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排序方式: 共有2244条查询结果,搜索用时 46 毫秒
1.
Dr. Kevin Neumann Alessia Gambardella Prof. Mark Bradley 《Chembiochem : a European journal of chemical biology》2019,20(7):872-876
Traditionally, prodrug activation has been limited to enzymatic triggers or gross physiological aberrations, such as pH, that offer low selectivity and control over dosage. In recent years, the field of prodrug activation chemistry has been transformed by the use of bioorthogonal reactions that can be carried out under biological conditions at sub-millimolar concentrations, with the tetrazine-mediated inverse electron demand Diels–Alder reaction amongst the most recognised. Their high reaction rates, chemoselectivity and excellent biocompatibility make tetrazines ideal small molecules for activating prodrugs. Recently the tetrazine moiety has been used as a prodrug for a pyridazine thus broadening the scope of prodrug systems. This article discusses the concept of using tetrazines as small-molecule activators for prodrugs, and provides an overview of tetrazine-based prodrug systems, with a particular focus on the recently reported prodrug–prodrug activation strategy. 相似文献
2.
Dr. Raysa Khan Tareque Dr. Storm Hassell-Hart Dr. Tobias Krojer Dr. Anthony Bradley Dr. Srikannathasan Velupillai Dr. Romain Talon Dr. Michael Fairhead Dr. Iain J. Day Kamlesh Bala Dr. Robert Felix Dr. Paul D. Kemmitt Prof. Paul Brennan Prof. Frank von Delft Dr. Laura Díaz Sáez Prof. Kilian Huber Prof. John Spencer 《ChemMedChem》2020,15(24):2513-2520
Combined photochemical arylation, “nuisance effect” (SNAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with SNAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified. 相似文献
3.
In a study of conversion from CH4 to H2, jet flame characteristics of these gases and their blends are compared on a burner diameter scale of mm. Low velocity H2 and CH4 jets, burned on pipes of different diameters, indicate higher blow-off limits for H2, but lower heat release rates, a consequence of its lower specific energy. Compensation for this might be obtained through increased H2 flow velocity, or a small increase in pipe diameter. Blended CH4/H2 flames have lower heat release rates than CH4 alone, yet small proportions of H2, with CH4 might still be burned, on a CH4 burner. Throughout, fundamental understanding is enhanced through two dimensionless groups: laminar flame thickness normalised by burner diameter, δk/D, and the dimensionless flow number, U1. These suggest an optimal role for H2 combustion, utilizing its high acoustic and blow-off velocities, in high intensity, subsonic, combustors, at low δk/D, and high U1. 相似文献
4.
Bradley J. Smith Brandon S. Harris Tyler J. Harris Lisa A. LaBudde Cari-Ann Hayer 《Journal of Great Lakes research》2018,44(4):798-804
The Asian clam Corbicula fluminea is among the most prolific aquatic invaders in the world; but in colder mid-latitude areas, like the Laurentian Great Lakes, their population expansion has likely been limited by poor overwinter survival. In these areas, Asian clams are typically found in thermal refugia like warmwater discharges from industrial facilities. We sought to identify the current extent of Asian clam populations in Lake Michigan and waters immediately adjacent to it, specifically at locations most likely to harbor overwintering populations – industrial warmwater discharges. During April–May 2017, we surveyed 17 locations around Lake Michigan. Evidence of Asian clam populations was found at four sites, though live specimens (n?=?3) were only found at the Indiana Harbor Ship Canal in East Chicago, IN. Shells or fragments of shells were found at Green Bay, WI, Waukegan, IL, and Port Sheldon, MI. Our findings indicate that although Asian clams are present in Lake Michigan, they are relatively rare, and remain isolated to a few small pockets of over-wintering habitat. 相似文献
5.
Phil Symonds David Rees Zornitza Daraktchieva Neil McColl Jane Bradley Ian Hamilton Michael Davies 《Indoor air》2019,29(5):854-864
Exposure to radon gas is the second leading cause of lung cancer worldwide behind smoking. Changing the energy characteristics of a dwelling can influence both its thermal and ventilative properties, which can affect indoor air quality. This study uses radon measurements made in 470 689 UK homes between 1980 and 2015, linked to dwelling information contained within the Home Energy Efficiency Database (HEED). The linked dataset, the largest of its kind, was used to analyze the association of housing and energy performance characteristics with indoor radon concentrations in the UK. The findings show that energy efficiency measures that increase the airtightness of properties are observed to have an adverse association with indoor radon levels. Homes with double glazing installed had radon measurements with a significantly higher geometric mean, 67% (95% CI: 44, 89) greater than those without a recorded fabric retrofit. Those with loft insulation (47%, 95% CI: 26, 69) and wall insulation (32%, 95% CI: 11, 53) were also found to have higher radon readings. Improving the energy performance of the UK's housing stock is vital in meeting carbon emission reduction targets. However, compromising indoor air quality must be avoided through careful assessment and implementation practices. 相似文献
6.
