Beam Test with a GridGEM TPC Prototype Module

The International Large Detector (ILD) --a detector concept for the International Linear Collider (ILC)-- foresees a Time Projection Chamber (TPC) as its main tracking detector. Currently, the R&D efforts for such a TPC focus on studies using a large prototype that can accommodate up to seven read-out modules which are comparable to the ones that would be used in the final ILD TPC. The DESY TPC group has developed such a module using GEMs for the gas amplification, which are mounted on thin ceramic frames. The module design and first results of a test beam campaign are presented.Comment: 6 pages, 11 figures, prepared for LCWS 2011 proceeding

Syndromic forms of congenital hyperinsulinism

Congenital hyperinsulinism (CHI), also called hyperinsulinemic hypoglycemia (HH), is a very heterogeneous condition and represents the most common cause of severe and persistent hypoglycemia in infancy and childhood. The majority of cases in which a genetic cause can be identified have monogenic defects affecting pancreatic β-cells and their glucose-sensing system that regulates insulin secretion. However, CHI/HH has also been observed in a variety of syndromic disorders. The major categories of syndromes that have been found to be associated with CHI include overgrowth syndromes (e.g. Beckwith-Wiedemann and Sotos syndromes), chromosomal and monogenic developmental syndromes with postnatal growth failure (e.g. Turner, Kabuki, and Costello syndromes), congenital disorders of glycosylation, and syndromic channelopathies (e.g. Timothy syndrome). This article reviews syndromic conditions that have been asserted by the literature to be associated with CHI. We assess the evidence of the association, as well as the prevalence of CHI, its possible pathophysiology and its natural course in the respective conditions. In many of the CHI-associated syndromic conditions, the mechanism of dysregulation of glucose-sensing and insulin secretion is not completely understood and not directly related to known CHI genes. Moreover, in most of those syndromes the association seems to be inconsistent and the metabolic disturbance is transient. However, since neonatal hypoglycemia is an early sign of possible compromise in the newborn, which requires immediate diagnostic efforts and intervention, this symptom may be the first to bring a patient to medical attention. As a consequence, HH in a newborn or infant with associated congenital anomalies or additional medical issues remains a differential diagnostic challenge and may require a broad genetic workup

Clinical and Genetic Evaluation of Patients with KATP Channel Mutations from the German Registry for Congenital Hyperinsulinism

Congenital hyperinsulinism (CHI) causes hypoglycemia due to irregular insulin secretion. In infants, a rapid diagnosis and appropriate management to avoid severe hypoglycemia is mandatory. CHI is a heterogeneous condition at the clinical and genetic level, and disease-causing genes have been identified in about half of the patients. The majority of mutations have been identified in the ABCC8 and KCNJ11 genes encoding subunits of the KATP channel responsible for two distinct histological forms. The diffuse form is caused by autosomal recessive or dominant inherited mutations, whereas the focal form is caused by a paternally transmitted recessive mutation and a second somatic event. We report on an unselected cohort of 136 unrelated patients from the German CHI registry. Mutations in either the ABCC8 or KCNJ11 gene were identified in 61 of these patients (45%). In total, 64 different mutations including 38 novel ones were detected in this cohort. We observed biparental (recessive) inheritance in 34% of mutation-positive patients, dominant inheritance in 11% and paternal transmission of a mutation associated with a focal CHI type in 38%. In addition, we observed inheritance patterns that do not exactly follow the classical recessive or dominant mode, further adding to the genetic complexity of this disease

Linear response within the projection-based renormalization method: Many-body corrections beyond the random phase approximation

The explicit evaluation of linear response coefficients for interacting many-particle systems still poses a considerable challenge to theoreticians. In this work we use a novel many-particle renormalization technique, the so-called projector-based renormalization method, to show how such coefficients can systematically be evaluated. To demonstrate the prospects and power of our approach we consider the dynamical wave-vector dependent spin susceptibility of the two-dimensional Hubbard model and also determine the subsequent magnetic phase diagram close to half-filling. We show that the superior treatment of (Coulomb) correlation and fluctuation effects within the projector-based renormalization method significantly improves the standard random phase approximation results.Comment: 17 pages, 7 figures, revised versio

