Evolution of supermassive black holes

Supermassive black holes (SMBHs) are nowadays believed to reside in most local galaxies, and the available data show an empirical correlation between bulge luminosity - or stellar velocity dispersion - and black hole mass, suggesting a single mechanism for assembling black holes and forming spheroids in galaxy halos. The evidence is therefore in favour of a co-evolution between galaxies, black holes and quasars. In cold dark matter cosmogonies, small-mass subgalactic systems form first to merge later into larger and larger structures. In this paradigm galaxy halos experience multiple mergers during their lifetime. If every galaxy with a bulge hosts a SMBH in its center, and a local galaxy has been made up by multiple mergers, then a black hole binary is a natural evolutionary stage. The evolution of the supermassive black hole population clearly has to be investigated taking into account both the cosmological framework and the dynamical evolution of SMBHs and their hosts. The seeds of SMBHs have to be looked for in the early Universe, as very luminous quasars are detected up to redshift higher than z=6. These black holes evolve then in a hierarchical fashion, following the merger hierarchy of their host halos. Accretion of gas, traced by quasar activity, plays a fundamental role in determining the two parameters defining a black hole: mass and spin. A particularly intriguing epoch is the initial phase of SMBH growth. It is very challenging to meet the observational constraints at z=6 if BHs are not fed at very high rates in their infancy.Comment: Extended version of the invited paper to appear in the Proceedings of the Conference "Relativistic Astrophysics and Cosmology - Einstein's Legacy

Transverse depinning in strongly driven vortex lattices with disorder

Using numerical simulations we investigate the transverse depinning of moving vortex lattices interacting with random disorder. We observe a finite transverse depinning barrier for vortex lattices that are driven with high longitudinal drives, when the vortex lattice is defect free and moving in correlated 1D channels. The transverse barrier is reduced as the longitudinal drive is decreased and defects appear in the vortex lattice, and the barrier disappears in the plastic flow regime. At the transverse depinning transition, the vortex lattice moves in a staircase pattern with a clear transverse narrow-band voltage noise signature.Comment: 4 pages, 4 figure

Percutaneous Venous Angioplasty in Patients With Multiple Sclerosis And Chronic Cerebrospinal Venous Insufficiency: A Randomized Wait List Control Study

Objectives: Venous percutaneous transluminal angioplasty (vPTA) in patients with multiple sclerosis (MS) and chronic cerebrospinal venous insufficiency (CCSVI) have shown contradictory results. Aim of the study is to evaluate the efficacy of the procedure in a randomized wait list control study. Materials: 66 adults with neurologist-confirmed diagnosis of MS and sonographic diagnosis of CCSVI were allocated in to vPTA-yes group (n=31) or vPTA-not group (n=35, control group). Venous PTA was performed immediately 15 days after randomization in PTA-yes group and 6 months later in the control group. Methods: Evoked potentials (EPs), clinical-functional measures (CFM) and upper limb kinematic measures (ULKM) were measured at baseline (T0) and six months after in both groups, just before the venous angioplasty in vPTA-not group (T1). Results: Comparing vPTA-yes and vPTA-not group, the CFM derived composite functional outcome showed 11(37%) versus 7(20%) improved, 1(3%) versus 3(8%) stable, 0 versus 7(20%) worsened and 19(61%) versus 18(51%) mixed patients (\u3c72=8.71, df=3, p=0.03). Unadjusted and adjusted (for baseline confounding variables) OR at 95% confident interval (95%CI) were respectively 1.93(1.3-2.8) P-value 0.0007 and 1.85(1.2-1.7) P-value 0.002. EPs and ULKM derived composite functional outcome showed no significant difference between the two groups. Conclusions: Venous angioplasty can positively impact a few CFM especially for the quality of life, but achieving disability improvement is unlikel

Identification of Two DNMT3A Mutations Compromising Protein Stability and Methylation Capacity in Acute Myeloid Leukemia

