Solvent-Free Continuous Operations Using Small Footprint Reactors: A Key Approach for Process Intensification

A solvent-free approach to intensification of chemical processes is reported. This concept, in which reactions are carried out solvent-free, without the need for further downstream processing, was highlighted first with a full reduction of ethyl nicotinate to ethylpiperidine-3-carboxylate under continuous flow conditions. Using a small footprint reactor, a throughput of 26.4 g h–1 was achieved. Similarly, this approach was used for the telescoped two-step synthesis of 2-propyl phenol (productivity 120 g h–1) and 2-propyl cyclohexanone (productivity 30 g h–1), starting from the commercially available allyl phenol ether via Claisen rearrangement and subsequent reduction.We would like to thank Pfizer Worldwide Research & Development (CB), the EPSRC (RJM, SVL, Grant Codes EP/K009494/1, EP/M004120/1 and EP/K039520/1) and the Woolf Fisher Trust (DEF) for financial support.This is the final version of the article. It first appeared from the American Chemical Society via https://doi.org/10.1021/acssuschemeng.6b0028

Trigger for group A streptococcal M1T1 invasive disease

The globally disseminated Streptococcus pyogenes M1T1 clone causes a number of highly invasive human diseases. The transition from local to systemic infection occurs by an unknown mechanism; however invasive M1T1 clinical isolates are known to express significantly less cysteine protease SpeB than M1T1 isolates from local infections. Here, we show that in comparison to the M1T1 strain 5448, the isogenic mutant ΔspeB accumulated 75‐fold more human plasmin activity on the bacterial surface following incubation in human plasma. Human plasminogen was an absolute requirement for M1T1 strain 5448 virulence following subcutaneous (s.c.) infection of humanized plasminogen transgenic mice. S. pyogenes M1T1 isolates from the blood of infected humanized plasminogen transgenic mice expressed reduced levels of SpeB in comparison with the parental 5448 used as inoculum. We propose that the human plasminogen system plays a critical role in group A streptococcal M1T1 systemic disease initiation. SpeB is required for S. pyogenes M1T1 survival at the site of local infection, however, SpeB also disrupts the interaction of S. pyogenes M1T1 with the human plasminogen activation system. Loss of SpeB activity in a subpopulation of S. pyogenes M1T1 at the site of infection results in accumulation of surface plasmin activity thus triggering systemic spread.—Cole, J. N., McArthur, J. D., McKay, F. C., Sanderson‐Smith, M. L., Cork, A. J., Ranson, M., Rohde, M., Itzek, A., Sun, H., Ginsburg, D., Kotb, M., Nizet, V., Chhatwal, G. S., Walker, M. J. Trigger for group A streptococcal M1T1 invasive disease. FASEB J. 20, E1139–E1145 (2006)Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154248/1/fsb2fj065804fje.pd

The Allen Telescope Array Pi GHz Sky Survey I. Survey Description and Static Catalog Results for the Bootes Field

The Pi GHz Sky Survey (PiGSS) is a key project of the Allen Telescope Array. PiGSS is a 3.1 GHz survey of radio continuum emission in the extragalactic sky with an emphasis on synoptic observations that measure the static and time-variable properties of the sky. During the 2.5-year campaign, PiGSS will twice observe ~250,000 radio sources in the 10,000 deg^2 region of the sky with b > 30 deg to an rms sensitivity of ~1 mJy. Additionally, sub-regions of the sky will be observed multiple times to characterize variability on time scales of days to years. We present here observations of a 10 deg^2 region in the Bootes constellation overlapping the NOAO Deep Wide Field Survey field. The PiGSS image was constructed from 75 daily observations distributed over a 4-month period and has an rms flux density between 200 and 250 microJy. This represents a deeper image by a factor of 4 to 8 than we will achieve over the entire 10,000 deg^2. We provide flux densities, source sizes, and spectral indices for the 425 sources detected in the image. We identify ~100$ new flat spectrum radio sources; we project that when completed PiGSS will identify 10^4 flat spectrum sources. We identify one source that is a possible transient radio source. This survey provides new limits on faint radio transients and variables with characteristic durations of months.Comment: Accepted for publication in ApJ; revision submitted with extraneous figure remove

The Allen Telescope Array Pi GHz Sky Survey I. Survey Description and Static Catalog Results for the Bootes Field

The Pi GHz Sky Survey (PiGSS) is a key project of the Allen Telescope Array. PiGSS is a 3.1 GHz survey of radio continuum emission in the extragalactic sky with an emphasis on synoptic observations that measure the static and time-variable properties of the sky. During the 2.5-year campaign, PiGSS will twice observe ~250,000 radio sources in the 10,000 deg^2 region of the sky with b > 30 deg to an rms sensitivity of ~1 mJy. Additionally, sub-regions of the sky will be observed multiple times to characterize variability on time scales of days to years. We present here observations of a 10 deg^2 region in the Bootes constellation overlapping the NOAO Deep Wide Field Survey field. The PiGSS image was constructed from 75 daily observations distributed over a 4-month period and has an rms flux density between 200 and 250 microJy. This represents a deeper image by a factor of 4 to 8 than we will achieve over the entire 10,000 deg^2. We provide flux densities, source sizes, and spectral indices for the 425 sources detected in the image. We identify ~100$ new flat spectrum radio sources; we project that when completed PiGSS will identify 10^4 flat spectrum sources. We identify one source that is a possible transient radio source. This survey provides new limits on faint radio transients and variables with characteristic durations of months.Comment: Accepted for publication in ApJ; revision submitted with extraneous figure remove

The Allen Telescope Array Twenty-centimeter Survey - A 690-Square-Degree, 12-Epoch Radio Dataset - I: Catalog and Long-Duration Transient Statistics

We present the Allen Telescope Array Twenty-centimeter Survey (ATATS), a multi-epoch (12 visits), 690 square degree radio image and catalog at 1.4GHz. The survey is designed to detect rare, very bright transients as well as to verify the capabilities of the ATA to form large mosaics. The combined image using data from all 12 ATATS epochs has RMS noise sigma = 3.94mJy / beam and dynamic range 180, with a circular beam of 150 arcsec FWHM. It contains 4408 sources to a limiting sensitivity of S = 20 mJy / beam. We compare the catalog generated from this 12-epoch combined image to the NRAO VLA Sky Survey (NVSS), a legacy survey at the same frequency, and find that we can measure source positions to better than ~20 arcsec. For sources above the ATATS completeness limit, the median flux density is 97% of the median value for matched NVSS sources, indicative of an accurate overall flux calibration. We examine the effects of source confusion due to the effects of differing resolution between ATATS and NVSS on our ability to compare flux densities. We detect no transients at flux densities greater than 40 mJy in comparison with NVSS, and place a 2-sigma upper limit on the transient rate for such sources of 0.004 per square degree. These results suggest that the > 1 Jy transients reported by Matsumura et al. (2009) may not be true transients, but rather variable sources at their flux density threshold.Comment: 41 pages, 19 figures, ApJ accepted; corrected minor typo in Table

Chemical Synergy between Ionophore PBT2 and Zinc Reverses Antibiotic Resistance.

The World Health Organization reports that antibiotic-resistant pathogens represent an imminent global health disaster for the 21st century. Gram-positive superbugs threaten to breach last-line antibiotic treatment, and the pharmaceutical industry antibiotic development pipeline is waning. Here we report the synergy between ionophore-induced physiological stress in Gram-positive bacteria and antibiotic treatment. PBT2 is a safe-for-human-use zinc ionophore that has progressed to phase 2 clinical trials for Alzheimer's and Huntington's disease treatment. In combination with zinc, PBT2 exhibits antibacterial activity and disrupts cellular homeostasis in erythromycin-resistant group A Streptococcus (GAS), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus (VRE). We were unable to select for mutants resistant to PBT2-zinc treatment. While ineffective alone against resistant bacteria, several clinically relevant antibiotics act synergistically with PBT2-zinc to enhance killing of these Gram-positive pathogens. These data represent a new paradigm whereby disruption of bacterial metal homeostasis reverses antibiotic-resistant phenotypes in a number of priority human bacterial pathogens.IMPORTANCE The rise of bacterial antibiotic resistance coupled with a reduction in new antibiotic development has placed significant burdens on global health care. Resistant bacterial pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus are leading causes of community- and hospital-acquired infection and present a significant clinical challenge. These pathogens have acquired resistance to broad classes of antimicrobials. Furthermore, Streptococcus pyogenes, a significant disease agent among Indigenous Australians, has now acquired resistance to several antibiotic classes. With a rise in antibiotic resistance and reduction in new antibiotic discovery, it is imperative to investigate alternative therapeutic regimens that complement the use of current antibiotic treatment strategies. As stated by the WHO Director-General, "On current trends, common diseases may become untreatable. Doctors facing patients will have to say, Sorry, there is nothing I can do for you.

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sity of differing M types is proposed. The vast majority of GAS infection is benign. Nonetheless, many divergent M types possess limited capacity to cause invasive infection. M1T1 GAS readily switch to a covRS mutant form that is neutrophil resistant and frequently associated with systemic infection. Whilst non-M1 GAS are shown in this study to less frequently accumulate covRS mutations in vivo, such mutants are isolated from invasive infections and exhibit neutrophil resistance and enhanced virulence. The reduced capacity of non-M1 GAS to switch to the hypervirulent covRS mutant form provides an explanation for the comparatively less frequent isolation of non-M1 serotypes from invasive human infections. Key Words Animal models ؒ Bacteriology ؒ Immunity ؒ Innate ؒ Neutrophils ؒ Streptococcus ؒ Virulence factors ؒ Invasive infection Abstract Group A Streptococcus (GAS) causes rare but life-threatening syndromes of necrotizing fasciitis and toxic shock-like syndrome in humans. The GAS serotype M1T1 clone has globally disseminated, and mutations in the control of virulence regulatory sensor kinase (covRS) operon correlate with severe invasive disease. Here, a cohort of non-M1 GAS was screened to determine whether mutation in covRS triggers systemic dissemination in divergent M serotypes. A GAS disease model defining parameters governing invasive propen

The calcium channel β2 (CACNB2) subunit repertoire in teleosts

© 2008 Ebert et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens