Search

Anaplastic large cell lymphoma (ALCL) expressing the anaplastic lymphoma kinase (ALK) (ALK+ ALCL) is a rare type of lymphoma which comprises 10-15% of all non-Hodgkin lymphomas in children and 2–3% in young adults. Relapsed/refractory disease occurs even more rarely (25–40% of all cases). There is as yet no standard treatment for relapsed/refractory ALK+ ALCL. Patients with ALK+ ALCL usually present at advanced stages of the disease with extranodal involvement (skin, soft tissues, bones, lungs, liver, spleen and bone marrow) and B symptoms. ALK-positive ALCL affects males more often than females. There are two morphological variants: the common type (65% of cases) and the non-common type which is associated with a poorer prognosis. ALK+ ALCLs are often associated with t(2;5) and t(1;2), resulting in the formation of the NPM-ALK and the TPM3-ALK fusion proteins, respectively. Data about the treatment of relapsed/refractory ALK+ ALCL are limited. Earlier, targeted therapies (brentuximab vedotin (BV), ALK inhibitors) and risk-adapted chemotherapy followed by hematopoietic stem cell transplantation (HSCT) for remission consolidation were shown to be highly effective. A total of 15 patients with relapsed/refractory ALK+ ALCL were treated at the R.M. Gorbacheva Research Institute starting from 2002. Fourteen (93%) patients had ALK-positive ALCL of common morphology and one (7%) patient had the non-common variant (histiocytic). The study was approved by the Independent Ethics Committee and the Scientific Council of the Pavlov University. The expression of CD3 on tumor cells was assessed (CD3 positive: n = 4 (27%), CD3 negative: n = 8 (53%), no data: n = 3 (20%). The median age at the diagnosis was 26 years (11 months– 37 years). The median follow-up from the diagnosis was 9 years (1–19 years). Nine (60%) patients were aged > 18 years and six (40%) patients were aged < 18 years. There were 10 (67%) males and 5 (33%) females. At onset, 2 (13%) patients were diagnosed with early-stage disease (stage II), while the others were diagnosed with advanced-stage disease: 2 (13%) patients had stage III disease and 11 (74%) had stage IV disease. Staging was performed according to the St. Jude staging system (in children) and the Ann Arbour staging classification (in adults). Thirteen (86%) patients had extranodal involvement. Four (27%) patients had refractory disease (progression within the first three months or the absence of complete remission after the first-line treatment) and the rest 11 (73%) patients had recurrent ALK-positive ALCL. Six patients developed early relapse (< 12 months after remission was achieved); 5 patients had late relapse (after > 12 months of remission); local (1 site) and systemic relapses were diagnosed in 7 and 4 patients, respectively. Our patients received from 2 to 7 lines of treatment (the median is 4). In the first line of therapy, the patients were treated according to NHL-BFM based regimens (n = 9; 60%), the CHOP (n = 5; 33%), and the HyperCVAD (n = 1; 7%) protocols. In the second line of therapy, 8 (53%) patients were treated according to NHL-BFM based regimens; 2 (13%) patients were treated with GDP; 1 (7%) patient received DHAP chemotherapy; 1 (7%) patient received a combination of methotrexate and vinblastine (MTX + V); 1 (7%) patient received bendamustine as a single agent. Two (13%) patients were treated with chemotherapy in combination with targeted drugs (GDP + BV, n = 1; NHL-BFM + crizotinib, n = 1). As a third or subsequent line of treatment, the patients received a variety of chemotherapy regimens (n = 5; 33%) and chemotherapy in combination with targeted drugs (n = 10; 67%). Five (33%) patients underwent ALK-inhibitor therapy (crizotinib (n = 4) and ceritinib (n = 1)). Seven (46%) patients were treated with BV (BV as a single agent (n = 4) and BV + chemotherapy (n = 3)). The median number of treatment lines before autologous HSCT (auto-HSCT) and allogeneic HSCT (allo-HSCT) was 2 (2–3) and 3 (3–4), respectively. Auto-HSCT was carried out in 11 (73%) cases. Nine (60%) patients underwent allo-HSCT (from a matched unrelated donor (n = 6), from a matched related donor (n = 2), and from a haploidentical donor (n = 1)). One patient received NK cells from a haploidentical donor as maintenance. In 5 (33%) cases, alloHSCT was carried out following auto-HSCT. The conditioning regimens (CR) used for auto-HSCT included BEAM (carmustine – 300 mg/m2, etoposide – 800 mg/m2, Cytosar – 1600 mg/m2, melphalan – 140 mg/m2) – in 5 (45%) patients; BeEAM (bendamustine – 320 mg/m2, etoposide – 800 mg/m2, Cytosar – 1600 mg/m2, melphalan – 140 mg/m2) – in 5 (45%) patients; and BuCy (Cyclophosphan – 100 mg/kg, busulfan – 14 mg/kg) – in 1 (10%) case. Seven (78%) patients undergoing allo-HSCT received the FluBenda conditioning regimen (fludarabine – 90–150 mg/m2, bendamustine – 390 mg/m2) and post-transplant Cyclophosphan and calcineurin inhibitors for the prevention of graft-versus-host disease (GVHD) (n = 7; 78%); one (11%) patient received the FluMel regimen (fludarabine – 150 mg/m2, melphalan – 140 mg/m2) and CsA/MTX (Cyclosporin А, methotrexate) for GVHD prevention; and in 1 case (11%) data on the RC and GVHD prophylaxis were missing. Overall response to the second line of treatment was achieved in 10 (67%) patients, with complete response observed in 7 (47%) cases, and partial response –in 3 (20%) cases. Five out of the 7 patients treated with BV during different lines of therapy managed to achieve complete response. Four out of the 5 patients who had undergone treatment with ALK inhibitors, demonstrated complete response. The 10-year overall survival (OS) rate of the study patients reached 90% (95% confidence interval (CI) 47–99). The 10-year progression-free survival (PFS) rate after the second line of treatment was 39% (95% CI 13–64). The 10-year OS and PFS rates after auto-HSCT were 100% and 35% (95% CI 8–64) respectively. The 5-year OS following allo-HSCT was 85% (95% CI 33–98), while PFS was 60% (95% CI 19–85). Four out of the 11 patients who had undergone auto-HSCT relapsed, and 2 patients progressed. Median time to relapse/progression was 8 (6–27) months. Three out of the 9 patients who had been treated with allo-HSCT ended up relapsing (median time: 8 (6–17) months). Two patients achieved repeated remission (in one case, it was the result of treatment with ceritinib, while in the other case it became possible after the resection of the lesion, radiotherapy and prescription of crizotinib), and 1 study patient died as a result of disease progression 17 months after allo-HSCT. The 6 patients who had achieved complete remission before undergoing allo-HSCT, are still in CR. Five out of the 9 patients developed grade I–II acute GVHD with skin involvement but did not show any signs of chronic GVHD. The observed complications of chemotherapy and auto-HSCT were standard and manageable and were not the focus of attention in this study. Taking into account the high probability of developing resistance to ALK inhibitors and the high risk of relapse after treatment with BV, targeted therapy should be used to prepare patients for HSCT. The use of ALK inhibitors and BV in our study led to repeated remission in 80% and 71% patients respectively. It was demonstrated that in the majority of cases even heavily pretreated patients with ALK+ ALCL can be cured (which is not the case with other non-Hodgkin lymphomas), especially if allogenic HSCT (allo-HSCT) is carried out. Still, we think that auto-HSCT can also be considered for remission consolidation since OS rates following auto-HSCT and allo-HSCT are comparable (100% and 85%). Moreover, auto-HSCT can also be a valid option in the absence of a fully matched donor, i.e. when only an alternative (haploidentical or partially matched) donor is available, since the use of haploidentical HSCT in ALCL patients has not been studied well enough yet. Further research on the matter is warranted. It was demonstrated that a non-myeloablative conditioning regimen before allo-HSCT (FluBenda) could be opted for in patients with relapsed/refractory ALK+ ALCL and that it was similarly effective as myeloablative RC when compared with a historical control group. Disease status before HSCT was proven to have a statistically significant influence on PFS (the best prognosis was associated with complete remission). At the same time, other factors did not impact the prognosis. This may be explained by the relatively small number of patients included in the study. Relapsed/refractory ALK+ ALCL is a disease with a relatively good prognosis even in heavily pretreated patients. Targeted therapy is a very important and effective step in preparation for HSCT. Allo-HSCT is more effective than auto-HSCT but the latter can also be considered a valid therapeutic option.

Fracture toughness of syntactic composites with various degrees of filling with hollow glass microspheres is studied. It is shown that the “area method” can be employed for calculation of the crack resistance of syntactic composites.

Multiple myeloma

For production seamless hot-rolled pipes, round continuously casted billets (CCB) are used, the diameter of which is restricted by the limit sizes of CCM moulds. The expansion of billets assortment necessary to provide pipe-rolling lines (PRL) by required diameters is possible through preliminary reduction of CCB, which is made mainly at three-roll screw-rolling mills having powerful drives. If a plant has no such mills, billets reduction can be accomplished at existing three-roll Assel’s mills being comprised by various PRLs. However, the possibilities of such mills are restricted by acceptable current loads for their drives, since they are designed to roll out pierced pipe stock, but not to reduce solid billet. To determine energy-power parameters of the process of pipe billet reduction at three-roll Assel’s mills, a mathematical model was elaborated accounting geometric, temperature, kinematic and deformation peculiarities by determination the volume of accumulated metal at each roll before rolling out, section of forming diameter of reduced pipe billet and temperature variation during the reduction. As a result, the software product “Reduction Motor Load 2020” (RML2020) was elaborated, which includes a computing kernel based on the elaborated mathematical model for determining the power parameters of the reduction process and a module for analyzing the initial data with a system of boundary conditions. The interface of the software product allows displaying the results of calculations and analysis both in numerical form and in the form of graphs. The elaborated software product contains a database of the main steel grades and allows calculating the current loads on the Assel’s mill drives during the reduction of billets made of various steel grades. The software allows also to accomplish analysis of the acceptable values of various initial parameters (diameters of the initial and reduced billets, temperature of the initial billet, feed angle and rotation frequency of rolls) to ensure the operation of the mills in the acceptable range of current loads. There is also a possibility of making a report in the form of an Excel document and collecting statistical data on the actual values of current loads. By application the RML2020 program, acceptable reduction modes of a pipe billet made of 15Х13Н2 steel (AISI 414) with a diameter of 156 mm into a billet with a diameter of 120 mm were calculated for screw Assel’s mills of PTL-1 of JSC VTZ.

The sizes of hollow glass microspheres were studied using three different methods. It is shown that the results of determining the average diameter of microspheres using a laser particle analyzer may differ markedly from the results of measurements made using sieve equipment. The most objective estimation of the size of hollow glass microspheres is provided by microscopic analysis.

Chronic lymphocytic leukemia/small lymphocytic lymphoma. Clinical recommendations

Mantle cell lymphoma. Clinical recommendations

The reaction of anilines containing a 1,2,4-oxadiazole moiety with the bis(xylylisocyanide) Pd(II) complex leads to the formation of acyclic diaminocarbene complexes. The oxadiazole ring is not involved in the reaction. Composition and structure of the obtained complexes have been confirmed by means of mass spectrometry, NMR spectroscopy, and single-crystal X-ray diffraction analysis.

Clinical recommendations.

Clinical recommendations.

Hairy cell leukemia. Clinical recommendations

A new diaminocarbene cis-palladium(II) complex containing a 2-aminobenzoxazole ligand was synthesized by reacting cis-[PdCl2(CNCy)2] and 2-aminobenzoxazole. The structure and composition of the obtained complex were proven by NMR spectroscopy and high-resolution mass spectrometry. The cytotoxicities of the obtained complex and structurally similar palladium(II) complexes containing a 2-aminothiazole ligand were tested against human cancer cells of various histogenesis (MCF-7, HL60, HeLa, DLD1, A431). The activities of several complexes against cancer cells were higher than those of the reference drug cisplatin and the free ligands, i.e., 2-aminooxazole and substituted 2-aminothiazoles.

The results of a simulation, performed using the code ATHLET/BIPR-VVER (Russia, Germany), of tests on connecting a single main circulation pump (MCP) unit with three operating units during operation of VVER-1200 at 26% normal power level are presented. A comparison of the calculation and experiment showed the accuracy of the computational model to be satisfactory. Modeling is sufficient from the stand-point of calculating the macroparameters of a reactor facility.

A method for calculating the optimal ratio of the fuel and solid propellant in the gas generator of a high-velocity flying vehicle is proposed. A thermodynamic approach is used to describe the processes in the gas generator. The ratio of the solid propellant and fuel in the gas generator is determined by their physical and chemical properties. An increase in the density and heat of combustion of the solid propellant and in the fuel porosity leads to reduction of the volume fraction of the solid propellant in the gas generator. An increase in the density, specific heat, specific heat of sublimation, and temperature of sublimation of the fuel leads to an increase in the volume fraction of the solid propellant in the gas generator.

The reaction of bis(cyclohexylisocyanide) complex of Pd(II) with substituted benzo[d]thiazole-2-amines in the presence of triethanolamine as the base has lead to the formation of deprotonated C,N-chelated carbene complexes with a structure similar to that described previously for the products of the reaction with unsubstituted benzo[d]thiazole-2-amine. The complexes have been isolated and characterized using high-resolution mass spectrometry, IR and NMR spectroscopy (1H, 13C{1H}, 1H-1H COSY, 1H-1H NOESY, 1H-13C HSQC, 1H-13C HMBC). The resulting complexes have exhibited moderate antibacterial activity against sensitive strains of gram-negative bacteria E. coli (C600) and P. fluorescens (P218), gram-positive bacteria S. aureus (ATCC-25923) and B. subtillis (B-3142D) as well as fungi C. albicans (401/NCTC-885-653).

The features of burning of solid propellant with a high metal content (over 40%) under conditions of a separately located gas generator of an air-jet engine were investigated. It was shown that solid propellant with a high metal content burns in the mode of dominant heat release in the condensed phase. It was found that metal propellant under conditions of the condensed phase is not a simple heat sink, but plays an active role in burning. The oxidation of the metal under the conditions of the condensed phase maintains the thermal balance of the condensed phase during burning of solid propellant.

3,5-Disubstituted 1,2,4-oxadiazoles were synthesized by the reaction of amidoximes with carboxylic acids or their esters under high-pressure conditions (10 kbar). The reaction proceeds without the use of other reagents or catalysts. Both aliphatic and aromatic carboxylic acids undergo this reaction. The obtained 1,2,4-oxadiazoles possess high fungicidal activity.

Current trends in increasing fuel efficiency and improving aircrafts flight characteristics place engineers before task of reducing the weight of onboard systems and decreasing power consumption with preserving required degree of reliability. In part of aircraft control system, the main stream is the actuators usage with power supply. In this article, three architecture options of the power part of the aircraft control system with different electrification levels are considered. The considered options of the power part of the control system are estimated by three criteria: reliability, mass, power consumption. The selected criteria allow for the preliminary conclusion about the prospects one or another aircraft control system architecture.

The objective of the study was to analyze clinical, immunological and morphological features of malignant non-Hodgkin lymphpomas (MNHL) in HIV-infected patients, evaluate the options and the results of the treatment for the patients in oncohematological hospital environment. Materials and methods. The study evaluated the data from Original Medical Records of 185 HIVinfected patients (mean age 36–40 years) with MNHL that was detected during the period from 1994 to 2017. The results of clinical, laboratory, morphological and immunohistochemical methods used for the study in HIV-infected patients with MNHL were represented. Results. During the period from 1994 to 2017, increasing in the number of HIV-infected patients with MNL, mean age of which was less than 40 years, had been marked. Duration of HIV-infection up to the time of detection the MNHL was 7 years but in 23% of cases the HIV-infection and tumor disease were diagnosed at the same time. Low number of CD4 lymphocyte cells (132 cells/μL) and high number of RNA HIV (more than 550 000 copies/μL) were detected in the blood of the patients. The following distribution was among morphological types of MNHL: diffuse large B-cell lymphoma (DLBCL) — 42%, Burkitt's lymphomas — 32%, plasmablastic lymphomas — 26%. Clinical lymphomas with the extranodal manifestations accompanied with large quantity of complications and opportunistic infections directly resulted from immunosuppression severity (p

One-pot convenient process was developed for the production of 3,5-disubstituted 1,2,4-oxadiazoles by reaction of amidoximes with anhydrides or acyl chlorides in a system NaOH‒DMSO. The reaction proceeds at room temperature with high yields.

The graft-versus-host disease is a life-threatening complication of allogeneic bone marrow transplantation, which demands fast and reliable diagnostics. Goal. To study clinical features of the graft-versus-host disease as well as differential and diagnostic value of histological and immunohistochemical signs in skin biopsy samples in case of graft-versus-host disease (GvHD). Materials and methods. The authors made a comparative assessment of clinical data available for patients suffering from acute GvHD (50 patients) and toxic dermatitis (10 patients). Skin biopsy samples taken from patients from both groups underwent postmortem and immunohistochemistry examinations: the drugs were stained with hematoxylin and eosin as well as by using anti-CD3, CD20, CD4, CD8, FOXP3, CD56, CD1a and CD 68 antibodies. Results. Based on the results of clinical data assessments, no significant differences in the groups were revealed. The morphological examination revealed that the number of eosinophils, CD8+, CD1a+, CD3+ and FOXP3+ cells and share of FOXP3+ cells among Т lymphocytes was higher in the group with toxic dermatitis. Conclusion. An integrated assessment of clinical data and morphological examination results accompanied by the analysis of the population composition of the infiltrate is needed to diagnose the acute GvHD.

A procedure has been developed for the synthesis of (5-alkenyl-1,2,4-oxadiazol-3-yl)anilines by selective reduction of the nitro group in 5-alkenyl-3-(nitrophenyl)-1,2,4-oxadiazoles. The resulting amines are promising monomers for oxidative and radical polymerizations.

The magnetic resonance coupling method is recognized as the most suitable to achieve highly efficient wireless energy transfer for battery charging. However, the performance of this method is highly sensitive to the magnetic coupling and the load parameters, whose variations cause the system to change its resonant frequency. In order to resolve the sensitivity problems of the magnetic resonant coupling in Wireless Energy Transfer (WET) systems, an effective method of frequency tuning is proposed. In this paper, the modelling, design, and implementation in a prototype of a two-coil WET system is presented. The system is keeping simultaneously the necessary data transfer between the receiver and transmitter of energy. The operation frequency of the prototype is kept below 100 kHz, while the data channel operates at 2.4 GHz. The application software which allows the tuning of the operating frequency of the prototype is specifically developed. The experimental results show that the WET system prototype together with the data transmission have the capability of tuning to the resonant frequency, or to another calculated one, allowing to achieve the best possible efficiency of the system at the energy transfer.

Modeling of allogeneic bone marrow transplantation and graft-versus-host disease (GVHD) plays a crucial role in the improvement of transplantation procedures and testing novel immunosuppressive drugs. In this study we evaluated the feasibility of busulfan and cyclophosphamide conditioning with posttransplantation cyclophosphamide (150 mg/kg) in donorrecipient pairs C57Bl/6-Balb/с and Balb/с-C57Bl/6. We observed that Balb/с mice as opposed to C57Bl/6 mice can’t be the recipients because of the unacceptably high acute mortality from acute toxicity of chemotherapeutic drug. Histological studies in the C57Bl/6 recipients revealed acute GVHD in 93 % of animals. All animals had only grade I–II severity of GVHD. This model has the potential for future studies in the field of transplantology, nonetheless a decrease in the intensity of prophylaxis is required to augment the manifestations of GVHD.

Primary presentation of intradural non-Hodgkin lymphoma (PDL) is rare. Most published cases of PDL are single-patient reports. This lesion occurs more often in middle-aged women, in contrast to brain parenchyma primary central nervous system lymphoma (PCNSL), which has a slight male predilection. In contrast with parenchymal PCNSL, there has been no clear association between acquired and congenital immunosuppression and the development of PDL. The pathogenesis of PDL is not well understood because the dura is devoid of any lymphoid tissue. One hypothesis is that a benign inflammatory condition of the dura could attract polyclonal lymphocytes from which a monoclonal lymphoma could arise. B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) have been recognized as an important pathologic subtype. A PDL is more indolent and has a better prognosis than parenchymal PCNSL or systemic lymphoma with CNS metastasis. However, further studies with longer clinical follow up are necessary to assess the final outcome in these patients. In general, patients with marginal zone lymphoma have a favorable outcome, with a 5-year overall survival rate greater than 86%, without significant differences between gastrointestinal and nongastrointestinal and between localized and disseminated disease.

A new approach to the synthesis of 4and 3-(5-R-1,2,4-oxadiazol-3-yl)benzoic acids via a selective oxidation of 5-R-3-tolyl-1,2,4-oxadiazoles with air oxygen in the presence of a catalytic system based on cobalt acetate was suggested. This synthesis allowed us to obtain the products in higher yields and with shorter sequence of steps as compared to the known procedures.

Different methods to study the elastic and strength properties of syntactics — materials based on epoxy resins filled with hollow glass microspheres (HGMs) — are presented. Measurement results for the shear modulus and strength of the materials are analyzed. The effect of microsphere volume fraction in the polymeric matrix on the characteristics is shown. Experiments are performed to investigate the failure mechanisms of syntactics under compression.

As part of the National Research Nuclear University of National Research Nuclear University MEPhI (MEPhI) at the Department of Computer Systems and Technologies working laboratory “Robotics.” University teachers and laboratory staff implement a training program for master’s program “Computer technology in robotics.” Undergraduates and graduate students conduct laboratory research and development in several promising areas in robotics. One of the methodologies that are actively used in carrying out dissertation research is the modeling of advanced hardware and software systems, robotics. This article presents the results of such a study. The purpose of this article is to simulate a sensor comprised of a group of laser rangefinders. The rangefinders should be simulated according to the following principle. Beams will originate from one point though with a deviation from normal, providing thereby simultaneous scanning of different points. The data obtained in our virtual test room should be used to indicate ...

The formation of N′-(benzoyloxy)benzenecarboximidamides and their subsequent cyclization to 3,5-disubstituted 1,2,4-oxadiazoles in different solvents were studied. A probable reaction mechanism was proposed on the basis of the obtained results.

A description of a microthruster operating on the single-component propellant-hydrazine with the Shell-405 catalyst is presented. The hydrazine decomposition reaction at the specified parameters occurs on the surface. The gas temperature entering the nozzle actually depends on the catalyst temperature. It is established that if the temperature of hydrazine decomposition products at the catalyst outlet is lower than 400 K, ammonia condensation takes place in the supersonic nozzle part. The temperature distribution in the working chamber microchannel is calculated, the microthruster thrust and specific impulse are evaluated on the basis of a physico-mathematical model. A fundamental possibility of obtaining 10−3−10−2 N level thrust is shown.

