Ab initio study of single-crystalline and polycrystalline elastic properties of Mg-substituted calcite crystals.

We employ ab initio calculations and investigate the single-crystalline elastic properties of (Ca,Mg)CO3 crystals covering the whole range of concentrations from pure calcite CaCO3 to pure magnesite MgCO3. Studying different distributions of Ca and Mg atoms within 30-atom supercells, our theoretical results show that the energetically most favorable configurations are characterized by elastic constants that nearly monotonously increase with the Mg content. Based on the first principles-derived single-crystalline elastic anisotropy, the integral elastic response of (Ca,Mg)CO3 polycrystals is determined employing a mean-field self-consistent homogenization method. As in case of single-crystalline elastic properties, the computed polycrystalline elastic parameters sensitively depend on the chemical composition and show a significant stiffening impact of Mg atoms on calcite crystals in agreement with the experimental findings. Our analysis also shows that it is not advantageous to use a higher-scale two-phase mix of stoichiometric calcite and magnesite instead of substituting Ca atoms by Mg ones on the atomic scale. Such two-phase composites are not significantly thermodynamically favorable and do not provide any strong additional stiffening effect.

Model-based investigation of the transcriptional activity of p53 and its feedback loop regulation via 14-3-3σ.

Experiments have recently shown that p53 expression can display oscillations in response to certain stress signals. In this work, mathematical modelling and bifurcation analysis are combined to investigate under which conditions the oscillation of p53 could propagate to its direct downstream transcription targets. The authors' analysis suggests that oscillations of p53 will propagate only to proteins with medium-fast mRNA and protein turnover rates. The authors retrieved data concerning the half-life of mRNA and protein for a number of p53-promoted genes and found that, according to their model, most of them are not able to inherit the oscillation of p53 because of their slow turnover rates. However, their analysis indicates that p53 oscillation may actually fine-tune the expression pattern of a protein when it is integrated with a second oscillatory signal. The authors also consider the case of additional regulatory loops affecting p53 oscillations and involving proteins transcriptionally induced by p53. Their results for 14-3-3σ, a protein that targets the p53 inhibitor MDM2 for degradation, suggest that the addition of feedback-loop regulation may modulate basic properties of p53 oscillation and induce quick cessation of them under certain physiological conditions. Moreover, the interplay between DNA damage and 14-3-3σ may induce bistability in the oscillation of p53.

Robustness and optimal use of design principles of arthropod exoskeletons studied by ab initio-based multiscale simulations.

Recently, we proposed a hierarchical model for the elastic properties of mineralized lobster cuticle using (i) ab initio calculations for the chitin properties and (ii) hierarchical homogenization performed in a bottom-up order through all length scales. It has been found that the cuticle possesses nearly extremal, excellent mechanical properties in terms of stiffness that strongly depend on the overall mineral content and the specific microstructure of the mineral-protein matrix. In this study, we investigated how the overall cuticle properties changed when there are significant variations in the properties of the constituents (chitin, amorphous calcium carbonate (ACC), proteins), and the volume fractions of key structural elements such as chitin-protein fibers. It was found that the cuticle performance is very robust with respect to variations in the elastic properties of chitin and fiber proteins at a lower hierarchy level. At higher structural levels, variations of design parameters such as the volume fraction of the chitin-protein fibers have a significant influence on the cuticle performance. Furthermore, we observed that among the possible variations in the cuticle ingredients and volume fractions, the experimental data reflect an optimal use of the structural variations regarding the best possible performance for a given composition due to the smart hierarchical organization of the cuticle design.

Effect of purified saponin mixture from Astragalus corniculatus on enzyme- and non-enzyme-induced lipid peroxidation in liver microsomes from spontaneously hypertensive rats and normotensive rats.

