Molecular theory of the tilting transition and computer simulations of the tilted lamellar phase of rod-coil diblock copolymers.

Symmetric rod-coil diblock copolymers have been simulated using the method of dissipative particle dynamics in the broad range of the Flory-Huggins parameter. It has been found that the tilted lamellar phase appears to be the most stable one at strong segregation. The rod-coil copolymer tilt angle and orientational order parameters have been determined as functions of the segregation strength. The density functional theory of rod-coil diblock copolymers has been generalized to the case of the tilted lamellar phase and used to study the stability of the orthogonal lamellar phase with respect to tilt. The orthogonal phase indeed appears to be unstable in the broad region of the parameter space in the case of relatively strong segregation. It has also been shown that the transition into the tilted lamellar phase is determined by a strong coupling between two independent tilt order parameters.

Ordering of ferromagnetic nanoparticles in nematic liquid crystals.

Dispersions of magnetic nanoparticles in a nematic liquid crystal were investigated as magnetic fields were applied in three different boundary condition geometries: (i) planar substrates and B⊥n, (ii) planar substrates and B‖n, and (iii) homeotropic substrates and B⊥n. Particle chaining is observed when a magnetic field is applied, with a periodicity perpendicular to the chains. Furthermore, linear chains are observed for the magnetic field applied perpendicular to the director, while zigzag chains are formed when the magnetic field direction is parallel to the director field. This is attributed to a change from a dipolar defect configuration around dispersed nanoparticles, to a quadrupolar one, i.e. the change from satellite to Saturn-ring defects. This effect is largely independent of the sample thickness. The dynamic development of the chain length, as well as their two-dimensional order parameter was studied in all cases. Chain lengths increased rapidly until saturation at approximately l = 30 µm after a time of about t = 10 s. Similarly, the chain order parameters increased until saturation between S = 0.8-0.9, independent of sample geometry.

Effect of polar intermolecular interactions on the elastic constants of bent-core nematics and the origin of the twist-bend phase.

A molecular theory of both elastic constants and the flexoelectric coefficients of bent-core nematic liquid crystals has been developed taking into account dipole-dipole interactions as well as polar interactions determined by the bent molecular shape. It has been shown that if polar interactions are neglected, the elastic constants are increasing monotonically with the decreasing temperature. On the other hand, dipolar interactions between bent-core molecules may result in a dramatic increase of the bend flexocoefficient. As a result, the flexoelectric contribution to the bend elastic constant increases significantly, and the bend elastic constant appears to be very small throughout the nematic range and may vanish at a certain temperature. This temperature may then be identified as a temperature of the elastic instability of the bent-core nematic phase which induces a transition into the modulated phases with bend deformations like recently reported twist-bend phase. The temperature variation of the elastic constants is qualitatively similar to the typical experimental data for bent-core nematics.

[Melatonin enhances antitumor effect of doxorubicin on a model of transplantable Ehrlich tumor in female sHR mice].

A combined antitumor effect of a single injection of doxorubicin and the indole hormone melatonin was investigated in the model of transplantable Ehrlich carcinoma in female SHR mice. Animals received melatonin either subcutaneous 10 mg/ kg in the evening or with water 10 mg/l at night (from 20 pm to 8 am) for 3 weeks. The results of an experiment showed that combined use of doxorubicin and melatonin both subcutaneous and with water leads to statistically significant inhibition of tumor growth compared with control and doxorubicin alone.

[Prospects of use of antidiabetic biguanides for cancer prevention and treatment: results of preclinical studies].

The critical analysis of preclinical testing of anticarcinogenic and antitumor activity of biguanides presented in this paper. Experiments have been conducted using in total more than 20 models of carcinogenesis including models of spontaneous , chemically- , radiation- and virus-induced carcinogenesis, as well as carcinoigenesis induced by special fat diets and by genetic modification in rodents. Cancer preventive effect of buiguanides has been studied in relation to total tumor incidence and to 17 target organs in animals of 3 species, including 25 various strains of mice, 4 strains of rats and 1 strain of hamsters using various routs of administration and doses. In the majority of cases (86%) the exposure to biguanides leads to inhibition of carcinogenesis. In 14% of the cases inhibitory effect of the drugs was not observed, however there was no any case of stimulation of carcinogenesis by antidiabetic biguanides., Metformin suppressed tumor growth in the majority of in vitro studies conducted in 46 different cell lines originated from malignant tumors of 15 localization as well as in athymic mice with xenografts of 31 tumor lines. It was concluded that there are sufficient experimental evidences of anticarcinogenic and antitumor effects of antidiabetic biguanides revealed in a number of models of induced and spontaneous carcinogenesis.

