Pediatric Kawasaki Disease and Adult Human Immunodeficiency Virus Kawasaki-Like Syndrome Are Likely the Same Malady.

Background. Pediatric Kawasaki disease (KD) and human immunodeficiency virus (HIV)+ adult Kawasaki-like syndrome (KLS) are dramatic vasculitides with similar physical findings. Both syndromes include unusual arterial histopathology with immunoglobulin (Ig)A+ plasma cells, and both impressively respond to pooled Ig therapy. Their distinctive presentations, histopathology, and therapeutic response suggest a common etiology. Because blood is in immediate contact with inflamed arteries, we investigated whether KD and KLS share an inflammatory signature in serum.Methods. A custom multiplex enzyme-linked immunosorbent assay (ELISA) defined the serum cytokine milieu in 2 adults with KLS during acute and convalescent phases, with asymptomatic HIV+ subjects not taking antiretroviral therapy serving as controls. We then prospectively collected serum and plasma samples from children hospitalized with KD, unrelated febrile illnesses, and noninfectious conditions, analyzing them with a custom multiplex ELISA based on the KLS data.Results. Patients with KLS and KD subjects shared an inflammatory signature including acute-phase reactants reflecting tumor necrosis factor (TNF)-α biologic activity (soluble TNF receptor I/II) and endothelial/smooth muscle chemokines Ccl1 (Th2), Ccl2 (vascular inflammation), and Cxcl11 (plasma cell recruitment). Ccl1 was specifically elevated in KD versus febrile controls, suggesting a unique relationship between Ccl1 and KD/KLS pathogenesis.Conclusions. This study defines a KD/KLS inflammatory signature mirroring a dysfunctional response likely to a common etiologic agent. The KD/KLS inflammatory signature based on elevated acute-phase reactants and specific endothelial/smooth muscle chemokines was able to identify KD subjects versus febrile controls, and it may serve as a practicable diagnostic test for KD

Zooming into local active galactic nuclei: The power of combining SDSS-IV MaNGA with higher resolution integral field unit observations

Ionised gas outflows driven by active galactic nuclei (AGN) are ubiquitous in high luminosity AGN with outflow speeds apparently correlated with the total bolometric luminosity of the AGN. This empirical relation and theoretical work suggest that in the range L_bol ~ 10^43-45 erg/s there must exist a threshold luminosity above which the AGN becomes powerful enough to launch winds that will be able to escape the galaxy potential. In this paper, we present pilot observations of two AGN in this transitional range that were taken with the Gemini North Multi-Object Spectrograph Integral Field Unit (IFU). Both sources have also previously been observed within the Sloan Digital Sky Survey-IV (SDSS) Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey. While the MaNGA IFU maps probe the gas fields on galaxy-wide scales and show that some regions are dominated by AGN ionization, the new Gemini IFU data zoom into the centre with four times better spatial resolution. In the object with the lower L_bol we find evidence of a young or stalled biconical AGN-driven outflow where none was obvious at the MaNGA resolution. In the object with the higher L_bol we trace the large-scale biconical outflow into the nuclear region and connect the outflow from small to large scales. These observations suggest that AGN luminosity and galaxy potential are crucial in shaping wind launching and propagation in low-luminosity AGN. The transition from small and young outflows to galaxy-wide feedback can only be understood by combining large-scale IFU data that trace the galaxy velocity field with higher resolution, small scale IFU maps.Comment: 14 pages, accepted for publication in MNRA

The Hamiltonian formulation of General Relativity: myths and reality

A conventional wisdom often perpetuated in the literature states that: (i) a 3+1 decomposition of space-time into space and time is synonymous with the canonical treatment and this decomposition is essential for any Hamiltonian formulation of General Relativity (GR); (ii) the canonical treatment unavoidably breaks the symmetry between space and time in GR and the resulting algebra of constraints is not the algebra of four-dimensional diffeomorphism; (iii) according to some authors this algebra allows one to derive only spatial diffeomorphism or, according to others, a specific field-dependent and non-covariant four-dimensional diffeomorphism; (iv) the analyses of Dirac [Proc. Roy. Soc. A 246 (1958) 333] and of ADM [Arnowitt, Deser and Misner, in "Gravitation: An Introduction to Current Research" (1962) 227] of the canonical structure of GR are equivalent. We provide some general reasons why these statements should be questioned. Points (i-iii) have been shown to be incorrect in [Kiriushcheva et al., Phys. Lett. A 372 (2008) 5101] and now we thoroughly re-examine all steps of the Dirac Hamiltonian formulation of GR. We show that points (i-iii) above cannot be attributed to the Dirac Hamiltonian formulation of GR. We also demonstrate that ADM and Dirac formulations are related by a transformation of phase-space variables from the metric $g_{\mu\nu}$ to lapse and shift functions and the three-metric $g_{km}$, which is not canonical. This proves that point (iv) is incorrect. Points (i-iii) are mere consequences of using a non-canonical change of variables and are not an intrinsic property of either the Hamilton-Dirac approach to constrained systems or Einstein's theory itself.Comment: References are added and updated, Introduction is extended, Subsection 3.5 is added, 83 pages; corresponds to the published versio

Human rights and community work. Complementary theories and practices

Much effort has been placed on developing international understandings of human rights without the corresponding attention to responsibilities. The authors argue that a community development framework may be useful in re-conceiving human rights in a more holistic way, and that social workers and community development workers are well placed to be 'grass roots human rights workers

Black Holes in the Early Universe

The existence of massive black holes was postulated in the sixties, when the first quasars were discovered. In the late nineties their reality was proven beyond doubt, in the Milky way and a handful nearby galaxies. Since then, enormous theoretical and observational efforts have been made to understand the astrophysics of massive black holes. We have discovered that some of the most massive black holes known, weighing billions of solar masses, powered luminous quasars within the first billion years of the Universe. The first massive black holes must therefore have formed around the time the first stars and galaxies formed. Dynamical evidence also indicates that black holes with masses of millions to billions of solar masses ordinarily dwell in the centers of today's galaxies. Massive black holes populate galaxy centers today, and shone as quasars in the past; the quiescent black holes that we detect now in nearby bulges are the dormant remnants of this fiery past. In this review we report on basic, but critical, questions regarding the cosmological significance of massive black holes. What physical mechanisms lead to the formation of the first massive black holes? How massive were the initial massive black hole seeds? When and where did they form? How is the growth of black holes linked to that of their host galaxy? Answers to most of these questions are work in progress, in the spirit of these Reports on Progress in Physics.Comment: Reports on Progress in Physics, in pres

On the co-evolution of supermassive black holes and their host galaxies since z = 3

[Abridged] To investigate the evolution in the relation between galaxy stellar and central black hole mass we construct a volume limited complete sample of 85 AGN with host galaxy stellar masses M_{*} > 10^{10.5} M_{sol}, and specific X-ray luminosities L_{X} > 2.35 x 10^{43} erg s^{-1} at 0.4 < z < 3. We calculate the Eddington limiting masses of the supermassive black holes residing at the centre of these galaxies, and observe an increase in the average Eddington limiting black hole mass with redshift. By assuming that there is no evolution in the Eddington ratio (\mu) and then that there is maximum possible evolution to the Eddington limit, we quantify the maximum possible evolution in the M_{*} / M_{BH} ratio as lying in the range 700 < M_{*}/M_{BH} < 10000, compared with the local value of M_{*}/M_{BH} ~ 1000. We furthermore find that the fraction of galaxies which are AGN (with L_{X} > 2.35 x 10^{43} erg s^{-1}) rises with redshift from 1.2 +/- 0.2 % at z = 0.7 to 7.4 +/- 2.0 % at z = 2.5. We use our results to calculate the maximum timescales for which our sample of AGN can continue to accrete at their observed rates before surpassing the local galaxy-black hole mass relation. We use these timescales to calculate the total fraction of massive galaxies which will be active (with L_{X} > 2.35 x 10^{43} erg s^{-1}) since z = 3, finding that at least ~ 40% of all massive galaxies will be Seyfert luminosity AGN or brighter during this epoch. Further, we calculate the energy density due to AGN activity in the Universe as 1.0 (+/- 0.3) x 10^{57} erg Mpc^{-3} Gyr^{-1}, potentially providing a significant source of energy for AGN feedback on star formation. We also use this method to compute the evolution in the X-ray luminosity density of AGN with redshift, finding that massive galaxy Seyfert luminosity AGN are the dominant source of X-ray emission in the Universe at z < 3.Comment: 25 pages, 10 figures, accepted for publication in MNRA

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio