IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma

Background: Cancer pain severely limits function and significantly reduces quality of life. Subtypes of sensory neurons involved in cancer pain and proliferation are not clear.Methods: We produced a cancer model by inoculating human oral squamous cell carcinoma (SCC) cells into the hind paw of athymic mice. We quantified mechanical and thermal nociception using the paw withdrawal assays. Neurotoxins isolectin B4-saporin (IB4-SAP), or capsaicin was injected intrathecally to selectively ablate IB4(+) neurons or TRPV1(+) neurons, respectively. JNJ-17203212, a TRPV1 antagonist, was also injected intrathecally. TRPV1 protein expression in the spinal cord was quantified with western blot. Paw volume was measured by a plethysmometer and was used as an index for tumor size. Ki-67 immunostaining in mouse paw sections was performed to evaluate cancer proliferation in situ.Results: We showed that mice with SCC exhibited both mechanical and thermal hypersensitivity. Selective ablation of IB4(+) neurons by IB4-SAP decreased mechanical allodynia in mice with SCC. Selective ablation of TRPV1(+) neurons by intrathecal capsaicin injection, or TRPV1 antagonism by JNJ-17203212 in the IB4-SAP treated mice completely reversed SCC-induced thermal hyperalgesia, without affecting mechanical allodynia. Furthermore, TRPV1 protein expression was increased in the spinal cord of SCC mice compared to normal mice. Neither removal of IB4(+) or TRPV1(+) neurons affected SCC proliferation.Conclusions: We show in a mouse model that IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Kinetic energy sum spectra in nonmesonic weak decay of hypernuclei

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Imigração e epidemias no estado de São Paulo

Esse artigo tem por objetivo apresentar e discutir aspectos de interesse sanitário no processo de imigração estrangeira para o estado de São Paulo, na primeira década após a proclamação da República. Objetiva também apresentar as relações da imigração com a formação dos serviços sanitários estaduais e com a elaboração do modelo tecno-assistencial por eles adotado a partir da década de 1890. Num momento em que a febre amarela era a mais freqüente e letal das epidemias que afetavam o estado, matando principalmente os estrangeiros, a defesa do fluxo migratório foi um dos fios condutores das ações em saúde pública. A combinação entre os interesses da cafeicultura, a expansão ferroviária, imigração e febre amarela definiu os rumos da ação sanitária promovida pelas oligarquias no poder nesse período em São Paulo. A organização autoritária do Estado brasileiro não dava espaço à implantação de ações individuais de assistência à saúde. Sempre reivindicada pela população urbana e rural, somente com o desenvolvimento da medicina previdenciária no país, na década de 1930, difundiram-se as ações de assistência individual à saúde.

Excluded volume effects in the quark meson coupling model

Excluded volume effects are incorporated in the quark-meson coupling model to take into account in a phenomenological way the hard-core repulsion of the nuclear force. The formalism employed is thermodynamically consistent and does not violate causality. The effects of the excluded volume on in-medium nucleon properties and the nuclear matter equation of state are investigated as a function of the size of the hard core. It is found that in-medium nucleon properties are not altered significantly by the excluded volume, even for large hard-core radii, and the equation of state becomes stiffer as the size of the hard core increases.

A Multi-Stage Stochastic Non-Linear Model for Reactive Power Planning Under Contingencies

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hopping-tunneling model to describe electric charge injection at metal/organic semiconductor heterojunctions

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estimativa da erodibilidade do solo para fins conservacionistas na microbacia córrego do Tijuco, SP

The soil erodibility factor is represented by the integrated effect of processes that regulate the water infiltration, soil resistance and the transport of soil particles. Therefore, this study had as objective to estimate the soil erodibility in the Corrego do Tijuco watershed, São Paulo State, Brazil, for guiding farmers in decision making for application of techniques for soil conservation. The soil samples were collected in a regular spacing of 500 m, resulting in a total of 310 points in a 0-20.0 m depth in an area of approximately 8,000 ha. For the estimation of soil erodibility (K) was applied a mathematical model which takes into account the soil organic matter content, the sand and silt size fractions, the soil permeability, and the particle mean diameter for each point of soil sampling. Estimated values greater than 0.040 Mg ha h ha(-1) MJ(-1) mm(-1) were considered very high for this factor. In areas with greater degree of erodibility occurs the Argisols order predominance, that shows high susceptibility to the development of interrill erosion due to its remarkable performance in relation to textural gradient, thereby, the interrill erosion rates can be very intensive due to rapid saturation of upper horizon, increasing the erosion process. At the Latosols (Oxisols) areas were also observed high soil erodibility values that under inappropriate conditions of soil occupation, concentrating runoff of rain water, leading to appear deep gullies.

