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Introduction: According to the literature, 20-50% of women will experience urinary tract infection (UTI) in their lifetime, and in 10-30% of cases, cystitis will recur. Despite the high prevalence of recurrent UTI, there are lack of studies dedicated to its impact on the quality of life, and the influence of postcoital cystitis on the quality of life and sexual function has not been previously evaluated., Aim: To assess the quality of life and sexual function in patients with recurrent postcoital cystitis before and after transposition of the urethra., Material and Methods: Women suffering from recurrent postcoital cystitis, who underwent urethral transposition from 2019 to 2021 were included the study. The SF-12v2 questionnaire was used to assess quality of life, while sexual function was evaluated using Female Sexual Function Index [FSFI]. Questionnaires were filled out by 70 patients, before and after surgery., Results: All domains of the quality of life were significantly different in the pre- and postoperative period. More pronounced changes were found in the mental health-related quality of life. In addition, there were significant differences in each domain of FSFI and the overall score postoperatively compared to baseline., Conclusion: Our study reports a high prevalence of sexual dysfunction among women with recurrent postcoital cystitis as well as a reduced quality of life. This work shows the social significance of the problem, as well as the high rehabilitation potential of urethral transposition.

Absolutely all over the world there is a constant increase in the number of people with disabilities, as a result of a number of economic, social, ecological, demographic reasons. The share of disabled people on the territory of the Pridnestrovian Moldavian Republic has remained high in recent years. The article touches upon the issues of qualitative indicators of the social health of people with disabilities, gives a fundamental characteristic of social health. A questionnaire survey was conducted in February 2018 among people with disabilities, and for the purpose of additional study, interviews with people of working age with disabilities were conducted in March 2022. The results of the author's research on the territory of the Pridnestrovian Moldavian Republic among people with disabilities on the subject of studying the processes of socialization and social adaptation in society are presented. Based on the conducted quantitative and qualitative research methods, the main trends regarding the social health of people with disabilities were identified. The main barriers on the way to successful integration processes hindering socialization and social adaptation are outlined. The above results necessitate the modernization of the current system of targeted support for people with disabilities.

The Baksan Experiment on Sterile Transitions (BEST) was designed to investigate the deficit of electron neutrinos ν_{e} observed in previous gallium-based radiochemical measurements with high-intensity neutrino sources, commonly referred to as the "gallium anomaly," which could be interpreted as evidence for oscillations between ν_{e} and sterile neutrino (ν_{s}) states. A 3.414-MCi ^{51}Cr ν_{e} source was placed at the center of two nested Ga volumes and measurements were made of the production of ^{71}Ge through the charged current reaction, ^{71}Ga(ν_{e},e^{-})^{71}Ge, at two average distances. The measured production rates for the inner and the outer targets, respectively, are [54.9_{-2.4}^{+2.5}(stat)±1.4(syst)] and [55.6_{-2.6}^{+2.7}(stat)±1.4(syst)] atoms of ^{71}Ge/d. The ratio (R) of the measured rate of ^{71}Ge production at each distance to the expected rate from the known cross section and experimental efficiencies are R_{in}=0.79±0.05 and R_{out}=0.77±0.05. The ratio of the outer to the inner result is 0.97±0.07, which is consistent with unity within uncertainty. The rates at each distance were found to be similar, but 20%-24% lower than expected, thus reaffirming the anomaly. These results are consistent with ν_{e}→ν_{s} oscillations with a relatively large Δm^{2} (>0.5  eV^{2}) and mixing sin^{2}2θ (≈0.4).

Aim: To study the pathogenetic factors in the development of postcoital cystitis and the efficiency of extravaginal transposition of the urethra., Materials and Methods: Literature data and our point of view on the causes of postcoital cystitis are described. Case histories of 438 patients aged 18 to 61 (mean 24+/-1.3) were analyzed. The efficiency of extravaginal transposition of the urethra for the prevention of recurrence of postcoital cystitis was evaluated., Results: The long-term results of operations in 315 patients were studied. A positive effect was noted in 297 (94.3%), which means the complete recovery or reduction in the frequency of cystitis to 2 or less times a year, while complete recovery occurred in 214 patients. In 18 (5.7%), the surgical procedure was ineffective, which required repeated interventions., Discussion: According to our observations, the external opening of the urethra is located in patients with postcoital cystitis and in healthy women at the same level - before the introitus. During sexual intercourse, everyone experiences vestibulo-vaginal frictional dislocation of the urethra, however, exacerbations of the inflammatory process in the bladder occur only in some females, which is associated with the multifactorial nature of the disease., Conclusion: Postcoital cystitis develops as a result of a complex of factors, the most significant ofwhich are the state of the vaginal microflora, the virulence of uropathogenic bacteria, the anatomical features of the urethra and vagina, its narrowness with a mismatch with the penile size, the intensity and duration of sexual intercourse, severe, complicated childbirth and surgical procedures in this area. Performing extravaginal transposition of the urethra according to Komyakov demonstrated high efficiency in the prevention of recurrence of postcoital cystitis.

