Systematic review of antitumour efficacy and mechanism of metformin activity in prostate cancer models

Metformin, the first line pharmacotherapy for type 2 diabetes has demonstrated favourable effects in prostate cancer (PCa) across a range of studies evaluating PCa patient outcomes amongst metformin users. However, a lack of rigorously conducted prospective studies has stalled clinical use in this setting. Despite multiple studies evaluating the mechanisms underpinning antitumour effects of metformin in PCa, to date, no reviews have compared these findings. This systematic review and meta-analysis consolidates the mechanisms accounting for the antitumour effect of metformin in PCa and evaluates the antitumour efficacy of metformin in preclinical PCa studies. Data were obtained through Medline and EMBASE, extracted by two independent assessors. Risk of bias was assessed using the TOXR tool. Meta-analysis compared in vivo reductions of PCa tumour volume with metformin. In total, 447 articles were identified with 80 duplicates, and 261 articles excluded based on eligibility criteria. The remaining 106 articles were assessed and 71 excluded, with 35 articles included for systematic review, and eight included for meta-analysis. The mechanisms of action of metformin regarding tumour growth, viability, migration, invasion, cell metabolism, and activation of signalling cascades are individually discussed. The mechanisms by which metformin inhibits PCa cell growth are multimodal. Metformin regulates expression of multiple proteins/genes to inhibit cellular proliferation, cell cycle progression, and cellular invasion and migration. Published in vivo studies also conclusively demonstrate that metformin inhibits PCa growth. This highlights the potential of metformin to be repurposed as an anticancer agent, warranting further investigation of metformin in the setting of PCa

Crystal growth and quantum oscillations in the topological chiral semimetal CoSi

We survey the electrical transport properties of the single-crystalline, topological chiral semimetal CoSi which was grown via different methods. High-quality CoSi single crystals were found in the growth from tellurium solution. The sample's high carrier mobility enables us to observe, for the first time, quantum oscillations (QOs) in its thermoelectrical signals. Our analysis of QOs reveals two spherical Fermi surfaces around the R point in the Brillouin zone corner. The extracted Berry phases of these electron orbits are consistent with the -2 chiral charge as reported in DFT calculations. Detailed analysis on the QOs reveals that the spin-orbit coupling induced band-splitting is less than 2 meV near the Fermi level, one order of magnitude smaller than our DFT calculation result. We also report the phonon-drag induced large Nernst effect in CoSi at intermediate temperatures

Quantification of optical pulsed-plane-wave-shaping by chiral sculptured thin films

The durations and average speeds of ultrashort optical pulses transmitted through chiral sculptured thin films (STFs) were calculated using a finite-difference time-domain algorithm. Chiral STFs are a class of nanoengineered materials whose microstructure comprises parallel helicoidal nanowires grown normal to a substrate. The nanowires are $\sim$10-300 nm in diameter and $\sim1-10 \mu$m in length. Durations of transmitted pulses tend to increase with decreasing (free-space) wavelength of the carrier plane wave, while average speeds tend to increase with increasing wavelength. An increase in nonlinearity, as manifested by an intensity-dependent refractive index in the frequency domain, tends to increase durations of transmitted pulses and decrease average speeds. The circular Bragg phenomenon exhibited by a chiral STFs manifests itself in the frequency domain as high reflectivity for normally incident carrier plane waves whose circular polarization state is matched to the structural handedness of the film and whose wavelength falls in a range known as the Bragg regime; films of the opposite structural handedness reflect such plane waves little. This effect tends to distort the shapes of transmitted pulses with respect to the incident pulses, and such shaping can cause sharp changes in some measures of average speed with respect to carrier wavelength. A local maximum in the variation of one measure of the pulse duration with respect to wavelength is noted and attributed to the circular Bragg phenomenon. Several of these effects are explained via frequency-domain arguments. The presented results serve as a foundation for future theoretical and experimental studies of optical pulse propagation through causal, nonlinear, nonhomogeneous, and anisotropic materials.Comment: To appear in Journal of Modern Optic

LAS: a software platform to support oncological data management

The rapid technological evolution in the biomedical and molecular oncology fields is providing research laboratories with huge amounts of complex and heterogeneous data. Automated systems are needed to manage and analyze this knowledge, allowing the discovery of new information related to tumors and the improvement of medical treatments. This paper presents the Laboratory Assistant Suite (LAS), a software platform with a modular architecture designed to assist researchers throughout diverse laboratory activities. The LAS supports the management and the integration of heterogeneous biomedical data, and provides graphical tools to build complex analyses on integrated data. Furthermore, the LAS interfaces are designed to ease data collection and management even in hostile environments (e.g., in sterile conditions), so as to improve data qualit

