Оцінка морфофункціонального стану організму щурів за вивчення токсичності препарату на основі тилмікозину

The article presents the study results of the acute and subacute toxicity of the veterinary drug “Tylmozyn 25” (solution for oral administration) based on tilmicosin. Intra-gastric administration of “Tylmozyn 25” to white mice at a dose of 25000 mg/kg of body weight caused the death of 100% of the animals, a dose of 15000 mg/kg of body weight caused the death of 66% of the white mice. The average time of death was 2 and 5 hours correspondingly. While determining the toxicity of “Tylmozyn 25” in white rats, we did not spot the death of any studied animal at any administered dose (5000, 15000, 25000 mg/kg of body weight). Based on the result of our study, we conclude that the veterinary drug Tylmozyn 25 belongs to the fourth of toxicity class – low toxic substances. LD50 of Tylmozyn 25 in white mice is 14167 mg/kg, while in white rats LD50 is higher than 25000 mg/kg. Testing on white rats intra-gastric drug “Tylmozyn 25” during for 14 days, both in therapeutic (80 mg/kg of body weight) and 10-fold doses (800 mg/kg of body weight) did not cause animal death, but caused a decrease in body weight, a significant decrease in the coefficients of weight of the liver and spleen and a tendency to increase the coefficients of weight of the heart and lungs compared with the animals of the control group. Animals which got the drug at a dose of 800 mg/kg of body weight showed erythrocytosis, leukopenia, increased enzymatic activity of AST, ALT, and LDH, the content of total protein against to decrease urea and creatinine, which may indicate impaired liver, kidney function and hematopoietic organs. The macroscopic and microscopic structure of the internal organs of the experimental rats is preserved. Rats receiving a tenfold therapeutic dose of the drug for 14 days, histologically revealed the most granular protein dystrophy in the liver and kidneys, which was manifested by discomplexation of the lamellae, presence of hepatocytes with uneven granular cytoplasm, slightly colored cytoplasm, hypertrophied nuclei, renal convoluted tubules and narrowing of their lumen, compaction of the mesh of the renal corpuscle. In the myocardium, the branching, swelling of the muscle fibers, swelling of the stroma with cell infiltrates, mainly of the lympho-histiocytic series, was observed, which indicated the development of serosa myocarditis. Structural changes in the liver, kidneys and heart were confirmed by biochemical parameters of the enzymatic activity of the serum of rats of this group.У статті наведені результати вивчення гострої та підгострої токсичності препарату “Тилмозин 25” (розчин для перорального застосування), виготовленого на основі тилмікозину. Внутрішньошлункове введення препарату “Тилмозин 25” білим мишам, у дозі 25000 мг/кг маси тіла викликало 100% загибель тварин, доза 15000 мг/кг – 66% загибелі тварин. Середній час загибелі становив 2 та 5 годин відповідно. При визначенні гострої токсичності препарату “Тилмозин 25” на білих щурах загибелі тварин не виявляли за введення жодної з доз (5000, 15000, 25000 мг/кг маси тіла). У результаті проведених досліджень було встановлено, що препарат “Тилмозин 25” належить до 4-го класу токсичності – малотоксичні речовини. ЛД50 при його внутрішньошлунковому введенні білим мишам становить 14167 мг/кг, а для білих щурів є більшою за 25000 мг/кг. Застосування білим щурам внутрішньошлунково препарату “Тилмозин 25” впродовж 14 діб як у терапевтичній (80 мг/кг маси тіла), так і 10-кратній дозах (800 мг/кг маси тіла) не викликало загибелі тварин, проте спричиняло зменшення маси тіла, достовірне зниження коефіцієнтів маси печінки та селезінки і тенденцію до збільшення коефіцієнтів маси серця і легень порівняно з тваринами контрольної групи. У тварин, які отримували досліджуваний препарат в дозі 800 мг/кг маси тіла, встановлено еритроцитоз, лейкопенію, підвищення активності АлАТ, АсАТ, ЛДГ, вмісту загального білка на фоні зниження вмісту сечовини та креатиніну, що може вказувати на порушення функції печінки, нирок та органів кровотворення. Макроскопічна та мікроскопічна структура внутрішніх органів досліджуваних груп щурів збережена. У щурів, які отримували 10-кратну терапевтичну дозу препарату впродовж 14 діб, гістологічно виявляли вогнища зернистої білкової дистрофії в печінці та нирках, що проявлялося дискомплексацією пластинчатої будови печінкових часточок, наявність гепатоцитів з неоднорідною, зернистою, слабо забарвленою цитоплазмою та гіпертрофованими ядрами, набуханням епітелію звивистих ниркових канальців та звуженням їхнього просвіту, ущільненням сітки ниркових клубочків. У міокарді спостерігали розволокнення, набухання м’язових волокон, набряк строми з клітинними інфільтратами переважно лімфо-гістіоцитарного ряду, що вказувало на розвиток серозного міокардиту. Встановлені структурні зміни у печінці, нирках, серці були підтверджені біохімічними показниками ферментативної активності сироватки крові щурів даної групи

