Role of the fast kinetics of pyroglutamate-modified amyloid-β oligomers in membrane binding and membrane permeability.

Membrane permeability to ions and small molecules is believed to be a critical step in the pathology of Alzheimer's disease (AD). Interactions of oligomers formed by amyloid-β (Aβ) peptides with the plasma cell membrane are believed to play a fundamental role in the processes leading to membrane permeability. Among the family of Aβs, pyroglutamate (pE)-modified Aβ peptides constitute the most abundant oligomeric species in the brains of AD patients. Although membrane permeability mechanisms have been studied for full-length Aβ1-40/42 peptides, these have not been sufficiently characterized for the more abundant AβpE3-42 fragment. Here we have compared the adsorbed and membrane-inserted oligomeric species of AβpE3-42 and Aβ1-42 peptides. We find lower concentrations and larger dimensions for both species of membrane-associated AβpE3-42 oligomers. The larger dimensions are attributed to the faster self-assembly kinetics of AβpE3-42, and the lower concentrations are attributed to weaker interactions with zwitterionic lipid headgroups. While adsorbed oligomers produced little or no significant membrane structural damage, increased membrane permeabilization to ionic species is understood in terms of enlarged membrane-inserted oligomers. Membrane-inserted AβpE3-42 oligomers were also found to modify the mechanical properties of the membrane. Taken together, our results suggest that membrane-inserted oligomers are the primary species responsible for membrane permeability

SMA and Spitzer Observations of Bok Glouble CB17: A Candidate First Hydrostatic Core?

We present high angular resolution SMA and Spitzer observations toward the Bok globule CB17. SMA 1.3mm dust continuum images reveal within CB17 two sources with an angular separation of about 21" (about 5250 AU at a distance of 250 pc). The northwestern continuum source, referred to as CB17 IRS, dominates the infrared emission in the Spitzer images, drives a bipolar outflow extending in the northwest-southeast direction, and is classified as a low luminosity Class0/I transition object (L_bol ~ 0.5 L_sun). The southeastern continuum source, referred to as CB17 MMS, has faint dust continuum emission in the SMA 1.3mm observations (about 6 sigma detection; ~3.8 mJy), but is not detected in the deep Spitzer infrared images at wavelengths from 3.6 to 70 micron. Its bolometric luminosity and temperature, estimated from its spectral energy distribution, are less than 0.04 L_sun and 16 K, respectively. The SMA CO(2-1) observations suggest that CB17 MMS may drive a low-velocity molecular outflow (about 2.5 km/s), extending in the east-west direction. Comparisons with prestellar cores and Class0 protostars suggest that CB17 MMS is more evolved than prestellar cores but less evolved than Class0 protostars. The observed characteristics of CB17 MMS are consistent with the theoretical predictions from radiative/magneto hydrodynamical simulations of a first hydrostatic core, but there is also the possibility that CB17 MMS is an extremely low luminosity protostar deeply embedded in an edge-on circumstellar disk. Further observations are needed to study the properties of CB17 MMS and to address more precisely its evolutionary stage.Comment: 33 pages, 11 figures, to be published by Ap

A Catalog of Low-Mass Star-Forming Cores Observed with SHARC-II at 350 microns

We present a catalog of low-mass dense cores observed with the SHARC-II instrument at 350 microns. Our observations have an effective angular resolution of 10", approximately 2.5 times higher than observations at the same wavelength obtained with the Herschel Space Observatory, albeit with lower sensitivity, especially to extended emission. The catalog includes 81 maps covering a total of 164 detected sources. For each detected source, we tabulate basic source properties including position, peak intensity, flux density in fixed apertures, and radius. We examine the uncertainties in the pointing model applied to all SHARC-II data and conservatively find that the model corrections are good to within ~3", approximately 1/3 of the SHARC-II beam. We examine the differences between two array scan modes and find that the instrument calibration, beam size, and beam shape are similar between the two modes. We also show that the same flux densities are measured when sources are observed in the two different modes, indicating that there are no systematic effects introduced into our catalog by utilizing two different scan patterns during the course of taking observations. We find a detection rate of 95% for protostellar cores but only 45% for starless cores, and demonstrate the existence of a SHARC-II detection bias against all but the most massive and compact starless cores. Finally, we discuss the improvements in protostellar classification enabled by these 350 micron observations.Comment: Accepted by A

The UN in the lab

We consider two alternatives to inaction for governments combating terrorism, which we term Defense and Prevention. Defense consists of investing in resources that reduce the impact of an attack, and generates a negative externality to other governments, making their countries a more attractive objective for terrorists. In contrast, Prevention, which consists of investing in resources that reduce the ability of the terrorist organization to mount an attack, creates a positive externality by reducing the overall threat of terrorism for all. This interaction is captured using a simple 3×3 “Nested Prisoner’s Dilemma” game, with a single Nash equilibrium where both countries choose Defense. Due to the structure of this interaction, countries can benefit from coordination of policy choices, and international institutions (such as the UN) can be utilized to facilitate coordination by implementing agreements to share the burden of Prevention. We introduce an institution that implements a burden-sharing policy for Prevention, and investigate experimentally whether subjects coordinate on a cooperative strategy more frequently under different levels of cost sharing. In all treatments, burden sharing leaves the Prisoner’s Dilemma structure and Nash equilibrium of the game unchanged. We compare three levels of burden sharing to a baseline in a between-subjects design, and find that burden sharing generates a non-linear effect on the choice of the efficient Prevention strategy and overall performance. Only an institution supporting a high level of mandatory burden sharing generates a significant improvement in the use of the Prevention strategy