PCSK9 has now become an important target to create new classes of lipid-lowering drugs. The prevention of its interaction with LDL receptors allows an increase in the number of these receptors on the surface of the cell membrane of hepatocytes, which leads to an increase in the uptake of cholesterol-rich atherogenic LDL from the bloodstream. The PCSK9 antagonists described in this review belong to different classes of compounds, may have a low molecular weight or belong to macromolecular structures, and also demonstrate different mechanisms of action. The mechanisms of action include preventing the effective binding of PCSK9 to LDLR, stimulating the degradation of PCSK9, and even blocking its transcription or transport to the plasma membrane/cell surface. Although several types of antihyperlipidemic drugs have been introduced on the market and are actively used in clinical practice, they are not without disadvantages, such as well-known side effects (statins) or high costs (monoclonal antibodies). Thus, there is still a need for effective cholesterol-lowering drugs with minimal side effects, preferably orally bioavailable. Low-molecular-weight PCSK9 inhibitors could be a worthy alternative for this purpose.

The purpose of the article is to study influence of various forms of physical activity on physical and psychological health of the elderly on the basis of content analysis of publications, secondary analysis of results of sociological studies of national and foreign researchers. The scientific novelty of studied question consists in critical comprehension of risk factors of development of somatic and mental diseases depending on degree of physical activity and also in elaboration of classification that included such macro- and micro-factors determining its dynamics as social cultural, social demographic, geographic, individual personal or motivational, promotional and managerial ones. The emphasis is made on necessity of additional research in this subject field to lay the foundation for making important management decisions concerning social protection and support of the elderly.

The explicit breaking of the axial symmetry by quantum fluctuations gives rise to the so-called axial anomaly. This phenomenon is solely responsible for the decay of the neutral pion π 0 into two photons (γγ), leading to its unusually short lifetime. We precisely measured the decay width Γ of the [Formula: see text] process. The differential cross sections for π 0 photoproduction at forward angles were measured on two targets, carbon-12 and silicon-28, yielding [Formula: see text], where stat. denotes the statistical uncertainty and syst. the systematic uncertainty. We combined the results of this and an earlier experiment to generate a weighted average of [Formula: see text] Our final result has a total uncertainty of 1.50% and confirms the prediction based on the chiral anomaly in quantum chromodynamics., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Aims: To evaluate the influence of minor differences in molecular weights of commercially available low molecular weight PLGA grades on the kinetics of doxorubicin release from the nanoparticles. Methods: Three low-molecular weight 50/50 PLGA polymers were thoroughly characterised concerning intrinsic viscosity, molecular weight (Mw), acid value, and residual monomer content. The doxorubicin-loaded nanoparticles prepared using these polymers were evaluated concerning the kinetics of drug release and hydrolytic degradation. Results: The Mw of the polymers were slightly different: 10.2, 10.3, and 4.7 kDa. The nanoparticles obtained from the polymer with Mw of 4.7 kDa exhibited considerably higher rates of drug release and polymer degradation. Conclusion: In the case of low molecular weight PLGA grades even a few kilodaltons could be important for the batch-to-batch reproducibility of the nanoformulation parameters. These results bring forward the importance of in-house characterisation of the polymers to be used for the nanoparticle preparation.

The objective of the study is to elucidate the effect of ultrasound treated salt solution on curing of pork meat. The interactions of salt (NaCl) solutions of 3 and 25% with the proteins of pork meat are studied. High intensity ultrasound operating at 20 kHz was used. The differential scanning calorimetry (DSC), NMR spin-spin relaxation time, unfrozen water and water diffusion coefficient measurements were carried out in meat cured with ultrasound treated and untreated salt solutions. The effect of ultrasonication was most evident from measured spin-spin relaxation times T 21 , the rate of chemical exchange of water protons k and the amount of unfrozen water W unf in the meat. The measured diffusion coefficient of water D w in meat cured with ultrasound treated and control salt solution did not show significant difference. The nuclear magnetic resonance (NMR) relaxation data, differential scanning calorimetry (DSC) and the diffusion coefficient data reliably show that the possible action of ultrasound to salt solution was manifested on the first 2 days of the experiment with a 3% salt solution., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Currently, Medical errors are a serious problem when examining patients. Creating information systems that use the capabilities of evidence-based medicine and artificial intelligence methods will allow the doctor to make an informed and proven decision. In this article, the authors offer a description of an information system that solves the problem of supporting medical decision making based on evidence-based medicine. This is achieved by using artificial intelligence methods. This work was supported by a grant from the Ministry of Education and Science of the Russian Federation, a unique project identifier RFMEFI60819X0278., (© 2020 The Author(s). Published by Elsevier B.V.)