Somatic mutations of DNMT3A occur in about 20% of acute myeloid leukemia (AML) patients. They mostly consist in heterozygous missense mutations targeting a hotspot site at R882 codon, which exhibit a dominant negative effect and are associated with high myeloblast count, advanced age, and poor prognosis. Other types of mutations such as truncations, insertions, or single-nucleotide deletion also affect the DNMT3A gene, though with lower frequency. The present study aimed to characterize two DNMT3A gene mutations identified by next-generation sequencing (NGS), through analysis of protein stability and DNA methylation status at CpG islands. The first mutation was a single-nucleotide variant of DNMT3A at exon 20 causing a premature STOP codon (c.2385G > A; p.Trp795 17; NM-022552.4). The DNMT3A mutation load increased from 4.5% to 38.2% during guadecitabine treatment, with a dominant negative effect on CpG methylation and on protein expression. The second mutation was a novel insertion of 35 nucleotides in exon 22 of DNMT3A (NM-022552.4) that introduced a STOP codon too, after the amino acid Glu863 caused by a frameshift insertion (c.2586-2587insTCATGAATGAGAAAGAGGACATCTTATGGTGCACT; p. Thr862-Glu863fsins). The mutation, which was associated with reduced DNMT3A expression and CpG methylation, persisted at relapse with minor changes in the methylation profile and at protein level. Our data highlight the need to better understand the consequences of DNMT3A mutations other than R882 substitutions in the leukemogenic process in order to tailor patient treatments, thus avoiding therapeutic resistance and disease relapse

Critical Currents and Vortex States at Fractional Matching Fields in Superconductors with Periodic Pinning

We study vortex states and dynamics in 2D superconductors with periodic pinning at fractional sub-matching fields using numerical simulations. For square pinning arrays we show that ordered states form at 1/1, 1/2, and 1/4 filling fractions while only partially ordered states form at other filling fractions, such as 1/3 and 1/5, in agreement with recent imaging experiments. For triangular pinning arrays we observe matching effects at filling fractions of 1/1, 6/7, 2/3, 1/3, 1/4, 1/6, and 1/7. For both square and triangular pinning arrays we also find that, for certian sub-matching fillings, vortex configurations depend on pinning strength. For weak pinning, ordering in which a portion of the vortices are positioned between pinning sites can occur. Depinning of the vortices at the matching fields, where the vortices are ordered, is elastic while at the incommensurate fields the motion is plastic. At the incommensurate fields, as the applied driving force is increased, there can be a transition to elastic flow where the vortices move along the pinning sites in 1D channels and a reordering transition to a triangular or distorted triangular lattice. We also discuss the current-voltage curves and how they relate to the vortex ordering at commensurate and incommensurate fields.Comment: 14 figure

Use of high-frequency ultrasound to study the prenatal development of cranial neural tube defects and hydrocephalus in Gldc-deficient mice

Objective: We used non-invasive high-frequency ultrasound (HFUS) imaging to investigate embryonic brain development in a mouse model for neural tube defects (NTDs) and non-ketotic hyperglycinemia (NKH). Method: Using HFUS, we imaged embryos carrying loss of function alleles of Gldc encoding glycine decarboxylase, a component of the glycine cleavage system in mitochondrial folate metabolism, which is known to be associated with cranial NTDs and NKH in humans. We serially examined the same litter during the second half of embryonic development and quantified cerebral structures. Genotype was confirmed using PCR. Histology was used to confirm ultrasound findings. Results: High-frequency ultrasound allowed in utero detection of two major brain abnormalities in Gldc-deficient mouse embryos, cranial NTDs (exencephaly) and ventriculomegaly (corresponding with the previous finding of post-natal hydrocephalus). Serial ultrasound allowed individual embryos to be analysed at successive gestational time points. From embryonic day 16.5 to 18.5, the lateral ventricle volume reduced in wild-type and heterozygous embryos but increased in homozygous Gldc-deficient embryos. Conclusion: Exencephaly and ventriculomegaly were detectable by HFUS in homozygous Gldc-deficient mouse embryos indicating this to be an effective tool to study CNS development. Longitudinal analysis of the same embryo allowed the prenatal onset and progression of ventricle enlargement in Gldc-deficient mice to be determined

Massive binary black holes in galactic nuclei and their path to coalescence

Massive binary black holes form at the centre of galaxies that experience a merger episode. They are expected to coalesce into a larger black hole, following the emission of gravitational waves. Coalescing massive binary black holes are among the loudest sources of gravitational waves in the Universe, and the detection of these events is at the frontier of contemporary astrophysics. Understanding the black hole binary formation path and dynamics in galaxy mergers is therefore mandatory. A key question poses: during a merger, will the black holes descend over time on closer orbits, form a Keplerian binary and coalesce shortly after? Here we review progress on the fate of black holes in both major and minor mergers of galaxies, either gas-free or gas-rich, in smooth and clumpy circum-nuclear discs after a galactic merger, and in circum-binary discs present on the smallest scales inside the relic nucleus.Comment: Accepted for publication in Space Science Reviews. To appear in hard cover in the Space Sciences Series of ISSI "The Physics of Accretion onto Black Holes" (Springer Publisher

Formation and Evolution of Supermassive Black Holes

The correlation between the mass of supermassive black holes in galaxy nuclei and the mass of the galaxy spheroids or bulges (or more precisely their central velocity dispersion), suggests a common formation scenario for galaxies and their central black holes. The growth of bulges and black holes can commonly proceed through external gas accretion or hierarchical mergers, and are both related to starbursts. Internal dynamical processes control and regulate the rate of mass accretion. Self-regulation and feedback are the key of the correlation. It is possible that the growth of one component, either BH or bulge, takes over, breaking the correlation, as in Narrow Line Seyfert 1 objects. The formation of supermassive black holes can begin early in the universe, from the collapse of Population III, and then through gas accretion. The active black holes can then play a significant role in the re-ionization of the universe. The nuclear activity is now frequently invoked as a feedback to star formation in galaxies, and even more spectacularly in cooling flows. The growth of SMBH is certainly there self-regulated. SMBHs perturb their local environment, and the mergers of binary SMBHs help to heat and destroy central stellar cusps. The interpretation of the X-ray background yields important constraints on the history of AGN activity and obscuration, and the census of AGN at low and at high redshifts reveals the downsizing effect, already observed for star formation. History appears quite different for bright QSO and low-luminosity AGN: the first grow rapidly at high z, and their number density decreases then sharply, while the density of low-luminosity objects peaks more recently, and then decreases smoothly.Comment: 31 pages, 13 figures, review paper for Astrophysics Update

Immunology of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) leading to demyelination, axonal damage, and progressive neurologic disability. The development of MS is influenced by environmental factors, particularly the Epstein-Barr virus (EBV), and genetic factors, which include specific HLA types, particularly DRB1*1501-DQA1*0102-DQB1*0602, and a predisposition to autoimmunity in general. MS patients have increased circulating T-cell and antibody reactivity to myelin proteins and gangliosides. It is proposed that the role of EBV is to infect autoreactive B cells that then seed the CNS and promote the survival of autoreactive T cells there. It is also proposed that the clinical attacks of relapsing-remitting MS are orchestrated by myelin-reactive T cells entering the white matter of the CNS from the blood, and that the progressive disability in primary and secondary progressive MS is caused by the action of autoantibodies produced in the CNS by ­meningeal lymphoid follicles with germinal centers

X-ray Survey Results on Active Galaxy Physics and Evolution

This "pedagogical" review describes the key Chandra and XMM-Newton extragalactic surveys to date and details some of their implications for AGN physics and evolution. We additionally highlight two topics of current widespread interest: (1) X-ray constraints on the AGN content of luminous submillimeter galaxies, and (2) the demography and physics of high-redshift (z > 4) AGN as revealed by X-ray observations. Finally, we discuss prospects for future X-ray surveys with Chandra, XMM-Newton, and upcoming missions.Comment: 26 pages, in Physics of Active Galactic Nuclei at All Scales, eds. Alloin D., Johnson R., Lira P. (Springer-Verlag, Berlin), version with all figures at http://www.astro.psu.edu/users/niel/papers/papers.htm