Extended Kramers-Moyal analysis applied to optical trapping

The Kramers-Moyal analysis is a well established approach to analyze stochastic time series from complex systems. If the sampling interval of a measured time series is too low, systematic errors occur in the analysis results. These errors are labeled as finite time effects in the literature. In the present article, we present some new insights about these effects and discuss the limitations of a previously published method to estimate Kramers-Moyal coefficients at the presence of finite time effects. To increase the reliability of this method and to avoid misinterpretations, we extend it by the computation of error estimates for estimated parameters using a Monte Carlo error propagation technique. Finally, the extended method is applied to a data set of an optical trapping experiment yielding estimations of the forces acting on a Brownian particle trapped by optical tweezers. We find an increased Markov-Einstein time scale of the order of the relaxation time of the process which can be traced back to memory effects caused by the interaction of the particle and the fluid. Above the Markov-Einstein time scale, the process can be very well described by the classical overdamped Markov model for Brownian motion.Comment: 14 pages, 18 figure

The {\eta}'-carbon potential at low meson momenta

The production of $\eta^\prime$ mesons in coincidence with forward-going protons has been studied in photon-induced reactions on $^{12}$C and on a liquid hydrogen (LH$_2$) target for incoming photon energies of 1.3-2.6 GeV at the electron accelerator ELSA. The $\eta^\prime$ mesons have been identified via the $\eta^\prime\rightarrow \pi^0 \pi^0\eta \rightarrow 6 \gamma$ decay registered with the CBELSA/TAPS detector system. Coincident protons have been identified in the MiniTAPS BaF$_2$ array at polar angles of $2^{\circ} \le \theta _{p} \le 11^{\circ}$. Under these kinematic constraints the $\eta^\prime$ mesons are produced with relatively low kinetic energy ($\approx$ 150 MeV) since the coincident protons take over most of the momentum of the incident-photon beam. For the C-target this allows the determination of the real part of the $\eta^\prime$-carbon potential at low meson momenta by comparing with collision model calculations of the $\eta^\prime$ kinetic energy distribution and excitation function. Fitting the latter data for $\eta^\prime$ mesons going backwards in the center-of-mass system yields a potential depth of V = $-$(44 $\pm$ 16(stat)$\pm$15(syst)) MeV, consistent with earlier determinations of the potential depth in inclusive measurements for average $\eta^\prime$ momenta of $\approx$ 1.1 GeV/$c$. Within the experimental uncertainties, there is no indication of a momentum dependence of the $\eta^\prime$-carbon potential. The LH$_2$ data, taken as a reference to check the data analysis and the model calculations, provide differential and integral cross sections in good agreement with previous results for $\eta^\prime$ photoproduction off the free proton.Comment: 9 pages, 13 figures. arXiv admin note: text overlap with arXiv:1608.0607

Photoproduction of eta mesons from the neutron: cross sections and double polarization observable E

Photoproduction of $\eta$ mesons from neutrons} \abstract{Results from measurements of the photoproduction of $\eta$ mesons from quasifree protons and neutrons are summarized. The experiments were performed with the CBELSA/TAPS detector at the electron accelerator ELSA in Bonn using the $\eta\to3\pi^{0}\to6\gamma$ decay. A liquid deuterium target was used for the measurement of total cross sections and angular distributions. The results confirm earlier measurements from Bonn and the MAMI facility in Mainz about the existence of a narrow structure in the excitation function of $\gamma n\rightarrow n\eta$. The current angular distributions show a forward-backward asymmetry, which was previously not seen, but was predicted by model calculations including an additional narrow $P_{11}$ state. Furthermore, data obtained with a longitudinally polarized, deuterated butanol target and a circularly polarized photon beam were analyzed to determine the double polarization observable $E$. Both data sets together were also used to extract the helicity dependent cross sections $\sigma_{1/2}$ and $\sigma_{3/2}$. The narrow structure in the excitation function of $\gamma n\rightarrow n\eta$ appears associated with the helicity-1/2 component of the reaction

Live Tissue Imaging Shows Reef Corals Elevate pH under Their Calcifying Tissue Relative to Seawater

The threat posed to coral reefs by changes in seawater pH and carbonate chemistry (ocean acidification) raises the need for a better mechanistic understanding of physiological processes linked to coral calcification. Current models of coral calcification argue that corals elevate extracellular pH under their calcifying tissue relative to seawater to promote skeleton formation, but pH measurements taken from the calcifying tissue of living, intact corals have not been achieved to date. We performed live tissue imaging of the reef coral Stylophora pistillata to determine extracellular pH under the calcifying tissue and intracellular pH in calicoblastic cells. We worked with actively calcifying corals under flowing seawater and show that extracellular pH (pHe) under the calicoblastic epithelium is elevated by ∼0.5 and ∼0.2 pH units relative to the surrounding seawater in light and dark conditions respectively. By contrast, the intracellular pH (pHi) of the calicoblastic epithelium remains stable in the light and dark. Estimates of aragonite saturation states derived from our data indicate the elevation in subcalicoblastic pHe favour calcification and may thus be a critical step in the calcification process. However, the observed close association of the calicoblastic epithelium with the underlying crystals suggests that the calicoblastic cells influence the growth of the coral skeleton by other processes in addition to pHe modification. The procedure used in the current study provides a novel, tangible approach for future investigations into these processes and the impact of environmental change on the cellular mechanisms underpinning coral calcification

Analysis of genetic systems using experimental evolution and whole-genome sequencing

The application of whole-genome sequencing to the study of microbial evolution promises to reveal the complex functional networks of mutations that underlie adaptation. A recent study of parallel evolution in populations of Escherichia coli shows how adaptation involves both functional changes to specific proteins as well as global changes in regulation

Impacts of chemical gradients on microbial community structure

Succession of redox processes is sometimes assumed to define a basic microbial community structure for ecosystems with oxygen gradients. In this paradigm, aerobic respiration, denitrification, fermentation and sulfate reduction proceed in a thermodynamically determined order, known as the ‘redox tower’. Here, we investigated whether redox sorting of microbial processes explains microbial community structure at low-oxygen concentrations. We subjected a diverse microbial community sampled from a coastal marine sediment to 100 days of tidal cycling in a laboratory chemostat. Oxygen gradients (both in space and time) led to the assembly of a microbial community dominated by populations that each performed aerobic and anaerobic metabolism in parallel. This was shown by metagenomics, transcriptomics, proteomics and stable isotope incubations. Effective oxygen consumption combined with the formation of microaggregates sustained the activity of oxygen-sensitive anaerobic enzymes, leading to braiding of unsorted redox processes, within and between populations. Analyses of available metagenomic data sets indicated that the same ecological strategies might also be successful in some natural ecosystems

Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.Peer reviewe

Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness

Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. Weevaluated whether PSVs inBRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 30 region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25-2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63-5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71-4.68; P = 0.00004) and elevated risk of Gleason 8+prostate cancer (HR = 4.95; 95% CI, 2.12-11.54; P = 0.0002). No genotype-phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.Peer reviewe

Copy number variants as modifiers of breast cancer risk for BRCA1/BRCA2 pathogenic variant carriers

The risk of germline copy number variants (CNVs) in BRCA1 and BRCA2 pathogenic variant carriers in breast cancer is assessed, with CNVs overlapping SULT1A1 decreasing breast cancer risk in BRCA1 carriers.The contribution of germline copy number variants (CNVs) to risk of developing cancer in individuals with pathogenic BRCA1 or BRCA2 variants remains relatively unknown. We conducted the largest genome-wide analysis of CNVs in 15,342 BRCA1 and 10,740 BRCA2 pathogenic variant carriers. We used these results to prioritise a candidate breast cancer risk-modifier gene for laboratory analysis and biological validation. Notably, the HR for deletions in BRCA1 suggested an elevated breast cancer risk estimate (hazard ratio (HR) = 1.21), 95% confidence interval (95% CI = 1.09-1.35) compared with non-CNV pathogenic variants. In contrast, deletions overlapping SULT1A1 suggested a decreased breast cancer risk (HR = 0.73, 95% CI 0.59-0.91) in BRCA1 pathogenic variant carriers. Functional analyses of SULT1A1 showed that reduced mRNA expression in pathogenic BRCA1 variant cells was associated with reduced cellular proliferation and reduced DNA damage after treatment with DNA damaging agents. These data provide evidence that deleterious variants in BRCA1 plus SULT1A1 deletions contribute to variable breast cancer risk in BRCA1 carriers.Peer reviewe

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions. Classifications were compared with information not yet included in the likelihood model, and evidence strengths aligned to those recommended for ACMG/AMP classification codes. Altered mRNA splicing or function relative to known nonpathogenic variant controls were moderately to strongly predictive of variant pathogenicity. Variant absence in population datasets provided supporting evidence for variant pathogenicity. These findings have direct relevance for BRCA1 and BRCA2 variant evaluation, and justify the need for gene-specific calibration of evidence types used for variant classification