Elastic electron-proton scattering (e-p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, r p . In 2010, a new method using muonic hydrogen atoms 1 found a substantial discrepancy compared with previous results 2 , which became known as the 'proton radius puzzle'. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen 3,4 . Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e-p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e-p experiments and enabled measurements at very small forward-scattering angles. Our result, r p  = 0.831 ± 0.007 stat  ± 0.012 syst  femtometres, is smaller than the most recent high-precision e-p measurement 5 and 2.7 standard deviations smaller than the average of all e-p experimental results 6 . The smaller r p we have now measured supports the value found by two previous muonic hydrogen experiments 1,7 . In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant 8 -one of the most accurately evaluated fundamental constants in physics.

We report on the measurement of the γp→J/ψp cross section from E_{γ}=11.8  GeV down to the threshold at 8.2 GeV using a tagged photon beam with the GlueX experiment. We find that the total cross section falls toward the threshold less steeply than expected from two-gluon exchange models. The differential cross section dσ/dt has an exponential slope of 1.67±0.39  GeV^{-2} at 10.7 GeV average energy. The LHCb pentaquark candidates P_{c}^{+} can be produced in the s channel of this reaction. We see no evidence for them and set model-dependent upper limits on their branching fractions B(P_{c}^{+}→J/ψp) and cross sections σ(γp→P_{c}^{+})×B(P_{c}^{+}→J/ψp).

Glucoamylolysis of maize starch at 55 °C has been studied by means of scanning electron microscopy (SEM), wide-angle X-ray diffraction spectroscopy (WAXD), and differential scanning calorimetry (DSC). It was found that hydrolysis is accompanied by changes in thermodynamic parameters of diluted aqueous dispersions of partially hydrolyzed starches. Such changes are ensured by two processes directly from hydrolysis and accompanying annealing. At relatively low degrees of hydrolysis (less than 30%), changes in thermodynamic parameters are mainly controlled by annealing. At the same time, at high degrees of hydrolysis (more than 40%), the main contribution to changes in thermodynamic parameters of partially hydrolyzed starch granules is due to the hydrolysis itself. It has been established that the main controlling parameter is the thickness of crystalline lamellae L crl , which, when annealed, increases, but tends to decrease at deeper glucoamylolisis. It has been established that the thickness L crl of crystalline lamellae, which increases with annealing, but shows a tendency to decrease with deeper glucoamylolysis is the most representative parameter of changes in maize starch after hydrolysis., (Copyright © 2019. Published by Elsevier Ltd.)

We studied dependences of T2 relaxation time on magnetic field and concentration of nanoparticles. It was found that nanocontrast media are effective under the influence of the magnetic fields in the range 0.3-7 T. Data of electron paramagnetic resonance confirm the assumption on aggregation of nanoparticles not coated with proteins in high magnetic fields.

The ESEEM spectroscopy was used to determine positions of the 143 Nd 3+ impurity ions in Y 2 SiO 5 single crystal. It is established that neodymium ions substitute yttrium ions in the Y2 positions with seven nearest oxygen ions. Crystal field parameters of 143 Nd 3+ impurity centers in isotopically pure Y 2 28 SiO 5 and Sc 2 28 SiO 5 single crystals were determined using data of CW EPR spectroscopy and the known energy level schemes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Using multiple parallel sequencing on Illumina platform, we identified eight microRNAs that showed significant opposite changes of gene expression in cells of the hormone-sensitive LNCaP prostate cancer cell line and in cells of the hormone-resistant DU-145 cell line, in comparison to the microRNA expression in the normal prostate tissue cells. We found that the insulin-like growth factor 1 receptor (IGF1R) gene is a target of five microRNAs whose expression is increased in LNCaP cells and reduced in DU-145 cells.

Magnetic vortices existing in soft magnetic nanoparticles with sizes larger than the single-domain diameter can be efficient nano-heaters in biomedical applications. Using micromagnetic numerical simulation we prove that in the optimal range of particle diameters the magnetization reversal of the vortices in spherical iron and magnetite nanoparticles is possible for moderate amplitudes of external alternating magnetic field, H 0  < 100 Oe. In contrast to the case of superparamagnetic nanoparticles, for the vortex configuration the hysteresis loop area increases as a function of frequency. Therefore, high values of the specific absorption rate, on the order of 1000 W/g, can be obtained at frequencies f = 0.5-1.0 MHz. Because the diameter D of a non single-domain particle is several times larger than the diameter d of a superparamagnetic particle, the volume of heat generation for the vortex turns out to be (D/d) 3 times larger. This shows the advantage of vortex configurations for heat generation in alternating magnetic field in biomedical applications.

The development of personality strongly depends on correspondence of chosen profession to capacities and interests of specialist, labor market demand and possibility of career making. The particular dynamics is observed in alteration of conception of professions and professional activities because information revolution resulted in shifting from mono-professionalism to mastering of several professions at once. The profession of pharmacist also passed through several alterations following development of pharmaceutical industry. The results of survey of opinions of students of pharmaceutical faculties concerning choice of profession of pharmacist demonstrate an actual situation at industry market and give an opportunity of forecasting its development in Moscow for nearest years.

A specific absorption rate of a dilute assembly of various random clusters of iron oxide nanoparticles in alternating magnetic field has been calculated using Landau-Lifshitz stochastic equation. This approach simultaneously takes into account both the presence of thermal fluctuations of the nanoparticle magnetic moments and magneto-dipole interaction between the nanoparticles of the clusters. It is shown that for usual 3D clusters, the intensity of the magneto-dipole interaction is determined mainly by the cluster packing density η = N p V/V cl , where N p is the average number of the particles in the cluster, V is the nanoparticle volume, and V cl is the cluster volume. The area of the low frequency hysteresis loop and the assembly-specific absorption rate have been found to be considerably reduced when the packing density of the clusters increases in the range of 0.005 ≤ η < 0.4. The dependence of the specific absorption rate on the mean nanoparticle diameter is retained with an increase of η, but becomes less pronounced. For fractal clusters of nanoparticles, which arise in biological media, in addition to a considerable reduction of the absorption rate, the absorption maximum is shifted to smaller particle diameters. It is found also that the specific absorption rate of fractal clusters increases appreciably with an increase of the thickness of nonmagnetic shells at the nanoparticle surfaces.

The dependence of expression of miRNAs and their precursors (pre-miRNAs) on the DNA methylation level in HeLa cells 8 days after mitomycin C treatment was studied. A massive parallel DNA sequencing method was applied to analyze miRNA expression. 5-Azacytidine (DNA methylation inhibitor) was added to the medium 6 days after mutagenic agent exposure. The results indicated that the change in expression for some mature miRNAs (39 of 61) was accompanied by the change in the expression of their pre-miRNAs, while there were no significant changes in the expression of pre-miRNA for other mature miRNAs (22 of 61). The aberrant expression was maintained by 8 of 61 mature miRNAs and 6 of 55 pre-miRNAs in the induced HeLa cells after 5-azacytidine treatment. In addition, the expression of more than 90% of miRNAs, which indicated a significant change in expression after mitomycin C treatment, does not depend or depends slightly on the DNA methylation level in HeLa cells without mitomycin C treatment. The results suggest that mitomycin C induces aberrant DNA methylation which affects maintenance of changes in the miRNA expression in cell generations after mutagen treatment.

It was first shown that DNA damage induction in mitomycin C-treated HeLa cells leads to a change in the selection of 5p and 3p microRNA duplex strands in the formation of the RNA-induced silencing complex (RISC).

The authors consider possibilities for the surgical treatment of patients with extensive malignant chest wall neoplasms. It is argued that combinedsugical interventions and resection of the affected parts of the chest wall together with the tumour and the use of plastic procedures allow to arrest further development of severe complications in the majority of patients and create conditions for the continuation of the anti-tumour treatment. Plastic and reconstructive surgery permits to extend operability limits and thereby improve the quality of the treatment and increase life expectancy of the patients with extensive tumorigenic process.

This paper reports successful combined cytoreductive surgical intervention on a patient with giant recurrent uterine leiomyosarcoma complicated by tumour thrombosis of left ovarian and left renal veins and inferior vena cava. After the comprehensive examination confirmed good prospects for conservative therapy, surgery was performed on 07.02.12 including laparotomic resection of the giant tumour from the abdominal cavity and small pelvis, sigmoid and rectal resection, formation of end-to-end descendorecto-anastomosis, left-hand nephrectomy, removal of tumour thrombus from the suprarenal part of inferior vena cava. The postoperative period was uneventful. No signs of pulmonary thromboembolism were recorded intra- and postoperatively. Wound healing occurred by primary intention, the sutures were removed on day 12 after surgery. The patient was discharged to be further treated on an outpatient basis. Pathological changes in the lower limbs were absent. The patient recovered and leads an active lifestyle. The follow-up examination (July 2012, March 2014) confirmed her healthy status and the absence of signs suggesting the risk of relapse and progress of the neoplastic process.

