Methylation age acceleration does not predict mortality in schizophrenia.

Schizophrenia (SCZ) is associated with high mortality. DNA methylation levels vary over the life course, and pre-selected combinations of methylation array probes can be used to estimate "methylation age" (mAge). mAge correlates highly with chronological age but when it differs, termed mAge acceleration, it has been previously associated with all-cause mortality. We tested the association between mAge acceleration and mortality in SCZ and controls. We selected 190 SCZ cases and 190 controls from the Sweden Schizophrenia Study. Cases were identified from the Swedish Hospital Discharge Register with ≥5 specialist treatment contacts and ≥5 antipsychotic prescriptions. Controls had no psychotic disorder or antipsychotics. Subjects were selected if they had died or survived during follow-up (2:1 oversampling). Extracted DNA was assayed on the Illumina MethylationEPIC array. mAge was regressed on age at sampling to obtain mAge acceleration. Using Cox proportional hazards regression, the association between mAge acceleration and mortality was tested. After quality control, the following were available: n = 126 SCZ died, 63 SCZ alive, 127 controls died, 62 controls alive. In the primary analyses, we did not find a significant association between mAge acceleration and SCZ mortality (adjusted p > 0.005). Sensitivity analyses excluding SCZ cases with pre-existing cancer demonstrated a significant association between the Hannum mAge acceleration and mortality (hazard ratio = 1.13, 95% confidence interval = 1.04-1.22, p = 0.005). Per our pre-specified criteria, we did not confirm our primary hypothesis that mAge acceleration would predict subsequent mortality in people with SCZ, but we cannot rule out smaller effects or effects in patient subsets

The Two Phases of Galaxy Formation

Cosmological simulations of galaxy formation appear to show a two-phase character with a rapid early phase at z>2 during which in-situ stars are formed within the galaxy from infalling cold gas followed by an extended phase since z<3 during which ex-situ stars are primarily accreted. In the latter phase massive systems grow considerably in mass and radius by accretion of smaller satellite stellar systems formed at quite early times (z>3) outside of the virial radius of the forming central galaxy. These tentative conclusions are obtained from high resolution re-simulations of 39 individual galaxies in a full cosmological context with present-day virial halo masses ranging from 7e11 M_sun h^-1 < M_vir < 2.7e13 M_sun h^-1 and central galaxy masses between 4.5e10 M_sun h^-1 < M_* < 3.6e11 M_sun h^-1. The simulations include the effects of a uniform UV background, radiative cooling, star formation and energetic feedback from SNII. The importance of stellar accretion increases with galaxy mass and towards lower redshift. In our simulations lower mass galaxies ($M_* < 9e10 M_sun h^-1) accrete about 60 per cent of their present-day stellar mass. High mass galaxy ($M_* > 1.7e11 M_sun h^-1) assembly is dominated by accretion and merging with about 80 per cent of the stars added by the present-day. In general the simulated galaxies approximately double their mass since z=1. For massive systems this mass growth is not accompanied by significant star formation. The majority of the in-situ created stars is formed at z>2, primarily out of cold gas flows. We recover the observational result of archaeological downsizing, where the most massive galaxies harbor the oldest stars. We find that this is not in contradiction with hierarchical structure formation. Most stars in the massive galaxies are formed early on in smaller structures, the galaxies themselves are assembled late.Comment: 13 pages, 13 figures, accepted for publication in Ap

3D multiphysics model for the simulation of electrochemical machining of stainless steel (SS316)

In Electrochemical Machining (ECM) - a method that uses anodic dissolution to remove metal - it is extremely difficult to predict material removal and resulting surface finish due to the complex interaction between the numerous parameters available in the machining conditions. In this paper, it is argued that a 3D coupled multiphysics finite element model is a suitable way to further develop the ability to model the ECM process. This builds on the work of previous researchers and further claims that the over-potential available at the surface of the workpiece is a crucial factor in ensuring satisfactory results. As a validation example, a real world problem for polishing via ECM of SS316 pipes is modelled and compared to empirical tests. Various physical and chemical effects, including those due to electrodynamics, fluid dynamic, and thermal and electrochemical phenomena were incorporated in the 3D geometric model of the proposed tool, workpiece and electrolyte. Predictions were made for current density, conductivity, fluid velocity, temperature, and crucially, with estimates of the deviations in over-potential. Results revealed a good agreement between simulation and experiment and these were sufficient to solve the immediate real problem presented but also to ensure that future additions to the technique could in the longer term lead to a better means of understanding a most useful manufacturing process

