Desarrollo del vocabulario temprano en ni??os con implante coclear escolarizados en centros con biling????smo oral-signado

Resumen basado en el de la publicaci??n

Candidate working set strategy based SMO algorithm in support vector machine

Sequential minimal optimization (SMO) is quite an efficient algorithm for training the support vector machine. The most important step of this algorithm is the selection of the working set, which greatly affects the training speed. The feasible direction strategy for the working set selection can decrease the objective function, however, may augment to the total calculation for selecting the working set in each of the iteration. In this paper, a new candidate working set (CWS) Strategy is presented considering the cost on the working set selection and cache performance. This new strategy can select several greatest violating samples from Cache as the iterative working sets for the next several optimizing steps, which can improve the efficiency of the kernel cache usage and reduce the computational cost related to the working set selection. The results of the theory analysis and experiments demonstrate that the proposed method can reduce the training time, especially on the large-scale datasets.

Farmacovigilância no Brasil: a relação entre polimorfi smo de fármacos, efetividade e segurança dos medicamentos

Apesar da política nacional de medicamentos propor que os mesmos tenham qualidade, efi cácia e segurança, os hospitais sentinelas têm recebido notifi cações de queixa técnica, reações adversas e suspeita de inefetividade terapêutica de medicamentos. Este estudo propôs identifi car os tipos de medicamentos notifi cados num hospital da Rede Sentinela, durante 18 meses, por suspeita de inefetividade terapêutica e verifi car a possibilidade de existência de polimorfos do fármaco, através de levantamento bibliográfi co. Foram identifi cadas 31 notifi cações de suspeita de inefetividade terapêutica de medicamentos similares, provenientes de onze fármacos diferentes, dos quais cinco podem apresentar polimorfos. No entanto, não signifi ca que os demais fármacos não apresentem polimorfos, sendo necessários estudos mais prolongados sobre o polimorfi smo, priorizando os estudos de fármacos com histórico de notifi cação de inefetividade terapêutica. Dados do presente estudo sugerem que testes de polimorfos sejam implantados na rotina do controle de qualidade da matéria-prima do fármaco, no desenvolvimento farmacotécnico do medicamento pela indústria farmacêutica e que o órgão sanitário federal exija os testes de polimorfi smo nos estudos de equivalência farmacêutica e estabilidade para o registro e pós-registro de medicamentos similares e genéricos, a fi m de assegurar a reprodutibilidade da qualidade, segurança e efi cácia comprovadas nos estudos in vivo de bioequivalência e biodisponibilidade relativa. Palavras-chave: polimorfi smo; vigilância sanitária; medicamento genérico; medicamento similar

SMO inhibitor specifically targets the Hedgehog Pathway and reverts the drug-resistance of Leukemic Stem Cells

Abnormal Hedgehog signaling is associated with human malignancies. Smo, a key player of that signaling, is the most suitable target to inhibit this pathway. To this aim several molecules, antagonists of Smo, have been synthesized, and some of them have started the phase I in clinical trials. Our hospital participated to one of these studies which investigated the oral administration of a new selective inhibitor of Smo (SMOi). To evaluate ex vivo SMOi efficacy and to identify new potential clinical biomarkers of responsiveness, we separated bone marrow CD34+ cells from 5 acute myeloid leukemia (AML), 1 myelofibrosis (MF), 2 blastic phases chronic myeloid leukemia (CML) patients treated with SMOi by immunomagnetic separation, and we analysed their gene expression profile using Affimetrix HG-U133 Plus 2.0 platform. This analysis, showed differential expression after 28 days start of therapy (p-value ≤ 0.05) of 1,197 genes in CML patients and 589 genes in AML patients. This differential expression is related to Hedgehog pathway with a p-value = 0.003 in CML patients and with a p-value = 0.0002 in AML patients, suggesting that SMOi targets specifically this pathway. Among the genes differentially expressed we observed strong up-regulation of Gas1 and Kif27 genes, which may work as biomarkers of responsiveness of SMOi treatment in CML CD34+ cells whereas Hedgehog target genes (such as Smo, Gli1, Gli2, Gli3), Bcl2 and Abca2 were down-regulated, in both AML and CML CD34+ cells. It has been reported that Bcl-2 expression could be correlated with cancer therapy resistance and that Hedgehog signaling modulate ATP-binding (ABC) cassette transporters, whose expression has been correlated with chemoresistance. Moreover we confirmed that in vitro SMOi treatment targets Hedgehog pathway, down-regulate ABC transporters, Abcg2 and Abcb1 genes, and in combination with tyrosine kinase inhibitors (TKIs) could revert the chemoresistance mechanism in K562 TKIs-resistant cell line.

