Impurity Concentration Profile Determination By Capacitance-Voltage Measurements

A FORTRAN program has been written to manipulate the data obtained from 1 MHZ C—V measurements. This program utilizes the data to compute information on the impurity profile of capacitors. Capacitors were fabricated with varying doping profiles and tested. The doping profiles obtained using this program were consistent with SUPREM models

Complex effects of rexinoids on ligand dependent activation or inhibition of the xenobiotic receptor, CAR

BACKGROUND: CAR/RXR heterodimers bind a variety of hormone response elements and activate transcription in the absence of added ligands. This constitutive activity of murine CAR can be inhibited by the inverse agonist ligand androstanol or increased by the agonist TCPOBOP. RXR agonists activate some RXR heterodimer complexes, which are termed permissive, while other non-permissive complexes are not responsive to such ligands. RESULTS: Direct protein-protein interaction studies demonstrate that the RXR agonist 9-cis-RA increases interaction of CAR/RXR heterodimers with the coactivator SRC-3, but also inhibits the ability of TCPOBOP to increase and androstanol to decrease coactivator binding. CAR transactivation of a response element with a five nucleotide spacer (DR-5) is unaffected by 9-cis-RA or the synthetic RXR agonist LG1069. In agreement with the inhibitory effect observed in vitro, these rexinoids block both the TCPOBOP mediated transactivation of this element and the androstanol dependent inhibition. In contrast, CAR transactivation of other response elements is increased by rexinoids. Stable expression of CAR in a HepG2 derived cell line increases expression of the endogenous CAR target CYP2B6. This expression is further increased by TCPOBOP but decreased by either androstanol or LG1069, and LG1069 blocks the stimulatory effect of TCPOBOP but not the inhibitory effect of androstanol. CONCLUSION: We conclude that CAR/RXR heterodimers are neither strictly permissive nor non-permissive for RXR signaling. Instead, rexinoids have distinct effects in different contexts. These results expand the potential regulatory mechanisms of rexinoids and suggest that such compounds may have complex and variable effects on xenobiotic responses

Perspectivas da função social do contrato: o adimplemento substancial no âmbito dos contratos de mútuo

O objetivo do presente trabalho é estudar de que maneira o novo princípio da função social do contrato se relaciona com a teoria do adimplemento substancial no âmbito dos contratos de mútuo, mais especificamente, nos contratos bancários de mútuo. Para isso, são explorados os conceitos elementares da teoria clássica do contrato, seus princípios tradicionais e sua evolução conforme novos paradigmas civis-constitucionais. Além disso, são trabalhados os conceitos de adimplemento e adimplemento substancial, com uma análise histórica de seu surgimento nos tribunais ingleses sob a common law. Adicionalmente, adentrando a parte específica do trabalho, apresenta-se a definição de contrato de mútuo e uma análise focada nos contratos de mútuo bancário feneratício. Por fim, todos os conceitos apresentados são entrelaçados de modo a evidenciar a relação entre o princípio da função social do contrato e o adimplemento substancial, tomando os contratos de mútuo bancário feneratício como base para tal ligação

Discrete Breathers in Two-Dimensional Anisotropic Nonlinear Schrodinger lattices

We study the structure and stability of discrete breathers (both pinned and mobile) in two-dimensional nonlinear anisotropic Schrodinger lattices. Starting from a set of identical one-dimensional systems we develop the continuation of the localized pulses from the weakly coupled regime (strongly anisotropic) to the homogeneous one (isotropic). Mobile discrete breathers are seen to be a superposition of a localized mobile core and an extended background of two-dimensional nonlinear plane waves. This structure is in agreement with previous results on onedimensional breather mobility. The study of the stability of both pinned and mobile solutions is performed using standard Floquet analysis. Regimes of quasi-collapse are found for both types of solutions, while another kind of instability (responsible for the discrete breather fission) is found for mobile solutions. The development of such instabilities is studied, examining typical trajectories on the unstable nonlinear manifold.Comment: 13 pages, 9 figure

Multistable Solitons in the Cubic-Quintic Discrete Nonlinear Schr\"odinger Equation

