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Fully-automated nuclear image segmentation is the prerequisite to ensure statistically significant, quantitative analyses of tissue preparations,applied in digital pathology or quantitative microscopy. The design of segmentation methods that work independently of the tissue type or preparation is complex, due to variations in nuclear morphology, staining intensity, cell density and nuclei aggregations. Machine learning-based segmentation methods can overcome these challenges, however high quality expert-annotated images are required for training. Currently, the limited number of annotated fluorescence image datasets publicly available do not cover a broad range of tissues and preparations. We present a comprehensive, annotated dataset including tightly aggregated nuclei of multiple tissues for the training of machine learning-based nuclear segmentation algorithms. The proposed dataset covers sample preparation methods frequently used in quantitative immunofluorescence microscopy. We demonstrate the heterogeneity of the dataset with respect to multiple parameters such as magnification, modality, signal-to-noise ratio and diagnosis. Based on a suggested split into training and test sets and additional single-nuclei expert annotations, machine learning-based image segmentation methods can be trained and evaluated.

Isoprene is emitted from the biosphere into the atmosphere, and may strengthen the defense mechanisms of plants against oxidative and thermal stress. Once in the atmosphere, isoprene is rapidly oxidized, either to isoprene-hydroxy-hydroperoxides (ISOPOOH) at low levels of nitrogen oxides, or to methyl vinyl ketone (MVK) and methacrolein at high levels. Here we combine uptake rates and deposition velocities that we obtained in laboratory experiments with observations in natural forests to show that 1,2-ISOPOOH deposits rapidly into poplar leaves. There, it is converted first to cytotoxic MVK and then most probably through alkenal/ one oxidoreductase (AOR) to less toxic methyl ethyl ketone (MEK). This detoxification process is potentially significant globally because AOR enzymes are ubiquitous in terrestrial plants. Our simulations with a global chemistry-transport model suggest that around 6.5 Tg yr - of MEK are re-emitted to the atmosphere. This is the single largest MEK source presently known, and recycles 1.5% of the original isoprene flux. Eddy covariance flux measurements of isoprene and MEK over different forest ecosystems confirm that MEK emissions can reach 1-2% those of isoprene. We suggest that detoxification processes in plants are one of the most important sources of oxidized volatile organic compounds in the atmosphere., Competing Interests: Competing interests The authors declare no competing interests.

We use a real-time temperature-programmed desorption chemical-ionization mass spectrometer (FIGAERO-CIMS) to measure particle-phase composition and volatility of nucleated particles, studying pure α-pinene oxidation over a wide temperature range (-50 °C to +25 °C) in the CLOUD chamber at CERN. Highly oxygenated organic molecules are much more abundant in particles formed at higher temperatures, shifting the compounds toward higher O/C and lower intrinsic (300 K) volatility. We find that pure biogenic nucleation and growth depends only weakly on temperature. This is because the positive temperature dependence of degree of oxidation (and polarity) and the negative temperature dependence of volatility counteract each other. Unlike prior work that relied on estimated volatility, we directly measure volatility via calibrated temperature-programmed desorption. Our particle-phase measurements are consistent with gas-phase results and indicate that during new-particle formation from α-pinene oxidation, gas-phase chemistry directly determines the properties of materials in the condensed phase. We now have consistency between measured gas-phase product concentrations, product volatility, measured and modeled growth rates, and the particle composition over most temperatures found in the troposphere.

Salts of the weakly coordinating anions [Ga(OTeF 5 ) 4 ] - as well as [Ga(Et)(OTeF 5 ) 3 ] - and the neutral Ga 2 (Et) 3 (OTeF 5 ) 3 were synthesized and characterized by spectroscopic methods and single-crystal X-ray diffraction. Ga 2 (Et) 3 (OTeF 5 ) 3 was formed by treating GaEt 3 with pentafluoroorthotelluric acid (HOTeF 5 ) and reacted with PPh 4 Cl and CPh 3 Cl to [PPh 4 ][Ga(Et)(OTeF 5 ) 3 ] and [CPh 3 ][Ga(Et)(OTeF 5 ) 3 ]. In contrast, Ag[Ga(OTeF 5 ) 4 ] was prepared from AgOTeF 5 and GaCl 3 and was used as a versatile starting material for further reactions. Starting with Ag[Ga(OTeF 5 ) 4 ] the substrates [PPh 4 ][Ga(OTeF 5 ) 4 ] and [CPh 3 ][Ga(OTeF 5 ) 4 ] were formed from PPh 4 Cl and CPh 3 Cl., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

