Genetic Modifiers of Mendelian Monogenic Collagen IV Nephropathies in Humans and Mice

Familial hematuria is a clinical sign of a genetically heterogeneous group of conditions, accompanied by broad inter- and intrafamilial variable expressivity. The most frequent condition is caused by pathogenic (or likely pathogenic) variants in the collagen-IV genes, COL4A3/A4/A5. Pathogenic variants in COL4A5 are responsible for the severe X-linked glomerulopathy, Alport syndrome (AS), while homozygous or compound heterozygous variants in the COL4A3 or the COL4A4 gene cause autosomal recessive AS. AS usually leads to progressive kidney failure before the age of 40-years when left untreated. People who inherit heterozygous COL4A3/A4 variants are at-risk of a slowly progressive form of the disease, starting with microscopic hematuria in early childhood, developing Alport spectrum nephropathy. Sometimes, they are diagnosed with benign familial hematuria, and sometimes with autosomal dominant AS. At diagnosis, they often show thin basement membrane nephropathy, reflecting the uniform thin glomerular basement membrane lesion, inherited as an autosomal dominant condition. On a long follow-up, most patients will retain normal or mildly affected kidney function, while a substantial proportion will develop chronic kidney disease (CKD), even kidney failure at an average age of 55-years. A question that remains unanswered is how to distinguish those patients with AS or with heterozygous COL4A3/A4 variants who will manifest a more aggressive kidney function decline, requiring prompt medical intervention. The hypothesis that a subgroup of patients coinherit additional genetic modifiers that exacerbate their clinical course has been investigated by several researchers. Here, we review all publications that describe the potential role of candidate genetic modifiers in patients and include a summary of studies in AS mouse models

A nonsmooth frictional contact formulation for multibody system dynamics

We present a new node-to-face frictional contact element for the simulation of the nonsmooth dynamics of systems composed of rigid and flexible bodies connected by kinematic joints. The equations of motion are integrated using a nonsmooth generalized-α time integration scheme and the frictional contact problem is formulated using a mixed approach, based on an augmented Lagrangian technique and a Coulomb friction law. The numerical results are independent of any user-defined penalty parameter for the normal or tangential component of the forces and, the bilateral and the unilateral constraints are exactly fulfilled both at position and velocity levels. Finally, the robustness and the performance of the proposed algorithm are demonstrated by solving several numerical examples of nonsmooth mechanical systems involving frictional contact.Fil: Galvez, Javier. Université de Liège; BélgicaFil: Cavalieri, Federico José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones en Métodos Computacionales. Universidad Nacional del Litoral. Centro de Investigaciones en Métodos Computacionales; ArgentinaFil: Cosimo, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones en Métodos Computacionales. Universidad Nacional del Litoral. Centro de Investigaciones en Métodos Computacionales; Argentina. Université de Liège; BélgicaFil: Brüls, Olivier. Université de Liège; BélgicaFil: Cardona, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones en Métodos Computacionales. Universidad Nacional del Litoral. Centro de Investigaciones en Métodos Computacionales; Argentin

A synchrotron self-Compton model with low energy electron cut-off for the blazar S5 0716+714