We analyze the existence and stability of localized solutions in the one-dimensional discrete nonlinear Schr\"{o}dinger (DNLS) equation with a combination of competing self-focusing cubic and defocusing quintic onsite nonlinearities. We produce a stability diagram for different families of soliton solutions, that suggests the (co)existence of infinitely many branches of stable localized solutions. Bifurcations which occur with the increase of the coupling constant are studied in a numerical form. A variational approximation is developed for accurate prediction of the most fundamental and next-order solitons together with their bifurcations. Salient properties of the model, which distinguish it from the well-known cubic DNLS equation, are the existence of two different types of symmetric solitons and stable asymmetric soliton solutions that are found in narrow regions of the parameter space. The asymmetric solutions appear from and disappear back into the symmetric ones via loops of forward and backward pitchfork bifurcations.Comment: To appear Physica D. 23 pages, 13 figure

Estrogen regulation of TRPM8 expression in breast cancer cells

<p>Abstract</p> <p>Background</p> <p>The calcium-permeable cation channel TRPM8 (melastatin-related transient receptor potential member 8) is over-expressed in several cancers. The present study aimed at investigating the expression, function and potential regulation of TRPM8 channels by ER alpha (estrogen receptor alpha) in breast cancer.</p> <p>Methods</p> <p>RT-PCR, Western blot, immuno-histochemical, and siRNA techniques were used to investigate TRPM8 expression, its regulation by estrogen receptors, and its expression in breast tissue. To investigate the channel activity in MCF-7 cells, we used the whole cell patch clamp and the calcium imaging techniques.</p> <p>Results</p> <p>TRPM8 channels are expressed at both mRNA and protein levels in the breast cancer cell line MCF-7. Bath application of the potent TRPM8 agonist Icilin (20 μM) induced a strong outwardly rectifying current at depolarizing potentials, which is associated with an elevation of cytosolic calcium concentration, consistent with established TRPM8 channel properties. RT-PCR experiments revealed a decrease in TRPM8 mRNA expression following steroid deprivation for 48 and 72 hours. In steroid deprived medium, addition of 17-beta-estradiol (E₂, 10 nM) increased both TRPM8 mRNA expression and the number of cells which respond to Icilin, but failed to affect the Ca²⁺entry amplitude. Moreover, silencing ERα mRNA expression with small interfering RNA reduced the expression of TRPM8. Immuno-histochemical examination of the expression of TRPM8 channels in human breast tissues revealed an over-expression of TRPM8 in breast adenocarcinomas, which is correlated with estrogen receptor positive (ER⁺) status of the tumours.</p> <p>Conclusion</p> <p>Taken together, these results show that TRPM8 channels are expressed and functional in breast cancer and that their expression is regulated by ER alpha.</p

TRPV6 Determines the Effect of Vitamin D3 on Prostate Cancer Cell Growth

Despite remarkable advances in the therapy and prevention of prostate cancer it is still the second cause of death from cancer in industrialized countries. Many therapies initially shown to be beneficial for the patients were abandoned due to the high drug resistance and the evolution rate of the tumors. One of the prospective therapeutical agents even used in the first stage clinical trials, 1,25-dihydroxyvitamin D3, was shown to be either unpredictable or inefficient in many cases. We have already shown that TRPV6 calcium channel, which is the direct target of 1,25-dihydroxyvitamin D3 receptor, positively controls prostate cancer proliferation and apoptosis resistance (Lehen'kyi et al., Oncogene, 2007). However, how the known 1,25-dihydroxyvitamin D3 antiproliferative effects may be compatible with the upregulation of pro-oncogenic TRPV6 channel remains a mystery. Here we demonstrate that in low steroid conditions 1,25-dihydroxyvitamin D3 upregulates the expression of TRPV6, enchances the proliferation by increasing the number of cells entering into S-phase. We show that these pro-proliferative effects of 1,25-dihydroxyvitamin D3 are directly mediated via the overexpression of TRPV6 channel which increases calcium uptake into LNCaP cells. The apoptosis resistance of androgen-dependent LNCaP cells conferred by TRPV6 channel is drastically inversed when 1,25-dihydroxyvitamin D3 effects were combined with the successful TRPV6 knockdown. In addition, the use of androgen-deficient DU-145 and androgen-insensitive LNCaP C4-2 cell lines allowed to suggest that the ability of 1,25-dihydroxyvitamin D3 to induce the expression of TRPV6 channel is a crucial determinant of the success or failure of 1,25-dihydroxyvitamin D3-based therapies