Functionalisation of Isoindolinones via a Calcium Catalysed Hosomi-Sakurai Allylation

A rapid and functionally tolerant calcium catalysed Hosomi-Sakurai reaction has been realised. Employing 1 mol% calcium, allylated isoindolinones can be synthesised in high yields and the reaction is shown to be tolerant to a range of medicinally relevant functional groups including heterocycles. The synthetic utility of the reaction has been shown, and a plausible reaction mechanism is provided

On the mass-radius relation of hot stellar systems

Most globular clusters have half-mass radii of a few pc with no apparent correlation with their masses. This is different from elliptical galaxies, for which the Faber-Jackson relation suggests a strong positive correlation between mass and radius. Objects that are somewhat in between globular clusters and low-mass galaxies, such as ultra-compact dwarf galaxies, have a mass-radius relation consistent with the extension of the relation for bright ellipticals. Here we show that at an age of 10 Gyr a break in the mass-radius relation at ~10^6 Msun is established because objects below this mass, i.e. globular clusters, have undergone expansion driven by stellar evolution and hard binaries. From numerical simulations we find that the combined energy production of these two effects in the core comes into balance with the flux of energy that is conducted across the half-mass radius by relaxation. An important property of this `balanced' evolution is that the cluster half-mass radius is independent of its initial value and is a function of the number of bound stars and the age only. It is therefore not possible to infer the initial mass-radius relation of globular clusters and we can only conclude that the present day properties are consistent with the hypothesis that all hot stellar systems formed with the same mass-radius relation and that globular clusters have moved away from this relation because of a Hubble time of stellar and dynamical evolution.Comment: 5 pages, 3 figures, MNRAS Letters (accepted

MUSTANG 3.3 Millimeter Continuum Observations of Class 0 Protostars

We present observations of six Class 0 protostars at 3.3 mm (90 GHz) using the 64-pixel MUSTANG bolometer camera on the 100-m Green Bank Telescope. The 3.3 mm photometry is analyzed along with shorter wavelength observations to derive spectral indices (S_nu ~ nu^alpha) of the measured emission. We utilize previously published dust continuum radiative transfer models to estimate the characteristic dust temperature within the central beam of our observations. We present constraints on the millimeter dust opacity index, beta, between 0.862 mm, 1.25 mm, and 3.3 mm. Beta_mm typically ranges from 1.0 to 2.4 for Class 0 sources. The relative contributions from disk emission and envelope emission are estimated at 3.3 mm. L483 is found to have negligible disk emission at 3.3 mm while L1527 is dominated by disk emission within the central beam. The beta_mm^disk <= 0.8 - 1.4 for L1527 indicates that grain growth is likely occurring in the disk. The photometry presented in this paper may be combined with future interferometric observations of Class 0 envelopes and disks.Comment: 19 pages, 3 figures, AJ accepted, in pres

Blueberry Progress Reports

The 1981 edition of the Blueberry Progress Reports was prepared for the Maine Blueberry Commission and the University of Maine Blueberry Advisory Committee by researchers with the Maine Life Sciences and Agriculture Experiment Station and Maine Cooperative Extension Service at the University of Maine, Orono. Projects in this report include: 1. Weed Control in Lowbush Blueberry Fields 2. Pruning of Blueberries 3. 1982 Blueberry Fruit Fly Monitoring IPM Program 4. Physiology and Culture of the Lowbush Blueberry 5. Blueberry Diseases: Incidence and Control 6. Control, biology, and ecology of insects affecting lowbush blueberries 7. Blueberry Extension Progress Report 8. Plan of Work - 1982 - Blueberry Extensio

Replication and Meta-Analysis of 13,000 Cases Defines the Risk for Interleukin-23 Receptor and Autophagy-Related 16-Like 1 Variants in Crohn’s Disease

