Synthetic epigenetics in yeast

Epigenetics is the study of heritable biological variation not related to changes in DNA sequence. Epigenetic processes are responsible for establishing and maintaining transcriptional programs that define cell identity. Defects to epigenetic processes have been linked to a host of disorders, including mental retardation, aging, cancer and neurodegenerative diseases. The ability to control and engineer epigenetic systems would be valuable both for the basic study of these critical cellular processes as well as for synthetic biology. Indeed, while synthetic biology has made progress using bottom-up approaches to engineer transcriptional and signaling circuitry, epigenetic systems have remained largely underutilized. The predictive engineering of epigenetic systems could enable new functions to be implemented in synthetic organisms, including programmed phenotypic diversity, memory, reversibility, inheritance, and hysteresis. This thesis broadly focuses on the development of foundational tools and intellectual frameworks for applying synthetic biology to epigenetic regulation in the model eukaryote, Saccharomyces cerevisiae. Epigenetic regulation is mediated by diverse molecular mechanisms: e.g. self-sustaining feedback loops, protein structural templating, modifications to chromatin, and RNA silencing. Here we develop synthetic tools and circuits for controlling epigenetic states through (1) modifications to chromatin and (2) self-templating protein conformations. On the former, the synthetic tools we develop make it possible to study and direct how chromatin regulators operate to produce distinct gene expression programs. On the latter, we focus our studies on yeast prions, which are self-templating protein conformations that act as elements of inheritance, developing synthetic tools for detecting and controlling prion states in yeast cells. This thesis explores the application of synthetic biology to these epigenetic systems through four aims: Aim 1. Development of inducible expression systems for precise temporal expression of epigenetic regulators Aim 2. Construction of a library of chromatin regulators to study and program chromatin-based epigenetic regulation. Aim 3. Development of a genetic tool for quantifying protein aggregation and prion states in high-throughput Aim 4. Dynamics and control of prion switching Our tools and studies enable a deeper functional understanding of epigenetic regulation in cells, and the repurposing of these systems for synthetic biology toward addressing industrial and medical applications.2019-10-08T00:00:00

ПИТАННЯ ВИЗНАЧЕННЯ ХАРАКТЕРИСТИК КОЛІСНИХ ТРАНСПОРТНИХ ЗАСОБІВ З ГІБРИДНИМИ ДВИГУНАМИ У ВІДПОВІДНОСТІ З УКРАЇНСЬКИМ КЛАСИФІКАТОРОМ ТОВАРІВ ЗОВНІШНЬОЕКОНОМІЧНОЇ ДІЯЛЬНОСТІ

This article discusses the problematic issues of the study of the characteristics of wheeled plug-in hybrid electric vehicles (PHEVs) in accordance with the requirements of the Ukrainian classification of goods of foreign economic activity. Existing types of hybrid power plants are considered. We consider the problems that are solved by experts in automotive industry in the study of wheeled vehicles with hybrid power plants. Problems of determining the type of hybrid power plant of a wheeled vehicle, the principle of its operation, and, consequently, the influence of this on the determination of the code according to the UKT ZED (Ukrainian Classification of Goods for Foreign Economic Activity) are considered. Currently, in expert practice, there is no single approach in carrying out research to determine which characteristics the wheeled vehicle meets according to the Ukrainian Classifier of Goods of Foreign Economic Activity. In this article the main types and types of hybrid power units, the principles of their operation and the effect on the definition of the code under the UKT ZED are given. In relation to wheeled vehicles to one or another code under the UKT ZED it is necessary to determine the scheme of the operation of the hybrid power plant. In this case, hybrid power units operating on a parallel and serially parallel circuit should be classified in the code of code 8703 2 "Other vehicles with spark ignition internal combustion engine and crankshaft coupling" or 8703 3 "Other vehicles from an internal combustion engine with compression ignition (diesel or semi-diesel), and hybrid power plants that operate in a sequential scheme to the code number 8703 90 90 00 "other" as not falling under the requirements of the other the position of the booty on the principle of its work.Рассмотрены проблемные вопросы исследования характеристик колесных транспортных средств с гибридными силовыми установками в соответствии с требованиями Украинского классификатора товаров внешнеэкономической деятельности. Названы существующие типы гибридных силовых установок. Очерчены задачи, которые решаются экспертами- автотовароведами при исследовании колесных транспортных средств с гибридными силовыми установками. Рассмотрены проблемы определения типа гибридной силовой установки колесного транспортного средства, принципа его работы и, как следствие, влияния этого на определение кода по УКТВЭД. В настоящее время в экспертной практике нет единого подхода к проведению исследований, позволяющих определить, каким характеристикам колесное транспортное средство соответствует украинскому классификатору товаров внешнеэкономической деятельности. Приведены основные типы и виды гибридных силовых агрегатов, принципы их работы и влияние на определение кода по УКТВЭД. При отнесении КТС к тому или иному коду по УКТВЭД необходимо определиться со схемой работы гибридной силовой установки. При этом гибридные силовые установки, работающие по параллельной и последовательно — параллельной схеме, должны быть отнесены к товарной позиции кода 8703 2 — «другие транспортные средства с двигателем внутреннего сгорания с искровым зажиганием и с кривошипно-шатунным механизмом» или 8703 3 — «другие транспортные средства с двигателем внутреннего сгорания с воспламенением от сжатия (дизелем или полудизелем)», а гибридные силовые установки, работающие по последовательной схеме, к товарной позиции кода 8703 90 90 00 — «другие», как такие, что не попадают под требования других товарных позиций по принципу своей работы.Розглянуто проблемні питання щодо дослідження характеристик колісних транспортних засобів з гібридними двигунами відповідно до вимог Українського класифікатора товарів зовнішньоекономічної діяльності. Розглянуто існуючі типи гібридних силових установок. Вивчено завдання, що вирішуються експертами автотоварознавцями при дослідженні колісних транспортних засобів з гібридними двигунами