A SMO inhibitor drug reduces the progenitor cell's maintenance in the Drosophila hematopoietic organ: a novel model to study Chronic Myelogenous Leukemia relapse

The chronic myeloid leukemia complexity and the difficulties of disease eradication have recently led to the development of drugs which, together with the inhibitors of TK, could eliminate leukemia stem cells preventing the occurrence of relapses in patients undergoing transplantation. The Hedgehog (Hh) signaling pathway positively regulates the self-renewal and the maintenance of leukemic stem cells and not, and this function is evolutionarily conserved. Using Drosophila as a model, we studied the efficacy of the SMO inhibitor drug that inhibit the human protein Smoothened (SMO). SMO is a crucial component in the signal transduction of Hh and its blockade in mammals leads to a reduction in the disease induction. Here we show that administration of the SMO inhibitor to animals has a specific effect directed against the Drosophila ortholog protein, causing loss of quiescence and hematopoietic precursors mobilization. The SMO inhibitor induces in L3 larvae the appearance of melanotic nodules generated as response by Drosophila immune system to the increase of its hemocytes. The same phenotype is induced even by the dsRNA:SMO specific expression in hematopoietic precursors of the lymph gland. The drug action is also confirmed at cellular level. The study of molecular markers has allowed us to demonstrate that SMO inhibitor leads to a reduction of the quiescent precursors and to an increase of the differentiated cells. Moreover administering the inhibitor to heterozygous for a null allele of Smo, we observe a significant increase in the phenotype penetrance compared to administration to wild type animals. This helps to confirm the specific effect of the drug itself. These data taken together indicate that the study of inhibitors of Smo in Drosophila can represent a useful way to dissect their action mechanism at the molecular-genetic level in order to collect information applicable to the studies of the disease in humans.

Oracion panegirica, que en la festiuidad del Smo. Sacramento, que celebró el convento de Corpus Christi de Religiosas Dominicas de la Villa de Carcagente dia 30 de mayo de 1728

Fecha de 1728 tomada de preliminares

Resumen historico de la portentosa llegada de la imagen del Smo. Christo del Salvador a los muros de la ciudad de Valencia ... en el año 1250, sacado de los escritores de la historia de dicha ciudad ... que publicaron D. Juan Bautista Ballester ... en el año 1672 ... y D. Josef Vicente Ortí y Mayor en el año 1709

Sign.: [A]-B2, C8

Resumen de la historia del Smo. Cristo del Salvador de Valencia

Sign.: [1]-4(4), 5(2)

Sermones que en las solemnes fiestas de la translacion del Smo. Sacramento, y milagrosa imagen de N. Sra. de las Mercedes al nuevo Templo del Real ... [Texto impreso]

Sign. : [ ]6, B-L4

Noticia de las Indulgencias concedidas por Ntro. Smo. P. Leon XVII ... a los 12 dias de Julio del año 1825, para todos los Fieles de ambos sexos, que confesados y comulgados, y verdaderamente contritos, visitaren la Capilla del Smo. Cristo de La Corona ... en la Parroquial Iglesia De Sta. Catalina Martir de la Ciudad de Valencia [Texto impreso]

Tit. tomado del texto

El Smo. Cristo del Salvador [Material gráfico]

Resumen: Descripción: Cristo del Salvador crucificado y acompañado por San Vicente Ferrer que le ofrece el Cáliz a la religiosa arrodillada a su lado, y por San Agustín Obispo que ofrece el Cáliz a Cristo crucificado, en segundo término el beato Gaspar Bono arrodillado