γδβ-thalassaemias 1 and 2 are the result of a 100 kpb deletion in the human β-globin cluster.

The DNA spanning two large deletions in the human beta-globin gene cluster (gamma beta-thalassaemia 1 and 2) has been cloned by cosmid cloning and chromosomal walking. The entire region was mapped and analyzed for the presence of repetitive sequences. The results show that the affected loci have lost almost 100 kb of DNA in a deletion event not involving homologous or repetitive sequences

GaN CVD Reactions: Hydrogen and Ammonia Decomposition and the Desorption of Gallium

Isotopic labeling experiments have revealed correlations between hydrogen reactions, Ga desorption, and ammonia decomposition in GaN CVD. Low energy electron diffraction (LEED) and temperature programmed desorption (TPD) were used to demonstrate that hydrogen atoms are available on the surface for reaction after exposing GaN(0001) to deuterium at elevated temperatures. Hydrogen reactions also lowered the temperature for Ga desorption significantly. Ammonia did not decompose on the surface before hydrogen exposure. However, after hydrogen reactions altered the surface, N15H3 did undergo both reversible and irreversible decomposition. This also resulted in the desorption of N2 of mixed isotopes below the onset of GaN sublimation, This suggests that the driving force of the high nitrogen-nitrogen bond strength (226 kcal/mol) can lead to the removal of nitrogen from the substrate when the surface is nitrogen rich. Overall, these findings indicate that hydrogen can influence G-aN CVD significantly, being a common factor in the reactivity of the surface, the desorption of Ga, and the decomposition of ammonia

Uncorking the potential of wine language for young wine tourists

Effective communication with consumers underpins growth in wine knowledge that, in turn, contributes to growth in wine consumption. Indeed, tasting notes may enhance consumers’ experiences of wine. Yet wine language is full of fuzzy concepts. In this chapter, we consider the language used to talk about wine, specifically the humanlike features of wine (e.g., wine is described as honest, sexy, shy, or brooding). We demonstrate that metaphoric language is integral to the experience of wine and influences consumer behaviour. We discuss practical implications for the cellar door experience, and for effective and ethical wine communication. We conclude that metaphoric language is a pedagogical and cultural platform for engaging younger wine tourists in the cellar door experience, which is a significant revenue source for micro, small, and medium wineries

Transport, Growth Mechanisms, and Material Quality in GaN Epitaxial Lateral Overgrowth

Growth kinetics, mechanisms, and material quality in GaN epitaxial lateral over-growth (ELO) were examined using a single mask of systematically varied patterns. A 2-D gas phase reaction/diffusion model describes how transport of the Ga precursor to the growth surface enhances the lateral rate in the early stages of growth. In agreement with SEM studies of truncated growth runs, the model also predicts the dramatic decrease in the lateral rate that occurs as GaN over-growth reduces the exposed area of the mask. At the point of convergence, a step-flow coalescence mechanism is observed to fill in the area between lateral growth-fronts. This alternative growth mode in which a secondary growth of GaN is nucleated along a single convergence line, may be responsible for producing smooth films observed to have uniform cathodoluminescence (CL) when using 1{micro}m nucleation zones. Although emission is comprised of both UV ({approximately}365nm) and yellow ({approximately}550nm) components, the spectra suggest these films have reduced concentrations of threading dislocations normally associated with non-radiative recombination centers and defects known to accompany growth-front convergence lines

Chromane derivatives from underground parts of Iris tenuifolia and their in vitro antimicrobial, cytotoxicity and antiproliferative evaluation

Phytochemical investigation of the ethanol extract of underground parts of Iris tenuifolia Pall. afforded five new compounds; an unusual macrolide termed moniristenulide (1), 5-methoxy-6,7-methylenedioxy-4-O-2′-cycloflavan (2), 5,7,2′,3′-tetrahydroxyflavanone (3), 5-hydroxy-6,7-dimethoxyisoflavone-2′-O-β-d-glucopyranoside (9), 5,2′,3′-dihydroxy-6,7-dimethoxyisoflavone (10), along with seven known compounds (4–8, 11–12). The structures of all purified compounds were established by analysis of 1D and 2D NMR spectroscopy and HR-ESI-MS. The antimicrobial activity of the compounds 1–3, 5, 9, and 10 was investigated using the agar diffusion method against fungi, Gram-positive and Gram-negative bacteria. In consequence, new compound 3 was found to possess the highest antibacterial activity against Enterococcus faecalis VRE and Mycobacterium vaccae. Cell proliferation and cytotoxicity tests were also applied on all isolated compounds and plant crude extract in vitro with the result of potent inhibitory effect against leukemia cells. In particular, the newly discovered isoflavone 10 was active against both of the leukemia cells K-562 and THP-1 while 4–6 of the flavanone type compounds were active against only THP-1

Accurate sample assignment in a multiplexed, ultrasensitive, high-throughput sequencing assay for minimal residual disease