Applying the method of multiple parallel sequencing on the MiSeq platform (Illumina, United States), a comparative analysis of miRNA expression in tumor and normal colon tissuie cells was performed. Forty miRNAs aberrantly expressed in cancer were detected. Among them, 15 and 25 miRNAs showed increased arid decreased expression, respectively, for all or most of the cases. Sixteen miRNA clusters were identified, which showed a coordinated or incompletely coordinated aberrant expression in colorectal cancer cells. In two (miR-183/182 and miR-106b/25) and four (miR-143/145, miR-497/195, miR-30e/30c-1, and miR-30a/30c-2) miRNA clusters, respectively, a statistically significant coordinated increase or decrease in expression was iegistered for all miRNAs withini the corresponding cluster. Three aberrantly expressed well-known miRNAs (miR-100-5p, mil-30d-5p, and miR-204-5p) were identified, which, however, had never 'before been associated with coloreictal cancer. The obtained results demonstrate the potential and promising application of 6 miRNA clusters with' coordinated aberrant expression as markers for colorectal cancer.

We identified 40 miRNAs with inherited aberrant expression by multiple parallel sequencing of human HeLa cells irradiated with X rays and mitomycin C. Twenty-two miRNAs were repressed and 15 miRNAs were induced after radiation and mytomycin C treatment. The expression of three miRNAs (miR-10b-5p, miR-148a-3p, and miR-340-5p) decreased after X-ray exposure and increased after mitomycin C treatment. The spectrum of aberrantly expressed miRNAs after X-ray and mitomycin C treatment is different, except for three miRNAs (mir-100-5p, miR-99b-5p, miR-501-3p), which showed the inherited decreased expression after both mutagens. It has been ascertained that for five miRNAs (miR-21-3p, miR-182-5p, miR-19b-3p, miR-30a-3p, and miR-30e-3p) with increased inherited expression, the targets are well-described tumor suppressor genes. For 9 miRNAs (miR-99b-5p, miR-148a-3p, miR-365a-3p, miR-193a-3p, miR-100-5p, miR-99a-5p, miR-29b-3p, miR-340-5p, and miR-23b-3p) with reduced inherited expression, the targets are oncogenes. The obtained results provide further support of the idea that induced epigenetic changes in the genome should be considered when assessing the long-term genetic effects of ionizing radiation and chemical compounds.

Using affinity chromatography, two-dimensional electrophoresis, and MALDI-TOF mass spectrometry, plasminogen isoforms were separated and identified in blood plasma. Healthy donors and patients with prostate cancer in various stages of development were included in the studied sample. With the development of prostate cancer, four additional specific plasminogen isoforms are registered in blood plasma; they are characterized by lower molecular weights and higher pI values compared to isoforms found in the control group.

Superior vena cava syndrome results from blood flow disturbances caused by compression or tumour invasion of the superior vena cava and its tributaries. In most cases, malignant lung tumours are responsible for its development. In 1995-2010, we performed surgical treatment of 55 patients with malignant chest neoplasms and superior vena cave syndrome. Vertical sternotomy was employed most frequently. Some patients additionally underwent antero-lateral thoracotomy to facilitate the surgical approach. Polytetrafluoroethylene prostheses 18-20 mm in diameter (Russia) were used to superior vena cava. Radical and cytoreductive surgery was the method of choice in 60 and 40% of the patients respectively. The signs of obstruction disappeared in all patients immediately after surgery. 21.8% of the patients died during the early postoperative period, 5 ones survived without signs of relapses. Median survival was 21 months.

Background: The halophilic archaeon Halobacterium salinarum expresses bacteriorhodopsin, a retinal-protein that allows photosynthetic growth. Transcription of the bop (bacterioopsin) gene is controlled by two transcription factors, Bat and Brz that induce bop when cells are grown anaerobically and under light., Results: A new gene was identified that is transcribed together with the brz gene that encodes a small basic protein designated as Brb (bacteriorhodopsin-regulating basic protein). The translation activity of the start codon of the brb gene was confirmed by BgaH reporter assays. In vivo site-directed mutagenesis of the brb gene showed that the Brb protein cooperates with Brz in the regulation of bop expression. Using a GFP reporter assay, it was demonstrated that Brb cooperates with both Brz and Bat proteins to activate bop transcription under phototrophic growth conditions., Conclusions: The activation of the bop promoter was shown to be dependent not only on two major factors, Bat and Brz, but is also tuned by the small basic protein, Brb.

