The Fraunhofer Quantum Computing Portal - www.qc.fraunhofer.de - A web-based Simulator of Quantum Computing Processes

Fraunhofer FIRST develops a computing service and collaborative workspace providing a convenient tool for simulation and investigation of quantum algorithms. To broaden the twenty qubit limit of workstation-based simulations to the next qubit decade we provide a dedicated high memorized Linux cluster with fast Myrinet interconnection network together with a adapted parallel simulator engine. This simulation service supplemented by a collaborative workspace is usable everywhere via web interface and integrates both hardware and software as collaboration and investigation platform for the quantum community. The beta test version realizes all common one, two and three qubit gates, arbitrary one and two bit gates, orthogonal measurements as well as special gates like Oracle, Modulo function, Quantum Fourier Transformation and arbitrary Spin-Hamiltonians up to 31 qubits. For a restricted gate set it feasible to investigate circuits with up to sixty qubits. URL: http://www.qc.fraunhofer.d

Vascular endothelial growth factor B (VEGF-B) is up-regulated and exogenous VEGF-B is neuroprotective in a culture model of Parkinson's disease

Parkinson's disease (PD) results from the degeneration of dopaminergic neurons in the substantia nigra and the consequent deficit of dopamine released in the striatum. Current oral dopamine replacement or surgical therapies do not address the underlying issue of neurodegeneration, they neither slow nor halt disease. Neurotrophic factors have shown preclinical promise, but the choice of an appropriate growth factor as well as the delivery has proven difficult. In this study, we used a rotenone rat midbrain culture model to identify genes that are changed after addition of the neurotoxin. (1) We challenged rat midbrain cultures with rotenone (20 nM), a pesticide that has been shown to be toxic for dopaminergic neurons and that has been a well-characterized model of PD. A gene chip array analysis demonstrated that several genes were up-regulated after the rotenone treatment. Interestingly transcriptional activation of vascular endothelial growth factor B (VEGF-B) was evident, while vascular endothelial growth factor A (VEGF-A) levels remained unaltered. The results from the gene chip array experiment were verified with real time PCR and semi-quantitative western analysis using β-actin as the internal standard. (2) We have also found evidence that exogenously applied VEGF-B performed as a neuroprotective agent facilitating neuron survival in an even more severe rotenone culture model of PD (40 nM rotenone). VEGF-B has very recently been added to the list of trophic factors that reduce effects of neurodegeneration, as was shown in an in vivo model of motor neuron degeneration, while lacking potential adverse angiogenic activity. The data of an in vivo protective effect on motor neurons taken together with the presented results demonstrate that VEGF-B is a new candidate trophic factor distinct from the GDNF family of trophic factors. VEGF-B is activated by neurodegenerative challenges to the midbrain, and exogenous application of VEGF-B has a neuroprotective effect in a culture model of PD. Strengthening this natural protective response by either adding exogenous VEGF-B or up-regulating the endogenous VEGF-B levels may have the potential to be a disease modifying therapy for PD. We conclude that the growth factor VEGF-B can improve neuronal survival in a culture model of PD

Analysis of a c0t-1 library enables the targeted identification of minisatellite and satellite families in Beta vulgaris

Zakrzewski F, Wenke T, Holtgräwe D, Weisshaar B, Schmidt T. Analysis of a c0t-1 library enables the targeted identification of minisatellite and satellite families in Beta vulgaris. BMC Plant Biology. 2010;10(1): 8.BACKGROUND: Repetitive DNA is a major fraction of eukaryotic genomes and occurs particularly often in plants. Currently, the sequencing of the sugar beet (Beta vulgaris) genome is under way and knowledge of repetitive DNA sequences is critical for the genome annotation. We generated a c0t-1 library, representing highly to moderately repetitive sequences, for the characterization of the major B. vulgaris repeat families. While highly abundant satellites are well-described, minisatellites are only poorly investigated in plants. Therefore, we focused on the identification and characterization of these tandemly repeated sequences. RESULTS: Analysis of 1763 c0t-1 DNA fragments, providing 442 kb sequence data, shows that the satellites pBV and pEV are the most abundant repeat families in the B. vulgaris genome while other previously described repeats show lower copy numbers. We isolated 517 novel repetitive sequences and used this fraction for the identification of minisatellite and novel satellite families. Bioinformatic analysis and Southern hybridization revealed that minisatellites are moderately to highly amplified in B. vulgaris. FISH showed a dispersed localization along most chromosomes clustering in arrays of variable size and number with exclusion and depletion in distinct regions. CONCLUSION: The c0t-1 library represents major repeat families of the B. vulgaris genome, and analysis of the c0t-1 DNA was proven to be an efficient method for identification of minisatellites. We established, so far, the broadest analysis of minisatellites in plants and observed their chromosomal localization providing a background for the annotation of the sugar beet genome and for the understanding of the evolution of minisatellites in plant genomes

Arthrofibrosis after TKA - Influence factors on the absolute flexion and gain in flexion after manipulation under anaesthesia