Zhuyun Li Cory M. Dungan Bradley Carrier Todd C. Rideout David L. Williamson 《Lipids》2014,49(12):1193-1201
The mammalian target of rapamycin (mTOR) signaling pathway is hyperactive in liver, adipose and skeletal muscle tissues of obese rodents. Alpha‐lipoic acid (αLA) has been well accepted as a weight‐loss treatment, though there are limited studies on its effect on mTOR signaling in high‐fat fed, obese rodents. Therefore, the goal of this study was to determine mTOR signaling and oxidative protein alterations in skeletal muscle of high‐fat fed, obese rats after αLA supplementation. Phosphorylation of the mTOR substrate, eukaryotic initiation factor (eIF) 4E‐binding protein 1 (4E‐BP1) and eIF4B were significantly reduced (p < 0.05) in muscle from αLA supplemented rats. Activation of AMP‐activated protein kinase (AMPK), an mTOR inhibitory kinase, was higher (p < 0.05) in the αLA group. Protein expression of markers of oxidative metabolism, acetyl CoA carboxylase (ACC), cytochrome c oxidase IV (COX IV), peroxisome proliferator‐activated receptor (PPAR), and PPAR gamma coactivator 1‐alpha (PGC‐1α) were significantly higher (p < 0.05) after αLA supplementation compared to non‐supplemented group. Our findings show that αLA supplementation limits the negative ramifications of consuming a high fat diet on skeletal muscle markers of oxidative metabolism and mTORC1 signaling. 相似文献
7.
Bradley F. Habenicht Dieh Teng Lymarie Semidey-Flecha David S. Sholl Ye Xu 《Topics in Catalysis》2014,57(1-4):69-79
To explore the possibility of using the graphene moiré superstructure formed on Ru(0001) (g/Ru(0001)) as a template to self-assemble super-lattices of metal nanoparticles as model catalysts, it is desirable to know the minimum-energy adsorption sites, adsorption energies, and diffusion properties of small metal species on this surface. Toward that end, density functional theory calculations have been carried out to investigate the adsorption and diffusion of 18 4d (Y–Ag) and 5d (La–Au) transition metal adatoms on g/Ru(0001), using small surface models representing different regions of the g/Ru(0001) surface. For each adatom, adsorption is the strongest in the fcc region and the weakest in the mound region of the moiré. Diffusion within the fcc region is facile for most adatoms, but an additional barrier is imposed by the corrugation of the graphene moiré for traversing between neighboring fcc regions. Overall, the earlier 4d and 5d metal adatoms have stronger adsorption energies and higher diffusion barriers on g/Ru(0001) than the later ones. The results are then interpreted to provide a better understanding of the conditions necessary to achieve dense super-lattices of monodisperse metal clusters on g/Ru(0001). 相似文献
8.
Immune and Anticancer Responses Elicited by Fully Synthetic Aberrantly Glycosylated MUC1 Tripartite Vaccines Modified by a TLR2 or TLR9 Agonist 下载免费PDF全文
Dr. Abu‐Baker M. Abdel‐Aal Dr. Vani Lakshminarayanan Dr. Pamela Thompson Nitin Supekar Judy M. Bradley Dr. Margreet A. Wolfert Prof. Dr. Peter A. Cohen Prof. Dr. Sandra J. Gendler Prof. Dr. Geert‐Jan Boons 《Chembiochem : a European journal of chemical biology》2014,15(10):1508-1513
The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O‐linked saccharides. Although tumor‐associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T‐lymphocytes (CTLs) and ADCC‐mediating antibodies specific for the tumor form of MUC1. We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous Thelper peptide, and a TLR2 (Pam3CysSK4) or TLR9 (CpG‐ODN 1826) agonist. It was found that the Pam3CysSK4‐containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor‐associated glycopeptide. The unique adjuvant properties of Pam3CysSK4, which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor‐specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1 . 相似文献
9.
Surin K. Mong Alexander A. Vinogradov Mark D. Simon Prof. Bradley L. Pentelute 《Chembiochem : a European journal of chemical biology》2014,15(5):721-733
We report the convergent total synthesis of two proteins: DARPin pE59 and Bacillus amyloliquefaciens RNase (Barnase). Leveraging our recently developed fast‐flow peptide‐synthesis platform, we rapidly explored numerous conditions for the assembly of long polypeptides, and were able to mitigate common side reactions, including deletion and aspartimide products. We report general strategies for improving the synthetic quality of difficult peptide sequences with our system. High‐quality protein fragments produced under optimal synthetic conditions were subjected to convergent native chemical ligation, which afforded native full‐length proteins after a final desulfurization step. Both DARPin and Barnase were folded and found to be as active as their recombinant analogues. 相似文献
10.
Quintin Bradley 《Housing Studies》2020,35(2):333-352
AbstractThe aim of this article is to reclaim the democratic legitimacy of self-selecting and informed publics in citizen engagement in housing development planning. It argues for an approach to public participation in which the issues, and the articulation of conflicting attachments to those issues, are understood as the occasion for democratic politics. The article illustrates this approach in an analysis of the use of direct democracy to decide housing allocations in the policy of neighbourhood planning in England. Drawing on literature from Science and Technology Studies and actor–network theory, it evidences the public articulation of house-building as a matter of concern and identifies the agency of housing in enrolling publics, translating interests and in fostering debate and contention. It concludes that the articulation of conflicting interests can deepen democratic engagement in housing development planning and open up the exclusions through which this issue is currently framed. 相似文献