First Measurement Using Elliptically Polarized Photons of the Double-Polarization Observable E for γp→pπ

We report the measurement of the helicity asymmetry E for the pπ^{0} and nπ^{+} final states using, for the first time, an elliptically polarized photon beam in combination with a longitudinally polarized target at the Crystal Ball experiment at MAMI. The results agree very well with data that were taken with a circularly polarized photon beam, showing that it is possible to simultaneously measure polarization observables that require linearly (e.g., G) and circularly polarized photons (e.g., E) and a longitudinally polarized target. The new data cover a photon energy range 270-1400 MeV for the pπ^{0} final state (230-842 MeV for the nπ^{+} final state) and the full range of pion polar angles, θ, providing the most precise measurement of the observable E. A moment analysis gives a clear observation of the pη cusp in the pπ^{0} final state.

Measurement of polarization observables T, P, and H in π0 and η photoproduction off quasi-free nucleons.

The target asymmetry T, recoil asymmetry P, and beam-target double polarization observable H were determined in exclusive π0 and η photoproduction off quasi-free protons and, for the first time, off quasi-free neutrons. The experiment was performed at the electron stretcher accelerator ELSA in Bonn, Germany, with the Crystal Barrel/TAPS detector setup, using a linearly polarized photon beam and a transversely polarized deuterated butanol target. Effects from the Fermi motion of the nucleons within deuterium were removed by a full kinematic reconstruction of the final state invariant mass. A comparison of the data obtained on the proton and on the neutron provides new insight into the isospin structure of the electromagnetic excitation of the nucleon. Earlier measurements of polarization observables in the γp→π0p and γp→ηp reactions are confirmed. The data obtained on the neutron are of particular relevance for clarifying the origin of the narrow structure in the ηn system at W=1.68GeV. A comparison with recent partial wave analyses favors the interpretation of this structure as arising from interference of the S11(1535) and S11(1650) resonances within the S11-partial wave.

[The new algorithm for stratification of the risk of venous thromboembolic events in elective neurosurgery and its prognostic significance]. / Novyi algoritm stratifikatsii riska venoznykh tromboembolicheskikh oslozhnenii v planovoi neirokhirurgii i ego prognosticheskaya znachimost'.

Early identification of risk groups is essential for effective and target prevention of venous thromboembolic events (VTE) in all areas of surgery. For this purpose, the authors has developed and put into practice an algorithm distinguishing the groups of low, moderate and high risk of VTE among neurosurgical patients. OBJECTIVE: To assess predictive value of the developed algorithm for elective neurosurgical interventions. MATERIAL AND METHODS: The study included 7914 patients who underwent surgery between January 2018 and December 2019. According to the algorithm, we identified the groups of low (1536 (19%) patients), moderate (4554 (58%) patients) and high risk (1824 (23%) patients). Moreover, patients were divided into subgroups depending on surgical procedure. We analyzed the incidence of VTE and mortality in all groups. RESULTS. INCIDENCE: Of VTE with a 95% confidence interval in the low-risk group was 0.65% [0.26; 1.04], in the moderate risk group - 1.82% [1.47; 2.24], in the high-risk group - 12.61% [11.02; 14.09]. When comparing various surgical interventions, we revealed more common VTE after vascular microsurgery (15.62%), in patients with brain tumors (12.63%) and spinal cord tumors (6.52%). CONCLUSION: The risk stratification algorithm has demonstrated its convenience and significant predictive value for determining the risk of VTE among elective neurosurgical patients. In addition, different incidence of VTE was demonstrated in patients with various neurosurgical diseases.

Measurement of Compton Scattering at MAMI for the Extraction of the Electric and Magnetic Polarizabilities of the Proton.

