Fractal properties of relaxation clusters and phase transition in a stochastic sandpile automaton

We study numerically the spatial properties of relaxation clusters in a two dimensional sandpile automaton with dynamic rules depending stochastically on a parameter p, which models the effects of static friction. In the limiting cases p=1 and p=0 the model reduces to the critical height model and critical slope model, respectively. At p=p_c, a continuous phase transition occurs to the state characterized by a nonzero average slope. Our analysis reveals that the loss of finite average slope at the transition is accompanied by the loss of fractal properties of the relaxation clusters.Comment: 11 page

Evolutionary Approach to Infrastructure Formation in Russia’s Economic Systems with Using Supply Chain Management Strategy for the Mineral Raw Material Specialization

The article presents the theoretical framework for the infrastructure formation in the economic systems specializing in mineral raw materials, by using supply chain strategy. It is determined by objective processes of economic development and sect oral peculiarities, in the form of synthesis of reproduction, structural-functional and systemic approaches in supply chain management. It allows developing adequate mechanisms aimed at maintaining and further developing infrastructure of territorial economic systems (TES)

Use of investment project implementation mechanism under production sharing agreement for the development of oil and gas

Strengthening the investment attractiveness of economic systems of Russia’s mineral raw material specialization by means of oil and gas project implementation under a production sharing agreement. Purpose of the article is formation of conceptual approaches to the use of the mechanism for implementing investment projects under a product sharing agreement in the development of oil and gas bearing regions of Russia. The techniques and methods of system analysis are used for understanding the procedural and institutional, economic and financial nature of the proposed mechanism for implementing investment projects under a PSA model in the development of oil and gas bearing territories of Russia.peer-reviewe

ViFi: accurate detection of viral integration and mRNA fusion reveals indiscriminate and unregulated transcription in proximal genomic regions in cervical cancer.

The integration of viral sequences into the host genome is an important driver of tumorigenesis in many viral mediated cancers, notably cervical cancer and hepatocellular carcinoma. We present ViFi, a computational method that combines phylogenetic methods with reference-based read mapping to detect viral integrations. In contrast with read-based reference mapping approaches, ViFi is faster, and shows high precision and sensitivity on both simulated and biological data, even when the integrated virus is a novel strain or highly mutated. We applied ViFi to matched genomic and mRNA data from 68 cervical cancer samples from TCGA and found high concordance between the two. Surprisingly, viral integration resulted in a dramatic transcriptional upregulation in all proximal elements, including LINEs and LTRs that are not normally transcribed. This upregulation is highly correlated with the presence of a viral gene fused with a downstream human element. Moreover, genomic rearrangements suggest the formation of apparent circular extrachromosomal (ecDNA) human-viral structures. Our results suggest the presence of apparent small circular fusion viral/human ecDNA, which correlates with indiscriminate and unregulated expression of proximal genomic elements, potentially contributing to the pathogenesis of HPV-associated cervical cancers. ViFi is available at https://github.com/namphuon/ViFi

CASC Global Experience in Chennai, India

CASC Global, Summer 2019 -- Chennai, India -- Partner Agencie(s): Madras Christian Collegehttps://deepblue.lib.umich.edu/bitstream/2027.42/152288/1/Langerman_Luebeck_Poster.pd

Pre-service Teachers in Mathematics Lesson Study

This paper presents qualitative evidence to answer the questions, “What are the outcomes of engaging pre-service and in-service teachers in a collaborative lesson study experience” and “How can the outcomes of this experience inform future ways to include preservice teachers in lesson study?” The data gathered demonstrate that including pre-service teachers in lesson study can introduce them to lesson-building as a process and cross-grades teacher collaboration. It can give them opportunities to be critical thinkers in the context of mathematics education and encourages them to think as teachers. One weakness the pre-service teachers demonstrated was an incomplete understanding of the appropriate use of technology in algebra. Consideration of prior knowledge and anticipation of student responses was lacking among both pre-service and in-service teachers. Overall, the data show that pre-service teachers can contribute to the lesson study process as researchers

CRISPR-Cas9 Gene Editing of Hematopoietic Stem Cells from Patients with Friedreich's Ataxia.

