Expression and activity profiles of DPP IV/CD26 and NEP/CD10 glycoproteins in the human renal cancer are tumor-type dependent

Background: Cell-surface glycoproteins play critical roles in cell-to-cell recognition, signal transduction and regulation, thus being crucial in cell proliferation and cancer etiogenesis and development. DPP IV and NEP are ubiquitous glycopeptidases closely linked to tumor pathogenesis and development, and they are used as markers in some cancers. In the present study, the activity and protein and mRNA expression of these glycoproteins were analysed in a subset of clear-cell (CCRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytomas (RO). Methods: Peptidase activities were measured by conventional enzymatic assays with fluorogen-derived substrates. Gene expression was quantitatively determined by qRT-PCR and membrane-bound protein expression and distribution analysis was performed by specific immunostaining. Results: The activity of both glycoproteins was sharply decreased in the three histological types of renal tumors. Protein and mRNA expression was strongly downregulated in tumors from distal nephron (ChRCC and RO). Moreover, soluble DPP IV activity positively correlated with the aggressiveness of CCRCCs (higher activities in high grade tumors). Conclusions: These results support the pivotal role for DPP IV and NEP in the malignant transformation pathways and point to these peptidases as potential diagnostic markers.

Effects of fundamental structure parameters on dynamic responses of submerged floating tunnel under hydrodynamic loads

This paper investigates the effects of structure parameters on dynamic responses of submerged floating tunnel (SFT) under hydrodynamic loads. The structure parameters includes buoyancy-weight ratio (BWR), stiffness coefficients of the cable systems, tunnel net buoyancy and tunnel length. First, the importance of structural damp in relation to the dynamic responses of SFT is demonstrated and the mechanism of structural damp effect is discussed. Thereafter, the fundamental structure parameters are investigated through the analysis of SFT dynamic responses under hydrodynamic loads. The results indicate that the BWR of SFT is a key structure parameter. When BWR is 1.2, there is a remarkable trend change in the vertical dynamic response of SFT under hydrodynamic loads. The results also indicate that the ratio of the tunnel net buoyancy to the cable stiffness coefficient is not a characteristic factor affecting the dynamic responses of SFT under hydrodynamic loads.

A simple method to simulate shrinkage-induced cracking in cement-based composites by lattice-type modeling

A new numerical procedure is proposed to investigate cracking behaviors induced by mismatch between the matrix phase and aggregates due to matrix shrinkage in cement-based composites. This kind of failure processes is simplified in this investigation as a purely spontaneous mechanical problem, therefore, one main difficulty during simulating the phenomenon lies that no explicit external load serves as the drive to propel development of this physical process. As a result, it is different from classical mechanical problems and seems hard to be solved by using directly the classical finite element method (FEM), a typical kind of "load -> medium -> response" procedures. As a solution, the actual mismatch deformation field is decomposed into two virtual fields, both of which can be obtained by the classical FEM. Then the actual response is obtained by adding together the two virtual displacement fields based on the principle of superposition. Then, critical elements are detected successively by the event-by-event technique. The micro-structure of composites is implemented by employing the generalized beam (GB) lattice model. Numerical examples are given to show the effectiveness of the method, and detailed discussions are conducted on influences of material properties.

Vortex dislocations in wake-type flow induced by spanwise disturbances

Vortex dislocations in wake-type flow induced by three types of spanwise disturbances superimposed on an upstream velocity profile are investigated by direct numerical simulations. Three distinct modes of vortex dislocations and flow transitions have been found. A local spanwise exponential decay disturbance leads to the appearance of a twisted chainlike mode of vortex dislocation. A stepped spanwise disturbance causes a streamwise periodic spotlike mode of vortex dislocation. A spanwise sinusoidal wavy disturbance with a moderate waviness causes a strong unsteadiness of wake behavior. This unsteadiness starts with a systematic periodic mode of vortex dislocation in the spanwise direction followed by the spanwise vortex shedding suppressed completely with increased time and the near wake becoming a steady shear flow. Characteristics of these modes of vortex dislocation and complex vortex linkages over the dislocation, as well as the corresponding dynamic processes related to the appearance of dislocations, are described by examining the variations of vortex lines and vorticity distribution. The nature of the vortex dislocation is demonstrated by the substantial vorticity modification of the spanwise vortex from the original spanwise direction to streamwise and vertical directions, accompanied by the appearance of noticeable vortex branching and complex vortex linking, all of which are produced at the locations with the biggest phase difference or with a frequency discontinuity between shedding cells. The effect of vortex dislocation on flow transition, either to an unsteady irregular vortex flow or suppression of the Kaacutermaacuten vortex shedding making the wake flow steady state, is analyzed. Distinct similarities are found in the mechanism and main flow phenomena between the present numerical results obtained in wake-type flows and the experimental-numerical results of cylinder wakes reported in previous studies.

Evidence of dopant type-inversion and other radiation damage effects of the CDF silicon detectors

xix, 213 p.

