In situ measurements of human cough aerosol hygroscopicity

The airborne dynamics of respiratory droplets, and the transmission routes of pathogens embedded within them, are governed primarily by the diameter of the particles. These particles are composed of the fluid which lines the respiratory tract, and is primarily mucins and salts, which will interact with the atmosphere and evaporate to reach an equilibrium diameter. Measuring organic volume fraction (OVF) of cough aerosol has proved challenging due to large variability and low material volume produced after coughing. Here, the diametric hygroscopic growth factors (GF) of the cough aerosol produced by healthy participants were measured in situ using a rotating aerosol suspension chamber and a humidification tandem differential mobility analyser. Using hygroscopicity models, it was estimated that the average OVF in the evaporated cough aerosol was 0.88 ± 0.07 and the average GF at 90% relative humidity (RH) was 1.31 ± 0.03. To reach equilibrium in dry air the droplets will reduce in diameter by a factor of approximately 2.8 with an evaporation factor of 0.36 ± 0.05. Hysteresis was observed in cough aerosol at RH = ∼35% and RH = ∼65% for efflorescence and deliquescence, respectively, and may depend on the OVF. The same behaviour and GF were observed in nebulized bovine bronchoalveolar lavage fluid.     

Improving storability,physiological disorders,and antioxidant properties of ‘Bartlett’ and ‘d’Anjou’ pears (Pyrus communis L.) by pre-harvest 1-methylcyclopropene spraying

Ethylene continues to be a major factor influencing quality of European pears during storage. Although research has been done on the effect of pre-harvest 1-methylcyclopropene (1-MCP) on physiological characteristics in pears, a full understanding of cultivar response and antioxidant metabolism remains elusive. Spraying 1-MCP on ‘Bartlett’ and ‘d’Anjou’ pears was studied with respect to physiology, storage and eating quality, disorders, and antioxidant properties at two harvest date (H1 and H2) during storage and ripening. Treatment with 1-MCP extended the harvest window of ‘Bartlett’ and ‘d’Anjou’ pears 3 and 4 days, respectively, without reducing storage or eating quality. Treatment with 1-MCP reduced ethylene production (EPR) and respiration rates (RR), maintained fruit firmness and green colour during storage and retarded development of desirable melting texture in both cultivars. Additionally, 1-MCP lowered the incidence of disorders by alleviating membrane lipid peroxidation, retaining high total flavonoids (TF) and antioxidant capacity, and enhancing superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity in both cultivars. Overall, pre-harvest 1-MCP applications could extend storage time of ‘Bartlett’ and ‘d’Anjou’ pears to 5 and 6 months, respectively, at −1.1 ± 0.5 °C, by reducing ethylene synthesis and enhancing antioxidant metabolism.     

Automatic breast tumor detection in ABVS images based on convolutional neural network and superpixel patterns

Breast cancer is one of the most common female malignancies, as well as the second leading cause of mortality for women. Early detection and treatment can dramatically decrease the mortality rate. Recently, automated breast volume scanner (ABVS) has become one of the most frequently used diagnose methods for breast tumor screening because of its operator-independent and reproducible advantages. However, it is a challenging job to obtain the tumors’ accurate locations and shapes by reviewing hundreds of ABVS slices. In this paper, a novel computer-aided detection (CADe) system is developed to reduce clinicians’ reading time and improve the efficiency. The CADe system mainly contains three parts: tumor candidate acquisition, false-positive reduction and tumor segmentation. Firstly, a local phase-based approach is built to obtain breast tumor candidates for further recognition. Subsequently, a convolutional neural network (CNN) is applied to reduce false positives (FPs). The introduction of CNN can help to avoid complicated feature extraction as well as elevate the accuracy and efficiency. Finally, superpixel-based segmentation is used to outline the breast tumor. Here, superpixel-based local binary pattern (SLBP) is proposed to assist the segmentation, which improves the performance. The methods were evaluated on a clinical ABVS dataset whose abnormal cases were manually labeled by an experienced radiologist. The experiment results were mainly composed of two parts. At the FP reduction stage, the proposed CNN achieved 100% and 78.12% sensitivity with FPs/case of 2.16 and 0. At the segmentation stage, our SLBP obtained 82.34% true positive, 15.79% false positive and 83.59% Dice similarity. In summary, the proposed CADe system demonstrated promising potential to detect and outline breast tumors in ABVS images.

     

Discovery of Affinity-Based Probes for Btk Occupancy Assays

Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon.