147 research outputs found
Design, Synthesis, and Biological Activity of 5\u27-Phenyl-1,2,5,6-tetrahydro-3,3\u27-bipyridine Analogues as Potential Antagonists of Nicotinic Acetylcholine Receptors
Starting from a known non-specific agonist (1) of nicotinic acetylcholine receptors (nAChRs), rationally guided structural-based design resulted in the discovery of a small series of 5′-phenyl-1,2,5,6-tetrahydro-3,3′-bipyridines (3a – 3e) incorporating a phenyl ring off the pyridine core of 1. The compounds were synthesized via successive Suzuki couplings on a suitably functionalized pyridine starting monomer 4 to append phenyl and pyridyl substituents off the 3- and 5-positions, respectively, and then make subsequent modifications on the flanking pyridyl ring to provide target compounds. Compound 3a is a novel antagonist which is highly selective for α3β4 nAChR (Ki = 123 nM) over the α4β2, and α7 receptors
Supervised geodesic propagation for semantic label transfer
Abstract. In this paper we propose a novel semantic label transfer method using supervised geodesic propagation (SGP). We use supervised learning to guide the seed selection and the label propagation. Given an input image, we first retrieve its similar image set from annotated databases. A Joint Boost model is learned on the similar image set of the input image. Then the recognition proposal map of the input image is inferred by this learned model. The initial distance map is defined by the proposal map: the higher probability, the smaller distance. In each iteration step of the geodesic propagation, the seed is selected as the one with the smallest distance from the undetermined superpixels. We learn a classifier as an indicator to indicate whether to propagate labels between two neighboring superpixels. The training samples of the indicator are annotated neighboring pairs from the similar image set. The geodesic distances of its neighbors are updated according to the combination of the texture and boundary features and the indication value. Experiments on three datasets show that our method outperforms the traditional learning based methods and the previous label transfer method for the semantic segmentation work
The influence of H2O or/and O2 introduction during the low-temperature gas-phase sulfation of organic COS + CS2 on the conversion and deposition of sulfur-containing species in the sulfated CeO2-OS catalyst for NH3-SCR
Herein, the typical components of blast furnace gas, including H O and O , were introduced to improve the NH -SCR activity of the sulfated CeO -OS catalyst during the gas-phase sulfation of organic COS + CS at 50 °C. The characterization results demonstrate that the introduction of O or H O during gas-phase sulfation enhances the conversion of organic COS + CS on a cubic fluorite CeO surface and reduces the formation of sulfur and sulfates in the catalyst, but decreases the BET surface area and pore volume of the sulfated CeO -OS catalyst. However, the introduction of O or H O during the gas-phase sulfation increases the molar ratios of Ce /(Ce + Ce ) and O /(O + O + O ) on the sulfated CeO -OS catalyst surface, thus promoting the formation of surface oxygen vacancies and chemisorbed oxygen, and these properties of the catalyst are further enhanced by the co-existence of O and H O. Furthermore, the reduction of sulfates formed under the action of O or H O decreases the weak acid sites of the sulfated CeO -OS catalyst, but the few and highly dispersive sulfates present stronger reducibility, and the proportion of medium-strong acid sites of the catalyst increases. These factors help to improve the NH -SCR activity of the sulfated CeO -OS catalyst. Thus, there exists a synergistic effect of H O and O introduction during gas-phase sulfation on the physical-chemical properties and catalytic performance of the sulfated CeO -OS catalyst by organic COS + CS at 50 °C
Generation of cardiomyocytes from human-induced pluripotent stem cells resembling atrial cells with ability to respond to adrenoceptor agonists
Atrial fibrillation (AF) is the most common chronic arrhythmia presenting a heavy disease burden. We report a new approach for generating cardiomyocytes (CMs) resembling atrial cells from human-induced pluripotent stem cells (hiPSCs) using a combination of Gremlin 2 and retinoic acid treatment. More than 40% of myocytes showed rod-shaped morphology, expression of CM proteins (including ryanodine receptor 2, α-actinin-2 and F-actin) and striated appearance, all of which were broadly similar to the characteristics of adult atrial myocytes (AMs). Isolated myocytes were electrically quiescent until stimulated to fire action potentials with an AM profile and an amplitude of approximately 100 mV, arising from a resting potential of approximately −70 mV. Single-cell RNA sequence analysis showed a high level of expression of several atrial-specific transcripts including NPPA, MYL7, HOXA3, SLN, KCNJ4, KCNJ5 and KCNA5. Amplitudes of calcium transients recorded from spontaneously beating cultures were increased by the stimulation of α-adrenoceptors (activated by phenylephrine and blocked by prazosin) or β-adrenoceptors (activated by isoproterenol and blocked by CGP20712A). Our new approach provides human AMs with mature characteristics from hiPSCs which will facilitate drug discovery by enabling the study of human atrial cell signalling pathways and AF. This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’
ENHANCED EXTERNAL COUNTERPULSATION REDUCES VASCULAR INFLAMMATION PROMOTED BY HYPERCHOLESTEROLEMIA
Review of solid–liquid phase change materials and their encapsulation technologies
Various types of solid–liquid phase change materials (PCMs) have been reviewed for thermal energy storage applications. The review has shown that organic solid–liquid PCMs have much more advantages and capabilities than inorganic PCMs but do possess low thermal conductivity and density as well as being flammable. Inorganic PCMs possess higher heat storage capacities and conductivities, cheaper and readily available as well as being non-flammable, but do experience supercooling and phase segregation problems during phase change process. The review has also shown that eutectic PCMs have unique advantage since their melting points can be adjusted. In addition, they have relatively high thermal conductivity and density but they possess low latent and specific heat capacities. Encapsulation technologies and shell materials have also been examined and limitations established. The morphology of particles was identified as a key influencing factor on the thermal and chemical stability and the mechanical strength of encapsulated PCMs. In general, in-situ polymerization method appears to offer the best technological approach in terms of encapsulation efficiency and structural integrity of core material. There is however the need for the development of enhancement methods and standardization of testing procedures for microencapsulated PCMs
Molecular epidemiology of hydropericardium syndrome outbreak-associated serotype 4 fowl adenovirus isolates in central China
31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two
Background
The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd.
Methods
We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background.
Results
First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001).
Conclusions
In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
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