Survey of Human Mitochondrial Diseases Using New Genomic/Proteomic Tools

BACKGROUND. We have constructed Bayesian prior-based, amino-acid sequence profiles for the complete yeast mitochondrial proteome and used them to develop methods for identifying and characterizing the context of protein mutations that give rise to human mitochondrial diseases. (Bayesian priors are conditional probabilities that allow the estimation of the likelihood of an event - such as an amino-acid substitution - on the basis of prior occurrences of similar events.) Because these profiles can assemble sets of taxonomically very diverse homologs, they enable identification of the structurally and/or functionally most critical sites in the proteins on the basis of the degree of sequence conservation. These profiles can also find distant homologs with determined three-dimensional structures that aid in the interpretation of effects of missense mutations. RESULTS. This survey reports such an analysis for 15 missense mutations one insertion and three deletions involved in Leber's hereditary optic neuropathy, Leigh syndrome, mitochondrial neurogastrointestinal encephalomyopathy, Mohr-Tranebjaerg syndrome, iron-storage disorders related to Friedreich's ataxia, and hereditary spastic paraplegia. We present structural correlations for seven of the mutations. CONCLUSIONS. Of the 19 mutations analyzed, 14 involved changes in very highly conserved parts of the affected proteins. Five out of seven structural correlations provided reasonable explanations for the malfunctions. As additional genetic and structural data become available, this methodology can be extended. It has the potential for assisting in identifying new disease-related genes. Furthermore, profiles with structural homologs can generate mechanistic hypotheses concerning the underlying biochemical processes - and why they break down as a result of the mutations.United States Department of Energy (DE-FG02-98ER62558); National Science Foundation (DBI-9807993

The massive star population of Cygnus OB2

We have compiled a significantly updated and comprehensive census of massive stars in the nearby Cygnus OB2 association by gathering and homogenizing data from across the literature. The census contains 169 primary OB stars, including 52 O-type stars and 3 Wolf–Rayet stars. Spectral types and photometry are used to place the stars in a Hertzsprung–Russell diagram, which is compared to both non-rotating and rotating stellar evolution models, from which stellar masses and ages are calculated. The star formation history and mass function of the association are assessed, and both are found to be heavily influenced by the evolution of the most massive stars to their end states. We find that the mass function of the most massive stars is consistent with a ‘universal’ power-law slope of Γ = 1.3.Peer reviewedFinal Accepted Versio

Massive stars in the hinterland of the young cluster, Westerlund 2

Accepted for publication in MNRAS, 13 July 2018. 16 pages, plus one-page table in an appendix.An unsettled question concerning the formation and distribution of massive stars is whether they must be born in massive clusters and, if found in less dense environments, whether they must have migrated there. With the advent of wide-area digital photometric surveys, it is now possible to identify massive stars away from prominent Galactic clusters without bias. In this study we consider 40 candidate OB stars found in the field around the young massive cluster, Westerlund 2, by Mohr-Smith et al.: these are located inside a box of 1.5 × 1.5 deg 2 and are selected on the basis of their extinctions and K magnitudes.We present VLT/X-shooter spectra of two of the hottest O stars, respectively 11 and 22 arcmin from the centre of Westerlund 2. They are confirmed as O4V stars, with stellar masses likely to be in excess of 40 M ·. Their radial velocities relative to the non-binary reference object, MSP 182, in Westerlund 2 are -29.4 ± 1.7 and -14.4 ± 2.2 km s -1, respectively. Using Gaia DR2 proper motions we find that between 8 and 11 early O/WR stars in the studied region (including the two VLT targets, plus WR 20c and WR 20aa) could have been ejected fromWesterlund 2 in the last one million years. This represents an efficiency of massive-star ejection of up to ~ 25 per cent. On sky, the positions of these stars and their proper motions show a near N-S alignment. We discuss the possibility that these results are a consequence of prior sub-cluster merging combining with dynamical ejection.Peer reviewe

Deconvolution of complex G protein-coupled receptor signaling in live cells using dynamic mass redistribution measurements

