Rapid iododeboronation with and without gold catalysis: application to radiolabelling of arenes

Radiopharmaceuticals incorporating radioactive iodine in combination with SPECT imaging play a key role in nuclear medicine, with applications in drug development and disease diagnosis. Despite this importance, there are relatively few general methods for incorporating radioiodine into small molecules. Here we describe a rapid, air- and moisture-stable ipso-iododeboronation procedure using NIS, in the non-toxic and green solvent dimethyl carbonate. The fast reaction and mild conditions of the gold-catalysed method led to the development of a highly efficient process for radiolabelling of arenes, which constitutes the first example of an application of homogenous gold catalysis to selective radiosynthesis. This has been exemplified with an effective synthesis of radiolabelled meta-[125I]iodobenzylguanidine, a radiopharmaceutical used for the imaging and therapy of human norepinephrine transporter-expressing tumours

Chirality Transfer in Gold(I)-Catalysed Hydroalkoxylation of 1,3-Disubstituted Allenes

Gold(I)‐catalysed intermolecular hydroalkoxylation of enantioenriched 1,3‐disubstituted allenes was previously reported to occur with poor chirality transfer due to rapid allene racemisation. The first intermolecular hydroalkoxylation of allenes with efficient chirality transfer is reported here, exploiting conditions that suppress allene racemisation. A full substrate scope study reveals that excellent regio‐ and stereoselectivities are achieved when a σ‐withdrawing substituent is present

Automated Reminders to Promote Radon Testing in a Lung Cancer Case Control Study

One of the four pilot projects of the Lung Cancer Initiative sponsored by the Department of Defense measures radon levels in the participants homes. Radon exposure is the second leading cause of Lung Cancer. The case-control study has a targeted accrual of 1800 with a case-control ratio of 1:4. The long-term radon kits remain in the home for 90 days and the participants are asked to mail the test kit to the company for analysis. In order to maximize the test kit return rate, reminder calls to the participants occurred 90 days after the home visit

The analysis of European lacquer : optimization of thermochemolysis temperature of natural resins

In order to optimize chromatographic analysis of European lacquer, thermochemolysis temperature was evaluated for the analysis of natural resins. Five main ingredients of lacquer were studied: sandarac, mastic, colophony, Manila copal and Congo copal. For each, five temperature programs were tested: four fixed temperatures (350, 480, 550, 650 degrees C) and one ultrafast thermal desorption (UFD), in which the temperature rises from 350 to 660 degrees C in 1 min. In total, the integrated signals of 27 molecules, partially characterizing the five resins, were monitored to compare the different methods. A compromise between detection of compounds released at low temperatures and compounds formed at high temperatures was searched. 650 degrees C is too high for both groups, 350 degrees C is best for the first, and 550 degrees C for the second. Fixed temperatures of 480 degrees C or UFD proved to be a consensus in order to detect most marker molecules. UFD was slightly better for the molecules released at low temperatures, while 480 degrees C showed best compounds formed at high temperatures

Neural predictive control of broiler chicken and pig growth

Active control of the growth of broiler chickens and pigs has potential benefits for farmers in terms of improved production efficiency, as well as for animal welfare in terms of improved leg health in broiler chickens. In this work, a differential recurrent neural network (DRNN) was identified from experimental data to represent animal growth using a nonlinear system identification algorithm. The DRNN model was then used as the internal model for nonlinear model predictive control (NMPC) to achieve a group of desired growth curves. The experimental results demonstrated that the DRNN model captured the underlying dynamics of the broiler and pig growth process reasonably well. The DRNN based NMPC was able to specify feed intakes in real time so that the broiler and pig weights accurately followed the desired growth curves ranging from to +12% and to +20% of the standard curve for broiler chickens and pigs, respectively. The overall mean relative error between the desired and achieved broiler or pig weight was 1.8% for the period from day 12 to day 51 and 10.5% for the period from week 5 to week 21, respectively

Impact of antiretroviral and tuberculosis therapies on CD4 + and CD8 + HIV/M. tuberculosis-specific T-cell in co-infected subjects

Background: Human Immunodeficiency Virus (HIV) infection is a risk factor for tuberculosis (TB). Antiretroviral therapy (ART) changed HIV clinical management but it is still unclear how pre-existing HIV/Mycobacterium tuberculosis (Mtb)-specific CD4 + and CD8 + T-cells are restored. Aim: to evaluate the impact of ART and TB therapies on the functional and phenotypic profile of Mtb-specific antigen-response of CD4 + and CD8 + T-cells in prospectively enrolled HIV-TB co-infected patients. Methods: ART-naïve HIV-infected patients, with or without active TB or latent TB infection (LTBI), were enrolled before and after starting ART and TB therapies. Peripheral blood mononuclear cells (PBMC) were stimulated overnight with Mtb and HIV antigens (GAG). Cytokine expression and phenotype profile were evaluated by flow cytometry. Cytomegalovirus (CMV) and staphylococcal enterotoxin B (SEB) were also used. Results: The median of absolute number of CD4 + T-cells increased after ART and TB therapies in all groups analyzed, while the median of absolute number of CD8 + T-cells decreases in HIV and HIV-LTBI groups. Treatments significantly increased the frequency of Mtb-specific CD4 + T-cells in the HIV-LTBI (p = 0.015) with a rise of the central memory compartment. The magnitude of the CD4 + T-cell response to HIV-GAG significantly increased in active TB (p = 0.03), whereas the magnitude of CMV-specific CD4 + T-cell response decreased in all the groups. Similarly, the treatments increased the number of Mtb-specific CD8 + responders in both HIV-LTBI and HIV-TB groups, whereas the phenotype distribution was dependent on the antigens used and on the stage of infection/disease. Conclusions: After therapies the median of absolute number and the proportion of CD4 + T-cells increased in all groups whereas the median of absolute count and proportion of CD8 + T-cells decreased in the HIV and HIV-LTBI subjects. Interestingly, an increased frequency of CD4 + T-cell response to RD1 proteins in HIV-LTBI subjects was found. These results contribute to a better understanding of the effect of ART and TB therapies on the modulation of Mtb-specific CD4 + and CD8 + T-cells subsets

