Analysis Center of Saint Petersburg University

This report briefly summarizes the activities of the Analysis Center of Saint Petersburg University during 2012. The current status, as well as our future plans, are described

Torque Teno Virus (TTV) distribution in healthy Russian population

<p>Abstract</p> <p>Background</p> <p>Torque teno virus (TTV) is a circular, single-stranded DNA virus that chronically infects healthy individuals of all ages worldwide. There is a lot of data on the prevalence and genetic heterogeneity of TTV in healthy populations and in patients with various diseases now available. However, little is known about TTV load among healthy human population. In this study we analyzed TTV load in the group of 512 Russian elite athletes, who are supposed to be, by some standards, the healthiest part of the human population.</p> <p>Results</p> <p>The prevalence rate of TTV among the Russian Olympic Reserve members was 94% (for test sensitivity about 1000 genome equivalents per 1 ml of blood). Quantities varied from 10³(which corresponded to detection limit) to 10¹⁰copies per 1 ml of blood, with median at 2.7 × 10⁶copies.</p> <p>Conclusion</p> <p>About 94% of healthy individuals in Russian population have more than 1000 TTV genome copies per 1 ml of blood. This result exceeds the previously published data, and can be explained by either more sensitive PCR test system or by higher TTV distribution in Russian population or both. TTV viral load neither depends on gender, nor age.</p

The limit diagram under hot sheet metal forming. A review of constitutive models of material, viscous failure criteria and standard tests

Methods of theoretical analysis and experimental verification of conditions of limit deformation are considered for a reasonable choice of the constitutive equations for mathematical modeling of processes of hot and warm treatment by pressure of sheet metal products with a deep drawing. Attention is focused on the forming limit curve of sheet metal on the plane of the principal strains (one of that corresponds to stretching, and the second can specify stretching or compression), the characteristic of the local state of the material corresponding to the critical growth of strain localization. Localization here is understood as a local thinning of the sheet and corresponds to diffuse form of localization. Other defects (shear bands, crack formation) develop from this limiting state or (formation of folds and wrinkles) are not local and require complete formulation of the problem. The forming limit curve (FLC) defines the conditions of realization of a technological process and can be theoretically predicted depending on the constitutive equations of plasticity, indicator of critical state and initial imperfections. The Marciniak–Kuczyński scheme is considered for getting FLC, where the sample has two zones of homogeneous strains and allows analytical reduction of the problem to the system of several ordinary differential equations solved numerically. The experimental methods assume testing by pressing a punch with a spherical or cylindrical tip into a specimen cut from a sheet. Depending on the depth of the lateral cutouts from the specimen, it can be provided tension or compression of the specimen in the transverse direction in these tests. Both approaches are analyzed as tools for selection and experimental verification of the constitutive model and the limit state indicator. They solve methodological problem of identification of mathematical models on a quite non-standard experiments involving strain localization. With the use of Marciniak–Kuczyński scheme the effect of a number of yield criteria for anisotropic sheet metal, hardening laws, damage accumulation models and criteria of viscous failure on qualitative and quantitative features of the FLC. To do this a proprietary algorithm has been developed. Experimental standard test methods of Hasek, Marciniak and Nakajima were implemented numerically in the software package LS-DYNA. The numerical FLD obtained were compared with theoretical and experimental ones. Possibilities of integration into Marciniak–Kuczyński scheme the dependence on temperature, strain rate and microstructure parameters for each basic rigid-plastic (scleronomous) model were discussed. It is noted this scheme is significantly limited by proportional changes of the main deformations in the sample outside and inside the strain localization zone. It is revealed this scheme is not adapted for determination of limit properties of the metals deformable in the conditions of deformation softening (aluminum, titanium alloys and some steels at temperatures of dynamic recrystallization). For a wider range of material deformation conditions, there is no alternative to the above-mentioned numerical method for predicting FLC. An open and relevant question is the description of the evolution of anisotropic plastic and fracture properties due to the anisotropic damage accumulation

Development of experimental approach for the phase equilibria study of arsenic-containing systems

The technique of arsenic-contained compounds synthesis has been developed. The experimental samples synthesis is proposed to be divided in\ua0two stages. The first stage includes the long-term heating of samples in specially developed high-pressure furnace with the excessive pressure to 50\ua0bar at 900\ua0°C. The second stage relates to conventional heating process at 1\ua0atm pressure and 1200\ua0°C. Results of differential thermal analysis, scanning electron microscopy and energy-dispersive x-ray spectroscopy has shown the consistency of obtained data to the preset phases and their compositions. The developed method can be used for studies of phase equilibria in multicomponent arsenic-contained systems or any complex systems with volatile compounds

Development of the covalent antibody-DNA conjugates technology for detection of IgE and IgM antibodies by immuno-PCR.

