during glycoprotein biosynthesis.

PubMed

Moore, S E; Spiro, R G

1994-04-29

The intracellular site for the degradation of free polymannose oligosaccharides released during glycoprotein biosynthesis has been studied by permeabilizing the plasma membrane of metabolically radiolabeled HepG2 cells with streptolysin O. This pore-forming agent permitted us to examine the breakdown in both the cytosolic and vesicular compartments of the previously recognized (Anumula, K. R., and Spiro, R. G. (1983) J. Biol. Chem. 258, 15274-15282) polymannose components terminating in a di-N-acetylchitobiose sequence (OS-Glc-NAc2) or a single N-acetylglucosamine residue (OS-Glc-NAc1) residue. Pulse-chase studies indicated that although the OS-GlcNAc2 saccharides were about equally distributed between vesicles and cytosol and rapidly disappeared after reaching the Man8 stage, the OS-GlcNAc1 species were found predominantly in the extravesicular compartment and there underwent a distinctive demannosylation sequence resulting in the formation of a Man5GlcNAc isomer (Man alpha 1-->2Man alpha 1-->2Man alpha 1-->3(Man alpha 1-->6)Man beta 1-->4GlcNAc) which was different from the product of Golgi processing enzymes. Further trimming of this cytosolic limit product required its translocation into a vesicular compartment, believed to be lysosomes, in which Man2-4GlcNAc components appeared as the metabolic chase progressed. The accumulation of Glc1Man5GlcNAc in the cytosol during the chase suggested that glucose interferes with the cytosolic-vesicular transfer and this became even more evident by the pronounced pile-up of extravesicular Glc3Man5GlcNAc when the cells were incubated in the presence of castanospermine. Although the biological significance and mechanism of free polymannose oligosaccharide entry into the cytosol is not yet known, the possibility that it may reflect an endoplasmic reticulum-situated degradative process of glycoproteins merits consideration.

Carbon Dioxide Landforms

NASA Technical Reports Server (NTRS)

2004-01-01

19 March 2004 The martian south polar residual ice cap is mostly made of frozen carbon dioxide. There is no place on Earth that a person can go to see the landforms that would be produced by erosion and sublimation of hundreds or thousands of cubic kilometers of carbon dioxide. Thus, the south polar cap of Mars is as alien as alien can get. This image, acquired in February 2004 by the Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC), shows how the cap appears in summer as carbon dioxide is subliming away, creating a wild pattern of pits, mesas, and buttes. Darker surfaces may be areas where the ice contains impurities, such as dust, or where the surface has been roughened by the removal of ice. This image is located near 86.3oS, 0.8oW. This picture covers an area about 3 km (1.9 mi) across. Sunlight illuminates the scene from the top/upper left.

Summer South Polar Cap

NASA Technical Reports Server (NTRS)

2004-01-01

13 April 2004 The martian south polar residual ice cap is composed mainly of frozen carbon dioxide. Each summer, a little bit of this carbon dioxide sublimes away. Pits grow larger, and mesas get smaller, as this process continues from year to year. This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a view of a small portion of the south polar cap as it appeared in mid-summer in January 2004. The dark areas may be places where the frozen carbon dioxide contains impurities, such as dust, or places where sublimation of ice has roughened the surface so that it appears darker because of small shadows cast by irregularities in the roughened surface. The image is located near 86.9oS, 7.6oW. The image covers an area about 3 km (1.9 mi) across. Sunlight illuminates the scene from the upper left.

Importance of the lid and cap domains for the catalytic activity of gastric lipases.

PubMed

Miled, N; Bussetta, C; De caro, A; Rivière, M; Berti, L; Canaan, S

2003-09-01

Human gastric lipase (HGL) is an enzyme secreted by the stomach, which is stable and active despite the highly acidic environment. It has been clearly established that this enzyme is responsible for 30% of the fat digestion processes occurring in human. This globular protein belongs to the alpha/beta hydrolase fold family and its catalytic serine is deeply buried under a domain called the extrusion domain, which is composed of a 'cap' domain and a segment consisting of 58 residues, which can be defined as a lid. The exact roles played by the cap and the lid domains during the catalytic step have not yet been elucidated. We have recently solved the crystal structure of the open form of the dog gastric lipase in complex with a covalent inhibitor. The detergent molecule and the inhibitor were mimicking a triglyceride substrate that would interact with residues belonging to both the cap and the lid domains. In this study, we have investigated the role of the cap and the lid domains, using site-directed mutagenesis procedures. We have produced truncated mutants lacking the lid and the cap. After expressing these mutants and purifying them, their activity was found to have decreased drastically in comparison with the wild type HGL. The lid and the cap domains play an important role in the catalytic reaction mechanism. Based on these results and the structural data (open form of DGL), we have pointed out the cap and the lid residues involved in the binding with the lipidic substrate.

miR-21 expression and clinical outcome in locally advanced pancreatic cancer: exploratory analysis of the pancreatic cancer Erbitux, radiotherapy and UFT (PERU) trial

PubMed Central

Khan, Khurum; Cunningham, David; Peckitt, Clare; Barton, Sarah; Tait, Diana; Hawkins, Maria; Watkins, David; Starling, Naureen; Rao, Sheela; Begum, Ruwaida; Thomas, Janet; Oates, Jacqui; Guzzardo, Vincenza; Fassan, Matteo; Braconi, Chiara; Chau, Ian

2016-01-01

Background Locally advanced pancreatic cancer (LAPC) is associated with high mortality, and biomarker-driven treatment approach is currently lacking. This study evaluated safety and efficacy of a combination approach of chemotherapy followed by chemo-radiotherapy (CRT) +/− cetuximab, and the prognostic role of miR-21 in patients with LAPC treated with a multimodality approach. Patients and Methods This was a randomised phase II trial in which patients with inoperable LAPC were offered gemcitabine and capecitabine (GEM-CAP) for 16 weeks. Patients with stable disease or response after GEM-CAP were randomised to capecitabine or UFT plus radiotherapy (RT) (A), or capecitabine or UFT plus cetuximab plus RT (B). The primary outcome of the study was overall survival (OS). Clinical outcome was compared according to baseline circulating miR-21 levels. Results 17 patients were enrolled and treated with GEM-CAP, with 13 patients achieving disease control and being randomised to arms A (n:7) and B (n:6). After a median follow-up of 61.2 months, median progression free survival (PFS) was 10.4 months and 12.7 months, median OS was 15.8 months and 22.0 months in arms A and B respectively (p > 0.05). Patients with high baseline plasma miR-21 had worse PFS (3.5 vs. 12.7 months; p:0.032) and OS (5.1 vs 15.3 months; p:0.5) compared to patients with low miR-21. Circulating miR-21 levels reflected miR-21 expression within the tissues. Conclusions Addition of Cetuximab to CRT following induction chemotherapy did not improve survival. High miR-21 baseline plasma expression was associated with poor clinical outcome in LAPC patients treated with induction chemotherapy followed by chemo-radiotherapy. PMID:26862857

Laser surface treatment for porous and textured Ca-P bio-ceramic coating on Ti-6Al-4V.

PubMed

Paital, Sameer R; Dahotre, Narendra B

2007-12-01

In the present paper the feasibility of depositing a porous calcium phosphate (CaP) bio-ceramic coating using a continuous wave Nd:YAG laser on a Ti-6Al-4V substrate has been demonstrated. The advantages offered by such porous bio-ceramic coating are its inertness combined with the mechanical stability of the highly convoluted interface that develops when bone grows into the pores of ceramic. The formation of different phases with varying laser fluences is studied using x-ray diffraction (XRD). A quantitative estimation of the crystallite size and relative amounts of Ti and other predominant phases such as TiO(2) and alpha-tricalcium phosphate (alpha-TCP) were obtained. An increase in the crystallite size with increasing laser fluence is observed for all the above three phases. It is observed that TiO(2) is the predominant phase for all laser fluences and there is an increase in the alpha-TCP phase with increasing laser fluence. Surface porosity measurements indicated a decreasing trend with increasing laser fluence. Microhardness measurements in the cross section of samples showed a maximum hardness within the coating. The bioactivity of the coatings was further demonstrated by the formation of an apatite-like layer on the surface of the sample after being immersed in a simulated biofluid.

Yang-Lee zeros, Julia sets, and their singularity spectra

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

Hu, B.; Lin, B.

1989-05-01

We have studied the global scaling properties of the Julia sets of the Yang-Lee zeros of the s-state Potts model on the diamond hierarchical lattice. The singularity spectrum f(..cap alpha..) and the generalized dimension D/sub q/ are calculated for different s values. General observations are made on their variations.

N-(/sup 11/C)-methyl-p-substituted phentermine analogs as potential brain blood flow agents for positron tomography

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

Kizuka, H.; Elmaleh, D.R.; Boudreaux, G.J.

The addition of a methyl group to the ..cap alpha..-position of amphetamine increases both the lipophilicity of the agent and its resistance to metabolism by monoamine oxidase. In addition, since tritium substituted phenteramine analog studies suggested that the p-halo phentermines had a greater concentration in the brain and prolonged retention time, the authors evaluated the biological behavior of positron labeled ..cap alpha..-methylamphetamine (phenteramine) in rats, dogs and monkeys. The N-(/sup 11/C) methyl analogs of p-chloro (I) and p-fluoro (II) phentermines were prepared by methylation of their primary amines using /sup 11/Ch/sub 3/I. Biodistribution studies in rats shows brain uptake ismore » in the range of 1% dose/gr at 5 and 15 min for both agents. The activity in blood and eyes is low. Sequential images of the dogs' brain over 1 hour revealed a clearance of <15%. Images of the monkey brain were also obtained using a MGH positron camera PCR-I.« less

Racemization of alanine by the alanine racemases from Salmonella typhimurium and Bacillus stearothermophilus: energetic reaction profiles

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

Faraci, W.S.; Walsh, C.T.

1988-05-03

Alanine racemases are bacterial pyridoxal 5'-phosphate (PLP) dependent enzymes providing D-alanine as an essential building block for biosynthesis of the peptidoglycan layer of the cell wall. Two isozymic alanine racemases, encoded by the dadB gene and the alr gene, from the Gram-negative mesophilic Salmonella typhimurium and one from the Gram-positive thermophilic Bacillus stearothermophilus have been examined for the racemization mechanism. Substrate deuterium isotope effects and solvent deuterium isotope effects have been measured in both L ..-->.. D and D..-->.. L directions for all three enzymes to assess the degree to which abstraction of the ..cap alpha..-proton or protonation of substratemore » PLP carbanion is limiting in catalysis. Additionally, experiments measuring internal return of ..cap alpha..-/sup 3/H from substrate to product and solvent exchange/substrate conversion experiments in /sup 3/H/sub 2/O have been used with each enzyme to examine the partitioning of substrate PLP carbanion intermediates and to obtain the relative heights of kinetically significant energy barriers in alanine racemase catalysis.« less

Mobilization of tissue cadmium in mice and calves and reversal of cadmium induced tissue damage in calves by zinc

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

Reddy, C.S.; Mohammad, F.K.; Ganjam, V.K.

1987-08-01

Earlier studies demonstrated that simultaneous dietary Zn supplementation to calves fed Cd, significantly decreased the accumulation of Cd in liver, kidney and muscle. However, studies are lacking in evaluating the effectiveness of zinc in reducing Cd-burden in animals with pre-existing tissue Cd-load, a situation encountered in chronic Cd intoxication. This study examined the effects of oral Zn (AnO) on tissue Cd levels in mice. N-acetylcysteine (NAC) and sodium sulfate (SS) were also used to evaluate the effects of providing organic and inorganic sources of sulfur on tissue Cd levels. Following demonstration of reduced Cd levels in tissues of mice receivingmore » antidotal Zn, subsequent investigation was aimed at studying the reversal of Cd-induced changes by Zn. The authors also examined whether Cd-induced reduction in epididymal 5 ..cap alpha..-reductase activity could explain previously reported low levels of circulating dihydrotestosterone (DHT) following Cd treatment. The ability of Zn to reverse the inhibition of 5 ..cap alpha..-reductase activity by Cd was also examined.« less

Study on great northern beans (Phaseolus vulgaris): effect of drum drying process on bean flour properties and effect on gamma radiation on bean starch properties

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

Rayas-Solis, P.

Great Northern bean (Phaseolus vulgaris L.) drum dried flours at native pH of 6.54, pH 6 and 7 showed reduced activities of trypsin inhibitor, ..cap alpha..-amylase inhibitor, hemagglutinating titer, and nitrogen solubility. Electrophoretic analyses showed a slight modification of the native bean proteins, and the presence of at least four trypsin inhibitors. The study of the effect of 2.5-20 kGy irradiation doses on Great Northern beans showed essentially no modification of the electrophoretic mobility of the storage proteins or the trypsin inhibitors. Nitrogen solubility and hemagglutinating activity were essentially unchanged. With the 20 kGy dose, decrease in ..cap alpha..-amylase inhibitormore » activity, decrease reactive/available lysine content, and decrease cooking time of the irradiated beans after 11 months of storage were observed. Taste panel results indicated that the control and 20 kGy irradiated bean were significantly different at 5% level. At 20 kGy dose, the beans developed a partially water soluble brown color.« less

Mutations in a gene encoding the. cap alpha. subunit of a Saccharomyces cerevisiae G protein indicate a role in mating pheromone signaling

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

Jahng, K.Y.; Ferguson, J.; Reed, S.I.

1988-06-01

Mutations which allowed conjugation by Saccharomyces cerevisiae cells lacking a mating pheromone receptor gene were selected. One of the genes defined by such mutations was isolated from a yeast genomic library by complementation of a temperature-sensitive mutation and is identically to the gene GPA1 (also known as SCG1), recently shown to be highly homologous to gene encoding the ..cap alpha.. subunits of mammalian G proteins. Physiological analysis of temperature-sensitive gpal mutations suggests that the encoded G protein is involved in signaling in response to mating pheromones. Mutational disruption of G-protein activity causes cell-cycle arrest in G/sub 1/, deposition of mating-specificmore » cell surface aggultinins, and induction of pheromone-specific mRNa, all of which are responses to pheromone in wild-type cells. In addition, mutants can conjugate without the benefit of mating pheromone or pheromone receptor. A model is presented where the activated G protein has a negative impact on a constitutive signal which normally keeps the pheromone response repressed.« less

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

Downes, R.A.

Galactic plane ultraviolet-excess (uv-excess) objects covering about 1000 square degrees of sky were surveyed. Photographic plates were obtained with both uv and blue filters, to select the uv-excess candidates, which were then observed spectroscopically to determine their classification. Most of the objects selected were nearby early-type stars with low interstellar reddening; however, a collection of hot white dwarfs, subdwarf O (sdO) stars, subdwarf B (sdB) stars, and cataclysmic variables was also found. Photoelectric photometry was obtained for these stars and a statistical analysis was performed to determine the space densities and scale heights for the four classes of objects. Severalmore » interesting objects (or class of objects) were discovered, and data for some of these stars are presented. Among the peculiar objects found are an emission-line white dwarf similar to the pulsating PG 1159 stars, a Population II Wolf-Rayet star, a previously catalogued object with a strong Fe II emission-line spectrum, and a new class of object, resembling the sdB stars, that shows variable strength H..cap alpha.. absorption, with the H..cap alpha.. line sometimes completely filled in.« less

Nucleotide sequence of the gene encoding the nitrogenase iron protein of Thiobacillus ferrooxidans

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

Pretorius, I.M.; Rawlings, D.E.; O'Neill, E.G.

1987-01-01

The DNA sequence was determined for the cloned Thiobacillus ferrooxidans nifH and part of the nifD genes. The DNA chains were radiolabeled with (..cap alpha..-/sup 32/P)dCTP (3000 Ci/mmol) or (..cap alpha..-/sup 35/S)dCTP (400 Ci/mmol). A putative T. ferrooxidans nifH promoter was identified whose sequences showed perfect consensus with those of the Klebsiella pneumoniae nif promoter. Two putative consensus upstream activator sequences were also identified. The amino acid sequence was deduced from the DNA sequence. In a comparison of nifH DNA sequences from T. ferrooxidans and eight other nitrogen-fixing microbes, a Rhizobium sp. isolated from Parasponia andersonii showed the greatest homologymore » (74%) and Clostridium pasteurianum (nifH1) showed the least homology (54%). In the comparison of the amino acid sequences of the Fe proteins, the Rhizobium sp. and Rhizobium japonicum showed the greatest homology (both 86%) and C. pasteurianum (nifH1 gene product) demonstrated the least homology (56%) to the T. ferrooxidans Fe protein.« less

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

Nomura, S.; Enna, S.J.

Tricyclic antidepressants (TCAs) have anticholinergic and ..cap alpha..-adrenergic blocking properties. The present study was undertaken to examine the effects of amitriptyline, imipramine, and desipramine on inositol phosphate accumulation, a brain second messenger system associated with cholinergic and adrenergic receptors. Whereas the TCAs were 28 to 400-fold weaker than atropine as inhibitors of /sup 3/H-QNB binding to brain cholinergic receptors, they were 600 to 2000-fold less active than atropine as inhibitors of carbachol-stimulated IP accumulation in brain. In contrast, the relative potencies of the TCAs and prazosin to inhibit norepinephrine-stimulated IP accumulation and /sup 3/H-prazosin binding appeared to be similar inmore » the two assays. The results suggest pharmacological differences between the cholinergic receptors labeled in the ONB binding assay and those mediating the IP response, whereas the ..cap alpha../sub 1/-adrenergic receptors appear to be similar in the two systems. Since atropine is considered a nonselective muscarinic antagonist, it is possible that the TCAs may differentiate between cholinergic receptor subtypes, which may be an important component of their clinical response.« less

Direct /sup 125/I-radioligand assays for serum progesterone compared with assays involving extraction of serum

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

Ratcliffe, W.A.; Corrie, J.E.T.; Dalziel, A.H.

1982-06-01

Two direct radioimmunoassays for progesterone in 50 ..mu..L of unextracted serum or plasma with assays involving extraction of serum were compared. The direct assays include the use of either danazol at pH 7.4 or 8-anilino-1-naphthalenesulfonic acid at pH 4.0 to displace progesterone from serum binding-proteins. Progesterone is then assayed by using an antiserum to a progesterone 11..cap alpha..-hemisuccinyl conjugate and the radioligand /sup 125/I-labeled progesterone 11..cap alpha..-glucuronyl tyramine, with separation by double-antibody techniques. Direct assays with either displacing agent gave good analytical recovery of progesterone added to human serum, and progesterone values for patients' specimens correlated well (r > 0.96)more » with results of assays involving extraction of serum. Precision was similar with each displacing agent over the working range 2.5-100 nmol/L and superior to that of extraction assays. We conclude that these direct assays of progesterone are analytically valid and more robust, precise, and technically convenient than many conventional methods involving extraction of serum.« less

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

Hall, J.; Richard, P.; Gray, T.J.

The systematics of single and double K-shell-vacancy production in titanium has been investigated in the limit of zero target thickness (approx.1 ..mu..g/cm/sup 2/) for incident C, N, O, F, Mg, Al, Si, S, and Cl ions over a maximum energy range of 0.5 to 6.5 MeV/amu. This corresponds to collision systems with 0.27< or =Z/sub 1//Z/sub 2/< or =0.77 and 0.24< or =v/sub 1//vK< or =0.85, where v/sub 1/ is the projectile nuclear velocity and vK is the mean velocity of an electron in the target K shell. The present work is divided into four major sections. (1) Single K-shell-vacancymore » production has been investigated by measuring K..cap alpha.. and K..beta.. p satellite x-ray-production cross sections for projectiles incident with no K-shell vacancies. For incident ions with Z/sub 1/> or =9, the contribution due to electron-transfer processes from the target K shell to outer shells of the projectile has also been noted. (2) Single K-shell--to--K-shell electron-transfer cross sections have been obtained indirectly by the measuring of the enhancement in the Ti K x-ray production cross section for bare incident projectiles over ions incident with no initial K-shell vacancies. (3) Double K-vacancy production has been investigated by measuring the K..cap alpha.. hypersatellite intensity in ratio to the total K..cap alpha.. intensity. (4) Double K-shell--to--K-shell electron-transfer cross sections have been obtained indirectly with the use of a procedure similar to that used for single K to K transfer. The measured cross sections have been compared to theoretical models for direct Coulomb ionization and inner-shell electron transfer and have been used to investigate the relative importance of these mechanisms for K-vacancy production in heavy-ion--atom collisions.« less

Absolute configurations of organometallic compounds. III. Structure and absolute configuration of the square-pyramidal complex ((+)/sub 579/-(C/sub 5/H/sub 5/)Mo(CO)/sub 2/(NN*))PF/sub 6/(NN* = Schiff base derived from pyridine-2-carbaldehyde and (S)-(-)-. cap alpha. -phenylethylamine)

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

Bernal, I.; LaPlaca, S.J.; Korp, J.

The structure of (+)/sub 579/-(eta/sup 5/-C/sub 5/H/sub 5/Mo(CO)/sub 2/(NN*))PF/sub 6/ with NN* = the Schiff base derived from pyridine-2-carbaldehyde and (S)-(--)-..cap alpha..-phenylethylamine was determined using standard single-crystal x-ray diffraction methods. The absolute configuration was determined by refinement of the data using the anomalous scattering contributions of Mo and P to a final R(F) = 0.056 for 2634 independent reflections having I greater than 3 sigma (I). The substance crystallizes in the space group P2/sub 1/2/sub 1/2/sub 1/ with unit cell dimensions of a = 12.249 (4), b = 9.236 (3), and c = 20.692 (9) A and Z = 4more » molecules/unit cell. The square-pyramidal coordination of the Mo atom is defined by two carbonyl carbons and two Schiff base nitrogens occupying the four basal plane sites and the five carbons of the eta/sup 5/-C/sub 5/H/sub 5/ ligand in the axial position. The Mo--ligand distances and the bond lengths and angles within the ligands are normal and compare closely with those of recent structure determinations of comparable precision. The Mo atom is 0.95 A above the plane formed by the four basal plane ligands. The conformation of the (S)-..cap alpha..-phenylethyl group with respect to the ligand plane, defined by the pyridine ring, the imine system, and the Mo atom, is discussed. The configuration at the metal atom in the (+)/sub 579/ isomer is specified as (S). The PF/sub 6//sup -/ anion executes large amplitude torsional motion in the lattice, as is commonly the case for this anion when not hydrogen bonded.« less

Biochemistry of snake venom neurotoxins and their application to the study of synapse. [Neurotoxins isolated from venom of the Formosan banded krait

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

Hanley, M.R.

1978-11-01

The crude venom of the Formosan banded krait, Bungarus multicinctus, was separated into eleven lethal protein fractions. Nine fractions were purified to final homogeneous toxins, designated ..cap alpha..-bungarotoxin, ..beta..-bungarotoxin, and toxins 7, 8, 9A, 11, 12, 13, and 14. Three of the toxins, ..cap alpha..-bungarotoxin, 7, and 8, were identified as post-synaptic curarimimetic neurotoxins. The remaining toxins were identified as pre-synaptic neurotoxins. ..cap alpha..-Bungarotoxin, toxin 7, and toxin 8 are all highly stable basic polypeptides of approx. 8000 daltons molecular weight. The pre-synaptic toxins fell into two structural groups: toxin 9A and 14 which were single basic chains of approx.more » 14,000 daltons, and ..beta..-bungarotoxin, and toxins 11 thru 13 which were composed of two chains of approx. 8000 and approx. 13,000 daltons covalently linked by disulfides. All the pre-synaptic neurotoxins were shown to have intrinsic calcium-dependent phospholipase A activities. Under certain conditions, intact synaptic membranes were hydrolyzed more rapidly than protein-free extracted synaptic-lipid liposomes which, in turn, were hydrolyzed more rapidly than any other tested liposomes. It was speculated that cell-surface arrays of phosphatidyl serine/glycolipids created high affinity target sites for ..beta..-bungarotoxin. Single-chain toxins were found to be qualitatively different from the two-chain toxins in their ability to block the functioning of acetylcholine receptors, and were quantitatively different in their enzymatic and membrane disruptive activities. ..beta..-Bungarotoxin was shown to be an extremely potent neuronal lesioning agent. There was no apparent selectivity for cholinergic over non-cholinergic neurons, nor for nerve terminals over cell bodies. It was suggested that ..beta..-bungarotoxin can be considered a useful new histological tool, which may exhibit some regional selectivity.« less

Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma.

PubMed

McSweeney, E N; Tobias, J S; Blackman, G; Goldstone, A H; Richards, J D

1993-01-01

In view of increasing controversy regarding the role of double hemibody irradiation (DHBI) in the treatment of multiple myeloma, we have analysed the use of this technique at our institution over a 6-year period. Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemoresistant to initial therapy. Fifteen patients received alpha IFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week, as part of a randomized trial. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. alpha IFN did not appear to prolong survival (OS or PFS) post-DHBI. Cytopenia was a significant problem, such that only 60% of patients had counts adequate enough to be eligible for alpha IFN. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Polar Cap Pits

NASA Technical Reports Server (NTRS)

2005-01-01

17 August 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows kidney bean-shaped pits, and other pits, formed by erosion in a landscape of frozen carbon dioxide. This images shows one of about a dozen different patterns that are common in various locations across the martian south polar residual cap, an area that has been receiving intense scrutiny by the MGS MOC this year, because it is visible on every orbit and in daylight for most of 2005.

Location near: 86.9oS, 6.9oW Image width: width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Spring

Residual Cap

NASA Technical Reports Server (NTRS)

2006-01-01

10 May 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a summertime view of the south polar residual cap of Mars. In this image, mesas composed largely of solid carbon dioxide are separated from one another by irregularly-shaped depressions. The variation in brightness across this scene is a function of several factors including, but not limited to, varying proportions of dust and solid carbon dioxide, undulating topography, and differences in the roughness of the slopes versus the flat surfaces.

Location near: 86.7oS, 343.3oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Summer

Molecular tagging of the Bph1 locus for resistance to brown planthopper (Nilaparvata lugens Stål) through representational difference analysis.

PubMed

Park, Dong-Soo; Song, Min-Young; Park, Soo-Kwon; Lee, Sang-Kyu; Lee, Jong-Hee; Song, Song-Yi; Eun, Moo Young; Hahn, Tae-Ryong; Sohn, Jae-Keun; Yi, Gihwan; Nam, Min-Hee; Jeon, Jong-Seong

2008-08-01

During brown planthopper (BPH) feeding on rice plants, we employed a modified representational difference analysis (RDA) method to detect rare transcripts among those differentially expressed in SNBC61, a BPH resistant near-isogenic line (NIL) carrying the Bph1 resistance gene. This identified 3 RDA clones: OsBphi237, OsBphi252 and OsBphi262. DNA gel-blot analysis revealed that the loci of the RDA clones in SNBC61 corresponded to the alleles of the BPH resistant donor Samgangbyeo. Expression analysis indicated that the RDA genes were up-regulated in SNBC61 during BPH feeding. Interestingly, analysis of 64 SNBC NILs, derived from backcrosses of Samgangbyeo with a BPH susceptible Nagdongbyeo, using a cleaved amplified polymorphic sequence (CAPS) marker indicated that OsBphi252, which encodes a putative lipoxygenase (LOX), co-segregates with BPH resistance. Our results suggest that OsBphi252 is tightly linked to Bph1, and may be useful in marker-assisted selection (MAS) for resistance to BPH.

Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma.

PubMed

Maio, Michele; Mackiewicz, Andrzej; Testori, Alessandro; Trefzer, Uwe; Ferraresi, Virginia; Jassem, Jacek; Garbe, Claus; Lesimple, Thierry; Guillot, Bernard; Gascon, Pere; Gilde, Katalin; Camerini, Roberto; Cognetti, Francesco

2010-04-01

Thymosin alpha 1 (Talpha1) is an immunomodulatory polypeptide that enhances effector T-cell responses. In this large randomized study, we evaluated the efficacy and safety of combining Talpha1 with dacarbazine (DTIC) and interferon alfa (IFN-alpha) in patients with metastatic melanoma. Four hundred eighty-eight patients were randomly assigned to five treatment groups: DTIC+IFN-alpha+Talpha1 (1.6 mg); DTIC+IFN-alpha+Talpha1 (3.2 mg); DTIC+IFN-alpha+Talpha1 (6.4 mg); DTIC+Talpha1 (3.2 mg); DTIC+IFN-alpha (control group). The primary end point was best overall response at study end (12 months). Secondary end points included duration of response, overall survival (OS), and progression-free survival (PFS). Patients were observed for up to 24 months. Ten and 12 tumor responses were observed in the DTIC+IFN-alpha+Talpha1 (3.2 mg) and DTIC+Talpha1 (3.2 mg) groups, respectively, versus four in the control group, which was sufficient to reject the null hypothesis that P(0) < or = .05 (expected response rate of standard therapy) in these two arms. Duration of response ranged from 1.9 to 23.2 months in patients given Talpha1 and from 4.4 to 8.4 months in the control group. Median OS was 9.4 months in patients given Talpha1 versus 6.6 months in the control group (hazard ratio = 0.80; 9% CI, 0.63 to 1.02; P = .08). An increase in PFS was observed in patients given Talpha1 versus the control group (hazard ratio = 0.80; 95% CI, 0.63 to 1.01; P = .06). Addition of Talpha1 to DTIC and IFN-alpha did not lead to any additional toxicity. These results suggest Talpha1 has activity in patients with metastatic melanoma and provide rationale for further clinical evaluation of this agent.

Cold Atmospheric Plasma (CAP) Changes Gene Expression of Key Molecules of the Wound Healing Machinery and Improves Wound Healing In Vitro and In Vivo

PubMed Central

Arndt, Stephanie; Unger, Petra; Wacker, Eva; Shimizu, Tetsuji; Heinlin, Julia; Li, Yang-Fang; Thomas, Hubertus M.; Morfill, Gregor E.; Zimmermann, Julia L.

2013-01-01

Cold atmospheric plasma (CAP) has the potential to interact with tissue or cells leading to fast, painless and efficient disinfection and furthermore has positive effects on wound healing and tissue regeneration. For clinical implementation it is necessary to examine how CAP improves wound healing and which molecular changes occur after the CAP treatment. In the present study we used the second generation MicroPlaSter ß® in analogy to the current clinical standard (2 min treatment time) in order to determine molecular changes induced by CAP using in vitro cell culture studies with human fibroblasts and an in vivo mouse skin wound healing model. Our in vitro analysis revealed that the CAP treatment induces the expression of important key genes crucial for the wound healing response like IL-6, IL-8, MCP-1, TGF-ß1, TGF-ß2, and promotes the production of collagen type I and alpha-SMA. Scratch wound healing assays showed improved cell migration, whereas cell proliferation analyzed by XTT method, and the apoptotic machinery analyzed by protein array technology, was not altered by CAP in dermal fibroblasts. An in vivo wound healing model confirmed that the CAP treatment affects above mentioned genes involved in wound healing, tissue injury and repair. Additionally, we observed that the CAP treatment improves wound healing in mice, no relevant side effects were detected. We suggest that improved wound healing might be due to the activation of a specified panel of cytokines and growth factors by CAP. In summary, our in vitro human and in vivo animal data suggest that the 2 min treatment with the MicroPlaSter ß® is an effective technique for activating wound healing relevant molecules in dermal fibroblasts leading to improved wound healing, whereas the mechanisms which contribute to these observed effects have to be further investigated. PMID:24265766

Time-resolved spectroscopy of dye-labeled photoactive yellow protein suggests a pathway of light-induced structural changes in the N-terminal cap.

PubMed

Hoersch, Daniel; Otto, Harald; Cusanovich, Michael A; Heyn, Maarten P

2009-07-14

The photoreceptor PYP responds to light activation with global conformational changes. These changes are mainly located in the N-terminal cap of the protein, which is approximately 20 A away from the chromophore binding pocket and separated from it by the central beta-sheet. The question of the propagation of the structural change across the central beta-sheet is of general interest for the superfamily of PAS domain proteins, for which PYP is the structural prototype. Here we measured the kinetics of the structural changes in the N-terminal cap by transient absorption spectroscopy on the ns to second timescale. For this purpose the cysteine mutants A5C and N13C were prepared and labeled with thiol reactive 5-iodoacetamidofluorescein (IAF). A5 is located close to the N-terminus, while N13 is part of helix alpha1 near the functionally important salt bridge E12-K110 between the N-terminal cap and the central anti-parallel beta-sheet. The absorption spectrum of the dye is sensitive to its environment, and serves as a sensor for conformational changes near the labeling site. In both labeled mutants light activation results in a transient red-shift of the fluorescein absorption spectrum. To correlate the conformational changes with the photocycle intermediates of the protein, we compared the kinetics of the transient absorption signal of the dye with that of the p-hydroxycinnamoyl chromophore. While the structural change near A5 is synchronized with the rise of the I(2) intermediate, which is formed in approximately 200 mus, the change near N13 is delayed and rises with the next intermediate I(2)', which forms in approximately 2 ms. This indicates that different parts of the N-terminal cap respond to light activation with different kinetics. For the signaling pathway of photoactive yellow protein we propose a model in which the structural signal propagates from the chromophore binding pocket across the central beta-sheet via the N-terminal region to helix alpha1, resulting in a large change in the protein conformation.

L-selectin-carbohydrate interactions: relevant modifications of the Lewis x trisaccharide.

PubMed

Sanders, W J; Katsumoto, T R; Bertozzi, C R; Rosen, S D; Kiessling, L L

1996-11-26

Protein-carbohydrate interactions are known to mediate cell-cell recognition and adhesion events. Specifically, three carbohydrate binding proteins termed selectins (E-, P-, and L-selectin) have been shown to be essential for leukocyte rolling along the vascular endothelium, the first step in the recruitment of leukocytes from the blood into inflammatory sites or into secondary lymphoid organs. Although this phenomenon is well-established, little is known about the molecular-level interactions on which it depends. All three selectins recognize sulfated and sialylated derivatives of the Lewis x [Le(x):Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc] and Lewis a [Le(a): Gal beta 1-->3(Fuc alpha 1-->4)GlcNAc] trisaccharide cores with affinities in the millimolar range, and it is believed that variants of these structures are the carbohydrate determinants of selectin recognition. Recently it was shown that the mucin GlyCAM-1, a secreted physiological ligand for L-selectin, is capped with sulfated derivatives of sialyl Lewis x [sLe(x): Sia alpha 2-->3Gal beta 1-->4(Fuc alpha 1-->3)GlcNAc] and that sulfation is required for the high-affinity interaction between GlyCAM-1 and L-selectin. To elucidate the important sites of sulfation on Le(x) with respect to L-selectin recognition, we have synthesized six sulfated Le(x) analogs and determined their abilities to block binding of a recombinant L-selectin-Ig chimera to immobilized GlyCAM-1. Our results suggest that 6-sulfo sLe(x) binds to L-selectin with higher affinity than does sLe(x) or 6'-sulfo sLe(x) and that sulfation of sLe(x) capping groups on GlyCAM-1 at the 6-position is important for L-selectin recognition.

Mo(CO)/sub 6/-promoted reductive cleavage of the carbon-sulfur bond

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

Luh, T.Y.; Wong, C.S.

1985-12-13

In order to study the reductive cleavage of carbon-sulfur bonds by Mo(CO/sub 6/, various organosulfur compounds are reacted with Mo(CO)/sub 6/ in THF. Results of these experiments demonstrate that benzylic-, aryl-, or ..cap alpha..-acyl-activated carbon-sulfur bonds are reduced by treatment with Mo(CO)/sub 6/. 1 table.

Inhibition of ribosome recruitment induces stress granule formation independently of eukaryotic initiation factor 2alpha phosphorylation.

PubMed

Mazroui, Rachid; Sukarieh, Rami; Bordeleau, Marie-Eve; Kaufman, Randal J; Northcote, Peter; Tanaka, Junichi; Gallouzi, Imed; Pelletier, Jerry

2006-10-01

Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2alpha phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2alpha phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2alpha to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2alpha phosphorylation-dependent and -independent pathways that target translation initiation.

Alpha3, a transposable element that promotes host sexual reproduction.

PubMed

Barsoum, Emad; Martinez, Paula; Aström, Stefan U

2010-01-01

Theoretical models predict that selfish DNA elements require host sex to persist in a population. Therefore, a transposon that induces sex would strongly favor its own spread. We demonstrate that a protein homologous to transposases, called alpha3, was essential for mating type switch in Kluyveromyces lactis. Mutational analysis showed that amino acids conserved among transposases were essential for its function. During switching, sequences in the 5' and 3' flanking regions of the alpha3 gene were joined, forming a DNA circle, showing that alpha3 mobilized from the genome. The sequences encompassing the alpha3 gene circle junctions in the mating type alpha (MATalpha) locus were essential for switching from MATalpha to MATa, suggesting that alpha3 mobilization was a coupled event. Switching also required a DNA-binding protein, Mating type switch 1 (Mts1), whose binding sites in MATalpha were important. Expression of Mts1 was repressed in MATa/MATalpha diploids and by nutrients, limiting switching to haploids in low-nutrient conditions. A hairpin-capped DNA double-strand break (DSB) was observed in the MATa locus in mre11 mutant strains, indicating that mating type switch was induced by MAT-specific DSBs. This study provides empirical evidence for selfish DNA promoting host sexual reproduction by mediating mating type switch.

Comment on de-averaged back-angle heavy-ion elastic scattering excitation functions

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

Hussein, M.S.; Canto, L.F.; Donangelo, R.

1984-06-01

It is suggested that the de-averaged 180/sup 0/ excitation function of /sup 16/O+ /sup 28/Si, recently considered by Frahn and Kaufmann, is strongly model dependent. Within a multistep ..cap alpha..-transfer description of the back-angle anomaly, we obtain a de-averaged 180/sup 0/ excitation function that exhibits a more regular gross structure.

Doppler-broadening measurements of x-ray lines for determination of the ion temperature in tokamak plasmas

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

Bitter, M.; von Goeler, S.; Horton, R.

1979-01-29

Ion-temperature results are deduced from Doppler-broadening measurements of the K..cap alpha.. (1s-2p) resonance line emitted from heliumlike iron impurity ions in the hot central core of PLT (Princeton Large Torus) tokamak discharges. The measurements were performed using a high-resolution Bragg-crystal spectrometer with a multiwire proportional counter.

Structural phase transitions in GaAs to 108 GPa

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

Weir, S.T.; Vohra, Y.K.; Vanderborgh, C.A.

1989-01-15

The III-V compound GaAs was studied using energy-dispersive x-ray diffraction with a synchro- tron source up to a pressure of 108 GPa. When the pressure was increased to 16.6 GPa, the GaAs sample transformed from the zinc-blende structure to an orthorhombic structure (GaAs(II)), space group Pmm2, consisting of a primitive orthorhombic lattice with a basis of (0,0,0) and (0,(1/2,..cap alpha..), where ..cap alpha.. = 0.35. Upon a further increase of pressure to 24 +- 1 GPa, GaAs(II) transformed to another orthorhombic structure (GaAs(III)), space group Imm2, consisting of a body-centered orthorhombic lattice with a basis of (0,0,0) and (0, (1/2,..delta..),more » where ..delta.. is 0.425 at 28.1 GPa. With increasing pressure, ..delta.. approached (1/2 and the GaAs(III) structure gradually assumed the symmetry of the simple hexagonal structure. The transition to the simple hexagonal structure (GaAs(IV)) was completed in the vicinity of 60--80 GPa. The structure remains simple hexagonal up to at least 108 GPa, the highest pressure reached in this study.« less

Use of antibodies specific to defined regions of scorpion. cap alpha. -toxin to study its interaction with its receptor site on the sodium channel

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

Ayeb, M.E.; Bahraoui, E.M.; Granier, C.

1986-10-21

Five antibody populations selected by immunoaffinity chromatography for the specificity toward various regions of toxin II of the scorpion Androctonus australis Hector were used to probe the interaction of this protein with its receptor site on the sodium channel. These studies indicate that two antigenic sites, one located around the disulfide bridge 12-63 and one encompassing residues 50-59, are involved in the molecular mechanisms of toxicity neutralization. Fab fragments specific to the region around disulfide bridge 12-63 inhibit binding of the /sup 125/I-labeled toxin to its receptor site. Also, these two antigenic regions are inaccessible to the antibodies when themore » toxin is bound to its receptor site. In contrast, the two other antigenic sites encompassing the only ..cap alpha..-helix region (residues 23-32) and a ..beta..-turn structure (residues 32-35) are accessible to the respective antibodies when the toxin is bound to its receptor. Together, these data support the recent proposal that a region made of residues that are conserved in the scorpion toxin family is involved in the binding of the toxin to the receptor.« less

Survey of the (. cap alpha. ,/sup 2/He) reaction on 1p- and 2s1d-shell nuclei

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

Jahn, R.; Stahel, D.P.; Wozniak, G.J.

A /sup 2/He detection system has been developed and used to investigate the (..cap alpha..,/sup 2/He) reaction at bombarding energies of 55 and 65 MeV on targets of /sup 12/C, /sup 13/C, /sup 14/N, /sup 15/N, /sup 16/O, /sup 18/O, /sup 20/Ne, /sup 22/Ne, /sup 24/Mg, /sup 26/Mg, /sup 28/Si, /sup 29/Si, /sup 32/S, /sup 36/Ar, /sup 38/Ar, and /sup 40/Ca. Preferential population of two-neutron states with dominant (d/sub 5/2/)/sup 2//sub 4/, (d/sub 3/2/f/sub 7/2/)/sub 5/, and (f/sub 7/2/)/sup 2//sub 6/ character was observed. A linear A dependence of the binding energies of the J/sup ..pi../ = 5/sup -/ andmore » 6/sup +/ states was obtained. This systematic behavior is well described by the Bansal-French model, using the parameters a = - 0.30 MeV and b = 2.6 MeV. Simple shell-model calculations for the 2n configurations are in good agreement with the experimental data.« less

Multiconfiguration resonating-group theory of the seven-nucleon system with realistic cluster wave functions

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

Fujiwara, Y.; Tang, Y.C.

1985-02-01

The properties of the seven-nucleon system are examined with a multiconfiguration and multi- channel resonating-group calculation. The cluster internal functions employed explain the charge-form-factor data over a wide range of q/sup 2/ and satisfy the variational stability condition quite well. The model space used is spanned by /sup 3/H+..cap alpha.., n+ /sup 6/Li, n+ /sup 6/Li(, and d+ /sup 5/He cluster configurations. The result shows that the specific distortion of the /sup 3/H+..cap alpha.. system is quite significant. With our multiconfiguration calculation, the ground-state energy is improved by more than 1 MeV. The calculated level spectrum agrees well with themore » level spectrum empirically determined. The energy positions of both natural-parity and unnatural-parity levels are reasonably explained. In addition, we find that, because of centrifugal-barrier effects, the aligned configuration generally makes the most sig- nificant contribution. The characteristics of nucleon-exchange terms are also briefly examined. Here it is found that, at sufficiently high energies where sharp resonance levels do not exist, the essential properties of these terms can already be learned by performing relatively simple single-configuration calculations.« less

Effects of capsaicin in the motor nerve.

PubMed

Pettorossi, V E; Bortolami, R; Della Torre, G; Brunetti, O

1994-08-01

The injection of capsaicin into the lateral gastrocnemius (LG) muscle of the rat induced an immediate and sustained reduction in the A delta and C components of the compound action potential (CAP) of the LG motor nerve. Conversely, the drug did not immediately affect the CAP wave belonging to fast-conducting fibers or the motor responses to LG nerve stimulation. It seems that capsaicin only affects the group III and IV afferents of LG nerve. However, a week after the injection the capsaicin also altered the motor responses, as shown by the threshold enhancement and amplitude reduction of the muscle twitch and by the decrease of the A alpha-beta CAP components. This late motor impairment was attributed to a central depression following a reduction of capsaicin-sensitive neuron input into the CNS. However, this motor effect was transient since the LG nerve regained the preinjection excitability level in a week and the muscle twitch amplitude reached the control value in a month.

Preparation and characterization of highly water-soluble magnetic Fe3O4 nanoparticles via surface double-layered self-assembly method of sodium alpha-olefin sulfonate

NASA Astrophysics Data System (ADS)

Li, Honghong; Qin, Li; Feng, Ying; Hu, Lihua; Zhou, Chunhua

2015-06-01

A kind of double-layered self-assembly sodium alpha-olefin sulfonate (AOS) capped Fe3O4 magnetic nanoparticles (Fe3O4-AOS-MN) with highly water-solubility was prepared by a wet co-precipitation method with a pH of 4.8. The resulting Fe3O4-AOS-MN could be dispersed into water to form stable magnetic fluid without other treatments. The result of X-ray diffraction (XRD) indicated that the Fe3O4-AOS-MN maintained original crystalline structure and exhibited a diameter of about 7.5 nm. The iron oxide phase of nanoparticles determined by Raman spectroscopy is Fe3O4. Transmission electron microscopy (TEM) analysis confirmed that the Fe3O4-AOS-MN with spherical morphology were uniformly dispersed in water. FT-IR spectroscopy (FT-IR) and thermo-gravimetric analysis (TGA) verified the successful preparation of Fe3O4-AOS-MN capped with double-layered self-assembled AOS. The corresponding capacities of monolayer chemical absorption and the second-layer self-assembly absorption were respectively 4.07 and 14.71 wt% of Fe3O4-MN, which were much lower than those of other surfactants. Vibrating sample magnetometer (VSM) test result showed Fe3O4-AOS-MN possessed superparamagnetic behavior with the saturation magnetization value of about 44.45 emu/g. The blocking temperature TB of Fe3O4-AOS-MN capped with double-layered AOS is 170 K.

Direct assays of radiation-induced DNA base lesions in mammalian cells: Technical progress report, July 1, 1986--December 1, 1988

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

Wheeler, K.T. Jr.

1988-01-01

Our cesium irradiator was installed in April 1987 and has the capability of irradiating DNA solutions, cells and animals at dose rates from >60 Gy/min to <10/sup /minus/2/ Gy/min. By early summer all of the dosimetry and set-ups were established to perform this research. In may 1987, Dr. Krystyna Lesiak left to return to the National Institutes of Health. However, she has remained a collaborator over the past 1/1/2/ years. She has synthesized a large lot of ..cap alpha..-deoxyadenosine, isolated a large batch of both the R and S isomer of cyclodeoxyadenosine and has capped the ..cap alpha..-deoxyadenonsine for usemore » in a DNA synthesizer that uses phosphoramidite chemistry. In November 1987, Dr. Andrzej Surowiec joined our unit as a Visiting Research Assistant Professor. Dr. Surowiec has a MS degree in electrical engineering and did his Ph.D. in Biophysics studying the conductivity of DNA in dilute solution. He has been performing the helix-coil transition experiments. In November 1987, Dr. Steven Swarts also joined our unit as a Postdoctoral Fellow. He received his Ph.D. from Oakland University under Dr. Michael Sevilla with whom we have a collaboration studying the induction of base damage in hydrated DNA. Dr. Swarts has a strong background in spectroscopy and, therefore, was a key individual for determination of the limitations of the HPLC assays and the establishment of a GC/MS capability equivalent to Dr. M. Dizdaroglu at the National Bureau of Standards. 9 refs., 1 tab.« less

Hydrothermal synthesis of alpha- and beta-HgS nanostructures

NASA Astrophysics Data System (ADS)

Galain, Isabel; María, Pérez Barthaburu; Ivana, Aguiar; Laura, Fornaro

2017-01-01

We synthesized HgS nanostructures by the hydrothermal method in order to use them as electron acceptors in hybrid organic-inorganic solar cells. We employed different mercury sources (HgO and Hg(CH3COO)2) and polyvinylpyrrolidone (PVP) or hexadecanethiol (HDT) as stabilizing/capping agent for controlling size, crystallinity, morphology and stability of the obtained nanostructures. We also used thiourea as sulfur source, and a temperature of 180 °C during 6 h. Synthesized nanostructures were characterized by powder X-Ray Diffraction, Diffuse Reflectance Infrared Fourier Transform and Transmission Electron Microscopy. When PVP acts as stabilizing agent, the mercury source has influence on the size -but not in morphology- of the beta-HgS obtained nansostructures. HDT has control over nanostructures' size and depending on the relation Hg:HDT, we obtained a mixture of alpha and beta HgS which can be advantageous in the application in solar cells, due their absorption in different spectral regions. The smallest nanostructures obtained have a mean diameter of 20 nm when using HDT as capping agent. Also, we deposited the aforementioned nanostructures onto flat glass substrates by the spin coating technique as a first approach of an active layer of a solar cell. The depositions were characterized by atomic force microscopy. We obtained smaller particle deposition and higher particle density -but a lower area coverage (5%) - in samples with HDT as capping agent. This work presents promising results on nanostructures for future application on hybrid solar cells. Further efforts will be focused on the deposition of organic-inorganic layers.

Treatment of catastrophic antiphospholipid syndrome with defibrotide, a proposed vascular endothelial cell modulator.

PubMed

Burcoglu-O'Ral, Arsinur; Erkan, Doruk; Asherson, Ronald

2002-09-01

To define at the molecular level the vascular endothelial cell (VEC) injury characteristics of catastrophic antiphospholipid syndrome (CAPS) and to report successful therapeutic use of a VEC modulator, defibrotide. We describe a 55-year-old man with primary APS with an intractable prothrombotic state (CAPS) resistant to combined therapy with heparin, warfarin, aspirin, and dipyridamole. Treatment with defibrotide was conducted in the context of an investigational phase II protocol where the dose was regulated and individualized by disease/patient-specific molecular and clinical markers. The patient entered complete remission with defibrotide treatment. During treatment, dose dependent pharmacological actions of defibrotide and key stress markers for VEC injury were identified. Evidence of defibrotide's polypharmacology included downregulation of cytokines, notably tumor necrosis factor-alpha, as the earliest effect, cellular differentiation of VEC, possibly with direct regulatory effect over cellular genes, and the reversal of platelet consumption and prothrombotic state. Von Willebrand antigen levels were used as the sole marker to guide therapy. This case demonstrates effective remission of CAPS with defibrotide treatment. In contrast to theories that CAPS is triggered by ischemic and thrombotic tissue damage, these data present VEC injury as the primary and representative lesion of CAPS. The pathogenesis may involve concurrent impairment of different VEC functions. Achieving remission may require a polypharmacologic approach, represented here by use of defibrotide.

Characterization of the primary interaction between the mating pheromone, alpha-factor, and its receptor in Saccharomyces cerevisiae

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

Raths, S.K.

1987-01-01

Alpha-factor is a peptide of thirteen amino acids which is required for mating between the haploid mating types, a and ..cap alpha.., in Saccharomyces cerevisiae. An analogue of alpha-factor, DHP/sup 8/ DHP/sup 11/ Nle/sup 12/ tridecapeptide, was catalytically reduced in the presence of /sup 3/H gas for production of a radiolabeled pheromone suitable for use in binding studies. Incorporation of tritium resulted in /sup 3/H-alpha-factor with high specific activity, purity, biological activity and long shelf-life. Binding studies revealed that alpha-factor interacts with its receptor via a simple, reversible process which obeys the law of mass action. Association and dissociation kineticsmore » indicate values of 2.92 x 10/sup 6/ M/sup /minus/1/ min/sup -1/ for k/sub 1/ and between 4 and 7 x 10/sup /minus/2/ min/sup /minus/1/ for k/sub /minus/1/. Saturation binding studies reveal an equilibrium dissociation constant equal to 2.32 x 10/sup /minus/8/ M which approximate the kinetically-derived K/sub D/ of 2.12 x 10/sup /minus/8/ M. Scatchard and Hill analyses as well as dissociation behavior in the presence of excess unlabeled ligand indicate alpha-factor interacts with a homogeneous population of binding sites which do not interact and exhibit one affinity for the alpha-factor pheromone.« less

A new genetic factor for root gravitropism in rice (Oryza sativa L.).

PubMed

Shi, Jiang-hua; Hao, Xi; Wu, Zhong-chang; Wu, Ping

2009-10-01

Root gravitropism is one of the important factors to determine root architecture. To understand the mechanism underlying root gravitropism, we isolated a rice (Xiushui63) mutant defective in root gravitropism, designated as gls1. Vertical sections of root caps revealed that gls1 mutant displayed normal distribution of amyloplast in the columella cells compared with the wild type. The gls1 mutant was less sensitive to 2,4-dichlorophenoxyacetic acid (2,4-D) and alpha-naphthaleneacetic acid (NAA) than the wild type. Genetic analysis indicated that the phenotype of gls1 mutant was caused by a single recessive mutation, which is mapped in a 255-kb region between RM16253 and CAPS1 on the short arm of chromosome 4.

Re/Os constraint on the time variability of the fine-structure constant.

PubMed

Fujii, Yasunori; Iwamoto, Akira

2003-12-31

We argue that the accuracy by which the isochron parameters of the decay 187Re-->187Os are determined by dating iron meteorites may constrain the possible time dependence of the decay rate and hence of the fine-structure constant alpha, not directly but only in a model-dependent manner. From this point of view, some of the attempts to analyze the Oklo constraint and the results of the quasistellar-object absorption lines are reexamined.

MERTK signaling in the retinal pigment epithelium regulates the tyrosine phosphorylation of GDP dissociation inhibitor alpha from the GDI/CHM family of RAB GTPase effectors.

PubMed

Shelby, Shameka J; Feathers, Kecia L; Ganios, Anna M; Jia, Lin; Miller, Jason M; Thompson, Debra A

2015-11-01

Photoreceptor outer segments (OS) in the vertebrate retina undergo a process of continual renewal involving shedding of disc membranes that are cleared by phagocytic uptake into the retinal pigment epithelium (RPE). In dystrophic Royal College of Surgeons (RCS) rats, OS phagocytosis is blocked by a mutation in the gene encoding the receptor tyrosine kinase MERTK. To identify proteins tyrosine-phosphorylated downstream of MERTK in the RPE, MALDI-mass spectrometry with peptide-mass fingerprinting was used in comparative studies of RCS congenic and dystrophic rats. At times corresponding to peak phagocytic activity, the RAB GTPase effector GDP dissociation inhibitor alpha (GDI1) was found to undergo tyrosine phosphorylation only in congenic rats. In cryosections of native RPE/choroid, GDI1 colocalized with MERTK and the intracellular tyrosine-kinase SRC. In cultured RPE-J cells, and in transfected heterologous cells, MERTK stimulated SRC-mediated tyrosine phosphorylation of GDI1. In OS-fed RPE-J cells, GDI1 colocalized with MERTK and SRC on apparent phagosomes located near the apical membrane. In addition, both GDI1 and RAB5, a regulator of vesicular transport, colocalized with ingested OS. Taken together, these findings identify a novel role of MERTK signaling in membrane trafficking in the RPE that is likely to subserve mechanisms of phagosome formation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Capecitabine/cisplatin doublet in anthracycline and taxane pretreated and HER-2 negative metastatic breast carcinoma patients.

PubMed

Ozdemir, N; Aksoy, S; Sendur, M A; Akinci, M B; Yazici, O; Budakoglu, B; Abali, H; Oksuzoglu, B; Zengin, N

2013-01-01

To evaluate the activity and toxicity of the combination of capecitabine and cisplatin (CapCisp) in anthracycline- and taxane-pretreated HER-2 negative metastatic breast carcinoma (MBC) female patients. Patients with HER-2 negative MBC pretreated with anthracycline and taxane and who were then treated with CapCisp combination were retrospectively evaluated. All patients received Cap 1000 mg/m(2) on days 1-14, and Cisp 60 mg/m(2) on day 1, repeated every 3 weeks. In case of disease control without severe toxicity, single agent Cap was continued until progression or unacceptable toxicities after Cisp cessation. Sixty-four MBC patients with median age 43 years (range 20-66) were included the study. Infiltrative ductal carcinoma prevailed (85.9%). Ten percent of the patients had grade I, 42% grade II, and 48.0% grade III tumors. Estrogen receptor (ER) and progesterone receptor (PR) were positive in 48.4 and 51.6% of the patients, respectively. Twenty-eight percent of the patients had triple negative tumors. Almost the entire patient group had this regimen as a third-line treatment. The median combination chemotherapy cycles were 6 (range 2-8). Twenty-seven non-progressive patients continued treatment with single-agent Cap. Median single-agent Cap cycles after the combination chemotherapy were 4 (range 1-38). Disease control rate was 81.3% (complete response 6.3%; partial response 48.4%, stable disease 26.6%, progressive disease 18.8%). Median follow-up time was 10.6 months. Median time to disease progression was 7 months, median overall survival (OS) was 17 months (95% CI, 6.9-16.1) measured from the start of CapCisp chemotherapy. There were no treatment-related deaths. The most frequent grade 3-4 toxicities were neutropenia (8.1%), nausea - vomiting (7.8%) and thrombocytopenia (6.3%). CapCisp doublet has an encouraging antitumor activity with acceptable and manageable toxicity in anthracycline- and taxane-pretreated HER-2 negative metastatic breast carcinoma patients.

Superconducting Properties and μSR Study of the Noncentrosymmetric Superconductor Nb_0.5Os_0.5.

PubMed

Singh, D; Barker, J A T; Arumugam, Thamizhavel; Hillier, A D; Paul, D McK; Singh, R P

2017-12-21

The properties of the noncentrosymmetric superconductor ($\\alpha$-$\\textit{Mn}$ structure) Nb$_{0.5}$Os$_{0.5}$ is investigated using resistivity, magnetization, specific heat, and muon spin relaxation and rotation ($\\mu$SR) measurements. These measurements suggest that Nb$_{0.5}$Os$_{0.5}$ is a weakly coupled ($\\lambda_{e-ph}$ $\\sim$ 0.53) type-II superconductor ($\\kappa_{GL}$ $\\approx$ 61) having a bulk superconducting transition temperature $T_c$ = 3.07 K. The specific heat data in the superconductive regime fits well with the single-gap BCS model indicating nodeless s-wave superconductivity in Nb$_{0.5}$Os$_{0.5}$. The $\\mu$SR measurements also confirm $\\textit{s}$-wave superconductivity with the preserved time-reversal symmetry. © 2017 IOP Publishing Ltd.

Polariton effects in naphthalene crystals

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

Robinette, Susan Louise

1977-10-01

The experimental verification of the two-step nature of energy dissipation of photon energy by a crystal is the subject of this dissertation. The ..cap alpha..(O,O) Davydov component of the lowest energy singlet transition in pure strain-free napthalene single crystals is shown to exhibit an increase in absorption with increasing temperature, due to an increase in polariton damping via polariton-phonon scattering processes. (GHT)

EFFECT OF POLONIUM /cap alpha/ RADIATION ON GELATINE (in French)

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

Ader, M.

1962-08-01

When a nuclear plate, which has been exposed to radiation, developed, and dried, is exposed to a Po source, no effect can be detected by either the eye or the microscope. However if the plate is placed in distilled water, the emulsion thickness of the irradiated region is reduced by approximately 20 mu . A ridge'' separates this region from the nonirradiated region. The ridge contains piles of silver grains, very deformed traces of the old radiation, and some gelatin fragments. It appears that the alpha particles penetrating the gelatine transforms this gelatin, reversible protein, into a substance soluble'' inmore » distilled water or entrained by the distilled water. (J.S.R.)« less

Role of N-linked polymannose oligosaccharides in targeting glycoproteins for endoplasmic reticulum-associated degradation.

PubMed

Spiro, R G

2004-05-01

Misfolded or incompletely assembled multisubunit glycoproteins undergo endoplasmic reticulum-associated degradation (ERAD) regulated in large measure by their N-linked polymannose oligosaccharides. In this quality control system lectin interaction with Glc(3)Man(9)GlcNAc(2) glycans after trimming with endoplasmic reticulum (ER) alpha-glucosidases and alpha-mannosidases sorts out persistently unfolded glycoproteins for N-deglycosylation and proteolytic degradation. Monoglucosylated (Glc(1)Man(9)GlcNAc(2)) glycoproteins take part in the calnexin/calreticulin glucosylation-deglucosylation cycle, while the Man(8)GlcNAc(2) isomer B product of ER mannosidase I interacts with EDEM. Proteasomal degradation requires retrotranslocation into the cytosol through a Sec61 channel and deglycosylation by peptide: N-glycosidase (PNGase); in alternate models both PNGase and proteasomes may be either free in the cytosol or ER membrane-imbedded/attached. Numerous proteins appear to undergo nonproteasomal degradation in which deglycosylation and proteolysis take place in the ER lumen. The released free oligosaccharides (OS) are transported to the cytosol as OS-GlcNAc(2) along with similar components produced by the hydrolytic action of the oligosaccharyltransferase, where they together with OS from the proteasomal pathway are trimmed to Man(5)GlcNAc(1) by the action of cytosolic endo-beta- N-acetylglucosaminidase and alpha-mannosidase before entering the lysosomes. Some misfolded glycoproteins can recycle between the ER, intermediate and Golgi compartments, where they are further processed before ERAD. Moreover, properly folded glycoproteins with mannose-trimmed glycans can be deglucosylated in the Golgi by endomannosidase, thereby releasing calreticulin and permitting formation of complex OS. A number of regulatory controls have been described, including the glucosidase-glucosyltransferase shuttle, which controls the level of Glc(3)Man(9)GlcNAc(2)-P-P-Dol, and the unfolded protein response, which enhances synthesis of components of the quality control system.

Comparison of U.S. Environmental Protection Agency’s CAP88 PC versions 3.0 and 4.0

DOE PAGES

Jannik, Tim; Farfan, Eduardo B.; Dixon, Ken; ...

2015-08-01

The Savannah River National Laboratory (SRNL) with the assistance of Georgia Regents University, completed a comparison of the U.S. Environmental Protection Agency's (EPA) environmental dosimetry code CAP88 PC V3.0 with the recently developed V4.0. CAP88 is a set of computer programs and databases used for estimation of dose and risk from radionuclide emissions to air. At the U.S. Department of Energy's Savannah River Site, CAP88 is used by SRNL for determining compliance with EPA's National Emission Standards for Hazardous Air Pollutants (40 CFR 61, Subpart H) regulations. Using standardized input parameters, individual runs were conducted for each radionuclide within itsmore » corresponding database. Some radioactive decay constants, human usage parameters, and dose coefficients changed between the two versions, directly causing a proportional change in the total effective 137Cs, 3H, 129I, 239Pu, and 90Sr) is provided. In general, the total effective doses will decrease for alpha/beta emitters because of reduced inhalation and ingestion rates in V4.0. However, for gamma emitters, such as 60Co and 137Cs, the total effective doses will increase because of changes EPA made in the external ground shine calculations.« less

The uteroglobin fold.

