14 research outputs found
%% [ ProductName: ESP Ghostscript]%% 1 Towards a Temporal Logic ttttLTL for the Verification of Rewriting Theories denoting ECATNets
No full textAbstract: The propositional linear temporal logic LTL [ Man89] is a well studied tool for specifying an
World Governance in Selected Writings By Bertrand Russell: Utopia or Ideology
Get PDFThis article studies the idea of “World Government” as envisioned in aseries of essays published by Bertrand Russell in the period of the Cold War. It drawsupon the theoretical categories introduced by Karl Mannheim in Ideology and Utopia(1936) to account for the nature of the reconstruction schemes the author advances tospare human society a possible apocalyptic nuclear confrontation. The study hasshown that Russell’s liberal outlook is utopian insofar as it has shown advancedpositions regarding self-determination, the dissemination of progress and cooperationtoward the reconstruction of a peaceful and prosperous world. However, given thetechnological abyss separating the industrial West in the 1950s from the rest, an open“World State” would be another form of imperialism in disguise. The risk involved isthat this “global utopia” whose rulers monopolize military, legislative as well aseconomic power, would turn into an institutional and ideological instrument ofcontrol in the hands of the technologically powerful few
Rethinking Utilitarian Ethics and the Gospel of Work in William Morris’s News from Nowhere (1892)
Get PDFThis paper discusses William Morris’s idea of a socialist revolution as envisioned in his utopian romance News from Nowhere (1892). It explores the factors which prompted the author to engage in the heated debates and actions of his time to reconstruct a commonwealth out of the late nineteenth century British society, plagued by growing inequality, shabbiness, injustice, ill health and unhappiness of the labouring majority. Drawing upon Karl Mannheim (1936) and Michael Bakhtin (1996), I attempt to situate Morris’s utopian mentality among the authors of the utopian tradition; and I read the text both as a perpetuation of the utopian tradition to inspire transformative action in times of crisis, and as a polemical rejoinder both to the conservatives’ “cacotopia”, and the liberals’ “Idea” of his time. Morris’s insistence on the baneful effects industrialism and urbanisation on the individual, the community, and environment are still relevant to our world.Keywords: Utopia- utopian mentality- revolution- “Nowhere”- work play-utilitarian ethics- trade unionism- socialist- liberal- ideology- fellowship- garden-environment- happiness
Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages
Get PDFGenetic depletion of macrophages in Polyoma Middle T oncoprotein (PyMT)-induced mammary tumors in mice delayed the angiogenic switch and the progression to malignancy. To determine whether vascular endothelial growth factor A (VEGF-A) produced by tumor-associated macrophages regulated the onset of the angiogenic switch, a genetic approach was used to restore expression of VEGF-A into tumors at the benign stages. This stimulated formation of a high-density vessel network and in macrophage-depleted mice, was followed by accelerated tumor progression. The expression of VEGF-A led to a massive infiltration into the tumor of leukocytes that were mostly macrophages. This study suggests that macrophage-produced VEGF regulates malignant progression through stimulating tumor angiogenesis, leukocytic infiltration and tumor cell invasion
Collagen hydrogel confinement of Amyloid-β (Aβ) accelerates aggregation and reduces cytotoxic effects
No full textAlzheimer's disease (AD) is the most common form of dementia and is associated with the accumulation of amyloid-β (Aβ), a peptide whose aggregation has been associated with neurotoxicity. Drugs targeting Aβ have shown great promise in 2D in vitro models and mouse models, yet preclinical and clinical trials for AD have been highly disappointing. We propose that current in vitro culture systems for discovering and developing AD drugs have significant limitations; specifically, that Aβ aggregation is vastly different in these 2D cultures carried out on flat plastic or glass substrates vs. in a 3D environment, such as brain tissue, where Aβ confinement alters aggregation kinetics and thermodynamics. In this work, we identified attenuation of Aβ cytotoxicity in 3D hydrogel culture compared to 2D cell culture. We investigated Aβ structure and aggregation in solution vs. hydrogel using Transmission Electron Microscopy (TEM), Fluorescence Correlation Spectroscopy (FCS), and Thioflavin T (ThT) assays. Our results reveal that the equilibrium is shifted to stable extended β-sheet (ThT positive) aggregates in hydrogels and away from the relatively unstable/unstructured presumed toxic oligomeric Aβ species in solution. Volume exclusion imparted by hydrogel confinement stabilizes unfolded, presumably toxic species, promoting stable extended β-sheet fibrils.The authors would like to thank Tagide deCarvalho for her assistance with TEM imaging and Dr. S. Maiti (Tata Institute of Fundamental Research) for sharing the Maximum Entropy Method program for FCS.
