Identification of Deletions in the Hdc Gene of Drosophila Melanogaster Generated Through Transposon-Excision Mutagenesis

Histamine is a biogenic amine that functions as a neurotransmitter in a number of vertebrate and invertebrate systems and is synthesized from its precursor histidine by the enzyme histidine decarboxylase (HDC). In Drosophila, histamine has been shown to have function in photoreceptors, mechanoreceptor cells, as well as centrally located neurons. Mutations of the Hdc gene, such as HdcJK910, exhibit defects in histamine synthesis and display altered behaviors such as blindness, inability to groom, impaired thermal tolerance, and altered sleep rhythms. However, all Hdc mutants obtained thus far demonstrate some transcriptional activity. In order to remove Hdc expression completely, part of the Hdc gene was removed via Minos transposon-excision mutagenesis using the Mi{ET1}HdcMB07212 fly, which bears a Minos transposon within the Hdc gene (a hypo-morphic allele). Minos excision mutagenesis of Hdc was achieved by mating flies from the HdcMB07212 strain with another fly carrying the Minos-specific transposase gene – to induce imprecise excision in the progeny\u27s genome to cause a deletion. The Mi{ET1} transposon also contains a gene encoding the green fluorescent protein (GFP) under the control of an eye-specific promoter, the loss of which can be used to visually identify a potential Minos excision. Once loss of GFP (GFP-) individuals were identified, breeding lines were established and flies from each line examined using histamine immunostaining to determine the presence or absence of histamine in the ventral nerve cord of larvae. Progeny obtained fell into the following categories: (1) flies with wild-type levels of histamine, indicating rescue of Hdc expression due to a precise Minos excision from Hdc; (2) flies with trace levels of histamine, indicating an excision event that disrupted GFP expression from the Mi{ET1} transposon but did not rescue Hdc expression; (3) flies having no histamine, 4 indicating an imprecise excision with an associated loss of expression from the Hdc gene. Molecular lesions associated with each class of flies were characterized using a PCR approach. Results indicate that of the 98 GFP- strains examined thus far each fell into one of the 3 expected categories, with 29 exhibiting elimination of Hdc expression

Opera omnia Desiderii Erasmi

• Adagiorum chilias IV, centuriae VI-X; chilias V, centuriae I-II. [Adagia 3501-4151

Multigrid optimization for space-time discontinuous Galerkin discretizations of advection dominated flows

The goal of this research is to optimize multigrid methods for higher order accurate space-time discontinuous Galerkin discretizations. The main analysis tool is discrete Fourier analysis of two- and three-level multigrid algorithms. This gives the spectral radius of the error transformation operator which predicts the asymptotic rate of convergence of the multigrid algorithm. In the optimization process we therefore choose to minimize the spectral radius of the error transformation operator. We specifically consider optimizing h-multigrid methods with explicit Runge-Kutta type smoothers for second and third order accurate space-time discontinuous Galerkin finite element discretizations of the 2D advection-diffusion equation. The optimized schemes are compared with current h-multigrid techniques employing Runge-Kutta type smoothers. Also, the efficiency of h-, p- and hp-multigrid methods for solving the Euler equations of gas dynamics with a higher order accurate space-time DG method is investigated

Subjektive Bewertung einer kieferorthopädisch-kieferchirurgischen Kombinationstherapie

In einer retrospektiven Studie wurden 756 Patienten, die sich zwischen Januar 1987 und April 2000 in der Mund- und Kiefergesichtschirurgischen Abteilung der Westfälischen Wilhelms-Universität Münster einer Dysgnathieoperation unterzogen, ein Fragebogen zugesandt. Die Rücklaufquote betrug 39,6%. Das Verhältnis von Frauen zu Männern betrug 68,2% zu 31,8%. 57,2% der Patienten unterzogen sich einem Eingriff im Unterkiefer, 19,7% im Oberkiefer und 23,1% der Patienten wurden bimaxillär operiert. Hauptgrund für die Durchführung der Operation war die Kieferfehlstellung , an zweiter Stelle die Ästhetik/das Aussehen. Die Erwartungen der Patienten in Bezug auf Ästhetik, Kau- und Sprachfunktion haben sich in fast ¾ der Fälle gut erfüllt. 81,6% der Patienten würden die Operation noch einmal durchführen lassen. Die Resonanz im Umfeld des Münsteraner Kollektivs war durchweg positiv, in etwas mehr als 75% der Fälle haben sich die Erwartungen in Bezug auf Ästhetik und Sprachfunktion erfüllt

Perinatal Inhibition of NF-KappaB Has Long-Term Antihypertensive and Renoprotective Effects in Fawn-Hooded Hypertensive Rats

BACKGROUND Inhibition of transcription factor nuclear factor-kappa B (NFκB) is beneficial in various models of hypertension and renal disease. We hypothesized first that NFκB inhibition during renal development ameliorates hereditary hypertensive renal disease and next whether this was mediated via suppression of peroxisome proliferator-activated receptor (PPAR)γ coactivator 1α (PGC-1α). METHODS AND RESULTS Prior to the development of renal injury in fawn-hooded hypertensive (FHH) rats, a model of hypertension, glomerular hyperfiltration, and progressive renal injury, NFkB activity, measured by nuclear protein expression of NFkB subunit p65, was enhanced twofold in 2-day-old male and female FHH kidneys as compared to normotensive Wistar-Kyoto (WKY) rats (P <0.05). Treating FHH dams with pyrrolidine di thio carbamate (PDTC), an NFκB inhibitor, from 2 weeks before birth to 4 weeks after birth diminished NFkB activity in 2-day-FHH offspring to 2-day-WKY levels (P <0.01). Perinatal PDTC reduced systolic blood pressure from 20 weeks onwards by on average 25mm Hg (P <0.001) and ameliorated proteinuria (P <0.05) and glomerulosclerosis (P <0.05). In kidneys of 2-day-, 2-week-, and adult offspring of PDTC-treated FHH dams, PGC-1α was induced on average by 67% (quantitative polymerase chain reaction (qPCR)) suggesting that suppression of this factor by NFkB could be involved in renal damage. Follow-up experiments with perinatal pioglitazone (Pio), a PPARγ agonist, failed to confer persistent antihypertensive or renoprotective effects. CONCLUSIONS Perinatal inhibition of enhanced active renal NFκB in 2-day FHH had persistent antihypertensive and renoprotective effects. However, this was not the case for PPARγ stimulation. NFkB stimulation is therefore involved in renal damage in the FHH model of proteinuric renal disease by pathways other than via PPARγ.</p

Finite Element Analysis of Custom Shoulder Implants Provides Accurate Prediction of Initial Stability

Custom reverse shoulder implants represent a valuable solution for patients with large bone defects. Since each implant has unique patient-specific features, finite element (FE) analysis has the potential to guide the design process by virtually comparing the stability of multiple configurations without the need of a mechanical test. The aim of this study was to develop an automated virtual bench test to evaluate the initial stability of custom shoulder implants during the design phase, by simulating a fixation experiment as defined by ASTM F2028-14. Three-dimensional (3D) FE models were generated to simulate the stability test and the predictions were compared to experimental measurements. Good agreement was found between the baseplate displacement measured experimentally and determined from the FE analysis (Spearman’s rank test, p < 0.05, correlation coefficient ¿s = 0.81). Interface micromotion analysis predicted good initial fixation (micromotion <150 µm, commonly used as bone ingrowth threshold). In conclusion, the finite element model presented in this study was able to replicate the mechanical condition of a standard test for a custom shoulder implants

Optimal, scalable forward models for computing gravity anomalies

We describe three approaches for computing a gravity signal from a density anomaly. The first approach consists of the classical "summation" technique, whilst the remaining two methods solve the Poisson problem for the gravitational potential using either a Finite Element (FE) discretization employing a multilevel preconditioner, or a Green's function evaluated with the Fast Multipole Method (FMM). The methods utilizing the PDE formulation described here differ from previously published approaches used in gravity modeling in that they are optimal, implying that both the memory and computational time required scale linearly with respect to the number of unknowns in the potential field. Additionally, all of the implementations presented here are developed such that the computations can be performed in a massively parallel, distributed memory computing environment. Through numerical experiments, we compare the methods on the basis of their discretization error, CPU time and parallel scalability. We demonstrate the parallel scalability of all these techniques by running forward models with up to $10^8$ voxels on 1000's of cores.Comment: 38 pages, 13 figures; accepted by Geophysical Journal Internationa

Geodynamo and mantle convection simulations on the Earth Simulator using the Yin-Yang grid

We have developed finite difference codes based on the Yin-Yang grid for the geodynamo simulation and the mantle convection simulation. The Yin-Yang grid is a kind of spherical overset grid that is composed of two identical component grids. The intrinsic simplicity of the mesh configuration of the Yin-Yang grid enables us to develop highly optimized simulation codes on massively parallel supercomputers. The Yin-Yang geodynamo code has achieved 15.2 Tflops with 4096 processors on the Earth Simulator. This represents 46% of the theoretical peak performance. The Yin-Yang mantle code has enabled us to carry out mantle convection simulations in realistic regimes with a Rayleigh number of $10^7$ including strongly temperature-dependent viscosity with spatial contrast up to $10^6$.Comment: Plenary talk at SciDAC 200