Rapid inverse Compton cooling sets in when the brightness temperature (T_B) of a self-absorbed synchrotron source with power-law electrons reaches ~10^{12} K. However, T_B inferred from observations of intra-day variable sources (IDV) are well above the "Compton catastrophe" limit. This can be understood if the underlying electron distribution cuts off at low energy. We approximate a low-energy cut-off with monoenergetic electrons. We compute the synchrotron self-Compton (SSC) spectrum of such distribution, and using the IDV source S5~0716+714 as an example, we compare it to the observed SED of S5~0716+714. The hard radio spectrum is well-fitted by this model, and the optical data can be accommodated by a power-law extension to the electron spectrum. We therefore examine the scenario of an injection of electrons that is a double power law in energy with a hard low-energy component that does not contribute to the synchrotron opacity. We show that the double power-law injection model is in good agreement with the observed SED of S5~0716+714. For intrinsic variability, we find that a Doppler factor of D\geq30 can explain the observed SED provided that low-frequency (<32 GHz) emission originates from a larger region than the higher-frequency emission. To fit the entire spectrum, D\geq65 is needed. We find the constraint imposed by induced Compton scattering at high T_B is insignificant in our model. We confirm that electron distribution with a low-energy cut-off can explain the high T_B in compact radio sources. We show that synchrotron spectrum from such distributions naturally accounts for the observed hard radio continuum with a softer optical component, without the need for an inhomogeneous source.Comment: 13 pages, 5 figures, 1 table, to appear in A&A; refereces removed from caption of Fig.3, added acknowledgemen

The extended counterpart of submm source Lockman850.1

The IRAM Plateau de Bure mm interferometer and deep K-band imaging have been used to identify the brightest submm source detected in the Lockman field of the UK 8mJy SCUBA survey. The near infrared counterpart is an extended (20-30kpc), clumpy, and extremely red object. The spectral energy distribution suggests it to be a dusty star forming object at a redshift of about 3 (2-4). Its star formation rate and near-infrared properties are consistent with Lockman850.1 being a massive elliptical in formation.Comment: 4 ps/eps figures. To appear in A&

A Herschel PACS and SPIRE study of the dust content of the Cassiopeia A supernova remnant

Using the 3.5-m Herschel Space Observatory, imaging photometry of Cas A has been obtained in six bands between 70 and 500 μm with the PACS and SPIRE instruments, with angular resolutions ranging from 6 to 37”. In the outer regions of the remnant the 70-μm PACS image resembles the 24-μm image Spitzer image, with the emission attributed to the same warm dust component, located in the reverse shock region. At longer wavelengths, the three SPIRE bands are increasingly dominated by emission from cold interstellar dust knots and filaments, particularly across the central, western and southern parts of the remnant. Nonthermal emission from the northern part of the remnant becomes prominent at 500 μm. We have estimated and subtracted the contributions from the nonthermal, warm dust and cold interstellar dust components. We confirm and resolve for the first time a cool (~35 K) dust component, emitting at 70-160 μm, that is located interior to the reverse shock region, with an estimated mass of 0.075

QUaD: A High-Resolution Cosmic Microwave Background Polarimeter

We describe the QUaD experiment, a millimeter-wavelength polarimeter designed to observe the Cosmic Microwave Background (CMB) from a site at the South Pole. The experiment comprises a 2.64 m Cassegrain telescope equipped with a cryogenically cooled receiver containing an array of 62 polarization-sensitive bolometers. The focal plane contains pixels at two different frequency bands, 100 GHz and 150 GHz, with angular resolutions of 5 arcmin and 3.5 arcmin, respectively. The high angular resolution allows observation of CMB temperature and polarization anisotropies over a wide range of scales. The instrument commenced operation in early 2005 and collected science data during three successive Austral winter seasons of observation.Comment: 23 pages, author list and text updated to reflect published versio

Second and third season QUaD CMB temperature and polarization power spectra

We report results from the second and third seasons of observation with the QUaD experiment. Angular power spectra of the Cosmic Microwave Background are derived for both temperature and polarization at both 100 GHz and 150 GHz, and as cross frequency spectra. All spectra are subjected to an extensive set of jackknife tests to probe for possible systematic contamination. For the implemented data cuts and processing technique such contamination is undetectable. We analyze the difference map formed between the 100 and 150 GHz bands and find no evidence of foreground contamination in polarization. The spectra are then combined to form a single set of results which are shown to be consistent with the prevailing LCDM model. The sensitivity of the polarization results is considerably better than that of any previous experiment -- for the first time multiple acoustic peaks are detected in the E-mode power spectrum at high significance.Comment: 24 pages, 23 figures, updated to reflect published versio