Plasma REST: A novel candidate biomarker of Alzheimer\u27s disease is modified by psychological intervention in an at-risk population

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain’s stress response. It is reduced in conditions of stress and Alzheimer’s disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention—mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit

Geophysical characterization of derelict coalmine workings and mineshaft detection: a case study from Shrewsbury, United Kingdom

A study site of derelict coalmine workings near Shrewsbury, United Kingdom was the focus for multi‐phase, near‐surface geophysical investigations. Investigation objectives were: 1) site characterization for remaining relict infrastructure foundations, 2) locate an abandoned coalmine shaft, 3) determine if the shaft was open, filled or partially filled and 4) determine if the shaft was capped (and if possible characterize the capping material). Phase one included a desktop study and 3D microgravity modelling of the relict coalmine shaft thought to be on site. In phase two, electrical and electromagnetic surveys to determine site resistivity and conductivity were acquired together with fluxgate gradiometry and an initial microgravity survey. Phase three targeted the phase two geophysical anomalies and acquired high‐resolution self potential and ground penetrating radar datasets. The phased‐survey approach minimised site activity and survey costs. Geophysical results were compared and interpreted to characterize the site, the microgravity models were used to validate interpretations. Relict buildings, railway track remains with associated gravel and a partially filled coalmine shaft were located. Microgravity proved optimal to locate the mineshaft with radar profiles showing ‘side‐swipe’ effects from the mineshaft that did not directly underlie survey lines. Geophysical interpretations were then verified with subsequent geotechnical intrusive investigations. Comparisons of historical map records with intrusive geotechnical site investigations show care must be taken using map data alone, as the latter mineshaft locations was found to be inaccurate

Numerical evaluation of shear strength of CFS shear wall panels for different height-to-width ratios

This paper presents a numerical evaluation of the shear strength of Cold Formed Steel Shear Wall Panels (CFS-SWPs) having 1.33:1 and 1:1 height-to-width aspect ratios with 0.76 mm steel plate sheathing thickness and 1:4,  1.33:1 and 1:1  height-to-width aspect ratios with 0.46 mm steel plate sheathing thickness, which are not provided by AISI S400. For this purpose, shell finite element (FE) models, validated with test results, are completed in ABAQUS v2018 with nonlinear geometry, material and connection. A good agreement is achieved between experimental and numerical results in terms of shear strength-lateral displacement and failure modes.It is concluded that, for a fixed height-to-width aspect ratio, the shear strength of SWPs having different screws spacing varying from 50.4 mm up to 152.4 can be assessed by interpolation using this FE method. However, by interloping the shear strength from 4:1 to 1:1 height-to-width aspect ratio, the shear strength can be underestimated; hence, it is more economical for practicing engineers to use the shear strength assessed by this proposed FE method for 1.33:1 and 1:1 height-to-width aspect ratios. Moreover, the effect of the sheathing thickness having 0.46 mm is evaluated and proposed as it lacks in data provided by the code (i.e., AISI S400)

Plasma REST: a novel candidate biomarker of Alzheimer's disease is modified by psychological intervention in an at-risk population.

The repressor element 1-silencing transcription (REST) factor is a key regulator of the aging brain's stress response. It is reduced in conditions of stress and Alzheimer's disease (AD), which suggests that increasing REST may be neuroprotective. REST can be measured peripherally in blood plasma. Our study aimed to (1) examine plasma REST levels in relation to clinical and biological markers of neurodegeneration and (2) alter plasma REST levels through a stress-reduction intervention-mindfulness training. In study 1, REST levels were compared across the following four well-characterized groups: healthy elderly (n=65), mild cognitive impairment who remained stable (stable MCI, n=36), MCI who later converted to dementia (converter MCI, n=29) and AD (n=65) from the AddNeuroMed cohort. REST levels declined with increasing severity of risk and impairment (healthy elderly>stable MCI>converter MCI>AD, F=6.35, P<0.001). REST levels were also positively associated with magnetic resonance imaging-based hippocampal and entorhinal atrophy and other putative blood-based biomarkers of AD (Ps<0.05). In study 2, REST was measured in 81 older adults with psychiatric risk factors for AD before and after a mindfulness-based stress reduction intervention or an education-based placebo intervention. Mindfulness-based training caused an increase in REST compared with the placebo intervention (F=8.57, P=0.006), and increased REST was associated with a reduction in psychiatric symptoms associated with stress and AD risk (Ps<0.02). Our data confirm plasma REST associations with clinical severity and neurodegeneration, and originally, that REST is modifiable by a psychological intervention with clinical benefit