PubMed

Callebaut, I; Poupon, A; Bally, R; Demaret, J P; Housset, D; Delettré, J; Hossenlopp, P; Mornon, J P

2000-01-01

Uteroglobin (UTG) forms a fascinating homodimeric structure that binds small- to medium-sized ligands through an internal hydrophobic cavity, located at the interface between the two monomers. Previous studies have shown that UTG fold is not limited to the UTG/CC10 family, whose sequence/structure relationships are highlighted here, but can be extended to the cap domain of Xanthobacter autotrophicus haloalkane dehalogenase. We show here that UTG fold is adopted by several other cap domains within the alpha/beta hydrolase family, making it a well-suited "geode" structure allowing it to sequester various hydrophobic molecules. Additionally, some data about a new crystal form of oxidized rabbit UTG are presented, completing previous structural studies, as well as results from molecular dynamics, suggesting an alternative way for the ligand to reach the internal cavity.

Dynamic Contrast-Enhanced Computed Tomography-Derived Blood Volume and Blood Flow Correlate With Patient Outcome in Metastatic Renal Cell Carcinoma.

PubMed

Mains, Jill Rachel; Donskov, Frede; Pedersen, Erik Morre; Madsen, Hans Henrik Torp; Rasmussen, Finn

2017-02-01

The aim was to explore the potential for using dynamic contrast-enhanced computed tomography as a noninvasive functional imaging biomarker before and during the early treatment of metastatic renal cell carcinoma (mRCC). Dynamic contrast-enhanced computed tomography scans were performed at baseline and after 5 and 10 weeks' treatment in 69 prospectively included mRCC patients receiving treatment with interferon alpha and interleukin 2 (n = 26); interferon alpha, interleukin 2, and bevacizumab (n = 24); sunitinib (n = 7); pazopanib (n = 5); or temsirolimus (n = 7). Using a prototype software program (Advanced Perfusion and Permeability Application, Philips Healthcare, Best, the Netherlands), blood volume (BV), blood flow (BF), and permeability surface area product (PS) were calculated for each tumor at baseline, week 5, and week 10. These parameters as well as relative changes between baseline and weeks 5 and 10 were tested for associations with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier curves and log-rank tests. Using the 25th percentile as the cutoff, baseline BV for all patients independent of subsequent treatment was statistically significantly associated with PFS (10.8 vs 5.3 months, P = 0.007) and OS (35.2 vs 13.3 months, P = 0.001), and baseline BF was significantly associated with OS (31.7 vs 14.6 months, P = 0.024) with high values for both parameters being associated with significantly longer PFS and OS. Baseline PS was not associated with PFS or OS.In patients treated with angiogenesis inhibitors (bevacizumab, sunitinib, pazopanib, or temsirolimus), the relative change in BV from baseline to week 5 using 25th percentile as the cutoff was associated with PFS (5.6 vs 24.8 months, P = 0.001) and OS (19.1 months vs not reached, P = 0.008) and from baseline to week 10 with PFS (8.1 vs 16.4 months, P = 0.014) and OS (15.5 months vs not reached, P = 0.002). The relative change in BF from baseline to week 5 using medians as the cutoff was associated with PFS (5.5 vs 14.3 months, P = 0.018) and OS (14.6 vs 31.7 months, P = 0.027). The relative change in BF from baseline to week 10 using 25th percentile as the cutoff was associated with PFS (8.3 vs 46.9 months, P = 0.011) and OS (19.1 vs 53.0 months, P = 0.006). For both parameters, the largest reductions during early treatment were associated with increased PFS and OS.In patients receiving immunotherapy only (interferon alpha and interleukin 2), relative changes in PS between baseline and weeks 5 and 10 were significantly associated with PFS with larger increases associated with longer PFS. In patients receiving angiogenesis inhibitors, the relative changes in PS between baseline and week 10 were significantly associated with PFS and OS with larger reductions associated with favorable outcomes. In patients with mRCC treated with angiogenesis inhibitors, the largest reductions in BV and BF between baseline and weeks 5 and 10 were associated with favorable outcomes. At baseline, the lowest BV and BF were associated with the poorest outcomes regardless of the subsequent treatment. Early reductions in PS were associated with favorable outcomes for those treated with angiogenesis inhibitors and with poor outcomes for those treated with immunotherapies.

Time variations of magnetospheric intensities of outer zone protons, alpha particles and ions (Z greater than or equal to 2). Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Randall, B. A.

1973-01-01

A comprehensive study of the temporal behavior of trapped protons, alpha particles and ions (Z 2) in outer zone of the earth's magnetosphere has been made. These observations were made by the Injun V satellite during the first 21 months of operation, August 1968 to May 1970. Rapid increases in the observed number of particles followed by slower exponential decay characterize the data. Comparisons are made with the temporal behavior of interplanetary particles of the same energy observed by Explorer 35. Increases in the trapped fluxes generally correspond to enhanced interplanetary activity. The energy spectra of protons and alpha particles at L = 3 have similar shapes when compared on an energy per charge basis while the respective polar cap spectra have similar shape on an energy per nucleon basis. Apparent inward trans-L motion of energetic protons is observed. These particles are diffused inward by a process involving fluctuating electric fields. The loss of trapped low altitude protons, alpha particles and ions (Z 2) is controlled by coulombic energy loss in the atmosphere.

Effect of alpha-tocopherol, pyridoxine and dexpanthenol on the stress in crease of nonesterified fatty acids levels in the brain.

PubMed

Chmela, Z; Sklenovský, A; Dostálová, K; Rypka, M

1993-01-01

The supposed antistress effect of vitamins-alpha-tocopherol, pyridoxine and dexpanthenol (pantothenic acid precursor)--was followed on the model of nociceptive stress in laboratory rats. The decrease of the stress enhancement of nonesterified fatty acids (NEFA), estimated in the brain cortex, hypothalamus and the brain stem, was taken for the indicator of the antistress effect. Nonesterified fatty acids were determined with the help of gas chromatography following the separation performed by thin layer chromatographic method. Five-day application of alpha-tocopherol acetate (per os, 300 mg.kg-1) led to a decrease of the stress enhancement of arachidonic acid level in the brain stem.

Age and seasonal differences in the synthesis and metabolism of testosterone by testicular tissue and pineal HIOMT activity of Uinta ground squirrels (Spermophilus armatus)

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

Ellis, L.C.; Balph, D.F.

Male Uinta ground squirrels (Spermophilus armatus) were sacrificed from a free-living population during the breeding season, which immediately followed emergence from hibernation; after the reproductive season; and just prior to aestivation/hibernation. HIOMT activity of the pineal gland was assayed and related to the ability of the gonads to synthesize and metabolize testosterone. Older squirrels had higher HIOMT activity than did the younger animals. The activity of this enzyme was lowest in squirrels during the breeding season. HIOMT activity increased after the breeding season to its highest level just before the squirrels enter aestivation/hibernation. At this time, testicular weight increased concomitantmore » with an apparent increase in HIOMT activity. Testicular size and weight were largest at the time of emergence of the animals from hibernation. Androgen synthesis was also greatest during the breeding season. As would be expected, both decreased rapidly thereafter. The testes formed little 17..cap alpha..,20..cap alpha..-dihydroxyprogesterone during or after the breeding season, contrary to what has been reported for rats and house sparrows. The older squirrels demonstrated a greater capacity for testosterone metabolism during the breeding season than did the younger animals.« less

Fluorescence alteration of MPA capped CdSe quantum dots by spontaneous biomarker protein adsorption.

PubMed

Rowley, Amber; Parks, Tegan; Parks, Kaden; Medley, Kyle; Cordner, Alex; Yu, Ming

2018-05-23

Quantum dots (QDs) have significant potentials in biomedical applications of bioimaging and biosensing. Spontaneous adsorption of proteins on QDs surface is a common phenomenon, which occurred to serum proteins in biological samples, and has been observed to enhance QDs fluorescence. In this study, fluorescence alteration of 3-mercaptopropionic acid (MPA) capped CdSe quantum dots by four individual biomarker proteins was investigated. By monitoring the fluorescence emission of QDs, the biomarker protein adsorbed spontaneously on QDs surface was recognized and quantified. When alpha fetoprotein (AFP) or heat shock protein 90 alpha (HSP90α) were present, the QDs became brighter. The presence of cytochrome C (CytoC) or lysozyme (Lyz) made the QDs dimmer first, and then brighter. Within 5 min response time all four biomarker proteins were detected individually with the estimated detection limit in the range of 1-10 ng/mL and good linear dynamic ranges. The results suggested that the fluorescence of QDs was responsive to not only serum proteins but also biomarker proteins. The fluorescence response was able to correlate quantitatively with the amount of biomarker proteins in relatively low concentrations. These results provide more information to understand QDs and support their applications in biomedical fields. Copyright © 2018. Published by Elsevier Inc.

Role of calcium in the constriction of isolated cerebral arteries

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

Wendling, W.W.

1987-01-01

Calcium entry blockers (CEB) have been used in the experimental treatment or prevention of many cerebrovascular disorders including stroke, post-ischemic hypoperfusion after cardiac arrest, cerebral vasospasm after subarachnoid hemorrhage, and migraine headache. However, the mechanism of action of these drugs on the cerebral circulation is poorly understood. This study examined the effects of calcium antagonists, Ca/sup 2 +/-deficient solutions, and vasocostrictors on cerebrovascular tone and /sup 45/Ca fluxes, to determine the role of calcium in cerebral arterial constriction. A Scatchard plot of /sup 45/Ca binding to BMCA showed that Ca/sup 2 +/ was bound at either low or high affinitymore » binding sties. The four vasoconstrictors (potassium, serotonin, PGF/sub 2 ..cap alpha../, or SQ-26,655) each increased low affinity /sup 45/Ca uptake into BMCA. The results demonstrate that: (1) Potassium and serotonin constrict BMCA mainly by promoting Ca/sup 2 +/ influx through CEB-sensitive channels; (2) PGF/sub 2 ..cap alpha../ and SQ-26,655 constrict BMCA in part by promoting Ca/sup 2 +/ influx through CEB-sensitive channels, and in part by releasing Ca/sup 2 +/ from depletable internal stores; (3) The major action of CEB on BMCA is to block vasoconstrictor-induced Ca/sup 2 +/ uptake through both potential-operated (K/sup +/-stimulated) and receptor-operated channels.« less

Neutral amino acid transport across brain microvessel endothelial cell monolayers

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

Audus, K.L.; Borchardt, R.T.

1986-03-01

Brain microvessel endothelial cells (BMEC) which form the blood-brain barrier (BBB) possess an amino acid carrier specific for large neutral amino acids (LNAA). The carrier is important for facilitating the delivery of nutrient LNAA's and centrally acting drugs that are LNAA's, to the brain. Bovine BMEC's were isolated and grown up to complete monolayers on regenerated cellulose-membranes in primary culture. To study the transendothelial transport of leucine, the monolayers were placed in a side-by-side diffusion cell, and transport across the monolayers followed with (/sup 3/H)-leucine. The transendothelial transport of leucine in this in vitro model was determined to be bidirectional,more » and time-, temperature-, and concentration-dependent. The transport of leucine was saturable and the apparent K/sub m/ and V/sub max/, 0.18 mM and 6.3 nmol/mg/min, respectively. Other LNAA's, including the centrally acting drugs, ..cap alpha..-methyldopa, L-DOPA, ..cap alpha..-methyl-tyrosine, and baclofen, inhibited leucine transport. The leucine carrier was also found to be stereospecific and not sensitive to inhibitors of active transport. These results are consistent with previous in vitro and in vivo studies. Primary cultures of BMEC's appear to be a potentially important tool for investigating at the cellular level, the transport mechanisms of the BBB.« less

Imidazoline ring cleavage in 1,3,6,10-tetraazatetracyclo-(7. 3. 1. 0/sup 2,7/. 0/sup 6,13/)trideca-4,11-dienes, leading to the formation of diquinoxalino(1,2-. cap alpha. :2',3'-d)pyrrole derivatives

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

Charushin, V.N.; Petrova, G.M.; Aleksandrov, G.G.

1987-10-01

Dibenzo(d,k)-1,3,6,10-tetraazatetracyclo(7.3.1.0/sup 2,7/.0/sup 6,13/) trideca-4,11-dienes undergo addition reactions at the C/sub (2)/ carbon atom with alcohols and thiols, accompanied by cleavage of the C-N bond of the imidazoline ring, to generate diquinoxalino(1,2-..cap alpha..:2',3'-d)pyrrole derivatives. /sup 1/H NMR spectra were recorded on Perkin-Elmer R 12B (60 MHz) and Bruker WH-90 spectrometer for CDCl/sub 3/ solutions at 40/sup 0/C and with TMS as internal standard. /sup 13/C NMR spectra were obtained on a Bruker WH-90 (22.62 MHz) spectrometer. /sup 13/C chemical shifts were measured relative to solvent signals (deltaCDCl/sub 3/ 77.0 ppm). /sup 13/C NMR spectra of compounds IIa and g were takenmore » using full spin-spin carbon-proton decoupling. In order to measure SSCC the spectrum was recorded both with proton coupling and also with selective decoupling of individual protons and their attached /sup 13/C carbon nuclei.« less

Characterization of HeLa 5'-nucleotidase: a stable plasma membrane marker

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

Brake, E.T.; Will, P.C.; Cook, J.S.

1977-11-22

The enzyme 5'-nucleotidase, assayed as 5'-AMPase, has been extensively characterized and established as a stable, quantitative plasma membrane marker in HeLa S3 cells. The 5'-AMPase has a K/sub m/ of 7.0 ..mu..m. There are activity optima at pH7 and 10; the latter is Mg/sup 2 +/-dependent. The membrane preparations have a small amount of acid phosphatase activity that is distinct from 5'-AMPase activity but no alkaline phosphatase. ADP, ATP and ..cap alpha.., ..beta..-methylene adenosine-5'-diphosphate are strongly inhibitory. Mg/sup 2 +/, Ca/sup 2 +/, or Co/sup 2 +/ do not affect the pH 7.0 activity; Mn/sup 2 +/ activates slightly, whereasmore » Zn/sup 2 +/, Cu/sup 2 +/, and Ni/sup 2 +/ are inhibitory. EDTA slowly inactivates, but removal of the EDTA without the addition of divalent cations restores activity. The inactivation is also substantially reversed by Co/sup 2 +/ or Mn/sup 2 +/. ConA strongly inhibits, and ..cap alpha..-methyl-D-mannoside or glucose relieves the inhibition, indicating that the 5'-AMPase is a glycoprotein. Histidine is also inhibitory. Ouabain, phloretin, cytochalasin B, cysteine, phenylalanine, N-ethylmaleimide, and iodoacetic acid are without effect.« less

Anisotropy of the Fermi surface, Fermi velocity, many-body enhancement, and superconducting energy gap in Nb

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

Crabtree, G.W.; Dye, D.H.; Karim, D.P.

1987-02-01

The detailed angular dependence of the Fermi radius k/sub F/, the Fermi velocity v/sub F/(k), the many-body enhancement factor lambda(k), and the superconducting energy gap ..delta..(k), for electrons on the Fermi surface of Nb are derived with use of the de Haas--van Alphen (dHvA) data of Karim, Ketterson, and Crabtree (J. Low Temp. Phys. 30, 389 (1978)), a Korringa-Kohn-Rostoker parametrization scheme, and an empirically adjusted band-structure calculation of Koelling. The parametrization is a nonrelativistic five-parameter fit allowing for cubic rather than spherical symmetry inside the muffin-tin spheres. The parametrized Fermi surface gives a detailed interpretation of the previously unexplained kappa,more » ..cap alpha..', and ..cap alpha..'' orbits in the dHvA data. Comparison of the parametrized Fermi velocities with those of the empirically adjusted band calculation allow the anisotropic many-body enhancement factor lambda(k) to be determined. Theoretical calculations of the electron-phonon interaction based on the tight-binding model agree with our derived values of lambda(k) much better than those based on the rigid-muffin-tin approximation. The anisotropy in the superconducting energy gap ..delta..(k) is estimated from our results for lambda(k), assuming weak anisotropy.« less

Institutional learning curve of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for peritoneal malignancies.

PubMed

Polanco, Patricio M; Ding, Ying; Knox, Jordan M; Ramalingam, Lekshmi; Jones, Heather; Hogg, Melissa E; Zureikat, Amer H; Holtzman, Matthew P; Pingpank, James; Ahrendt, Steven; Zeh, Herbert J; Bartlett, David L; Choudry, Haroon A

2015-05-01

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemoperfusion (HIPEC) is routinely used to treat certain peritoneal carcinomatoses (PC), but it can be associated with relatively high complication rates, prolonged hospital length of stay, and potential mortality. Our objective was to determine the learning curve (LC) of CRS/HIPEC in our high-volume institution. A total of 370 patients with PC from mucinous appendiceal neoplasms (MAN = 282), malignant peritoneal mesothelioma (MPM = 60), and gastric cancer (GC = 24) were studied. Outcomes analyzed included incomplete cytoreduction (IC), severe morbidity (SM), 60-day mortality, progression-free survival (PFS), and overall survival (OS). Risk-adjusted sequential probability ratio test (RA-SPRT) was employed to assess the LC of CRS/HIPEC for IC and SM using prespecified odds ratio (OR) boundaries derived from previously published data. Risk adjusted-cumulative average probability (RA-CAP) was used to analyze 1-year PFS and 2-year OS. Complete cytoreduction, severe morbidity, and 60-day mortality were 84.2, 30, and 1.9 % respectively. Higher simplified peritoneal cancer index was the major independent risk factor for IC, whereas high-grade histology, IC, and diagnosis of MPM and GC (compared with MAN) were predictors of SM after CRS/HIPEC (p < 0.05). RA-SPRT showed that approximately 180 cases are needed to achieve the lowest risk of IC and SM. Ninety cases were needed to achieve a steady 1-year PFS and 2-year OS in RA-CAP plots. The completeness of cytoreduction, morbidity, and mortality rates for CRS/HIPEC at our institution are comparable to previously reported data. Approximately 180 and 90 procedures are required to improve operative and oncologic outcomes respectively.

Polyamidoamine dendrimers-capped carbon dots/Au nanocrystal nanocomposites and its application for electrochemical immunosensor.

PubMed

Gao, Qi; Han, Jingman; Ma, Zhanfang

2013-11-15

In this work, polyamidoamine dendrimers capped-carbon dots (PAMAM-CDs) were fabricated by one-step microwave assisted pyrolysis of citric acid (CA) and PAMAM, where the formation of CDs and the surface passivation were accomplished simultaneously. The obtained graphitic PAMAM-CDs, with abundant amine groups, were employed as reducing and capping agents for the formation of PAMAM-CDs/Au nanocrystal nanocomposites. The resulting nanocomposites exhibited excellent conductivity, stability and biocompatibility on the surface of electrode and were designed as an immobilized matrix for sensitive immunosensing of alpha-fetoprotein (AFP). The proposed immunosensor showed a wide linear detection range from 100 fg mL(-1) to 100 ng mL(-1). The detection limit for AFP was 0.025 pg mL(-1). Importantly, the immunosensor was evaluated for the analysis of clinical serum samples, obtaining a good correlation with enzyme-linked immunosorbent assay (ELISA). The results indicated that the immunosensor provided a possible application for the detection of AFP in clinical diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

South Polar Polygons

NASA Technical Reports Server (NTRS)

2005-01-01

4 July 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a polgyon-cracked surface, into which deep, somewhat kidney-bean-shaped pits have formed. These are landscapes of the martian south polar residual cap. This view was captured during May 2005.

Location near: 86.9oS, 5.1oW Image width: 1.5 km (0.9 mi) Illumination from: upper left Season Southern Spring

A Rb1 promoter variant with reduced activity contributes to osteosarcoma susceptibility in irradiated mice

PubMed Central

2014-01-01

Background Syndromic forms of osteosarcoma (OS) account for less than 10% of all recorded cases of this malignancy. An individual OS predisposition is also possible by the inheritance of low penetrance alleles of tumor susceptibility genes, usually without evidence of a syndromic condition. Genetic variants involved in such a non-syndromic form of tumor predisposition are difficult to identify, given the low incidence of osteosarcoma cases and the genetic heterogeneity of patients. We recently mapped a major OS susceptibility QTL to mouse chromosome 14 by comparing alpha-radiation induced osteosarcoma in mouse strains which differ in their tumor susceptibility. Methods Tumor-specific allelic losses in murine osteosacoma were mapped along chromosome 14 using microsatellite markers and SNP allelotyping. Candidate gene search in the mapped interval was refined using PosMed data mining and mRNA expression analysis in normal osteoblasts. A strain-specific promoter variant in Rb1 was tested for its influence on mRNA expression using reporter assay. Results A common Rb1 allele derived from the BALB/cHeNhg strain was identified as the major determinant of radiation-induced OS risk at this locus. Increased OS-risk is linked with a hexanucleotide deletion in the promoter region which is predicted to change WT1 and SP1 transcription factor-binding sites. Both in-vitro reporter and in-vivo expression assays confirmed an approx. 1.5 fold reduced gene expression by this promoter variant. Concordantly, the 50% reduction in Rb1 expression in mice bearing a conditional hemizygous Rb1 deletion causes a significant rise of OS incidence following alpha-irradiation. Conclusion This is the first experimental demonstration of a functional and genetic link between reduced Rb1 expression from a common promoter variant and increased tumor risk after radiation exposure. We propose that a reduced Rb1 expression by common variants in regulatory regions can modify the risk for a malignant transformation of bone cells after radiation exposure. PMID:25092376

Validation of the French version of the Child Post-Traumatic Stress Reaction Index: psychometric properties in French speaking school-aged children.

PubMed

Olliac, Bertrand; Birmes, Philippe; Bui, Eric; Allenou, Charlotte; Brunet, Alain; Claudet, Isabelle; Sales de Gauzy, Jérôme; Grandjean, Hélène; Raynaud, Jean-Philippe

2014-01-01

Although the reliable and valid Child Post-Traumatic Stress Reaction Index (CPTS-RI) is a widely used measure of posttraumatic stress disorder (PTSD) symptoms in children, it has not been validated in French-speaking populations. The present study aims to assess the psychometric properties of the CPTS-RI in three samples of French-speaking school-children. Data was obtained from three samples. Sample 1 was composed of 106 children (mean (SD) age = 11.7(0.7), 50% females) victims of an industrial disaster. Sample 2 was composed of 50 children (mean (SD) age = 10.8(2.6), 44% females) who had received an orthopaedic surgical procedure after an accident. Sample 3 was composed of 106 children (mean (SD) age = 11.7(2.2), 44% females) admitted to an emergency department after a road traffic accident. We tested internal consistency using Cronbach's alpha. We examined test-retest reliability using intraclass correlation coefficient. In order to assess the convergent validity of the French version of the CPTS-RI and the Clinician Administered PTS Scale-Child and Adolescent (CAPS-CA), spearman-correlation coefficient was computed. To verify the validity of the cut-off scores, a ROC curve was constructed which evaluated the sensitivity and specificity of each score compared to the diagnosis with the CAPS-CA. We also used principal components analysis with varimax rotation to study the structure of the French version of the CPTS-RI. Cronbach's alpha coefficient was 0.87 for the French version of the CPTS-RI. Two-week test-retest intraclass correlation coefficient (n = 30) was 0.67. The French version of the CPTS-RI was well correlated with the CAPS-CA (r = 0.76, p < 0.001). Taking the CAPS-CA as the diagnostic reference, with a diagnostic cut-off of >24 for the CPTS-RI, the sensitivity and specificities were 100% and 62.6%, respectively. The French version of the CPTS-RI demonstrated a three-factor structure. The CPTS-RI is reliable and valid in French-speaking children.

Introduction of potential helix-capping residues into an engineered helical protein.

PubMed

Parker, M H; Hefford, M A

1998-08-01

MB-1 is an engineered protein that was designed to incorporate high percentages of four amino acid residues and to fold into a four-alpha-helix bundle motif. Mutations were made in the putative loop I and III regions of this protein with the aim of increasing the stability of the helix ends. Four variants, MB-3, MB-5, MB-11 and MB-13, have replacements intended to promote formation of an 'N-capping box'. The loop I and III sequences of MB-3 (both GDLST) and MB-11 (GGDST) were designed to cause alphaL C-terminal 'capping' motifs to form in helices I and III. MB-5 has a sequence, GPDST, that places proline in a favourable position for forming beta-turns, whereas MB-13 (GLDST) has the potential to form Schellman C-capping motifs. Size-exclusion chromatography suggested that MB-1, MB-3, MB-5, MB-11 and MB-13 all form dimers, or possibly trimers. Free energies for the unfolding of each of these variants were determined by urea denaturation, with the loss of secondary structure followed by CD spectroscopy. Assuming an equilibrium between folded dimer and unfolded monomer, MB-13 had the highest apparent stability (40.5 kJ/mol, with +/-2.5 kJ/mol 95% confidence limits), followed by MB-11 (39.3+/-5.9 kJ/mol), MB-3 (36.4+/-1.7 kJ/mol), MB-5 (34.7+/-2.1 kJ/mol) and MB-1 (29.3+/-1.3 kJ/mol); the same relative stabilities of the variants were found when a folded trimer to unfolded monomer model was used to calculate stabilities. All of the variants were relatively unstable for dimeric proteins, but were significantly more stable than MB-1. These findings suggest that it might be possible to increase the stability of a protein for which the three-dimensional structure is unknown by placing amino acid residues in positions that have the potential to form helix- and turn-stabilizing motifs.

All-night EEG power spectral analysis of the cyclic alternating pattern components in young adult subjects.

PubMed

Ferri, Raffaele; Bruni, Oliviero; Miano, Silvia; Plazzi, Giuseppe; Terzano, Mario G

2005-10-01

To analyze in detail the frequency content of the different EEG components of the Cyclic Alternating Pattern (CAP), taking into account the ongoing EEG background and the nonCAP (NCAP) periods in the whole night polysomnographic recordings of normal young adults. Sixteen normal healthy subjects were included in this study. Each subject underwent one polysomnographic night recording; sleep stages were scored following standard criteria. Subsequently, each CAP A phase was detected in all recordings, during NREM sleep, and classified into 3 subtypes (A1, A2, and A3). The same channel used for the detection of CAP A phases (C3/A2 or C4/A1) was subdivided into 2-s mini-epochs. For each mini-epoch, the corresponding CAP condition was determined and power spectra calculated in the frequency range 0.5-25 Hz. Average spectra were obtained for each CAP condition, separately in sleep stage 2 and SWS, for each subject. Finally, the first 6h of sleep were subdivided into 4 periods of 90 min each and the same spectral analysis was performed for each period. During sleep stage 2, CAP A subtypes differed from NCAP periods for all frequency bins between 0.5 and 25 Hz; this difference was most evident for the lowest frequencies. The B phase following A1 subtypes had a power spectrum significantly higher than that of NCAP, for frequencies between 1 and 11 Hz. The B phase after A2 only differed from NCAP for a small but significant reduction in the sigma band power; this was evident also after A3 subtypes. During SWS, we found similar results. The comparison between the different CAP subtypes also disclosed significant differences related to the stage in which they occurred. Finally, a significant effect of the different sleep periods was found on the different CAP subtypes during sleep stage 2 and on NCAP in both sleep stage 2 and SWS. CAP subtypes are characterized by clearly different spectra and also the same subtype shows a different power spectrum, during sleep stage 2 or SWS. This finding underlines a probable different functional meaning of the same CAP subtype during different sleep stages. We also found 3 clear peaks of difference between CAP subtypes and NCAP in the delta, alpha, and beta frequency ranges which might indicate the presence of 3 frequency components characterizing CAP subtypes, in different proportion in each of them. The B component of CAP differs from NCAP because of a decrease in power in the sigma frequency range. This study shows that A components of CAP might correspond to periods in which the very-slow delta activity of sleep groups a range of different EEG activities, including the sigma and beta bands, while the B phase of CAP might correspond to a period in which this activity is quiescent or inhibited.

Mars South Polar Cap 'Fingerprint' Terrain

NASA Technical Reports Server (NTRS)

2000-01-01

This picture is illuminated by sunlight from the upper left.

Some portions of the martian south polar residual cap have long, somewhat curved troughs instead of circular pits. These appear to form in a layer of material that may be different than that in which 'swiss cheese' circles and pits form, and none of these features has any analog in the north polar cap or elsewhere on Mars. This picture shows the 'fingerprint' terrain as a series of long, narrow depressions considered to have formed by collapse and widening by sublimation of ice. Unlike the north polar cap, the south polar region stays cold enough in summer to retain frozen carbon dioxide. Viking Orbiter observations during the late 1970s showed that very little water vapor comes off the south polar cap during summer, indicating that any frozen water that might be there remains solid throughout the year.

This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image was obtained in early southern spring on August 4, 1999. It shows an area 3 x 5 kilometers (1.9 x 3.1 miles) at a resolution of about 7.3 meters (24 ft) per pixel. Located near 86.0oS, 53.9oW.

Malin Space Science Systems and the California Institute of Technology built the MOC using spare hardware from the Mars Observer mission. MSSS operates the camera from its facilities in San Diego, CA. The Jet Propulsion Laboratory's Mars Surveyor Operations Project operates the Mars Global Surveyor spacecraft with its industrial partner, Lockheed Martin Astronautics, from facilities in Pasadena, CA and Denver, CO.

Mechanism of the lysosomal membrane enzyme acetyl coenzyme A: alpha-glucosaminide N-acetyltransferase

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

Bame, K.J.

1986-01-01

Acetyl-CoA:..cap alpha..-glucosaminide N-acetyltransferase is a lysosomal membrane enzyme, deficient in the genetic disease Sanfilippo C syndrome. The enzyme catalyzes the transfer of an acetyl group from cytoplasmic acetyl-CoA to terminal ..cap alpha..-glucosamine residues of heparan sulfate within the organelle. The reaction mechanism was examined using high purified lysosomal membranes from rat liver and human fibroblasts. The N-acetyltransferase reaction is optimal above pH 5.5 and a 2-3 fold stimulation of activity is observed in the presence of 0.1% taurodeoxycholate. Double reciprocal analysis and product inhibition studies indicate that the enzyme works by a Di-Iso Ping Pong Bi Bi mechanism. The bindingmore » of acetyl-CoA to the enzyme is measured by exchange label from (/sup 3/H)CoA to acetyl-CoA, and is optimal at pH's above 7.0. The acetyl-enzyme intermediate is formed by incubating membranes with (/sup 3/H)acetyl-CoA. The acetyl group can be transferred to glucosamine, forming (/sup 3/H)N-acetylglucosamine; the transfer is optimal between pH 4 and 5. Lysosomal membranes from Sanfilippo C fibroblasts confirm that these half reactions carried out by the N-acetyltransferase. The enzyme is inactivated by N-bromosuccinimide and diethylpyrocarbonate, indicating that a histidine is involved in the reaction. These results suggest that the histidine residue is at the active site of the enzyme. The properties of the N-acetyltransferase in the membrane, the characterization of the enzyme kinetics, the chemistry of a histidine mediated acetylation and the pH difference across the lysosomal membrane all support a transmembrane acetylation mechanism.« less

CheckMate 141: 1-Year Update and Subgroup Analysis of Nivolumab as First-Line Therapy in Patients with Recurrent/Metastatic Head and Neck Cancer.

PubMed

Gillison, Maura L; Blumenschein, George; Fayette, Jerome; Guigay, Joel; Colevas, A Dimitrios; Licitra, Lisa; Harrington, Kevin J; Kasper, Stefan; Vokes, Everett E; Even, Caroline; Worden, Francis; Saba, Nabil F; Iglesias Docampo, Lara Carmen; Haddad, Robert; Rordorf, Tamara; Kiyota, Naomi; Tahara, Makoto; Monga, Manish; Lynch, Mark; Li, Li; Ferris, Robert L

2018-06-04

Nivolumab significantly improved overall survival (OS) vs investigator's choice (IC) of chemotherapy at the primary analysis of randomized, open-label, phase 3 CheckMate 141 in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). Here, we report that OS benefit with nivolumab was maintained at a minimum follow-up of 11.4 months. Further, OS benefit with nivolumab vs IC was also noted among patients who received first-line treatment for R/M SCCHN after progressing on platinum therapy for locally advanced disease in the adjuvant or primary (i.e., with radiation) setting. The Oncologist 2018. © AlphaMed Press 2018.

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

Hawkins, C.A.

Tests of QED to order ..cap alpha../sup 4/ performed with the ASP detector at PEP are presented. Measurements have been made of exclusive e/sup +/e/sup -/e/sup +/e/sup -/, e/sup +/e/sup -/..gamma gamma.. and ..gamma gamma gamma gamma.. final states with all particles above 50 milliradians with respect to the e/sup +/e/sup -/ beam line. These measurements represent a significant increase in statistics over previous measurements. All measurements agree well with theoretical predictions. 5 refs., 1 tab.

Multiple-Purpose Project, Kansas River Basin, Republican River, Kansas, Milford Lake Operation and Maintenance Manual. Appendix IV. Construction Foundation Report. Revision.

DTIC Science & Technology

1983-10-01

NUMBERS oundaton and Materia s Branch (MKED-F) PB-2b and Konsas Rity Dlstrict Corps Q neers ER 1110-1-1801, Change 2, 601 E. 12th Street, kansa City...34 ,A M’LFORD DA BLASTING RECORD TABLE 2 I3ALA’N CRLS DELA PRIMA ONV 04W b 0 r C L,- A NIA A . A A A . 4 AACOR-.ESULT NETTOORERAA.uALL2AAO4 48...,,e...4 to 6 X to I-os 55 0 2 SIX) MILFORD AM BLASTING RECORD - TABLE 4 LOADING CAPS DELAYS PRIMA BPYC u OS U .Oo 0 0 2 A N 1R.0.p’ot LIR tO I I 2 3 4 S

Binding Linkage in a Telomere DNA–Protein Complex at the Ends of Oxytricha nova Chromosomes

PubMed Central

Buczek, Pawel; Orr, Rochelle S.; Pyper, Sean R.; Shum, Mili; Ota, Emily Kimmel Irene; Gerum, Shawn E.; Horvath, Martin P.

2005-01-01

Alpha and beta protein subunits of the telomere end binding protein from Oxytricha nova (OnTEBP) combine with telomere single strand DNA to form a protective cap at the ends of chromosomes. We tested how protein–protein interactions seen in the co-crystal structure relate to DNA binding through use of fusion proteins engineered as different combinations of domains and subunits derived from OnTEBP. Joining alpha and beta resulted in a protein that bound single strand telomere DNA with high affinity (KD-DNA=1.4 nM). Another fusion protein, constructed without the C-terminal protein–protein interaction domain of alpha, bound DNA with 200-fold diminished affinity (KD-DNA=290 nM) even though the DNA-binding domains of alpha and beta were joined through a peptide linker. Adding back the alpha C-terminal domain as a separate protein restored high-affinity DNA binding. The binding behaviors of these fusion proteins and the native protein subunits are consistent with cooperative linkage between protein-association and DNA-binding equilibria. Linking DNA–protein stability to protein–protein contacts at a remote site may provide a trigger point for DNA–protein disassembly during telomere replication when the single strand telomere DNA must exchange between a very stable OnTEBP complex and telomerase. PMID:15967465

Incomplete Puzzle

NASA Technical Reports Server (NTRS)

2006-01-01

15 April 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a mid-summer view of a portion of the south polar residual cap of Mars. The large, relatively flat-lying, puzzle-like pieces in this scene are mesas composed largely of solid carbon dioxide.

Location near: 85.5oS, 76.8oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Summer

No evidence of extraterrestrial noble metal and helium anomalies at Marinoan glacial termination

NASA Astrophysics Data System (ADS)

Peucker-Ehrenbrink, Bernhard; Waters, Christine A.; Kurz, Mark D.; Hoffman, Paul F.

2016-03-01

High concentrations of extraterrestrial iridium have been reported in terminal Sturtian and Marinoan glacial marine sediments and are used to argue for long (likely 3-12 Myr) durations of these Cryogenian glaciations. Reanalysis of the Marinoan sedimentary rocks used in the original study, supplemented by sedimentary rocks from additional terminal Marinoan sections, however, does not confirm the initial report. New platinum group element concentrations, and 187Os/188Os and 3He/4He signatures are consistent with crustal origin and minimal extraterrestrial contributions. The discrepancy is likely caused by different sample masses used in the two studies, with this study being based on much larger samples that better capture the stochastic distribution of extraterrestrial particles in marine sediments. Strong enrichment of redox-sensitive elements, particularly rhenium, up-section in the basal postglacial cap carbonates, may indicate a return to more fully oxygenated seawater in the aftermath of the Marinoan snowball earth. Sections dominated by hydrogenous osmium indicate increasing submarine hydrothermal sources and/or continental inputs that are increasingly dominated by young mantle-derived rocks after deglaciation. Sedimentation rate estimates for the basal cap carbonates yield surprisingly slow rates of a few centimeters per thousand years. This study highlights the importance of using sedimentary rock samples that represent sufficiently large area-time products to properly sample extraterrestrial particles representatively, and demonstrates the value of using multiple tracers of extraterrestrial matter.

Generation of human induced pluripotent stem cells using non-synthetic mRNA.

PubMed

Rohani, L; Fabian, C; Holland, H; Naaldijk, Y; Dressel, R; Löffler-Wirth, H; Binder, H; Arnold, A; Stolzing, A

2016-05-01

Here we describe some of the crucial steps to generate induced pluripotent stem cells (iPSCs) using mRNA transfection. Our approach uses a V. virus-derived capping enzyme instead of a cap-analog, ensuring 100% proper cap orientation for in vitro transcribed mRNA. V. virus' 2'-O-Methyltransferase enzyme creates a cap1 structure found in higher eukaryotes and has higher translation efficiency compared to other methods. Use of the polymeric transfection reagent polyethylenimine proved superior to other transfection methods. The mRNA created via this method did not trigger an intracellular immune response via human IFN-gamma (hIFN-γ) or alpha (hIFN-α) release, thus circumventing the use of suppressors. Resulting mRNA and protein were expressed at high levels for over 48h, thus obviating daily transfections. Using this method, we demonstrated swift activation of pluripotency associated genes in human fibroblasts. Low oxygen conditions further facilitated colony formation. Differentiation into different germ layers was confirmed via teratoma assay. Reprogramming with non-synthetic mRNA holds great promise for safe generation of iPSCs of human origin. Using the protocols described herein we hope to make this method more accessible to other groups as a fast, inexpensive, and non-viral reprogramming approach. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Comparison of U.S. Environmental Protection Agency's CAP88 PC Versions 3.0 and 4.0.

PubMed

Jannik, Tim; Farfan, Eduardo B; Dixon, Ken; Newton, Joseph; Sailors, Christopher; Johnson, Levi; Moore, Kelsey; Stahman, Richard

2015-08-01

The Savannah River National Laboratory (SRNL) with the assistance of Georgia Regents University, completed a comparison of the U.S. Environmental Protection Agency's (U.S. EPA) environmental dosimetry code CAP88 PC V3.0 with the recently developed V4.0. CAP88 is a set of computer programs and databases used for estimation of dose and risk from radionuclide emissions to air. At the U.S. Department of Energy's Savannah River Site, CAP88 is used by SRNL for determining compliance with U.S. EPA's National Emission Standards for Hazardous Air Pollutants (40 CFR 61, Subpart H) regulations. Using standardized input parameters, individual runs were conducted for each radionuclide within its corresponding database. Some radioactive decay constants, human usage parameters, and dose coefficients changed between the two versions, directly causing a proportional change in the total effective dose. A detailed summary for select radionuclides of concern at the Savannah River Site (60Co, 137Cs, 3H, 129I, 239Pu, and 90Sr) is provided. In general, the total effective doses will decrease for alpha/beta emitters because of reduced inhalation and ingestion rates in V4.0. However, for gamma emitters, such as 60Co and 137Cs, the total effective doses will increase because of changes U.S. EPA made in the external ground shine calculations.

Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

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

Patterson, Edward I.; EH Graham Centre for Agricultural Innovation; Dombrovski, Andrew K.

2013-09-06

Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediatemore » nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface.« less

Quantitative analysis of sleep EEG microstructure in the time-frequency domain.

PubMed

De Carli, Fabrizio; Nobili, Lino; Beelke, Manolo; Watanabe, Tsuyoshi; Smerieri, Arianna; Parrino, Liborio; Terzano, Mario Giovanni; Ferrillo, Franco

2004-06-30

A number of phasic events influence sleep quality and sleep macrostructure. The detection of arousals and the analysis of cyclic alternating patterns (CAP) support the evaluation of sleep fragmentation and instability. Sixteen polygraphic overnight recordings were visually inspected for conventional Rechtscaffen and Kales scoring, while arousals were detected following the criteria of the American Sleep Disorders Association (ASDA). Three electroencephalograph (EEG) segments were associated to each event, corresponding to background activity, pre-arousal period and arousal. The study was supplemented by the analysis of time-frequency distribution of EEG within each subtype of phase A in the CAP. The arousals were characterized by the increase of alpha and beta power with regard to background. Within NREM sleep most of the arousals were preceded by a transient increase of delta power. The time-frequency evolution of the phase A of the CAP sequence showed a strong prevalence of delta activity during the whole A1, but high amplitude delta waves were found also in the first 2/3 s of A2 and A3, followed by desynchronization. Our results underline the strict relationship between the ASDA arousals, and the subtype A2 and A3 within the CAP: in both the association between a short sequence of transient slow waves and the successive increase of frequency and decrease of amplitude characterizes the arousal response.

Passive radon/thoron personal dosimeter using an electrostatic collector and a diffused-junction detector

NASA Astrophysics Data System (ADS)

Bigu, J.; Raz, R.

1985-01-01

A solid-state alpha dosimeter has been designed and tested suitable for personal and environmental radon/thoron monitoring. The dosimeter basically consists of an electrostatic collector and an alpha-particle counting system with spectroscopy capabilities. The sensitive volume (˜20 cm3) of the electrostatic collector consists of a cylindrically shaped metal wire screen and a diffused-junction silicon alpha-detector covered with a thin aluminized Mylar sheet. A dc voltage (˜500 V) is applied between the wire screen and the Mylar sheet, with the latter held at negative potential relative to the former. Data can be retrieved during or after sampling by means of a microcomputer (Epson HX20) via a RS-232 communication interface unit. The dosimeter has been calibrated in a large (26 m3) radon/thoron test facility. A linear relationship was found between the dosimeter's alpha-count and both radon gas concentration and radon daughter working level. The dosimeter is mounted on top of an ordinary miner's cap lamp battery and is ideally suited for personal monitoring in underground uranium mines and other working areas. The dosimeter presented here is a considerably improved version of an earlier prototype.

Prevalence of type I sensitization to alpha-gal in forest service employees and hunters.

PubMed

Fischer, J; Lupberger, E; Hebsaker, J; Blumenstock, G; Aichinger, E; Yazdi, A S; Reick, D; Oehme, R; Biedermann, T

2017-10-01

The production of IgE molecules specific to the carbohydrate galactose-α-1,3-galactose (alpha-gal) is known to induce delayed anaphylaxis against mammalian meat. Tick bites constitute the primary sensitization source, as ticks transfer alpha-gal in their saliva to a host during a bite. The reported prevalence of alpha-gal-specific IgE (alpha-gal-sIgE) positivity varies between different populations from diverse geographic regions. To investigate the prevalence of alpha-gal-sIgE positivity in a population of forest service employees who are highly exposed to ticks in comparison with a residential population and a historic sample. A cross-sectional study evaluating 300 forest service employees and hunters from southwest Germany was performed. Alpha-gal-sIgE levels were assessed by ImmunoCAP assay. The prevalence of alpha-gal-sIgE-positive individuals was compared with a matched cohort composed of a residential population and blood samples from forest service employees collected 15 years ago. In the study population, the prevalence of alpha-gal-sIgE-positive (≥0.10 kU A /L) individuals was 35.0%, whereas the prevalence of individuals with alpha-gal-sIgE levels ≥0.35 kU A /L was 19.3%. Alpha-gal-sIgE positivity was associated with total IgE levels and recent tick bites. Mammalian meat-induced delayed anaphylaxis was found in 8.6% of the participants with alpha-gal-sIgE levels ≥0.35 kU A /L. For forest service employees and hunters, the odds ratio for alpha-gal-sIgE positivity was 2.48 compared to the residential population. The prevalence of alpha-gal-sIgE positivity in the current and historic cohort was comparable. Forest service employees and hunters compose a population with a high prevalence of alpha-gal-sIgE positivity and carry a considerable risk of red meat allergy. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Revealing the X-Ray Emission Processes of Old Rotation-Powered Pulsars: XMM-Newton Observations of PSR B0950+08, PSR B0823+26 and PSR J2043+2740

NASA Technical Reports Server (NTRS)

Becker, Werner; Weisskopf, Martin C.; Tenant, Allyn F.; Jessmer, Axel; Zhang, Shiang N.

2004-01-01

We have completed part of a program to study the X-ray emission properties of old rotation-powered pulsars with XMM-Newton in order to probe and identify the origin of their X radiation. The X-ray emission from these old pulsars is largely dominated by non-thermal processes. None of the observed spectra required adding a thermal component consisting of either a hot polar cap or surface cooling emission to model the data. The energy spectrum of PSR B0950+08 is best described by a single power law of photon-index alpha = 1.93(sup +0.14)(sub -0.12). Three-sigma temperature upper limits for possible contributions from a heated polar cap or the whole neutron star surface are T(sup infinity)(sub pc) < 0.87 x 10(exp 6) K and T(sup infinity)(sub s) < 0.48 x 10(exp 6) K, respectively. We also find that the X-ray emission from PSR B0950+08 is pulsed with two peaks per rotation period. The phase separation between the two X-ray peaks is approx. 144 deg (maximum to maximum) which is similar to the pulse peak separation observed in the radio band at 1.4 GHz. The fraction of X-ray pulsed photons is approx. 30%. A phase resolved spectral analysis confirms the nonthermal nature of the pulsed emission and finds power law slopes of alpha = 2.4(sup +0.52)(sub -0.42) and alpha = 1.93(sup +0.29)(sub -0.24) for the pulse peaks P1 and P2, respectively. The spectral emission properties observed for PSR B0823+26 are similar to those of PSR B0950+08. Its energy spectrum is very well described by a single power law with photon-index alpha = 2.5(sup +0.52)(sub -0.24. Three-sigma temperature upper limits for thermal contributions from a hot polar cap or from the entire neutron star surface are T(sup infinity)(sub pc) < 1.17 x 10(exp 6) K and T(sup infinity)(sub s) < 0.5 x 10(exp 6) K, respectively. There is evidence for pulsed X-ray emission at the - 97% confidence level with a pulsed fraction of 49 +/- 22%. For PSR 52043+2740 we report the first detection of X-ray emission. A power law spectrum, or a combination of a thermal and a power law spectrum all yield acceptable descriptions of its X-ray spectrum. No X-ray pulses are detected from PSR J2043+2740 but the sensitivity is low - the 2-sigma pulsed fraction upper limit is 57% assuming a sinusoidal pulse profile.

Link between microstability and macrostability of plasmas

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

Litwin, C.

A mechanism linking high-frequency microinstabilities and the low-frequencymacrostability is proposed. The coupling is provided by the time-averagedforce, ponderomotive force, of unstable high-frequency waves. Two specificexamples of this phenomenon are discussed. It is shown that an..cap alpha..-particle loss-cone instability stabilizes the flute mode of anignited, axisymmetric mirror plasma. In tokamaks, the ion-whistler instability,driven by an anisotropic population of energetic particles, stabilizes theinternal kink mode for JET range of parameters.

Coupling ligand recognition to protein folding in an engineered variant of rabbit ileal lipid binding protein.

PubMed

Kouvatsos, Nikolaos; Meldrum, Jill K; Searle, Mark S; Thomas, Neil R

2006-11-28

We have engineered a variant of the beta-clam shell protein ILBP which lacks the alpha-helical motif that caps the central binding cavity; the mutant protein is sufficiently destabilised that it is unfolded under physiological conditions, however, it unexpectedly binds its natural bile acid substrates with high affinity forming a native-like beta-sheet rich structure and demonstrating strong thermodynamic coupling between ligand binding and protein folding.

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

Anderson, W.F.; Martinell, J.; Whitney, J.B. III

The group of diseases called the thalassemias is the largest single-gene health problem in the world according the World Health Organization. The thalassemias are lethal hereditary anemias in which the infants cannot make their own blood. Three mouse mutants are shown to be models of the human disease ..cap alpha..-thalassemia. However, since an additional gene is affected, these mutants represent a particularly severe condition in which death occurs in the homozygous embryo even before globin genes are activated. Phenotypic and genotypic characteristics are described. (ACR)

In-vivo measurement of lithium in the brain and other organs

DOEpatents

Vartsky, D.; Wielopolski, L.; LoMonte, A.F.; Ellis, K.J.; Cohn, S.H.

1983-08-26

An in-vivo method of measurement of the amount of lithium present in tissue and organs of breathing animals is described. The basis for the technique is the lithium-1 neutron interaction - /sup 6/Li(n,..cap alpha..)T. The lithium is irradiated with thermal neutrons to produce tritium atoms. The tritium diffuses into the tissues and is exhaled. By measuring the amount of tritium exhaled, the lithium concentration in the irradiated zone is determined.

Investigations in the ionosphere on Kosmos 378. VII. Simultaneous ground-based and satellite measurements of the parameters of the high latitude ionosphere

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

Afonin, V.V.; Gdalevich, G.L.; Gubskii, V.F.

1975-01-01

The parameters of the high-latitude ionospheric plasma at night were measured simultaneously in the winter of 1970 by Kosmos 378 and by the ground-based observatory at Noril'sk. A comparison of ground-based and satellite measurements showed good agreement of n/sub e/ when the Chapman approximation for the ..cap alpha..-layer and Jacchia's 1971 model of the upper atmosphere are used.

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

Akhtar, R.A.; Abdel-Latif, A.A.

Muscarinic cholinergic and ..cap alpha../sub 1/-adrenergic agonists provoke hydrolysis of PIP/sub 2/ into diacylglycerol (DG) and inositol trisphosphate (IP/sub 3/) in a wide variety of tissue. Recently, IP/sub 3/ has been shown to mobilize Ca/sup 2 +/ from ER in several permeabilized tissue preparations. Although rabbit cornea is enriched in ACh and NE, the physiological function of these neurotransmitters is unclear. The present studies were initiated to determine the effects of cholinergic and adrenergic agonists on PIP/sub 2/ turnover in the cornea. Addition of ACh or NE (50 ..mu..M each) to the /sup 32/P-labeled corneas for 10 min decreased themore » radioactivity in PIP/sub 2/ by 33 and 36%, and increased the radioactivity in phosphatidic acid by 72 and 52%, respectively. When the corneas were labeled with myo-(/sup 3/H)inositol, ACh and NE increased the accumulation of IP/sub 3/ by 92 and 48%, respectively. The effects of ACh and NE on phospholipid labeling and IP/sub 3/ accumulation were specifically inhibited by atropine (10 ..mu..M) and prazosin (10 ..mu..M), respectively. The data suggest the presence of muscarinic cholinergic and ..cap alpha../sub 1/-adrenergic receptors in the rabbit cornea. Furthermore, activation of these receptors leads to cleavage of PIP/sub 2/ into DG and IP/sub 3/ which may function as second messengers in this tissue.« less

Prevalence of. cap alpha. /sub 1/-antitrypsin heterozygotes (Pi MZ) in patients with obstructive pulmonary disease

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

Shigeoka, J.W.; Hall, W.J.; Hyde, R.W.

1976-01-01

An increased incidence of intermediate deficiency of serum ..cap alpha../sub 1/-antitrypsin resulting from Pi phenotype MZ has been reported in patients with chronic obstructive pulmonary disease (COPD) by some laboratories but not confirmed by others. Prevalence of Pi MZ was determined in patients with COPD among 502 subjects referred to a pulmonary function testing laboratory in a region with low concentrations of air pollutants. Control prevalences were obtained from 930 randomly selected subjects in the same community as well as from patients without COPD referred to the laboratory. Depending on criteria used to define COPD, 155 to 306 subjects hadmore » COPD. Pi MZ prevalence in subjects with COPD varied from 1.5 to 4 times the prevalence in the community control group and in the patients without COPD. This difference approached significance or was significant. Because Pi MZ was present in only 3.5 to 4.5% of patients with COPD, Pi MZ is not a major factor in the etiology of COPD in this community. The higher incidence of Pi MZ in patients with COPD reported by other investigators may be explained by small sample size, bias in selection of study or control population groups, or the development of COPD from interaction between Pi MZ and air pollutants or other factors not present in this community.« less

ROAM mutations causing increased expression of yeast genes: their activation by signals directed toward conjugation functions and their formation by insertion of tyl repetitive elements

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

Errede, B.; Cardillo, T.S.; Wever, G.

1980-01-01

Mechanisms available to eukaryotic organisms for the coordinate regulation of gene expression are being examined by genetic and biochemical characterization of an unusual mutation, CYC7-H2, which causes overproduction of iso-2-cytochrome c in the yeast Saccharomyces cerevisiae. The CYC7-H2 mutation causes approximately a twenty fold overproduction of iso-2-cytochrome c in haploid strains but only a one to four fold overproduction in MATa/MAT..cap alpha.. diploid strains. This regulation of overproduction has been characterized as a response to signals controlling conjugation in yeast. The CYC7-H2 mutation is closely related to other regulatory mutations occurring at the cargA, cargB and DUR1,2 loci which aremore » the structural genes for arginase, ornithine transaminase and urea amidolyase, respectively. Similar to the CYC7-H2 mutation, the mutations designated cargA/sup +/O/sup h/, cargB/sup +/O/sup h/ and durO/sup h/ cause constitutive production of their respective gene products at much lower levels in MATa/MAT..cap alpha.. diploid strains than in the corresponding haploid strains. Observations characterizing the regulation of overproduction in the CYC7-H2 mutant are presented with the additional and parallel observations for the O/sup h/ mutants.« less

Proteases induce secretion of collagenase and plasminogen activator by fibroblasts

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

Werb, Z.; Aggeler, J.

1978-04-01

We have observed that treatment of rabbit synovial fibroblasts with proteolytic enzymes can induce secretion of collagenase (EC 3.4.24.7) and plasminogen activator (EC 3.4.21.-). Cells treated for 2 to 24 hr with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin, or ..cap alpha..-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16 to 48 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10/sup 6/ cells per 24 hr) only when treatment produced decreased cell adhesion. Collagenase production did not depend on continuedmore » presence of proteolytic activity or on subsequent cell adhesion, spreading, or proliferation. Routine subculturing with crude trypsin also induced collagenase secretion by cells. Secretion of collagenase was prevented and normal spreading was obtained if the trypsinized cells were placed into medium containing fetal calf serum. Soybean trypsin inhibitor, ..cap alpha../sub 1/-antitrypsin, bovine serum albumin, collagen, and fibronectin did not inhibit collagenase production. Although proteases that induced collagenase secretion also removed surface glycoprotein, the kinetics of induction of cell protease secretion were different from those for removal of fibronectin. Physiological inducers of secretion of collagenase and plasminogen activator by cells have not been identified. These results suggest that extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells.« less

[Effect of TNF-alpha gene polymorphism on outcome of thalidomide-based regimens for multiple myeloma].

PubMed

DU, Juan; Yuan, Zhen-Gang; Zhang, Chun-Yang; Fu, Wei-Jun; Jiang, Hua; Chen, Bao-An; Hou, Jian

2009-10-01

To evaluate the effect of polymorphism at the -238 and -308 position of the TNF-alpha promotor region on the clinical outcome of thalidomide (Thal)-based regimens for the treatment of multiple myeloma (MM). The polymorphism at the -238 and -308 position of the TNF-alpha promotor region of 168 MM patients treated with Thal-based regimens were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotypes were tested for association with overall response by logistic regression, and survival was evaluated by univariate and multivariate analysis. In TNF-alpha -238 position, 11 (6.5%) patients had GA genotype and 1 (0.6%) AA genotype. In TNF-alpha -308 position, 19 (11.3%) had GA genotype and 1 (0.6%) AA genotype. In univariate analysis, the TNF-alpha -238 GA + AA genotypes were associated with a significantly prolonged progression free survival (PFS) (P = 0.017), and a better overall survival (OS) (P = 0.150). Multivariate COX regression analysis showed that TNF-alpha -238 polymorphic status was an independent prognostic factor for prolonged PFS (P = 0.049). The TNF-alpha -238 polymorphic status is associated with a favorable clinical outcome in MM patients treated with thalidomide-based regimen. The polymorphism status of TNF-alpha gene might be of promise for developing a more informative stratification system for MM.

South Polar Cap Erosion and Aprons

NASA Technical Reports Server (NTRS)

2000-01-01

This scene is illuminated by sunlight from the upper left.

While Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) images have shown that the north and south polar cap surfaces are very different from each other, one thing that the two have in common is that they both seem to have been eroded. Erosion in the north appears mostly to come in the form of pits from which ice probably sublimed to vapor and was transported away from the polar cap by wind. Erosion in the south takes on a wider range of possible processes that include collapse, slumping and mass-movement on slopes, and probably sublimation. Among the landforms created by these process on the south polar cap are the 'aprons' that surround mesas and buttes of remnant layers such as the two almost triangular features in the lower quarter of this image. The upper slopes of the two triangular features show a stair-stepped pattern that suggest these hills are layered.

This image shows part of the south polar residual cap near 86.9oS, 78.5oW, and covers an area approximately 1.2 by 1.0 kilometers (0.7 x 0.6 miles) in size. The image has a resolution of 2.2 meters per pixel. The picture was taken on September 11, 1999.

Malin Space Science Systems and the California Institute of Technology built the MOC using spare hardware from the Mars Observer mission. MSSS operates the camera from its facilities in San Diego, CA. The Jet Propulsion Laboratory's Mars Surveyor Operations Project operates the Mars Global Surveyor spacecraft with its industrial partner, Lockheed Martin Astronautics, from facilities in Pasadena, CA and Denver, CO.

Polar Landforms

NASA Technical Reports Server (NTRS)

2005-01-01

10 August 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows eroded remnants of carbon dioxide ice in the south polar residual cap of Mars. The scarps that outline each small mesa have retreated about 3 meters (10 feet) per Mars year since MGS began orbiting the red planet in 1997.

Location near: 87.0oS, 31.9oW Image width: width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Spring

Mirrors in the PDB: left-handed alpha-turns guide design with D-amino acids.

PubMed

Annavarapu, Srinivas; Nanda, Vikas

2009-09-22

Incorporating variable amino acid stereochemistry in molecular design has the potential to improve existing protein stability and create new topologies inaccessible to homochiral molecules. The Protein Data Bank has been a reliable, rich source of information on molecular interactions and their role in protein stability and structure. D-amino acids rarely occur naturally, making it difficult to infer general rules for how they would be tolerated in proteins through an analysis of existing protein structures. However, protein elements containing short left-handed turns and helices turn out to contain useful information. Molecular mechanisms used in proteins to stabilize left-handed elements by L-amino acids are structurally enantiomeric to potential synthetic strategies for stabilizing right-handed elements with D-amino acids. Propensities for amino acids to occur in contiguous alpha(L) helices correlate with published thermodynamic scales for incorporation of D-amino acids into alpha(R) helices. Two backbone rules for terminating a left-handed helix are found: an alpha(R) conformation is disfavored at the amino terminus, and a beta(R) conformation is disfavored at the carboxy terminus. Helix capping sidechain-backbone interactions are found which are unique to alpha(L) helices including an elevated propensity for L-Asn, and L-Thr at the amino terminus and L-Gln, L-Thr and L-Ser at the carboxy terminus. By examining left-handed alpha-turns containing L-amino acids, new interaction motifs for incorporating D-amino acids into right-handed alpha-helices are identified. These will provide a basis for de novo design of novel heterochiral protein folds.

Crystal Structure of the GRAS Domain of SCARECROW-LIKE7 in Oryza sativa

PubMed Central

Li, Shengping; Zhao, Yanhe; Zhao, Zheng; Wu, Xiuling; Sun, Lifang; Liu, Qingsong; Wu, Yunkun

2016-01-01

GRAS proteins belong to a plant-specific protein family with many members and play essential roles in plant growth and development, functioning primarily in transcriptional regulation. Proteins in the family are minimally defined as containing the conserved GRAS domain. Here, we determined the structure of the GRAS domain of Os-SCL7 from rice (Oryza sativa) to 1.82 Å. The structure includes cap and core subdomains and elucidates the features of the conserved GRAS LRI, VHIID, LRII, PFYRE, and SAW motifs. The structure is a dimer, with a clear groove to accommodate double-stranded DNA. Docking a DNA segment into the groove to generate an Os-SCL7/DNA complex provides insight into the DNA binding mechanism of GRAS proteins. Furthermore, the in vitro DNA binding property of Os-SCL7 and model-defined recognition residues are assessed by electrophoretic mobility shift analysis and mutagenesis assays. These studies reveal the structure and preliminary DNA interaction mechanisms of GRAS proteins and open the door to in-depth investigation and understanding of the individual pathways in which they play important roles. PMID:27081181

The OsSPL16-GW7 regulatory module determines grain shape and simultaneously improves rice yield and grain quality.

PubMed

Wang, Shaokui; Li, Shan; Liu, Qian; Wu, Kun; Zhang, Jianqing; Wang, Shuansuo; Wang, Yi; Chen, Xiangbin; Zhang, Yi; Gao, Caixia; Wang, Feng; Huang, Haixiang; Fu, Xiangdong

2015-08-01

The deployment of heterosis in the form of hybrid rice varieties has boosted grain yield, but grain quality improvement still remains a challenge. Here we show that a quantitative trait locus for rice grain quality, qGW7, reflects allelic variation of GW7, a gene encoding a TONNEAU1-recruiting motif protein with similarity to C-terminal motifs of the human centrosomal protein CAP350. Upregulation of GW7 expression was correlated with the production of more slender grains, as a result of increased cell division in the longitudinal direction and decreased cell division in the transverse direction. OsSPL16 (GW8), an SBP-domain transcription factor that regulates grain width, bound directly to the GW7 promoter and repressed its expression. The presence of a semidominant GW7(TFA) allele from tropical japonica rice was associated with higher grain quality without the yield penalty imposed by the Basmati gw8 allele. Manipulation of the OsSPL16-GW7 module thus represents a new strategy to simultaneously improve rice yield and grain quality.

Two-protein signature of novel serological markers apolipoprotein-A2 and serum amyloid alpha predicts prognosis in patients with metastatic renal cell cancer and improves the currently used prognostic survival models.