Immuno-PCR (iPCR) is one of the methods used for the detection of a wide range of analytes and features the high sensitivity of the polymerase chain reaction (PCR) method. iPCR uses antibodies coupled to DNA, followed by the amplification of the attached DNA using RT-PCR. Two major types of antibody-DNA conjugates are currently used, which are obtained as a result of non-covalent (biotin-streptavidin) or covalent interactions. Using a strain-promoted azide-alkyne cycloaddition (SPAAC), we synthesized covalent DNA-antibody conjugates, optimized the reaction conditions, and developed an efficient protocol for the purification of conjugates, with which all unreacted antibodies and oligonucleotides are separated. Covalent DNA-antibody conjugates were tested with iPCR assays that were previously developed for the detection of IgE and IgM antibodies with the use of the supramolecular complex of 5'- and 3'-biotinylated DNA and streptavidin. The results show that the modification of antibodies with amino groups did not allow us to obtain monolabeled antibodies or antibodies with a strictly defined number of DNA-labels. The degree of labeling determined by the dyes introduced through the azido group reflects the actual labeling degree statistically. If the average labeling degree for azido groups is 1.1, the conjugates contain 25% mono-labeled antibodies, 50% double-labeled antibodies, and 25% unlabeled ones. The specificity of the monoclonal antibody to human IgE (BE5) changed after conjugation with the oligonucleotide. The sensitivity of iPCR in the detection of IgM antibodies produced against the LeC disaccharide using a covalent conjugate was similar to that of a supramolecular complex of 5'- and 3'-biotinylated DNA and streptavidin, but the new procedure is two steps shorter

On the reconstruction of residual stresses and strains of a plate after shot peening

The subject of this research is a mathematical description of the shape and the stress-strain state of a steel plate subjected to unilateral shot peening, its experimental verification and application of the results for verification of methods for reconstruction of residual stress and strain fields according to experimental data. Such plate is used in manufacturing as a calibrating sample to determine of shot peening duration required for formation of proper compressive tangential stress in the surface layer of the processed product. The method of calibration is convenient and widely applied in different technologies of surface hardening. In that case the source of the residual stresses is plastic strains in surface layer produced by shot peening. For the statement of the problem a plastic strain tensor field is defined up to an arbitrary function. The shape and the stress-strain state of an elastic plate with the surface layer of plastic strains were calculated numerically. The qualitative behavior of numerical solution allowed us to accept the set of hypotheses to find an analytical solution of the spatial problem of elasticity theory and to weaken the boundary conditions. The exact solution has been found analytically. Within the framework of the plane stress state along the thickness and transverse directions, the result exactly corresponds to the Davidenkov–Birger formula connected the tangential residual stress distribution on depth with the function of deflections. An explicit formula for the dependence of the residual (plastic) deformation on the thickness coordinate is obtained. Sources of errors of the received expressions and methods of their correction are analyzed. An experiment has been carried out on the one-sided shot peening of calibration plate made of hardened 65G steel, for which the layer-by-layer etching of the treated surface and the measurement of the flexure of the plate were made (by Davidenkov method). The profiles of residual stresses and strains were reconstructed numerically with reasonable accuracy using the obtained experimental data. The result is applicable to a wide class of problems for elastic bodies with hardened surface layers. It may serve as a base for experimental research of such problems, help to formulate hypotheses and test them by experiment, help to study relation between physical fields in asymptotic case, help to verify applicability of different ways to account residual stresses in numerical solution. The solution found can be used for verification of stress and displacement fields in different cases of preliminarily stressed shell elements in engineering software for calculation of fatigue endurance of different machine parts with hardened surface layer. It also seems to be a reference for the study of surface-hardened bodies with curved free boundary, to which most of the practically important tasks are reduced

The State of Trace Elements (In, Cu, Ag) in Sphalerite Studied by X-Ray Absorption Spectroscopy of Synthetic Minerals

The oxidation state and local atomic environment of admixtures of In, Cu, and Ag in synthetic sphalerite crystals were determined by X-ray absorption spectroscopy (XAS). The sphalerite crystals doped with In, Cu, Ag, In&ndash;Cu, and In&ndash;Ag were synthesized utilizing gas transport, salt flux, and dry synthesis techniques. Oxidation states of dopants were determined using X-ray absorption near edge structure (XANES) technique. The local atomic structure was studied by X-ray absorption fine structure spectroscopy (EXAFS). The spectra were recorded at Zn, In, Ag, and Cu K-edges. In all studied samples, In was in the 3+ oxidation state and replaced Zn in the structure of sphalerite, which occurs with the expansion of the nearest coordination shells due to the large In ionic radius. In the presence of In, the oxidation state of Cu and Ag is 1+, and both metals can form an isomorphous solid solution where they substitute for Zn according to the coupled substitution scheme 2Zn2+ &harr; Me+ + In3+. Moreover, Ag K-edges EXAFS spectra fitting, combined with the results obtained for In- and Au-bearing sphalerite shows that the Me-S distances in the first coordination shell in the solid solution state are correlated with the ionic radii and increase in the order of Cu &lt; Ag &lt; Au. The distortion of the atomic structure increases in the same order. The distant (second and third) coordination shells of Cu and Ag in sphalerite are split into two subshells, and the splitting is more pronounced for Ag. Analysis of the EXAFS spectra, coupled with the results of DFT (Density Function Theory) simulations, showed that the In&ndash;In and Me+&ndash;In3+ clustering is absent when the metals are present in the sphalerite solid solution. Therefore, all studied admixtures (In, Cu, Ag), as well as Au, are randomly distributed in the matrix of sphalerite, where the concentration of the elements in the &ldquo;invisible&rdquo; form can reach a few tens wt.%

