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Shedding light on the retina to see healthy and pathological aging

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Neural Regeneration Research 2025年第12期20卷 3537-3538页

作者： Marília Inês Móvio Maria Camila Almeida Sergio T.Ferreira alexandre Hiroaki Kihara Neurogenetics Laboratory Federal University of ABCSão Bernardo do CampoSPBrazil Center for Mathematics Computing and CognitionFederal University of ABCSão Bernardo do CampoSPBrazil Center for Natural and Human Sciences Federal University of ABCSao Bernardo do CampoSPBrazil Institute of Medical Biochemistry Leopoldo de Meis Federal University of Rio de JaneiroRio de JaneiroRJBrazil Institute of Biophysics Carlos Chagas Filho Federal University of Rio de JaneiroRio de JaneiroRJBrazil

With the advances in medicine and technology,life expectancy has increased significantly in recent *** this is positive news,it also brings major challenges to public health *** people live longer,the number of cases of agerelated disorders,including neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD),has also grown.

关键词： diseases Alzheimer cases

Research and development of VUV optical coatings for micro mirror applications

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光学精密工程 2005年第4期13卷 465-470页

作者： alexandre Gatto Norbert Kaiser Fraunhofer IOF Albert-Einstein-Str. 7 D-07745 Jena GermanyFraunhofer IOF Albert-Einstein-Str. 7 D-07745 Jena Germany

This paper deals with vacuum UV optical coatings for micro mirror applications. High reflecting low-stress optical coatings have been developed for the next-generation of micro mechanical mirrors. The optimized metal systems are applicable in the VUV spectral region and can be integrated in the technology of MOEMS, such as spatial light modulators (SLM) and micro scanning mirrors.

关键词： VUV 光学涂覆技术微镜技术薄膜调节器

Towards a modular and scalable holographic display

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Light(Science & Applications) 2022年第5期11卷 739-740页

作者： Pierre-alexandre Blanche Wyant College of Optical Sciences University of ArizonaTucsonAZUSA

Holographic three-dimensional(3D)display can be made very large using a modular system that allows seamless spatial tiling of multiple coarse integral holographic images.

关键词： holographic system integral

Pharmaceutical applications of spouted beds: A review on solid dosage forms

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Particuology 2019年第1期17卷 126-136页

作者： Luis alexandre Pedro de Freitas Faculdade de Ciencias Farmaceuticas de Ribeirao Preto University of Sao PauloVia do Cafe s/n. Campus USPRibeirao Preto14040-903Sao Paulo. Brazil

Spouted beds (SBs) have a long history of successful applications for preparation of solid dosage forms of pharmaceuticals. The well-known versatility of SBs, provided by different design and operational factors, and their efficient mixing of solids allow for engineering of technological characteristics of pharmaceutical solid forms. Particle properties like morphology, size, porosity, flowability, and dissolution rate can be improved by managing geometric and operational conditions for spouting. Drying is probably the most disseminated operation for pharmaceutical processing in SBs, and many studies have investigated drying of medicinal plant extracts such as achiote (Bixa orellana sp.), guarana (Paullinia cupana sp.), passion flower (Passiflora alata D.), and rosemary (Rosmarinus officinalis L.) with excellent pharmacotechnical and stability results. Another important application is coating of tablets and gelatin capsules, and previous studies have shown that SBs and spout–fluid beds may be advantageous over traditional pan coating, especially for polymeric film coating. Recently, an alternative process for improving drug bioavailability has involved preparation of β-cyclodextrin inclusion complexes in SBs. The first study to propose SBs for this pharmaceutical application explored the advantage of obtaining solid forms of inclusion complexes in just one step, and obtained expressive increases in drug solubility. The technique has been applied in subsequent studies on inclusion complexes of the medication carvedilol and uxi (Endopleura uchi L.) extracts.

关键词： Coating Drying Granulation Inclusion Microencapsulation

Colon mucus in colorectal neoplasia and beyond

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World Journal of Gastroenterology 2022年第32期28卷 4475-4492页

作者： alexandre Loktionov DiagNodus Ltd Cambridge CB40WSUnited Kingdom

Little was known about mammalian colon mucus(CM)until the beginning of the 21^(st) *** that time considerable progress has been made in basic research addressing CM structure and *** CM is formed by two distinct layers composed of gel-forming glycosylated mucins that are permanently secreted by goblet cells of the colonic *** inner layer is dense and impenetrable for bacteria,whereas the loose outer layer provides a habitat for abundant commensal *** barrier integrity is essential for preventing bacterial contact with the mucosal epithelium and maintaining homeostasis in the gut,but it can be impaired by a variety of factors,including CM-damaging switch of commensal bacteria to mucin glycan consumption due to dietary fiber *** is proven that impairments in CM structure and function can lead to colonic barrier deterioration that opens direct bacterial access to the ***-induced damage dysregulates epithelial proliferation and causes mucosal inflammatory responses that may expand to the loosened CM and eventually result in severe disorders,including colitis and neoplastic *** described formation of bacterial biofilms within the inner CM layer was shown to be associated with both inflammation and *** obvious gaps in our knowledge of human CM remain,its importance for the pathogenesis of major colorectal diseases,comprising inflammatory bowel disease and colorectal cancer,is already *** progress in CM exploration is likely to result in the development of a range of new useful clinical applications addressing colorectal disease diagnosis,prevention and therapy.

关键词： Colon Colon mucus Mucins Goblet cells Gut microbiota Inflammatory bowel disease Colorectal cancer

Eosinophils in the gastrointestinal tract and their role in the pathogenesis of major colorectal disorders

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World Journal of Gastroenterology 2019年第27期25卷 3503-3526页

作者： alexandre Loktionov DiagNodus Ltd Babraham Research Campus

Eosinophils are currently regarded as versatile mobile cells controlling and regulating multiple biological pathways and responses in health and *** cells store in their specific granules numerous biologically active substances(cytotoxic cationic proteins, cytokines, growth factors, chemokines,enzymes) ready for rapid release. The human gut is the main destination of eosinophils that are produced and matured in the bone marrow and then transferred to target tissues through the circulation. In health the most important functions of gut-residing eosinophils comprise their participation in the maintenance of the protective mucosal barrier and interactions with other immune cells in providing immunity to microbiota of the gut lumen. Eosinophils are closely involved in the development of inflammatory bowel disease(IBD),when their cytotoxic granule proteins cause damage to host tissues. However,their roles in Crohn’s disease and ulcerative colitis appear to follow different immune response patterns. Eosinophils in IBD are especially important in altering the structure and protective functions of the mucosal barrier and modulating massive neutrophil influx to the lamina propria followed by transepithelial migration to colorectal mucus. IBD-associated inflammatory process involving eosinophils then appears to expand to the mucus overlaying the internal gut surface. The author hypothesises that immune responses within colorectal mucus as well as ETosis exerted by both neutrophils and eosinophils on the both sides of the colonic epithelial barrier act as additional pathogenetic factors in IBD. Literature analysis also shows an association between elevated eosinophil levels and better colorectal cancer(CRC) prognosis, but mechanisms behind this effect remain to be elucidated. In conclusion, the author emphasises the importance of investigating colorectal mucus in IBD and CRC patients as a previously unexplored milieu of disease-related inflammatory responses.

关键词： Eosinophils Eosinophilopoiesis Gut lamina propria Colorectal mucus Normal human small intestine Normal human colon Inflammatory bowel disease Crohn’s disease Ulcerative colitis Colorectal cancer

A POSTERIORI ENERGY-NORM ERROR ESTIMATES FOR ADVECTION-DIFFUSION EQUATIONS APPROXIMATED BY WEIGHTED INTERIOR PENALTY METHODS

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Journal of Computational Mathematics 2008年第4期26卷 488-510页

作者： alexandre Ern AnnetteF.Stephansen Université Paris-Est CermicsEcole des Ponts6 et 8 avenue Blaise PascalChamps sur Marne77455 Marne la Vallée Cedex 2France Université Paris-Est CermicsEcole des Ponts6 et 8 avenue Blaise PascalChamps sur Marne77455 Marne la Vallée Cedex 2France AndraParc de la Croix-Blanche1-7 rue Jean Monnet92298 Ch■tenay-Malabry cedexFrance

We propose and analyze a posteriori energy-norm error estimates for weighted interior penalty discontinuous Galerkin approximations of advection-diffusion-reaction equations with heterogeneous and anisotropic diffusion. The weights, which play a key role in the analysis, depend on the diffusion tensor and are used to formulate the consistency terms in the discontinuous Galerkin method. The error upper bounds, in which all the constants are specified, consist of three terms： a residual estimator which depends only on the elementwise fluctuation of the discrete solution residual, a diffusive flux estimator where the weights used in the method enter explicitly, and a non-conforming estimator which is nonzero because of the use of discontinuous finite element spaces. The three estimators can be bounded locally by the approximation error. A particular attention is given to the dependency on problem parameters of the constants in the local lower error bounds. For moderate advection, it is shown that full robustness with respect to diffusion heterogeneities is achieved owing to the specific design of the weights in the discontinuous Galerkin method, while diffusion anisotropies remain purely local and impact the constants through the square root of the condition number of the diffusion tensor. For dominant advection, it is shown, in the spirit of previous work by Verfiirth on continuous finite elements, that the local lower error bounds can be written with constants involving a cut-off for the ratio of local mesh size to the reciprocal of the square root of the lowest local eignevalue of the diffusion tensor.

关键词： Discontinuous Galerkin Weighted interior penalty A posteriori error estimate,Heterogeneous diffusion Advection-diffusion.

Biomarkers for detecting colorectal cancer non-invasively: DNA,RNA or proteins?

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World Journal of Gastrointestinal Oncology 2020年第2期12卷 124-148页

作者： alexandre Loktionov Diag Nodus Ltd Babraham Research Campus

Colorectal cancer(CRC)is a global problem affecting millions of people *** disease is unique because of its slow progress that makes it preventable and often *** symptoms usually emerge only at advanced stages of the disease,consequently its early detection can be achieved only through active population screening,which markedly reduces mortality due to this *** screening tests that employ non-invasively detectable biomarkers are currently being actively developed and,in most cases,samples of either stool or blood are ***,alternative biological substances that can be collected non-invasively(colorectal mucus,urine,saliva,exhaled air)have now emerged as new sources of diagnostic *** main categories of currently explored CRC biomarkers are:(1)Proteins(comprising widely used haemoglobin);(2)DNA(including mutations and methylation markers);(3)RNA(in particular microRNAs);(4)Low molecular weight metabolites(comprising volatile organic compounds)detectable by metabolomic techniques;and(5)Shifts in gut microbiome *** tests for early CRC detection employing such non-invasive biomarkers have been proposed and clinically *** some of these studies generated promising early results,very few of the proposed tests have been transformed into clinically validated diagnostic/screening *** DNA-based tests as Food and Drug Administration-approved multitarget stool test(marketed as Cologuard®)or blood test for methylated septin 9(marketed as Epi proColon®2.0 CE)show good diagnostic performance but remain too expensive and technically complex to become effective CRC screening *** can be concluded that,despite its deficiencies,the protein(haemoglobin)detection-based faecal immunochemical test(FIT)today presents the most cost-effective option for non-invasive CRC *** combination of non-invasive FIT and confirmatory invasive colonoscopy is the current strategy of choice for CRC ***

关键词： Colorectal cancer screening Biomarkers Non-invasive testing Stool Colorectal mucus Blood

Dynamical machine learning volumetric reconstruction of objects’ interiors from limited angular views

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Light(Science & Applications) 2021年第5期10卷 824-844页

作者： Iksung Kang alexandre Goy George Barbastathis Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology77 Massachusetts AveCambridgeMAUSA Department of Mechanical Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA Singapore-MIT Alliance for Research and Technology(SMART)Centre 1 Create WaySingapore 117543Singapore Omnisens SA Morges 1110Switzerland

Limited-angle tomography of an interior volume is a challenging, highly ill-posed problem with practical implications in medical and biological imaging, manufacturing, automation, and environmental and food security. Regularizing priors are necessary to reduce artifacts by improving the condition of such problems. Recently, it was shown that one effective way to learn the priors for strongly scattering yet highly structured 3D objects, e.g. layered and Manhattan, is by a static neural network [Goy et al. Proc. Natl. Acad. Sci. 116, 19848–19856 (2019)]. Here, we present a radically different approach where the collection of raw images from multiple angles is viewed analogously to a dynamical system driven by the object-dependent forward scattering operator. The sequence index in the angle of illumination plays the role of discrete time in the dynamical system analogy. Thus, the imaging problem turns into a problem of nonlinear system identification, which also suggests dynamical learning as a better fit to regularize the reconstructions. We devised a Recurrent Neural Network (RNN) architecture with a novel Separable-Convolution Gated Recurrent Unit (SC-GRU) as the fundamental building block. Through a comprehensive comparison of several quantitative metrics, we show that the dynamic method is suitable for a generic interior-volumetric reconstruction under a limited-angle scheme. We show that this approach accurately reconstructs volume interiors under two conditions: weak scattering, when the Radon transform approximation is applicable and the forward operator well defined;and strong scattering, which is nonlinear with respect to the 3D refractive index distribution and includes uncertainty in the forward operator.

关键词： interior dynamical angular