We introduce a liquid application method for time-resolved analyses (LAMA), an in situ mixing approach for serial crystallography. Picoliter-sized droplets are shot onto chip-mounted protein ...crystals, achieving near-full ligand occupancy within theoretical diffusion times. We demonstrate proof-of-principle binding of GlcNac to lysozyme, and resolve glucose binding and subsequent ring opening in a time-resolved study of xylose isomerase.
Black carbon (BC) aerosol loadings were measured during the High‐performance Instrumented Airborne Platform for Environmental Research Pole‐to‐Pole Observations (HIPPO) campaign above the remote ...Pacific from 85°N to 67°S. Over 700 vertical profiles extending from near the surface to max ~14 km altitude were obtained with a single‐particle soot photometer between early 2009 and mid‐2011. The data provides a climatology of BC in the remote regions that reveals gradients of BC concentration reflecting global‐scale transport and removal of pollution. BC is identified as a sensitive tracer of extratropical mixing into the lower tropical tropopause layer and trends toward surprisingly uniform loadings in the lower stratosphere of ~1 ng/kg. The climatology is compared to predictions from the AeroCom global model intercomparison initiative. The AeroCom model suite overestimates loads in the upper troposphere/lower stratosphere (~10×) more severely than at lower altitudes (~3×), with bias roughly independent of season or geographic location; these results indicate that it overestimates BC lifetime.
Key Points
A BC climatology is provided for the remote Pacific and Polar regions
AeroCom overestimates remote BC with strong altitude dependence
Extratropical mixing into the TTL is estimated from BC latitudinal gradients
Context.
To understand galaxy evolution, it is essential to measure star formation rates (SFRs) across cosmic time.
Aims.
The use of radio continuum emission as an extinction-free tracer of star ...formation necessitates a good understanding of the influence of cosmic-ray electron (CRE) transport. Our aim in this work is to improve this understanding.
Methods.
We analysed the spatially resolved radio continuum-star formation rate (radio-SFR) relation in 15 nearby galaxies using data from the LOw Frequency ARray (LOFAR) and the Westerbork Synthesis Radio Telescope (WSRT) at 144 and 1365 MHz, respectively. The hybrid SFR maps are based on observations with
Spitzer
at 24 μm and with GALEX at 156 nm. Our pixel-by-pixel analysis at 1.2 kpc resolution reveals the usual sublinear radio-SFR relation for local measurements. This can be linearised with a smoothing experiment, convolving the hybrid SFR map with a Gaussian kernel that provides us with the CRE transport length.
Results.
CRE transport can be described as energy-independent isotropic diffusion. If we consider only young CREs as identified with the radio spectral index, we find a linear relation showing the influence of cosmic-ray transport. We then define the CRE calorimetric efficiency as the ratio of radio-to-hybrid SFR surface density and show that it is a function of the radio spectral index. If we correct the radio-SFR relation for the CRE calorimetric efficiency parametrised by the radio spectral index, it becomes nearly linear with a slope of 1.01 ± 0.02, independent of frequency.
Conclusions.
The corrected radio-SFR relation is universal and it holds for both global and local measurements.
Context.
The details of cosmic-ray transport have a strong impact on galaxy evolution. The peak of the cosmic-ray energy distribution is observable in the radio continuum using the electrons as ...proxy.
Aims.
We aim to measure the distance that the cosmic-ray electrons (CREs) are transported during their lifetime in the nearby galaxy M 51 across one order of magnitude in cosmic-ray energy (approximately 1–10 GeV). To this end, we use new ultra-low frequency observations from the LOw Frequency ARay (LOFAR) at 54 MHz and ancillary data between 144 and 8350 MHz.
Methods.
As the CREs originate from supernova remnants, the radio maps are smoothed in comparison to the distribution of the star formation. By convolving the map of the star formation rate (SFR) surface density with a Gaussian kernel, we can linearise the radio–SFR relation. The best-fitting convolution kernel is then our estimate of the CRE transport length.
Results.
We find that the CRE transport length increases at low frequencies, as expected since the CRE have longer lifetimes. The CRE transport length is
l
CRE
= √4
Dt
syn
, where
D
is the isotropic diffusion coefficient and
t
syn
is the CRE lifetime as given by synchrotron and inverse Compton losses. We find that the data can be well fitted by diffusion, where
D
= (2.14 ± 0.13)×10
28
cm
2
s
−1
. With
D
∝
E
0.001 ± 0.185
, the diffusion coefficient is independent of the CRE energy
E
in the range considered.
Conclusions.
Our results suggest that the transport of GeV-cosmic ray electrons in the star-forming discs of galaxies is governed by energy-independent diffusion.
In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, the impact of fasting regimens on the regulation ...of AT immune infiltration is still elusive. Here we show that intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, this increase in LAM abundance is strongly p53 dependent and partly mediated by p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation during IF, increases the catabolic state of adipocytes, and enhances systemic metabolic flexibility and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to efficacy of a fasting-mimicking diet and that the expression of p53 and TREM2 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signalling in adipocytes dictates LAM accumulation in AT under IF and modulates fasting effectiveness in mice and humans.
THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Overview Alexander, Stephen PH; Kelly, Eamonn; Marrion, Neil V ...
British journal of pharmacology,
December 2017, Letnik:
174, Številka:
S1
Journal Article, Web Resource
Recenzirano
Odprti dostop
The Concise Guide to PHARMACOLOGY 2017/18 is the third in this series of biennial publications. This version provides concise overviews of the key properties of nearly 1800 human drug targets with an ...emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13882/full. In addition to this overview, in which are identified ‘Other protein targets’ which fall outside of the subsequent categorisation, there are eight areas of focus: G protein‐coupled receptors, ligand‐gated ion channels, voltage‐gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
These "Guidelines for training in Cardiovascular Magnetic Resonance" were developed by the Certification Committee of the Society for Cardiovascular Magnetic Resonance (SCMR) and approved by the SCMR ...Board of Trustees.
The future of radiation therapy Schulz, R. J.
Journal of applied clinical medical physics,
January 2021, Letnik:
22, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Since the development of one‐ and two‐million volt x‐ray machines in the 1930s, which led to the reduction of both skin erythema and bone necrosis as well as an increase in depth dose, medical ...physicists have worked steadily to develop radiation sources and techniques for increasing the therapeutic ratios for most solid tumors. ...proton‐beam therapy (PBT) provides treatment plans with higher therapeutic ratios, which may result in reduced radiation toxicities, but evidence that PBT offers patients longer survival times is in short supply. Clearly, differences in survival times and levels of toxicity for PBT as compared with those for x rays are likely to be small. ...to obtain statistically valid comparisons would require that relatively large numbers of patients be studied over long periods of time, and that the methodology of the randomized prospective clinical trial (RPCT) be employed.
The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug ...targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties from the IUPHAR database. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full.
This compilation of the major pharmacological targets is divided into seven areas of focus: G protein‐coupled receptors, ligand‐gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets.
It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors & Channels. It is produced in conjunction with NC‐IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR‐DB and GRAC and provides a permanent, citable, point‐in‐time record that will survive database updates.
Emerging evidence implicates white matter (WM) abnormalities in the pathophysiology of schizophrenia. However, there is considerable heterogeneity in the presentation of WM abnormalities in the ...existing studies. The object of this study was to evaluate WM integrity in a large sample of patients with first-episode (FE) and chronic schizophrenia in comparison to matched control groups. Our goal was to assess whether WM findings occurred early in the illness or whether these abnormalities developed with the illness over time.
Participants included 114 patients with schizophrenia (31 FE and 83 chronic patients) and 138 matched controls. High-resolution structural and diffusion tensor images were obtained on all participants. Measures of fractional anisotropy (FA) were calculated for the 4 cortical lobes and the cerebellum and brain stem.
FA was significant lower in patients vs controls in the whole brain and individually in the frontal, parietal, occipital, and temporal lobes. FA was not significantly different in the brain stem or cerebellum. FA differences were significant only in patients with chronic schizophrenia and not in the FE group.
We found global differences in the WM microstructure in patients with chronic but not FE schizophrenia. These findings suggest progressive alterations in WM microstructure.
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