Simulation of time evolution with the MERA

We describe an algorithm to simulate time evolution using the Multi-scale Entanglement Renormalization Ansatz (MERA) and test it by studying a critical Ising chain with periodic boundary conditions and with up to L ~ 10^6 quantum spins. The cost of a simulation, which scales as L log(L), is reduced to log(L) when the system is invariant under translations. By simulating an evolution in imaginary time, we compute the ground state of the system. The errors in the ground state energy display no evident dependence on the system size. The algorithm can be extended to lattice systems in higher spatial dimensions.Comment: final version with data improvement (precision and size), 4.1 pages, 4 figures + extra on X

DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells

Within 2–3 months of in vitro culture-expansion, mesenchymal stromal cells (MSC) undergo replicative senescence characterized by cell enlargement, loss of differentiation potential and ultimate growth arrest. In this study, we have analyzed DNA methylation changes upon long-term culture of MSC by using the HumanMethylation27 BeadChip microarray assessing 27 578 unique CpG sites. Furthermore, we have compared MSC from young and elderly donors. Overall, methylation patterns were maintained throughout both long-term culture and aging but highly significant differences were observed at specific CpG sites. Many of these differences were observed in homeobox genes and genes involved in cell differentiation. Methylation changes were verified by pyrosequencing after bisulfite conversion and compared to gene expression data. Notably, methylation changes in MSC were overlapping in long-term culture and aging in vivo. This supports the notion that replicative senescence and aging represent developmental processes that are regulated by specific epigenetic modifications

Oligo targeting for profiling drug resistance mutations in the parasitic trypanosomatids

Trypanosomatids cause the neglected tropical diseases, sleeping sickness, Chagas disease and the leishmaniases. Studies on these lethal parasites would be further facilitated by new and improved genetic technologies. Scalable precision editing methods, for example, could be used to improve our understanding of potential mutations associated with drug resistance, a current priority given that several new anti-trypanosomal drugs, with known targets, are currently in clinical development. We report the development of a simple oligo targeting method for rapid and precise editing of priority drug targets in otherwise wild type trypanosomatids. In Trypanosoma brucei, approx. 50-b single-stranded oligodeoxynucleotides were optimal, multiple base edits could be incorporated, and editing efficiency was substantially increased when mismatch repair was suppressed. Resistance-associated edits were introduced in T. brucei cyclin dependent kinase 12 (CRK12, L(482)F) or cleavage and polyadenylation specificity factor 3 (N(232)H), in the Trypanosoma cruzi proteasome β5 subunit (G(208)S), or in Leishmania donovani CRK12 (G(572)D). We further implemented oligo targeting for site saturation mutagenesis, targeting codon G(492) in T. brucei CRK12. This approach, combined with amplicon sequencing for codon variant scoring, revealed fourteen resistance conferring G(492) edits encoding six distinct amino acids. The outputs confirm on-target drug activity, reveal a variety of resistance-associated mutations, and facilitate rapid assessment of potential impacts on drug efficacy

Российская судебная практика по таможенным спорам: методология анализа, современная динамика и значение в развитии системы таможенного права

Актуальность данной темы заключается в том, что вопрос правовой природы российской судебной практики, понимания ее места и значения в таможенном праве России всегда привлекал ученых-правоведов и юристов, которые занимаются практической стороной данного вопроса. В дипломной работе рассмотрена российская судебная практика по таможенным спорам, возникающим между таможенными органами и участниками ВЭД в процессе совершения таможенных формальностей. Кроме того, описаны методологические особенности обобщения российской судебной практики по таможенным спорам, проанализированы современные тенденции в развитии судебной практики в указанной области, а также обозначено значение судебного прецедента в национальной системе таможенного права.This topic is relevant in connection with the fact that the issue of the legal nature of Russian judicial practice, the understanding of its place and significance in the customs law of Russia has always attracted scholars of jurisprudence and lawyers who deal with the practical side of this issue. The graduate work is about the Russian judicial practice on customs disputes arising between customs authorities and foreign trade participants in the process of customs formalities. In addition, the methodological features of the generalization of the Russian judicial practice in customs disputes are described, current trends in the development of judicial practice in this area are analyzed, and the significance of the judicial precedent in the national system of customs law is indicated

