Spatial mapping of splicing factor complexes involved in exon and intron definition

We have analyzed the interaction between serine/arginine-rich (SR) proteins and splicing components that recognize either the 5′ or 3′ splice site. Previously, these interactions have been extensively characterized biochemically and are critical for both intron and exon definition. We use fluorescence resonance energy transfer (FRET) microscopy to identify interactions of individual SR proteins with the U1 small nuclear ribonucleoprotein (snRNP)–associated 70-kD protein (U1 70K) and with the small subunit of the U2 snRNP auxiliary factor (U2AF35) in live-cell nuclei. We find that these interactions occur in the presence of RNA polymerase II inhibitors, demonstrating that they are not exclusively cotranscriptional. Using FRET imaging by means of fluorescence lifetime imaging microscopy (FLIM), we map these interactions to specific sites in the nucleus. The FLIM data also reveal a previously unknown interaction between HCC1, a factor related to U2AF65, with both subunits of U2AF. Spatial mapping using FLIM-FRET reveals differences in splicing factors interactions within complexes located in separate subnuclear domains

On the metric dimension of corona product graphs

Given a set of vertices $S=\{v_1,v_2,...,v_k\}$ of a connected graph $G$, the metric representation of a vertex $v$ of $G$ with respect to $S$ is the vector $r(v|S)=(d(v,v_1),d(v,v_2),...,d(v,v_k))$, where $d(v,v_i)$, $i\in \{1,...,k\}$ denotes the distance between $v$ and $v_i$. $S$ is a resolving set for $G$ if for every pair of vertices $u,v$ of $G$, $r(u|S)\ne r(v|S)$. The metric dimension of $G$, $dim(G)$, is the minimum cardinality of any resolving set for $G$. Let $G$ and $H$ be two graphs of order $n_1$ and $n_2$, respectively. The corona product $G\odot H$ is defined as the graph obtained from $G$ and $H$ by taking one copy of $G$ and $n_1$ copies of $H$ and joining by an edge each vertex from the $i^{th}$-copy of $H$ with the $i^{th}$-vertex of $G$. For any integer $k\ge 2$, we define the graph $G\odot^k H$ recursively from $G\odot H$ as $G\odot^k H=(G\odot^{k-1} H)\odot H$. We give several results on the metric dimension of $G\odot^k H$. For instance, we show that given two connected graphs $G$ and $H$ of order $n_1\ge 2$ and $n_2\ge 2$, respectively, if the diameter of $H$ is at most two, then $dim(G\odot^k H)=n_1(n_2+1)^{k-1}dim(H)$. Moreover, if $n_2\ge 7$ and the diameter of $H$ is greater than five or $H$ is a cycle graph, then $dim(G\odot^k H)=n_1(n_2+1)^{k-1}dim(K_1\odot H).

Near-bed hydrodynamics and turbulence below a large-scale plunging breaking wave over a mobile barred bed profile

Funded by The research presented in this paper is part of the SINBAD project. Grant Number: STW (12058) and EPSRC (EP/J00507X/1, EP/J005541/1)Peer reviewedPublisher PDFPublisher PD

Anelastic Phenomena in Mg-Al Alloys

Cyclic loading-unloading in tension and compression has been used to quantify the anelastic behaviour, in the form of hysteresis loops, of pure Mg and three Mg-Al alloys (0.5, 2, and 9 at.% Al). The effect reached a maximum at a plastic strain of approximate to 0.02 for all of the materials, and decreased at higher strains. The amount of anelasticity at any given strain was smaller for the dilute alloys in comparison with the pure Mg whereas it increased above that of pure Mg for the most concentrated alloy. Possible reasons for this behaviour are discussed in terms of reversible twinning, solid solution softening, and hardening and short range order

Qualitative classification of extraterrestrial civilizations

Abridged: The interest towards searches for extraterrestrial civilizations (ETCs) was boosted by the discovery of thousands of exoplanets. We turn to the classification of ETCs for new considerations that may help to design better strategies for ETCs searches. We take a basic taxonomic approach to ETCs and investigate the implications of the new classification on ETCs observational patterns. We use as a counter-example to our qualitative classification the quantitative scheme of Kardashev. We propose a classification based on the abilities of ETCs to modify their environment and to integrate with it: Class 0 uses the environment as it is, Class 1 modifies the it to fit its needs, Class 2 modifies itself to fit the environment and Class 3 ETC is fully integrated with the environment. Combined with the classical Kardashev's scale our scheme forms a 2d scheme for interpreting ETC properties. The new framework makes it obvious that the available energy is not an unique measure of ETCs, it may not even correlate with how well that energy is used. The possibility for progress without increased energy consumption implies lower detectability, so the existence of a Kardashev Type III ETC in the Milky Way cannot be ruled out. This reasoning weakens the Fermi paradox, allowing the existence of advanced, yet not energy hungry, low detectability ETCs. The integration of ETCs with environment makes it impossible to tell apart technosignatures from natural phenomena. Thus, the most likely opportunity for SETI searches is to look for beacons, specifically set up by them for young civilizations like us (if they want to do that is a matter of speculation). The other SETI window is to search for ETCs at technological level close to ours. To rephrase the saying of A. Clarke, sufficiently advanced civilizations are indistinguishable from nature.Comment: accepted in A&A; 7 pages, 1 figure; the acknowledgements were updated in the new versio

Diagnosis of progressive disseminated histoplasmosis in advanced HIV: A meta-analysis of assay analytical performance

Histoplasmosis is an important cause of mortality in people with advanced HIV, especially in countries with limited access to diagnostic assays. Histoplasmosis can be diagnosed using culture, histopathology, and antibody, antigen, and molecular assays. Several factors may affect the analytical performance of these laboratory assays, including sample type, clinical stage of the disease, and previous use of antifungal treatment, among others. Here we describe the results of a systematic literature review, followed by ameta-analysis of the analytical performances of the diagnostic laboratory assays employed. Our initial search identified 1631 references, of which 1559 references were excluded after title and abstract screening, leaving 72 references identified as studies relevant to the validation of histoplasmosis diagnostic assays. After evaluating the full text, 30 studies were selected for final review, including one paper not identified in the initial search. The meta-analysis for assay analytical performance shows the following results for the overall sensitivity (Sen) and specificity (Spe) of the various methods evaluated: Culture, Sen 77%(no data for specificity calculation); antibody detection assays, Sen 58%/Spe 100%; antigen detection assays, Sen 95%/Spe 97%; and DNA detection assays (molecular), Sen 95%/Spe 99%. Of the 30 studies reviewed, nearly half (n = 13) evaluated Histoplasma antigen assays, which were determined to be the most accurate methodology for diagnosis of progressive disseminated histoplasmosis in advanced HIV (inverse of the negative likelihood ratio was 13.2). Molecular assays appear promising for accurate diagnosis of histoplasmosis, but consensus on exact techniques is needed. Cultures showed variable sensitivity related to sample type and laboratory handling. Finally, antibody assays presented high specificity but low sensitivity. This poor sensitivity is most likely due the highly immunosuppressed state of this patient population. Diagnostic assays are crucial for accurate diagnosis of progressive disseminated histoplasmosis (PDH) with advanced HIV disease. © 2019 by the authors. All rights reserved

Diagnostic Laparoscopy and Adhesiolysis: Does It Help with Complex Abdominal and Pelvic Pain Syndrome (CAPPS) in General Surgery?

This study was conducted to determine if lysis of bowel adhesions has a role in the surgical management of adhesions for treating complex abdominal and pelvic pain syndrome