A Developmentally Regulated Deletion Element with Long Terminal Repeats Has \u3cem\u3eCis\u3c/em\u3e-Acting Sequences in the Flanking DNA

Approximately 6000 specific DNA deletion events occur during development of the somatic macronucleus of the ciliate Tetrahymena. The eliminated Tlr1 element is 13 kb or more in length and has an 825 bp inverted repeat near the rearrangement junctions. A functional analysis of the cis-acting sequences required for Tlr1 rearrangement was performed. A construct consisting of the entire inverted repeat and several hundred base pairs of flanking DNA on each side was rearranged accurately in vivo and displayed junctional variability similar to the chromosomal Tlr1 rearrangement. Thus, 11 kb or more of internal element DNA is not required in cis for DNA rearrangement. A second construct with only 51 bp of Tetrahymena DNA flanking the right junction underwent aberrant rearrangement. Thus, a signal for determination of the Tlr1 junction is located in the flanking DNA, 51 bp or more from the right junction. Within the Tlr1 inverted repeat are 19 bp tandem repeats. A construct with the 19mer repeat region deleted from the right half of the inverted repeat utilized normal rearrangement junctions. Thus, despite its transposon-like structure, Tlr1 is similar to other DNA rearrangements in Tetrahymena in possessing cis-acting sequences outside the deleted DNA

Stochastic Properties of Static Friction

The onset of frictional motion is mediated by rupture-like slip fronts, which nucleate locally and propagate eventually along the entire interface causing global sliding. The static friction coefficient is a macroscopic measure of the applied force at this particular instant when the frictional interface loses stability. However, experimental studies are known to present important scatter in the measurement of static friction; the origin of which remains unexplained. Here, we study the nucleation of local slip at interfaces with slip-weakening friction of random strength and analyze the resulting variability in the measured global strength. Using numerical simulations that solve the elastodynamic equations, we observe that multiple slip patches nucleate simultaneously, many of which are stable and grow only slowly, but one reaches a critical length and starts propagating dynamically. We show that a theoretical criterion based on a static equilibrium solution predicts quantitatively well the onset of frictional sliding. We develop a Monte-Carlo model by adapting the theoretical criterion and pre-computing modal convolution terms, which enables us to run efficiently a large number of samples and to study variability in global strength distribution caused by the stochastic properties of local frictional strength. The results demonstrate that an increasing spatial correlation length on the interface, representing geometric imperfections and roughness, causes lower global static friction. Conversely, smaller correlation length increases the macroscopic strength while its variability decreases. We further show that randomness in local friction properties is insufficient for the existence of systematic precursory slip events. Random or systematic non-uniformity in the driving force, such as potential energy or stress drop, is required for arrested slip fronts. Our model and observations..

Progeny of Germ Line Knockouts of \u3cem\u3eASI2\u3c/em\u3e, a Gene Encoding a Putative Signal Transduction Receptor in \u3cem\u3eTetrahymena Thermophila\u3c/em\u3e, Fail to Make the Transition from Sexual Reproduction to Vegetative Growth

The ciliated protozoan Tetrahymena has two nuclei: a germ line micronucleus and a somatic macronucleus. The transcriptionally active macronucleus has about 50 copies of each chromosome. At sexual reproduction (conjugation), the parental macronucleus is degraded and new macronucleus develops from a mitotic product of the zygotic micronucleus. Development of the macronucleus involves massive genome remodeling, including deletion of about 6000 specific internal eliminated sequences (IES) and multiple rounds of DNA replication. A gene encoding a putative signal transduction receptor, ASI2, (anlagen stage induced 2) is up-regulated during development of the new macronuclei (anlagen). Macronuclear ASI2 is nonessential for vegetative growth. Homozygous ASI2 germ line knockout cells with wild type parental macronuclei proceed through mating but arrest at late macronuclear anlagen development and die before the first post-conjugation fission. IES elimination occurs in these cells. Two rounds of postzygotic DNA replication occur normally in progeny of ASI2 germ line knockouts, but endoreduplication of the macronuclear genome is arrested. The germ line ASI2 null phenotype is rescued in a mating of a knockout strain with wild type cells