<p>Abstract</p> <p>Background</p> <p>Stiffness with decreased range of motion (ROM) has been described as a frustrating complication after TKA. If all methods of physiotherapeutic treatment have been exhausted trying to develop ROM, manipulation under anaesthesia (MUA) can be discussed. The aim of the present study was to show the effect of MUA and to determine the influence of BMI, number of previous surgical procedures, pre-MUA ROM and timing of MUA for the results after MUA in regard to absolute flexion and gain in flexion.</p> <p>Methods</p> <p>858 patients underwent TKA at our institution between 2004 and 2009. 39 of these patients underwent MUA because of postoperative knee stiffness. The data were retrospective analysed for the influence of BMI, pre-MUA flexion (</≥ 70°), timing of MUA (>/≤ 30 days after TKA) and number of previous surgery on the results after MUA (absolute Flexion/gain in flexion).</p> <p>Results</p> <p>The prevalence for stiffness after TKA was 4.54%. There was a statistically significant improvement in flexion not only directly after MUA but also 6 weeks after MUA. Patients with two or more previous operations before TKA showed statistically significant worse results six weeks after MUA in absolute flexion and gain in flexion</p> <p>(p = 0.039) than patients with one or two previous operations. No statistical significance in absolute flexion (p = 0.655) and gain in flexion (p = 0.328) after MUA between "early" and "late" was detected. The stiffer knees with a flexion below 70° showed significantly worse results (p = 0.044) in absolute flexion six weeks after MUA, but they also had statistical statistically better results with regard to gain in flexion (p ≤ 0.001).</p> <p>Conclusion</p> <p>MUA is a good instrument for improving ROM after TKA. The time between TKA and MUA seems less important, so different types of physiotherapeutic treatment could be tried before the procedure is started. MUA in patients with many previous operations and a flexion of less than 70° before MUA is not as effective as in other patients, but they also benefit from MUA.</p

Ten-Hour Exposure to Low-Dose Ketamine Enhances Corticostriatal Cross-Frequency Coupling and Hippocampal Broad-Band Gamma Oscillations

Introduction: Treatment-resistant depression, post-traumatic stress disorder, chronic pain, and L-DOPA-induced dyskinesia in Parkinson’s disease are characterized by hypersynchronous neural oscillations. Sub-anesthetic ketamine is effective at treating these conditions, and this may relate to ketamine’s capacity to reorganize oscillatory activity throughout the brain. For example, a single ketamine injection increases gamma (∼40 Hz) and high-frequency oscillations (HFOs, 120–160 Hz) in the cortex, hippocampus, and striatum. While the effects of single injections have been investigated, clinical ketamine treatments can involve 5-h up to 3-day sub-anesthetic infusions. Little is known about the effects of such prolonged exposure on neural synchrony. We hypothesized that hours-long exposure entrains circuits that generate HFOs so that HFOs become sustained after ketamine’s direct effects on receptors subside.Methods: Local-field recordings were acquired from motor cortex (M1), striatum, and hippocampus of behaving rats (n = 8), and neural responses were measured while rats received 5 ketamine injections (20 mg/kg, i.p., every 2 h, 10-h exposure). In a second experiment, the same animals received injections of D1-receptor antagonist (SCH-23390, 1 mg/kg, i.p.) prior to ketamine injection to determine if D1 receptors were involved in producing HFOs.Results: Although HFOs remained stable throughout extended ketamine exposure, broad-band high-frequency activity (40–140 Hz) in the hippocampus and delta-HFO cross-frequency coupling (CFC) in dorsal striatum increased with the duration of exposure. Furthermore, while ketamine-triggered HFOs were not affected by D1 receptor blockade, ketamine-associated gamma in motor cortex was suppressed, suggesting involvement of D1 receptors in ketamine-mediated gamma activity in motor cortex.Conclusion: Prolonged ketamine exposure does not enhance HFOs in corticostriatal circuits, but, instead, enhances coordination between low and high frequencies in the striatum and reduces synchrony in the hippocampus. Increased striatal CFC may facilitate spike-timing dependent plasticity, resulting in lasting changes in motor activity. In contrast, the observed wide-band high-frequency “noise” in the hippocampus suggests that ketamine disrupts action-potential timing and reorganizes connectivity in this region. Differential restructuring of corticostriatal and limbic circuits may contribute to ketamine’s clinical benefits

Innovative Abluftreinigung in der Tierhaltung: Machbarkeitsstudie zur Prüfung der Übertragbarkeit von Erkenntnissen der industriellen Abluftreinigung und innovativer Abluftreinigungsverfahren zur Minderung von Bioaerosol- und Geruchsemissionen aus der Geflügelhaltung

Die Studie wendet sich an Tierhalter, die Probleme mit der Reduzierung von Gerüchen und Bioaerosolen beim Betrieb ihrer Anlagen haben sowie an Genehmigungsbehörden und Hersteller von Abluftreinigungsanlagen. Am Beispiel der Geflügelhaltung wurde die Übertragbarkeit von Erkenntnissen der industriellen Abgasreinigung auf Anlagen der Landwirtschaft geprüft. Es wird aufgezeigt, ob und welche Möglichkeiten bestehen, um eine deutliche Minderung von Bioaerosol- und Geruchsemissionen zu erreichen

Characterization of the novel mitochondrial genome segregation factor TAP110 in Trypanosoma brucei.

