Shaping the future of architectural education in Scotland

In recent years there has been a strong focus on the impact of research on policy and practice within the UK. The devolved government in Scotland has been particularly supportive of innovation and change relating to environmental improvement and this has been seen for example in the creation of Architecture & Design Scotland (A&DS) to champion good practice in architecture and design. The 2016, year-long 'Festival of Architecture' provides a plethora of opportunities to celebrate and reflect on the richness of Scottish architecture, as part of the Year of Innovation, Architecture and Design, and a catalyst to generate a discourse on architecture and design pedagogy

Two Small Planets Transiting HD 3167

We report the discovery of two super-Earth-sized planets transiting the bright (V = 8.94, K = 7.07) nearby late G-dwarf HD 3167, using data collected by the K2 mission. The inner planet, HD 3167 b, has a radius of 1.6 R_e and an ultra-short orbital period of only 0.96 days. The outer planet, HD 3167 c, has a radius of 2.9 R_e and orbits its host star every 29.85 days. At a distance of just 45.8 +/- 2.2 pc, HD 3167 is one of the closest and brightest stars hosting multiple transiting planets, making HD 3167 b and c well suited for follow-up observations. The star is chromospherically inactive with low rotational line-broadening, ideal for radial velocity observations to measure the planets' masses. The outer planet is large enough that it likely has a thick gaseous envelope which could be studied via transmission spectroscopy. Planets transiting bright, nearby stars like HD 3167 are valuable objects to study leading up to the launch of the James Webb Space Telescope.Comment: Accepted by ApJL. 6 pages, 1 figure, 2 table

GC-Biased Evolution Near Human Accelerated Regions

Regions of the genome that have been the target of positive selection specifically along the human lineage are of special importance in human biology. We used high throughput sequencing combined with methods to enrich human genomic samples for particular targets to obtain the sequence of 22 chromosomal samples at high depth in 40 kb neighborhoods of 49 previously identified 100–400 bp elements that show evidence for human accelerated evolution. In addition to selection, the pattern of nucleotide substitutions in several of these elements suggested an historical bias favoring the conversion of weak (A or T) alleles into strong (G or C) alleles. Here we found strong evidence in the derived allele frequency spectra of many of these 40 kb regions for ongoing weak-to-strong fixation bias. Comparison of the nucleotide composition at polymorphic loci to the composition at sites of fixed substitutions additionally reveals the signature of historical weak-to-strong fixation bias in a subset of these regions. Most of the regions with evidence for historical bias do not also have signatures of ongoing bias, suggesting that the evolutionary forces generating weak-to-strong bias are not constant over time. To investigate the role of selection in shaping these regions, we analyzed the spatial pattern of polymorphism in our samples. We found no significant evidence for selective sweeps, possibly because the signal of such sweeps has decayed beyond the power of our tests to detect them. Together, these results do not rule out functional roles for the observed changes in these regions—indeed there is good evidence that the first two are functional elements in humans—but they suggest that a fixation process (such as biased gene conversion) that is biased at the nucleotide level, but is otherwise selectively neutral, could be an important evolutionary force at play in them, both historically and at present

Surface-Based Morphometric Analysis of Hippocampal Subfields in Mild Cognitive Impairment and Alzheimer's Disease

The hippocampus is widely studied with neuroimaging techniques given its importance in learning and memory and its potential as a biomarker for Alzheimer's disease (AD). Its complex folding anatomy often presents analytical challenges. In particular, the critical subfield information is typically not addressed by the existing hippocampal shape studies. To bridge this gap, we present a computational framework for surface-based morphometric analysis of hippocampal subfields. The major strengths of this framework are as follows: (a) it performs detailed hippocampal shape analysis, (b) it embraces, rather than ignores, the important hippocampal subfield information, and (c) it analyzes regular magnetic resonance imaging scans and is applicable to large scale studies. We demonstrate its effectiveness by applying it to the identification of regional hippocampal subfield atrophy patterns associated with mild cognitive impairment and AD

Differential co-expression analysis reveals early stage transcriptomic decoupling in Alzheimer’s disease

Background: Alzheimer's disease (AD) is one of the leading causes of death in the US and there is no validated drugs to stop, slow or prevent AD. Despite tremendous effort on biomarker discovery, existing findings are mostly individual biomarkers and provide limited insights into the transcriptomic decoupling underlying AD. We propose to explore the gene co-expression patterns in multiple AD stages, including cognitively normal (CN), early mild cognitive impairment (EMCI), late MCI and AD. Methods: We modified traiditonal joint graphical lasso to model our asusmption that the co-expression networks in consecutive disease stages are largely similar with critical differences. In addition, we performed subsequent network comparison analysis for identification of stage specific transcriptomic decoupling. We focused our analysis on top AD-enriched pathways. Results: We observed that 419 edges in CN, 420 edges in EMCI, 381 edges in LMCI and 250 edges in AD were frequently estimated with non zero weights. With modified JGL, the weight of all estimated edges in CN, EMCI and LMCI are zero. In AD group, 299 edges were occasionally estimated to be nonzero and the average correlation between genes was 0.0023. For co-expression change during AD progression, there are 66 pairs of genes that demonstrated a continuously decreasing or increasing co-expression from CN to EMCI, LMCI and AD.The network level clustering coefficient remains stable from CN to LMCI and then decreases significantly when progressing to AD. When evaluating edge level differences, we identified eight gene modules with continuously decreasing or increasing co-expression patterns during AD progression. Five of them shows significant changes from CN to EMCI and thus have the potential to serve system biomarkers for early screening of AD. Conclusion: We employed a modified joint graphical lasso for estimation of co-expression networks for multiple stages of AD. Comparing with graphical lasso, our modified joint graphical lasso model accounts for the similarity in consecutive disease stages. Our results on real data set revealed five gene clusters with obvious co-expression pattern change from CN to EMCI, which could be used as potential system-level biomarkers for early screening of AD

