Culture, space, and metapopulation: a simulation-based study for evaluating signals of blending and branching

This paper explores the robustness of phylogenetic methods for detecting variations in branching and blending signals in the archaeological record. Both processes can generate a spatial structure whereby cultural similarity between different sites decays with increasing spatial distance. By generating a series of artificial records through the controlled and parameterised environment of an agent-based simulation, we: a) illustrate the weakness and the strength of different analytical techniques (empirical distogram, Mantel test, Retention Index, and d-score); b) determine whether they are capable of assessing how spatial isolation determines cultural diversity; and c) establish whether they can detect variations in the nature of horizontal transmission over time. Results suggest that variables other than the spatial range of interaction (e.g. the frequency of fission events, population dynamics, and rates of cultural innovation) have different effects on the output of some phylogenetic analyses

Feynman Rules in the Type III Natural Flavour-Conserving Two-Higgs Doublet Model

We consider a two Higgs-doublet model with $S_3$ symmetry, which implies a $\pi \over 2$ rather than 0 relative phase between the vacuum expectation values $$and$$. The corresponding Feynman rules are derived accordingly and the transformation of the Higgs fields from the weak to the mass eigenstates includes not only an angle rotation but also a phase transformation. In this model, both doublets couple to the same type of fermions and the flavour-changing neutral currents are naturally suppressed. We also demonstrate that the Type III natural flavour-conserving model is valid at tree-level even when an explicit $S_3$ symmetry breaking perturbation is introduced to get a reasonable CKM matrix. In the special case $\beta = \alpha$, as the ratio $\tan\beta = {v_2 \over v_1}$ runs from 0 to $\infty$, the dominant Yukawa coupling will change from the first two generations to the third generation. In the Feynman rules, we also find that the charged Higgs currents are explicitly left-right asymmetric. The ratios between the left- and right-handed currents for the quarks in the same generations are estimated.Comment: 16 pages (figures not included), NCKU-HEP/93-1

Germline tp53 testing in breast cancers: Why, when and how?

Germline TP53 variants represent a main genetic cause of breast cancers before 31 years of age. Development of cancer multi-gene panels has resulted in an exponential increase of germline TP53 testing in breast cancer patients. Interpretation of TP53 variants, which are mostly missense, is complex and requires excluding clonal haematopoiesis and circulating tumour DNA. In breast cancer patients harbouring germline disease-causing TP53 variants, radiotherapy contributing to the development of subsequent tumours should be, if possible, avoided and, within families, annual follow-up including whole-body MRI should be offered to carriers. We consider that, in breast cancer patients, germline TP53 testing should be performed before treatment and offered systematically only to patients with: (i) invasive breast carcinoma or ductal carcinoma in situ (DCIS) before 31; or (ii) bilateral or multifocal or HER2+ invasive breast carcinoma/DCIS or phyllode tumour before 36; or (iii) invasive breast carcinoma before 46 and another TP53 core tumour (breast cancer, soft-tissue sarcoma, osteosarcoma, central nervous system tumour, adrenocortical carcinoma); or (iv) invasive breast carcinoma before 46 and one first-or second-degree relative with a TP53 core tumour before 56. In contrast, women presenting with breast cancer after 46, without suggestive personal or familial history, should not be tested for TP53.D.G.E. and E.R.W. are supported by the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007)

Hepatocyte cholesterol content modulates glucagon receptor signalling

Objective To determine whether glucagon receptor (GCGR) actions are modulated by cellular cholesterol levels. Methods We determined the effects of experimental cholesterol depletion and loading on glucagon-mediated cAMP production, ligand internalisation and glucose production in human hepatoma cells, mouse and human hepatocytes. GCGR interactions with lipid bilayers were explored using coarse-grained molecular dynamic simulations. Glucagon responsiveness was measured in mice fed a high cholesterol diet with or without simvastatin to modulate hepatocyte cholesterol content. Results GCGR cAMP signalling was reduced by higher cholesterol levels across different cellular models. Ex vivo glucagon-induced glucose output from mouse hepatocytes was enhanced by simvastatin treatment. Mice fed a high cholesterol diet had increased hepatic cholesterol and a blunted hyperglycaemic response to glucagon, both of which were partially reversed by simvastatin. Simulations identified likely membrane-exposed cholesterol binding sites on the GCGR, including a site where cholesterol is a putative negative allosteric modulator. Conclusions Our results indicate that cellular cholesterol content influences glucagon sensitivity and indicate a potential molecular basis for this phenomenon. This could be relevant to the pathogenesis of non-alcoholic fatty liver disease, which is associated with both hepatic cholesterol accumulation and glucagon resistance

Isolation-by-distance, homophily, and “core” vs. “package” cultural evolution models in Neolithic Europe

Recently there has been growing interest in characterising population structure in cultural data in the context of ongoing debates about the potential of cultural group selection as an evolutionary process. Here we use archaeological data for this purpose, which brings in a temporal as well as spatial dimension. We analyse two distinct material cultures (pottery and personal ornaments) from Neolithic Europe, in order to: a) determine whether archaeologically defined “cultures” exhibit marked discontinuities in space and time, supporting the existence of a population structure, or merely isolation-by-distance; and b) investigate the extent to which cultures can be conceived as structuring “cores” or as multiple and historically independent “packages”. Our results support the existence of a robust population structure comparable to previous studies on human culture, and shows how the two material cultures exhibit profound differences in their spatial and temporal structuring, signalling different evolutionary trajectories

Distance Properties of Short LDPC Codes and their Impact on the BP, ML and Near-ML Decoding Performance