PubMed

Vermaat, J S; van der Tweel, I; Mehra, N; Sleijfer, S; Haanen, J B; Roodhart, J M; Engwegen, J Y; Korse, C M; Langenberg, M H; Kruit, W; Groenewegen, G; Giles, R H; Schellens, J H; Beijnen, J H; Voest, E E

2010-07-01

In metastatic renal cell cancer (mRCC), the Memorial Sloan-Kettering Cancer Center (MSKCC) risk model is widely used for clinical trial design and patient management. To improve prognostication, we applied proteomics to identify novel serological proteins associated with overall survival (OS). Sera from 114 mRCC patients were screened by surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF MS). Identified proteins were related to OS. Three proteins were subsequently validated with enzyme-linked immunosorbent assays and immunoturbidimetry. Prognostic models were statistically bootstrapped to correct for overestimation. SELDI-TOF MS detected 10 proteins associated with OS. Of these, apolipoprotein A2 (ApoA2), serum amyloid alpha (SAA) and transthyretin were validated for their association with OS (P = 5.5 x 10(-9), P = 1.1 x 10(-7) and P = 0.0004, respectively). Combining ApoA2 and SAA yielded a prognostic two-protein signature [Akaike's Information Criteria (AIC) = 732, P = 5.2 x 10(-7)]. Including previously identified prognostic factors, multivariable Cox regression analysis revealed ApoA2, SAA, lactate dehydrogenase, performance status and number of metastasis sites as independent factors for survival. Using these five factors, categorization of patients into three risk groups generated a novel protein-based model predicting patient prognosis (AIC = 713, P = 4.3 x 10(-11)) more robustly than the MSKCC model (AIC = 729, P = 1.3 x 10(-7)). Applying this protein-based model instead of the MSKCC model would have changed the risk group in 38% of the patients. Proteomics and subsequent validation yielded two novel prognostic markers and survival models which improved prediction of OS in mRCC patients over commonly used risk models. Implementation of these models has the potential to improve current risk stratification, although prospective validation will still be necessary.

A negative regulator encoded by a rice WRKY gene represses both abscisic acid and gibberellins signaling in aleurone cells.

PubMed

Zhang, Zhong-Lin; Shin, Margaret; Zou, Xiaolu; Huang, Jianzhi; Ho, Tun-hua David; Shen, Qingxi J

2009-05-01

Abscisic acid (ABA) and gibberellins (GAs) control several developmental processes including seed maturation, dormancy, and germination. The antagonism of these two hormones is well-documented. However, recent data from transcription profiling studies indicate that they can function as agonists in regulating the expression of many genes although the underlying mechanism is unclear. Here we report a rice WRKY gene, OsWRKY24, which encodes a protein that functions as a negative regulator of both GA and ABA signaling. Overexpression of OsWRKY24 via particle bombardment-mediated transient expression in aleurone cells represses the expression of two reporter constructs: the beta-glucuronidase gene driven by the GA-inducible Amy32b alpha-amylase promoter (Amy32b-GUS) and the ABA-inducible HVA22 promoter (HVA22-GUS). OsWRKY24 is unlikely a general repressor because it has little effect on the expression of the luciferase reporter gene driven by a constitutive ubiquitin promoter (UBI-Luciferase). As to the GA signaling, OsWRKY24 differs from OsWRKY51 and -71, two negative regulators specifically function in the GA signaling pathway, in several ways. First, OsWRKY24 contains two WRKY domains while OsWRKY51 and -71 have only one; both WRKY domains are essential for the full repressing activity of OsWRKY24. Second, binding of OsWRKY24 to the Amy32b promoter appears to involve sequences in addition to the TGAC cores of the W-boxes. Third, unlike OsWRKY71, OsWRKY24 is stable upon GA treatment. Together, these data demonstrate that OsWRKY24 is a novel type of transcriptional repressor that inhibits both GA and ABA signaling.

Comment on radiative magnetic energy shifts in hydrogen

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

Calmet, J.; Grotch, H.; Owen, D.A.

It is shown that the magnetic radiative energy shift derived from the relativistic-Lamb-shift expression of Erickson and Yennie reduces in the nonrelativistic limit to a formula given by Grotch and Hegstrom, which was derived starting from the nonrelativistic theory. This clears up a discrepancy between those two approaches. The corresponding correction to the g factor, which exists only for states with l not = 0, is estimated to be -0.24 ..cap alpha../sup 3/ for the 2P state of hydrogen.

Prognostic significance of an early decline in serum alpha-fetoprotein during chemotherapy for ovarian yolk sac tumors.

PubMed

de la Motte Rouge, Thibault; Pautier, Patricia; Genestie, Catherine; Rey, Annie; Gouy, Sébastien; Leary, Alexandra; Haie-Meder, Christine; Kerbrat, Pierre; Culine, Stéphane; Fizazi, Karim; Lhommé, Catherine

2016-09-01

The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact. This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively. Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73%-91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS. An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs. No conflict of interest. Copyright © 2016. Published by Elsevier Inc.

Hard Hitters!

ERIC Educational Resources Information Center

Dupont, Stephen

2000-01-01

Presents a selection of computers and peripherals designed to enhance the classroom. They include personal digital assistants (the AlphaSmart 30001R, CalcuScribe Duo, and DreamWriter IT); new Apple products (the iBook laptop, improved iMac, and OS 9 operating system); PC options (new Gateway and Compaq computers); and gadgets (imagiLab, the QX3…

ALPHACAL: A new user-friendly tool for the calibration of alpha-particle sources.

PubMed

Timón, A Fernández; Vargas, M Jurado; Gallardo, P Álvarez; Sánchez-Oro, J; Peralta, L

2018-05-01

In this work, we present and describe the program ALPHACAL, specifically developed for the calibration of alpha-particle sources. It is therefore more user-friendly and less time-consuming than multipurpose codes developed for a wide range of applications. The program is based on the recently developed code AlfaMC, which simulates specifically the transport of alpha particles. Both cylindrical and point sources mounted on the surface of polished backings can be simulated, as is the convention in experimental measurements of alpha-particle sources. In addition to the efficiency calculation and determination of the backscattering coefficient, some additional tools are available to the user, like the visualization of energy spectrum, use of energy cut-off or low-energy tail corrections. ALPHACAL has been implemented in C++ language using QT library, so it is available for Windows, MacOs and Linux platforms. It is free and can be provided under request to the authors. Copyright © 2018 Elsevier Ltd. All rights reserved.

[The primary structure of the alpha-amylase inhibitor Hoe 467A from Streptomyces tendae 4158. A new class of inhibitors].

PubMed

Aschauer, H; Vértesy, L; Nesemann, G; Braunitzer, G

1983-10-01

The native or modified alpha-amylase inhibitor Hoe 467A - isolated from the culture medium of Streptomyces tendae 4158 - and overlapping peptides were degraded by the automatic Edman technique. The oxidized or aminoethylated or oxidized and maleoylated inhibitor was digested with trypsin and the native inhibitor with pepsin. Further digestion with Staphylococcus aureus proteinase was also carried out. After peptic digestion two cystin peptides were isolated, which allowed the establishment of the disulfide bonds. The alpha-amylase inhibitor is a polypeptid consisting of 74 amino-acid residues with a molecular mass of 7958 Da. The inhibitor is composed of all naturally occurring amino acids except methionine and phenylalanine and shows no sequence homology to known inhibitors. The clinical and pharmacological importance in respect to the inhibitors ability for inactivation of human salivary and pancreatic alpha-amylase is discussed. Especially the proteinase resistance of the inhibitor enables a clinical application in human (e.g. Diabetes mellitus) per os.

HER2 Gene Amplification Testing by Fluorescent In Situ Hybridization (FISH): Comparison of the ASCO-College of American Pathologists Guidelines With FISH Scores Used for Enrollment in Breast Cancer International Research Group Clinical Trials

PubMed Central

Sauter, Guido; Buyse, Marc; Fourmanoir, Hélène; Quinaux, Emmanuel; Tsao-Wei, Denice D.; Eiermann, Wolfgang; Robert, Nicholas; Pienkowski, Tadeusz; Crown, John; Martin, Miguel; Valero, Vicente; Mackey, John R.; Bee, Valerie; Ma, Yanling; Villalobos, Ivonne; Campeau, Anaamika; Mirlacher, Martina; Lindsay, Mary-Ann; Slamon, Dennis J.

2016-01-01

Purpose ASCO and the College of American Pathologists (ASCO-CAP) recently recommended further changes to the evaluation of human epidermal growth factor receptor 2 gene (HER2) amplification by fluorescent in situ hybridization (FISH). We retrospectively assessed the impact of these new guidelines by using annotated Breast Cancer International Research Group (BCIRG) -005, BCIRG-006, and BCIRG-007 clinical trials data for which we have detailed outcomes. Patients and Methods The HER2 FISH status of BCIRG-005/006/007 patients with breast cancers was re-evaluated according to current ASCO-CAP guidelines, which designates five different groups according to HER2 FISH ratio and average HER2 gene copy number per tumor cell: group 1 (in situ hybridization [ISH]–positive): HER2-to-chromosome 17 centromere ratio ≥ 2.0, average HER2 copies ≥ 4.0; group 2 (ISH-positive): ratio ≥ 2.0, copies < 4.0; group 3 (ISH-positive): ratio < 2.0, copies ≥ 6.0; group 4 (ISH-equivocal): ratio < 2.0, copies ≥ 4.0 and < 6.0; and group 5 (ISH-negative): ratio < 2.0, copies < 4.0. We assessed correlations with HER2 protein, clinical outcomes by disease-free survival (DFS) and overall survival (OS) and benefit from trastuzumab therapy (hazard ratio [HR]). Results Among 10,468 patients with breast cancers who were successfully screened for trial entry, 40.8% were in ASCO-CAP ISH group 1, 0.7% in group 2; 0.5% in group 3, 4.1% in group 4, and 53.9% in group 5. Distributions were similar in screened compared with accrued subpopulations. Among accrued patients, FISH group 1 breast cancers were strongly correlated with immunohistochemistry 3+ status (P < .0001), whereas groups 2, 3, 4, and 5 were not; however, groups 2, 4 and, 5 were strongly correlated with immunohistochemistry 0/1+ status (all P < .0001), whereas group 3 was not. Among patients accrued to BCIRG-005, group 4 was not associated with significantly worse DFS or OS compared with group 5. Among patients accrued to BCIRG-006, only group 1 showed a significant benefit from trastuzumab therapy (DFS HR, 0.71; 95% CI, 0.60 to 0.83; P < .0001; OS HR, 0.69; 95% CI, 0.55 to 0.85; P = .0006), whereas group 2 did not. Conclusion Our findings support the original categorizations of HER2 by FISH status in BCIRG/Translational Research in Oncology trials. PMID:27573653

HER2 Gene Amplification Testing by Fluorescent In Situ Hybridization (FISH): Comparison of the ASCO-College of American Pathologists Guidelines With FISH Scores Used for Enrollment in Breast Cancer International Research Group Clinical Trials.

PubMed

Press, Michael F; Sauter, Guido; Buyse, Marc; Fourmanoir, Hélène; Quinaux, Emmanuel; Tsao-Wei, Denice D; Eiermann, Wolfgang; Robert, Nicholas; Pienkowski, Tadeusz; Crown, John; Martin, Miguel; Valero, Vicente; Mackey, John R; Bee, Valerie; Ma, Yanling; Villalobos, Ivonne; Campeau, Anaamika; Mirlacher, Martina; Lindsay, Mary-Ann; Slamon, Dennis J

2016-10-10

Purpose ASCO and the College of American Pathologists (ASCO-CAP) recently recommended further changes to the evaluation of human epidermal growth factor receptor 2 gene (HER2) amplification by fluorescent in situ hybridization (FISH). We retrospectively assessed the impact of these new guidelines by using annotated Breast Cancer International Research Group (BCIRG) -005, BCIRG-006, and BCIRG-007 clinical trials data for which we have detailed outcomes. Patients and Methods The HER2 FISH status of BCIRG-005/006/007 patients with breast cancers was re-evaluated according to current ASCO-CAP guidelines, which designates five different groups according to HER2 FISH ratio and average HER2 gene copy number per tumor cell: group 1 (in situ hybridization [ISH]-positive): HER2-to-chromosome 17 centromere ratio ≥ 2.0, average HER2 copies ≥ 4.0; group 2 (ISH-positive): ratio ≥ 2.0, copies < 4.0; group 3 (ISH-positive): ratio < 2.0, copies ≥ 6.0; group 4 (ISH-equivocal): ratio < 2.0, copies ≥ 4.0 and < 6.0; and group 5 (ISH-negative): ratio < 2.0, copies < 4.0. We assessed correlations with HER2 protein, clinical outcomes by disease-free survival (DFS) and overall survival (OS) and benefit from trastuzumab therapy (hazard ratio [HR]). Results Among 10,468 patients with breast cancers who were successfully screened for trial entry, 40.8% were in ASCO-CAP ISH group 1, 0.7% in group 2; 0.5% in group 3, 4.1% in group 4, and 53.9% in group 5. Distributions were similar in screened compared with accrued subpopulations. Among accrued patients, FISH group 1 breast cancers were strongly correlated with immunohistochemistry 3+ status (P < .0001), whereas groups 2, 3, 4, and 5 were not; however, groups 2, 4 and, 5 were strongly correlated with immunohistochemistry 0/1+ status (all P < .0001), whereas group 3 was not. Among patients accrued to BCIRG-005, group 4 was not associated with significantly worse DFS or OS compared with group 5. Among patients accrued to BCIRG-006, only group 1 showed a significant benefit from trastuzumab therapy (DFS HR, 0.71; 95% CI, 0.60 to 0.83; P < .0001; OS HR, 0.69; 95% CI, 0.55 to 0.85; P = .0006), whereas group 2 did not. Conclusion Our findings support the original categorizations of HER2 by FISH status in BCIRG/Translational Research in Oncology trials.

Fluids of the ocular surface: concepts, functions and physics.

PubMed

Cher, Ivan

2012-08-01

General adoption of the ocular surface (OS) concept has advanced the therapy of the external eye. Fresh physical findings have prompted new concepts; examples taken from each section of the text are: (i) ever-present lipid sealant bridges the palpebral fissure capping the three-dimensional 'OS' sac. The muco-aqueous pool (MAP) is thus enclosed, secluded from atmosphere, evaporation mitigated. Hence, the OS is conceptually, a compartment. The term 'dacruon' (otherwise 'tear film') has been coined for the combined fluids of the OS, viz. lipid film and MAP. (ii) Investigative techniques of physics yield data on (say) surface tension and viscosity, and on functions such as anchorage of dacruon base to the varied mucosae of the OS, lubrication, renovation of intermarginal fluid layers as the eye opens after each blink, and refinement of optics and vision by the fluids attached to the cornea. (iii) Physical events in the opening eye produce the unique 'black line' phenomenon in which capillary force induces subsurface flows into thirsty menisci, bringing about parameniscal dark grooves, pupil-ward of each meniscus. Attenuation of fluorescein in the shallowed fluid gaps behind each groove makes the dye appear unilluminated ('black lines') relative to adjacent full-thickness MAP fluid glowing under cobalt-blue illumination. Isolated from cornea by grooves and gaps, the meniscal fluid cannot pass freely over the cornea. It therefore streams through the menisci to nasolacrimal outflow. © 2012 The Author. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

Prebiotic syntheses of vitamin coenzymes: II. Pantoic acid, pantothenic acid, and the composition of coenzyme A

NASA Technical Reports Server (NTRS)

Miller, S. L.; Schlesinger, G.

1993-01-01

Pantoic acid can by synthesized in good prebiotic yield from isobutyraldehyde or alpha-ketoisovaleric acid + H2CO + HCN. Isobutyraldehyde is the Strecker precursor to valine and alpha-ketoisovaleric acid is the valine transamination product. Mg2+ and Ca2+ as well as several transition metals are catalysts for the alpha-ketoisovaleric acid reaction. Pantothenic acid is produced from pantoyl lactone (easily formed from pantoic acid) and the relatively high concentrations of beta-alanine that would be formed on drying prebiotic amino acid mixtures. There is no selectivity for this reaction over glycine, alanine, or gamma-amino butyric acid. The components of coenzyme A are discussed in terms of ease of prebiotic formation and stability and are shown to be plausible choices, but many other compounds are possible. The gamma-OH of pantoic acid needs to be capped to prevent decomposition of pantothenic acid. These results suggest that coenzyme A function was important in the earliest metabolic pathways and that the coenzyme A precursor contained most of the components of the present coenzyme.

Origin of ice-rafted debris: Pleistocene paleoceanography in the western Arctic Ocean

NASA Astrophysics Data System (ADS)

Bischof, Jens; Clark, David L.; Vincent, Jean-Serge

1996-12-01

The composition of Pleistocene ice-rafted debris (IRD) >250 µm was analyzed quantitatively by grain counting in five sediment cores from the western central Arctic Ocean and compared with the composition of till clasts from NW Canada in order to determine the dropstone origin and to reconstruct the Pleistocene ice driftways and surface currents. The IRD composition alternates repeatedly between carbonate- and quartz-dominated assemblages, along with metamorphic and igneous rocks, clastic rocks, and some chert. The highest quartz content is found on the Alpha Ridge, while carbonate percentages are highest on the Northwind Ridge (NWR) and the Chukchi Cap. The source for the carbonates is the area around Banks and Victoria Islands and parts of northern Canada. Quartz most likely originated from the central Queen Elizabeth Islands. IRD on the southeastern Alpha Ridge is dominated by mafic crystalline rocks from northern Ellesmere Island and northern Greenland. At least six major glacial intervals are identified within the last 1 million years, during which icebergs drifted toward the west in the Beaufort Sea, straight northward in the central Arctic Ocean, and northeastward on the SE Alpha Ridge.

Regulation of nicotinic acetylcholine receptor phosphorylation in rat myotubes by forskolin and cAMP

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

Miles, K.; Anthony, D.T.; Rubin, L.L.

1987-09-01

The nicotinic acetylcholine receptor (Ac-ChoR) from rat myotubes prelabeled in culture with (/sup 32/P)orthophosphate was isolated by acetylcholine affinity chromatography followed by immunoaffinity chromatography. Under basal conditions, the nicotinic AcChoR was shown to be phosphorylated in situ on the ..beta.. and delta subunits. Regulation of AcChoR phosphorylation by cAMP-dependent protein kinase was explored by the addition of forskolin or cAMP analogues to prelabeled cell cultures. Forskolin, an activator of adenylate cyclase, stimulated the phosphorylation of the delta subunit 20-fold over basal phosphorylation and induced phosphorylation of the ..cap alpha.. subunit. The effect of forskolin was dose dependent with a half-maximalmore » response at 8 ..mu..M in the presence of 35 ..mu..M Ro 20-1724, a phosphodiesterase inhibitor. Stimulation of delta subunit phosphorylation was almost maximal within 5 min, whereas stimulation of ..cap alpha.. subunit phosphorylation was not maximal until 45 min after forskolin treatment. Stimulation of AcChoR phosphorylation by 8-benzylthioadenosine 3',5'-cyclic monophosphate was identical to that obtained by forskolin. Two-dimensional thermolytic phosphopeptide maps of the delta subunit revealed a single major phosphopeptide. These results correlate closely with the observed effects of forskolin on AcChoR desensitization in muscle and suggest that cAMP-dependent phosphorylation of the delta subunit increases the rate of AcChoR desensitization in rat myotubes.« less

South Polar Depression

NASA Technical Reports Server (NTRS)

2005-01-01

14 August 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a circular depression and a suite of eroding mesas of carbon dioxide. These features occur in the south polar residual cap of Mars. The eroding carbon dioxide creates landforms reminiscent of 'Swiss cheese.' The circular feature might indicate the location of a filled, buried impact crater.

Location near: 86.8oS, 111.0oW Image width: width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Spring

Installing the Unix Starlink Software

NASA Astrophysics Data System (ADS)

Bly, M. J.

This note is the release note and installation instructions for the DEC Alpha AXP / Digital UNIX, Sun Sparc / Solaris v2.x, and Sun Sparc / SunOS 4.1.x versions of the Starlink Software Collection (USSC). You will be supplied with pre-built (and installed) versions on tape and will just need to copy the tape to disk to have a working version. The tapes (where appropriate) will contain in addition, copies of the NAG and MEMSYS libraries, and Tcl, Tk, Expect, Mosaic, TeX, Pine, Perl, Jed, Ispell, Ghostscript, LaXeX2html and Ftnchek for the relevant system. The Sun Sparc SunOS 4.1.x version of the USSC was frozen at USSC111 and no further updates are available. The instructions for installing the main section of the USSC may continue to be used for installing Sun Sparc SunOS 4.1.x version.

Occurrence of rhombic prisms in some structures

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

Nyman, H.

1976-02-01

An ideal rhombic prism is defined as two regular trigonal prisms sharing a square face. In terms of such rhombic prisms, the structures of CrB and ..cap alpha..-PdCl/sub 2/, U/sub 3/Si/sub 2/ and Au/sub 3/Zn, and CoCa/sub 3/ and PdS are easily described. A network of rhombic prisms, with cubic symmetry, is also used to describe the structures of CoAs/sub 3/, Sc(OH)/sub 3/, WAl/sub 12/, and NaMn/sub 7/O/sub 12/.

In vitro histamine H/sub 2/-antagonist activity of the novel compound HUK 978

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

Coombes, J.D.; Norris, D.B.; Rising, T.J.

1985-11-04

Histamine stimulated adenylate cyclase from guinea-pig fundic mucosa and /sup 3/H-tiotidine binding in guinea-pig cerebral cortex were used to assess the in-vitro histamine H/sub 2/-activity of the novel H/sub 2/-antagonist HUK 978. The results showed that HUK 978 was a more potent H/sub 2/-antagonist than either cimetidine or ranitidine. HUK 978 was also shown to be devoid of activity at the histamine H-/sub 1/-receptor, the muscarinic receptor and the ..cap alpha.. and ..beta..-adrenergic receptors.

[Cytochemical localization and properties of selected nucleolytic enzymes].

PubMed

Sierakowska, Halina

2015-01-01

In the article there are shortly outlined studies on cytochemical localization of selected nucleolytic enzymes carried out between 1957-1986 by David Shugar and his coworkers. The histochemical localization of several nucleolytic enzymes in animal and plant tissues was determined by synthesis of specific substrates, alpha-naphthyl esters of 5'- and 3'-nucleotides and their derivatives. In rat tissues phosphodiesterase I was localized in the plasma membrane whereas phosphodiesterase II in the lizosomes, reflecting their physiological roles. The localization of pancreatic type ribonuclease in animal tissues was determined, indicating its role in extracellular digestion. Plant nucleotide pyrophosphatase was localized in several tissues, purified to near homogeneity from potato tubers and its properties and substrate specificity were determined. Application of this enzyme for removal of m7GMP from the "cap" of eukaryotic mRNA allowed to elucidate the role of "cap" in mRNA binding to ribosomes in the process of translation. Furthermore, cyclic nucleotide phosphodiesterase was isolated from potato tubers and its physicochemical properties, oligomeric structure and substrate specificity were elucidated.

Optimized Design and Synthesis of Cell Permeable Biarsenical Cyanine Probe for Imaging Tagged Cytosolic Bacterial Proteins

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

Fu, Na; Xiong, Yijia; Squier, Thomas C.

2013-01-21

To optimize cellular delivery and specific labeling of tagged cytosolic proteins by biarsenical fluorescent probes build around a cyanine dye scaffold, we have systematically varied the polarity of the hydrophobic tails (i.e., 4-5 methylene groups appended by a sulfonate or methoxy ester moiety) and arsenic capping reagent (ethanedithiol versus benzenedithiol). Targeted labeling of the cytosolic proteins SlyD and the alpha subunit of RNA polymerase engineered with a tetracysteine tagging sequences demonstrate the utility of the newly synthesized probes for live-cell visualization, albeit with varying efficiencies and background intensities. Optimal routine labeling and visualization is apparent using the ethanedithiol capping reagentmore » with the uncharged methoxy ester functionalized acyl chains. These measurements demonstrate the general utility of this class of photostable and highly fluorescent biarsenical reagents based on the cyanine scaffold for in vivo targeting of tagged cellular proteins for live cell measurements of protein dynamics.« less

Proteomic Profile of Unstable Atheroma Plaque: Increased Neutrophil Defensin 1, Clusterin, and Apolipoprotein E Levels in Carotid Secretome.

PubMed

Aragonès, Gemma; Auguet, Teresa; Guiu-Jurado, Esther; Berlanga, Alba; Curriu, Marta; Martinez, Salomé; Alibalic, Ajla; Aguilar, Carmen; Hernández, Esteban; Camara, María-Luisa; Canela, Núria; Herrero, Pol; Ruyra, Xavier; Martín-Paredero, Vicente; Richart, Cristóbal

2016-03-04

Because of the clinical significance of carotid atherosclerosis, the search for novel biomarkers has become a priority. The aim of the present study was to compare the protein secretion profile of the carotid atherosclerotic plaque (CAP, n = 12) and nonatherosclerotic mammary artery (MA, n = 10) secretomes. We used a nontargeted proteomic approach that incorporated tandem immunoaffinity depletion, iTRAQ labeling, and nanoflow liquid chromatography coupled to high-resolution mass spectrometry. In total, 162 proteins were quantified, of which 25 showed statistically significant differences in secretome levels between carotid atherosclerotic plaque and nondiseased mammary artery. We found increased levels of neutrophil defensin 1, apolipoprotein E, clusterin, and zinc-alpha-2-glycoprotein in CAP secretomes. Results were validated by ELISA assays. Also, differentially secreted proteins are involved in pathways such as focal adhesion and leukocyte transendothelial migration. In conclusion, this study provides a subset of identified proteins that are differently expressed in secretomes of clinical significance.

Biological response to pre-mineralized starch based scaffolds for bone tissue engineering.

PubMed

Salgado, A J; Figueiredo, J E; Coutinho, O P; Reis, R L

2005-03-01

It is known that calcium-phosphate (Ca-P) coatings are able not only to improve the bone bonding behaviour of polymeric materials, but at the same time play a positive role on enhancing cell adhesion and inducing the differentiation of osteoprogenitor cells. Recently an innovative biomimetic methodology, in which a sodium silicate gel was used as a nucleative agent, was proposed as an alternative to the currently available biomimetic coating methodologies. This methodology is especially adequate for coating biodegradable porous scaffolds. In the present work we evaluated the influence of the referred to treatment on the mechanical properties of 50/50 (wt%) blend of corn starch/ethylene-vinyl alcohol (SEVA-C) based scaffolds. These Ca-P coated scaffolds presented a compressive modulus of 224.6 +/- 20.6 and a compressive strength of 24.2 +/- 2.20. Cytotoxicity evaluation was performed according ISO/EN 10993 part 5 guidelines and showed that the biomimetic treatment did not have any deleterious effect on L929 cells and did not inhibit cell growth. Direct contact assays were done by using a cell line of human osteoblast like cells (SaOS-2). 3 x 10(5) cells were seeded per scaffold and allowed to grow for two weeks at 37( composite function)C in a humidified atmosphere containing 5% CO(2). Total protein quantification and scanning electron microscopy (SEM) observation showed that cells were able to grow in the pre-mineralized scaffolds. Furthermore cell viability assays (MTS test) also show that cells remain viable after two weeks in culture. Finally, protein expression studies showed that after two weeks osteopontin and collagen type I were being expressed by SaOS-2 cells seeded on the pre-mineralized scaffolds. Moreover, alkaline phosphatase (ALP) activity was higher in the supernatants collected from the pre-mineralized samples, when compared to the control samples (non Ca-P coated). This may indicate that a faster mineralization of the ECM produced on the pre-mineralized samples was occurring. Consequently, biomimetic pre-mineralization of starch based scaffolds can be a useful route for applying these materials on bone tissue engineering.

In vivo optophysiology reveals that G-protein activation triggers osmotic swelling and increased light scattering of rod photoreceptors.

PubMed

Zhang, Pengfei; Zawadzki, Robert J; Goswami, Mayank; Nguyen, Phuong T; Yarov-Yarovoy, Vladimir; Burns, Marie E; Pugh, Edward N

2017-04-04

The light responses of rod and cone photoreceptors have been studied electrophysiologically for decades, largely with ex vivo approaches that disrupt the photoreceptors' subretinal microenvironment. Here we report the use of optical coherence tomography (OCT) to measure light-driven signals of rod photoreceptors in vivo. Visible light stimulation over a 200-fold intensity range caused correlated rod outer segment (OS) elongation and increased light scattering in wild-type mice, but not in mice lacking the rod G-protein alpha subunit, transducin (Gα t ), revealing these responses to be triggered by phototransduction. For stimuli that photoactivated one rhodopsin per Gα t the rod OS swelling response reached a saturated elongation of 10.0 ± 2.1%, at a maximum rate of 0.11% s -1 Analyzing swelling as osmotically driven water influx, we find the H 2 O membrane permeability of the rod OS to be (2.6 ± 0.4) × 10 -5 cm⋅s -1 , comparable to that of other cells lacking aquaporin expression. Application of Van't Hoff's law reveals that complete activation of phototransduction generates a potentially harmful 20% increase in OS osmotic pressure. The increased backscattering from the base of the OS is explained by a model combining cytoplasmic swelling, translocation of dissociated G-protein subunits from the disc membranes into the cytoplasm, and a relatively higher H 2 O permeability of nascent discs in the basal rod OS. Translocation of phototransduction components out of the OS may protect rods from osmotic stress, which could be especially harmful in disease conditions that affect rod OS structural integrity.

[Ocular Manifestation of Mucopolysaccharidosis I-S (Scheie's Syndrome)].

PubMed

Viestenz, Arne; Shin, Yoon S; Viestenz, Anja; Naumann, Gottfried O H

2002-10-01

Bilateral stromal corneal opacifications are a differential diagnostical challenge to identify associated systemic diseases. A 47-year old civil engineer (height 167 cm) with bilateral stromal corneal clouding presented with visual loss for the last 27 years: VA 20/100 OD and 20/50 OS (following penetrating keratoplasty OS). The cornea showed milky-whitish, cloudy, diffuse stromal deposits without a separate lipoid arc. The posterior segment showed tapetoretinal degeneration. Scotopic ERG was decreased. A suspicious stiffness of interphalangeal joints on both hands was observed. There was an aortic and mitral insufficiency grade I. Serum levels of LDL, HDL and triglycerides were normal. The biomicroscopical diagnosis of Scheie's syndrome (mucopolysaccharidosis I-S) was confirmed by a deficiency of alpha-L-iduronidase in leukocytes (0.02 nmol/min/mg protein, normal range: 0.3 - 1.5). The differential diagnosis of bilateral corneal stromal opacification includes in addition to the mucopolysaccharidoses HDL-deficiency diseases (LCAT deficiency, Tangier disease, Fish eye disease), Schnyder's crystalline stromal dystrophy, cystinosis, gout and mucolipidoses. MPS I-S may easily be detected by alpha-L-iduronidase deficiency in leukocytes and increased mucopolysaccharides in the urine. Furthermore, patients with MPS I-S need general medical care because of cardiovascular abnormalities, joint stiffness and myopathies.

Metabolism of ochratoxin A by rats.

PubMed Central

Støren, O; Holm, H; Størmer, F C

1982-01-01

Albino rats were given ochratoxin A (6.6 mg/kg body weight) intraperitoneally or per os. Independent of route administration, 6% of a given dose was excreted as the toxin, 1 to 1.5% as (4R)-4-hydroxyochratoxin A, and 25 to 27% as ochratoxin alpha in the urine. The metabolite (4S)-4-hydroxyochratoxin A, which is formed by rat liver microsomes in the presence of NADPH, was not detected. Only traces of ochratoxins A and alpha were found in feces. Identical experiments were carried out with brown rats, since the Km value for the formation of the 4S epimer was considerably lower when brown rat microsomes were used. About the same ratios of metabolites and metabolite recoveries as those found for albino rats were found for brown rats. Brown rats were also given the two hydroxylated metabolites and ochratoxin alpha (0.66 mg/kg body weight) intraperitoneally. The three compounds were excreted in the urine; within 48 h, 90% recovery of ochratoxin alpha and 54 and 35%, respectively, of the 4R and 4S isomers were observed. PMID:7149712

Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis.

PubMed

Clarke, Murray C H; Figg, Nichola; Maguire, Janet J; Davenport, Anthony P; Goddard, Martin; Littlewood, Trevor D; Bennett, Martin R

2006-09-01

Vascular smooth muscle cell (VSMC) apoptosis occurs in many arterial diseases, including aneurysm formation, angioplasty restenosis and atherosclerosis. Although VSMC apoptosis promotes vessel remodeling, coagulation and inflammation, its precise contribution to these diseases is unknown, given that apoptosis frequently accompanies vessel injury or alterations to flow. To study the direct consequences of VSMC apoptosis, we generated transgenic mice expressing the human diphtheria toxin receptor (hDTR, encoded by HBEGF) from a minimal Tagln (also known as SM22alpha) promoter. Despite apoptosis inducing loss of 50-70% of VSMCs, normal arteries showed no inflammation, reactive proliferation, thrombosis, remodeling or aneurysm formation. In contrast, VSMC apoptosis in atherosclerotic plaques of SM22alpha-hDTR Apoe-/- mice induced marked thinning of fibrous cap, loss of collagen and matrix, accumulation of cell debris and intense intimal inflammation. We conclude that VSMC apoptosis is 'silent' in normal arteries, which have a large capacity to withstand cell loss. In contrast, VSMC apoptosis alone is sufficient to induce features of plaque vulnerability in atherosclerosis. SM22alpha-hDTR Apoe-/- mice may represent an important new model to test agents proposed to stabilize atherosclerotic plaques.

A New Conjugation Method Used for the Development of an Immunoassay for the Detection of Amanitin, a Deadly Mushroom Toxin.

PubMed

Bever, Candace S; Barnych, Bogdan; Hnasko, Robert; Cheng, Luisa W; Stanker, Larry H

2018-06-28

One of the deadliest mushrooms is the death cap mushroom, Amanita phalloides . The most toxic constituent is α-amanitin, a bicyclic octapeptide, which damages the liver and kidneys. To develop a new tool for detecting this toxin, polyclonal antibodies were generated and characterized. Both α- and β-amanitin were coupled to carrier proteins through four different linking chemistries, one of which has never before been described. These conjugates were evaluated for their effectiveness in generating antibodies specific for the free toxin, as well as their utility in formatting heterogeneous assays with high sensitivity. Ultimately, these efforts yielded a newly described conjugation procedure utilizing periodate oxidation followed by reductive amination that successfully resulted in generating sensitive immunoassays (limit of detection (LOD), ~1.0 µg/L). The assays were characterized for their selectivity and were found to equally detect α-, β-, and γ-amanitin, and not cross-react with other toxins tested. Toxin detection in mushrooms was possible using a simple sample preparation method. This enzyme-linked immunosorbent assay (ELISA) is a simple and fast test, and readily detects amatoxins extracted from A. phalloides .

Auto-Assembling Detoxified Staphylococcus aureus Alpha-Hemolysin Mimicking the Wild-Type Cytolytic Toxin.

PubMed

Fiaschi, Luigi; Di Palo, Benedetta; Scarselli, Maria; Pozzi, Clarissa; Tomaszewski, Kelly; Galletti, Bruno; Nardi-Dei, Vincenzo; Arcidiacono, Letizia; Mishra, Ravi P N; Mori, Elena; Pallaoro, Michele; Falugi, Fabiana; Torre, Antonina; Fontana, Maria Rita; Soriani, Marco; Bubeck Wardenburg, Juliane; Grandi, Guido; Rappuoli, Rino; Ferlenghi, Ilaria; Bagnoli, Fabio

2016-06-01

Staphylococcus aureus alpha-hemolysin (Hla) assembles into heptameric pores on the host cell membrane, causing lysis, apoptosis, and junction disruption. Herein, we present the design of a newly engineered S. aureus alpha-toxin, HlaPSGS, which lacks the predicted membrane-spanning stem domain. This protein is able to form heptamers in aqueous solution in the absence of lipophilic substrata, and its structure, obtained by transmission electron microscopy and single-particle reconstruction analysis, resembles the cap of the wild-type cytolytic Hla pore. HlaPSGS was found to be impaired in binding to host cells and to its receptor ADAM10 and to lack hemolytic and cytotoxic activity. Immunological studies using human sera as well as sera from mice convalescent from S. aureus infection suggested that the heptameric conformation of HlaPSGS mimics epitopes exposed by the cytolytic Hla pore during infection. Finally, immunization with this newly engineered Hla generated high protective immunity against staphylococcal infection in mice. Overall, this study provides unprecedented data on the natural immune response against Hla and suggests that the heptameric HlaPSGS is a highly valuable vaccine candidate against S. aureus. Copyright © 2016 Fiaschi et al.

Auto-Assembling Detoxified Staphylococcus aureus Alpha-Hemolysin Mimicking the Wild-Type Cytolytic Toxin

PubMed Central

Fiaschi, Luigi; Di Palo, Benedetta; Scarselli, Maria; Pozzi, Clarissa; Tomaszewski, Kelly; Galletti, Bruno; Nardi-Dei, Vincenzo; Arcidiacono, Letizia; Mishra, Ravi P. N.; Mori, Elena; Pallaoro, Michele; Falugi, Fabiana; Torre, Antonina; Fontana, Maria Rita; Soriani, Marco; Bubeck Wardenburg, Juliane; Grandi, Guido; Rappuoli, Rino

2016-01-01

Staphylococcus aureus alpha-hemolysin (Hla) assembles into heptameric pores on the host cell membrane, causing lysis, apoptosis, and junction disruption. Herein, we present the design of a newly engineered S. aureus alpha-toxin, HlaPSGS, which lacks the predicted membrane-spanning stem domain. This protein is able to form heptamers in aqueous solution in the absence of lipophilic substrata, and its structure, obtained by transmission electron microscopy and single-particle reconstruction analysis, resembles the cap of the wild-type cytolytic Hla pore. HlaPSGS was found to be impaired in binding to host cells and to its receptor ADAM10 and to lack hemolytic and cytotoxic activity. Immunological studies using human sera as well as sera from mice convalescent from S. aureus infection suggested that the heptameric conformation of HlaPSGS mimics epitopes exposed by the cytolytic Hla pore during infection. Finally, immunization with this newly engineered Hla generated high protective immunity against staphylococcal infection in mice. Overall, this study provides unprecedented data on the natural immune response against Hla and suggests that the heptameric HlaPSGS is a highly valuable vaccine candidate against S. aureus. PMID:27030589

Clinical characteristics of hepatocellular carcinoma patients with normal serum alpha-fetoprotein level: A study of 112 consecutive cases.

PubMed

Li, Li; Chen, Jinglong; Xu, Weiran; Ding, Xiaosheng; Wang, Xiangyi; Liang, Jun

2017-10-26

Serum alpha-fetoprotein (AFP) level is normal in 30-40% of hepatocellular carcinoma (HCC) patients, and knowledge on its characteristics and clinical outcome is limited. The purpose of this observational study was to determine the clinical presentation, biological behavior and outcome of HCC patients with normal AFP level. Data of 112 consecutive HCC patients with normal AFP level were analyzed retrospectively. Statistical analysis including survival and factors associated with serum AFP level were performed by Kaplan-Meier method and t-test, respectively. Hepatitis B virus infection exited in 83.0% of all 112 HCC patients with normal AFP level. During a mean 52 ± 20 months (range 5-85 months) follow-up, the 1-, 2-, 3-year overall survival (OS) rate was 97.2%, 85.3% and 81.7%, respectively. The OS rates at 3 years stratified by stages at diagnosis were 100%, 96.2%, 85.7%, 11.1% and 0%, respectively for Barcelona Clinic Liver Cancer (BCLC) stage 0-D diseases. Significant difference in OS was observed among patients with BCLC stage 0-D diseases, P < 0.05. Using 8.78 ng/mL as the cut off value, serum AFP level elevated beyond normal figure during follow-up (AFP conversion) in 16 patients, which related with deterioration of liver function, quantitative changes of T helper cell subsets, rapid tumor progression and shorter survival. Patients with sustained normal AFP level had better survival than patients with AFP conversion, P < 0.05. There was significant difference between the time of diagnosis with HCC to serum AFP level elevation and the time of AFP elevation to death, P < 0.05. Prognosis of HCC patients with normal AFP level was relatively optimal. Serum AFP level elevation during follow-up was significantly associated with clinical outcome in terms of OS. © 2017 John Wiley & Sons Australia, Ltd.

Polar Polygon Patterns

NASA Technical Reports Server (NTRS)

2003-01-01

MGS MOC Release No. MOC2-338, 22 April 2003

This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image was taken during southern spring, as the seasonal carbon dioxide frost cap was subliming away. Frost remaining in shallow cracks and depressions reveals a fantastic polygonal pattern. Similar polygons occur in the Earth's arctic and antarctic regions-on Earth such polygons are related to the freeze and thaw of ground ice. The picture covers an area about 3 km (about 1.9 mi) wide near 71.9oS, 11.1oW. Sunlight illuminates the scene from the left.

Effect of capping and particle size on Raman laser-induced degradation of {gamma}-Fe{sub 2}O{sub 3} nanoparticles

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

Varadwaj, K.S.K.; Panigrahi, M.K.; Ghose, J.

2004-11-01

Diol capped {gamma}-Fe{sub 2}O{sub 3} nanoparticles are prepared from ferric nitrate by refluxing in 1,4-butanediol (9.5nm) and 1,5-pentanediol (15nm) and uncapped particles are prepared by refluxing in 1,2-propanediol followed by sintering the alkoxide formed. X-ray diffraction (XRD) shows that all the samples have the spinel phase. Raman spectroscopy shows that the samples prepared in 1,4-butanediol and 1,5-pentanediol and 1,2-propanediol (sintered at 573 and 673K) are {gamma}-Fe{sub 2}O{sub 3} and the 773K-sintered sample is Fe{sub 3}O{sub 4}. Raman laser studies carried out at various laser powers show that all the samples undergo laser-induced degradation to {alpha}-Fe{sub 2}O{sub 3} at higher lasermore » power. The capped samples are however, found more stable to degradation than the uncapped samples. The stability of {gamma}-Fe{sub 2}O{sub 3} sample with large particle size (15.4nm) is more than the sample with small particle size (10.2nm). Fe{sub 3}O{sub 4} having a particle size of 48nm is however less stable than the smaller {gamma}-Fe{sub 2}O{sub 3} nanoparticles.« less

Phase field models for heterogeneous nucleation: Application to inoculation in alpha-solidifying Ti-Al-B alloys

NASA Astrophysics Data System (ADS)

Apel, M.; Eiken, J.; Hecht, U.

2014-02-01

This paper aims at briefly reviewing phase field models applied to the simulation of heterogeneous nucleation and subsequent growth, with special emphasis on grain refinement by inoculation. The spherical cap and free growth model (e.g. A.L. Greer, et al., Acta Mater. 48, 2823 (2000)) has proven its applicability for different metallic systems, e.g. Al or Mg based alloys, by computing the grain refinement effect achieved by inoculation of the melt with inert seeding particles. However, recent experiments with peritectic Ti-Al-B alloys revealed that the grain refinement by TiB2 is less effective than predicted by the model. Phase field simulations can be applied to validate the approximations of the spherical cap and free growth model, e.g. by computing explicitly the latent heat release associated with different nucleation and growth scenarios. Here, simulation results for point-shaped nucleation, as well as for partially and completely wetted plate-like seed particles will be discussed with respect to recalescence and impact on grain refinement. It will be shown that particularly for large seeding particles (up to 30 μm), the free growth morphology clearly deviates from the assumed spherical cap and the initial growth - until the free growth barrier is reached - significantly contributes to the latent heat release and determines the recalescence temperature.

Cholinergic anti-inflammatory pathway in the non-obese diabetic mouse model.

PubMed

Koopman, F A; Vosters, J L; Roescher, N; Broekstra, N; Tak, P P; Vervoordeldonk, M J

2015-10-01

Activation of the cholinergic anti-inflammatory pathway (CAP) has been shown to reduce inflammation in animal models, while abrogation of the pathway increases inflammation. We investigated whether modulation of CAP influences inflammation in the non-obese diabetic (NOD) mouse model for Sjögren's syndrome and type 1 diabetes. The alpha-7 nicotinic acetylcholine receptor (α7nAChR) was stimulated with AR-R17779 or nicotine in NOD mice. In a second study, unilateral cervical vagotomy was performed. α7nAChR expression, focus scores, and salivary flow were evaluated in salivary glands (SG) and insulitis score in the pancreas. Cytokines were measured in serum and SG. α7nAChR was expressed on myoepithelial cells in SG. Monocyte chemotactic protein-1 levels were reduced in SG after AR-R17779 treatment and tumor necrosis factor production was increased in the SG of the vagotomy group compared to controls. Focus score and salivary flow were unaffected. NOD mice developed diabetes more rapidly after vagotomy, but at completion of the study there were no statistically significant differences in number of mice that developed diabetes or in insulitis scores. Intervention of the CAP in NOD mice leads to minimal changes in inflammatory cytokines, but did not affect overall inflammation and function of SG or development of diabetes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of vitamin E administration on the elevated oxygen stress and the telomeric and subtelomeric status in Alzheimer's disease.

PubMed

Guan, Jing-Zhi; Guan, Wei-Ping; Maeda, Toyoki; Makino, Naoki

2012-01-01

Oxidative stress (OS) may be involved in the neurodegenerative process in Alzheimer's disease (AD). Telomeres, the repeated sequences that cap chromosome ends, undergo shortening with each cell division, are sensitive to OS, and serve as markers of a cell's replicative history. Telomere length shortening has been reported to relate to OS with aging process and aging-associated diseases, but the telomeric changes were not always identical, especially in change of telomere length distribution and subtelomeric methylation. The involvement of an OS-associated telomere change in the pathogenesis of AD has been discussed for decades, and the telomere length and telomerase activity were analyzed. However, other telomeric factors, such as the telomere distribution and subtelomeric methylation status, have not yet been analyzed. The subtelomeric methylation status as well as the telomere length were studied in AD with an antioxidant vitamin in terms of OS. We measured urinary 8-iso-PGF2α, a lipid-peroxidation product as an OS marker, and methylated and non-methylated telomere lengths in the peripheral blood mononuclear cells by Southern blotting in AD patients before and after vitamin E treatment. The level of urinary 8-iso-PGF2α was found to have increased in AD. Middle-ranged telomeres (4.4-9.4 kb) increased and the shortest telomeres (<4.4 kb) decreased in AD patients. Telomeres were more methylated in both long telomeres and in short telomeres in AD compared with the control. The oral administration of the antioxidant vitamin E in 400 mg/day for 6 months in AD patients partly reversed AD-associated alterations in OS marker levels. AD patients showed an elevated OS marker level, and vitamin E lowered the OS level. In comparison with controls, AD patients showed shorter telomere lengths. Cells with short and long telomeres bore relatively hypermethylated subtelomeres in AD patients. Aging-associated accumulation of cells bearing short telomeres was not observed in AD. These results imply that long telomeres with hypomethylation tend to shorten faster, and cells bearing short telomeres with hypomethylation tend to more easily enter into a senescent state under elevated OS stress in AD. However, no significant effect on the altered telomeric profiles in AD patients could be detected after a 6-month administration of vitamin E. Copyright © 2011 S. Karger AG, Basel.

Ballistocardiogram Artifact Removal with a Reference Layer and Standard EEG Cap

PubMed Central

Luo, Qingfei; Huang, Xiaoshan; Glover, Gary H.

2014-01-01

Background In simultaneous EEG-fMRI, the EEG recordings are severely contaminated by ballistocardiogram (BCG) artifacts, which are caused by cardiac pulsations. To reconstruct and remove the BCG artifacts, one promising method is to measure the artifacts in the absence of EEG signal by placing a group of electrodes (BCG electrodes) on a conductive layer (reference layer) insulated from the scalp. However, current BCG reference layer (BRL) methods either use a customized EEG cap composed of electrode pairs, or need to construct the custom reference layer through additional model-building experiments for each EEG-fMRI experiment. These requirements have limited the versatility and efficiency of BRL. The aim of this study is to propose a more practical and efficient BRL method and compare its performance with the most popular BCG removal method, the optimal basis sets (OBS) algorithm. New Method By designing the reference layer as a permanent and reusable cap, the new BRL method is able to be used with a standard EEG cap, and no extra experiments and preparations are needed to use the BRL in an EEG-fMRI experiment. Results The BRL method effectively removed the BCG artifacts from both oscillatory and evoked potential scalp recordings and recovered the EEG signal. Comparison with Existing Method Compared to the OBS, this new BRL method improved the contrast-to-noise ratios of the alpha-wave, visual, and auditory evoked potential signals by 101%, 76%, and 75% respectively, employing 160 BCG electrodes. Using only 20 BCG electrodes, the BRL improved the EEG signal by 74%/26%/41% respectively. Conclusion The proposed method can substantially improve the EEG signal quality compared with traditional methods. PMID:24960423

Exposure to concentrated ambient PM2.5 alters the composition of gut microbiota in a murine model.

PubMed

Wang, Wanjun; Zhou, Ji; Chen, Minjie; Huang, Xingke; Xie, Xiaoyun; Li, Weihua; Cao, Qi; Kan, Haidong; Xu, Yanyi; Ying, Zhekang

2018-04-17

Exposure to ambient fine particulate matter (PM 2.5 ) correlates with abnormal glucose homeostasis, but the underlying biological mechanism has not been fully understood. The gut microbiota is an emerging crucial player in the homeostatic regulation of glucose metabolism. Few studies have investigated its role in the PM 2.5 exposure-induced abnormalities in glucose homeostasis. C57Bl/6J mice were exposed to filtered air (FA) or concentrated ambient PM 2.5 (CAP) for 12 months using a versatile aerosol concentration enrichment system (VACES) that was modified for long-term whole-body exposures. Their glucose homeostasis and gut microbiota were examined and analysed by correlation and mediation analysis. Intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) showed that CAP exposure markedly impaired their glucose and insulin tolerance. Faecal microbiota analysis demonstrated that the impairment in glucose homeostasis was coincided with decreased faecal bacterial ACE and Chao-1 estimators (the indexes of community richness), while there was no significant change in all faecal fungal alpha diversity estimators. The Pearson's correlation analyses showed that the bacterial richness estimators were correlated with glucose and insulin tolerance, and the mediation analyses displayed a significant mediation of CAP exposure-induced glucose intolerance by the alteration in the bacterial Chao-1 estimator. LEfSe analyses revealed 24 bacterial and 21 fungal taxa differential between CAP- and FA-exposed animals. Of these, 14 and 20 bacterial taxa were correlated with IPGTT AUC and ITT AUC, respectively, and 5 fungal taxa were correlated with abnormalities in glucose metabolism. Chronic exposure to PM 2.5 causes gut dysbiosis and may subsequently contribute to the development of abnormalities in glucose metabolism.

Perfil das alterações vasculares periféricas em dependentes de crack acompanhados em Centro de Atenção Psicossocial para Álcool e Drogas (CAPS-AD)

PubMed Central

da Costa, Antônio Fagundes; Baldaçara, Leonardo Rodrigo; da Silva, Sílvio Alves; Tavares, Ana Célia de Freitas Ramos; Orsolin, Ederson de Freitas; Prehl, Vinícius Barros; Gondo, Fernando Hirohito Beltran; Santana, Hernani Lopes

2016-01-01

Resumo Contexto O consumo de crack é um dos grandes desafios em saúde pública, e o uso dessa droga tem efeitos diretos na saúde de seus usuários. Objetivos Avaliar o perfil das alterações vasculares em pacientes com dependência de crack em Centro de Atenção Psicossocial para Álcool e Drogas (CAPS-AD) e observar os possíveis efeitos vasculares periféricos. Métodos Trata-se de um estudo observacional, descritivo, de corte transversal. Os pacientes da amostra foram submetidos a um questionário objetivo para avaliar questões demográficas, padrão de uso da droga, coexistência de diabetes melito, hipertensão arterial ou tabagismo, exame físico e ecográfico. Os dados foram sumarizados e analisados estatisticamente com teste qui-quadrado ou teste exato de Fisher. Resultados A média de idade da amostra foi de 33,29 (±7,15) anos, e 74% eram do gênero masculino. A média de idade de início de uso da droga foi de 23,4 (±7,78) anos, com tempo médio de uso de 9,58 (±5,64) anos. O consumo médio diário de pedras de crack foi de 21,45 (±8,32) pedras. A alteração de pulsos em membros inferiores foi mais frequente em mulheres. A prevalência do espessamento da parede arterial nos membros inferiores foi de 94,8%. O tempo de uso da droga apresentou associação estatística (p = 0,0096) com alteração do padrão de curva espectral das artérias dos membros inferiores. Conclusões Há alterações vasculares periféricas em usuários de crack. O tempo de uso da droga exerceu um maior impacto nesse sistema, o que sugere associação entre o uso do crack e a diminuição de fluxo arterial.

Cleavage of the actin-capping protein alpha -adducin at Asp-Asp-Ser-Asp633-Ala by caspase-3 is preceded by its phosphorylation on serine 726 in cisplatin-induced apoptosis of renal epithelial cells.

PubMed

van de Water, B; Tijdens, I B; Verbrugge, A; Huigsloot, M; Dihal, A A; Stevens, J L; Jaken, S; Mulder, G J

2000-08-18

Decreased phosphorylation of focal adhesion kinase and paxillin is associated with loss of focal adhesions and stress fibers and precedes the onset of apoptosis (van de Water, B., Nagelkerke, J. F., and Stevens, J. L. (1999) J. Biol. Chem. 274, 13328-13337). The cortical actin cytoskeletal network is also lost during apoptosis, yet little is known about the temporal relationship between altered phosphorylation of proteins that are critical in the regulation of this network and their potential cleavage by caspases during apoptosis. Adducins are central in the cortical actin network organization. Cisplatin caused apoptosis of renal proximal tubular epithelial cells, which was associated with the cleavage of alpha-adducin into a 74-kDa fragment; this was blocked by a general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk). Hemagglutinin-tagged human alpha-adducin was cleaved into a similar 74-kDa fragment by caspase-3 in vitro but not by caspase-6 or -7. Asp-Arg-Val-Asp(29)-Glu, Asp-Ile-Val-Asp(208)-Arg, and Asp-Asp-Ser-Asp(633)-Ala were identified as the principal caspase-3 cleavage sites; Asp-Asp-Ser-Asp(633)-Ala was key in the formation of the 74-kDa fragment. Cisplatin also caused an increased phosphorylation of alpha-adducin and gamma-adducin in the MARCKS domain that preceded alpha-adducin cleavage and was associated with loss of adducins from adherens junctions; this was not affected by z-VAD-fmk. In conclusion, the data support a model in which increased phosphorylation of alpha-adducin due to cisplatin leads to dissociation from the cytoskeleton, a situation rendered irreversible by caspase-3-mediated cleavage of alpha-adducin at Asp-Asp-Ser-Asp(633)-Ala.

Function of the two Xenopus smad4s in early frog development.

PubMed

Chang, Chenbei; Brivanlou, Ali H; Harland, Richard M

2006-10-13

Signals from the transforming growth factor beta family members are transmitted in the cell through specific receptor-activated Smads and a common partner Smad4. Two Smad4 genes (alpha and beta/10, or smad4 and smad4.2) have been isolated from Xenopus, and conflicting data are reported for Smad4beta/10 actions in mesodermal and neural induction. To further understand the functions of the Smad4s in early frog development, we analyzed their activities in detail. We report that Smad10 is a mutant form of Smad4beta that harbors a missense mutation of a conserved arginine to histidine in the MH1 domain. The mutation results in enhanced association of Smad10 with the nuclear transcription corepressor Ski and leads to its neural inducing activity through inhibition of bone morphogenetic protein (BMP) signaling. In contrast to Smad10, both Smad4alpha and Smad4beta enhanced BMP signals in ectodermal explants. Using antisense morpholino oligonucleotides (MOs) to knockdown endogenous Smad4 protein levels, we discovered that Smad4beta was required for both activin- and BMP-mediated mesodermal induction in animal caps, whereas Smad4alpha affected only the BMP signals. Neither Smad4 was involved directly in neural induction. Expression of Smad4beta-MO in early frog embryos resulted in reduction of mesodermal markers and defects in axial structures, which were rescued by either Smad4alpha or Smad4beta. Smad4alpha-MO induced only minor deficiency at late stages. As Smad4beta, but not Smad4alpha, is expressed at high levels maternally and during early gastrulation, our data suggest that although Smad4alpha and Smad4beta may have similar activities, they are differentially utilized during frog embryogenesis, with only Smad4beta being essential for mesoderm induction.

In vivo optophysiology reveals that G-protein activation triggers osmotic swelling and increased light scattering of rod photoreceptors

PubMed Central

Nguyen, Phuong T.; Yarov-Yarovoy, Vladimir; Burns, Marie E.; Pugh, Edward N.

2017-01-01

The light responses of rod and cone photoreceptors have been studied electrophysiologically for decades, largely with ex vivo approaches that disrupt the photoreceptors’ subretinal microenvironment. Here we report the use of optical coherence tomography (OCT) to measure light-driven signals of rod photoreceptors in vivo. Visible light stimulation over a 200-fold intensity range caused correlated rod outer segment (OS) elongation and increased light scattering in wild-type mice, but not in mice lacking the rod G-protein alpha subunit, transducin (Gαt), revealing these responses to be triggered by phototransduction. For stimuli that photoactivated one rhodopsin per Gαt the rod OS swelling response reached a saturated elongation of 10.0 ± 2.1%, at a maximum rate of 0.11% s−1. Analyzing swelling as osmotically driven water influx, we find the H2O membrane permeability of the rod OS to be (2.6 ± 0.4) × 10−5 cm⋅s−1, comparable to that of other cells lacking aquaporin expression. Application of Van’t Hoff’s law reveals that complete activation of phototransduction generates a potentially harmful 20% increase in OS osmotic pressure. The increased backscattering from the base of the OS is explained by a model combining cytoplasmic swelling, translocation of dissociated G-protein subunits from the disc membranes into the cytoplasm, and a relatively higher H2O permeability of nascent discs in the basal rod OS. Translocation of phototransduction components out of the OS may protect rods from osmotic stress, which could be especially harmful in disease conditions that affect rod OS structural integrity. PMID:28320964

Long Noncoding RNA PANDA Positively Regulates Proliferation of Osteosarcoma Cells.

PubMed

Kotake, Yojiro; Goto, Taiki; Naemura, Madoka; Inoue, Yasutoshi; Okamoto, Haruna; Tahara, Keiichiro

2017-01-01

A long noncoding RNA, p21-associated ncRNA DNA damage-activated (PANDA), associates with nuclear transcription factor Y subunit alpha (NF-YA) and inhibits its binding to promoters of apoptosis-related genes, thereby repressing apoptosis in normal human fibroblasts. Here, we show that PANDA is involved in regulating proliferation in the U2OS human osteosarcoma cell line. U2OS cells were transfected with siRNAs against PANDA 72 h later and they were subjected to reverse transcription-polymerase chain reaction (RT-PCR), quantitative RT-PCR and cell-cycle analysis. PANDA was highly expressed in U2OS cells, and its expression was induced by DNA damage. Silencing PANDA caused arrest at the G 1 phase of the cell cycle, leading to inhibition of cell proliferation. Quantitative RT-PCR showed that silencing PANDA increased mRNA levels of the cyclin-dependent kinase inhibitor p18, which caused G 1 phase arrest. These results suggest that PANDA promotes G 1 -S transition by repressing p18 transcription, and thus promotes U2OS cell proliferation. Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Free Body Dynamics of a Spinning Cylinder With Planar Restraint (a.k.a. Barrel of Fun)

NASA Technical Reports Server (NTRS)

Moraru, Laurentiu; Dimofte, Florin; Hendricks, Robert C.

2006-01-01

The dynamic motion of a cylinder on a floor or hard surface is both entertaining and instructive. With maintenance torques, motion can be sustained and controlled as illustrated in a video clip that can be viewed in the PDF file of this document. The analysis of such a cylinder with and without end caps is burned on rotation about its center of mass and restrained by a plane normal to the axis passing through its center of mass at an angle alpha. For small values of alpha, the governing equations are simplified, and for symmetric bodies, stability requires rotation greater than [2 square root of(JWL*)]/J(sub X), where J is the transverse mass moment of inertia, W is the weight of the cylinder, L* is the cylinder length from the base to the center of mass, and JX is the mass moment of inertia about the longitudinal axis OX of the barrel. Comparisons to data are made and some applications are discussed.

Identification of high-mannose and multiantennary complex-type N-linked glycans containing alpha-galactose epitopes from Nurse shark IgM heavy chain.

PubMed

Harvey, David J; Crispin, Max; Moffatt, Beryl E; Smith, Sylvia L; Sim, Robert B; Rudd, Pauline M; Dwek, Raymond A

2009-11-01

MALDI-TOF mass spectrometry, negative ion nano-electrospray MS/MS and exoglycosidase digestion were used to identify 36 N-linked glycans from 19S IgM heavy chain derived from the nurse shark (Ginglymostoma cirratum). The major glycan was the high-mannose compound, Man(6)GlcNAc(2) accompanied by small amounts of Man(5)GlcNAc(2), Man(7)GlcNAc(2) and Man(8)GlcNAc(2). Bi- and tri-antennary (isomer with a branched 3-antenna) complex-type glycans were also abundant, most contained a bisecting GlcNAc residue (beta1-->4-linked to the central mannose) and with varying numbers of alpha-galactose residues capping the antennae. Small amounts of monosialylated glycans were also found. This appears to be the first comprehensive study of glycosylation in this species of animal. The glycosylation pattern has implications for the mechanism of activation of the complement system by nurse shark IgM.

The ionosphere of Uranus - A myriad of possibilities

NASA Astrophysics Data System (ADS)

Chandler, M. O.; Waite, J. H.

1986-01-01

A one-dimensional model has been used to study the effects of exospheric temperature, methane and water influx, ionospheric outflow, and electron precipitation on the composition and structure of the ionosphere of Uranus. Peak ion concentrations range from 1000 to 1 million per cu cm with a wide variation in peak altitude, which depends strongly on the exospheric temperature. In all the cases considered, H(+) is the major ion in the topside ionosphere. At altitudes near or below the peak, H3(+) and CH5(+) can dominate, depending on the magnitude of CH4 and H2O influx. Atomic hydrogen column depths above the methane absorbing layer exceed 10 to the 17th per sq cm and can produce large (400 R) emissions of resonantly scattered Lyman-alpha. In the sunlit polar cap, electron precipitation with energy fluxes of 0.6 to 1.0 erg/sq cm s results in direct production of Lyman-alpha emissions that exceed 1 kR.

