How green in our library?

An environment group has had a presence within Leeds Met Libraries since December 2004. Initially the group chose to look at simple things which could have a positive impact on how we use resources in the workplace. We introduced recycling bins for plastic cups and cans in the staff tearooms, provided dispensers for plastic carrier bags near the self-service machines and arranged training hours for library staff to learn more about environmental issues and to look at their carbon footprint. In May 2006, the group decided to continue their work via an e-mail discussion forum where any issues of environmental concern were raised, with dedicated members of the group continuing to action if appropriate. We found that as time went on, there was an increased interest in environmental matters, so much so that in April 2009 the group reformed, with a new membership and a new title of Green Initiatives Group. The remit of the group is: - To raise awareness of and promote green issues amongst library staff. - To exchange best practice in the university and in the Higher Education library sector. - To build relationships with other ethical organisations working in the Leeds area. One of our aims is to be aware of initiatives taking place in the wider university and to be able to communicate relevant information to library staff about what the university is involved in environmentally. Below is a brief outline of what we have achieved as a group and current projects we are working on

A novel homozygous variant extending the peripheral myelin protein 22 by 9 AMino acids causes early-onset Charcot-Marie-Tooth disease with predominant severe sensory ataxia

Peripheral myelin protein 22 (PMP22) related neuropathies account for over 50% of inherited peripheral neuropathies. A gene copy variation results in CMT1A (duplication) and hereditary neuropathy with liability to pressure palsies (HNPP; single deletion). Point mutations comprise both phenotypes. The underlying pathological mechanisms are incompletely understood and biallelic mutations of PMP22 are very rare. We describe a 9‐year‐old girl who presented before the age of 1 year with severe locomotor delay. She now requires support for standing and walking in view of her severe sensory ataxia. Strikingly, her muscle power and bulk are close to normal in all segments. Nerve conduction studies showed sensory‐motor velocities below 5 m/s. Genetic analysis revealed a homozygous sequence change in the PMP22 gene causing the loss of termination codon (c.483A > G; p.[*161Trpext*10]), extending the protein by 9 amino acids. Both heterozygous parents have neurophysiological abnormalities consistent with HNPP, consistent with this being a loss‐of‐function mutation. PMP22‐deficient human models are rare but important to decipher the physiological function of the PMP22 protein in vivo. The predominance of large fiber sensory involvement in this and other rare similar cases suggests a pivotal role played by PMP22 in the embryogenesis of dorsal root ganglia in humans

Minimal Synthesis of String To String Functions From Examples

We study the problem of synthesizing string to string transformations from a set of input/output examples. The transformations we consider are expressed using deterministic finite automata (DFA) that read pairs of letters, one letter from the input and one from the output. The DFA corresponding to these transformations have additional constraints, ensuring that each input string is mapped to exactly one output string. We suggest that, given a set of input/output examples, the smallest DFA consistent with the examples is a good candidate for the transformation the user was expecting. We therefore study the problem of, given a set of examples, finding a minimal DFA consistent with the examples and satisfying the functionality and totality constraints mentioned above. We prove that, in general, this problem (the corresponding decision problem) is NP-complete. This is unlike the standard DFA minimization problem which can be solved in polynomial time. We provide several NP-hardness proofs that show the hardness of multiple (independent) variants of the problem. Finally, we propose an algorithm for finding the minimal DFA consistent with input/output examples, that uses a reduction to SMT solvers. We implemented the algorithm, and used it to evaluate the likelihood that the minimal DFA indeed corresponds to the DFA expected by the user.Comment: SYNT 201

The time-profile of cell growth in fission yeast: model selection criteria favoring bilinear models over exponential ones

BACKGROUND: There is considerable controversy concerning the exact growth profile of size parameters during the cell cycle. Linear, exponential and bilinear models are commonly considered, and the same model may not apply for all species. Selection of the most adequate model to describe a given data-set requires the use of quantitative model selection criteria, such as the partial (sequential) F-test, the Akaike information criterion and the Schwarz Bayesian information criterion, which are suitable for comparing differently parameterized models in terms of the quality and robustness of the fit but have not yet been used in cell growth-profile studies. RESULTS: Length increase data from representative individual fission yeast (Schizosaccharomyces pombe) cells measured on time-lapse films have been reanalyzed using these model selection criteria. To fit the data, an extended version of a recently introduced linearized biexponential (LinBiExp) model was developed, which makes possible a smooth, continuously differentiable transition between two linear segments and, hence, allows fully parametrized bilinear fittings. Despite relatively small differences, essentially all the quantitative selection criteria considered here indicated that the bilinear model was somewhat more adequate than the exponential model for fitting these fission yeast data. CONCLUSION: A general quantitative framework was introduced to judge the adequacy of bilinear versus exponential models in the description of growth time-profiles. For single cell growth, because of the relatively limited data-range, the statistical evidence is not strong enough to favor one model clearly over the other and to settle the bilinear versus exponential dispute. Nevertheless, for the present individual cell growth data for fission yeast, the bilinear model seems more adequate according to all metrics, especially in the case of wee1Δ cells

