Requirement of the NPXY motif in the integrin beta 3 subunit cytoplasmic tail for melanoma cell migration in vitro and in vivo.

The NPXY sequence is highly conserved among integrin beta subunit cytoplasmic tails, suggesting that it plays a fundamental role in regulating integrin-mediated function. Evidence is provided that the NPXY structural motif within the beta 3 subunit, comprising residues 744-747, is essential for cell morphological and migratory responses mediated by integrin alpha v beta 3 in vitro and in vivo. Transfection of CS-1 melanoma cells with a cDNA encoding the wild-type integrin beta 3 subunit, results in de novo alpha v beta 3 expression and cell attachment, spreading, and migration on vitronectin. CS-1 cells expressing alpha v beta 3 with mutations that disrupt the NPXY sequence interact with soluble vitronectin or an RGD peptide, yet fail to attach, spread, or migrate on immobilized ligand. The biological consequences of these observations are underscored by the finding that CS-1 cells expressing wild-type alpha v beta 3 acquire the capacity to form spontaneous pulmonary metastases in the chick embryo when grown on the chorioallantoic membrane. However, migration-deficient CS-1 cells expressing alpha v beta 3 with mutations in the NPXY sequence lose this ability to metastasize. These findings demonstrate that the NPXY motif within the integrin beta 3 cytoplasmic tail is essential for alpha v beta 3-dependent post-ligand binding events involved in cell migration and the metastatic phenotype of melanoma cells

Signature and escape of highly fractionated plasma in an active region

Accurate forecasting of space weather requires knowledge of the source regions where solar energetic particles (SEP) and eruptive events originate. Recent work has linked several major SEP events in 2014, January, to specific features in the host active region (AR 11944). In particular, plasma composition measurements in and around the footpoints of hot, coronal loops in the core of the active region were able to explain the values later measured in situ by the Wind spacecraft. Due to important differences in elemental composition between SEPs and the solar wind, the magnitude of the Si/S elemental abundance ratio emerged as a key diagnostic of SEP seed population and solar wind source locations. We seek to understand if the results are typical of other active regions, even if they are not solar wind sources or SEP productive. In this paper, we use a novel composition analysis technique, together with an evolutionary magnetic field model, in a new approach to investigate a typical solar active region (AR 11150), and identify the locations of highly fractionated (high Si/S abundance ratio) plasma. Material confined near the footpoints of coronal loops, as in AR 11944, that in this case have expanded to the AR periphery, show the signature, and can be released from magnetic field opened by reconnection at the AR boundary. Since the fundamental characteristics of closed field loops being opened at the AR boundary is typical of active regions, this process is likely to be general

The source of the major solar energetic particle events from super active region 11944

Shock waves associated with fast coronal mass ejections (CMEs) accelerate solar energetic particles (SEPs) in the long duration, gradual events that pose hazards to crewed spaceflight and near-Earth technological assets, but the source of the CME shock-accelerated plasma is still debated. Here, we use multi-messenger observations from the Heliophysics System Observatory to identify plasma confined at the footpoints of the hot, core loops of active region 11944 as the source of major gradual SEP events in January 2014. We show that the elemental composition signature detected spectroscopically at the footpoints explains the measurements made by particle counting techniques near Earth. Our results localize the elemental fractionation process to the top of the chromosphere. The plasma confined closest to that region, where the coronal magnetic field strength is high (a few hundred Gauss), develops the SEP composition signature. This source material is continually released from magnetic confinement and accelerated as SEPs following M-, C-, and X-class flares

Conditions that Stabilize Membrane Domains Also Antagonize n-Alcohol Anesthesia

Diverse molecules induce general anesthesia with potency strongly correlated with both their hydrophobicity and their effects on certain ion channels. We recently observed that several n -alcohol anesthetics inhibit heterogeneity in plasma-membrane-derived vesicles by lowering the critical temperature (Tc) for phase separation. Here, we exploit conditions that stabilize membrane heterogeneity to further test the correlation between the anesthetic potency of n -alcohols and effects on Tc. First, we show that hexadecanol acts oppositely to n -alcohol anesthetics on membrane mixing and antagonizes ethanol-induced anesthesia in a tadpole behavioral assay. Second, we show that two previously described “intoxication reversers” raise Tc and counter ethanol’s effects in vesicles, mimicking the findings of previous electrophysiological and behavioral measurements. Third, we find that elevated hydrostatic pressure, long known to reverse anesthesia, also raises Tc in vesicles with a magnitude that counters the effect of butanol at relevant concentrations and pressures. Taken together, these results demonstrate that ΔTc predicts anesthetic potency for n-alcohols better than hydrophobicity in a range of contexts, supporting a mechanistic role for membrane heterogeneity in general anesthesia

Dosimetry of 3 CBCT devices for oral and maxillofacial radiology: CB Mercuray, NewTom 3G and i-CAT

