Safe and Efficient Tetrazole Synthesis in a Continuous Flow Microreactor

Safer flow: The synthesis of 5-substituted tetrazoles in flow (see scheme) is safe, efficient, scalable, requires no metal promoter, and uses a near-equimolar amount of NaN[subscript 3], yet nonetheless displays a broad substrate scope. The hazards associated with HN[subscript 3] are essentially eliminated, shock-sensitive metal azides such as Zn(N[subscript 3])[subscript 2] are avoided, and residual NaN[subscript 3] is quenched in-line with NaNO[subscript 2].Novartis Foundation (MIT Center for Continuous Manufacturing

Applications of isothermal titration calorimetry - the research and technical developments from 2011 to 2015

Isothermal titration calorimetry is a widely used biophysical technique for studying the formation or dissociation of molecular complexes. Over the last 5years, much work has been published on the interpretation of isothermal titration calorimetry (ITC) data for single binding and multiple binding sites. As over 80% of ITC papers are on macromolecules of biological origin, this interpretation is challenging. Some researchers have attempted to link the thermodynamics constants to events at the molecular level. This review highlights work carried out using binding sites characterized using x-ray crystallography techniques that allow speculation about individual bond formation and the displacement of individual water molecules during ligand binding and link these events to the thermodynamic constants for binding. The review also considers research conducted with synthetic binding partners where specific binding events like anion-π and π-π interactions were studied. The revival of assays that enable both thermodynamic and kinetic information to be collected from ITC data is highlighted. Lastly, published criticism of ITC research from a physical chemistry perspective is appraised and practical advice provided for researchers unfamiliar with thermodynamics and its interpretation

Company's "MADARA Cosmetics" ANTI AGE product line's promotion into Luxembourg market.

Bakalaura darba “Uzņēmuma “MADARA Cosmetics” ANTI AGE produktu līnijas virzīšana Luksemburgas tirgū” mērķis ir, pamatojoties uz produkta virzīšanas ārvalstu tirgū teorētiskajiem aspektiem, nozares analīzi, Eiropas un Luksemburgas kosmētikas tirgus novērtējumu, izvērtēt iespējas un izstrādāt prekšlikumus uzņēmuma “MADARA Cosmetics” ANTI AGE produktu līniju Luksemburgas virzīšanai tirgū. Bakalaura darba objekts ir Latvijā radīts dabīgās kosmētikas nozares uzņēmums A/S “MADARA Cosmetics”, kas nodarbojas ar dabīgās kosmētikas produktu ražošanu un izplatīšanu patērētājiem. Bakalaura darba struktūra ir sekojoša: ievads, 4 pamatdaļas, secinājumi un priekšlikumi. Bakalaura darba pirmajā daļā autore aplūko produkta virzīšanas ārvalstu tirgū teorētiskos aspektus. Otrajā daļā tiek apskatītas kosmētikas nozares Eiropā attīstības tendences. Trešajā daļā tiek raksturots un analizēts uzņēmums “MADARA Cosmetics”. Tālāk darba autore veic secinājumus un izvirza priekšlikumus uzņēmuma veiksmīgai ieejai Luksemburgas tirgū. Darbā izmantoti 18 attēli ,3 tabulas, 2 pielikumi. Izmantotās literatūras un avotu saraksts satur 83 vienības. Darba kopējais apjoms ir 69 lappuses. Atslēgvārdi: MADARA Cosmetics, Madara, eko kosmētika, Luksemburga, produkta virzība.The aim of the bachelor’s degree diploma paper “Company’s “MADARA Cosmetics” ANTI AGE product line’s promotion into Luxembourg market” is to do an industry analysis, the evaluation of the European and Luxembourg markets based on the theoretical aspects and to evaluate the possibilities of promoting company’s “MADARA Cosmetics” ANTI AGE product line into Luxembourg market. The object of the bachelor’s degree diploma paper is a Latvian eco cosmetics company “MADARA Cosmetics” specializing in the production and distribution of natural cosmetics products to consumers. The structure of the bachelor’s degree diploma paper is as follows: introduction, 3 main parts, conclusions and suggestions. In the first part of the bachelor’s degree diploma paper the author examines the theoretical aspects of product promotion into the foreign market. The second part examines trends in the cosmetics industry in Europe. The third part describes and analyses the company "MADARA Cosmetics". Further, the author of the paper makes conclusions and makes proposals for the company's successful entrance into the Luxembourg market. The paper includes 18 images, 3 tables, 2 attachments. The list of literature and sources used contains 83 units. The total amount of work is 69 pages. Key words: MADARA Cosmetics, MADARA, eco cosmetics, Luxembourg, product promotion

