A produção racional em regime histórico de fé: com vistas à ciência

Because of the difference of their own pertinences, there is no possible direct dialogue between science and theologal faith. Indeed, there is nothing strange in this, because the same occurs between one science and another, between one science and philosophy and even between science and general culture. Each science is a close structure, and it speaks only its own language, ignoring all the others. But it does not mean that the dialogue among several kinds and genera of discourses is impossible. It is the interpreter's mediation that makes it possible, and philosophy is its privileged place and agent. By its own nature, and it is assisted by competent interpreters, who may be accumulated in the philosopher himself, philosophy is able to lead an universal dialogue. Through the aspects that it transcends, philosophy keeps borders with science and with general culture; through those that transcend it, philosophy keeps borders with theology. That, philosophy owes to the state, in which it is found, the historical conditions of revelation and faith.Em razão das diferenças das respectivas pertinencias, não há diálogo direto possível entre ciência e fé teologal. Não há nada de estranho nisso, pois o mesmo ocorre entre uma ciência e outra, entre ciência e filosofia e até entre ciência e cultura geral. Cada ciência é uma estrutura fechada, fala apenas sua língua, ignorando as demais. Mas isso não quer dizer que não seja possível o diálogo entre diversas espécies ou diversos gêneros de discurso. É a mediação de intérpretes que o viabiliza, e a filosofia é o seu agente privilegiado. Por sua natureza, e desde que assistida por intérpretes que podem estar acumulados no próprio filósofo, a filosofia é apta a conduzir um diálogo universal. Por aquilo que ela transcende, a filosofia mantém fronteiras com as ciências e com a cultura geral; por aquilo que a transcende, ela mantém fronteiras com a teologia. Esta última marca, ela a deve ao estado em que se encon tra, que é de um regime histórico de revelação e de fé

Mutation signature analysis identifies increased mutation caused by tobacco smoke associated DNA adducts in larynx squamous cell carcinoma compared with oral cavity and oropharynx.

Squamous cell carcinomas of the head and neck (HNSCC) arise from mucosal keratinocytes of the upper aero-digestive tract. Despite a common cell of origin and similar driver-gene mutations which divert cell fate from differentiation to proliferation, HNSCC are considered a heterogeneous group of tumors categorized by site of origin within the aero-digestive mucosa, and the presence or absence of HPV infection. Tobacco use is a major driver of carcinogenesis in HNSCC and is a poor prognosticator that has previously been associated with poor immune cell infiltration and higher mutation numbers. Here, we study patterns of mutations in HNSCC that are derived from the specific nucleotide changes and their surrounding nucleotide context (also known as mutation signatures). We identify that mutations linked to DNA adducts associated with tobacco smoke exposure are predominantly found in the larynx. Presence of this class of mutation, termed COSMIC signature 4, is responsible for the increased burden of mutation in this anatomical sub-site. In addition, we show that another mutation pattern, COSMIC signature 5, is positively associated with age in HNSCC from non-smokers and that larynx SCC from non-smokers have a greater number of signature 5 mutations compared with other HNSCC sub-sites. Immunohistochemistry demonstrates a significantly lower Ki-67 proliferation index in size matched larynx SCC compared with oral cavity SCC and oropharynx SCC. Collectively, these observations support a model where larynx SCC are characterized by slower growth and increased susceptibility to mutations from tobacco carcinogen DNA adducts

Imaging spectroscopic performances for a Si based detection system

We present the imaging and spectroscopic capabilities of a system based on a single photon counting chip (PCC) bump-bonded on a Si pixel detector. The system measures the energy spectrum and the flux, produced by a standard mammographic tube. We have also made some images of low contrast details, achieving good results

MCT1 in Invasive Ductal Carcinoma: Monocarboxylate Metabolism and Aggressive Breast Cancer.

Introduction: Monocarboxylate transporter 1 (MCT1) is an importer of monocarboxylates such as lactate and pyruvate and a marker of mitochondrial metabolism. MCT1 is highly expressed in a subgroup of cancer cells to allow for catabolite uptake from the tumor microenvironment to support mitochondrial metabolism. We studied the protein expression of MCT1 in a broad group of breast invasive ductal carcinoma specimens to determine its association with breast cancer subtypes and outcomes. Methods: MCT1 expression was evaluated by immunohistochemistry on tissue micro-arrays (TMA) obtained through our tumor bank. Two hundred and fifty-seven cases were analyzed: 180 cases were estrogen receptor and/or progesterone receptor positive (ER+ and/or PR+), 62 cases were human epidermal growth factor receptor 2 positive (HER2+), and 56 cases were triple negative breast cancers (TNBC). MCT1 expression was quantified by digital pathology with Aperio software. The intensity of the staining was measured on a continuous scale (0-black to 255-bright white) using a co-localization algorithm. Statistical analysis was performed using a linear mixed model. Results: High MCT1 expression was more commonly found in TNBC compared to ER+ and/or PR+ and compared to HER-2+ (p \u3c 0.001). Tumors with an in-situ component were less likely to stain strongly for MCT1 (p \u3c 0.05). High nuclear grade was associated with higher MCT1 staining (p \u3c 0.01). Higher T stage tumors were noted to have a higher expression of MCT1 (p \u3c 0.05). High MCT1 staining in cancer cells was associated with shorter progression free survival, increased risk of recurrence, and larger size independent of TNBC status (p \u3c 0.05). Conclusion: MCT1 expression, which is a marker of high catabolite uptake and mitochondrial metabolism, is associated with recurrence in breast invasive ductal carcinoma. MCT1 expression as quantified with digital image analysis may be useful as a prognostic biomarker and to design clinical trials using MCT1 inhibitors

