56 research outputs found

    Probability Theory Compatible with the New Conception of Modern Thermodynamics. Economics and Crisis of Debts

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    We show that G\"odel's negative results concerning arithmetic, which date back to the 1930s, and the ancient "sand pile" paradox (known also as "sorites paradox") pose the questions of the use of fuzzy sets and of the effect of a measuring device on the experiment. The consideration of these facts led, in thermodynamics, to a new one-parameter family of ideal gases. In turn, this leads to a new approach to probability theory (including the new notion of independent events). As applied to economics, this gives the correction, based on Friedman's rule, to Irving Fisher's "Main Law of Economics" and enables us to consider the theory of debt crisis.Comment: 48p., 14 figs., 82 refs.; more precise mathematical explanations are added. arXiv admin note: significant text overlap with arXiv:1111.610

    Antifungal drug resistance evoked via RNAi-dependent epimutations

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    Microorganisms evolve via mechanisms spanning sexual/parasexual reproduction, mutators, aneuploidy, Hsp90, and even prions. Mechanisms that may seem detrimental can be repurposed to generate diversity. Here we show the human fungal pathogen Mucor circinelloides develops spontaneous resistance to the antifungal drug FK506 (tacrolimus) via two distinct mechanisms. One involves Mendelian mutations that confer stable drug resistance; the other occurs via an epigenetic RNA interference (RNAi)-mediated pathway resulting in unstable drug resistance. The peptidyl-prolyl isomerase FKBP12 interacts with FK506 forming a complex that inhibits the protein phosphatase calcineurin1. Calcineurin inhibition by FK506 blocks M. circinelloides transition to hyphae and enforces yeast growth2. Mutations in the fkbA gene encoding FKBP12 or the calcineurin cnbR or cnaA genes confer FK506 resistance (FK506R) and restore hyphal growth. In parallel, RNAi is spontaneously triggered to silence the FKBP12 fkbA gene, giving rise to drug-resistant epimutants. FK506R epimutants readily reverted to the drug-sensitive wild-type (WT) phenotype when grown without drug. The establishment of these epimutants is accompanied by generation of abundant fkbA small RNA (sRNA) and requires the RNAi pathway as well as other factors that constrain or reverse the epimutant state. Silencing involves generation of a double-stranded RNA (dsRNA) trigger intermediate from the fkbA mature mRNA to produce antisense fkbA RNA. This study uncovers a novel epigenetic RNAi-based epimutation mechanism controlling phenotypic plasticity, with possible implications for antimicrobial drug resistance and RNAi-regulatory mechanisms in fungi and other eukaryotes

    Mathematical Conception of "Phenomenological" Equilibrium Thermodynamics

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    In the paper, the principal aspects of the mathematical theory of equilibrium thermodynamics are distinguished. It is proved that the points of degeneration of a Bose gas of fractal dimension in the momentum space coincide with critical points or real gases, whereas the jumps of critical indices and the Maxwell rule are related to the tunnel generalization of thermodynamics. Semiclassical methods are considered for the tunnel generalization of thermodynamics and also for the second and ultrasecond quantization (operators of creation and annihilation of pairs). To every pure gas there corresponds a new critical point of the limit negative pressure below which the liquid passes to a dispersed state (a foam). Relations for critical points of a homogeneous mixture of pure gases are given in dependence on the concentration of gases.Comment: 37 pages, 9 figure, more precise explanations, more references. arXiv admin note: substantial text overlap with arXiv:1202.525

    Avicin D: A Protein Reactive Plant Isoprenoid Dephosphorylates Stat 3 by Regulating Both Kinase and Phosphatase Activities

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    Avicins, a class of electrophilic triterpenoids with pro-apoptotic, anti-inflammatory and antioxidant properties, have been shown to induce redox-dependant post-translational modification of cysteine residues to regulate protein function. Based on (a) the cross-talk that occurs between redox and phosphorylation processes, and (b) the role of Stat3 in the process of apoptosis and carcinogenesis, we chose to study the effects of avicins on the processes of phosphorylation/dephosphorylation in Stat3. Avicins dephosphorylate Stat3 in a variety of human tumor cell lines, leading to a decrease in the transcriptional activity of Stat3. The expression of Stat3-regulated proteins such as c-myc, cyclin D1, Bcl2, survivin and VEGF were reduced in response to avicin treatment. Underlying avicin-induced dephosphorylation of Stat3 was dephosphorylation of JAKs, as well as activation of protein phosphatase-1. Downregulation of both Stat3 activity and expression of Stat 3-controlled pro-survival proteins, contributes to the induction of apoptosis in avicin treated tumor cells. Based on the role of Stat3 in inflammation and wounding, and the in vivo inhibition of VEGF by avicins in a mouse skin carcinogenesis model, it is likely that avicin-induced inhibition of Stat3 activity results in the suppression of the pro-inflammatory and pro-oxidant stromal environment of tumors. Activation of PP-1, which also acts as a cellular economizer, combined with the redox regulation by avicins, can aid in redirecting metabolism from growth promoting anabolic to energy sparing pathways

    Spatiotemporal DNA methylome dynamics of the developing mouse fetus

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    Cytosine DNA methylation is essential for mammalian development but understanding of its spatiotemporal distribution in the developing embryo remains limited. Here, as part of the mouse Encyclopedia of DNA Elements (ENCODE) project, we profiled 168 methylomes from 12 mouse tissues or organs at 9 developmental stages from embryogenesis to adulthood. We identified 1,808,810 genomic regions that showed variations in CG methylation by comparing the methylomes of different tissues or organs from different developmental stages. These DNA elements predominantly lose CG methylation during fetal development, whereas the trend is reversed after birth. During late stages of fetal development, non-CG methylation accumulated within the bodies of key developmental transcription factor genes, coinciding with their transcriptional repression. Integration of genome-wide DNA methylation, histone modification and chromatin accessibility data enabled us to predict 461,141 putative developmental tissue-specific enhancers, the human orthologues of which were enriched for disease-associated genetic variants. These spatiotemporal epigenome maps provide a resource for studies of gene regulation during tissue or organ progression, and a starting point for investigating regulatory elements that are involved in human developmental disorders

    An Evaluation Schema for the Ethical Use of Autonomous Robotic Systems in Security Applications

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