Unknown God, Known in His Activities

What can man know about God? This question became one of the main problems during the 4th-century Trinitarian controversy, which is the focus of this book. Especially during the second phase of the conflict, the claims of Anomean Eunomius caused an emphatic response of Orthodox writers, mainly Basil of Caesarea and Gregory of Nyssa. Eunomius formulated two ways of theology to show that we can know both the substance (ousia) and activities (energeiai) of God. The Orthodox Fathers demonstrated that we can know only the external activities of God, while the essence is entirely incomprehensible. Therefore the 4th-century discussion on whether the Father and the Son are of the same substance was the turning point in the development of negative theology and shaping the Christian conception of God

Interdependence of the Rad50 hook and globular domain functions

Rad50 contains a conserved Zn2+ coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here we focused on rad50 mutations flanking the Zn2+-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 (ATM) activation, nonhomologous end-joining, and DNA double strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled coil and globular ATPase domain, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions

Debundling and Selective Enrichment of SWNTs for Applications in Dye-Sensitized Solar Cells

We present an overview of the recent developments in de-bundling and sorting of Single-Wall Carbon Nanotubes (SWNTs), which are useful for hi-tech applications in dye sensitized solar cells (DSSCs). Applications of SWNTs as transparent and conductive films, catalyst, and scaffold in DSSCs are also reviewed.Peer Reviewe

Unknown God, Known in His Activities

What can man know about God? This question became one of the main problems during the 4th-century Trinitarian controversy, which is the focus of this book. Especially during the second phase of the conflict, the claims of Anomean Eunomius caused an emphatic response of Orthodox writers, mainly Basil of Caesarea and Gregory of Nyssa. Eunomius formulated two ways of theology to show that we can know both the substance (ousia) and activities (energeiai) of God. The Orthodox Fathers demonstrated that we can know only the external activities of God, while the essence is entirely incomprehensible. Therefore the 4th-century discussion on whether the Father and the Son are of the same substance was the turning point in the development of negative theology and shaping the Christian conception of God

DEVELOPING SKILLS IN SECURING SAFETY WHEN TRAVELLING AS AN ADDITIONAL EDUCATIONAL NEED OF SCHOOL CHILDREN AND YOUNG PEOPLE

Safeguarding the functioning of local and international tourism is one of the most important social challenges. Mastering its principles is a prerequisite for success in the fulfi lment of such human needs as relaxation, wellbeing and exploration of the world. The effectiveness of any steps to limit the risk and its consequences in tourism stems from multiannual observation of social phenomena, but it is also dependent on the level of theoretical preparation to take practical action for increased security at every stage of the journey. The aim of this article is to explore the idea of developing skills in securing safety in travel as an additional educational need of school children and young people. The article recommends supplementing the school curriculum at the primary and secondary school level in order to help create a profi le of a student able to secure broadly understood safety for himself and for others

Dynamics of COVID-19 pandemic at constant and time-dependent contact rates

We constructed a simple Susceptible−Exposed–Infectious–Removed model of the spread of COVID-19. The model is parametrised only by the average incubation period, τ, and two rate parameters: contact rate, β, and exclusion rate, γ. The rates depend on nontherapeutic interventions and determine the basic reproduction number, R0 = β/γ R0=β/γ , and, together with τ, the daily multiplication coefficient in the early exponential phase, θ. Initial R0 R0 determines the reduction of β required to contain the spread of the epidemic. We demonstrate that introduction of a cascade of multiple exposed states enables the model to reproduce the distributions of the incubation period and the serial interval reported by epidemiologists. Using the model, we consider a hypothetical scenario in which β is modulated solely by anticipated changes of social behaviours: first, β decreases in response to a surge of daily new cases, pressuring people to self-isolate, and then, over longer time scale, β increases as people gradually accept the risk. In this scenario, initial abrupt epidemic spread is followed by a plateau and slow regression, which, although economically and socially devastating, grants time to develop and deploy vaccine or at least limit daily cases to a manageable number

Feedbacks, Bifurcations, and Cell Fate Decision-Making in the p53 System.