Charges and fluxes in Maxwell theory on compact manifolds with boundary

We investigate the charges and fluxes that can occur in higher-order Abelian gauge theories defined on compact space-time manifolds with boundary. The boundary is necessary to supply a destination to the electric lines of force emanating from brane sources, thus allowing non-zero net electric charges, but it also introduces new types of electric and magnetic flux. The resulting structure of currents, charges, and fluxes is studied and expressed in the language of relative homology and de Rham cohomology and the corresponding abelian groups. These can be organised in terms of a pair of exact sequences related by the Poincare-Lefschetz isomorphism and by a weaker flip symmetry exchanging the ends of the sequences. It is shown how all this structure is brought into play by the imposition of the appropriately generalised Maxwell's equations. The requirement that these equations be integrable restricts the world-volume of a permitted brane (assumed closed) to be homologous to a cycle on the boundary of space-time. All electric charges and magnetic fluxes are quantised and satisfy the Dirac quantisation condition. But through some boundary cycles there may be unquantised electric fluxes associated with quantised magnetic fluxes and so dyonic in nature.

Dissipation and its consequences in the scaling exponents for a family of two-dimensional mappings

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Absolute configuration reassignment of two chromanes from Peperomia obtusifolia (Piperaceae) using VCD and DFT calculations

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Study of stress distribution with finite element method in a root with prefabricated threaded split shaft post - Part I

A finite element analysis was carried out to study the role of prefabricated threaded split shaft post (Flexi-Post) on dentinal stress in pulpless tooth. Three dimensional plane strain model of mesio-distal section of a human maxillary central incisor without restoration was analysed with the MSC/NASTRAN (MacNeal/ Schwendler) general purpose finite analysis program was executed on a microcomputer. The model as discretized into 48.954 axisymmetric finite elements defined by 10.355 nodes. Each element was assigned unique elastic properties to represent the materials modeled. Homogeneity, isotropy and linear elasticity were assume for all material. A simulation of static load of 100N was applied to the incisal edge of the post; vertical. Maximal principal stresses and von Mises equivalent stress were calculated. Using the element analysis model employed in this study, the following can be concluded concerning threaded split shaft post (Flexi-Post): Maximum principal stresses in dentin were located at cervical place and at the post apex. The apical threads of the post not redirecting stresses away from the root.

Electric characterization of a hybrid composite based on POMA/P(VDF- TrFE)/Zn2SiO4 : Mn using impedance spectroscopy

Understanding the microscopic origin of the dielectric properties of disordered materials has been a challenge for many years, especially in the case of samples with more than one phase. For polar dielectrics, for instance, the Lepienski approach has indicated that the random free energy barrier model of Dyre must be extended. Here we analyse the dielectric properties of a polymer blend made up with the semiconducting poly(o-methoxyaniline) and poly( vinylidene fluoride-trifluorethylene) POMA/P(VDF-TrFE), and of a hybrid composite of POMA/P(VDF-TrFE)/Zn2SiO4:Mn. For the blend, the Lepienski model, which takes into account the rotation or stretching of electric dipoles, provided excellent fitting to the ac impedance data. Because two phases had to be assumed for the hybrid composite, we had to extend the Lepienski model to fit the data, by incorporating a second transport mechanism. The two mechanisms were associated with the electronic transport in the polymeric matrix and with transport at the interfaces between Zn2SiO4: Mn microparticles and the polymeric matrix, with the relative importance of the interfacial component increasing with the percentage of Zn2SiO4: Mn in the composite. The analysis of impedance data at various temperatures led to a prediction of the theoretical model of a change in morphology at 190 +/- 40 K, and this was confirmed experimentally with a differential scanning calorimetry experiment.

Separation of particles in time-dependent focusing billiards

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Solution approaches for the soft drink integrated production lot sizing and scheduling problem

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Usage of enterprise modeling processes and information systems design to forecast demand

Managing the great complexity of enterprise system, due to entities numbers, decision and process varieties involved to be controlled results in a very hard task because deals with the integration of its operations and its information systems. Moreover, the enterprises find themselves in a constant changing process, reacting in a dynamic and competitive environment where their business processes are constantly altered. The transformation of business processes into models allows to analyze and redefine them. Through computing tools usage it is possible to minimize the cost and risks of an enterprise integration design. This article claims for the necessity of modeling the processes in order to define more precisely the enterprise business requirements and the adequate usage of the modeling methodologies. Following these patterns, the paper concerns the process modeling relative to the domain of demand forecasting as a practical example. The domain of demand forecasting was built based on a theoretical review. The resulting models considered as reference model are transformed into information systems and have the aim to introduce a generic solution and be start point of better practical forecasting. The proposal is to promote the adequacy of the information system to the real needs of an enterprise in order to enable it to obtain and accompany better results, minimizing design errors, time, money and effort. The enterprise processes modeling are obtained with the usage of CIMOSA language and to the support information system it was used the UML language.