Notch Signaling in Cancer

Notch signaling plays a key role in the normal development of many tissues and cell types, through diverse effects on differentiation, survival, and/or proliferation that are highly dependent on signal strength and cellular context. Because perturbations in the regulation of differentiation, survival, and/or proliferation underlie malignant transformation, pathophysiologic Notch signals potentially contribute to cancer development in several different ways. Notch signaling was first linked to tumorigenesis through identification of a recurrent t(7;9)(q34;q34.3) chromosomal translocation involving the human Notch 1 gene that is found in a small subset of human pre-T-cell acute lymphoblastic leukemias (T-ALL).1 Since this discovery, aberrant Notch signaling has been suggested to be involved in a wide variety of human neoplasms. In this review, we will focus on recent studies linking aberrant Notch signaling with cancer. First, we discuss various mechanisms through which Notch signaling may influence cellular transformation. Then, we critically review literature pertaining to the role of Notch signaling in several cancers, and discuss possible therapeutic targets in the Notch pathway

A TV-Gaussian prior for infinite-dimensional Bayesian inverse problems and its numerical implementations

Many scientific and engineering problems require to perform Bayesian inferences in function spaces, in which the unknowns are of infinite dimension. In such problems, choosing an appropriate prior distribution is an important task. In particular we consider problems where the function to infer is subject to sharp jumps which render the commonly used Gaussian measures unsuitable. On the other hand, the so-called total variation (TV) prior can only be defined in a finite dimensional setting, and does not lead to a well-defined posterior measure in function spaces. In this work we present a TV-Gaussian (TG) prior to address such problems, where the TV term is used to detect sharp jumps of the function, and the Gaussian distribution is used as a reference measure so that it results in a well-defined posterior measure in the function space. We also present an efficient Markov Chain Monte Carlo (MCMC) algorithm to draw samples from the posterior distribution of the TG prior. With numerical examples we demonstrate the performance of the TG prior and the efficiency of the proposed MCMC algorithm

The First Second of Volcanic Eruptions from the Erebus Volcano Lava Lake, Antarctica—Energies, Pressures, Seismology, and Infrasound

[1] We describe a multiparameter experiment at Erebus volcano, Antarctica, employing Doppler radar, video, acoustic, and seismic observations to estimate the detailed energy budget of large (up to 40 m-diameter) bubble bursts from a persistent phonolite lava lake. These explosions are readily studied from the crater rim at ranges of less than 500 m and present an ideal opportunity to constrain the dynamics and mechanism of magmatic bubble bursts that can drive Strombolian and Hawaiian eruptions. We estimate the energy budget of the first second of a typical Erebus explosion as a function of time and energy type. We constrain gas pressures and forces using an analytic model for the expansion of a gas bubble above a conduit that incorporates conduit geometry and magma and gas parameters. The model, consistent with video and radar observations, invokes a spherical bulging surface with a base diameter equal to that of the lava lake. The model has no ad hoc free parameters, and geometrical calculations predict zenith height, velocity, and acceleration during shell expansion. During explosions, the energy contained in hot overpressured gas bubbles is freed and partitioned into other energy types, where by far the greatest nonthermal energy component is the kinetic and gravitational potential energy of the accelerated magma shell (\u3e109 J). Seismic source energy created by explosions is estimated from radar measurements and is consistent with source energy determined from seismic observations. For the generation of the infrasonic signal, a dual mechanism incorporating a terminally disrupted slug is proposed, which clarifies previous models and provides good fits to observed infrasonic pressures. A new and straightforward method is presented for determining gas volumes from slug explosions at volcanoes from remote infrasound recordings

Glacial Earthquakes and Precursory Seismicity Associated With Thwaites Glacier Calving

We observe two (~MS 3) long‐period (10–30 s) seismic events that originate from the terminus of Thwaites Glacier, Antarctica. Serendipitous acquisition of satellite images confirm that the seismic events were glacial earthquakes generated during the capsizing of icebergs. The glacial earthquakes were preceded by 6 days of discrete high‐frequency seismic events that can be observed at distances exceeding 250 km. The high‐frequency seismicity displays an increasing rate of occurrence, culminating in several hours of sustained tremor coeval with the long‐period events. A series of satellite images collected during this precursory time period show that the high‐frequency events and tremor are the result of accelerating growth of ancillary fractures prior to the culminating calving event. This study indicates that seismic data have the potential to elucidate the processes by which Thwaites Glacier discharges into the ocean, thus improving our ability to constrain future sea level rise

The Seismic Noise Environment of Antarctica

This characterization of the seismic noise environment of Antarctica, documentation of instrument performance, and comparisons of installation conditions (e.g., ice vaults vs. rock sites) is intended to facilitate optimization of future seismological deployments in such environments. We analyze data from a range of recent experiments to provide a broad geographical characterization of Antarctica’s seismic noise environment, which can now include more substantial observations from regions that are free from anthropogenic noise contamination

Upper Mantle Structure of Central and West Antarctica from Array Analysis of Rayleigh Wave Phase Velocities

The seismic velocity structure of Antarctica is important, both as a constraint on the tectonic history of the continent and for understanding solid Earth interactions with the ice sheet. We use Rayleigh wave array analysis methods applied to teleseismic data from recent temporary broadband seismograph deployments to image the upper mantle structure of central and West Antarctica. Phase velocity maps are determined using a two–plane wave tomography method and are inverted for shear velocity using a Monte Carlo approach to estimate three-dimensional velocity structure. Results illuminate the structural dichotomy between the East Antarctic Craton and West Antarctica, with West Antarctica showing thinner crust and slower upper mantle velocity. West Antarctica is characterized by a 70–100 km thick lithosphere, underlain by a low-velocity zone to depths of at least 200 km. The slowest anomalies are beneath Ross Island and the Marie Byrd Land dome and are interpreted as upper mantle thermal anomalies possibly due to mantle plumes. The central Transantarctic Mountains are marked by an uppermost mantle slow-velocity anomaly, suggesting that the topography is thermally supported. The presence of thin, higher-velocity lithosphere to depths of about 70 km beneath the West Antarctic Rift System limits estimates of the regionally averaged heat flow to less than 90 mW/m2. The Ellsworth-Whitmore block is underlain by mantle with velocities that are intermediate between those of the West Antarctic Rift System and the East Antarctic Craton. We interpret this province as Precambrian continental lithosphere that has been altered by Phanerozoic tectonic and magmatic activity

The Shearing HI Spiral Pattern of NGC 1365

The Tremaine-Weinberg equations are solved for a pattern speed that is allowed to vary with radius. The solution method transforms an integral equation for the pattern speed to a least squares problem with well established procedures for statistical analysis. The method applied to the HI spiral pattern of the barred, grand-design galaxy NGC 1365 produced convincing evidence for a radial dependence in the pattern speed. The pattern speed behaves approximately as 1/r, and is very similar to the material speed. There are no clear indications of corotation or Lindblad resonances. Tests show that the results are not selection biased, and that the method is not measuring the material speed. Other methods of solving the Tremaine-Weinberg equations for shearing patterns were found to produce results in agreement with those obtained using the current method. Previous estimates that relied on the assumptions of the density-wave interpretation of spiral structure are inconsistent with the results obtained using the current method. The results are consistent with spiral structure theories that allow for shearing patterns, and contradict fundamental assumptions in the density-wave interpretation that are often used for finding spiral arm pattern speeds. The spiral pattern is winding on a characteristic timescale of ~ 500 Myrs.Comment: Accepted for publication in The Astrophysical Journa