Reasoning about goal-directed real-time teleo-reactive programs

The teleo-reactive programming model is a high-level approach to developing real-time systems that supports hierarchical composition and durative actions. The model is different from frameworks such as action systems, timed automata and TLA+, and allows programs to be more compact and descriptive of their intended behaviour. Teleo-reactive programs are particularly useful for implementing controllers for autonomous agents that must react robustly to their dynamically changing environments. In this paper, we develop a real-time logic that is based on Duration Calculus and use this logic to formalise the semantics of teleo-reactive programs. We develop rely/guarantee rules that facilitate reasoning about a program and its environment in a compositional manner. We present several theorems for simplifying proofs of teleo-reactive programs and present a partially mechanised method for proving progress properties of goal-directed agents. © 2013 British Computer Society

Public perceptions of tidal energy: Can you predict social acceptability across coastal communities in England?

Early consideration of potential societal issues faced by the nascent tidal industry is important to facilitate public engagement and potentially avoid levels of conflict that have arisen within other renewable energy sectors; general expressions of public support (as reported in national-scale attitude surveys) do not always translate into approval for local developments. It is a very appealing idea that the likely response of different types of communities to marine energy developments can be mapped and used to support planning. This study examined the attitudes of 963 people in South West England to hypothetical local tidal energy projects, analysing the results both by geographic location and according to the coastal community typology developed for England by the Marine Management Organisation. With the exception of age, demographic variables had little influence on the level of opposition to tidal energy, which instead was affected more by factors such as attitudes towards tidal energy in general (in particular its likely environmental impact), activities undertaken at the coast, and place attachment. These significant factors are typically not captured by the national census data used to determine community types. Any predictions about the acceptability of energy projects made as a result of community mapping based on demographic variables will not be a substitute for thorough public engagement and consultation, which should centre on the implications of tidal developments for the environment

ShapeMOD: Macro Operation Discovery for 3D Shape Programs

A popular way to create detailed yet easily controllable 3D shapes is via procedural modeling, i.e. generating geometry using programs. Such programs consist of a series of instructions along with their associated parameter values. To fully realize the benefits of this representation, a shape program should be compact and only expose degrees of freedom that allow for meaningful manipulation of output geometry. One way to achieve this goal is to design higher-level macro operators that, when executed, expand into a series of commands from the base shape modeling language. However, manually authoring such macros, much like shape programs themselves, is difficult and largely restricted to domain experts. In this paper, we present ShapeMOD, an algorithm for automatically discovering macros that are useful across large datasets of 3D shape programs. ShapeMOD operates on shape programs expressed in an imperative, statement-based language. It is designed to discover macros that make programs more compact by minimizing the number of function calls and free parameters required to represent an input shape collection. We run ShapeMOD on multiple collections of programs expressed in a domain-specific language for 3D shape structures. We show that it automatically discovers a concise set of macros that abstract out common structural and parametric patterns that generalize over large shape collections. We also demonstrate that the macros found by ShapeMOD improve performance on downstream tasks including shape generative modeling and inferring programs from point clouds. Finally, we conduct a user study that indicates that ShapeMOD's discovered macros make interactive shape editing more efficient

An integrated and multi-purpose microscope for the characterization of atomically thin optoelectronic devices

This is the author accepted manuscript. The final version is available from AIP Publishing via the DOI in this record.Optoelectronic devices based on graphene and other two-dimensional (2D) materials, such as transition metal dichalcogenides (TMDs) are the focus of wide research interest. They can be the key to improving bandwidths in telecommunications, capacity in data storage, new features in consumer electronics, safety devices and medical equipment. The characterization these emerging atomically thin materials and devices strongly relies on a set of measurements involving both optical and electronic instrumentation ranging from scanning photocurrent mapping to Raman and photoluminescence (PL) spectroscopy. Current state-of-the-art commercial instruments offer the ability to characterize individual properties of these materials with no option for the in situ characterization of a wide enough range of complementary optical and electrical properties. Presently, the requirement to switch atomically-thin materials from one system to another often radically affects the properties of these uniquely sensitive materials through atmospheric contamination. Here, we present an integrated, multi-purpose instrument dedicated to the optical and electrical characterization of devices based on 2D materials which is able to perform low frequency electrical measurements, scanning photocurrent mapping, Raman, absorption and PL spectroscopy in one single set-up with full control over the polarization and wavelength of light. We characterize this apparatus by performing multiple measurements on graphene, transition metal dichalcogenides (TMDs) and Si. The performance and resolution is equivalent to commercially available instruments with the significant added value of being a compact, multi-purpose unit. Our design offers a versatile solution to face the challenges imposed by the advent of atomically-thin materials in optoelectronic devices