The lowest excited triplet (T(1)) states of magnesium and zinc tetraphenylporphines (MgTPP and ZnTPP) were studied by time-resolved (TR) high-frequency/high-field W-band electron paramagnetic resonance (hf-EPR) spectroscopy in rigid glasses at low temperatures. Inspections of the TR-hf-EPR spectra of the spin-polarized triplets revealed that the zero field splitting (ZFS) parameters, D and E, for MgTPP and ZnTPP triplets were nearly the same. At the same time, their g-tensors were found to be different. These results are interpreted quantitatively in terms of spin-orbit couplings (SOCs) and angular momenta among the excited states, giving a magnitude of SOC in the T(1) state of ZnTPP. For the first time, both the TR-hf-EPR spectra and corresponding time profiles were acquired on the ZnTPP's triplet at room temperature in liquid paraffin solution with the populations of the electron spin states being in Boltzmann equilibrium. Because of relatively fast paramagnetic relaxation in rotating triplet at room temperature, the spectra and time profiles were free from the effects of microwave saturation that allowed for the direct measurement of the absolute intersystem crossing ratios P(x):P(y):P(z) 0.085:0.085:0.83. All of these results have demonstrated advantages and new perspectives of the W-band EPR spectroscopy.

Background: Archaea combine bacterial-as well as eukaryotic-like features to regulate cellular processes. Halobacterium salinarum R1 encodes eight leucine-responsive regulatory protein (Lrp)-homologues. The function of two of them, Irp (OE3923F) and lrpA1 (OE2621R), were analyzed by gene deletion and overexpression, including genome scale impacts using microarrays., Results: It was shown that Lrp affects the transcription of multiple target genes, including those encoding enzymes involved in amino acid synthesis, central metabolism, transport processes and other regulators of transcription. In contrast, LrpA1 regulates transcription in a more specific manner. The aspB3 gene, coding for an aspartate transaminase, was repressed by LrpA1 in the presence of L-aspartate. Analytical DNA-affinity chromatography was adapted to high salt, and demonstrated binding of LrpA1 to its own promoter, as well as L-aspartate dependent binding to the aspB3 promoter., Conclusion: The gene expression profiles of two archaeal Lrp-homologues report in detail their role in H. salinarum R1. LrpA1 and Lrp show similar functions to those already described in bacteria, but in addition they play a key role in regulatory networks, such as controlling the transcription of other regulators. In a more detailed analysis ligand dependent binding of LrpA1 was demonstrated to its target gene aspB3.

The genome of the archaeon Halobacterium salinarum contains two copies of the pst (phosphate-specific transport) operon, the genes of which are related to well-studied bacterial homologues. Both operons (pst1 and pst2) were shown to be polycistronic and, when under P(i)-limited conditions, transcription initiated 1 bp upstream of the translational starts. Under P(i) saturation, the pst1 operon utilized an additional transcription start site 59 bp upstream of the first one. The leaderless pst1 transcript was found to be more efficiently translated than the leadered transcript. Promoter strengths differed significantly between the two operons and when P(i) levels changed. The basal pst1 promoter activity in P(i)-saturated conditions was minimal while the pst2 promoter was active. In contrast, phosphate limitation induced the pst1 operon threefold more than the pst2 operon. We identified basic and phosphate-dependent cis-acting elements in both promoters. Phosphate-uptake assays conducted with several Pst1 and Pst2 mutant strains revealed differences in the substrate affinities between the two transporters and also suggested that the P(i)-binding proteins PstS1 and PstS2 can interact with either of the two permease subunits of the transporters. The tactic behaviour of wild type and pst-deletion strains showed that the Pst1 transporter plays an important role for phosphate-directed chemotaxis.

Inheritance of anthocyanidins in sweet pea flowers was studied. A relationship was revealed between the colour of flowers in plants of mutant lines and the presence of different types of anthocyanidins in petal cells. Forms synthesizing anthocyanidins with a large number of OH groups in the B ring of their structure were found to be dominant with respect to less hydroxylated pigments. The functions of three earlier undescribed nonallelic genes of sweet pea have been identified for the first time. Gene R determines the synthesis of pelargonidin that has one OH group in the B ring. The formation of dihydroxylated cyanidin is controlled by the Sm 1 gene. Gene E1 is involved in the biosynthesis oftrihydroxylated delphinidin. A scheme of genetic control of anthocyanidin biosynthesis in sweet pea flowers is proposed on the basis of the data obtained. Possible mechanisms of the action of the identified genes are discussed.