A precise measurement of the differential cross sections dσ/dΩ and the linearly polarized photon beam asymmetry Σ_{3} for Compton scattering on the proton below pion threshold has been performed with a tagged photon beam and almost 4π detector at the Mainz Microtron. The incident photons were produced by the recently upgraded Glasgow-Mainz photon tagging facility and impinged on a cryogenic liquid hydrogen target, with the scattered photons detected in the Crystal Ball/TAPS setup. Using the highest statistics Compton scattering data ever measured on the proton along with two effective field theories (both covariant baryon and heavy-baryon) and one fixed-t dispersion relation model, constraining the fits with the Baldin sum rule, we have obtained the proton electric and magnetic polarizabilities with unprecedented precision: α_{E1}=10.99±0.16±0.47±0.17±0.34, ß_{M1}=3.14±0.21±0.24±0.20±0.35; in units of 10^{-4} fm^{3} where the errors are statistical, systematic, spin polarizability dependent, and model dependent.

Single π 0 production off neutrons bound in deuteron with linearly polarized photons.

The quasifree γ → d → π 0 n ( p ) photon beam asymmetry, Σ , has been measured at photon energies, E γ , from 390 to 610 MeV, corresponding to center of mass energy from 1.271 to 1.424 GeV, for the first time. The data were collected in the A2 hall of the MAMI electron beam facility with the Crystal Ball and TAPS calorimeters covering pion center-of-mass angles from 49 ∘ to 148 ∘ . In this kinematic region, polarization observables are sensitive to contributions from the Δ ( 1232 ) and N(1440) resonances. The extracted values of Σ have been compared to predictions based on partial-wave analyses (PWAs) of the existing pion photoproduction database. Our comparison includes the SAID, MAID and Bonn-Gatchina analyses; while a revised SAID fit, including the new Σ measurements, has also been performed. In addition, isospin symmetry is examined as a way to predict π 0 n photoproduction observables, based on fits to published data in the channels π 0 p , π + n and π - p .

Helicity-Dependent Cross Sections for the Photoproduction of π

The double-polarization observable E and helicity-dependent cross sections σ_{1/2}, σ_{3/2} have been measured for the photoproduction of π^{0} pairs off quasifree protons and neutrons at the Mainz MAMI accelerator with the Crystal Ball/TAPS setup. A circularly polarized photon beam was produced by bremsstrahlung from longitudinally polarized electrons and impinged on a longitudinally polarized deuterated butanol target. The reaction products were detected with an almost 4π covering calorimeter. The results reveal for the first time the helicity- and isospin-dependent structure of the γN→Nπ^{0}π^{0} reaction. They are compared to predictions from reaction models in view of nucleon resonance contributions and also to a refit of one model that predicted results for the proton and for the neutron target. The comparison of the prediction and the refit demonstrates the large impact of the new data.

[Physical training in patients with chronic heart failure: level of involvement, as well as psychosocial, anamnestic and iatrogenic factors that determine the motivation to practice].

Introduction Physical exercise (PE) is a necessary part in the treatment of patients with chronic heart failure (CHF), which is stated in the European Society of Cardiology guidelines and the Russian Heart Failure Society guidelines. However, this type of non-drug treatment is still not sufficiently used in HF patients in Russia.Aim To study the current involvement of HF patients in PT and to describe psychosocial factors that influence the patients' willingness to exercise and potential barriers and motivations for PE.Methods This study was designed as an in-moment survey. Patients with CHF who visited clinics in 7 cities of the Russian Federation in 2018 as a part of European Heart Failure Awareness Days were provided with a self-administered questionnaire containing questions about their social and educational status, attitude to PT as a method of treatment, and factors motivating and demotivating them to participation in training sessions. The survey participants were also asked a question about their source of information about exercise in HF. Physicians filled in the items describing HF clinical manifestations (left ventricular ejection fraction (EF) and HF functional class (FC)). Code numbers were used for further identification of the participants and to protect their confidentiality. Statistical analysis was performed with the StatXcat-8 program. Limits of exact confidence intervals (CIs) were provided both for fractions and parameters of polynomial distribution. CI limits for differences and fractions were calculated using MOVER. Age was analyzed using the PAST program.Results The study included 560 patients with HF; 52 % of them were women (mean age, 64; 95 % CI: 63-65 years). Women were 3 years older than men (95 % CI: 1.3-4.9 years). 501 (89.5 %) patients had FC II-III; 265 (49 %) patients had HF with low EF. 350 (62 %) patients had comorbidities: 41.4 % of patients had diabetes mellitus and 25.4 % of patients had arthritis. Only 91 (17 %) patients reported exercising. Patients younger than 65 exercised significantly more frequently than older ones (odds ratio (OR), 1.7, 95 % CI: 1.0-2.7, р<0.001). Patients with higher education had better chances to be involved in PT or were more anxious to start training (OR, 2.7; 95 % CI: 1.6-4.7, р<0.001). The capability for influencing the disease was the major motivation for PT for both sexes. Probability of this answer was 48 % (95 % CI: 33-61) for men and 46 % (95 % CI: 29-63) for women. 62 % of patients indicated poor health as the major barrier for participation in PT. Only 55 % of patients knew that PT could be a method for HF treatment, and only 50 % were informed about that by their physician.Conclusion The factors that positively influence the willingness to exercise include male sex, higher level of education, younger age, and better perception of the own health condition. 62 % of patients indicated poor health as the major barrier for participation in training. On the whole, the awareness of patients about PT benefits for health in HF was low. To our opinion, this was a serious factor of the extremely low involvement of patients in PT. Only 55 % of patients knew that PT could be a method for HF treatment, and, furthermore, only 50 % of patients received this information from their physicians.

Signatures of the d

We report a measurement of the spin polarization of the recoiling neutron in deuterium photodisintegration, utilizing a new large acceptance polarimeter within the Crystal Ball at MAMI. The measured photon energy range of 300-700 MeV provides the first measurement of recoil neutron polarization at photon energies where the quark substructure of the deuteron plays a role, thereby providing important new constraints on photodisintegration mechanisms. A very high neutron polarization in a narrow structure centered around E_{γ}∼570 MeV is observed, which is inconsistent with current theoretical predictions employing nucleon resonance degrees of freedom. A Legendre polynomial decomposition suggests this behavior could be related to the excitation of the d^{*}(2380) hexaquark.

Insight into the Narrow Structure in η Photoproduction on the Neutron from Helicity-Dependent Cross Sections.

The double polarization observable E and the helicity dependent cross sections σ_{1/2} and σ_{3/2} were measured for η photoproduction from quasifree protons and neutrons. The circularly polarized tagged photon beam of the A2 experiment at the Mainz MAMI accelerator was used in combination with a longitudinally polarized deuterated butanol target. The almost 4π detector setup of the Crystal Ball and TAPS is ideally suited to detect the recoil nucleons and the decay photons from η→2γ and η→3π^{0}. The results show that the narrow structure previously observed in η photoproduction from the neutron is only apparent in σ_{1/2} and hence, most likely related to a spin-1/2 amplitude. Nucleon resonances that contribute to this partial wave in η production are only N 1/2^{-} (S_{11}) and N 1/2^{+} (P_{11}). Furthermore, the extracted Legendre coefficients of the angular distributions for σ_{1/2} are in good agreement with recent reaction model predictions assuming a narrow resonance in the P_{11} wave as the origin of this structure.

[Correct statistical analysis of genotype frequencies for UCP and PPAR gene families in residents of besieged Leningrad and the control group].

Correct harmonized statistical re-analysis of the data published in this Journal by I.V.Polyakova et al. (2014) clearly shows that, contrary to the authors' opinion, the distribution of genotypes among residents of besieged Leningrad and the residents of the North-West region of Russia appeared to be statistically indistinguishable in all five genes studied. The main causes of the erroneous conclusions of the authors are neglecting the problem of multiple comparisons and fundamental impossibility of sampling adequate control group. A scheme for harmonized statistical analysis of such data is presented. It implies not only frequentist but Bayesian point and interval estimates for genotype proportions and their differences, for fixation index (coefficient of inbreeding) FIS, for the effect size φ based on χ2 statistic (contingency coefficient) and for the achieved power (1 - ß), as well as estimates of posterior probabilities for the null hypothesis P(H_0 |D), Bayes factors 〖BF〗_01, observed p-values, p_obs, with the prediction intervals, and p-values adjusted for the multiplicity of null hypotheses tested (P_S).

