618 research outputs found
Saturation of dephasing time in mesoscopic devices produced by a ferromagnetic state
We consider an exchange model of itinerant electrons in a Heisenberg
ferromagnet and we assume that the ferromagnet is in a fully polarized state.
Using the Holstein-Primakoff transformation we are able to obtain a
boson-fermion Hamiltonian that is well-known in the interaction between light
and matter. This model describes the spontaneous emission in two-level atoms
that is the proper decoherence mechanism when the number of modes of the
radiation field is taken increasingly large, the vacuum acting as a reservoir.
In the same way one can see that the interaction between the bosonic modes of
spin waves and an itinerant electron produces decoherence by spin flipping with
a rate proportional to the size of the system. In this way we are able to show
that the experiments on quantum dots, described in D. K. Ferry et al. [Phys.
Rev. Lett. {\bf 82}, 4687 (1999)], and nanowires, described in D. Natelson et
al. [Phys. Rev. Lett. {\bf 86}, 1821 (2001)], can be understood as the
interaction of itinerant electrons and an electron gas in a fully polarized
state.Comment: 10 pages, no figure. Changed title. Revised version accepted for
publication in Physical Review
Electron transport and energy relaxation in dilute magnetic alloys
We consider the effect of the RKKY interaction between magnetic impurities on
the electron relaxation rates in a normal metal. The interplay between the RKKY
interaction and the Kondo effect may result in a non-monotonic temperature
dependence of the electron momentum relaxation rate, which determines the Drude
conductivity. The electron phase relaxation rate, which determines the
magnitude of the weak localization correction to the resistivity, is also a
non-monotonic function of temperature. For this function, we find the
dependence of the position of its maximum on the concentration of magnetic
impurities. We also relate the electron energy relaxation rate to the
excitation spectrum of the system of magnetic impurities. The energy relaxation
determines the distribution function for the out-of-equilibrium electrons.
Measurement of the electron distribution function thus may provide information
about the excitations in the spin glass phase.Comment: 15 pages, 5 figure
Review of health-related quality of life data in multiple myeloma patients treated with novel agents
In multiple myeloma (MM), health-related quality of life (HRQoL) data is becoming increasingly important, owing to improved survival outcomes and the impact of treatment-related toxicity on HRQoL. Researchers are more frequently including HRQoL assessments in clinical trials, but analysis and reporting of this data has not been consistent. A systematic literature review assessed the effect of novel agents (thalidomide, bortezomib and lenalidomide) on HRQoL in MM patients, and evaluated the subsequent reporting of these HRQoL results. A relatively small body of literature addresses HRQoL data in MM patients treated with novel MM therapeutic agents: 9 manuscripts and 15 conference proceedings. The literature demonstrates the complementary value of HRQoL when assessing clinical response, progression, overall survival and toxicity. However, weaknesses and inconsistencies in analysis and presentation of HRQoL data were observed, often complicating interpretation of the impact of treatment on HRQoL in MM. Further evaluation of HRQoL in MM patients treated with novel agents is required in larger cohorts, and ideally in head-to-head comparative studies. Additionally, the development of standardised MM-specific best practice guidelines in HRQoL data collection and analysis is recommended. These would ensure that future data are more useful in guiding predictive models and clinical decisions
Kondo Effect on Mesoscopic Scale (Review)
Following the discovery of the Kondo effect the bulk transport and magnetic
behavior of the dilute magnetic alloys have been successfully described. In the
last fifteen years new directions have been developed as the study of the
systems of reduced dimensions and the artificial atoms so called quantum dots.
In this review the first subject is reviewed starting with the scanning
tunneling microscope (STM) study of a single magnetic impurity. The next
subject is the reduction of the amplitude of the Kondo effect in samples of
reduced dimension which was explained by the surface magnetic anisotropy which
blocks the motion of the integer spin nearby the surface. The electron
dephasing and energy relaxation experiments are discussed with the possible
explanation including the surface anisotropy, where the situation in cases of
integer and half-integer spins is very different. Finally, the present
situation of the theory of dynamical structural defects is briefly presented
which may lead to two-channel Kondo behavior.Comment: 8 pages, submitted to the JPSJ Special Issue "Kondo effect -- 40
years after the Discovery
Five Tyrosines and Two Serines in Human Albumin Are Labeled by the Organophosphorus Agent FP-Biotin
Functionals of the Brownian motion, localization and metric graphs
We review several results related to the problem of a quantum particle in a
random environment.