Aging and Replicative Senescence Have Related Effects on Human Stem and Progenitor Cells

The regenerative potential diminishes with age and this has been ascribed to functional impairments of adult stem cells. Cells in culture undergo senescence after a certain number of cell divisions whereby the cells enlarge and finally stop proliferation. This observation of replicative senescence has been extrapolated to somatic stem cells in vivo and might reflect the aging process of the whole organism. In this study we have analyzed the effect of aging on gene expression profiles of human mesenchymal stromal cells (MSC) and human hematopoietic progenitor cells (HPC). MSC were isolated from bone marrow of donors between 21 and 92 years old. 67 genes were age-induced and 60 were age-repressed. HPC were isolated from cord blood or from mobilized peripheral blood of donors between 27 and 73 years and 432 genes were age-induced and 495 were age-repressed. The overlap of age-associated differential gene expression in HPC and MSC was moderate. However, it was striking that several age-related gene expression changes in both MSC and HPC were also differentially expressed upon replicative senescence of MSC in vitro. Especially genes involved in genomic integrity and regulation of transcription were age-repressed. Although telomerase activity and telomere length varied in HPC particularly from older donors, an age-dependent decline was not significant arguing against telomere exhaustion as being causal for the aging phenotype. These studies have demonstrated that aging causes gene expression changes in human MSC and HPC that vary between the two different cell types. Changes upon aging of MSC and HPC are related to those of replicative senescence of MSC in vitro and this indicates that our stem and progenitor cells undergo a similar process also in vivo

Evaluation eines deutschsprachigen Instrumentes zur Erfassung positiver und negativer automatischer Gedanken bei Kindern und Jugendlichen (Evaluation of a German-language tool for measuring positive and negative automatic thoughts in children and adolescents).

Theoretischer Hintergrund: Negative automatische Gedanken stellen nach Beck eine wichtige Ursache für depressive Störungen dar. Fragestellung: Überprüfung der psychometrischen Gütekriterien des deutschen „Fragebogens für negative und positive automatische Gedanken” (FAG) bei Kindern und Jugendlichen. Methode: Der Fragebogen wurde an einer unselektierten Stichprobe aus der Allgemeinbevölkerung (n = 952) zwischen 11 und 16 Jahren untersucht. Die Stichprobe wurde in die beiden Gruppen ≤ 13 Jahre und \u3e 13 Jahre aufgeteilt. Ergebnisse: In der Gruppe ≤ 13 Jahre wurden die Skalen „negative Selbstaussagen” und „positive Selbstaussagen”, in der Gruppe \u3e 13 Jahre die Skalen „negative Selbstaussagen”, „Selbstvertrauen” und „Wohlbefinden” faktorenanalytisch extrahiert. Die internen Konsistenzen der FAG-Skalen lagen zwischen .75 und .89. Alle Skalen wiesen signifikante Zusammenhänge mit Depressivität auf und differenzierten zwischen höher und niedriger depressiven Teilnehmern. Schlussfolgerung: Insgesamt bestätigen die Ergebnisse die Reliabilität und Validität des FAG bei Kindern und Jugendlichen. Background: Beck postulates that negative automatic thoughts area risk factors for depression. Objective: The study presented here examines that psychometric properties of the German version of the Automatic Thoughts Questionnaire Revised (”Fragebogen für negative und positive automatische Gedanken”, FAG) in children and adolescents. Method: The study investigated an unselected community sample aged between 11 and 16 years (n = 952), which was divided into the two groups (≤ 13 years and \u3e 13 years). Results: Factor analyses revealed the scales ”negative self-statements” and ”positive self-statements” in the group ≤ 13 years and the scales ”negative self-statements”, ”self-confidence”, and ”well-being” in the group \u3e 13 years. Internal consistencies ranked between .75 and .89. All scales were significantly associated with depression and differentiated between more and less depressed participants. Conclusion: The FAG is a reliable and valid instrument to measure negative and positive automatic thoughts in children and adolescents