A Time Projection Chamber with GEM-Based Readout

For the International Large Detector concept at the planned International Linear Collider, the use of time projection chambers (TPC) with micro-pattern gas detector readout as the main tracking detector is investigated. In this paper, results from a prototype TPC, placed in a 1 T solenoidal field and read out with three independent GEM-based readout modules, are reported. The TPC was exposed to a 6 GeV electron beam at the DESY II synchrotron. The efficiency for reconstructing hits, the measurement of the drift velocity, the space point resolution and the control of field inhomogeneities are presented.Comment: 22 pages, 19 figure

Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency

Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease cases. A mutation in 1 of over 40 monogenic genes can be detected in approximately 30% of individuals with SRNS whose symptoms manifest before 25 years of age. However, in many patients, the genetic etiology remains unknown. Here, we have performed whole exome sequencing to identify recessive causes of SRNS. In 7 families with SRNS and facultative ichthyosis, adrenal insufficiency, immunodeficiency, and neurological defects, we identified 9 different recessive mutations in SGPL1, which encodes sphingosine-1-phosphate (S1P) lyase. All mutations resulted in reduced or absent SGPL1 protein and/or enzyme activity. Overexpression of cDNA representing SGPL1 mutations resulted in subcellular mislocalization of SGPL1. Furthermore, expression of WT human SGPL1 rescued growth of SGPL1-deficient dpl1. yeast strains, whereas expression of disease-associated variants did not. Immunofluorescence revealed SGPL1 expression in mouse podocytes and mesangial cells. Knockdown of Sgpl1 in rat mesangial cells inhibited cell migration, which was partially rescued by VPC23109, an S1P receptor antagonist. In Drosophila, Sply mutants, which lack SGPL1, displayed a phenotype reminiscent of nephrotic syndrome in nephrocytes. WT Sply, but not the disease-associated variants, rescued this phenotype. Together, these results indicate that SGPL1 mutations cause a syndromic form of SRNS

A Garfield++ interface for CST

This document introduces an interface developed for Garfield++, which allows to use field data calculated with the finite element based program CST. In addition, a comparison with a different finite element based program (ANSYS) is presented

Study of electrostatic distortions and possible corrections for a GEM based TPC readout module

In test beam data a partial reduced signal sensitivity of a GEM based readout module was observed. Electrostatic field simulations and subsequent electron drift studies to understand this problem were done and are presented here. It is shown, that distortions of the drift field introduced by the module itself can explain the observed effect. In addition, from the results of this study different possibilities of improvement are deduced and presented here. The presented approach to study field distortion is also applicable also to other problems

Vermessung von Feldinhomogenitäten in einem TPC Prototypen mittels eines UV Lasers

Einer der für den International Linear Collider (ILC) geplanten Detektoren (ILD) setzt auf die Verwendung einer Time Projection Chamber (TPC) als zentrale Spurkammer. Für die Signalverstärkung, welche zur Signalauslese im Fall einer TPC notwendig ist, werden im Rahmen der LCTPC Kollaboration verschiedene Ansätze untersucht. Einer dieser Ansätze beruht auf der Verwendung von Gas Electron Multiplier (GEM).Im November 2013 wurde ein TPC Prototyp mit 3 Auslesemodulen, welche GEMs zur Signalverstärkung nutzen, bestückt. Auf der Kathodenseite dieses Prototypen ist an bestimmmten Stellen die Kupferoberfläche entfernt worden unter der sich Aluminium befindet. Das sich daraus ergebende regelmäßige Muster aus Aluminium Punkten und Linien wurde mit Laserlicht der Wellenlänge 266 nm bestrahlt. Durch den Photoeffekt wurden dadurch Elektronen aus dem Aluminium gelöst, welche durch die Verstärkung der Auslesemodule aufgezeichnet wurden. Der Prototyp befand sich in einem Magneten der ein Magnetfeld von bis zu 1 T erzeugen kann. Es wurden Daten bei 0 T und 1 T genommen und die Ergebnisse der Datenauswertung werden hier vorgestellt. Durch eine Analyse der rekonstruierten Aluminiumpunkte lassen sich Erkenntnisse über Inhomogenitäten des elektrischen und magnetischen Feldes bzw. deren Kombination gewinnen