Generalized Fourier Integral Operators on spaces of Colombeau type

Generalized Fourier integral operators (FIOs) acting on Colombeau algebras are defined. This is based on a theory of generalized oscillatory integrals (OIs) whose phase functions as well as amplitudes may be generalized functions of Colombeau type. The mapping properties of these FIOs are studied as the composition with a generalized pseudodifferential operator. Finally, the microlocal Colombeau regularity for OIs and the influence of the FIO action on generalized wave front sets are investigated. This theory of generalized FIOs is motivated by the need of a general framework for partial differential operators with non-smooth coefficients and distributional data

Biochemical evaluation of a series of synthetic chalcone and hydrazide derivatives as novel inhibitors of cruzain from Trypanosoma cruzi

Chagas’ disease, a parasitic infection widely distributed throughout Latin America, is a major public health problem with devastating consequences in terms of human morbidity and mortality. The enzyme cruzain is the major cysteine protease from Trypanosoma cruzi, the etiologic agent of American trypanosomiasis or Chagas’ disease, and has been selected as an attractive target for the development of novel trypanocidal drugs. In the present work, we describe the synthesis and inhibitory effects of a series of thirty-three chalcone and seven hydrazide derivatives against the enzyme cruzain from T. cruzi. Most of the compounds showed promising in vitro inhibition (IC50 values in the range of 20-60 μM), which suggest the potential of these compounds as lead candidates for further development. Twelve compounds have not been reported before, and four of them (7, 13, 16 e 18) are among the most potent inhibitors of the series.A doença de Chagas, uma infecção parasitária amplamente distribuída na América Latina, é um problema grave de saúde pública com conseqüências devastadoras em termos de morbidade e mortalidade humana. A enzima cruzaína é a principal cisteíno protease do Trypanosoma cruzi, agente etiológico da tripanossomíase Americana ou doença de Chagas, e foi selecionada como alvo atrativo para o desenvolvimento de novos fármacos tripanocidas. No presente trabalho, a síntese e os efeitos inibitórios de uma série de trinta e três chalconas e sete hidrazidas são descritos contra a enzima cruzaína de T.cruzi. A maioria dos compostos mostraram inibição promissora in vitro (valores de IC50 na faixa de 20-60 μM), o que sugere o potencial desses compostos como candidatos a líderes para contínuo desenvolvimento. Doze compostos são inéditos, sendo que quatro destes (7, 13, 16 e 18) estão entre os inibidores mais potentes da série.CNPqFAPESPCAPE

Chagas disease in Italy: breaking an epidemiological silence

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Gevrey local solvability in locally integrable structures

We consider a locally integrable real-analytic structure, and we investigate the local solvability in the category of Gevrey functions and ultradistributions of the complex d' naturally induced by the de Rham complex. We prove that the so-called condition Y(q) on the signature of the Levi form, for local solvability of d' u=f, is still necessary even if we take f in the classes of Gevrey functions and look for solutions u in the corresponding spaces of ultradistributions.Comment: 12 page

Evaluation of gene amplification and protein expression of HER-2/neu in esophageal squamous cell carcinoma using Fluorescence in situ Hybridization (FISH) and immunohistochemistry

<p>Abstract</p> <p>Background</p> <p>Esophageal squamous cell carcinoma (ESCC) is the sixth most frequent neoplasia in Brazil. It is usually associated with a poor prognosis because it is often at an advanced stage when diagnosed and there is a high frequency of lymph node metastases. It is important to know what prognostic factors can facilitate diagnosis, optimize therapeutic decisions, and improve the survival of these patients. A member of the epidermal growth factor receptor (EGFR) family, c-erbB-2, has received much attention because of its therapeutic implications; however, few studies involving fluorescence <it>in situ </it>hybridization (FISH) analysis of HER-2/neu gene amplification and protein expression in ESCC have been conducted. The aim of this study was to verify the presence of HER-2/neu gene amplification using FISH, and to correlate the results with immunohistochemical expression and clinical-pathological findings.</p> <p>Methods</p> <p>One hundred and ninety-nine ESCC cases were evaluated using the Tissue Microarray (TMA) technique. A polyclonal antibody against c-erbB-2 was used for immunohistochemistry. Analyses were based on the membrane staining pattern. The results were classified according to the Herceptest criteria (DAKO): negative (0/1+), potential positive (2+) and positive (3+). The FISH reactions were performed according to the FISH HER2 PharmDx (DAKO) protocol. In each case, 100 tumor nuclei were evaluated. Cases showing a gene/CEN17 fluorescence ratio ≥ 2 were considered positive for gene amplification.</p> <p>Results</p> <p>The c-erbB-2 expression was negative in 117/185 cases (63.2%) and positive in 68 (36.8%), of which 56 (30.3%) were 2+ and 12 (6.5%) were 3+. No significant associations were found among protein expression, clinicopathological data and overall survival. Among the 47 cases analyzed, 38 (80.9%) showed no gene amplification while 9 (19.1%) showed amplification, as demonstrated by FISH. Cases that were negative (0/1+) and potential positive (2+) for c-erbB-2 expression by immunohistochemistry showed no gene amplification. However, all cases with gene amplification were positive (3+) by immunohistochemistry. According to univariate analysis, there was a significant difference (p = 0.003) in survival rates when cases with and without HER-2/neu amplification were compared.</p> <p>Conclusion</p> <p>Our data demonstrate the correspondence between gene amplification and protein expression of HER-2/neu. Gene amplification is an indicator of poor prognosis in ESCC.</p