Random acyclic networks

Directed acyclic graphs are a fundamental class of networks that includes citation networks, food webs, and family trees, among others. Here we define a random graph model for directed acyclic graphs and give solutions for a number of the model's properties, including connection probabilities and component sizes, as well as a fast algorithm for simulating the model on a computer. We compare the predictions of the model to a real-world network of citations between physics papers and find surprisingly good agreement, suggesting that the structure of the real network may be quite well described by the random graph.Comment: 4 pages, 2 figure

Stochastic blockmodels and community structure in networks

Stochastic blockmodels have been proposed as a tool for detecting community structure in networks as well as for generating synthetic networks for use as benchmarks. Most blockmodels, however, ignore variation in vertex degree, making them unsuitable for applications to real-world networks, which typically display broad degree distributions that can significantly distort the results. Here we demonstrate how the generalization of blockmodels to incorporate this missing element leads to an improved objective function for community detection in complex networks. We also propose a heuristic algorithm for community detection using this objective function or its non-degree-corrected counterpart and show that the degree-corrected version dramatically outperforms the uncorrected one in both real-world and synthetic networks.Comment: 11 pages, 3 figure

A Spectral Algorithm with Additive Clustering for the Recovery of Overlapping Communities in Networks

This paper presents a novel spectral algorithm with additive clustering designed to identify overlapping communities in networks. The algorithm is based on geometric properties of the spectrum of the expected adjacency matrix in a random graph model that we call stochastic blockmodel with overlap (SBMO). An adaptive version of the algorithm, that does not require the knowledge of the number of hidden communities, is proved to be consistent under the SBMO when the degrees in the graph are (slightly more than) logarithmic. The algorithm is shown to perform well on simulated data and on real-world graphs with known overlapping communities.Comment: Journal of Theoretical Computer Science (TCS), Elsevier, A Para\^itr

Disseminated Toxoplasmosis in a Patient with Non-Hodgkin Lymphoma

Abstract : Toxoplasmosis is a well-recognized opportunistic disease in HIV-infected individuals that is caused by the reactivation of a previous infection, primarily in the central nervous system, during profound immunodeficiency. Toxoplasmosis has been described more rarely in patients with cancer and chemotherapy. We report a case of a patient with a history of chemotherapy for non-Hodgkin lymphoma who developed pain and progressive paresthesia of the right arm 6 weeks after remission. Relapsing lymphoma was suspected, and steroid and radiation treatment were initiated, but the patient died 5 days later due to multiple organ failure. Autopsy revealed disseminated toxoplasmosis. This case illustrates that toxoplasmosis should be suspected in patients with neoplastic disease, especially lymphomas, who present with unexplained neurologic, pulmonary, or febrile symptoms during or after chemotherap

Progeny of germ line knockouts of ASI2, a gene encoding a putative signal transduction receptor in Tetrahymena thermophila, fail to make the transition from sexual reproduction to vegetative growth

AbstractThe ciliated protozoan Tetrahymena has two nuclei: a germ line micronucleus and a somatic macronucleus. The transcriptionally active macronucleus has about 50 copies of each chromosome. At sexual reproduction (conjugation), the parental macronucleus is degraded and new macronucleus develops from a mitotic product of the zygotic micronucleus. Development of the macronucleus involves massive genome remodeling, including deletion of about 6000 specific internal eliminated sequences (IES) and multiple rounds of DNA replication. A gene encoding a putative signal transduction receptor, ASI2, (anlagen stage induced 2) is up-regulated during development of the new macronuclei (anlagen). Macronuclear ASI2 is nonessential for vegetative growth. Homozygous ASI2 germ line knockout cells with wild type parental macronuclei proceed through mating but arrest at late macronuclear anlagen development and die before the first post-conjugation fission. IES elimination occurs in these cells. Two rounds of postzygotic DNA replication occur normally in progeny of ASI2 germ line knockouts, but endoreduplication of the macronuclear genome is arrested. The germ line ASI2 null phenotype is rescued in a mating of a knockout strain with wild type cells