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The negative situation revealed promising directions for the development of various segments of IT services, and entrepreneurs received a driver for development in the form of new information technologies. In modern conditions, the IT market is developing much more dynamically than most industries. Together with fundamental factors, the development of the IT services market is accelerated by current socio-economic processes. So the pandemic for three years provokes stagnation in many industries and sectors of the economy, but at the same time activates the development of new IT. The object of this study is the dynamics and prospects of the Russian IT services market. The main purpose of the article is to analyze the current state of the IT services market, assess the risks and potential development opportunities. The article presents the results of a statistical analysis of the time series of the IT services market, some data from an econometric analysis. The results of a correlation-regression analysis to determine the relationship between GDP and the IT services market, calculations of correlation coefficients, elasticity and β-coefficient are presented. Preliminary calculations of predictive dynamics of the IT services market are given. As a result of the analysis, potential opportunities and threats for forecasting are identified, which are required in the subsequent integrated forecasting model and structural modeling using discrete mathematics.

BACKGROUND: This study on gait biomechanics is based on a functional test (FT) performed at free and fast walking speeds. OBJECTIVE: We investigated the pattern of changes in gait biomechanical parameters and the knee function in patients after anterior cruciate ligament (ACL) injury or its reconstruction. METHODS: The study included 51 patients (33 males, 18 females) with a confirmed recent or old history of ACL tear, before or after reconstruction (26 patients). Mocap data was obtained using an inertial system. All patients were divided into three groups: 41 patients with physiological response (compensation), 6 patients with signs of decompensation, and 4 non-assessable patients. RESULTS: Increase in gait speed was associated with decrease in the walking cycle duration, stance and double support phases. In the compensation group, the physiological response of the knee was manifested in increased amplitudes. In the decompensation group, the amplitudes remained unchanged or decreased. In the compensation group, there were increases in the symmetrical muscle activity. The decompensation group was characterized by electromyography asymmetry. CONCLUSION: The observed universal physiological mechanism limiting the load on the damaged joint can be used for accurate assessment of the knee functional state in various periods of rehabilitation. [ABSTRACT FROM AUTHOR]

Azacarbazoles have attracted significant interest due to their valuable properties, such as anti-pathogenic and antitumor activity. In this study, a series of structurally related tricyclic benzo[4,5]- and tertacyclic naphtho[2′,1′:4,5]imidazo[1,2-c]pyrimidinone derivatives with one or two positively charged tethers were synthesized and evaluated for anti-proliferative activity. Lead tetracyclic derivative 5b with two amino-bearing arms inhibited the metabolic activity of A549 lung adenocarcinoma cells with a CC50 value of 3.6 μM, with remarkable selectivity (SI = 17.3) over VA13 immortalized fibroblasts. Cell-cycle assays revealed that 5b triggers G2/M arrest without signs of apoptosis. A study of its interaction with various DNA G4s and duplexes followed by dual luciferase and intercalator displacement assays suggests that intercalation, rather than the modulation of G4-regulated oncogene expression, might contribute to the observed activity. Finally, a water-soluble salt of 5b was shown to cause no acute toxic effects, changes in mice behavior, or any decrease in body weight after a 72 h treatment at concentrations up to 20 mg/kg. Thus, 5b is a promising candidate for studies in vivo; however, further investigations are needed to elucidate its molecular target(s). [ABSTRACT FROM AUTHOR]

Tubulin-targeting agents attract undiminished attention as promising compounds for the design of anti-cancer drugs. Verubulin is a potent tubulin polymerization inhibitor, binding to colchicine-binding sites. In the present work, a series of verubulin analogues containing a cyclohexane or cycloheptane ring 1,2-annulated with pyrimidine moiety and various substituents in positions 2 and 4 of pyrimidine were obtained and their cytotoxicity towards cancer and non-cancerous cell lines was estimated. The investigated compounds revealed activity against various cancer cell lines with IC50 down to 1–4 nM. According to fluorescent microscopy data, compounds that showed cytotoxicity in the MTT test disrupt the normal cytoskeleton of the cell in a pattern similar to that for combretastatin A-4. The hit compound (N-(4-methoxyphenyl)-N,2-dimethyl-5,6,7,8-tetrahydroquinazolin-4-amine) was encapsulated in biocompatible nanocontainers based on Ca2+ or Mg2+ cross-linked alginate and it was demonstrated that its cytotoxic activity was preserved after encapsulation. [ABSTRACT FROM AUTHOR]

Purpose: There is still controversy over the criteria for acute ACL tear. In this paper, knee joint function and walking were considered possible ones. Method: The study included 21 subjects with acute ACL tear and 20 healthy volunteers as a control group. Biomechanical gait analysis was performed using the inertial sensor system including EMG recording. All subjects (but for controls) were divided into two groups: Group 1—"up to 4 weeks" and Group 2—"from 4 weeks to 3 months". Results: Temporal gait parameters in subjects from Group 1 demonstrate the asymmetry of 4% and more in terms of the gait cycle with a decrease in the affected limb, and are within normal range in Group 2. The amplitudes at the hip and knee joints in the affected limb are reduced which is especially pronounced in Group 1 (2–4 and 6–10 degrees, respectively). The affected knee joint shows a decrease in the range of motion by up to 5 degrees in the first half of the stance phase and flexion by less than 40 degrees in the swing phase. The tibialis anterior and quadriceps femoris muscle function is decreased in the affected limb only in Group 1 (72% and 78% from normal, respectively). Conclusions: The severity of the condition after an ACL tear is largely determined by functional changes. The time factor is of secondary importance. [ABSTRACT FROM AUTHOR]

The treatment of many bacterial diseases remains a significant problem due to the increasing antibiotic resistance of their infectious agents. Among others, this is related to Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA) and Mycobacterium tuberculosis. In the present article, we report on antibacterial compounds with activity against both S. aureus and MRSA. A straightforward approach to 2-(1H-indol-3-yl)quinazolin-4(3H)-one and their analogues was developed. Their structural and functional relationships were also considered. The antimicrobial activity of the synthesized compounds against Mycobacterium tuberculosis H37Rv, S. aureus ATCC 25923, MRSA ATCC 43300, Candida albicans ATCC 10231, and their role in the inhibition of the biofilm formation of S. aureus were reported. 2-(5-Iodo-1H-indol-3-yl)quinazolin-4(3H)-one (3k) showed a low minimum inhibitory concentration (MIC) of 0.98 μg/mL against MRSA. The synthesized compounds were assessed via molecular docking for their ability to bind long RSH (RelA/SpoT homolog) proteins using mycobacterial and streptococcal (p)ppGpp synthetase structures as models. The cytotoxic activity of some synthesized compounds was studied. Compounds 3c, f, g, k, r, and 3z displayed significant antiproliferative activities against all the cancer cell lines tested. Indolylquinazolinones 3b, 3e, and 3g showed a preferential suppression of the growth of rapidly dividing A549 cells compared to slower growing fibroblasts of non-tumor etiology. [ABSTRACT FROM AUTHOR]

Prostate cancer is the second most common cancer among men. We designed and synthesized new ligands targeting prostate-specific membrane antigen and suitable for bimodal conjugates with diagnostic and therapeutic agents. In vitro studies of the affinity of the synthesized compounds to the protein target have been carried out. Based on these ligands, a series of bimodal conjugates with a combination of different mitosis inhibitors and antiandrogenic drugs were synthesized. The cytotoxicity of the compounds obtained in vitro was investigated on three different cell lines. The efficacy of the two obtained conjugates was evaluated in vivo in xenograft models of prostate cancer. These compounds have been shown to be highly effective in inhibiting the growth of PSMA-expressing tumors. [ABSTRACT FROM AUTHOR]

An efficient route for the synthesis of a series of new hybrid isoxazole‐triazole compounds in high yields and excellent regioselectivity starting from either 2‐aryl‐1,1‐dichlorocyclopropanes or N‐hydroxybenzimidoyl chlorides was developed. The synthesized isoxazole‐triazole hybrids were evaluated for their biological activity. [ABSTRACT FROM AUTHOR]

Currently, inertial sensors are often used to study balance in an upright stance. There are various options for recording balance data with different locations and numbers of sensors used. Methods of data processing and presentation also differ significantly in published studies. We propose a certain technical implementation of the method and a previously tested method for processing primary data. In addition, the data were processed along three mutually perpendicular planes. The study was conducted on 109 healthy adults. A specially developed inertial sensor, commercially available for medical purposes, was used. Thus, this work can outline the limits of normative values for the calculated stabilometric measures. Normative data were obtained for three oscillation planes with the sensor located on the sacrum. The obtained parameters for the vertical component of the oscillations are of the same order as for the frontal and sagittal components. Normative parameters are required in any clinical study, as the basis from which we start in the evaluation of clinical data. In this study, such normative parameters are given for one of the most commonly used Romberg's tests. The obtained normative data can be used for scientific and clinical research. [ABSTRACT FROM AUTHOR]

A foot placement of inertial sensors is commonly used for heel-strike (HS) and toe-off (TO) event detection. However, in clinical practice, such sensor placement may be difficult or even impossible due to the deformity of patients' feet. The first contribution of this paper is a new algorithm for HS and TO event detection for cases when the sensors are placed on the lateral malleolus. Such sensor placement allows gait analysis in patients with foot deformities. In addition, the placement of the sensor directly on the wide bone surface of the lateral malleolus ensures secure fixation of the sensor during walking. The proposed algorithm is based on deep neural networks, which can be easily adapted (by retraining the neural networks) for analysis of various pathological gait patterns. It is especially important in clinical practice when the number of possible pathological gait patterns is very large. The algorithm proposed in this paper was implemented in a new wearable system for the clinical gait analysis. The second contribution is a validation of this new wearable system. The performance of both proposed algorithm and gait analysis system was evaluated against a reference treadmill system where a capacitance–based pressure platform was used. A total of 117 healthy volunteers participated in the comparison (62 males and 55 females, age 24–55 years, height 162–183 cm). They were asked to perform 2 min walking trials with different speed. Mean accuracy ± precision was – 0.021 ± 0.091 s for gait cycle, 0.589 ± 1.144 steps/min for cadence, – 0.051 ± 0.544 % for stance phase, – 0.37 ± 0.649 % for single support, 0.296 ± 0.711 % for double support, 0.132 ± 0.561 % for load response, and 0.106 ± 0.661 % for preswing. Limitations of the proposed algorithm and its compassion with state-of-the-art algorithms were discussed. [ABSTRACT FROM AUTHOR]

We investigate the dynamics of ultra-short optical pulses in carbon nanotubes under the influence of an acoustic field in two-dimensional geometry. We obtain an effective equation for the vector potential of the electromagnetic field, taking into account the stress field described in the framework of the gauge theory. And, we study the effects, which observed with a change of the magnitude of the external strain.

Novel hydantion and thiohydantoin-based spiro-compounds were prepared via theDiels–Alder reactions between 5-methylidene-hydantoins or 5-methylidene-2-thiohydantoins and 1,3-dienes (cyclopentadiene, cyclohexadiene, 2,3-dimethylbutadiene, isoprene). It was shown that the cycloaddition reactions proceed regioselectively and stereoselectively with the formation of exo-isomers in the reactions with cyclic dienes andthe less sterically hindered products in the reactions with isoprene. Reactions of methylideneimidazolones with cyclopentadiene proceed viaco-heating the reactants; reactions with cyclohexadiene, 2,3-dimethylbutadiene, and isoprene require catalysis by Lewis acids. It was demonstrated that ZnI2 is an effective catalyst in the Diels–Alder reactions of methylidenethiohydantoins with non-activated dienes. The possibility of alkylation and acylation of the obtained spiro-hydantoinsat the N(1)nitrogen atoms with PhCH2Cl or Boc2O and the alkylation of the spiro-thiohydantoinsat the S atoms with MeI or PhCH2Cl in high yields have been demonstrated. The preparativetransformation of spiro-thiohydantoins into corresponding spiro-hydantoinsin mild conditions by treating with 35% aqueous H2O2 or nitrile oxide has been carried out. The obtained compounds show moderate cytotoxicity in the MTT test on MCF7, A549, HEK293T, and VA13 cell lines. Some of the tested compounds demonstrated some antibacterial effect against Escherichia coli (E. coli) BW25113 DTC-pDualrep2 but were almost inactive against E. coli BW25113 LPTD-pDualrep2. [ABSTRACT FROM AUTHOR]

Novel variously substituted thiohydantoin-based dispiro-indolinones were prepared using a regio- and diastereoselective synthetic route from 5-arylidene-2-thiohydantoins, isatines, and sarcosine. The obtained molecules were subsequently evaluated in vitro against the cancer cell lines LNCaP, PC3, HCTwt, and HCT(−/−). Several compounds demonstrated a relatively high cytotoxic activity vs. LNCaP cells (IC50 = 1.2–3.5 µM) and a reasonable selectivity index (SI = 3–10). Confocal microscopy revealed that the conjugate of propargyl-substituted dispiro-indolinone with the fluorescent dye Sulfo-Cy5-azide was mainly localized in the cytoplasm of HEK293 cells. P388-inoculated mice and HCT116-xenograft BALB/c nude mice were used to evaluate the anticancer activity of compound 29 in vivo. Particularly, the TGRI value for the P388 model was 93% at the final control timepoint. No mortality was registered among the population up to day 31 of the study. In the HCT116 xenograft model, the compound (170 mg/kg, i.p., o.d., 10 days) provided a T/C ratio close to 60% on day 8 after the treatment was completed. The therapeutic index—estimated as LD50/ED50—for compound 29 in mice was ≥2.5. Molecular docking studies were carried out to predict the possible binding modes of the examined molecules towards MDM2 as the feasible biological target. However, such a mechanism was not confirmed by Western blot data and, apparently, the synthesized compounds have a different mechanism of cytotoxic action. [ABSTRACT FROM AUTHOR]

A design of Pt(IV) prodrugs with tumor cell targeting moieties leading to increased selectivity is of interest. Herein, we designed a novel Pt(IV) prodrugs with COX-inhibitor naproxen, long-chain hydrophobic stearic acid moiety and biotin as axial ligands. We have established that for Pt(IV) prodrugs with biotin and naproxen or stearate in axial position, the lipophilicity rather than biotin receptors expression is the main factor of cytotoxicity. We also monitored the reduction speed of Pt(IV) prodrug 3 with naproxen and biotin in axial positions in A549 cells using XANES and demonstrated that the prodrug gradually releases cisplatin within 20 hours of incubation. [ABSTRACT FROM AUTHOR]

An improved series of ligands targeting prostatic specific membrane antigen has been reported. Varying compounds and their biological parameters were due to changes in the linker structure. Highly selective compounds with nanomolar IC50 values were obtained. As an example, a conjugate with Sulfo-Cy5 and MMAE was obtained and pre-studied. [ABSTRACT FROM AUTHOR]

In order to obtain antimicrobial compounds with improved properties, new conjugates comprising two different biologically active agents within a single chimeric molecule based on chloramphenicol (CHL) and a hydrophobic cation were synthesized and studied. Chloramphenicol amine (CAM), derived from the ribosome-targeting antibiotic CHL, and the plant isoquinoline alkaloid berberine (BER) are connected by alkyl linkers of different lengths in structures of these conjugates. Using competition binding, double reporter system, and toeprinting assays, we showed that synthesized CAM-Cn-BER compounds bound to the bacterial ribosome and inhibited protein synthesis like the parent CHL. The mechanism of action of CAM-C5-BER and CAM-C8-BER on the process of bacterial translations was similar to CHL. Experiments with bacteria demonstrated that CAM-Cn-BERs suppressed the growth of laboratory strains of CHL and macrolides-resistant bacteria. CAM-C8-BER acted against mycobacteria and more selectively inhibited the growth of Gram-positive bacteria than the parent CHL and the berberine derivative lacking the CAM moiety (CH3-C8-BER). Using a potential-sensitive fluorescent probe, we found that CAM-C8-BER significantly reduced the membrane potential in B. subtilis cells. Crystal violet assays were used to demonstrate the absence of induction of biofilm formation under the action of CAM-C8-BER on E. coli bacteria. Thus, we showed that CAM-C8-BER could act both on the ribosome and on the cell membrane of bacteria, with the alkylated berberine fragment of the compound making a significant contribution to the inhibitory effect on bacterial growth. Moreover, we showed that CAM-Cn-BERs did not inhibit eukaryotic translation in vitro and were non-toxic for eukaryotic cells. [ABSTRACT FROM AUTHOR]