In this study, we present reactions of NH 4 + with a series of analytes (A): acetone (C 3 H 6 O), methyl vinyl ketone (C 4 H 6 O), methyl ethyl ketone (C 4 H 8 O), and eight monoterpene isomers (C 10 H 16 ) using a Selective Reagent Ionization Time-of-Flight Mass Spectrometer (SRI-ToF-MS). We studied the ion-molecule reactions at collision energies of 55 and 80 meV. The ketones, having a substantially lower proton affinity than NH 3 , produce only cluster ions NH 4 + (A) in detectable amounts at 55 meV. At 80 meV, no cluster ions were detected meaning that these adduct ions are formed by strongly temperature dependent association reactions. Bond energies of cluster ions and proton affinities for most monoterpenes are not known and were estimated by high level quantum chemical calculations. The calculations reveal monoterpene proton affinities, which range from slightly smaller to substantially higher than the proton affinity of NH 3 . Proton affinities and cluster bond energies allow to group the monoterpenes as a function of the enthalpy for the dissociation reaction N H 4 + A → A H + + N H 3 . We find that this enthalpy can be used to predict the NH 4 + (A) cluster ion yield. The present study explains product ion formation involving NH 4 + ion chemistry. This is of importance for chemical ionization mass spectrometry (CIMS) utilizing NH 4 + as well as NH 4 + (H 2 O) as reagent ions to quantitatively detect atmospherically important organic compounds in real-time.

Hydrocarbons are emitted into the Earth's atmosphere in very large quantities by human and biogenic activities. Their atmospheric oxidation processes almost exclusively yield RO 2 radicals as reactive intermediates whose atmospheric fate is not yet fully unraveled. Herein, we show that gas-phase reactions of two RO 2 radicals produce accretion products composed of the carbon backbone of both reactants. The rates for accretion product formation are very high for RO 2 radicals bearing functional groups, competing with those of the corresponding reactions with NO and HO 2 . This pathway, which has not yet been considered in the modelling of atmospheric processes, can be important, or even dominant, for the fate of RO 2 radicals in all areas of the atmosphere. Moreover, the vapor pressure of the formed accretion products can be remarkably low, characterizing them as an effective source for the secondary organic aerosol., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The magnitude of aerosol radiative forcing caused by anthropogenic emissions depends on the baseline state of the atmosphere under pristine preindustrial conditions. Measurements show that particle formation in atmospheric conditions can occur solely from biogenic vapors. Here, we evaluate the potential effect of this source of particles on preindustrial cloud condensation nuclei (CCN) concentrations and aerosol-cloud radiative forcing over the industrial period. Model simulations show that the pure biogenic particle formation mechanism has a much larger relative effect on CCN concentrations in the preindustrial atmosphere than in the present atmosphere because of the lower aerosol concentrations. Consequently, preindustrial cloud albedo is increased more than under present day conditions, and therefore the cooling forcing of anthropogenic aerosols is reduced. The mechanism increases CCN concentrations by 20-100% over a large fraction of the preindustrial lower atmosphere, and the magnitude of annual global mean radiative forcing caused by changes of cloud albedo since 1750 is reduced by [Formula: see text] (27%) to [Formula: see text] Model uncertainties, relatively slow formation rates, and limited available ambient measurements make it difficult to establish the significance of a mechanism that has its dominant effect under preindustrial conditions. Our simulations predict more particle formation in the Amazon than is observed. However, the first observation of pure organic nucleation has now been reported for the free troposphere. Given the potentially significant effect on anthropogenic forcing, effort should be made to better understand such naturally driven aerosol processes., Competing Interests: The authors declare no conflict of interest.

Vascular gene therapy is the focus of multiple experimental and clinical research efforts. While several genes with therapeutic potential have been identified, the best method of gene delivery is unknown. Viral vectors have the capacity to transfer genes at high efficiency rates. Several viral-based vectors have been used in experimental vascular gene therapy for in vivo and ex vivo gene transfer. Adenoviral-based vectors are being used for the induction of angiogenesis in phase 1 and 2 clinical trials. In the present review, the characteristics of the 'ideal' viral vector are discussed and the major types of viral vectors used in vascular gene transfer are reviewed. Basic knowledge of the use of viral vectors for direct in vivo gene transfer (adenoviral-based vectors, etc) and for ex vivo gene transfer (retroviral-based vectors) is provided. New developments in the field of viral vectorology, such as pseudotyping of retroviral vectors and targeting of other viral vectors to a specific cell type, will enhance the more rapid transition of vascular gene therapy from the experimental arena to the clinical setting.