Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics

Background: Lipids have critical functions in cellular energy storage, structure and signaling. Many individual lipid molecules have been associated with the evolution of prostate cancer; however, none of them has been approved to be used as a biomarker. The aim of this study is to identify lipid molecules from hundreds plasma apparent lipid species as biomarkers for diagnosis of prostate cancer. Methodology/Principal Findings: Using lipidomics, lipid profiling of 390 individual apparent lipid species was performed on 141 plasma samples from 105 patients with prostate cancer and 36 male controls. High throughput data generated from lipidomics were analyzed using bioinformatic and statistical methods. From 390 apparent lipid species, 35 species were demonstrated to have potential in differentiation of prostate cancer. Within the 35 species, 12 were identified as individual plasma lipid biomarkers for diagnosis of prostate cancer with a sensitivity above 80%, specificity above 50% and accuracy above 80%. Using top 15 of 35 potential biomarkers together increased predictive power dramatically in diagnosis of prostate cancer with a sensitivity of 93.6%, specificity of 90.1% and accuracy of 97.3%. Principal component analysis (PCA) and hierarchical clustering analysis (HCA) demonstrated that patient and control populations were visually separated by identified lipid biomarkers. RandomForest and 10-fold cross validation analyses demonstrated that the identified lipid biomarkers were able to predict unknown populations accurately, and this was not influenced by patient's age and race. Three out of 13 lipid classes, phosphatidylethanolamine (PE), ether-linked phosphatidylethanolamine (ePE) and ether-linked phosphatidylcholine (ePC) could be considered as biomarkers in diagnosis of prostate cancer. Conclusions/Significance: Using lipidomics and bioinformatic and statistical methods, we have identified a few out of hundreds plasma apparent lipid molecular species as biomarkers for diagnosis of prostate cancer with a high sensitivity, specificity and accuracy

Social interaction, noise and antibiotic-mediated switches in the intestinal microbiota

The intestinal microbiota plays important roles in digestion and resistance against entero-pathogens. As with other ecosystems, its species composition is resilient against small disturbances but strong perturbations such as antibiotics can affect the consortium dramatically. Antibiotic cessation does not necessarily restore pre-treatment conditions and disturbed microbiota are often susceptible to pathogen invasion. Here we propose a mathematical model to explain how antibiotic-mediated switches in the microbiota composition can result from simple social interactions between antibiotic-tolerant and antibiotic-sensitive bacterial groups. We build a two-species (e.g. two functional-groups) model and identify regions of domination by antibiotic-sensitive or antibiotic-tolerant bacteria, as well as a region of multistability where domination by either group is possible. Using a new framework that we derived from statistical physics, we calculate the duration of each microbiota composition state. This is shown to depend on the balance between random fluctuations in the bacterial densities and the strength of microbial interactions. The singular value decomposition of recent metagenomic data confirms our assumption of grouping microbes as antibiotic-tolerant or antibiotic-sensitive in response to a single antibiotic. Our methodology can be extended to multiple bacterial groups and thus it provides an ecological formalism to help interpret the present surge in microbiome data.Comment: 20 pages, 5 figures accepted for publication in Plos Comp Bio. Supplementary video and information availabl

Real-time train driver rescheduling by actor-agent techniques

Passenger railway operations are based on an extensive planning process for generating the timetable, the rolling stock circulation, and the crew duties for train drivers and conductors. In particular, crew scheduling is a complex process. After the planning process has been completed, the plans are carried out in the real-time operations. Preferably, the plans are carried out as scheduled. However, in case of delays of trains or large disruptions of the railway system, the timetable, the rolling stock circulation and the crew duties may not be feasible anymore and must be rescheduled. This paper presents a method based on multi-agent techniques to solve the train driver rescheduling problem in case of a large disruption. It assumes that the timetable and the rolling stock have been rescheduled already based on an incident scenario. In the crew rescheduling model, each train driver is represented by a driver-agent. A driver-agent whose duty has become infeasible by the disruption starts a recursive task exchange process with the other driver-agents in order to solve this infeasibility. The task exchange process is supported by a route-analyzer-agent, which determines whether a proposed task exchange is feasible, conditionally feasible, or not feasible. The task exchange process is guided by several cost parameters, and the aim is to find a feasible set of duties at minimal total cost. The train driver rescheduling method was tested on several realistic disruption instances of Netherlands Railways (NS), the main operator of passenger trains in the Netherlands. In general the rescheduling method finds an appropriate set of rescheduled duties in a short amount of time. This research was carried out in close cooperation by NS and the D-CIS Lab

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

Spectropolarimetry and photometry of the early afterglow of the gamma-ray burst GRB191221B

We report on results of spectropolarimetry of the afterglow of the long gamma-ray burst GRB 191221B, obtained with SALT/RSS and VLT/FORS2, as well as photometry from two telescopes in the MASTER Global Robotic Network, at the MASTER-SAAO (South Africa) and MASTER-OAFA (Argentina) stations. Prompt optical emission was detected by MASTER-SAAO 38 s after the alert, which dimmed from a magnitude (white-light) of ~10 to 16.2 mag over a period of ~10 ks, followed by a plateau phase lasting ~10 ks and then a decline to ~18 mag after 80 ks. The light curve shows complex structure, with four or five distinct breaks in the power-law decline rate. SALT/RSS linear spectropolarimetry of the afterglow began ~2.9 h after the burst, during the early part of the plateau phase of the light curve. Absorption lines seen at ~6010 \r{A} and 5490 \r{A} are identified with the Mg II 2799 \r{A} line from the host galaxy at z=1.15 and an intervening system located at z=0.96. The mean linear polarisation measured over 3400-8000 \r{A} was ~1.5% and the mean equatorial position angle theta ~65 degrees. VLT/FORS2 spectropolarimetry was obtained ~10 h post-burst, during a period of slow decline (alpha = -0.44), and the polarisation was measured to be p = 1.2% and theta = 60 degrees. Two observations with the MeerKAT radio telescope, taken 30 and 444 days after the GRB trigger, detected radio emission from the host galaxy only. We interpret the light curve and polarisation of this long GRB in terms of a slow-cooling forward-shock

Quantum Dots for Multiplexed Detection and Characterisation of Prostate Cancer Cells Using a Scanning Near-Field Optical Microscope

In this study scanning near-field optical microscopy (SNOM) has been utilised in conjunction with quantum dot labelling to interrogate the biomolecular composition of cell membranes. The technique overcomes the limits of optical diffraction found in standard fluorescence microscopy and also yields vital topographic information. The technique has been applied to investigate cell-cell adhesion in human epithelial cells. This has been realised through immunofluorescence labelling of the cell-cell adhesion protein E-cadherin. Moreover, a dual labelling protocol has been optimised to facilitate a comparative study of the adhesion mechanisms and the effect of aberrant adhesion protein expression in both healthy and cancerous epithelial cells. This study reports clear differences in the morphology and phenotype of healthy and cancerous cells. In healthy prostate epithelial cells (PNT2), E-cadherin was predominantly located around the cell periphery and within filopodial extensions. The presence of E-cadherin appeared to be enhanced when cell-cell contact was established. In contrast, examination of metastatic prostate adenocarcinoma cells (PC-3) revealed no E-cadherin labelling around the periphery of the cells. This lack of functional E-cadherin in PC-3 cells coincided with a markedly different morphology and PC-3 cells were not found to form close cell-cell associations with their neighbours. We have demonstrated that with a fully optimised sample preparation methodology, multiplexed quantum dot labelling in conjunction with SNOM imaging can be successfully applied to interrogate biomolecular localisation within delicate cellular membranes

The unpolarized macronova associated with the gravitational wave event GW 170817

The merger of two dense stellar remnants including at least one neutron star (NS) is predicted to produce gravitational waves (GWs) and short duration gamma ray bursts (GRBs). In the process, neutron-rich material is ejected from the system and heavy elements are synthesized by r-process nucleosynthesis. The radioactive decay of these heavy elements produces additional transient radiation termed "kilonova" or "macronova". We report the detection of linear optical polarization P = (0.50 +/- 0.07)% at 1.46 days after detection of the GWs from GW170817, a double neutron star merger associated with an optical macronova counterpart and a short GRB. The optical emission from a macronova is expected to be characterized by a blue, rapidly decaying, component and a red, more slowly evolving, component due to material rich of heavy elements, the lanthanides. The polarization measurement was made when the macronova was still in its blue phase, during which there is an important contribution from a lanthanide-free outflow. The low degree of polarization is consistent with intrinsically unpolarized emission scattered by Galactic dust, suggesting a symmetric geometry of the emitting region and low inclination of the merger system. Stringent upper limits to the polarization degree from 2.45 - 9.48 days post-burst are consistent with the lanthanides-rich macronova interpretation.Comment: 18 pages, 1 figure, 2 tables, Nature Astronomy, in pres

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

X-ray free electron laser heating of water and gold at high static pressure

The study of water at high pressure and temperature is essential for understanding planetary interiors but is hampered by the high reactivity of water at extreme conditions. Here, indirect X-ray laser heating of water in a diamond anvil cell is realized via a gold absorber, showing no evidence of reactivity