Optimización de la geometría de la bomba hidráulica tipo jet

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Towards Immunotherapy-Induced Normalization of the Tumor Microenvironment

Immunotherapies modulate the function of immune cells to eradicate cancer cells through various mechanisms. These therapies are successful across a spectrum of cancers, but they are curative only in a subset of patients. Indeed, a major obstacle to the success of immunotherapies is the immunosuppressive nature of the tumor microenvironment (TME), comprising the stromal component and immune infiltrate of tumors. Importantly, the TME in most solid cancers is characterized by sparsely perfused blood vessels resulting from so-called pathological angiogenesis. In brief, dysregulated development of new vessels results in leaky tumor blood vessels that inefficiently deliver oxygen and other nutrients. Moreover, the occurrence of dysregulated fibrosis around the lesion, known as pathological desmoplasia, further compresses tumor blood vessels and impairs blood flow. TME normalization is a clinically tested treatment strategy to reverse these tumor blood vessel abnormalities resulting in stimulated antitumor immunity and enhanced immunotherapy efficacy. TME normalization includes vascular normalization to reduce vessel leakiness and reprogramming of cancer-associated fibroblast to decompress vessels. How immunotherapies themselves normalize the TME is poorly understood. In this review, we summarize current concepts and progress in TME normalization. Then, we review observations of immunotherapy-induced TME normalization and discuss the considerations for combining vascular normalizing and immunotherapies. If TME could be more completely normalized, immunotherapies could be more effective in more patients

Composición y análisis químico de la especie Ilex guayusa Loes

A phytochemical analysis of the species Ilex guayusa was performed. This included determining the antioxidant capacity by testing the ferric reducing antioxidant power (FRAP) and determining the amount of caffeine and theobromine by high performance liquid chromatography (HPLC). The samples of Ilex guayusa leaves were collected from different geographical sites of the Ecuadorian Amazon, in order to obtain more comprehensive analysis. The methods used for quantitative and qualitative analysis proved high accuracy and good reproducibility and the results were shown to be comparable to those obtained from similar plants such as Camellia sinensis. The antioxidant capacity was found to be relatively high and the contents of caffeine and theobromine presented maximum values of 16.64 and 0.56 mg/g per fresh leaf weight respectively.Se realizó un análisis fitoquímico de la especie Ilex guayusa que incluyó determinar la capacidad antioxidante mediante el ensayo del poder antioxidante reductor férrico (FRAP, por sus siglas en inglés) y determinación de la cantidad de cafeína y teobromina mediante cromatografía líquida de alta eficiencia (HPLC, por sus siglas en inglés). Las muestras de Ilex guayusa consistieron en hojas que fueron recolectadas en diferentes lugares geográficos de la amazonía ecuatoriana, con el fin de obtener resultados más amplios. Los métodos empleados para los análisis cuantitativos y cualitativos demostraron ser de alta precisión y de buena reproducibilidad, ya que los resultados mostraron ser comparables a los obtenidos con plantas similares como Camellia sinensis. La capacidad antioxidante resultó ser relativamente alta y los contenidos de cafeína y teobromina presentaron valores máximos de 16.64 y 0.56 mg/g de peso de hoja fresca respectivamente

Prediction of operational variables involved in the Production Process of Crude Oil by Steam Assisted Gravity Drainage (SAGD)

(Received: 2015/04/16 - Accepted: 2015/05/29)This paper presents the oil deposit and operational variables that influence the implementation of the Steam Assisted Gravity Drainage (SAGD) process for the Production of Heavy and Extra-heavy Crude Oil. This process consists of drilling two parallel horizontal wells, one above the other, where the upper well is used for steam injection and the lower well is used for production. The efficiency of the process is greatly affected by the deposit and operating parameters (vertical spacing of wells, injection pressure, preheating period, among others). Furthermore, the prediction of the maximum rate of oil extraction was determined using an example with currently available real data of Block 20 of the Pungarayacu Field

CD40- and 41BB-specific antibody fusion proteins with PDL1 blockade-restricted agonism