Music genre classification via joint sparse low-rank representation of audio features

A novel framework for music genre classification, namely the joint sparse low-rank representation (JSLRR) is proposed in order to: 1) smooth the noise in the test samples, and 2) identify the subspaces that the test samples lie onto. An efficient algorithm is proposed for obtaining the JSLRR and a novel classifier is developed, which is referred to as the JSLRR-based classifier. Special cases of the JSLRR-based classifier are the joint sparse representation-based classifier and the low-rank representation-based one. The performance of the three aforementioned classifiers is compared against that of the sparse representation-based classifier, the nearest subspace classifier, the support vector machines, and the nearest neighbor classifier for music genre classification on six manually annotated benchmark datasets. The best classification results reported here are comparable with or slightly superior than those obtained by the state-of-the-art music genre classification methods

Aproximación enfermera a los cuidados no profesionales a través de las vivencias de una cuidadora

Introducción: El envejecimiento progresivo de la población española, y la creciente disminución de los recursos institucionales para el cuidado de las personas dependientes, implica que cada día sea mayor la necesidad de disponer de cuidadoras no profesionales. En la mayoría de los casos la calidad de vida de las personas dependientes depende de los cuidados no profesionales prestados por mujeres y familiares en general de la persona dependiente. Cuidados y cuidadores son a menudo invisibilizados y/o poco reconocidos desde el punto de vista social, institucional y legislativo. Es función de enfermería conocer esta problemática, identificar a las cuidadoras no profesionales y las necesidades derivadas de su rol, y dispensarles la ayuda, conocimiento y apoyo necesario para realizar esta tarea en las mejores condiciones posibles. Objetivos: Definir los conceptos relacionados con "el cuidar" dentro del sector popular de la salud para poder comprender las vivencias y la problemática de las personas que ejercen de cuidadoras dentro de este sector. Analizar e interpretar el discurso de una cuidadora informal relacionándolo con las categorías diagnósticas propuestas por la NANDA para poder descubrir los problemas relacionados con el cuidado donde sería posible la intervención enfermera al cuidador. Material y métodos: Revisión bibliográfica sistemática con inclusión de textos legislativos relevantes para este trabajo. Entrevista semiestructurada a una cuidadora no profesional. Análisis del discurso. Codificación abierta e inductiva de la información con establecimiento de dominios y categorías de análisis, tomando como modelo la “Teoría Fundamentada” de Glaser y Strauss. Resultados: dominios y categorías diagnósticas NANDA en base al discurso de una cuidadora. Conclusiones: Dada la importancia los cuidados no profesionales es fundamental que los programas de atención sanitaria de nuestra cultura y nuestra sociedad, creen las bases para garantizar el bienestar biopsicosocial de la cuidadora no profesional. Por otra parte, las cuidadoras no profesionales sufren numerosos problemas de salud en los que el profesional de enfermería puede actuar, especialmente detectando y previniendo los factores de riesgo para el cuidador

A Micro Molecular Bipolar Outflow From HL Tau

We present detailed geometry and kinematics of the inner outflow toward HL Tau observed using Near Infrared Integral Field Spectograph (NIFS) at the Gemini-North 8-m Observatory. We analyzed H2 2.122 um emission and [Fe II] 1.644 um line emission as well as the adjacent continuum observed at a <0".2 resolution. The H2 emission shows (1) a bubble-like geometry to the northeast of the star, as briefly reported in the previous paper, and (2) faint emission in the southwest counterflow, which has been revealed through careful analysis. The emission on both sides of the star show an arc 1".0 away from the star, exhibiting a bipolar symmetry. Different brightness and morphologies in the northeast and southwest flows are attributed to absorption and obscuration of the latter by a flattened envelope and a circumstellar disk. The H2 emission shows a remarkably different morphology from the collimated jet seen in [Fe II] emission. The positions of some features coincide with scattering continuum, indicating that these are associated with cavities in the dusty envelope. Such properties are similar to millimeter CO outflows, although the spatial scale of the H2 outflow in our image (~150 AU) is strikingly smaller than the mm outflows, which often extend over 1000-10000 AU scales. The position-velocity diagram of the H2 and [Fe II] emission do not show any evidence for kinematic interaction between these flows. All results described above support the scenario that the jet is surrounded by an unseen wide-angled wind, which interacts with the ambient gas and produce the bipolar cavity and shocked H2 emission.Comment: 13 pages, 4 figures, accepted for publication in ApJ