Atmospheric River Tracking Method Intercomparison Project (ARTMIP): project goals and experimental design

The Atmospheric River Tracking Method Intercomparison Project (ARTMIP) is an international collaborative effort to understand and quantify the uncertainties in atmospheric river (AR) science based on detection algorithm alone. Currently, there are many AR identification and tracking algorithms in the literature with a wide range of techniques and conclusions. ARTMIP strives to provide the community with information on different methodologies and provide guidance on the most appropriate algorithm for a given science question or region of interest. All ARTMIP participants will implement their detection algorithms on a specified common dataset for a defined period of time. The project is divided into two phases: Tier 1 will utilize the Modern-Era Retrospective analysis for Research and Applications, version 2 (MERRA-2) reanalysis from January 1980 to June 2017 and will be used as a baseline for all subsequent comparisons. Participation in Tier 1 is required. Tier 2 will be optional and include sensitivity studies designed around specific science questions, such as reanalysis uncertainty and climate change. High-resolution reanalysis and/or model output will be used wherever possible. Proposed metrics include AR frequency, duration, intensity, and precipitation attributable to ARs. Here, we present the ARTMIP experimental design, timeline, project requirements, and a brief description of the variety of methodologies in the current literature. We also present results from our 1-month proof-of-concept trial run designed to illustrate the utility and feasibility of the ARTMIP project

Cerebrospinal fluid levels of glial marker YKL-40 strongly associated with axonal injury in HIV infection

Background: HIV-1 infects the central nervous system (CNS) shortly after transmission. This leads to a chronic intrathecal immune activation. YKL-40, a biomarker that mainly reflects activation of astroglial cells, has not been thoroughly investigated in relation to HIV. The objective of our study was to characterize cerebrospinal fluid (CSF) YKL-40 in chronic HIV infection, with and without antiretroviral treatment (ART). Methods: YKL-40, neopterin, and the axonal marker neurofilament light protein (NFL) were analyzed with ELISA in archived CSF samples from 120 HIV-infected individuals (85 untreated neuroasymptomatic patients, 7 with HIVassociated dementia, and 28 on effective ART) and 39 HIV-negative controls. Results: CSF YKL-40 was significantly higher in patients with HIV-associated dementia compared to all other groups. It was also higher in untreated neuroasymptomatic individuals with CD4 cell count < 350 compared to controls. Significant correlations were found between CSF YKL-40 and age (r = 0.38, p < 0.001), CD4 (r = − 0.36, p < 0. 001), plasma HIV RNA (r = 0.35, p < 0.001), CSF HIV RNA (r = 0.35, p < 0.001), CSF neopterin (r = 0.40, p < 0.001), albumin ratio (r = 0.44, p < 0.001), and CSF NFL (r = 0.71, p < 0.001). Age, CD4 cell count, albumin ratio, and CSF HIV RNA were found as independent predictors of CSF YKL-40 concentrations in multivariable analysis. In addition, CSF YKL-40 was revealed as a strong independent predictor of CSF NFL together with age, CSF neopterin, and CD4 cell count. Conclusions: CSF YKL-40 is a promising biomarker candidate for understanding the pathogenesis of HIV in the CNS. The strong correlation between CSF YKL-40 and NFL suggests a pathogenic association between astroglial activation and axonal injury, and implies its utility in assessing the prognostic value of YKL-40

