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Abstract We continue the study of n-dependent groups, fields and related structures, largely motivated by the conjecture that every n-dependent field is dependent. We provide evidence toward this conjecture by showing that every infinite n-dependent valued field of positive characteristic is henselian, obtaining a variant of Shelah’s Henselianity Conjecture in this case and generalizing a recent result of Johnson for dependent fields. Additionally, we prove a result on intersections of type-definable connected components over generic sets of parameters in n-dependent groups, generalizing Shelah’s absoluteness of $G^{00}$ in dependent theories and relative absoluteness of $G^{00}$ in $2$ -dependent theories. In an effort to clarify the scope of this conjecture, we provide new examples of strictly $2$ -dependent fields with additional structure, showing that Granger’s examples of non-degenerate bilinear forms over dependent fields are $2$ -dependent. Along the way, we obtain some purely model-theoretic results of independent interest: we show that n-dependence is witnessed by formulas with all but one variable singletons; provide a type-counting criterion for $2$ -dependence and use it to deduce $2$ -dependence for compositions of dependent relations with arbitrary binary functions (the Composition Lemma); and show that an expansion of a geometric theory T by a generic predicate is dependent if and only if it is n-dependent for some n, if and only if the algebraic closure in T is disintegrated. An appendix by Martin Bays provides an explicit isomorphism in the Kaplan-Scanlon-Wagner theorem.

Relevance. Long-term results of treatment of patients with widespread drug-resistant tuberculosis are not presented in the medical literature. Objective. Study the efficacy and long-term results of treatment of patients with widespread drug-resistant tuberculosis using bedaquiline. Material and methods. Two groups of patients with widespread drug-resistant tuberculosis were formed, who received bedaquiline as the base drug of the chemotherapy course: bedaquiline in the main group (49 people) and moxifloxacin in the control group (76 people). The results of treatment at the end of the course of chemotherapy and after three years of follow-up were studied. Results. 87.8±9.2% of patients from the main group completed an effective course of treatment with sputum culture control. In 67.3±13.1%, the cessation of bacillus excretion was achieved at 1–2 months of treatment. Undesirable effects of chemotherapy were noted in 10.2–32.7% of cases, with prolongation of the QT interval only in 8.2±7.7% of patients. After a three-year dispensary follow-up, there was no recurrence of tuberculosis in the main group, chronic obstructive pulmonary disease was less common for the fifirst time, no cases of treatment by a cardiologist and gynecologist were found, the transfer of patients from the second disability group to the third was more often observed. Conclusion. The use of bedaquiline for the treatment of patients with widespread drug-resistant tuberculosis makes it possible to achieve early cessation of bacillus excretion with transfer to outpatient treatment, reduce the frequency of adverse reactions of chemotherapy. The long-term results of dispensary observation indicate a low risk of reactivation of tuberculosis, a significant reduction in the need for dispensary observation by other specialists, including a cardiologist, and improvement in the results of complex rehabilitation.

Abstract Background Primary hyperparathyroidism (PHPT) is a common endocrine disorder caused by a parathyroid tumor or hyperplasia, which is often accompanied with quality of life (QoL) impairment. A parathyroidectomy (PTX) is the preferred standard treatment for PHPT patients. In this single center study we aimed to evaluate the impact of PHPT on patient’s QoL and identify QoL changes at early and long-term follow-up after surgery. Methods All the patients underwent routine PTX with the removal of the suspected hyperparathyroid gland(s). Patients filled out generic QoL questionnaire RAND SF-36, specific questionnaire PHPQoL and specific symptom assessment questionnaire PAS upon admission to the hospital before surgery, at 3 months, 12 months and 24 months after surgery. Results A total of 92 patients with PHPT (median age was 56 years, 95.7% females) were included in the study. Before PTX patient’s QoL by SF-36 scores was significantly lower as compared to healthy controls (p

Abstract: A bipartite graph$H = \left (V_1, V_2; E \right )$with$\lvert V_1\rvert + \lvert V_2\rvert = n$issemilinearif$V_i \subseteq \mathbb {R}^{d_i}$for some$d_i$and the edge relationEconsists of the pairs of points$(x_1, x_2) \in V_1 \times V_2$satisfying a fixed Boolean combination ofslinear equalities and inequalities in$d_1 + d_2$variables for somes. We show that for a fixedk, the number of edges in a$K_{k,k}$-free semilinearHis almost linear inn, namely$\lvert E\rvert = O_{s,k,\varepsilon }\left (n^{1+\varepsilon }\right )$for any$\varepsilon> 0$; and more generally,$\lvert E\rvert = O_{s,k,r,\varepsilon }\left (n^{r-1 + \varepsilon }\right )$for a$K_{k, \dotsc ,k}$-free semilinearr-partiter-uniform hypergraph. As an application, we obtain the following incidence bound: given$n_1$points and$n_2$open boxes with axis-parallel sides in$\mathbb {R}^d$such that their incidence graph is$K_{k,k}$-free, there can be at most$O_{k,\varepsilon }\left (n^{1+\varepsilon }\right )$incidences. The same bound holds if instead of boxes, one takes polytopes cut out by the translates of an arbitrary fixed finite set of half-spaces. We also obtain matching upper and (superlinear) lower bounds in the case of dyadic boxes on the plane, and point out some connections to the model-theoretic trichotomy ino-minimal structures (showing that the failure of an almost-linear bound for some definable graph allows one to recover the field operations from that graph in a definable manner).

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding their applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

The article presents a brief review of cooling systems that ensure various temperature levels (from 0.1 K to 230 K) for radio astronomical receivers of photonic and electronic (or optical and radio) devices. The features of various cooling levels and the requirements for the design of the cooling systems are considered in detail, as well as the approaches to designing interfaces for cooled receivers: vacuum, cryogenic, electrical, mechanical, optical, and other interfaces required for effective operation. The presented approaches to design are illustrated by a series of joint developments of the authors carried out over the past 45 years, including those produced over the past year.

Cholesterol siRNA conjugates attract attention because they allow the delivery of siRNA into cells without the use of transfection agents. In this study, we compared the efficacy and duration of silencing induced by cholesterol conjugates of selectively and totally modified siRNAs and their heteroduplexes of the same sequence and explored the impact of linker length between the 3′ end of the sense strand of siRNA and cholesterol on the silencing activity of “light” and “heavy” modified siRNAs. All 3′-cholesterol conjugates were equally active under transfection, but the conjugate with a C3 linker was less active than those with longer linkers (C8 and C15) in a carrier-free mode. At the same time, they were significantly inferior in activity to the 5′-cholesterol conjugate. Shortening the sense strand carrying cholesterol by two nucleotides from the 3′-end did not have a significant effect on the activity of the conjugate. Replacing the antisense strand or both strands with fully modified ones had a significant effect on silencing as well as improving the duration in transfection-mediated and carrier-free modes. A significant 78% suppression of MDR1 gene expression in KB-8-5 xenograft tumors developed in mice promises an advantage from the use of fully modified siRNA cholesterol conjugates in combination chemotherapy.

We establish a cutting lemma for definable families of sets in distalstructures, as well as the optimality of the distal cell decomposition fordefinable families of sets on the plane in $o$-minimal expansions of fields.Using it, we generalize the results in [J. Fox, J. Pach, A. Sheffer, A. Suk,and J. Zahl. "A semi-algebraic version of Zarankiewicz's problem"] on thesemialgebraic planar Zarankiewicz problem to arbitrary $o$-minimal structures,in particular obtaining an $o$-minimal generalization of theSzemer\'edi-Trotter theorem.

AbstractWe prove that every ultraproduct of p-adics is inp-minimal (i.e., of burden 1). More generally, we prove an Ax-Kochen type result on preservation of inp-minimality for Henselian valued fields of equicharacteristic 0 in the RV language.

Circadian rhythms of physiological processes, constantly being in a state of dynamic equilibrium and plastically associated with changes in environmental conditions, are the basis of homeostasis of an organism of human and other mammals. Violation of circadian rhythms due to significant disturbances in parameters of main environmental effectors (desynchronosis) leads to the development of pathological conditions and a more severe course of preexisting pathologies. We conducted the study of the ultrastructure of cells of mice transplantable malignant melanoma B16 under the condition of normal (fixed) lighting regime and under the influence of constant lighting. Results of the study show that melanoma B16 under fixed light regime represents a characteristic picture of this tumor—predominantly intact tissue with safe junctions of large, functionally active cells with highly irregular nuclei, developed organelles and a relatively low content of melanin. The picture of the B16 melanoma tissue structure and the ultrastructure of its cells under the action of constant lighting stand in marked contrast to the group with fixed light: under these conditions the tumor exhibits accelerated growth, a significant number of cells in the state of apoptosis and necrosis, ultrastructural signs of degradation of the structure and functions, and signs of embryonization of cells with the background of adaptation to oxygen deficiency.

Sarcoidosis, as systemic epithelioid cell granulomatosis, can be accompanied by damage not only to the intrathoracic lymph nodes and lungs, but also to other organs, in particular, the central nervous system and peripheral lymph nodes. In the spectrum of extrathoracic lesions, spinal cord sarcoidosis occurs only in 6-8 % of cases of all brain lesions. The presented clinical example illustrates the lesion of the spinal cord at the level of the thoracic region, although the literature more often describes the lesion of the cervical region. The disease was accompanied by sarcoidosis of the intrathoracic lymph nodes with rapid spontaneous regression and sarcoidosis of the supraclavicular lymph node. The diagnosis was confirmed after a peripheral lymph node biopsy. Spinal cord sarcoidosis in this patient was characterized by rapid regression against the background of parenteral administration of dexamethasone for 14 days, followed by transfer to tablet forms of prednisone. The positive dynamics of spinal cord sarcoidosis refuted the assumption of the presence of a sarcoid reaction in the lymph nodes against the background of a spinal cord tumor. The use of a course of rehabilitation techniques contributed to the recovery of working capacity.

Background. For many years the primary aim of treatment strategy for ph-negative myeloproliferative neoplasms has been to restrain disease progression, with lasting relief and management of symptoms to improve patients’ quality of life. Generally, this did not lead to a significant increase in life expectancy with primary myelofibrosis and didn’t decrease the risk of fibrosis in patients with polycythemia vera and essential thrombocythemia. To date a new class of targeted drugs has been developed, it is JAK2 inhibitors with pathogenetic effects. The results of clinical trials showed the high efficacy of the first registered drug of this its kind – ruxolitinib – that includes a faster reduction in the symptoms of tumor intoxication and in symptoms associated with the development of splenomegaly and increase in the overall survival rates. It is known that the data obtained during clinical trials of medicines may differ from the results obtained in routine clinical practice. In actual practice drugs are used in a much wider heterogeneous population of patients, less limited first of all by age and comorbid characteristics. It is possible to analyze cohorts of patients including a larger number of clinical cases with a longer follow-up period. In this regard of great interest is the actual clinical experience of long-term use of ruxolitinib in patients whose set is limited only by clinical contraindications for prescribing the drug.Aim. To present our own actual experience of targeted therapy of myelofibrosis and compare the results obtained with the data of clinical trials.Materials and methods. Our analysis includes data from 141 patients (67 (47.5 %) men and 74 (52.5 %) women) in a chronic phase myelofibrosis. All patients received ruxolitinib. Of these, 109 (69 %) patients had primary myelofibrosis, 26 (16 %) – postpolycythemia myelofibrosis, 6 (4 %) – postessential thrombocythemia myelofibrosis. The median age at the start of therapy was 62 (18–84) years. The median disease duration before ruxolitinib was prescribed – 79 (1–401) months. According to the dIpSS (dynamic International prognostic Scoring System) criteria, 13 % of patients were assigned to the low risk group, 38 % – to the intermediate-1, 36 % – to the intermediate-2, 13 % – to the high risk group. Most patients (52 %) had grade 3 bone marrow fibrosis.Results. The median duration of treatment was 18 (range from 1 to 115) months. Symptoms of intoxication were relieved 74 (81 %) of 91 patients, the spleen size decreased in 81 % of patients (the spleen size returned to normal in 25 % of patients). The increase in the median hemoglobin level was 15 %. The proportion of patients requiring blood transfusion decreased by 4 times (from 39 to 9 %). Mean platelet levels normalized in most patients with baseline high and low platelet levels. A complete clinical and hematological response was achieved in 16 % (n = 23) of cases, a partial response – in 26 % (n = 37) of cases, clinical improvement – in 21 % (n = 30), disease stabilization – in 33 % (n = 46) of cases. No response was received in 1 (1 %) patient and in 3 (3 %) cases there was progression of the disease. At the time of analysis, 81 (57 %) of 141 patients were continuing the ruxolitinib treatment. The fatal outcome in 33 (22 %) patients was associated with concomitant diseases, among which 20 (14 %) died from proven COvId-19 infection. Overall survival: 1-year 81 %, 2-year 73 %, 5-year 50 %. Overall survival excluding deaths due to COvId-19: 1-year 92 %, 2-year 85 %, 5-year 70 %. Massive splenomegaly and a high degree of fibrosis were unfavorable predictors of prognosis of overall survival.Conclusion. Target therapy with Janus kinase inhibitor ruxolitinib has demonstrated high efficacy in patients with myelofibrosis in routine clinical practice. The most rapid effect ruxolitinib had on the spleen size and the symptoms of intoxication. Tolerability of ruxolitinib therapy was generally satisfactory. The overall and progression-free survival rates in patients with myelofibrosis, receiving ruxolitinib in the clinical setting was consistent with the results of international multicenter clinical trials.

Here, the authors observe tightly bound, valley-polarized, UV-emissive trions in monolayer transition metal dichalcogenide transistors. These are quasiparticles composed of an electron from a high-lying conduction band with negative effective mass, a hole from the first valence band, and an additional charge from a band-edge state.

Background. Health Related Quality of Life (HRQL) is a person’s perception of the effect of a disease on physical, social and psychological functioning and wealth. Questionnaires that help assess the HRQL can give a concept of child’s state, identify arcane issues and they are of great importance for a full understanding of how the state of health affects the child. Universal HRQL tools allow to compare results with general parameters, indicators with specific symptoms better reflect clinically significant moments. The most widespread in the Russian Federation was the general PedsQLTM 4.0 questionnaire, widely used in practice to assess HRQL in children with various pathologies. Objective.The aim of the study is to describe the analysis of linguistic accuracy and authenticity of the content of the Russian version of the module of gastrointestinal symptoms of the PedsQLTM questionnaire, measuring HRQL, in children with gastrointestinal disorders (GIDs).Materials and methods. The establishment of linguistic accuracy and authenticity of the content was carried out according to international standards. The process included forward translation, scientific assessment and coordination, reverse translation, verification of the reverse translation and interviews with 17 children aged 5–18 years with symptoms of GIDs and 20 parents of children with symptoms of GIDs aged 2–18 years.Results. The Russian version of PedsQLTM module of gastrointestinal symptoms (report from children 5-18 years old, report from parents for children 2–18 years old) was developed without significant difficulties. Eight questions required discussion after the forward translation, one change was made after the reverse translation, and three changes were made after the study of the symptom’s module by patients and parents.Conclusion. A conceptually equivalent version of the of PedsQLTM module of gastrointestinal symptoms in Russian has been developed for children aged 2–18 years. It allows to improve the assessment of HRQL in children with GIDs in the Russian Federation. To assess authenticity and reliability of the Russian version of the module, it’s recommended to conduct further research using a larger sample

The development of a model for the analysis of the undisturbed state of a heat-power hydraulic system - a heat supply system, which is an important stage in the design and optimization of the system, is considered. The main parameters of the system, such as thermal loads, heat flows, heat transfer through pipes and heat exchangers, the location and characteristics of equipment (boilers, pumps, etc.) are analyzed. The development of a mathematical model of the system, which should take into account all the main factors affecting heat exchange and the efficiency of the system is completed. The model as a system of equations and includes such parameters as temperature, pressure, coolant flow, etc. is presented. Based on this model, it is possible to analyze various operating modes of the system, optimize parameters and make decisions to improve it. When developing the model, the possibility of various perturbations is taken into account. To analyze the undisturbed state of the system, the influence of such disturbances is excluded and its basic operation is considered. When developing a flow distribution analysis model for a thermal power system, energy equivalence was applied. The developed model of analysis of the undisturbed state of the thermal energy system will allow more accurately design and control such a hydraulic system, improve its efficiency and reliability.

Reviewing the experience in construction and operation of sewerage networks in areas with deep seasonal ground freezing across different regions of the Russian Federation. Methods: analyzing the sewer pipeline laying, in-situ observations of wastewater temperature regime at sewer outlets from residential buildings. Results: designs of sewer pipelines laid in different regions are presented, as well as their dependence on the depth of seasonal ground freezing in different regions of the Russian Federation. The actual values of sewage water temperature at sewage outlets from residential buildings are established. Practical significance: In a number of regions the laying of sewerage pipes at a depth of 1.5-1.8 m led to normal and stable operation of sewerage pipelines. In terms of capital expenditures, sewer pipelines account for more than 50% of the estimated cost of the entire wastewater disposal system. Their operation claims a significant share of the costs.

In this study, a new l-rhamnose-binding lectin (GYL-R) from the hemolymph of bivalve Glycymeris yessoensis was purified using affinity and ion-exchange chromatography and functionally characterized. Lectin antimicrobial activity was examined in different ways. The lectin was inhibited by saccharides possessing the same configuration of hydroxyl groups at C-2 and C-4, such as l-rhamnose, d-galactose, lactose, l-arabinose and raffinose. Using the glycan microarray approach, natural carbohydrate ligands were established for GYL-R as l-Rha and glycans containing the α-Gal residue in the terminal position. The GYL-R molecular mass determined by MALDI-TOF mass spectrometry was 30,415 Da. The hemagglutination activity of the lectin was not affected by metal ions. The lectin was stable up to 75 °C and between pH 4.0 and 12.0. The amino acid sequence of the five GYL-R segments was obtained with nano-ESI MS/MS and contained both YGR and DPC-peptide motifs which are conserved in most of the l-rhamnose-binding lectin carbohydrate recognition domains. Circular dichroism confirmed that GYL is a α/β-protein with a predominance of the random coil. Furthermore, GYL-R was able to bind and suppress the growth of the Gram-negative bacteria E. coli by recognizing lipopolysaccharides. Together, these results suggest that GYL-R is a new member of the RBL family which participates in the self-defense mechanism against bacteria and pathogens with a distinct carbohydrate-binding specificity.

Chemical chaperones are low-molecular-weight compounds that suppress protein aggregation. They can influence different stages of the aggregation process—the stage of protein denaturation, the nucleation stage and the stage of aggregate growth—and this may lead to a change in the aggregation kinetic regime. Here, the possibility of changing the kinetic regime in the presence of a chemical chaperone 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) was investigated for a test system based on the thermally induced aggregation of yeast alcohol dehydrogenase (yADH) at 56 °C. According to differential scanning calorimetry data, 2-HP-β-CD did not affect the stage of the protein molecule unfolding. Dynamic light scattering data indicated changes in the aggregation kinetics of yADH during the nucleation and aggregate growth stages in the presence of the chaperone. The analysis of kinetic curves showed that the order of aggregation with respect to protein (nc), calculated for the stage of aggregate growth, changed from nc = 1 to nc = 2 with the addition of 100 mM 2-HP-β-CD. The mechanism of 2-HP-β-CD action on the yADH thermal aggregation leading to a change in its kinetic regime of aggregation is discussed.

This research paper addresses the issues in evaluating the effectiveness of magnetic-pulse treatment for healing continuity defects in the metal of oil and gas pipelines. A theoretical analysis of the magnetic-pulse action mechanism on continuity defects in the metal was carried out. The results of experimental studies of the effect of magnetic-pulse action on continuity defects of thick-walled samples, cut from used gas pipelines containing microcracks with different geometries, are also presented. The samples were processed under two different technological operating modes of the magnetic-pulse unit: the applied energy was 10 kJ for the first mode and 20 kJ for the second mode. The state of the cracks’ microstructure before and after the magnetic pulse treatment was studied using an optical microscope. As a result of the studies, it was found that magnetic-pulse treatment led to local heating of the crack tips, which was confirmed by the formation of a heat-affected zone in the vicinity of the crack tips. The temperature at the crack tips reached the metal’s melting point at the applied energy of 20 kJ, whereas at the energy of 10 kJ, signs of metal melting were not noted. In the course of the conducted experiments, it was found that the cracks were not completely eliminated after magnetic-pulse treatment; however, the edges of the crack tips melted, with subsequent filling by molten material. Magnetic-pulse treatment resulted in blunting of the crack tips, as their shape became smoother. It was established that the geometry and shape of the crack tip have significant influences on the effectiveness of this technology, as a narrow and sharp crack tip required less energy to reach the metal’s melting point compared to smoother one. The effect of magnetic pulse treatment on the microstructure of pipeline metal and its strength characteristics was also studied. It was found that this treatment leads to structural changes in the area of the crack tip in the form of grain refinement and subsequent strengthening of the pipeline metal.

This article presents the main results and new plans for the development of receivers which are cooled cryogenically to deep cryogenic temperatures and used in optical and radio astronomy research at the Special Astrophysical Observatory of the Russian Academy of Sciences (SAO RAS) on both the Big Telescope Alt-Azimuthal optical telescope (BTA) and the Radio Astronomical Telescope Academy of Sciences (RATAN-600) radio telescope, 600 m in diameter. These two instruments almost completely cover the frequency range from long radio waves to the IR and optical bands (0.25–8 mm on RATAN and 10–0.3 μm, on BTA) with a certain gap in the terahertz part (8–0.01 mm) of the spectrum. Today, this range is of the greatest interest for astronomers. In particular, the ALMA (Atacama Large Millimeter Array) observatory and the worldwide network of modern telescopes called the EVH (Event Horizon Telescope) operate in this range. New developments at SAO RAS are aimed at mastering this part of the spectrum. Cryogenic systems of receivers in these ranges are a key element of the system and differ markedly from the cooling systems of optical and radio receivers that ensure cooling of the receivers to sub-Kelvin temperatures.