Enzymatic transformation of nonfood biomass to starch

PubMed Central

You, Chun; Chen, Hongge; Myung, Suwan; Sathitsuksanoh, Noppadon; Ma, Hui; Zhang, Xiao-Zhou; Li, Jianyong; Zhang, Y.-H. Percival

2013-01-01

The global demand for food could double in another 40 y owing to growth in the population and food consumption per capita. To meet the world’s future food and sustainability needs for biofuels and renewable materials, the production of starch-rich cereals and cellulose-rich bioenergy plants must grow substantially while minimizing agriculture’s environmental footprint and conserving biodiversity. Here we demonstrate one-pot enzymatic conversion of pretreated biomass to starch through a nonnatural synthetic enzymatic pathway composed of endoglucanase, cellobiohydrolyase, cellobiose phosphorylase, and alpha-glucan phosphorylase originating from bacterial, fungal, and plant sources. A special polypeptide cap in potato alpha-glucan phosphorylase was essential to push a partially hydrolyzed intermediate of cellulose forward to the synthesis of amylose. Up to 30% of the anhydroglucose units in cellulose were converted to starch; the remaining cellulose was hydrolyzed to glucose suitable for ethanol production by yeast in the same bioreactor. Next-generation biorefineries based on simultaneous enzymatic biotransformation and microbial fermentation could address the food, biofuels, and environment trilemma. PMID:23589840

Formation and self-organization kinetics of alpha-CD/PEO-based pseudo-polyrotaxanes in water. A specific behavior at 30 degrees C.

PubMed

Travelet, Christophe; Schlatter, Guy; Hébraud, Pascal; Brochon, Cyril; Lapp, Alain; Hadziioannou, Georges

2009-08-04

alpha-Cyclodextrins (alpha-CDs) have the ability to form inclusion complexes with poly(ethylene oxide) (PEO) polymer chains. These pseudo-polyrotaxanes (PPRs) can be obtained by quenching an alpha-CD/PEO mixture in water from 70 degrees C down to a lower temperature (typically in the range from 5 to 30 degrees C) thanks to favorable interactions between alpha-CD cavities and PEO chains. Moreover, starting from a liquid alpha-CD/PEO mixture at a total mass fraction of 15% w/w at 70 degrees C, the formation of PPRs with time at a lower temperature induces a white physical gel with time, and phase separation is observed. We established that PPR molecules are exclusively found in the precipitated phase although unthreaded alpha-CD molecules and unthreaded PEO chains are in the liquid phase. At 30 degrees C, the physical gel formation is much slower than at 5 degrees C. At 30 degrees C, we established that, in a first step, alpha-CDs thread onto PEO chains, forming PPR molecules which are not in good solvent conditions in water. At a higher length scale, rapid aggregation of the PPR molecules occurs, and threaded alpha-CD-based nanocylinders form (cylinder length L = 5.7 nm and cylinder radius R = 4.7 nm). At a higher length scale, alpha-CD-based nanocylinders associate in a Gaussian way, engendering the formation of precipitated domains which are responsible for the high turbidity of the studied system. At the end of this first step (i.e., after 20 min), the system still remains liquid and the PPRs are totally formed. Then, in a second step (i.e., after 150 min), the system undergoes its reorganization characterized by a compacity increase of the precipitated domains and forms a physical gel. We found that PPRs are totally formed after 20 min at 30 degrees C and that the system stays in a nongel state up to 150 min. This opens new perspectives regarding the PPR chemical modification: between these two characteristic times, we can easily envisage an efficient chemical modification of the PPR molecules in water, as for instance an end-capping reaction leading to the synthesis of polyrotaxanes.

Measuring alcohol-related consequences and motives among students attending Historically Black Colleges and Universities.

PubMed

Messina, Bryan G; Tseng, Andy; Correia, Christopher J

2015-07-01

College student drinkers have the propensity to engage in heavy alcohol consumption. These consumption patterns can be problematic given the well-established relationship between heavy drinking and negative consequences of alcohol consumption. Though the research on college student drinking is abundant, much of the work conducted has been with Caucasian samples and less so with African American samples or at Historically Black Colleges and Universities (HBCUs). The current paper assessed the internal reliability and concurrent validity of two popular measures of alcohol related negative consequences (CAPS-r and YAACQ) and a measure of drinking motives (DMQ-R) within a HBCU sample. Total scores for the CAPS-r and YAACQ and all five subscales of the DMQ-R were internally reliable as determined by Cronbach's alpha. Correlations and regressions established concurrent validity for both measures of negative consequences as well as the subscales for the DMQ-R. Findings support the use of these measures in the assessment of negative consequences and motivations for alcohol consumption within a HBCU population. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of low-dose experimental zearalenone intoxication on the immunoexpression of estrogen receptors in the ovaries of pre-pubertal bitches.

PubMed

Gajecka, M

2012-01-01

Zearalenone is an estrogenic mycotoxin that often contaminates plant material used in the production of feeds for companion animals. Small daily doses of ingested zearalenone--a competitive substrate modulating the activity of enzymes participating in estrogen biosynthesis at the pre-receptor level--can induce subclinical symptoms of hyperestrogenism in bitches. The objective of this study was to determine the effects of low zearalenone doses on the presence of estrogen receptors in the ovaries of pre-pubertal Beagle bitches. The bitches were divided into three groups of 10 animals each: experimental group I--50 microg zearalenone/kg body weight administered once daily per os; experimental group II--75 microg zearalenone/kg body weight administered once daily per os; control group--placebo containing no ZEN administered per os. The animals were ovariorectomized at the end of the experiment, at 112 days of age. Estrogen receptors were detected in ovarian specimens by immunohistochemical methods. The results revealed an absence of estrogen receptors alpha in all groups. In both experimental groups a decrease in the positive response of estrogen receptors beta in specified structures of ovaries was observed. Very low alpha-zearalenol levels probably attested to the slowing down (hypostimulation) of the biotransformation process. Overall, zearalenone intoxication led to hyperestrogenism during a specific developmental stage of pre-pubertal bitches. As regards hormesis, the threshold dose of zearalenone (adaptive capability) was exceeded in the ovaries of experimental group II animals. The results obtained in both experimental groups suggest that long-term exposure to low-dose zearalenone intoxication decreased the degree of estrogen receptors beta staining in particular structures of ovaries in the experimental bitches, which initiated epigenetic modification mechanisms that inhibited ovarian development.

Magnetism of a Co monolayer on Pt(111) capped by overlayers of 5 d elements: A spin-model study

NASA Astrophysics Data System (ADS)

Simon, E.; Rózsa, L.; Palotás, K.; Szunyogh, L.

2018-04-01

Using first-principles calculations, we study the magnetic properties of a Co monolayer on a Pt(111) surface with a capping monolayer of selected 5 d elements (Re, Os, Ir, Pt, and Au). First we determine the tensorial exchange interactions and magnetic anisotropies characterizing the Co monolayer for all considered systems. We find a close relationship between the magnetic moment of the Co atoms and the nearest-neighbor isotropic exchange interaction, which is attributed to the electronic hybridization between the Co and the capping layers, in the spirit of the Stoner picture of ferromagnetism. The Dzyaloshinskii-Moriya interaction is decreased for all overlayers compared to the uncapped Co/Pt(111) system, while even the sign of the Dzyaloshinskii-Moriya interaction changes in the case of the Ir overlayer. We conclude that the variation of the Dzyaloshinskii-Moriya interaction is well correlated with the change of the magnetic anisotropy energy and of the orbital moment anisotropy. The unique influence of the Ir overlayer on the Dzyaloshinskii-Moriya interaction is traced by scaling the strength of the spin-orbit coupling of the Ir atoms in Ir/Co/Pt(111) and by changing the Ir concentration in the Au1 -xIrx /Co/Pt(111) system. Our spin dynamics simulations indicate that the magnetic ground state of Re/Co/Pt(111) thin film is a spin spiral with a tilted normal vector, while the other systems are ferromagnetic.

Proecdysial changes in serum ecdysone titers, gastrolith formation, and limb regeneration following molt induction by limb autotomy and/or eyestalk removal in the land crab, Gecarcinus lateralis

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

McCarthy, J.F.; Skinner, D.M.

1977-01-01

The changes in serum ecdysone titers, gastrolith deposition, and limb regeneration were monitored at each stage of the molt cycle in the land crab, Gecarcinus lateralis. Animals were induced to molt by multiple-limb autotomy or eyestalk removal. The presence of ..cap alpha..-ecdysone and b-ecdysone (20-hydroxyecdysone) in the animals' serum was demonstrated chromatographically. ..beta..-ecdysone was the major circulating ecdysone, while ..cap alpha..-ecdysone was present only at very low concentrations. Four other components reacting with the ecdysone antiserum were separated chromatographically; one of these, a nonpolar compound, became a major component of the serum ecdysones at the time of maximum hormone titers.more » Ecdysone titers in the serum remained at the level characteristic of intermolt (approximately 10 ng/ml) during basal regeneration and rose linearly during the premolt period, reaching a maximum when regeneration of limbs had ceased and exoskeleton was deposited. Ecdysone decreased during stages D/sub 3/ and D/sub 4/, approaching intermolt levels at the time of ecdysis, where they remained through postmolt stages A and B. The patterns of premolt changes in ecdysone titers, gastroliths, and regeneration were very similar in ''normal'' animals (stimulated to molt by the loss of eight pereiopods) and in animals without eyestalks; however, in crabs without eyestalks, the changes were completed in about half the time as in crabs with eyestalks. Basal regeneration is associated with low ecdysone levels even in crabs without eyestalks. The normal sequence of proecdysial events is not initiated until the completion of basal regeneration. It is suggested that there exists a yet-unidentified mechanism outside the eyestalk capable of preventing increases in ecdysone titers while limbs engage in basal regeneration.« less

Interaction of tachykinins with their receptors studied with cyclic analogues of substance P and neurokinin B

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

Ploux, O.; Lavielle, S.; Chassaing, G.

1987-11-01

The activities of two groups of cyclic agonists of substance P (SP) have been studied. The disulfide bridge constraints have been designed on the basis of conformational studies on SP and physalaemin indicating an ..cap alpha..-helical structure for the core of these two tachykinins (group I) and a folding of the C-terminal carboxamide towards the side chains of the glutamines 5 and 6 (group II). Only peptides simulating the ..cap alpha..-helix present substantial potencies. (Cys/sup 3,6/)SP is as active as SP in inhibiting /sup 125/I-labeled Bolton and Hunter SP-specific binding on rat brain synaptosomes and on dog carotid bioassay, twomore » assays specific for the neurokinin 1 receptor. Moreover, (Cys/sup 3,6/)SP is a potent as neurokinin B in inhibiting /sup 125/I-labeled Bolton and Hunter eledoisin-specific binding on rat cortical synaptosomes as well as in stimulating rat portal vein, two tests specific for the neurokinin 3 receptor. Interestingly, in contrast to neurokinin B, (Cys/sup 3,6/)SP is a weak agonist of the neurokinin 2 receptor subtype, as evidenced by its binding potency in inhibiting /sup 3/H-labeled neurokinin A-specific binding on rat duodenum and in inducing the contractions of the rabbit pulmonary artery, a neurokinin 2-type bioassay. To increase the specificity of the cyclic analogue (Cys/sup 3,6/)SP positions 8 and 9 were modified. Collectively, these results suggest that the neurokinin 1 and neurokinin 3 tachykinin receptors may recognize a similar three-dimensional structure of the core of the tachykinins. Different orientations of the common C-terminal tripeptide may be related to the selectivity for the different receptor subtypes.« less

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

Inbar, S.; Linschitz, H.; Cohen, S.G.

Nanosecond flash photolysis, steady irradiation, and deuterium substitution studies have been carried out on solutions of benzophenone with added reductants. Quantum yields (phi/sub ketyl/) for reduction in benzene of benzophenone triplet to ketyl radical, based on phi = 2 for benzhydrol (I), were approx. 1 for cyclohexane (II), tert-butylamine (III), 2-aminobutane (IV), cyclohexylamine (V), di-n-propylamine (VI), and triethylamine (VII), approx. 0.7 for 1,4-diazabicyclo(2.2.2)octane (VIII), and approx. 0 for tert-butyl alcohol (IX). Thus, quenching, without radical formation by H abstraction from N and/or ..cap alpha..-C, does not occur with common aliphatic amines but does with Dabco (VIII). The latter quenching ismore » markedly increased by small additions of acetonitrile; the flash spectrum from this compound indicates formation of a triplet amine CT complex or radical ion pair. Triplet-reductant interaction rate constants, k/sur ir/, are high for the amines (approx. 10/sup 8/-10/sup 9/ M/sup -1/ s/sup -1/) but also show significant deuterium kinetic isotope effects: 1.9 with III-N-d/sub 2/; 1.4 with IV-N-d/sub 2/; 1.2-1.3 with IV-..cap alpha..-C-d. It is proposed that k/sub ir/ measures H atom abstraction, favored in the transition state by an initial charge-transfer interaction. Overall steady irradiation quantum yields of reduction by amines, phi/sub Red/, are much lower than phi/sub ketyl/. This is attributed to disproportionationreactions of ketyl and alkylaminyl radicals for primary and secondary amines, and, possibly, aminoalkyl radicals for tertiary amines. In the case of tert-butylamine, the rate constant for disproportionation is obtained from the decay kinetics of ketyl radical and leads to phi/sub Red/ in agreement with that directly measured.« less

The Effect of an Offset Polar Cap Dipolar Magnetic Field on the Modeling of the Vela Pulsar's Gamma-Ray Light Curves

NASA Technical Reports Server (NTRS)

Barnard, M.; Venter, C.; Harding, A. K.

2016-01-01

We performed geometric pulsar light curve modeling using static, retarded vacuum, and offset polar cap (PC) dipole B-fields (the latter is characterized by a parameter epsilon), in conjunction with standard two-pole caustic (TPC) and outer gap (OG) emission geometries. The offset-PC dipole B-field mimics deviations from the static dipole (which corresponds to epsilon equals 0). In addition to constant-emissivity geometric models, we also considered a slot gap (SG) E-field associated with the offset-PC dipole B-field and found that its inclusion leads to qualitatively different light curves. Solving the particle transport equation shows that the particle energy only becomes large enough to yield significant curvature radiation at large altitudes above the stellar surface, given this relatively low E-field. Therefore, particles do not always attain the radiation-reaction limit. Our overall optimal light curve fit is for the retarded vacuum dipole field and OG model, at an inclination angle alpha equals 78 plus or minus 1 degree and observer angle zeta equals 69 plus 2 degrees or minus 1 degree. For this B-field, the TPC model is statistically disfavored compared to the OG model. For the static dipole field, neither model is significantly preferred. We found that smaller values of epsilon are favored for the offset-PC dipole field when assuming constant emissivity, and larger epsilon values favored for variable emissivity, but not significantly so. When multiplying the SG E-field by a factor of 100, we found improved light curve fits, with alpha and zeta being closer to best fits from independent studies, as well as curvature radiation reaction at lower altitudes.

Structural features of the exocellular polysaccharides of Mycobacterium tuberculosis.

PubMed Central

Lemassu, A; Daffé, M

1994-01-01

The cell envelope which surrounds pathogenic mycobacteria is postulated to be a defence barrier against phagocytic cells and its outermost constituents have a tendency to accumulate in the culture medium. The present work demonstrates that the exocellular material of Mycobacterium tuberculosis contains large amounts of polysaccharides with only traces, if any at all, of lipids. Three types of polysaccharides were purified by anion-exchange and gel-filtration chromatography; all were found to be neutral compounds devoid of acyl substituents. They consisted of D-glucan, D-arabino-D-mannan and D-mannan, which were eluted from gel-filtration columns in positions corresponding to molecular masses of 123, 13 and 4 kDa respectively. Their predominant structural features were determined by the characterization of the per-O-methyl derivatives of enzymic, acetolysis and Smith-degradation products and by 1H- and 13C-n.m.r. spectroscopy of the purified polysaccharides, using mono- and two-dimensional homonuclear chemical-shift correlated spectroscopy and two-dimensional heteronuclear (1H/13C) spectroscopy. The glucan which represented up to 90% of the polysaccharides was composed of repeating units of five or six-->4-alpha-D-Glcp-1--> residues and a -->4-alpha-D-Glcp substituted at position 6 with an alpha-D-Glcp, indicating a glycogen-like highly branched structure not related to the so-called polysaccharide-II previously identified in tuberculin. The arabinomannan consisted of a mannan segment composed of a -->6-alpha-D-Man-1--> core substituted at some positions 2 with an alpha-D-Manp. The arabinan termini of the arabinomannan were found to be extensively capped with mannosyl residues. The possibility that these polysaccharides contribute to the persistence of the tubercle bacillus in the macrophage by molecular mimicry is discussed. PMID:8297342

Structural features of the exocellular polysaccharides of Mycobacterium tuberculosis.

PubMed

Lemassu, A; Daffé, M

1994-01-15

The cell envelope which surrounds pathogenic mycobacteria is postulated to be a defence barrier against phagocytic cells and its outermost constituents have a tendency to accumulate in the culture medium. The present work demonstrates that the exocellular material of Mycobacterium tuberculosis contains large amounts of polysaccharides with only traces, if any at all, of lipids. Three types of polysaccharides were purified by anion-exchange and gel-filtration chromatography; all were found to be neutral compounds devoid of acyl substituents. They consisted of D-glucan, D-arabino-D-mannan and D-mannan, which were eluted from gel-filtration columns in positions corresponding to molecular masses of 123, 13 and 4 kDa respectively. Their predominant structural features were determined by the characterization of the per-O-methyl derivatives of enzymic, acetolysis and Smith-degradation products and by 1H- and 13C-n.m.r. spectroscopy of the purified polysaccharides, using mono- and two-dimensional homonuclear chemical-shift correlated spectroscopy and two-dimensional heteronuclear (1H/13C) spectroscopy. The glucan which represented up to 90% of the polysaccharides was composed of repeating units of five or six-->4-alpha-D-Glcp-1--> residues and a -->4-alpha-D-Glcp substituted at position 6 with an alpha-D-Glcp, indicating a glycogen-like highly branched structure not related to the so-called polysaccharide-II previously identified in tuberculin. The arabinomannan consisted of a mannan segment composed of a -->6-alpha-D-Man-1--> core substituted at some positions 2 with an alpha-D-Manp. The arabinan termini of the arabinomannan were found to be extensively capped with mannosyl residues. The possibility that these polysaccharides contribute to the persistence of the tubercle bacillus in the macrophage by molecular mimicry is discussed.

Outer Dregs

NASA Technical Reports Server (NTRS)

2006-01-01

15 May 2006 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows the very edge of the south polar residual cap of Mars. The bright areas, which appear somewhat like pieces of sliced Swiss cheese, are composed mainly of frozen carbon dioxide. The scarps around the edges of the carbon dioxide mesas have been retreating at a rate of roughly 3 meters (3 yards) per martian year; in this case, exposing a darker surface that lies below.

Location near: 85.4oS, 88.6oW Image width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Summer

Frost in Charitum Montes

NASA Technical Reports Server (NTRS)

2003-01-01

MGS MOC Release No. MOC2-387, 10 June 2003

This is a Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) wide angle view of the Charitum Montes, south of Argyre Planitia, in early June 2003. The seasonal south polar frost cap, composed of carbon dioxide, has been retreating southward through this area since spring began a month ago. The bright features toward the bottom of this picture are surfaces covered by frost. The picture is located near 57oS, 43oW. North is at the top, south is at the bottom. Sunlight illuminates the scene from the upper left. The area shown is about 217 km (135 miles) wide.

Individual neurophysiological profile in external effects investigation

NASA Astrophysics Data System (ADS)

Schastlivtseva, Daria; Tatiana Kotrovskaya, D..

Cortex biopotentials are the significant elements in human psychophysiological individuality. Considered that cortical biopotentials are diverse and individually stable, therefore there is the existence of certain dependence between the basic properties of higher nervous activity and cerebral bioelectric activity. The main purpose of the study was to reveal the individual neurophysiological profile and CNS initial functional state manifestation in human electroencephalogram (EEG) under effect of inert gases (argon, xenon, helium), hypoxia, pressure changes (0.02 and 0.2 MPa). We obtained 5-minute eyes closed background EEG on 19 scalp positions using Ag/AgCl electrodes mounted in an electrode cap. All EEG signals were re-referenced to average earlobes; Fast Furies Transformation analysis was used to calculate the relative power spectrum of delta-, theta-, alpha- and beta frequency band in artifact-free EEG. The study involved 26 healthy men who provided written informed consent, aged 20 to 35 years. Data obtained depend as individual EEG type and initial central nervous functional state as intensity, duration and mix of factors. Pronounced alpha rhythm in the raw EEG correlated with their adaptive capacity under studied factor exposure. Representation change and zonal distribution perversion of EEG alpha rhythm were accompanied by emotional instability, increased anxiety and difficulty adapting subjects. High power factor or combination factor with psychological and emotional or physical exertion minimizes individual EEG pattern.

Alzheimer’s Toxic Amyloid Beta Oligomers: Unwelcome Visitors to the Na/K ATPase alpha3 Docking Station

PubMed Central

DiChiara, Thomas; DiNunno, Nadia; Clark, Jeffrey; Bu, Riana Lo; Cline, Erika N.; Rollins, Madeline G.; Gong, Yuesong; Brody, David L.; Sligar, Stephen G.; Velasco, Pauline T.; Viola, Kirsten L.; Klein, William L.

2017-01-01

Toxic amyloid beta oligomers (AβOs) are known to accumulate in Alzheimer’s disease (AD) and in animal models of AD. Their structure is heterogeneous, and they are found in both intracellular and extracellular milieu. When given to CNS cultures or injected ICV into non-human primates and other non-transgenic animals, AβOs have been found to cause impaired synaptic plasticity, loss of memory function, tau hyperphosphorylation and tangle formation, synapse elimination, oxidative and ER stress, inflammatory microglial activation, and selective nerve cell death. Memory loss and pathology in transgenic models are prevented by AβO antibodies, while Aducanumab, an antibody that targets AβOs as well as fibrillar Aβ, has provided cognitive benefit to humans in early clinical trials. AβOs have now been investigated in more than 3000 studies and are widely thought to be the major toxic form of Aβ. Although much has been learned about the downstream mechanisms of AβO action, a major gap concerns the earliest steps: How do AβOs initially interact with surface membranes to generate neuron-damaging transmembrane events? Findings from Ohnishi et al (PNAS 2005) combined with new results presented here are consistent with the hypothesis that AβOs act as neurotoxins because they attach to particular membrane protein docks containing Na/K ATPase-α3, where they inhibit ATPase activity and pathologically restructure dock composition and topology in a manner leading to excessive Ca++ build-up. Better understanding of the mechanism that makes attachment of AβOs to vulnerable neurons a neurotoxic phenomenon should open the door to therapeutics and diagnostics targeting the first step of a complex pathway that leads to neural damage and dementia. PMID:28356893

Interaction of insulin with colloidal ZnS quantum dots functionalized by various surface capping agents.

PubMed

Hosseinzadeh, Ghader; Maghari, Ali; Farniya, Seyed Morteza Famil; Keihan, Amir Homayoun; Moosavi-Movahedi, Ali A

2017-08-01

Interaction of quantum dots (QDs) and proteins strongly influenced by the surface characteristics of the QDs at the protein-QD interface. For a precise control of these surface-related interactions, it is necessary to improve our understanding in this field. In this regard, in the present work, the interaction between the insulin and differently functionalized ZnS quantum dots (QDs) were studied. The ZnS QDs were functionalized with various functional groups of hydroxyl (OH), carboxyl (COOH), amine (NH 2 ), and amino acid (COOH and NH 2 ). The effect of surface hydrophobicity was also studied by changing the alkyl-chain lengths of mercaptocarboxylic acid capping agents. The interaction between insulin and the ZnS QDs were investigated by fluorescence quenching, synchronous fluorescence, circular dichroism (CD), and thermal aggregation techniques. The results reveal that among the studied QDs, mercaptosuccinic acid functionalized QDs has the strongest interaction (∆G ° =-51.50kJ/mol at 310K) with insulin, mercaptoethanol functionalized QDs destabilize insulin by increasing the beta-sheet contents, and only cysteine functionalized QDs improves the insulin stability by increasing the alpha-helix contents of the protein, and. Our results also indicate that by increasing the alkyl-chain length of capping agents, due to an increase in hydrophobicity of the QDs surface, the beta-sheet contents of insulin increase which results in the enhancement of insulin instability. Copyright © 2017 Elsevier B.V. All rights reserved.

Venus 2004: east and west elongations and solar transit

NASA Astrophysics Data System (ADS)

McKim, R. J.; Blaxall, K.; Heath, A.

2007-04-01

The year 2004 was exceptional in producing the first solar transit of Venus since the late Victorian era. The bright aureole and atmospheric ring were re-observed, and the entire phenomenon was witnessed for the first time ever in hydrogen alpha light. Although routine observations throughout 2004 were unexceptional, patterns of visibility of bright and dark markings, cusp extensions and cusp-caps were recorded. No correlation was found between the latitude of the sub-Earth point and the visibility of either cusp-cap, with the S. cap predominating for most of the year. It was possible to accurately follow individual ultraviolet dark markings over many consecutive rotations, extending from the E. to W. elongations, and thereby to make a current measurement of the synodic atmospheric rotation period for the near-equatorial features: 3.996 ± 0.001 days. The true Ashen Light was reported visually on only a few occasions, but these correspond closely to times when infrared emission from the surface of the dark side was recorded in 1-micron waveband images. Some of the stable dark side albedo features were also visible upon the 1-micron images, and have been tentatively identified with known surface features. Infrared imaging at the same waveband showed little detail on the sunlit disk, but a few bright spots were sufficiently well observed to suggest a synodic rotation period close to 5.0 days, not atypical for the lower cloud decks.

Evaluation of the Re-Os Geochronometer in Organic-rich Mudrocks as a Method for Constraining the Absolute Ages of Neoproterozoic Glaciogenic Deposits

NASA Astrophysics Data System (ADS)

Kendall, B. S.; Creaser, R. A.; Ross, G. M.

2002-12-01

Absolute-age constraints on the Neoproterozoic glaciations are generally poor due to a paucity of suitable plutonic and volcanic igneous rocks that are temporally and spatially related to Neoproterozoic glaciogenic deposits and are amenable to radiometric dating methods. In this study, the Re-Os isotope systematics of dark gray, sulfidic slates from the Old Fort Point Formation (OFP) of the Windermere Supergroup (near Jasper, Alberta) were examined to test the ability of the Re-Os geochronometer to provide an absolute age constraint for a Neoproterozoic glaciogenic deposit. The OFP has been interpreted as the deep water expression of post-glacial sea level rise and therefore is comparable stratigraphically to cap carbonates that immediately overlie glaciogenic deposits worldwide. Despite the relatively low Re (6-16 ppb) and Os (0.07-0.14 ppb) concentrations and total organic contents (~ 0.5% TOC) of the slates compared to other organic-rich mudrocks used in previous Re-Os isotope studies, precise well-fitted Re-Os isochrons have been obtained with two different dissolution methods. An age of 620.8 +/- 8.1 Ma (MSWD = 0.9; initial 187Os/188Os = 0.68 +/- 0.06) is obtained using conventional aqua regia dissolution. Using a method designed to selectively dissolve organic matter alone, an age of 609.0 +/- 8.3 Ma (MSWD = 1.5; initial 187Os/188Os = 0.62 +/- 0.05) is obtained. These absolute age results are in accord with existing age constraints (e.g., stratigraphically younger Hamill Group with a U-Pb zircon age of 569 Ma). The well-defined Re-Os systematics of the OFP slates demonstrates for the first time that the Re-Os system is not disturbed in organic-rich sediments during lower greenschist (-chlorite) grade metamorphic conditions. The whole-rock analysis of each individual sample yields consistently higher initial 187Os/188Os isotope ratios than the corresponding organic matter analysis and suggests that a significant radiogenic detrital Os component is present within the OFP slates. Because organic matter is likely dominated by the hydrogenous (seawater) Os budget, the initial 187Os/188Os ratio of 0.62 +/- 0.05 calculated from the organic matter regression represents the best estimate of the Os isotopic composition of the contemporaneous seawater at the time of sediment deposition. The corresponding age of 609.0 +/- 8.3 Ma is then considered to be the best depositional age determination for the OFP and provides a minimum absolute age constraint on the stratigraphically underlying glaciogenic Mount Vreeland Formation (northeastern British Columbia) and the correlative Ice Brook diamictites (Mackenzie Mountains, northwestern Canada). Thus, we conclude that the Mount Vreeland and Ice Brook diamictites are older than the ~ 580-570 Ma glaciogenic deposits of Eastern North America and may thus be considered as lower Marinoan in age. Further application of the Re-Os geochronometer to other organic-rich mudrock horizons spatially and temporally related to Neoproterozoic glaciogenic deposits will allow further opportunities for their correlation and provide better age constraints on the timing, number, and duration of the Neoproterozoic glaciations. This will allow a further assessment of the Snowball Earth Theory and its prediction of global, synchronous glaciations.

Association between in vitro platinum resistance in the EDR assay and clinical outcomes for ovarian cancer patients.

PubMed

Holloway, Robert W; Mehta, Rita S; Finkler, Neil J; Li, Kuo-Tung; McLaren, Christine E; Parker, Ricardo J; Fruehauf, John P

2002-10-01

The initial clinical response to platinum is a major determinant of outcome for patients with ovarian cancer. This retrospective study was undertaken to correlate the response and survival of newly diagnosed advanced ovarian cancer patients who received platinum-based therapy with in vitro drug response to cisplatin or carboplatin measured as percentage cell inhibition (PCI) in the in vitro Extreme Drug Resistance (EDR) assay. Outcomes for newly diagnosed ovarian cancer patients with tumor specimens submitted in a serial fashion for the EDR assay were studied. EDR assay results for cisplatin and carboplatin were correlated with clinical outcome for 79 evaluable chemotherapy nai;ve cases who presented with advanced (stages IIC, III, and IV) ovarian cancer. Stage IV and suboptimally debulked stage IIIc accounted for 16 cases, while 63 cases were optimally debulked Stage III/IIc. All patients were treated with platinum-based combination chemotherapy at a single institution. In vitro results for patient tumors were classified as low drug resistance (PCI > median), intermediate drug resistance [PCI between the median and 1 standard deviation (SD) below the median], or extreme drug resistance (PCI more than 1 SD below the median). For the purpose of this analysis, in vitro EDR to either cisplatin or carboplatin was considered to represent extreme resistance to platinum (EDRP), while the absence of EDR to either cisplatin or carboplatin was considered to represent low resistance to platinum (LDRP). Patients demonstrating relative in vitro resistance to paclitaxel and non-cross-resistance to cyclophosphamide and/or doxorubicin received cyclophosphamide plus platinum (CP); cyclophosphamide, doxorubicin, and platinum (CAP); or platinum alone in place of paclitaxel plus platinum (TP). Progression-free survival (PFS) and overall survival (OS) were correlated with EDR assay results. Median PFS was 6 months for the 17 cases exhibiting EDRP, compared to 24 months for the 62 cases exhibiting LDRP in vitro [relative risk (RR) 3.78, confidence intervals (CI) 1.82-7.83], adjusted for stage, debulking status, in vitro response to 3-OH-cyclophosphamide, and histological grade. Estimated overall 5-year survival was 19% for patients with tumors showing EDRP, compared to 68% for patients with tumors showing LDRP (RR 2.32, CI 1.06-5.07). Patients treated with CP (n = 20) showed no significant difference in OS compared to patients treated with TP (n = 54), CAP (n = 4), or cisplatin (n = 1) alone. In vitro platinum response remained an independent predictor of PFS and OS in multivariate analyses adjusted for CP versus TP, CAP, or platinum administration, and adjusted for debulking status. Median PFS for all 79 patients was 22 months, with an estimated 5-year survival of 57%. Patients with tumors demonstrating in vitro EDR to platinum were at significantly increased risk for progression and death when treated with standard platinum-based regimens. Such patients may therefore benefit from entry onto trials with novel agents or combinations.

Orientation dependence of grain-boundary energy in metals in the view of a pseudoheterophase dislocation core model

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

Missol, W.

A new dislocation model for symmetric tilt grain boundaries was developed as a basis for deriving the quantitative dependence of grain-boundary energy upon misorientation angle in the form of an expression similar to that given by Read and Shockley (Phys. Rev. 78: 275(1950)). The range of applicability of this equation was extended to over 20 degrees. A comparison of theory and experiment was made for Bi, Ag, Cu, and Fe--Si 3 percent in the teen-degree range of misorientation angles and for Au, ..cap alpha..-Fe, Mo, and W in the high-angle range.

Real-time volume rendering of digital medical images on an iOS device

NASA Astrophysics Data System (ADS)

Noon, Christian; Holub, Joseph; Winer, Eliot

2013-03-01

Performing high quality 3D visualizations on mobile devices, while tantalizingly close in many areas, is still a quite difficult task. This is especially true for 3D volume rendering of digital medical images. Allowing this would empower medical personnel a powerful tool to diagnose and treat patients and train the next generation of physicians. This research focuses on performing real time volume rendering of digital medical images on iOS devices using custom developed GPU shaders for orthogonal texture slicing. An interactive volume renderer was designed and developed with several new features including dynamic modification of render resolutions, an incremental render loop, a shader-based clipping algorithm to support OpenGL ES 2.0, and an internal backface culling algorithm for properly sorting rendered geometry with alpha blending. The application was developed using several application programming interfaces (APIs) such as OpenSceneGraph (OSG) as the primary graphics renderer coupled with iOS Cocoa Touch for user interaction, and DCMTK for DICOM I/O. The developed application rendered volume datasets over 450 slices up to 50-60 frames per second, depending on the specific model of the iOS device. All rendering is done locally on the device so no Internet connection is required.

[The effect of prolonged treatment of hypertensive rats with antihypertensive drugs of various actions on the arterial tension and noradrenaline level in the myocardium, brain and aortal].

PubMed

Kiriakov, A; Khlebarova, M; Staneva-stoicheva, D; Panova, I

1975-01-01

The authors examined the changes in arterial blood pressure and the content of Noradrenaline in the myocardium, brain and aorta of rats with hypertension due to nephrectomy and treatment with desoxycorticosterone and NaCl, and after a chronic 6-month treatment of hypertension with various antihypertensive means. The most significant reduction of noradrenaline in the three of the examined tissues was found in rats, which received dic. sulfyram (100 mg/kg per os). Clondine (10 mkg/kg, per os) manifested the strongest hypotensive effect and lowered the level of noradrenaline in the myocardium, while it was raised in the aorta. Reserpine (10 mkg/kg, s. c) induced a clear reduction of Noradrenaline content in the brain, but an increase in the other two tissues. Insignificant hypotensive effect was observed in animals, treated with guanetidine (0.5 mg/kg, per os), which did not affect substantially noradrenaline in the examined organs. The increase of noradrenaline level was established in the three of the organs of animals, treated with alpha-methyl-DOFA (25 mg/kg, per os). Furosemide (1 mg/kg, s.c.) induced a statistically significant elevation of noradrenaline in the aorta, but was noneffective to noradrenaline in the myocardium and brain.

Apatite formation on bioactive calcium-silicate cements for dentistry affects surface topography and human marrow stromal cells proliferation.

PubMed

Gandolfi, Maria Giovanna; Ciapetti, Gabriela; Taddei, Paola; Perut, Francesca; Tinti, Anna; Cardoso, Marcio Vivan; Van Meerbeek, Bart; Prati, Carlo

2010-10-01

The effect of ageing in phosphate-containing solution of bioactive calcium-silicate cements on the chemistry, morphology and topography of the surface, as well as on in vitro human marrow stromal cells viability and proliferation was investigated. A calcium-silicate cement (wTC) mainly based on dicalcium-silicate and tricalcium-silicate was prepared. Alpha-TCP was added to wTC to obtain wTC-TCP. Bismuth oxide was inserted in wTC to prepare a radiopaque cement (wTC-Bi). A commercial calcium-silicate cement (ProRoot MTA) was tested as control. Cement disks were aged in DPBS for 5 h ('fresh samples'), 14 and 28 days, and analyzed by ESEM/EDX, SEM/EDX, ATR-FTIR, micro-Raman techniques and scanning white-light interferometry. Proliferation, LDH release, ALP activity and collagen production of human marrow stromal cells (MSC) seeded for 1-28 days on the cements were evaluated. Fresh samples exposed a surface mainly composed of calcium-silicate hydrates CSH (from the hydration of belite and alite), calcium hydroxide, calcium carbonate, and ettringite. Apatite nano-spherulites rapidly precipitated on cement surfaces within 5 h. On wTC-TCP the Ca-P deposits appeared thicker than on the other cements. Aged cements showed an irregular porous calcium-phosphate (Ca-P) coating, formed by aggregated apatite spherulites with interspersed calcite crystals. All the experimental cements exerted no acute toxicity in the cell assay system and allowed cell growth. Using biochemical results, the scores were: fresh cements>aged cements for cell proliferation and ALP activity (except for wTC-Bi), whereas fresh cements

The prognostic utility of baseline alpha-fetoprotein for hepatocellular carcinoma patients.

PubMed

Silva, Jack P; Gorman, Richard A; Berger, Nicholas G; Tsai, Susan; Christians, Kathleen K; Clarke, Callisia N; Mogal, Harveshp; Gamblin, T Clark

2017-12-01

Alpha-fetoprotein (AFP) has a valuable role in postoperative surveillance for hepatocellular carcinoma (HCC) recurrence. The utility of pretreatment or baseline AFP remains controversial. The present study hypothesized that elevated baseline AFP levels are associated with worse overall survival in HCC patients. Adult HCC patients were identified using the National Cancer Database (2004-2013). Patients were stratified according to baseline AFP measurements into the following groups: Negative (<20), Borderline (20-199), Elevated (200-1999), and Highly Elevated (>2000). The primary outcome was overall survival (OS), which was analyzed by log-rank test and graphed using Kaplan-Meier method. Multivariate regression modeling was used to determine hazard ratios (HR) for OS. Of 41 107 patients identified, 15 809 (33.6%) were Negative. Median overall survival was highest in the Negative group, followed by Borderline, Elevated, and Highly Elevated (28.7 vs 18.9 vs 8.8 vs 3.2 months; P < 0.001). On multivariate analysis, overall survival hazard ratios for the Borderline, Elevated, and Highly Elevated groups were 1.18 (P = 0.267), 1.94 (P < 0.001), and 1.77 (P = 0.007), respectively (reference Negative). Baseline AFP independently predicted overall survival in HCC patients regardless of treatment plan. A baseline AFP value is a simple and effective method to assist in expected survival for HCC patients. © 2017 Wiley Periodicals, Inc.

More South Polar 'Swiss Cheese'

NASA Technical Reports Server (NTRS)

2000-01-01

This image is illuminated by sunlight from the upper left.

Some of the surface of the residual south polar cap has a pattern that resembles that of sliced, swiss cheese. Shown here at the very start of southern spring is a frost-covered surface in which there are two layers evident--a brighter upper layer into which are set swiss cheese-like holes, and a darker, lower layer that lies beneath the 'swiss cheese' pattern. Nothing like this exists anywhere on Mars except within the south polar cap.

This is a Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image acquired on August 2,1999. It is located near 84.8oS, 71.8oW, and covers an area 3 km across and about 6.1 km long (1.9 by 3.8 miles).

Malin Space Science Systems and the California Institute of Technology built the MOC using spare hardware from the Mars Observer mission. MSSS operates the camera from its facilities in San Diego, CA. The Jet Propulsion Laboratory's Mars Surveyor Operations Project operates the Mars Global Surveyor spacecraft with its industrial partner, Lockheed Martin Astronautics, from facilities in Pasadena, CA and Denver, CO.

A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan.

PubMed

Raskind, Murray A; Peterson, Kris; Williams, Tammy; Hoff, David J; Hart, Kimberly; Holmes, Hollie; Homas, Dallas; Hill, Jeffrey; Daniels, Colin; Calohan, Jess; Millard, Steven P; Rohde, Kirsten; O'Connell, James; Pritzl, Denise; Feiszli, Kevin; Petrie, Eric C; Gross, Christopher; Mayer, Cynthia L; Freed, Michael C; Engel, Charles; Peskind, Elaine R

2013-09-01

The authors conducted a 15-week randomized controlled trial of the alpha-1 adrenoreceptor antagonist prazosin for combat trauma nightmares, sleep quality, global function, and overall symptoms in active-duty soldiers with posttraumatic stress disorder (PTSD) returned from combat deployments to Iraq and Afghanistan. Sixty-seven soldiers were randomly assigned to treatment with prazosin or placebo for 15 weeks. Drug was titrated based on nightmare response over 6 weeks to a possible maximum dose of 5 mg midmorning and 20 mg at bedtime for men and 2 mg midmorning and 10 mg at bedtime for women. Mean achieved bedtime doses were 15.6 mg of prazosin (SD=6.0) and 18.8 mg of placebo (SD=3.3) for men and 7.0 mg of prazosin (SD=3.5) and 10.0 mg of placebo (SD=0.0) for women. Mean achieved midmorning doses were 4.0 mg of prazosin (SD=1.4) and 4.8 mg of placebo (SD=0.8) for men and 1.7 mg of prazosin (SD=0.5) and 2.0 mg of placebo (SD=0.0) mg for women. Primary outcome measures were the nightmare item of the Clinician-Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index, and the change item of the Clinical Global Impressions Scale anchored to functioning. Secondary outcome measures were the 17-item CAPS, the Hamilton Depression Rating Scale, the Patient Health Questionnaire-9, and the Quality of Life Index. Maintenance psychotropic medications and supportive psychotherapy were held constant. Prazosin was effective for trauma nightmares, sleep quality, global function, CAPS score, and the CAPS hyperarousal symptom cluster. Prazosin was well tolerated, and blood pressure changes did not differ between groups. Prazosin is effective for combat-related PTSD with trauma nightmares in active-duty soldiers, and benefits are clinically meaningful. Substantial residual symptoms suggest that studies combining prazosin with effective psychotherapies might demonstrate further benefit.

Performance of Distributed CFAR Processors in Pearson Distributed Clutter

NASA Astrophysics Data System (ADS)

Messali, Zoubeida; Soltani, Faouzi

2006-12-01

This paper deals with the distributed constant false alarm rate (CFAR) radar detection of targets embedded in heavy-tailed Pearson distributed clutter. In particular, we extend the results obtained for the cell averaging (CA), order statistics (OS), and censored mean level CMLD CFAR processors operating in positive alpha-stable (P&S) random variables to more general situations, specifically to the presence of interfering targets and distributed CFAR detectors. The receiver operating characteristics of the greatest of (GO) and the smallest of (SO) CFAR processors are also determined. The performance characteristics of distributed systems are presented and compared in both homogeneous and in presence of interfering targets. We demonstrate, via simulation results, that the distributed systems when the clutter is modelled as positive alpha-stable distribution offer robustness properties against multiple target situations especially when using the "OR" fusion rule.

South Polar 'Poodle'

NASA Technical Reports Server (NTRS)

2003-01-01

MGS MOC Release No. MOC2-422, 15 July 2003

Have you ever stared up at the clouds in the sky and seen the shapes of animals, people, or objects? Sometimes when the Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) team is looking at newly-returned pictures from Mars, the same thing happens. This is a picture of pits and scarps in the frozen south polar carbon dioxide ice cap. Sunlight illuminates the scene from the upper right. At the bottom of the picture is a feature that resembles a long, thin poodle; its head faces to the left, the tail to the right. This picture is located near 86.9oS, 55.8oW.

A Perspective on the Unprecedented Impact of the 2015/16 El Niño on the Tropical Quelccaya Ice Cap, Peru from Four Decades of Surface Sampling and Deep Drilling

NASA Astrophysics Data System (ADS)

Thompson, L. G.; Mosley-Thompson, E.; Davis, M. E.; Beaudon, E.; Lin, P. N.

2016-12-01

Atmospheric warming ( 0.10oC/decade in the last 70 years) has been observed over the Peruvian Andes and is likely the most dominant forcing for recent glacier wasting. The margin of the Quelccaya ice cap (QIC, 13o56'S; 70o50'W 5670 m asl) has been retreating for the last 50 years as the 0oC isotherm now rises seasonally above the QIC summit. Recent major El Niños have augmented the effects of this warming trend, and the impacts of the 2015/16 El Niño were more devastating than those experienced during the 1982/83 event of similar magnitude. The ice margin has retreated and thinned dramatically over the last year, and currently the QIC is smaller than it has been in over 6 millennia. Since 1974 we have conducted a program of surface sampling and deep drilling on the QIC. The seasonal δ18O oscillations which are obvious in the fresh snow (and underlying firn) deposited within each thermal year are attenuated at depth due to melting and percolation through the firn, and this has become increasingly pronounced over 43 years. Although the trend in δ18O of the top layers has remained constant, the increasing density and decreasing seasonal amplitude suggest that surface warming is enhancing post-depositional effects even on fresh snow. Snow deposited during the 1982/83 and 2015/16 El Niños show comparable isotopic enrichment ( 5‰) over the average of "normal" and La Niña years, but the net balance during the latest event was 55% below average, while that for the 82/83 event was 10% below average. These observations suggest the possibility that a threshold has been crossed such that future El Niños may exert stronger impacts on Peruvian glaciers than in the past. The surface studies on the QIC show that the δ18O composition of the snow is affected by synoptic-scale variations in the upper atmosphere over the tropical western Atlantic and the northern Amazon Basin and by sea surface temperatures in the equatorial Pacific Ocean. During major El Niños the latter have a much stronger influence on δ18O than the former while the opposite situation is observed during non-El Niño events. Better documentation and understanding of these recent relationships can facilitate interpretation of the atmospheric and oceanic controls on δ18O in the 1800-year old ice core records from Quelccaya.

A controlled evaluation of oral screen effects on intra-oral pressure curve characteristics.

PubMed

Knösel, Michael; Jung, Klaus; Kinzinger, Gero; Bauss, Oskar; Engelke, Wilfried

2010-10-01

The purpose of this study was to quantify the impact of oral screen (OS) application on intra-oral pressure characteristics in three malocclusion groups. Fifty-six randomly recruited participants (26 males and 30 females) who met the inclusion criteria of either an Angle Class I occlusal relationships or Angle Class II1 or II2 malocclusions, were assigned by dentition to group I (n = 31), group II1 (n = 12), or group II2 (n = 13). Two 3 minute periods of intra-oral pressure monitoring were conducted on each participant, using two different oral end fittings connected to a piezo-resistive relative pressure sensor: (1) a flexible OS and (2) a small-dimensioned air-permeable end cap (EC), which was placed laterally in the premolar region, thus recording intra-oral pressure independent of the influence of the OS. Pressure curve characteristics for both periods and between the malocclusion groups were evaluated with reference to the frequency of swallowing peaks, duration, and altitude of negative pressure plateau phases and the area under the pressure curve. Statistical analysis was undertaken using analysis of variance (ANOVA), the Wilcoxon Mann-Whitney test, and spearman correlation coefficient. A median number of two peaks (median height -20.9 mbar) and three plateau phases (median height of -2.3 mbar) may be regarded as normative for normal occlusion subjects during a 3 minute period, at rest. OS application raised the median average duration and height of intra-oral negative pressure plateau phases in the II1 subjects, exceeding those of group I, but less than the plateau duration in group II2. Median peak heights were distinctively lower in groups I and II1 during OS application. It is concluded that additional training for extension of intra-oral pressure phases may be a promising approach to pre-orthodontic Class II division 1 treatment.

Elastic and inelastic scattering of alpha particles from /sup 40,44/Ca over a broad range of energies and angles

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

Delbar, T.; Gregoire, G.; Paic, G.

1978-09-01

Angular distributions for ..cap alpha.. particle elastic scattering by /sup 40,44/Ca and excitation of the 3.73 MeV 3/sup -/ collective state of /sup 40/Ca were measured for incident energies ranging from 40 to 62 MeV. An extensive optical model analysis of these elastic scattering cross sections and other available data, using squared Woods-Saxon form factors, results in potentials with fixed geometry for both real and imaginary parts and depths with smooth energy behavior over a broad incident energy range. These results are discussed in the frame of the semi-classical approximation developed by Brink and Takigawa. The sensitiveness of the calculatedmore » elastic scattering cross sections to the real part of the potentials as a function of the projectile-target distance has been investigated by means of a notch test. Distorted-wave Born-approximtion calculations for the excitation of the 3.73 MeV 3/sup -/ state of /sup 40/Ca are presented.« less

Hydrogen absorption by thin Pd/Nb films deposited on glass

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

Reisfeld, G.; Jisrawi, N.M.; Ruckman, M.W.

Hydrogen absorption by 200{endash}2000-A-thick Pd-capped Nb films, between 5 and 110{degree}C, was studied by simultaneous four-probe resistivity and volumetric measurements. The resistivity as a function of hydrogen concentration was measured while charging the films with hydrogen, and was used to compute the change in hydrogen concentration in the film, during the reaction with oxygen. For the thinnest films (200 A thick), the hydrogen charging and discharging curves indicate that a first-order gas-liquid-like phase transition with a {ital T}{sub {ital c}} of 70{endash}75{degree}C takes place. The H-Nb phase diagram for the 200-A film looks like the H/bulk Nb {alpha}-{alpha}{prime} phase diagrammore » which has a higher {ital T}{sub {ital c}} (173{degree}C). We attribute the substantial modifications of the film{close_quote}s phase diagram to the clamping of the Nb film at its interfaces with glass and Pd and to the nanostructure of the films. {copyright} {ital 1996 The American Physical Society.}« less

Canine candidate genes for dilated cardiomyopathy: annotation of and polymorphic markers for 14 genes.

PubMed

Wiersma, Anje C; Leegwater, Peter Aj; van Oost, Bernard A; Ollier, William E; Dukes-McEwan, Joanna

2007-10-19

Dilated cardiomyopathy is a myocardial disease occurring in humans and domestic animals and is characterized by dilatation of the left ventricle, reduced systolic function and increased sphericity of the left ventricle. Dilated cardiomyopathy has been observed in several, mostly large and giant, dog breeds, such as the Dobermann and the Great Dane. A number of genes have been identified, which are associated with dilated cardiomyopathy in the human, mouse and hamster. These genes mainly encode structural proteins of the cardiac myocyte. We present the annotation of, and marker development for, 14 of these genes of the dog genome, i.e. alpha-cardiac actin, caveolin 1, cysteine-rich protein 3, desmin, lamin A/C, LIM-domain binding factor 3, myosin heavy polypeptide 7, phospholamban, sarcoglycan delta, titin cap, alpha-tropomyosin, troponin I, troponin T and vinculin. A total of 33 Single Nucleotide Polymorphisms were identified for these canine genes and 11 polymorphic microsatellite repeats were developed. The presented polymorphisms provide a tool to investigate the role of the corresponding genes in canine Dilated Cardiomyopathy by linkage analysis or association studies.

Leiomodin and tropomodulin in smooth muscle

NASA Technical Reports Server (NTRS)

Conley, C. A.

2001-01-01

Evidence is accumulating to suggest that actin filament remodeling is critical for smooth muscle contraction, which implicates actin filament ends as important sites for regulation of contraction. Tropomodulin (Tmod) and smooth muscle leiomodin (SM-Lmod) have been found in many tissues containing smooth muscle by protein immunoblot and immunofluorescence microscopy. Both proteins cofractionate with tropomyosin in the Triton-insoluble cytoskeleton of rabbit stomach smooth muscle and are solubilized by high salt. SM-Lmod binds muscle tropomyosin, a biochemical activity characteristic of Tmod proteins. SM-Lmod staining is present along the length of actin filaments in rat intestinal smooth muscle, while Tmod stains in a punctate pattern distinct from that of actin filaments or the dense body marker alpha-actinin. After smooth muscle is hypercontracted by treatment with 10 mM Ca(2+), both SM-Lmod and Tmod are found near alpha-actinin at the periphery of actin-rich contraction bands. These data suggest that SM-Lmod is a novel component of the smooth muscle actin cytoskeleton and, furthermore, that the pointed ends of actin filaments in smooth muscle may be capped by Tmod in localized clusters.

Heat-transfer test results for a .0275-scale space shuttle external tank with a 10 deg/40 deg double cone-ogive nose in the NASA/AMES 3.5-foot hypersonic wind tunnel (FH14), volume 2

NASA Technical Reports Server (NTRS)

Carroll, H. R.

1977-01-01

A .0275 scale forebody model of the new baseline configuration of the space shuttle external tank vent cap configuration was tested to determine the flow field due to the double cone configuration. The tests were conducted in a 3.5 foot hypersonic wind tunnel at alpha = -5 deg, -4.59 deg, 0 deg, 5 deg, and 10 deg; beta = 0 deg, -3 deg, -5.51 deg, -6 deg, -9 deg, and +6 deg; nominal freestream Reynolds numbers per foot of 1.5 x 1 million, 3.0 x 1 million, and 5.0 x 1 million; and a nominal Mach number of 5. Separation and reattached flow from thermocouple data, shadowgraphs, and oil flows indicate that separation begins about 80% from the tip of the 10 deg cone, then reattaches on the vent cap and produces fully turbulent flow over most of the model forebody. The hardware disturbs the flow over a much larger area than present TPS application has assumed. A correction to the flow disturbance was experimentally suggested from the results of an additional test run.

Evaluating the Quality of Competency Assessment in Pharmacy: A Framework for Workplace Learning.

PubMed

Shah, Shailly; McLaughlin, Jacqueline E; Eckel, Stephen F; Mangun, Jesica; Hawes, Emily

2016-01-19

Demonstration of achieved competencies is critical in the pharmacy workplace. The purpose of this study was to evaluate the quality of the competency assessment program for pharmacy residents at an academic medical center. The competency assessment program (CAP) survey is a validated, 48-item instrument that evaluates the quality of an assessment program based on 12 criteria, each measured by four questions on a scale of 0 to 100. The CAP was completed by residents ( n = 23) and preceptors ( n = 28) from the pharmacy residency program between 2010 and 2013. Results were analyzed using descriptive statistics, Cronbach's alpha, and non-parametric tests. Educational Consequences was the only quality criteria falling below the standard for "good quality." Participants that completed residency training elsewhere rated the Comparability (0.04) and Meaningfulness (0.01) of the assessment program higher than those that completed residency at the academic medical center. There were no significant differences between resident and preceptor scores. Overall, the quality of the assessment program was rated highly by residents and preceptors. The process described here provides a useful framework for understanding the quality of workplace learning assessments in pharmacy practice.

[Role of rostral ventrolateral medulla in the pressor response to intraventricular (4th) injection of substance P].

PubMed

Zhang, X H; Ni, H

1998-04-01

Experiments were done in rabbits anaesthetized with urethane and immobilized under artificial respiration. It was found that substance P (SP, 0.8 ng/kg dissolved in 100 microliters artificial cerebro-spinal fluid, CSF) injected into the 4th ventricle induced either a rise or a drop of pulmonary arterial pressure (PAP) with predominated pressor response. In addition, a rise in carotid arterial pressure (CAP) and reduction in heart rate (HR) were also observed, whereas no significant alteration in PAP, CAP and HR was observed. Microinjection of SP receptor antagonist [D-Pro2, D-Phe7, D-Trp9]--SP (5-10 ng dissolved in 0.5 microliter CSF) or phentolamine (2-3 micrograms dissolved in 0.5 microliter CSF) into the bilateral rostral ventrolateral medulla (rVLM) prior to intraventricular injection of SP could block the SP-induced pressor responses in pulmonary and carotid arteries, while microinjection of SP receptor antagonist or phentolamine into bilateral caudal ventrolateral medulla (cVLM) at the same dosage had no effect. The results show that SP-induced pulmonary and carotid pressor responses may be mediated through SP-receptor and alpha-adrenergic receptors in the rostral ventro-lateral medulla (rVLM).

Alterations in the function of circulating mononuclear cells derived from patients with Crohn’s disease treated with mastic

PubMed Central

Kaliora, Andriana C; Stathopoulou, Maria G; Triantafillidis, John K; Dedoussis, George VZ; Andrikopoulos, Nikolaos K

2007-01-01

AIM: To assess the effects of mastic administration on cytokine production of circulating mononuclear cells of patients with active Crohn's disease (CD). METHODS: The study was conducted in patients with established mildly to moderately active CD, attending the outpatient clinics of the hospital, and in healthy controls. Recruited to a 4 wk treatment with mastic caps (6 caps/d,0.37 g/cap) were 10 patients and 8 controls, all of who successfully completed the protocol. Interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), macrophage migration inhibitory factor (MIF) and intracellular antioxidant glutathione (GSH) were evaluated in peripheral blood mononuclear cells (PBMC) before and after treatment. RESULTS: Treating CD patients with mastic resulted in the reduction of TNF-α secretion (2.1 ± 0.9 ng/mL vs 0.5 ± 0.4 ng/mL, P = 0.028). MIF release was significantly increased (1.2 ± 0.4 ng/mL vs 2.5 ± 0.7 ng/mL, P = 0.026) meaning that random migration and chemotaxis of monocytes/macrophages was inhibited. No significant changes were observed in IL-6, MCP-1 and GSH concentrations. CONCLUSION: This study shows that mastic acts as an immunomodulator on PBMC, acting as a TNF-α inhibitor and a MIF stimulator. Although further double-blind, placebo-controlled studies in a large number of patients is required to clarify the role of this natural product, this finding provides strong evidence that mastic might be an important regulator of immunity in CD. PMID:18023095

Recoil /sup 18/F chemistry. XI. High pressure investigation of 1,1-difluoroethane

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

Manning, R.G.; Root, J.W.

1980-06-15

Nuclear recoil /sup 18/F reactions in CH/sub 3/CHF/sub 2/ have been investigated throughout the effective pressure range 0.3--190 atm. The principal reaction channel is F-to-HF abstraction for which the combined yield from quasithermal and energetic processes in the presence of 5 mole% H/sub 2/S additive is 83.4% +- 0.2%. A reaction mechanism is proposed that involves the organic product forming channels F-for-F, F-for-..cap alpha..H, F-for-..beta..H, F-for-CH/sub 3/ and F-for-CHF/sub 2/. The results are compared with those reported for the /sup 18/F+CH/sub 3/CF/sub 3/ system.

Angular distributions of the protons in the reaction. pi. /sup +/+Xe. -->. p+xxx at 2. 34 GeV/c as a background for the shock-wave effect

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

Slowinski, B.; Strugalski, Z.

1977-02-20

Results are presented of an analysis of the angular distributions of protons with E/sub p/> or =30 MeV emitted with different numbers of secondary charged particles in ..pi../sup +/+Xe interactions at 2.34 GeV/c. The obtained distributions are compared with the analogous characteristics of the protons emitted in collisions of protons or ..cap alpha.. particles with heavy emulsion nuclei and with lead at 70 and 17 GeV/c. It is concluded that the investigated distributions reveal no irregularities capable of attesting to a noticable role of the shock-wave mechanism in the target nuclei.

A comparison of the characteristics of iOS and Android users of a smoking cessation app.

PubMed

Ubhi, Harveen Kaur; Kotz, Daniel; Michie, Susan; van Schayck, Onno C P; West, Robert

2017-06-01

iOS and Android smartphone users may differ in ways that affect their use and likelihood of success when using a smoking cessation application (app). If so, it may be necessary to take the device type (iOS and Android) into account when designing smoking cessation apps and in studies evaluating app effectiveness. How do socio-demographic and smoking characteristics, potentially relevant to engagement and cessation outcomes, of the SF28 app users differ between those using the iOS version and those using the Android version? Data were collected between October 2013 and April 2015. The variables measured were age, gender, social grade, time since the most recent quit attempt, choice of medication use (nicotine replacement therapy or varenicline), weekly expenditure on cigarettes, cigarettes smoked per day, reason for using the app and quit date set. The alpha was set to p < 0.006 to adjust for multiple comparisons. A total of 1368 users were included in the analysis. iOS and Android device users were similar in terms of age, social grade, weekly expenditure on cigarettes and cigarettes smoked per day. Compared with Android users, iOS users were more likely to have downloaded the app for a serious quit attempt (74.3 versus 69.6%, p = 0.001), made a quit attempt within the last 12 months (59.6 versus 45.9%, p < 0.001) and set their quit date on the day of registration (61 versus 46.2%, p < 0.001). They were less likely to have used stop-smoking medication to support their quit attempt (31.5 versus 48.6%, p < 0.001). Differences between smokers using the iOS version of smoking cessation apps and those using the Android version may influence quit success.

Anti-inflammatory effects of sucrose-derived oligosaccharides produced by a constitutive mutant L. mesenteroides B-512FMCM dextransucrase in high fat diet-fed mice.

PubMed

Kang, Min-Gyung; Lee, Hee Jae; Cho, Jae-Young; Kim, Kanghwa; Yang, Soo Jin; Kim, Doman

2016-08-26

Oligosaccharide (OS) is used as a sugar replacement as well as an ingredient in functional foods because of its beneficial effects, mainly on reducing calorie content and promoting intestinal health. By contrast, the effects of OS on inflammation are less well investigated. The purpose of this study was to investigate the effects of sucrose-derived OS on glucose control and inflammation in high fat (HF) diet-fed mice. Male C57BL6 mice were randomly assigned to six treatment groups (n = 10-14 mice per group): 1) lean control (CON), 2) HF control, 3) HF-low sucrose (LS, 100 mg/kg/day), 4) HF-high sucrose (HS, 1000 mg/kg/day), 5) HF-low OS (LOS, 100 mg/kg/day), and 6) HF-high OS (HOS, 1000 mg/kg/day). PBS (vehicle), sucrose, and OS were administered by stomach gavage. Body weight, food intake, and markers of liver function (activities of aspartate aminotransferase and alanine aminotransferase) were not affected by the treatments. HOS treatment decreased levels of serum glucose, insulin, and homeostasis model assessment-insulin resistance compared with sucrose treatment. However, serum adiponectin levels of the HOS group were higher than those of the sucrose groups. Serum levels of the pro-inflammatory cytokines interleukin-6 (IL-6) and fetuin-A were lower in the HOS group than in the sucrose groups. Hepatic gene expression levels of pro-inflammatory cytokines and related factors (fetuin-A, NF-κB, TLR4, TNF-alpha, and IL-6) were decreased and the levels of insulin signaling-related molecules (sirtuin 1, insulin receptor, and Akt) were increased in HOS-treated mice as compared with sucrose-treated mice. These results demonstrate that OS treatment is effective in improving glucose control and inflammation in high fat diet-fed mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Boldenone, boldione, and milk replacers in the diet of veal calves: the effects of phytosterol content on the urinary excretion of boldenone metabolites.