Shotgun Lipidomics for Differential Diagnosis of HPV-Associated Cervix Transformation

A dramatic increase in cervical diseases associated with human papillomaviruses (HPV) in women of reproductive age has been observed over the past decades. An accurate differential diagnosis of the severity of cervical intraepithelial neoplasia and the choice of the optimal treatment requires the search for effective biomarkers with high diagnostic and prognostic value. The objective of this study was to introduce a method for rapid shotgun lipidomics to differentiate stages of HPV-associated cervix epithelium transformation. Tissue samples from 110 HPV-positive women with cervicitis (n = 30), low-grade squamous intraepithelial lesions (LSIL) (n = 30), high-grade squamous intraepithelial lesions (HSIL) (n = 30), and cervical cancers (n = 20) were obtained. The cervical epithelial tissue lipidome at different stages of cervix neoplastic transformation was studied by a shotgun label-free approach. It is based on electrospray ionization mass spectrometry (ESI-MS) data of a tissue extract. Lipidomic data were processed by the orthogonal projections to latent structures discriminant analysis (OPLS-DA) to build statistical models, differentiating stages of cervix transformation. Significant differences in the lipid profile between the lesion and surrounding tissues were revealed in chronic cervicitis, LSIL, HSIL, and cervical cancer. The lipids specific for HPV-induced cervical transformation mainly belong to glycerophospholipids: phosphatidylcholines, and phosphatidylethanolamines. The developed diagnostic OPLS-DA models were based on 23 marker lipids. More than 90% of these marker lipids positively correlated with the degree of cervix transformation. The algorithm was developed for the management of patients with HPV-associated diseases of the cervix, based on the panel of 23 lipids as a result. ESI-MS analysis of a lipid extract by direct injection through a loop, takes about 25 min (including preparation of the lipid extract), which is significantly less than the time required for the HPV test (several hours for hybrid capture and about an hour for PCR). This makes lipid mass spectrometric analysis a promising method for express diagnostics of HPV-associated neoplastic diseases of the cervix

Accounting for variance in machine learning benchmarks

International audienceStrong empirical evidence that one machine-learning algorithm A outperforms another one B ideally calls for multiple trials optimizing the learning pipeline over sources of variation such as data sampling, augmentation, parameter initialization, and hyperparameters choices. This is prohibitively expensive, and corners are cut to reach conclusions. We model the whole benchmarking process, revealing that variance due to data sampling, parameter initialization and hyperparameter choice impact markedly the results. We analyze the predominant comparison methods used today in the light of this variance. We show a counter-intuitive result that adding more sources of variation to an imperfect estimator approaches better the ideal estimator at a 51× reduction in compute cost. Building on these results, we study the error rate of detecting improvements, on five different deep-learning tasks/architectures. This study leads us to propose recommendations for performance comparisons

CAMK2D De Novo Missense Variant in Patient with Syndromic Neurodevelopmental Disorder: A Case Report

Background: Intellectual disability with developmental delay is the most common developmental disorder. However, this diagnosis is rarely associated with congenital cardiomyopathy. In the current report, we present the case of a patient suffering from dilated cardiomyopathy and developmental delay. Methods: Neurological pathology in a newborn was diagnosed immediately after birth, and the acquisition of psychomotor skills lagged behind by 3–4 months during the first year of life. WES analysis of the proband did not reveal a causal variant, so the search was extended to trio. Results: Trio sequencing revealed a de novo missense variant in the CAMK2D gene (p.Arg275His), that is, according to the OMIM database and available literature, not currently associated with any specific inborn disease. The expression of Ca2+/calmodulin-dependent protein kinase II delta (CaMKIIδ) protein is known to be increased in the heart tissues from patients with dilated cardiomyopathy. The functional effect of the CaMKIIδ Arg275His mutant was recently reported; however, no specific mechanism of its pathogenicity was proposed. A structural analysis and comparison of available three-dimensional structures of CaMKIIδ confirmed the probable pathogenicity of the observed missense variant. Conclusions: We suggest that the CaMKIIδ Arg275His variant is highly likely the cause of dilated cardiomyopathy and neurodevelopmental disorders