Incommensurate One-Dimensional Fluctuations in YBa₂Cu₃O₆.₉₃

A novel neutron scattering technique has been utilized to discover one-dimensional fluctuations with a very sharply defined modulation period of 16.65 Å along the b(a) direction in YBa2Cu3O6.93. The fluctuations are found to be absent in the reduced oxygen compound YBa2Cu3O6.15. The wave vector of the fluctuations is consistent with accepted values of 2kF for the Cu-O chains

Five Planets Transiting a Ninth Magnitude Star

The Kepler mission has revealed a great diversity of planetary systems and architectures, but most of the planets discovered by Kepler orbit faint stars. Using new data from the K2 mission, we present the discovery of a five planet system transiting a bright (V = 8.9, K = 7.7) star called HIP 41378. HIP 41378 is a slightly metal-poor late F-type star with moderate rotation (v sin(i) = 7 km/s) and lies at a distance of 116 +/- 18 from Earth. We find that HIP 41378 hosts two sub-Neptune sized planets orbiting 3.5% outside a 2:1 period commensurability in 15.6 and 31.7 day orbits. In addition, we detect three planets which each transit once during the 75 days spanned by K2 observations. One planet is Neptune sized in a likely ~160 day orbit, one is sub-Saturn sized likely in a ~130 day orbit, and one is a Jupiter sized planet in a likely ~1 year orbit. We show that these estimates for the orbital periods can be made more precise by taking into account dynamical stability considerations. We also calculate the distribution of stellar reflex velocities expected for this system, and show that it provides a good target for future radial velocity observations. If a precise orbital period can be determined for the outer Jovian planet through future observations, it will be an excellent candidate for follow-up transit observations to study its atmosphere and measure its oblateness.Comment: Accepted by ApJL. 12 pages, 6 figures, 2 table

Volumetric comparison of hippocampal subfields extracted from 4-minute accelerated vs. 8-minute high-resolution T2-weighted 3T MRI scans

The hippocampus has been widely studied using neuroimaging, as it plays an important role in memory and learning. However, hippocampal subfield information is difficult to capture by standard magnetic resonance imaging (MRI) techniques. To facilitate morphometric study of hippocampal subfields, ADNI introduced a high resolution (0.4 mm in plane) T2-weighted turbo spin-echo sequence that requires 8 min. With acceleration, the protocol can be acquired in 4 min. We performed a comparative study of hippocampal subfield volumes using standard and accelerated protocols on a Siemens Prisma 3T MRI in an independent sample of older adults that included 10 cognitively normal controls, 9 individuals with subjective cognitive decline, 10 with mild cognitive impairment, and 6 with a clinical diagnosis of Alzheimer’s disease (AD). The Automatic Segmentation of Hippocampal Subfields (ASHS) software was used to segment 9 primary labeled regions including hippocampal subfields and neighboring cortical regions. Intraclass correlation coefficients were computed for reliability tests between 4 and 8 min scans within and across the four groups. Pairwise group analyses were performed, covaried for age, sex and total intracranial volume, to determine whether the patterns of group differences were similar using 4 vs. 8 min scans. The 4 and 8 min protocols, analyzed by ASHS segmentation, yielded similar volumetric estimates for hippocampal subfields as well as comparable patterns of differences between study groups. The accelerated protocol can provide reliable imaging data for investigation of hippocampal subfields in AD-related MRI studies and the decreased scan time may result in less vulnerability to motion

Identification of functionally connected multi-omic biomarkers for Alzheimer’s disease using modularity-constrained Lasso

Large-scale genome wide association studies (GWASs) have led to discovery of many genetic risk factors in Alzheimer’s disease (AD), such as APOE, TOMM40 and CLU. Despite the significant progress, it remains a major challenge to functionally validate these genetic findings and translate them into targetable mechanisms. Integration of multiple types of molecular data is increasingly used to address this problem. In this paper, we proposed a modularity-constrained Lasso model to jointly analyze the genotype, gene expression and protein expression data for discovery of functionally connected multi-omic biomarkers in AD. With a prior network capturing the functional relationship between SNPs, genes and proteins, the newly introduced penalty term maximizes the global modularity of the subnetwork involving selected markers and encourages the selection of multi-omic markers with dense functional connectivity, instead of individual markers. We applied this new model to the real data collected in the ROS/MAP cohort where the cognitive performance was used as disease quantitative trait. A functionally connected subnetwork involving 276 multi-omic biomarkers, including SNPs, genes and proteins, were identified to bear predictive power. Within this subnetwork, multiple trans-omic paths from SNPs to genes and then proteins were observed. This suggests that cognitive performance deterioration in AD patients can be potentially a result of genetic variations due to their cascade effect on the downstream transcriptome and proteome level