[Genetic risk assessment of the joint effect of several genes: Critical appraisal].

When assessing the combined action of genes on the quantitative or qualitative phenotype we encounter a phenomenon that could be named the "paradox of the risk score summation." It arises when the search of risk allele and assessment of their combined action are performed with the same single dataset. Too often such methodological error occurs when calculating the so called genetic risk score (GRS), which refers to the total number of alleles associated with the disease. Examples from numerous published genetic association studies are considered in which the claimed statistically significant effects can be attributed to the "risk score summation paradox." In the second section of the review we discuss the current modifications of multiple regression analysis addressed to the so called "n ≪ p problem" (the number of points is much smaller than the number of possible predictors). Various algorithms for the model selection (searching the significant predictor combinations) are considered, beginning from the common marginal screening of the "top" predictors to LASSO and other modern algorithms of compressed sensing.

Measurements of double-polarized compton scattering asymmetries and extraction of the proton spin polarizabilities.

The spin polarizabilities of the nucleon describe how the spin of the nucleon responds to an incident polarized photon. The most model-independent way to extract the nucleon spin polarizabilities is through polarized Compton scattering. Double-polarized Compton scattering asymmetries on the proton were measured in the Δ(1232) region using circularly polarized incident photons and a transversely polarized proton target at the Mainz Microtron. Fits to asymmetry data were performed using a dispersion model calculation and a baryon chiral perturbation theory calculation, and a separation of all four proton spin polarizabilities in the multipole basis was achieved. The analysis based on a dispersion model calculation yields γ(E1E1)=-3.5±1.2, γ(M1M1)=3.16±0.85, γ(E1M2)=-0.7±1.2, and γ(M1E2)=1.99±0.29, in units of 10(-4) fm(4).

Measurement of the transverse target and beam-target asymmetries in η meson photoproduction at MAMI.

We present new data for the transverse target asymmetry T and the very first data for the beam-target asymmetry F in the γ[over →]p[over →]→ηp reaction up to a center-of-mass energy of W=1.9 GeV. The data were obtained with the Crystal-Ball/TAPS detector setup at the Glasgow tagged photon facility of the Mainz Microtron MAMI. All existing model predictions fail to reproduce the new data indicating a significant impact on our understanding of the underlying dynamics of η meson photoproduction. The peculiar nodal structure observed in existing T data close to threshold is not confirmed.

Silencing AML1-ETO gene expression leads to simultaneous activation of both pro-apoptotic and proliferation signaling.

The t(8;21)(q22;q22) rearrangement represents the most common chromosomal translocation in acute myeloid leukemia (AML). It results in a transcript encoding for the fusion protein AML1-ETO (AE) with transcription factor activity. AE is considered to be an attractive target for treating t(8;21) leukemia. However, AE expression alone is insufficient to cause transformation, and thus the potential of such therapy remains unclear. Several genes are deregulated in AML cells, including KIT that encodes a tyrosine kinase receptor. Here, we show that AML cells transduced with short hairpin RNA vector targeting AE mRNAs have a dramatic decrease in growth rate that is caused by induction of apoptosis and deregulation of the cell cycle. A reduction in KIT mRNA levels was also observed in AE-silenced cells, but silencing KIT expression reduced cell growth but did not induce apoptosis. Transcription profiling of cells that escape cell death revealed activation of a number of signaling pathways involved in cell survival and proliferation. In particular, we find that the extracellular signal-regulated kinase 2 (ERK2; also known as mitogen-activated protein kinase 1 (MAPK1)) protein could mediate activation of 23 out of 29 (79%) of these upregulated pathways and thus may be regarded as the key player in establishing the t(8;21)-positive leukemic cells resistant to AE suppression.

