1,718 research outputs found
Speed of Publication of Statutes and Regulations in the United Kingdom, Canada, and the United States
No full textExamines reasons for typical delays in publication of statutes & regulations in UK,US, & Canada. Finds US federal laws published more slowly because of time taken to add marginal notes after enactmen
Legal Citation Form: Theory and Practice
No full textSets forth 13 principles as a basis for a system of legal citation forms, and critically reviews various rules in the 13th edition of A Uniform System of Citation
The roles of intratumour heterogeneity in the biology and treatment of pancreatic ductal adenocarcinoma
No full textIntratumour heterogeneity (ITH) has become an important focus of cancer research in recent years. ITH describes the cellular variation that enables tumour evolution, including tumour progression, metastasis and resistance to treatment. The selection and expansion of genetically distinct treatment-resistant cancer cell clones provides one explanation for treatment failure. However, tumour cell variation need not be genetically encoded. In pancreatic ductal adenocarcinoma (PDAC) in particular, the complex tumour microenvironment as well as crosstalk between tumour and stromal cells result in exceptionally variable tumour cell phenotypes that are also highly adaptable. In this review we discuss four different types of phenotypic heterogeneity within PDAC, from morphological to metabolic heterogeneity. We suggest that these different types of ITH are not independent, but, rather, can inform one another. Lastly, we highlight recent findings that suggest how therapeutic efforts may halt PDAC progression by constraining cellular heterogeneity
Multivariate nonparametric Behrens-Fisher-Problem with covariates
No full textIn der vorliegenden Arbeit wird das Behrens-Fisher-Problem auf den Fall multivariater nicht-normalverteilter Daten und für die Berücksichtigung von Kovariablen erweitert. Dabei werden Punkt- und Intervallschätzer und Hypothesentests hergeleitet. Anschließend werden die Simulationsstudien durchgeführt um die Eigenschaften der entwickelten Verfahren zu überprüfen. Sämtliche Methoden werden auf zwei Beispieldatensätze angewendet.In this thesis the Behrens-Fisher-Problem is extended to the case of multivariate non-normal-distributed data and for the case of existing covariates. Point- and intervall-estimators and hypotheses-tests are developed. Afterwards simulation studies are performed to validate the developed methods. All methods are applied to two example-datasets
Are There Specific Cancer Stem Cell Markers?
No full textThe cancer stem cell (CSC) model states that heterogeneous tumor cell populations are organized in a hierarchical manner, with a small population of CSCs at the apex. These CSCs are capable of self-renewal and giving rise to other cancer cell populations, conceptually analogous to the function of normal adult stem cells present in almost all organs. However, there has been significant controversy regarding the existence and identification of CSCs. We argue that technical differences in experimentation and CSC assays, CSC niche-dependency and plasticity, and CSC heterogeneity itself may explain some of the differences observed
Cep55 promotes cytokinesis of neural progenitors but is dispensable for most mammalian cell divisions
No full textIn mammalian cell lines, the endosomal sorting complex required for transport (ESCRT)-III mediates abscission, the process that physically separates daughter cells and completes cell division. Cep55 protein is regarded as the master regulator of abscission, because it recruits ESCRT-III to the midbody (MB), the site of abscission. However, the importance of this mechanism in a mammalian organism has never been tested. Here we show that Cep55 is dispensable for mouse embryonic development and adult tissue homeostasis. Cep55-knockout offspring show microcephaly and primary neural progenitors require Cep55 and ESCRT for survival and abscission. However, Cep55 is dispensable for cell division in embryonic or adult tissues. In vitro, division of primary fibroblasts occurs without Cep55 and ESCRT-III at the midbody and is not affected by ESCRT depletion. Our work defines Cep55 as an abscission regulator only in specific tissue contexts and necessitates the re-evaluation of an alternative ESCRT-independent cell division mechanism.</p
Micro-CT acquisition and image processing to track and characterize pulmonary nodules in mice
No full textX-ray computed tomography is a reliable technique for the detection and longitudinal monitoring of pulmonary nodules. In preclinical stages of diagnostic or therapeutic development, the miniaturized versions of the clinical computed tomography scanners are ideally suited for carrying out translationally-relevant research in conditions that closely mimic those found in the clinic. In this Protocol, we provide image acquisition parameters optimized for low radiation dose, high-resolution and high-throughput computed tomography imaging using three commercially available micro-computed tomography scanners, together with a detailed description of the image analysis tools required to identify a variety of lung tumor types, characterized by specific radiological features. For each animal, image acquisition takes 4-8 min, and data analysis typically requires 10-30 min. Researchers with basic training in animal handling, medical imaging and software analysis should be able to implement this protocol across a wide range of lung cancer models in mice for investigating the molecular mechanisms driving lung cancer development and the assessment of diagnostic and therapeutic agents
