Kraichnan model of passive scalar advection

A simple model of a passive scalar quantity advected by a Gaussian non-solenoidal ("compressible") velocity field is considered. Large order asymptotes of quantum-field expansions are investigated by instanton approach. The existence of finite convergence radius of the series is proved, a position and a type of the corresponding singularity of the series in the regularization parameter are determined. Anomalous exponents of the main contributions to the structural functions are resummed using new information about the series convergence and two known orders of the expansion.Comment: 21 page

LONG-LIVED BONE MARROW PLASMA CELLS DURING IMMUNE RESPONSE TO ALPHA (1→3) DEXTRAN

Production kinetics and some functional properties of long-lived marrow plasma cells were studied in mice immunized with T-independent type 2 antigens. Alpha (1→3) dextran was used as an antigen for immunization. The mice were immunized by dextran, and the numbers of IgM antibody producing cells were determined by ELISPOT method. The cell phenotype was determined by cytofluorimetric technique. In the area of normal bone marrow lymphocytes ~4% of T and ~85% of B cells were detected. About 35% of the cells expressed a plasmocyte marker (CD138); 3% were CD138+IgM+, and about 6% of the lymphocytes were double-positive for CD138+IgA+. Among spleen lymphocytes, 50% of T and 47% of B cells were detected. About 1.5% lymphocytes were CD138+, and 0.5% were positive for CD138 and IgM. Time kinetics of antibody-producing cells in bone marrow and spleen was different. In spleen populations, the peak amounts of antibody-secreting cells have been shown on the day 4; the process abated by the day 28. Vice versa, the numbers of the antibody-producing cells in bone marrow started to increase on the day 4. The process reached its maximum on day 14, and after 28th day became stationary. The in vitro experiments have shown that supplementation of bone marrow cells from immune mice with dextran did not influence their functional activity. It was previously shown for cells responding to T-dependent antigens only. A specific marker for the long-lived plasma cells is still unknown. However, these cells possess a common CD138 marker specific for all plasma cells. A method for isolation of bone marrow CD138+ cells was developed. The CD138+ cells were of 87-97% purity, being enriched in long-lived bone marrow cells, and produced monospecific antibodies

HR‐pQCT measures of bone microarchitecture predict fracture : systematic review and meta‐analysis

HR‐pQCT is a non‐invasive imaging modality for assessing volumetric bone mineral density (vBMD) and microarchitecture of cancellous and cortical bone. The objective was to (i) assess fracture‐associated differences in HR‐pQCT bone parameters and (ii) to determine if HR‐pQCT is sufficiently precise to reliably detect these differences in individuals. We systematically identified 40 studies that used HR‐pQCT (39/40 used XtremeCT scanners) to assess 1291‐3253 and 3389‐10,687 individuals with and without fractures, respectively, ranging in age from 10.9 to 84.7 years with no comorbid conditions. Parameters describing radial and tibial bone density, microarchitecture, and strength were extracted and percentage differences between fracture and control subjects were estimated using a random effects meta‐analysis. An additional meta‐analysis of short‐term in vivo reproducibility of bone parameters assessed by XtremeCT was conducted to determine whether fracture‐associated differences exceeded the least significant change (LSC) required to discern measured differences from precision error. Radial and tibial HR‐pQCT parameters, including failure load, were significantly altered in fracture subjects, with differences ranging from −2.6% (95% CI: −3.4 to −1.9) in radial cortical vBMD to −12.6% (95% CI: −15.0 to −10.3) in radial trabecular vBMD. Fracture‐associated differences reported by prospective studies were consistent with those from retrospective studies, indicating that HR‐pQCT can predict incident fracture. Assessment of study quality, heterogeneity and publication biases verified the validity of these findings. Finally, we demonstrated that fracture‐associated deficits in total and trabecular vBMD, and certain tibial cortical parameters, can be reliably discerned from HR‐pQCT‐related precision error and can be used to detect fracture‐associated differences in individual patients. Although differences in other HR‐pQCT measures, including failure load, were significantly associated with fracture, improved reproducibility is needed to ensure reliable individual cross‐sectional screening and longitudinal monitoring. In conclusion, our study supports the use of HR‐pQCT in clinical fracture prediction

Optimizing Combination Therapies with Existing and Future CML Drugs

Small-molecule inhibitors imatinib, dasatinib and nilotinib have been developed to treat Chromic Myeloid Leukemia (CML). The existence of a triple-cross-resistant mutation, T315I, has been a challenging problem, which can be overcome by finding new inhibitors. Many new compounds active against T315I mutants are now at different stages of development. In this paper we develop an algorithm which can weigh different combination treatment protocols according to their cross-resistance properties, and find the protocols with the highest probability of treatment success. This algorithm also takes into account drug toxicity by minimizing the number of drugs used, and their concentration. Although our methodology is based on a stochastic model of CML microevolution, the algorithm itself does not require measurements of any parameters (such as mutation rates, or division/death rates of cells), and can be used by medical professionals without a mathematical background. For illustration, we apply this algorithm to the mutation data obtained in [1], [2]

Комплексная оценка сортов календулы лекарственной по содержанию основных фармакологически значимых соединений

Relevance. The demand for medicinal raw materials of Calendula officinalis L. is determined by the high content of pharmacologically significant compounds. Comparison of the most common ornamental cultivars of Calendula officinalis L.) in terms of yield and content of biologically active substances in the raw material helps to identify the most promising cultivars in terms of a set of indicators.Materials and methods.The decorative cultivars Apricot, Art Shads, Fiesta Gitana, Kabluna golden-yellow, Orange King, Orange Balls, Yellow Gitana and Golden Balls, characterized by large inflorescences and terry, were used as prototypes. The cultivar Kalta, widely used for the production of medicinal raw materials, was chosen as a control. The experiments were laid on the experimental plots of the Fruit Growing Laboratory of the Russian State Agricultural University – Moscow Timiryazev Agricultural Academy. Productivity was determined as the total weight of inflorescences harvested during the entire season per unit area. The amount of flavonoids was determined by spectrophotometry. The amount of polysaccharides was determined according to the modified Draywood method. The lutein content was determined by HPLC.Results.To obtain inflorescences we can recommend to use the variety Orange King, which, with a satisfactory yield (0.363 kg/m2), was characterized by a high content of flavonoids (1.2%) and satisfactory (35.9%) extractives and corresponds to the quality of raw materials required by GF XIV. In addition, this variety was characterized by an increased content of polysaccharides (20.3%). The Varieties Apricot and Yellow Gitana were characterized by high productivity (562±49 and 507±41 g/m2, respectively). Their raw materials can be used by production of herbal teas, where the content of flavonoids is not regulated. As sources of lutein, one should pay attention to the ligulate flowers of the varieties Apricot, Fiesta Gitana, Golden balls. In the variety Kabluna, with the maximum lutein content, the proportion of reed flowers in the inflorescence was only 38%. In varieties with large inflorescences, the content of lutein in reed flowers was higher (R=0.685). Large non-double inflorescences will be most productive in this indicator.Актуальность. Ценность лекарственного сырья Calendula officinalis L. определяется высоким содержанием фармакологически значимых соединений (ФЗС). Комплексная оценка содержания ФЗС и взаимосвязей между их содержанием в декоративных сортах может служить обоснованием для их отбора и дальнейшего выращивания с целью получения высококачественного лекарственного растительного сырья.Материалы и методы. В качестве опытных образцов использовались сорта декоративного назначения Абрикос, Арт Шедс, Фиеста Гитана, Каблуна золотисто-желтая, Оранжевый Король, Оранжевые Шары, Еллоу Гитана и Золотые Шары, характеризующиеся крупными соцветиями и махровостью. В качестве контроля был выбран сорт Кальта, широко используемый для получения лекарственного сырья. Опыты закладывали на опытных участках Лаборатории плодоводства ФГБОУ ВО РГАУ-МСХА имени К.А. Тимирязева. Урожайность определяли как суммарную массу соцветий, собранных в течение всего сезона с единицы площади. Сумму флавоноидов определяли спектрофотометрическим методом по реакции комплексообразования с AlCl3 в пересчёте на рутин. Сумму полисахаридов определяли по модифицированному методу Дрейвуда. Содержание лютеина определяли методом ВЭЖХ.Результаты. Для получения соцветий, являющихся в нашей стране основным видом лекарственного сырья, можно рекомендовать использование сорта Оранжевый король, который при удовлетворительной урожайности (0,363 кг/м2) характеризовался высоким содержанием флавоноидов (1,2%) и удовлетворительным (35,9%) экстрактивных веществ, что соответствует требуемому ГФ XIV качеству сырья. Данный сорт характеризовался повышенным содержанием полисахаридов (20,3%). Абрикос и Еллоу Гитана характеризовались высокой урожайностью соцветий (562±49 и 507±41 г/м2 соответственно). Их сырьё возможно использовать при производстве фиточаёв, где содержание флавоноидов не регламентировано. В качестве источников лютеина следует обратить внимание на язычковые цветки сортов Абрикос, Фиеста Гитана, Золотые шары. У сорта Каблуна при максимальном содержании лютеина, доля язычковых цветков в соцветии составила всего 38%. У сортов с крупными соцветиями содержание лютеина в язычковых цветках было больше (R=0,685). Максимально продуктивны по этому показателю будут крупные немахровые соцветия

Analysis of a microscopic stochastic model of microtubule dynamic instability

A novel theoretical model of dynamic instability of a system of linear (1D) microtubules (MTs) in a bounded domain is introduced for studying the role of a cell edge in vivo and analyzing the effect of competition for a limited amount of tubulin. The model differs from earlier models in that the evolution of MTs is based on the rates of single unit (e.g., a heterodimer per protofilament) transformations, in contrast to postulating effective rates/frequencies of larger-scale changes, extracted, e.g., from the length history plots of MTs. Spontaneous GTP hydrolysis with finite rate after polymerization is assumed, and theoretical estimates of an effective catastrophe frequency as well as other parameters characterizing MT length distributions and cap size are derived. We implement a simple cap model which does not include vectorial hydrolysis. We demonstrate that our theoretical predictions, such as steady state concentration of free tubulin, and parameters of MT length distributions, are in agreement with the numerical simulations. The present model establishes a quantitative link between microscopic parameters governing the dynamics of MTs and macroscopic characteristics of MTs in a closed system. Lastly, we use a computational Monte Carlo model to provide an explanation for non-exponential MT length distributions observed in experiments. In particular, we show that appearance of such non-exponential distributions in the experiments can occur because the true steady state has not been reached, and/or due to the presence of a cell edge.Comment: 14 pages, 7 figure

Термодинамико-топологический анализ бутанольно-толуольной смеси

The object of the research is a butanol-toluene mixture (BLS), which is a waste product of organosilicon enamels and consists of organic substances. In order to create a basic technological scheme of separation, thermodynamic-topological analysis was applied that takes into account the peculiarities of the rectification process in the poly-azeotrope mixture. The presence of 7 binary and 5 ternary azeotropes in the system was found. Singular points of the pentatope are considered. The distillation and rectification zones are determined. Flow graphs options separation were drawn, which can be the basis for the development of a technological scheme for the separation of the studied mixtures.В работе проведен термодинамико-топологический анализ бутанольно-толуольной смеси, образующейся в качестве отхода в лакокрасочной промышленности. Представлен анализ концентрационного образа изучаемой смеси - пентатопа, рассмотрены составляющие его симплексы меньшей размерности - тетраэдры. Синтезированы основные пути разделения бутанольно-толуольной смеси в виде потоковых графов

A Patient with 38 Years of Smoking History and Severe Shortness of Breath

Aim: to present a clinical case of post-COVID bronchiolitis in an adult.Key points. A 54-year-old female patient with a long history of smoking was hospitalized in the pulmonology department of the Clinic with a leading complaint of progressive shortness of breath after a COVID-19 infection. The diagnosis was established: bilateral bronchiolitis associated with a new coronavirus infection (SARS-CoV-2 polymerase chain reaction — positive); chronic obstructive pulmonary disease stage II according to GOLD (Global Initiative for Chronic Obstructive Lung Disease), exacerbation. Against the background of the therapy, there was a significant positive dynamics in well-being and in CT-picture of bronchiolitis. The patient was discharged for outpatient follow-up treatment. One of the most common symptoms of post-COVID syndrome is shortness of breath. Diagnosis of bronchiolitis, in which this symptom may be the only one, is difficult, especially in patients with a long history of smoking and the presence of comorbid pulmonary pathology.Conclusion. A clinical case of bilateral bronchiolitis in the framework of the post-COVID syndrome is presented. The key to successful diagnosis of bronchiolitis is a thorough differential analysis of the totality of anamnestic and clinical laboratory data, as well as a characteristic CT pattern

Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib

Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF), together with imatinib, has led to a significant reduction in leukemic stem cells in vitro. In this paper, we design a novel mathematical model of stem cell quiescence to investigate the treatment response to imatinib and G-CSF. We find that the addition of G-CSF to an imatinib treatment protocol leads to observable effects only if the majority of leukemic stem cells are quiescent; otherwise it does not modulate the leukemic cell burden. The latter scenario is in agreement with clinical findings in a pilot study administering imatinib continuously or intermittently, with or without G-CSF (GIMI trial). Furthermore, our model predicts that the addition of G-CSF leads to a higher risk of resistance since it increases the production of cycling leukemic stem cells. Although the pilot study did not include enough patients to draw any conclusion with statistical significance, there were more cases of progression in the experimental arms as compared to continuous imatinib. Our results suggest that the additional use of G-CSF may be detrimental to patients in the clinic