Organic Synthesis without Stoichiometric Reagents: A Guiding Principle for Reaction Development

A common theme of our research program is the development of new organic transformations that operate under catalytic conditions or as ligation reactions that do not require the addition of any reagents or other additives. Our catalysis program features the transient generation of reactive species from alpha-functionalized aldehydes via intramolecular redox reactions using N-heterocyclic carbenes as multifunctional catalysts. This approach makes possible the catalytic generation of enolates, homoenolates, and activated carboxylates and their application to diastereo- and enantioselective transformation. Intermolecular redox couplings are key to a general, highly chemoselective amide-forming ligation reaction and its use for oligopeptide synthesis. The concepts behind these transformation and examples of their use as well as current and future directions of our research program are presented

Laboratory literature boards in the digital age

ISSN:2504 - 185

Correspondence of the Ukrainian Legislation in the Labor Sphere to European Standards

У статті проаналізовано європейські стандарти у сфері праці та досліджено їх вплив на українське законодавство, запропоновано впровадження нових положень до нього. Наведено дефініцію терміну «європейські стандарти в сфері охорони праці» в широкому розумінні як принципів та норм, які закріплюють єдині та загальноприйняті правові, соціально-економічні, організаційно-технічні, санітарно-гігієнічні і лікувально-профілактичні заходи та засоби, спрямовані на збереження життя, здоров’я і працездатності людини під час трудової діяльності, в якій би державі вона не жила. Зазначається позитивні зрушення українського законодавства у результаті адаптації його до європейських стандартів, на основі чого громадяни України отримають охорону і захист своїх прав у даній сфері не тільки на території своєї держави, а й за межами її (зокрема, в Європейському Союзі). Визначено існуючі європейські стандарти у сфері праці. Виокремлено перші прийняті Європейською конвенцією 1950 року стандарти у вищезазначеній сфері, які поклали основу розвитку прав у сфері праці, такі як: заборона рабства та примусової праці, а також свобода зібрань і об’єднань. Завдяки проведеному аналізу Європейської соціальної хартії (переглянутої) досліджено стандарти, до яких поступово адаптується українське законодавство, розвиваючи нове трудове право, тим самим відводячи морально застарілі положення на задній план. Виокремлено норми українського законодавства, що не відповідають вимогам європейського (зокрема, положення щодо права працівників на захист їхніх прав у випадку банкрутства їхнього роботодавця). Обґрунтовано вплив норм європейського права на вітчизняне завдяки Річному звіту про діяльність Європейського комітету з соціальних прав 2009-2015 р.р. шляхом зіставлення європейських вимог до України для прийняття до Європейського Союзу та українських нормативно-правових актів у сфері праці.In the article we analyzed European standards in the labor sphere and studied their influence on the Ukrainian Law, suggested the introduction of new regulations to it. The definition of the term “European standards in the labor protection sphere” is given; in the wide sense these are principles and standards that consolidate unique and general legal, social and economic, organizational and technical, hygiene and treatment-and prophylactic measures and instruments that are aimed at saving life, health and person’s employability, no matter where he/she lives. Positive changes of the Ukrainian Law are mentioned as a result of its adaptation to the European standards, on this basis the citizens of Ukraine obtain the protection and security of their rights in this sphere not only on the territory of Ukraine, but also outside the country (in particular in the European Union). The current European standards in the labor sphere are determined. European Convention (1950) distinguished the first accepted standards in the above-mentioned field, that were a basis for rights development in the labor sphere such as the prohibition of the slavery and the forced labor, the freedom of meetings and associations. Due to the analysis of the European Social Charter (revised) the standards were studied and Ukrainian Law is adjusted to them, it develops new labor law thereby the outdated standards are overshadowed. Some standards of Ukrainian Law are distinguished that don’t meet European requirements (in particular, the regulations on worker rights to protect their rights in case of firm bankruptcy). The influence of standards of European Law on the Law of our country is explained due to Annual Report on the activities of the European Committee of social rights 2009-2015 by means of comparison of European requirements to Ukraine to admit it to the European Union and Ukrainian statuary legal act in the labor sphere

Monolayer and bilayer pentacene on Cu(111)

The morphology and electronic structure of pentacene (Pn) deposited on Cu(111) was studied using scanning tunneling microscopy (STM) and spectroscopy (STS). Deposition of a multilayer followed by annealing to reduce coverage to a monolayer results in the formation of either of two unique phases: a 2D herringbone structure previously unobserved for any linear acene, or a 'random- tiling' structure. Coverage greater than a monolayer promotes the formation of a bilayer phase similar to that observed for Pn/Ag(111). STS shows that the electronic structure of the first layer is strongly modified due to its proximity to the substrate while the second layer exhibits nearly bulk-like electronic structure

Discovery and Validation of a New Class of Small Molecule Toll-Like Receptor 4 (TLR4) Inhibitors

Many inflammatory diseases may be linked to pathologically elevated signaling via the receptor for lipopolysaccharide (LPS), toll-like receptor 4 (TLR4). There has thus been great interest in the discovery of TLR4 inhibitors as potential anti-inflammatory agents. Recently, the structure of TLR4 bound to the inhibitor E5564 was solved, raising the possibility that novel TLR4 inhibitors that target the E5564-binding domain could be designed. We utilized a similarity search algorithm in conjunction with a limited screening approach of small molecule libraries to identify compounds that bind to the E5564 site and inhibit TLR4. Our lead compound, C34, is a 2-acetamidopyranoside (MW 389) with the formula C17H27NO9, which inhibited TLR4 in enterocytes and macrophages in vitro, and reduced systemic inflammation in mouse models of endotoxemia and necrotizing enterocolitis. Molecular docking of C34 to the hydrophobic internal pocket of the TLR4 co-receptor MD-2 demonstrated a tight fit, embedding the pyran ring deep inside the pocket. Strikingly, C34 inhibited LPS signaling ex-vivo in human ileum that was resected from infants with necrotizing enterocolitis. These findings identify C34 and the β-anomeric cyclohexyl analog C35 as novel leads for small molecule TLR4 inhibitors that have potential therapeutic benefit for TLR4-mediated inflammatory diseases. © 2013 Neal et al