BACKGROUND/OBJECTIVE: Variants in the interleukin-23 receptor (IL23R) and the autophagy-related 16-like 1 (ATG16L1) genes have been associated with an increased risk of Crohn’s disease (CD). Both genes were identified through genome-wide association scans and subsequent studies have validated these associations. To assess the effect size of these variants, an independent case-control association study and meta-analysis were performed. METHODS: British Caucasian subjects with inflammatory bowel disease (n=500) and 877 ethnically matched controls were genotyped for the disease-associated variants in IL23R and ATG16L1. In addition, meta-analyses of 12,991 patients and 14,598 controls, and 11,909 patients and 15,798 controls, were conducted on independently published data for the associations between IL23R and ATG16L1 variants and CD, respectively. RESULTS: In the present cohort, both susceptibility variants showed highly significant associations, including IL23R (rs11209026, P=0.0006; OR 0.37; 95% CI 0.21 to 0.67) and ATG16L1 (rs2241880, P=0.0017; OR 1.36; 95% CI 1.12 to 1.66). The meta-analysis based on the random effects model showed similar combined effects for rs11209026 (n=26, OR 0.41; 95% CI 0.37 to 0.46) and rs2241880 (n=25, OR 1.33; 95% CI 1.28 to 1.39). There was no statistically significant gene-gene interaction between caspase recruitment domain (CARD15) variants and the IL23R or ATG16L1 polymorphisms (P=0.44 and P=0.24, respectively). CONCLUSION: The present cohort and meta-analysis provides strong evidence that, in addition to CARD15, polymorphisms in both IL23R and ATG16L1 alter susceptibility to CD and that these effects are consistent across all populations of European ancestry; however, only ATG16L1 is relevant to inflammatory bowel disease in the Asian population

Development of Targeted Alpha Particle Therapy for Solid Tumors

Abstract: Targeted alpha-particle therapy (TAT) aims to selectively deliver radionuclides emitting α-particles (cytotoxic payload) to tumors by chelation to monoclonal antibodies, peptides or small molecules that recognize tumor-associated antigens or cell-surface receptors. Because of the high linear energy transfer (LET) and short range of alpha (α) particles in tissue, cancer cells can be significantly damaged while causing minimal toxicity to surrounding healthy cells. Recent clinical studies have demonstrated the remarkable efficacy of TAT in the treatment of metastatic, castration-resistant prostate cancer. In this comprehensive review, we discuss the current consensus regarding the properties of the α-particle-emitting radionuclides that are potentially relevant for use in the clinic; the TAT-mediated mechanisms responsible for cell death; the different classes of targeting moieties and radiometal chelators available for TAT development; current approaches to calculating radiation dosimetry for TATs; and lead optimization via medicinal chemistry to improve the TAT radiopharmaceutical properties. We have also summarized the use of TATs in pre-clinical and clinical studies to dat

Blueberry Progress Reports

The 1982 edition of the Blueberry Progress Reports was prepared for the Maine Blueberry Commission and the University of Maine Blueberry Advisory Committee by researchers with the Maine Life Sciences and Agriculture Experiment Station and Maine Cooperative Extension Service at the University of Maine, Orono. Projects in this report include: 1. Introduction 2. Blueberry IPM Program 3. Guthion Drift Study 4. Control, Biology, and Ecology of Insects 5. Blueberry Diseases: Incidence and Control 6. Physiology and Culture of the Lowbush Blueberry 7. Weed Control in Lowbush Blueberries 8. Pruning Blueberrie

Multi-scale temporal variability in meltwater contributions in a tropical glacierized watershed

Climate models predict amplified warming at high elevations in low latitudes, making tropical glacierized regions some of the most vulnerable hydrological systems in the world. Observations reveal decreasing streamflow due to retreating glaciers in the Andes, which hold 99&thinsp;% of all tropical glaciers. However, the timescales over which meltwater contributes to streamflow and the pathways it takes – surface and subsurface – remain uncertain, hindering our ability to predict how shrinking glaciers will impact water resources. Two major contributors to this uncertainty are the sparsity of hydrologic measurements in tropical glacierized watersheds and the complication of hydrograph separation where there is year-round glacier melt. We address these challenges using a multi-method approach that employs repeat hydrochemical mixing model analysis, hydroclimatic time series analysis, and integrated watershed modeling. Each of these approaches interrogates distinct timescale relationships among meltwater, groundwater, and stream discharge. Our results challenge the commonly held conceptual model that glaciers buffer discharge variability. Instead, in a subhumid watershed on Volcán Chimborazo, Ecuador, glacier melt drives nearly all the variability in discharge (Pearson correlation coefficient of 0.89 in simulations), with glaciers contributing a broad range of 20&thinsp;%–60&thinsp;% or wider of discharge, mostly (86&thinsp;%) through surface runoff on hourly timescales, but also through infiltration that increases annual groundwater contributions by nearly 20&thinsp;%. We further found that rainfall may enhance glacier melt contributions to discharge at timescales that complement glacier melt production, possibly explaining why minimum discharge occurred at the study site during warm but dry El Niño conditions, which typically heighten melt in the Andes. Our findings caution against extrapolations from isolated measurements: stream discharge and glacier melt contributions in tropical glacierized systems can change substantially at hourly to interannual timescales, due to climatic variability and surface to subsurface flow processes.</p