The aim of the following study was to evaluate the effect of a purified saponin mixture (PSM), isolated from Astragalus corniculatus Bieb. (Fabaceae), on enzyme-induced and non-enzyme-induced lipid peroxidation (LPO), in liver microsomes from spontaneously hypertensive rats (SHRs) - strain Okamoto Aoki, as compared to normotensive Wistar rats (NTRs). The enzyme-induced lipid peroxidation was performed by incubating rat liver microsomes with carbonetetrachloride (CCl(4)) in the presence of NADPH. In nonenzyme-induced LPO, the microsomes were incubated with a solution of iron sulphate and ascorbinic acid (Fe(2+)/AA). The effect of PSM (196.5 microg/ml) was assessed at 20 minutes' incubation time. MDA, a product of LPO, was measured spectrophotometrically. The results of our study showed that the initial MDA quantity in SHRs was significantly higher, than in NTRs. The incubation of the microsomes from both strains with PSM (196.5 microg/ml), resulted in significant reduction of MDA level, by 25% in SHRs. In NTRs, the formation of MDA was unchanged. In enzyme-induced LPO model, PSM significantly decreased the formation of MDA, by 55% in NTRs and by 35% in SHRs, compared to the respective control groups. In the model of non-enzyme induced LPO, PSM significantly decreased the formation of MDA by 95% in NTRs and practically restored it to the control level. The MDA quantity in SHR's microsomes was reduced by 25%. According to the results of this experiment we could conclude that PSM, isolated from Astragalus corniculatus, shows antioxidant activity both in SHRs and NTRs and the effect in NTRs is more pronounced.

Role of inhibitory proteins as modulators of oscillations in NFB signalling.

The authors discuss the role of the Raf kinase inhibitory protein (RKIP) as a modulator of oscillations in NFB signalling. A mathematical model of the NFB signalling pathway was derived and the Lyapunov-Andronov theory was used to analyse dynamical properties of the system. The analytical results were complemented by predictive numerical simulations. Our results suggest that the nature of oscillations, emerging under sustained stimulation of the system, depends on the interplay between the IB kinase (IKK) stimulation and the inhibitory action of RKIP. The authors found a mathematical relation that defines isoclines in IKK and RKIP levels for which the properties of oscillations are conserved and changes in the stimulation can be compensated by modulating RKIP inhibition. On the other hand, the shifting from the current isocline provokes modulation in either the amplitude (for stronger stimulation) or the frequency (for weaker stimulation).

Immunorestoration and augmentation of mitogen lymphocyte response in Graffi tumor bearing hamsters by purified saponin mixture from Astragalus corniculatus.

Investigations on the effect of purified saponin mixture (PSM) obtained from the aerial parts of Astragalus corniculatus Bieb. (Fabaceae) on mitogen response of the spleen cells in Graffi tumor bearing (GTBH) and healthy hamsters were reported. The saponin mixture in a doses of 50mg/kg b.w. was injected i.p. 4 times starting simultaneously with implantation of tumor cells. Stimulation indices to phytohemagglutinine (PHA) and lipopolysaccharide (LPS) of lymphocytes in spleens of tumor bearing hamsters (TBH) were significantly decreased during the whole period of the observation. It was established that PSM stimulated the functions of spleen cells in Graffi-TBH, resulting in increased mitogen response to PHA and LPS. The stimulation was better expressed in healthy PSM-treated hamsters. The proliferation response of spleen lymphocytes to PSM was also found. PSM did not change the in vitro proliferation ability of Graffi tumor cells. The results obtained proved the immunostimulating and immunorestorating activity of PSM on the T- and B-spleen cells in healthy and GTBH hamsters, as well as the proliferative response of it to PSM.

Influence of purified saponin mixture from Astragalus corniculatus Bieb. on phagocytic cells in Graffi-tumor bearing hamsters.

A purified saponin mixture (PSM) from Astragalus corniculatus Bieb. protected significantly hamsters against the experimental Graffi myeloid tumor. The application of PSM increased the survival rates, prolonged mean survival time and the tumor growth was markedly reduced. A purified saponin mixture (PSM) of Astragalus corniculatus Bieb. was evaluated for its immunostimulating potentials on the phagocytic cells in Graffi-tumor bearing hamsters. The number, migration and phagocytic indexes of peritoneal macrophages (pMøs) and of blood polymorphonuclear leukocytes (PMNs) were evaluated in healthy and Graffi-tumor bearing hamsters (G-TBH) treated with PSM. It was established that the Graffi myeloid tumor induced suppression of the phagocytic abilities of pMøs and PMNs. The number and migration of pMøs was significantly decreased during the whole period of observation. All tested parameters-number, migration and phagocytic activities of pMøs, as well as phagocytic ability of PMNs increased significantly in healthy and G-TBH after i.p. application of the 50 mg/kg body weight PSM. The PMS extracts from Astragalus corniculatus Bieb. are isolated and examined and their immunostimulating and immunorestorating impact on phagocitic cells was proven for the first time. This effect could be due to their high content of purified saponins.

