SACOBRA with Online Whitening for Solving Optimization Problems with High Conditioning

Real-world optimization problems often have expensive objective functions in terms of cost and time. It is desirable to find near-optimal solutions with very few function evaluations. Surrogate-assisted optimizers tend to reduce the required number of function evaluations by replacing the real function with an efficient mathematical model built on few evaluated points. Problems with a high condition number are a challenge for many surrogate-assisted optimizers including SACOBRA. To address such problems we propose a new online whitening operating in the black-box optimization paradigm. We show on a set of high-conditioning functions that online whitening tackles SACOBRA's early stagnation issue and reduces the optimization error by a factor between 10 to 1e12 as compared to the plain SACOBRA, though it imposes many extra function evaluations. Covariance matrix adaptation evolution strategy (CMA-ES) has for very high numbers of function evaluations even lower errors, whereas SACOBRA performs better in the expensive setting (less than 1e03 function evaluations). If we count all parallelizable function evaluations (population evaluation in CMA-ES, online whitening in our approach) as one iteration, then both algorithms have comparable strength even on the long run. This holds for problems with dimension D Algorithms and the Foundations of Software technolog

Relativistic Quark Spin Coupling Effects in the Nucleon Electromagnetic Form Factors

We investigate the effect of different forms of relativistic spin coupling of constituent quarks in the nucleon electromagnetic form factors. The four-dimensional integrations in the two-loop Feynman diagram are reduced to the null-plane, such that the light-front wave function is introduced in the computation of the form factors. The neutron charge form factor is very sensitive to different choices of spin coupling schemes, once its magnetic moment is fitted to the experimental value. The scalar coupling between two quarks is preferred by the neutron data, when a reasonable fit of the proton magnetic momentum is found.Comment: 13 pages, needs axodraw.ps and axodraw.sty for diagrams of Fig.

Circulating endothelial cells as biomarker for cardiovascular diseases.

Background: Endothelial dysfunction is involved in several cardiovascular diseases. Elevated levels of circulating endothelial cells (CECs) and low levels of endothelial progenitor cells (EPCs) have been described in different cardiovascular conditions, suggesting their potential use as diagnostic biomarkers for endothelial dysfunction. Compared to typical peripheral blood leukocyte subsets, CECs and EPCs occur at very low frequency. The reliable identification and characterization of CECs and EPCs is a prerequisite for their clinical use, however, a validated method to this purpose is still missing but a key for rare cell events. Objectives: To establish a validated flow cytometric procedure in order to quantify CECs and EPCs in human whole blood. Methods: In the establishment phase, the assay sensitivity, robustness, and the sample storage conditions were optimized as prerequisite for clinical use. In a second phase, CECs and EPCs were analyzed in heart failure with preserved (HFpEF) and reduced (HFrEF) ejection fraction, in arterial hypertension (aHT), and in diabetic nephropathy (DN) in comparison to age-matched healthy controls. Results: The quantification procedure for CECs and EPCs showed high sensitivity and reproducibility. CEC values resulted significantly increased in patients with DN and HFpEF in comparison to healthy controls. CEC quantification showed a diagnostic sensitivity of 90% and a sensitivity of 68.0%, 70.4%, and 66.7% for DN, HFpEF, and aHT, respectively. Conclusion: A robust and precise assay to quantify CECs and EPCs in pre-clinical and clinical studies has been established. CEC counts resulted to be a good diagnostic biomarker for DN and HFpEF

Relativistic Quark Spin Coupling Effects in the Correlations Between Nucleon Electroweak Properties

We investigate the effect of different relativistic spin couplings of constituent quarks on nucleon electroweak properties. Within each quark spin coupling scheme the correlations between static electroweak observables are found to be independent of the particular shape of the momentum part of the nucleon light-front wave function. The neutron charge form factor is very sensitive to different choices of spin coupling schemes once the magnetic moment is fitted to the experimental value. However, it is found rather insensitive to the details of the momentum part of the three-quark wave function model.Comment: 23 pages, 13 figures, requires axodraw.sty 1 figure corrected, 1 refs. added, some changes in tex

Hadronic properties of the S_{11}(1535) studied by electroproduction off the deuteron

Properties of excited baryonic states are investigated in the context of electroproduction of baryon resonances off the deuteron. In particular, the hadronic radii and the compositeness of baryon resonances are studied for kinematic situations in which their hadronic reinteraction is the dominant contribution. Specifically, we study the reaction $d(e,e'S_{11})N$ at $Q^2\ge 1 GeV^2$ for kinematics in which the produced hadronic state reinteracts predominantly with the spectator nucleon. A comparison of constituent quark model and effective chiral Lagrangian calculations of the $S_{11}$ shows substantial sensitivity to the structure of the produced resonance.Comment: 24 pages, 5 figure

Pair term in the Electromagnetic Current within the Front-Form Dynamics: Spin-0 Case

The frame and scale dependence of the pair-term contribution to the electromagnetic form factor of a spin-zero composite system of two-fermions is studied within the Light Front. The form factor is evaluated from the plus-component of the current in the Breit frame, using for the first time a nonconstant, symmetric ansatz for the Bethe-Salpeter amplitude. The frame dependence is analyzed by allowing a nonvanishing plus component of the momentum transfer, while the dynamical scale is set by the masses of the constituents and by mass and size of the composite system. A transverse momentum distribution, associated with the Bethe-Salpeter amplitude, is introduced which allows to define strongly and weakly relativistic systems. In particular, for strongly relativistic systems, the pair term vanishes for the Drell-Yan condition, while is dominant for momentum transfer along the light-front direction. For a weakly relativistic system, fitted to the deuteron scale, the pair term is negligible up to momentum transfers of 1(GeV/c)$^2$. A comparison with results obtained within the Front-Form Hamiltonian dynamics with a fixed number of constituents is also presented.Comment: 25 pages + 7 figures; axodraw.sty included. To appear in Nucl. Phys.