Quantifying turbulence from field measurements at a mixed low tidal energy site

© 2015 Elsevier Ltd. This study explores typical characteristics of the mean and turbulent profiles at a mixed low tidal energy site (40 m mean water depth) where the waves have limited effects on the currents. The turbulence profiles were derived from secondary current data using a 5-beam ADCP which was optimised for wave measurements. The tidal currents have peak flows of ~1 m/s during spring tide. The turbulence intensity is no less than 10% at peak flows and compares well with values at other tidal channels (at ~5 m from seabed). The Reynolds stresses show symmetry at the neap tide but less so for the spring tide. Although the qualitative profiles of TKE are similar between the neap and spring tides, the values of TKE for flood flow are the largest throughout the deployment. The integral length scales are in good agreement with theory, and with estimates based on the mixing length concept. The measured turbulence parameters are sensitive to flow inhomogeneity, Doppler noise, and ADCP tilt. The findings demonstrate the practical benefits of exploiting secondary current data at a mixed low tidal energy site for estimating typical turbulence characteristics; such information can be used to define design standards and protocols for marine energy devices

Jet-induced star formation in gas-rich galaxies

Feedback from active galactic nuclei (AGN) has become a major component in simulations of galaxy evolution, in particular for massive galaxies. AGN jets have been shown to provide a large amount of energy and are capable of quenching cooling flows. Their impact on the host galaxy, however, is still not understood. Subgrid models of AGN activity in a galaxy evolution context so far have been mostly focused on the quenching of star formation. To shed more light on the actual physics of the "radio mode" part of AGN activity, we have performed simulations of the interaction of a powerful AGN jet with the massive gaseous disc (10^11 solar masses) of a high-redshift galaxy. We spatially resolve both the jet and the clumpy, multi-phase interstellar medium (ISM) and include an explicit star formation model in the simulation. Following the system over more than 10^7 years, we find that the jet activity excavates the central region, but overall causes a significant change to the shape of the density probability distribution function and hence the star formation rate due to the formation of a blast wave with strong compression and cooling in the ISM. This results in a ring- or disc-shaped population of young stars. At later times, the increase in star formation rate also occurs in the disc regions further out since the jet cocoon pressurizes the ISM. The total mass of the additionally formed stars may be up to 10^10 solar masses for one duty cycle. We discuss the details of this jet-induced star formation (positive feedback) and its potential consequences for galaxy evolution and observable signatures.Comment: 14 pages, 10 figures. Accepted for publication in MNRAS. Added more details and clarifications after referee report. For associated movies, see http://www.mpe.mpg.de/~vgaibler/jet-disk-sf

IL-13 is a driver of COVID-19 severity

Immune dysregulation is characteristic of the more severe stages of SARS-CoV-2 infection. Understanding the mechanisms by which the immune system contributes to COVID-19 severity may open new avenues to treatment. Here, we report that elevated IL-13 was associated with the need for mechanical ventilation in 2 independent patient cohorts. In addition, patients who acquired COVID-19 while prescribed Dupilumab, a mAb that blocks IL-13 and IL-4 signaling, had less severe disease. In SARS-CoV-2–infected mice, IL-13 neutralization reduced death and disease severity without affecting viral load, demonstrating an immunopathogenic role for this cytokine. Following anti–IL-13 treatment in infected mice, hyaluronan synthase 1 (Has1) was the most downregulated gene, and accumulation of the hyaluronan (HA) polysaccharide was decreased in the lung. In patients with COVID-19, HA was increased in the lungs and plasma. Blockade of the HA receptor, CD44, reduced mortality in infected mice, supporting the importance of HA as a pathogenic mediator. Finally, HA was directly induced in the lungs of mice by administration of IL-13, indicating a new role for IL-13 in lung disease. Understanding the role of IL-13 and HA has important implications for therapy of COVID-19 and, potentially, other pulmonary diseases. IL-13 levels were elevated in patients with severe COVID-19. In a mouse model of the disease, IL-13 neutralization reduced the disease and decreased lung HA deposition. Administration of IL-13–induced HA in the lung. Blockade of the HA receptor CD44 prevented mortality, highlighting a potentially novel mechanism for IL-13–mediated HA synthesis in pulmonary pathology

Anti-phospholipid human monoclonal antibodies inhibit CCR5-tropic HIV-1 and induce β-chemokines

Traditional antibody-mediated neutralization of HIV-1 infection is thought to result from the binding of antibodies to virions, thus preventing virus entry. However, antibodies that broadly neutralize HIV-1 are rare and are not induced by current vaccines. We report that four human anti-phospholipid monoclonal antibodies (mAbs) (PGN632, P1, IS4, and CL1) inhibit HIV-1 CCR5-tropic (R5) primary isolate infection of peripheral blood mononuclear cells (PBMCs) with 80% inhibitory concentrations of <0.02 to ∼10 µg/ml. Anti-phospholipid mAbs inhibited PBMC HIV-1 infection in vitro by mechanisms involving binding to monocytes and triggering the release of MIP-1α and MIP-1β. The release of these β-chemokines explains both the specificity for R5 HIV-1 and the activity of these mAbs in PBMC cultures containing both primary lymphocytes and monocytes