Spectral transformation in the SOFI complex for processing photographic images on the ES computer, part 1

A description is given of three programs catalogued in the form of object modules in the library of a system for processing photographic images computer. PFT is the subprogram of the multi-dimensional BPF of real-valued information, in the operative computer memory. INRECO is a subprogram-interface between the real and complex formats for representing two-dimensional spectra and images. FFT2 is a subprogram for calculating the correlation functions of the image using the previous subprograms

Programs for high-speed Fourier, Mellin and Fourier-Bessel transforms

Several FORTRAN program modules for performing one-dimensional and two-dimensional discrete Fourier transforms, Mellin, and Fourier-Bessel transforms are described along with programs that realize the algebra of high speed Fourier transforms on a computer. The programs can perform numerical harmonic analysis of functions, synthesize complex optical filters on a computer, and model holographic image processing methods

Enzyme-catalyzed uridine phosphorolysis: SN2 mechanism with phosphate activation by desolvation

AbstractThe rate of uridine phosphorolysis catalyzed by uridine phosphorylase from Escherichia coli decreases with increasing ionic strength. In contrast, the rate was increased about twofold after preincubation of uridine phosphorylase with 60% acetonitrile. These data correlate with known effects of polar and bipolar aprotic solvents on SN2 nucleophilic substitution reactions. The enzyme modified with fluorescein-5′-isothiocyanate (fluorescein residue occupies an uridine-binding subsite [Komissarov et al., (1994) Biochim. Biophys. Acta 1205, 54–58]) was selectively modified with irreversible inhibitor SA-423, which reacts near the phosphate-binding subsite. The double-modified uridine phosphorylase is assumed to imitate the enzyme—substrate complex. Modification with SA-423 was accompanied with dramatic changes in the absorption spectrum of active site-linked fluorescein, which were identical to those for fluorescein in a hydrophobic medium, namely 80% acetonitrile. The data obtained suggest that an increase in active site hydrophobicity leads to phosphate desolvation and facilitates the enzymatic SN2 uridine phosphorolysis reaction

Разработка лекарств и открытый доступ: подходы и перспективы

The development of a new medicine is a process that requires enormous time and tremendous financing. It takes 10-15 years from the discovery of an active compound to the launch of its production and the start of drug marketing with the total costs of the project reaching 1.8 billion US dollars. These large time and financial costs stem from repeated testing and elimination of a large percentage of compounds over the course of screening at each stage of preclinical and clinical trials. Many investors have lost interest in financing new drug discovery projects (or pharmaceutical start-up companies) due to the high risk and extensive time required to produce a return on investments. Since all the research data are considered confidential by pharmaceutical companies and thus never shared with scientific community, different scientific groups waste significant resources repeating the same costly experiments in drug discovery. In this article, we discuss new approaches to drug discovery involving open access to the research data and alternative financing that could significantly streamline the search for new cures for human diseases.Разработка нового лекарства – процесс, требующий колоссальных затрат времени и финансовых средств. От нахождения активных химических соединений до выхода препарата на рынок проходит 10-15 лет и расходуется порядка 1.8 миллиарда долларов. Такие сроки и суммы обусловлены большим процентом отсева химических соединений на каждой стадии доклинических и клинических испытаний. Многие инвесторы потеряли интерес к финансированию фармацевтических стартапов и проектов по разработке новых препаратов из-за высокого риска и продолжительного времени, необходимого для получения прибыли от инвестиций. Поскольку все результаты исследований принадлежат фармацевтическим компаниям, считаются конфиденциальными и поэтому недоступны для научного сообщества, научные коллективы тратят значительные ресурсы, повторяя одни и те же дорогостоящие эксперименты. В этом обзоре мы рассматриваем современные принципы организации работы по созданию новых лекарств – открытый доступ к результатам исследований и альтернативное финансирование. Применение этих принципов позволит значительно упростить и удешевить поиск новых лекарственных препаратов для лечения людей

Atomic structure at 2.5 Å resolution of uridine phosphorylase from E. coli as refined in the monoclinic crystal lattice

AbstractUridine phosphorylase from E. coli (Upase) has been crystallized using vapor diffusion technique in a new monoclinic crystal form. The structure was determined by the molecular replacement method at 2.5 Å resolution. The coordinates of the trigonal crystal form were used as a starting model and the refinement by the program XPLOR led to the R-factor of 18.6%. The amino acid fold of the protein was found to be the same as that in the trigonal crystals. The positions of flexible regions were refined. The conclusion about the involvement in the active site is in good agreement with the results of the biochemical experiments

Biosensing for the Environment and Defence: Aqueous Uranyl Detection Using Bacterial Surface Layer Proteins

The fabrication of novel uranyl (UO22+) binding protein based sensors is reported. The new biosensor responds to picomolar levels of aqueous uranyl ions within minutes using Lysinibacillus sphaericus JG-A12 S-layer protein tethered to gold electrodes. In comparison to traditional self assembled monolayer based biosensors the porous bioconjugated layer gave greater stability, longer electrode life span and a denser protein layer. Biosensors responded specifically to UO22+ ions and showed minor interference from Ni2+, Cs+, Cd2+ and Co2+. Chemical modification of JG-A12 protein phosphate and carboxyl groups prevented UO22+ binding, showing that both moieties are involved in the recognition to UO22+

Identification of surface proteins in Enterococcus faecalis V583

<p>Abstract</p> <p>Background</p> <p>Surface proteins are a key to a deeper understanding of the behaviour of Gram-positive bacteria interacting with the human gastro-intestinal tract. Such proteins contribute to cell wall synthesis and maintenance and are important for interactions between the bacterial cell and the human host. Since they are exposed and may play roles in pathogenicity, surface proteins are interesting targets for drug design.</p> <p>Results</p> <p>Using methods based on proteolytic "shaving" of bacterial cells and subsequent mass spectrometry-based protein identification, we have identified surface-located proteins in <it>Enterococcus faecalis </it>V583. In total 69 unique proteins were identified, few of which have been identified and characterized previously. 33 of these proteins are predicted to be cytoplasmic, whereas the other 36 are predicted to have surface locations (31) or to be secreted (5). Lipid-anchored proteins were the most dominant among the identified surface proteins. The seemingly most abundant surface proteins included a membrane protein with a potentially shedded extracellular sulfatase domain that could act on the sulfate groups in mucin and a lipid-anchored fumarate reductase that could contribute to generation of reactive oxygen species.</p> <p>Conclusions</p> <p>The present proteome analysis gives an experimental impression of the protein landscape on the cell surface of the pathogenic bacterium <it>E. faecalis</it>. The 36 identified secreted (5) and surface (31) proteins included several proteins involved in cell wall synthesis, pheromone-regulated processes, and transport of solutes, as well as proteins with unknown function. These proteins stand out as interesting targets for further investigation of the interaction between <it>E. faecalis </it>and its environment.</p

Novel Biodegradable Polymeric Microparticles Facilitate Scarless Wound Healing by Promoting Re-epithelialization and Inhibiting Fibrosis

Despite decades of research, the goal of achieving scarless wound healing remains elusive. One of the approaches, treatment with polymeric microcarriers, was shown to promote tissue regeneration in various in vitro models of wound healing. The in vivo effects of such an approach are attributed to transferred cells with polymeric microparticles functioning merely as inert scaffolds. We aimed to establish a bioactive biopolymer carrier that would promote would healing and inhibit scar formation in the murine model of deep skin wounds. Here we characterize two candidate types of microparticles based on fibroin/gelatin or spidroin and show that both types increase re-epithelialization rate and inhibit scar formation during skin wound healing. Interestingly, the effects of these microparticles on inflammatory gene expression and cytokine production by macrophages, fibroblasts, and keratinocytes are distinct. Both types of microparticles, as well as their soluble derivatives, fibroin and spidroin, significantly reduced the expression of profibrotic factors Fgf2 and Ctgf in mouse embryonic fibroblasts. However, only fibroin/gelatin microparticles induced transient inflammatory gene expression and cytokine production leading to an influx of inflammatory Ly6C+ myeloid cells to the injection site. The ability of microparticle carriers of equal proregenerative potential to induce inflammatory response may allow their subsequent adaptation to treatment of wounds with different bioburden and fibrotic content

Перспектива применения биогенных квантовых точек наночастиц сульфидов серебра, кадмия и цинка для создания полимерных бионанокомпозитных материалов

The possibility of applying silver, cadmium and zinc sulfide nanoparticles (npAg2S, npCdS and npZnS) obtained using Shewanella oneidensis MR-1 and Bacillus subtilis 168 bacterial cultures for the creation of a new class of polymeric bionanocomposite materials was investigated. Biogenic nanoparticles obtained in aqueous solutions of the corresponding salts in the presence of various types of microorganisms are characterized by the presence of protein molecules on their surface. The molecules composition is determined by the bacterial culture. Proteins stabilize them and allow the nanoparticles to covalently join the active groups of polymeric carriers. Aminated chloromethylated polystyrene microspheres, as well as ion-exchange resins of various types, were used as polymeric matrices. Analysis of interaction with them can be used as a method for studying the properties of biogenic nanoparticles of metal sulfides for subsequent successful selection of a polymeric carrier. The immobilization of biogenic nanoparticles of metal sulfides onto the surface of aminated chloromethylated polystyrene microspheres was found to depend on the level of stability of aqueous nanoparticle suspensions and is determined by the negative charge of biogenic npAg2S, npCdS and npZnS, which suggests covalent binding and the electrostatic interaction of the components in the composition of the polymer bionanocomposite. A comparative analysis of the parameters of nanoparticles depending on the strain used in the biosynthesis was carried out. Analysis of the main physicochemical characteristics of npCdS and npZnS showed that the small size of nanoparticles (npCdS - 5 nm, npZnS - up to 2 nm) and the presence of luminescence peaks at wavelengths less than 400 nm classify them in the blue region of the fluorescence spectrum and identify them as quantum dots. Thus, the possibility of introducing fluorescent quantum dots of nanoparticles of metal sulfides of biogenic origin into various polymeric matrices has been demonstrated, which contributes to the expansion of the horizons for using a new class of nanoparticles to create polymeric bionanocomposites.Исследована возможность применения наночастиц сульфида серебра, кадмия и цинка (npAg2S, npCdS и npZnS), полученных с использованием бактериальных культур Shewanella oneidensis MR-1 и Bacillus subtilis 168, для создания нового класса полимерных бионанокомпозитных материалов. Биогенные наночастицы, полученные в водных растворах соответствующих солей в присутствии различных типов микроорганизмов, характеризуются наличием на их поверхности белковых молекул, состав которых определяется бактериальной культурой. Белки стабилизируют наночастицы и позволяют им ковалентно присоединяться к активным группам полимерных носителей. В качестве полимерных матриц использовали аминированные хлорм,етилирован-ные полистирольные микросферы, а также ионообменные смолы различных типов. Анализ взаилюдействия с ними люжет быть использован в качестве лъетода изучения свойств биогенных наночастиц сульфидов металлов для последующего успешного выбора полимерного носителя. Установлено, что иммобилизация биогенных наночастиц сульфидов металлов на поверхности аминированных хлорметилированных полистирольных микросфер зависит от уровня стабильности водных суспензий наночастиц и определяется отрицательным зарядом биогенных npAg2S, npCdS и npZnS, что предполагает ковалентное связывание и электростатическое взаимодействие компонентов в составе полимерного бионанокомпозита. Проведен сравнительный анализ параметров наночастиц в зависимости от штамма, используемого в биосинтезе. Анализ основных физико-химических характеристик npCdS и npZnS показал, что небольшие размеры наночастиц (npCdS - 5 нм, npZnS - до 2 нм) и наличие люминесцентных пиков на длинах волн менее 400 нм, что относит их к синей области спектра флуоресценции, позволяет классифицировать их как квантовые точки. Таким образом, была продемонстрирована возможность введения флуоресцентных квантовых точек наночастиц сульфидов металлов биогенного происхождения в различные полимерные матрицы, что способствует расширению горизонтов использования нового класса наночастиц для создания полимерных бионанокомпозитов