PubMed

Gallina, G; Ferretti, G; Merlanti, R; Civitareale, C; Capolongo, F; Draisci, R; Montesissa, C

2007-10-03

Twenty-six veal calves were split into two groups and fed two milk replacers with a different content of phytosterols for 26 days; then, 14 calves (7 animals from each diet) were kept as controls and 12 calves (6 per diet) received daily, per os, a combination of 17beta-boldenone (17beta-Bol) and androsta-1,4-dien-3,17-dione (ADD) for 38 days. The urinary elimination of 17 alpha-/17beta-boldenone conjugates (17 alpha/beta-Bol) and androsta-1,4-dien-3,17-dione (ADD) was followed by liquid chromatography-tandem mass spectrometry from all of the animals until slaughtering. In urine from treated animals, 17 alpha-Bol concentrations, despite a great variability, were greater than 17beta-Bol, both detected always as conjugates. At days 1, 2, and 3, the mean urine concentration of 17 alpha-Bol was higher than 12 ng/mL. A remarkable decrease was observed during the following days, but the 17 alpha-Bol concentration was still higher than the attention level of 2 ng/mL in 58% of the samples; the concentration of 17beta-Bol was around the action level of 1 ng/mL; two days after treatment withdrawal, no 17beta-Bol was detected in the urine. In urine from control animals, the 17 alpha-Bol concentration was strictly related to the phytosterol content of the diet, while, in urine from treated animals, the much higher 17 alpha-Bol levels were not modified by the production from diet precursors. The results confirmed that a 17 alpha-Bol level higher than 2 ng/mL should be considered as evidence of suspected illegal treatment and that the urinary excretion of 17beta-Bol is due to exogenous administration of 17beta-Bol. The discontinuous rate of elimination of both 17 alpha- and 17beta-Bol, despite the daily administration of 17beta-Bol plus ADD, indicates the necessity for further research to detect other urinary boldenone metabolites to strength surveillance strategy.

Xmsx-1 modifies mesodermal tissue pattern along dorsoventral axis in Xenopus laevis embryo.

PubMed

Maeda, R; Kobayashi, A; Sekine, R; Lin, J J; Kung, H; Maéno, M

1997-07-01

This study analyzes the expression and the function of Xenopus msx-1 (Xmsx-1) in embryos, in relation to the ventralizing activity of bone morphogenetic protein-4 (BMP-4). Expression of Xmsx-1 was increased in UV-treated ventralized embryos and decreased in LiCl-treated dorsalized embryos at the neurula stage (stage 14). Whole-mount in situ hybridization analysis showed that Xmsx-1 is expressed in marginal zone and animal pole areas, laterally and ventrally, but not dorsally, at mid-gastrula (stage 11) and late-gastrula (stage 13) stages. Injection of BMP-4 RNA, but not activin RNA, induced Xmsx-1 expression in the dorsal marginal zone at the early gastrula stage (stage 10+), and introduction of a dominant negative form of BMP-4 receptor RNA suppressed Xmsx-1 expression in animal cap and ventral marginal zone explants at stage 14. Thus, Xmsx-1 is a target gene specifically regulated by BMP-4 signaling. Embryos injected with Xmsx-1 RNA in dorsal blastomeres at the 4-cell stage exhibited a ventralized phenotype, with microcephaly and swollen abdomen. Histological observation and immunostaining revealed that these embryos had a large block of muscle tissue in the dorsal mesodermal area instead of notochord. On the basis of molecular marker analysis, however, the injection of Xmsx-1 RNA did not induce the expression of alpha-globin, nor reduce cardiac alpha-actin in dorsal marginal zone explants. Furthermore, a significant amount of alpha-actin was induced and alpha-globin was turned off in the ventral marginal zone explants injected with Xmsx-1. These results indicated that Xmsx-1 is a target gene of BMP-4 signaling, but possesses a distinct activity on dorsal-ventral patterning of mesodermal tissues.

Effect of low-magnitude, high-frequency vibration on osteogenic differentiation of rat mesenchymal stromal cells.

PubMed

Lau, Esther; Lee, W David; Li, Jason; Xiao, Andrew; Davies, John E; Wu, Qianhong; Wang, Liyun; You, Lidan

2011-07-01

Whole body vibration (WBV), consisting of a low-magnitude, high-frequency (LMHF) signal, is anabolic to bone in vivo and may act through alteration of the lineage commitment of mesenchymal stromal cells (MSC). We investigated the effect of LMHF vibration on rat bone marrow-derived MSCs (rMSCs) in an in vitro system. We subjected rMSCs to repeated (six) bouts of 1-h vibration at 0.3g and 60 Hz in the presence of osteogenic (OS) induction medium. The OS differentiation of rMSCs under the loaded and non-loaded conditions was assessed by examining cell proliferation, alkaline phosphatase (ALP) activity, mRNA expression of various osteoblast-associated markers [ALP, Runx2, osterix (Osx), collagen type I alpha 1 (COL1A1), bone sialoprotein (BSP), osteopontin (OPN), and osteocalcin (OCN)], and matrix mineralization. LMHF vibration did not enhance the OS differentiation of rMSCs. Surprisingly, the mRNA level of Osx, a transcription factor necessary for osteoblast formation, was decreased, and matrix mineralization was inhibited. Our findings suggest that LMHF vibration may exert its anabolic effects in vivo via mechanosensing of a cell type different from MSCs. Copyright © 2011 Orthopaedic Research Society.

A new triclinic modification of the pyrochlore-type KOs{sub 2}O{sub 6} superconductor

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

Katrych, S.; Gu, Q.F.; Bukowski, Z.

2009-03-15

A new modification of KOs{sub 2}O{sub 6}, the representative of a new structural type (Pearson symbol aP18, a=5.5668(1) A, b=6.4519(2) A, c=7.2356(2) A, {alpha}=65.377(3){sup o}, {beta}=70.572(3){sup o}, {gamma}=75.613(2){sup o} space group P-1, no. 2 was synthesized employing high pressure technique. Its structure was determined by single-crystal X-ray diffraction. The structure can be described as two OsO{sub 6} octahedral chains relating to each other through inversion and forming big voids with K atoms inside. Quantum chemical calculations were performed on the novel compound and structurally related cubic compound. High-pressure X-ray study showed that cubic KOs{sub 2}O{sub 6} phase was stable upmore » to 32.5(2) GPa at room temperature. - Graphical abstract: A new modification of KOs{sub 2}O{sub 6}, the representative of a new structural type (Pearson symbol aP18, a=5.5668(1) A, b=6.4519(2) A, c=7.2356(2) A, {alpha}=65.377(3){sup o}, {beta}=70.572(3){sup o}, {gamma}=75.613(2){sup o} space group P-1, no. 2 was synthesized employing high pressure technique. The structure can be described as two OsO{sub 6} octahedral chains relating to each other through inversion and forming big voids with K atoms inside.« less

Functional reconstitution of prostaglandin E receptor from bovine adrenal medulla with guanine nucleotide binding proteins

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

Negishi, M.; Ito, S.; Yokohama, H.

1988-05-15

Prostaglandin E/sub 2/ (PEG/sub 2/) was found to bind specifically to a 100,000 x g pellet prepared from bovine adrenal medulla. The PGE receptor was associated with a GTP-binding protein (G-protein) and could be covalently cross-linked with this G-protein by dithiobis(succinimidyl propionate) in the 100,000 x g pellet. In order to characterize the G-protein associated with the PGE receptor and reconstitute these proteins in phospholipid vesicles, the authors purified the G-protein to apparent homogeneity from the 100,000 x g pellet. The G-protein served as a substrate of pertussis toxin but differed in its ..cap alpha.. subunit from two known pertussismore » toxin substrate G-proteins (G/sub i/ and G/sub 0/) purified from bovine brain. The molecular weight of the ..cap alpha.. subunit was 40,000, which is between those of G/sub i/ and G/sub 0/. The purified protein was also distinguished immunologically from G/sub i/ and G/sub 0/ and was referred to as G/sub am/. Reconstitution of the PGE receptor with pure C/sub am/, G/sub i/, or G/sub 0/ in phospholipid vesicles resulted in a remarkable restoration of (/sup 3/H)PGE/sub 2/ binding activity in a GTP-dependent manner. The efficiency of these three G-proteins in this capacity was roughly equal. When pertussis toxin- or N-ethylmaleimide-treated G-proteins, instead of the native ones, were reconstituted into vesicles, the restoration of binding activity was no longer observed. These results indicate that the PGE receptor can couple functionally with G/sub am/, G/sub i/, or G/sub 0/ in phospholipid vesicles and suggest that G/sub am/ may be involved in signal transduction of the PGE receptor in bovine adrenal medulla.« less

Structural features of lipoarabinomannan from Mycobacterium bovis BCG. Determination of molecular mass by laser desorption mass spectrometry.

PubMed

Venisse, A; Berjeaud, J M; Chaurand, P; Gilleron, M; Puzo, G

1993-06-15

It was recently shown that mycobacterial lipoarabinomannan (LAM) can be classified into two types (Chatterjee, D., Lowell, K., Rivoire B., McNeil M. R., and Brennan, P. J. (1992) J. Biol. Chem. 267, 6234-6239) according to the presence or absence of mannosyl residues (Manp) located at the nonreducing end of the oligoarabinosyl side chains. These two types of LAM were found in a pathogenic Mycobacterium tuberculosis strain and in an avirulent M. tuberculosis strain, respectively, suggesting that LAM with Manp characterizes virulent and "disease-inducing strains." We now report the structure of the LAM from Mycobacterium bovis Bacille Calmette-Guérin (BCG) strain Pasteur, largely used throughout the world as vaccine against tuberculosis. Using an up-to-date analytical approach, we found that the LAM of M. bovis BCG belongs to the class of LAMs capped with Manp. By means of two-dimensional homonuclear and heteronuclear scalar coupling NMR analysis and methylation data, the sugar spin system assignments were partially established, revealing that the LAM contained two types of terminal Manp and 2-O-linked Manp. From the following four-step process: (i) partial hydrolysis of deacylated LAM (dLAM), (ii) oligosaccharide derivatization with aminobenzoic ethyl ester, (iii) HPLC purification, (iv) FAB/MS-MS analysis; it was shown that the dimannosyl unit alpha-D-Manp-(1-->2)-alpha-D-Manp is the major residue capping the termini of the arabinan of the LAM. In this report, LAM molecular mass determination was established using matrix-assisted UV-laser desorption/ionization mass spectrometry which reveals that the LAM molecular mass is around 17.4 kDa. The similarity of the LAM structures between M. bovis BCG and M. tuberculosis H37Rv is discussed in regard to their function in the immunopathology of mycobacterial infection.

Studies on transposable elements in yeast. I. ROAM mutations causing increased expression of yeast genes: their activation by signals directed toward conjugation functions and their formation by insertion of Tyl repetitive elements

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

Errede, B.; Cardillo, T.S.; Wever, G.

1981-01-01

Mechanisms available to eukaryotic organisms for the coordinate regulation of gene expression are being examined by genetic and biochemical characterization of an unusual mutation, CYC7-H2, which causes over-production of iso-2-cytochrome c in the yeast Saccharomyces cerevisiae. The CYC7-H2 mutation causes overproduction in haploid strains but only a 1- to 40-fold overproduction in MATa/MAT..cap alpha.. diploid strains. This regulation of overproduction has been characterized as a response to signals controlling conjugation in yeast. Furthermore, the abnormal controlling region has been identified as an insertion of a transposable and reiterated Ty1 element adjacent to the structural gene. Therefore, we suggest that Ty1more » elements or portions of Ty1 elements occur adjacent to some of the genes required for conjugation and that they normally function to control expression of this process. The suggested role of reiterated sequences may represent a general mechanism of coordinate regulation in eukaryotes. The CYC7-H2 mutation is closely related to other regulatory mutations occurring at the cargA, cargB and DUR1,2 loci. Similar to the CYC7-H2 mutation, the mutations designated cargA/sup +/O/sup h/, cargB/sup +/O/sup h/, and durO/sup h/ cause constitutive production of their respective gene products at much lower levels of MATa/MAT..cap alpha.. diploid strains than in the corresponding haploid strains. A consistent relationship between conjugation competence and the level of overproduction in all four mutants has been established. Observations characterizing the regulation of overproduction in the CYC7-H2 mutant are presented with the additional and parallel observations for the O/sup h/ mutants. Together these results provide a demonstration of the specificity and equivalence of regulatory control exhibited by ROAM mutants.« less

Formation of glutamine from (/sup 13/N)ammonia, (/sup 13/N)dinitrogen, and (/sup 14/C)glutamate by heterocysts isolated from Anabaena cylindrica

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

Thomas, J.; Meeks, J.C.; Wolk, C.P.

A method is described for the isolation of metabolically active heterocysts from Anabaena cylindrica. These isolated heterocysts accounted for up to 34% of the acetylene-reducing activity of whole filaments and had a specific activity of up to 1,560 nmol of C/sub 2/H/sub 4/ formed per mg of heterocyst chlorophyll per min. Activity of glutamine synthetase was coupled to activity of nitrogenase in isolated heterocysts as shown by acetylene-inhibitable formation of (/sup 13/N)NH/sub 3/ and of amide-labeled (/sup 13/N)glutamine from (/sup 13/N)N/sub 2/. A method is also described for the production of 6-mCi amounts of (/sup 13/N)NH/sub 3/. Isolated heterocysts formedmore » (/sup 13/N)glutamine from (/sup 13/N)NH/sub 3/ and glutamate, and (/sup 14/C)glutamine from NH/sub 3/ and (/sup 14/C)glutamate, in the presence of magnesium adenosine 5'-triphosphate. Methionine sulfoximine strongly inhibited these syntheses. Glutamate synthase is, after nitrogenase and glutamine synthetase, the third sequential enzyme involved in the assimilation of N/sub 2/ by intact filaments. However, the kinetics of solubilization of the activity of glutamate synthase during cavitation of suspensions of A. cylindrica indicated that very little, if any, of the activity of that enzyme was located in heterocysts. Concordantly, isolated heterocysts failed to form substantial amounts of radioactive glutamate from either (/sup 13/N)glutamine or ..cap alpha..-(/sup 14/C)ketoglutarate in the presence of other substrates and cofactors of the glutamate synthase reaction. However, they formed (/sup 14/C)glutamate rapidly from ..cap alpha..-(/sup 14/C)ketoglutarate by aminotransferase reactions, with various amino acids as the nitrogen donor. The implications of these findings with regard to the identities of the substances moving between heterocysts and vegetative cells are discussed.« less

NMR analyses of the conformations of L-isoleucine and L-valine bound to Escherichia coli isoleucyl-tRNA synthetase

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

Kohda, D.; Kawai, G.; Yokoyama, S.

1987-10-06

The 400-MHz /sup 1/H NMR spectra of L-isoleucine and L-valine were measured in the presence of Escherichia coli isoleucyl-tRNA synthetase (IleRS). Because of chemical exchange of L-isoleucine or L-valine between the free state and the IleRS-bound state, a transferred nuclear Overhauser effect (TRNOE) was observed among proton resonances of L-isoleucine or L-valine. However, in the presence of isoleucyl adenylate tightly bound to the amino acid activation site of IleRS, no TRNOE for L-isoleucine or L-valine was observed. This indicates that the observed TRNOE is due to the interaction of L-isoleucine or L-valine with the amino acid activation site of IleRS.more » The conformations of these amino acids in the amino acid activation site of IleRS were determined by the analyses of time dependences of TRNOEs and TRNOE action spectra. The IleRS-bound L-isoleucine takes the gauche/sup +/ form about the C/sub ..cap alpha../-C/sub ..beta../ bond and the trans form about the C/sub ..beta../-C/sub ..gamma../sub 1// bond. The IleRS-bound L-valine takes the guache/sup -/ form about the C/sub ..cap alpha../-C/sub ..beta../ bond. Thus, the conformation of the IleRS-bound L-valine is the same as that of IleRS-bound L-isoleucine except for the delta-methyl group. The side chain of L-isoleucine or L-valine lies in an aliphatic hydrophobic pocket of the active site of IleRS. Such hydrophobic interaction with IleRS is more significant for L-isoleucine than for L-valine. The TRNOE analysis is useful for studying the amino acid discrimination mechanism of aminoacyl-tRNA synthetases.« less

Kinetics and mechanisms of 1,5-dihydroflavin reduction of carbonyl compounds and flavin oxidation of alcohols. III. Oxidation of benzoin by flavin and reduction of benzil by 1,5-dihydroflavin

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

Bruice, T.C.; Taulane, J.P.

1976-11-24

The oxidation of benzoin by lumiflavin-3-acetic acid (Fl/sub ox/) to provide benzil and 1,5-dihydrolumiflavin-3-acetic acid (FlH/sub 2/) is a readily reversible reaction. It has been established that the mechanism involves general base ionization of benzoin carbon acid (..cap alpha..-ketol) to yield endiolate anion, followed by partitioning of the endiolate anion back to benzoin through general acid proton donation and to benzil by reaction with Fl/sub ox/. The reaction of endiolate anion with Fl/sub ox/ is not subject to acid or base catalysis. Evidence that ionization of benzoin precedes its oxidation by Fl/sub ox/ stems from the observation that the ratemore » attributed to the latter process possesses a constant equal to that for racemization of (+)-benzoin and O/sub 2/ oxidation of benzoin and that this rate constant is characterized by a primary deuterium kinetic isotope effect (k/sup benzoin//k/sup ..cap alpha..-/sup 2/H-benzoin/) of 7.24 +- 1.5. Reduction of benzil to benzoin by FlH/sub 2/ is pH and buffer insensitive below the pK/sub a/ of FlH/sub 2/. These results are consistent with either general acid catalyzed attack of benzoin carbanion at the 4a-position of Fl/sub ox/, followed by a specific base catalyzed collapse of adduct to diketone and dihydroflavin (Scheme III), or to the uncatalyzed reaction of carbanion (endiolate anion) with flavin to provide a semidione-flavin radical pair which then goes on to diketone and dihydroflavin in a non-acid-base catalyzed reaction (Scheme V). These mechanisms are discussed in terms of the kinetics of reaction of other carbanion species with flavin.« less

Direct radioimmunoassay of urinary estrogen and pregnanediol glucuronides during the menstrual cycle

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

Stanczyk, F.Z.; Miyakawa, I.; Goebelsmann, U.

Assays measuring immunoreactive estrone glucuronide (E/sub 1/G), estradiol-3-glucuronide (E/sub 2/-3G), estradiol-17..beta..-glucuronide (E/sub 2/-17G), estriol-3-glucuronide (E/sub 3/-3G), estriol-16..cap alpha..-glucuronide (E/sub 3/-16G), and pregnanediol-3..cap alpha..-glucuronide (Pd-3G) directly in diluted urine were developed and validated. These estrogen and pregnanediol glucuronide fractions were measured in aliquots of 24-hour and overnight samples of urine collected daily from seven women for one menstrual cycle. Urinary hormone excretion was correlated with daily serum estradiol (E/sub 2/), progesterone (P), and lutenizing hormonee (LH) levels. A sharp midcycle LH peak preceded by a preovulatory rise in serum E/sub 2/ and followed by luteal phase serum P levels were notedmore » in each of the seven apparently ovulatory cycles. Twenty-four-hour and overnight urinary excretion patterns of estrogen glucuronides were similar to those of serum E/sub 2/. Of the five estrogen glucuronide fractions tested, excretion of E/sub 2/-17G exhibited the earliest and steepest ascending slope of the preovulatory estrogen surge and correlated best with serum E/sub 2/ levels. Urinary excretion of E/sub 1/-G, E/sub 2/-3G, and E/sub 3/-16G also showed an early and steep preovulatory rise and preceded that of E/sub 3/-3G, whereas urinary excretion of E/sub 3/-3G exhibited the poorest correlation with serum E/sub 2/ concentrations. The urinary excretion of Pd-3G rose parallel to serum P levels and was markedly elevated 2 to 3 days after the midcycle LH peak in both 24-hour and overnight collections of urine. These results indicate that among the urinary estrogen conjugate fractions tested, E/sub 2/-17G is the one that most suitably predicts ovulation.« less

Finite field equation of Yang--Mills theory

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

Brandt, R.A.; Wing-Chiu, N.; Yeung, W.

1980-03-01

We consider the finite local field equation -)(1+1/..cap alpha.. (1+f/sub 4/))g/sup munu/D'Alembertian-partial/sup ..mu../partial/sup ..nu../)A/sup nua/ =-(1+f/sub 3/) g/sup 2/N(A/sup c/..nu..A/sup a/..mu..A/sub ..nu..//sup c/) +xxx+(1-s)/sup 2/M/sup 2/A/sup a/..mu.., introduced by Lowenstein to rigorously describe SU(2) Yang--Mills theory, which is written in terms of normal products. We also consider the operator product expansion A/sup c/..nu..(x+xi) A/sup a/..mu..(x) A/sup b/lambda(x-xi) approx...sigma..M/sup c/ab..nu mu..lambda/sub c/'a'b'..nu..'..mu..'lambda' (xi) N(A/sup nuprimec/'A/sup muprimea/'A/sup lambdaprimeb/')(x), and using asymptotic freedom, we compute the leading behavior of the Wilson coefficients M/sup ...//sub .../(xi) with the help of a computer, and express the normal products in the field equation in terms ofmore » products of the c-number Wilson coefficients and of operator products like A/sup c/..nu..(x+xi) A/sup a/..mu..(x) A/sup b/lambda(x-xi) at separated points. Our result is -)(1+(1/..cap alpha..)(1+f/sub 4/))g/sup munu/D'Alembertian-partial/sup ..mu../partial/sup ..nu../)A/sup nua/ =-(1+f/sub 3/) g/sup 2/lim/sub xiarrow-right0/) (lnxi)/sup -0.28/2b/(A/sup c/..nu.. (x+xi) A/sup a/..mu..(x) A/sub ..nu..//sup c/(x-xi) +epsilon/sup a/bcA/sup muc/(x+xi) partial/sup ..nu../A/sup b//sub ..nu../(x)+xxx) +xxx)+(1-s)/sup 2/M/sup 2/A/sup a/..mu.., where ..beta.. (g) =-bg/sup 3/, and so (lnxi)/sup -0.28/2b/ is the leading behavior of the c-number coefficient multiplying the operator products in the field equation.« less

Observations of the boundary layer, cloud, and aerosol variability in the southeast Pacific near-coastal marine stratocumulus during VOCALS-REx

NASA Astrophysics Data System (ADS)

Zheng, X.; Albrecht, B.; Jonsson, H. H.; Khelif, D.; Feingold, G.; Minnis, P.; Ayers, K.; Chuang, P.; Donaher, S.; Rossiter, D.; Ghate, V.; Ruiz-Plancarte, J.; Sun-Mack, S.

2011-09-01

Aircraft observations made off the coast of northern Chile in the Southeastern Pacific (20° S, 72° W; named Point Alpha) from 16 October to 13 November 2008 during the VAMOS Ocean-Cloud- Atmosphere-Land Study-Regional Experiment (VOCALS-REx), combined with meteorological reanalysis, satellite measurements, and radiosonde data, are used to investigate the boundary layer (BL) and aerosol-cloud-drizzle variations in this region. On days without predominately synoptic and meso-scale influences, the BL at Point Alpha was typical of a non-drizzling stratocumulus-topped BL. Entrainment rates calculated from the near cloud-top fluxes and turbulence in the BL at Point Alpha appeared to be weaker than those in the BL over the open ocean west of Point Alpha and the BL near the coast of the northeast Pacific. The cloud liquid water path (LWP) varied between 15 g m-2 and 160 g m-2. The BL had a depth of 1140 ± 120 m, was generally well-mixed and capped by a sharp inversion without predominately synoptic and meso-scale influences. The wind direction generally switched from southerly within the BL to northerly above the inversion. On days when a synoptic system and related mesoscale costal circulations affected conditions at Point Alpha (29 October-4 November), a moist layer above the inversion moved over Point Alpha, and the total-water mixing ratio above the inversion was larger than that within the BL. The accumulation mode aerosol varied from 250 to 700 cm-3 within the BL, and CCN at 0.2 % supersaturation within the BL ranged between 150 and 550 cm-3. The main aerosol source at Point Alpha was horizontal advection within the BL from south. The average cloud droplet number concentration ranged between 80 and 400 cm-3. While the mean LWP retrieved from GOES was in good agreement with the in situ measurements, the GOES-derived cloud droplet effective radius tended to be larger than that from the aircraft in situ observations near cloud top. The aerosol and cloud LWP relationship reveals that during the typical well-mixed BL days the cloud LWP increased with the CCN concentrations. On the other hand, meteorological factors and the decoupling processes have large influences on the cloud LWP variation as well.

Biological influence of Ca/P ratio on calcium phosphate coatings by sol-gel processing.

PubMed

Catauro, M; Papale, F; Sapio, L; Naviglio, S

2016-08-01

The objective of this work has been to develop low temperature sol-gel glass coatings to modify the substrate surface and to evaluate their bioactivity and biocompatibility. Glasses, based on SiO2·CaO·P2O5, were synthesized by the sol-gel technique using tetraethyl orthosilicate, calcium nitrate tetrahydrate and triethyl phosphate as precursors of SiO2, CaO and P2O5, respectively. Those materials, still in the sol phase, have been used to coat substrates by means of the dip-coating technique. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) has been used for characterize coatings and a microstructural analysis has been obtained using scanning electron microscopy (SEM). The potential applications of the coatings in the biomedical field were evaluated by bioactivity and biocompatibility tests. The coated substrate was immersed in simulated body fluid (SBF) for 21days and the hydroxyapatite deposition on its surface was subsequently evaluated via SEM-EDXS analysis, as an index of bone-bonding capability. In order to study the cell behavior and response to our silica based materials, prepared via the sol-gel method, with various Ca/P ratio and coating substrate, we have used the human osteoblast-like U2OS cell line. Copyright © 2016 Elsevier B.V. All rights reserved.

[Factorial Structure of the Cardiff Anomalous Perceptions Scale (CAPS) in a Colombian Population Sample].

PubMed

Tamayo-Agudelo, William; Jaén-Moreno, María José; Luque-Luque, Rogelio

2015-01-01

The continuum hypothesis of psychosis assumes that hallucinations are not exclusive of psychotic disorders. A number of psychometric tests have been developed to assess psychosis using a dimensional model. To determine the factorial structure of the Cardiff Anomalous Perceptions Scale (CAPS) for the Colombian population, and to contrast the fit of two factor models previously reported in the literature by conducting a confirmatory factor analysis (CFA). This was a cross-sectional study in which 207 subjects from the general population were assessed using the Cardiff Anomalous Perceptions Scale. A two-factor structure with acceptable ordinal alpha coefficients (α=.88 and α=.87) was found. One factor gathered items related to multimodal perceptual alterations, and a second factor grouped items related with experiences linked to the temporal lobe. The analysis of the first factor indicated that it was dependent on cultural issues for the interpretation of sensations. The second factor appeared almost unchanged on diverse populations, suggesting its transcultural character. When comparing the models proposed by Bell et al. and Jaen-Moreno et al. using the data obtained from the sample, the confirmatory factor analysis conducted indicated inadequate goodness-of-fit indexes (χ(2)). However, some incremental goodness-of-fit indexes (normalized χ(2) [RMSEA]) were acceptable. The Jaén-Moreno et al. model showed the best fit to the data collected from the Colombian sample. The factorial structure of CAPS for the Colombian population appears to be sensitive to cultural issues, especially when describing anomalous sensorial experiences. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

A process for the chemical preparation of high-field ZnO varistors

DOEpatents

Brooks, R.A.; Dosch, R.G.; Tuttle, B.A.

1986-02-19

Chemical preparation techniques involving co-precipitation of metals are used to provide microstructural characteristics necessary in order to produce ZnO varistors and their precursors for high field applications. The varistors produced have homogeneous and/or uniform dopant distributions and a submicron average grain size with a narrow size distribution. Precursor powders are prepared via chemical precipitation techniques and varistors made by sintering uniaxially and/or isostatically pressed pellets. Using these methods, varistors were made which were suitable for high-power applications, having values of breakdown field, E/sub B/, in the 10 to 100 kV/cm range, ..cap alpha.. > 30 and densities in the range of 65 to 99% of theoretical, depending on both composition and sintering temperature.

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

Wemmer, D.E.; Kumar, N.V.; Metrione, R.M.

Toxin II from Radianthus paumotensis (Rp/sub II/) has been investigated by high-resolution NMR and chemical sequencing methods. Resonance assignments have been obtained for this protein by the sequential approach. NMR assignments could not be made consistent with the previously reported primary sequence for this protein, and chemical methods have been used to determine a sequence with which the NMR data are consistent. Analysis of the 2D NOE spectra shows that the protein secondary structure is comprised of two sequences of ..beta..-sheet, probably joined into a distorted continuous sheet, connected by turns and extended loops, without any regular ..cap alpha..-helical segments.more » The residues previously implicated in activity in this class of proteins, D8 and R13, occur in a loop region.« less

Electrical resistivity of La

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

Legvold, S.; Burgardt, P.; Beaudry, B.J.

1977-09-15

The electrical resistivity of high-purity double hexagonal-close-packed (dhcp) ..cap alpha..-La from 5 to 300 K is reported. Measurements were made on small-grained samples prepared by heat treatment of cold-worked lanthanum. Measurements were also made on samples cut in different directions from an ingot slowly cooled from the molten state. The room-temperature results were all within 2% of the mean value. Chemically pure ..beta..-La (fcc) cannot be retained at room temperature, hence, measurements were made on an fcc sample of La containing 0.2-at. % Gd and approx. 0.8-at. % total interstitial nonmetallic impurities. The cubic form has almost the same typemore » of temperature dependence as the dhcp form, but has a 10% lower magnitude.« less

VMEbus based computer and real-time UNIX as infrastructure of DAQ

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

Yasu, Y.; Fujii, H.; Nomachi, M.

1994-12-31

This paper describes what the authors have constructed as the infrastructure of data acquisition system (DAQ). The paper reports recent developments concerned with HP VME board computer with LynxOS (HP742rt/HP-RT) and Alpha/OSF1 with VMEbus adapter. The paper also reports current status of developing a Benchmark Suite for Data Acquisition (DAQBENCH) for measuring not only the performance of VME/CAMAC access but also that of the context switching, the inter-process communications and so on, for various computers including Workstation-based systems and VME board computers.

Voroprot: an interactive tool for the analysis and visualization of complex geometric features of protein structure.

PubMed

Olechnovic, Kliment; Margelevicius, Mindaugas; Venclovas, Ceslovas

2011-03-01

We present Voroprot, an interactive cross-platform software tool that provides a unique set of capabilities for exploring geometric features of protein structure. Voroprot allows the construction and visualization of the Apollonius diagram (also known as the additively weighted Voronoi diagram), the Apollonius graph, protein alpha shapes, interatomic contact surfaces, solvent accessible surfaces, pockets and cavities inside protein structure. Voroprot is available for Windows, Linux and Mac OS X operating systems and can be downloaded from http://www.ibt.lt/bioinformatics/voroprot/.

Numerical Electromagnetic Code (NEC)-Reflector Antenna Code: Part II. Code Manual.

DTIC Science & Technology

1979-09-01

SI N*I~iSl NTE. L%) I 82 GO 󈧏) 242 182 1b8. 3 ZL=P3 84 [) HHO =ZL-HOS( I) b5 If- (r)RH,.L[-..21.AND.DRIIO.GF.O.) ZL=RiOS(1)-9).05 80DFHO=ZL-PHOS(2...ALPHA(2) ,X(2),Y(2),Z(2),XS(3), HHOS (2) DIMENSION MI.J(2 ),.ML(2 ),SIGN(2) I]I LOGI CAL L’f[ST, LI)E13! * 12 COMMON /RFFr)Y/fHOS I -"’ICOMMAON /FOCAL

Effects of age and sedentary lifestyle on skeletal muscle NF-kappaB signaling in men.

PubMed

Buford, Thomas W; Cooke, Matthew B; Manini, Todd M; Leeuwenburgh, Christiaan; Willoughby, Darryn S

2010-05-01

Nuclear factor kappa B (NF-kappaB) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and age. The present study examined lean mass, maximal force production, and skeletal muscle NF-kappaB signaling in 41 men categorized as sedentary (OS, N = 13, 63.85 +/- 6.59 year), physically active (OA, N = 14, 60.71 +/- 5.54 year), or young and sedentary (YS, N = 14, 21.35 +/- 3.84 year). Muscle tissue from the vastus lateralis was assayed for messenger RNA (mRNA) expression of the beta subunit of IkB kinase (IKKbeta), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKBalpha), and nuclear content of NF-kappaB subunits p50 and p65. When compared with YS, OS demonstrated age-related muscle atrophy and reduced isokinetic knee extension torque. Physical activity in older individuals preserved maximal isokinetic knee extension torque. OS muscle contained 50% more pIKBalpha than OA and 61% more pIKBalpha than YS. Furthermore, nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not differ from either of the other two groups for nuclear p50 or for mRNA expression of IKKbeta. These results indicate that skeletal muscle content of nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound p65 appears to be at least partially due to significant increases in pIKBalpha. A sedentary lifestyle appears to play some role in increased IKBalpha; however, further research is needed to identify downstream effects of this increase.

Effects of Age and Sedentary Lifestyle on Skeletal Muscle NF-κB Signaling in Men

PubMed Central

Buford, Thomas W.; Cooke, Matthew B.; Manini, Todd M.; Leeuwenburgh, Christiaan

2010-01-01

Background. Nuclear factor kappa B (NF-κB) is a critical signaling molecule of disuse-induced skeletal muscle atrophy. However, few studies have carefully investigated whether similar pathways are modulated with physical activity and age. Methods. The present study examined lean mass, maximal force production, and skeletal muscle NF-κB signaling in 41 men categorized as sedentary (OS, N = 13, 63.85 ± 6.59 year), physically active (OA, N = 14, 60.71 ± 5.54 year), or young and sedentary (YS, N = 14, 21.35 ± 3.84 year). Muscle tissue from the vastus lateralis was assayed for messenger RNA (mRNA) expression of the β subunit of IkB kinase (IKKβ), cytosolic protein content of phosphorylated inhibitor of kappa B alpha (pIKBα), and nuclear content of NF-κB subunits p50 and p65. Results. When compared with YS, OS demonstrated age-related muscle atrophy and reduced isokinetic knee extension torque. Physical activity in older individuals preserved maximal isokinetic knee extension torque. OS muscle contained 50% more pIKBα than OA and 61% more pIKBα than YS. Furthermore, nuclear p65 was significantly elevated in OS compared with YS. OS muscle did not differ from either of the other two groups for nuclear p50 or for mRNA expression of IKKβ. Conclusions. These results indicate that skeletal muscle content of nuclear-bound p65 is elevated by age in humans. The elevation in nuclear-bound p65 appears to be at least partially due to significant increases in pIKBα. A sedentary lifestyle appears to play some role in increased IKBα; however, further research is needed to identify downstream effects of this increase. PMID:20045871

The growth and aggressive behavior of human osteosarcoma is regulated by a CaMKII-controlled autocrine VEGF signaling mechanism.

PubMed

Daft, Paul G; Yang, Yang; Napierala, Dobrawa; Zayzafoon, Majd

2015-01-01

Osteosarcoma (OS) is a hyperproliferative malignant tumor that requires a high vascular density to maintain its large volume. Vascular Endothelial Growth Factor (VEGF) plays a crucial role in angiogenesis and acts as a paracrine and autocrine agent affecting both endothelial and tumor cells. The alpha-Ca2+/Calmodulin kinase two (α-CaMKII) protein is an important regulator of OS growth. Here, we investigate the role of α-CaMKII-induced VEGF in the growth and tumorigenicity of OS. We show that the pharmacologic and genetic inhibition of α-CaMKII results in decreases in VEGF gene expression (50%) and protein secretion (55%), while α- CaMKII overexpression increases VEGF gene expression (250%) and protein secretion (1,200%). We show that aggressive OS cells (143B) express high levels of VEGF receptor 2 (VEGFR-2) and respond to exogenous VEGF (100nm) by increasing intracellular calcium (30%). This response is ameliorated by the VEGFR inhibitor CBO-P11, suggesting that secreted VEGF results in autocrine stimulated α-CaMKII activation. Furthermore, we show that VEGF and α-CaMKII inhibition decreases the transactivation of the HIF-1α and AP-1 reporter constructs. Additionally, chromatin immunoprecipitation assay shows significantly decreased binding of HIF-1α and AP-1 to their responsive elements in the VEGF promoter. These data suggest that α-CaMKII regulates VEGF transcription by controlling HIF-1α and AP-1 transcriptional activities. Finally, CBO-P11, KN-93 (CaMKII inhibitor) and combination therapy significantly reduced tumor burden in vivo. Our results suggest that VEGF-induced OS tumor growth is controlled by CaMKII and dual therapy by CaMKII and VEGF inhibitors could be a promising therapy against this devastating adolescent disease.

The Growth and Aggressive Behavior of Human Osteosarcoma Is Regulated by a CaMKII-Controlled Autocrine VEGF Signaling Mechanism

PubMed Central

Daft, Paul G.; Yang, Yang; Napierala, Dobrawa; Zayzafoon, Majd

2015-01-01

Osteosarcoma (OS) is a hyperproliferative malignant tumor that requires a high vascular density to maintain its large volume. Vascular Endothelial Growth Factor (VEGF) plays a crucial role in angiogenesis and acts as a paracrine and autocrine agent affecting both endothelial and tumor cells. The alpha-Ca2+/Calmodulin kinase two (α-CaMKII) protein is an important regulator of OS growth. Here, we investigate the role of α-CaMKII-induced VEGF in the growth and tumorigenicity of OS. We show that the pharmacologic and genetic inhibition of α-CaMKII results in decreases in VEGF gene expression (50%) and protein secretion (55%), while α- CaMKII overexpression increases VEGF gene expression (250%) and protein secretion (1,200%). We show that aggressive OS cells (143B) express high levels of VEGF receptor 2 (VEGFR-2) and respond to exogenous VEGF (100nm) by increasing intracellular calcium (30%). This response is ameliorated by the VEGFR inhibitor CBO-P11, suggesting that secreted VEGF results in autocrine stimulated α-CaMKII activation. Furthermore, we show that VEGF and α-CaMKII inhibition decreases the transactivation of the HIF-1α and AP-1 reporter constructs. Additionally, chromatin immunoprecipitation assay shows significantly decreased binding of HIF-1α and AP-1 to their responsive elements in the VEGF promoter. These data suggest that α-CaMKII regulates VEGF transcription by controlling HIF-1α and AP-1 transcriptional activities. Finally, CBO-P11, KN-93 (CaMKII inhibitor) and combination therapy significantly reduced tumor burden in vivo. Our results suggest that VEGF-induced OS tumor growth is controlled by CaMKII and dual therapy by CaMKII and VEGF inhibitors could be a promising therapy against this devastating adolescent disease. PMID:25860662

Spectroscopic and Magnetic Investigations of Rhenium(i)chlorine(carbon MONOXIDE)(3)(ALPHA, - Complexes and Group (1B, 8B) Bimetallic Complexes.

NASA Astrophysics Data System (ADS)

Striplin, Durwin Ray

Complexes with the generic formula, Re(I)Cl(CO) _3(alpha,alpha-diimine), where alpha,alpha-diimine = 2,2^'-bipyridine, 1,10 -phenanthroline, or methyl-substituted analogs, were subjected to detailed optical investigations in the 77-4 K range, both in rigid glasses and in PMMA plastics. Excitation spectra, absorption spectra, and decay kinetics of the phosphorescing manifolds were complemented by detailed measurements of polarization ratios to arrive at a coherent picture of the emitting manifolds. Symmetry assignments and energy orderings of the ^3MLCT (metal-to-ligand charge transfer) spin sublevels were made. Analogous assignments for the ^3MLCT spin -sublevels of Ru(alpha, alpha -diimine)_3^{2+} and Os(alpha,alpha-diimine) _{3}^{2+} ions are implied by this analysis. Increases in luminescence decay rates and emission intensities with increasing external magnetic field strength were observed at 4 K. The decay rates were found to be non-quadratic with respect to magnetic field strength. A simple parametric model that includes spin-orbit coupling and a magnetic field perturbation was developed to describe the MLCT excited states. The energies, symmetry assignments, and magnetic field mixing of the ^3MLCT states were rationalized by the model. Fluorescence, phosphorescence, and excitation spectra were measured on a series of mu -bridged bis(diphenylphosphinomethane) homo- and heterobimetallic compounds of Rh(I), Ir(I), Pt(II), and Au(I). These results were augmented with polarization ratios obtained at 77 K and detailed studies of the temperature dependence of the phosphorescence in the 77-4 K range. The triplet manifold is split by spin-orbit coupling into a forbidden state lying lowest in energy followed by a quasi-degenerate pair lying a few wavenumbers higher that decays two orders of magnitude faster. A quadratic dependence of the decay rate on magnetic field strength was recorded at 4 K for ail complexes. The results are consistent with a rm d_{sigma*}to p_sigma orbital promotion, and the direction of charge-transfer for heterobimetallic complexes was unambiguously assigned. Electronic structural models based on D_{rm 4h}, D_{rm 2h}, and C _{rm 2v} micro-symmetries about the axial chromophore were employed to make explicit symmetry assignments of the excited states.

Is oxidative stress, a link between nephrolithiasis and obesity, hypertension, diabetes, chronic kidney disease, metabolic syndrome?

PubMed Central

2017-01-01

Epidemiological studies have provided the evidence for association between nephrolithiasis and a number of cardiovascular diseases including hypertension, diabetes, chronic kidney disease, metabolic syndrome. Many of the co-morbidities may not only lead to stone disease but also be triggered by it. Nephrolithiasis is a risk factor for development of hypertension and have higher prevalence of diabetes mellitus and some hypertensive and diabetic patients are at greater risk for stone formation. An analysis of the association between stone disease and other simultaneously appearing disorders, as well as factors involved in their pathogenesis, may provide an insight into stone formation and improved therapies for stone recurrence and prevention. It is our hypothesis that association between stone formation and development of co-morbidities is a result of certain common pathological features. Review of the recent literature indicates that production of reactive oxygen species (ROS) and development of oxidative stress (OS) may be such a common pathway. OS is a common feature of all cardiovascular diseases (CVD) including hypertension, diabetes mellitus, atherosclerosis and myocardial infarct. There is increasing evidence that ROS are also produced during idiopathic calcium oxalate (CaOx) nephrolithiasis. Both tissue culture and animal model studies demonstrate that ROS are produced during interaction between CaOx/calcium phosphate (CaP) crystals and renal epithelial cells. Clinical studies have also provided evidence for the development of oxidative stress in the kidneys of stone forming patients. Renal disorders which lead to OS appear to be a continuum. Stress produced by one disorder may trigger the other under the right circumstances. PMID:22213019

Is oxidative stress, a link between nephrolithiasis and obesity, hypertension, diabetes, chronic kidney disease, metabolic syndrome?

PubMed

Khan, Saeed R

2012-04-01

Epidemiological studies have provided the evidence for association between nephrolithiasis and a number of cardiovascular diseases including hypertension, diabetes, chronic kidney disease, metabolic syndrome. Many of the co-morbidities may not only lead to stone disease but also be triggered by it. Nephrolithiasis is a risk factor for development of hypertension and have higher prevalence of diabetes mellitus and some hypertensive and diabetic patients are at greater risk for stone formation. An analysis of the association between stone disease and other simultaneously appearing disorders, as well as factors involved in their pathogenesis, may provide an insight into stone formation and improved therapies for stone recurrence and prevention. It is our hypothesis that association between stone formation and development of co-morbidities is a result of certain common pathological features. Review of the recent literature indicates that production of reactive oxygen species (ROS) and development of oxidative stress (OS) may be such a common pathway. OS is a common feature of all cardiovascular diseases (CVD) including hypertension, diabetes mellitus, atherosclerosis and myocardial infarct. There is increasing evidence that ROS are also produced during idiopathic calcium oxalate (CaOx) nephrolithiasis. Both tissue culture and animal model studies demonstrate that ROS are produced during interaction between CaOx/calcium phosphate (CaP) crystals and renal epithelial cells. Clinical studies have also provided evidence for the development of oxidative stress in the kidneys of stone forming patients. Renal disorders which lead to OS appear to be a continuum. Stress produced by one disorder may trigger the other under the right circumstances.

Closure Report for Corrective Action Unit 573: Alpha Contaminated Sites Nevada National Security Site, Nevada

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

Matthews, Patrick

This Closure Report (CR) presents information supporting the closure of Corrective Action Unit (CAU) 573: Alpha Contaminated Sites, Nevada National Security Site, Nevada. CAU 573 comprises the two corrective action sites (CASs): 05-23-02-GMX Alpha Contaminated Are-Closure in Place and 05-45-01-Atmospheric Test Site - Hamilton- Clean Closure. The purpose of this CR is to provide justification and documentation supporting the recommendation that no further corrective action is needed for CAU 573 based on the implementation of the corrective actions. Corrective action activities were performed at Hamilton from May 25 through June 30, 2016; and at GMX from May 25 to Octobermore » 27, 2016, as set forth in the Corrective Action Decision Document (CADD)/Corrective Action Plan (CAP) for Corrective Action Unit 573: Alpha Contaminated Sites; and in accordance with the Soils Activity Quality Assurance Plan, which establishes requirements, technical planning, and general quality practices. Verification sample results were evaluated against data quality objective criteria developed by stakeholders that included representatives from the Nevada Division of Environmental Protection and the DOE, National Nuclear Security Administration Nevada Field Office (NNSA/NFO) during the corrective action alternative (CAA) meeting held on November 24, 2015. Radiological doses exceeding the final action level were assumed to be present within the high contamination areas associated with CAS 05-23-02, thus requiring corrective action. It was also assumed that radionuclides were present at levels that require corrective action within the soil/debris pile associated with CAS 05-45-01. During the CAU 573 CAA meeting, the CAA of closure in place with a use restriction (UR) was selected by the stakeholders as the preferred corrective action of the high contamination areas at CAS 05-23-02 (GMX), which contain high levels of removable contamination; and the CAA of clean closure was selected by the stakeholders as preferred corrective action for the debris pile at CAS 05-45-01 (Hamilton). The closure in place was accomplished by posting signs containing a warning label on the existing contamination area fence line; and recording the FFACO UR and administrative UR in the FFACO database, the NNSA/NFO CAU/CAS files, and the management and operating contractor Geographic Information Systems. The clean closure was accomplished by excavating the soil/debris pile, disposing of the contents at the Area 5 Radioactive Waste Management Complex, and collecting verification samples. The corrective actions were implemented as stipulated in the CADD/CAP, and verification sample results confirm that the criteria for the completion of corrective actions have been met. Based on the implementation of these corrective actions, NNSA/NFO provides the following recommendations: No further corrective actions are necessary for CAU 573; The Nevada Division of Environmental Protection should issue a Notice of Completion to NNSA/NFO for closure of CAU 573; CAU 573 should be moved from Appendix III to Appendix IV of the FFACO.« less

Carbon Dioxide Landscape

NASA Technical Reports Server (NTRS)

2005-01-01

23 July 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a view of some of the widely-varied terrain of the martian south polar residual cap. The landforms here are composed mainly of frozen carbon dioxide. Each year since MGS arrived in 1997, the scarps that bound each butte and mesa, or line the edges of each pit, in the south polar region, have changed a little bit as carbon dioxide is sublimed away. The scarps retreat at a rate of about 3 meters (3 yards) per martian year. Most of the change occurs during each southern summer.

Location near: 86.7oS, 9.8oW Image width: width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Spring

Preliminary Inventory of the Retired Records of the 1st United States Army Infantry Division during the Vietnam War, 2 October 1965-14 April 1970. Sanitized Version.

DTIC Science & Technology

1982-05-01

con Oft uh 6 to the appdsb feual Rec"It Comer for RECORDS TRANSMITTAL AND RECEIPT apm pro to shipaat of f Spse arcns aon rese. PAMIf A. TO 4i5 ASd5 * pv... gmo -M IN nm nd 10mi AV No*5 m General Orders; General Correspondence; Daily Staff Journals; Tactical Operatiod Center (TOC) Logs; Cmand Reports...AGENiCYwo m a gewn.uirm DIPSL " 1n 2,I (w l6_t 4,11A 4s. 41) pollo~ 01)S 10~e 1~e (1) (A)A. IndiOs Cap Ill StA SAC(G3O4NID: Th.&. record. were pros edfor

Carbon Dioxide Landscape

NASA Technical Reports Server (NTRS)

2004-01-01

7 July 2004 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a mid-summer view of the south polar residual cap at full MOC resolution, 1.5 m (5 ft) per pixel. During each of the three summers since the start of the MGS mapping mission in March 1999, the scarps that form mesas and pits in the 'Swiss cheese'-like south polar terrain have retreated an average of about 3 meters (1 yard). The material is frozen carbon dioxide; another 3 meters or so of each scarp is expected to be removed during the next summer, in late 2005. This image is located near 86.0oS, 350.8oW, and covers an area about 1.5 km (0.9 mi) wide. Sunlight illuminates the scene from the top/upper left.

South Polar Artwork

NASA Technical Reports Server (NTRS)

2003-01-01

MGS MOC Release No. MOC2-456, 18 August 2003

Nature has created some interesting artwork on the south polar residual cap of Mars. This July 2003 Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows an example. The patterns in this picture are formed by erosion and sublimation of multiple layers of frozen carbon dioxide. The artwork is ephemeral and changing with each passing summer. By the end of the coming southern summer, the scarps in this area will have retreated an average of 3 meters (3.3 yards); some of the smaller buttes and ridges will have vanished. This picture covers an area 3 km (1.9 mi) wide and is located near 86.6oS, 358.2oW. Sunlight illuminates the scene from the upper left.

Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies.

PubMed

Bruix, Jordi; Cheng, Ann-Lii; Meinhardt, Gerold; Nakajima, Keiko; De Sanctis, Yoriko; Llovet, Josep

2017-11-01

Sorafenib, an oral multikinase inhibitor, significantly prolonged overall survival (OS) vs. placebo in patients with unresectable hepatocellular carcinoma (HCC) in two phase III studies, SHARP (Sorafenib HCC Assessment Randomized Protocol) and Asia Pacific (AP). To assess prognostic factors for HCC and predictive factors of sorafenib benefit, we conducted a pooled exploratory analysis from these placebo-controlled phase III studies. To identify potential prognostic factors for OS, univariate and multivariate (MV) analyses were performed for baseline variables by Cox proportional hazards model. Hazard ratios (HRs) and median OS were evaluated across pooled subgroups. To assess factors predictive of sorafenib benefit, the interaction term between treatment for each subgroup was evaluated by Cox proportional hazard model. In 827 patients (448 sorafenib; 379 placebo) analyzed, strong prognostic factors for poorer OS identified from MV analysis in both treatment arms were presence of macroscopic vascular invasion (MVI), high alpha-fetoprotein (AFP), and high neutrophil-to-lymphocyte ratio (NLR; ⩽ vs. >median [3.1]). Sorafenib OS benefit was consistently observed across all subgroups. Significantly greater OS sorafenib benefit vs. placebo was observed in patients without extrahepatic spread (EHS; HR, 0.55 vs. 0.84), with hepatitis C virus (HCV) (HR, 0.47 vs. 0.81), and a low NLR (HR, 0.59 vs. 0.84). In this exploratory analysis, presence of MVI, high AFP, and high NLR were prognostic factors of poorer OS. Sorafenib benefit was consistently observed irrespective of prognostic factors. Lack of EHS, HCV, and lower NLR were predictive of a greater OS benefit with sorafenib. This exploratory pooled analysis showed that treatment with sorafenib provides a survival benefit in all subgroups of patients with HCC; however, the magnitude of benefit is greater in patients with disease confined to the liver (without extrahepatic spread), or in those with hepatitis C virus, or a lower neutrophil-to-lymphocyte ratio, an indicator of inflammation status. These results help inform the prognosis of patients receiving sorafenib therapy and provide further refinements for the design of trials testing new agents vs. sorafenib. Clinical Trial Numbers: NCT00105443 and NCT00492752. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

ROS signaling pathways and biological rhythms: perspectives in crustaceans.

PubMed

Fanjul-Moles, Maria Luisa

2013-01-01

This work reviews concepts regarding the endogenous circadian clock and the relationship between oxidative stress (OS), light and entrainment in different organisms including crustaceans, particularly crayfish. In the first section, the molecular control of circadian rhythms in invertebrates, particularly in Drosophila, is reviewed, and this model is contrasted with recent reports on the circadian genes and proteins in crayfish. Second, the redox mechanisms and signaling pathways that participate in the entrainment of the circadian clock in different organisms are reviewed. Finally, the light signals and transduction pathways involved in the entrainment of the circadian clock, specifically in relation to cryptochromes (CRYs) and their dual role in the circadian clock of different animal groups and their possible relationship to the circadian clock and redox mechanisms in crustaceans is discussed. The relationship between metabolism, ROS signals and transcription factors, such as HIF-1 alpha in crayfish, as well as the possibility that HIF-1 alpha participates in the regulation of circadian control genes (ccgs) in crustaceans is discussed.

Detection system for a gas chromatograph. [. cap alpha. -methylnaphthalene,. beta. -methylnapthalene

DOEpatents

Hayes, J.M.; Small, G.J.

1982-04-26

A method and apparatus are described for the quantitative analysis of vaporizable compounds, and in particular of polycyclic aromatic hydrocarbons which may be induced to fluoresce. The sample to be analyzed is injected into a gas chromatography column and is eluted through a narrow orifice into a vacuum chamber. The free expansion of the eluted sample into the vacuum chamber creates a supersonic molecular beam in which the sample molecules are cooled to the extent that the excited vibrational and rotational levels are substantially depopulated. The cooled molecules, when induced to fluoresce by laser excitation, give greatly simplified spectra suitable for analytical purposes. The laser induced fluorimetry provides great selectivity, and the gas chromatograph provides quantitative transfer of the sample to the molecular beam. 3 figures, 2 tables.

Screening of beta-glucan contents in commercially cultivated and wild growing mushrooms.

PubMed

Sari, Miriam; Prange, Alexander; Lelley, Jan I; Hambitzer, Reinhard

2017-02-01

Mushrooms have unique sensory properties and nutritional values as well as health benefits due to their bioactive compounds, especially beta-glucans. Well-known edible and medicinal mushroom species as well as uncommon or unknown species representing interesting sources of bioactive beta-glucans have been widely studied. Commercially cultivated and wild growing mushrooms were analysed for their beta-glucan contents. Enzymatic determinations of all glucans, alpha-glucans and beta-glucans in 39 mushrooms species were performed, leading to very remarkable results. Many wild growing species present high beta-glucan contents, especially Bracket fungi. The well-known cultivated species Agaricus bisporus, Lentinula edodes and Cantharellus cibarius as well as most screened wild growing species show higher glucan contents in their stipes than caps. Copyright © 2016 Elsevier Ltd. All rights reserved.

Observations of 85. cap alpha. recombination lines from M16

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

Higgs, L.A.; Doherty, L.H.; MacLeod, J.M.

1979-01-01

Hydrogen and helium recombination-line observations have been made at eight positions in M16. These observations are compatible with a two-component model of the ionized gas, one component being an extended low-excitation region, the other being a higher-excitation region (with the helium ionized) at a radial velocity about 10 km s/sup -1/ greater than the mean velocity of the first component. The observed radial-velocity variations in the first component appear to be related to streaming motions from ionization fronts. The helium line emission is at a velocity comparable to that of the hottest exciting stars. The continuum radio emission is verymore » low considering the number of O stars in the nebula, indicating that it is probably density bounded.« less

POLYMERIZATION OF /cap alpha/-METHYLSTYRENE BY ELECTRON IRRADIATION (in German)

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

Braun, D.; Heufer, G.; Seufert, W.

1964-01-01

Ampoules of alpha -methylstyrene sealed under vacuum were irradiated with 1-Mev electrons in a type JS Van de Graaff generator; comparative experiments with gamma rays were carried out with a /sup 60/Co source of 3000 deg C. High doses of electrons (ca. 10/sup 8/ rad) are necessary for polymerization. The conversion is graphed as a function of dose at 0 deg C; it reaches a maximum plateau of 65% at 4 x 10/sup 8/ rad; this may point to radiolysis of the polymer at doses above this. Polymerization conversion increases with decreasing dose rate, when dose and temperature are heldmore » constant; and conversion increases with decreasing temperature (22% at --22 deg C; 10% at 15 deg C; <1% at 60 deg C), as has been found with gamma rays. In the solid state between --40 deg C and --80 deg C the maximum yield is only about 5%. The molecular weights of all poly- alpha -methylstyrenes thus formed lie between 3000 and 12,000, independently of dose rate and temperature. All polymethylstyrenes formed in the liquid state have approximately the same tacticity independent of temperature (isotactic about 20%; syndiotactic about 80%). This corresponds to the tacticity of polymers formed cationically with Lewis acids. In the solid state the tacticity is: isotactic 38%, syndiotactic, 62%, comparable with the tacticity of anionic polymerization. In the liquid state the tacticity and the sensitivity towards water indicate a cationic mechanism for the reaction. NMR studies also indicate a cationic mechanism. (BBB)« less

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

Loginova, Y.F.; Dezhurov, S.V.; Zherdeva, V.V.

Highlights: Black-Right-Pointing-Pointer New QDs coated with combination of polythiol ligands and silica shell were synthesized. Black-Right-Pointing-Pointer We examine the QDs stability in digestive tract of mice after per os administration. Black-Right-Pointing-Pointer The polymer/silica shell prevents QDs degradation and fluorescence quenching in vivo. -- Abstract: CdSe-core, ZnS-capped semiconductor quantum dots (QDs) are of great potential for biomedical applications. However, applications in the gastrointestinal tract for in vivo imaging and therapeutic purposes are hampered by their sensitivity to acidic environments and potential toxicity. Here we report the use of coatings with a combination of polythiol ligands and silica shell (QDs PolyT-APS) tomore » stabilize QDs fluorescence under acidic conditions. We demonstrated the stability of water-soluble QDs PolyT-APS both in vitro, in strong acidic solutions, and in vivo. The biodistribution, stability and photoluminescence properties of QDs in the gastrointestinal tract of mice after per os administration were assessed. We demonstrated that QDs coated with current traditional materials - mercapto compounds (QDs MPA) and pendant thiol group (QDs PolyT) - are not capable of protecting QDs from chemically induced degradation and surface modification. Polythiol ligands and silica shell quantum dots (QDs PolyT-APS) are suitable for biological and biomedical applications in the gastrointestinal tract.« less

Predictive factors in patients with hepatocellular carcinoma receiving sorafenib therapy using time-dependent receiver operating characteristic analysis.

PubMed

Nishikawa, Hiroki; Nishijima, Norihiro; Enomoto, Hirayuki; Sakamoto, Azusa; Nasu, Akihiro; Komekado, Hideyuki; Nishimura, Takashi; Kita, Ryuichi; Kimura, Toru; Iijima, Hiroko; Nishiguchi, Shuhei; Osaki, Yukio

2017-01-01

To investigate variables before sorafenib therapy on the clinical outcomes in hepatocellular carcinoma (HCC) patients receiving sorafenib and to further assess and compare the predictive performance of continuous parameters using time-dependent receiver operating characteristics (ROC) analysis. A total of 225 HCC patients were analyzed. We retrospectively examined factors related to overall survival (OS) and progression free survival (PFS) using univariate and multivariate analyses. Subsequently, we performed time-dependent ROC analysis of continuous parameters which were significant in the multivariate analysis in terms of OS and PFS. Total sum of area under the ROC in all time points (defined as TAAT score) in each case was calculated. Our cohort included 175 male and 50 female patients (median age, 72 years) and included 158 Child-Pugh A and 67 Child-Pugh B patients. The median OS time was 0.68 years, while the median PFS time was 0.24 years. On multivariate analysis, gender, body mass index (BMI), Child-Pugh classification, extrahepatic metastases, tumor burden, aspartate aminotransferase (AST) and alpha-fetoprotein (AFP) were identified as significant predictors of OS and ECOG-performance status, Child-Pugh classification and extrahepatic metastases were identified as significant predictors of PFS. Among three continuous variables (i.e., BMI, AST and AFP), AFP had the highest TAAT score for the entire cohort. In subgroup analyses, AFP had the highest TAAT score except for Child-Pugh B and female among three continuous variables. In continuous variables, AFP could have higher predictive accuracy for survival in HCC patients undergoing sorafenib therapy.

Termination of pregnancy by extraamniotic prostaglandins and the synergistic action of oxytocin.

PubMed

Embrey, M P; Hillier, K; Mahendran, P

1973-01-01

This study determines the efficacy of extraamniotic administration of prostaglandins E2 and F2alpha (PGE2 and PGF2alpha) in abortion induction. The method consists of introducing a Foley catheter (14 gauge) through the cervix with the aid of a speculum so that the inflated balloon lies just within the internal os. The balloon volume varies from 30 ml at 12 weeks to 40 ml at 16 weeks gestation and over. Following an initial test dose, a fully effective dose of 200 mcg PGE2 or 750 mcg PGF2alpha is instilled for diffusion into the extraovular space; this dose is repeated at 2 hourly intervals. An automatic pump may also be used to administer the PG. The pattern of uterine contractility with this method is similar to that seen with intravenous therapy. Of 163 consecutive cases analyzed, 144 (88%) achieved abortions within 36 hours, 72% aborted within 24 hours and 94% within 48 hours. Mean abortion time was 22.2 hours. No significant difference was seen in the success rate or abortion time between 21 patients in their 1st trimester of pregnancy and 142 patients in the 2nd trimester. In primigravidas, abortion (within 36 hours) was successful in 87% of the cases; mean abortion time was 24.0 hours. Multigravidas had higher success rate (90%) and shorter mean abortion time (20.4 hours). Comparison of results obtained separately with PGF2alpha and PGE2 shows the superiority of PGE2. Of 93 patients receiving PGF2alpha, 85% aborted within 36 hours (mean abortion time, 24.9 hours). Of 70 PGE2-treated patients, 93% aborted within 36 hours (p=.01) (mean abortion time, 19.4 hours). When parity was considered, PGE2 came out superior again over PGF2alpha. In primigravidas, only 84% of PGF2alpha-treated patients had abortion within 36 hours compared to 90% for PGE2-treated patients. In multigravidas, the success rates at 36 hours were 86% for PGF2alpha and 95% for PGE2. Side effects were minimal. In another trial, intravenous oxytocin was used in addition to extraamniotic PG, resulting in a very substantial decrease in mean abortion time. This method is a simple, effective abortion technique which can be carried out in most cases on a 24-hour basis.

Sequence variations of the alpha-globin genes: scanning of high CG content genes with DHPLC and DG-DGGE.