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by expansion of GAA repeats in intron 1 of the frataxin (FXN) gene, leading to significant decreased expression of frataxin, a mitochondrial iron-binding protein. We previously reported that syngeneic hematopoietic stem and progenitor cell (HSPC) transplantation prevented neurodegeneration in the FRDA mouse model YG8R. We showed that the mechanism of rescue was mediated by the transfer of the functional frataxin from HSPC-derived microglia/macrophage cells to neurons/myocytes. In this study, we report the first step toward an autologous HSPC transplantation using the CRISPR-Cas9 system for FRDA. We first identified a pair of CRISPR RNAs (crRNAs) that efficiently removes the GAA expansions in human FRDA lymphoblasts, restoring the non-pathologic level of frataxin expression and normalizing mitochondrial activity. We also optimized the gene-editing approach in HSPCs isolated from healthy and FRDA patients' peripheral blood and demonstrated normal hematopoiesis of gene-edited cells in vitro and in vivo. The procedure did not induce cellular toxic effect or major off-target events, but a p53-mediated cell proliferation delay was observed in the gene-edited cells. This study provides the foundation for the clinical translation of autologous transplantation of gene-corrected HSPCs for FRDA

Number and Size Distribution of Colorectal Adenomas under the Multistage Clonal Expansion Model of Cancer

Colorectal cancer (CRC) is believed to arise from mutant stem cells in colonic crypts that undergo a well-characterized progression involving benign adenoma, the precursor to invasive carcinoma. Although a number of (epi)genetic events have been identified as drivers of this process, little is known about the dynamics involved in the stage-wise progression from the first appearance of an adenoma to its ultimate conversion to malignant cancer. By the time adenomas become endoscopically detectable (i.e., are in the range of 1–2 mm in diameter), adenomas are already comprised of hundreds of thousands of cells and may have been in existence for several years if not decades. Thus, a large fraction of adenomas may actually remain undetected during endoscopic screening and, at least in principle, could give rise to cancer before they are detected. It is therefore of importance to establish what fraction of adenomas is detectable, both as a function of when the colon is screened for neoplasia and as a function of the achievable detection limit. To this end, we have derived mathematical expressions for the detectable adenoma number and size distributions based on a recently developed stochastic model of CRC. Our results and illustrations using these expressions suggest (1) that screening efficacy is critically dependent on the detection threshold and implicit knowledge of the relevant stem cell fraction in adenomas, (2) that a large fraction of non-extinct adenomas remains likely undetected assuming plausible detection thresholds and cell division rates, and (3), under a realistic description of adenoma initiation, growth and progression to CRC, the empirical prevalence of adenomas is likely inflated with lesions that are not on the pathway to cancer

An ordinary differential equation model for the multistep transformation to cancer

Cancer is viewed as a multistep process whereby a normal cell is transformed into a cancer cell through the acquisition of mutations. We reduce the complexities of cancer progression to a simple set of underlying rules that govern the transformation of normal cells to malignant cells. In doing so, we derive an ordinary differential equation model that explores how the balance of angiogenesis, cell death rates, genetic instability, and replication rates give rise to different kinetics in the development of cancer. The key predictions of the model are that cancer develops fastest through a particular ordering of mutations and that mutations in genes that maintain genomic integrity would be the most deleterious type of mutations to inherit. In addition, we perform a sensitivity analysis on the parameters included in the model to determine the probable contribution of each. This paper presents a novel approach to viewing the genetic basis of cancer from a systems biology perspective and provides the groundwork for other models that can be directly tied to clinical and molecular data.Comment: 12 pages, submitted to Journal of Theoretical Biolog