Improving energy efficiency of traction rolling stock

The paper considers relevant to the rail industry the problem of energy efficiency of traction rolling stock through the introduction of energy-saving technologies.В работе рассмотрена актуальная для железнодорожной отрасли проблема повышения энергетической эффективности тягового подвижного состава за счет внедрения энерго- и ресурсосберегающих технологий

Анализ и разработка рекомендаций по совершенствованию действующей интегрированной системы менеджмента химического предприятия

The integrated management system (IMS) process model of Saratovorgsintez, Ltd. has been built. The system includes quality management subsystem, environmental protection subsystem, employment protection subsystem. Probable fields for improvement of Saratovorgsintez, Ltd. system has been shown. IMS improvement recommendations has been also developed.Построена процессная модель интегрированной системы менеджмента (ИСМ) ООО «Саратоворгсинтез», включающая подсистемы менеджмента качества, охраны окружающей среды, профессиональной безопасности и охраны труда. Показаны возможные области для улучшения системы ООО «Саратоворгсинтез» и разработаны рекомендации по совершенствованию ИСМ

Подход к разработке интегрированной системы менеджмента на химических предприятиях.

On the base of systems approach the selection task of integrated management system structure was analyzed. Integrated management system on the chemical enterprises includes as a rule several systems: quality management system as a base system, environmental protection system, professional safety and employment protection system, GMP system, etc. It was suggested the solve method of structure selection task and business-processes distribution among enterprise departmentsПроанализирована задача выбора структуры интегрированной системы менеджмента (ИСМ) химического предприятия. Интегрированная система менеджмента (ИСМ) на химических предприятиях, как правило, включает несколько подсистем: менеджмента качества как базовую систему, систему охраны окружающей среды, систему профессиональной безопасности и охраны труда, систему GMP и т.п. Предложен метод решения задачи выбора структуры и распределения бизнес-процессов по подразделениям с учетом особенностей химического предприятия

Antiviral Properties of Chemical Inhibitors of Cellular Anti-Apoptotic Bcl-2 Proteins

Viral diseases remain serious threats to public health because of the shortage of effective means of control. To combat the surge of viral diseases, new treatments are urgently needed. Here we show that small-molecules, which inhibit cellular anti-apoptotic Bcl-2 proteins (Bcl-2i), induced the premature death of cells infected with different RNA or DNA viruses, whereas, at the same concentrations, no toxicity was observed in mock-infected cells. Moreover, these compounds limited viral replication and spread. Surprisingly, Bcl-2i also induced the premature apoptosis of cells transfected with viral RNA or plasmid DNA but not of mock-transfected cells. These results suggest that Bcl-2i sensitizes cells containing foreign RNA or DNA to apoptosis. A comparison of the toxicity, antiviral activity, and side effects of six Bcl-2i allowed us to select A-1155463 as an antiviral lead candidate. Thus, our results pave the way for the further development of Bcl-2i for the prevention and treatment of viral diseases.Peer reviewe

Study of the decay K+→π+π−π+γK^{+}\to\pi^{+}\pi^{-}\pi^{+}\gamma in the OKA experiment

A high statistics data sample of the decays of $K^+$ mesons to three charged particles was accumulated by the OKA experiment in 2012 and 2013. This allowed to select a clean sample of about 450 events with $K^{+}\to\pi^{+}\pi^{-}\pi^{+}\gamma$ decays with the energy of the photon in the kaon rest frame greater than 30 MeV. The measured branching fraction of the $K^{+}\to\pi^{+}\pi^{-}\pi^{+}\gamma$, with $E_{\gamma}^{*}$ > 30 MeV is $(0.71 \pm 0.05) \times 10^{-5}$. The measured energy spectrum of the decay photon is compared with the prediction of the chiral perturbation theory to O$(p^{4})$. A search for an up-down asymmetry of the photon with respect to the hadronic system decay plane is also performed.Comment: 9 pages, 7 figures, 1 tabl

CPP-ZFN: A potential DNA-targeting anti-malarial drug

<p>Abstract</p> <p>Background</p> <p>Multidrug-resistant <it>Plasmodium </it>is of major concern today. Effective vaccines or successful applications of RNAi-based strategies for the treatment of malaria are currently unavailable. An unexplored area in the field of malaria research is the development of DNA-targeting drugs that can specifically interact with parasitic DNA and introduce deleterious changes, leading to loss of vital genome function and parasite death.</p> <p>Presentation of the hypothesis</p> <p>Advances in the development of zinc finger nuclease (ZFN) with engineered DNA recognition domains allow us to design and develop nuclease of high target sequence specificity with a mega recognition site that typically occurs only once in the genome. Moreover, cell-penetrating peptides (CPP) can cross the cell plasma membrane and deliver conjugated protein, nucleic acid, or any other cargo to the cytoplasm, nucleus, or mitochondria. This article proposes that a drug from the combination of the CPP and ZFN systems can effectively enter the intracellular parasite, introduce deleterious changes in its genome, and eliminate the parasite from the infected cells.</p> <p>Testing the hypothesis</p> <p>Availability of a DNA-binding motif for more than 45 triplets and its modular nature, with freedom to change number of fingers in a ZFN, makes development of customized ZFN against diverse target DNA sequence of any gene feasible. Since the <it>Plasmodium </it>genome is highly AT rich, there is considerable sequence site diversity even for the structurally and functionally conserved enzymes between <it>Plasmodium </it>and humans. CPP can be used to deliver ZFN to the intracellular nucleus of the parasite. Signal-peptide-based heterologous protein translocation to <it>Plasmodium</it>-infected RBCs (iRBCs) and different <it>Plasmodium </it>organelles have been achieved. With successful fusion of CPP with mitochondrial- and nuclear-targeting peptides, fusion of CPP with 1 more <it>Plasmodium </it>cell membrane translocation peptide seems achievable.</p> <p>Implications of the hypothesis</p> <p>Targeting of the <it>Plasmodium </it>genome using ZFN has great potential for the development of anti-malarial drugs. It allows the development of a single drug against all malarial infections, including multidrug-resistant strains. Availability of multiple ZFN target sites in a single gene will provide alternative drug target sites to combat the development of resistance in the future.</p

Human Cytomegalovirus UL29/28 Protein Interacts with Components of the NuRD Complex Which Promote Accumulation of Immediate-Early RNA

Histone deacetylation plays a pivotal role in regulating human cytomegalovirus gene expression. In this report, we have identified candidate HDAC1-interacting proteins in the context of infection by using a method for rapid immunoisolation of an epitope-tagged protein coupled with mass spectrometry. Putative interactors included multiple human cytomegalovirus-coded proteins. In particular, the interaction of pUL38 and pUL29/28 with HDAC1 was confirmed by reciprocal immunoprecipitations. HDAC1 is present in numerous protein complexes, including the HDAC1-containing nucleosome remodeling and deacetylase protein complex, NuRD. pUL38 and pUL29/28 associated with the MTA2 component of NuRD, and shRNA-mediated knockdown of the RBBP4 and CHD4 constituents of NuRD inhibited HCMV immediate-early RNA and viral DNA accumulation; together this argues that multiple components of the NuRD complex are needed for efficient HCMV replication. Consistent with a positive acting role for the NuRD elements during viral replication, the growth of pUL29/28- or pUL38-deficient viruses could not be rescued by treating infected cells with the deacetylase inhibitor, trichostatin A. Transient expression of pUL29/28 enhanced activity of the HCMV major immediate-early promoter in a reporter assay, regardless of pUL38 expression. Importantly, induction of the major immediate-early reporter activity by pUL29/28 required functional NuRD components, consistent with the inhibition of immediate-early RNA accumulation within infected cells after knockdown of RBBP4 and CHD4. We propose that pUL29/28 modifies the NuRD complex to stimulate the accumulation of immediate-early RNAs