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

C-Jun N-terminal kinase (JNK) isoforms play differing roles in otitis media

BACKGROUND: Innate immunity and tissue proliferation play important roles in otitis media (OM), the most common disease of childhood. CJUN terminal kinase (JNK) is potentially involved in both processes. RESULTS: Genes involved in both innate immune and growth factor activation of JNK are upregulated during OM, while expression of both positive and negative JNK regulatory genes is altered. When compared to wildtypes (WTs), C57BL/6 mice deficient in JNK1 exhibit enhanced mucosal thickening, with delayed recovery, enhanced neutrophil recruitment early in OM, and delayed bacterial clearance. In contrast, JNK2(−/−) mice exhibit delayed mucosal hyperplasia that eventually exceeds that of WTs and is slow to recover, delayed recruitment of neutrophils, and failure of bacterial clearance. CONCLUSIONS: The results suggest that JNK1 and JNK2 play primarily opposing roles in mucosal hyperplasia and neutrophil recruitment early in OM. However, both isoforms are required for the normal resolution of middle ear infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-014-0046-z) contains supplementary material, which is available to authorized users

MMP-2 siRNA Inhibits Radiation-Enhanced Invasiveness in Glioma Cells

Our previous work and that of others strongly suggests a relationship between the infiltrative phenotype of gliomas and the expression of MMP-2. Radiation therapy, which represents one of the mainstays of glioma treatment, is known to increase cell invasion by inducing MMP-2. Thus, inhibition of MMP-2 provides a potential means for improving the efficacy of radiotherapy for malignant glioma.We have tested the ability of a plasmid vector-mediated MMP-2 siRNA (p-MMP-2) to modulate ionizing radiation-induced invasive phenotype in the human glioma cell lines U251 and U87. Cells that were transfected with p-MMP-2 with and without radiation showed a marked reduction of MMP-2 compared to controls and pSV-transfected cells. A significant reduction of proliferation, migration, invasion and angiogenesis of cells transfected with p-MMP-2 and in combination with radiation was observed compared to controls. Western blot analysis revealed that radiation-enhanced levels of VEGF, VEGFR-2, pVEGFR-2, p-FAK, and p-p38 were inhibited with p-MMP-2-transfected cells. TUNEL staining showed that radiation did not induce apoptosis in U87 and U251 cells while a significant increase in TUNEL-positive cells was observed when irradiated cells were simultaneously transfected with p-MMP-2 as compared to controls. Intracranial tumor growth was predominantly inhibited in the animals treated with p-MMP-2 alone or in combination with radiation compared to controls.MMP-2 inhibition, mediated by p-MMP-2 and in combination with radiation, significantly reduced tumor cell migration, invasion, angiogenesis and tumor growth by modulating several important downstream signaling molecules and directing cells towards apoptosis. Taken together, our results demonstrate the efficacy of p-MMP-2 in inhibiting radiation-enhanced tumor invasion and progression and suggest that it may act as a potent adjuvant for radiotherapy in glioma patients

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Binary systems and their nuclear explosions

Peer ReviewedPreprin