Nephronophthisis: a genetically diverse ciliopathy.

Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease and a leading genetic cause of established renal failure (ERF) in children and young adults. Early presenting symptoms in children with NPHP include polyuria, nocturia, or secondary enuresis, pointing to a urinary concentrating defect. Renal ultrasound typically shows normal kidney size with increased echogenicity and corticomedullary cysts. Importantly, NPHP is associated with extra renal manifestations in 10-15% of patients. The most frequent extrarenal association is retinal degeneration, leading to blindness. Increasingly, molecular genetic testing is being utilised to diagnose NPHP and avoid the need for a renal biopsy. In this paper, we discuss the latest understanding in the molecular and cellular pathogenesis of NPHP. We suggest an appropriate clinical management plan and screening programme for individuals with NPHP and their families

Liquid–liquid equilibrium in polymer–fullerene mixtures; an in situ neutron reflectivity study

The composition profiles of a series of model polystyrene/fullerene bilayers are measured, before, during and after thermal annealing, using in situ neutron reflectometry. In combination with grazing-incidence X-ray diffraction measurements, these experiments, which quantify layer compositions as a function of molecular weight using changes in both scattering length density and layer thickness, extend and corroborate recent measurements on ex situ annealed samples and demonstrate that the composition profiles rapidly formed in these systems correspond to two co-existing liquid–liquid phases in thermodynamic equilibrium. The measurements also demonstrate a clear and systematic onset temperature for diffusion of the fullerenes into the PS layer that correlates with the known glass-transition temperatures of both the polymer (as a function of molecular weight) and the fullerene, revealing that the molecular mobility of the fullerenes in these systems is controlled by the intrinsic mobility of the fullerenes themselves and the ability of the polymer to plasticise the fullerenes at the interface. Over the temperature range investigated (up to 145 °C), measurements of equilibrated composition profiles as a function of temperature (during gradual cooling) reveal no significant changes in composition profile, other than those associated with the known thermal expansion/contraction of polystyrene thin-films

Functional modelling of a novel mutation in BBS5.

BACKGROUND: Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy disorder with 18 known causative genes (BBS1-18). The primary clinical features are renal abnormalities, rod-cone dystrophy, post-axial polydactyly, learning difficulties, obesity and male hypogonadism. RESULTS: We describe the clinical phenotype in three Saudi siblings in whom we have identified a novel mutation in exon 12 of BBS5 (c.966dupT; p.Ala323CysfsX57). This single nucleotide duplication creates a frame shift results in a predicted elongated peptide. Translation blocking Morpholino oligonucleotides were used to create zebrafish bbs5 morphants. Morphants displayed retinal layering defects, abnormal cardiac looping and dilated, cystic pronephric ducts with reduced cilia expression. Morphants also displayed significantly reduced dextran clearance via the pronephros compared to wildtype embryos, suggesting reduced renal function in morphants. The eye, kidney and heart defects reported in morphant zebrafish resemble the human phenotype of BBS5 mutations. The pathogenicity of the novel BBS5 mutation was determined. Mutant mRNA was unable to rescue pleiotropic phenotypes of bbs5 morphant zebrafish and in cell culture we demonstrate a mislocalisation of mutant BBS5 protein which fails to localise discretely with the basal body. CONCLUSIONS: We conclude that this novel BBS5 mutation has a deleterious function that accounts for the multisystem ciliopathy phenotype seen in affected human patients

Мультипарадигмальний підхід до аналізу феномену нігілізму

У статті розглянуто нігілізм як неоднозначне й поліморфне поняття. Досліджено різні підходи до тлумачення та розв’язання питань, пов’язаних із нігілізмом. Розкрито людиномірність нігілізму в контексті відстеження варіативного смислового навантаження феномену. Встановлено, що нігілізм потрібно позиціонувати як спосіб пробудження людського духу, заперечення деструктивного конформізму й відсутності опору (пасивний песимізм).В статье рассмотрен нигилизм как неоднозначное и полиморфное понятие. Исследованы различные подходы к толкованию и решению вопросов, связанных с нигилизмом. Раскрыта человекомерность нигилизма в контексте отслеживания вариативной смысловой нагрузки феномена. Установлено, что нигилизм нужно позиционировать как способ пробуждения человеческого духа, отрицание деструктивного конформизма и отсутствия сопротивления (пассивный пессимизм).Nihilism is considered as ambiguous and polymorphic concept. Different approaches to the interpretation and solution of issues associated with nihilism are investigated. Human measurement of nihilism in the context of tracking meaning of varied semantic capacity of the phenomenon is revealed. It is determined that nihilism must be positioned as a way of awakening of the human spirit, denial of destructive conformism and absence of resistance (passive pessimism)

Modelling spectral and timing properties of accreting black holes: the hybrid hot flow paradigm

The general picture that emerged by the end of 1990s from a large set of optical and X-ray, spectral and timing data was that the X-rays are produced in the innermost hot part of the accretion flow, while the optical/infrared (OIR) emission is mainly produced by the irradiated outer thin accretion disc. Recent multiwavelength observations of Galactic black hole transients show that the situation is not so simple. Fast variability in the OIR band, OIR excesses above the thermal emission and a complicated interplay between the X-ray and the OIR light curves imply that the OIR emitting region is much more compact. One of the popular hypotheses is that the jet contributes to the OIR emission and even is responsible for the bulk of the X-rays. However, this scenario is largely ad hoc and is in contradiction with many previously established facts. Alternatively, the hot accretion flow, known to be consistent with the X-ray spectral and timing data, is also a viable candidate to produce the OIR radiation. The hot-flow scenario naturally explains the power-law like OIR spectra, fast OIR variability and its complex relation to the X-rays if the hot flow contains non-thermal electrons (even in energetically negligible quantities), which are required by the presence of the MeV tail in Cyg X-1. The presence of non-thermal electrons also lowers the equilibrium electron temperature in the hot flow model to <100 keV, making it more consistent with observations. Here we argue that any viable model should simultaneously explain a large set of spectral and timing data and show that the hybrid (thermal/non-thermal) hot flow model satisfies most of the constraints.Comment: 26 pages, 13 figures. To be published in the Space Science Reviews and as hard cover in the Space Sciences Series of ISSI - The Physics of Accretion on to Black Holes (Springer Publisher

Interfacial width and phase equilibrium in polymer-fullerene thin-films

Domain composition and interfacial structure are critical factors in organic photovoltaic performance. Here, we report neutron reflectivity, grazing-incidence X-ray diffraction and atomic force microscopy measurements of polymer/fullerene thin-films to test a hypothesis that these partially miscible blends rapidly develop composition profiles consisting of co-existing phases in liquid-liquid equilibrium. We study a range of polymer molecular weights between 2 and 300 kg mol−1, annealing temperatures between 120 and 170 oC, and timescales up to 10 min, yielding over 50 distinct measurement conditions. Model bilayers of fullerene-derivatives and polystyrene enable a rigorous examination of theoretical predictions of the effect of polymer mass and interaction parameter on the compositions, ϕ, and interfacial width, w, of the coexistent phases. We independently measure ϕ and w and find that both Flory-Huggins mean-field-theory and key aspects of self-consistent-field-theory are remarkably consistent with experiment. Our findings pave the way for predictive composition and interface design in organic photovoltaics based on simple experimental measurements and equilibrium thermodynamic theory

Jet disc coupling in black hole binaries

In the last decade multi-wavelength observations have demonstrated the importance of jets in the energy output of accreting black hole binaries. The observed correlations between the presence of a jet and the state of the accretion flow provide important information on the coupling between accretion and ejection processes. After a brief review of the properties of black hole binaries, I illustrate the connection between accretion and ejection through two particularly interesting examples. First, an INTEGRAL observation of Cygnus X-1 during a 'mini-' state transition reveals disc jet coupling on time scales of orders of hours. Second, the black hole XTEJ1118+480 shows complex correlations between the X-ray and optical emission. Those correlations are interpreted in terms of coupling between disc and jet on time scales of seconds or less. Those observations are discussed in the framework of current models.Comment: Invited talk at the Fifth Stromlo Symposium: Disks, Winds & Jets - from Planets to Quasars. Accepted for publication in Astrophysics & Space Scienc

Radio emission and jets from microquasars

To some extent, all Galactic binary systems hosting a compact object are potential `microquasars', so much as all galactic nuclei may have been quasars, once upon a time. The necessary ingredients for a compact object of stellar mass to qualify as a microquasar seem to be: accretion, rotation and magnetic field. The presence of a black hole may help, but is not strictly required, since neutron star X-ray binaries and dwarf novae can be powerful jet sources as well. The above issues are broadly discussed throughout this Chapter, with a a rather trivial question in mind: why do we care? In other words: are jets a negligible phenomenon in terms of accretion power, or do they contribute significantly to dissipating gravitational potential energy? How do they influence their surroundings? The latter point is especially relevant in a broader context, as there is mounting evidence that outflows powered by super-massive black holes in external galaxies may play a crucial role in regulating the evolution of cosmic structures. Microquasars can also be thought of as a form of quasars for the impatient: what makes them appealing, despite their low number statistics with respect to quasars, are the fast variability time-scales. In the first approximation, the physics of the jet-accretion coupling in the innermost regions should be set by the mass/size of the accretor: stellar mass objects vary on 10^5-10^8 times shorter time-scales, making it possible to study variable accretion modes and related ejection phenomena over average Ph.D. time-scales. [Abridged]Comment: 28 pages, 13 figures, To appear in Belloni, T. (ed.): The Jet Paradigm - From Microquasars to Quasars, Lect. Notes Phys. 794 (2009

The evolutionary status of the semiregular variable QYSge

Repeated spectroscopic observations made with the 6m telescope of yielded new data on the radial-velocity variability of the anomalous yellow supergiant QYSge. The strongest and most peculiar feature in its spectrum is the complex profile of NaI D lines, which contains a narrow and a very wide emission components. The wide emission component can be seen to extend from -170 to +120 km/s, and at its central part it is cut by an absorption feature, which, in turn, is split into two subcomponents by a narrow (16km/s at r=2.5) emission peak. An analysis of all the Vr values leads us to adopt for the star a systemic velocity of Vr=-21.1 km/s, which corresponds to the position of the narrow emission component of NaI. The locations of emission-line features of NaI D lines are invariable, which point to their formation in regions that are external to the supergiant's photosphere. Differential line shifts of about 10km/s are revealed. The absorption lines in the spectrum of QYSge have a substantial width of FWHM~45 km/s. The method of model atmospheres is used to determine the following parameters: Teff=6250K, lg g=2.0, and microturbulence Vt=4.5km/s. The metallicity of the star is found to be somewhat higher than the solar one with an average overabundance of iron-peak elements of [Met/H]=+0.20. The star is found to be slightly overabundant in carbon and nitrogen, [C/Fe]=+0.25, [N/Fe]=+0.27. The alpha-process elements Mg, Si, and Ca are slightly overabundant [alpha/H]=+0.12. The strong sodium excess, [Na/Fe]=+0.75, is likely to be due to the dredge-up of the matter processed in the NeNa cycle. Heavy elements of the s-process are underabundant relative to the Sun. On the whole, the observed properties of QYSge do not give grounds for including this star into the group of RCrB or RVTau-type type objects.Comment: 29 pages, 8 figures, 4 tables; accepted by Astrophys. Bulleti

The balance of power: accretion and feedback in stellar mass black holes

In this review we discuss the population of stellar-mass black holes in our galaxy and beyond, which are the extreme endpoints of massive star evolution. In particular we focus on how we can attempt to balance the available accretion energy with feedback to the environment via radiation, jets and winds, considering also possible contributions to the energy balance from black hole spin and advection. We review quantitatively the methods which are used to estimate these quantities, regardless of the details of the astrophysics close to the black hole. Once these methods have been outlined, we work through an outburst of a black hole X-ray binary system, estimating the flow of mass and energy through the different accretion rates and states. While we focus on feedback from stellar mass black holes in X-ray binary systems, we also consider the applicability of what we have learned to supermassive black holes in active galactic nuclei. As an important control sample we also review the coupling between accretion and feedback in neutron stars, and show that it is very similar to that observed in black holes, which strongly constrains how much of the astrophysics of feedback can be unique to black holes.Comment: To be published in Haardt et al. Astrophysical Black Holes. Lecture Notes in Physics. Springer 201