Quantification of functionalised gold nanoparticle-targeted knockdown of gene expression in HeLa cells

Introduction: Gene therapy continues to grow as an important area of research, primarily because of its potential in the treatment of disease. One significant area where there is a need for better understanding is in improving the efficiency of oligonucleotide delivery to the cell and indeed, following delivery, the characterization of the effects on the cell. Methods: In this report, we compare different transfection reagents as delivery vehicles for gold nanoparticles functionalized with DNA oligonucleotides, and quantify their relative transfection efficiencies. The inhibitory properties of small interfering RNA (siRNA), single-stranded RNA (ssRNA) and single-stranded DNA (ssDNA) sequences targeted to human metallothionein hMT-IIa are also quantified in HeLa cells. Techniques used in this study include fluorescence and confocal microscopy, qPCR and Western analysis. Findings: We show that the use of transfection reagents does significantly increase nanoparticle transfection efficiencies. Furthermore, siRNA, ssRNA and ssDNA sequences all have comparable inhibitory properties to ssDNA sequences immobilized onto gold nanoparticles. We also show that functionalized gold nanoparticles can co-localize with autophagosomes and illustrate other factors that can affect data collection and interpretation when performing studies with functionalized nanoparticles. Conclusions: The desired outcome for biological knockdown studies is the efficient reduction of a specific target; which we demonstrate by using ssDNA inhibitory sequences targeted to human metallothionein IIa gene transcripts that result in the knockdown of both the mRNA transcript and the target protein

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

Survey of attitudes, materials and methods employed in endodontic treatment by general dental practitioners in North Jordan

BACKGROUND: General dental practitioners provide the majority of endodontic treatment in Jordan. The aim of this study was to gather information on the methods, materials and attitudes employed in root canal treatment by dentists in North Jordan, in order to evaluate and improve the quality of current practice. METHODS: A questionnaire was posted to all registered general dental practitioners working in private practice in Irbid Governate in North Jordan (n = 181). The questionnaire included information on methods, materials and techniques used in endodontic treatment. RESULTS: Reply rate was 72% (n = 131). The results demonstrated that only five dentists used rubber dam occasionally and not routinely. The majority used cotton rolls for isolation solely or in combination with a high volume saliva ejector (n = 116). The most widely used irrigants were sodium hypochlorite and hydrogen peroxide, which were used by 32.9% (n = 43) and 33.6% (n = 44) of the respondents, respectively. Forty eight percent of the respondents (n = 61) used the cold lateral condensation technique for canal obturation, 31.3% (n = 41) used single cone, 9.9% (n = 13) used vertical condensation and 12.2% (n = 16) used paste or cement only for the obturation. The majority used zinc oxide eugenol as a sealer (72.5%). All, but one, respondents used hand instruments for canal preparation and the technique of choice was step back (52.7%). More than 50% (n = 70) of the dentists took one radiograph for determining the working length, whilst 22.9% (n = 30) did not take any radiograph at all. Most practitioners performed treatment in three visits for teeth with two or more root canals, and in two visits for teeth with a single root canal. CONCLUSIONS: This study indicates that dentists practicing in North Jordan do not comply with international quality standards and do not use recently introduced techniques. Many clinicians never take a radiograph for determining the working length and never used rubber dam or intra-canal medicaments

Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study

<p>Background: High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT[1]study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study.</p> <p>The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting.</p> <p>Methods/design: The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios.</p> <p>Primary Objective – To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios.</p> <p>Secondary Objectives – To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendrofluazide.</p> <p>Discussion: The numerous deleterious effects of hypertension dictate the need for a systematic approach for its treatment. In spite of various therapies, resistant hypertension is widely prevalent. Among various factors, primary aldosteronism is an important cause of resistant hypertension and is now more commonly recognised. More significantly, hypertensives with primary aldosteronism are also exposed to various other deleterious effects of excess aldosterone. Hence treating hypertension with specific aldosterone antagonists may be a better approach in this group of patients. It may lead on to better blood pressures with fewer medications.</p&gt