Comparative phenotypic characterization of human cord blood monocytes and placental macrophages at term.

The expression of surface molecules in cord blood monocytes and placental macrophages was studied using flow cytometry. When compared with monocytes, macrophages presented a decrease in HLA-DR and LAP/TGF-ß1 levels and increased expression of alternative activation markers, especially CD206. No difference in the production of the apoptotic factors TRAIL and TWEAK was observed, whereas the levels of cytokine receptors in monocytes were significantly higher than in macrophages. Most remarkable was the difference in the expression of IL-17 and TNFα receptors. A strong correlation between VEGF and TNFα receptors was revealed in both cell populations. The results obtained in this study provide antigenic phenotypes for two related cell populations and outline the feasible functional alterations during tissue macrophage differentiation.

[Enterovirus infection as a risk factor of acute coronary syndrome and its complications].

Antigens of enteroviruses were detected quantitatively in the modified complement-binding reaction in blood samples from 102 of the 208 (49%) patients with ACS, in coronary artery tissues from 23 of 24 and heart from 51 of 94 (54.3%) patients with MI who died from cardiogenic shock and/or cardiac rupture. The relative level of enterovirus antigen (RLEVA) in the blood of patients with MI complicated and uncomplicated by cardiogenic shock and/or cardiac rupture was 0.42 +/- 0.04 and 0.29 +/- 0.02 arbitrary units respectively (p = 0.032) compared with 0.21 +/- 0.07 in patients with unstable angina (UA) (p = 0.0001). RLEVA in patients with UA was significantly lower than in those with uncomplicated MI (p < 0.011). RLEVA in necrotized myocardial areas after death from cardiogenic shock (0.54 +/- 0.18) and/or cardiac rupture (0.46 +/- 0.15) was higher than outside MI zones (0.30 +/- 0.14 and 0.26 +/- 0.10 respectively) (p < 0.01). RLEVA in coronary vessels feeding the necrotic zones of patients with MI complicated by cardiogenic shock (0.44 +/- 0.18) was higher (p = 0.03) than in the vessel feeding tissues outside the MI zone (0.29 +/- 0.19). It is concluded that enterovirus infection is a factor of ACS; it is directly involved in its pathogenesis and promotes the development of cardiogenic shock and/or cardiac rupture.

Domain-oriented reduction of rule-based network models.

The coupling of membrane-bound receptors to transcriptional regulators and other effector functions is mediated by multi-domain proteins that form complex assemblies. The modularity of protein interactions lends itself to a rule-based description, in which species and reactions are generated by rules that encode the necessary context for an interaction to occur, but also can produce a combinatorial explosion in the number of chemical species that make up the signalling network. The authors have shown previously that exact network reduction can be achieved using hierarchical control relationships between sites/domains on proteins to dissect multi-domain proteins into sets of non-interacting sites, allowing the replacement of each 'full' (progenitor) protein with a set of derived auxiliary (offspring) proteins. The description of a network in terms of auxiliary proteins that have fewer sites than progenitor proteins often greatly reduces network size. The authors describe here a method for automating domain-oriented model reduction and its implementation as a module in the BioNetGen modelling package. It takes as input a standard BioNetGen model and automatically performs the following steps: 1) detecting the hierarchical control relationships between sites; 2) building up the auxiliary proteins; 3) generating a raw reduced model and 4) cleaning up the raw model to provide the correct mass balance for each chemical species in the reduced network. The authors tested the performance of this module on models representing portions of growth factor receptor and immunoreceptor-mediated signalling networks and confirmed its ability to reduce the model size and simulation cost by at least one or two orders of magnitude. Limitations of the current algorithm include the inability to reduce models based on implicit site dependencies or heterodimerisation and loss of accuracy when dynamics are computed stochastically.