[Theoretical and practical aspects of development of biscuits with a modified carbohydrate profile for patients with type 2 diabetes].

The purpose of this research was to develop formulation and technology of flour confectionery products in the form of biscuits with a modified carbohydrate profile, a study of physico-chemical and structural-mechanical properties. The оbjects of this research were: basic food matrix, are the prototype of the designed product without modification of the carbohydrate profile prepared by the classic recipe and traditional technologies; model samples of cookies with a modified carbohydrate profile; the experimental sample cookie with a modified carbohydrate profile and optimized physic-chemical, structural-mechanical and organoleptic indicators. Determination of physic-chemical and organoleptic characteristics of biscuits was carried out by standard methods. The water activity was determined on the analyzer using a cooled mirror dew point sensor, structural-mechanical properties ­ on texturename with conical and cylindrical nozzles, imitating the processes of breakage and bite, describing the hardness, brittleness, breakage, and other properties of a food product. The modification of the carbohydrate profile of biscuit, consisting in the replacement of wheat flour traditionally used in the recipe of flour confectionery products, by the composition containing oat, barley and buckwheat flour, and in the exclusion of sugar and the introduction of ingredients that do not cause hyperglycemic effect: maltitol as a sweetener and beta-glucans. The technological scheme of production of new kinds of cookies has been developed, the parameters of the production process have been worked out, physical-chemical, structural-mechanical and organoleptic properties of a new type of cookie have been optimized. Analysis of the chemical composition of the cookies showed that 100 g contains 9.3 g of protein, 17.0 g of fat and 44.5 g of carbohydrates, including 42.4 g of starch, and 2.1 g mono- and disaccharides, 2.2 g dietary fiber, 20 g maltitol; caloric value of 420 kcal/1760 kJ. In accordance with the developed technology an experimental batch of cookies with a modified carbohydrate profile has been produced to evaluate its impact on postprandial glycemia in patients with type 2 diabetes.

Molecular theory of proper ferroelectricity in bent-core liquid crystals.

Antiferro- and ferro-electric ordering has been discovered in orthogonal smectic phases composed of nonchiral bent-core molecules. These systems are the only proper fluid ferroelectrics confirmed experimentally so far. We consider a molecular theory of proper ferroelectric ordering in isotropic, nematic and smectic A phases and conclude that the delicate balance between the tendencies for local parallel and antiparallel ordering of molecular electric and steric dipoles is strongly shifted in restricted geometries. This is a reason why dipolar ordering is more likely to occur within a smectic layer. We derive model interaction potentials for polar bent-core molecules and present the results of the mean-field theory of ferroelectric ordering in the orthogonal smectic phase taking into account also the molecular biaxiality. Order parameter profiles have been calculated numerically and phase diagrams are presented which enable one to analyze the relative importance of dipole-dipole interaction and intermolecular attraction modulated by polar bent-core molecular shape.

[Markers of effectiveness of preoperative taxane-based chemotherapy for locally advanced breast cancer].

The absolute sensitivity signs of breast cancer to the drug have not yet been developed. Data from clinical trials on the study of experimental laboratory predictive markers of chemosensitivity: TOP2alpha (topoisomerase 2-alpha), beta-tubulin (subunit of dimeric protein tubulin), and BRCA1 (breast cancer 1) are contradictory and not numerous. Analysis of the results by the end of the clinical trial will allow examining the correlation between the effectiveness of preoperative taxane-chemotherapy and the level of experimental and standard molecular markets that is important for development of algorithm of treatment tactics for patients with locally advanced breast cancer.

A phase Ib/II dose expansion study of subcutaneous sasanlimab in patients with locally advanced or metastatic non-small-cell lung cancer and urothelial carcinoma.