In an introductory part, we recall how several functionals of the Brownian
motion arise in the study of electronic transport in weakly disordered metals
(weak localization).
Two aspects of the physics of the one-dimensional strong localization are
reviewed : some properties of the scattering by a random potential (time delay
distribution) and a study of the spectrum of a random potential on a bounded
domain (the extreme value statistics of the eigenvalues).
Then we mention several results concerning the diffusion on graphs, and more
generally the spectral properties of the Schr\"odinger operator on graphs. The
interest of spectral determinants as generating functions characterizing the
diffusion on graphs is illustrated.
Finally, we consider a two-dimensional model of a charged particle coupled to
the random magnetic field due to magnetic vortices. We recall the connection
between spectral properties of this model and winding functionals of the planar
Brownian motion.Comment: Review article. 50 pages, 21 eps figures. Version 2: section 5.5 and
conclusion added. Several references adde
Lysosome-mediated processing of chromatin in senescence
Cellular senescence is a stable proliferation arrest, a potent tumor suppressor mechanism, and a likely contributor to tissue aging. Cellular senescence involves extensive cellular remodeling, including of chromatin structure. Autophagy and lysosomes are important for recycling of cellular constituents and cell remodeling. Here we show that an autophagy/lysosomal pathway processes chromatin in senescent cells. In senescent cells, lamin A/C–negative, but strongly γ-H2AX–positive and H3K27me3-positive, cytoplasmic chromatin fragments (CCFs) budded off nuclei, and this was associated with lamin B1 down-regulation and the loss of nuclear envelope integrity. In the cytoplasm, CCFs were targeted by the autophagy machinery. Senescent cells exhibited markers of lysosomal-mediated proteolytic processing of histones and were progressively depleted of total histone content in a lysosome-dependent manner. In vivo, depletion of histones correlated with nevus maturation, an established histopathologic parameter associated with proliferation arrest and clinical benignancy. We conclude that senescent cells process their chromatin via an autophagy/lysosomal pathway and that this might contribute to stability of senescence and tumor suppression
Polyclonality of BRAF mutations in primary melanoma and the selection of mutant alleles during progression
Cooperation between CYB5R3 and NOX4 via coenzyme Q mitigates endothelial inflammation
NADPH oxidase 4 (NOX4) regulates endothelial inflammation by producing hydrogen peroxide (H2O2) and to a lesser extent O2•-. The ratio of NOX4-derived H2O2 and O2•- can be altered by coenzyme Q (CoQ) mimics. Therefore, we hypothesize that cytochrome b5 reductase 3 (CYB5R3), a CoQ reductase abundant in vascular endothelial cells, regulates inflammatory activation. To examine endothelial CYB5R3 in vivo, we created tamoxifen-inducible endothelium-specific Cyb5r3 knockout mice (R3 KO). Radiotelemetry measurements of systolic blood pressure showed systemic hypotension in lipopolysaccharides (LPS) challenged mice, which was exacerbated in R3 KO mice. Meanwhile, LPS treatment caused greater endothelial dysfunction in R3 KO mice, evaluated by acetylcholine-induced vasodilation in the isolated aorta, accompanied by elevated mRNA expression of vascular adhesion molecule 1 (Vcam-1). Similarly, in cultured human aortic endothelial cells (HAEC), LPS and tumor necrosis factor α (TNF-α) induced VCAM-1 protein expression was enhanced by Cyb5r3 siRNA, which was ablated by silencing the Nox4 gene simultaneously. Moreover, super-resolution confocal microscopy indicated mitochondrial co-localization of CYB5R3 and NOX4 in HAECs. APEX2-based electron microscopy and proximity biotinylation also demonstrated CYB5R3's localization on the mitochondrial