Q2Q^2 Independence of QF2/F1QF_2/F_1, Poincare Invariance and the Non-Conservation of Helicity

A relativistic constituent quark model is found to reproduce the recent data regarding the ratio of proton form factors, $F_2(Q^2)/F_1(Q^2)$. We show that imposing Poincare invariance leads to substantial violation of the helicity conservation rule, as well as an analytic result that the ratio $F_2(Q^2)/F_1(Q^2)\sim 1/Q$ for intermediate values of $Q^2$.Comment: 13 pages, 7 figures, to be submitted to Phys. Rev. C typos corrected, references added, 1 new figure to show very high Q^2 behavio

New Concepts of the Chemistry of Electric-Discharge Oxygen-Iodine Lasers

ABSTRACT The chemistry of electric discharge driven oxygen iodine lasers (EOIL) has long been believed to have O 2 (a 1 Δ g ) as the sole energy carrier for excitation of the lasing state I( 2 P 1/2 ), and O( 3 P) as the primary quencher of this state. In many sets of experimental measurements over a wide range of conditions, we have observed persistent evidence to the contrary. In this paper, we review our experimental data base in both room-temperature discharge-flow measurements and EOIL reactor results, in comparison to model predictions and kinetics analysis, to identify the missing production and loss terms in the EOIL reaction mechanism. The analysis points to a significantly higher level of understanding of this energetic chemical system, which can support advanced concepts in power scaling investigations

Quantification of AMPA receptor subunits and RNA editing-related proteins in the J20 mouse model of Alzheimer’s disease by capillary western blotting

IntroductionAccurate modelling of molecular changes in Alzheimer’s disease (AD) dementia is crucial for understanding the mechanisms driving neuronal pathology and for developing treatments. Synaptic dysfunction has long been implicated as a mechanism underpinning memory dysfunction in AD and may result in part from changes in adenosine deaminase acting on RNA (ADAR) mediated RNA editing of the GluA2 subunit of AMPA receptors and changes in AMPA receptor function at the post synaptic cleft. However, few studies have investigated changes in proteins which influence RNA editing and notably, AD studies that focus on studying changes in protein expression, rather than changes in mRNA, often use traditional western blotting.MethodsHere, we demonstrate the value of automated capillary western blotting to investigate the protein expression of AMPA receptor subunits (GluA1-4), the ADAR RNA editing proteins (ADAR1-3), and proteins known to regulate RNA editing (PIN1, WWP2, FXR1P, and CREB1), in the J20 AD mouse model. We describe extensive optimisation and validation of the automated capillary western blotting method, demonstrating the use of total protein to normalise protein load, in addition to characterising the optimal protein/antibody concentrations to ensure accurate protein quantification. Following this, we assessed changes in proteins of interest in the hippocampus of 44-week-old J20 AD mice.ResultsWe observed an increase in the expression of ADAR1 p110 and GluA3 and a decrease in ADAR2 in the hippocampus of 44-week-old J20 mice. These changes signify a shift in the balance of proteins that play a critical role at the synapse. Regression analysis revealed unique J20-specific correlations between changes in AMPA receptor subunits, ADAR enzymes, and proteins that regulate ADAR stability in J20 mice, highlighting potential mechanisms mediating RNA-editing changes found in AD.DiscussionOur findings in J20 mice generally reflect changes seen in the human AD brain. This study underlines the importance of novel techniques, like automated capillary western blotting, to assess protein expression in AD. It also provides further evidence to support the hypothesis that a dysregulation in RNA editing-related proteins may play a role in the initiation and/or progression of AD

Brain activity during a visuospatial working memory task predicts arithmetical performance 2 years later

Visuospatial working memory (WM) capacity is highly correlated with mathematical reasoning abilities and can predict future development of arithmetical performance. Activity in the intraparietal sulcus (IPS) during visuospatial WM tasks correlates with interindividual differences in WM capacity. This region has also been implicated in numerical representation, and its structure and activity reflect arithmetical performance impairments (e.g., dyscalculia). We collected behavioral (N = 246) and neuroimaging data (N = 46) in a longitudinal sample to test whether IPS activity during a visuospatial WM task could provide more information than psychological testing alone and predict arithmetical performance 2 years later in healthy participants aged 6–16 years. Nonverbal reasoning and verbal and visuospatial WM measures were found to be independent predictors of arithmetical outcome. In addition, WM activation in the left IPS predicted arithmetical outcome independently of behavioral measures. A logistic model including both behavioral and imaging data showed improved sensitivity by correctly classifying more than twice as many children as poor arithmetical performers after 2 years than a model with behavioral measures only. These results demonstrate that neuroimaging data can provide useful information in addition to behavioral assessments and be used to improve the identification of individuals at risk of future low academic performance