BACKGROUND: Sasanlimab is an antibody to the programmed cell death protein 1 receptor. We report updated data of subcutaneous sasanlimab in non-small-cell lung cancer (NSCLC) and urothelial carcinoma dose expansion cohorts from a first-in-human phase Ib/II study. PATIENTS AND METHODS: Patients were ≥18 years of age with NSCLC or urothelial carcinoma, and no prior immunotherapies, who progressed on or were intolerant to systemic therapy, or for whom systemic therapy was refused or unavailable. Patients received subcutaneous sasanlimab at 300 mg every 4 weeks (q4w). Primary objectives were to evaluate safety, tolerability, and clinical efficacy by objective response rate (ORR). RESULTS: Sixty-eight and 38 patients with NSCLC and urothelial carcinoma, respectively, received subcutaneous sasanlimab. Overall, sasanlimab was well tolerated; 13.2% of patients experienced grade ≥3 treatment-related adverse events. Confirmed ORR was 16.4% and 18.4% in the NSCLC and urothelial carcinoma cohorts, respectively. ORR was generally higher in patients with high programmed death-ligand 1 (PD-L1) expression (≥25%) and high tumor mutational burden (TMB; >75%). In the NSCLC and urothelial carcinoma cohorts, median progression-free survival (PFS) was 3.7 and 2.9 months, respectively; corresponding median overall survival (OS) was 14.7 and 10.9 months. Overall, longer median PFS and OS correlated with high PD-L1 expression and high TMB. Longer median PFS and OS were also associated with T-cell inflamed gene signature in the urothelial carcinoma cohort. CONCLUSIONS: Subcutaneous sasanlimab at 300 mg q4w was well tolerated with promising clinical efficacy observed. Phase II and III clinical trials of sasanlimab are ongoing to validate clinical benefit. Subcutaneous sasanlimab may be a potential treatment option for patients with NSCLC or urothelial carcinoma.

Order parameter dependence of the viscosity coefficients of a biaxial nematic liquid crystal.

We derive expressions for the order parameter dependence of the viscosity coefficients of a biaxial nematic liquid crystal by comparing its dissipation function expressed in terms of directors with that expressed in terms of order tensors. The results enable us to identify the dominant flow viscosity coefficients and to compare their temperature variation according to their dependence on the dominant scalar order parameters. By considering different orientations of an external field, we identify three characteristic switching times corresponding to three rotational viscosities, and we estimate the ratio of the switching times of the primary and the secondary directors.

Molecular-statistical theory of elasticity in nematic liquid crystals composed of polar and nonpolar molecules.

A molecular-statistical theory of the orientational elasticity of nematic liquid crystals has been developed employing the orientational deformation tensor which describes the rotation of the director. An explicit expression for the general elasticity tensor of the nematic phase has been obtained and the Frank elastic constants are expressed in terms of the three independent parameters of this tensor. Explicit expressions for the Frank elastic constants have been derived in the molecular field approximation in terms of the orientational order parameters and the corresponding coefficients of expansion of the intermolecular potential in spherical invariants. Frank elastic constants have been calculated numerically for nematic liquid crystals composed of both polar and nonpolar molecules together with the orientational order parameters using the classical Gay-Berne model interaction potential and the two of its popular modifications. The polarity of the uniaxial molecular shape has been directly introduced into the model potential by modifying the distance of closest approach. The elastic constants are presented as functions of temperature for different values of the molecular elongation, the anisotropy of the potential well and the molecular shape polarity. It has been shown that the elastic constants are much more sensitive to the details of the intermolecular interaction potential in comparison with the orientational order parameters. In particular, a relatively weak polarity of the molecular shape may result in an unusual decrease of the splay constant K_{11} which may vanish at some temperature leading to the instability of the homogeneous nematic phase. This may represent a mechanism of the formation of the splay-bend phase.

Molecular theory of liquid-crystal ordering in rod-coil diblock copolymers.

