DichroMatch: a website for similarity searching of circular dichroism spectra

Circular dichroism (CD) spectroscopy is a widely used method for examining the structure, folding and conformational changes of proteins. A new online CD analysis server (DichroMatch) has been developed for identifying proteins with similar spectral characteristics by detecting possible structurally and functionally related proteins and homologues. DichroMatch includes six different methods for determining the spectral nearest neighbours to a query protein spectrum and provides metrics of how similar these spectra are and, if corresponding crystal structures are available for the closest matched proteins, information on their secondary structures and fold classifications. By default, DichroMatch uses all the entries in the Protein Circular Dichroism Data Bank (PCDDB) for its comparison set, providing the broadest range of publicly available protein spectra to match with the unknown protein. Alternatively, users can download or create their own specialized data sets, thereby enabling comparisons between the structures of related proteins such as wild-type versus mutants or homologues or a series of spectra of the same protein under different conditions. The DichroMatch server is freely available at http://dichromatch.cryst.bbk.ac.uk

Novel actions of next-generation taxanes benefit advanced stages of prostate cancer.

PURPOSE: To improve the outcomes of patients with castration-resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individualize specific treatments for patients with CRPC. These studies compared the novel taxane cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond. EXPERIMENTAL DESIGN: Cabazitaxel and docetaxel were compared via in vitro modeling to determine the molecular mechanism, biochemical and cell biologic impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro and in xenograft tumors for cabazitaxel response. RESULTS: The data herein show that (i) cabazitaxel exerts stronger cytostatic and cytotoxic response compared with docetaxel, especially in CRPC; (ii) cabazitaxel induces aberrant mitosis, leading to pyknotic and multinucleated cells; (iii) taxanes do not act through the androgen receptor (AR); (iv) gene-expression profiling reveals distinct molecular actions for cabazitaxel; and (v) tumors that have progressed to castration resistance via loss of RB show enhanced sensitivity to cabazitaxel. CONCLUSIONS: Cabazitaxel not only induces improved cytostatic and cytotoxic effects, but also affects distinct molecular pathways, compared with docetaxel, which could underlie its efficacy after docetaxel treatment has failed in patients with CRPC. Finally, RB is identified as the first potential biomarker that could define the therapeutic response to taxanes in metastatic CRPC. This would suggest that loss of RB function induces sensitization to taxanes, which could benefit up to 50% of CRPC cases

The theory of quantum levitators

We develop a unified theory for clocks and gravimeters using the interferences of multiple atomic waves put in levitation by traveling light pulses. Inspired by optical methods, we exhibit a propagation invariant, which enables to derive analytically the wave function of the sample scattering on the light pulse sequence. A complete characterization of the device sensitivity with respect to frequency or to acceleration measurements is obtained. These results agree with previous numerical simulations and confirm the conjecture of sensitivity improvement through multiple atomic wave interferences. A realistic experimental implementation for such clock architecture is discussed.Comment: 11 pages, 6 Figures. Minor typos corrected. Final versio

Optimal parameter regions and the time-dependence of control parameter values for the particle swarm optimization algorithm

The particle swarm optimization (PSO) algorithm is a stochastic search technique based on the social dynamics of a flock of birds. It has been established that the performance of the PSO algorithm is sensitive to the values assigned to its control parameters. Many studies have examined the long-term behaviours of various PSO parameter configurations, but have failed to provide a quantitative analysis across a variety of benchmark problems. Furthermore, two important questions have remained unanswered. Specifically, the effects of the balance between the values of the acceleration coefficients on the optimal parameter regions, and whether the optimal parameters to employ are time-dependent, warrant further investigation. This study addresses both questions by examining the performance of a global-best PSO using 3036 different parameter configurations on a set of 22 benchmark problems. Results indicate that the balance between the acceleration coefficients does impact the regions of parameter space that lead to optimal performance. Additionally, this study provides concrete evidence that, for the examined problem dimensions, larger acceleration coefficients are preferred as the search progresses, thereby indicating that the optimal parameters are, in fact, time-dependent. Finally, this study provides a general recommendation for the selection of PSO control parameter values.The National Research Foundation (NRF) of South Africa (Grant Number 46712) and the Natural Sciences and Engineering Research Council of Canada (NSERC).http://www.elsevier.com/locate/swevo2019-08-01hj2018Computer Scienc

