Propositional unity and representation : theories of judgement from Kant to Wittgenstein

The aim of the thesis is to provide a fresh look at the beginning of the British analytic tradition, represented by early G. E. Moore and B. Russell and later by a young L. Wittgenstein, and emphasize especially the way in which this tradition was influenced by Kant’s transcendental-idealistic epistemology in general, and the notion of judgment in particular. In doing so, I open my account by focusing on how Moore’s ground-breaking notion of a “proposition” as a mentally-independent entity emerged out of his critical reflections on Kant’s account of judgment as a mental activity of bringing representations under the unity of transcendental apperception. Subsequently, I present Russell as adopting this notion of a proposition, providing a thoroughgoing analysis of it and, after discovering its philosophical shortcomings, finally abandoning it in favour of his multiple relation theory of judgment. Based on the detailed description of the nature and changes within Russell’s multiple relation theory, I then attempt to disentangle Wittgenstein’s famous, oft discussed argument against it and introduce the notion of a “proposition” from the Tractatus as Wittgenstein’s attempt at the more appropriate theory of judgment. Eventually, I illuminate how the approaches to judgement and proposition under consideration may all be considered particular responses to Kant’s transcendental-idealistic epistemology, something I do by paying attention in particular to the notions of unity of single propositions and judgments as opposed to the overall unity within the body of all propositions or judgments."This work was supported by School of Arts and Humanities Research Postgraduare Bursary (2013/2014-2015/2016)." -- Fundin

Kupffer cells ameliorate hepatic insulin resistance induced by high-fat diet rich in monounsaturated fatty acids: the evidence for the involvement of alternatively activated macrophages

<p>Abstract</p> <p>Background</p> <p>Resident macrophages (Kupffer cells, KCs) in the liver can undergo both pro- or anti-inflammatory activation pathway and exert either beneficiary or detrimental effects on liver metabolism. Until now, their role in the metabolically dysfunctional state of steatosis remains enigmatic. Aim of our study was to characterize the role of KCs in relation to the onset of hepatic insulin resistance induced by a high-fat (HF) diet rich in monounsaturated fatty acids.</p> <p>Methods</p> <p>Male Wistar rats were fed either standard (SD) or high-fat (HF) diet for 4 weeks. Half of the animals were subjected to the acute GdCl₃treatment 24 and 72 hrs prior to the end of the experiment in order to induce the reduction of KCs population. We determined the effect of HF diet on activation status of liver macrophages and on the changes in hepatic insulin sensitivity and triacylglycerol metabolism imposed by acute KCs depletion by GdCl₃.</p> <p>Results</p> <p>We found that a HF diet rich in MUFA itself triggers an alternative but not the classical activation program in KCs. In a steatotic, but not in normal liver, a reduction of the KCs population was associated with a decrease of alternative activation and with a shift towards the expression of pro-inflammatory activation markers, with the increased autophagy, elevated lysosomal lipolysis, increased formation of DAG, PKCε activation and marked exacerbation of HF diet-induced hepatic insulin resistance.</p> <p>Conclusions</p> <p>We propose that in the presence of a high MUFA content the population of alternatively activated resident liver macrophages may mediate beneficial effects on liver insulin sensitivity and alleviate the metabolic disturbances imposed by HF diet feeding and steatosis. Our data indicate that macrophage polarization towards an alternative state might be a useful strategy for treating type 2 diabetes.</p

The Increased Activity of Liver Lysosomal Lipase in Nonalcoholic Fatty Liver Disease Contributes to the Development of Hepatic Insulin Resistance

We tested the hypothesis that TAG accumulation in the liver induced by short-term high-fat diet (HFD) in rats leads to the dysregulation of endogenous TAG degradation by lysosomal lipase (LIPA) via lysosomal pathway and is causally linked with the onset of hepatic insulin resistance. We found that LIPA could be translocated between qualitatively different depots (light and dense lysosomes). In contrast to dense lysosomal fraction, LIPA associated with light lysosomes exhibits high activity on both intracellular TAG and exogenous substrate and prandial- or diet-dependent regulation. On standard diet, LIPA activity was upregulated in fasted and downregulated in fed animals. In the HFD group, we demonstrated an increased TAG content, elevated LIPA activity, enhanced production of diacylglycerol, and the abolishment of prandial-dependent LIPA regulation in light lysosomal fraction. The impairment of insulin signalling and increased activation of PKCε was found in liver of HFD-fed animals. Lipolysis of intracellular TAG, mediated by LIPA, is increased in steatosis probably due to the enhanced formation of phagolysosomes. Consequent overproduction of diacylglycerol may represent the causal link between HFD-induced hepatic TAG accumulation and hepatic insulin resistance via PKCε activation

Analysis of HIF-1α expression and genetic polymorphisms in human clear cell renal cell carcinoma

Introduction: Clear cell renal cell carcinoma (ccRCC) is mostly diagnosed incidentally and has relatively high recurrence rates. Alterations in VHL/HIF and mTOR pathways are commonly present in ccRCC. The present study attempted to identify potential diagnostic markers at the biochemical and molecular level.Methods: In total, 54 subjects (36 patients with ccRCC and 18 cancer-free controls) were enrolled. ELISA was used to measure the levels of HIF-1α in the tumor and healthy kidney tissue. The association between five selected SNPs (rs779805, rs11549465, rs2057482, rs2295080 and rs701848) located in genes of pathologically relevant pathways (VHL/HIF and mTOR) and the risk of ccRCC in the Slovak cohort was studied using real-time PCR.Results: Significant differences in HIF-1α tissue levels were observed between the tumor and healthy kidney tissue (p &lt; 0.001). In the majority (69%) of cases, the levels of HIF-1α were higher in the kidney than in the tumor. Furthermore, the concentration of HIF-1α in the tumor showed a significant positive correlation with CCL3 and IL-1β (p (R2) 0.007 (0.47); p (R2) 0.011 (0.38). No relationship between intratumoral levels of HIF-1α and clinical tumor characteristics was observed. Rs11549465, rs2057482 in the HIF1A gene did not correlate with the expression of HIF-1α either in the tumor or in the normal kidney. None of the selected SNPs has influenced the susceptibility to ccRCC.Conclusion: More research is neccesary to elucidate the role of HIF-1α in the pathogenesis of ccRCC and the association between selected SNPs and susceptibility to this cancer

SURFACE AND STRUCTURE STUDY OF CLAY-BASED COMPOSITES AFTER THERMAL TREATMENT

The composite materials prepared from clay and iron oxides in different weight ratios and temperatures denoted as A85 and E20 were heated at 300 °C in reductive atmosphere and up to 650 °C in inert atmosphere. The changes in the structure, surface and pore properties were examined by XRD, N2 adsorption method and TG, DTA method. The morphology was studied using scanning electron microscope. The heating of composites up to temperature 300 °C in the reductive atmosphere caused the transformation of the present oxide phases. The distribution curve of the heated composites is narrower and is shifted to the lower pores. The composites heated up to 650 °C in the N2 atmosphere showed to the transformation of iron oxide phases to hematite; the composites contained less pores, became denser and due to sintering of iron oxides particles a decrease in specific surface area was observed

The Possibility of Using BCI Applications in Physiotherapy

Brain-Computer Interface (BCI) is an interface connecting the human neural system and computer. This article explains the fundamental principles of BCI and devices, which can be controlled using electroencephalography (EEG). Firstly, this article describes Brain-Computer interface according to obtaining brain activity. After that, the applications of BCI are proposed, which can be used in clinical practice. In the experimental part, the external systems are defined. These external systems are operated by BCI technology. This technology is developed at the Department of Informatics and Artificial Intelligence of the Faculty of Applied Informatics, Tomas Bata University in Zlin. This BCI system contains EEG technology, which is responsible for scanning a brain activity with a fourteen-channel device developed by Emotiv company. In the near future, this design of peripheral systems can be involved in clinical practice in various medical branches, especially physiotherapy