A new graphical user interface for fast construction of computation phantoms and MCNP calculations: application to calibration of in vivo measurement systems.

The paper reports on a new utility for development of computational phantoms for Monte Carlo calculations and data analysis for in vivo measurements of radionuclides deposited in tissues. The individual properties of each worker can be acquired for a rather precise geometric representation of his (her) anatomy, which is particularly important for low energy gamma ray emitting sources such as thorium, uranium, plutonium and other actinides. The software discussed here enables automatic creation of an MCNP input data file based on scanning data. The utility includes segmentation of images obtained with either computed tomography or magnetic resonance imaging by distinguishing tissues according to their signal (brightness) and specification of the source and detector. In addition, a coupling of individual voxels within the tissue is used to reduce the memory demand and to increase the calculational speed. The utility was tested for low energy emitters in plastic and biological tissues as well as for computed tomography and magnetic resonance imaging scanning information.

Dose finding in the Ames Salmonella assay.

Threshold dose/concentration values, such as the lowest effective dose, minimum effective dose or the lowest effective concentration (LED, MED or LEC, respectively) are in use as an alternative to the mutagen potency measures based on the 'rate' measurements (e.g., the slope of the initial part of the dose-response curve). In this respect, several statistical procedures for the corresponding so-called 'dose finding' were proposed during the last decades. However, most of them disregard the discrete nature of responses such as the plate colony count in the Ames Salmonella assay. When the plate counts agree with the Poisson assumption, two procedures considered here seem to be appropriate for the dose finding. One is based on the stepwise collapsing of the homogeneous control and dose counts; another consists of constructing the confidence limits for the mutation induction factor (MIF). When the dose and control counts are non-overlapping, the simple 'visual' non-parametric estimation of LED is possible. Applicability and validity of the methods is demonstrated with the two data sets on the mutagenicity of the beta-carboline alkaloid, harmine, and one of the oxidation products of apomorphine.

Similarity pattern analysis in mutational distributions.

The validity and applicability of the statistical procedure - similarity pattern analysis (SPAN) - to the study of mutational distributions (MDs) was demonstrated with two sets of data. The first was mutational spectra (MS) for 697 GC to AT transitions produced with eight alkylating agents (AAs) in the lacI gene of Escherichia coli. The second was a recently summarized data on the distributions of 11562 spontaneous, radiation- and chemical-induced forward mutations in the ad-3 region of heterokaryon 12 of Neurospora crassa. They were analyzed as large two-way contingency tables (CTs) where two kinds of profiles were compared: site (or genotypic class) profiles and origin (or mutagen) profiles. To measure similarity (homogeneity) between any pair of profiles, the relevant sufficient statistics, Kastenbaum-Hirotsu squared distance (KHi(2)), was used. Collapsing the similar profiles into distinct internally homogeneous clusters named 'collapsets' revealed their similarity pattern. To facilitate the procedure, the computer program, COLLAPSE, was elaborated. The results of SPAN for the lacI spectra were found comparable with the results of their previous analysis with two multivariate statistical methods, the factor and cluster analyses. In the ad-3 data set, five collapsets were revealed among origin profiles (OPs): (I) ENU = 4NQO = 4HAQO = FANFT = SQ18506; (II) AF-2 = EI = MMS = DEP; (III) ETO = UV; (IV) AHA = PROCARB; and (V) He ions = protons. Moreover, the previous observation that MDs are dose-dependent was confirmed for X-ray-induced MDs. Profiles induced with the low doses of X-rays are similar to that induced with 85Sr, and profiles induced with the medium X-ray doses to those induced with protons and He ions. Evaluated similarities appear to be rather reasonable: mutagens with similar mode of action induce similar MDs. Similarity pattern revealed among genotypic class profiles (GCPs) seems to be also interpretable. When supplemented with descriptive cluster analysis, SPAN appears to be a fruitful methodology in MS analysis.