Molecular-statistical theory of rod-coil diblock copolymers is proposed using the general density functional approach which enables one to consider the cases of both weak and strong segregation. The free energy of the system is expressed as a functional of the phase-space densities of rod and coil monomers, which depend on the orientational and translational order parameters. Temperature-concentration phase diagrams are obtained and the profiles of all order parameters are calculated numerically by minimizing the polymer free energy. The lamellar phase is shown to possess strong orientational order which is partially induced by the phase structural anisotropy. The enhanced stability of the lamellar phase is determined by a combination of the microphase separation effects and the emergence of long-range smectic order.

Continuously rotating chiral liquid crystal droplets in a linearly polarized laser trap.

The transfer of optical angular momentum to birefringent particles via circularly polarized light is common. We report here on the unexpected, continuous rotation of chiral nematic liquid crystal droplets in a linearly polarized optical trap. The rotation is non-uniform, occurs over a timescale of seconds, and is observed only for very specific droplet sizes. Synchronized vertical motion of the droplet occurs during the rotation. The motion is the result of photo-induced molecular reorganization, providing a micron sized opto-mechanical transducer that twists and translates.

Ferroelectric ordering in chiral smectic-C* liquid crystals determined by nonchiral intermolecular interactions.

General microscopic mechanism of ferroelectric ordering in chiral smectic-C* liquid crystals is considered. It is shown that if the mesogenic molecules have a sufficiently low symmetry, the spontaneous polarization is proportional to one of the biaxial vector order parameters of the smectic-C phase. This order parameter may be determined by intermolecular interactions which are not sensitive to molecular chirality. At the same time, the polarization is also proportional to a pseudoscalar parameter which vanishes if the molecules are nonchiral. The general statistical theory of ferroelectric ordering is illustrated by two particular models. The first model is based on electrostatic quadrupole-quadrupole interactions, and it enables one to obtain explicit analytical expressions for the spontaneous polarization. In the second model, the molecular chirality and polarity are determined by a pair of off-center nonparallel dipoles. For this case, the spontaneous polarization is calculated numerically as a function of temperature. The theory provides a more general interpretation of the previous approaches including the classical Boulder model.

Unexpected field-induced phase transitions between ferrielectric and antiferroelectric liquid crystal structures.

Liquid crystals are intriguing electrically responsive soft matter systems. We report previously unexplored field-induced changes in the structures of some frustrated liquid crystal phases and describe them theoretically. Specifically, we have discovered using resonant x-ray scattering that the four-layer intermediate smectic phase can undergo either a transition to the ferrielectric (three-layer) phase or to the ferroelectric phase, depending on temperature. Our studies of intermediate phases using electric fields offer a way to test theories that describe ferroelectricity in self-assembling fluids.

Molecular theory of layer contraction in smectic liquid crystals.

The period of the layered structure in smectic A and smectic C liquid crystal phases has been calculated numerically by direct minimization of the mean-field free energy which takes into account the interaction between molecules in adjacent smectic layers. The smectic layer spacing is calculated for two systems characterized by conventional and anomalously weak layer contraction in the smectic C phase. It is then compared with the simple estimate based on the average projection of the molecular long axis on the smectic layer normal. For both systems, temperature variation of the average molecular projection is qualitatively similar to that of the calculated layer spacing although certain quantitative deviations exist.

[Microbial intestinal biocenosis in lingering and complicated course of community pneumonia].

AIM: To characterize species and quantitative composition of intestinal microflora in lingering and complicated course of community pneumonia (CP). MATERIAL AND METHODS. The trial enrolled 130 CP patients and 30 healthy controls. Severe and moderate CP was diagnosed in 118 patients, mild CP--in 12 patients. In 36 (27.6%) patients the disease stayed long. Among the complications (47.7%) there were respiratory insufficiency of degree I-II (n = 29), exudative pleurisy (n = 7), toxic shock (n = 6), abscess of the lung (n = 5), acute vascular failure (n = 5), chronic renal failure (n = 5), DIC syndrome (n = 3), myocarditis (n = 2). Intestinal microflora was studied quantitatively and qualitatively using domestic materials. RESULTS: Dysbacteriosis often accompanies CP--42.3% in acute period, 18.8% in convalescence. Dysbacteriosis was more severe in severe CP. Compared to healthy controls, CP patients' intestine contains low content of bifidobacteria (100-fold), nonpathogenic enterococci and escherichia with normal enzymatic activity (10-fold and more). The number of saprophytic and epidermal staphylococci is very high- a 100-fold rise. In lingering pneumonia 2-3 times more often than in mild acute CP feces contain escherichia with low enzymatic activity, lactose-negative, staphylococci. Patients with pneumonia complications had dysbacteriosis of degree I, II, III and IV in 19.4, 30.4, 8.1 and 6.5% cases, respectively. CONCLUSION: Long-term administration of antibiotics in patients with lingering and complicated CP destroys balance of intestinal microflora and thus influences the course of CP. This dictates the necessity to conduct fecal microflora analysis in patients with CP irrespective of intestinal diseases.