This work was supported by funding from the National Science Foundation (NSF) [EAGER CBET-1447057] and the National Institute of Health (NIH) [R01GM117159]. NSF provided support for TAG to contribute to this project through their Independent Research and Development program. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.https://www.sciencedirect.com/science/article/abs/pii/S174270612030300
Impact of Four Common Hydrogels on Amyloid-β (Aβ) Aggregation and Cytotoxicity: Implications for 3D Models of Alzheimer’s Disease
No full textThe physiochemical properties of hydrogels utilized in 3D culture can be used to modulate cell phenotype and morphology with a striking resemblance to cellular processes that occur in vivo. Indeed, research areas including regenerative medicine, tissue engineering, in vitro cancer models, and stem cell differentiation have readily utilized 3D biomaterials to investigate cell biological questions. However, cells are only one component of this biomimetic milieu. In many models of disease such as Alzheimer’s disease (AD) that could benefit from the in vivo-like cell morphology associated with 3D culture, other aspects of the disease such as protein aggregation have yet to be methodically considered in this 3D context. A hallmark of AD is the accumulation of the peptide amyloid-β (Aβ), whose aggregation is associated with neurotoxicity. We have previously demonstrated the attenuation of Aβ cytotoxicity when cells were cultured within type I collagen hydrogels versus on 2D substrates. In this work, we investigated the extent to which this phenomenon is conserved when Aβ is confined within hydrogels of varying physiochemical properties, notably mesh size and bioactivity. We investigated the Aβ structure and aggregation kinetics in solution and hydrogels composed of type I collagen, agarose, hyaluronic acid, and polyethylene glycol using fluorescence correlation spectroscopy and thioflavin T assays. Our results reveal that all hydrogels tested were associated with enhanced Aβ aggregation and Aβ cytotoxicity attenuation. We suggest that confinement itself imparts a profound effect, possibly by stabilizing Aβ structures and shifting the aggregate equilibrium toward larger species. If this phenomenon of altered protein aggregation in 3D hydrogels can be generalized to other contexts including the in vivo environment, it may be necessary to reevaluate aspects of protein aggregation disease models used for drug discovery.The authors would like to thank Tagide deCarvalho for her assistance with TEM imaging and Dr. S. Maiti (Tata Institute of Fundamental Research) for sharing the Maximum Entropy Method program for FCS. This work was supported by funding from NSF (EAGER CBET-1447057) and NIH (R01GM117159). NSF provided support for T.A.G. to contribute to this project through their Independent Research and Development program. Any opinion, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation.https://pubs.acs.org/doi/10.1021/acsomega.0c0204
VaRaPS: A Python Package for Estimating SARS-CoV-2 lineages Proportions from Pooled Sequencing Data (ANRS0160)
No full textBackground: Wastewater-based epidemiology has been investigated as a very effective way of monitoring SARS-CoV-2 variants. This can be achieved through accurate lineage deconvolution of wastewater sequencing data. Variants Ratios from Pooled Sequencing (VaRaPS) is a Python package designed for this purpose, utilizing pooled sequencing data and lineage mutation profiles to estimate their proportions. Results: VaRaPS re-implements core algorithms from the literature, achieving significant improvements in computational speed and efficiency. Comparative analyzes with synthetic data sets demonstrate its superior performance in lineage prevalence estimation, underscored by its user-oriented design for broader accessibility.Conclusions: By improving speed and accuracy in SARS-CoV-2 variant analysis, VaRaPS offers valuable insights into viral evolution, supporting ongoing surveillance efforts in the post-pandemic landscape
Metformin regulates TRPM6, a potential explanation for magnesium imbalance in type 2 diabetes patients
Get PDFMetformin therapy is associated with lower serum magnesium (Mg2+) levels in type 2 diabetes patients. The TRPM6 channel determines the fine-tuning of Mg2+ (re)absorption in intestine and kidney. Therefore, we aimed to investigate the short- and long-term effects of metformin on TRPM6. Patch clamp recordings and biotinylation assays were performed upon 1 h of incubation with metformin in TRPM6-transfected HEK293 cells. Additionally, 24 h of treatment of mDCT15 kidney and hCaco-2 colon cells with metformin was applied to measure the effects on endogenous TRPM6 expression by quantitative real-time PCR. To assess Mg2+ absorption, 25Mg2+ uptake measurements were performed using inductively coupled plasma mass spectrometry. Short-term effects of metformin significantly increased TRPM6 activity and its cell surface trafficking. In contrast, long-term effects significantly decreased TRPM6 mRNA expression and 25Mg2+ uptake. Metformin lowered TRPM6 mRNA levels independently of insulin- and AMPK-mediated pathways. Moreover, in type 2 diabetes patients, metformin therapy was associated with lower plasma Mg2+ concentrations and fractional excretion of Mg2+. Thereby, short-term metformin treatment increases TRPM6 activity explained by enhanced cell surface expression. Conversely, long-term metformin treatment results in downregulation of TRPM6 gene expression in intestine and kidney cells. This long-term effect translated in an inverse correlation between metformin and plasma Mg2+ concentration in type 2 diabetes patients.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
