Computation of protein geometry and its applications: Packing and function prediction

This chapter discusses geometric models of biomolecules and geometric constructs, including the union of ball model, the weigthed Voronoi diagram, the weighted Delaunay triangulation, and the alpha shapes. These geometric constructs enable fast and analytical computaton of shapes of biomoleculres (including features such as voids and pockets) and metric properties (such as area and volume). The algorithms of Delaunay triangulation, computation of voids and pockets, as well volume/area computation are also described. In addition, applications in packing analysis of protein structures and protein function prediction are also discussed.Comment: 32 pages, 9 figure

COVID-19 Life Events Spill-Over on Family Functioning and Adolescent Adjustment

We examined US parent and youth perceptions of how life events, both positive and negative, associated with COVID-19 resulted in changes in family and youth functioning. Families (n = 105, 80% white, 48% male, and 87% mothers) completed surveys during the pandemic (May to July 2020) and 3 years prior (for youth ages M = 10.6, SD = 1.17 and M = 13.6, SD = 1.19). Declines in youth, though not parent, report of open family communication, parental support, and family satisfaction were found. Declines were associated with various domains of pandemic-related stress in parent report, though positive life events served as buffers. Pre-pandemic family functioning also predicted pandemic stress. Spillover effects in turn impacted youth functioning. The current findings shed light on how experiences of the pandemic are linked with family functioning and have implications for how to support families during this time

Women, men and coronary heart disease: a review of the qualitative literature

Aim. This paper presents a review of the qualitative literature which examines the experiences of patients with coronary heart disease. The paper also assesses whether the experiences of both female and male patients are reflected in the literature and summarizes key themes. Background. Understanding patients' experiences of their illness is important for coronary heart disease prevention and education. Qualitative methods are particularly suited to eliciting patients' detailed understandings and perceptions of illness. As much previous research has been 'gender neutral', this review pays particular attention to gender. Methods. Published papers from 60 qualitative studies were identified for the review through searches in MEDLINE, EMBASE, CINAHL, PREMEDLINE, PsychINFO, Social Sciences Citation Index and Web of Science using keywords related to coronary heart disease. Findings. Early qualitative studies of patients with coronary heart disease were conducted almost exclusively with men, and tended to generalize from 'male' experience to 'human' experience. By the late 1990s this pattern had changed, with the majority of studies including women and many being conducted with solely female samples. However, many studies that include both male and female coronary heart disease patients still do not have a specific gender focus. Key themes in the literature include interpreting symptoms and seeking help, belief about coronary 'candidates' and relationships with health professionals. The influence of social roles is important: many female patients have difficulties reconciling family responsibilities and medical advice, while male patients worry about being absent from work. Conclusions. There is a need for studies that compare the experiences of men and women. There is also an urgent need for work that takes masculinity and gender roles into account when exploring the experiences of men with coronary heart disease

Craig Rhos-y-felin: A Welsh bluestone megalith quarry for Stonehenge

The long-distance transport of the bluestones from south Wales to Stonehenge is one of the most remarkable achievements of Neolithic societies in north-west Europe. Where precisely these stones were quarried, when they were extracted and how they were transported has long been a subject of speculation, experiment and controversy. The discovery of a megalithic bluestone quarry at Craig Rhos-y-felin in 2011 marked a turning point in this research. Subsequent excavations have provided details of the quarrying process along with direct dating evidence for the extraction of bluestone monoliths at this location, demonstrating both Neolithic and Early Bronze Age activity

Negative Parity 70-plet Baryon Masses in the 1/Nc Expansion

The masses of the negative parity SU(6) 70-plet baryons are analyzed in the 1/Nc expansion to order 1/Nc and to first order in SU(3) breaking. At this level of precision there are twenty predictions. Among them there are the well known Gell-Mann Okubo and equal spacing relations, and four new relations involving SU(3) breaking splittings in different SU(3) multiplets. Although the breaking of SU(6) symmetry occurs at zeroth order in 1/Nc, it turns out to be small. The dominant source of the breaking is the hyperfine interaction which is of order 1/Nc. The spin-orbit interaction, of zeroth order in 1/Nc, is entirely fixed by the splitting between the singlet states Lambda(1405) and Lambda(1520), and the spin-orbit puzzle is solved by the presence of other zeroth order operators involving flavor exchange.Comment: 31 pages, 3 figure

Targeting the adrenomedullin-2 receptor for the discovery and development of novel anti-cancer agents

INTRODUCTION Adrenomedullin (AM) is a peptide responsible for many physiological processes including vascular health and hormone regulation. Dysregulation of AM signaling can stimulate cancers by promoting proliferation, angiogenesis and metastasis. Two AM receptors contribute to tumor progression in different ways. Adrenomedullin-1 receptor (AM1R) regulates blood pressure and blocking AM signaling via AM1R would be clinically unacceptable. Therefore, antagonizing adrenomedullin-2 receptor (AM2R) presents as an avenue for anti-cancer drug development. AREAS COVERED We review the literature to highlight AM’s role in cancer as well as delineating the specific roles AM1R and AM2R mediate in the development of a pro-tumoral microenvironment. We highlight the importance of exploring the residue differences between the receptors that led to the development of first-in-class selective AM2R small molecule antagonists. We also summarize the current approaches targeting AM and its receptors, their anti-tumor effects and their limitations. EXPERT OPINION As tool compounds, AM2R antagonists will allow the dissection of the functions of CGRPR (calcitonin gene-related peptide receptor), AM1R and AM2R, and has considerable potential as a first-in-class oncology therapy. Furthermore, the lack of detectable side effects and good drug-like pharmacokinetic properties of these AM2R antagonists support the promise of this class of compounds as potential anti-cancer therapeutics

Combenefit: an interactive platform for the analysis and visualization of drug combinations.

Motivation: Many drug combinations are routinely assessed to identify synergistic interactions in the attempt to develop novel treatment strategies. Appropriate software is required to analyze the results of these studies. Results: We present Combenefit, new free software tool that enables the visualization, analysis and quantification of drug combination effects in terms of synergy and/or antagonism. Data from combinations assays can be processed using classical Synergy models (Loewe, Bliss, HSA), as single experiments or in batch for High Throughput Screens. This user-friendly tool provides laboratory scientists with an easy and systematic way to analyze their data. The companion package provides bioinformaticians with critical implementations of routines enabling the processing of combination data. Availability and Implementation: Combenefit is provided as a Matlab package but also as standalone software for Windows (http://sourceforge.net/projects/combenefit/). Contact: [email protected]. Supplementary information:Supplementary data are available at Bioinformatics online

Using the Wigner-Ibach Surmise to Analyze Terrace-Width Distributions: History, User's Guide, and Advances

A history is given of the applications of the simple expression generalized from the surmise by Wigner and also by Ibach to extract the strength of the interaction between steps on a vicinal surface, via the terrace width distribution (TWD). A concise guide for use with experiments and a summary of some recent extensions are provided.Comment: 11 pages, 4 figures, reformatted (with revtex) version of refereed paper for special issue of Applied Physics A entitled "From Surface Science to Device Physics", in honor of the retirements of Prof. H. Ibach and Prof. H. L\"ut

Excited Baryons in Lattice QCD

We present first results for the masses of positive and negative parity excited baryons calculated in lattice QCD using an O(a^2)-improved gluon action and a fat-link irrelevant clover (FLIC) fermion action in which only the irrelevant operators are constructed with APE-smeared links. The results are in agreement with earlier calculations of N^* resonances using improved actions and exhibit a clear mass splitting between the nucleon and its chiral partner. An correlation matrix analysis reveals two low-lying J^P=(1/2)^- states with a small mass splitting. The study of different Lambda interpolating fields suggests a similar splitting between the lowest two Lambda1/2^- octet states. However, the empirical mass suppression of the Lambda^*(1405) is not evident in these quenched QCD simulations, suggesting a potentially important role for the meson cloud of the Lambda^*(1405) and/or a need for more exotic interpolating fields.Comment: Correlation matrix analysis performed. Increased to 400 configurations. 22 pages, 13 figures, 15 table