Phase behavior and orientational ordering in block copolymers doped with anisotropic nanoparticles.

A molecular field theory and coarse-grained computer simulations with dissipative particle dynamics have been used to study the spontaneous orientational ordering of anisotropic nanoparticles in the lamellar and hexagonal phases of diblock copolymers and the effect of nanoparticles on the phase behavior of these systems. Both the molecular theory and computer simulations indicate that strongly anisotropic nanoparticles are ordered orientationally mainly in the boundary region between the domains and the nematic order parameter possesses opposite signs in adjacent domains. The orientational order is induced by the boundary and by the interaction between nanoparticles and the monomer units in different domains. In simulations, sufficiently long and strongly selective nanoparticles are ordered also inside the domains. The nematic order parameter and local concentration profiles of nanoparticles have been calculated numerically using the model of a nanoparticle with two interaction centers and also determined using the results of computer simulations. A number of phase diagrams have been obtained which illustrate the effect of nanoparticle selectivity and molar fraction of the stability ranges of various phases. Different morphologies have been identified by analyzing the static structure factor and a phase diagram has been constructed in coordinates' nanoparticle concentration-copolymer composition. Orientational ordering of even a small fraction of nanoparticles may result in a significant increase of the dielectric anisotropy of a polymer nanocomposite, which is important for various applications.

Flexoelectric instability and a spontaneous chiral-symmetry breaking in a nematic liquid crystal cell with asymmetric boundary conditions.

Using both numerical simulations and an approximate analytical theory we describe a flexoelectric-induced instability in a thin nematic liquid crystal layer with asymmetric boundary conditions subjected to an applied electric field. The dependence of the threshold value of the electric field on principal material parameters of the nematic liquid crystal and the director distribution in different regions of the cell have been studied in detail numerically. The results have been compared with a simple analytical theory that enables us to obtain explicit expressions for the threshold electric field and the period of modulation above the threshold. It has been found that in the hybrid aligned nematic cell with homeotropic anchoring on one surface and planar homogeneous anchoring on the other surface, a periodic flexoelectric-induced domain structure appears, above a critical threshold, with a chiral director distribution. The director rotates about the alignment axis when moving along a perpendicular direction in the plane of the cell. The absolute value of the threshold field has been found to depend on the direction of the field due to the initial symmetry of the hybrid aligned cell and the presence of flexoelectricity.

Order-disorder molecular model of the smectic-A-smectic-C phase transition in materials with conventional and anomalously weak layer contraction.

We develop a molecular-statistical theory of the smectic-A-smectic-C transition which is described as a transition of the order-disorder type. The theory is based on a general expansion of the effective interaction potential and employs a complete set of orientational order parameters. All the order parameters of the smectic-C phase including the tilt angle are calculated numerically as functions of temperature for a number of systems which correspond to different transition scenario. The effective interaction potential and the parameters of the transition are also calculated for specific molecular models based on electrostatic and induction interaction between molecular dipoles. The theory successfully reproduces the main properties of both conventional and so-called "de Vries-type" smectic liquid crystals, clarifies the origin of the anomalously weak layer contraction and describes the tricritical behavior at the smectic-A-smectic-C transition. The "de Vries behavior," i.e., anomalously weak layer contraction is also obtained for a particular molecular model based on interaction between longitudinal molecular dipoles. A simple phenomenological model is presented enabling one to obtain explicit expressions for the layer spacing and the tilt angle which are used to fit the experimental data for a number of materials.