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

On differential equation on four-point correlation function in the Conformal Toda Field Theory

The properties of completely degenerate fields in the Conformal Toda Field Theory are studied. It is shown that a generic four-point correlation function that contains only one such field does not satisfy ordinary differential equation in contrast to the Liouville Field Theory. Some additional assumptions for other fields are required. Under these assumptions we write such a differential equation and solve it explicitly. We use the fusion properties of the operator algebra to derive a special set of three-point correlation function. The result agrees with the semiclassical calculations.Comment: 5 page

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

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

Nucleocytoplasmic transport: a thermodynamic mechanism

The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.Comment: in press at HFSP Journal, vol 3 16 text pages, 1 table, 4 figures, plus Supplementary Material include

Metabolic activity in dormant conidia ofAspergillus nigerand developmental changes during conidial outgrowth

The early stages of development of Aspergillus niger conidia during outgrowth were explored by combining genome-wide gene expression analysis (RNAseq), proteomics, Warburg manometry and uptake studies. Resting conidia suspended in water were demonstrated for the first time to be metabolically active as low levels of oxygen uptake and the generation of carbon dioxide were detected, suggesting that low-level respiratory metabolism occurs in conidia for maintenance. Upon triggering of spore germination, generation of CO2 increased dramatically. For a short period, which coincided with mobilisation of the intracellular polyol, trehalose, there was no increase in uptake of O2 indicating that trehalose was metabolised by fermentation. Data from genome-wide mRNA profiling showed the presence of transcripts associated with fermentative and respiratory metabolism in resting conidia. Following triggering of conidial outgrowth, there was a clear switch to respiration after 25 min, confirmed by cyanide inhibition. No effect of SHAM, salicylhydroxamic acid, on respiration suggests electron flow via cytochrome c oxidase. Glucose entry into spores was not detectable before 1 h after triggering germination. The impact of sorbic acid on germination was examined and we showed that it inhibits glucose uptake. O2 uptake was also inhibited, delaying the onset of respiration and extending the period of fermentation. In conclusion, we show that conidia suspended in water are not completely dormant and that conidial outgrowth involves fermentative metabolism that precedes respiration

Generalized Structural Description of Calcium–Sodium Aluminosilicate Hydrate Gels: The Cross-Linked Substituted Tobermorite Model

Structural models for the primary strength and durability-giving reaction product in modern cements, a calcium (alumino)silicate hydrate gel, have previously been based solely on non-cross-linked tobermorite structures. However, recent experimental studies of laboratory-synthesized and alkali-activated slag (AAS) binders have indicated that the calcium–sodium aluminosilicate hydrate [C-(N)-A-S-H] gel formed in these systems can be significantly cross-linked. Here, we propose a model that describes the C-(N)-A-S-H gel as a mixture of cross-linked and non-cross-linked tobermorite-based structures (the cross-linked substituted tobermorite model, CSTM), which can more appropriately describe the spectroscopic and density information available for this material. Analysis of the phase assemblage and Al coordination environments of AAS binders shows that it is not possible to fully account for the chemistry of AAS by use of the assumption that all of the tetrahedral Al is present in a tobermorite-type C-(N)-A-S-H gel, due to the structural constraints of the gel. Application of the CSTM can for the first time reconcile this information, indicating the presence of an additional activation product that contains highly connected four-coordinated silicate and aluminate species. The CSTM therefore provides a more advanced description of the chemistry and structure of calcium–sodium aluminosilicate gel structures than that previously established in the literature