Using an on-line image analysis technique to characterize sucrose crystal morphology during a crystallization run

The morphological forms and habits of crystals and agglomeration are important properties on crystallization processes. Online techniques for realtime measurement of these properties are mandatory for a better comprehension of crystal growth phenomenon. The present paper presents and describes a new online method to determine the complexity level of a crystal or a population of crystals during a crystallization process. An image analysis technique is combined with discriminant factorial analysis leading to results that allow the computation of the complexity of crystals through the parameter agglomeration degree of crystals. With this methodology, it has been possible to distinguish online and automatically among three different classes of crystals according to their complexity. It further describes the application of such methodology on the study of CaCl2, D-fructose, and D-glucose influence on the crystallization of sucrose, namely, on crystal size, morphology, and complexity. The effect of supersaturation, growth rate, and impurity concentration on the type, amount, and complexity level of the agglomerates was determined at different temperatures. The combination of image analysis and kinetic results allowed to understand better the crystallization phenomena in the presence and absence of impurities. The image analysis results suggest the possible application of this tool for process control, optimizing, by this way, laboratory and industrial crystallizers.This work was supported by Fundacao para a Ciencia e Tecnologia under program contract numbers SFRH/BD/11315/2002 and SFRH/BPD/45637/2008

Operation and performance of the ATLAS Tile Calorimeter in Run 1

The Tile Calorimeter is the hadron calorimeter covering the central region of the ATLAS experiment at the Large Hadron Collider. Approximately 10,000 photomultipliers collect light from scintillating tiles acting as the active material sandwiched between slabs of steel absorber. This paper gives an overview of the calorimeter’s performance during the years 2008–2012 using cosmic-ray muon events and proton–proton collision data at centre-of-mass energies of 7 and 8TeV with a total integrated luminosity of nearly 30 fb−1. The signal reconstruction methods, calibration systems as well as the detector operation status are presented. The energy and time calibration methods performed excellently, resulting in good stability of the calorimeter response under varying conditions during the LHC Run 1. Finally, the Tile Calorimeter response to isolated muons and hadrons as well as to jets from proton–proton collisions is presented. The results demonstrate excellent performance in accord with specifications mentioned in the Technical Design Report

Deconstruction of Activity-Dependent Covalent Modification of Heme in Human Neutrophil Myeloperoxidase by Multistage Mass Spectrometry (MS⁴)

Myeloperoxidase (MPO) is known to be inactivated and covalently modified by treatment with hydrogen peroxide and agents similar to 3-(2-ethoxypropyl)-2-thioxo-2,3-dihydro-1<i>H</i>-purin-6­(9<i>H</i>)-one (<b>1</b>), a 254.08 Da derivative of 2-thioxanthine. Peptide mapping by liquid chromatography and mass spectrometry detected modification by <b>1</b> in a labile peptide–heme–peptide fragment of the enzyme, accompanied by a mass increase of 252.08 Da. The loss of two hydrogen atoms was consistent with mechanism-based oxidative coupling. Multistage mass spectrometry (MS⁴) of the modified fragment in an ion trap/Orbitrap spectrometer demonstrated that <b>1</b> was coupled directly to heme. Use of a 10 amu window delivered the full isotopic envelope of each precursor ion to collision-induced dissociation, preserving definitive isotopic profiles for iron-containing fragments through successive steps of multistage mass spectrometry. Iron isotope signatures and accurate mass measurements supported the structural assignments. Crystallographic analysis confirmed linkage between the methyl substituent of the heme pyrrole D ring and the sulfur atom of <b>1</b>. The final orientation of <b>1</b> perpendicular to the plane of the heme ring suggested a mechanism consisting of two consecutive one-electron oxidations of <b>1</b> by MPO. Multistage mass spectrometry using stage-specific collision energies permits stepwise deconstruction of modifications of heme enzymes containing covalent links between the heme group and the polypeptide chain

Chromogenic Sensing of Biogenic Amines Using a Chameleon Probe and the Red−Green−Blue Readout of Digital Camera Images

We report on sensing spots containing an amine reactive chromogenic probe and a green fluorescent (amine insensitive) reference dye incorporated in a hydrogel matrix on a solid support. Such spots enable rapid and direct determination of primary amines and, especially, biogenic amines (BA). A distinct color change from blue to red occurs on dipping the test spots into a pH 9.0 sample containing primary amines. BAs can be determined in the concentration range from 0.01 to 10 mM within 15 min, enabling rapid, qualitative, and semiquantitative evaluation. In the “photographic” approach, the typically 4−7.5-fold increase in fluorescence intensity of the probe at 620 nm along with the constant green fluorescence at 515 nm of a reference dye are used for quantitation of BAs. The sensing spots are photoexcited with high-power 505 nm light-emitting diodes (LEDs) in a black box. A digital picture is acquired with a commercially available digital camera, and the color information is extracted via red−green−blue (RGB) readout. The ratio of the intensities of the red (signal) channel and the green (reference) channel yields pseudocolor pictures and calibration plots

Discovery of an <i>in Vivo</i> Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment

Recent studies in adipose tissue, pancreas, muscle, and macrophages suggest that MAP4K4, a serine/threonine protein kinase may be a viable target for antidiabetic drugs. As part of the evaluation of MAP4K4 as a novel antidiabetic target, a tool compound, <b>16</b> (PF-6260933) and a lead <b>17</b> possessing excellent kinome selectivity and suitable properties were delivered to establish proof of concept <i>in vivo</i>. The medicinal chemistry effort that led to the discovery of these lead compounds is described herein together with <i>in vivo</i> pharmacokinetic properties and activity in a model of insulin resistance

Safety of hospital discharge before return of bowel function after elective colorectal surgery

Background Ileus is common after colorectal surgery and is associated with an increased risk of postoperative complications. Identifying features of normal bowel recovery and the appropriateness for hospital discharge is challenging. This study explored the safety of hospital discharge before the return of bowel function. Methods A prospective, multicentre cohort study was undertaken across an international collaborative network. Adult patients undergoing elective colorectal resection between January and April 2018 were included. The main outcome of interest was readmission to hospital within 30 days of surgery. The impact of discharge timing according to the return of bowel function was explored using multivariable regression analysis. Other outcomes were postoperative complications within 30 days of surgery, measured using the Clavien-Dindo classification system. Results A total of 3288 patients were included in the analysis, of whom 301 (9 center dot 2 per cent) were discharged before the return of bowel function. The median duration of hospital stay for patients discharged before and after return of bowel function was 5 (i.q.r. 4-7) and 7 (6-8) days respectively (P &lt; 0 center dot 001). There were no significant differences in rates of readmission between these groups (6 center dot 6 versus 8 center dot 0 per cent; P = 0 center dot 499), and this remained the case after multivariable adjustment for baseline differences (odds ratio 0 center dot 90, 95 per cent c.i. 0 center dot 55 to 1 center dot 46; P = 0 center dot 659). Rates of postoperative complications were also similar in those discharged before versus after return of bowel function (minor: 34 center dot 7 versus 39 center dot 5 per cent; major 3 center dot 3 versus 3 center dot 4 per cent; P = 0 center dot 110). Conclusion Discharge before return of bowel function after elective colorectal surgery appears to be safe in appropriately selected patients