Cone beam computed tomography (CBCT), which provides a lower dose, lower cost alternative to conventional CT, is being used with increasing frequency in the practice of oral and maxillofacial radiology. This study provides comparative measurements of effective dose for three commercially available, large (12'') field-of-view (FOV), CBCT units: CB Mercuray, NewTom 3G and i-CAT. Thermoluminescent dosemeters (TLDs) were placed at 24 sites throughout the layers of the head and neck of a tissue-equivalent human skull RANDO phantom. Depending on availability, the 12'' FOV and smaller FOV scanning modes were used with similar phantom positioning geometry for each CBCT unit. Radiation weighted doses to individual organs were summed using 1990 (E(1990)) and proposed 2005 (E(2005 draft)) ICRP tissue weighting factors to calculate two measures of whole-body effective dose. Dose as a multiple of a representative panoramic radiography dose was also calculated. For repeated runs dosimetry was generally reproducible within 2.5%. Calculated doses in microSv [corrected] (E(1990), E(2005 draft)) were NewTom3G (45, 59), i-CAT (135, 193) and CB Mercuray (477, 558). These are 4 to 42 times greater than comparable panoramic examination doses (6.3 microSv [corrected] 13.3 mSv). Reductions in dose were seen with reduction in field size and mA and kV technique factors. CBCT dose varies substantially depending on the device, FOV and selected technique factors. Effective dose detriment is several to many times higher than conventional panoramic imaging and an order of magnitude or more less than reported doses for conventional CT

Agile methods for agile universities

We explore a term, Agile, that is being used in various workplace settings, including the management of universities. The term may have several related but slightly different meanings. Agile is often used in the context of facilitating more creative problem-solving and advocating for the adoption, design, tailoring and continual updating of more innovative organizational processes. We consider a particular set of meanings of the term from the world of software development. Agile methods were created to address certain problems with the software development process. Many of those problems have interesting analogues in the context of universities, so a reflection on agile methods may be a useful heuristic for generating ideas for enabling universities to be more creative

Beyond persons: extending the personal / subpersonal distinction to non-rational animals and artificial agents

The distinction between personal level explanations and subpersonal ones has been subject to much debate in philosophy. We understand it as one between explanations that focus on an agent’s interaction with its environment, and explanations that focus on the physical or computational enabling conditions of such an interaction. The distinction, understood this way, is necessary for a complete account of any agent, rational or not, biological or artificial. In particular, we review some recent research in Artificial Life that pretends to do completely without the distinction, while using agent-centered concepts all the way. It is argued that the rejection of agent level explanations in favour of mechanistic ones is due to an unmotivated need to choose among representationalism and eliminativism. The dilemma is a false one if the possibility of a radical form of externalism is considered

Evolution of Plasma Composition in an Eruptive Flux Rope

Magnetic flux ropes are bundles of twisted magnetic field enveloping a central axis. They harbor free magnetic energy and can be progenitors of coronal mass ejections (CMEs). However, identifying flux ropes on the Sun can be challenging. One of the key coronal observables that has been shown to indicate the presence of a flux rope is a peculiar bright coronal structure called a sigmoid. In this work, we show Hinode EUV Imaging Spectrometer observations of sigmoidal active region (AR) 10977. We analyze the coronal plasma composition in the AR and its evolution as a sigmoid (flux rope) forms and erupts as a CME. Plasma with photospheric composition was observed in coronal loops close to the main polarity inversion line during episodes of significant flux cancellation, suggestive of the injection of photospheric plasma into these loops driven by photospheric flux cancellation. Concurrently, the increasingly sheared core field contained plasma with coronal composition. As flux cancellation decreased and a sigmoid/flux rope formed, the plasma evolved to an intermediate composition in between photospheric and typical AR coronal compositions. Finally, the flux rope contained predominantly photospheric plasma during and after a failed eruption preceding the CME. Hence, plasma composition observations of AR 10977 strongly support models of flux rope formation by photospheric flux cancellation forcing magnetic reconnection first at the photospheric level then at the coronal level

A Novel, All-Optical Tool for Controllable and Non- Destructive Poration of Cells with Single-Micron Resolution

We demonstrate controllable poration within ≈1 µm regions of individual cells, mediated by a near-IR laser interacting with thin-layer amorphous silicon substrates. This technique will allow new experiments in single-cell biology, particularly in neuroscience. As our understanding of the fundamental mechanistic processes underpinning biology expands, so does the need for high-precision tools to allow the dissection of the heterogeneity and stochastic processes that dominate at the single- and sub-cellular level. Here, we demonstrate a highly controllable and reproducible optical technique for inducing poration within specific regions of a target cell’s plasma membrane, permitting localized delivery of payloads, depolarization and lysis experiments to be conducted in unprecedented detail. Experiments support a novel mechanism for the process, based upon a thermally-induced change triggered by the interactions of a near-IR laser with a biocompatible thin film substrate at powers substantially below that used in standard optoporation experiments