The Opposite Effects of High-Sucrose and High-Fat Diet on Fatty Acid Oxidation and Very Low Density Lipoprotein Secretion in Rat Model of Metabolic Syndrome

Aims. To determine the effect of two different diets (high-sucrose (HS) and high-fat (HF)) on the main metabolic pathways potentially contributing to the development of steatosis: (1) activity of the liver lysosomal and heparin-releasable lipases; (2) fatty acid (FFA) oxidation; (3) FFA synthesis de novo; (4) VLDL output in vivo in a rat model of metabolic syndrome (MetS), hereditary hypertriglyceridemic (HHTg) rats fed HS or HF diets. Results. Both diets resulted in triacylglycerol (TAG) accumulation in the liver (HF > HS). The intracellular TAG lipolysis by lysosomal lipase was increased in both groups and positively correlated with the liver TAG content. Diet type significantly affected partitioning of intracellular TAG-derived fatty acids among FFA-utilizing metabolic pathways as HS feeding accentuated VLDL secretion and downregulated FFA oxidation while the HF diet had an entirely opposite effect. FFA de novo synthesis from glucose was significantly enhanced in the HS group (fed ≫ fasted) while being completely eradicated in the HF group. Conclusions. We found that in rats prone to the development of MetS associated diseases dietary-induced steatosis is not simply a result of impaired TAG degradation but that it depends on other mechanisms (elevated FFA synthesis or attenuated VLDL secretion) that are specific according to diet composition

Aberrantly Methylated cfDNA in Body Fluids as a Promising Diagnostic Tool for Early Detection of Breast Cancer

Breast malignancies are the leading type of cancer among women. Its prevention and early detection, particularly in young women, remains challenging. To this end, cell-free DNA (cfDNA) detected in body fluids demonstrates great potential for early detection of tissue transformation and altered molecular setup, such as epigenetic profiles. Aberrantly methylated cfDNA in body fluids could therefore serve as a potential diagnostic and prognostic tool in breast cancer management. Abnormal methylation may lead to both an activation of oncogenes via hypomethylation and an inactivation of tumor suppressor genes by hypermethylation. We update the state of the art in the area of aberrant cfDNA methylation analyses as a diagnostic and prognostic tool in breast cancer, report on the main technological challenges, and provide an outlook for advancing the overall management of breast malignancies based on cfDNA as a target for diagnosis and tailored therapies. (C) 2020 Elsevier Inc. All rights reserved

The Ability to Normalise Energy Metabolism in Advanced COVID-19 Disease Seems to Be One of the Key Factors Determining the Disease Progression—A Metabolomic NMR Study on Blood Plasma

Background: COVID-19 represents a severe inflammatory condition. Our work was designed to monitor the longitudinal dynamics of the metabolomic response of blood plasma and to reveal presumable discrimination in patients with positive and negative outcomes of COVID-19 respiratory symptoms. Methods: Blood plasma from patients, divided into subgroups with positive (survivors) and negative (worsening condition, non-survivors) outcomes, on Days 1, 3, and 7 after admission to hospital, was measured by NMR spectroscopy. Results: We observed changes in energy metabolism in both groups of COVID-19 patients; initial hyperglycaemia, indicating lowered glucose utilisation, was balanced with increased production of 3-hydroxybutyrate as an alternative energy source and accompanied by accelerated protein catabolism manifested by an increase in BCAA levels. These changes were normalised in patients with positive outcome by the seventh day, but still persisted one week after hospitalisation in patients with negative outcome. The initially decreased glutamine plasma level normalised faster in patients with positive outcome. Patients with negative outcome showed a more pronounced Phe/Tyr ratio, which is related to exacerbated and generalised inflammatory processes. Almost ideal discrimination from controls was proved. Conclusions: Distinct metabolomic responses to severe inflammation initiated by SARS-CoV-2 infection may serve towards complementary personalised pharmacological and nutritional support to improve patient outcomes