Distinct Mitochondrial Pathologies Caused by Mutations of the Proximal Tubular Enzymes EHHADH and GATM

The mitochondria of the proximal tubule are essential for providing energy in this nephron segment, whose ATP generation is almost exclusively oxygen dependent. In addition, mitochondria are involved in a variety of metabolic processes and complex signaling networks. Proximal tubular mitochondrial dysfunction can therefore affect renal function in very different ways. Two autosomal dominantly inherited forms of renal Fanconi syndrome illustrate how multifaceted mitochondrial pathology can be: Mutation of EHHADH, an enzyme in fatty acid metabolism, results in decreased ATP synthesis and a consecutive transport defect. In contrast, mutations of GATM, an enzyme in the creatine biosynthetic pathway, leave ATP synthesis unaffected but do lead to mitochondrial protein aggregates, inflammasome activation, and renal fibrosis with progressive renal failure. In this review article, the distinct pathophysiological mechanisms of these two diseases are presented, which are examples of the spectrum of proximal tubular mitochondrial diseases

2500-Channel single-shot areal profilometer using hyperspectral interferometry with a pinhole array

Surface profilometry techniques such as coherent scanning interferometry or focus variation require long scan times and are thus vulnerable to environmental disturbance. Hyperspectral interferometry (HSI) overcomes the problem by recording all the spatial and spectral information necessary to reconstruct a 2D surface height map in a single shot. In this paper, we present a new HSI system that uses a pinhole array to provide the necessary gaps for the spectral information. It is capable of measuring 2500 independent points, twice the previous maximum number, with a maximum unambiguous depth range of ∼825 µm and a larger maximum surface tilt angle of 33.3 mrad. The use of phase information allows height to be measured to a precision of ∼6 nm, an order of magnitude improvement on previous HSI systems

Double-shot 3-D displacement field measurement using hyperspectral interferometry

A combination of a Michelson interferometer, a micro-optic element and a hyperspectral imager is used with broadband illumination to measure depth-resolved out-of-plane displacements without any scanning. Reference and deformed states of a transparent sample are recorded in single shots and used to evaluate the displacement field at different interfaces

Reconstruction of longitudinal electrons bunch profiles at FACET, SLAC

Work supported by funding from Universite Paris Sud, program "Attractivite" and by the ANR under contract ANR-12-JS05-0003-01 - http://accelconf.web.cern.ch/AccelConf/IPAC2014/papers/thpme093.pdfInternational audienceThe E-203 collaboration is testing a device on FACET at SLAC to measure the longitudinal profile of electron bunches using Smith-Purcell radiation [1]. At FACET the electron bunches have an energy of 20 GeV and a duration of a few hundred femtoseconds [2]. Smith-Purcell radiation is emitted when a charged particle passes close to the sur- face of a metallic grating. We have studied the stability of the measurement from pulse to pulse and the resolution of the measure depending on the number of gratings used

Renal Fanconi syndrome: taking a proximal look at the nephron

Renal Fanconi syndrome (RFS) refers to the generalized dysfunction of the proximal tubule (PT) (Kleta R. Fanconi or not Fanconi? Lowe syndrome revisited. Clin J Am Soc Nephrol 2008; 3: 1244-1245). In its isolated form, RFS only affects the PT, but not the other nephron segments. The study of isolated RFS can thus provide specific insights into the function of the PT. In a recent paper, Klootwijk et al. investigated one such form of isolated RFS and revealed the underlying molecular basis (Klootwijk ED, Reichold M, Helip-Wooley A et al. Mistargeting of peroxisomal EHHADH and inherited renal Fanconi's syndrome. N Engl J Med 2014; 370: 129-138). The affected family had been described previously, demonstrating the typical features of RFS, such as low-molecular weight proteinuria, aminoaciduria, glycosuria and phosphaturia with consequent rickets; yet, importantly, patients had no evidence of impaired glomerular filtration (Tolaymat A, Sakarcan A, Neiberger R. Idiopathic Fanconi syndrome in a family. Part I. Clinical aspects. J Am Soc Nephrol 1992; 2: 1310-1317). Inheritance was consistent with an autosomal dominant mode. Klootwijk et al. discovered a surprising explanation: a heterozygous missense mutation causing partial mistargeting of the peroxisomal enzyme EHHADH to the mitochondria. Notably, disease causing was not the absence of the enzyme in the peroxisome, but its interference with mitochondrial function. The discovery of this novel disease mechanism not only confirmed the importance of mitochondrial function for PT transport, but also demonstrated the critical dependence of PT on fatty acid metabolism for energy generation

The STAR Time Projection Chamber: A Unique Tool for Studying High Multiplicity Events at RHIC

The STAR Time Projection Chamber (TPC) is used to record collisions at the Relativistic Heavy Ion Collider (RHIC). The TPC is the central element in a suite of detectors that surrounds the interaction vertex. The TPC provides complete coverage around the beam-line, and provides complete tracking for charged particles within +- 1.8 units of pseudo-rapidity of the center-of-mass frame. Charged particles with momenta greater than 100 MeV/c are recorded. Multiplicities in excess of 3,000 tracks per event are routinely reconstructed in the software. The TPC measures 4 m in diameter by 4.2 m long, making it the largest TPC in the world.Comment: 28 pages, 11 figure

Longitudinal Profile Monitor Using Smith-Purcell Radiation: Recent Results from the E-203 Collaboration

TUPC38 - Work supported by seed funding from the John Fell Fund, University of Oxford, Université Paris-Sud, program "Attractivité" and by the ANR under contract ANR-12-JS05-0003-01International audienceWe report on recent measurements made at FACET by the E-203 collaboration to test a longitudinal bunch profile monitor based on Coherent Smith-Purcell radiation. The capacity of this monitor to resolve sub-picosecond bunches will be shown as well as a comparison of profile reconstructed for different beam compression settings. We will also present recent electromagnetic simulations of the interactions between the beam and the grating as well as the expected resolution of such monitor. Comparison between Coherent Smith-Purcell radiation measurement and those made with other techniques will also be discussed. Finally future upgrades of the experiment and steps toward the construction of a single shot longitudinal profile monitor will be presented

One and two dimensional analysis of 3pi correlations measured in Pb+Pb interactions

3pi- correlations from Pb+Pb collisions at 158 GeV/c per nucleon are presented as measured by the focusing spectrometer of the NA44 experiment at CERN. The three-body effect is found to be stronger for PbPb than for SPb. The two-dimensional three-particle correlation function is also measured and the longitudinal extension of the source is larger than the transverse extension

Inclusive Search for Anomalous Production of High-pT Like-Sign Lepton Pairs in Proton-Antiproton Collisions at sqrt{s}=1.8 TeV

We report on a search for anomalous production of events with at least two charged, isolated, like-sign leptons with pT > 11 GeV/c using a 107 pb^-1 sample of 1.8 TeV ppbar collisions collected by the CDF detector. We define a signal region containing low background from Standard Model processes. To avoid bias, we fix the final cuts before examining the event yield in the signal region using control regions to test the Monte Carlo predictions. We observe no events in the signal region, consistent with an expectation of 0.63^(+0.84)_(-0.07) events. We present 95% confidence level limits on new physics processes in both a signature-based context as well as within a representative minimal supergravity (tanbeta = 3) model.Comment: 15 pages, 4 figures. Minor textual changes, cosmetic improvements to figures and updated and expanded reference