Social spammer detection: A multi-relational embedding approach

© Springer International Publishing AG, part of Springer Nature 2018. Since the relation is the main data shape of social networks, social spammer detection desperately needs a relation-dependent but content-independent framework. Some recent detection method transforms the social relations into a set of topological features, such as degree, k-core, etc. However, the multiple heterogeneous relations and the direction within each relation have not been fully explored for identifying social spammers. In this paper, we make an attempt to adopt the Multi-Relational Embedding (MRE) approach for learning latent features of the social network. The MRE model is able to fuse multiple kinds of different relations and also learn two latent vectors for each relation indicating both sending role and receiving role of every user, respectively. Experimental results on a real-world multi-relational social network demonstrate the latent features extracted by our MRE model can improve the detection performance remarkably

Are voltage-gated sodium channels on the dorsal root ganglion involved in the development of neuropathic pain?

Neuropathic pain is a common clinical condition. Current treatments are often inadequate, ineffective, or produce potentially severe adverse effects. Understanding the mechanisms that underlie the development and maintenance of neuropathic pain will be helpful in identifying new therapeutic targets and developing effective strategies for the prevention and/or treatment of this disorder. The genesis of neuropathic pain is reliant, at least in part, on abnormal spontaneous activity within sensory neurons. Therefore, voltage-gated sodium channels, which are essential for the generation and conduction of action potentials, are potential targets for treating neuropathic pain. However, preclinical studies have shown unexpected results because most pain-associated voltage-gated channels in the dorsal root ganglion are down-regulated after peripheral nerve injury. The role of dorsal root ganglion voltage-gated channels in neuropathic pain is still unclear. In this report, we describe the expression and distribution of voltage-gated sodium channels in the dorsal root ganglion. We also review evidence regarding changes in their expression under neuropathic pain conditions and their roles in behavioral responses in a variety of neuropathic pain models. We finally discuss their potential involvement in neuropathic pain

Generic master equations for quasi-normal frequencies

Generic master equations governing the highly-damped quasi-normal frequencies [QNFs] of one-horizon, two-horizon, and even three-horizon spacetimes can be obtained through either semi-analytic or monodromy techniques. While many technical details differ, both between the semi-analytic and monodromy approaches, and quite often among various authors seeking to apply the monodromy technique, there is nevertheless widespread agreement regarding the the general form of the QNF master equations. Within this class of generic master equations we can establish some rather general results, relating the existence of "families" of QNFs of the form omega_{a,n} = (offset)_a + i n (gap) to the question of whether or not certain ratios of parameters are rational or irrational.Comment: 23 pages; V2: Minor additions, typos fixed. Matches published versio

Total coloring of 1-toroidal graphs of maximum degree at least 11 and no adjacent triangles

A {\em total coloring} of a graph $G$ is an assignment of colors to the vertices and the edges of $G$ such that every pair of adjacent/incident elements receive distinct colors. The {\em total chromatic number} of a graph $G$, denoted by \chiup''(G), is the minimum number of colors in a total coloring of $G$. The well-known Total Coloring Conjecture (TCC) says that every graph with maximum degree $\Delta$ admits a total coloring with at most $\Delta + 2$ colors. A graph is {\em $1$-toroidal} if it can be drawn in torus such that every edge crosses at most one other edge. In this paper, we investigate the total coloring of $1$-toroidal graphs, and prove that the TCC holds for the $1$-toroidal graphs with maximum degree at least~$11$ and some restrictions on the triangles. Consequently, if $G$ is a $1$-toroidal graph with maximum degree $\Delta$ at least~$11$ and without adjacent triangles, then $G$ admits a total coloring with at most $\Delta + 2$ colors.Comment: 10 page

Automated annotation and visualisation of high-resolution spatial proteomic mass spectrometry imaging data using HIT-MAP.

Spatial proteomics has the potential to significantly advance our understanding of biology, physiology and medicine. Matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) is a powerful tool in the spatial proteomics field, enabling direct detection and registration of protein abundance and distribution across tissues. MALDI-MSI preserves spatial distribution and histology allowing unbiased analysis of complex, heterogeneous tissues. However, MALDI-MSI faces the challenge of simultaneous peptide quantification and identification. To overcome this, we develop and validate HIT-MAP (High-resolution Informatics Toolbox in MALDI-MSI Proteomics), an open-source bioinformatics workflow using peptide mass fingerprint analysis and a dual scoring system to computationally assign peptide and protein annotations to high mass resolution MSI datasets and generate customisable spatial distribution maps. HIT-MAP will be a valuable resource for the spatial proteomics community for analysing newly generated and retrospective datasets, enabling robust peptide and protein annotation and visualisation in a wide array of normal and disease contexts