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Evaluation of peak-picking algorithms for protein mass spectrometry
Peak picking is an early key step in MS data analysis. We compare three commonly used approaches to peak picking and discuss their merits by means of statistical analysis. Methods investigated encompass signal-to-noise ratio, continuous wavelet transform, and a correlation-based approach using a Gaussian template.
Functionality of the three methods is illustrated and discussed in a practical context using a mass spectral data set created with MALDI-TOF technology. Sensitivity and specificity are investigated using a manually defined reference set of peaks. As an additional criterion, the robustness of the three methods is assessed by a perturbation analysis and illustrated using ROC curves
Cytosolic targeting factor AKR2A captures chloroplast outer membrane-localized client proteins at the ribosome during translation
In eukaryotic cells, organellar proteome biogenesis is pivotal for cellular function. Chloroplasts contain a complex proteome, the biogenesis of which includes post-translational import of nuclear-encoded proteins. However, the mechanisms determining when and how nascent chloroplast-targeted proteins are sorted in the cytosol are unknown. Here, we establish the timing and mode of interaction between ankyrin repeat-containing protein 2 (AKR2A), the cytosolic targeting factor of chloroplast outer membrane (COM) proteins, and its interacting partners during translation at the single-molecule level. The targeting signal of a nascent AKR2A client protein residing in the ribosomal exit tunnel induces AKR2A binding to ribosomal RPL23A. Subsequently, RPL23A-bound AKR2A binds to the targeting signal when it becomes exposed from ribosomes. Failure of AKR2A binding to RPL23A in planta severely disrupts protein targeting to the COM; thus, AKR2A-mediated targeting of COM proteins is coupled to their translation, which in turn is crucial for biogenesis of the entire chloroplast proteome.open1178Ysciescopu
Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review
Background: Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual
participant data. For continuous outcomes, especially those with naturally skewed distributions, summary
information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal,
we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis.
Methods: We undertook two systematic literature reviews to identify methodological approaches used to deal with
missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane
Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited
reference searching and emailed topic experts to identify recent methodological developments. Details recorded
included the description of the method, the information required to implement the method, any underlying
assumptions and whether the method could be readily applied in standard statistical software. We provided a
summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios.
Results: For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in
addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis
level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical
approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following
screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and
three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when
replacing a missing SD the approximation using the range minimised loss of precision and generally performed better
than omitting trials. When estimating missing means, a formula using the median, lower quartile and upper quartile
performed best in preserving the precision of the meta-analysis findings, although in some scenarios, omitting trials
gave superior results.
Conclusions: Methods based on summary statistics (minimum, maximum, lower quartile, upper quartile, median)
reported in the literature facilitate more comprehensive inclusion of randomised controlled trials with missing mean or
variability summary statistics within meta-analyses
Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1
Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context
ILK Induces Cardiomyogenesis in the Human Heart
Integrin-linked kinase (ILK) is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal heart.Primary cultures of human fetal myocardial cells (19-22 weeks gestation) yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk × 2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C × 43) and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT) and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p<0.001). The number of cardioblast colonies was significantly decreased (p<0.05) when ILK expression was knocked down with ILK targeted siRNA. Interestingly, overexpression of the activation resistant ILK mutant (ILK(R211A)) resulted in much greater increase in the number of new cell aggregates as compared to overexpression of wild-type ILK (ILK(WT)). The cardiomyogenic effects of ILK(R211A) and ILK(WT) were accompanied by concurrent activation of β-catenin (p<0.001) and increase expression of progenitor cell marker islet-1, which was also observed in lysates of transgenic mice with cardiac-specific over-expression of ILK(R211A) and ILK(WT). Finally, endogenous ILK expression was shown to increase in concert with those of cardiomyogenic markers during directed cardiomyogenic differentiation in human embryonic stem cells (hESCs).In the human fetal heart ILK activation is instructive to the specification of mesodermal precursor cells towards a cardiomyogenic lineage. Induction of cardiomyogenesis by ILK overexpression bypasses the requirement of proximal PI3K activation for transduction of growth factor- and β1-integrin-mediated differentiation signals. Altogether, our data indicate that ILK represents a novel regulatory checkpoint during human cardiomyogenesis
Target Detection Performance Bounds in Compressive Imaging
This paper describes computationally efficient approaches and associated
theoretical performance guarantees for the detection of known targets and
anomalies from few projection measurements of the underlying signals. The
proposed approaches accommodate signals of different strengths contaminated by
a colored Gaussian background, and perform detection without reconstructing the
underlying signals from the observations. The theoretical performance bounds of
the target detector highlight fundamental tradeoffs among the number of
measurements collected, amount of background signal present, signal-to-noise
ratio, and similarity among potential targets coming from a known dictionary.
The anomaly detector is designed to control the number of false discoveries.
The proposed approach does not depend on a known sparse representation of
targets; rather, the theoretical performance bounds exploit the structure of a
known dictionary of targets and the distance preservation property of the
measurement matrix. Simulation experiments illustrate the practicality and
effectiveness of the proposed approaches.Comment: Submitted to the EURASIP Journal on Advances in Signal Processin
Music-aided affective interaction between human and service robot
This study proposes a music-aided framework for affective interaction of service robots with humans. The framework consists of three systems, respectively, for perception, memory, and expression on the basis of the human brain mechanism. We propose a novel approach to identify human emotions in the perception system. The conventional approaches use speech and facial expressions as representative bimodal indicators for emotion recognition. But, our approach uses the mood of music as a supplementary indicator to more correctly determine emotions along with speech and facial expressions. For multimodal emotion recognition, we propose an effective decision criterion using records of bimodal recognition results relevant to the musical mood. The memory and expression systems also utilize musical data to provide natural and affective reactions to human emotions. For evaluation of our approach, we simulated the proposed human-robot interaction with a service robot, iRobiQ. Our perception system exhibited superior performance over the conventional approach, and most human participants noted favorable reactions toward the music-aided affective interaction.open0
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
Particle-yield modification in jet-like azimuthal di-hadron correlations in Pb-Pb collisions at = 2.76 TeV
The yield of charged particles associated with high- trigger
particles ( GeV/) is measured with the ALICE detector in
Pb-Pb collisions at = 2.76 TeV relative to proton-proton
collisions at the same energy. The conditional per-trigger yields are extracted
from the narrow jet-like correlation peaks in azimuthal di-hadron correlations.
In the 5% most central collisions, we observe that the yield of associated
charged particles with transverse momenta GeV/ on the
away-side drops to about 60% of that observed in pp collisions, while on the
near-side a moderate enhancement of 20-30% is found.Comment: 15 pages, 2 captioned figures, 1 table, authors from page 10,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/350
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