The promotion if child self-awarness development in plays with movemebts for 5 years old children

Kvalifikācijas darbs izstrādāts par tēmu “Piecgadīgu bērnu pašapziņas attīstība kustību rotaļās”. Pētījuma mērķis ir pētīt piecgadīgu bērnu pašapziņas attīstības iespējas kustību rotaļās. Tēma aktuāla, jo sabiedrībā ar vien vairāk tiek runāts par bērniem ar dažādām psihiskām problēmām, taču, kad tās jau konstatētas, lielākoties iespējams tikai cīnīties ar sekām. Autorei šķita interesanti izpētīt kā ar kustību rotaļu palīdzību attīstīt bērnu pašapziņu, kas ir kā rezultāts labākai psihiskajai un fiziskajai attīstībai. Pētījums izstrādāts 2 daļās. Pirmā- teorētiskā, otrā- praktiskā. Teorētiskajā daļā sniegts pašapziņas jēdziena skaidrojums, kā arī pašapziņu ietekmējošie faktori. Īpaša uzmanība pievērsta piecgadīgu bērnu pašapziņai, kā arī tās attīstības iespējām kustību rotaļās. Darbā apskatītas tādu autoru kā I. Kona, D. Dzinteres, I. Puškareva, E. Eriksona, K. Dēķēna, O. Svennes u.c. atziņas. Darba pētījumā aprakstīta pētījuma metodika, raksturota pētāmā grupa un sniegts pētījuma norises apraksts, kurš ietver sevī pedagoga anketēšanu (tikai viena, jo pētāmā grupa ir privātās pirmsskolas izglītības iestādes pilot grupa, kurā strādā 1 pedagogs un 1 pedagoga palīgs), pedagoģiskos novērojumus, kā arī pārrunas ar katru bērnu individuāli. Apkopojot iegūtos rezultātus kopumā bērniem ir labs pašapziņas līmenis, taču pāris bērniem tika novērota pazemināta pašapziņa. Pēc pētījuma tika vērots neliels progress bērnu aktivitātēs grupā, kas nozīmē, ka bērns sāka atvērties, iejusties grupā un viņa pašapziņa bija pozitīvi attīstījusies. Tāpat vērojams progress bērnu savstarpējās attiecībās un saskarsmē. Bērni, kuri bija noslēgti, vairāk iesaistās grupas nodarbībās un brīvajās rotaļās. Kā arī bērni, kuriem bija agresīvas uzvedības izpausmes, kļuva līdzjūtīgāki pret grupas biedriem Pēc pētījumā iegūtās informācijas iespējams secināt, ka kustību rotaļas pozitīvi ietekmē bērnu pašapziņu. Atslēgas vārdi: kustību rotaļas, pašapziņa, savstarpējās attiecības, saskarsme. Kvalifikācijas darba apjoms: 44 lpp, 24 attēli, 8 tabulas, 33 informācijas avoti, 3 pielikumi.Classification work is designed about topic called “The development of self-awareness of five-year-old children by movement activities”. The goal of this study is to learn more about the development of self-awareness of five-year-old children in movement activities. These topic is pressing nowadays because people in the modern society are talking more and more about children with various psychological issues, but once they have already been detected, the only way is to fight with consequences. Author found it interesting how the development of the child’s movement can improve their self-awareness, which is the result of better psychological and physical development. The study was made in two parts. The first part is thetheoretical part, the second part is a practical part. The theoretical part gives an explanation of the concept of the self-awareness, as well as factors influencing self- awareness of five-year-old children, as well as its development possibilities in the movements activities. The Author used literature of such writers as I. Kona, D. Dzinteres, I. Puškareva, E. Eriksona, K. Deķēna, O. Svennes and other quotes from different material. The study method described in the study paper describes the research group and provides a description of the study process, which includes the pedagogs questionaire (only one since the research group is a private pre-school educational institution pilot group with 1 pedagogue and 1 assistant of the pedagogue) pedagogical observations as well as discussions with each child individually. In summary, the results obtained from this study have a good increase of self-awareness for children, but still children had lower self-awareness. After the study, we saw some progress in childrens activities which means thatthe children begin to open up to the group and has developed self-awareness more to positive side. There is also progress in children’s relationships and contact inbetween each other. Children who were closed in to them selves more involved in group activities and other interactions. As well as children who had agressive manifestations of behavior became more sympathetic to the members of the group. Keywords: movement activities, self-confidence, mutual relationships, communication This study contains: 44 pages, 24 pictures, 8 tables, 33 sources of information, 3 attachments

