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51.
Lalisa Stutts Prof. Aaron P. Esser‐Kahn 《Chembiochem : a European journal of chemical biology》2015,16(12):1744-1748
The spatial and temporal aspects of immune cell signaling are key parameters in defining the magnitude of an immune response. Toll‐like receptors (TLRs) on innate immune cells are important in the early detection of pathogens and initiation of an immune response. Controlling the spatial and temporal signaling of TLRs would enable further study of immune synergies and assist in the development of new vaccines. Here, we show a light‐based method for the spatial control of TLR4 signaling. A TLR4 agonist, pyrimido[5,4‐b]indole, was protected with a cage at a position critical for receptor binding. This afforded a photocontrollable agonist that was inactive while caged, yet effected NF‐κB activity in cells following UV photocontrolled deprotection. We demonstrated spatial control of NF‐κB activation within a population of cells by treating all cells with the caged TLR4 agonist and constraining light exposure and consequent activation to a region of interest. 相似文献
52.
Aaron J. DeBono Jin Han Xie Dr. Sabatino Ventura Prof. Colin W. Pouton Dr. Ben Capuano Prof. Peter J. Scammells 《ChemMedChem》2012,7(12):2122-2133
Noscapine is a phthalideisoquinoline alkaloid isolated from the opium poppy Papaver somniferum. It has long been used as an antitussive agent, but has more recently been found to possess microtubule‐modulating properties and anticancer activity. Herein we report the synthesis and pharmacological evaluation of a series of 6′‐substituted noscapine derivatives. To underpin this structure–activity study, an efficient synthesis of N‐nornoscapine and its subsequent reduction to the cyclic ether derivative of N‐nornoscapine was developed. Reaction of the latter with a range of alkyl halides, acid chlorides, isocyanates, thioisocyanates, and chloroformate reagents resulted in the formation of the corresponding N‐alkyl, N‐acyl, N‐carbamoyl, N‐thiocarbamoyl, and N‐carbamate derivatives, respectively. The ability of these compounds to inhibit cell proliferation was assessed in cell‐cycle cytotoxicity assays using prostate cancer (PC3), breast cancer (MCF‐7), and colon cancer (Caco‐2) cell lines. Compounds that showed activity in the cell‐cycle assay were further evaluated in cell viability assays using PC3 and MCF‐7 cells. 相似文献
53.
Aaron D. Krabill Hao Chen Dr. Sajjad Hussain Dr. Chao Feng Dr. Ammara Abdullah Prof. Chittaranjan Das Dr. Uma K. Aryal Prof. Carol Beth Post Prof. Michael K. Wendt Prof. Paul J. Galardy Prof. Daniel P. Flaherty 《Chembiochem : a European journal of chemical biology》2020,21(5):712-722
The deubiquitinase (DUB) ubiquitin C-terminal hydrolase L1 (UCHL1) is expressed primarily in the central nervous system under normal physiological conditions. However, UCHL1 is overexpressed in various aggressive forms of cancer with strong evidence supporting UCHL1 as an oncogene in lung, glioma, and blood cancers. In particular, the level of UCHL1 expression in these cancers correlates with increased invasiveness and metastatic behavior, as well as poor patient prognosis. Although UCHL1 is considered an oncogene with potential as a therapeutic target, there remains a significant lack of useful small-molecule probes to pharmacologically validate in vivo targeting of the enzyme. Herein, we describe the characterization of a new covalent cyanopyrrolidine-based UCHL1 inhibitory scaffold in biochemical and cellular studies to better understand the utility of this inhibitor in elucidating the role of UCHL1 in cancer biology. 相似文献
54.
Jonathan H. Christian Kevin M. Fox Aaron L. Washington II 《International Journal of Applied Glass Science》2017,8(2):158-164
The microwave heating of a crystal-free and a partially trevorite-crystallized nuclear waste glass simulant was evaluated. Our results show that a 500-mg monolith of partially crystallized waste glass can be heated from room temperature to above 1600°C within 2 minutes using a single-mode, highly focused, 2.45-GHz microwave, operating at 300 W. Using X-ray diffraction measurements, we show that trevorite is no longer detectable after irradiation and thermal quenching. When a crystal-free analog of the same waste glass simulant composition was exposed to the same microwave radiation, it could not be heated above 450°C regardless of the heating time. The reduction in crystalline content achieved by selectively heating spinels in the presence of glass suggests that microwave-specific heating should be further explored as a technique for remediating crystal accumulation in a glass melt. 相似文献
55.
Jagadeesh Nagendra Manda Milica Markovic Prof. Ellen M. Zimmermann Prof. Shimon Ben-Shabat Prof. Arik Dahan Prof. Aaron Aponick 《ChemMedChem》2020,15(17):1639-1644
Novel phospholipid (PL)-cyclosporine conjugates were prepared and studied as potential prodrugs for inflammatory bowel disease (IBD). Our approach relies on phospholipase A2 (PLA2), which is overexpressed in the inflamed intestinal tissues, as the prodrug activator to potentially release cyclosporine at the site of inflammation. PL-cyclosporine prodrug conjugates with methylene linkers of various lengths between the sn-2 position of the PL and cyclosporine were synthesized and evaluated for in vitro activation. Surprisingly, despite previous work indicating that conjugates with six methylene linkers between the lipid and drug would suffer rapid enzymatic hydrolysis, with cyclosporine this was not observed. However, compounds with longer linkers (n=10, 12 methylene units) display complete release of the drug by PLA2-catalyzed hydrolysis, thus demonstrating the importance and profound impact of structural fine-tuning. This study represents a proof-of-concept for our hypothesis and a first step towards a truly targeted IBD treatment with cyclosporine that could be administered throughout the GI tract. 相似文献
56.
Kinetic study of crude oil-to-chemicals via steam-enhanced catalytic cracking in a fixed-bed reactor
Qi Xu Aaron C. Akah Mansour AlHerz Abdullah Aitani Ziyauddin S. Qureshi M. Abdul Bari Siddiqui Nabeel Abo-Ghander 《加拿大化工杂志》2023,101(7):4042-4053
This study presents new experimental results on the direct conversion of crude oil to chemicals via steam-enhanced catalytic cracking. We have organized the experimental results with a kinetics model using crude oil and steam co-feed in a fixed-bed flow reactor at reaction temperatures of 625, 650, and 675°C over the Ce-Fe/ZSM-5 catalyst. The model let us find optimum conditions for crude oil conversion, and the order of the steam cracking reaction was 2.0 for heavy oil fractions and 1.0 for light oil fractions. The estimated activation energies for the steam cracking reactions ranged between 20 and 200 kJ/mol. Interestingly, the results from kinetic modelling helped in identifying a maximum yield of light olefins at an optimized residence time in the reactor at each temperature level. An equal propylene and ethylene yield was observed between 650 and 670°C, indicating a transition from dominating catalytic cracking at a lower temperature to a dominating thermal cracking at a higher temperature. The results illustrate that steam-enhanced catalytic cracking can be utilized to effectively convert crude oil into basic chemicals (52.1% C2-C4 light olefins and naphtha) at a moderate severity (650°C) as compared to the conventional high-temperature steam cracking process. 相似文献
57.
A multiphase chemical equilibrium algorithm is developed which can be used with aqueous systems. The algorithm uses an average chemical potential for each species as a reference chemical potential. Incipient phases can be identified and their proximity to appearance can be determined through their tangent plane distance. Illustrative examples include the calculation of CaSO4 solubility and the calculation of vapour pressures above an SO2‐NaCl‐H2O system, including the prediction of a three‐phase equilibrium. The algorithm proved robust and versatile. The appearance of incipient phases was easily tracked. Future work needs to be done to optimize damping/acceleration coefficients in the calculations. 相似文献
58.
A generalized approach for the determination of yield stress by slump and slump flow 总被引:2,自引:0,他引:2
The slump test (ASTM C-143) is the most common method for assessing the flow properties of fresh concrete. Although slump provides a qualitative measure of workability, the relationship between slump and more quantitative rheological parameters is not fully understood. In this study, a dimensionless model relating slump to yield stress is further developed and generalized as a function of cone geometry. Yield stress measurements of cement paste are performed using a vane technique and compared with slump measurements using cylindrical and conical geometries. The cylindrical slump model is in excellent agreement with the experimental yield stress data obtained using the vane method. The data for the conical slump measurements fit the cylindrical model at low yield stress values, but the results deviate as the yield stress of the paste increases. Most of the other slump models available in the literature, including finite element models, predict the same yield stress for a given slump when converted to dimensionless form. The results suggest that a fundamental relationship exists between yield stress and slump that is independent of the material under investigation and largely independent of cone geometry. 相似文献
59.
Front Cover: A Possible Path to Prebiotic Peptides Involving Silica and Hydroxy Acid‐Mediated Amide Bond Formation (ChemBioChem 18/2018) 下载免费PDF全文
60.
William J. R. Gilbert Stephen J. Johnson Jyun‐Syung Tsau Jenn‐Tai Liang Aaron M. Scurto 《应用聚合物科学杂志》2017,134(10)
Polyacrylamides are often used in water‐based hydraulic fracturing for natural gas and oil production. However, residual polymer remaining in the fractured rock can limit production. A novel approach for degrading partially hydrolyzed polyacrylamide (HPAM) was investigated using hydrogen peroxide and horseradish peroxidase (HRP). This sustainable HRP/H2O2 system degraded the polymer in solution, reducing its viscosity in both pure water and brine solutions. Molecular weight measurements confirmed that the viscosity reduction was due to a significant degradation of the polymer backbone and not primarily by other mechanisms such as amide hydrolysis or rearrangement, and so forth. The reduction in viscosity and molecular weight was first order with respect to H2O2 concentration. The kinetics of viscosity reduction and molecular weight are closely correlated which would allow the quicker and simpler viscosity method to help engineer future processes. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44560. 相似文献