PubMed

Lacerra, Giuseppina; Fiorito, Mirella; Musollino, Gennaro; Di Noce, Francesca; Esposito, Maria; Nigro, Vincenzo; Gaudiano, Carlo; Carestia, Clementina

2004-10-01

The alpha-globin chains are encoded by two duplicated genes (HBA2 and HBA1, 5'-3') showing overall sequence homology >96% and average CG content >60%. alpha-Thalassemia, the most prevalent worldwide autosomal recessive disorder, is a hereditary anemia caused by sequence variations of these genes in about 25% of carriers. We evaluated the overall sensitivity and suitability of DHPLC and DG-DGGE in scanning both the alpha-globin genes by carrying out a retrospective analysis of 19 variant alleles in 29 genotypes. The HBA2 alleles c.1A>G, c.79G>A, and c.281T>G, and the HBA1 allele c.475C>A were new. Three pathogenic sequence variations were associated in cis with nonpathogenic variations in all families studied; they were the HBA2 variation c.2T>C associated with c.-24C>G, and the HBA2 variations c.391G>C and c.427T>C, both associated with c.565G>A. We set up original experimental conditions for DHPLC and DG-DGGE and analyzed 10 normal subjects, 46 heterozygotes, seven homozygotes, seven compound heterozygotes, and six compound heterozygotes for a hybrid gene. Both the methodologies gave reproducible results and no false-positive was detected. DHPLC showed 100% sensitivity and DG-DGGE nearly 90%. About 100% of the sequence from the cap site to the polyA addition site could be scanned by DHPLC, about 87% by DG-DGGE. It is noteworthy that the three most common pathogenic sequence variations (HBA2 alleles c.2T>C, c.95+2_95+6del, and c.523A>G) were unambiguously detected by both the methodologies. Genotype diagnosis must be confirmed with PCR sequencing of single amplicons or with an allele-specific method. This study can be helpful for scanning genes with high CG content and offers a model suitable for duplicated genes with high homology. Copyright 2004 Wiley-Liss, Inc.

Effects of Nd:YAG laser-heated metal cap on human platelets in vitro

NASA Astrophysics Data System (ADS)

Liu, Xia; Guo, You-chi

1993-03-01

Human platelet-rich plasma (PRP) was irradiated in vitro with a fiberoptic Nd:YAG laser-heated metal cap to study its effects on platelets. The energy of the laser was 5 and 10 watts with an irradiation time of 0, 3, 6, and 9 seconds and 14 watts with an irradiation time of 0, 3, 4, and 5 seconds, respectively. The irradiated PRPs were analyzed for platelet count, aggregation reaction, thromboxane (TX)B2 measurement and electron microscopy. Various degrees of decrease in platelet count were observed in all groups. Except the 5Wx3S group, the other groups showed an increase in the maximum aggregation rate of platelets, which corresponded to the enhancement of TXB2 formation. It was also demonstrated by a transmission electron microscopy in 10Wx3S, 10Wx6S, 10Wx9S, 14Wx3S, 14Wx4S, and 14Wx5S energy groups that alpha- and dense-particles in irradiated platelets became sparse in number or even disappeared, less electron density, irregularity in size and shape, and a tendency for these particles to cluster around platelet membranes and open canalicular systems, which dilated apparently. Furthermore, scanning electron microscopy depicted the appearance of short and thick pseudopods on the surfaces of some irradiated platelets and an increase in the axis rate in most of the irradiated platelets.

Burden of hospitalized childhood community-acquired pneumonia: A retrospective cross-sectional study in Vietnam, Malaysia, Indonesia and the Republic of Korea

PubMed Central

Tan, Kah Kee; Dang, Duc Anh; Kim, Ki Hwan; Kartasasmita, Cissy; Zhang, Xu-Hao; Shafi, Fakrudeen; Yu, Ta-Wen; Ledesma, Emilio; Meyer, Nadia

2018-01-01

ABSTRACT Background: Few studies describe the community-acquired pneumonia (CAP) burden in children in Asia. We estimated the proportion of all CAP hospitalizations in children from nine hospitals across the Republic of Korea (high-income), Indonesia, Malaysia (middle-income), and Vietnam (low/middle-income). Methods: Over a one or two-year period, children <5 years hospitalized with CAP were identified using ICD-10 discharge codes. Cases were matched to standardized definitions of suspected (S-CAP), confirmed (C-CAP), or bacterial CAP (B-CAP) used in a pneumococcal conjugate vaccine efficacy study (COMPAS). Median total direct medical costs of CAP-related hospitalizations were calculated. Results: Vietnam (three centers): 7591 CAP episodes were identified with 4.3% (95% confidence interval 4.2;4.4) S-CAP, 3.3% (3.2;3.4) C-CAP and 1.4% (1.3;1.4) B-CAP episodes of all-cause hospitalization in children aged <5 years. The B-CAP case fatality rate (CFR) was 1.3%. Malaysia (two centers): 1027 CAP episodes were identified with 2.7% (2.6;2.9); 2.6% (2.4;2.8); 0.04% (0.04;0.1) due to S-CAP, C-CAP, and B-CAP, respectively. One child with B-CAP died. Indonesia (one center): 960 CAP episodes identified with 18.0% (17.0;19.1); 16.8% (15.8;17.9); 0.3% (0.2;0.4) due to S-CAP, C-CAP, and B-CAP, respectively. The B-CAP CFR was 20%. Korea (three centers): 3151 CAP episodes were identified with 21.1% (20.4;21.7); 11.8% (11.2;12.3); 2.4% (2.1;2.7) due to S-CAP, C-CAP, and B-CAP, respectively. There were no deaths. Costs: CAP-related hospitalization costs were highest for B-CAP episodes: 145.00 (Vietnam) to 1013.3 USD (Korea) per episode. Conclusion: CAP hospitalization causes an important health and cost burden in all four countries studied (NMRR-12-50-10793). PMID:29125809

Complex Burial and Exhumation of South Polar Cap Pitted Terrain

NASA Technical Reports Server (NTRS)

2000-01-01

This image is illuminated by sunlight from the upper left. The two prominent bright stripes at the left/center of the image are covered with bright frost and thus create the illusion that they are sunlit from the lower left.

The large pits, troughs, and 'swiss cheese' of the south polar residual cap appear to have been formed in the upper 4 or 5 layers of the polar material. Each layer is approximately 2 meters (6.6 feet) thick. Some Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) images of this terrain show examples in which older pitted and eroded layers have been previously buried and are now being exhumed. The example shown here includes two narrow, diagonal slopes that trend from upper left toward lower right at the left/center portion of the frame. Along the bottoms of these slopes are revealed a layer that underlies them in which there are many more pits and troughs than in the upper layer. It is likely in this case that the lower layer formed its pits and troughs before it was covered by the upper layer. This observation suggests that the troughs, pits, and 'swiss cheese' features of the south polar cap are very old and form over long time scales.

The picture is located near 84.6oS, 45.1oW, and covers an area 3 km by 5 km (1.9 x 3.1 mi) at a resolution of about 3.8 meters (12 ft) per pixel. The image was taken during southern spring on August 29, 1999.

Malin Space Science Systems and the California Institute of Technology built the MOC using spare hardware from the Mars Observer mission. MSSS operates the camera from its facilities in San Diego, CA. The Jet Propulsion Laboratory's Mars Surveyor Operations Project operates the Mars Global Surveyor spacecraft with its industrial partner, Lockheed Martin Astronautics, from facilities in Pasadena, CA and Denver, CO.

Flavor and baryon quantum numbers and their nondiffractive renormalizations of the Pomeron

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

Dash, J.W.; Jones, S.T.; Manesis, E.K.

We present a theoretical review and a detailed phonomenological description of the ''flavoring'' of the bare Pomeron pole at t = 0 (i.e., the nondiffractive renormalization of its multiperipheral unitarity sum by strange quarks, charmed quarks, diquarks,...) from an ''unflavored'' intercept alpha-circumflex = 0.85 to a ''flavored'' intercept ..cap alpha.. approx. = 1.08. Experimentally, flavoring effects seem to converge rapidly; hence this number is probably close to the bare intercept of the Reggeon field theory. We treat NN, ..pi..N, and KN total cross sections and real to imaginary amplitude ratios. We do not observe oscillations. We pay particular attention tomore » 2sigma/sub K/N - sigma/sub piN/ which rises monotonically. We present a closely related combination of inelastic diffraction cross sections which decreases monotonically, indicating that vacuum amplitudes are not simply the sum of a Pomeron pole and an ideally mixed f. In fact we argue that a Pomeron + f structure is neither compatible with flavoring nor with schemes in which flavoring is somehow absorbed away. In contrast, flavoring is required for consistency with experiment by the Chew-Rosenzweig hypothesis of the Pomeron-f identity. We close with a description of flavoring threshold effects on the Reggeon field theory at current energies.« less

Effect of interferons and other biological response modifiers (BRMS) on macrophage-mediated inhibition of Listeria monocytogenes

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

Badger, A.M.; Swift, B.; Sung, C.P.

1986-03-05

Recombinant murine gamma interferon (IFN-..gamma..) activates oil elicited C57BL/6 peritoneal macrophages to inhibit the growth of Listeria. Maximum activity is obtained with 10-20 units/ml, can be demonstrated in the absence of antibiotics and is not due to LPS contamination. Studies of the kinetics of this phenomenon demonstrate that a 30 minute incubation with IFN-..gamma.. is sufficient to initiate the antiproliferative state and full activity can be obtained with a 4 hour incubation. Alpha/beta interferon (IFN-..cap alpha../..beta..) is also active but requires 100X more units to obtain equivalent activity. The evaluation of a number of other BRMS demonstrated that MDP andmore » LPS could stimulate phagocytosis of Listeria but could not inhibit their growth. Bestatin, tuftsin, Con A, A23187 and Poly I:C did not stimulate either phagocytosis or growth inhibitory activity. These compounds were also tested for their ability to enhance the release of superoxide anion from PMA stimulated macrophages. With the exception of tuftsin and bestatin all of the BRMS tested were able to enhance the production of oxidative burst products confirming the findings of others of the dissociation between the two functions.« less

Elastic and inelastic scattering of alpha particles on /sup 5/8Ni and /sup 6/0Ni in a broad range of energy and angle

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

Budzanowski, A.; Dabrowski, H.; Freindl, L.

1978-03-01

The differential cross sections for ..cap alpha.. particles elastically and inelastically scattered from /sup 5/8Ni (at 29, 34, 38, and 58 MeV) and elastically scattered from /sup 6/0Ni (at 29 and 34 MeV), are measured together with excitation functions in the 25--38 MeV region at 178.5/sup 0/ lab. These data together with the data of 26.5, 32.3, 104, and 139 MEV for /sup 5/8Ni and 32.3 and 104 MeV for /sup 6/0Ni from other sources were analyzed using an optical model with volume and surface absorptions and the Saxon-Woods square form factors. The analysis yielded energy dependent depths of bothmore » real and imaginary parts of the potential and constant geometric parameters. The analytical expressions for depths of the real and both absorption potentials are obtained. The coupled channel calculations using the above optical potential were performed for the first excited state of /sup 5/8Ni. Both elastic scattering data and coupling with the first excited state of /sup 5/8Ni are well reproduced using the above potential in the wide scattering energy range.« less

Formation of [b3 - 1 + cat]+ ions from metal-cationized tetrapeptides containing beta-alanine, gamma-aminobutyric acid or epsilon-aminocaproic acid residues.

PubMed

Osburn, Sandra M; Ochola, Sila O; Talaty, Erach R; Van Stipdonk, Michael J

2008-11-01

The presence and position of a single beta-alanine (betaA), gamma-aminobutyric acid (gammaABu) or epsilon-aminocaproic acid (Cap) residue has been shown to have a significant influence on the formation of b(n)+ and y(n)+ product ions from a series of model, protonated peptides. In this study, we examined the effect of the same residues on the formation of analogous [b3 - 1 + cat]+ products from metal (Li+, Na+ and Ag+)-cationized peptides. The larger amino acids suppress formation of b3+ from protonated peptides with general sequence AAXG (where X = beta-alanine, gamma-aminobutyric acid or epsilon-aminocaproic acid), presumably because of the prohibitive effect of larger cyclic intermediates in the 'oxazolone' pathway. However, abundant [b3 - 1 + cat]+ products are generated from metal-cationized versions of AAXG. Using a group of deuterium-labeled and exchanged peptides, we found that formation of [b3 - 1 + cat]+ involves transfer of either amide or alpha-carbon position H atoms, and the tendency to transfer the atom from the alpha-carbon position increases with the size of the amino acid in position X. To account for the transfer of the H atom, a mechanism involving formation of a ketene product as [b3 - 1 + cat]+ is proposed.

The legumin gene family: structure of a B type gene of Vicia faba and a possible legumin gene specific regulatory element.

PubMed Central

Bäumlein, H; Wobus, U; Pustell, J; Kafatos, F C

1986-01-01

The field bean, Vicia faba L. var. minor, possesses two sub-families of 11 S legumin genes named A and B. We isolated from a genomic library a B-type gene (LeB4) and determined its primary DNA sequence. Gene LeB4 codes for a 484 amino acid residue prepropolypeptide, encompassing a signal peptide of 22 amino acid residues, an acidic, very hydrophilic alpha-chain of 281 residues and a basic, somewhat hydrophobic beta-chain of 181 residues. The latter two coding regions are immediately contiguous, but each is interrupted by a short intron. Type A legumin genes from soybean and pea are known to have introns in the same two positions, in addition to an extra intron (within the alpha-coding sequence). Sequence comparisons of legumin genes from these three plants revealed a highly conserved sequence element of at least 28 bp, centered at approximately 100 bp upstream of each cap site. The element is absent from the equivalent position of all non-legumin and other plant and fungal genes examined. We tentatively name this element "legumin box" and suggest that it may have a function in the regulation of legumin gene expression. PMID:3960730

Evolução química em galáxias compactas azuis (BCGs)

NASA Astrophysics Data System (ADS)

Lanfranchi, G. A.; Matteucci, F.

2003-08-01

Neste trabalho, a formação estelar e evolução quí mica em galáxias Compactas Azuis (Blue Compact Galaxies - BCGs) foram estudadas através da comparação de previsões de modelos de evolução quí mica a várias razões de abundância quí mica observadas nestas galáxias. Modelos detalhados com recentes dados de nucleossí ntese e que levam em consideração o papel desempenahdo por supernovas de ambos os tipos (II e Ia) na evolução galáctica foram desenvolvidos para as BCGs permitindo seguir a evolução de vários elementos quí micos (H, D, He, C, N, O, Mg, Si, S, Ca, e Fe). O modelo é caracterizado pelas prescrições adotadas para a formação estelar, a qual ocorre em vários surtos de atividade separados por longos perí odos quiescentes. Após ajustar os melhores modelos aos dados observacionais, as previsões destes modelos foram comparadas também a razões de abundância observadas em sistemas Damped Lyman alpha (DLAs) e a origem do N (primária ou secundária) foi discutida. Alguns dos resultados obtidos são: i) as razões de abundância observadas nas BCGs são reproduzidas por modelos com 2 a 7 surtos de formação estelar com eficiência entre n = 0.2-0.9 Gano-1; ii) os baixos valores de N/O observados nestas galáxias são um resultado natural de uma formação estelar em surtos; iii) os modelos para BCGs podem reproduzir os dados dos DLAs, iv) uma quantidade "baixa" de N primário produzido em estrelas de alta massa pode ser uma explicação para os baixos valores de [N/a] observados em DLAs.

A comparative study of sorafenib and metronomic chemotherapy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma with poor liver function.

PubMed

Yang, Hyun; Woo, Hyun Young; Lee, Soon Kyu; Han, Ji Won; Jang, Bohyun; Nam, Hee Chul; Lee, Hae Lim; Lee, Sung Won; Song, Do Seon; Song, Myeong Jun; Oh, Jung Suk; Chun, Ho Jong; Jang, Jeong Won; Lozada, Angelo; Bae, Si Hyun; Choi, Jong Young; Yoon, Seung Kew

2017-06-01

Metronomic chemotherapy (MET) is frequently administered in comparatively low doses as a continuous chemotherapeutic agent. The aim of this study was to evaluate the feasibility and overall survival (OS) of MET compared to sorafenib for advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). A total of 54 patients with advanced HCC and PVTT who had undergone MET were analyzed between 2005 and 2013. A total of 53 patients who had undergone sorafenib therapy were analyzed as the control group. The primary endpoint of this study was OS. The median number of MET cycles was two (1-15). The OS values for the MET group and sorafenib group were 158 days (132-184) and 117 days (92-142), respectively ( P =0.029). The Cox proportional-hazard model showed that a higher risk of death was correlated with higher serum alpha fetoprotein level (≥400 mg/dL, hazard ratio [HR]=1.680, P =0.014) and Child-Pugh class B (HR=1.856, P =0.008). MET was associated with more favorable outcomes in terms of overall survival than was sorafenib in patients with advanced HCC with PVTT, especially in patients with poor liver function. Therefore, MET can be considered as a treatment option in patients with advanced HCC with PVTT and poor liver function.

Effect of Parenteral Antioxidant Supplementation During the Dry Period on Postpartum Glucose Tolerance in Dairy Cows.

PubMed

Abuelo, A; Alves-Nores, V; Hernandez, J; Muiño, R; Benedito, J L; Castillo, C

2016-05-01

Exacerbated postparturient insulin resistance (IR) has been associated with several pathologic conditions in dairy cattle. Oxidative stress (OS) plays a causative role in IR in humans, and an association, but not direct relationship, between OS and IR recently has been reported in transition dairy cattle. Supplementation with antioxidants shortly before calving improves glucose tolerance after parturition in dairy cattle. Ten late-pregnant Holstein cows entering their 2nd to 5th lactation. Randomized placebo-controlled trial: 15 ± 2 days before expected calving, the treatment group received an injection of DL-alpha-tocopheryl acetate at a dosage of 6 mg/kg body weight (BW) and 0.06 mg/kg BW of sodium selenite, and the control group was injected with isotonic saline. During the first week after calving, both groups underwent glucose tolerance testing (0.25 g glucose/kg BW). Commercial assays were used to quantify the concentrations of glucose, insulin, nonesterified fatty acids (NEFA), beta-hydroxybutyrate, and markers of redox status in blood. Data were analyzed using the Mann-Whitney U-test (α = 0.05). Supplemented cows showed a lower risk for OS, as reflected by a lower OS index (P = .036), different areas under the curve for the concentrations of glucose (P < .01), insulin (P = .043), and NEFA (P = .041), more rapid elimination rates (P = .080, <.01 and .047 respectively), and shorter half-lives (P = .040, <.01 and .032) of these metabolites. Supplementation with antioxidants before calving resulted in greater insulin sensitivity after calving, thereby suggesting the role of OS in the development of IR in cattle and the potential benefits of antioxidant supplementation in minimizing the consequences of negative energy balance. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

78 FR 18335 - Central Arizona Project-Rate Order No. WAPA-158

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... Project, reflected in Transmission Service Rate Schedules CAP-FT2, CAP-NFT2, and CAP-NITS2, from January 1... existing Rate Schedules CAP-FT2, CAP-NFT2, CAP-NITS2 under Rate Order No. WAPA-124,\\1\\ were approved for a... Transmission Service Rate Schedules CAP-FT2, CAP-NFT2, and CAP-NITS2 on an interim basis effective as of...

Chios mastic treatment of patients with active Crohn’s disease

PubMed Central

Kaliora, Andriana C; Stathopoulou, Maria G; Triantafillidis, John K; Dedoussis, George VZ; Andrikopoulos, Nikolaos K

2007-01-01

AIM: To evaluate the effectiveness of mastic administration on the clinical course and plasma inflammatory mediators of patients with active Crohn’s disease (CD). METHODS: This pilot study was conducted in patients with established mild to moderately active CD, attending the outpatient clinics of the hospital, and in healthy controls. Ten patients and 8 controls were recruited for a 4-wk treatment with mastic caps (6 caps/d, 0.37 g/cap). All patients successfully completed the protocol. CD Activity Index (CDAI), Nutritional Risk Index (NRI), C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein-1 (MCP-1), and total antioxidant potential (TAP) were evaluated in the plasma at baseline and at the end of the treatment period. Results were expressed as mean values ± SE and P < 0.05 was considered to indicate statistical significance. RESULTS: Patients exhibited significant reduction of CDAI (222.9 ± 18.7 vs 136.3 ± 12.3, P = 0.05) as compared to pretreament values. Plasma IL-6 was significantly decreased (21.2 ± 9.3 pg/mL vs 7.2 ± 2.8 pg/ mL, P = 0.027), and so did CRP (40.3 ± 13.1 mg/mL vs 19.7 ± 5.5, P = 0.028). TAP was significantly increased (0.15 ± 0.09 vs 0.57 ± 0.15 mmol/L uric acid, P = 0.036). No patient or control exhibited any kind of side effects. CONCLUSION: The results suggest that mastic significantly decreased the activity index and the plasma levels of IL-6 and CRP in patients with mildly to moderately active CD. Further double-blind, placebo-controlled studies in a larger number of patients are required to clarify the role of this natural product in the treatment of patients with CD. PMID:17278198

The Changing South Polar Cap of Mars: 1999-2005

NASA Technical Reports Server (NTRS)

2005-01-01

13 July 2005 The south polar residual cap of Mars is composed of layered, frozen carbon dioxide. In 1999, the Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) showed that the carbon dioxide layers have been eroded to form a variety of circular pits, arcuate scarps, troughs, buttes, and mesas. In 2001, MOC images designed to provide repeated views of the areas imaged in 1999 -- with the hope of creating stereo (3-D) images, so that the height of scarps and depth of pits could be measured -- showed that the scarps had retreated, pits enlarged, and buttes and mesas shrank. Only carbon dioxide is volatile enough in the martian environment to have caused such dramatic changes -- the scarps were seen to retreat at an average rate of 3 meters (about 3 yards) per Mars year. Most of the scarp retreat occurs during the southern summer season; in some areas the scarps move as much as 8 meters, in others, only 1 meter per Mars year.

Three Mars years have now elapsed since MOC first surveyed the south polar cap in 1999. Over the past several months, MGS MOC has been re-imaging areas that were seen in 1999, 2001, and 2003, to develop a detailed look at how the landscape has been changing. This animated GIF provides an example of the dramatic changes that have occurred during the past three martian years. The first image, a sub-frame of M09-05244, was acquired on 21 November 1999. The second image, a sub-frame of S06-00973, was obtained on 11 May 2005. The animation shows the changes that have occurred between 1999 and 2005. Each summer, the cap has lost more carbon dioxide. This may mean that the carbon dioxide content of the martian atmosphere has been increasing, bit by very tiny little bit, each of the years that MGS has been orbiting the red planet. These observations also imply that there was once a time, in the not-too-distant past (because there are no impact craters on the polar cap), when the atmosphere was somewhat thinner and colder, to permit the layers of carbon dioxide to form in the first place. Just as Earth's environment is very different today than it was just 11,000 or so years ago, the martian environment has also been changing on a similar time scale.

Location near: 88.9oS, 25.7oW Image width: width: 0.6 km (0.4 mi) Illumination from: upper left Season: Southern Spring

The self-absorption effect of gamma rays in /sup 239/Pu

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

Hsu, Hsiao-Hua

1989-01-01

Nuclear materials assay with gamma-ray spectrum measurement is a well-established method for safeguards. However, for a thick source, the self-absorption of characteristic low-energy gamma rays has been a handicap to accurate assay. I have carried out Monte Carlo simulations to study this effect using the /sup 239/Pu ..cap alpha..-decay gamma-ray spectrum as an example. The thickness of a plutonium metal source can be considered a function of gamma-ray intensity ratios. In a practical application, gamma-ray intensity ratios can be obtained from a measured spectrum. With the help of calculated curves, scientists can find the source thickness and make corrections tomore » gamma-ray intensities, which then lead to an accurate quantitative determination of radioactive isotopes in the material. 2 refs., 9 figs.« less

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

Bernstein, S.E.

Hereditary anemias of mice are the chief objects of investigation, specificially four macrocytic anemias, 3 types of hemolytic anemia, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, the autoimmune hemolytic anemia of NZB mice, an ..cap alpha..-thalassemia and a new hypochromic anemia with hemochromatosis. New types of anemia may be analyzed as new mutations appear. Three new mutations have been identified during the past 18 months. These anemias are studied through characterization of peripheral blood values, determinations of radiosensitivity under a variety of conditions, measurements of iron metabolism and heme synthesis, study of normal and abnormal erythrocyte membrane proteins,more » histological and biochemical characterization of blood-forming tissue, functional tests of the stem-cell component, examination of responses to erythroid stimuli, and transplantation of tissue and parabiosis between individuals of differently affected genotypes. 31 refs.« less

Reactions of bis(2,2,3,3-tetrafluoropropyl) phosphorisocyanatidite and tris(2,2,3,3-tetrafluoropropyl) phosphite with carbonyl compounds

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

Konovalova, I.V.; Burnaeva, L.A.; Khusnutdinova, E.K.

1986-11-20

The authors studied the reactions of bis(2,2,3,3-tetrafluoropropyl) phosphorisocyanatidite with carbonyl and ..cap alpha..-halo carbonyl compounds, namely, benzil, ethyl phenylglyoxylate, methyl chloropyruvate, and diethyl (trichloroacetyl)phosphonate. The reaction of bis(2,2,3,3-tetrachloropropyl) phosphorisocyanatidite with benzil required severe conditions (3 h at 40/sup 0/C). The /sup 31/P NMR spectrum of the reaction mixture contains two signals at 12 and -55 ppm, which probably belong to the azaphospholine and its dimer. By vacuum fractionation they isolated a thick liquid, the /sup 31/P NMR spectrum of which contains a signal 12 ppm corresponding to 5-benzoyl-4-oxo-5-phenyl-2,2-bis(2,2,3,3-tetrafluoropropoxy)-..delta../sup 2/-1,3,2lambda/sup 5/-oxazaphospholine.

Magnetic ordering in Ce-La and Nd-La alloys

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

Petersen, T.S.; Legvold, S.; Gschneidner, K.A. Jr.

1978-03-01

Heat capacity, magnetic susceptibility, and electrical resistivity measurements have been made on a wide ranging set of Ce-La and Nd-La alloys. In the case of Ce it is found that less than 5 at. % of La will prevent the ..beta.. (dhcp) to ..cap alpha.. (collapsed fcc) transition at T9 or approx. =50 K. In the case of Nd-La only the dhcp allotrope is formed. Two magnetic ordering temperatures have been found for many of the samples. These are believed to be caused by antiferromagnetic ordering on the two different atomic sites in the dhcp structure, cubic and hexagonal. Inmore » both sets of alloys the two ordering temperatures coalesce into one for La concentrations > or approx. =30%. Additional magnetic features in Ce-La alloys are explained by the formation of the fcc phase.« less

Real-World Data on Prognostic Factors for Overall Survival in EGFR Mutation-Positive Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Gefitinib.

PubMed

Yao, Zong-Han; Liao, Wei-Yu; Ho, Chao-Chi; Chen, Kuan-Yu; Shih, Jin-Yuan; Chen, Jin-Shing; Lin, Zhong-Zhe; Lin, Chia-Chi; Chih-Hsin Yang, James; Yu, Chong-Jen

2017-09-01

This study aimed to identify independent prognostic factors for overall survival (OS) of patients with advanced non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation and receiving gefitinib as first-line treatment in real-world practice. We enrolled 226 patients from June 2011 to May 2013. During this period, gefitinib was the only EGFR-tyrosine kinase inhibitor reimbursed by the Bureau of National Health Insurance of Taiwan. The median progression-free survival and median OS were 11.9 months (95% confidence interval [CI]: 9.7-14.2) and 26.9 months (21.2-32.5), respectively. The Cox proportional hazards regression model revealed that postoperative recurrence, performance status (Eastern Cooperative Oncology Grade [ECOG] ≥2), smoking index (≥20 pack-years), liver metastasis at initial diagnosis, and chronic hepatitis C virus (HCV) infection were independent prognostic factors for OS (hazard ratio [95% CI] 0.3 [0.11-0.83], p  = .02; 2.69 [1.60-4.51], p  < .001; 1.92 [1.24-2.97], p  = .003; 2.26 [1.34-3.82], p  = .002; 3.38 [1.85-7.78], p  < .001, respectively). However, brain metastasis (BM) at initial diagnosis or intracranial progression during gefitinib treatment had no impact on OS (1.266 [0.83-1.93], p  = .275 and 0.75 [0.48-1.19], p  = .211, respectively). HCV infection, performance status (ECOG ≥2), newly diagnosed advanced NSCLC without prior operation, and liver metastasis predicted poor OS in EGFR mutation-positive advanced NSCLC patients treated with first-line gefitinib; however, neither BM at initial diagnosis nor intracranial progression during gefitinib treatment had an impact on OS. The finding that chronic hepatitis C virus (HCV) infection might predict poor overall survival (OS) in epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer (NSCLC) patients treated with first-line gefitinib may raise awareness of benefit from anti-HCV treatment in this patient population. Brain metastasis in the initial diagnosis or intracranial progression during gefitinib treatment is not a prognostic factor for OS. This study, which enrolled a real-world population of NSCLC patients, including sicker patients who were not eligible for a clinical trial, may have impact on guiding usual clinical practice. © AlphaMed Press 2017.

Alpha-Tocopherol Supplementation Restricts Aluminium- and Ethanol-Induced Oxidative Damage in Rat Brain but Fails to Protect Against Neurobehavioral Damage.

PubMed

Nayak, Prasunpriya; Sharma, Shiv Bhushan; Chowdary, N V S

2018-04-05

The concurrent presence of oxidative stress (OS) and aluminium exposure is an inducer of neurodegenerative changes. Aluminium can augment OS in a pro-oxidant dominant condition. Antioxidative property of α-tocopherol may be useful in restricting these degenerative changes in the brain. OS parameters are tested in frontal cortex (FC), hippocampus (HC), and cerebellum (CL) of α-tocopherol-supplemented (5 IU/day) male Wistar rats exposed to aluminium (10 mg Al/Kg/day; "Al"), ethanol (0.6 g ethanol/Kg/day; "Et"), and both ("Al-Et") and vehicle-treated control ("C") for 4 weeks. The α-tocopherol supplementation restricted regional alterations of reduced glutathione, superoxide dismutase, catalase, and glutathione peroxidase. Accordingly, the regional superoxide and peroxide handling capacities (SPHC) also remain unaltered. Al-Et group demonstrated significant elevation in the lipid peroxidation level in FC and CL regions compared to the group C; similar elevations in lipid peroxidation were noted in all the tested brain regions of Al group. Likewise, declines in glutathione reductase activity were noted in HC (versus Et group) and CL (versus Al and Et groups) of Al-Et group. Interestingly, changes in behavioral patterns of all the treatment groups are comparable while differing from that of the control group. Significant difference with group C is observed during first through fourth weeks, third to fourth weeks, and second to third weeks in terms of spontaneous motor activity, Rota Rod performance, and Hebb-Williams maze performance, respectively. Hence, the current dose and duration of α-tocopherol supplementation failed to provide full protection against the aluminium-induced neurodegeneration; nevertheless, it could provide only partial protection toward aluminium-induced augmentation of OS in specific brain regions.

CapZyme-Seq Comprehensively Defines Promoter-Sequence Determinants for RNA 5' Capping with NAD.

PubMed

Vvedenskaya, Irina O; Bird, Jeremy G; Zhang, Yuanchao; Zhang, Yu; Jiao, Xinfu; Barvík, Ivan; Krásný, Libor; Kiledjian, Megerditch; Taylor, Deanne M; Ebright, Richard H; Nickels, Bryce E

2018-05-03

Nucleoside-containing metabolites such as NAD + can be incorporated as 5' caps on RNA by serving as non-canonical initiating nucleotides (NCINs) for transcription initiation by RNA polymerase (RNAP). Here, we report CapZyme-seq, a high-throughput-sequencing method that employs NCIN-decapping enzymes NudC and Rai1 to detect and quantify NCIN-capped RNA. By combining CapZyme-seq with multiplexed transcriptomics, we determine efficiencies of NAD + capping by Escherichia coli RNAP for ∼16,000 promoter sequences. The results define preferred transcription start site (TSS) positions for NAD + capping and define a consensus promoter sequence for NAD + capping: HRRASWW (TSS underlined). By applying CapZyme-seq to E. coli total cellular RNA, we establish that sequence determinants for NCIN capping in vivo match the NAD + -capping consensus defined in vitro, and we identify and quantify NCIN-capped small RNAs (sRNAs). Our findings define the promoter-sequence determinants for NCIN capping with NAD + and provide a general method for analysis of NCIN capping in vitro and in vivo. Copyright © 2018 Elsevier Inc. All rights reserved.

High-pressure jet cutters improve capping operations

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

Abel, L.W.; Campbell, P.J.; Bowden, J.R. Sr.

1995-05-08

Advances in abrasive cutting technology have improved the methods for removing damaged equipment and preparing wellheads for capping. This technology, much of which was refined during well control operations in Kuwait in 1991, can improve the safety and efficiency of capping jobs by cutting wellheads or casing quickly and cleanly. The majority of well control jobs involve one of three types of capping operations: capping to a flange, capping by installing a wellhead, or capping to a casing stub. Capping operations are often the first major step in regaining control of the well during blowout intervention. Proper planning of amore » capping operation must take into account the mass flow rate, combustible nature of the flow, well bore geometry, and operations in the post-capping phase of the project. The paper discusses capping vehicles, tree removal, jet cutters, capping to a flange, capping to a stub, swallowing the stub, spin-on technique, capping on fire, stinging, offshore blowouts, firefighting, pollution control, intervention equipment, and rig removal.« less

Serum tryptase level is a better predictor of systemic side effects than prostaglandin D2 metabolites during venom immunotherapy in children.

PubMed

Cichocka-Jarosz, E; Sanak, M; Szczeklik, A; Brzyski, P; Gielicz, A; Pietrzyk, J J

2011-01-01

We performed a prospective study to analyze mast cell mediators as predictors of systemic adverse reactions during rush venom-specific immunotherapy (VIT) in children. Nineteen children aged 5-17 years received VIT with Venomenhal (HALAllergy). We analyzed serum tryptase (CAP, Phadia), plasma prostaglandin (PG) D2 metabolites (9alpha, 11beta-PGF2), and urine PGD2 metabolites (9alpha, 11beta-PGF2, tetranor-PGD-M) using gas chromatography mass spectrometry before and after the rush protocol. Three boys with high baseline serum tryptase values (>7.76 g/L) (P < .001) and low 9alpha, 11beta-PGF2 concentrations developed grade III systemic adverse reactions during VIT. Baseline serum tryptase was lowest in children who had a Mueller grade II reaction (1.93 [0.36]) before VIT and highest in children with a Mueller grade III reaction (6.31 [4.80]) (P = .029). Repeated measures analysis of variance confirmed that, in children who developed systemic adverse reactions during VIT, serum tryptase was higher both before and after desensitization and increased significantly following the procedure. Analysis of PGD2 metabolites in the prediction of systemic adverse reactions during VIT was inadequate (sensitivity 67% and specificity 0.53%), whilst prediction based on serum tryptase was accurate. In children with severe systemic adverse reactions to Hymenoptera sting, the evaluation of baseline tryptase levels should be a standard procedure. Children with Apis mellifera venom allergy and baseline tryptase levels higher than 7.75 g/L are at risk of anaphylaxis during buildup. Lower baseline values of plasma and urinary PGD2 metabolite concentration in patients with systemic adverse reaction during VIT suggest that prostaglandin catabolism is altered.

All-Sky Observational Evidence for An Inverse Correlation Between Dust Temperature and Emissivity Spectral Index

NASA Technical Reports Server (NTRS)

Liang, Z.; Fixsen, D. J.; Gold, B.

2012-01-01

We show that a one-component variable-emissivity-spectral-index model (the free- model) provides more physically motivated estimates of dust temperature at the Galactic polar caps than one- or two-component fixed-emissivity-spectral-index models (fixed- models) for interstellar dust thermal emission at far-infrared and millimeter wavelengths. For the comparison we have fit all-sky one-component dust models with fixed or variable emissivity spectral index to a new and improved version of the 210-channel dust spectra from the COBE-FIRAS, the 100-240 micrometer maps from the COBE-DIRBE and the 94 GHz dust map from the WMAP. The best model, the free-alpha model, is well constrained by data at 60-3000 GHz over 86 per cent of the total sky area. It predicts dust temperature (T(sub dust)) to be 13.7-22.7 (plus or minus 1.3) K, the emissivity spectral index (alpha) to be 1.2-3.1 (plus or minus 0.3) and the optical depth (tau) to range 0.6-46 x 10(exp -5) with a 23 per cent uncertainty. Using these estimates, we present all-sky evidence for an inverse correlation between the emissivity spectral index and dust temperature, which fits the relation alpha = 1/(delta + omega (raised dot) T(sub dust) with delta = -.0.510 plus or minus 0.011 and omega = 0.059 plus or minus 0.001. This best model will be useful to cosmic microwave background experiments for removing foreground dust contamination and it can serve as an all-sky extended-frequency reference for future higher resolution dust models.

Acclimation to cold and warm temperatures is associated with differential expression of male carp blood proteins involved in acute phase and stress responses, and lipid metabolism.

PubMed

Dietrich, Mariola A; Hliwa, Piotr; Adamek, Mikołaj; Steinhagen, Dieter; Karol, Halina; Ciereszko, Andrzej

2018-05-01

The environmental temperature affects plasma biochemical indicators, antioxidant status and hematological and immunological parameters in fish. So far, only single blood proteins have been identified in response to temperature changes. The aim of this study was to compare the proteome of carp blood plasma from males acclimated to warm (30 °C) and cold (10 °C) temperatures by two-dimensional differential gel electrophoresis followed by MALDI-TOF/TOF mass spectrometry. A total of 47 spots were found to be differentially regulated by temperature (>1.2-fold change, p < 0.05): 25 protein spots were more abundant in warm-acclimated males and 22 were enriched in cold-acclimated males. The majority of differentially regulated proteins were associated with acute phase response signalling involved in: i) activation of the complement system (complement C3-H1), ii) neutralization of proteolytic enzymes (inter-alpha inhibitor H3, fetuin, serpinA1, antithrombin, alpha2-macroglobulin), iii) scavenging of free hemoglobin and radicals (haptoglobin, Wap65 kDa), iv) clot-formation (fibrinogen beta and alpha chain, T-kininogen) and v) the host's immune response modulation (ApoA1 and ApoA2). However, quite different sets of these proteins or proteoforms were involved in response to cold and warm temperatures. In addition, cold acclimation seems to be related to the proteins involved in lipid metabolism (apolipoproteins A and 14 kDa) and stress response (corticosteroid binding globulin). We discovered a strongly regulated protein Cap31 upon cold acclimation, which can serve as a potential blood biomarker of cold response in carp. These studies significantly extend our knowledge concerning mechanisms underlying thermal adaptation in poikilotherms. Copyright © 2018. Published by Elsevier Ltd.

Modulatory effects of alpha-lipoic acid (ALA) administration on insulin sensitivity in obese PCOS patients.

PubMed

Genazzani, A D; Shefer, K; Della Casa, D; Prati, A; Napolitano, A; Manzo, A; Despini, G; Simoncini, T

2018-05-01

To evaluate the efficacy of alpha-lipoic acid (ALA) administration on hormonal and metabolic parameters of obese PCOS patients. A group of 32 obese PCOS patients were selected after informed consent. 20 patients referred to have first grade relatives with diabetes type I or II. Hormonal and metabolic parameters as well as OGTT were evaluated before and after 12 weeks of ALA integrative administration (400 mg per os every day). ALA administration significantly decreased insulin, glucose, BMI and HOMA index. Hyperinsulinemia and insulin response to OGTT decreased both as maximal response (Δmax) and as AUC. PCOS with diabetes relatives showed the decrease also of triglyceride and GOT. Interestingly in all PCOS no changes occurred on all hormonal parameters involved in reproduction such as LH, FSH, and androstenedione. ALA integrative administration at a low dosage as 400 mg daily improved the metabolic impairment of all PCOS patients especially in those PCOS with familiar diabetes who have a higher grade of risk of NAFLD and predisposition to diabetes.

Cradle Cap (For Parents)

MedlinePlus

... Safe Videos for Educators Search English Español Cradle Cap (Infantile Seborrheic Dermatitis) KidsHealth / For Parents / Cradle Cap ( ... many babies develop called cradle cap. About Cradle Cap Cradle cap is the common term for seborrheic ...

Observations of the boundary layer, cloud, and aerosol variability in the southeast Pacific coastal marine stratocumulus during VOCALS-REx

NASA Astrophysics Data System (ADS)

Zheng, X.; Albrecht, B.; Jonsson, H. H.; Khelif, D.; Feingold, G.; Minnis, P.; Ayers, K.; Chuang, P.; Donaher, S.; Rossiter, D.; Ghate, V.; Ruiz-Plancarte, J.; Sun-Mack, S.

2011-05-01

Aircraft observations made off the coast of northern Chile in the Southeastern Pacific (20° S, 72° W; named Point Alpha) from 16 October to 13 November 2008 during the VAMOS Ocean-Cloud-Atmosphere-Land Study-Regional Experiment (VOCALS-REx), combined with meteorological reanalysis, satellite measurements, and radiosonde data, are used to investigate the boundary layer (BL) and aerosol-cloud-drizzle variations in this region. The BL at Point Alpha was typical of a non-drizzling stratocumulus-topped BL on days without predominately synoptic and meso-scale influences. The BL had a depth of 1140 ± 120 m, was well-mixed and capped by a sharp inversion. The wind direction generally switched from southerly within the BL to northerly above the inversion. The cloud liquid water path (LWP) varied between 15 g m-2 and 160 g m-2. From 29 October to 4 November, when a synoptic system affected conditions at Point Alpha, the cloud LWP was higher than on the other days by around 40 g m-2. On 1 and 2 November, a moist layer above the inversion moved over Point Alpha. The total-water specific humidity above the inversion was larger than that within the BL during these days. Entrainment rates (average of 1.5 ± 0.6 mm s-1) calculated from the near cloud-top fluxes and turbulence (vertical velocity variance) in the BL at Point Alpha appeared to be weaker than those in the BL over the open ocean west of Point Alpha and the BL near the coast of the northeast Pacific. The accumulation mode aerosol varied from 250 to 700 cm-3 within the BL, and CCN at 0.2 % supersaturation within the BL ranged between 150 and 550 cm-3. The main aerosol source at Point Alpha was horizontal advection within the BL from south. The average cloud droplet number concentration ranged between 80 and 400 cm-3, which was consistent with the satellite-derived values. The relationship of cloud droplet number concentration and CCN at 0.2 % supersaturation from 18 flights is Nd =4.6 × CCN0.71. While the mean LWP retrieved from GOES was in good agreement with the in situ measurements, the GOES-derived cloud droplet effective radius tended to be larger than that from the aircraft {in situ} observations near cloud top. The aerosol and cloud LWP relationship reveals that during the typical well-mixed BL days the cloud LWP increased with the CCN concentrations. On the other hand, meteorological factors and the decoupling processes have large influences on the cloud LWP variation as well.

PERMANGANATE FIXATION OF THE GOLGI COMPLEX AND OTHER CYTOPLASMIC STRUCTURES OF MAMMALIAN TESTES

PubMed Central

Mollenhauer, Hilton H.; Zebrun, William

1960-01-01

Observations on the fine structure of KMnO4-fixed testes of small mammals (guinea pig, rat, and mouse) reveal certain morphological differences between the spermatogenic and Sertoli cells which have not been demonstrated in the same tissue fixed with OsO4. Aggregates of minute circular profiles, much smaller than the spherical Golgi vesicles, are described in close association with the Golgi complex of developing spermatids. Groups of dense flattened vesicles, individually surrounded by a membrane of different dimensions than that which bounds most of the other cell organelles, appear dispersed within the cytoplasm of some spermatogenic cells. Flattened vesicles of greater density than those belonging to the Golgi complex are reported confined to the inner Golgi zone of developing guinea pig spermatids between the Golgi cisternae and the head cap. The profiles of endoplasmic reticulum within spermatocytes appear shorter, wider, and more tortuous than those of Sertoli cells. Minute cytoplasmic particles approximately 300 A in diameter and of high electron opacity appear randomly disposed in some Sertoli cells. Groups of irregular-shaped ovoid bodies within the developing spermatids are described as resembling portions of cytoplasm from closely adjacent spermatids. Interpretation is presented regarding the fine structure of KMnO4-fixed testes in view of what has already been reported for mammalian testes fixed in OsO4. PMID:13771855

Frozen Carbon Dioxide

NASA Technical Reports Server (NTRS)

2005-01-01

1 August 2005 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a south polar residual cap landscape, formed in frozen carbon dioxide. There is no place on Earth that one can go to visit a landscape covering thousands of square kilometers with frozen carbon dioxide, so mesas, pits, and other landforms of the martian south polar region are as alien as they are beautiful. The scarps of the south polar region are known from thousands of other MGS MOC images to retreat at a rate of about 3 meters (3 yards) per martian year, indiating that slowly, over the course of the MGS mission, the amount of carbon dioxide in the martian atmosphere has probably been increasing.

Location near: 86.9oS, 25.5oW Image width: width: 3 km (1.9 mi) Illumination from: upper left Season: Southern Spring

A new SNP in cyOsPPDK gene is associated with floury endosperm in Suweon 542.

PubMed

Wang, Heng; Mo, Young-Jun; Im, Da-Eun; Jang, Seong-Gyu; Ham, Tae-Ho; Lee, Joohyun; Jeung, Ji-Ung; Kwon, Soon-Wook

2018-05-09

Pyruvate orthophosphate dikinase (PPDK) is a component of glycolysis to mediate endosperm energy charge by adjusting the ratio of ATP to ADP and AMP that proposed to balance the flow of carbon into starch, protein, fatty acid and amino acid biosynthesis. However, these were inconsistent with the first report of a T-DNA insertional knockout mutant of the rice PPDK gene (flo4) showed that rice with inactivated PPDK gene failed to produce a opaque seeds. Therefore, the PPDK might have multifaceted functions in grain filling stage, which in some ways might depend on the direction of the reversible catalysis. Suweon 542 is a rice (Oryza sativa L.) mutant developed from Oryza sativa ssp. japonica cv. Namil. Suweon 542 has a milky-white floury endosperm suitable for dry filling, with low starch damage, low grain hardness, and fine flour particle size. The mutant locus on chromosome 5 controls the floury endosperm phenotype of Suweon 542. Fine mapping of this locus is required for efficient breeding of rice germplasm suitable for dry milling. In this study, whole genome of Suweon 542 and Milyang 23 were re-sequenced using Illumina HiSeq 2500. Co-segregation analysis of F 3:4 family populations derived from Suweon 542/Milyang 23 was performed using eight CAPS markers and phenotypic evaluation of the endosperm. The target region was mapped to a 33 kb region and identified to encode cytosolic pyruvate orthophosphate dikinase protein (cyOsPPDK). A G→A SNP in exon 8 of cyOsPPDK resulting in a missense mutation from Gly to Asp at amino acid position 404 was responsible for the floury endosperm of Suweon 542. qRT-PCR experiments revealed that FLO4-4 was expressed to a considerably higher level in Suweon 542 than in Namil during the grain filling stage. Overall, fine mapping of FLO4-4 and candidate gene analysis provided further insight into the floury endosperm of rice, and reveal a novel SNP in cyOsPPDK gene can affect the floury endosperm phenotype through active PPDK gene during grain filling stage.

The involvement of hypoxia-inducible transcription factor-1-dependent pathway in nickel carcinogenesis.

PubMed

Salnikow, Konstantin; Davidson, Todd; Zhang, Qunwei; Chen, Lung Chi; Su, Weichen; Costa, Max

2003-07-01

Nickel is a potent environmental pollutant in industrial countries. Because nickel compounds are carcinogenic, exposure to nickel represents a serious hazard to human health. The understanding of how nickel exerts its toxic and carcinogenic effects at a molecular level may be important in risk assessment, as well as in the treatment and prevention of occupational diseases. Previously, using human and rodent cells in vitro, we showed that hypoxia-inducible signaling pathway was activated by carcinogenic nickel compounds. Acute exposure to nickel resulted in the accumulation of hypoxia-inducible transcription factor (HIF)-1, which strongly activated hypoxia-inducible genes, including the recently discovered tumor marker NDRG1 (Cap43). To further identify HIF-1-dependent nickel-inducible genes and to understand the role of the HIF-dependent signaling pathway in nickel-induced transformation, we used the Affymetrix GeneChip to compare the gene expression profiles in wild-type cells or in cells from HIF-1 alpha knockout mouse embryos exposed to nickel chloride. As expected, when we examined 12,000 genes for expression changes, we found that genes coding for glycolytic enzymes and glucose transporters, known to be regulated by HIF-1 transcription factor, were induced by nickel only in HIF-1 alpha-proficient cells. In addition, we found a number of other hypoxia-inducible genes up-regulated by nickel in a HIF-dependent manner including BCL-2-binding protein Nip3, EGLN1, hypoxia-inducible gene 1 (HIG1), and prolyl 4-hydroxylase. Additionally, we found a number of genes induced by nickel in a HIF-independent manner, suggesting that Ni activated other signaling pathways besides HIF-1. Finally, we found that in HIF-1 alpha knockout cells, nickel strongly induced the expression of the whole group of genes that were not expressed in the presence of HIF-1. Because the majority of modulated genes were induced or suppressed by nickel in a HIF-1-dependent manner, we elucidated the role of HIF-1 transcription factor in cell transformation. In HIF-1 alpha-proficient cells, nickel exposure increased soft agar growth, whereas it decreased soft agar growth in HIF-1 alpha-deficient cells. We hypothesize that the induction of HIF-1 transcription factor by nickel may be important during the nickel-induced carcinogenic process.

42 CFR 414.917 - Dispute resolution and process for suspension or termination of approved CAP contract and...

Code of Federal Regulations, 2010 CFR

2010-10-01

... quality of a CAP drug supplied by the approved CAP vendor to be unsatisfactory, then the physician may address the issue first through the approved CAP vendor's grievance process, and second through an... approved CAP vendor's service or the quality of a CAP drug supplied by the approved CAP vendor, then the...

Child psychiatry: what are we teaching medical students?

PubMed

Dingle, Arden D

2010-01-01

The author describes child and adolescent psychiatry (CAP) undergraduate teaching in American and Canadian medical schools. A survey asking for information on CAP teaching, student interest in CAP, and opinions about the CAP importance was sent to the medical student psychiatry director at 142 accredited medical schools in the United States and Canada. The results were summarized and various factors considered relevant to CAP student interest were analyzed statistically. Approximately 81% of the schools returned surveys. Most teach required CAP didactics in the preclinical and clinical years. Almost 63% of the schools have CAP clinical rotations; most are not required. Twenty-three percent of all medical students have a clinical CAP experience during their psychiatry clerkship. The majority of schools have CAP electives, and approximately 4.8% of students participate. Child and adolescent psychiatry leadership, early exposure to CAP, and CAP clinical experiences were related to student CAP interest, but these relationships were not statistically significant. The time allotted to teaching CAP in the undergraduate medical curriculum is minimal, consistent with previous survey results. Most schools require didactic instruction averaging about 12 hours and offer elective clinical opportunities. The survey findings should help direct future planning to improve CAP medical student education.

Ability of barrier coat S-PRG coating to arrest artificial enamel lesions in primary teeth.

PubMed

Hosoya, Yumiko; Ando, Susumu; Otani, Hideji; Yukinari, Tetsuhiro; Miyazaki, Masashi; Garcia-Godoy, Franklin

2013-10-01

To evaluate the effects of a surface pre-reacted glass-ionomer (S-PRG) filled coating material to arrest artificial enamel lesions in primary teeth. Buccal and lingual enamel was demineralized in 0.1 M lactic acid buffer solution (pH 4.75) for 5 days and then divided in the PRG-applied and non-PRG areas. Proximal surfaces were used as a control area without demineralization and coating application. Teeth were divided into three groups (n = 4) according to the 1-week immersion in different solutions: Group 1 (distilled water), Group 2 (demineralizing solution) and Group 3 (artificial saliva). Hardness and Young's modulus by nano-indentation test, and elemental contents and ultrastructure by SEM/EDX analysis were obtained. Data were statistically analyzed using ANOVA and Fisher's PLSD at alpha = 0.05. Only for the non-PRG area in Group 1, the hardness and Young's modulus of the demineralized surface enamel were significantly lower than those of the enamel 30-60 microm beneath the surface. Demineralized enamel of non-PRG and PRG-applied areas showed similar SEM views. Only for the non-PRG area in Group 2 and control area in Group 3, the Ca/P of the surface enamel was significantly higher than that of the enamel 5-10 microm beneath the surface. There was no significant difference of the Ca/P among the measuring points from the surface to 10 microm depth of enamel for the PRG applied area in Group 2.

Nuclear Data Sheets for A = 168

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

Baglin, Coral M.

2010-07-15

Nuclear structure data pertaining to all nuclei with mass A=168 (Tb, Dy, Ho, Er, Tm, Yb, Lu, Hf, Ta, W, Re, Os, Ir, Pt) have been evaluated and incorporated into the ENSDF data file. This evaluation supersedes the previous publication (V.S. Shirley, Nuclear Data Sheets 71, 261 (1994) (literature cutoff date July 1993)) and subsequent ENSDF file revisions for Tb and Dy (C. Baglin, literature cutoff date of 15 June 1999) and Hf (B. Singh, literature cutoff date of 30 April 2001), and includes literature available by 15 June 2010. Since the above evaluations, the first excited states in {supmore » 168}Pt have been identified (1998Ki20, 2009Go16) and {alpha} decay from {sup 172}Hg has been observed (2009Sa27, 2004Ke06, 1999Se14). New levels in {sup 168}Dy have been excited using the {sup 170}Er({sup 82}Se,{sup 84}Kr{gamma}) reaction (2010So03). (HI,xn{gamma}) studies have significantly expanded our knowledge of level structure in {sup 168}Lu (1999Ka17, 2002Ha33), {sup 168}Ta (2008QiZZ), {sup 168}Yb (1995Fi01), {sup 168}Tm (2007CaZW), {sup 168}Hf (2009Ya21), {sup 168}Os (2001Jo11, 2009Od02) and, for {sup 168}Tm, important information has come also from (d,2n{gamma}) and ({alpha},n{gamma}) reactions (1995Si20). Revised decay schemes are available following new studies of {sup 168}Hf {epsilon} decay (6.7 min) (1997Ba26), {sup 168}Lu {epsilon} decay (1999Ba65), {sup 168}Ta {epsilon} decay (2007Mc08) and {sup 172}Au {alpha} decay (2009Ha42). Significant new information for {sup 168}Er is available from (p,t) (2006Bu09), (d,p) and (t,d) (1996Ma50), ({gamma},{gamma}') (1996Ma18), (136Xe, X{gamma}) (2010Dr02), ({sup 238}U,{sup 238}U{sup '{gamma}}) (2003Wu07) and (n,n{sup '{gamma}}) (1998Be20, 1998Be62) reactions, and the availability of {gamma}{gamma} coin data (1994Ju02, 1996Gi09) for the (n,{gamma}) E=thermal reaction has resulted in some significant level scheme revisions.« less

Influence of Different Container Closure Systems and Capping Process Parameters on Product Quality and Container Closure Integrity (CCI) in GMP Drug Product Manufacturing.

PubMed

Mathaes, Roman; Mahler, Hanns-Christian; Roggo, Yves; Huwyler, Joerg; Eder, Juergen; Fritsch, Kamila; Posset, Tobias; Mohl, Silke; Streubel, Alexander

2016-01-01

Capping equipment used in good manufacturing practice manufacturing features different designs and a variety of adjustable process parameters. The overall capping result is a complex interplay of the different capping process parameters and is insufficiently described in literature. It remains poorly studied how the different capping equipment designs and capping equipment process parameters (e.g., pre-compression force, capping plate height, turntable rotating speed) contribute to the final residual seal force of a sealed container closure system and its relation to container closure integrity and other drug product quality parameters. Stopper compression measured by computer tomography correlated to residual seal force measurements.In our studies, we used different container closure system configurations from different good manufacturing practice drug product fill & finish facilities to investigate the influence of differences in primary packaging, that is, vial size and rubber stopper design on the capping process and the capped drug product. In addition, we compared two large-scale good manufacturing practice manufacturing capping equipment and different capping equipment settings and their impact on product quality and integrity, as determined by residual seal force.The capping plate to plunger distance had a major influence on the obtained residual seal force values of a sealed vial, whereas the capping pre-compression force and the turntable rotation speed showed only a minor influence on the residual seal force of a sealed vial. Capping process parameters could not easily be transferred from capping equipment of different manufacturers. However, the residual seal force tester did provide a valuable tool to compare capping performance of different capping equipment. No vial showed any leakage greater than 10(-8)mbar L/s as measured by a helium mass spectrometry system, suggesting that container closure integrity was warranted in the residual seal force range tested for the tested container closure systems. Capping equipment used in good manufacturing practice manufacturing features different designs and a variety of adjustable process parameters. The overall capping result is a complex interplay of the different capping process parameters and is insufficiently described in the literature. It remains poorly studied how the different capping equipment designs and capping equipment process parameters contribute to the final capping result.In this study, we used different container closure system configurations from different good manufacturing process drug product fill & finish facilities to investigate the influence of the vial size and the rubber stopper design on the capping process. In addition, we compared two examples of large-scale good manufacturing process capping equipment and different capping equipment settings and their impact on product quality and integrity, as determined by residual seal force. © PDA, Inc. 2016.

A large-scale field trial of thin-layer capping of PCDD/F-contaminated sediments: Sediment-to-water fluxes up to 5 years post-amendment.

PubMed

Cornelissen, Gerard; Schaanning, Morten; Gunnarsson, Jonas S; Eek, Espen

2016-04-01

The longer-term effect (3-5 y) of thin-layer capping on in situ sediment-to-surface water fluxes was monitored in a large-scale field experiment in the polychlorinated dibenzodioxin and dibenzofuran (PCDD/F) contaminated Grenlandfjords, Norway (4 trial plots of 10,000 to 40,000 m(2) at 30 to 100 m water depth). Active caps (designed thickness 2.5 cm) were established in 2 fjords, consisting of dredged clean clay amended with powdered activated carbon (PAC) from anthracite. These active caps were compared to 2 nonactive caps in one of the fjords (designed thickness 5 cm) consisting of either clay only (i.e., without PAC) or crushed limestone. Sediment-to-water PCDD/F fluxes were measured in situ using diffusion chambers. An earlier study showed that during the first 2 years after thin-layer capping, flux reductions relative to noncapped reference fields were more extensive at the fields capped with nonactive caps (70%-90%) than at the ones with PAC-containing caps (50%-60%). However, the present work shows that between 3 and 5 years after thin-layer capping, this trend was reversed and cap effectiveness in reducing fluxes was increasing to 80% to 90% for the PAC caps, whereas cap effectiveness of the nonactive caps decreased to 20% to 60%. The increasing effectiveness over time of PAC-containing "active" caps is explained by a combination of slow sediment-to-PAC mass transfer of PCDD/Fs and bioturbation by benthic organisms. The decreasing effectiveness of "nonactive" limestone and clay caps is explained by deposition of contaminated particles on top of the caps. The present field data indicate that the capping efficiency of thin active caps (i.e., enriched with PAC) can improve over time as a result of slow diffusive PCDD/F transfer from sediment to PAC particles and better mixing of the PAC by bioturbation. © 2015 SETAC.

Impact of out-of-pocket spending caps on financial burden of those with group health insurance.

PubMed

Riggs, Kevin R; Buttorff, Christine; Alexander, G Caleb

2015-05-01

The Affordable Care Act (ACA) mandates that all private health insurance include out-of-pocket spending caps. Insurance purchased through the ACA's Health Insurance Marketplace may qualify for income-based caps, whereas group insurance will not have income-based caps. Little is known about how out-of-pocket caps impact individuals' health care financial burden. We aimed to estimate what proportion of non-elderly individuals with group insurance will benefit from out-of-pocket caps, and the effect that various cap levels would have on their financial burden. We applied the expected uniform spending caps, hypothetical reduced uniform spending caps (reduced by one-third), and hypothetical income-based spending caps (similar to the caps on Health Insurance Marketplace plans) to nationally representative data from the Medical Expenditure Panel Survey (MEPS). Participants were non-elderly individuals (aged < 65 years) with private group health insurance in the 2011 and 2012 MEPS surveys (n =26,666). (1) The percentage of individuals with reduced family out-of-pocket spending as a result of the various caps; and (2) the percentage of individuals experiencing health care services financial burden (family out-of-pocket spending on health care, not including premiums, greater than 10% of total family income) under each scenario. With the uniform caps, 1.2% of individuals had lower out-of-pocket spending, compared with 3.8% with reduced uniform caps and 2.1% with income-based caps. Uniform caps led to a small reduction in percentage of individuals experiencing financial burden (from 3.3% to 3.1%), with a modestly larger reduction as a result of reduced uniform caps (2.9%) and income-based caps (2.8%). Mandated uniform out-of-pocket caps for those with group insurance will benefit very few individuals, and will not result in substantial reductions in financial burden.

Structure of a two-CAP-domain protein from the human hookworm parasite Necator americanus

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

Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu

2011-05-01

The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite N. americanus refined to a resolution limit of 2.2 Å is presented. Major proteins secreted by the infective larval stage hookworms upon host entry include Ancylostoma secreted proteins (ASPs), which are characterized by one or two CAP (cysteine-rich secretory protein/antigen 5/pathogenesis related-1) domains. The CAP domain has been reported in diverse phylogenetically unrelated proteins, but has no confirmed function. The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite Necator americanus was refined to a resolution limit of 2.2 Å. The structuremore » was solved by molecular replacement (MR) using Na-ASP-2, a one-CAP-domain ASP, as the search model. The correct MR solution could only be obtained by truncating the polyalanine model of Na-ASP-2 and removing several loops. The structure reveals two CAP domains linked by an extended loop. Overall, the carboxyl-terminal CAP domain is more similar to Na-ASP-2 than to the amino-terminal CAP domain. A large central cavity extends from the amino-terminal CAP domain to the carboxyl-terminal CAP domain, encompassing the putative CAP-binding cavity. The putative CAP-binding cavity is a characteristic cavity in the carboxyl-terminal CAP domain that contains a His and Glu pair. These residues are conserved in all single-CAP-domain proteins, but are absent in the amino-terminal CAP domain. The conserved His residues are oriented such that they appear to be capable of directly coordinating a zinc ion as observed for CAP proteins from reptile venoms. This first structure of a two-CAP-domain ASP can serve as a template for homology modeling of other two-CAP-domain proteins.« less

A comparative study of internally and externally capped balloons using small scale test balloons

NASA Technical Reports Server (NTRS)

Bell, Douglas P.

1994-01-01

Caps have been used to structurally reinforce scientific research balloons since the late 1950's. The scientific research balloons used by the National Aeronautics and Space Administration (NASA) use internal caps. A NASA cap placement specification does not exist since no empirical information exisits concerning cap placement. To develop a cap placement specification, NASA has completed two in-hangar inflation tests comparing the structural contributions of internal caps and external caps. The tests used small scale test balloons designed to develop the highest possible stresses within the constraints of the hangar and balloon materials. An externally capped test balloon and an internally capped test balloon were designed, built, inflated and simulated to determine the structural contributions and benefits of each. The results of the tests and simulations are presented.

