Asymmetric Total Synthesis of GlaxoSmithKline’s Potent Phosphodiesterase PDE IVb Inhibitor

Phosphodiestarase of subtype PDE IVb inhibitors are considered as perspective drugs for the treatment of the central nervous system disorders (depression, Alzheimer’s disease, Parkinson’s disease). Pyrrolizidinone Glaxo-1, proposed by GlaxoSmithKline, is a highly potent PDE IVb inhibitor (IC50 = 63 nM), then conventional phosphodiesterase inhibitors Ro-20-1724, Rolipram and Cilomilast. However the activity of the Glaxo-1 was studied on a racemic sample, since the asymmetric approach to its synthesis has not been developed. Therefore the purpose of this research was the development of an efficient synthetic scheme enabling enantioselective excess to both (-)- and (+)-Glaxo-1, which can be than subjected to biological studies. \r The key stage in proposed asymmetric synthesis (-)- and (+)-Glaxo-1 is stereoselective [4+2]-cycloaddition of the nitroolefin to an optically activity vinyl ethers, derived from (-)- or (+)-trans-2-phenylcyclohexanols. The resulting chiral cyclic nitronates are transformed into a functionalized cyclic oxime ethers using tandem sylilation-nucleophilic substitution procedure. Reduction and decarboxylation of these products lead to optically pure Glaxo-1 and the regeneration of chiral 2-phenylcyclohexanols (91%). \r Thus both enantiomers (+) and (-)-Glaxo-1 were obtained selectively in average yield 12% from isovaniline and nitroethane. The study of biological profiles of each enantiomer of Glaxo-1 will be conducted in near future.

Mathematics in Music

Mathematics and music are two poles of human culture. Listening to music we get into the magic world of sounds. Solving problems we are immersed in strict space of numbers and we do not reflect that the world of sounds and space of numbers have been adjoining with each other for a long time. Interrelation of mathematics and music is one of the vital topics. It hasn’t been completely opened and investigated up to now. This is the point why it draws attention of a lot of scientists and mathematicians to itself. This is the point why it draws attention of a lot of scientists and mathematicians to itself. Having considered the value of these two sciences, it seems to us that they are completely non-comparable. In fact can there be a similarity between mathematics – the queen of all sciences, a symbol of wisdom and music – the most abstract kind of art? But if you peer deeply into it you can notice that the worlds of sounds and space of numbers have been adjoining with each other for a long time. In the work I will try to establish the connection between mathematics and music and to find their common elements, to analyze pieces of music with the help of laws and concepts of mathematics to find a secret of mastery of musicians using mathematics and also to investigate the connection of music with mathematics with the “research part”. They are my own calculations and researches which are an integral part of the work. The connection of mathematic and music is caused both historically and internally in spite of the fact that mathematics is the most abstract of sciences and music is the most abstract kind of art. V. Shafutinskiy, I. Matvienko, m. Fadeev, K. Miladze, Dominik the Joker – modern composers of the XXI century – have used the golden proportion only in 4% of their pieces of music and more often in romances or children’s songs. I have revealed this fact after investigating their pieces of music of different genres. However there is a question: why does modern music attracts all of us more but the classics is being forgotten? Investigating connection between mathematics and music I had come to the conclusion that the more deeply the piece of music gives in to the mathematical analysis, to research and submits to any mathematical laws, the more harmonious and fine its sounding is, the more it excites human soul. Besides I am convinced that many important, interesting and entertaining things have not been opened in this field. We can safely continue our research of these things. I think that I have managed to lift a veil over mathematics in music, to find something common for apparently incompatible science and art. In due time English mathematician D. Silvestre called music as mathematics of feelings, and mathematics – as music of intellect. He expressed hope that each of them should receive the end from the part of the other one. In the future he expected the occurrence of a person in which Beethoven and Gauss’ greatness would unite. Terms ‘science’ and ‘art’ practically didn’t differ during far times of antiquity. And though roads of mathematics and music have gone away since then music is penetrated with mathematics and mathematics is full of poetry and music!

