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Based on the principle of equivalence of the general theory of relativity and the definition of the non-Euclidean metric of space in a non-inertial frame of reference associated with rotation, a geometric (topological) phase is found that occurs when traversing any closed loop. This approach made it possible to establish a deep physical analogy between various wave effects (both classical and quantum) in closed waveguides that arise under the conditions of their rotation. Due to the coherence of the wave function of spinless charge carriers (Cooper pairs of conduction electrons with oppositely directed spins) in superconductors in the ground quantum state (superconducting state), the appearance of a geometric phase in closed loops under rotation conditions can lead to interference effects in the presence of weak bonds in the loop. To register interference effects, it was proposed to use superconducting quantum interferometers placed in the electric field of a cylindrical or spherical capacitor. In accordance with the general theory of the geometric phase of rotation, the study obtained the basic relations between the geometric phase of rotation and the phase of the wave function induced by an external magnetic field, and an estimate of their values was obtained for acceptable values of the angular velocity of rotation, dimensions of superconducting quantum interferometers, and voltages on the capacitor. The errors in measuring the magnetic flux during the rotation of the measuring complex are determined. Taking into account the dependence of the magnitude of the geometric phase of rotation on the voltage across the capacitor and the size of the superconducting quantum interferometers, and also taking into account the specific range of angular velocities of rotation, the sensitivity of superconducting quantum interferometers to the angular velocity can be regulated by a rational choice of these parameters. Based on the results obtained, a new method for measuring magnetic fields was proposed using two superconducting quantum interferometers with different values of areas bounded by closed contours under conditions of rotational movements, which makes it possible to compensate for the disturbing influence of rotations on magnetic measurements, as well as to simultaneously determine the magnetic induction and angular velocity of rotation.

The article deals with the problem of obtaining a qualitative assessment of the energy concealment degree of radio signals. Energy concealment is regarded as the most significant form of signal concealment, since a designer of radio transmitting devices has the most influence and the greatest freedom in defining these properties. The purpose of the article is to systematize the available knowledge about the methods of assessment of energy concealment in order to conduct a mutual comparison of the characteristics of various signals. The authors describe and analyze a number of methods for assessment of energy concealment of signals based on the number of necessary measurements of the signal level range of the signal reconnaissance, as well as probabilistic assessment of signal disclosure. The results of the analysis showed that described methods are not suitable for obtaining a comparative assessment. Based on the conclusions made in the study energy concealment assessment methods, the author's method for assessment the degree of energy concealment of signals in terms of transmitted symbol energy is proposed. The article clarifies the application of the method to assess the parameters of chirp signals, narrowband and wideband FM, BPSK, QPSK, as well as quadrature signals. A comparative assessment of the chirp, FM, BPSK, QPSK and QAM-16 signal parameters for the decimeter VHF band is obtained, taking into account the transmission speed and power. Assessment of energy concealment of signals were obtained at typical information transfer rates. On the basis of the results, some regularities were described that make it possible to evaluate the effect of changing individual parameters of a radio transmitting device on final energy concealment.

Single-cascade 1.56-to-2.84 μm SRS conversion is demonstrated in a hollow-core revolver fibre filled with methane at a pressure of 25 atm under pumping by positively chirped pulses of a high-power erbium-doped all-fibre laser. At a maximum pump pulse energy of 34 μJ (average power 3.74 W) and a pump pulse duration of about 260 ps, ultrashort pulses (USPs) with a duration of 110 ps and an energy of 1.33 μJ (average power 133 mW) are achieved at the centre wavelength of 2.84 μm. The gas fibre Raman lasers based on hollow-core fibres with pumping by high-power fibre sources are promising for producing all-fibre systems emitting USPs in the mid-IR range.

Cyclobenzaprine is a tricyclic dimethylpropanamine skeletal muscle relaxant, which is used clinically to decrease muscle spasm and hypercontractility, as well as acute musculoskeletal pain. Although the absolute mechanism of action of cyclobenzaprine remains elusive, it is known to mediate its effects centrally via inhibition of tonic somatic motor function, likely through modulation of noradrenergic and serotonergic systems. While cyclobenzaprine is effective as a muscle relaxant, greater than 30% of patients experience drowsiness and sedative-hypnotic effects, yet the mechanisms that cause this adverse effect are also undescribed. Based on this common adverse effect profile and the structural similarity of cyclobenzaprine to tricyclic antidepressants, as well as ethanolamine first-generation antihistamines, we hypothesized that cyclobenzaprine facilitates sedative effects via off-target antagonism of central histamine H1 receptors (H1Rs). Here, for the first time, we present data that demonstrate that cyclobenzaprine exhibits low nanomolar affinity for the cloned human H1R, as well as that expressed in both rat and mouse brain. Using saturation radioligand binding, we also demonstrate that cyclobenzaprine binds to the H1R in a noncompetitive manner. Similarly, functional assays measuring both Ca

The automatic robotic complex will obviously become one of the main subjects in the conduct of military actions in the near future. To control movement parameters, as well as search, target detection and aiming, the complex includes a technical vision system. The minimum sufficient configuration of such a system includes a television search camera with a wide field of view, television and thermal imaging sights, and a rangefinder. The use of laser rangefinders ensures high accuracy of aiming weapons, but generates a powerful unmasking feature. To ensure the secrecy of the functioning of the robotic complex, range finders can operate in a passive mode using information from on-board television cameras. But at the same time, the metrological characteristics of the information measuring channel are significantly deteriorated. Accuracy of five methods of passive distance measurement with application of TV-systems of land unmanned complex is assessed in paper. Classic method of TV-sight external-base range-finder with scale, designed on human height 1,65 m, is ensuring measurement accuracy 135 m on distance 1000 m. External base method, when a range finger scale is forming on remote display as variable length vertical line in process of target framing, is ensuring measurement accuracy 100,3 m on dis-tance 1000 m. Fixed-base range-finder method, when distance between entrance pupils of TV-sight and wide viewing field camera using as base, is ensuring measurement accuracy 76 m on distance 1000 m. Distance measurement method due to displacement of land unmanned complex ensures a measurement accuracy up to 168 m on distance 1000 m. Measurement method due to using zoom-objective is not suitable for land unmanned complex. Proposals have been formulated for the spatial layout of the computer vision system, in which the method of the fixed-base rangefinder is implemented, which ensures the highest measurement accuracy.

Following design principles are important for helmet-mounted targeting systems. Two scanners on base of the polygonal reflector-type prisms forming the fanned field of view are fastened to head-up display. Three LEDs installed on pilot helmet form a plane, the normal of which is collinear to helmet indi-cator viewing line. Angles of LED bearings are measured with triangulation method and angular position of viewing line is calculat-ed. Two options for organization of scanning process are analyzed in the paper. In the first variant, one prism rotates in clockwise and the other in counterclockwise direction. In the second variant both prisms rotate in the same direction, clockwise for example. It is shown that if the prisms rotate in the same direction the targeting accuracy is greater. The algorithm developed for determination of targeting accuracy may be used to matching the rate of scanning and geometric parameters of helmet-mounted targeting system at prescribed accuracy of targeting.