Heterocyclization of toluic acid amidoximes with acetic or propionic anhydrides affords 5-alkyl-3-tolyl-1,2,4-oxadiazoles, whose air oxidation in the same vessel gives (5-alkyl-1,2,4-oxadiazol-3-yl)benzoic acids.

We have derived the qualitative dependence of the ejection energy in a type-II supernova on the regime of accretion onto the central body, including the influence of high-energy neutrinos on the ejection energy. We have also obtained a qualitative picture for the behavior of the shock that leads to the ejection of the envelope as a function of the accretion regime and the character of the neutrino emission. These results are necessary for the construction of effective multidimensional models for supernovae, which we are in the process of developing.

The basic effects that restrict the potentialities of the ultrasonic imaging of brain structures by echo sounding through thick skull bones are considered. It is demonstrated that the main interfering factors are the echo signals from multiple reflections in the bone, its unknown inhomogeneity in depth, and the strong attenuation. To eliminate these effects, the use of a matched spatial processing and complex wideband signals with their subsequent correlation compression is proposed. A simulation of the proposed signal processing techniques confirmed the possibility of brain structure imaging with a spatial resolution of about 1 mm by ultrasonic echo sounding with acceptable intensities through bones up to 20 mm thick at frequencies of 1–2 MHz.

An experimental evaluation of the space resolution of a prototype ultrasonic imaging camera with an immersion acoustic lens is performed. It is shown that the measured parameters agree well with the theoretical calculations. The measurements of the level of internal noise and the absolute sensitivity of the imaging camera are performed; the sensitivity is found to be 0.008 Pa/Hz1/2.

Gas well testing (GWT) is one of the principal methods for estimating its flow potential and to determine reservoir properties and bottom-hole area conditions. Further, it allows to make use of non-linear filtration influence. Reliability of GWT results is important for the choice of field development strategy and production stimulation. The paper focuses on non-linear filtration research, but unlike to well-known purely theoretical results, we developed a set of guidelines designed to conveniently process and interpret field data. We state that modern mathematical methods such as wavelet analysis and accurate planning of field experiments are key in order to acquire more reliable information about reservoir and well properties. This approach can further be applied to lay out the Arctic shelf gas reservoir engineering and planning the well intervention techniques.

In this paper an interaction method is proposed for estimating the buoyancy frequency as a function of depth based on the frequency dependence of wave numbers of internal normal waves. Examples are given of the numerical reconstruction of buoyancy frequency profiles demonstrating convergence of the algorithm. An iterative scheme for the solution of the given problem with an expanded convergence area is obtained on the basis of iteration by stages.

Summary Development of low-permeability reservoirs (less than 1 mD) is carried out with intensive flooding. Injection is performed at pressure above the formation fracturing pressure that is why in almost every well a spontaneous growth of (injection) induced fractures takes place. The main problem of pressure transient analysis in a low permeability reservoir with spontaneous fracturing is a long linear regime flow observed in the log-log plot and the absence of a basis to achieve a pseudo-radial flow. To increase the accuracy of well testing in spontaneously fractured injection wells, certain field tests were developed and run. While testing, an injection well with spontaneously induced fractures was shut-in before the bottom-hole pressure went below the fracture closing pressure, then injection resumed for a short period of time, and then the well was shut-in again to record the pressure fall-off curve. The second pressure fall-off curve shows that the pseudo-radial flow developed, because the close of the part of the fracture without proppant occurred. The paper shows field examples of interference well tests exhibiting fracture growth up to 1700 m diagnosed in injection wells. Examples of successful restriction of injection well operation and application of correlation relationships of fracture closing pressure vs. formation pressure to lower water-cut in production wells with water breakthroughs are described.