First Probe of Sub-GeV Dark Matter beyond the Cosmological Expectation with the COHERENT CsI Detector at the SNS.

The COHERENT Collaboration searched for scalar dark matter particles produced at the Spallation Neutron Source with masses between 1 and 220 MeV/c^{2} using a CsI[Na] scintillation detector sensitive to nuclear recoils above 9 keV_{nr}. No evidence for dark matter is found and we thus place limits on allowed parameter space. With this low-threshold detector, we are sensitive to coherent elastic scattering between dark matter and nuclei. The cross section for this process is orders of magnitude higher than for other processes historically used for accelerator-based direct-detection searches so that our small, 14.6 kg detector significantly improves on past constraints. At peak sensitivity, we reject the flux consistent with the cosmologically observed dark-matter concentration for all coupling constants α_{D}<0.64, assuming a scalar dark-matter particle. We also calculate the sensitivity of future COHERENT detectors to dark-matter signals which will ambitiously test multiple dark-matter spin scenarios.

Measurement of Electron-Neutrino Charged-Current Cross Sections on

Using an 185-kg NaI[Tl] array, COHERENT has measured the inclusive electron-neutrino charged-current cross section on ^{127}I with pion decay-at-rest neutrinos produced by the Spallation Neutron Source at Oak Ridge National Laboratory. Iodine is one the heaviest targets for which low-energy (≤50 MeV) inelastic neutrino-nucleus processes have been measured, and this is the first measurement of its inclusive cross section. After a five-year detector exposure, COHERENT reports a flux-averaged cross section for electron neutrinos of 9.2_{-1.8}^{+2.1}×10^{-40} cm^{2}. This corresponds to a value that is ∼41% lower than predicted using the MARLEY event generator with a measured Gamow-Teller strength distribution. In addition, the observed visible spectrum from charged-current scattering on ^{127}I has been measured between 10 and 55 MeV, and the exclusive zero-neutron and one-or-more-neutron emission cross sections are measured to be 5.2_{-3.1}^{+3.4}×10^{-40} and 2.2_{-0.5}^{+0.4}×10^{-40} cm^{2}, respectively.

Measurement of the Coherent Elastic Neutrino-Nucleus Scattering Cross Section on CsI by COHERENT.

We measured the cross section of coherent elastic neutrino-nucleus scattering (CEvNS) using a CsI[Na] scintillating crystal in a high flux of neutrinos produced at the Spallation Neutron Source at Oak Ridge National Laboratory. New data collected before detector decommissioning have more than doubled the dataset since the first observation of CEvNS, achieved with this detector. Systematic uncertainties have also been reduced with an updated quenching model, allowing for improved precision. With these analysis improvements, the COHERENT Collaboration determined the cross section to be (165_{-25}^{+30})×10^{-40} cm^{2}, consistent with the standard model, giving the most precise measurement of CEvNS yet. The timing structure of the neutrino beam has been exploited to compare the CEvNS cross section from scattering of different neutrino flavors. This result places leading constraints on neutrino nonstandard interactions while testing lepton flavor universality and measures the weak mixing angle as sin^{2}θ_{W}=0.220_{-0.026}^{+0.028} at Q^{2}≈(50 MeV)^{2}.

[Management of the patient with renal artery fibromuscular dysplasia: clinical case].

Fibromuscular dysplasia (FMD) is a rare disease that affects small and medium-sized arteries. Clinical manifestations of FMD depend on its localization. In many cases, FMD of renal arteries (RA) is associated with arterial hypertension. Young age, particularly of female patients, suspected RA dissection or kidney infarction, absence of atherosclerosis or presence of FMD in other arteries of such patients evidence for RA FMD. In invasive treatment of hemodynamically significant stenoses, transluminal balloon angioplasty (TBA) of renal arteries is preferrable. Taking into account initial alterations of the vascular wall and unevenness of the lumen of the affected blood vessel, stent implantation is associated with an increased risk of complications and is recommended only if ballooning complications develop. An open reconstructive surgery is indicated in complicated narrowing anatomy, a high risk of the endovascular treatment, or after failure of the endovascular intervention. This article presents a clinical case of a young female patient with RA FMD and renovascular arterial hypertension who successfully underwent renal TBA with a drug-coated balloon.

First Measurement of Coherent Elastic Neutrino-Nucleus Scattering on Argon.

We report the first measurement of coherent elastic neutrino-nucleus scattering (CEvNS) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer CEvNS over the background-only null hypothesis with greater than 3σ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2±0.7)×10^{-39} cm^{2}-consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the CEvNS process and provides improved constraints on nonstandard neutrino interactions.

The microbiome of oral cavity patients with periodontitis, adhesive and biofilm forming properties.

The microbiome of oral cavity in healthy people and patients with periodontitis was analyzed to determine their adhesive properties and the ability to form biofilms. The study involved 2 groups: healthy, 18 people, and an experimental group, 20 patients with chronic generalized periodontitis moderate severity of the disease. The average age of the studied people was 35-45 years. Material - dental plaque, scraping from the mucous membrane of the back of the tongue, the contents of the periodontal groove and periodontal pocket, as well as oral fluid. The main method of diagnostic was bacteriological. The average adhesion index (AAI) was used to determine adhesion level of microorganisms to epithelial cells of oral cavity's mucous membrane. The microbiota's ability to form biofilm was tested on glass and plastic surface. The microbiota of oral cavity of patients with periodontitis was characterized by decrease in the frequency of bacteria of the genera: Streptococcus, Peptostreptococcus, Peptococcus, and an increase in Staphylococcus aureus, Veillonella spp., Bacillus spp. The microbiota of the oral cavity of patients with generalized periodontitis has a greater ability to adhere to the cells of the mucous membrane than in healthy people, while their ability to form biofilms and exhibit pathogenic properties is enhanced. The biofilm formation of microorganisms in healthy and sick people differs both on glass and on plastic surfaces.

Clinical and prognostic significance of the soluble form of the VISTA immunity control point in patients with primary bone tumors.

The data of a comparative enzyme-linked immunosorbent assay of the content of the soluble form of the immunity checkpoint VISTA in the blood serum of 30 healthy donors (control group), 79 patients with primary malignant (osteosarcoma - 30, chondrosarcoma - 31, chordoma - 14) and 14 borderline (giant cell tumor) bone neoplasms are presented. In the general group of patients with malignant neoplasms of bones, the median sVISTA content in blood serum is statistically significant lower than in the control (p = 0.040). In patients with bone tumors and healthy donors over 18 years of age, there was a decrease with age in serum sVISTA levels. There were no significant differences in sVISTA concentration between patients with osteosarcoma, chondrosarcoma and healthy donors. Only in patients with chordoma were sVISTA levels statistically significant lower than in controls (p = 0.013). In the groups of patients with chondrosarcoma and osteosarcoma of the bone, there were no significant associations between the serum sVISTA content and the main clinical and morphological characteristics of the disease. In patients with osteosarcoma, no relationship was found between sVISTA levels and overall survival rates, while in patients with bone chondrosarcoma, there was a tendency towards a favorable prognosis with a high content of the marker in the blood serum.

Atomic force microscopy study of red blood cell membrane nanostructure during oxidation-reduction processes.

The morphology and functional state of red blood cells (RBCs) mainly depends on the configuration of the spectrin network, which can be broken under the influence of intoxication because of oxidation processes in the cells. Measurement of these processes is a complex problem. The most suitable and prospective method that resolves this problem is atomic force microscopy (AFM). We used AFM to study the changes in the spectrin matrix and RBC morphology during oxidation processes caused by ultraviolet (UV) irradiation in RBC suspension. The number of discocytes decreased from 98% (in control) to 12%. We obtained AFM images of the spectrin matrix in RBC ghosts. Atomic force microscopy allows for the direct observation and quantitative measurement of the disturbances in the structure of the spectrin matrix during oxidation processes in RBCs. The typical section size of the spectrin network changed from approximately 80 to 200 nm (in control) to 600 nm and even to 1000 nm after UV irradiation. An AFM study showed that incubation of RBCs with Cytoflavin® after UV irradiation preserved the forms of RBCs almost at control levels; 89% of the cells remained as discocytes. To quantify the intensity of the oxidation-reduction processes, the percentage of haemoglobin derivatives was measured. The content of methaemoglobin varied in the range of 1% to 70% during the experiments. These evidence-based studies are important for the fundamental research of interactions during redox processes in RBCs at the molecular level.

Neural crest stem cells protect spinal cord neurons from excitotoxic damage and inhibit glial activation by secretion of brain-derived neurotrophic factor.

The acute phase of spinal cord injury is characterized by excitotoxic and inflammatory events that mediate extensive neuronal loss in the gray matter. Neural crest stem cells (NCSCs) can exert neuroprotective and anti-inflammatory effects that may be mediated by soluble factors. We therefore hypothesize that transplantation of NCSCs to acutely injured spinal cord slice cultures (SCSCs) can prevent neuronal loss after excitotoxic injury. NCSCs were applied onto SCSCs previously subjected to N-methyl-D-aspartate (NMDA)-induced injury. Immunohistochemistry and TUNEL staining were used to quantitatively study cell populations and apoptosis. Concentrations of neurotrophic factors were measured by ELISA. Migration and differentiation properties of NCSCs on SCSCs, laminin, or hyaluronic acid hydrogel were separately studied. NCSCs counteracted the loss of NeuN-positive neurons that was otherwise observed after NMDA-induced excitotoxicity, partly by inhibiting neuronal apoptosis. They also reduced activation of both microglial cells and astrocytes. The concentration of brain-derived neurotrophic factor (BDNF) was increased in supernatants from SCSCs cultured with NCSCs compared to SCSCs alone and BDNF alone mimicked the effects of NCSC application on SCSCs. NCSCs migrated superficially across the surface of SCSCs and showed no signs of neuronal or glial differentiation but preserved their expression of SOX2 and Krox20. In conclusion, NCSCs exert neuroprotective, anti-apoptotic and glia-inhibitory effects on excitotoxically injured spinal cord tissue, some of these effects mediated by secretion of BDNF. However, the investigated NCSCs seem not to undergo neuronal or glial differentiation in the short term since markers indicative of an undifferentiated state were expressed during the entire observation period.

EPI-peptide designer: a tool for designing peptide ligand libraries based on epitope-paratope interactions.

MOTIVATION: Antibodies are an important class of biological drugs, but with limitations, such as inadequate pharmacokinetics, adverse immunogenicity and high production costs. Synthetic peptides for the desired target represent an important alternative to antibodies. However, no computational tool exists to guide the design of these peptides. RESULTS: To identify the interacting residues in a given antibody-antigen (Ab-Ag) interface we used Interface Interacting Residue (I2R), a selection method based on computed molecular interactions. The aggregation of all the molecular interactions between epitope and paratope residues allowed us to transform the 3D Ab-Ag complex structures into interface graphs. Based on these data and the probability of molecular interaction we developed EPI-Peptide Designer tool that uses predicted paratope residues for an epitope of interest to generate targeted peptide ligand libraries. EPI-Peptide Designer successfully predicted 301 peptides able to bind to LiD1 target protein (65% of the experimentally tested peptides), an enrichment of 22% compared to randomly generated peptides. This tool should enable the development of a new generation of synthetic interacting peptides that could be very useful in the biosensor, diagnostic and therapeutic fields. AVAILABILITY AND IMPLEMENTATION: All software developed in this work are available at http://www.biocomp.icb.ufmg.br/biocomp/ CONTACT: liza@icb.ufmg.br SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Tight focusing of laser light using a chromium Fresnel zone plate.

Using near-field scanning microscopy, we demonstrate that a 15-µm zone plate fabricated in a 70-nm chromium film sputtered on a glass substrate and having a focal length and outermost zone's width equal to the incident wavelength λ = 532 nm, focuses a circularly polarized Gaussian beam into a circular subwavelength focal spot whose diameter at the full-width of half-maximum intensity is FWHM = 0.47λ. This value is in near-accurate agreement with the FDTD-aided numerical estimate of FWHM = 0.46λ. When focusing a Gaussian beam linearly polarized along the y-axis, an elliptic subwavelength focal spot is experimentally found to measure FWHMx = 0.42λ (estimated value FWHMx = 0.40λ) and FWHMy = 0.64λ. The subwavelength focal spots presented here are the tightest among all attained so far for homogeneously polarized beams by use of non-immersion amplitude zone plates.

[Endovideosurgery (minimally invasive surgery) in treatment for malignant tumors of female genital organs: a 5-year experience of the clinic of the N.N.Petrov Research Institute of Oncology].