Aging involves a decline in neural function that contributes to cognitive impairment and disease. However, the causes of the transition from a “young-and-healthy” to “aged-and-dysfunctional” brain are not well understood. The following studies all address the mechanisms by which the blood-brain barrier (BBB) declines during aging, and how genetic and pharmacological inhibition of inflammatory signaling ameliorates aging-related neuropathology. Chapter 2 describes how the blood-brain barrier (BBB) deteriorates during aging, starting as early as middle age and continuing to the end of the lifespan. This vascular damage activates inflammatory transforming growth factor β (TGFβ) signaling in astrocytes. Using gain-of-function and loss-of-function manipulations in mice, we show that astrocytic TGFβ signaling is necessary and sufficient to cause neural dysfunction and pathological outcomes, including aberrant electrocorticographic activity, vulnerability to seizures, and cognitive impairment. Furthermore, inhibition of TGFβ signaling reverses these symptomatic hallmarks of aging. Chapter 3 delves deeper into the mechanism by which molecular correlates of neurosynaptic transmission become dysregulated during aging, focusing specifically on how TGFβ signaling contributes to aging-related cognitive decline via selective remodeling of glutamatergic and GABAergic receptor subunits. Chapter 4 investigates the core mechanism of decline of the transcriptional machinery that governs BBB permeability during aging, and also explores the potential of a novel pharmacological approach aimed at restoring the structural and functional integrity of the BBB. Together, these studies reveal the neurovascular unit as one of the earliest triggers of neurological aging, indicating that the aging brain may retain considerable latent capacity which can be revitalized by therapeutic inhibition against TGFβ signaling.

Analysis of the leading world states trends on development of armament and military equipment permits to determine a clear tendency - simplification of armament operation at simultaneous upgrading it durability. Concerning to small armament it means, in perspective it should insure no-failure the battle task execution in the hard operation condition. Paper purpose is to elaborate a methodology for designing improved telescopic sight optical scheme without movable nodes and air spaces between optical components. Methodology for designing solid telescopic sight on base of afocal lens is elaborated in paper. Telescopic sight on base of afocal lens with thickness 100 mm from STF 3 grade glass is designed. Afocal lens linear aperture (36 mm) is determined on base of aberration calculation for channel of «red dot» type aiming reticle image formation at prescribed sighting line error. The technical solutions deal with illumination of aiming reticle at it coupling with the second refracting surface of afocal lens are considered in paper and the methodology for using that sight at battle task execution is proposed. Air spaces between optical components within sight and movable elements are absent when telescopic sight is designed as solid monobloc unit. As result, this all increases a sight durability and simplifies it operation in military units. There is reasonably to install a sight on small arms instead collimator sight «red dot» type, because a methodological aiming error is decreased and distance for target detection and recognition is increased in that case. There are aspired the ways for further improving sight with purpose to decrease a sight weight due-to implementation of aiming methodology with specific form aiming reticle (pat Ukraine 37105А).

Although several ATR inhibitors are in development, there are unresolved questions regarding their differential potency, molecular signatures of patients with cancer for predicting activity, and most effective therapeutic combinations. Here, we elucidate how to improve ATR-based chemotherapy with the newly developed ATR inhibitor, M4344 using in vitro and in vivo models. The potency of M4344 was compared with the clinically developed ATR inhibitors BAY1895344, berzosertib, and ceralasertib. The anticancer activity of M4344 was investigated as monotherapy and combination with clinical DNA damaging agents in multiple cancer cell lines, patient-derived tumor organoids, and mouse xenograft models. We also elucidated the anticancer mechanisms and potential biomarkers for M4344. We demonstrate that M4344 is highly potent among the clinically developed ATR inhibitors. Replication stress (RepStress) and neuroendocrine (NE) gene expression signatures are significantly associated with a response to M4344 treatment. M4344 kills cancer cells by inducing cellular catastrophe and DNA damage. M4344 is highly synergistic with a broad range of DNA-targeting anticancer agents. It significantly synergizes with topotecan and irinotecan in patient-derived tumor organoids and xenograft models. Taken together, M4344 is a promising and highly potent ATR inhibitor. It enhances the activity of clinical DNA damaging agents commonly used in cancer treatment including topoisomerase inhibitors, gemcitabine, cisplatin, and talazoparib. RepStress and NE gene expression signatures can be exploited as predictive markers for M4344.

