Regulation of cell-­nonautonomous proteostasis in metazoans

Cells have developed robust adaptation mechanisms to survive environmental conditions that challenge the integrity of their proteome and ensure cellular viability. These are stress-­signalling pathways that integrate extracellular signals with the ability to detect and efficiently respond to protein-­folding perturbations within the cell. Within the context of an organism, the cell autonomous effects of these signalling mechanisms are superimposed by cell-­nonautonomous stress signalling pathways that allow coordination of stress responses across tissues. These transcellular stress signalling pathways orchestrate and maintain the cellular proteome at an organismal level. This review focuses on mechanisms in both invertebrate and vertebrate organisms that activate stress responses in a cell-­nonautonomous manner. We discuss emerging insights and provide specific examples on how components of the cell-­nonautonomous proteostasis network are used in cancer and protein-­folding diseases to drive disease progression across tissues

Galaxy Disks

The formation and evolution of galactic disks is particularly important for understanding how galaxies form and evolve, and the cause of the variety in which they appear to us. Ongoing large surveys, made possible by new instrumentation at wavelengths from the ultraviolet (GALEX), via optical (HST and large groundbased telescopes) and infrared (Spitzer) to the radio are providing much new information about disk galaxies over a wide range of redshift. Although progress has been made, the dynamics and structure of stellar disks, including their truncations, are still not well understood. We do now have plausible estimates of disk mass-to-light ratios, and estimates of Toomre's $Q$ parameter show that they are just locally stable. Disks are mostly very flat and sometimes very thin, and have a range in surface brightness from canonical disks with a central surface brightness of about 21.5 $B$-mag arcsec$^{-2}$ down to very low surface brightnesses. It appears that galaxy disks are not maximal, except possibly in the largest systems. Their HI layers display warps whenever HI can be detected beyond the stellar disk, with low-level star formation going on out to large radii. Stellar disks display abundance gradients which flatten at larger radii and sometimes even reverse. The existence of a well-defined baryonic Tully-Fisher relation hints at an approximately uniform baryonic to dark matter ratio. Thick disks are common in disk galaxies and their existence appears unrelated to the presence of a bulge component; they are old, but their formation is not yet understood. Disk formation was already advanced at redshifts of $\sim 2$, but at that epoch disks were not yet quiescent and in full rotational equilibrium. Downsizing is now well-established. The formation and history of star formation in S0s is still not fully understood.Comment: This review has been submitted for Annual Reviews of Astronomy & Astrophysics, vol. 49 (2011); the final printed version will have fewer figures and a somewhat shortened text. A pdf-version of this preprint with high-resolution figures is available from http://www.astro.rug.nl/~vdkruit/jea3/homepage/disks-ph.pdf. (table of contents added; 71 pages, 24 figures, 529 references

Passwords and the evolution of imperfect authentication

Theory on passwords has lagged practice, where large providers use back-end smarts to survive with imperfect technology.This is the author accepted manuscript. The final version is available from ACM via http://dx.doi.org/10.1145/269939

High molar mass segmented macromolecular architectures by nitroxide mediated polymerisation

A straightforward synthetic pathway based on nitroxide mediated polymerisation (NMP) for the synthesis of a variety of high molar mass segmented copolymers comprising both polystyrene (PS) and polyether segments is reported. First, various precursors such as linear or star-shaped polyether macromonomers, containing either a-methylstyrene or styrene functions at one polymer terminus, as well as PS and polyether macroalkoxyamines bearing either 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) or N-tert-butyl-1-diethylphosphono-2,2-dimethylpropyl nitroxide (SG1) end-groups, were prepared. In a second step, these prepolymers were used to design different copolymer architectures such as block, graft, star-grafted, toothbrush and palm tree structures, in which PS constituted the backbone and polyether the side chains. Block copolymers were obtained by NMP of styrene initiated with polyether macroalkoxyamines. Copolymerisation of styrene with linear and star-shaped polyether macromonomers by NMP resulted in graft and star-grafted copolymers, respectively. A toothbrush copolymer was produced in a similar way with the exception of the initiator, which was a PS macroalkoxyamine. Likewise, palm tree architectures were obtained by homopolymerising polyether macromonomers initiated by PS macroinitiators. Advanced characterisation of the different polymer structures was performed, including 2D chromatography

Temperature induced solubility transitions of various poly(2-oxazoline)s in ethanol-water solvent mixtures

The solution behavior of a series of poly(2-oxazoline)s with different side chains, namely methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, pentyl, hexyl, heptyl, octyl, nonyl, phenyl and benzyl, are reported in ethanol-water solvent mixtures based on turbidimetry investigations. The LCST transitions of poly(2-oxazoline) s with propyl side chains and the UCST transitions of the poly(2-oxazoline) s with more hydrophobic side chains are discussed in relation to the ethanol-water solvent composition and structure. The poly(2-alkyl-2-oxazoline) s with side chains longer than propyl only dissolved during the first heating run, which is discussed and correlated to the melting transition of the polymers

A Meta-Analysis of Genome-Wide Association Scans Identifies IL18RAP, PTPN2, TAGAP, and PUS10 As Shared Risk Loci for Crohn's Disease and Celiac Disease

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02-6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (</=40: HR: 1.79; 95%-CI: 1.28-2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35-1.84) and node positivity (HR: 2.00; 95%-CI: 1.74-2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55-0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy

Energy detection based spectrum sensing over enriched multipath fading channels

Energy detection has been for long constituting the most popular sensing method in RADAR and cognitive radio systems. The present paper investigates the sensing behaviour of an energy detector over Hoyt fading channels, which have been extensively shown to provide rather accurate characterization of enriched multipath fading conditions. To this end, a simple series representation and an exact closed-form expression are firstly derived for the corresponding average probability of detection for the conventional single-channel communication scenario. These expressions are subsequently employed in deriving novel analytic results for the case of both collaborative detection and square-law selection diversity reception. The derived expressions have a relatively tractable algebraic representation which renders them convenient to handle both analytically and numerically. As a result, they can be utilized in quantifying the effect of fading in energy detection based spectrum sensing and in the determination of the trade-offs between sensing performance and energy efficiency in cognitive radio communications. Based on this, it is shown that the performance of the energy detector depends highly on the severity of fading as even slight variations of the fading conditions affect the value of the average probability of detection. It is also clearly shown that the detection performance improves substantially as the number of branches or collaborating users increase. This improvement is substantial in both moderate and severe fading conditions and can practically provide full compensation for the latter cases