Modeling of Interstellar Scintillation Arcs from Pulsar B1133+16

The parabolic arc phenomenon visible in the Fourier analysis of the scintillation spectra of pulsars provides a new method of investigating the small scale structure in the ionized interstellar medium (ISM). We report archival observations of the pulsar B1133+16 showing both forward and reverse parabolic arcs sampled over 14 months. These features can be understood as the mutual interference between an assembly of discrete features in the scattered brightness distribution. By model-fitting to the observed arcs at one epoch we obtain a ``snap-shot'' estimate of the scattered brightness, which we show to be highly anisotropic (axial ratio >10:1), to be centered significantly off axis and to have a small number of discrete maxima, which are coarser the speckle expected from a Kolmogorov spectrum of interstellar plasma density. The results suggest the effects of highly localized discrete scattering regions which subtend 0.1-1 mas, but can scatter (or refract) the radiation by angles that are five or more times larger.Comment: 14 pages, 4 figures, submitted to Astrophysical Journa

Theory of Parabolic Arcs in Interstellar Scintillation Spectra

Our theory relates the secondary spectrum, the 2D power spectrum of the radio dynamic spectrum, to the scattered pulsar image in a thin scattering screen geometry. Recently discovered parabolic arcs in secondary spectra are generic features for media that scatter radiation at angles much larger than the rms scattering angle. Each point in the secondary spectrum maps particular values of differential arrival-time delay and fringe rate (or differential Doppler frequency) between pairs of components in the scattered image. Arcs correspond to a parabolic relation between these quantities through their common dependence on the angle of arrival of scattered components. Arcs appear even without consideration of the dispersive nature of the plasma. Arcs are more prominent in media with negligible inner scale and with shallow wavenumber spectra, such as the Kolmogorov spectrum, and when the scattered image is elongated along the velocity direction. The arc phenomenon can be used, therefore, to constrain the inner scale and the anisotropy of scattering irregularities for directions to nearby pulsars. Arcs are truncated by finite source size and thus provide sub micro arc sec resolution for probing emission regions in pulsars and compact active galactic nuclei. Multiple arcs sometimes seen signify two or more discrete scattering screens along the propagation path, and small arclets oriented oppositely to the main arc persisting for long durations indicate the occurrence of long-term multiple images from the scattering screen.Comment: 22 pages, 11 figures, submitted to the Astrophysical Journa

A Biomaterial Screening Approach Reveals Microenvironmental Mechanisms of Drug Resistance

Traditional drug screening methods lack features of the tumor microenvironment that contribute to resistance. Most studies examine cell response in a single biomaterial platform in depth, leaving a gap in understanding how extracellular signals such as stiffness, dimensionality, and cell–cell contacts act independently or are integrated within a cell to affect either drug sensitivity or resistance. This is critically important, as adaptive resistance is mediated, at least in part, by the extracellular matrix (ECM) of the tumor microenvironment. We developed an approach to screen drug responses in cells cultured on 2D and in 3D biomaterial environments to explore how key features of ECM mediate drug response. This approach uncovered that cells on 2D hydrogels and spheroids encapsulated in 3D hydrogels were less responsive to receptor tyrosine kinase (RTK)-targeting drugs sorafenib and lapatinib, but not cytotoxic drugs, compared to single cells in hydrogels and cells on plastic. We found that transcriptomic differences between these in vitro models and tumor xenografts did not reveal mechanisms of ECM-mediated resistance to sorafenib. However, a systems biology analysis of phospho-kinome data uncovered that variation in MEK phosphorylation was associated with RTK-targeted drug resistance. Using sorafenib as a model drug, we found that co-administration with a MEK inhibitor decreased ECM-mediated resistance in vitro and reduced in vivo tumor burden compared to sorafenib alone. In sum, we provide a novel strategy for identifying and overcoming ECM-mediated resistance mechanisms by performing drug screening, phospho-kinome analysis, and systems biology across multiple biomaterial environments

Aggregation Number-Based Degrees of Counterion Dissociation in Sodium n-Alkyl Sulfate Micelles

Values of the degree of counterion dissociation, R, for sodium n-alkyl sulfate micelles, denoted by SN c S, where N c is the number of carbon atoms in the alkyl chain, are defined by asserting that the aggregation number, N, is dependent only on the concentration, C aq , of counterions in the aqueous pseudophase. By using different combinations of surfactant and added salt concentrations to yield the same value of N, R can be determined, independent of the experimental method. Electron paramagnetic resonance measurements of the hyperfine spacings of two nitroxide spin probes, 16-and 5-doxylstearic acid methyl ester (16DSE and 5DSE, respectively), are employed to determine whether micelles from two samples have the same value of N to high precision. The EPR spectra are different for the two spin probes, but the values of R are the same, within experimental error, as they must be. In agreement with recent work on S12S and with prevailing thought in the literature, values of R are constant as a function of N. This implies that the value of R is constant whether the surfactant or added electrolyte concentrations are varied. Interestingly, R varies with chain length as follows: However, the theory also predicts that, for a given value of N c , R decreases as N increases. Moreover, this decrease is predicted to be different if N is increased by adding salt or by increasing the surfactant concentration. A modification to the theory in which dissociated counterions contribute to the ionic strength while added co-ions (Cl -) do not, brings theory and experiment into closer accord. Assuming R to be constant versus N permits a direct application of the aggregation number-based definition of R using time-resolved fluorescence quenching to measure values of N as well as other experimental parameters that vary monotonically with N, such as the microviscosity measured with spin probes and the quenching rate constant. For S13S micelles at 40°C, R ) 0.20 ( 0.02 is derived from N; R ) 0.21 ( 0.02 from the microvisicosity, and R ) 0.21 ( 0.02 from the quenching rate constants, in agreement with the hyperfine spacing results. The aggregation numbers for S13S are well described by the power law N ) N°(C aq /cmc 0 ) γ , where cmc 0 is the critical micelle concentration in the absence of added salt, N°) 67, and γ ) 0.26