Charmed particles production in pA-interactions at 70 GeV

The results of the SERP-E-184 experiment at the U-70 accelerator (IHEP, Protvino) are presented. Interactions of the 70 GeV proton beam with carbon, silicon and lead targets were studied to detect decays of charmed $D^0$, $\bar D^0$, $D^+$, $D^-$ mesons and $\Lambda_c^+$ baryon near their production threshold. Measurements of lifetimes and masses have shown a good agreement with PDG data. The inclusive cross sections of charm production and their A-dependencies have been obtained. The yields of these particles are compared with the theoretical predictions and the data of other experiments. The measured cross section of the total open charm production $\sigma(c\bar c) = 7.1 \pm 2.3(stat) \pm 1.4(syst)$ $\mu$b/nucleon at the collision c.m. energy $\surd s$ = 11.8 GeV is well above the QCD model predictions. The contributions of different kinds of charmed particles to the total cross section of the open charm production in proton-nucleus interactions vary with energy.Comment: Presented at 19th International Seminar on High Energy Physics QUARKS-2016 (Pushkin, Russia, 29 May - 4 June, 2016.). 11 pages, 9 figure

Properties of Neutral Charmed Mesons in Proton--Nucleus Interactions at 70 GeV

The results of treatment of data obtained in the SERP-E-184experiment "Investigation of mechanisms of the production of charmed particles in proton-nucleus interactions at 70 GeV and their decays" by irradiating the active target of the SVD-2 facility consisting of carbon, silicon, and lead plates, are presented. After separating a signal from the two-particle decay of neutral charmed mesons and estimating the cross section for charm production at a threshold energy {\sigma}(c\v{c})=7.1 \pm 2.4(stat.) \pm 1.4(syst.) \mub/nucleon, some properties of D mesons are investigated. These include the dependence of the cross section on the target mass number (its A dependence); the behavior of the differential cross sections d{\sigma}/dpt2 and d{\sigma}/dxF; and the dependence of the parameter {\alpha} on the kinematical variables xF, pt2, and plab. The experimental results in question are compared with predictions obtained on the basis of the FRITIOF7.02 code.Comment: 9 pages, 9 figures,3 table

Strategy and Tactics of International Mergers and Acquisitions

The article reviews contemporary strategy and tactics issues in terms of international mergers and acquisitions, along with displaying cyclical waves of mergers and acquisitions over the last century as well as motivation thereof. Five strategies adhered to by international companies initiating conclusion of such agreements as well as challenges accompanying execution thereof have been analyzed. Modern strategic and tactical tools of international mergers and acquisitions process management have been researched on exemplary buyer (a corporation) case-study