Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain.

Overproduction of immunoglobulin light chains leads to systemic amyloidosis, a lethal disease characterized by the formation of amyloid fibrils in patients' tissues. Excess light chains are in equilibrium between dimers and less stable monomers which can undergo irreversible aggregation to the amyloid state. The dimers therefore must disassociate into monomers prior to forming amyloid fibrils. Here we identify ligands that inhibit amyloid formation by stabilizing the Mcg light chain variable domain dimer and shifting the equilibrium away from the amyloid-prone monomer

Improving Multiple-CMP Systems Using Token Coherence

Improvements in semiconductor technology now enable Chip Multiprocessors (CMPs). As many future computer systems will use one or more CMPs and support shared memory, such systems will have caches that must be kept coherent. Coherence is a particular challenge for Multiple-CMP (M-CMP) systems. One approach is to use a hierarchical protocol that explicitly separates the intra-CMP coherence protocol from the inter-CMP protocol, but couples them hierarchically to maintain coherence. However, hierarchical protocols are complex, leading to subtle, difficult-to-verify race conditions. Furthermore, most previous hierarchical protocols use directories at one or both levels, incurring indirections—and thus extra latency—for sharing misses, which are common in commercial workloads. In contrast, this paper exploits the separation of correctness substrate and performance policy in the recently-proposed token coherence protocol to develop the first M-CMP coherence protocol that is flat for correctness, but hierarchical for performance. Via model checking studies, we show that flat correctness eases verification. Via simulation with micro-benchmarks, we make new protocol variants more robust under contention. Finally, via simulation with commercial workloads on a commercial operating system, we show that new protocol variants can be 10-50% faster than a hierarchical directory protocol

Truthmakers and modality

This paper attempts to locate, within an actualist ontology, truthmakers for modal truths: truths of the form or . In section 1 I motivate the demand for substantial truthmakers for modal truths. In section 2 I criticise Armstrong’s account of truthmakers for modal truths. In section 3 I examine essentialism and defend an account of what makes essentialist attributions true, but I argue that this does not solve the problem of modal truth in general. In section 4 I discuss, and dismiss, a theistic account of the source of modal truth proposed by Alexander Pruss. In section 5 I offer a means of (dis)solving the problem

NASA'S Standard Measures During Bed Rest: Adaptations in the Cardiovascular System

Bed rest is a well-accepted analog of space flight that has been used extensively to investigate physiological adaptations in a larger number of subjects in a shorter amount of time than can be studied with space flight and without the confounding effects associated with normal mission operations. However, comparison across studies of different bed rest durations, between sexes, and between various countermeasure protocols have been hampered by dissimilarities in bed rest conditions, measurement protocols, and testing schedules. To address these concerns, NASA instituted standard bed rest conditions and standard measures for all physiological disciplines participating in studies conducted at the Flight Analogs Research Unit (FARU) at the University of Texas-Medical Branch. Investigators for individual studies employed their own targeted study protocols to address specific hypothesis-driven questions, but standard measures tests were conducted within these studies on a non-interference basis to maximize data availability while reducing the need to implement multiple bed rest studies to understand the effects of a specific countermeasure. When possible, bed rest standard measures protocols were similar to tests nominally used for medically-required measures or research protocols conducted before and after Space Shuttle and International Space Station missions. Specifically, bed rest standard measures for the cardiovascular system implemented before, during, and after bed rest at the FARU included plasma volume (carbon monoxide rebreathing), cardiac mass and function (2D, 3D and Doppler echocardiography), and orthostatic tolerance testing (15- or 30-minutes of 80 degree head-up tilt). Results to-date indicate that when countermeasures are not employed, plasma volume decreases and the incidence of presyncope during head-up tilt is more frequent even after short-duration bed rest while reductions in cardiac function and mass are progressive as bed rest duration increases. Additionally, while plasma volume loss can be corrected and cardiac mass can be prevented with properly applied countermeasures, orthostatic tolerance is more difficult to protect when supine exercise is the only countermeasure. Similar results have been observed after space flight. Plasma volume, cardiac chamber volume, and orthostatic tolerance recover relatively quickly with resumption of ambulation and normal activity levels after bed rest but restoration of cardiac mass is prolonged

Protocol for uniformly measuring and expressing the performance of energy storage systems.

The U.S. Department of Energy's Energy Storage Systems (ESS) Program, through the support of Pacific Northwest National Laboratory (PNNL) and Sandia National Laboratories (SNL), facilitated the development of the protocol provided in this report. The focus of the protocol is to provide a uniform way of measuring, quantifying, and reporting the performance of ESSs in various applications; something that does not exist today and, as such, is hampering the consideration and use of this technology in the market. The availability of an application-specific protocol for use in measuring and expressing performance-related metrics of ESSs will allow technology developers, power-grid operators and other end-users to evaluate the performance of energy storage technologies on a uniform and comparable basis. This will help differentiate technologies and products for specific application(s) and provide transparency in how performance is measured. It also will assist utilities and other consumers of ESSs to make more informed decisions as they consider the potential application and use of ESSs, as well as form the basis for documentation that might be required to justify utility investment in such technologies

Arctic ocean chronology confirmed by accelerator 14C dating

The role of the Arctic Ocean in Earth's climatic and oceanographic development is significant but has become controversial because of disagreements concerning a reliable Arctic chronology. The first Arctic Ocean chronology based on U-Th and 14C data was in agreement with magnetostratigraphy developed later but these data have been challenged by recent amino acid diagenesis dates. New accelerator 14C data support the earlier U-Th-magnetostratigraphic dates and confirm the reliability of the established Arctic Ocean chronology

The PAndAS Field of Streams: stellar structures in the Milky Way halo toward Andromeda and Triangulum

We reveal the highly structured nature of the Milky Way stellar halo within the footprint of the PAndAS photometric survey from blue main sequence and main sequence turn-off stars. We map no fewer than five stellar structures within a heliocentric range of ~5 to 30 kpc. Some of these are known (the Monoceros Ring, the Pisces/Triangulum globular cluster stream), but we also uncover three well-defined stellar structures that could be, at least partly, responsible for the so-called Triangulum/Andromeda and Triangulum/Andromeda 2 features. In particular, we trace a new faint stellar stream located at a heliocentric distance of ~17 kpc. With a surface brightness of \Sigma_V ~ 32-32.5 mag/arcsec^2, it follows an orbit that is almost parallel to the Galactic plane north of M31 and has so far eluded surveys of the Milky Way halo as these tend to steer away from regions dominated by the Galactic disk. Investigating our follow-up spectroscopic observations of PAndAS, we serendipitously uncover a radial velocity signature from stars that have colors and magnitudes compatible with the stream. From the velocity of eight likely member stars, we show that this stellar structure is dynamically cold, with an unresolved velocity dispersion that is lower than 7.1 km/s at the 90-percent confidence level. Along with the width of the stream (300-650 pc), its dynamics points to a dwarf-galaxy-accretion origin. The numerous stellar structures we can map in the Milky Way stellar halo between 5 and 30 kpc and their varying morphology is a testament to the complex nature of the stellar halo at these intermediate distances.Comment: 11 pages, 8 figures, accepted for publication in the ApJ, Figure 3 is the money plo

Developing and enhancing biodiversity monitoring programmes: a collaborative assessment of priorities

1.Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized. 2.We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa. 3.We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes. 4.People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims. 5.Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes

Anomalous Purcell decay of strongly driven inhomogeneous emitters coupled to a cavity

We perform resonant fluorescence lifetime measurements on a nanocavity-coupled erbium ensemble as a function of cavity-laser detuning and pump power. Our measurements reveal an anomalous suppression of the ensemble decay lifetime at zero cavity detuning and high pump fluence. We capture qualitative aspects of this decay rate suppression using a Tavis-Cummings model of non-interacting spins coupled to a common cavity.Comment: 4 figure

The HIPASS Catalogue - II. Completeness, Reliability, and Parameter Accuracy

The HI Parkes All Sky Survey (HIPASS) is a blind extragalactic HI 21-cm emission line survey covering the whole southern sky from declination -90 to +25. The HIPASS catalogue (HICAT), containing 4315 HI-selected galaxies from the region south of declination +2, is presented in Meyer et al. (2004a, Paper I). This paper describes in detail the completeness and reliability of HICAT, which are calculated from the recovery rate of synthetic sources and follow-up observations, respectively. HICAT is found to be 99 per cent complete at a peak flux of 84 mJy and an integrated flux of 9.4 Jy km/s. The overall reliability is 95 per cent, but rises to 99 per cent for sources with peak fluxes >58 mJy or integrated flux > 8.2 Jy km/s. Expressions are derived for the uncertainties on the most important HICAT parameters: peak flux, integrated flux, velocity width, and recessional velocity. The errors on HICAT parameters are dominated by the noise in the HIPASS data, rather than by the parametrization procedure.Comment: Accepted for publication in MNRAS. 12 pages, 11 figures. Paper with higher resolution figures can be downloaded from http://hipass.aus-vo.or