Novel 3D-printing technique for caps to enable tailored therapeutic endoscopy.

PubMed

Ko, Weon Jin; Song, Ga Won; Hong, Sung Pyo; Kwon, Chang-il; Hahm, Ki Baik; Cho, Joo Young

2016-03-01

To evaluate the feasibility of a tailored endoscopic cap created using 3D-printing technology that is customized according to esophagogastric lesions of each patient. Tailored endoscopic caps, which were designed and fabricated with a 3D printer, were inserted in 35 patients. The types of cap were side-hole cap made for cap-assisted endoscopic mucosal resection (EMRC), oblique-head cap designed for endoscopic submucosal dissection (ESD), wide-head cap used for Trucut biopsy (TCB), and narrow-tip cap to facilitate peroral endoscopic myotomy (POEM). EMRC in the esophagus and gastroesophageal junction was carried out using a side-hole cap in seven patients. Median total procedure time for successful removal of lesions was 14 min (range 8-50 min). Gastric ESD was carried out using with an oblique-head cap in 16 patients, for which the median total procedure time was 53 min. TCB in the esophagus was done using a wide-head cap in eight patients. While carrying out POEM for tunneling, a narrow-tip cap was used in four patients with achalasia. Based on the current proof-of-concept study, we anticipate that creating a tailored endoscopic cap is feasible for therapeutic endoscopy. © 2015 Japan Gastroenterological Endoscopy Society.

Incorporating spatial constraint in co-activation pattern analysis to explore the dynamics of resting-state networks: An application to Parkinson's disease.

PubMed

Zhuang, Xiaowei; Walsh, Ryan R; Sreenivasan, Karthik; Yang, Zhengshi; Mishra, Virendra; Cordes, Dietmar

2018-05-15

The dynamics of the brain's intrinsic networks have been recently studied using co-activation pattern (CAP) analysis. The CAP method relies on few model assumptions and CAP-based measurements provide quantitative information of network temporal dynamics. One limitation of existing CAP-related methods is that the computed CAPs share considerable spatial overlap that may or may not be functionally distinct relative to specific network dynamics. To more accurately describe network dynamics with spatially distinct CAPs, and to compare network dynamics between different populations, a novel data-driven CAP group analysis method is proposed in this study. In the proposed method, a dominant-CAP (d-CAP) set is synthesized across CAPs from multiple clustering runs for each group with the constraint of low spatial similarities among d-CAPs. Alternating d-CAPs with less overlapping spatial patterns can better capture overall network dynamics. The number of d-CAPs, the temporal fraction and spatial consistency of each d-CAP, and the subject-specific switching probability among all d-CAPs are then calculated for each group and used to compare network dynamics between groups. The spatial dissimilarities among d-CAPs computed with the proposed method were first demonstrated using simulated data. High consistency between simulated ground-truth and computed d-CAPs was achieved, and detailed comparisons between the proposed method and existing CAP-based methods were conducted using simulated data. In an effort to physiologically validate the proposed technique and investigate network dynamics in a relevant brain network disorder, the proposed method was then applied to data from the Parkinson's Progression Markers Initiative (PPMI) database to compare the network dynamics in Parkinson's disease (PD) and normal control (NC) groups. Fewer d-CAPs, skewed distribution of temporal fractions of d-CAPs, and reduced switching probabilities among final d-CAPs were found in most networks in the PD group, as compared to the NC group. Furthermore, an overall negative association between switching probability among d-CAPs and disease severity was observed in most networks in the PD group as well. These results expand upon previous findings from in vivo electrophysiological recording studies in PD. Importantly, this novel analysis also demonstrates that changes in network dynamics can be measured using resting-state fMRI data from subjects with early stage PD. Copyright © 2018 Elsevier Inc. All rights reserved.

Actin protofilament orientation in deformation of the erythrocyte membrane skeleton.

PubMed Central

Picart, C; Dalhaimer, P; Discher, D E

2000-01-01

The red cell's spectrin-actin network is known to sustain local states of shear, dilation, and condensation, and yet the short actin filaments are found to maintain membrane-tangent and near-random azimuthal orientations. When calibrated with polarization results for single actin filaments, imaging of micropipette-deformed red cell ghosts has allowed an assessment of actin orientations and possible reorientations in the network. At the hemispherical cap of the aspirated projection, where the network can be dilated severalfold, filaments have the same membrane-tangent orientation as on a relatively unstrained portion of membrane. Likewise, over the length of the network projection pulled into the micropipette, where the network is strongly sheared in axial extension and circumferential contraction, actin maintains its tangent orientation and is only very weakly aligned with network extension. Similar results are found for the integral membrane protein Band 3. Allowing for thermal fluctuations, we deduce a bound for the effective coupling constant, alpha, between network shear and azimuthal orientation of the protofilament. The finding that alpha must be about an order of magnitude or more below its tight-coupling value illustrates how nanostructural kinematics can decouple from more macroscopic responses. Monte Carlo simulations of spectrin-actin networks at approximately 10-nm resolution further support this conclusion and substantiate an image of protofilaments as elements of a high-temperature spin glass. PMID:11106606

Proposed Trace Gas Measurements Over the Western United States for TROPOMI Validation

NASA Technical Reports Server (NTRS)

Parworth, Caroline L.; Marrero, Josette E.; Yates, Emma L.; Ryoo, Ju-Mee; Iraci, Laura T.

2018-01-01

The Alpha Jet Atmospheric eXperiment (AJAX), located in the Bay Area of California, is a joint effort between NASA Ames Research Center and H211, LCC. AJAX makes in-situ airborne measurements of trace gases 2-4 times per month, resulting in over 216 flights since 2011. Current measurements include ozone (O3), carbon dioxide (CO2), methane (CH4), water (H2O), formaldehyde (HCHO), and meteorological measurements (i.e., ambient pressure, temperature, and 3D winds). Currently, the AJAX team is working to incorporate nitrogen dioxide (NO2) measurements with a Cavity Attenuated Phase Shift Spectrometer (CAPS). Successful science flights coincident with satellite overpasses have been performed since 2011 by the Alpha Jet, with more than 40 flights under the Greenhouse Observing SATellite (GOSAT) and several flights under the Orbiting Carbon Observatory-2 (OCO-2). Results from these flights, which have covered a range of different surfaces and seasonal conditions, will be presented. In-situ vertical profiles of O3, CO2, CH4, H2O, HCHO, and NO2 from the surface to 28,000 feet made by AJAX will also be valuable for satellite validation of data products obtained from the TROPOspheric Montoring Instrument (TROPOMI). TROPOMI is on board the Copernicus Sentinel-5 precursor (S5p) satellite, with level 2 products including O3, CO, CH4, HCHO, NO2, and aerosols.

Mono-PEGylation of Alpha-MMC and MAP30 from Momordica charantia L.: Production, Identification and Anti-Tumor Activity.

PubMed

Sun, Yun; Sun, Fenghui; Li, Jianlong; Wu, Minlu; Fan, Xiang; Meng, Yanfa; Meng, Yao

2016-10-31

PEGylation is a well-established and effective strategy to decrease immunogenicity, which can increase the stability and in vivo half-life time. However, the generation of multi-site modified products is inevitable due to the lysine chemistry, which will bring difficulties in subsequent research, such as purification and quantification. Site-specific modification by mPEG-succinimidyl carbonate (mPEG-SC) is a widely used method for N -terminal conjugation. In this study, we used it for site-directed modification on two ribosome-inactivating proteins (RIPs), alpha-momorcharin (α-MMC) and momordica anti-HIV protein (MAP30), from Momordica charantia L. According to the optimization of previous modification conditions, we compared Macro-Cap SP with SP-Sepharose FF chromatography for separating the final mPEGylated RIPs. Two kinds of methods both can obtain homogenous mPEGylated RIPs which were identified by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing electrophoresis (IEF), and matrix-assisted laser desorption ionization-time of flight/time of flight (MALDI-TOF/TOF) analysis. We also used iodine staining method to detect the amount of unmodified PEG. Furthermore, the inhibition activity of both mPEGylated and non-PEGylated RIPs against human lung adenocarcinoma epithelial A549 cells was detected. All of the results suggested that the mPEGylated α-MMC/MAP30 might be potentially developed as new anti-tumor drugs.

Crystal Structure of MpPR-1i, a SCP/TAPS protein from Moniliophthora perniciosa, the fungus that causes Witches’ Broom Disease of Cacao

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

Baroni, Renata M.; Luo, Zhipu; Darwiche, Rabih

The pathogenic fungi Moniliophthora perniciosa causes Witches’ Broom Disease (WBD) of cacao. The structure of MpPR-1i, a protein expressed by M. perniciosa when it infects cacao, are presented. This is the first reported de novo structure determined by single-wavelength anomalous dispersion phasing upon soaking with selenourea. Each monomer has flexible loop regions linking the core alpha-beta-alpha sandwich topology that comprise ~50% of the structure, making it difficult to generate an accurate homology model of the protein. MpPR-1i is monomeric in solution but is packed as a high ~70% solvent content, crystallographic heptamer. The greatest conformational flexibility between monomers is foundmore » in loops exposed to the solvent channel that connect the two longest strands. MpPR-1i lacks the conserved CAP tetrad and is incapable of binding divalent cations. MpPR-1i has the ability to bind lipids, which may have roles in its infection of cacao. These lipids likely bind in the palmitate binding cavity as observed in tablysin-15, since MpPR-1i binds palmitate with comparable affinity as tablysin-15. Further studies are required to clarify the possible roles and underlying mechanisms of neutral lipid binding, as well as their effects on the pathogenesis of M. perniciosa so as to develop new interventions for WBD.« less

Forskolin promotes the development of ethanol tolerance in 6-hydroxydopamine-treated mice

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

Szabo, G.; Hoffman, P.L.; Tabakoff, B.

1988-01-01

Partial depletion of brain norepinephrine by 6-hydroxydopamine prevents the development of functional tolerance to ethanol in mice. This blockade of tolerance development was overcome by daily intracerebroventricular injections of forskolin. These results suggest that interaction of norepinephrine with post-synaptic ..beta..-adrenergic receptors, and activation of adenylate cyclase, is important for the development of ethanol tolerance. Interaction of norepinephrine with ..cap alpha../sub 1/-adrenergic receptors may be less crucial, since treatment with a phorbol ester activator of protein kinase C did not restore the development of tolerance in mice treated with 6-hydroxydopamine. The importance of the ..beta..-adrenergic receptor-coupled adenylate cyclase system for developmentmore » of ethanol tolerance, in addition to its previously-reported role in long-term potentiation, suggests that this system may influence neuroadaptive processes in general. 26 references, 2 figures.« less

Recognition and invasion of human erythrocytes by malarial parasites: contribution of sialoglycoproteins to attachment and host specificity

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

Friedman, M.J.; Blankenberg, T.; Sensabaugh, G.

1984-05-01

The receptivity of human erythrocytes to invasion by Plasmodium falciparum merozoites can be decreased by neuraminidase or trypsin treatment, an observation that supports a role for the erythrocyte sialoglycoproteins (glycophorins) in invasion. We have found that ..cap alpha../sub 1/-acid glycoprotein (AGP), added to in vitro cultures, can restore invasion of enzyme-treated human erythrocytes. AGP is structurally different from the glycophorins although it does carry 12% sialic acid. Its ability to restore receptivity to desialylated cells is dependent on its sialic acid complement, its concentration, and its binding to the erythrocyte surface. We present evidence that AGP forms a bridge betweenmore » the merozoite and the enzyme-treated erythrocyte that allows the stronger and more complex interactions of invasion to proceed. We suggest that the glycophorins play the same role on the surface of the intact erythrocyte. 31 references, 3 figures, 6 tables.« less

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

Ayeb, M.E.; Bahraoui, E.M.; Granier, C.

Two antibody subpopulations directed against Anemonia sulcata toxin I or II have been purified by immunoaffinity chromatography. These antibodies are specific for a single antigenic region and were used in a structure-antigenicity relationship study using homologous toxins and chemically modified derivatives of A. sulcata toxin II. Asp-7 and/or Asp=9 and Gln-47 of toxin II were found to be implicated in the antigenic region recognized by the two antibody subpopulations. On the contrary, Arg-14, Lys-35, -36, and -46, and ..cap alpha..-NH/sub 2/ of the glycine residue of A. sulcata toxin II are not involved in the corresponding antigenic region. When assayedmore » for interaction with the sodium channel, the antigenic region of toxin II, including Asp-9 and Gln-47, appeared fully accessible to its specific antibodies, suggesting that it is not involved in the binding of the toxin to its receptor.« less

Experimental oral lead toxicity in young dogs

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

Stowe, H.D.; Goyer, R.A.; Krigman, M.M.

1973-02-01

Litter-mate male pups were fed a calcium-and-phosphorus-low purified diet with and without 100 ppm of lead as lead acetate from age 6 to 18 weeks. Lead-toxic dogs exhibited cyclic but terminally severe anorexia and cachexia, significant anemia, normoblastocytosis and leukopenia within six weeks, hypoproteinemia, decreased serum albumin, ..cap alpha../sub 1/-globulin, ..beta../sub 2/-globulin, alkaline phosphatase and lactic dehydrogenase 1, elevated serum glutamic oxaloacetic and pyruvic transaminases, delayed closure of the thoracic vertebral epiphyses, lead lines in the distal radii and thoracic spinous processes, enlargement of liver, kidney, and brain, hepatic fatty metamorphosis, focal proximal renal tubular necrosis, hydropic degeneration of spermatognia,more » and lead inclusion body formation. Approximately 97% of the tissue lead was estimated to be skeletal; the greatest concentration of lead in the brain was found in the occipital gray matter.« less

Ruthenium-97 hepatobiliary agents for delayed studies of the bilary tract I: Ru-97 PIPIDA: concise communication

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

Schachner, E.R.; Gil, M.C.; Atkins, H.L.

1981-04-01

Failure of early diagnosis of biliary atresia results in the development of cirrhosis and death. Commonly used hepatobiliary agents are not ideal for follow-up studies because of their unfavorable physical properties or short half-life. The excellent physical properties of Ru-97 should overcome these limitations. Therefore, Ru-97 PIPIDA (N,..cap alpha..-(p-isopropyl acetanilide) iminoacetic acid) is being investigated as a potential hepatobiliary agent that would allow an improved diagnosis of the disease. Ruthenium-97 PIPIDA and Tc-99m PIPIDA showed similar blood clearance rates in dogs. Ru-97 PIPIDA scintigrams in dogs showed early uptake in liver and gallbladder and slow excretion through the gastrointestinal tract.more » Biodistribution studies were performed in normal rats and rats with biliary obstruction. The findings suggest that Ru-97 PIPIDA should be useful for delayed studies ( 1 to 3 days) of the biliary tract.« less

Determination of molybdenum in sea and estuarine water with BETA-naphthoin oxime and neutron activation

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

Kuathilake, A.I.; Chatt, A.

1980-05-01

An analytical method has been developed for the determination of submicrogram quantities of molybdenum in sea and esturaine water. The method consists of preconcentration of molybdenum with BETA-naphthoin oxime followed by the determination of the element employing neutron activation analysis. Various factors that can influence yield and selectivity of the preconcentration process have been investigated in detail. A comparison study between ..cap alpha..-benzoin oxime and BETA-naphthoin oxime in preconcentrating molybdenum has been carried out using a standard steel sample. The method has been applied to determine molybdenum content of sea and estuarine water. A detection limit of 0.32 ..mu..g Momore » L/sup -1/ seawater has been acheived. The precision and accuracy of the method have been evaluated using an intercomparison fresh water and a biological standard reference material. 1 figure, 9 tables.« less

The human fatty acid-binding protein family: Evolutionary divergences and functions

PubMed Central

2011-01-01

Fatty acid-binding proteins (FABPs) are members of the intracellular lipid-binding protein (iLBP) family and are involved in reversibly binding intracellular hydrophobic ligands and trafficking them throughout cellular compartments, including the peroxisomes, mitochondria, endoplasmic reticulum and nucleus. FABPs are small, structurally conserved cytosolic proteins consisting of a water-filled, interior-binding pocket surrounded by ten anti-parallel beta sheets, forming a beta barrel. At the superior surface, two alpha-helices cap the pocket and are thought to regulate binding. FABPs have broad specificity, including the ability to bind long-chain (C16-C20) fatty acids, eicosanoids, bile salts and peroxisome proliferators. FABPs demonstrate strong evolutionary conservation and are present in a spectrum of species including Drosophila melanogaster, Caenorhabditis elegans, mouse and human. The human genome consists of nine putatively functional protein-coding FABP genes. The most recently identified family member, FABP12, has been less studied. PMID:21504868

Magnetic ordering in Ce--La and Nd--La alloys

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

Petersen, T.S.; Legvold, S.; Gschneidner, K.A. Jr.

1977-01-01

Heat capacity, magnetic susceptibility, and electrical resistivity measurements have been made on a wide ranging set of Ce--La and Nd--La alloys. In the case of Ce it is found that less than 5 at. percent of La will prevent the ..beta..(dhcp) to ..cap alpha.. (collapsed fcc) transition at T approximately less than 50K. In the case of Nd--La only the dhcp allotrope is formed. Two magnetic ordering temperatures have been found for many of the samples. These are believed to be caused by antiferromagnetic ordering on the two different atomic sites in the dhcp structure, cubic and hexagonal. In bothmore » sets of alloys the two ordering temperatures coalesce into one for La concentrations approximately greater than 30 percent. Additional magnetic features in Ce--La alloys are explained by the formation of the fcc phase.« less

Higher rate of severe toxicities in obese patients receiving dose-dense (dd) chemotherapy according to unadjusted body surface area: results of the prospectively randomized GAIN study.

PubMed

Furlanetto, J; Eiermann, W; Marmé, F; Reimer, T; Reinisch, M; Schmatloch, S; Stickeler, E; Thomssen, C; Untch, M; Denkert, C; von Minckwitz, G; Lederer, B; Nekljudova, V; Weber, K; Loibl, S; Möbus, V

2016-11-01

In routine clinical practice, chemotherapy doses are frequently capped at a body surface area (BSA) of 2.0 m 2 or adjusted to an ideal weight for obese patients due to safety reasons. Between August 2004 and July 2008, a total of 3023 patients were enrolled in the GAIN study, a randomized phase III adjuvant trial, comparing two types of dose-dense (dd) regimen [epirubicin, docetaxel and cyclophosphamide (iddETC) versus epirubicin and cyclophosphamide (EC) followed by docetaxel (T) plus capecitabine (X)]. We retrospectively evaluated a total of 555 patients with a BMI of ≥30 for safety and outcome. Eighteen percent of all patients were obese: 31% of those received chemotherapy according to an unadjusted BSA. For the remaining patients, BSA was adjusted to ideal weight or was capped at 2.0 m 2 . A total of 15% of obese patients receiving full (unadjusted) dose of chemotherapy versus 6% of obese patients with an adjusted BSA experienced febrile neutropenia (P = 0.003) and 9% versus 3% high-grade thrombopenia (P = 0.002). Overall, 17% versus 10% had a thromboembolic event (P = 0.017), which was high grade in 13% versus 6%, respectively (P = 0.019), and 3% versus 0.3% high-grade hot flushes (P = 0.013). Dizziness (5% versus 11%; P = 0.016), diarrhea (19% versus 27%; P = 0.033) and an increase in serum creatinine (7% versus 14%; P = 0.019) were higher in the adjusted group. However, no differences in disease-free survival (DFS) and overall survival (OS) were observed between non-obese patients, obese patients receiving full-dose chemotherapy or according to an adjusted BSA [5-year DFS 81% (confidence interval 79% to 83%) versus 82% (75% to 87%) versus 81% (76% to 84%); P = 0.761; 5-year OS 90% (88% to 91%) versus 86% (80% to 91%) versus 88% (84% to 91%); P = 0.143]. Obese patients receiving dd chemotherapy according to their real BSA have a higher risk of developing severe toxicities without influencing survival. Therefore, a dose adjustment of intense dd chemotherapy should be carried out to avoid life-threatening complications. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Cervical Cap

MedlinePlus

... Videos for Educators Search English Español The Cervical Cap KidsHealth / For Teens / The Cervical Cap What's in ... Call the Doctor? Print What Is a Cervical Cap? A cervical cap is a small cup made ...

75 FR 49527 - Caps Visual Communications, LLC; Black Dot Group; Formerly Known as Caps Group Acquisition, LLC...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-13

... DEPARTMENT OF LABOR Employment and Training Administration [TA-W-74,195] Caps Visual Communications, LLC; Black Dot Group; Formerly Known as Caps Group Acquisition, LLC Chicago, IL; Amended... of Caps Visual Communications, LLC, Black Dot Group, formerly known as Caps Group Acquisition, LLC...

Polygons and adhesion plaques and the disassembly and assembly of myofibrils in cardiac myocytes.

PubMed

Lin, Z X; Holtzer, S; Schultheiss, T; Murray, J; Masaki, T; Fischman, D A; Holtzer, H

1989-06-01

Successive stages in the disassembly of myofibrils and the subsequent assembly of new myofibrils have been studied in cultures of dissociated chick cardiac myocytes. The myofibrils in trypsinized and dispersed myocytes are sequentially disassembled during the first 3 d of culture. They split longitudinally and then assemble into transitory polygons. Multiples of single sarcomeres, the cardiac polygons, are analogous to the transitory polygonal configurations assumed by stress fibers in spreading fibroblasts. They differ from their counterparts in fibroblasts in that they consist of muscle alpha-actinin vertices and muscle myosin heavy chain struts, rather than of the nonmuscle contractile protein isoforms of stress fiber polygons. EM sections reveal the vertices and struts in cardiac polygons to be typical Z and A bands. Most cardiac polygons are eliminated by day 5 of culture. Concurrent with the disassembly and elimination of the original myofibrils new myofibrils are rapidly assembled elsewhere in the same myocyte. Without exception both distal tips of each nascent myofibril terminate in adhesion plaques. The morphology and composition of the adhesion plaques capping each end of each myofibril are similar to those of the termini of stress fibers in fibroblasts. However, whereas the adhesion complexes involving stress fibers in fibroblasts consist of vinculin/nonmuscle alpha-actinin/beta- and gamma-actins, the analogous structures in myocytes involving myofibrils consist of vinculin/muscle alpha-actinin/alpha-actin. The addition of 1.7-2.0 microns sarcomeres to the distal tips of an elongating myofibril, irrespective of whether the myofibril consists of 1, 10, or several hundred tandem sarcomeres, occurs while the myofibril appears to remain linked to its respective adhesion plaques. The adhesion plaques in vitro are the equivalent of the in vivo intercalated discs, both in terms of their molecular composition and with respect to their functioning as initiating sites for the assembly of new sarcomeres. How 1.7-2.0 microns nascent sarcomeres can be added distally during elongation while the tips of the myofibrils remain inserted into submembranous adhesion plaques is unknown.

Polygons and adhesion plaques and the disassembly and assembly of myofibrils in cardiac myocytes

PubMed Central

1989-01-01

Successive stages in the disassembly of myofibrils and the subsequent assembly of new myofibrils have been studied in cultures of dissociated chick cardiac myocytes. The myofibrils in trypsinized and dispersed myocytes are sequentially disassembled during the first 3 d of culture. They split longitudinally and then assemble into transitory polygons. Multiples of single sarcomeres, the cardiac polygons, are analogous to the transitory polygonal configurations assumed by stress fibers in spreading fibroblasts. They differ from their counterparts in fibroblasts in that they consist of muscle alpha-actinin vertices and muscle myosin heavy chain struts, rather than of the nonmuscle contractile protein isoforms of stress fiber polygons. EM sections reveal the vertices and struts in cardiac polygons to be typical Z and A bands. Most cardiac polygons are eliminated by day 5 of culture. Concurrent with the disassembly and elimination of the original myofibrils new myofibrils are rapidly assembled elsewhere in the same myocyte. Without exception both distal tips of each nascent myofibril terminate in adhesion plaques. The morphology and composition of the adhesion plaques capping each end of each myofibril are similar to those of the termini of stress fibers in fibroblasts. However, whereas the adhesion complexes involving stress fibers in fibroblasts consist of vinculin/nonmuscle alpha-actinin/beta- and gamma-actins, the analogous structures in myocytes involving myofibrils consist of vinculin/muscle alpha-actinin/alpha-actin. The addition of 1.7-2.0 microns sarcomeres to the distal tips of an elongating myofibril, irrespective of whether the myofibril consists of 1, 10, or several hundred tandem sarcomeres, occurs while the myofibril appears to remain linked to its respective adhesion plaques. The adhesion plaques in vitro are the equivalent of the in vivo intercalated discs, both in terms of their molecular composition and with respect to their functioning as initiating sites for the assembly of new sarcomeres. How 1.7-2.0 microns nascent sarcomeres can be added distally during elongation while the tips of the myofibrils remain inserted into submembranous adhesion plaques is unknown. PMID:2472405

The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5): Development and initial psychometric evaluation in military veterans.

PubMed

Weathers, Frank W; Bovin, Michelle J; Lee, Daniel J; Sloan, Denise M; Schnurr, Paula P; Kaloupek, Danny G; Keane, Terence M; Marx, Brian P

2018-03-01

The Clinician-Administered PTSD Scale (CAPS) is an extensively validated and widely used structured diagnostic interview for posttraumatic stress disorder (PTSD). The CAPS was recently revised to correspond with PTSD criteria in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; American Psychiatric Association, 2013). This article describes the development of the CAPS for DSM-5 (CAPS-5) and presents the results of an initial psychometric evaluation of CAPS-5 scores in 2 samples of military veterans (Ns = 165 and 207). CAPS-5 diagnosis demonstrated strong interrater reliability (к = .78 to 1.00, depending on the scoring rule) and test-retest reliability (к = .83), as well as strong correspondence with a diagnosis based on the CAPS for DSM-IV (CAPS-IV; к = .84 when optimally calibrated). CAPS-5 total severity score demonstrated high internal consistency (α = .88) and interrater reliability (ICC = .91) and good test-retest reliability (ICC = .78). It also demonstrated good convergent validity with total severity score on the CAPS-IV (r = .83) and PTSD Checklist for DSM-5 (r = .66) and good discriminant validity with measures of anxiety, depression, somatization, functional impairment, psychopathy, and alcohol abuse (rs = .02 to .54). Overall, these results indicate that the CAPS-5 is a psychometrically sound measure of DSM-5 PTSD diagnosis and symptom severity. Importantly, the CAPS-5 strongly corresponds with the CAPS-IV, which suggests that backward compatibility with the CAPS-IV was maintained and that the CAPS-5 provides continuity in evidence-based assessment of PTSD in the transition from DSM-IV to DSM-5 criteria. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Comparative study of two precision overdenture attachment designs.

PubMed

Cohen, B I; Pagnillo, M; Condos, S; Deutsch, A S

1996-08-01

In this study two precision overdenture attachment designs were tested for retention--a nylon overdenture cap system and a new cap and keeper system. The new cap and keeper system was designed to reduce the time involved in replacing a cap worn by the conditions of the oral environment. Six groups were tested at two different angles and retentive failure was examined at two different angles (26 and 0 degrees). Failure was measured in pounds with a force gauge over a 2000 pull cycle. The amount of force required to remove caps for two overdenture caps and a replaced cap for the metal keeper system was determined. Two dependent variables were absolute force and relative force. Repeated measures analysis of variance (RMANOVA) was used to compare the between-subjects effects of cap and angle, and the within-subjects effect of pull. The results indicated a significant difference between cap types (p < 0.0001) with respect to the relative force required to remove the cap. There was no effect of angle. For absolute force, RMANOVA revealed a highly significant interaction between pull and cap (p < 0.0001). Thus, the way that force changed over pulls depended on which cap was used (no effect of angle). For relative force, RMANOVA revealed no interaction between pull and cap, but there was a main effect of cap type (p < 0.0001) (no effect of angle). The nylon cap design required less force for removal but showed more consistency in the force required over the course of the 2000 pulls when compared with the keeper with cap insert. The results obtained in this study were consistent with similar studies in literature.

Inflammatory response in mixed viral-bacterial community-acquired pneumonia.

PubMed

Bello, Salvador; Mincholé, Elisa; Fandos, Sergio; Lasierra, Ana B; Ruiz, María A; Simon, Ana L; Panadero, Carolina; Lapresta, Carlos; Menendez, Rosario; Torres, Antoni

2014-07-29

The role of mixed pneumonia (virus+bacteria) in community-acquired pneumonia (CAP) has been described in recent years. However, it is not known whether the systemic inflammatory profile is different compared to monomicrobial CAP. We wanted to investigate this profile of mixed viral-bacterial infection and to compare it to monomicrobial bacterial or viral CAP. We measured baseline serum procalcitonin (PCT), C reactive protein (CRP), and white blood cell (WBC) count in 171 patients with CAP with definite etiology admitted to a tertiary hospital: 59 (34.5%) bacterial, 66 (39.%) viral and 46 (27%) mixed (viral-bacterial). Serum PCT levels were higher in mixed and bacterial CAP compared to viral CAP. CRP levels were higher in mixed CAP compared to the other groups. CRP was independently associated with mixed CAP. CRP levels below 26 mg/dL were indicative of an etiology other than mixed in 83% of cases, but the positive predictive value was 45%. PCT levels over 2.10 ng/mL had a positive predictive value for bacterial-involved CAP versus viral CAP of 78%, but the negative predictive value was 48%. Mixed CAP has a different inflammatory pattern compared to bacterial or viral CAP. High CRP levels may be useful for clinicians to suspect mixed CAP.

Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

NASA Astrophysics Data System (ADS)

Matsushita, Y.; Murakawa, T.; Shimamura, K.; Oishi, M.; Ohyama, T.; Kurita, N.

2015-02-01

The catabolite activator protein (CAP) is one of the regulatory proteins controlling the transcription mechanism of gene. Biochemical experiments elucidated that the complex of CAP with cyclic AMP (cAMP) is indispensable for controlling the mechanism, while previous molecular simulations for the monomer of CAP+cAMP complex revealed the specific interactions between CAP and cAMP. However, the effect of cAMP-binding to CAP on the specific interactions between CAP and DNA is not elucidated at atomic and electronic levels. We here considered the ternary complex of CAP, cAMP and DNA in solvating water molecules and investigated the specific interactions between them at atomic and electronic levels using ab initio molecular simulations based on classical molecular dynamics and ab initio fragment molecular orbital methods. The results highlight the important amino acid residues of CAP for the interactions between CAP and cAMP and between CAP and DNA.

The pharmaceutical vial capping process: Container closure systems, capping equipment, regulatory framework, and seal quality tests.

PubMed

Mathaes, Roman; Mahler, Hanns-Christian; Buettiker, Jean-Pierre; Roehl, Holger; Lam, Philippe; Brown, Helen; Luemkemann, Joerg; Adler, Michael; Huwyler, Joerg; Streubel, Alexander; Mohl, Silke

2016-02-01

Parenteral drug products are protected by appropriate primary packaging to protect against environmental factors, including potential microbial contamination during shelf life duration. The most commonly used CCS configuration for parenteral drug products is the glass vial, sealed with a rubber stopper and an aluminum crimp cap. In combination with an adequately designed and controlled aseptic fill/finish processes, a well-designed and characterized capping process is indispensable to ensure product quality and integrity and to minimize rejections during the manufacturing process. In this review, the health authority requirements and expectations related to container closure system quality and container closure integrity are summarized. The pharmaceutical vial, the rubber stopper, and the crimp cap are described. Different capping techniques are critically compared: The most common capping equipment with a rotating capping plate produces the lowest amount of particle. The strength and challenges of methods to control the capping process are discussed. The residual seal force method can characterize the capping process independent of the used capping equipment or CCS. We analyze the root causes of several cosmetic defects associated with the vial capping process. Copyright © 2015 Elsevier B.V. All rights reserved.

Resident CAPS on dense-core vesicles docks and primes vesicles for fusion

PubMed Central

Kabachinski, Greg; Kielar-Grevstad, D. Michelle; Zhang, Xingmin; James, Declan J.; Martin, Thomas F. J.

2016-01-01

The Ca2+-dependent exocytosis of dense-core vesicles in neuroendocrine cells requires a priming step during which SNARE protein complexes assemble. CAPS (aka CADPS) is one of several factors required for vesicle priming; however, the localization and dynamics of CAPS at sites of exocytosis in live neuroendocrine cells has not been determined. We imaged CAPS before, during, and after single-vesicle fusion events in PC12 cells by TIRF micro­scopy. In addition to being a resident on cytoplasmic dense-core vesicles, CAPS was present in clusters of approximately nine molecules near the plasma membrane that corresponded to docked/tethered vesicles. CAPS accompanied vesicles to the plasma membrane and was present at all vesicle exocytic events. The knockdown of CAPS by shRNA eliminated the VAMP-2–dependent docking and evoked exocytosis of fusion-competent vesicles. A CAPS(ΔC135) protein that does not localize to vesicles failed to rescue vesicle docking and evoked exocytosis in CAPS-depleted cells, showing that CAPS residence on vesicles is essential. Our results indicate that dense-core vesicles carry CAPS to sites of exocytosis, where CAPS promotes vesicle docking and fusion competence, probably by initiating SNARE complex assembly. PMID:26700319

Clinical and laboratory features of children with community-acquired pneumonia are associated with distinct radiographic presentations.

PubMed

Falup-Pecurariu, Oana G; Diez-Domingo, Javier; Esposito, Susanna; Finn, Adam; Rodrigues, Fernanda; Spoulou, Vana; Syrogiannopoulos, George A; Usonis, Vytautas; Greenberg, David

2018-07-01

Chest radiographs from children with community-acquired pneumonia (CAP) were categorized into three distinct presentations and each presentation was correlated to clinical and laboratory findings. Children < 59 months with CAP presenting to pediatric emergency rooms during two years were enrolled prospectively in eight centers across Europe. Clinical and laboratory data were documented and radiographs obtained from patients. Of the 1107 enrolled patients, radiographs were characterized as 74.9% alveolar CAP, 8.9% non-alveolar CAP, and 16.3% clinical CAP. Alveolar CAP patients had significantly higher rates of fever (90.7%), vomiting (27.6%), and abdominal pain (18.6%), while non-alveolar CAP patients presented more with cough (96.9%). A model using independent parameters that characterize alveolar, non-alveolar, and clinical CAP demonstrated that alveolar CAP patients were significantly older (OR = 1.02) and had significantly lower oxygen saturation than non-alveolar CAP patients (OR = 0.54). Alveolar CAP patients had significantly higher mean WBC (17,760 ± 8539.68 cells/mm 3 ) and ANC (11.5 ± 7.5 cells/mm 3 ) than patients categorized as non-alveolar CAP (WBC 15,160 ± 5996 cells/mm 3 , ANC 9.2 ± 5.1 cells/mm 3 ) and clinical CAP (WBC 13,180 ± 5892, ANC 7.3 ± 4.7). Alveolar CAP, non-alveolar CAP, and clinical CAP are distinct entities differing not only by chest radiographic appearance but also in clinical and laboratory characteristics. Alveolar CAP has unique characteristics, which suggest association with bacterial etiology. Trial number 3075 (Soroka Hospital, Israel) What is Known: • Community-acquired pneumonia in children is diagnosed based on clinical and radiological definitions. • Radiological criteria were standardized by WHO-SICR and have been utilized in vaccine studies. What is New: • Correlation between the WHO-SICR radiological definitions and clinical and laboratory parameters has not been studied. • Using the WHO-SICR radiological definitions for alveolar community-acquired pneumonia (CAP) and non-alveolar CAP and the study definition for clinical CAP, it was found that the groups are distinct, differing clinically and in laboratory parameters.

The Incidence Rate and Economic Burden of Community-Acquired Pneumonia in a Working-Age Population

PubMed Central

Broulette, Jonah; Yu, Holly; Pyenson, Bruce; Iwasaki, Kosuke; Sato, Reiko

2013-01-01

Background Community-acquired pneumonia (CAP) is frequently associated with the very young and the elderly but is a largely underrecognized burden among working-age adults. Although the burden of CAP among the elderly has been established, there are limited data on the economic burden of CAP in the employed population. Objective To assess the economic impact of CAP in US working-age adults from an employer perspective by estimating the incidence rate and costs of healthcare, sick time, and short-term disability for this patient population. Methods This retrospective cohort study is based on data from 2 Truven Health Analytics databases. The study population consisted of commercially insured active employees aged 18 to 64 years, early retirees aged <65 years, and adult dependents of both cohorts. CAP was identified using medical claims with pneumonia diagnosis codes during the 2009 calendar year. Incidence rate, episode level, and annual costs were stratified by age and by risk based on the presence of comorbidities. Descriptive statistics were used to compare healthcare (ie, medical and pharmacy) costs, sick time, and short-term disability costs between the cohorts with and without CAP. Linear regression was used to estimate the average annual incremental healthcare cost in employed patients with inpatient or outpatient CAP versus individuals without CAP. Results Study eligibility was met by 12,502,017 employed individuals, including 123,920 with CAP and 12,378,097 without CAP; the overall incidence rate of CAP was 10.6 per 1000 person-years. Among individuals with and without CAP, the costs of healthcare, sick time, and short-term disability increased with advancing age and with higher risk status. The mean annual healthcare costs were $20,961 for patients with CAP and $3783 for individuals without CAP. Overall, the mean costs of sick time and short-term disability were $1129 and $1016, respectively, in active employees with CAP, and $853 and $322, respectively, in their counterparts without CAP. Compared with individuals without CAP, the average annual incremental healthcare cost ranged from $39,889 to $113,837 for inpatient management of patients with CAP and from $4170 to $31,524 for outpatient management of patients with CAP, depending on the risk level. Conclusions CAP is a common and costly infection among working-age individuals, especially in patients with comorbidities. Prevention strategies, such as influenza and pneumococcal vaccination, that target working-age adults with underlying medical conditions may be the most valuable in reducing the morbidity and costs associated with CAP. PMID:24991378

The incidence rate and economic burden of community-acquired pneumonia in a working-age population.

PubMed

Broulette, Jonah; Yu, Holly; Pyenson, Bruce; Iwasaki, Kosuke; Sato, Reiko

2013-09-01

Community-acquired pneumonia (CAP) is frequently associated with the very young and the elderly but is a largely underrecognized burden among working-age adults. Although the burden of CAP among the elderly has been established, there are limited data on the economic burden of CAP in the employed population. To assess the economic impact of CAP in US working-age adults from an employer perspective by estimating the incidence rate and costs of healthcare, sick time, and short-term disability for this patient population. This retrospective cohort study is based on data from 2 Truven Health Analytics databases. The study population consisted of commercially insured active employees aged 18 to 64 years, early retirees aged <65 years, and adult dependents of both cohorts. CAP was identified using medical claims with pneumonia diagnosis codes during the 2009 calendar year. Incidence rate, episode level, and annual costs were stratified by age and by risk based on the presence of comorbidities. Descriptive statistics were used to compare healthcare (ie, medical and pharmacy) costs, sick time, and short-term disability costs between the cohorts with and without CAP. Linear regression was used to estimate the average annual incremental healthcare cost in employed patients with inpatient or outpatient CAP versus individuals without CAP. Study eligibility was met by 12,502,017 employed individuals, including 123,920 with CAP and 12,378,097 without CAP; the overall incidence rate of CAP was 10.6 per 1000 person-years. Among individuals with and without CAP, the costs of healthcare, sick time, and short-term disability increased with advancing age and with higher risk status. The mean annual healthcare costs were $20,961 for patients with CAP and $3783 for individuals without CAP. Overall, the mean costs of sick time and short-term disability were $1129 and $1016, respectively, in active employees with CAP, and $853 and $322, respectively, in their counterparts without CAP. Compared with individuals without CAP, the average annual incremental healthcare cost ranged from $39,889 to $113,837 for inpatient management of patients with CAP and from $4170 to $31,524 for outpatient management of patients with CAP, depending on the risk level. CAP is a common and costly infection among working-age individuals, especially in patients with comorbidities. Prevention strategies, such as influenza and pneumococcal vaccination, that target working-age adults with underlying medical conditions may be the most valuable in reducing the morbidity and costs associated with CAP.

Chloro-, methyl-, and (tetrahydroborato)tris((hexamethyldisilyl)amido)thorium(IV) and -uranium(IV). Crystal structure of (tetrahydroborato)tris((hexamethyldisilyl)amido)thorium(IV)

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

Turner, H.W.; Andersen, R.A.; Zalkin, A.

1979-05-01

Reaction of sodium (hexamethyldisilyl)amide with thorium tetrachloride or uranium tetrachloride yields chlorotris-((hexamethyldisilyl)amido)thorium(IV) or -uranium(IV), respectively. The chloroamides of thorium or uranium react with dimethylmagnesium or methyllithium yielding the methyl derivatives MeTh(N(SiMe/sub 3/)/sub 2/)/sub 3/ or MeU(N(SiMe/sub 3/)/sub 2/)/sub 3/, respectively. The chloro compounds yield BH/sub 4/M(N(SiMe/sub 3/)/sub 2/)/sub 3/ upon reaction with lithium tetrahydroborate, where M is thorium or uranium. Infrared spectra of the tetrahydroborate derivatives suggest that BH/sub 4/ is bonded in a tridentate fashion in both compounds, the metal atoms being six-coordinate. Single-crystal X-ray analysis of the thorium borohydride confirms the infrared result. The white BH/sub 4/Th(N(Si(CH/sub 3/))/submore » 2/)/sub 3/ crystals are rhombohedral with cell dimensions a/sub r/ = 11.137 A and ..cap alpha../sub r/ = 113.61/sup 0/; the triply primitive hexagonal cell has a/sub h/ = 18.640 (3) A c/sub h/ = 8.604 (1) A, V = 2489 A/sup 3/, Z = 3, and D/sub x/ = 1.40 g/cm/sup 3/, space group R3m. The structure was refined by full-matrix least squares to a conventional R factor of 0.031 for 1014 data. The Th atom is on a threefold axis 2.32 A from three nitrogen atoms and 2.61 A from the boron atom, a distance which represents a triple bridge bond between Th and B. The three (dimethylsilyl)amide ligands are disordered by a mirror plane parallel to the threefold axis. CH/sub 3/Th(N(Si(CH/sub 3/)/sub 3/)/sub 2/)/sub 3/ is isomorphous with BH/sub 4/Th(N(Si(CH/sub 3/)/sub 3/)/sub 2/)/sub 3/ with cell dimensions a/sub h/ = 18.68 (1) A and c/sub h/ = 8.537 (6) A. The diffraction data yielded integral'' = 12.16 +- 0.33 e for the imaginary scattering term for Th with Cu K..cap alpha.. radiation.« less

A hydrolysed rice-based formula is tolerated by children with cow's milk allergy: a multi-centre study.

PubMed

Fiocchi, A; Restani, P; Bernardini, R; Lucarelli, S; Lombardi, G; Magazzù, G; Marseglia, G L; Pittschieler, K; Tripodi, S; Troncone, R; Ranzini, C

2006-03-01

Children allergic to cow's milk are fed a soy- or a hydrolysed cow's milk-based substitute. Neither can rule out a sensitization risk. Previous studies have shown that hydrolysed rice is tolerated by animals and children with multiple food hypersensitivities. A prospective clinical assessment of tolerance to a rice-based hydrolysed formula was carried out in children allergic to cow's milk. Patients and methods One hundred children (42 girls and 58 boys, mean age 3.17+/-2.93 years, median 2.20, range 0.18-14.6 years) with a history of immediate reactions to cow's milk and confirmed at double-blind, placebo-controlled food challenge (DBPCFC) when not contraindicated were assessed for clinical tolerance to cow's milk proteins. Their allergy work-up included skin prick tests with whole milk, alpha-lactalbumin (ALA), beta-lactoglobulin (BLG) and total caseins, and specific IgE determinations using CAP technology were performed against whole milk, ALA, BLG and casein. Sensitization to rice and rice-based hydrolysed formula was similarly investigated. Patients' sera were evaluated at immunoblotting for specific IgE to cow's milk proteins, rice and rice-based hydrolysed formula. DBPCFC was carried out with increasing doses of a rice-based hydrolysed formula. All patients were sensitized to cow's milk and/or at least one cow's milk protein fraction. Eighty-seven out of 99 were positive to cow's milk and/or a cow's milk protein fraction at skin prick test. Positive (>0.35 kUA/L) specific IgE determinations were found for cow's milk and/or milk fractions (92/95), rice (21/91) and hydrolysed rice infant formula (4/91). At immunoblotting, sera from 96 children were positive to alpha-casein (n=54), beta-casein (n=38), ALA (n=57), BLG (n=37) and bovine serum albumin (n=61). Similarly, although patients' sera often contained specific IgE against rice proteins at CAP (21/91) and immunoblotting (70/96), only six very weakly positive responses were observed against rice-based hydrolysed formula. All DBPCFC with rice-based hydrolysed formula were negative. Rice-based hydrolysed formula is a possible alternative not only for children with multiple allergies, but also for children with cow's milk allergy.

Bronchoalveolar carcinoma (adenocarcinoma) mimicking recurrent bacterial community-acquired pneumonia (CAP).

PubMed

Cunha, Burke A; Syed, Uzma; Mikail, Nardeen

2012-01-01

Depending on the community-acquired pneumonia (CAP) pathogen, host factors, and immune status, CAPs resolve on chest x-rays at different rates. CAPs that resolve more slowly than expected, or not at all, are termed "slowly or non-resolving CAPs." In contrast, recurrent CAPs may be due to host defense defects (eg, multiple myelomas) or post-obstructive bronchogenic carcinomas. There are a variety of noninfectious disorders that may mimic CAPs on chest x-ray: alveolar hemorrhage, pulmonary drug reactions, radiation pneumonitis, Wegener's granulomatosis, bronchiolitis obliterans organizing pneumonia, bronchogenic carcinomas, and lymphomas. Noninfectious mimics of recurrent CAPs include congestive heart failure, pulmonary emboli, infarctions, sarcoidosis, and systemic lupus erythematosus pneumonitis. We present the case of a middle-aged man who presented with recurrent right middle lobe and right lower lobe CAPs. Diagnostic bronchoscopy showed no bronchial obstruction, but open lung biopsy showed bronchoalveolar carcinoma (well-differentiated adenocarcinoma). Bronchoalveolar carcinomas presenting as post-obstructive or recurrent CAPs are rare because the spread is along tissue planes and not endobronchially. The case described demonstrates a rare cause of bronchogenic carcinoma mimicking recurrent CAP. Copyright © 2012 Elsevier Inc. All rights reserved.

NEOSCOPE: A randomised phase II study of induction chemotherapy followed by oxaliplatin/capecitabine or carboplatin/paclitaxel based pre-operative chemoradiation for resectable oesophageal adenocarcinoma.

PubMed

Mukherjee, Somnath; Hurt, Christopher Nicholas; Gwynne, Sarah; Sebag-Montefiore, David; Radhakrishna, Ganesh; Gollins, Simon; Hawkins, Maria; Grabsch, Heike I; Jones, Gareth; Falk, Stephen; Sharma, Ricky; Bateman, Andrew; Roy, Rajarshi; Ray, Ruby; Canham, Jo; Griffiths, Gareth; Maughan, Tim; Crosby, Tom

2017-03-01

Oxaliplatin-capecitabine (OxCap) and carboplatin-paclitaxel (CarPac) based neo-adjuvant chemoradiotherapy (nCRT) have shown promising activity in localised, resectable oesophageal cancer. A non-blinded, randomised (1:1 via a centralised computer system), 'pick a winner' phase II trial. Patients with resectable oesophageal adenocarcinoma ≥ cT3 and/or ≥ cN1 were randomised to OxCapRT (oxaliplatin 85 mg/m 2  day 1, 15, 29; capecitabine 625 mg/m 2 bd on days of radiotherapy) or CarPacRT (carboplatin AUC2; paclitaxel 50 mg/m 2  day 1, 8, 15, 22, 29). Radiotherapy dose was 45 Gy/25 fractions/5 weeks. Both arms received induction OxCap chemotherapy (2 × 3 week cycles of oxaliplatin 130 mg/m 2  day 1, capecitabine 625 mg/m 2 bd days 1-21). Surgery was performed 6-8 weeks after nCRT. Primary end-point was pathological complete response (pCR). Secondary end-points included toxicity, surgical morbidity/mortality, resection rate and overall survival. Based on pCR ≤ 15% not warranting future investigation, but pCR ≥ 35% would, 76 patients (38/arm) gave 90% power (one-sided alpha 10%), implying that arm(s) having ≥10 pCR out of first 38 patients could be considered for phase III trials. ClinicalTrials.gov: NCT01843829. Funder: Cancer Research UK (C44694/A14614). Eighty five patients were randomised between October 2013 and February 2015 from 17 UK centres. Three of 85 (3.5%) died during induction chemotherapy. Seventy-seven patients (OxCapRT = 36; CarPacRT = 41) underwent surgery. The 30-d post-operative mortality was 2/77 (2.6%). Grade III/IV toxicity was comparable between arms, although neutropenia was higher in the CarPacRT arm (21.4% versus 2.6%, p = 0.01). Twelve of 41 (29.3%) (10 of first 38 patients) and 4/36 (11.1%) achieved pCR in the CarPacRT and OxcapRT arms, respectively. Corresponding R0 resection rates were 33/41 (80.5%) and 26/36 (72.2%), respectively. Both regimens were well tolerated. Only CarPacRT passed the predefined pCR criteria for further investigation. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

40 CFR 80.271 - How can a small refiner obtain an adjustment of its 2004-2007 per-gallon cap standard?

Code of Federal Regulations, 2010 CFR

2010-07-01

... adjustment of its 2004-2007 per-gallon cap standard? 80.271 Section 80.271 Protection of Environment...-2007 per-gallon cap standard? (a) EPA may in its discretion adjust the small refiner per-gallon cap... that the per-gallon cap creates; (2) The refiner's proposed adjusted per-gallon cap standard and the...

Severe community-acquired Enterobacter pneumonia: a plea for greater awareness of the concept of health-care-associated pneumonia

PubMed Central

2011-01-01

Background Patients with Enterobacter community-acquired pneumonia (EnCAP) were admitted to our intensive care unit (ICU). Our primary aim was to describe them as few data are available on EnCAP. A comparison with CAP due to common and typical bacteria was performed. Methods Baseline clinical, biological and radiographic characteristics, criteria for health-care-associated pneumonia (HCAP) were compared between each case of EnCAP and thirty age-matched typical CAP cases. A univariate and multivariate logistic regression analysis was performed to determine factors independently associated with ENCAP. Their outcome was also compared. Results In comparison with CAP due to common bacteria, a lower leukocytosis and constant HCAP criteria were associated with EnCAP. Empiric antibiotic therapy was less effective in EnCAP (20%) than in typical CAP (97%) (p < 0.01). A delay in the initiation of appropriate antibiotic therapy (3.3 ± 1.6 vs. 1.2 ± 0.6 days; p < 0.01) and an increase in duration of mechanical ventilation (8.4 ± 5.2 vs. 4.0 ± 4.3 days; p = 0.01) and ICU stay were observed in EnCAP patients. Conclusions EnCAP is a severe infection which is more consistent with HCAP than with typical CAP. This retrospectively suggests that the application of HCAP guidelines should have improved EnCAP management. PMID:21569334

Synthesis of capped RNA using a DMT group as a purification handle.

PubMed

Veliath, Elizabeth; Gaffney, Barbara L; Jones, Roger A

2014-01-01

We report a new method for synthesis of capped RNA or 2'-OMe RNA that uses a N(2-)4,4'-dimethoxytrityl (DMT) group as a lipophilic purification handle to allow convenient isolation and purification of the capped RNA. The DMT group is easily removed under mild conditions without degradation of the cap. We have used this approach to prepare capped 10- and 20-mers. This method is compatible with the many condensation reactions that have been reported for preparation of capped RNA or cap analogues.

In vitro and in vivo assessment of cellular permeability and pharmacodynamics of S-nitrosylated Captopril, a nitric oxide donor

PubMed Central

Jia, Lee; Wong, Hong

2001-01-01

The present studies were aimed at testing the hypothesis that S-nitrosylated captopril (CapNO), a novel crystalline nitric oxide (NO) donor, readily permeates both in vitro and in vivo endothelial monolayers, resulting in its pharmacodynamic effects. CapNO and Captopril (Cap) were added to apical side of endothelial monolayers formed on microporous membranes, and the permeated drugs were collected from basolateral side and detected by a HPLC method. The permeability coefficient (Papp; cm sec−1) of CapNO across the endothelial monolayers was 6.0×10−5, higher than that of Cap (3.13×10−5), indicating the enhancement effect of the attached NO group in CapNO on cellular permeability. The Papp of CapNO and Cap across Caco-2 cells were 3.15×10−5 and 1.53×10−5, respectively. The low Papp of CapNO to Caco-2 cells may be attributed to the high membrane resistance of Caco-2 cells. A bolus injection of CapNO to epicardial coronary artery of chronically-instrumented awake dogs caused significant increases in coronary blood flow and coronary diameters dose-dependently without significant changes in aortic pressure. In contrast, the equimolar doses of Cap did not produce haemodynamic responses. Intravenous CapNO caused an instant increase in the regional cerebral blood flow determined by H2-clearance, whereas the equimolar doses of Cap did not enhance the cerebral blood flow. These results conclude that the NO group, an active component of CapNO, enhances both in vitro and in vivo endothelial permeability to the entire compound, resulting in instant increases in blood flow and vascular diameters. In contrast, the equimolar Cap does not have the instant vascular effects. PMID:11739246

In vitro and in vivo assessment of cellular permeability and pharmacodynamics of S-nitrosylated captopril, a nitric oxide donor.

PubMed

Jia, L; Wong, H

2001-12-01

1. The present studies were aimed at testing the hypothesis that S-nitrosylated captopril (CapNO), a novel crystalline nitric oxide (NO) donor, readily permeates both in vitro and in vivo endothelial monolayers, resulting in its pharmacodynamic effects. 2. CapNO and Captopril (Cap) were added to apical side of endothelial monolayers formed on microporous membranes, and the permeated drugs were collected from basolateral side and detected by a HPLC method. The permeability coefficient (P(app); cm sec(-1)) of CapNO across the endothelial monolayers was 6.0 x 10(-5), higher than that of Cap (3.13 x 10(-5)), indicating the enhancement effect of the attached NO group in CapNO on cellular permeability. The P(app) of CapNO and Cap across Caco-2 cells were 3.15 x 10(-5) and 1.53 x 10(-5), respectively. The low P(app) of CapNO to Caco-2 cells may be attributed to the high membrane resistance of Caco-2 cells. 3. A bolus injection of CapNO to epicardial coronary artery of chronically-instrumented awake dogs caused significant increases in coronary blood flow and coronary diameters dose-dependently without significant changes in aortic pressure. In contrast, the equimolar doses of Cap did not produce haemodynamic responses. 4. Intravenous CapNO caused an instant increase in the regional cerebral blood flow determined by H(2)-clearance, whereas the equimolar doses of Cap did not enhance the cerebral blood flow. 5. These results conclude that the NO group, an active component of CapNO, enhances both in vitro and in vivo endothelial permeability to the entire compound, resulting in instant increases in blood flow and vascular diameters. In contrast, the equimolar Cap does not have the instant vascular effects.

Long-interval Cytapheresis as a Novel Therapeutic Strategy Leading to Dosage Reduction and Discontinuation of Steroids in Steroid-dependent Ulcerative Colitis

PubMed Central

Iizuka, Masahiro; Etou, Takeshi; Kumagai, Makoto; Matsuoka, Atsushi; Numata, Yuka; Sagara, Shiho

2017-01-01

Objective This study was performed to confirm the efficacy of long-interval cytapheresis on steroid-dependent ulcerative colitis (UC). Methods To discontinue steroids in patients with steroid-dependent UC, we previously designed a novel regimen of cytapheresis (CAP), which we termed “long-interval cytapheresis (LI-CAP)”, in which CAP was performed as one session every two or three weeks and continued during the whole period of tapering steroid dosage. In this study, we performed LI-CAP therapy 20 times (11 male and 9 female; mean age 41.8 years) between April 2010 and April 2015 for 14 patients with steroid-dependent UC. We evaluated the effectiveness of LI-CAP by examining the improvement in Lichtiger's clinical activity index (CAI), the rate of clinical remission, and the rate of steroid discontinuation. We further examined the rate of sustained steroid-free clinical remission at 6 and 12 months after LI-CAP in patients who successfully discontinued steroid-use after LI-CAP. The primary endpoint was the rate of discontinuation of steroids after LI-CAP. Results The mean CAI score before LI-CAP (7.550) significantly decreased to 1.65 after LI-CAP (p<0.0001). The rate of clinical remission after LI-CAP was 80%. The rate of steroid discontinuation after LI-CAP was 60.0%. The mean dose of daily prednisolone was significantly decreased after LI-CAP (2.30 mg) compared with that before therapy (17.30 mg) (p=0.0003). The rate of sustained steroid-free clinical remission after LI-CAP was 66.7% at 6 months and 66.7% at 12 months. Conclusion We confirmed that LI-CAP has therapeutic effects on reducing the dosage and discontinuing steroids in patients with steroid-dependent UC. PMID:28924114

Long-interval Cytapheresis as a Novel Therapeutic Strategy Leading to Dosage Reduction and Discontinuation of Steroids in Steroid-dependent Ulcerative Colitis.

PubMed

Iizuka, Masahiro; Etou, Takeshi; Kumagai, Makoto; Matsuoka, Atsushi; Numata, Yuka; Sagara, Shiho

2017-10-15

Objective This study was performed to confirm the efficacy of long-interval cytapheresis on steroid-dependent ulcerative colitis (UC). Methods To discontinue steroids in patients with steroid-dependent UC, we previously designed a novel regimen of cytapheresis (CAP), which we termed "long-interval cytapheresis (LI-CAP)", in which CAP was performed as one session every two or three weeks and continued during the whole period of tapering steroid dosage. In this study, we performed LI-CAP therapy 20 times (11 male and 9 female; mean age 41.8 years) between April 2010 and April 2015 for 14 patients with steroid-dependent UC. We evaluated the effectiveness of LI-CAP by examining the improvement in Lichtiger's clinical activity index (CAI), the rate of clinical remission, and the rate of steroid discontinuation. We further examined the rate of sustained steroid-free clinical remission at 6 and 12 months after LI-CAP in patients who successfully discontinued steroid-use after LI-CAP. The primary endpoint was the rate of discontinuation of steroids after LI-CAP. Results The mean CAI score before LI-CAP (7.550) significantly decreased to 1.65 after LI-CAP (p<0.0001). The rate of clinical remission after LI-CAP was 80%. The rate of steroid discontinuation after LI-CAP was 60.0%. The mean dose of daily prednisolone was significantly decreased after LI-CAP (2.30 mg) compared with that before therapy (17.30 mg) (p=0.0003). The rate of sustained steroid-free clinical remission after LI-CAP was 66.7% at 6 months and 66.7% at 12 months. Conclusion We confirmed that LI-CAP has therapeutic effects on reducing the dosage and discontinuing steroids in patients with steroid-dependent UC.

The cervical cap.

PubMed

1988-10-07

The US Food and Drug Administration has approved marketing of the Prentif cavity-rim cervical cap. This contraceptive device is being distributed in the US and Canada by Cervical Cap Ltd, Los Gatos, California. The Prentif cap is available in 4 sizes: 22, 25, 28, and 31 mm inside diameter, with a length of 1 1/4-1 1/2 inches. In a multicenter trial involving 522 diaphragm users and 581 cap users followed for 2 years, the cap was 82.6% effective and the diaphragm was 83.3% effective in preventing pregnancy. When pregnancies attributable to user failure were excluded, these rates were increased to 93.6% for the cap and 95.4% for the diaphragm. 4% of cap users compared with only 1.7% of diaphragm users in this study developed abnormal Pap smears after 3 months of use; in addition, a higher proportion of cap users became infected with Gardnerella vaginalis and Monilia. Theoretical hazards include toxic shock syndrome and endometriosis due to backflow of menstrual fluids. Cap users are advised to undergo a Pap test after 3 months of use and discontinue cap use if the results are abnormal. The cap should not be used during menstruation. Although the cap can be left in place for up to 48 hours, its position should be checked before and after each episode of intercourse. The cervical cap requires less spermicide than the diaphragm and is not as messy. In addition, it can be left in the vagina twice as long as the diaphragm, without additional spermicide. Since the cap is smaller than the diaphragm and does not cover the vaginal wall, some women find intercourse more pleasurable with this device.

PCT theorem for fields with arbitrary high-energy behavior

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

Luecke, W.

1986-07-01

A neutral scalar field A(x) is considered that has to be smeared by Fourier transforms of C/sup infinity/ functions with compact support but otherwise fulfills all the Wightman axioms, except strict local commutativity. It is shown to fulfill the PCT symmetry condition (where ..cap omega.. denotes the vacuum state vector) <..cap omega..Vertical BarA(x/sub 1/) xxx A(x/sub n/)..cap omega..> = <..cap omega..Vertical BarA(-x/sub n/) xxx A(-x/sub 1/)..cap omega..> if and only if <..cap omega..Vertical BarA(x/sub 1/) xxx A(x/sub n/)..cap omega..> -<..cap omega..Vertical BarA(x/sub n/) xxx A(x/sub 1/)..cap omega..> can be represented, in a sense, as an infinite sum of derivatives ofmore » measures with supports containing no Jost points.« less

The rebirth of the cervical cap.

PubMed

Cappiello, J D; Grainger-Harrison, M

1981-01-01

In an effort to dispel myths surrounding the cervical cap, the historical and political factors affecting the cap's use in the U.S. are described. Clinical aspects of cap fitting are also included. The cervical cap has found only limited acceptance in the U.S. Skepticisms on the part of physicians may be the result of 2 factors: confusion of the cervical cap with intracervical devices used for artificial insemination and confusion with stem pessaries; and the lack of clinical research and statistical evaluation of efficacy rates. The latter factor prompted Tietze et al. to conduct the only U.S. statistical study of the cap in 1953. Of the 143 women studied, the pregnancy rate was 7.6/100 years of use. Of the 28 unplanned pregnancies, 6 were related to faulty technique or omission of a spermicide and 10 were instances of admittedly irregular use. When these failures are omitted, the theoretical effectiveness rate is about 98%. Some practitioners are concerned about an increased incidence of cervical erosion with cap use. Possibly currently conducted studies will show that cap and spermicide users have a lower incidence of cervical erosion than women using no contraceptive method. Study findings suggest that the cervical cap may afford protection without any spermicidal supplement, but the use of spermicides continues to be recommended to clients. Advantages of the cervical cap include the following: it can be left in place longer than a diaphragm without additional applications of spermicide in the vagina; and the insertion of the cap is unrelated to the time of intercourse. Despite research on toleration of the cap for 3 weeks at a time, it is recommended that the cap be worn for only a few days at a time. At this time there are no manufacturers of cervical caps for contraceptive use in the U.S. The cap is now being imported from England and it costs $6.00. A factor that has made the cap unpopular with many physicians is the lengthy time required for fitting. An assessment guide that physicians can use to incorporate cervical caps in their practice is included. The guide covers medical/gynecological history; informed consent; pelvic examinations; assessment; fitting the cap; and instructing the client. Instructions for client use are also outlined.