Complete local response to radio- and chemoradiation for anal cancer was improved due to use of high-energy dosage of intraluminal brachytherapy (complete clinical regression (chemoradiation)--85.7%; combined irradiaton--75%). No signs of tumor progression have been reported in 20 survivors (median duration--21.6 months) (mean recurrence-free survival--12.5 months). Loco-regional relapse was in 4, local--2 patients. Intrapelvic lymph nodes were involved in 2 cases of previously morphologically confirmed regression of primary tumor. 18-month-long recurrence-free survival was in 86.3%, colostomy-free--91.6%. When combined with distant irradiation (+/-chemotherapy), brachytherapy is a relatively effective, safe and well tolerated procedure.

The authors have got their first experience with chemohyperthermal perfusion of the lung in 4 patients. The method and technique of the operation of ablation of metastases in the lungs with preliminary chemohyperthermal perfusion are described. All the patients survived the operative interventions.

The efficiency of estimating the carcinogenic activity of chemical substances was compared for five short-term tests and structure-activity relationships (SAR) analysis. The sample included 84 substances with known biological testing results obtained by the Ames test, bacterial SOS chromotest (SOS), chromosome aberration (CA) cytogenetic test, sister chromatid exchange (SHE) test, and gene mutation (GM) test with mammalian cells in vitro and by carcinogenicity assays in rodents in vivo. Structural descriptors were selected using an original database, which included the structural formulas of substances with known carcinogenic activity in rodents. Original software was created to generate and select the descriptors that statistically coincided with carcinogenic activity. The descriptors that were associated exclusively with carcinogenic substances from the database and the tests that produced positive results exclusively with carcinogens were used to evaluate the carcinogenic activity of the substances. A combination of three short-term tests (Ames, SOS, and CA tests) and the SAR model proved to identify carcinogenicity for more than 60% of carcinogens.

A system was created to obtain and select Arabidopsis thaliana genes whose superexpression causes development of a mutant phenotype. Three morphological mutants (two with a markedly retarded growth and one with a fasciated stem) associated with the superexpression of genes At5g10080, At1g33390, and At5g13760 were generated with the use of this system. Localization, structure, and a possible functional organization of these genes were determined.

Recently, we and others identified the microRNA miR-34a as a target of the tumor suppressor gene product p53. Ectopic miR-34a induces a G(1) cell cycle arrest, senescence and apoptosis. Here we report that miR-34a expression is silenced in several types of cancer due to aberrant CpG methylation of its promoter. 19 out of 24 (79.1%) primary prostate carcinomas displayed CpG methylation of the miR-34a promoter and concomitant loss of miR-34a expression. CpG methylation of the miR-34a promoter was also detected in breast (6/24; 25%), lung (7/24; 29.1%), colon (3/23; 13%), kidney (3/14; 21.4%), bladder (2/6; 33.3%) and pancreatic (3/19; 15.7%) carcinoma cell lines, as well as in melanoma cell lines (19/44; 43.2%) and primary melanoma (20/32 samples; 62.5%). Silencing of miR-34a was dominant over its transactivation by p53 after DNA damage. Re-expression of miR-34a in prostate and pancreas carcinoma cell lines induced senescence and cell cycle arrest at least in part by targeting CDK6. These results show that miR-34a represents a tumor suppressor gene which is inactivated by CpG methylation and subsequent transcriptional silencing in a broad range of tumors.

An explicitly polarizable force field based exclusively on quantum data is applied to calculations of relative binding affinities of ligands to proteins. Five ligands, differing by replacement of an atom or functional group, in complexes with three serine proteases-trypsin, thrombin, and urokinase-type plasminogen activator-with available experimental binding data are used as test systems. A special protocol of thermodynamic integration was developed and used to provide sufficiently low levels of systematic error along with high numerical efficiency and statistical stability. The calculated results are in excellent quantitative (rmsd = 1.0 kcal/mol) and qualitative (R(2) = 0.90) agreement with experimental data. The potential of the methodology to explain the observed differences in the ligand affinities is also demonstrated.

EPR spectra of the excited quartet and doublet molecular states of (tetraphenylporphinato)zinc(II) covalently bounded to 3-(N-nitronyl-notroxide) pyridine stable radical are modeled in terms of the spin-Hamiltonian given by the sum of the contributions from the radical and triplet moieties, and the interaction between them. The later is represented by anisotropic point dipolar and isotropic exchange electron spin-spin interactions. It is shown that the high field (W-band) EPR spectra depend on energy separation between the electronic doublet (D) and quartet (Q) states. This dependence was utilized to estimate the upper limit of the intensity of exchange interaction between the radical and porphyrin moieties.

We consider a chain of nonlinear oscillators with long-range interaction of the type 1l(1+alpha), where l is a distance between oscillators and 0

We demonstrate, for the first time to the best of our knowledge, low-loss, Si-CMOS-compatible fabrication of single-mode chalcogenide strip waveguides. As a novel route of chalcogenide glass film patterning, lift-off allows several benefits: leverage with Si-CMOS process compatibility; ability to fabricate single-mode waveguides with core sizes down to submicron range; and reduced sidewall roughness. High-index-contrast Ge(23)Sb(7)S(70) strip waveguides have been fabricated using lift-off with excellent uniformity of loss propagation and the lowest loss figure of reported to date. We also show that small core Ge(23)Sb(7)S(70) rib waveguides can be fabricated via lift-off as well, with loss figures lower than 0.5 dB/cm. Additionally, we find through waveguide modal analysis that although overall transmission loss is low, the predominant source of this loss comes from scattering at the sidewalls.

In a genome-wide screen for microRNAs regulated by the transcription factor encoded by the p53 tumor suppressor gene we found that after p53-activation the abundance of thirty-four miRNAs was significantly increased, whereas sixteen miRNAs were suppressed. The induction of miR-34a was most pronounced among all differential regulations. Also expression of the primary miR-34a transcript was induced after p53 activation and by DNA damage in a p53-dependent manner. p53 occupied an evolutionarily conserved binding site proximal to the first non-coding exon of miR-34a. Ectopic miR-34a induced apoptosis and a cell cycle arrest in the G1-phase, thereby suppressing tumor cell proliferation. Other p53-induced miRNAs identified here may also have tumor suppressive potential as they are known to suppress the anti-apoptotic factor Bcl2 (miR-15a/16) and the oncogenes RAS and HMGA2 (let-7a). Our results for the first time directly integrate the regulation of miRNA expression into the transcriptional network regulated by p53. siRNAs corresponding to p53-induced miRNAs may have potential as cancer therapeutic agents as RNA interference based therapies are currently emerging.

A quantum mechanical polarizable force field (QMPFF) has been applied to the noncovalent interactions of molecular hydrogen as well as closed-shell monoatomic species (CSMS): rare gases, alkali cations, and halide anions. The importance of all the main energy components is demonstrated: electrostatics (including penetration effect), exchange repulsion, dispersion, and induction. As the MP2 level of quantum mechanics, which is used to parametrize QMPFF, significantly underestimates the H2-H2 dimer binding energy, the force field was refined using state-of-the-art CCSD(T) data. The approach demonstrates excellent transferability, which is confirmed by accurate reproduction of mixed H2-CSMS dimers and the second virial coefficient of hydrogen vapor.

We have fabricated and tested, to the best of our knowledge, the first microfluidic device monolithically integrated with planar chalcogenide glass waveguides on a silicon substrate. High-quality Ge(23)Sb(7)S(70) glass films have been deposited onto oxide coated silicon wafers using thermal evaporation, and high-index-contrast channel waveguides have been defined using SF(6) plasma etching. Microfluidic channel patterning in photocurable resin (SU8) and channel sealing by a polydimethylsiloxane (PDMS) cover completed the device fabrication. The chalcogenide waveguides yield a transmission loss of 2.3 dB/cm at 1550 nm. We show in this letter that using this device, N-methylaniline can be detected using its well-defined absorption fingerprint of the N-H bond near 1496 nm. Our measurements indicate linear response of the sensor to varying N-methylaniline concentrations. From our experiments, a sensitivity of this sensor down to a N-methylaniline concentration 0.7 vol. % is expected. Given the low-cost fabrication process used, and robust device configuration, our integration scheme provides a promising device platform for chemical sensing applications.

A system of two vectors, pEnLox and pCre. was developed. The pEnLox vector is used to induce insertional mutations, while pCre is used to obtain transgenic plants expressing the Cre recombinase gene. The T-DNA enhancer is flanked by the loxP sites in the pEnLox vector. As an Arahidopsis thaliana insertional mutant obtained by transformation with pEnLox is crossed with another transgenic line carrying the cre gene. the enhancer sequence is eliminated. The vector system makes it possible to induce insertional mutations and to determine whether the mutant phenotype is caused by the loss-of-function insertional mutation or by overespression of nearby genes in response to the enhancer contained in the insert.

Method for detection of pathogenic microorganisms in different microbiological assays (water, faeces, punctate etc.) has been developed. Device for preparation of samples and filtration of studied material through transparent tracking membranes with fixed size of pores and subsequent microscopy of filtrate was developed also as well as device for filtration of different liquids in closed cylinder under pressure. Method significantly increases informativeness and reliability of analyses, and decreases of their labor and financial costs.