Revista Jurídica Digital UANDES
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Controlling Phase Separation of Lysozyme with Polyvalent Anions
No full textThe ability of polyvalent anions to influence protein–protein interactions and protein net charge was investigated through solubility and turbidity experiments, determination of osmotic second virial coefficients (B22), and ζ-potential values for lysozyme solutions. B22 values showed that all anions reduce protein–protein repulsion between positively charged lysozyme molecules, and those anions with higher net valencies are more effective. The polyvalent anions pyrophosphate and tripolyphosphate were observed to induce protein reentrant condensation, which has been previously observed with negatively charged proteins in the presence of trivalent cations. Reentrant condensation is a phenomenon in which low concentrations of polyvalent ions induce protein precipitation, but further increasing polyvalent ion concentration causes the protein precipitate to resolubilize. Interestingly, citrate does not induce lysozyme reentrant condensation despite having a similar charge, size, and shape to pyrophosphate. We observe qualitative differences in protein behavior when compared against negatively charged proteins in solutions of trivalent cations. The polyphosphate ions induce a much stronger protein–protein attraction, which correlates with the occurrence of a liquid–gel transition that replaces the liquid–liquid transition observed with trivalent cations. The results indicate that solutions of polyphosphate ions provide a model system for exploring the link between the protein-phase diagram and model interaction potentials and also highlight the importance that ion-specific effects can have on protein solubility
Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study
No full textBACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).METHODS: The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.</p
Machine learning algorithms for systematic review:Reducing workload in a preclinical review of animal studies and reducing human screening error
No full textBackground: Here, we outline a method of applying existing machine learning (ML) approaches to aid citation screening in an on-going broad and shallow systematic review of preclinical animal studies. The aim is to achieve a high-performing algorithm comparable to human screening that can reduce human resources required for carrying out this step of a systematic review. Methods: We applied ML approaches to a broad systematic review of animal models of depression at the citation screening stage. We tested two independently developed ML approaches which used different classification models and feature sets. We recorded the performance of the ML approaches on an unseen validation set of papers using sensitivity, specificity and accuracy. We aimed to achieve 95% sensitivity and to maximise specificity. The classification model providing the most accurate predictions was applied to the remaining unseen records in the dataset and will be used in the next stage of the preclinical biomedical sciences systematic review. We used a cross-validation technique to assign ML inclusion likelihood scores to the human screened records, to identify potential errors made during the human screening process (error analysis). Results: ML approaches reached 98.7% sensitivity based on learning from a training set of 5749 records, with an inclusion prevalence of 13.2%. The highest level of specificity reached was 86%. Performance was assessed on an independent validation dataset. Human errors in the training and validation sets were successfully identified using the assigned inclusion likelihood from the ML model to highlight discrepancies. Training the ML algorithm on the corrected dataset improved the specificity of the algorithm without compromising sensitivity. Error analysis correction leads to a 3% improvement in sensitivity and specificity, which increases precision and accuracy of the ML algorithm. Conclusions: This work has confirmed the performance and application of ML algorithms for screening in systematic reviews of preclinical animal studies. It has highlighted the novel use of ML algorithms to identify human error. This needs to be confirmed in other reviews with different inclusion prevalence levels, but represents a promising approach to integrating human decisions and automation in systematic review methodology.</p
Emotion regulation strategies in bipolar disorder:A systematic and critical review
No full textBackgroundTheoretical frameworks emphasise associations between interpretations and responses to affect and bipolar disorder (BD). This review (PROSPERO CRD42016043801) investigated which emotion regulation (ER) strategies have been applied to BD, are elevated in BD compared to clinical and non-clinical controls, and are associated with clinical and functional outcomes in BDMethodsSearch terms relating to emotion regulation, coping and bipolar disorder were entered into Embase, MedLine and PsycInfo. Quantitative studies investigating relationships between ER strategies and BD were eligible for this narrative synthesisResultsA large volume of research (n = 47) investigated specific ER strategies in BD. Maladaptive strategies such as rumination and dampening were elevated in BD compared to controls and these particular strategies had a detrimental impact on outcomes such as mood symptoms. BD had a similar profile of ER strategies to unipolar depression, but there was limited comparison to other clinical groups. People with BD did not generally have deficits in using adaptive strategies, as evidenced by comparisons with controls and experimental studiesLimitationsMethodological heterogeneity and a lack of ecologically valid ER assessmentsConclusionsEmpirical literature is critiqued in line with contemporary theories of BD and of emotion regulation more generally, in order to inform future research recommendations. This includes investigation of the importance of context in the impact of ER strategies, and discrepancies between trait and state use of ER strategies, particularly through experience sampling
Acoustic scattering from a one-dimensional array; tail-end asymptotics for efficient evaluation of the quasi-periodic Green's function
