Semirigid inclusions in elastic bodies: Mechanical interplay and optimal control

The paper concerns an analysis of an equilibrium problem for 2D elastic body with two semirigid inclusions. It is assumed that inclusions have a joint point, and we investigate a junction problem for these inclusions. The existence of solutions is proved, and different equivalent formulations of the problem are proposed. We investigate a convergence to infinity of a rigidity parameter of the semirigid inclusion. It is proved that in the limit, we obtain an equilibrium problem for the elastic body with a rigid inclusion and a semirigid one. A parameter identification problem is investigated. In particular, the existence of a solution to a suitable optimal control problem is proved.     

Dynamic Effects of Submillimeter Wave Radiation on Biological Objects of Various Levels of Organization

We have presented an overview of the literature and of our experimental data on the influence of electromagnetic radiation in the submillimeter spectral region on biological objects of molecular, cellular, and organism levels. Possible physical mechanisms involved and the reasons for limited development of the research in this spectral range are discussed.     

Waveguide probe structures for a multilayer magnetodielectric: An inverse problem

Direct and inverse problems are considered for diffraction by an open end of a rectangular waveguide (RW) with a flange that adjoins a piecewise inhomogeneous planar layered lossy medium. Also considered are similar diffraction problems for a junction of an RW and a rectangular resonator filled with a multilayer medium and a junction of two RWs, one of which contains a multilayer plate. Such open and shielded waveguide probe structures (WPSs) are used for determination and nondestructive testing of parameters of multilayer samples. The direct problem is formulated on the basis of admittance and impedance algorithms with consideration for losses existing in the medium, flange, and screens. In this case, the approximation of the given aperture field allows obtainment of explicit solutions for open and shielded WPSs in the form of integrals. Solution of the inverse problem that lies in determining thicknesses, permittivities, and permeabilities of the layers from measured values of the magnitude of the reflection coefficient is obtained by minimizing the corresponding least-squares error and by constructing artificial neural networks. In order to increase the accuracy, it is proposed to use a two-port of errors and perform measurements for several positions of the sample with respect to the flange and different impedance conditions behind the sample.     

Cytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines

BACKGROUND: Topotecan (TPT) is a topoisomerase I poison that exhibits antineoplastic activity. Analysis of the cytotoxic effects of combinations of TPT and other anticancer agents has been limited. PURPOSE: We assessed the cytotoxic effects produced by combinations of TPT and other antineoplastic agents in experiments involving multiple human cancer cell lines of diverse histologic origins. METHODS: The cytotoxic effects of various antimetabolites (fluorouracil, methotrexate, or cytarabine), antimicrotubule agents (vincristine or paclitaxel [Taxol]), DNA alkylating agents (melphalan, bis[chloroethyl]nitrosourea [BCNU], or 4-hydroperoxycyclophosphamide [4HC]), and a DNA-platinating agent (cisplatin), alone and in combination with TPT, were measured in clonogenic (i.e., colony-forming) assays. HCT8 ileocecal adenocarcinoma, A549 non-small-cell lung carcinoma, NCI-H82ras(H) lung cancer, T98G glioblastoma, and MCF-7 breast cancer cell lines were used in these assays. The data were analyzed by the median effect method, primarily under the assumption that drug mechanisms of action were mutually nonexclusive (i.e., completely independent of one another). For each level of cytotoxicity (ranging from 5% to 95%), a drug combination index (CI) was calculated. A CI less than 1 indicated synergy (i.e., the effect of the combination was greater than that expected from the additive effects of the component agents), a CI equal to 1 indicated additivity, and a CI greater than 1 indicated antagonism (the effect of the combination was less than that expected from the additive effects of the component agents). RESULTS: When the mechanisms of drug action were assumed to be mutually nonexclusive, virtually all CIs for combinations of TPT and either antimetabolites or antimicrotubule agents revealed cytotoxic effects that were less than additive. The CIs calculated at low-to-intermediate levels of cytotoxicity for combinations of TPT and the DNA alkylating agents melphalan, BCNU, and 4HC also showed drug effects that were less than additive; in most cases, however, nearly additive or even synergistic effects were observed with these same drug combinations at high levels of cytotoxicity (i.e., at > or = 90% inhibition of colony formation). Results obtained with combinations of TPT and cisplatin varied according to the cell line examined. With A549 cells, less than additive effects were seen at low-to-intermediate levels of cytotoxicity, and more than additive effects were seen at high levels of cytotoxicity. With NCI-H82ras(H) cells, synergy was observed over most of the cytotoxicity range. CONCLUSIONS AND IMPLICATIONS: TPT cytotoxicity appears to be enhanced more by combination with certain DNA-damaging agents than by combination with antimetabolites or antimicrotubule agents. Interactions between TPT and other drugs can vary depending on the cell type examined. Further investigation is required to determine the basis of the observed effects and to determine whether these in vitro findings are predictive of results obtained in vivo.     