Protective effect of Astragalus corniculatus saponins against myeloid graffi tumour in hamsters.

A purified mixture containing mostly saponins (PMS) from Astragalus corniculatus Bieb. was used in an in vivo model to demonstrate its protective effect against myeloid Graffi tumour in hamsters. Survivability, tumour growth and tumour transplantability were followed. Comparative studies revealed that the intraperitoneal administration of PMS: (i) decreased the tumour transplantability; (ii) inhibited tumour growth in the early stages of tumour progression; (iii) increased the mean survival time; (iv) reduced the percentage mortality. These results suggest that appropriate use of PMS could outline a promising strategy for the treatment of myeloid Graffi tumour.

[Micrometastases in patients with colorectal cancer: markers for metastatic potential or proofs for residual disease]. / Mikrometastazi pri patsienti s kolorektalen kartsinom: markeri za matastatichen potentsial ili dokazatelstvo za rezidualna bolest.

It is know that bone marrow micrometastases are an indicator of poor prognosis in patients with epithelial tumors. At the same time little is known if they reflect minimal residual disease or cells distribution and marked metastatic potential. We aimed to perform a clinical study, which though with little gathered clinical material has a direction--investigation of bone marrow in patients with colorectal cancer by the time of surgery, carefully rendering an account of staging and performing curative resection. In intraoperatively done bone marrow biopsy with following investigation for cytoceratin 19 positive cells we found ol presence of metastatic cells in some the studied patients. Finding micrometastases in patients with colorectal cancer is a marker for more agressive course of the disease and for the need to change some of recent methods of treatment.

[A new approach for discovering minimal residual disease in patients with operable breast cancer]. / Nov podkhod za otkrivane na minimalna ostatuchna bolest pri patsienti s operabilen rak na gurdata.

The striving of surgeon for achieving better long-term results of surgical treatment of patients with breast cancer put the searching of new independent prognostic factors for the exit of the treatment. This has become possible in the last decade of XX century when new diagnostic methods as immunochistochemistry, polimerase chain reaction (PCR), cytomorphology etc. entered the clinical practice. With bone marrow biopsy in patients with breast cancer earlier diagnosis of minimal residual disease is achieved, the approach to those patients is changed and a possibility for discovering women at higher risk is given. By immunochistochemistry method in the diagnostics of minimal residual disease in patients with breast cancer, more precise staging is achieved. This will change the therapeutic approach to these patients.

Application of different spatial sampling patterns for sparse array transducer design.

In the last few years, the efforts of many researchers have been focused on developing 3D real-time scanners. The use of 2D phased-array transducers makes it possible to steer the ultrasonic beam in all directions in the scanned volume. An unacceptably large amount of transducer channels (more than 4,000) must be used, if the conventional phased array transducers are extrapolated to the 2D case. To decrease the number of channels, sparse arrays with different aperture apodization functions in transmit and receive apertures have to be designed. The design is usually carried out in 1D, and then transferred to a 2D rectangular grid. In this paper, five different 2D array transducers have been considered and their performance was compared with respect to spatial and contrast resolution. An optimization of the element placement along the diagonals using vernier arrays is suggested. The simulation results of the ultrasound fields show a decrease in the grating-lobe level of 10 dB for the diagonally optimized 2D array transducers compared to the previously designed 2D arrays which did not consider the diagonals.

[Genetic changes in breast cancer - an overview]. / Obzor na genetichnite promeni pri rak na g'rdata.

Current understandings about development of breast cancer from genetic point of view are discussed. Information about the hereditary forms of cancer is presented. Different forms of screening and problems connected with their application are discussed.

[Radioimmunoguided surgery - a new stage of therapeutic management of oncological patients]. / Radioimunor'kovodena khirurgiia - nov etap na povedenie pri onkologichno bolnite.

Thanks to the fast development of nuclear medicine and radiodiagnostics with highly informative techniques it became possible to use the application methods the surgical practice. The methods that are used the nowadays intraoperative techniques aim to help the malignant disease, to stage more precisely the process; to help visualisation of the metastases and to evaluate the volume of the used surgical techniques that highly informative. This is possible through the last 1-2 years by application monoclonal antibodies labeled by radioisotopes, whose specific accumulation is evaluated by the help of gamma-tetector probe (GDP).

Rheodynamic model of cardiac pressure pulsations.

To analyse parametrically (in terms of the qualitative theory of dynamical systems) the mechanical influence of inertia, resistance (positive and negative), elasticity and other global properties of the heart-muscle on the left ventricular pressure, an active rheodynamic model based on the Newtons's principles is proposed. The equation of motion of the heart mass centre is derived from an energy conservation law balancing the rate of mechanical (kinetic and potential) energy variation and the power of chemical energy influx and dissipative energy outflux. A corresponding dynamical system of two ordinary differential equations is obtained and parametrically analysed in physiological conditions. As a result, the following main conclusion is made: in physiological norm, because of the heart electrical activity, its equilibrium state is unstable and around it, mechanical self-oscillations emerge. In case the electrical activity ceases, an inverse phase reconstruction occurs during which the unstable equilibrium state of the system becomes stable and the self-oscillations disappear.

[Serious infections associated with transurethral operations for lower urinary tract obstruction]. / Signifikantni infektsii pri transuretralni operatsii za obstruktsiia na dolniia urinaren trakt.

Serious urinary infections associated with transurethral surgery are a problem of current interest. The underlying causes of their occurrence and the therapeutic approach used are discussed. The study covers 139 patients treated over a two-year period. The types of diseases giving rise to lower urinary tract obstruction and the transurethral operations performed--optic urethrotomy, laser photocoagulation and transurethral resection--are analyzed. In all patients sterile urine assessment is done before, during and after treatment. Identification of the bacterial strains and antimicrobial sensitivity testing are conducted with mini API system--Bio-Merieux, France. The frequency of microbical causing agents and their antibacterial resistance are studied. The tactics in selecting the most adequate drug is discussed. Pseudomonas aeruginosa is identified as urinary infection cause in 49.5 per cent. Good results are obtained in 118 patients (84.9%); among those without urethral catheter prior to operation--97.3 per cent, and in the group with urethral catheter--70.3 per cent. Conclusions are drawn concerning the necessity of microbiological study of the urine in transurethral operations, and undertaking treatment in due course. Retaining of the indwelling urethral catheter prior to intervention should be reduced to a minimum. The clinical efficacy of oral beta-lactams is lower by comparison with fluoroquinolines owing to the multiple resistance of strains. The tenets of picking out an antibiotic for handling significant urinary infections are outlined.

[Treatment of benign prostatic hyperplasia with tamsulosin]. / [Lechenie na dobrokachestvena prostatna khiperplaziia s tamsulosin]

The past few decades mark a rejuvenation of the contingent of benign prostate hyperplasia (BPH) patients. The condition affects mainly the active age in men, with the substantial financial burden of treatment leading to a surge of interest in the disease. The hazards of postoperative complications development constrain modern urologists to seek for new, safer and more effective methods of conservative management. The task undertaken is to assay the effect of application and possible side phenomena of Tamsulosin treatment in BPH patients, administered at dose 0.4 mg a single time on a daily basis over 12 to 24 weeks. A nationwide multicenter, parallel, randomized study is conducted in seven urological clinical units throughout the country, covering a one year period. For the purpose a total of 310 men, aged 52 to 68 years, presenting moderately expressed BPH symptomatology are investigated. IPSS improvement is documented in 229 patients (74%), and a significant MUD improvement is observed in 115 patients (37%), with the residual urine quantity decreasing significantly in 108 patients (35%). In conclusion, it is believed that Tamsulosin administration as a superselective alpha-1-A adrenoblocker is one of major achievements in the conservative therapeutic approach to prostate adenoma.