Lower Bounds for Heights in Relative Galois Extensions

The goal of this paper is to obtain lower bounds on the height of an algebraic number in a relative setting, extending previous work of Amoroso and Masser. Specifically, in our first theorem we obtain an effective bound for the height of an algebraic number $\alpha$ when the base field $\mathbb{K}$ is a number field and $\mathbb{K}(\alpha)/\mathbb{K}$ is Galois. Our second result establishes an explicit height bound for any non-zero element $\alpha$ which is not a root of unity in a Galois extension $\mathbb{F}/\mathbb{K}$, depending on the degree of $\mathbb{K}/\mathbb{Q}$ and the number of conjugates of $\alpha$ which are multiplicatively independent over $\mathbb{K}$. As a consequence, we obtain a height bound for such $\alpha$ that is independent of the multiplicative independence condition

‘The longest suicide vote in history’: the Labour Party leadership election of 2015

The Labour leadership contest of 2015 resulted in the election of the veteran Left-wing backbencher, Jeremy Corbyn, who clearly defeated the early favourite, Andy Burnham. Yet Corbyn enjoyed very little support among Labour MPs, and his victory plunged the PLP into turmoil, particularly as he was widely viewed as incapable of leading the Party to victory in the 2020 general election. Given that, much of the established academic literature on Party leadership contests emphasises the ability to foster unity, and thereby render a party electable, as two of the key criteria for electing a new leader, coupled with overall competence, important questions are raised about how and why the Labour Party chose someone to lead them who clearly does not meet these criteria. We will argue that whilst these are the natural priorities of MPs when electing a new leader, in Corbyn’s case, much of the extra-parliamentary Labour Party was more concerned about ideological conviction and purity of principles, regardless of how far these diverged from public opinion. This was especially true of those who signed-up to the Labour Party following the 2015 general election defeat. Indeed, many of these only did so after Corbyn had become a candidate. This clearly suggests a serious tension between maximising intra-party democracy and ensuring the electability of the parliamentary party itself

PocketMatch: A new algorithm to compare binding sites in protein structures

Background: Recognizing similarities and deriving relationships among protein molecules is a fundamental
requirement in present-day biology. Similarities can be present at various levels which can be detected through comparison of protein sequences or their structural folds. In some cases similarities obscure at these levels could be present merely in the substructures at their binding sites. Inferring functional similarities between protein molecules by comparing their binding sites is still largely exploratory and not as yet a routine protocol. One of
the main reasons for this is the limitation in the choice of appropriate analytical tools that can compare binding sites with high sensitivity. To benefit from the enormous amount of structural data that is being rapidly accumulated, it is essential to have high throughput tools that enable large scale binding site comparison.

Results: Here we present a new algorithm PocketMatch for comparison of binding sites in a frame invariant
manner. Each binding site is represented by 90 lists of sorted distances capturing shape and chemical nature of the site. The sorted arrays are then aligned using an incremental alignment method and scored to obtain PMScores for pairs of sites. A comprehensive sensitivity analysis and an extensive validation of the algorithm have been carried out. Perturbation studies where the geometry of a given site was retained but the residue types were changed randomly, indicated that chance similarities were virtually non-existent. Our analysis also demonstrates that shape information alone is insufficient to discriminate between diverse binding sites, unless
combined with chemical nature of amino acids.

Conclusions: A new algorithm has been developed to compare binding sites in accurate, efficient and
high-throughput manner. Though the representation used is conceptually simplistic, we demonstrate that along
with the new alignment strategy used, it is sufficient to enable binding comparison with high sensitivity. Novel methodology has also been presented for validating the algorithm for accuracy and sensitivity with respect to geometry and chemical nature of the site. The method is also fast and takes about 1/250th second for one comparison on a single processor. A parallel version on BlueGene has also been implemented

InterMitoBase: An annotated database and analysis platform of protein-protein interactions for human mitochondria

<p>Abstract</p> <p>Background</p> <p>The mitochondrion is an essential organelle which plays important roles in diverse biological processes, such as metabolism, apoptosis, signal transduction and cell cycle. Characterizing protein-protein interactions (PPIs) that execute mitochondrial functions is fundamental in understanding the mechanisms underlying biological functions and diseases associated with mitochondria. Investigations examining mitochondria are expanding to the system level because of the accumulation of mitochondrial proteomes and human interactome. Consequently, the development of a database that provides the entire protein interaction map of the human mitochondrion is urgently required.</p> <p>Results</p> <p>InterMitoBase provides a comprehensive interactome of human mitochondria. It contains the PPIs in biological pathways mediated by mitochondrial proteins, the PPIs between mitochondrial proteins and non-mitochondrial proteins as well as the PPIs between mitochondrial proteins. The current version of InterMitoBase covers 5,883 non-redundant PPIs of 2,813 proteins integrated from a wide range of resources including PubMed, KEGG, BioGRID, HPRD, DIP and IntAct. Comprehensive curations have been made on the interactions derived from PubMed. All the interactions in InterMitoBase are annotated according to the information collected from their original sources, GenBank and GO. Additionally, InterMitoBase features a user-friendly graphic visualization platform to present functional and topological analysis of PPI networks identified. This should aid researchers in the study of underlying biological properties.</p> <p>Conclusions</p> <p>InterMitoBase is designed as an integrated PPI database which provides the most up-to-date PPI information for human mitochondria. It also works as a platform by integrating several on-line tools for the PPI analysis. As an analysis platform and as a PPI database, InterMitoBase will be an important database for the study of mitochondria biochemistry, and should be particularly helpful in comprehensive analyses of complex biological mechanisms underlying mitochondrial functions.</p

Graph Zeta Function and Gauge Theories

Along the recently trodden path of studying certain number theoretic properties of gauge theories, especially supersymmetric theories whose vacuum manifolds are non-trivial, we investigate Ihara's Graph Zeta Function for large classes of quiver theories and periodic tilings by bi-partite graphs. In particular, we examine issues such as the spectra of the adjacency and whether the gauge theory satisfies the strong and weak versions of the graph theoretical analogue of the Riemann Hypothesis.Comment: 35 pages, 7 Figure

Searching the protein structure database for ligand-binding site similarities using CPASS v.2

<p>Abstract</p> <p>Background</p> <p>A recent analysis of protein sequences deposited in the NCBI RefSeq database indicates that ~8.5 million protein sequences are encoded in prokaryotic and eukaryotic genomes, where ~30% are explicitly annotated as "hypothetical" or "uncharacterized" protein. Our Comparison of Protein Active-Site Structures (CPASS v.2) database and software compares the sequence and structural characteristics of experimentally determined ligand binding sites to infer a functional relationship in the absence of global sequence or structure similarity. CPASS is an important component of our Functional Annotation Screening Technology by NMR (FAST-NMR) protocol and has been successfully applied to aid the annotation of a number of proteins of unknown function.</p> <p>Findings</p> <p>We report a major upgrade to our CPASS software and database that significantly improves its broad utility. CPASS v.2 is designed with a layered architecture to increase flexibility and portability that also enables job distribution over the Open Science Grid (OSG) to increase speed. Similarly, the CPASS interface was enhanced to provide more user flexibility in submitting a CPASS query. CPASS v.2 now allows for both automatic and manual definition of ligand-binding sites and permits pair-wise, one versus all, one versus list, or list versus list comparisons. Solvent accessible surface area, ligand root-mean square difference, and Cβ distances have been incorporated into the CPASS similarity function to improve the quality of the results. The CPASS database has also been updated.</p> <p>Conclusions</p> <p>CPASS v.2 is more than an order of magnitude faster than the original implementation, and allows for multiple simultaneous job submissions. Similarly, the CPASS database of ligand-defined binding sites has increased in size by ~ 38%, dramatically increasing the likelihood of a positive search result. The modification to the CPASS similarity function is effective in reducing CPASS similarity scores for false positives by ~30%, while leaving true positives unaffected. Importantly, receiver operating characteristics (ROC) curves demonstrate the high correlation between CPASS similarity scores and an accurate functional assignment. As indicated by distribution curves, scores ≥ 30% infer a functional similarity. Software URL: <url>http://cpass.unl.edu</url>.</p

FLORA: a novel method to predict protein function from structure in diverse superfamilies

Predicting protein function from structure remains an active area of interest, particularly for the structural genomics initiatives where a substantial number of structures are initially solved with little or no functional characterisation. Although global structure comparison methods can be used to transfer functional annotations, the relationship between fold and function is complex, particularly in functionally diverse superfamilies that have evolved through different secondary structure embellishments to a common structural core. The majority of prediction algorithms employ local templates built on known or predicted functional residues. Here, we present a novel method (FLORA) that automatically generates structural motifs associated with different functional sub-families (FSGs) within functionally diverse domain superfamilies. Templates are created purely on the basis of their specificity for a given FSG, and the method makes no prior prediction of functional sites, nor assumes specific physico-chemical properties of residues. FLORA is able to accurately discriminate between homologous domains with different functions and substantially outperforms (a 2–3 fold increase in coverage at low error rates) popular structure comparison methods and a leading function prediction method. We benchmark FLORA on a large data set of enzyme superfamilies from all three major protein classes (α, β, αβ) and demonstrate the functional relevance of the motifs it identifies. We also provide novel predictions of enzymatic activity for a large number of structures solved by the Protein Structure Initiative. Overall, we show that FLORA is able to effectively detect functionally similar protein domain structures by purely using patterns of structural conservation of all residues

The impact of ageing reveals distinct roles for human dentate gyrus and CA3 in pattern separation and object recognition memory

© 2017 The Author(s). Both recognition of familiar objects and pattern separation, a process that orthogonalises overlapping events, are critical for effective memory. Evidence is emerging that human pattern separation requires dentate gyrus. Dentate gyrus is intimately connected to CA3 where, in animals, an autoassociative network enables recall of complete memories to underpin object/event recognition. Despite huge motivation to treat age-related human memory disorders, interaction between human CA3 and dentate subfields is difficult to investigate due to small size and proximity. We tested the hypothesis that human dentate gyrus is critical for pattern separation, whereas, CA3 underpins identical object recognition. Using 3 T MR hippocampal subfield volumetry combined with a behavioural pattern separation task, we demonstrate that dentate gyrus volume predicts accuracy and response time during behavioural pattern separation whereas CA3 predicts performance in object recognition memory. Critically, human dentate gyrus volume decreases with age whereas CA3 volume is age-independent. Further, decreased dentate gyrus volume, and no other subfield volume, mediates adverse effects of aging on memory. Thus, we demonstrate distinct roles for CA3 and dentate gyrus in human memory and uncover the variegated effects of human ageing across hippocampal regions. Accurate pinpointing of focal memory-related deficits will allow future targeted treatment for memory loss

CMASA: an accurate algorithm for detecting local protein structural similarity and its application to enzyme catalytic site annotation

<p>Abstract</p> <p>Background</p> <p>The rapid development of structural genomics has resulted in many "unknown function" proteins being deposited in Protein Data Bank (PDB), thus, the functional prediction of these proteins has become a challenge for structural bioinformatics. Several sequence-based and structure-based methods have been developed to predict protein function, but these methods need to be improved further, such as, enhancing the accuracy, sensitivity, and the computational speed. Here, an accurate algorithm, the CMASA (Contact MAtrix based local Structural Alignment algorithm), has been developed to predict unknown functions of proteins based on the local protein structural similarity. This algorithm has been evaluated by building a test set including 164 enzyme families, and also been compared to other methods.</p> <p>Results</p> <p>The evaluation of CMASA shows that the CMASA is highly accurate (0.96), sensitive (0.86), and fast enough to be used in the large-scale functional annotation. Comparing to both sequence-based and global structure-based methods, not only the CMASA can find remote homologous proteins, but also can find the active site convergence. Comparing to other local structure comparison-based methods, the CMASA can obtain the better performance than both FFF (a method using geometry to predict protein function) and SPASM (a local structure alignment method); and the CMASA is more sensitive than PINTS and is more accurate than JESS (both are local structure alignment methods). The CMASA was applied to annotate the enzyme catalytic sites of the non-redundant PDB, and at least 166 putative catalytic sites have been suggested, these sites can not be observed by the Catalytic Site Atlas (CSA).</p> <p>Conclusions</p> <p>The CMASA is an accurate algorithm for detecting local protein structural similarity, and it holds several advantages in predicting enzyme active sites. The CMASA can be used in large-scale enzyme active site annotation. The CMASA can be available by the mail-based server (<url>http://159.226.149.45/other1/CMASA/CMASA.htm</url>).</p

Access and utilisation of maternity care for disabled women who experience domestic abuse:a systematic review

BACKGROUND: Although disabled women are significantly more likely to experience domestic abuse during pregnancy than non-disabled women, very little is known about how maternity care access and utilisation is affected by the co-existence of disability and domestic abuse. This systematic review of the literature explored how domestic abuse impacts upon disabled women’s access to maternity services. METHODS: Eleven articles were identified through a search of six electronic databases and data were analysed to identify: the factors that facilitate or compromise access to care; the consequences of inadequate care for pregnant women’s health and wellbeing; and the effectiveness of existing strategies for improvement. RESULTS: Findings indicate that a mental health diagnosis, poor relationships with health professionals and environmental barriers can compromise women’s utilisation of maternity services. Domestic abuse can both compromise, and catalyse, access to services and social support is a positive factor when accessing care. Delayed and inadequate care has adverse effects on women’s physical and psychological health, however further research is required to fully explore the nature and extent of these consequences. Only one study identified strategies currently being used to improve access to services for disabled women experiencing abuse. CONCLUSIONS: Based upon the barriers and facilitators identified within the review, we suggest that future strategies for improvement should focus on: understanding women’s reasons for accessing care; fostering positive relationships; being women-centred; promoting environmental accessibility; and improving the strength of the evidence base