During the period of 2010-2015 laparoscopic surgery was performed in 1263 patients: 1113 with endometrial cancer (588 hysterectomies, 509 hysterectomies with pelvic lymphadenectomy, among them 16 with sentinel lymph node (SLN) mapping with Indocyanine green (ICG)); 86 with cervical cancer (80 nerve-sparing radical hysterectomies (NSRH), among them 15 with SLN mapping, 6 radical vaginal trachelectomies with endovideoassisted lymphadenectomy); 64 with ovarian malignancies. The average operating time in the group of hysterectomies was 101 minutes, in the group of hysterectomies with pelvic lymphadenectomy - 184 minutes, in the group of NSRH - 230 minutes. Average blood loss was less than 50 ml. No intraoperative complications were registered. Asymptomatic lymph cysts were observed in 122 cases. Symptomatic lymph cysts requiring surgical treatment were registered in 9 cases. Inconsistencies of vaginal sutures after radical hysterectomy were in two cases, ureterovaginal fistulas - in two cases. During a 3-year follow-up period twelve recurrences were observed in endometrial cancer patients (12/443; 2,7%), four patients (0,9%) died from disease. After NSRH two local recurrences (2,5%) were registered in patients with cervical cancer, after radical trachelectomy -two local recurrences (33%). One patient became pregnant in the group of vaginal trachelectomies. Therefore laparoscopic approach in treatment of female genital malignacies allows performing an adequate volume of surgery with minimal risk of intra- and postoperative complications, favorable course of the rehabilitation period, and oncological safety.

Disorders in the Morphology and Nanostructure of Erythrocyte Membranes after Long-term Storage of Erythrocyte Suspension: Atomic Force Microscopy Study.

Disorders in the erythrocyte morphology and structure of their membranes during long-term storage of erythrocyte suspension (30 days at 4°C) were studied by atomic force microscopy. The morphology and nanostructure of erythrocyte membranes, biochemical parameters, ion exchange parameters, and hemoglobin spectra were recorded. The transformation of erythrocyte morphology and destruction of their membranes were observed throughout the storage period. Irreversible forms of spheroechinocytes and their fragments formed by the end of storage. The concentrations of potassium ions and lactate in solution of the blood preservatiive increased, while pH value decreased. Hemolysis detected by the erythrocyte "leakage" effect was observed starting from days 16-23 of storage.

[FUNCTIONAL CONDITION OF KIDNEYS IN NEWBORNS WITH CONGENITAL MALFORMATIONS IN THE PERIOPERATIVE PERIOD].

The article deals with results of the study of functional condition of kidneys in newborns with congenital surgical pathology in the perioperative period. Serum cystatin C and urine ß2-microglobulin were used as a marker of acute kidney injury (AKI). The evaluation of parameters was given in dynamics--before and after surgery, and on 1st, 5th and 10th postoperative day. We analyzed prospects of using these markers in the diagnosis of AKI.

[Role of children physical development in radiation hygienic monitoring system].

The article deals with longstanding work on studies of physical development parameters among preschoolers aged 4-7 and dwelling on territories near to objects with potential radiation danger, also on radiation-connected anxiety in parents of the examined children. The stated objects when exploited in normal mode were proved to cause no influence on the children's development. Social and economical factors appeared to play leading role in developmental parameters formation. Increased level of radiation-connected anxiety in parents of the children examined appeared to be out of proportion to real favorable radiation background of the territories examined.

Differentiating neural crest stem cells induce proliferation of cultured rodent islet beta cells.

AIMS/HYPOTHESIS: Efficient stimulation of cycling activity in cultured beta cells would allow the design of new strategies for cell therapy in diabetes. Neural crest stem cells (NCSCs) play a role in beta cell development and maturation and increase the beta cell number in co-transplants. The mechanism behind NCSC-induced beta cell proliferation and the functional capacity of the new beta cells is not known. METHODS: We developed a new in vitro co-culture system that enables the dissection of the elements that control the cellular interactions that lead to NCSC-dependent increase in islet beta cells. RESULTS: Mouse NCSCs were cultured in vitro, first in medium that stimulated their proliferation, then under conditions that supported their differentiation. When mouse islet cells were cultured together with the NCSCs, more than 35% of the beta cells showed cycle activity. This labelling index is more than tenfold higher than control islets cultured without NCSCs. Beta cells that proliferated under these culture conditions were fully glucose responsive in terms of insulin secretion. NCSCs also induced beta cell proliferation in islets isolated from 1-year-old mice, but not in dissociated islet cells isolated from human donor pancreas tissue. To stimulate beta cell proliferation, NCSCs need to be in intimate contact with the beta cells. CONCLUSIONS/INTERPRETATION: Culture of islet cells in contact with NCSCs induces highly efficient beta cell proliferation. The reported culture system is an excellent platform for further dissection of the minimal set of factors needed to drive this process and explore its potential for translation to diabetes therapy.