Antibody-drug conjugates (ADCs) are promising targeted cancer therapy; however, patient selection based solely on target antigen expression without consideration for cytotoxic payload vulnerabilities has plateaued clinical benefits. Biomarkers to capture patients who might benefit from specific ADCs have not been systematically determined for any cancer. We present a comprehensive therapeutic and biomarker analysis of a B7H3-ADC with pyrrolobenzodiazepine(PBD) payload in 26 treatment-resistant, metastatic prostate cancer(mPC) models. B7H3 is a tumor-specific surface protein widely expressed in mPC, and PBD is a DNA cross-linking agent. B7H3 expression was necessary but not sufficient for B7H3-PBD-ADC responsiveness. RB1 deficiency and/or replication stress, characteristics of poor prognosis, conferred sensitivity and were associated with complete tumor regression in both neuroendocrine (NEPC) and androgen receptor positive(ARPC) prostate cancer models, even with low B7H3 levels. Non-ARPC models, which are currently lacking efficacious treatment, demonstrated the highest replication stress and were most sensitive to treatment. In RB1 wild-type ARPC tumors, SLFN11 expression or select DNA repair mutations in SLFN11 non-expressors governed response. Significantly, wild-type TP53 predicted non-responsiveness (7/8 models). Overall, biomarker-focused selection of models led to high efficacy of in vivo treatment. These data enable a paradigm shift to biomarker-driven trial designs for maximizing clinical benefit of ADC therapies.

An analysis of modern devices boresighting the optical-electronic sights and taking into consideration peculiarities of their installation on unmanned weapon platforms is given in the paper. A universal barrel collimator is described, which ensures a boresighting for television and thermal sights for different kinds of unmanned weapon platforms.

We investigated both experimentally and numerically self-phase modulation-induced spectrum compression dynamics of negatively chirped picosecond Gaussian pulses in the low-loss dispersion-shifted telecom fiber near its zero dispersion wavelength (ZDW). It was experimentally observed linearly interpolated monotonous increase in spectrum compression ratio (SCR) with negative chirp growth of the incident pulse in the range from -5.9 to -91.9. According to numerical simulations, despite its small values in the vicinity of ZDW, fiber dispersion limits both SCR growth and spectrum compression quality expressed in terms of time-bandwidth product value and energy confinement ratio at larger chirp values (|C| > 100), in a combined action with self-phase modulation (SPM). Having optimized fiber length and pulse energy, we achieved record 49.2-fold spectrum compression of 38.3-ps, 2.08 nJ negatively chirped Gaussian pulses with compressed spectrum FWHM of 0.23 nm and ≈50% energy confinement at 1560 nm wavelength, leading to ≈13.3-times spectral brightness magnification. We believe that results obtained can be promising for ultra-short pulse laser systems development with enhanced spectral brightness.

Method of the sights viewing line control on base of optical and electronic systems using the modern element base (laser source of irradiation and digital photo detector) is considered in paper. Essence of method is in determining of the viewing line coordinates of a sight under control relatively to laser beam or normal to mirror, which are connected unmistakably with base elements of small arms. Algebraic difference of the viewing line projection and laser beam axis or normal to mirror before and after shooting is determining a value of sight viewing line deviation after serial stage of shooting tests. There are assessed three variants of the optical and electronic complexes from view point their accuracy at control of viewing line stability at shooting tests. In the first variant, a complex includes the collimation-measuring unit and laser, which is basing unmistakably on weapon barrel and determining channel axis of it barrel. TV camera is mounting behind ocular of sight under control for increasing of accuracy of sight reticle direction to control point. In the second variant, a laser source is integrated in receiving channel structure and dismountable mirror is mounting on weapon instead of laser. Normal of that mirror is determining the axis of weapon barrel channel. In the third variant, a complex includes reflective element in view of rhombic prism. Semitransparent beam splitter is plotted on exit plane of prism. Besides that, a prism is equipped with special means for unmistakably orientation of it normal to reflective plane relatively to axis of weapon barrel channel. Prism body made from magnetic material for stable contact with edge of weapon barrel executes function of that means. Analysis of there variants accuracy has shown advantage of the third variant.