The p53 transcription factor is a regulator of key cellular processes including DNA repair, cell cycle arrest, and apoptosis. In this theoretical study, we investigate how the complex circuitry of the p53 network allows for stochastic yet unambiguous cell fate decision-making. The proposed Markov chain model consists of the regulatory core and two subordinated bistable modules responsible for cell cycle arrest and apoptosis. The regulatory core is controlled by two negative feedback loops (regulated by Mdm2 and Wip1) responsible for oscillations, and two antagonistic positive feedback loops (regulated by phosphatases Wip1 and PTEN) responsible for bistability. By means of bifurcation analysis of the deterministic approximation we capture the recurrent solutions (i.e., steady states and limit cycles) that delineate temporal responses of the stochastic system. Direct switching from the limit-cycle oscillations to the "apoptotic" steady state is enabled by the existence of a subcritical Neimark-Sacker bifurcation in which the limit cycle loses its stability by merging with an unstable invariant torus. Our analysis provides an explanation why cancer cell lines known to have vastly diverse expression levels of Wip1 and PTEN exhibit a broad spectrum of responses to DNA damage: from a fast transition to a high level of p53 killer (a p53 phosphoform which promotes commitment to apoptosis) in cells characterized by high PTEN and low Wip1 levels to long-lasting p53 level oscillations in cells having PTEN promoter methylated (as in, e.g., MCF-7 cell line)

SARS-CoV-2 Variant of Concern 202012/01 Has about Twofold Replicative Advantage and Acquires Concerning Mutations

The novel SARS-CoV-2 Variant of Concern (VOC)-202012/01 (also known as B.1.1.7), first collected in United Kingdom on 20 September 2020, is a rapidly growing lineage that in January 2021 constituted 86% of all SARS-CoV-2 genomes sequenced in England. The VOC has been detected in 40 out of 46 countries that reported at least 50 genomes in January 2021. We have estimated that the replicative advantage of the VOC is in the range 1.83–2.18 [95% CI: 1.71–2.40] with respect to the 20A.EU1 variant that dominated in England in November 2020, and in range 1.65–1.72 [95% CI: 1.46–2.04] in Wales, Scotland, Denmark, and USA. As the VOC strain will likely spread globally towards fixation, it is important to monitor its molecular evolution. We have estimated growth rates of expanding mutations acquired by the VOC lineage to find that the L18F substitution in spike has initiated a fast growing VOC substrain. The L18F substitution is of significance because it has been found to compromise binding of neutralizing antibodies. Of concern are immune escape mutations acquired by the VOC: E484K, F490S, S494P (in the receptor binding motif of spike) and Q677H, Q675H (in the proximity of the polybasic cleavage site at the S1/S2 boundary). These mutants may hinder efficiency of existing vaccines and expand in response to the increasing after-infection or vaccine-induced seroprevalence

Antagonism between viral infection and innate immunity at the single-cell level.

When infected with a virus, cells may secrete interferons (IFNs) that prompt nearby cells to prepare for upcoming infection. Reciprocally, viral proteins often interfere with IFN synthesis and IFN-induced signaling. We modeled the crosstalk between the propagating virus and the innate immune response using an agent-based stochastic approach. By analyzing immunofluorescence microscopy images we observed that the mutual antagonism between the respiratory syncytial virus (RSV) and infected A549 cells leads to dichotomous responses at the single-cell level and complex spatial patterns of cell signaling states. Our analysis indicates that RSV blocks innate responses at three levels: by inhibition of IRF3 activation, inhibition of IFN synthesis, and inhibition of STAT1/2 activation. In turn, proteins coded by IFN-stimulated (STAT1/2-activated) genes inhibit the synthesis of viral RNA and viral proteins. The striking consequence of these inhibitions is a lack of coincidence of viral proteins and IFN expression within single cells. The model enables investigation of the impact of immunostimulatory defective viral particles and signaling network perturbations that could potentially facilitate containment or clearance of the viral infection