Exploring Small Molecules as Receptors in Carbohydrate Recognition and as Ligands Targeting RNA Sequences Relevant to HIV-1

Thesis (Ph.D.)--University of Rochester. School of Medicine and Dentistry. Dept. of Biochemistry and Biophysics, 2009.The description of the ‘central dogma’, which has information flowing from DNA to RNA to proteins, is incomplete without the inclusion of small molecules. This is simply because small molecules play a variety of important functions in many biological processes. For example, they function as modulators of signaling pathways, they are important elements in memory and cognition, they are extremely useful as probes to unravel cellular processes, and most importantly they are used as drugs to treat most if not all diseases. Their potential is yet relatively unexplored and this thesis explores applications of small molecules in investigating and modulating two important biological processes: as “receptors” to aid in understanding carbohydrate recognition, and as ligands capable of manipulating the ribosomal frameshifting process in human immunodeficiency virus 1 (HIV-1). Carbohydrates in biological systems are often associated with specific recognition and signaling processes leading to important biological functions and diseases. The precise mechanisms of many carbohydrate mediated recognition processes are, however, not well understood. Synthetic organic compounds that can bind to different carbohydrates with high affinity and selectivity can serve as a potential source of information on the type of forces involved in the recognition of carbohydrates as well as probes to manipulate biological function. Carbohydrates, due to their complex structure, are challenging yet very attractive targets for the development of such synthetic organic “receptors”. A part of research presented in this thesis focuses on the development of synthetic receptors capable of binding different carbohydrates with high affinity and selectivity. We have designed, synthesized, and tested a novel class of small molecules that bind to carbohydrates, specifically monosaccharides, with high affinity and selectivity in apolar as well as polar protic solvents. In this process we have also discovered a novel single-step methodology for the synthesis of these molecules via a tri-directional Minisci reaction. A highlight of this research is the potential shown by one of our molecules to be developed into a “turn-on” fluorescent carbohydrate sensor. The second part of this thesis focuses on targeting a therapeutically important RNA for development of selective and high affinity small molecule ligands. RNA regulates several critical biological processes, and small molecules that can selectively bind to a particular RNA modulating its function can be of immense therapeutic potential. However, from previous experience it is known that selectivity in RNA binding small molecules is difficult to achieve, which makes RNA a very challenging target for small molecules. We have targeted a stem-loop RNA that serves as a stimulatory signal for programmed ribosomal frameshifting in HIV-1, a process used by the virus to synthesize its vital proteins. Targeting this process by small molecules can lead to novel compounds for the intervention of the deadly disease, AIDS. Research presented herein focuses on the synthesis and binding characterization of compounds binding to the HIV-1 frameshift-stimulating stem-loop RNA. Our compounds have shown very high selectivity along with micromolar affinities to the stem-loop structure and evaluation of the binding kinetics suggests that they are promising candidates for further biological investigation