Optimized Synthesis, Structural Investigations, Ligand Tuning and Synthetic Evaluation of Silyloxy-Based Alkyne Metathesis Catalysts

Nitride- and alkylidyne complexes of molybdenum endowed with triarylsilanolate ligands are excellent (pre)catalysts for alkyne-metathesis reactions of all sorts, since they combine high activity with an outstanding tolerance toward polar and/or sensitive functional groups. Structural and reactivity data suggest that this promising application profile results from a favorable match between the characteristics of the high-valent molybdenum center and the electronic and steric features of the chosen Ar3SiO groups. This interplay ensures a well-balanced level of Lewis acidity at the central atom, which is critical for high activity. Moreover, the bulky silanolates, while disfavoring bimolecular decomposition of the operative alkylidyne unit, do not obstruct substrate binding. In addition, Ar3SiO groups have the advantage that they are more stable within the coordination sphere of a high-valent molybdenum center than tert-alkoxides, which commonly served as ancillary ligands in previous generations of alkyne metathesis catalysts. From a practical point of view it is important to note that complexes of the general type [(Ar3SiO)3MoΞX] (X = N, CR; R = aryl, alkyl, Ar = aryl) can be rendered air-stable with the aid of 1,10-phenanthroline, 2,2′-bipyridine or derivatives thereof. Although the resulting adducts are themselves catalytically inert, treatment with Lewis acidic additives such as ZnCl2 or MnCl2 removes the stabilizing N-donor ligand and gently releases the catalytically active template into the solution. This procedure gives excellent results in alkyne metathesis starting from air-stable and hence user-friendly precursor complexes. The thermal and hydrolytic stability of representative molybdenum alkylidyne and -nitride complexes of this series was investigated and the structure of several decomposition products elucidated

Correlation functions in conformal Toda field theory I

Two-dimensional sl(n) quantum Toda field theory on a sphere is considered. This theory provides an important example of conformal field theory with higher spin symmetry. We derive the three-point correlation functions of the exponential fields if one of the three fields has a special form. In this case it is possible to write down and solve explicitly the differential equation for the four-point correlation function if the fourth field is completely degenerate. We give also expressions for the three-point correlation functions in the cases, when they can be expressed in terms of known functions. The semiclassical and minisuperspace approaches in the conformal Toda field theory are studied and the results coming from these approaches are compared with the proposed analytical expression for the three-point correlation function. We show, that in the framework of semiclassical and minisuperspace approaches general three-point correlation function can be reduced to the finite-dimensional integral.Comment: 54 pages, JHEP styl

The Crowd in Requirements Engineering: The Landscape and Challenges

Crowd-based requirements engineering (CrowdRE) could significantly change RE. Performing RE activities such as elicitation with the crowd of stakeholders turns RE into a participatory effort, leads to more accurate requirements, and ultimately boosts software quality. Although any stakeholder in the crowd can contribute, CrowdRE emphasizes one stakeholder group whose role is often trivialized: users. CrowdRE empowers the management of requirements, such as their prioritization and segmentation, in a dynamic, evolved style through collecting and harnessing a continuous flow of user feedback and monitoring data on the usage context. To analyze the large amount of data obtained from the crowd, automated approaches are key. This article presents current research topics in CrowdRE; discusses the benefits, challenges, and lessons learned from projects and experiments; and assesses how to apply the methods and tools in industrial contexts. This article is part of a special issue on Crowdsourcing for Software Engineering

Interaction of eukaryotic translation initiation factor 4G with the nuclear cap-binding complex provides a link between nuclear and cytoplasmic functions of the m7 guanosine cap

In eukaryotes the majority of mRNAs have an m7G cap that is added cotranscriptionally and that plays an important role in many aspects of mRNA metabolism. The nuclear cap-binding complex (CBC; consisting of CBP20 and CBP80) mediates the stimulatory functions of the cap in pre-mRNA splicing, 3' end formation, and U snRNA export. As little is known about how nuclear CBC mediates the effects of the cap in higher eukaryotes, we have characterized proteins that interact with CBC in HeLa cell nuclear extracts as potential mediators of its function. Using cross-linking and coimmunoprecipitation, we show that eukaryotic translation initiation factor 4G (eIF4G), in addition to its function in the cytoplasm, is a nuclear CBC-interacting protein. We demonstrate that eIF4G interacts with CBC in vitro and that, in addition to its cytoplasmic localization, there is a significant nuclear pool of eIF4G in mammalian cells in vivo. Immunoprecipitation experiments suggest that, in contrast to the cytoplasmic pool, much of the nuclear eIF4G is not associated with eIF4E (translation cap binding protein of eIF4F) but is associated with CBC. While eIF4G stably associates with spliceosomes in vitro and shows close association with spliceosomal snRNPs and splicing factors in vivo, depletion studies show that it does not participate directly in the splicing reaction. Taken together the data indicate that nuclear eIF4G may be recruited to pre-mRNAs via its interaction with CBC and accompanies the mRNA to the cytoplasm, facilitating the switching of CBC for eIF4F. This may provide a mechanism to couple nuclear and cytoplasmic functions of the mRNA cap structure