Reversible zinc-induced injuries to erythrocyte membrane nanostructure.

Zinc-induced injuries to red blood cell membrane nanostructures at different zinc concentrations were studied by atomic force microscopy. In order to distinguish the intrinsic characteristics of membrane nanostructures, the membrane surfaces were represented by three orders using 3D Fourier transform. Increasing the concentrations of zinc ions modified the pattern of induced injuries: their depths and diameters and their number on the membrane surface test area increased. The injuries and their distribution for each order of membrane surface were analyzed. Albumin restored membrane nanosurface.

The Toxic Influence of Excess Free Iron on Red Blood Cells in the Biophysical Experiment: An In Vitro Study.

Iron is needed for life-essential processes, but free iron overload causes dangerous clinical consequences. The study of the role of red blood cells (RBCs) in the influence of excess free iron in the blood on the pathological consequences in an organism is relevant. Here, in a direct biophysical experiment in vitro, we studied the action of free iron overload on the packed red blood cell (pRBC) characteristics. In experiments, we incubated pRBCs with the ferrous sulfate solution (Fe2+). Wе used free iron in a wide range of concentrations. High Fe2+ concentrations made us possible to establish the pattern of the toxic effect of excess iron on pRBCs during a reduced incubation time in a biophysical experiment in vitro. It was found that excess free iron causes changes in pRBC morphology, the appearance of bridges between cells, and the formation of clots, increasing the membrane stiffness and methemoglobin concentration. We created a kinetic model of changes in the hemoglobin derivatives. The complex of simultaneous distortions of pRBCs established in our experiments can be taken into account when studying the mechanism of the toxic influence of excess free iron in the blood on pathological changes in an organism.

Comparative Global Gene Expression Profiles of Wild-Type Yersinia pestis CO92 and Its Braun Lipoprotein Mutant at Flea and Human Body Temperatures.

Braun/murein lipoprotein (Lpp) is involved in inflammatory responses and septic shock. We previously characterized a Deltalpp mutant of Yersinia pestis CO92 and found that this mutant was defective in surviving in macrophages and was attenuated in a mouse inhalation model of plague when compared to the highly virulent wild-type (WT) bacterium. We performed global transcriptional profiling of WT Y. pestis and its Deltalpp mutant using microarrays. The organisms were cultured at 26 and 37 degrees Celsius to simulate the flea vector and mammalian host environments, respectively. Our data revealed vastly different effects of lpp mutation on the transcriptomes of Y. pestis grown at 37 versus 26 degrees C. While the absence of Lpp resulted mainly in the downregulation of metabolic genes at 26 degrees C, the Y. pestis Deltalpp mutant cultured at 37 degrees C exhibited profound alterations in stress response and virulence genes, compared to WT bacteria. We investigated one of the stress-related genes (htrA) downregulated in the Deltalpp mutant relative to WT Y. pestis. Indeed, complementation of the Deltalpp mutant with the htrA gene restored intracellular survival of the Y. pestis Deltalpp mutant. Our results support a role for Lpp in Y. pestis adaptation to the host environment, possibly via transcriptional activation of htrA.

[The effect of 2,4-dinitrophenol on the intensity of oxidative processes in the rat liver during prolonged experiment].

The effect of uncoupler 2,4-dinitrophenol on the oxidative processes intensity in liver biomembranes of different age and sex of rats during longitudinal experiment was studied. It was established that 2,4-dinitrophenol in the used concentration hadn't essential negative effect on the organism of females and their posterity. On the young, 3-3,5-month old males it was shown that long-term xenobiotic administration had been accompanied by intensification of the rate of oxygen consumption, decrease of the rate of reactive oxygen species formation in microsomal redox-chain, decline in lipid hydroperoxides and protein carbonils levels in blood serum and liver microsomes, and also by increase of their mean lifespan. The obtained results may testify the possibility of correction of oxidative processes intensity in tissues of mammals and their lifespan by means of modulation of membrane electron transport chains activity.