Brain type II calcium and calmodulin-dependent protein kinase: characterization of a brain-region specific isozyme and regulation by autophosphorylation

A variety of molecular approaches have been used to investigate the structural and enzymatic properties of rat brain type ll Ca^(2+) and calmodulin-dependent protein kinase (type ll CaM kinase). This thesis describes the isolation and biochemical characterization of a brain-region specific isozyme of the kinase and also the regulation the kinase activity by autophosphorylation.

The cerebellar isozyme of the type ll CaM kinase was purified and its biochemical properties were compared to the forebrain isozyme. The cerebellar isozyme is a large (500-kDa) multimeric enzyme composed of multiple copies of 50-kDa α subunits and 60/58-kDa β/β’ subunits. The holoenzyme contains approximately 2 α subunits and 8 β subunits. This contrasts to the forebrain isozyme, which is also composed of and β/β'subunits, but they are assembled into a holoenzyme of approximately 9 α subunits and 3 β/β ' subunits. The biochemical and enzymatic properties of the two isozymes are similar. The two isozymes differ in their association with subcellular structures. Approximately 85% of the cerebellar isozyme, but only 50% of the forebrain isozyme, remains associated with the particulate fraction after homogenization under standard conditions. Postsynaptic densities purified from forebrain contain the forebrain isozyme, and the kinase subunits make up about 16% of their total protein. Postsynaptic densities purified from cerebellum contain the cerebellar isozyme, but the kinase subunits make up only 1-2% of their total protein.

The enzymatic activity of both isozymes of the type II CaM kinase is regulated by autophosphorylation in a complex manner. The kinase is initially completely dependent on Ca^(2+)/calmodulin for phosphorylation of exogenous substrates as well as for autophosphorylation. Kinase activity becomes partially Ca^(2+) independent after autophosphorylation in the presence of Ca^(2+)/calmodulin. Phosphorylation of only a few subunits in the dodecameric holoenzyme is sufficient to cause this change, suggesting an allosteric interaction between subunits. At the same time, autophosphorylation itself becomes independent of Ca^(2+) These observations suggest that the kinase may be able to exist in at least two stable states, which differ in their requirements for Ca^(2+)/calmodulin.

The autophosphorylation sites that are involved in the regulation of kinase activity have been identified within the primary structure of the α and β subunits. We used the method of reverse phase-HPLC tryptic phosphopeptide mapping to isolate individual phosphorylation sites. The phosphopeptides were then sequenced by gas phase microsequencing. Phosphorylation of a single homologous threonine residue in the α and β subunits is correlated with the production of the Ca^(2+) -independent activity state of the kinase. In addition we have identified several sites that are phosphorylated only during autophosphorylation in the absence of Ca^(2+)/ calmodulin.

A perturbation procedure for nonlinear oscillations (The dynamics of two oscillators with weak nonlinear coupling)

This thesis considers in detail the dynamics of two oscillators with weak nonlinear coupling. There are three classes of such problems: non-resonant, where the Poincaré procedure is valid to the order considered; weakly resonant, where the Poincaré procedure breaks down because small divisors appear (but do not affect the O(1) term) and strongly resonant, where small divisors appear and lead to O(1) corrections. A perturbation method based on Cole's two-timing procedure is introduced. It avoids the small divisor problem in a straightforward manner, gives accurate answers which are valid for long times, and appears capable of handling all three types of problems with no change in the basic approach.

One example of each type is studied with the aid of this procedure: for the nonresonant case the answer is equivalent to the Poincaré result; for the weakly resonant case the analytic form of the answer is found to depend (smoothly) on the difference between the initial energies of the two oscillators; for the strongly resonant case we find that the amplitudes of the two oscillators vary slowly with time as elliptic functions of ϵ t, where ϵ is the (small) coupling parameter.

Our results suggest that, as one might expect, the dynamical behavior of such systems varies smoothly with changes in the ratio of the fundamental frequencies of the two oscillators. Thus the pathological behavior of Whittaker's adelphic integrals as the frequency ratio is varied appears to be due to the fact that Whittaker ignored the small divisor problem. The energy sharing properties of these systems appear to depend strongly on the initial conditions, so that the systems not ergodic.

The perturbation procedure appears to be applicable to a wide variety of other problems in addition to those considered here.

Serie Vídeos tutoriales para fonética. Video 9. Praat: doing phonetics by computer (Parte 5: Propiedades lingüísticas observables en curvas de frecuencia fundamental y de intensidad)

Esta es una colección de 10 vídeos tutoriales que pueden ser empleados como material educativo en los cursos de fonética básica en el ámbito universitario. Los vídeos 1-3 tratan aspectos relacionados con la grabación: el tipo de micrófonos que se emplean, las clases de espacios en las que se suelen llevar a cabo la captura de señales de audio y las grabadoras que se suelen emplear. El vídeo 4 explora técnicas de captura y observación de datos de flujo y presión en fonética aerodinámica. Los vídeos 5-10 presentan información sobre los principales usos que se le brindan al programa Praat (Boersma y Weenink, 2014) en los estudios actuales de fonética acústica, desde la clase de información sobre modos de articulación de las consonantes que se puede identificar en oscilogramas hasta la creación de señales sonoras sintetizadas por medio de unos procedimientos que tiene el programa para tal propósito, los cuales son susceptibles de ser empleados en experimentos de percepción auditiva.