High-throughput sequencing (HTS) (next-generation sequencing) of the rearranged Ig and T-cell receptor genes promises to be less expensive and more sensitive than current methods of monitoring minimal residual disease (MRD) in patients with acute lymphoblastic leukemia. However, the adoption of new approaches by clinical laboratories requires careful evaluation of all potential sources of error and the development of strategies to ensure the highest accuracy. Timely and efficient clinical use of HTS platforms will depend on combining multiple samples (multiplexing) in each sequencing run. Here we examine the Ig heavy-chain gene HTS on the Illumina MiSeq platform for MRD. We identify errors associated with multiplexing that could potentially impact the accuracy of MRD analysis. We optimize a strategy that combines high-purity, sequence-optimized oligonucleotides, dual indexing, and an error-aware demultiplexing approach to minimize errors and maximize sensitivity. We present a probability-based, demultiplexing pipeline Error-Aware Demultiplexer that is suitable for all MiSeq strategies and accurately assigns samples to the correct identifier without excessive loss of data. Finally, using controls quantified by digital PCR, we show that HTS-MRD can accurately detect as few as 1 in 10(6) copies of specific leukemic MRD

Sanitary inspection, microbial water quality analysis, and water safety in handpumps in rural sub-Saharan Africa

In sub-Saharan Africa, over half of the population is exposed to contaminated drinking water. The WHO recommends both sanitary inspection and water quality analysis to assess the risk of water source contamination, but the relationship between these tools is poorly understood. We explore the relationship between sanitary inspection and water quality analysis using data from 1028 boreholes with handpumps in 12 countries in sub-Saharan Africa. Sanitary inspection scores and E. coli occurrence were compared using the models described in published literature, and an alternative model that better reflects causal pathways of contamination. In the alternative model, sanitary risk factors were categorized as contamination sources, carriers, or barrier breakdowns, and the relationships between risk factor combinations and E. coli occurrence were assessed. We found no associations between sanitary risk score and E. coli occurrence using either the established or alternative model. These results confirm that sanitary inspections and microbial analyses convey distinct information, and perfect correlation is neither expected nor desired. The alternative model demonstrated a slightly better model fit than most established models, and the model fit further improved when the occurrence of rainfall in the past two days was added as a carrier. We recommend that: implementers train water system operators to conduct sanitary inspection; and researchers work to improve our understanding of the effect of individual sanitary risk factors, as well as incorporate contextual data into their assessments of sanitary inspection and water quality

Experimental Investigation of Rotorcraft Outwash in Ground Effect

The wake characteristics of a rotorcraft are affected by the proximity of a rotor to the ground surface, especially during hover. Ground effect is encountered when the rotor disk is within a distance of a few rotor radii above the ground surface and results in an increase in thrust for a given power relative to that same power condition with the rotor out of ground effect. Although this phenomenon has been highly documented and observed since the beginning of the helicopter age, there is still a relatively little amount of flow-field data existing to help understand its features. Joint Army and NASA testing was conducted at NASA Langley Research Center using a powered rotorcraft model in hover at various rotor heights and thrust conditions in order to contribute to the complete outwash data set. The measured data included outwash velocities and directions, rotor loads, fuselage loads, and ground pressures. The researchers observed a linear relationship between rotor height and percent download on the fuselage, peak mean outwash velocities occurring at radial stations between 1.7 and 1.8 r/R regardless of rotor height, and the measurement azimuthal dependence of the outwash profile for a model incorporating a fuselage. Comparisons to phase-locked PIV data showed similar contours but a more contracted wake boundary for the PIV data. This paper describes the test setup and presents some of the averaged results

Estimating Systemic Risk in the International Financial System

Using a unique and comprehensive dataset, this paper develops and uses three distinct methods to quantify the risk of a systemic failure in the global banking system. We examine a sample of 334 banks (representing 80% of global bank equity) in 28 countries around 6 global financial crises (such as the Asian and Russian crises and September 11, 2001), and show that these crises did not create large probabilities of global financial system failure. First, we show that cumulative negative abnormal returns for the subset of banks not directly exposed to a negative shock (unexposed banks) rarely exceed a few percent. Second, we use structural models to obtain more precise point estimates of the likelihood of systemic failure. These estimates suggest that systemic risk is limited even during major financial crises. For example, maximum likelihood estimation of bank failure probabilities implied by equity prices suggests the Asian crisis induced less than a 1% increase in the probability of systemic failure. Third, we also obtain estimates of systemic risk implied by equity option prices of U.S. and European banks. The largest values are obtained for the Russian crisis and September 11 and these show increases in estimated average default probabilities of only around 1-2%. Taken together our results suggest statistically significant, but economically small, increases in systemic risk around even the worst financial crises of the last 10 years. Although policy responses are endogenous, the low estimated probabilities suggest that the distress of central bankers, regulators and politicians about the events we study may be overstated, and that current policy responses to financial crises and the existing institutional framework may be adequate to handle major macroeconomic events

Clonal origin of KMT2A wild-type lineage-switch leukemia following CAR-T cell and blinatumomab therapy

Children with acute lymphoblastic leukemia (ALL) undergoing anti-CD19 therapy occasionally develop acute myeloid leukemia (AML). The clonal origin of such lineage-switch leukemias 1–4 remains unresolved. Here, we reconstructed the phylogeny of multiple leukemias in a girl who, following multiply relapsed ALL, received anti-CD19 cellular and antibody treatment and subsequently developed AML. Whole genome sequencing unambiguously revealed the AML derived from the initial ALL, with distinct driver mutations that were detectable before emergence. Extensive prior diversification and subsequent clonal selection underpins this fatal lineage switch. Genomic monitoring of primary leukemias and recurrences may predict therapy resistance, especially regarding anti-CD19 treatment