Structure and composition of guanidine acrylate, guanidine methacrylate, their homopolymers, and copolymers with diallyldimethylammonium chloride

Structures and compositions of the monomers guanidine acrylate and guanidine methacrylate, their homopolymers, and copolymers with diallyldimethylammonium chloride enriched in acrylate comonomer units were determined. It was shown that ampholytic copolymers, owing to their ionic nature, contained comonomeric guanidine acrylate or methacrylate units and diallyldimethylammonium chloride units, as well as the acrylate comonomer with the diallyl counterion and polymeric acrylate and diallyl ion pairs. It follows from IR and ¹H NMR data that guanidine methacrylate has the same structure (with two hydrogen bonds) in the solid state and in solutions. Guanidine acrylate structures in the solid state and in dimethylsulfoxide are identical and analogous to guanidine methacrylate structure in this solvent. In water, the guanidine acrylate structure has another type of hydrogen bonding (with one hydrogen bond, where the proton is shifted toward the guanidine group). These features of hydrogen bonding of guanidine acrylate and guanidine methacrylate are also retained in their homopolymers and copolymers with diallyldimethylammonium chloride. It was shown that the thermal stability of the copolymers was higher than that of their homopolymers, confirming the formation of intramolecular ion pairs of oppositely charged units of ampholytic copolymers. Moreover, the thermal stability of guanidine methacrylate-diallyldimethylammonium chloride copolymers is higher than that of guanidine acrylate-diallyldimethylammonium chloride copolymers.     

Evidence for distinct signaling mechanisms in two mammalian olfactory sense organs

In mammals, olfactory stimuli are detected by sensory neurons at two distinct sites: the olfactory epithelium (OE) of the nasal cavity and the neuroepithelium of the vomeronasal organ (VNO). While the OE can detect volatile chemicals released from numerous sources, the VNO appears to be specialized to detect pheromones that are emitted by other animals and that convey information of behavioral or physiological importance. The mechanisms underlying sensory transduction in the OE have been well studied and a number of components of the transduction cascade have been cloned. Here, we investigated sensory transduction in the VNO by asking whether VNO neurons express molecules that have been implicated in sensory transduction in the OE. Using in situ hybridization and Northern blot analyses, we found that most of the olfactory transduction components examined, including the guanine nucleotide binding protein alpha subunit (G-alpha-olf), adenylyl cyclase type III, and an olfactory cyclic nucleotide-gated (CNG) channel subunit (oCNC1), are not expressed by VNO sensory neurons. In contrast, VNO neurons do express a second olfactory CNG channel subunit (oCNC2). These results indicate that VNO sensory transduction is distinct from that in the OE but raise the possibility that, like OE sensory transduction, sensory transduction in the VNO might involve cyclic nucleotide-gated ion channels.     

Role of hepatic resection in surgery for bilateral intrahepatic stones

The effect of phenylephrine-induced reflex parasympathetic stimulation on QT interval and its dispersion was studied in 16 healthy subjects with a history of paroxysmal supraventricular tachycardia, both during sinus rhythm and during atrial pacing. Results demonstrate that rapid reflex parasympathetic stimulation does not influence QT interval duration or QT dispersion, and also emphasize the inappropriateness of Bazett's formula, the need for comparison of QT intervals during identical heart rates, and the importance of analyzing all 12 leads of a standard electrocardiogram when assessing the effects of various interventions on the QT interval.     

Dependence on the motif YIPP for the physical association of Jak2 kinase with the intracellular carboxyl tail of the angiotensin II AT1 receptor

Angiotensin II is the effector molecule of the renin-angiotensin system. Virtually all of its biochemical actions are mediated through a single class of cell-surface receptors called AT1. These receptors contain the structural features of the seven-transmembrane, G-protein-coupled receptor superfamily. Angiotensin II, acting through the AT1 receptor, also stimulates the Jak/STAT pathway by inducing ligand-dependent Jak2 tyrosine phosphorylation and activation. Here, we show that a glutathione S-transferase fusion protein containing the carboxyl-terminal 54 amino acids of the rat AT1A receptor physically binds to Jak2 in an angiotensin II-dependent manner. Deletional analysis, using both in vitro protocols and cell transfection analysis, showed that this association is dependent on the AT1A receptor motif YIPP (amino acids 319-322). The wild-type AT1A receptor can induce Jak2 tyrosine phosphorylation. In contrast, an AT1A receptor lacking the YIPP motif is unable to induce ligand-dependent phosphorylation of Jak2. Competition experiments with synthetic peptides suggest that each of the YIPP amino acids, including tyrosine 319, is important in Jak2 binding to the AT1A receptor. The binding of the AT1A receptor to the intracellular tyrosine kinase Jak2 supports the concept that the seven-transmembrane superfamily of receptors can physically associate with enzymatically active intracellular proteins, creating a signaling complex mechanistically similar to that observed with growth factor and cytokine receptors.