Increasing the Structural Span of Alkyne Metathesis

A new generation of alkyne metathesis catalysts, which are distinguished by high activity and an exquisite functional group tolerance, allows the scope of this transformation to be extended beyond its traditional range. They accept substrates that were previously found problematic or unreactive, such as propargyl alcohol derivatives, electron-deficient and electron-rich acetylenes of various types, and even terminal alkynes. Moreover, post-metathetic transformations other than semi-reduction increase the structural portfolio, as witnessed by the synthesis of a annulated phenol derivative via ring-closing alkyne metathesis (RCAM) followed by a transannular gold-catalyzed Conia-ene reaction. Further examples encompass a post-metathetic transannular ketone–alkyne cyclization with formation of a trisubstituted furan, a ruthenium-catalyzed redox isomerization, and a Meyer–Schuster rearrangement/oxa-Michael cascade. These reaction modes fueled model studies toward salicylate macrolides, furanocembranolides, and the cytotoxic macrolides acutiphycin and enigmazole A; moreover, they served as the key design elements of concise total syntheses of dehydrocurvularin (27) and the antibiotic agent A26771B (36)

Health-related quality of life of Canadian children and youth prenatally exposed to alcohol

BACKGROUND: In Canada, the incidence of Fetal Alcohol Spectrum Disorder (FASD) has been estimated to be 1 in 100 live births. Caused by prenatal exposure to alcohol, FASD is the leading cause of neuro-developmental disabilities among Canadian children, and youth. Objective: To measure the health-related quality of life (HRQL) of Canadian children and youth diagnosed with FASD. METHODS: A prospective cross-sectional study design was used. One-hundred and twenty-six (126) children and youth diagnosed with FASD, aged 8 to 21 years, living in urban and rural communities throughout Canada participated in the study. Participants completed the Health Utilities Index Mark 3 (HUI3). HUI3 measures eight health attributes: vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain. Utilities were used to measure a single cardinal value between 0 and 1.0 (0 = all-worst health state; 1 = perfect health) to reflect the global HRQL for that child. Mean HRQL scores and range of scores of children and youth with FASD were calculated. A one-sample t-test was used to compare mean HRQL scores of children and youth with FASD to those from the Canadian population. RESULTS: Mean HRQL score of children and youth with FASD was 0.47 (95% CI: 0.42 to 0.52) as compared to a mean score of 0.93 (95% CI: 0.92 to 0.94) in those from the general Canadian population (p < 0.001). Children demonstrated moderate to severe dysfunction on the single-attributes of cognition and emotion. CONCLUSION: Children and youth with FASD have significantly lower HRQL than children and youth from the general Canadian population. This finding has significant implications for practice, policy development, and research

Survival probability of mutually killing Brownian motions and the O'Connell process

Recently O'Connell introduced an interacting diffusive particle system in order to study a directed polymer model in 1+1 dimensions. The infinitesimal generator of the process is a harmonic transform of the quantum Toda-lattice Hamiltonian by the Whittaker function. As a physical interpretation of this construction, we show that the O'Connell process without drift is realized as a system of mutually killing Brownian motions conditioned that all particles survive forever. When the characteristic length of interaction killing other particles goes to zero, the process is reduced to the noncolliding Brownian motion (the Dyson model).Comment: v2: AMS-LaTeX, 20 pages, 2 figures, minor corrections made for publication in J. Stat. Phy

Variation of health-related quality of life assessed by caregivers and patients affected by severe childhood infections.

BACKGROUND: The agreement between self-reported and proxy measures of health status in ill children is not well established. This study aimed to quantify the variation in health-related quality of life (HRQOL) derived from young patients and their carers using different instruments. METHODS: A hospital-based cross-sectional survey was conducted between August 2010 and March 2011. Children with meningitis, bacteremia, pneumonia, acute otitis media, hearing loss, chronic lung disease, epilepsy, mild mental retardation, severe mental retardation, and mental retardation combined with epilepsy, aged between five to 14 years in seven tertiary hospitals were selected for participation in this study. The Health Utilities Index Mark 2 (HUI2), and Mark 3 (HUI3), and the EuroQoL Descriptive System (EQ-5D) and Visual Analogue Scale (EQ-VAS) were applied to both paediatric patients (self-assessment) and caregivers (proxy-assessment). RESULTS: The EQ-5D scores were lowest for acute conditions such as meningitis, bacteremia, and pneumonia, whereas the HUI3 scores were lowest for most chronic conditions such as hearing loss and severe mental retardation. Comparing patient and proxy scores (n = 74), the EQ-5D exhibited high correlation (r = 0.77) while in the HUI2 and HUI3 patient and caregiver scores were moderately correlated (r = 0.58 and 0.67 respectively). The mean difference between self and proxy-assessment using the HUI2, HUI3, EQ-5D and EQ-VAS scores were 0.03, 0.05, -0.03 and -0.02, respectively. In hearing-impaired and chronic lung patients the self-rated HRQOL differed significantly from their caregivers. CONCLUSIONS: The use of caregivers as proxies for measuring HRQOL in young patients affected by pneumococcal infection and its sequelae should be employed with caution. Given the high correlation between instruments, each of the HRQOL instruments appears acceptable apart from the EQ-VAS which exhibited low correlation with the others