Co-transcriptional RNA cleavage provides a failsafe termination mechanism for yeast RNA polymerase I

Ribosomal RNA, transcribed by RNA polymerase (Pol) I, accounts for most cellular RNA. Since Pol I transcribes rDNA repeats with high processivity and polymerase density, transcription termination is a critical process. Early in vitro studies proposed polymerase pausing by Reb1 and transcript release at the T-rich element T1 determined transcription termination. However recent in vivo studies revealed a ‘torpedo’ mechanism for Pol I termination: co-transcriptional RNA cleavage by Rnt1 provides an entry site for the 5′–3′ exonuclease Rat1 that degrades Pol I-associated transcripts destabilizing the transcription complex. Significantly Rnt1 inactivation in vivo reveals a second co-transcriptional RNA cleavage event at T1 which provides Pol I with an alternative termination pathway. An intact Reb1-binding site is also required for Rnt1-independent termination. Consequently our results reconcile the original Reb1-mediated termination pathway as part of a failsafe mechanism for this essential transcription process

Role of Echocardiography in Percutaneous Mitral Valve Interventions

Intraprocedural imaging continues to evolve in parallel with advances in percutaneous mitral valve interventions. This didactic review uses several illustrations and rich intraprocedural videos to further describe and demonstrate the role of the most up-to-date echocardiographic and advanced imaging technologies in the patient selection and intraprocedural guidance of percutaneous mitral valve interventions. We will focus on 3 interventions: 1) percutaneous balloon mitral valvuloplasty for mitral stenosis; 2) transcatheter edge-to-edge repair of mitral valve regurgitation; and 3) transcatheter closure of periprosthetic mitral regurgitation. In addition, we discuss potential pitfalls of 3-dimensional transesophageal echocardiography and show examples of this technique

Characterization of Knots and Links Arising From Site-specific Recombination on Twist Knots

We develop a model characterizing all possible knots and links arising from recombination starting with a twist knot substrate, extending previous work of Buck and Flapan. We show that all knot or link products fall into three well-understood families of knots and links, and prove that given a positive integer $n$, the number of product knots and links with minimal crossing number equal to $n$ grows proportionally to $n^5$. In the (common) case of twist knot substrates whose products have minimal crossing number one more than the substrate, we prove that the types of products are tightly prescribed. Finally, we give two simple examples to illustrate how this model can help determine previously uncharacterized experimental data.Comment: 32 pages, 7 tables, 27 figures, revised: figures re-arranged, and minor corrections. To appear in Journal of Physics

Knots, Braids and BPS States in M-Theory

In previous work we considered M-theory five branes wrapped on elliptic Calabi-Yau threefold near the smooth part of the discriminant curve. In this paper, we extend that work to compute the light states on the worldvolume of five-branes wrapped on fibers near certain singular loci of the discriminant. We regulate the singular behavior near these loci by deforming the discriminant curve and expressing the singularity in terms of knots and their associated braids. There braids allow us to compute the appropriate string junction lattice for the singularity and,hence to determine the spectrum of light BPS states. We find that these techniques are valid near singular points with N=2 supersymmetry.Comment: 38 page

Cross-species epigenetics identifies a critical role for VAV1 in SHH subgroup medulloblastoma maintenance

The identification of key tumorigenic events in Sonic Hedgehog (SHH) subgroup medulloblastomas (MBSHH) will be essential for the development of individualized therapies and improved outcomes. However, beyond confirmation of characteristic SHH pathway mutations, recent genome-wide sequencing studies have not revealed commonly mutated genes with widespread relevance as potential therapeutic targets. We therefore examined any role for epigenetic DNA methylation events in MBSHH using a cross-species approach to candidate identification, prioritization and validation. MBSHH-associated DNA methylation events were first identified in 216 subgrouped human medulloblastomas (50 MBSHH, 28 Wnt/Wingless, 44 Group 3 and 94 Group 4) and their conservation then assessed in tumors arising from four independent murine models of Shh medulloblastoma, alongside any role in tumorigenesis using functional assessments in mouse and human models. This strategy identified widespread regional CpG hypo-methylation of VAV1, leading to its elevated expression, as a conserved aberrant epigenetic event, which characterizes the majority of MBSHH tumors in both species, and is associated with a poor outcome in MBSHH patients. Moreover, direct modulation of VAV1 in mouse and human models revealed a critical role in tumor maintenance, and its abrogation markedly reduced medulloblastoma growth. Further, Vav1 activity regulated granule neuron precursor germinal zone exit and migration initiation in an ex vivo model of early postnatal cerebellar development. These findings establish VAV1 as a critical epigenetically regulated oncogene with a key role in MBSHH maintenance, and highlight its potential as a validated therapeutic target and prognostic biomarker for the improved therapy of medulloblastoma

TCO evaluation in physical asset management : benefits and limitations for industrial adoption

Part 1: Knowledge-Based Performance ImprovementInternational audienceNowadays, the evaluation of the total cost of ownership (TCO) of an asset for supporting informed decision-making both for investments and managerial issues within the asset management framework is gaining increasing attention in industry. Nevertheless its application in practice is still limited. The aim of this paper is to analyze the benefits and limitations of the adoption of TCO evaluation in asset management. Based on a literature review, the paper defines a framework that categorizes the benefits and potential applications that a TCO model can have for different stakeholders. Together with that, industry related issues that influence its implementation are also considered. Finally, empirical evidences are analyzed through a multiple case study to understand if those benefits are recognized in practice and which are the limitations for the practical adoption of a TCO model that should allow exploiting such benefits

Three Small Planets Transiting a Hyades Star

We present the discovery of three small planets transiting K2-136 (LP 358 348, EPIC 247589423), a late K dwarf in the Hyades. The planets have orbital periods of $7.9757 \pm 0.0011$, $17.30681^{+0.00034}_{-0.00036}$, and $25.5715^{+0.0038}_{-0.0040}$ days, and radii of $1.05 \pm 0.16$, $3.14 \pm 0.36$, and $1.55^{+0.24}_{-0.21}$ $R_\oplus$, respectively. With an age of 600-800 Myr, these planets are some of the smallest and youngest transiting planets known. Due to the relatively bright (J=9.1) host star, the planets are compelling targets for future characterization via radial velocity mass measurements and transmission spectroscopy. As the first known star with multiple transiting planets in a cluster, the system should be helpful for testing theories of planet formation and migration.Comment: Accepted to The Astronomical Journa

Describing semigroups with defining relations of the form xy=yz xy and yx=zy and connections with knot theory

We introduce a knot semigroup as a cancellative semigroup whose defining relations are produced from crossings on a knot diagram in a way similar to the Wirtinger presentation of the knot group; to be more precise, a knot semigroup as we define it is closely related to such tools of knot theory as the twofold branched cyclic cover space of a knot and the involutory quandle of a knot. We describe knot semigroups of several standard classes of knot diagrams, including torus knots and torus links T(2, n) and twist knots. The description includes a solution of the word problem. To produce this description, we introduce alternating sum semigroups as certain naturally defined factor semigroups of free semigroups over cyclic groups. We formulate several conjectures for future research