Smooth Muscle Stiffness Sensitivity is Driven by Soluble and Insoluble ECM Chemistry

Smooth muscle cell (SMC) invasion into plaques and subsequent proliferation is a major factor in the progression of atherosclerosis. During disease progression, SMCs experience major changes in their microenvironment, such as what integrin-binding sites are exposed, the portfolio of soluble factors available, and the elasticity and modulus of the surrounding vessel wall. We have developed a hydrogel biomaterial platform to examine the combined effect of these changes on SMC phenotype. We were particularly interested in how the chemical microenvironment affected the ability of SMCs to sense and respond to modulus. To our surprise, we observed that integrin binding and soluble factors are major drivers of several critical SMC behaviors, such as motility, proliferation, invasion, and differentiation marker expres- sion, and these factors modulated the effect of stiffness on proliferation and migration. Overall, modulus only modestly affected behaviors other than proliferation, relative to integrin binding and soluble factors. Surprisingly, patho- logical behaviors (proliferation, motility) are not inversely related to SMC marker expression, in direct conflict with previous studies on substrates coupled with single extracel- lular matrix (ECM) proteins. A high-throughput bead-based ELISA approach and inhibitor studies revealed that differ- entiation marker expression is mediated chiefly via focal adhesion kinase (FAK) signaling, and we propose that integrin binding and FAK drive the transition from a migratory to a proliferative phenotype. We emphasize the importance of increasing the complexity of in vitro testing platforms to capture these subtleties in cell phenotypes and signaling, in order to better recapitulate important features of in vivo disease and elucidate potential context-dependent therapeutic targets

Gastroparesia diabética: revisión corta con viñeta clínica ilustrativa. Actualización y puntos más relevantes para la práctica clínica

La gastroparesia diabética es una entidad conocida, aunque en oportunidades se torna difícil su manejo con tratamiento médico, por lo que se deben contemplar otras opciones terapéuticas avanzadas. Es una enfermedad que amerita el tratamiento en conjunto entre gastroenterólogo, endocrinólogo y nutricionista

Commissioning and performance of the Preshower off-detector readout electronics in the CMS experiment

The CMS Preshower is a fine grain detector that comprises 4288 silicon sensors, each containing 32 strips. The data are transferred from the detector to the counting room via 1208 optical fibres producing a total data flow of ~72GB/s. For their readout, 40 multi-FPGA 9U VME boards are used. This article is focused on the commissioning of the VME readout system using two tools: a custom connectivity test system based on FPGA embedded logic analyzers read out through JTAG and an FPGA-based system that emulates the data-traffic from the detector. Additionally, the performance of the VME readout system in the CMS experiment, including the 2009 Cosmic ray at Four Tesla (CRAFT) run, is discussed

Making Rules to Dispose of Manifestly Unfounded Assertions: An Exorcism of the Bogy of Non-Trans-Substantive Rules of Civil Procedure

Since the concept of universal design is already extending the boundary of disabilities, it is significant to include different aspects of information technology where universal design enabled efforts can contribute towards better designed systems, products and services. Sustainability is an important and growing public concern in today’s world. Nevertheless, attempts of designing IT system that can be called sustainable in nature are not so evident at present. In this paper we propose a framework originating from sustainable IT system design principles (also described in the paper). The universal design principles are used as a foundation upon which the resultant sustainable IT system design principles were derived. The concept of ‘sustainable IT system’ addressed in this research paper is beyond the common phenomenon of sustainability like green IT, CO2 emission etc. Rather, the framework proposed in this paper incorporates more user inclusion and increased user satisfaction together towards higher usability. And an IT system designed in this manner is a sustainable IT system according to the argument of this paper which can therefore be designed by following the proposed design principles and framework

New Frontiers for Organismal Biology

Understanding how complex organisms function as integrated units that constantly interact with their environment is a long-standing challenge in biology. To address this challenge, organismal biology reveals general organizing principles of physiological systems and behavior—in particular, in complex multicellular animals. Organismal biology also focuses on the role of individual variability in the evolutionary maintenance of diversity. To broadly advance these frontiers, cross-compatibility of experimental designs, methodological approaches, and data interpretation pipelines represents a key prerequisite. It is now possible to rapidly and systematically analyze complete genomes to elucidate genetic variation associated with traits and conditions that define individuals, populations, and species. However, genetic variation alone does not explain the varied individual physiology and behavior of complex organisms. We propose that such emergent properties of complex organisms can best be explained through a renewed emphasis on the context and life-history dependence of individual phenotypes to complement genetic data.Organismic and Evolutionary Biolog