Self-adaptive particle swarm optimization : a review and analysis of convergence

Particle swarm optimization (PSO) is a population-based, stochastic search algorithm inspired by the flocking behaviour of birds. The PSO algorithm has been shown to be rather sensitive to its control parameters, and thus, performance may be greatly improved by employing appropriately tuned parameters. However, parameter tuning is typically a time-intensive empirical process. Furthermore, a priori parameter tuning makes the implicit assumption that the optimal parameters of the PSO algorithm are not time-dependent. To address these issues, self-adaptive particle swarm optimization (SAPSO) algorithms adapt their control parameters throughout execution. While there is a wide variety of such SAPSO algorithms in the literature, their behaviours are not well understood. Specifically, it is unknown whether these SAPSO algorithms will even exhibit convergent behaviour. This paper addresses this lack of understanding by investigating the convergence behaviours of 18 SAPSO algorithms both analytically and empirically. This paper also empirically examines whether the adapted parameters reach a stable point and whether the final parameter values adhere to a well-known convergence criterion. The results depict a grim state for SAPSO algorithms; over half of the SAPSO algorithms exhibit divergent behaviour while many others prematurely converge.The National Research Foundation (NRF) of South Africa (Grant Number 46712) and the Natural Sciences and Engineering Research Council of Canada (NSERC).http://link.springer.com/journal/117212019-09-01hj2018Computer Scienc

Lack of association between angiotensin-converting enzyme and dementia of the Alzheimer’s type in an elderly Arab population in Wadi Ara, Israel

The angiotensin-converting enzyme (ACE), a protease involved in blood pressure regulation, has been implicated as an important candidate gene for Alzheimer’s disease (AD). This study investigated whether the ACE gene insertion–deletion (ID) polymorphism is associated with risk of developing dementia of Alzheimer’s type (DAT) in an Arab–Israeli community, a unique genetic isolate where there is a high prevalence of DAT. In contrast to several other studies, we found no evidence of an association between this polymorphism and either DAT or age-related cognitive decline (ARCD)

Suicide inhibition of alpha-oxamine synthases:structures of the covalent adducts of 8-amino-7-oxononanoate synthase with trifluoroalanine

The suicide inhibition of the α-oxamine synthases by the substrate analog, L-trifluoroalanine was investigated. The inhibition resulted in the formation of a complex with loss of all three fluorine atoms. Decarboxylation and loss of fluoride occurred immediately after aldimine formation. The inherent flexibility could allow the difluorinated intermediate complex to adopt a suitable conformation. Decarboxylation in the normal mechanism occurs after formation of the ketoacid intermediate.link_to_subscribed_fulltex

Lancaster County, Virginia Shoreline Inventory Report Methods and Guidelines

The data inventory developed for the Shoreline Inventory is based on a three tiered shoreline assessment approach. This assessment characterizes conditions that can be observed from a small boat navigating along the shoreline or by using observations made remotely at the desktop using high resolution imagery. The three tiered shoreline assessment approach divides the shorezone into three regions: the immediate riparian zone, evaluated for land use the bank, evaluated for height, cover and natural protection the shoreline, describing the presence of shoreline structures for shore protection and recreational purposes. The 2015 Inventory for Lancaster County was generated using on-screen, digitizing techniques in ArcGIS&tm; - ArcMap v10.2.2 while viewing conditions observed in 2015 Bing high resolution oblique imagery and 2013 imagery from the Virginia Base Mapping Program (VBMP). These data sources allowed the inventory to be generated without additional field work. Three GIS shapefiles are developed. The first describes land use and bank conditions (LancasterCo _lubc_2015). The second reports shoreline structures that are described as arcs or lines (LancasterCo _sstru_2015). The final shapefile includes all structures that are represented as points (LancasterCo_astru_2015). The shapefiles use a shoreline basemap updated in-house from the 2013 VBMP high resolution digital terrain model. The shoreline is re-coded to reflect features and attributes observed. The metadata file accompanies the shapefiles and defines attribute accuracy, data development, and any use restrictions that pertain to data

Noninvasive detection of graft injury after heart transplant using donor-derived cell-free DNA: A prospective multicenter study

Standardized donor-derived cell-free DNA (dd-cfDNA) testing has been introduced into clinical use to monitor kidney transplant recipients for rejection. This report describes the performance of this dd-cfDNA assay to detect allograft rejection in samples from heart transplant (HT) recipients undergoing surveillance monitoring across the United States. Venous blood was longitudinally sampled from 740 HT recipients from 26 centers and in a single-center cohort of 33 patients at high risk for antibody-mediated rejection (AMR). Plasma dd-cfDNA was quantified by using targeted amplification and sequencing of a single nucleotide polymorphism panel. The dd-cfDNA levels were correlated to paired events of biopsy-based diagnosis of rejection. The median dd-cfDNA was 0.07% in reference HT recipients (2164 samples) and 0.17% in samples classified as acute rejection (35 samples; P = .005). At a 0.2% threshold, dd-cfDNA had a 44% sensitivity to detect rejection and a 97% negative predictive value. In the cohort at risk for AMR (11 samples), dd-cfDNA levels were elevated 3-fold in AMR compared with patients without AMR (99 samples, P = .004). The standardized dd-cfDNA test identified acute rejection in samples from a broad population of HT recipients. The reported test performance characteristics will guide the next stage of clinical utility studies of the dd-cfDNA assay