TP53-inducible Glycolysis and Apoptosis Regulator (TIGAR) Metabolically Reprograms Carcinoma and Stromal Cells in Breast Cancer.

A subgroup of breast cancers has several metabolic compartments. The mechanisms by which metabolic compartmentalization develop in tumors are poorly characterized. TP53 inducible glycolysis and apoptosis regulator (TIGAR) is a bisphosphatase that reduces glycolysis and is highly expressed in carcinoma cells in the majority of human breast cancers. Hence we set out to determine the effects of TIGAR expression on breast carcinoma and fibroblast glycolytic phenotype and tumor growth. The overexpression of this bisphosphatase in carcinoma cells induces expression of enzymes and transporters involved in the catabolism of lactate and glutamine. Carcinoma cells overexpressing TIGAR have higher oxygen consumption rates and ATP levels when exposed to glutamine, lactate, or the combination of glutamine and lactate. Coculture of TIGAR overexpressing carcinoma cells and fibroblasts compared with control cocultures induce more pronounced glycolytic differences between carcinoma and fibroblast cells. Carcinoma cells overexpressing TIGAR have reduced glucose uptake and lactate production. Conversely, fibroblasts in coculture with TIGAR overexpressing carcinoma cells induce HIF (hypoxia-inducible factor) activation with increased glucose uptake, increased 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), and lactate dehydrogenase-A expression. We also studied the effect of this enzyme on tumor growth. TIGAR overexpression in carcinoma cells increases tumor growth in vivo with increased proliferation rates. However, a catalytically inactive variant of TIGAR did not induce tumor growth. Therefore, TIGAR expression in breast carcinoma cells promotes metabolic compartmentalization and tumor growth with a mitochondrial metabolic phenotype with lactate and glutamine catabolism. Targeting TIGAR warrants consideration as a potential therapy for breast cancer

Mapping Cortical Degeneration in ALS with Magnetization Transfer Ratio and Voxel-Based Morphometry

Pathological and imaging data indicate that amyotrophic lateral sclerosis (ALS) is a multisystem disease involving several cerebral cortical areas. Advanced quantitative magnetic resonance imaging (MRI) techniques enable to explore in vivo the volume and microstructure of the cerebral cortex in ALS. We studied with a combined voxel-based morphometry (VBM) and magnetization transfer (MT) imaging approach the capability of MRI to identify the cortical areas affected by neurodegeneration in ALS patients. Eighteen ALS patients and 18 age-matched healthy controls were examined on a 1.5T scanner using a high-resolution 3D T1 weighted spoiled gradient recalled sequence with and without MT saturation pulse. A voxel-based analysis (VBA) was adopted in order to automatically compute the regional atrophy and MT ratio (MTr) changes of the entire cerebral cortex. By using a multimodal image analysis MTr was adjusted for local gray matter (GM) atrophy to investigate if MTr changes can be independent of atrophy of the cerebral cortex. VBA revealed several clusters of combined GM atrophy and MTr decrease in motor-related areas and extra-motor frontotemporal cortex. The multimodal image analysis identified areas of isolated MTr decrease in premotor and extra-motor frontotemporal areas. VBM and MTr are capable to detect the distribution of neurodegenerative alterations in the cortical GM of ALS patients, supporting the hypothesis of a multi-systemic involvement in ALS. MT imaging changes exist beyond volume loss in frontotemporal cortices

Dynamics of Quantum Collapse in Energy Measurements

The influence of continuous measurements of energy with a finite accuracy is studied in various quantum systems through a restriction of the Feynman path-integrals around the measurement result. The method, which is equivalent to consider an effective Schr\"odinger equation with a non-Hermitian Hamiltonian, allows one to study the dynamics of the wavefunction collapse. A numerical algorithm for solving the effective Schr\"odinger equation is developed and checked in the case of a harmonic oscillator. The situations, of physical interest, of a two-level system and of a metastable quantum-well are then discussed. In the first case the Zeno inhibition observed in quantum optics experiments is recovered and extended to nonresonant transitions, in the second one we propose to observe inhibition of spontaneous decay in mesoscopic heterostructures. In all the considered examples the effect of the continuous measurement of energy is a freezing of the evolution of the system proportional to the accuracy of the measurement itself.Comment: 20 pages with figures, compressed and uuencoded ps fil