TP53 in Biology and Treatment of Osteosarcoma

The TP53 gene is mutated in 50% of human tumors. Oncogenic functions of mutant TP53 maintain tumor cell proliferation and tumor growth also in osteosarcomas. We collected data on TP53 mutations in patients to indicate which are more common and describe their role in in vitro and animal models. We also describe animal models with TP53 dysfunction, which provide a good platform for testing the potential therapeutic approaches. Finally, we have indicated a whole range of pharmacological compounds that modulate the action of p53, stabilize its mutated versions or lead to its degradation, cause silencing or, on the contrary, induce the expression of its functional version in genetic therapy. Although many of the described therapies are at the preclinical testing stage, they offer hope for a change in the approach to osteosarcoma treatment based on TP53 targeting in the future.

COVID-19 Mass Vaccination Resource Calculator

Background Despite the recent emergency use authorization of two vaccines for the prevention of the 2019 novel coronavirus (COVID-19) disease, vaccination rates are lower than expected. Vaccination efforts may be hampered by supply, delivery, storage, patient prioritization, administration infrastructure or logistics problems. To address the last issue, our institution is sharing publically a calculator to optimize the management of staffing and facility resources in an outpatient mass vaccination effort. Objective By sharing our calculator locally and through this paper, we aim to help health organizations administering vaccines optimize resource allocation while maximizing efficiency. Methods Our calculator determines the maximum number of vaccinations that can be administered per hour, the number of check-in staff (clerks) needed, the number of vaccination staff (nurses) needed, and the required room capacity needed for the vaccination and the mandatory 15-minute observation period after inoculation. Results We provide a functional version of the calculator, allowing users to replicate the calculation for their own vaccine events. Conclusion An efficient and organized vaccination program is critical to halting the spread of COVID-19. By sharing this calculator, it is our hope that other organizations may use it to facilitate rapid and efficient vaccination.

Prospects for the Development of Payment Institutions in Russia

The current structure of the Russian payment market is almost ten years old—in the summer of 2011,the Federal Law “On the National Payment System” was adopted. This was the start of a “Russian noncash miracle,” a fantastic increase of non-cash payments in retail turnover. Having solved numerous problems, the new market structure today also needs to be updated. During this decade, the range of challenges faced by the industry and the regulator has changed significantly: those are unbalanced competition, the presence of types of companies with similar functionality on the market, complex licensing procedures, and so on. This article aims to consider a new perspective of market transformation based on the introduction of payment institution into the Russian system. The article analyzes the current and future types of payments; examines in detail the structure of the Russian payment market, its advantages and disadvantages; and describes the payment institution, identifying the risks and prospects of its introduction into Russian banking practice. The authors suggest the feasibility of introducing payment institutions as a more functional version of the payment agents operating in Russia to simplify the complex structure of payment service providers. Payment institutions should become conduits for new payment services (such as PISP and AISP). In addition, payment institutions should be supervised by the regulator. At the same time, the introduction of a new type of companies should not put existing players at a disadvantage. Therefore, existing credit institutions and payment agents should have the ability to easily change their status and transform into payment institutions and back again.

An Lp-Functional Busemann–Petty Centroid Inequality

For a convex body $K\subset \mathbb{R}^n$, let $\Gamma _pK$ be its $L_p$-centroid body. The $L_p$-Busemann–Petty centroid inequality states that $\operatorname{vol}(\Gamma _pK) \geq \operatorname{vol}(K)$, with equality if and only if $K$ is an ellipsoid centered at the origin. In this work, we prove inequalities for a type of functional $L_r$-mixed volume for $1 \leq r < n$ and establish, as a consequence, a functional version of the $L_p$-Busemann–Petty centroid inequality.

Architecture of the Mto1/2 microtubule nucleation complex

ABSTRACTProteins that contain a Centrosomin Motif 1 (CM1) domain are key regulators ofγ-tubulin complex-dependent microtubule nucleation, but how they are organized in higher-order structures is largely unknown. Mto1[bonsai], a truncated functional version of theSchizosaccharomyces pombeCM1 protein Mto1, interacts with Mto2 to form an Mto1/2[bonsai] complexin vivo. Here we show that recombinant Mto1/2[bonsai] forms higher-order multimersin vitroand that Mto2 alone can also multimerize. We demonstrate that Mto2 multimerization involves two separate homodimerization domains, the near N-terminal domain (NND) and the twin-cysteine domain (TCD). The TCD crystal structure reveals a stable homodimer with a novel dimerization interface. While the NND homodimer is intrinsically less stable, using crosslinking mass spectrometry we show that within Mto1/2[bonsai] complexes, it can be reinforced by additional cooperative interactions involving both Mto2 and Mto1[bonsai]. We propose a model for Mto1/2[bonsai] complex architecture that is supported by functional analysis of mutantsin vivo.

Electronic Democracy in Belarus, Moldova, and Ukraine. Patterns and Comparative Perspectives

In recent years, numerous e-participation opportunities have emerged. Their scope and impact vary across countries. This contribution reviews the performance of observed e-democracy initiatives in Belarus, Ukraine, and Moldova, based on expert interviews, content analysis of online cases, and related self-reported statistics. The studied countries demonstrate a wide spectrum of e-democracy forms, tools, their usage rates, and influences on policy making. Belarus has the fewest e-participation opportunities, Moldova has more tools but little e-participation, while Ukraine has a more functional version of digital democracy in terms of numbers of available e-participation formats, instruments, their usage rates, and impact on public policy.

The functional Meyer–Tanaka formula

The functional Itô formula, firstly introduced by Bruno Dupire for continuous semimartingales, might be extended in two directions: different dynamics for the underlying process and/or weaker assumptions on the regularity of the functional. In this paper, we pursue the former type by proving the functional version of the Meyer–Tanaka formula. Following the idea of the proof of the classical time-dependent Meyer–Tanaka formula, we study the mollification of functionals and its convergence properties. As an example, we study the running maximum and the max-martingales of Yor and Obłój.

Second-order limit laws for occupation times of fractional Brownian motion

We prove a second-order limit law for additive functionals of a d-dimensional fractional Brownian motion with Hurst index H = 1 / d, using the method of moments and extending the Kallianpur–Robbins law, and then give a functional version of this result. That is, we generalize it to the convergence of the finite-dimensional distributions for corresponding stochastic processes.