Development of a Method for Isolation of Mature Cardiomyocytes from Human Heart Biopsy Specimens.

To increase the yield of living cells and their survival, studies were carried out to optimize the method for isolating cardiomyocytes from biopsy specimens excised from the right atrial appendages. It was found that creatine, blebbistatin, and taurine are necessary components of the buffer solution during cardiomyocyte isolation, and that composition of the solutions is a more important factor than their oxygenation.

[Preoperative predictors of obesity recurrence after laparoscopic gastrectomy]. / Predoperatsionnye prediktory retsidiva ozhireniya posle laparoskopicheskoi prodol'noi rezektsii zheludka.

OBJECTIVE: To find the preoperative predictors of obesity recurrence. MATERIAL AND METHODS: We analyzed 81 patients with obesity who underwent laparoscopic sleeve gastrectomy. Patients were followed-up for 5 years and divided into 2 groups (64 (79.0%) patients were in the persistent weight loss group and 17 (21.0%) ones were in the obesity recurrence group). RESULTS: We tried to make a mathematical model for predicting obesity recurrence after bariatric surgery based on various parameters (age, height, weight, hemoglobin A1C, lipoprotein A, T3, T4, triglycerides, TSH, cholesterol, arterial hypertension, diabetes, metabolic syndrome, percentage of fat mass). We trained the following classification models: logistic regression, naive Bayes classifier, decision tree. None classifier provided sufficient prediction quality. This may indicate that these data do not allow predicting of obesity recurrence after sleeve gastrectomy. CONCLUSION: We failed to construct a mathematical model based on preoperative data of patients with obesity predicting recurrence in long-term period after sleeve gastrectomy.

[Efficacy of bioregulative drugs in the treatment of otitis media with effusion associated with rhinosinusitis and adenoiditis]. / Effektivnost' preparatov bioregulyatsionnoi meditsiny pri lechenii ekssudativnogo srednego otita, sopryazhennogo s rinosinusitom i adenoiditom.

PURPOSE: Improving of otitis media with effusion (OME) with rhinosinusitis (RS) and adenoiditis treatment effectiveness. MATERIALS AND METHODS: The study included 112 patients 12-18 y.o. with otitis media with effusion, who were divided into 2 groups depending on the treatment scheme. The Group I (the main group) patients treatment included Traumeel S and Euphorbium compositum Nasentropfen S in addition to the standard treatment, and the Group II (comparison), children were prescribed standard therapy. Patients of both groups were divided into 3 subgroups depending on the upper respiratory tract inflammation symptoms: A - patients with adenoiditis; B - with rhinosinusitis and C - combination of adenoiditis and rhinosinusitis. The comparison group (groups IIB and IIC) treatment scheme (children with rhinosinusitis) included topical corticosteroids and the main group patients didn't receive corticosteroids. All patients went through complaints and anamnesis collection, routine otorhinolaryngological and instrumental examination before and after treatment. RESULTS: Analysis of treatment results demonstrated high efficacy of multicomponent drugs with low doses of active ingredients in the therapy of patients with OME, regardless of comorbid pathology. Significantly better results were obtained in the patients treated with bioregulatory drugs when comparing the outcomes of OME therapy in combination with adenoiditis (groups IA and IIA). Comparable efficacy results were obtained in the treatment group of patients with OME associated with RS (in groups IB and IIB as well as in groups IC and IIC), where GCS was received in the comparison group. The high efficacy and safety of bioregulatory drugs makes the use of these agents a promising treatment for patients with OME, RS and adenoiditis.

Stability of Aqueous Suspensions of COOH-Decorated Carbon Nanotubes to Organic Solvents, Esterification, and Decarboxylation.

Carbon nanotubes are among the most widely used nanosystems, and stability of carbon nanotube suspensions is critical for nanotechnology and environmental science. Remaining in aqueous environment alone misses important factors that regulate colloidal stability in the presence of electrolytes. Indeed, introduction of (80-95) vol % organic solvents leads to sharp changes in suspension properties depending on the solvent. For example, the critical coagulation concentrations for a given inorganic or organic coagulating ion can change by 2 orders of magnitude when going from dimethyl sulfoxide to acetonitrile. We establish and explain these trends by Lewis acid-base interactions and show that a strong interaction extending beyond the standard theory of aggregation plays an important role.

Search for a New B-L Z

A search for a new Z^{'} gauge boson associated with (un)broken B-L symmetry in the keV-GeV mass range is carried out for the first time using the missing-energy technique in the NA64 experiment at the CERN SPS. From the analysis of the data with 3.22×10^{11} electrons on target collected during 2016-2021 runs, no signal events were found. This allows us to derive new constraints on the Z^{'}-e coupling strength, which, for the mass range 0.3≲m_{Z^{'}}≲100 MeV, are more stringent compared to those obtained from the neutrino-electron scattering data.

Positive and negative signal and line shape in stimulated Raman spectroscopy: Resonance femtosecond Raman spectra of diphenylbutadiene.

Resonance stimulated Raman signal and line shape are evaluated analytically under common electronic/vibrational dephasing and exponential Raman/probe pulse, exp(-|t|/τ). Generally, the signal from a particular state includes contributions from higher and lower electronic states. Thus, with S0 → S1 actinic excitation, the Raman signal consists of 15 Feynman diagrams entering with different signs. The negative sign indicates vibrational coherences in S1 or higher Sn, whereas the positive sign reveals coherences in S0 or Sn via S1 → Sn → Sm (n < m) coupling. The signal complexity is in contrast to spontaneous Raman with its single diagram only. The results are applied to femtosecond stimulated Raman spectra of trans-trans, cis-trans (ct), and cis-cis (cc) 1,4-diphenyl-1,3-butadiene, the ct and cc being reported for the first time. Upon actinic excitation, the Stokes spectra show negative bands from S1 or Sn. When approaching higher resonances Sn → Sm, some Raman bands switch their sign from negative to positive, thus, indicating new coherences in Sn. The results are discussed, and the measured Raman spectra are compared to the computed quantum-chemical spectra.

Probing the explanation of the muon (g-2) anomaly and thermal light dark matter with the semi-visible dark photon channel.

We report the results of a search for a new vector boson ( A ' ) decaying into two dark matter particles χ 1 χ 2 of different mass. The heavier χ 2 particle subsequently decays to χ 1 and an off-shell Dark Photon A ' ∗ → e + e - . For a sufficiently large mass splitting, this model can explain in terms of new physics the recently confirmed discrepancy observed in the muon anomalous magnetic moment at Fermilab. Remarkably, it also predicts the observed yield of thermal dark matter relic abundance. A detailed Monte-Carlo simulation was used to determine the signal yield and detection efficiency for this channel in the NA64 setup. The results were obtained re-analyzing the previous NA64 searches for an invisible decay A ' → χ χ ¯ and axion-like or pseudo-scalar particles a → γ γ . With this method, we exclude a significant portion of the parameter space justifying the muon g-2 anomaly and being compatible with the observed dark matter relic density for A ' masses from 2 m e up to 390 MeV and mixing parameter ε between 3 × 10 - 5 and 2 × 10 - 2 .

On the intersystem crossing rate in a Platinum(II) donor-bridge-acceptor triad.

The rates of ultrafast intersystem crossing in acceptor-bridge-donor molecules centered on Pt(II) acetylides are investigated. Specifically, a Pt(II) trans-acetylide triad NAP--Pt--Ph-CH2-PTZ [1], with acceptor 4-ethynyl-N-octyl-1,8-naphthalimide (NAP) and donor phenothiazine (PTZ), is examined in detail. We have previously shown that optical excitation in [1] leads to a manifold of singlet charge-transfer states, S*, which evolve via a triplet charge-transfer manifold into a triplet state 3NAP centered on the acceptor ligand and partly to a charge-separated state 3CSS (NAP--Pt-PTZ+). A complex cascade of electron transfer processes was observed, but intersystem crossing (ISC) rates were not explicitly resolved due to lack of spin selectivity of most ultrafast spectroscopies. Here we revisit the question of ISC with a combination and complementary analysis of (i) transient absorption, (ii) ultrafast broadband fluorescence upconversion, FLUP, which is only sensitive to emissive states, and (iii) femtosecond stimulated Raman spectroscopy, FSR. Raman resonance conditions allow us to observe S* and 3NAP exclusively by FSR, through vibrations which are pertinent only to these two states. This combination of methods enabled us to extract the intersystem crossing rates that were not previously accessible. Multiple timescales (1.6 ps to ∼20 ps) are associated with the rise of triplet species, which can now be assigned conclusively to multiple ISC pathways from a manifold of hot charge-transfer singlet states. The analysis is consistent with previous transient infrared spectroscopy data. A similar rate of ISC, up to 20 ps, is observed in the trans-acetylide NAP--Pt--Ph [2] which maintains two acetylide groups across the platinum center but lacks a donor unit, whilst removal of one acetylide group in mono-acetylide NAP--Pt-Cl [3] leads to >10-fold deceleration of the intersystem crossing process. Our work provides insight on the intersystem crossing dynamics of the organo-metallic complexes, and identifies a general method based on complementary ultrafast spectroscopies to disentangle complex spin, electronic and vibrational processes following photoexcitation.

Constraints on New Physics in Electron g-2 from a Search for Invisible Decays of a Scalar, Pseudoscalar, Vector, and Axial Vector.

We performed a search for a new generic X boson, which could be a scalar (S), pseudoscalar (P), vector (V), or an axial vector (A) particle produced in the 100 GeV electron scattering off nuclei, e^{-}Z→e^{-}ZX, followed by its invisible decay in the NA64 experiment at CERN. No evidence for such a process was found in the full NA64 dataset of 2.84×10^{11} electrons on target. We place new bounds on the S, P, V, A coupling strengths to electrons, and set constraints on their contributions to the electron anomalous magnetic moment a_{e}, |Δa_{X}|≲10^{-15}-10^{-13} for the X mass region 1 MeV≲m_{X}≲1 GeV. These results are an order of magnitude more sensitive compared to the current accuracy on a_{e} from the electron g-2 experiments and recent high-precision determination of the fine structure constant.

Hunting down the X17 boson at the CERN SPS.

Recently, the ATOMKI experiment has reported new evidence for the excess of e + e - events with a mass ∼ 17 MeV in the nuclear transitions of 4 He, that they previously observed in measurements with 8 Be. These observations could be explained by the existence of a new vector X 17 boson. So far, the search for the decay X 17 → e + e - with the NA64 experiment at the CERN SPS gave negative results. Here, we present a new technique that could be implemented in NA64 aiming to improve the sensitivity and to cover the remaining X 17 parameter space. If a signal-like event is detected, an unambiguous observation is achieved by reconstructing the invariant mass of the X 17 decay with the proposed method. To reach this goal an optimization of the X 17 production target, as well as an efficient and accurate reconstruction of two close decay tracks, is required. A dedicated analysis of the available experimental data making use of the trackers information is presented. This method provides independent confirmation of the NA64 published results [1], validating the tracking procedure. The detailed Monte Carlo study of the proposed setup and the background estimate show that the goal of the proposed search is feasible.

Search for Axionlike and Scalar Particles with the NA64 Experiment.

We carried out a model-independent search for light scalar (s) and pseudoscalar axionlike (a) particles that couple to two photons by using the high-energy CERN SPS H4 electron beam. The new particles, if they exist, could be produced through the Primakoff effect in interactions of hard bremsstrahlung photons generated by 100 GeV electrons in the NA64 active dump with virtual photons provided by the nuclei of the dump. The a(s) would penetrate the downstream HCAL module, serving as a shield, and would be observed either through their a(s)→γγ decay in the rest of the HCAL detector, or as events with a large missing energy if the a(s) decays downstream of the HCAL. This method allows for the probing of the a(s) parameter space, including those from generic axion models, inaccessible to previous experiments. No evidence of such processes has been found from the analysis of the data corresponding to 2.84×10^{11} electrons on target, allowing us to set new limits on the a(s)γγ-coupling strength for a(s) masses below 55 MeV.

Photoisomerization dynamics of trans-trans, cis-trans, and cis-cis diphenylbutadiene from broadband transient absorption spectroscopy and calculations.

The photoisomerization path and dynamics of trans-trans (ttD), cis-trans (ctD), and cis-cis (ccD) 1,4-diphenyl-1,3-butadiene (DPB) in solution are studied with broadband transient absorption (TA) spectroscopy and quantum chemical calculations. For ttD in n-hexane, 2-photon-excited TA spectra indicate that the 2Ag state is located above 1-photon allowed 1Bu (S1) by ∼1000 cm-1. Following S0 → S1 optical excitation, the isomerization occurs via torsion about a butadiene double bond to perpendicular molecular configuration P. The P-state is detected in ccD with an excited-state absorption band at 390 nm. This P-band develops during S1 → P half-torsion with time of 0.15 ps, followed further by P → S0 half-torsion and simultaneous decay with 1.6 ps in acetonitrile and 5 ps in n-hexane. In addition, two oscillation cycles between P and S1 population are observed before equilibration in n-hexane. For ctD, an indication of rising and decaying P is found in acetonitrile. The vast majority of ctD species photoisomerizes to ttD and not to ccD, in agreement a with calculated low torsional barrier about the cis double bond and high barrier about the trans double bond. Photoisomerization yield Y and time τi depend drastically on the solvent polarity. Thus, in n-hexane, the isomerization ttD → ctD has yield Ytt,ct = 0.1 and time τi = 829 ps, while in acetonitrile, Ytt,ct = 0.4 and τi = 27 ps. The 30-fold acceleration of the isomerization in acetonitrile clearly reflects a highly polar character of P, consistent with a dipole moment µP > 9.6 D. The results for DPB are discussed in comparison to stilbene.

Transient Rotamerism and Photoisomerization Dynamics of trans- and cis-Naphthylstilbene.

The rotamerism and photoisomerization of trans- and cis-1,2-di-(2-naphthyl)ethylene (tN and cN) are studied with stationary and transient absorption spectroscopies assisted by quantum chemical calculations. Absorption and emission spectra of rotamers (rotational isomers) tN-S (C2h-symmetric), tN-A (C1), and tN-S' (C2) are derived with a 53:47 ratio of tN-S to tN-A. Upon photoexcitation, the equilibration of the rotamers in S0 (rotamerization) is observed in the bleach region with characteristic time τrotamer ≈ 0.5 ns. With excitation at 364 nm, the S0 equilibrium shifts because, mainly, tN-A is bleached and the rotamerization becomes traceable, whereas with excitation at 345 nm, the equilibrium is preserved and the bleach spectrum remains unchanged. It is just long-lived (∼2 ns) S1 that allows for monitoring the rotamer dynamics in S0. Replacement of the stilbene phenyl rings with larger naphthyls increases the S1 → P torsional barrier E1act toward perpendicular configuration P both from cis and trans configurations. In tN, the radiative relaxation with τR ≈ 3.7 ns becomes the main deactivation channel, and accordingly, the measured decays show nearly no dependence on the solvent viscosity. The cis-to-trans photoisomerization occurs via two paths: adiabatic cS1 → P → tS1 (20%) and more common nonadiabatic cS1 → P → S0 (80%). The barrier cS1 → P in the cis-isomer is reduced in polar solvents because of a zwitterionic character of P. The P-state is directly detected with the cN isomer in acetonitrile by an excited-state absorption band at 400 nm developing with 0.7 ps and decaying with 1.6 ps. Two dihydrophenanthrene (DHP)-like products result from photoexcited cN. The metastable DHP-A builds up transiently from cN-A, and its spectrum at about 550 nm matches the published DHP absorption. The stable DHP-S' accumulates under stationary illumination and is formed either from excited cN-S' or metastable DHP-A.

Dark Matter Search in Missing Energy Events with NA64.

A search for sub-GeV dark matter production mediated by a new vector boson A^{'}, called a dark photon, is performed by the NA64 experiment in missing energy events from 100 GeV electron interactions in an active beam dump at the CERN SPS. From the analysis of the data collected in the years 2016, 2017, and 2018 with 2.84×10^{11} electrons on target no evidence of such a process has been found. The most stringent constraints on the A^{'} mixing strength with photons and the parameter space for the scalar and fermionic dark matter in the mass range ≲0.2 GeV are derived, thus demonstrating the power of the active beam dump approach for the dark matter search.

EXPERIMENTAL STUDY OF PAIN-RELIEVING MECHANISMS OF 4-[4-OXO-(4H)-QUINAZOLIN-3-YL]-BENZOIC ACID (PK-66 COMPOUND).

An in-depth study of the pharmacological properties of 4-[4-oxo-(4h)-quinazolin-3-yl]-benzoic acid as an analgesic agent established that it had a sufficiently high analgesic effect on models of somatic and neuropathic pain syndromes. Study objective was to study the mechanisms of analgesic action of PK-66 compound in rats using the pharmacological analysis. We evaluated the mechanisms of analgesic effect of PK-66 (1 mg/kg, intraperitoneal) compound on the thermal irritation model on Hours 1, 2, 4 and 6 after administration of study compounds. To evaluate the mechanisms of PK-66 compound pain killing, we determined the changes in its efficacy against the effects of pharmacological analyzers - Naloxon, Tramadolum, Clophelinum (Clonidine), Yohimbine, Noraepinephrine, Reserpinum, Chlorpromazine (Aminazin), Levodopa, Diazepam, and Memantine). The anti-nociceptive effect of PK-66 compound was virtually unchanged during all study terms with underlying administration of Naloxon, an opioid receptor antagonist. The results of administration of Reserpinum in rats and the concomitant administration of Noradrenaline, Clophelinum, Yohimbine and quinazoline derivative demonstrated that the adrenergic system, in particular alpha-2 adrenergic receptors, was involved in the mechanisms of PK-66 activity. Changes in the PK-66 compound effect with underlying previous administration of Levodopa and Chlorpromazine suggested that the dopaminergic system was unquestionably involved in the analgesic activity of the compound. Further study of the involvement of inhibitory and exhilarating amino acids, GABA and glutamate, showed that administration of Diazepam potentiated and extended the PK-66 analgesic effect on the thermal nociception models throughout the experiment. At the same time, increased antinociception with underlying Memantine administration preceding PK-66 was observed only in the first hours of the experiment. Therefore, the studies conducted have shown that the adrenergic system, in particular alpha-2 adrenergic receptors, dopaminergic and GABAergic systems, is involved in the mechanisms of analgesic action of 4-[4-oxo-(4h) -quinazolin-3-yl]-benzoic acid (PK-66) without any effect of PK-66 on opioid receptors.

SYNTHESIS OF THE NEW 2-(3,4-DIHYDRO-3-OXO-2H-[1,2,4]TRIAZINO[4,3-C]QUINAZOLIN-4-YL) ACETIC ACID DERIVATIVES AND ANALYSIS OF THEIR ANTIOXIDANT ACTIVITY IN NITROSATIVE STRESS MODELS.

Today we know that NO· and ONOO- are clue pathophysiological factors for progression some ischemic diseases of the central nervous system. So investigation of the antioxidants which will be able to decrease NO· and ONOO- toxicity seems to be very of current interest. The six esters and three amides of 2-(3,4-dihydro-3-oxo-2H-[1,2,4]triazino[4,3-c]quinazolin-4-yl)acetic acid were synthesized for this study, and we showed evidence of antioxidant activity of these new original derivatives. We studied the effect of 2-(3,4-dihydro-3-oxo-2H-[1,2,4]triazino[4,3-c]quinazolin-4-yl)acetic acid derivatives on superoxide dismutase activity under the condition of excessive NO· and ONOO- production. NO· induction was performed by the action of light on sodium nitroprusside Na2[Fe(NO)(CN)5]×2H2O in vitro. Also, the investigation of the substances was carried out in the brain supernatant obtained from the white Wistar rats in vivo. For nitrosative stress modeling dinitrozolic complex of Fe2+ and cysteine were utilized. Our data showed that 2-(3,4-dihydro-3-oxo-2H-[1,2,4]triazino[4,3-c]quinazolin-4-yl)acetic acid is not active compound while its esters and amides have antioxidant activity. Compound benzyl ester of this acid revealed the most effective antioxidant activity.