Analyzing high resolution topography for advancing the understanding of mass and energy transfer through landscapes: A review

International audienceThe study of mass and energy transfer across landscapes has recently evolved to comprehensive considerations acknowledging the role of biota and humans as geomorphic agents, as well as the importance of small-scale landscape features. A contributing and supporting factor to this evolution is the emergence over the last two decades of technologies able to acquire high resolution topography (HRT) (meter and sub-meter resolution) data. Landscape features can now be captured at an appropriately fine spatial resolution at which surface processes operate; this has revolutionized the way we study Earth-surface processes. The wealth of information contained in HRT also presents considerable challenges. For example, selection of the most appropriate type of HRT data for a given application is not trivial. No definitive approach exists for identifying and filtering erroneous or unwanted data, yet inappropriate filtering can create artifacts or eliminate/distort critical features. Estimates of errors and uncertainty are often poorly defined and typically fail to represent the spatial heterogeneity of the dataset, which may introduce bias or error for many analyses. For ease of use, gridded products are typically preferred rather than the more information-rich point cloud representations. Thus many users take advantage of only a fraction of the available data, which has furthermore been subjected to a series of operations often not known or investigated by the user. Lastly, standard HRT analysis work-flows are yet to be established for many popular HRT operations, which has contributed to the limited use of point cloud data.In this review, we identify key research questions relevant to the Earth-surface processes community within the theme of mass and energy transfer across landscapes and offer guidance on how to identify the most appropriate topographic data type for the analysis of interest. We describe the operations commonly performed from raw data to raster products and we identify key considerations and suggest appropriate work-flows for each, pointing to useful resources and available tools. Future research directions should stimulate further development of tools that take advantage of the wealth of information contained in the HRT data and address the present and upcoming research needs such as the ability to filter out unwanted data, compute spatially variable estimates of uncertainty and perform multi-scale analyses. While we focus primarily on HRT applications for mass and energy transfer, we envision this review to be relevant beyond the Earth-surface processes community for a much broader range of applications involving the analysis of HRT

Domestication reshaped the genetic basis of inbreeding depression in a maize landrace compared to its wild relative, teosinte

Inbreeding depression is the reduction in fitness and vigor resulting from mating of close relatives observed in many plant and animal species. The extent to which the genetic load of mutations contributing to inbreeding depression is due to large-effect mutations versus variants with very small individual effects is unknown and may be affected by population history. We compared the effects of outcrossing and self-fertilization on 18 traits in a landrace population of maize, which underwent a population bottleneck during domestication, and a neighboring population of its wild relative teosinte. Inbreeding depression was greater in maize than teosinte for 15 of 18 traits, congruent with the greater segregating genetic load in the maize population that we predicted from sequence data. Parental breeding values were highly consistent between outcross and selfed offspring, indicating that additive effects determine most of the genetic value even in the presence of strong inbreeding depression. We developed a novel linkage scan to identify quantitative trait loci (QTL) representing large-effect rare variants carried by only a single parent, which were more important in teosinte than maize. Teosinte also carried more putative juvenile-acting lethal variants identified by segregation distortion. These results suggest a mixture of mostly polygenic, smalleffect partially recessive effects in linkage disequilibrium underlying inbreeding depression, with an additional contribution from rare larger-effect variants that was more important in teosinte but depleted in maize following the domestication bottleneck. Purging associated with the maize domestication bottleneck may have selected against some large effect variants, but polygenic load is harder to purge and overall segregating mutational burden increased in maize compared to teosinte

A Spitzer Survey for Dust in Type IIn Supernovae

Recent observations suggest that Type IIn supernovae (SNe IIn) may exhibit late-time (>100 days) infrared (IR) emission from warm dust more than other types of core-collapse SNe. Mid-IR observations, which span the peak of the thermal spectral energy distribution, provide useful constraints on the properties of the dust and, ultimately, the circumstellar environment, explosion mechanism, and progenitor system. Due to the low SN IIn rate (<10% of all core-collapse SNe), few IR observations exist for this subclass. The handful of isolated studies, however, show late-time IR emission from warm dust that, in some cases, extends for five or six years post-discovery. While previous Spitzer/IRAC surveys have searched for dust in SNe, none have targeted the Type IIn subclass. This article presents results from a warm Spitzer/IRAC survey of the positions of all 68 known SNe IIn within a distance of 250 Mpc between 1999 and 2008 that have remained unobserved by Spitzer more than 100 days post-discovery. The detection of late-time emission from ten targets (~15%) nearly doubles the database of existing mid-IR observations of SNe IIn. Although optical spectra show evidence for new dust formation in some cases, the data show that in most cases the likely origin of the mid-IR emission is pre-existing dust, which is continuously heated by optical emission generated by ongoing circumstellar interaction between the forward shock and circumstellar medium. Furthermore, an emerging trend suggests that these SNe decline at ~1000--2000 days post-discovery once the forward shock overruns the dust shell. The mass-loss rates associated with these dust shells are consistent with luminous blue variable (LBV) progenitors.Comment: Accepted for publication to ApJ, 17 pages, 10 figures, 10 table