Investigation of reactivity of launch vehicle materials with liquid oxygen Quarterly report, 23 Jul. - 22 Oct. 1968

Reactivity of launch vehicle organic materials with liquid oxyge

Investigation of Reactivity of Launch Vehicle Materials with Liquid Oxygen

Impact sensitivity and ignition mechanism of organic compounds in liquid oxygen correlated with chemical and physical propertie

Spatial processing is frequency-specific in auditory cortex but not in the midbrain

The cochlea behaves like a bank of band-pass filters, segregating information into different frequency channels. Some aspects of perception reflect processing within individual channels, but others involve the integration of information across them. One instance of this is sound localization, which improves with increasing bandwidth. The processing of binaural cues for sound location has been extensively studied. However, while the advantage conferred by bandwidth is clear we currently know little about how this additional information is combined to form our percept of space. We investigated the ability of cells in the auditory system of guinea pigs to compare interaural level differences (ILDs), a key localization cue, between tones of disparate frequencies in each ear. Cells in auditory cortex, believed to be integral to ILD processing (Excitatory from one ear, Inhibitory from the other: EI cells), separately compare ILDs over restricted frequency ranges, not consistent with their monaural tuning. In contrast, cortical EE (Excitatory from both ears) cells showed no evidence of frequency-specific processing. Both cell types are explained by a model in which ILDs are computed within separate frequency channels and subsequently combined in a single cortical cell. Interestingly, ILD processing in all inferior colliculus cell types (EE and EI) is largely consistent with processing within single matched frequency channels from each ear. Our data suggests a clear constraint on the way that localisation cues are integrated: cortical ILD tuning to broadband sounds is a composite of separate frequency-specific binaurally sensitive channels. This frequency-specific processing appears after the midbrain

Low X-Ray Luminosity Galaxy Clusters: Main goals, sample selection, photometric and spectroscopic observations

We present the study of nineteen low X-ray luminosity galaxy clusters (L$_X \sim$ 0.5--45 $\times$ $10^{43}$ erg s$^{-1}$), selected from the ROSAT Position Sensitive Proportional Counters (PSPC) Pointed Observations (Vikhlinin et al. 1998) and the revised version of Mullis et al. (2003) in the redshift range of 0.16 to 0.7. This is the introductory paper of a series presenting the sample selection, photometric and spectroscopic observations and data reduction. Photometric data in different passbands were taken for eight galaxy clusters at Las Campanas Observatory; three clusters at Cerro Tololo Interamerican Observatory; and eight clusters at the Gemini Observatory. Spectroscopic data were collected for only four galaxy clusters using Gemini telescopes. With the photometry, the galaxies were defined based on the star-galaxy separation taking into account photometric parameters. For each galaxy cluster, the catalogues contain the PSF and aperture magnitudes of galaxies within the 90\% completeness limit. They are used together with structural parameters to study the galaxy morphology and to estimate photometric redshifts. With the spectroscopy, the derived galaxy velocity dispersion of our clusters ranged from 507 km~s$^{-1}$ for [VMF98]022 to 775 km~s$^{-1}$ for [VMF98]097 with signs of substructure. Cluster membership has been extensively discussed taking into account spectroscopic and photometric redshift estimates. In this sense, members are the galaxies within a projected radius of 0.75 Mpc from the X-ray mission peak and with cluster centric velocities smaller than the cluster velocity dispersion or 6000 km~s$^{-1}$, respectively. These results will be used in forthcoming papers to study, among the main topics, the red cluster sequence, blue cloud and green populations; the galaxy luminosity function and cluster dynamics.Comment: 13 pages, 6 tables, 9 figures. Uses emulateapj. Accepted for publication in The Astronomical Journal. Some formatting errors fixe

Modelling the Emergence and Dynamics of Perceptual Organisation in Auditory Streaming

Many sound sources can only be recognised from the pattern of sounds they emit, and not from the individual sound events that make up their emission sequences. Auditory scene analysis addresses the difficult task of interpreting the sound world in terms of an unknown number of discrete sound sources (causes) with possibly overlapping signals, and therefore of associating each event with the appropriate source. There are potentially many different ways in which incoming events can be assigned to different causes, which means that the auditory system has to choose between them. This problem has been studied for many years using the auditory streaming paradigm, and recently it has become apparent that instead of making one fixed perceptual decision, given sufficient time, auditory perception switches back and forth between the alternatives—a phenomenon known as perceptual bi- or multi-stability. We propose a new model of auditory scene analysis at the core of which is a process that seeks to discover predictable patterns in the ongoing sound sequence. Representations of predictable fragments are created on the fly, and are maintained, strengthened or weakened on the basis of their predictive success, and conflict with other representations. Auditory perceptual organisation emerges spontaneously from the nature of the competition between these representations. We present detailed comparisons between the model simulations and data from an auditory streaming experiment, and show that the model accounts for many important findings, including: the emergence of, and switching between, alternative organisations; the influence of stimulus parameters on perceptual dominance, switching rate and perceptual phase durations; and the build-up of auditory streaming. The principal contribution of the model is to show that a two-stage process of pattern discovery and competition between incompatible patterns can account for both the contents (perceptual organisations) and the dynamics of human perception in auditory streaming

Wnt2 and WISP-1/CCN4 induce intimal thickening via promotion of smooth muscle cell migration

Objective—Increased vascular smooth muscle cell (VSMC) migration leads to intimal thickening which acts as a soil for atherosclersosis, as well as causing coronary artery restenosis after stenting and vein graft failure. Investigating factors involved in VSMC migration may enable us to reduce intimal thickening and improve patient outcomes. In this study, we determined whether Wnt proteins regulate VSMC migration and thereby intimal thickening. Approach and Results—Wnt2 mRNA and protein expression were specifically increased in migrating mouse aortic VSMCs. Moreover, VSMC migration was induced by recombinant Wnt2 in vitro. Addition of recombinant Wnt2 protein increased Wnt1-inducible signaling pathway protein-1 (WISP-1) mRNA by ≈1.7-fold, via β-catenin/T-cell factor signaling, whereas silencing RNA knockdown of Wnt-2 reduced WISP-1 mRNA by ≈65%. Treatment with rWISP-1 significantly increased VSMC migration by ≈1.5-fold, whereas WISP-1 silencing RNA knockdown reduced migration by ≈40%. Wnt2 and WISP-1 effects were integrin-dependent and not additive, indicating that Wnt2 promoted VSMC migration via WISP-1. Additionally, Wnt2 and WISP-1 were significantly increased and colocated in human coronary arteries with intimal thickening. Reduced Wnt2 and WISP-1 levels in mouse carotid arteries from Wnt2+/− and WISP-1−/− mice, respectively, significantly suppressed intimal thickening in response to carotid artery ligation. In contrast, elevation of plasma WISP-1 via an adenovirus encoding WISP-1 significantly increased intimal thickening by ≈1.5-fold compared with mice receiving control virus. Conclusions—Upregulation of Wnt2 expression enhanced WISP-1 and promoted VSMC migration and thereby intimal thickening. As novel regulators of VSMC migration and intimal thickening, Wnt2 or WISP-1 may provide a potential therapy for restenosis and vein graft failure

Law, Liberty and the Rule of Law (in a Constitutional Democracy)

In the hunt for a better--and more substantial--awareness of the “law,” The author intends to analyze the different notions related to the “rule of law” and to criticize the conceptions that equate it either to the sum of “law” and “rule” or to the formal assertion that “law rules,” regardless of its relationship to certain principles, including both “negative” and “positive” liberties. Instead, he pretends to scrutinize the principles of the “rule of law,” in general, and in a “constitutional democracy,” in particular, to conclude that the tendency to reduce the “democratic principle” to the “majority rule” (or “majority principle”), i.e. to whatever pleases the majority, as part of the “positive liberty,” is contrary both to the “negative liberty” and to the “rule of law” itself