Steady-state EB cap size fluctuations are determined by stochastic microtubule growth and maturation

PubMed Central

Rickman, Jamie; Duellberg, Christian; Cade, Nicholas I.; Griffin, Lewis D.; Surrey, Thomas

2017-01-01

Growing microtubules are protected from depolymerization by the presence of a GTP or GDP/Pi cap. End-binding proteins of the EB1 family bind to the stabilizing cap, allowing monitoring of its size in real time. The cap size has been shown to correlate with instantaneous microtubule stability. Here we have quantitatively characterized the properties of cap size fluctuations during steady-state growth and have developed a theory predicting their timescale and amplitude from the kinetics of microtubule growth and cap maturation. In contrast to growth speed fluctuations, cap size fluctuations show a characteristic timescale, which is defined by the lifetime of the cap sites. Growth fluctuations affect the amplitude of cap size fluctuations; however, cap size does not affect growth speed, indicating that microtubules are far from instability during most of their time of growth. Our theory provides the basis for a quantitative understanding of microtubule stability fluctuations during steady-state growth. PMID:28280102

[Clinical evaluation of bedridden patients with pneumonia receiving home health care].

PubMed

Fukuyama, Hajime; Ishida, Tadashi; Tachibana, Hiromasa; Iga, Chiya; Nakagawa, Hiroaki; Ito, Akihiro; Ubukata, Satoshi; Yoshioka, Hiroshige; Arita, Machiko; Hashimoto, Toru

2010-12-01

Pneumonia which develops in patients while living in their own home is categorized as community-acquired pneumonia (CAP), even if these patients are bedridden and receiving home health care. However, because of the differences in patient backgrounds, we speculated that the clinical outcomes and pathogens of bedridden patients with pneumonia who are receiving home health care would be different from those of CAP. We conducted a prospective study of patients with CAP who were hospitalized at our hospital from April 2007 through September 2009. We compared home health care bedridden pneumonia (performance status 4, PS4-CAP) with non-PS4-CAP in a total of 505 enrolled patients in this study. Among these, 66 had PS4-CAP, mostly associated with aspiration. Severity scores, mortality rate, recurrence rate and length of hospital stay of those with PS4-CAP were significantly higher than those with non-PS4-CAP. Drug resistant pathogens were more frequently isolated from patients with PS4-CAP than from those of non-PS4-CAP. The results of patients with PS4-CAP were in agreement with those of previous health care-associated pneumonia (HCAP) reports. The present study suggested home health care bedridden pneumonia should be categorized as HCAP, not CAP.

Experimental landfill caps for semi-arid and arid climates.

PubMed

Blight, Geoffrey E; Fourie, Andries B

2005-04-01

The United States EPA Subtitle D municipal solid waste landfill requirements specify that the permeability of a cap to a landfill be no greater than the permeability of the underliner. In recent years the concept of the evapotranspirative (ET) cap has been developed in which the cap is designed to store all rain infiltration and re-evapotranspire it during dry weather. Concern at the long period required for landfilled municipal solid waste to decompose and stabilize in arid and semi-arid climates has led to an extension of the concept of the ET cap. With the infiltrate-stabilize-evapotranspire (ISE) cap, rain infiltration during wet weather is permitted to enter the underlying waste, thus accelerating the decomposition and stabilization process. Excess infiltration is then removed from both waste and cap by evaporation during dry weather. The paper describes the construction and operation of two sets of experimental ISE caps, one in a winter rainfall semi-arid climate, and the other in a summer rainfall semi-arid climate. Observation of the rainfall, soil evaporation and amount of water stored in the caps has allowed water balances to be constructed for caps of various thicknesses. These observations show that the ISE concept is viable. In the limit, when there is insufficient rainfall to infiltrate the waste, an ISE cap operates as an ET cap.

Interferon-alpha in chronic myeloid leukemia revisited: a long-term retrospective study in Central and Northern Moravia.

PubMed

Faber, Edgar; Kuba, Adam; Zapletalova, Jana; Divoka, Martina; Rohon, Peter; Holzerova, Milena; Jarosova, Marie; Indrak, Karel

2013-09-01

We assessed the long-term outcome of consecutive patients in the chronic phase of chronic myeloid leukemia (CML) treated with interferon-alpha (INF-α) in Central and Northern Moravia between 1989 and 2006. A retrospective study focused on the response, prognostic factors and side-effects of INF-α. 118 patients (67 males and 51 females, median age 50 years; range 18-71) were analyzed. The median follow-up was 82.6 months (12.4-212.6). Thirty-six patients (30.5%) achieved major cytogenetic response (CyR) in median of 18.3 months (3.7-47.3) and maintained it for a median of 64.0 months (7.0-176.0). Sixty-one patients treated with INF-α for more than 12 months had an overall survival (OS) of 137.0 months (95% CI 117.6-156.4). Eighteen (29.5%) achieved complete CyR (CCyR). 109 patients discontinued the treatment with INF-α because of hematologic or cytogenetic resistance in 53 (48.7%), progression of CML in 31 (28.4%) and intolerance to INF-α in 17 (15.6%) patients. The percentage of peripheral blasts, leukocyte count (>50x10(9)/L), splenomegaly, anemia (Hgb≤110 g/L) and Sokal score had statistical impact on the OS in univariate assessment but only the Sokal score remained significant in multivariate analysis. Additional cytogenetic abnormalities at diagnosis were associated with poor prognosis. In most patients, treatment with INF-α had to be stopped because of a failure to induce response, progression of CML or side-effects but nearly one third of patients treated at least for one year had a long-term benefit from INF-α. The best prognosis was associated with achievement of CCyR and negativity of BCR-ABL in nested RT-PCR.

30 CFR 250.1608 - Well casing and cementing.

Code of Federal Regulations, 2012 CFR

2012-07-01

... rock casing, (iv) Bobtail cap rock casing (required when the cap rock casing does not penetrate into the cap rock), (v) Second cap rock casing (brine wells), and (vi) Production liner. (2) The lessee... lessee shall initiate remedial action as approved by the District Manager. For cap rock casing, the test...

30 CFR 250.1608 - Well casing and cementing.

Code of Federal Regulations, 2013 CFR

2013-07-01

... rock casing, (iv) Bobtail cap rock casing (required when the cap rock casing does not penetrate into the cap rock), (v) Second cap rock casing (brine wells), and (vi) Production liner. (2) The lessee... lessee shall initiate remedial action as approved by the District Manager. For cap rock casing, the test...

30 CFR 250.1608 - Well casing and cementing.

Code of Federal Regulations, 2014 CFR

2014-07-01

... rock casing, (iv) Bobtail cap rock casing (required when the cap rock casing does not penetrate into the cap rock), (v) Second cap rock casing (brine wells), and (vi) Production liner. (2) The lessee... lessee shall initiate remedial action as approved by the District Manager. For cap rock casing, the test...

47 CFR 61.43 - Annual price cap filings required.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Annual price cap filings required. 61.43... (CONTINUED) TARIFFS General Rules for Dominant Carriers § 61.43 Annual price cap filings required. Carriers subject to price cap regulation shall submit annual price cap tariff filings that propose rates for the...

29 CFR 1926.914 - Definitions applicable to this subpart.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., including but not limited to trucks, trailers, rail cars, barges, and vessels. (i) Detonating cord—A... caps, electric blasting caps, delay electric blasting caps, and nonelectric delay blasting caps. (k) Electric blasting cap—A blasting cap designed for and capable of detonation by means of an electric current...

77 FR 31899 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing of Proposed Rule Change Relating...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-30

... Trading of iShares Strategic Beta U.S. Large Cap Fund and iShares Strategic Beta U.S. Small Cap Fund Under... Fund Shares''): iShares Strategic Beta U.S. Large Cap Fund and iShares Strategic Beta U.S. Small Cap...: \\3\\ iShares Strategic Beta U.S. Large Cap Fund and iShares Strategic Beta U.S. Small Cap Fund (each...

RNA Cap Methyltransferase Activity Assay

PubMed Central

Trotman, Jackson B.; Schoenberg, Daniel R.

2018-01-01

Methyltransferases that methylate the guanine-N7 position of the mRNA 5′ cap structure are ubiquitous among eukaryotes and commonly encoded by viruses. Here we provide a detailed protocol for the biochemical analysis of RNA cap methyltransferase activity of biological samples. This assay involves incubation of cap-methyltransferase-containing samples with a [32P]G-capped RNA substrate and S-adenosylmethionine (SAM) to produce RNAs with N7-methylated caps. The extent of cap methylation is then determined by P1 nuclease digestion, thin-layer chromatography (TLC), and phosphorimaging. The protocol described here includes additional steps for generating the [32P]G-capped RNA substrate and for preparing nuclear and cytoplasmic extracts from mammalian cells. This assay is also applicable to analyzing the cap methyltransferase activity of other biological samples, including recombinant protein preparations and fractions from analytical separations and immunoprecipitation/pulldown experiments. PMID:29644259

The antioxidative and hepatoprotective effects comparison of Chinese angelica polysaccharide(CAP)and selenizing CAP (sCAP) in CCl4 induced hepatic injury mice.

PubMed

Gao, Zhenzhen; Zhang, Chao; Tian, Weijun; Liu, Kuanhui; Hou, Ranran; Yue, Chanjuan; Wu, Yi; Wang, Deyun; Liu, Jiaguo; Hu, Yuanliang; Yang, Ying

2017-04-01

Chinese angelica polysaccharides (CAP) and selenizing CAP (sCAP) were prepared and identified through FTIR and SEM observation. Their antioxidant activities in vitro and hepatoprotective effects in vivo were compared by free radical-scavenging tests or with CCl 4 -induced hepatic injury model mice. The results showed that for DPPH radical, superoxide anion and hydroxyl radical, the scavenging capabilities of sCAP were significantly stronger than those of CAP . In hepatic injury model mice, sCAP could significantly reduce ALT, AST and ALP contents and raised TP content in serum, significantly reduce MDA and ROS contents and raised SOD and T-AOC activities in liver homogenate in comparison with CAP; obviously relieve the pathological changes of liver and significantly inhibit the expressions of p-ERK, p-JNK and p-p38 protein as compared with those in model control group. These results indicate that selenylation modification can enhance the antioxidant and hepatoprotective actions of Chinese angelica polysaccharide. A action mechanism of sCAP is suppressing the protein expression of MAPK signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Fluorescence microscopic analysis of antifungal effects of cold atmospheric pressure plasma in Saccharomyces cerevisiae.

PubMed

Itooka, Koki; Takahashi, Kazuo; Izawa, Shingo

2016-11-01

Cold atmospheric pressure plasma (CAP) has potential to be utilized as an alternative method for sterilization in food industries without thermal damage or toxic residues. In contrast to the bactericidal effects of CAP, information regarding the efficacy of CAP against eukaryotic microorganisms is very limited. Therefore, herein we investigated the effects of CAP on the budding yeast Saccharomyces cerevisiae, with a focus on the cellular response to CAP. The CAP treatment caused oxidative stress responses including the nuclear accumulation of the oxidative stress responsive transcription factor Yap1, mitochondrial fragmentation, and enhanced intracellular oxidation. Yeast cells also induced the expression of heat shock protein (HSP) genes and formation of Hsp104 aggregates when treated with CAP, suggesting that CAP denatures proteins. As phenomena unique to eukaryotic cells, the formation of cytoplasmic mRNP granules such as processing bodies and stress granules and changes in the intracellular localization of Ire1 were caused by the treatment with CAP, indicating that translational repression and endoplasmic reticulum (ER) stress were induced by the CAP treatment. These results suggest that the fungicidal effects of CAP are attributed to the multiple severe stresses.

Medicaid prescription limits: policy trends and comparative impact on utilization.

PubMed

Lieberman, Daniel A; Polinski, Jennifer M; Choudhry, Niteesh K; Avorn, Jerry; Fischer, Michael A

2016-01-15

Medicaid programs face growing pressure to control spending. Despite evidence of clinical harms, states continue to impose policies limiting the number of reimbursable prescriptions (caps). We examined the recent use of prescription caps by Medicaid programs and the impact of policy implementation on prescription utilization. We identified Medicaid cap policies from 2001-2010. We classified caps as applying to all prescriptions (overall caps) or only branded prescriptions (brand caps). Using state-level, aggregate prescription data, we developed interrupted time-series analyses to evaluate the impact of implementing overall caps and brand caps in a subset of states with data available before and after cap initiation. For overall caps, we examined the use of essential medications, which were classified as preventive or as providing symptomatic benefit. For brand caps, we examined the use of all branded drugs as well as branded and generic medications among classes with available generic replacements. The number of states with caps increased from 12 in 2001 to 20 in 2010. Overall cap implementation (n = 3) led to a 0.52% (p < 0.001) annual decrease in the proportion of essential prescriptions but no change in cost. For preventive essential medications, overall caps led to a 1.12% (p = 0.001) annual decrease in prescriptions (246,000 prescriptions annually) and a 1.20% (p < 0.001) decrease in spending (-$12.2 million annually), but no decrease in symptomatic essential medication use. Brand cap implementation (n = 6) led to an immediate 2.29% (p = 0.16) decrease in branded prescriptions and 1.26% (p = 0.025) decrease in spending. For medication classes with generic replacements, the decrease in branded prescriptions (0.74%, p = 0.003) approximately equaled the increase in generics (0.79%, p = 0.009), with estimated savings of $17.4 million. An increasing number of states are using prescription caps, with mixed results. Overall caps decreased the use of preventive but not symptomatic essential medications, suggesting that patients assign higher priority to agents providing symptomatic benefit when faced with reimbursement limits. Among medications with generic replacements, brand caps shifted usage from branded drugs to generics, with considerable savings. Future research should analyze the patient-level impact of these policies to measure clinical outcomes associated with these changes.

Real-life effectiveness of canakinumab in cryopyrin-associated periodic syndrome.

PubMed

Kuemmerle-Deschner, Jasmin B; Hofer, Ferdinand; Endres, Theresa; Kortus-Goetze, Birgit; Blank, Norbert; Weißbarth-Riedel, Elisabeth; Schuetz, Catharina; Kallinich, Tilmann; Krause, Karoline; Rietschel, Christoph; Horneff, Gerd; Benseler, Susanne M

2016-04-01

Cryopyrin-associated periodic syndrome (CAPS) is a heterogeneous group of diseases characterized by excessive IL-1β release resulting in severe systemic and organ inflammation. Canakinumab targets IL-1β and is approved at standard dose for children and adults with all CAPS phenotypes. Limited data are available for the real-life effectiveness of canakinumab in patients living with CAPS. Therefore the aim of the study was to evaluate the real-life dosing and effectiveness of canakinumab in CAPS. A multi-centre study of consecutive children and adults with CAPS treated with canakinumab was performed. Demographics, CAPS phenotype and disease activity, inflammatory markers and canakinumab treatment strategy were recorded. Treatment response was assessed using CAPS disease activity scores, CRP and/or serum amyloid A levels. Comparisons between age groups, CAPS phenotypes and centres were conducted. A total of 68 CAPS patients at nine centres were included. All CAPS phenotypes were represented. Thirty-seven (54%) patients were females, the median age was 25 years and 27 (40%) were children, and the median follow-up was 28 months. Overall, complete response (CR) was seen in 72% of CAPS patients, significantly less often in severe (14%) than in mild CAPS phenotypes (79%). Only 53% attained CR on standard dose canakinumab. Dose increase was more commonly required in children (56%) than in adults (22%). Centres with a treat-to-target approach had significantly higher CR rates (94 vs 50%). Real-life effectiveness of canakinumab in CAPS was significantly lower than in controlled trials. Treat-to-target strategies may improve the outcome of children and adults living with CAPS. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Increased Severity and Mortality of CAP in COPD: Results from the German Competence Network, CAPNETZ

PubMed Central

Braeken, Dionne C.W.; Franssen, Frits M.E.; Schütte, Hartwig; Pletz, Mathias W.; Bals, Robert; Martus, Peter; Rohde, Gernot G.U.

2015-01-01

Background:Mortality of community acquired pneumonia (CAP) remains high despite significant research efforts. Knowledge about comorbidities including chronic obstructive pulmonary disease (COPD) might help to improve management and ultimately, survival. The impact of COPD on CAP severity and mortality remains a point of discussion. Objectives:Assess the prevalence and clinical characteristics of COPD in the observational German Competence Network for CAP, CAPNETZ, and to study the impact of COPD on CAP severity and mortality. Methods:1307 consecutive patients with CAP (57.0% males, age 59.0±18.5), classified as CAP-only (n=1043; 78.0%) and CAP-COPD (n=264; 20.2%) were followed up for 180 days. Associations between CAP, COPD and mortality were evaluated by univariate/multivariate and Kaplan-Meier survival analyses. Results:CAP-COPD patients were older, more often males, current/former smokers, with higher confusion-urea-respiratory rate-blood pressure, (CURB) scores. Length of hospital stay, urea, glucose and leucocytes plasma levels, and arterial carbon dioxide tension (PaCO2) were significantly increased in CAP-COPD. Thirty, 90- and 180-day mortality rates were significantly increased in CAP-COPD (p=0.046, odds ratio [OR]=2.48, 95% confidence interval [CI] 1.015-6.037; p=0.003, OR=2.80, 95%CI 1.430-5.468; p=0.001, OR=2.57, 95%CI 1.462-4.498; respectively). Intensive care unit (ICU)-admission and age, but not COPD, were identified as independent predictors of short- and long-term mortality. Conclusion:Severity as well as mortality was significantly higher in COPD patients with CAP. To improve CAP management with the aim to decrease its still-too-high mortality, underlying comorbidities, particularly COPD, need to be assessed. PMID:28848837

Capped RNA primer binding to influenza polymerase and implications for the mechanism of cap-binding inhibitors

PubMed Central

Pflug, Alexander; Gaudon, Stephanie; Resa-Infante, Patricia; Lethier, Mathilde; Reich, Stefan; Schulze, Wiebke M

2018-01-01

Abstract Influenza polymerase uses short capped primers snatched from nascent Pol II transcripts to initiate transcription of viral mRNAs. Here we describe crystal structures of influenza A and B polymerase bound to a capped primer in a configuration consistent with transcription initiation (’priming state’) and show by functional assays that conserved residues from both the PB2 midlink and cap-binding domains are important for positioning the capped RNA. In particular, mutation of PB2 Arg264, which interacts with the triphosphate linkage in the cap, significantly and specifically decreases cap-dependent transcription. We also compare the configuration of the midlink and cap-binding domains in the priming state with their very different relative arrangement (called the ‘apo’ state) in structures where the potent cap-binding inhibitor VX-787, or a close analogue, is bound. In the ‘apo’ state the inhibitor makes additional interactions to the midlink domain that increases its affinity beyond that to the cap-binding domain alone. The comparison suggests that the mechanism of resistance of certain mutations that allow virus to escape from VX-787, notably PB2 N510T, can only be rationalized if VX-787 has a dual mode of action, direct inhibition of capped RNA binding as well as stabilization of the transcriptionally inactive ‘apo’ state. PMID:29202182

Overexpression of adenylate cyclase-associated protein 2 is a novel prognostic marker in malignant melanoma.

PubMed

Masugi, Yohei; Tanese, Keiji; Emoto, Katsura; Yamazaki, Ken; Effendi, Kathryn; Funakoshi, Takeru; Mori, Mariko; Sakamoto, Michiie

2015-12-01

Malignant melanoma is one of the lethal malignant tumors worldwide. Previously we reported that adenylate cyclase-associated protein 2 (CAP2), which is a well-conserved actin regulator, was overexpressed in hepatocellular carcinoma; however, CAP2 expression in other clinical cancers remains unclear. The aim of the current study was to clarify the clinicopathological significance of CAP2 overexpression in malignant melanoma. Immunohistochemical analyses revealed that many melanoma cells exhibited diffuse cytoplasmic expression of CAP2, whereas no normal melanocytes showed detectable immunostaining for CAP2. A high level of CAP2 expression was seen in 14 of 50 melanomas and was significantly correlated with greater tumor thickness and nodular melanoma subtypes. In addition, a high level of CAP2 expression was associated with poor overall survival in univariate and multivariate analyses. For 13 patients, samples of primary and metastatic melanoma tissue were available: four patients exhibited higher levels of CAP2 expression in metastatic tumor compared to the primary site, whereas no patient showed lower levels of CAP2 expression in metastatic melanomas. Our findings show that CAP2 overexpression is a novel prognostic marker in malignant melanoma and that CAP2 expression seems to increase stepwise during tumor progression, suggesting the involvement of CAP2 in the aggressive behavior of malignant melanoma. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

The differential impact of clerk interest and participation in a child and adolescent psychiatry clerkship rotation upon psychiatry and pediatrics residency matches.

PubMed

Hanson, Mark D; Szatmari, Peter; Eva, Kevin W

2011-01-01

The authors evaluated the differential impact of clerk interest and participation in a Child and Adolescent Psychiatry (CAP) clerkship rotation upon psychiatry and pediatrics residency matches. Authors studied clerks from the McMaster University M.D. program graduating years of 2005-2007. Participants were categorized as 1) clerks with CAP clerkship interest and CAP clerkship participation; 2) clerks with CAP clerkship interest but without CAP clerkship participation; and 3) clerks with neither CAP clerkship interest nor CAP clerkship participation. The outcome variable was residency matches, with Psychiatry and Pediatrics residency matches highlighted. Descriptive statistics were used, and chi-squared tests performed to compare proportions of residency matches across these three clerkship groups. Residency matches of 390 clerks were reviewed. CAP clerkship interest was expressed by 23.9% of clerks. Comparison across the two CAP clerkship interest groups revealed match rates to Psychiatry and Pediatrics not to be significantly different, although the proportion of each match was significantly different from the third clerkship group (without CAP clerkship interest) in both instances. CAP clerkship interest, but not participation, was associated with Psychiatry and Pediatrics residency matches. CAP clerkship interest among clerks presents recruitment and educational opportunities; a recruitment opportunity for clerks heading toward a Psychiatry residency, and an educational opportunity for clerks heading toward a Pediatrics residency.

22 CFR 121.11 - Military demolition blocks and blasting caps.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Military demolition blocks and blasting caps... blasting caps. Military demolition blocks and blasting caps referred to in Category IV(a) do not include the following articles: (a) Electric squibs. (b) No. 6 and No. 8 blasting caps, including electric...

49 CFR 230.41 - Flexible staybolts with caps.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Flexible staybolts with caps. 230.41 Section 230... Appurtenances Staybolts § 230.41 Flexible staybolts with caps. (a) General. Flexible staybolts with caps shall have their caps removed during every 5th annual inspection for the purpose of inspecting the bolts for...

CAPS drives trans-SNARE complex formation and membrane fusion through syntaxin interactions.

PubMed

James, Declan J; Kowalchyk, Judith; Daily, Neil; Petrie, Matt; Martin, Thomas F J

2009-10-13

Ca(2+)-dependent activator protein for secretion (CAPS) is an essential factor for regulated vesicle exocytosis that functions in priming reactions before Ca(2+)-triggered fusion of vesicles with the plasma membrane. However, the precise events that CAPS regulates to promote vesicle fusion are unclear. In the current work, we reconstituted CAPS function in a SNARE-dependent liposome fusion assay using VAMP2-containing donor and syntaxin-1/SNAP-25-containing acceptor liposomes. The CAPS stimulation of fusion required PI(4,5)P(2) in acceptor liposomes and was independent of Ca(2+), but Ca(2+) dependence was restored by inclusion of synaptotagmin. CAPS stimulated trans-SNARE complex formation concomitant with the stimulation of full membrane fusion at physiological SNARE densities. CAPS bound syntaxin-1, and CAPS truncations that competitively inhibited syntaxin-1 binding also inhibited CAPS-dependent fusion. The results revealed an unexpected activity of a priming protein to accelerate fusion by efficiently promoting trans-SNARE complex formation. CAPS may function in priming by organizing SNARE complexes on the plasma membrane.

Historical photometric evidence for volatile migration on Triton

NASA Technical Reports Server (NTRS)

Buratti, Bonnie J.; Goguen, Jay D.; Gibson, James; Mosher, Joel

1994-01-01

Analysis of CCD images of Triton obtained with the 1.5-m telescope on Palomar Mountain shows that in the time period surrounding the Voyager 2 encounter with the satellite (1985-1990), no changes in the satellite's visual albedo or color occurred. The published observations of Triton in the 0.35- to 0.60-micrometer spectral region obtained between 1950 and 1990 were reanalyzed to detect historical variability in both its albedo and visual color. Analysis of the photometry indicates that there is little, if any, change in Triton's visual geometric albedo. This result is consistent with the albedo pattern observed by Voyager and the change in sub-Earth latitude. Two distinct types of color changes are evident: a significant secular increase in the blue region of the visual spectrum since at least the 1950s, and the reported dramatic reddening of Triton's spectrum in the late 1970s. The latter change can be explained only by a short-lived geological phenomenon. Triton's changing pole orientation with respect to a terrestrial observer cannot explain the secular color changes. These changes imply volatile transport on a global scale on Triton's surface during the past 4 decades. We present two models which show that either removal of a red volatile from Triton's polar cap or deposition of a blue volatile in the equatorial regions can explain the secular color changes. A third possibility is that the changes are the result of the alpha-beta phase transition of nitrogen and subsequent fracturing of the polar cap region (N. S. Duxbury and R. H. Brown (1993).

An analytical method for computing atomic contact areas in biomolecules.

PubMed

Mach, Paul; Koehl, Patrice

2013-01-15

We propose a new analytical method for detecting and computing contacts between atoms in biomolecules. It is based on the alpha shape theory and proceeds in three steps. First, we compute the weighted Delaunay triangulation of the union of spheres representing the molecule. In the second step, the Delaunay complex is filtered to derive the dual complex. Finally, contacts between spheres are collected. In this approach, two atoms i and j are defined to be in contact if their centers are connected by an edge in the dual complex. The contact areas between atom i and its neighbors are computed based on the caps formed by these neighbors on the surface of i; the total area of all these caps is partitioned according to their spherical Laguerre Voronoi diagram on the surface of i. This method is analytical and its implementation in a new program BallContact is fast and robust. We have used BallContact to study contacts in a database of 1551 high resolution protein structures. We show that with this new definition of atomic contacts, we generate realistic representations of the environments of atoms and residues within a protein. In particular, we establish the importance of nonpolar contact areas that complement the information represented by the accessible surface areas. This new method bears similarity to the tessellation methods used to quantify atomic volumes and contacts, with the advantage that it does not require the presence of explicit solvent molecules if the surface of the protein is to be considered. © 2012 Wiley Periodicals, Inc. Copyright © 2012 Wiley Periodicals, Inc.

High-Pressure NMR and SAXS Reveals How Capping Modulates Folding Cooperativity of the pp32 Leucine-rich Repeat Protein.

PubMed

Zhang, Yi; Berghaus, Melanie; Klein, Sean; Jenkins, Kelly; Zhang, Siwen; McCallum, Scott A; Morgan, Joel E; Winter, Roland; Barrick, Doug; Royer, Catherine A

2018-04-27

Many repeat proteins contain capping motifs, which serve to shield the hydrophobic core from solvent and maintain structural integrity. While the role of capping motifs in enhancing the stability and structural integrity of repeat proteins is well documented, their contribution to folding cooperativity is not. Here we examined the role of capping motifs in defining the folding cooperativity of the leucine-rich repeat protein, pp32, by monitoring the pressure- and urea-induced unfolding of an N-terminal capping motif (N-cap) deletion mutant, pp32-∆N-cap, and a C-terminal capping motif destabilization mutant pp32-Y131F/D146L, using residue-specific NMR and small-angle X-ray scattering. Destabilization of the C-terminal capping motif resulted in higher cooperativity for the unfolding transition compared to wild-type pp32, as these mutations render the stability of the C-terminus similar to that of the rest of the protein. In contrast, deletion of the N-cap led to strong deviation from two-state unfolding. In both urea- and pressure-induced unfolding, residues in repeats 1-3 of pp32-ΔN-cap lost their native structure first, while the C-terminal half was more stable. The residue-specific free energy changes in all regions of pp32-ΔN-cap were larger in urea compared to high pressure, indicating a less cooperative destabilization by pressure. Moreover, in contrast to complete structural disruption of pp32-ΔN-cap at high urea concentration, its pressure unfolded state remained compact. The contrasting effects of the capping motifs on folding cooperativity arise from the differential local stabilities of pp32, whereas the contrasting effects of pressure and urea on the pp32-ΔN-cap variant arise from their distinct mechanisms of action. Copyright © 2018 Elsevier Ltd. All rights reserved.

Prognostic nomogram for patients with hepatocellular carcinoma underwent adjuvant transarterial chemoembolization following curative resection

PubMed Central

Jing, Chu-Yu; Fu, Yi-Peng; Zheng, Su-Su; Yi, Yong; Shen, Hu-Jia; Huang, Jin-Long; Xu, Xin; Lin, Jia-Jia; Zhou, Jian; Fan, Jia; Ren, Zheng-Gang; Qiu, Shuang-Jian; Zhang, Bo-Heng

2017-01-01

Abstract Adjuvant transarterial chemoembolization (TACE) is a major option for postoperative hepatocellular carcinoma (HCC) patients with recurrence risk factors. However, individualized predictive models for subgroup of these patients are limited. This study aimed to develop a prognostic nomogram for patients with HCC underwent adjuvant TACE following curative resection. A cohort comprising 144 HCC patients who received adjuvant TACE following curative resection in the Zhongshan Hospital were analyzed. The nomogram was formulated based on independent prognostic indicators for overall survival (OS). The performance of the nomogram was evaluated by the concordance index (C-index), calibration curve, and decision curve analysis (DCA) and compared with the conventional staging systems. The results were validated in an independent cohort of 86 patients with the same inclusion criteria. Serum alpha-fetoprotein (AFP), hyper-sensitive C-reactive protein (hs-CRP), incomplete tumor encapsulation, and double positive staining of Cytokeratin 7 and Cytokeratin 19 on tumor cells were identified as independent predictors for OS. The C-indices of the nomogram for OS prediction in the training cohort and validation cohort were 0.787 (95%CI 0.775–0.799) and 0.714 (95%CI 0.695–0.733), respectively. In both the training and validation cohorts, the calibration plot showed good consistency between the nomogram-predicted and the observed survival. Furthermore, the established nomogram was superior to the conventional staging systems in terms of C-index and clinical net benefit on DCA. The proposed nomogram provided an accurate prediction on risk stratification for HCC patients underwent adjuvant TACE following curative resection. PMID:28296727

Prognostic value of combined preoperative fibrinogen and neutrophil–lymphocyte ratio in patients with hepatocellular carcinoma after liver transplantation

PubMed Central

Chen, Mao-Gen; Wang, Xiao-Ping; Ju, Wei-Qiang; Zhao, Qiang; Wu, Lin-Wei; Ren, Qing-Qi; Guo, Zhi-Yong; Wang, Dong-Ping; Zhu, Xiao-Feng; Ma, Yi; He, Xiao-Shun

2017-01-01

Objectives Elevated plasma fibrinogen (Fib) correlated with patient's prognosis in several solid tumors. However, few studies have illuminated the relationship between preoperative Fib and prognosis of HCC after liver transplantation. We aimed to clarify the prognostic value of Fib and whether the prognostic accuracy can be enhanced by the combination of Fib and neutrophil–lymphocyte ratio (NLR). Results Fib was correlated with Child-pugh stage, alpha-fetoprotein (AFP), size of largest tumor, macro- and micro-vascular invasion. Univariate analysis showed preoperative Fib, AFP, NLR, size of largest tumor, tumor number, macro- and micro- vascular invasion were significantly associated with disease-free survival (DFS) and overall survival (OS) in HCC patients with liver transplantation. After multivariate analysis, only Fib and macro-vascular invasion were independently correlated with DFS and OS. Survival analysis showed that preoperative Fib > 2.345 g/L predicted poor prognosis of patients HCC after liver transplantation. Preoperative Fib showed prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of Fib and NLR. Materials and Methods Data were collected retrospectively from 130 HCC patients who underwent liver transplantation. Preoperative Fib, NLR and clinicopathologic variables were analyzed. The survival analysis was performed by the Kaplan-Meier method, and compared by the log-rank test. Univariate and multivariate analyses were performed to identify the prognostic factors for DFS and OS. Conclusions Preoperative Fib is an independent effective predictor of prognosis for HCC patients, higher levels of Fib predict poorer outcomes and the combination of Fib and NLR enlarges the prognostic accuracy of testing. PMID:27935864

Translation and cross-cultural adaptation of the Clinical Competence Questionnaire for use in Brazil.

PubMed

Kwiatkoski, Danielle Ritter; Mantovani, Maria de Fátima; Pereira, Evani Marques; Bortolato-Major, Carina; Mattei, Ângela Taís; Peres, Aida Maris

2017-06-05

translating and transculturally adapting the Clinical Competence Questionnaire to Brazilian senior undergraduate Nursing students, as well as measuring psychometric properties of the questionnaire. a methodological study carried out in six steps: translation of the Clinical Competence Questionnaire instrument, consensus of the translations, back-translation, analysis by an expert committee, pre-testing and then presentation of the cross-cultural adaptation process to the developers. Psychometric properties were measured using Cronbach's alpha, intraclass correlation coefficient and content validity index. the instrument was translated, transculturally adapted and its final version consisted of 48 items. Cronbach's alpha coefficient was 0.90, and the agreement index of the items was 99% for students and 98% for evaluators. the Clinical Competence Questionnaire was translated and adapted to Brazilian students, and the psychometric properties of the Portuguese version of the questionnaire presented satisfactory internal consistency regarding the studied sample. traduzir e adaptar transculturalmente o Clinical Competence Questionnaire aos estudantes brasileiros concluintes da graduação em enfermagem, bem como mensurar as propriedades psicométricas do questionário. estudo metodológico realizado em seis etapas: tradução do instrumento Clinical Competence Questionnaire, consenso das traduções, retrotradução, análise pelo comitê de especialistas, pré-teste e apresentação do processo de adaptação transcultural para os desenvolvedores. As propriedades psicométricas foram mensuradas utilizando-se o alfa de Cronbach, coeficiente de correlação intraclasse e índice de validade de conteúdo. o instrumento foi traduzido, adaptado transculturalmente e sua versão final foi constituída de 48 itens. O coeficiente alfa de Cronbach foi de 0,90, e o índice de concordância dos itens foi de 99% para os estudantes e de 98% para os avaliadores. o Clinical Competence Questionnaire foi traduzido e adaptado a estudantes brasileiros, e as propriedades psicométricas da versão em português do questionário apresentaram consistência interna satisfatória quanto à amostra estudada. traducir y adaptar transculturalmente el Clinical Competence Questionnaire para uso de los estudiantes brasileños que concluyen la graduación en enfermería, así como para medir las propiedades psicométricas del cuestionario. estudio metodológico realizado en seis etapas: traducción del instrumento Clinical Competence Questionnaire, obtención de consenso de las traducciones, retrotraducción, análisis por el comité de especialistas, pretest y presentación del proceso de adaptación transcultural para los desarrolladores. Las propiedades psicométricas fueron medidas utilizando el alfa de Cronbach, coeficiente de correlación intraclase e índice de validez de contenido. el instrumento fue traducido, adaptado transculturalmente y su versión final estuvo constituida por 48 ítems. El coeficiente alfa de Cronbach fue de 0,90; el índice de concordancia de los ítems fue de 99% para los estudiantes y de 98% para los evaluadores. el Clinical Competence Questionnaire fue traducido y adaptado para uso de estudiantes brasileños; las propiedades psicométricas, de la versión en portugués del cuestionario, presentaron consistencia interna satisfactoria encontrada en la muestra estudiada.

On dual and three space problems for the compact approximation property

NASA Astrophysics Data System (ADS)

Choi, Changsun; Kim, Ju Myung

2006-11-01

We introduce the properties W*D and BW*D for the dual space of a Banach space. And then solve the dual problem for the compact approximation property (CAP): if X* has the CAP and the W*D, then X has the CAP. Also, we solve the three space problem for the CAP: for example, if M is a closed subspace of a Banach space such that M[perpendicular] is complemented in X* and X* has the W*D, then X has the CAP whenever X/M has the CAP and M has the bounded CAP. Corresponding problems for the bounded compact approximation property are also addressed.

Variability of child access prevention laws and pediatric firearm injuries.

PubMed

Hamilton, Emma C; Miller, Charles C; Cox, Charles S; Lally, Kevin P; Austin, Mary T

2018-04-01

State-level child access prevention (CAP) laws impose criminal liability on adults who negligently allow children access to firearms. The CAP laws can be further divided into strong CAP laws which impose criminal liability for negligently stored firearms and weak CAP laws that prohibit adults from intentionally, knowingly, and/or recklessly providing firearms to a minor. We hypothesized that strong CAP laws would be associated with a greater reduction in pediatric firearm injuries than weak CAP laws. We constructed a cross-sectional national study using the Healthcare Cost and Utilization Project-Kids Inpatient Database from 2006 and 2009 using weighted counts of firearm-related admissions among children younger than 18 years. Poisson regression was used to estimate the association of CAP laws with pediatric firearm injuries. After adjusting for race, sex, age, and socioeconomic income quartile, strong CAP laws were associated with a significant reduction in all (incidence rate ratio, 0.70; 95% confidence interval, 0.52-0.93), self-inflicted (incidence rate ratio, 0.46; 95% confidence interval, 0.26-0.79), and unintentional (incidence rate ratio, 0.56; 95% confidence interval, 0.43-0.74) pediatric firearm injuries. Weak CAP laws, which only impose liability for reckless endangerment, were associated with an increased risk of all pediatric firearm injuries. The association of CAP laws on hospitalizations for pediatric firearm injuries differed greatly depending on whether a state had adopted a strong CAP law or a weak CAP law. Implementation of strong CAP laws by each state, which require safe storage of firearms, has the potential to significantly reduce pediatric firearm injuries. Prognostic and epidemiology study, level III.

Notochord alters the permissiveness of myotome for pathfinding by an identified motoneuron in embryonic zebrafish.

PubMed

Beattie, C E; Eisen, J S

1997-02-01

During zebrafish development, identified motoneurons innervate cell-specific regions of each trunk myotome. One motoneuron, CaP, extends an axon along the medial surface of the ventral myotome. To learn how this pathway is established during development, the CaP axon was used as an assay to ask whether other regions of the myotome were permissive for normal CaP pathfinding. Native myotomes were replaced with donor myotomes in normal or reversed dorsoventral orientations and CaP pathfinding was assayed. Ventral myotomes were permissive for CaP axons, even when they were taken from older embryos, suggesting that the CaP pathway remained present on ventral myotome throughout development. Dorsal myotomes from young embryos were also permissive for CaP axons, however, older dorsal myotomes were non-permissive, showing that permissiveness of dorsal myotome for normal CaP pathfinding diminished over time. This process appears to depend on signals from the embryo, since dorsal myotomes matured in vitro remained permissive for CaP axons. Genetic mosaics between wild-type and floating head mutant embryos revealed notochord involvement in dorsal myotome change of permissiveness. Dorsal and ventral myotomes from both younger and older floating head mutant embryos were permissive for CaP axons. These data suggest that initially both dorsal and ventral myotomes are permissive for CaP axons but as development proceeds, there is a notochord-dependent decrease in permissiveness of dorsal myotome for CaP axonal outgrowth. This change participates in restricting the CaP pathway to the ventral myotome and thus to neuromuscular specificity.

Genetic ablation of root cap cells in Arabidopsis

NASA Technical Reports Server (NTRS)

Tsugeki, R.; Fedoroff, N. V.

1999-01-01

The root cap is increasingly appreciated as a complex and dynamic plant organ. Root caps sense and transmit environmental signals, synthesize and secrete small molecules and macromolecules, and in some species shed metabolically active cells. However, it is not known whether root caps are essential for normal shoot and root development. We report the identification of a root cap-specific promoter and describe its use to genetically ablate root caps by directing root cap-specific expression of a diphtheria toxin A-chain gene. Transgenic toxin-expressing plants are viable and have normal aerial parts but agravitropic roots, implying loss of root cap function. Several cell layers are missing from the transgenic root caps, and the remaining cells are abnormal. Although the radial organization of the roots is normal in toxin-expressing plants, the root tips have fewer cytoplasmically dense cells than do wild-type root tips, suggesting that root meristematic activity is lower in transgenic than in wild-type plants. The roots of transgenic plants have more lateral roots and these are, in turn, more highly branched than those of wild-type plants. Thus, root cap ablation alters root architecture both by inhibiting root meristematic activity and by stimulating lateral root initiation. These observations imply that the root caps contain essential components of the signaling system that determines root architecture.

Immunogenicity of adenovirus vaccines expressing the PCV2 capsid protein in pigs.

PubMed

Li, Delong; Du, Qian; Wu, Bin; Li, Juejun; Chang, Lingling; Zhao, Xiaomin; Huang, Yong; Tong, Dewen

2017-08-24

Porcine circovirus type 2 (PCV2) is the main pathogen of porcine circovirus associated disease (PCVAD), causing great economic losses in pig industry. In previous study, we constructed adenovirus vector vaccines expressing PCV2 Cap either modified with Intron A and WPRE, or CD40L and GMCSF, and evaluated all of these vaccines in mice and in pigs. Although Ad-A-C-W and Ad-CD40L-Cap-GMCSF could induce stronger immune responses than Ad-Cap, neither of them was better than commercial inactivated vaccine PCV2 SH-strain. In this study, secretory recombinant adenoviruses (Ad-A-spCap-W and Ad-A-spCD40L-spCap-spGMCSF-W) and non-secretory recombinant adenovirus Ad-A-CD40L-Cap-GMCSF-W were constructed, and identified by western blot and confocal laser microscope observation. The results of ELISA and VN showed that humoral immune responses induced by Ad-A-spCap-W and Ad-A-CD40L-Cap-GMCSF-W were not significantly different from SH-strain, but Ad-A-spCD40L-spCap-spGMCSF-W could induce significantly higher humoral immune response than SH-strain. Lymphocytes proliferative and cytokines releasing levels of Ad-A-spCap-W and Ad-A-CD40L-Cap-GMCSF-W were not significantly different from SH-strain, but Ad-A-spCD40L-spCap-spGMCSF-W was significantly higher than SH-strain. PCV2-challenge experiment showed that virus loads were significantly reduced in Ad-A-spCD40L-spCap-spGMCSF-W vaccinated group, and no obviously clinical and microscopic lesions were observed in Ad-A-spCD40L-spCap-spGMCSF-W vaccinated group. Altogether, these results demonstrate that recombinant adenovirus vaccine Ad-A-spCD40L-spCap-spGMCSF-W induces stronger immune responses and provides better protection than commercial inactivated vaccine PCV2 SH-strain, and suggest that Ad-A-spCD40L-spCap-spGMCSF-W could be a potential vaccine candidate against PCVAD. Copyright © 2017 Elsevier Ltd. All rights reserved.

34 CFR 370.42 - What access must the CAP be afforded to policymaking and administrative personnel?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 2 2010-07-01 2010-07-01 false What access must the CAP be afforded to policymaking... What access must the CAP be afforded to policymaking and administrative personnel? The CAP must be... programs, projects, and community rehabilitation programs. One way in which the CAP may be provided that...

31 CFR 50.15 - Cap disclosure.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Cap disclosure. 50.15 Section 50.15... Disclosures as Conditions for Federal Payment § 50.15 Cap disclosure. (a) General. Under section 103(e)(2) of... existence of the $100,000,000,000 cap under section 103(e)(2). The cap disclosure must be made at the time...

Genetics Home Reference: cap myopathy

MedlinePlus

... Email Facebook Twitter Home Health Conditions Cap myopathy Cap myopathy Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Cap myopathy is a disorder that primarily affects skeletal ...

Characterizing pathways by which gravitropic effectors could move from the root cap to the root of primary roots of Zea mays

NASA Technical Reports Server (NTRS)

Moore, R.; McClelen, C. E.

1989-01-01

Plasmodesmata linking the root cap and root in primary roots Zea mays are restricted to approx. 400 protodermal cells bordering approx. 110000 microns2 of the calyptrogen of the root cap. This area is less than 10% of the cross-sectional area of the root-tip at the cap junction. Therefore, gravitropic effectors moving from the root cap to the root can move symplastically only through a relatively small area in the centre of the root. Decapped roots are non-responsive to gravity. However, decapped roots whose caps are replaced immediately after decapping are strongly graviresponsive. Thus, gravicurvature occurs only when the root cap contacts the root, and symplastic continuity between the cap and root is not required for gravicurvature. Completely removing mucilage from the root tip renders the root non-responsive to gravity. Taken together, these data suggest that gravitropic effectors move apoplastically through mucilage from the cap to the root.

Medical Malpractice Reform: Noneconomic Damages Caps Reduced Payments 15 Percent, With Varied Effects By Specialty

PubMed Central

Seabury, Seth A.; Helland, Eric; Jena, Anupam B.

2014-01-01

The impact of medical malpractice reforms on the average size of malpractice payments in specific physician specialties is unknown and subject to debate. We analyzed a national sample of 220,653 malpractice claims from 1985–2010 merged with information on state liability reforms. We estimated the impact of state noneconomic damage caps on average malpractice payment size for physicians overall and for 10 different specialties, and compared how the effects differed according to the restrictiveness of the cap ($250,000 vs. $500,000 cap). We found noneconomic damage caps reduced payments by $42,980 (15%; p<0.001), with a $250,000 cap reducuing average payments by $59,331 (20%; p<0.001), while a $500,000 cap had no significant effect. Effects varied according to specialty and were largest in specialties with high average payments, such as pediatrics. This suggests that the effect of noneconomic damage caps differs by specialty, and only more restrictive caps result in lower average payments. PMID:25339633

Ratio of cyclase activating and cyclase inactive parathormone (CAP/CIP) in dialysis patients: correlations with other markers of bone disease.

PubMed

Grzegorzewska, A E; Młot, M

2004-01-01

We checked correlation of CAP/CIP with osteoprotegrin (OPG), its soluble ligand (OPGL) and routinely measured parameters of bone turnover in patients treated with peritoneal dialysis (PD) and hemodialysis (HD). In 30 patients (22 HD, 8 PD) we determined serum concentrations of intact parathormone (iPTH), CAP, OPG, OPGL, total Ca, inorganic phosphates (Pi), creatinine, urea, total alkaline phosphatase (AP) and blood pH. CIP was calculated by subtraction of CAP from iPTH. Controls (Cs) included 9 healthy persons in whom iPTH, CAP, OPG and OPGL were measured as well as CIP, CAP/CIP and OPGL/OPG were calculated. Differences between HD and PD patients included dialysis duration, OPGL, OPGL/OPG, AP, Pi, Ca and pH. After adjustment to dialysis duration differences in OPGL/OPG, Pi, Ca and pH remained significant. HD patients differed from Cs in terms of iPTH, CAP, CIP, OPGL, OPG and OPGL/OPG. In whole group of patients iPTH, CAP, CIP but not CAP/CIP correlated negatively with OPGL and OPGL/OPG as well as positively with dialysis duration, OPG and AP. Despite more advanced uremic bone disease in longer dialyzed HD patients than in shorter dialyzed PD ones, CAP/CIP is not different neither between these groups nor Cs persons. CAP/CIP does not seem to be more powerful tool in noninvasive diagnosis of bone disease than iPTH or CAP and CIP alone.

Geochemical constraints on the origin of Doushantuo cap carbonates in the Yangtze Gorges area, South China

NASA Astrophysics Data System (ADS)

Wang, Qinxian; Lin, Zhijia; Chen, Duofu

2014-05-01

Marinoan cap carbonates have been suggested to be primarily deposited in glacial meltwater and upwelled seawater. However, elemental geochemistry evidence for this depositional model is lacking. Here, we report high-spatial-resolution measurements of major, trace and rare earth elements of the Doushantuo cap carbonates from the Jiulongwan section in the Yangtze Gorges area, South China. Our results show that: 1) the basal cap carbonates display slight MREE enrichment, weak positive La anomalies, near-chondritic Y/Ho ratios, and slight negative Ce anomalies; 2) the lower-middle cap carbonates show slight LREE depletion or MREE enrichment, weak positive La and Eu anomalies, supra-chondritic Y/Ho ratios, and slight negative Ce anomalies; 3) the upper-middle cap carbonates have consistent enrichment of P, Fe, and trace metals, slight LREE depletion, and weak positive Ce, La and Eu anomalies; and 4) the upper cap carbonates exhibit LREE enrichment, weak positive La and Eu anomalies, supra-chondritic Y/Ho ratios, and mild negative Ce anomalies. These findings indicate that the Doushantuo cap carbonates did not precipitate from normal contemporaneous seawater, rather, the basal cap carbonates were deposited in oxygenated, relatively pure deglacial meltwater; the lower-middle cap carbonates in oxygenated brackish water; the upper-middle cap carbonates in upwelled anoxic brine water; and the upper cap carbonates in oxygenated brackish water. Our depositional model is consistent with the proposed sequence of events after the meltdown of Marinoan glaciation by Shields (2005).

Animation control of surface motion capture.

PubMed

Tejera, Margara; Casas, Dan; Hilton, Adrian

2013-12-01

Surface motion capture (SurfCap) of actor performance from multiple view video provides reconstruction of the natural nonrigid deformation of skin and clothing. This paper introduces techniques for interactive animation control of SurfCap sequences which allow the flexibility in editing and interactive manipulation associated with existing tools for animation from skeletal motion capture (MoCap). Laplacian mesh editing is extended using a basis model learned from SurfCap sequences to constrain the surface shape to reproduce natural deformation. Three novel approaches for animation control of SurfCap sequences, which exploit the constrained Laplacian mesh editing, are introduced: 1) space–time editing for interactive sequence manipulation; 2) skeleton-driven animation to achieve natural nonrigid surface deformation; and 3) hybrid combination of skeletal MoCap driven and SurfCap sequence to extend the range of movement. These approaches are combined with high-level parametric control of SurfCap sequences in a hybrid surface and skeleton-driven animation control framework to achieve natural surface deformation with an extended range of movement by exploiting existing MoCap archives. Evaluation of each approach and the integrated animation framework are presented on real SurfCap sequences for actors performing multiple motions with a variety of clothing styles. Results demonstrate that these techniques enable flexible control for interactive animation with the natural nonrigid surface dynamics of the captured performance and provide a powerful tool to extend current SurfCap databases by incorporating new motions from MoCap sequences.

The Claim of Anti-Cataract Potential of Heliotropium indicum: A Myth or Reality?

PubMed

Kyei, Samuel; Koffuor, George Asumeng; Ramkissoon, Paul; Afari, Clement; Asiamah, Emmanuel Akomanin

2015-12-01

Heliotropium indicum has several uses in traditional medicine attributable to its numerous bioactive compounds. It is used as a traditional remedy for cataracts in Ghana without any scientific verification. This study aimed at verifying the anti-cataract properties of an aqueous whole plant extract of H. indicum. The effect (cataract score) of 30, 100, and 300 mg kg(-1) extract (bid for 21 days, per os) on the development of 30 µmol kg(-1) sodium selenite-induced cataract in 10-day-old rat pups was investigated. Soluble lens proteins alpha A and alpha B crystallins, total lens protein, total lens glutathione, and aquaporin 0 in enucleated lens homogenates were determined spectrophotometrically using commercially available kits. Histopathological studies on the lenses were also performed. The 2,2-diphenyl-1-picrylhydrazyl scavenging effect and linoleic acid autoxidation (antioxidant properties) of the extract (0.1-3.0 mg ml(-1)), compared to n-propyl gallate, were ascertained using standard procedures. Cataract scores showed that the extract, at all dose levels, significantly alleviated selenite-induced cataracts (P ≤ 0.001). Markers of lens transparency (aquaporin 0, alpha A and B crystallins), as well as total lens proteins and lens glutathione levels, were significantly preserved (P ≤ 0.01-0.001). The extract exhibited activity relevant for scavenging free radicals and inhibition of lipid peroxidation. Epithelial and lens fiber integrity in the histopathological assessment were maintained with HIE treatment. The aqueous whole plant extract of H. indicum significantly inhibited the development of cataracts in rats via multiple mechanisms.

Validity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter.

PubMed

Wong, Vincent Wai-Sun; Petta, Salvatore; Hiriart, Jean-Baptiste; Cammà, Calogero; Wong, Grace Lai-Hung; Marra, Fabio; Vergniol, Julien; Chan, Anthony Wing-Hung; Tuttolomondo, Antonino; Merrouche, Wassil; Chan, Henry Lik-Yuen; Le Bail, Brigitte; Arena, Umberto; Craxì, Antonio; de Lédinghen, Victor

2017-09-01

Controlled attenuation parameter (CAP) can be performed together with liver stiffness measurement (LSM) by transient elastography (TE) and is often used to diagnose fatty liver. We aimed to define the validity criteria of CAP. CAP was measured by the M probe prior to liver biopsy in 754 consecutive patients with different liver diseases at three centers in Europe and Hong Kong (derivation cohort, n=340; validation cohort, n=414; 101 chronic hepatitis B, 154 chronic hepatitis C, 349 non-alcoholic fatty liver disease, 37 autoimmune hepatitis, 49 cholestatic liver disease, 64 others; 277 F3-4; age 52±14; body mass index 27.2±5.3kg/m 2 ). The primary outcome was the diagnosis of fatty liver, defined as steatosis involving ≥5% of hepatocytes. The area under the receiver-operating characteristics curve (AUROC) for CAP diagnosis of fatty liver was 0.85 (95% CI 0.82-0.88). The interquartile range (IQR) of CAP had a negative correlation with CAP (r=-0.32, p<0.001), suggesting the IQR-to-median ratio of CAP would be an inappropriate validity parameter. In the derivation cohort, the IQR of CAP was associated with the accuracy of CAP (AUROC 0.86, 0.89 and 0.76 in patients with IQR of CAP <20 [15% of patients], 20-39 [51%], and ≥40dB/m [33%], respectively). Likewise, the AUROC of CAP in the validation cohort was 0.90 and 0.77 in patients with IQR of CAP <40 and ≥40dB/m, respectively (p=0.004). The accuracy of CAP in detecting grade 2 and 3 steatosis was lower among patients with body mass index ≥30kg/m 2 and F3-4 fibrosis. The validity of CAP for the diagnosis of fatty liver is lower if the IQR of CAP is ≥40dB/m. Lay summary: Controlled attenuation parameter (CAP) is measured by transient elastography (TE) for the detection of fatty liver. In this large study, using liver biopsy as a reference, we show that the variability of CAP measurements based on its interquartile range can reflect the accuracy of fatty liver diagnosis. In contrast, other clinical factors such as adiposity and liver enzyme levels do not affect the performance of CAP. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A molecular study of a family with Greek hereditary persistence of fetal hemoglobin and beta-thalassemia.

PubMed Central

Giglioni, B; Casini, C; Mantovani, R; Merli, S; Comi, P; Ottolenghi, S; Saglio, G; Camaschella, C; Mazza, U

1984-01-01

A family was studied in which two inherited defects of the non-alpha-globin cluster segregate: Greek hereditary persistence of fetal hemoglobin (HPFH) and beta-thalassemia. Fragments of the non-alpha-globin cluster from two patients were cloned in cosmid and phage lambda vectors, and assigned to either the HPFH or beta-thalassemic chromosome on the basis of the demonstration of a polymorphic BglII site in the HPFH gamma-globin cluster. The thalassemic beta-globin gene carries a mutation at nucleotide 1 of the intervening sequence I, known to cause beta zero-thalassemia; the beta-globin gene from the HPFH chromosome is entirely normal, both in the intron-exon sequence and in 5' flanking regions required for transcription. As the compound HPFH/beta-thalassemia heterozygote synthesizes HbA, these data prove that the HPFH beta-globin gene is functional, although at a decreased rate; its lower activity is likely to be due to a distant mutation. The HPFH A gamma-globin gene shows only two mutations: a T----C substitution in the large intervening sequence (responsible for the BglII polymorphic site) and a C----T substitution 196 nucleotides 5' to the cap site; the 5' flanking sequence is normal up to -1350 nucleotides upstream from the gene. Circumstantial evidence suggests that the mutation at -196 may be responsible for the abnormally high expression of the A gamma-globin gene. Images Fig. 1. Fig. 3. Fig. 4. Fig. 5. PMID:6210198

Integrative assessment of brain function in PTSD: brain stability and working memory.

PubMed

Veltmeyer, Melinda D; McFarlane, Alexander C; Bryant, Richard A; Mayo, Therese; Gordon, Evian; Clark, C Richard

2006-03-01

Posttraumatic Stress Disorder (PTSD) is characterized by symptoms of hyperarousal, avoidance and intrusive trauma-related memories and deficits in everyday memory and attention. Separate studies in PTSD have found abnormalities in electroencephalogram EEG, in event-related potential (ERP) and behavioral measures of working memory and attention. The present study seeks to determine whether these abnormalities are related and the extent to which they share this relationship with clinical symptoms. EEG data were collected during an eyes-open paradigm and a one-back working memory task. Behavioral and clinical data (CAPS) were also collected. The PTSD group showed signs of altered cortical arousal as indexed by reduced alpha power and an increased theta/alpha ratio, and clinical and physiological measures of arousal were found to be related. The normal relationship between theta power and ERP indices of working memory was not affected in PTSD, with both sets of measures reduced in the disordered group. Medication appeared to underpin a number of abnormal parameters, including P3 amplitude to targets and the accuracy, though not speed, of target detection. The present study helps to overcome a limitation of earlier studies that assess such parameters independently in different groups of patients that vary in factors such as comorbidity, medication status, gender and symptom profile. The present study begins to shed light on the relationship between these measures and suggests that abnormalities in brain working memory may be linked to underlying abnormalities in brain stability.

Care coordination in PMAQ-AB: an Item Response Theory-based analysis.

PubMed

Souza, Miriam Francisco de; Santos, Alaneir de Fatima Dos; Reis, Ilka Afonso; Santos, Marcos Antônio da Cunha; Jorge, Alzira de Oliveira; Machado, Antônio Tomaz Gonzaga da Matta; Andrade, Eli Iola Gurgel; Cherchiglia, Mariangela Leal

2017-01-01

Analyze the quality of the National Program for Primary Care Access and Quality Improvement variables to evaluate the coordination of primary care. A cross-sectional study based on data from 17,202 primary care teams that participated in the National Program for Primary Care Access and Quality Improvement in 2012. Based on the Item Response Theory, Samejima's Gradual Response Model was used to estimate the score related to the level of coordination. The Cronbach's alpha and Spearman' coefficients and the point-biserial correlation were used to analyze the internal consistency and the correlation between the items and between the items and the total score. We evaluated the assumptions of unidimensionality and local independence of the items. Cloud-type word charts aided in the interpretation of coordination levels. The Program items with the greatest discrimination in coordination level were: telephone/Internet existence, institutional communication flows, and matrix support actions. The specialists' contact frequency with the primary care and integrated electronic medical record required a greater level of coordination among the teams. The Cronbach' alpha was 0.8018. The institutional communication flows and telephone/Internet items had a higher correlation with the total score. Coordination scores ranged from -2.67 (minimum) to 2.83 (maximum). More communication, information exchange, matrix support, health care in the territory and the domicile had a significant influence on the levels of coordination. The ability to provide information and the frequency of contact among professionals are important elements for a comprehensive, continuous and high-quality care. Analisar a qualidade das variáveis do Programa de Melhoria do Acesso e da Qualidade da Atenção Básica para avaliar a coordenação na atenção básica do cuidado. Estudo transversal baseado em dados de 17.202 equipes de atenção básica que participaram do Programa de Melhoria do Acesso e da Qualidade da Atenção Básica em 2012. Baseado na Teoria de Resposta ao Item, o Modelo de Resposta Gradual de Samejima foi utilizado para estimação do escore relacionado ao nível de coordenação. Os coeficientes alfa de Cronbach, Spearman e ponto bisserial foram utilizados para análise da consistência interna e da correlação entre os itens e de itens com o escore total. Foram avaliadas as suposições de unidimensionalidade e de independência local dos itens. Gráficos do tipo nuvem de palavras auxiliaram na interpretação dos níveis de coordenação. Os itens do Programa com maior discriminação do nível de coordenação foram: existência de telefone/internet, fluxos institucionais de comunicação e ações de apoio matricial. A frequência de contato de especialistas com a atenção básica e prontuário eletrônico integrado exigiram maior nível de coordenação das equipes. O coeficiente alfa de Cronbach total 0,8018. Os itens fluxos institucional de comunicação e telefone/internet tiveram maior correlação com o escore total. Os escores de coordenação variaram entre -2,67 (mínimo) e 2,83 (máximo). Maior grau de comunicação, troca de informações, apoio matricial, cuidado no território e domicílio tiveram peso relevante nos níveis de coordenação. A capacidade de disponibilizar a informação e a frequência de contato entre os profissionais são elementos importantes para o cuidado abrangente, contínuo e de qualidade.

Principles of using Cold Atmospheric Plasma Stimulated Media for Cancer Treatment

PubMed Central

Yan, Dayun; Talbot, Annie; Nourmohammadi, Niki; Cheng, Xiaoqian; Canady, Jerome; Sherman, Jonathan; Keidar, Michael

2015-01-01

To date, the significant anti-cancer capacity of cold atmospheric plasma (CAP) on dozens of cancer cell lines has been demonstrated in vitro and in mice models. Conventionally, CAP was directly applied to irradiate cancer cells or tumor tissue. Over past three years, the CAP irradiated media was also found to kill cancer cells as effectively as the direct CAP treatment. As a novel strategy, using the CAP stimulated (CAPs) media has become a promising anti-cancer tool. In this study, we demonstrated several principles to optimize the anti-cancer capacity of the CAPs media on glioblastoma cells and breast cancer cells. Specifically, using larger wells on a multi-well plate, smaller gaps between the plasma source and the media, and smaller media volume enabled us to obtain a stronger anti-cancer CAPs media composition without increasing the treatment time. Furthermore, cysteine was the main target of effective reactive species in the CAPs media. Glioblastoma cells were more resistant to the CAPs media than breast cancer cells. Glioblastoma cells consumed the effective reactive species faster than breast cancer cells did. In contrast to nitric oxide, hydrogen peroxide was more likely to be the effective reactive species. PMID:26677750