Label-free biosensor technology based on dynamic mass redistribution (DMR) of cellular constituents promises to translate GPCR signaling into complex optical 'fingerprints' in real time in living cells. Here we present a strategy to map cellular mechanisms that define label-free responses, and we compare DMR technology with traditional second-messenger assays that are currently the state of the art in GPCR drug discovery. The holistic nature of DMR measurements enabled us to (i) probe GPCR functionality along all four G-protein signaling pathways, something presently beyond reach of most other assay platforms; (ii) dissect complex GPCR signaling patterns even in primary human cells with unprecedented accuracy; (iii) define heterotrimeric G proteins as triggers for the complex optical fingerprints; and (iv) disclose previously undetected features of GPCR behavior. Our results suggest that DMR technology will have a substantial impact on systems biology and systems pharmacology as well as for the discovery of drugs with novel mechanisms

Analyzing stage and duration of Anglo-Chinese business-to-business relationships

This is the post-print version of the final paper published in Industrial Marketing Management. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2010 Elsevier B.V.The manuscript reports on a study aimed at analyzing a series of relational variables derived from the Western industrial buyer–seller relationship and Chinese guanxi literature. The findings based on data collected from over 200 Taiwanese trading firms reveal that buyer's perceptions of organizational trust, communication, cooperation, social bonding and the saving of face are higher in Anglo-Chinese relationships that venture beyond the short-term. It is also found that cooperation, social bonding and performance are greater in those b2b relationships surveyed that are relatively more mature than in emerging states. The findings also reveal that relationship duration and stage have a significant moderating effect on various Inter-organizational and Interpersonal–Outcome relationships. Several managerial implications are extracted to help Western firms better manage their international relations, as well as help new exporting firms penetrate such well-established guanxi networks

Convergence Acceleration via Combined Nonlinear-Condensation Transformations

A method of numerically evaluating slowly convergent monotone series is described. First, we apply a condensation transformation due to Van Wijngaarden to the original series. This transforms the original monotone series into an alternating series. In the second step, the convergence of the transformed series is accelerated with the help of suitable nonlinear sequence transformations that are known to be particularly powerful for alternating series. Some theoretical aspects of our approach are discussed. The efficiency, numerical stability, and wide applicability of the combined nonlinear-condensation transformation is illustrated by a number of examples. We discuss the evaluation of special functions close to or on the boundary of the circle of convergence, even in the vicinity of singularities. We also consider a series of products of spherical Bessel functions, which serves as a model for partial wave expansions occurring in quantum electrodynamic bound state calculations.Comment: 24 pages, LaTeX, 12 tables (accepted for publication in Comput. Phys. Comm.

Burmese amber fossils bridge the gap in the Cretaceous record of polypod ferns

publisher: Elsevier articletitle: Burmese amber fossils bridge the gap in the Cretaceous record of polypod ferns journaltitle: Perspectives in Plant Ecology, Evolution and Systematics articlelink: http://dx.doi.org/10.1016/j.ppees.2016.01.003 content_type: article copyright: Copyright © 2016 Elsevier GmbH. All rights reserved.Copyright © 2016 Elsevier GmbH. All rights reserved. This document is the authors' final accepted version of the journal article. You are advised to consult the publisher's version if you wish to cite from it

Analogies between the crossing number and the tangle crossing number

Tanglegrams are special graphs that consist of a pair of rooted binary trees with the same number of leaves, and a perfect matching between the two leaf-sets. These objects are of use in phylogenetics and are represented with straightline drawings where the leaves of the two plane binary trees are on two parallel lines and only the matching edges can cross. The tangle crossing number of a tanglegram is the minimum crossing number over all such drawings and is related to biologically relevant quantities, such as the number of times a parasite switched hosts. Our main results for tanglegrams which parallel known theorems for crossing numbers are as follows. The removal of a single matching edge in a tanglegram with $n$ leaves decreases the tangle crossing number by at most $n-3$, and this is sharp. Additionally, if $\gamma(n)$ is the maximum tangle crossing number of a tanglegram with $n$ leaves, we prove $\frac{1}{2}\binom{n}{2}(1-o(1))\le\gamma(n)<\frac{1}{2}\binom{n}{2}$. Further, we provide an algorithm for computing non-trivial lower bounds on the tangle crossing number in $O(n^4)$ time. This lower bound may be tight, even for tanglegrams with tangle crossing number $\Theta(n^2)$.Comment: 13 pages, 6 figure