In this work, we present the first synthesis of dispirooxindole-β-lactams employing optimized methodology of one-pot Staudinger ketene-imine cycloaddition with N-aryl-2-oxo-pyrrolidine-3-carboxylic acids as the ketene source. Spiroconjugation of indoline-2-one with β-lactams ring is considered to be able to provide stabilization and wide scope of functionalization to resulting scaffolds. The dispipooxindoles obtained demonstrated medium cytotoxicity in the MTT test on A549, MCF7, HEK293, and VA13 cell lines, and one of the compounds demonstrated antibacterial activity against E. coli strain LPTD. [ABSTRACT FROM AUTHOR]

A new two‐stage regioselective access to non‐symmetric 3,5‐diarylisoxazoles starting from readily available 2‐aryl‐1,1‐dibromocyclopropanes is developed. The strategy based on the nitrosation/Suzuki arylation sequence ensures good yields of the products and a wide scope of substituents in both aryl rings. Using this strategy, a panel of combretastatin A‐4 (CA‐4) analogues presented by 3,5‐diarylisoxazole structural motif was synthesized and evaluated for their biological activity [ABSTRACT FROM AUTHOR]

Featured Application: The results of this study can be useful for further research into features related to the development of military crawl locomotion in groups of different ages, and for understanding the development of this type of locomotion in ontogenesis. In rehabilitation clinics, it is possible to compare patients' indicators with the norm registered in this study (which could be further expanded), to assess the degree of violations in the motor control system. The biomechanics of military crawl locomotion is poorly covered in scientific literature so far. Crawl locomotion may be used as a testing procedure which allows for the detection of not only obvious, but also hidden locomotor dysfunctions. The aim of the study was to investigate the biomechanics of crawling among healthy adult participants. Eight healthy adults aged 15–31 (four women and four men) were examined by means of a 3D kinematic analysis with Optitrack optical motion-capture system which consists of 12 Flex 13 cameras. The movements of the shoulder, elbow, knee, and hip joints were recorded. A person was asked to crawl 4 m on his/her belly. The obtained results including space-time data let us characterize military crawling in terms of pelvic and lower limb motions as a movement similar to walking but at a more primitive level. Progressive and propulsive motions are characterized as normal; additional right–left side motions—with high degree of reciprocity. It was found that variability of the left-side motions is significantly lower than that of the right side (Z = 4.49, p < 0.0001). The given normative data may be used as a standard to estimate the test results for patients with various pathologies of motor control (ataxia, abasia, etc.). [ABSTRACT FROM AUTHOR]

In a recent research paper Dr. Suxing Jin et al. reported two multispecific PtIV complexes DNP and NP with non-steroidal anti-inflammatory drug naproxen (NPX) as the axial ligand(s). Herein, we clarify the mechanism of action of DNP, its therapeutic target and intracellular redox-status. [ABSTRACT FROM AUTHOR]

A series of novel hydantoin-based dispiroindolinones as potential small-molecule inhibitors of p53–MDM2 protein–protein interaction were synthesized by two methods, using 2-arylidenehydantoins as starting materials. Some compounds demonstrate moderate cytotoxicity against cancer cell lines with IC50 in micromolar concentration range, which is comparable to nutlin-3. Two of the synthesized dispiroindolinones show p53-related activity in p53 reporter activation test. [ABSTRACT FROM AUTHOR]

Featured Application: Authors are encouraged to provide a concise description of the specific application or a potential application of the work. This section is not mandatory. The objective of the study was to evaluate the clinical, functional, and biomechanical symptoms in patients with anterior cruciate ligament (ACL) rupture before and after ACL reconstruction. The study enrolled 20 patients and 20 healthy subjects as controls. Walking biomechanics was assessed at three time points: before surgery and three months and a year or more after surgical reconstruction. Impact loads on both sides differed significantly from the respective values before surgery (p<0.05). Walking cycle duration decreased with time after surgery. On both sides (affected and unaffected), hip movement amplitudes were significantly smaller than in control (p<0.05). They remained so in the follow-up periods after the reconstruction. Before ACL reconstruction, the amplitude of the main flexion of the knee was significantly reduced both on the affected and unaffected sides. The amplitude gradually increased after the reconstruction, and a year post-surgery, it reached, on the operated side, the same values as in the control group. Complete functional recovery of the knee joint was not achieved within a year after the ACL surgical reconstruction. The remaining changes, however, were not clinically pronounced and could only be detected by instrumental gait analysis. The compensatory processes developed bilaterally, in both the hip and knee joints. [ABSTRACT FROM AUTHOR]