No full textMotivated by the problem of acoustic plane wave scattering from an infinite periodic array of cylindrical scatterers, we present a new and easily-implemented way of calculating the quasiperiodic Greens function. This approach is based on an asymptotic expansion of the summand in the quasi-periodic Greens function in order to derive a tail-end correction term, allowing for a rapid and accurate approximation of the function. The tail-end approximation is shown to have much better and faster convergence properties than the usual truncation approach and competes very well with state-of-the-art alternative techniques. This method is then combined with a boundary element scheme to calculate the transmission and reflection coefficients associated with arrays of cylinders of different cross-sections and varying aspect ratios. The results are validated against the existing literature and by independent finite element calculations
A meta-analysis portal for human breast cancer transcriptomics data: BreastCancerVis
No full textBreast cancer is a major disease posing many therapeutic and societal challenges. The major problem remains the diversity of the disease. Breast cancers are divided in several distinct subtypes, but the specific mechanisms involved in each subtype are not understood. We apply advanced network medicine techniques to the analysis of transcriptomics data of several breast cancer cell lines. We show that different subtypes are characterized by highly heterogeneous pathway activity. Using the overlap between differentially expressed genes and drug-induced expression changes, we present candidate drugs for repurposing. Furthermore, we find different active subnetworks across the subtypes, regulated by distinct transcription factors. All these results are made available via a user-friendly portal at http://phenome.manchester.ac.uk/breastcancer
Violin Concerto: A Day in the Life
No full textA violin concerto for solo violin and medium orchestra which chronicles 24 hours in a typical day in the life of indentured child Northern textile mill worker Robert Blincoe in the year 1802. It was performed by The Orchestra of Opera North on 3, 4, 5, 11, 25 May 2019 throughout Leeds and Bradford. The commission is funded by Arts Council England, The RVW Trust and the Ida Carroll Trust
A recurrent nova super-remnant in the Andromeda galaxy
No full textThe accretion of hydrogen onto a white dwarf star ignites a classical nova eruption — a thermonuclear runaway in the accumulated envelope of gas, leading to luminosities up to a million times that of the Sun and a high-velocity mass ejection that produces a remnant shell (mainly consisting of interstellar medium). Close to the upper mass limit of a white dwarf (1.4 solar masses), rapid accretion of hydrogen (about 10^−7 solar masses per year) from a stellar companion leads to frequent eruptions on timescales of years to decades. Such binary systems are known as recurrent novae. The ejecta of recurrent novae, initially moving at velocities of up to 10,000 kilometres per second, must ‘sweep up’ the surrounding interstellar medium, creating cavities in space around the nova binary. No remnant larger than one parsec across from any single classical or recurrent nova eruption is known, but thousands of successive recurrent nova eruptions should be capable of generating shells hundreds of parsecs across. Here we report that the most frequently recurring nova, M31N 2008-12a in the Andromeda galaxy (Messier 31 or NGC 224), which erupts annually, is indeed surrounded by such a super-remnant with a projected size of at least 134 by 90 parsecs. Larger than almost all known remnants of even supernova explosions, the existence of this shell demonstrates that the nova M31N 2008-12a has erupted with high frequency for millions of years
Polymer-modified Liquid Crystals
No full textBridging soft matter physics, materials science and engineering, polymer-modified liquid crystals are an exciting class of materials. They represent a vibrant field of research, promising advances in display technologies, as well as non-display uses. Describing all aspects of polymer-dispersed and polymer-stabilized liquid crystals, the broad coverage of this book makes it a must-have resource for anyone working in the area. The reader will find expert accounts covering basic concepts, materials synthesis and polymerization techniques, properties of various dispersed and stabilized phases, and critical overviews of their applications
The effect of cold work on the transformation kinetics and texture of a zirconium alloy during fast thermal cycling
No full textThe effect of cold-work on the transformation kinetics and texture evolution after fast temperature cycling were studied in a dilute zirconium alloy. It was found that cold-work delays the onset of phase transformation and helps randomise the texture after the transformation. Samples of Zircaloy-4 in two conditions, cold-rolled to 70% reduction and fully recrystallised, were heated above the β-transus at a fast rate of 100 °C s−1 using resistive heating and without constraint. Electrical resistivity was used to measure the phase fraction during heating and electron back-scatter diffraction was used to measure the texture before and after the thermal cycle. Whereas previous work on titanium suggested that cold-work leads to texture strengthening after transformation, these new experiments show that, when the heating rate is fast enough, recrystallisation is incomplete on heating, which slows down the start of transformation, leading to a random α-texture after cooling. The texture in the recrystallised material after β heat-treatment is non-random but different from the start, a consequence of both a stronger β-texture after grain growth and stronger variant selection on cooling. This variant selection can be mostly explained by α-nucleation at special β-grain boundaries. These results demonstrate that prior deformation has a strong effect on the textures produced after β-heat treatment when heating rates are fast. This has implications for the anisotropy of nuclear cladding components after loss-of-coolant (LOCA) and reactivity-initiated accidents (RIA) but also more widely for the manufacturing of zirconium and titanium using welding or additive layer manufacturing where the heating rates are high.</p