Proper mitochondrial genome inheritance is important for eukaryotic cell survival. Trypanosoma brucei, a protozoan parasite, contains a singular mitochondrial genome, the kinetoplast (k)DNA. The kDNA is anchored to the basal body via the tripartite attachment complex (TAC) to ensure proper segregation. Several components of the TAC have been described; however, the connection of the TAC to the kDNA remains elusive. Here, we characterize the TAC-associated protein TAP110. We find that both depletion and overexpression of TAP110 leads to a delay in the separation of the replicated kDNA networks. Proteome analysis after TAP110 overexpression identified several kDNA-associated proteins that changed in abundance, including a TEX-like protein that dually localizes to the nucleus and the kDNA, potentially linking replication and segregation in the two compartments. The assembly of TAP110 into the TAC region seems to require the TAC but not the kDNA itself; however, once TAP110 has been assembled, it also interacts with the kDNA. Finally, we use ultrastructure expansion microscopy in trypanosomes for the first time, and reveal the precise position of TAP110 between TAC102 and the kDNA, showcasing the potential of this approach.This article has an associated First Person interview with the first author of the paper

PEDF and VEGF-A Output from Human Retinal Pigment Epithelial Cells Grown on Novel Microcarriers

Human retinal pigment epithelial (hRPE) cells have been tested as a cell-based therapy for Parkinson's disease but will require additional study before further clinical trials can be planned. We now show that the long-term survival and neurotrophic potential of hRPE cells can be enhanced by the use of FDA-approved plastic-based microcarriers compared to a gelatin-based microcarrier as used in failed clinical trials. The hRPE cells grown on these plastic-based microcarriers display several important characteristics of hRPE found in vivo: (1) characteristic morphological features, (2) accumulation of melanin pigment, and (3) high levels of production of the neurotrophic factors pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor-A (VEGF-A). Growth of hRPE cells on plastic-based microcarriers led to sustained levels (>1 ng/ml) of PEDF and VEGF-A in conditioned media for two months. We also show that the expression of VEGF-A and PEDF is reciprocally regulated by activation of the GPR143 pathway. GPR143 is activated by L-DOPA (1 μM) which decreased VEGF-A secretion as opposed to the previously reported increase in PEDF secretion. The hRPE microcarriers are therefore novel candidate delivery systems for achieving long-term delivery of the neuroprotective factors PEDF and VEGF-A, which could have a value in neurodegenerative conditions such as Parkinson's disease

Characterization of two novel proteins involved in mitochondrial DNA anchoring in Trypanosoma brucei.

Trypanosoma brucei is a single celled eukaryotic parasite in the group of the Kinetoplastea. The parasite harbors a single mitochondrion with a singular mitochondrial genome that is known as the kinetoplast DNA (kDNA). The kDNA consists of a unique network of thousands of interlocked circular DNA molecules. To ensure proper inheritance of the kDNA to the daughter cells, the genome is physically linked to the basal body, the master organizer of the cell cycle in trypanosomes. The connection that spans, cytoplasm, mitochondrial membranes and the mitochondrial matrix is mediated by the Tripartite Attachment Complex (TAC). Using a combination of proteomics and RNAi we test the current model of hierarchical TAC assembly and identify TbmtHMG44 and TbKAP68 as novel candidates of a complex that connects the TAC to the kDNA. Depletion of TbmtHMG44 or TbKAP68 each leads to a strong kDNA loss but not missegregation phenotype as previously defined for TAC components. We demonstrate that the proteins rely on both the TAC and the kDNA for stable localization to the interface between these two structures. In vitro experiments suggest a direct interaction between TbmtHMG44 and TbKAP68 and that recombinant TbKAP68 is a DNA binding protein. We thus propose that TbmtHMG44 and TbKAP68 are part of a distinct complex connecting the kDNA to the TAC

Autoantikörpernachweis mittels indirekter Immunfluoreszenz an HEp-2-Zellen

Systemic autoimmune diseases are characterized by the presence of antinuclear autoantibodies (ANAs). Diluted patient sera are typically used to screen for the presence of ANAs by immunofluorescence microscopy with fixed HEp-2 cells. Despite high quality test kits, reports of different laboratories frequently present controversial results. This study presents a recommendation for a unified processing and interpretation of HEp-2 based screening for autoantibodies. We provide suggestions for selection of high quality test kits, optimized processing, and diagnostic procedures. For good laboratory practice, in addition to a relevant clinical diagnosis and an experienced laboratory specialist, the following procedure is highly recommended: initial HEp-2 based screening by indirect immunofluorescence, starting with a 1:80 serum dilution and evaluation in a bright fluorescence microscope, pathological values from a titer of 1:160, internal quality checks, and unified interpretation. We aim to improve diagnostics and care for patients with autoimmune diseases as a central focus of the European Autoimmunity Standardization Initiative (EASI)