Background: A strategy to broaden the applicability of checkpoint inhibitors is the combined use with antibodies targeting the immune stimulatory receptors CD40 and 41BB. However, the use of anti-CD40 and anti-41BB antibodies as agonists is problematic in two ways. First, anti-CD40 and anti-41BB antibodies need plasma membrane-associated presentation by FcγR binding to exert robust agonism but this obviously limits their immune stimulatory efficacy by triggering ADCC, CDC or anti-inflammatory FcγRIIb activities. Second, off tumor activation of CD40 and 41BB may cause dose limiting systemic inflammation. Methods: To overcome the FcγR-dependency of anti-41BB and anti-CD40 antibodies, we genetically fused such antibodies with a PDL1-specific blocking scFv as anchoring domain to enable FcγR-independent plasma membrane-associated presentation of anti-CD40- and anti-41BB antibodies. By help of GpL-tagged variants of the resulting bispecific antibodies, binding to their molecular targets was evaluated by help of cellular binding studies. Membrane PDL1-restricted engagement of CD40 and 41BB but also inhibition of PDL1-induced PD1 activation were evaluated in coculture assays with PDL1-expressing tumor cell lines and 41BB, CD40 and PD1 responsible cell lines or T-cells. Results: The binding properties of the bispecific antibody fusion proteins remained largely unchanged compared to their parental molecules. Upon anchoring to membrane PDL1, the bispecific antibody fusion proteins activated CD40/41BB signaling as efficient as the parental anti-CD40/anti-41BB antibodies when bound to FcγRs or cells expressing membrane-bound CD40L/41BBL. PD1 inhibition remained intact and the anti-41BB fusion protein thus showed PDL1-restricted costimulation of T-cells activated in vitro with anti-CD3 or a BiTe. Conclusions: Targeting of anti-CD40 and anti-41BB fusion proteins to membrane PDL1 with a blocking PDL1 scFv links PD1-PDL1 checkpoint blockade intrinsically with engagement of CD40 or 41BB

EGFR-selective activation of CD27 co-stimulatory signaling by a bispecific antibody enhances anti-tumor activity of T cells

A higher density of tumor infiltrating lymphocytes (TILs) in the tumor microenvironment, particularly cytotoxic CD8 + T cells, is associated with improved clinical outcome in various cancers. However, local inhibitory factors can suppress T cell activity and hinder anti-tumor immunity. Notably, TILs from various cancer types express the co-stimulatory Tumor Necrosis Factor receptor CD27, making it a potential target for co-stimulation and re-activation of tumor-infiltrated and tumor-reactive T cells. Anti-cancer therapeutics based on exploiting CD27-mediated T cell co-stimulation have proven safe, but clinical responses remain limited. This is likely because current monoclonal antibodies fail to effectively activate CD27 signaling, as this receptor requires higher-order receptor cross-linking. Here, we report on a bispecific antibody, CD27xEGFR, that targets both CD27 and the tumor antigen, epidermal growth factor receptor (EGFR). By targeting EGFR, which is commonly expressed on carcinomas, CD27xEGFR induced cancer cell-localized crosslinking and activation of CD27. The design of CD27xEGFR includes an Fc-silent domain, which is designed to minimize potential toxicity by reducing Fc gamma receptor-mediated binding and activation of immune cells. CD27xEGFR bound to both of its targets simultaneously and triggered EGFR-restricted co-stimulation of T cells as measured by T cell proliferation, T cell activation markers, cytotoxicity and IFN-γ release. Further, CD27xEGFR augmented T cell cytotoxicity in a panel of artificial antigen-presenting carcinoma cell line models, leading to Effector-to-Target ratio-dependent elimination of cancer cells. Taken together, we present the in vitro characterization of a novel bispecific antibody that re-activates T cell immunity in EGFR-expressing cancers through targeted co-stimulation of CD27. </p

BIODIESEL NO BRASIL: OBTENÇÃO DE DADOS DEPOSITADOS EM PATENTES

O presente trabalho tem como principal objetivo analisar as potencialidades, características e evolução das competências tecnológicas, traduzidas através de dados estatísticos de patentes, no que se refere ao processo de produção do biodiesel no Brasil. Para tanto se realizou pesquisas nos bancos de dados do IPC (International Patent Classification), com o intuito de elaborar uma prospecção, que servirá como base de dados para o desenvolvimento de pesquisa. A problemática que motivou a investigação visa apontar em qual situação encontra-se a produção de biodiesel no Brasil, desde os anos 80 até os dias atuais

Caminhando por Araranguá: um roteiro histórico, cultural e ambiental

O projeto “Caminhando por Araranguá: um roteiro histórico, cultural e ambiental” foi desenvolvido entre 2017 e 2018 no IFSC-Araranguá, entendendo a cidade como um território educativo (SINGER, 2015). Foi criado um roteiro educacional realizado a pé pelo centro histórico de Araranguá (SC), abordando aspectos patrimoniais e ambientais com enfoque interdisciplinar. O roteiro foi conduzido por alunos dos cursos técnicos integrados em eletromecânica e vestuário, com suporte de sinalização afixadas na Praça Hercílio Luz, cuja finalidade é indicar um website onde se encontra acessível o roteiro local. doi.org/10.35700/ca.2021.ano8n14.p144-148.307

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio