Non-perturbative renormalization of the quark condensate in Ginsparg-Wilson regularizations

We present a method to compute non-perturbatively the renormalization constant of the scalar density for Ginsparg-Wilson fermions. It relies on chiral symmetry and is based on a matching of renormalization group invariant masses at fixed pseudoscalar meson mass, making use of results previously obtained by the ALPHA Collaboration for O(a)-improved Wilson fermions. Our approach is quite general and enables the renormalization of scalar and pseudoscalar densities in lattice regularizations that preserve chiral symmetry and of fermion masses in any regularization. As an application we compute the non-perturbative factor which relates the renormalization group invariant quark condensate to its bare counterpart, obtained with overlap fermions at beta=5.85 in the quenched approximation.Comment: 21 pages, 4 postscript files, LaTe

Scalar condensate and light quark masses from overlap fermions

We have studied pseudoscalar correlation functions computed using the overlap operator. Within the accuracy of our calculation we find that the quark mass dependence agrees with the prediction of lowest-order Chiral Perturbation Theory (ChPT) for quark masses in the range of m ~ m_s/2-2m_s. We present the results of an analysis which assumes lowest-order ChPT to be valid to extract the low-energy constants Sigma and f_P, as well as the strange quark mass. Non-perturbative renormalization is implemented via a matching procedure with data obtained using Wilson fermions in the Schroedinger functional set-up. We find that the scalar condensate computed here agrees with the one obtained previously through a finite-size scaling analysis.Comment: Lattice2001(chiral), 6 pages, 5 PostScript figure

First results on the running coupling in QCD with two massless flavours

We report on the non-perturbative computation of the running coupling of two-flavour QCD in the Schr"odinger functional scheme. The corresponding Lambda-parameter, which describes the coupling strength at high energy, is related to a low energy scale which still remains to be connected to a hadronic ``experimentally'' observable quantity. We find the non-perturbative evolution of the coupling indispensable to avoid untolerable errors in the estimated Lambda-parameter.Comment: 14 pages, 5 figures, 3 tables, some changes in the data analysis after discovery and correction of an error in Nucl. Phys. B 525, 387 (1998) by C. Christou et al. (hep-lat/9801007v2, Erratum to appear

Bruchprozesse an Innenkippenböschungen verschiedener Ausgangsgeometrien nach Verflüssigung, deren geokinematischer Ablauf und die zu erwartenden Endgeometrien

Beim Wiederanstieg des Grundwassers in den Innenkippen ist davon auszugehen, dass sich die Kippe ständig verändert, im Übergangsbereich zum erdfeuchten wird der dort vorhandene Pseudoporenanteil n sofort verringert und die Kippe verformt sich ständig durch die veränderten Spannungszustände. Auf den Innenkippen nehmen mit dem Anstieg des Grundwassers die Zahl der Verflüssigungsereignisse und auch die Größe der verflüssigten Bereiche zu. Die erfassten Bereiche wurden geokinematisch analysiert, um charakteristische Bewegungsmuster erkennen und beschreiben zu können. Im Ergebnis lassen sich die auf Innenkippen auftretenden Verformungsvorgänge auf drei Formen zurückführen, die eine Klassifizierung aus standsicherheitlicher Sicht ermöglichen. Diese drei Formen sind: 1. lokal begrenzte Einbrüche auftretend schon bei großem Grundwasserflurabstand bei nahezu ebener Kippenoberfläche, 2. vertikale Geländeveränderungen auf Kippen mit geneigtem Geländeoberfläche, die zu einer Einebnung oder einem Geländeausgleich führen, 3. Horizontale Böschungsbewegungen an Böschungen in der Form von relativ schnell ablaufenden Rutschungen mit erheblichen Massenbewegungen

Improved imaging of magnetically labeled cells using rotational magnetomotive optical coherence tomography

In this paper, we present a reliable and robust method for magnetomotive optical coherence tomography (MM-OCT) imaging of single cells labeled with iron oxide particles. This method employs modulated longitudinal and transverse magnetic fields to evoke alignment and rotation of anisotropic magnetic structures in the sample volume. Experimental evidence suggests that magnetic particles assemble themselves in elongated chains when exposed to a permanent magnetic field. Magnetomotion in the intracellular space was detected and visualized by means of 3D OCT as well as laser speckle reflectometry as a 2D reference imaging method. Our experiments on mesenchymal stem cells embedded in agar scaffolds show that the magnetomotive signal in rotational MM-OCT is significantly increased by a factor of ˜3 compared to previous pulsed MM-OCT, although the solenoid's power consumption was 16 times lower. Finally, we use our novel method to image ARPE-19 cells, a human retinal pigment epithelium cell line. Our results permit magnetomotive imaging with higher sensitivity and the use of low power magnetic fields or larger working distances for future three-dimensional cell tracking in target tissues and organs

Space Debris Removal: Learning to Cooperate and the Price of Anarchy

In this paper we study space debris removal from a game-theoretic perspective. In particular we focus on the question whether and how self-interested agents can cooperate in this dilemma, which resembles a tragedy of the commons scenario. We compare centralised and decentralised solutions and the corresponding price of anarchy, which measures the extent to which competition approximates cooperation. In addition we investigate whether agents can learn optimal strategies by reinforcement learning. To this end, we improve on an existing high fidelity orbital simulator, and use this simulator to obtain a computationally efficient surrogate model that can be used for our subsequent game-theoretic analysis. We study both single- and multi-agent approaches using stochastic (Markov) games and reinforcement learning. The main finding is that the cost of a decentralised, competitive solution can be significant, which should be taken into consideration when forming debris removal strategies

ATP synthase deficiency due to TMEM70 mutation leads to ultrastructural mitochondrial degeneration and is amenable to treatment.