Number system with non-natural base

In this work I make the analysis of the possibility of the existence of the number system with non-natural base & its investigation. The question examined in my work is totally opened:\r ‧ making the list of new characteristics, rules of the translation of the numbers, and also rules of the simple calculating operations, checked the operations of subtraction & division;\r ‧ checked the Euclidean algorithm, its characteristics by means of estimating the coefficients;\r ‧ found the practical appliance of new method in compiling & solving of the tasks.\r Investigation I’ve suggested stipulates for independence of new system & its appliance in type of tasks, that is beyond the course of school program & also beyond the whole system of school education.

The garnets of the schlich of the winter coast (the White Sea)

During an expedition to the White Sea Winter Coast, samples of schlich with numerous garnets were collected. The coast itself is primarily a set of high steeps of sandstones and mudstones with no garnets. On the beach, however, there are numerous pebbles of metamorphic rocks, and many of them contain garnets. They were brought there by the Quaternary glacier and the present day glacier activity. Their source could be the existing or fully eroded metamorphic rocks of the Kola Penninsila and Northern Karelia.\r Goal of the research: To discover the possible origin of the garnets.\r Tasks: 1) To analyze the structure and the chemical composition of the garnets. 2) To study the works on the garnets of the Kola Penninsila and Northern Karelia in order to compare the information to the results of the analysis.\r Methods: 1) Granulometric analysis; 2) Magnetic and electromagnetic separation; 3) Microscope study of the garnets; 4) X-ray diffraction analysis; 5) X-ray fluorescence analysis. \r RESULTS\r 1. The sample garnets could be divided into two types: the bright red and the pale pink.\r 2. Both types are almandines with spessartine components. The pale-pink one contains Arizona ruby components, and the bright red contains andradite ones. \r 3. Only a few samples from Khangaz Varaki, Malye Keivy, and Tersky Coast are similar to the garnets that we collected. It is possible that the glacier brought them from the Kola Penninsula, but it is also possible that the rocks, where the glacier brought our garnets from, have been totally eroded.

Montioring of Cryogenic Features along Roads in Megino-Kangalassky Region,Yakutia

One of the anthropogenic influences on the permafrost landscapes is deforestation and breach of the surface cover at the road constructions. On these areas a development of various cryogenic and postcryogenic processes and features (thermosubsidence, knobs (bilars, baydjarakhs), ravines, small lakes - djyodje) is being observed. Such features can be observed on the territory of Megino- Kangalassky Region, which is situated in the Central Yakutia, as well. During the period from 1998 to 2003 the author carried out monitoring studies of cryogenic features along three roads. Ten areas measuring twenty square metres were put in all. During 6 years of research about 1520 measurements of cryogenic formations parameters were made. Based on the results, it is concluded that elimination of the shadowing effect by trees and removal of the surface cover along the roads have caused thawing of shallow-lying ice wedges, as well as development of various cryogenic processes and features. In this paper, the author presents the basic technologies which are used in road construction in permafrost areas and, based on the research results, proposes a set of measures for rehabilitation of the roadside areas.

A method of searching for all the integer solutions of any equation of markov's type of paralolic ty

This work presents fundamental research in the field of algebra and the theory of number. The subject of the work is equations of Markov's type (the type of the equations introduced by me earlier which generalizes the classic equation of Markov (x2+y2+z2=3xyz)) of parabolic type with two unknown quantities and their genealogical trees. The following questions appeared when I was working on the equations of Markov's type and constructing genealogical trees to them: are there any other trees besides one for a certain equation; how to find all the genealogical trees for the equation of Markov's type; how to find all the integer solutions with the help of the genealogical trees. This work is devoted to the analysis of these questions. The aim of the work: to create the method of finding all the integer solutions of the equations of Markov's type of parabolic type. The tasks of the work: 1. Carrying out some experimental works to find all the genealogical trees for a concrete equation. 2. Formulating a hypothesis that the curve has a specific part. 3. Research the parabolic type in order to apply the hypothesis to it. 4. To formulate and prove the theorems about the necessary and sufficient conditions of the existence of the genealogical trees of the integer solutions of equations of Markov's type of parabolic type with two unknown quantities. As the result of the work all the tasks have been solved. I worked the method of finding all the integer solutions: : to find all the integer solutions by means finding all genealogical trees of the equations of Markov's type of parabolic type with two unknown quantities you need : 1. To investigate if there any integer solutions‧ a special part of the parabola (if it is a parabola)‧ a special part of the parallel lines (if it is a pair of the parallel lines) 2. To build a genealogical tree from every solution (if they exist). 3. All the integer solutions will be on the constructed trees. I also worked out a computer program which is based on the usage of this method.

Reduction fuel's amount when working the Internal-combustion engine

The aim of the work is inventing the way in which the power of the ICE is the same and consuming of the fuel decreases. The following methods of investigation were used: analysis of the experience of the improvement of ICE, modeling, the brainstorming, methods of Decition Theory of Invention’s Tasks (DTIT). In this work Ivan Semyonov based on a hypothesis that if the non-supporting combustion exhausts will be drawn with the vacuum from cylinder fuel for the same power it needed less. The practical meaning of this work is in the attempt of studying the question of improving the ICE for getting and making the more perfect ICE.

Universal computing sorting machine

The purpose of the study was to develop and create a semi-automatic multi-purpose sorting and counting machine of standard articles. Currently, there is a problem of equipping industrial enterprises as well as small trade companies and large retailers with computing sorting machines of standard products of a certain shape. We would like to fill this missing link up with a simple, compact and inexpensive device. Procedures The proposed research consisted of a consistent design of a virtual model of the device and its electronic-mechanical implementation. The virtual model is simulated by a computer program "SolidWorks" object, which graphically shows the operation of the future device. In the development of the computing sorting device standard electronic devices and their associated software have been used. The created simplified real model demonstrates the basic principles and characteristics of the proposed device. Data As an example for the implementation of the concept device a computing device for sorting coins, in circulation in Russia has been created. As a basic principle of sorting objects by their geometric and weight characteristics were used. It is important that the device is focused on the correct form of the objects of sorting (balls, rings, coins, regular polyhedrons, screws, nuts, etc). To confirm the effectiveness of the computing device of this type of sorting, a series of tests of counting of objects manually have been carried out . The effectiveness of the device is determined by comparing the time characteristics of manual and automatic sorting. Findings and conclusions As a result of research and work performed, we have concluded that: 1) The proposed device can be used in various industries. (for example, while sorting ball bearings.) 2) Such a computing sorting device may find it's application in various commercial enterprises: to assist cashiers in retail ATMs. 3) Can be used in payment terminals. 4) 4) After a certain modernization of the device it can be used for money encashment.

Technology of web site advancement

Internet by its content represents a fountain of information, while from the point of view of its arrangement it is a huge dump. There are an enormous number of web sites. Multiple web sites are commercially directed, i.e. are aimed at profit earning. As profit depends on the number of visits to web site, no visitors means no profit. So, to obtain more orders, web site producers should first of all ensure good inflow of visitors (web site attendance). Every year this task becomes more and more critical for commercial web site owners (and not only for them), as the number of similar content web sites increases steadily along with competition intensifying correspondingly. The process of establishing conditions to attract more visitors is called web site advancement. The present paper discusses various ways of how to increase the number of web site visitors, it also describes the particular process of "Theater to Children" (www.teatrbaby.ru) web site advancement. Based on the paper outcomes a CD multimedia manual "Technology of web site advancement" has been developed that will help web site producers to achieve good attendance for their network resources. As the purpose of web site advancement is visitor number increase then the main criterion of web site advancement efficiency should be the number of visitors for a certain time period, e.g. for 24 hours, a week or a month. Taking into consideration that about 80% of Internet users retrieve information through search systems, the major growth of visitors will occur owing to the enhancement of web site visibility in search systems.

Problems of Safe Storage, Collecting and Recycling of Luminescent Lamps

Our research is connected with the problem of the mercurious wasre products (MWP) recycling, luminescent lamps take a great part among them. The problem of recycling MWP is topical not only in Yakutsk, but also in other cities of Russia because of its toxic influence on the human’s body. Mercury is the top among eight the most dangerous metals. I have analyzed the conditions of recycling of luminescent lamps in Yakutsk schools. I have got data on the problem. There is a great amount of the fused luminescent lamps is stored in the territory of schools, it produces danger for the pupils’ health. On the research work I have proposed some ways of solution of the problem.