K2 Observations of SN 2018oh Reveal a Two-Component Rising Light Curve for a Type Ia Supernova

We present an exquisite, 30-min cadence Kepler (K2) light curve of the Type Ia supernova (SN Ia) 2018oh (ASASSN-18bt), starting weeks before explosion, covering the moment of explosion and the subsequent rise, and continuing past peak brightness. These data are supplemented by multi-color Pan-STARRS1 and CTIO 4-m DECam observations obtained within hours of explosion. The K2 light curve has an unusual two-component shape, where the flux rises with a steep linear gradient for the first few days, followed by a quadratic rise as seen for typical SNe Ia. This "flux excess" relative to canonical SN Ia behavior is confirmed in our $i$-band light curve, and furthermore, SN 2018oh is especially blue during the early epochs. The flux excess peaks 2.14$\pm0.04$ days after explosion, has a FWHM of 3.12$\pm0.04$ days, a blackbody temperature of $T=17,500^{+11,500}_{-9,000}$ K, a peak luminosity of $4.3\pm0.2\times10^{37}\,{\rm erg\,s^{-1}}$, and a total integrated energy of $1.27\pm0.01\times10^{43}\,{\rm erg}$. We compare SN 2018oh to several models that may provide additional heating at early times, including collision with a companion and a shallow concentration of radioactive nickel. While all of these models generally reproduce the early K2 light curve shape, we slightly favor a companion interaction, at a distance of $\sim$$2\times10^{12}\,{\rm cm}$ based on our early color measurements, although the exact distance depends on the uncertain viewing angle. Additional confirmation of a companion interaction in future modeling and observations of SN 2018oh would provide strong support for a single-degenerate progenitor system

Photometric and Spectroscopic Properties of Type Ia Supernova 2018oh with Early Excess Emission from the Kepler 2 Observations

Supernova (SN) 2018oh (ASASSN-18bt) is the first spectroscopically confirmed Type Ia supernova (SN Ia) observed in the Kepler field. The Kepler data revealed an excess emission in its early light curve, allowing us to place interesting constraints on its progenitor system. Here we present extensive optical, ultraviolet, and near-infrared photometry, as well as dense sampling of optical spectra, for this object. SN 2018oh is relatively normal in its photometric evolution, with a rise time of 18.3 ± 0.3 days and Δm 15(B) = 0.96 ± 0.03 mag, but it seems to have bluer B − V colors. We construct the "UVOIR" bolometric light curve having a peak luminosity of 1.49 × 1043 erg s−1, from which we derive a nickel mass as 0.55 ± 0.04 M ⊙ by fitting radiation diffusion models powered by centrally located 56Ni. Note that the moment when nickel-powered luminosity starts to emerge is +3.85 days after the first light in the Kepler data, suggesting other origins of the early-time emission, e.g., mixing of 56Ni to outer layers of the ejecta or interaction between the ejecta and nearby circumstellar material or a nondegenerate companion star. The spectral evolution of SN 2018oh is similar to that of a normal SN Ia but is characterized by prominent and persistent carbon absorption features. The C ii features can be detected from the early phases to about 3 weeks after the maximum light, representing the latest detection of carbon ever recorded in an SN Ia. This indicates that a considerable amount of unburned carbon exists in the ejecta of SN 2018oh and may mix into deeper layers

Extruded bread classification on the basis of acoustic emission signal with application of artificial neural networks

The presented work covers the problem of developing a method of extruded bread classification with the application of artificial neural networks. Extruded flat graham, corn, and rye breads differening in water activity were used. The breads were subjected to the compression test with simultaneous registration of acoustic signal. The amplitude-time records were analyzed both in time and frequency domains. Acoustic emission signal parameters: single energy, counts, amplitude, and duration acoustic emission were determined for the breads in four water activities: initial (0.362 for rye, 0.377 for corn, and 0.371 for graham bread), 0.432, 0.529, and 0.648. For classification and the clustering process, radial basis function, and self-organizing maps (Kohonen network) were used. Artificial neural networks were examined with respect to their ability to classify or to cluster samples according to the bread type, water activity value, and both of them. The best examination results were achieved by the radial basis function network in classification according to water activity (88%), while the self-organizing maps network yielded 81% during bread type clustering