Search for a Hypothetical 16.7 MeV Gauge Boson and Dark Photons in the NA64 Experiment at CERN.

We report the first results on a direct search for a new 16.7 MeV boson (X) which could explain the anomalous excess of e^{+}e^{-} pairs observed in the excited ^{8}Be^{*} nucleus decays. Because of its coupling to electrons, the X could be produced in the bremsstrahlung reaction e^{-}Z→e^{-}ZX by a 100 GeV e^{-} beam incident on an active target in the NA64 experiment at the CERN Super Proton Synchrotron and observed through the subsequent decay into a e^{+}e^{-} pair. With 5.4×10^{10} electrons on target, no evidence for such decays was found, allowing us to set first limits on the X-e^{-} coupling in the range 1.3×10^{-4}≲ε_{e}≲4.2×10^{-4} excluding part of the allowed parameter space. We also set new bounds on the mixing strength of photons with dark photons (A^{'}) from nonobservation of the decay A^{'}→e^{+}e^{-} of the bremsstrahlung A^{'} with a mass ≲23 MeV.

Variability of the Expression of Reference Genes in Samples of Human Olfactory Epithelium.

We analyzed variability of the expression of three reference genes in biopsy samples of the olfactory epithelium obtained from healthy volunteers. The expression of B2M, HPRT1, and CASC3 genes was analyzed by real-time PCR. The pairs of genes B2M-HPRT1 and B2M-CASC3 were found to possess minimum individual variability of expression and can be reliable candidates for the reference genes in analysis of gene expression in neural cells.

Theoretical Estimation of the Optimum Cooling Rate of a Cell Suspension at Linear Freezing Modes Based on a Two Factor Theory of Cryodamage.

BACKGROUND: According to the two-factor theory cryodamage arises from intracellular crystallization and solution effects due to freeze concentration. OBJECTIVE: The study aims to evaluate the contribution of two types of cryodamages that are related to extra- and intracellular crystallization. METHODS: The probability of intracellular crystal formation during cooling of cell suspension in cryoprotective solution has been determined based on general thermodynamics theory. RESULTS: According to the obtained correlations and taking into account of the individual characteristics of yeast cells and murine enterocytes, the optimal cooling rates during freezing of these cells in cryoprotectant solutions were determined. CONCLUSION: The proposed algorithm for the estimation of the optimal cooling rates at linear freezing mode of a particular cellular suspension can be utilized to develope methods for cryopreservation of different cell suspensions.

Rotamer-Specific Photoisomerization of Difluorostilbenes from Transient Absorption and Transient Raman Spectroscopy.

Photoisomerization of 2,2'-, 3,3'-, and 4,4'-difluorostilbene (F2, F3, F4, respectively) in n-hexane, perfluoro-n-hexane, and acetonitrile is studied with broadband transient absorption (TA) and femtosecond stimulated Raman (FSR) spectroscopy and by DFT/TDDFT calculations. F2 and F3 possess three rotamers (rotational isomers) each, while F4 has one single conformation only. These differences are reflected in TA and FSR spectra. Thus F4 reveals a monoexponential decay of TA with τ1 = 172 ps in n-hexane, as expected for a single species. For F2 and F3, the decays are biexponential in all solvents, corresponding to two distinctly discerned rotamers or rotamer fractions. Specifically, for F2 in n-hexane, τ1 = 357 ps (83%) and τ2 = 62 ps (17%), and for F3 in the same solvent, τ1 = 222 ps (57%), and τ2 = 81 ps (43%). The weights in brackets agree with theoretically estimated ground-state abundances of the rotamers. Furthermore, a global fit of the TA and FSR data allows us to extract the spectra of the pure rotamers. The Raman spectra of S0 and S1 are in qualitative agreement with calculations.