Imported Infectious Diseases in Mobile Populations, Spain

Health screening of immigrant populations is needed to ensure early diagnosis and treatment

Comparative Analyses by Sequencing of Transcriptomes during Skeletal Muscle Development between Pig Breeds Differing in Muscle Growth Rate and Fatness

Understanding the dynamics of muscle transcriptome during development and between breeds differing in muscle growth is necessary to uncover the complex mechanism underlying muscle development. Herein, we present the first transcriptome-wide longissimus dorsi muscle development research concerning Lantang (LT, obese) and Landrace (LR, lean) pig breeds during 10 time-points from 35 days-post-coitus (dpc) to 180 days-post-natum (dpn) using Solexa/Illumina's Genome Analyzer. The data demonstrated that myogenesis was almost completed before 77 dpc, but the muscle phenotypes were still changed from 77 dpc to 28 dpn. Comparative analysis of the two breeds suggested that myogenesis started earlier but progressed more slowly in LT than in LR, the stages ranging from 49 dpc to 77 dpc are critical for formation of different muscle phenotypes. 595 differentially expressed myogenesis genes were identified, and their roles in myogenesis were discussed. Furthermore, GSK3B, IKBKB, ACVR1, ITGA and STMN1 might contribute to later myogenesis and more muscle fibers in LR than LT. Some myogenesis inhibitors (ID1, ID2, CABIN1, MSTN, SMAD4, CTNNA1, NOTCH2, GPC3 and HMOX1) were higher expressed in LT than in LR, which might contribute to more slow muscle differentiation in LT than in LR. We also identified several genes which might contribute to intramuscular adipose differentiation. Most important, we further proposed a novel model in which MyoD and MEF2A controls the balance between intramuscular adipogenesis and myogenesis by regulating CEBP family; Myf5 and MEF2C are essential during the whole myogenesis process while MEF2D affects muscle growth and maturation. The MRFs and MEF2 families are also critical for the phenotypic differences between the two pig breeds. Overall, this study contributes to elucidating the mechanism underlying muscle development, which could provide valuable information for pig meat quality improvement

Antimicrobial resistance (AMR) nanomachines: mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation

In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics—the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that trigger and regulate a wide variety of possible resistance mechanisms, we propose that these antimicrobial resistance mechanisms might be considered complex ‘nanomachines’ that drive survival of bacterial cells in antibiotic environments

Simple to be Useful: Ecosystem Base for Coastal Management

Os processos de Gerenciamento Costeiro (GC) nas últimas décadas vêm evoluindo, apresentando diferentes métodos de gestão, sendo que uma nova fronteira se encontra na Gestão com Base Ecossistêmica (GBE). No entanto, para colocar em prática a GBE, a qual leva em consideração as funções, os processos e os serviços ecossistêmicos dos ambientes costeiros e marinhos, entendendo-os como um conjunto de ecossistemas compostos por elementos ecológicos (naturais), econômicos e sociais, se faz necessária a base de informação ecossistêmica. O presente trabalho propõe, apresentando resultados aplicados, um roteiro metodológico de seis etapas: 1. Identificar os ecossistemas como “Unidades de Gestão”; 2. Mapear, modelar e simular os ecossistemas; 3. Identificar e classificar os serviços ecossistêmicos; 4. Definir os valores e a qualidade dos serviços; 5. Identificar os espaços de gestão; e 6. Integrar com políticas e demais instrumentos de gestão e legais. As aplicações práticas apresentadas vão desde trabalhos acadêmicos de identificação e caracterização de ambientes costeiros e marinhos a aplicações nos processos de gestão ambiental portuários, passando também pelo desenvolvimento de Zoneamentos Ecológico-Econômicos (ZEEs) em nível regional, por exemplo. Na apreciação integral do conjunto de exemplos e iniciativas para todas as etapas do modelo, depreende-se que a sua aplicação é ampla, variada e consideravelmente simples. Da mesma forma, a multiplicidade de possíveis aplicações do modelo em ações voltadas ao suporte de uma GBE sugere que seu uso pode crescer e buscar iniciativas inovadoras. A expectativa dos autores é de que tal ferramenta possa, de fato, delinear e estimular pesquisas e aplicações com base ecossistêmica na busca da sustentabilidade da costa e do bem-estar de seus atores sociais.In the last decades Coastal Management (CM) processes have been evolving, presenting different management methods, and the new frontier is at the so-called Ecosystem Based Management (EBM). However, to put into practice EBM, which takes into account ecosystem functions, processes and services of coastal and marine environments, understanding them as a set of ecosystems composed of ecological (natural), economic and social elements, it is necessary an ecosystem-based information. The present work proposes, presenting practical results, a methodological path of six stages: 1. Identification of ecosystems as "Management Units"; 2. Mapping, modeling and simulating ecosystems and their connections; 3. Identification and classification of ecosystem services; 4. Definition of values and quality of services; 5. Identification of related management procedures; and 6. Integration with policies and other management and legal tools. The concrete applications range from academic studies of identification and characterization of coastal and marine environments, to port’s environmental management processes, and the development of ecological-economic zoning at regional level, for example. In the full appreciation of the set of examples and initiatives for all stages of the model, it can be concluded that its application is wide, varied and considerably simple. Likewise, the multiplicity of possible applications of the model in practical actions aimed to support of an EBM, suggests that its use can grow and pursue innovative initiatives. The authors' expectation is that such a tool may, in fact, delineate and stimulate research and applications based on ecosystems in the quest for the sustainability of the coast and the well-being of its social actors