outer membrane and its interaction with NOX4, which was further confirmed by the proximity ligation assay. Notably, Cyb5r3 knockdown HAECs showed less total H2O2 but more mitochondrial O2•-. Using inactive or non-membrane bound active CYB5R3, we found that CYB5R3 activity and membrane translocation are needed for optimal generation of H2O2 by NOX4. Lastly, cells lacking the CoQ synthesizing enzyme COQ6 showed decreased NOX4-derived H2O2, indicating a requirement for endogenous CoQ in NOX4 activity. In conclusion, CYB5R3 mitigates endothelial inflammatory activation by assisting in NOX4-dependent H2O2 generation via CoQ.This work was supported by National Institutes of Health (NIH) R01 awards [R01 HL 133864 (A.C.S), R01 HL 128304 (A.C.S), R01 HL 149825 (A.C.S), R01 HL 153532 (A.C.S), R01 GM 125944 (F.J.S.), R01 DK 112854 (F.J.S.), 1S10OD021540-01 (Center for Biologic Imaging, University of Pittsburgh), 1S10RR019003-01 (Simon Watkins (S.W.)), 1S10RR025488-01 (S.W.), 1S10RR016236-01 (S.W)]. American Heart Association (AHA) [Established Investigator Award 19EIA34770095 (A.C.S.)], Post-doctoral Fellowship 19POST34410028 (S.Y.)]. American Society of Hematology (ASH) Minority Hematology Graduate Award (A.M.D-O.). Junta de Andalucía grant BIO-177 (P.N.), the FEDER Funding Program from the European Union and Spanish Ministry of Science, Innovation and Universities grant RED2018-102576-T (P.N.)
Loss of cardiomyocyte CYB5R3 impairs redox equilibrium and causes sudden cardiac death
Sudden cardiac death (SCD) in patients with heart failure (HF) is allied with an imbalance in reduction and oxidation (redox) signaling in cardiomyocytes; however, the basic pathways and mechanisms governing redox homeostasis in cardiomyocytes are not fully understood. Here, we show that cytochrome b5 reductase 3 (CYB5R3), an enzyme known to regulate redox signaling in erythrocytes and vascular cells, is essential for cardiomyocyte function. Using a conditional cardiomyocyte-specific CYB5R3-knockout mouse, we discovered that deletion of CYB5R3 in male, but not female, adult cardiomyocytes causes cardiac hypertrophy, bradycardia, and SCD. The increase in SCD in CYB5R3-KO mice is associated with calcium mishandling, ventricular fibrillation, and cardiomyocyte hypertrophy. Molecular studies reveal that CYB5R3-KO hearts display decreased adenosine triphosphate (ATP), increased oxidative stress, suppressed coenzyme Q levels, and hemoprotein dysregulation. Finally, from a translational perspective, we reveal that the high-frequency missense genetic variant rs1800457, which translates into a CYB5R3 T117S partial loss-of-function protein, associates with decreased event-free survival (~20%) in Black persons with HF with reduced ejection fraction (HFrEF). Together, these studies reveal a crucial role for CYB5R3 in cardiomyocyte redox biology and identify a genetic biomarker for persons of African ancestry that may potentially increase the risk of death from HFrEF.These studies were supported by NIH grants R35 HL 161177 (to ACS), R01 HL 133864 (to ACS), R01 HL 128304 (to ACS), R41 HL15098 (to GS), R01 GM 122091 (to PHT), GM125944 (to FJS), R01 DK112854 (to FJS), R21 NS112787 (to MF), NS121706 (to YLW), EB023507 (to YLW), F31 HL149241 (to HMS), and F31 HL151173 (to JCG). Support was also provided by American Heart Association grants 19EIA34770095 (to ACS), AHA 18CDA34140024 (to YLW), and 19PRE34380152 (to NTC); the Spanish Ministry of Health (grant FIS PI17-01286); Junta de Andalucía BIO-177 and the FEDER Funding Program from the European Union and CIBERER (U729)-ISCIII (to PN); Department of Defense W81XWH1810070 (to YLW); and Vitalant. This research was supported in part by the University of Pittsburgh Center for Research Computing through the resources provided. Specifically, this work used the HTC cluster, which is supported by NIH award number S10OD028483.Peer reviewe
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