A solution NMR approach to determine the chemical structures of carbohydrates using the hydroxyl groups as starting points

An efficient NMR approach is described for determining the chemical structures of the monosaccharide glucose and four disaccharides, namely, nigerose, gentiobiose, leucrose and isomaltulose. This approach uses the 1H resonances of the −OH groups, which are observable in the NMR spectrum of a supercooled aqueous solution, as the starting point for further analysis. The 2D-NMR technique, HSQC-TOCSY, is then applied to fully define the covalent structure (i.e., the topological relationship between C–C, C–H, and O–H bonds) that must be established for a novel carbohydrate before proceeding to further conformational studies. This process also leads to complete assignment of all 1H and 13C resonances. The approach is exemplified by analyzing the monosaccharide glucose, which is treated as if it were an “unknown”, and also by fully assigning all the NMR resonances for the four disaccharides that contain glucose. It is proposed that this technique should be equally applicable to the determination of chemical structures for larger carbohydrates of unknown composition, including those that are only available in limited quantities from biological studies. The advantages of commencing the structure elucidation of a carbohydrate at the −OH groups are discussed with reference to the now well-established 2D-/3D-NMR strategy for investigation of peptides/proteins, which employs the −NH resonances as the starting point

Imaging the Haro 6-10 Infrared Companion

We present an infrared imaging study of the low-mass pre-main-sequence binary system Haro 6-10. This system is one of a handful in which the optically visible primary has the characteristics of a normal T Tauri star, while the secondary is a so-called "infrared companion" (IRC), a strongly extincted object that emits most of its luminosity in the infrared. A speckle holographic technique was used to produce nearly diffraction-limited images on three nights over a 1 yr period starting in late 1997. The images show that the IRC is obscured and surrounded by a compact, irregular, and variable nebula. This structure is in striking contrast to the well-ordered edge-on disk associated with HK Tauri B, the extincted companion to another T Tauri star of similar age. A new, resolved intensity peak was found 0".4 southwest of the IRC. We suggest that it may represent light scattered by a clump of dusty material illuminated by starlight escaping along an outflow-carved cavity in the IRC envelope. The primary star became fainter and the companion became more extended during the observing period

Adaptively-refined overlapping grids for the numerical solution of systems of hyperbolic conservation laws

Adaptive mesh refinement (AMR) in conjunction with higher-order upwind finite-difference methods have been used effectively on a variety of problems in two and three dimensions. In this paper we introduce an approach for resolving problems that involve complex geometries in which resolution of boundary geometry is important. The complex geometry is represented by using the method of overlapping grids, while local resolution is obtained by refining each component grid with the AMR algorithm, appropriately generalized for this situation. The CMPGRD algorithm introduced by Chesshire and Henshaw is used to automatically generate the overlapping grid structure for the underlying mesh

Filaggrin-stratified transcriptomic analysis of pediatric skin identifies mechanistic pathways in patients with atopic dermatitis

BackgroundAtopic dermatitis (AD; eczema) is characterized by a widespread abnormality in cutaneous barrier function and propensity to inflammation. Filaggrin is a multifunctional protein and plays a key role in skin barrier formation. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a highly significant risk factor for atopic disease, but the molecular mechanisms leading to dermatitis remain unclear.ObjectiveWe sought to interrogate tissue-specific variations in the expressed genome in the skin of children with AD and to investigate underlying pathomechanisms in atopic skin.MethodsWe applied single-molecule direct RNA sequencing to analyze the whole transcriptome using minimal tissue samples. Uninvolved skin biopsy specimens from 26 pediatric patients with AD were compared with site-matched samples from 10 nonatopic teenage control subjects. Cases and control subjects were screened for FLG genotype to stratify the data set.ResultsTwo thousand four hundred thirty differentially expressed genes (false discovery rate, P < .05) were identified, of which 211 were significantly upregulated and 490 downregulated by greater than 2-fold. Gene ontology terms for “extracellular space” and “defense response” were enriched, whereas “lipid metabolic processes” were downregulated. The subset of FLG wild-type cases showed dysregulation of genes involved with lipid metabolism, whereas filaggrin haploinsufficiency affected global gene expression and was characterized by a type 1 interferon–mediated stress response.ConclusionThese analyses demonstrate the importance of extracellular space and lipid metabolism in atopic skin pathology independent of FLG genotype, whereas an aberrant defense response is seen in subjects with FLG mutations. Genotype stratification of the large data set has facilitated functional interpretation and might guide future therapy development

A Parallactic Distance of 389 +24/-21 parsecs to the Orion Nebula Cluster from Very Long Baseline Array Observations

We determine the parallax and proper motion of the flaring, non-thermal radio star GMR A, a member of the Orion Nebula Cluster, using Very Long Baseline Array observations. Based on the parallax, we measure a distance of 389 +24/-21 parsecs to the source. Our measurement places the Orion Nebula Cluster considerably closer than the canonical distance of 480 +/- 80 parsecs determined by Genzel et al. (1981). A change of this magnitude in distance lowers the luminosities of the stars in the cluster by a factor of ~ 1.5. We briefly discuss two effects of this change--an increase in the age spread of the pre-main sequence stars and better agreement between the zero-age main-sequence and the temperatures and luminosities of massive stars.Comment: 10 pages, 4 figures, emulateapj, accepted to Ap

First Remote Sensing Observations of Trifluoromethane (HFC-23) in the Upper Troposphere and Lower Stratosphere

This work reports the first remote sensing measurements of atmospheric HFC-23 (CHF3) using solar occultation measurements made by the Atmospheric Chemistry Experiment Fourier transform spectrometer (ACE-FTS) and the Jet Propulsion Laboratory Mark IV (MkIV) balloon interferometer. A total of 8809 ACE occultations measured between 2004 and 2010 have been processed, along with 24 MkIV occultations measured between 1989 and 2007. ACE data (yearly averages over the 10-25 km altitude range) in the tropics/subtropics (40°S-40°N) reveal a trend of 4.0 ± 1.6% per year in the growth of HFC-23 for 2004-2009 (or 3.9 ± 1.2% per year for 2004-2010), slightly smaller than surface measurements from Cape Grim air archive samples over the same time period (4.7 ± 0.3% per year). The northern midlatitude and high-latitude MkIV data (averaged over the 10-25 km altitude range) indicate a growth rate of 5.8 ± 0.3% per year over the period 1989-2007 (5.3 ± 0.4% per year for just the midlatitude data), similar to the Cape Grim surface trend of 5.7 ± 0.1% per year over the same period. The absolute HFC-23 volume mixing ratios measured by ACE and MkIV in the upper troposphere/lower stratosphere are in good agreement (\u3c5% bias) with each other but are ∼30% larger than ground-based measurements. The source of this bias has not been definitively ascertained; however, spectroscopic errors are the most likely cause. Copyright 2012 by the American Geophysical Union

Asymmetric cyclopropanation of conjugated cyanosulfones using a novel cupreine organocatalyst: rapid access to d3-amino acids

An organocatalytic asymmetric synthesis of a novel, highly functionalised cyclopropane system furnished with versatile substituents and containing a quaternary centre is described. The process utilises a new bifunctional catalyst based on the cinchona alkaloid framework and the products made using this catalyst were obtained as single diastereoisomers, with very high enantioselectivities (up to 96% ee). We have also demonstrated that these resulting cyclopropanes are very useful synthetic intermediates to interesting products, such as the difficult to access d3-amino acids