Parameters of LDPC codes, such as minimum distance, stopping distance, stopping redundancy, girth of the Tanner graph, and their influence on the frame error rate performance of the BP, ML and near-ML decoding over a BEC and an AWGN channel are studied. Both random and structured LDPC codes are considered. In particular, the BP decoding is applied to the code parity-check matrices with an increasing number of redundant rows, and the convergence of the performance to that of the ML decoding is analyzed. A comparison of the simulated BP, ML, and near-ML performance with the improved theoretical bounds on the error probability based on the exact weight spectrum coefficients and the exact stopping size spectrum coefficients is presented. It is observed that decoding performance very close to the ML decoding performance can be achieved with a relatively small number of redundant rows for some codes, for both the BEC and the AWGN channels

Anisotropic Radial Layout for Visualizing Centrality and Structure in Graphs

This paper presents a novel method for layout of undirected graphs, where nodes (vertices) are constrained to lie on a set of nested, simple, closed curves. Such a layout is useful to simultaneously display the structural centrality and vertex distance information for graphs in many domains, including social networks. Closed curves are a more general constraint than the previously proposed circles, and afford our method more flexibility to preserve vertex relationships compared to existing radial layout methods. The proposed approach modifies the multidimensional scaling (MDS) stress to include the estimation of a vertex depth or centrality field as well as a term that penalizes discord between structural centrality of vertices and their alignment with this carefully estimated field. We also propose a visualization strategy for the proposed layout and demonstrate its effectiveness using three social network datasets.Comment: Appears in the Proceedings of the 25th International Symposium on Graph Drawing and Network Visualization (GD 2017

DFT Study of Planar Boron Sheets: A New Template for Hydrogen Storage

We study the hydrogen storage properties of planar boron sheets and compare them to those of graphene. The binding of molecular hydrogen to the boron sheet (0.05 eV) is stronger than that to graphene. We find that dispersion of alkali metal (AM = Li, Na, and K) atoms onto the boron sheet markedly increases hydrogen binding energies and storage capacities. The unique structure of the boron sheet presents a template for creating a stable lattice of strongly bonded metal atoms with a large nearest neighbor distance. In contrast, AM atoms dispersed on graphene tend to cluster to form a bulk metal. In particular the boron-Li system is found to be a good candidate for hydrogen storage purposes. In the fully loaded case this compound can contain up to 10.7 wt. % molecular hydrogen with an average binding energy of 0.15 eV/H2.Comment: 19 pages, 7 figures, and 3 table

On Embeddability of Buses in Point Sets

Set membership of points in the plane can be visualized by connecting corresponding points via graphical features, like paths, trees, polygons, ellipses. In this paper we study the \emph{bus embeddability problem} (BEP): given a set of colored points we ask whether there exists a planar realization with one horizontal straight-line segment per color, called bus, such that all points with the same color are connected with vertical line segments to their bus. We present an ILP and an FPT algorithm for the general problem. For restricted versions of this problem, such as when the relative order of buses is predefined, or when a bus must be placed above all its points, we provide efficient algorithms. We show that another restricted version of the problem can be solved using 2-stack pushall sorting. On the negative side we prove the NP-completeness of a special case of BEP.Comment: 19 pages, 9 figures, conference version at GD 201

Diagnostic Yield of Genetic Testing in Young Athletes with T-wave Inversion.

Background -T-wave inversion (TWI) is common in patients with cardiomyopathy. However, up to 25% of athletes of African/Afro-Caribbean descent (black athletes) and 5% of white athletes also have TWI of unclear clinical significance despite comprehensive clinical evaluation and long-term follow-up. The aim of this study was to determine the diagnostic yield from genetic testing, beyond clinical evaluation, when investigating athletes with TWI. Methods -We investigated 50 consecutive asymptomatic black and 50 white athletes aged 14-35-years-old with TWI and a normal echocardiogram who were referred to a UK tertiary center for cardiomyopathy and sports cardiology. Subjects underwent exercise testing, 24-hour ECG, signal-averaged ECG, cardiac magnetic resonance imaging, and a blood-based analysis of a comprehensive 311 gene panel for cardiomyopathies including hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, left ventricular non-compaction, and ion channel disorders such as long QT syndrome and Brugada syndrome. Results -In total, 21 athletes (21%) were diagnosed with cardiac disease on the basis of comprehensive clinical investigations. Of these, 8 (38.1%) were gene positive (MYPBC3, MYH7, GLA, and ACTC1 genes) and 13 (61.9%) were gene negative. Of the remaining 79 athletes (79%), 2 (2.5%) were gene positive (TTR and SCN5A genes) in the absence of a clinical phenotype. The prevalence of newly diagnosed cardiomyopathy was higher in white athletes compared with black athletes (30.0% vs. 12%, P=0.027). Hypertrophic cardiomyopathy accounted for 90.5% of all clinical diagnoses. All black athletes and 93.3% of white athletes with a clinical diagnosis of cardiomyopathy or a genetic mutation capable of causing cardiomyopathy exhibited lateral TWI as opposed to isolated anterior or inferior TWI; the genetic yield of diagnoses from lateral TWI was 14.0%. Conclusions -Up to 10% of athletes with TWI revealed mutations capable of causing cardiac disease. Despite the substantial cost, the positive diagnostic yield from genetic testing was one-half of that from clinical evaluation (10% vs. 21%) and contributed to additional diagnoses in only 2.5% of athletes with TWI in the absence of a clear clinical phenotype, making it of negligible use in routine clinical practice