Active mesh and neural network pipeline for cell aggregate segmentation
No full textSegmenting cells within cellular aggregates in 3D is a growing challenge in cell biology due to improvements in capacity and accuracy of microscopy techniques. Here, we describe a pipeline to segment images of cell aggregates in 3D. The pipeline combines neural network segmentations with active meshes. We apply our segmentation method to cultured mouse mammary gland organoids imaged over 24 h with oblique plane microscopy, a high-throughput light-sheet fluorescence microscopy technique. We show that our method can also be applied to images of mouse embryonic stem cells imaged with a spinning disc microscope. We segment individual cells based on nuclei and cell membrane fluorescent markers, and track cells over time. We describe metrics to quantify the quality of the automated segmentation. Our segmentation pipeline involves a Fiji plugin that implements active mesh deformation and allows a user to create training data, automatically obtain segmentation meshes from original image data or neural network prediction, and manually curate segmentation data to identify and correct mistakes. Our active meshes-based approach facilitates segmentation postprocessing, correction, and integration with neural network prediction
Normative reconstruction and social character of freedom in Axel Honneth
No full textO presente objeto de pesquisa busca proceder ao estudo e identificação dos traços essenciais envolvidos na abordagem teórica das relações sociais e políticas trazidas na obra O Direito da Liberdade do filósofo alemão Axel Honneth. Faz-se uma análise da influência hegeliana sobre o conceito de liberdade, assim como dos fatores relacionados com o suprimento das carências subjetivas, mediadas pelas diferentes “esferas” sociais. Honneth, assim, procura trazer à tona a compreensão de um novo modelo de liberdade advindo da Filosofia do Direito de Hegel, o qual se distingue substancialmente dos modelos tradicionais. O autor busca evidenciar a limitação das teorias da justiça de tradição liberal, invocando a necessidade de uma visão integrada das relações sociais experimentadas nas esferas referidas por Hegel, concebendo-se uma experiência concreta de liberdade social. Nesse sentido, evidencia-se o caráter interdisciplinar e emancipatório do método de reconstrução normativa como base teórica para a justificação pública nas sociedades modernas.This research object aims to study and identify the essential traits involved in the theoretical approach of social and political relations brought in the work Freedom’s Right by the german philosopher Axel Honneth. It analyses the hegelian influence on the concept of freedom, as well as the factors related to the supply of subjective needs, mediated by the different social "spheres". Honneth thus seeks to bring to light the understanding of a new model of freedom stemming from Hegel’s Philosophy of Law, which differs substantially from traditional models. The author seeks to highlight the limitation of liberal theories of justice, invoking the need for an integrated view of the social relations experienced in the spheres referred to by Hegel, conceiving a concrete experience of social freedom. In this sense, the interdisciplinary and emancipatory character of the normative reconstruction method is evidenced, as a theorical basis for public justification in modern societies
The deubiquitinase USP9X regulates FBW7 stability and suppresses colorectal cancer
No full textThe tumor suppressor FBW7 targets oncoproteins such as c-MYC for ubiquitylation and is mutated in several human cancers. We noted that in a substantial percentage of colon cancers, FBW7 protein is undetectable despite the presence of FBW7 mRNA. To understand the molecular mechanism of FBW7 regulation in these cancers, we employed proteomics and identified the deubiquitinase (DUB) USP9X as an FBW7 interactor. USP9X antagonized FBW7 ubiquitylation, and Usp9x deletion caused Fbw7 destabilization. Mice lacking Usp9x in the gut showed reduced secretory cell differentiation and increased progenitor proliferation, phenocopying Fbw7 loss. In addition, Usp9x inactivation impaired intestinal regeneration and increased tumor burden in colitis-associated intestinal cancer. c-Myc heterozygosity abrogated increased progenitor proliferation and tumor burden in Usp9x-deficient mice, suggesting that Usp9x suppresses tumor formation by regulating Fbw7 protein stability and thereby reducing c-Myc. Thus, we identify a tumor suppressor mechanism in the mammalian intestine that arises from the posttranslational regulation of FBW7 by USP9X independent of somatic FBW7 mutations.Full Tex
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