The oxidation of pure Co and two Co–Y alloys containing 2
at.% and 5
at.% Y has been studied at 600–800°C in air. The oxidation of pure cobalt at all temperatures followed the parabolic rate law. The ...oxidation of the two alloys approximately followed the parabolic rate law at 800°C, but was closer to cubic behavior at 600 and 700°C except Co–5Y at 600°C, which deviated from the cubic and parabolic rate law. The corrosion of both alloys at the three temperatures produced an external scale containing Co oxides (Co
3O
4, CoO) and Y
2O
3 and an internal oxidation region where Co
17Y
2 was converted into Co and Y
2O
3. The distribution of Y
2O
3 closely followed that of the intermetallic compound (Co
17Y
2) in the original alloy. The corrosion mechanism of the alloys is examined.
The c-rel protooncogene encodes a member of the Rel/nuclear factor (NF)-kappaB family of transcriptional factors. To assess the role of the transcriptional activation domain of c-Rel in vivo, we ...generated mice expressing a truncated c-Rel (Deltac-Rel) that lacks the COOH-terminal region, but retains a functional Rel homology domain. Mice with an homozygous mutation in the c-rel region encoding the COOH terminus of c-Rel (c-relDeltaCT/DeltaCT) display marked defects in proliferative and immune functions. c-relDeltaCT/DeltaCT animals present histopathological alterations of hemopoietic tissues, such as an enlarged spleen due to lymphoid hyperplasia, extramedullary hematopoiesis, and bone marrow hypoplasia. In older c-relDeltaCT/DeltaCT mice, lymphoid hyperplasia was also detected in lymph nodes, liver, lung, and stomach. These animals present a more severe phenotype than mice lacking the entire c-Rel protein. Thus, in c-relDeltaCT/DeltaCT mice, the lack of c-Rel activity is less efficiently compensated by other NF-kappaB proteins.
The prompt γ radiation originating from the dynamical dipole mode decay was investigated in the 192Pb composite system employing the 40Ca + 152Sm and 48Ca + 144Sm reactions at Elab=11 and 10.1 ...MeV/nucleon, respectively. The γ-ray energy spectra at various polar angles were obtained for fusion-evaporation and fission events by detecting the high energy γ rays with the MEDEA experimental apparatus in coincidence with evaporation residues and fission fragments. Preliminary results of this experiment show that the dynamical dipole mode survives in collisions involving heavier mass reaction partners than those studied previously. As a fast cooling mechanism on the fusion path, the prompt dipole γ radiation could be of interest for the synthesis of super-heavy elements through "hot" fusion reactions.
Quantum-mechanical calculations of muon transfer between muonic hydrogen and an oxygen nuclei for s waves and collision energies in the range 10{sup -3}-10{sup 3} eV are presented. Close-coupling ...time-independent Schroedinger equations, written in terms of hyperspherical elliptic coordinates, were integrated along the hyperradius to obtain the partial and total muon-transfer probabilities. The results show the expected Wigner-Bethe threshold behavior up to collision energies of the order of 10{sup -2} eV and pronounced maxima at 10{sup 2} eV which can be interpreted in terms of crossings between potential energy curves corresponding to the entrance channel state ({mu}p){sub 1s}+O and two product channels which asymptotically correlate to p+(O{mu}){sub n=5,6}. The population of the final states with different orbital angular momenta is found to be essentially independent of energy in the range considered in this work. This can be attributed to a strong selection rule for the conservation of the quantum number associated with one of the elliptic hyperangles.
Sulfidopeptide leukotrienes (LTs) C4, D4 and E4 are important mediators in the pathophysiology of bronchial asthma. Sch 37224, 1-(1,2-dihydro-4-hydroxy-2-oxo-1-phenyl-1,8-naphthyridin-3-yl) ...pyrrolidinium, hydroxide inner salt, has been found to inhibit the formation of these autocoids. Although Sch 37224 did not inhibit 5-lipoxygenase, cyclooxygenase or phospholipase A2, it inhibited LTD4 and thromboxane B2 release by anaphylactic guinea pig lung (IC40 = 3.9 and 1.9 microM, respectively). At 5 microM Sch 37224 also inhibited superoxide anion radical generation from activated human polymorphonuclear neutrophilic leukocytes. When administered p.o. to guinea pigs, Sch 37224 decreased a LT-mediated allergic bronchospasm (ED40 = 1.1 mg/kg) for 6 hr and did not exhibit tolerance. In addition to its activities in allergen-induced bronchospasm in guinea pigs, Sch 37224 also inhibited hyperventilation-induced bronchospasm in guinea pigs at 0.5 to 5 mg/kg and anaphylactic bronchospasm in rats at 0.1 to 10 mg/kg. Sch 37224 was weak or ineffective as an antagonist of histamine, methacholine, serotonin, LTC4 or platelet activating factor induced bronchospasms in guinea pigs. Also, Sch 37224 was not a bronchodilator or calcium influx blocker and had only weak relaxant activity on guinea pig trachea in vitro (IC40 = 51 microM). Sch 37224 is, therefore, a potential antiallergic agent that inhibits LT release. It is p.o. effective in animal models of allergic and nonallergic-mediated bronchospasms.
Five bilateral forearms allograft have been performed between January 2000 and July 2009 in Lyon (France). The first four patients (three males, one female) have been the subject of an assessment of ...the bone quality of those allografts. The techniques selected for this study were: radioclinical analysis, bone scintigraphy, MRI, bone densitometry and High Resolution peripheral Quantitative Computed Tomography (HR-PQCT). Histology has been performed only on the first patient unilaterally grafted in 1998 who did not take part in this clinical research protocol, after amputation of his rejected graft. On the clinical, radiological and scintigraphical aspects, donor bone integration in hands allograft are good on a macroscopic point of view considering the healing and the general reaction of the bone in situation of fractures, infection and growth. The scintigraphy does not show important variations compared to the ones we can observe on contact with osteosynthesis material or during bone autografts. MRI found neither focal nor periosteal anomaly on grafted bone. The bone densitometry did not show significant difference with secondary osteoporosis one can observe in other grafted patients under immunosuppressive treatment. The HR-PQCT showed for the three males patients, a higher loss in volumetric density, for grafted bone than in the recipient patient control skeleton. Due to the few patients of this series, and the discrepancies in follow-up duration, the presented data have to be confirmed with further studies.
1,N super(2)-Etheno( epsilon )guanine ( epsilon ) is formed in DNA as a result of exposure to certain vinyl monomers (e.g., vinyl chloride) or from lipid peroxidation. This lesion has been shown to ...be mutagenic in bacteria and mammalian cells. 1,N super(2)- epsilon -G has been shown to block several model replicative DNA polymerases (pols), with limited bypass. Recently, an archebacterial DNA pol, Sulfolobus solfataricus Dpo4, has been shown to copy past 1,N super(2)- epsilon -G. In this study, we examined the abilities of recombinant, full-length human pol epsilon and three human translesion DNA pols to copy past 1,N super(2)- epsilon -G. The replicative pol, pol delta , was completely blocked. Pols (i) and (k) showed similar rates of incorporation of dTTP and dCTP. Pol eta was clearly the most active of these pols in copying past 1,N super(2)- epsilon -G, incorporating in the order dGTP > dATP > dCTP, regardless of whether the base 5' of 1,N super(2)- epsilon -G in the template was C or T. Pol eta also had the highest error frequency opposite 1,N super(2)- epsilon -G. Analysis of the extended products of the pol eta reactions by mass spectrometry indicated only two products, both of which had G incorporated opposite 1,N super(2)- epsilon -G and all other base pairing being normal (i.e., G:C and A:T). One-half of the products contained an additional A at the 3'-end, presumably arising from a noninformational blunt end addition or possibly a slipped insertion mechanism at the end of the primer-template replication process. In summary, the most efficient of the four human DNA pols was pol eta , which appeared to insert G opposite 1,N super(2)- epsilon -G and then copy correctly. This pattern differs with the same oligonucleotide sequences and 1,N super(2)- epsilon -G observed using Dpo4, emphasizing the importance of pols in mutagenesis events.
The increasing use of medical marijuana highlights the importance of developing a better understanding of cannabinoid metabolism. Phytocannabinoids, including ∆
-tetrahydrocannabinol (THC), are ...metabolized and inactivated by cytochrome P450 enzymes primarily within the liver. The lipophilic nature of cannabinoids necessitates mechanism(s) to facilitate their intracellular transport to metabolic enzymes. Here, we test the central hypothesis that liver-type fatty acid binding protein (FABP1) mediates phytocannabinoid transport and subsequent inactivation. Using X-ray crystallography, molecular modeling, and in vitro binding approaches we demonstrate that FABP1 accommodates one molecule of THC within its ligand binding pocket. Consistent with its role as a THC carrier, biotransformation of THC was reduced in primary hepatocytes obtained from FABP1-knockout (FABP1-KO) mice. Compared to their wild-type littermates, administration of THC to male and female FABP1-KO mice potentiated the physiological and behavioral effects of THC. The stark pharmacodynamic differences were confirmed upon pharmacokinetic analyses which revealed that FABP1-KO mice exhibit reduced rates of THC biotransformation. Collectively, these data position FABP1 as a hepatic THC transport protein and a critical mediator of cannabinoid inactivation. Since commonly used medications bind to FABP1 with comparable affinities to THC, our results further suggest that FABP1 could serve a previously unrecognized site of drug-drug interactions.
The dynamical dipole mode was investigated in the mass region of the 192Pb compound nucleus, by using the 40Ca + 152Sm and 48Ca + 144Sm reactions at Elab=11 and 10.1 MeV/nucleon, respectively. Both ...fusion–evaporation and fission events were studied simultaneously for the first time. Our results show that the dynamical dipole mode survives in reactions involving heavier nuclei than those studied previously, however, its yield is lower than that expected within BNV calculations.
Background/Aims
: The aim of the present, open-labeled, randomized study was to determine the efficacy and safety of different doses of consensus interferon plus ribavirin in the initial treatment of ...chronic hepatitis C.
Methods
: One hundred and one genotype 2/3 patients were randomized to receive 9 mcg (group A,
n=
48
) or 18 mcg (group B,
n=
53
) of consensus interferon thrice weekly plus ribavirin (1000/1200 mg/daily) for 24 weeks and 92 genotype 1 patients to receive 9 mcg (group C,
n=
47
) or 18 mcg (group D,
n=
45
) of consensus interferon plus ribavirin for 48 weeks.
Results
: In an intention-to-treat analysis, the sustained virologic response at 24-week follow-up was 69% and 66% for group A and B (
P=
0.77
) and 40% and 36% for group C and D (
P=
0.63
). The overall sustained response was 67% and 38% in patients with genotype 2/3 and 1, respectively. Among genotype 1 patients the sustained virologic response was 39% and 41% for high or low baseline viremia levels.
Conclusions
: Higher consensus interferon dose does not increase sustained virologic response. Naive genotype 1 patients may achieve significant response rate of approximately 40% if treated with 9 mcg of consensus interferon plus ribavirin for 48 weeks.
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