TMEM70 is involved in the biogenesis of mitochondrial ATP synthase and mutations in the TMEM70 gene impair oxidative phosphorylation. Herein, we report on pathology and treatment of ATP synthase deficiency in four siblings. A consanguineous family of Roma (Gipsy) ethnic origin gave birth to 6 children of which 4 were affected presenting with dysmorphic features, failure to thrive, cardiomyopathy, metabolic crises, and 3-methylglutaconic aciduria as clinical symptoms. Genetic testing revealed a homozygous mutation (c.317-2A>G) in the TMEM70 gene. While light microscopy was unremarkable, ultrastructural investigation of muscle tissue revealed accumulation of swollen degenerated mitochondria with lipid crystalloid inclusions, cristae aggregation, and exocytosis of mitochondrial material. Biochemical analysis of mitochondrial complexes showed an almost complete ATP synthase deficiency. Despite harbouring the same mutation, the clinical outcome in the four siblings was different. Two children died within 60 h after birth; the other two had recurrent life-threatening metabolic crises but were successfully managed with supplementation of anaplerotic amino acids, lipids, and symptomatic treatment during metabolic crisis. In summary, TMEM70 mutations can cause distinct ultrastructural mitochondrial degeneration and almost complete deficiency of ATP synthase but are still amenable to treatment

Imaging of nanoparticle-labeled stem cells using magnetomotive optical coherence tomography, laser speckle reflectometry, and light microscopy

Cell transplantation and stem cell therapy are promising approaches for regenerative medicine and are of interest to researchers and clinicians worldwide. However, currently, no imaging technique that allows three-dimensional in vivo inspection of therapeutically administered cells in host tissues is available. Therefore, we investigate magnetomotive optical coherence tomography (MM-OCT) of cells labeled with magnetic particles as a potential noninvasive cell tracking method. We develop magnetomotive imaging of mesenchymal stem cells for future cell therapy monitoring. Cells were labeled with fluorescent iron oxide nanoparticles, embedded in tissue-mimicking agar scaffolds, and imaged using a microscope setup with an integrated MM-OCT probe. Magnetic particle-induced motion in response to a pulsed magnetic field of 0.2 T was successfully detected by OCT speckle variance analysis, and cross-sectional and volumetric OCT scans with highlighted labeled cells were obtained. In parallel, fluorescence microscopy and laser speckle reflectometry were applied as two-dimensional reference modalities to image particle distribution and magnetically induced motion inside the sample, respectively. All three optical imaging modalities were in good agreement with each other. Thus, magnetomotive imaging using iron oxide nanoparticles as cellular contrast agents is a potential technique for enhanced visualization of selected cells in OCT

The endothelial-enriched lncRNA LINC00607 mediates angiogenic function

Long non-coding RNAs (lncRNAs) can act as regulatory RNAs which, by altering the expression of target genes, impact on the cellular phenotype and cardiovascular disease development. Endothelial lncRNAs and their vascular functions are largely undefined. Deep RNA-Seq and FANTOM5 CAGE analysis revealed the lncRNA LINC00607 to be highly enriched in human endothelial cells. LINC00607 was induced in response to hypoxia, arteriosclerosis regression in non-human primates, post-atherosclerotic cultured endothelial cells from patients and also in response to propranolol used to induce regression of human arteriovenous malformations. siRNA knockdown or CRISPR/Cas9 knockout of LINC00607 attenuated VEGF-A-induced angiogenic sprouting. LINC00607 knockout in endothelial cells also integrated less into newly formed vascular networks in an in vivo assay in SCID mice. Overexpression of LINC00607 in CRISPR knockout cells restored normal endothelial function. RNA- and ATAC-Seq after LINC00607 knockout revealed changes in the transcription of endothelial gene sets linked to the endothelial phenotype and in chromatin accessibility around ERG-binding sites. Mechanistically, LINC00607 interacted with the SWI/SNF chromatin remodeling protein BRG1. CRISPR/Cas9-mediated knockout of BRG1 in HUVEC followed by CUT&RUN revealed that BRG1 is required to secure a stable chromatin state, mainly on ERG-binding sites. In conclusion, LINC00607 is an endothelial-enriched lncRNA that maintains ERG target gene transcription by interacting with the chromatin remodeler BRG1 to ultimately mediate angiogenesis

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10−6, odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10−4). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical R