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Pilgrim S Kociok-Köhn G Lloyd MD Lewis SE 《Chemical communications (Cambridge, England)》2011,47(16):4799-4801
Microbial 1,2-dihydroxylation of sodium benzoate permits the rapid construction of novel inositol-amino acid hybrid structures. Both β- and γ-amino acids are accessible by means of an acylnitroso Diels-Alder cycloaddition. 相似文献
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Jackson PJ Douglas NR Chai B Binkley J Sidow A Barsh GS Millhauser GL 《Chemistry & biology》2006,13(12):1297-1305
Agouti (ASIP) and Agouti-related protein (AgRP) are endogenous antagonists of melanocortin receptors that play critical roles in the regulation of pigmentation and energy balance, respectively, and which arose from a common ancestral gene early in vertebrate evolution. The N-terminal domain of ASIP facilitates antagonism by binding to an accessory receptor, but here we show that the N-terminal domain of AgRP has the opposite effect and acts as a prodomain that negatively regulates antagonist function. Computational analysis reveals similar patterns of evolutionary constraint in the ASIP and AgRP C-terminal domains, but fundamental differences between the N-terminal domains. These studies shed light on the relationships between regulation of pigmentation and body weight, and they illustrate how evolutionary structure function analysis can reveal both unique and common mechanisms of action for paralogous gene products. 相似文献
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H Pilgrim P Tappenden J Chilcott M Bending P Trueman A Shorthouse J Tappenden 《The Journal of the Operational Research Society》2009,60(10):1305-1314
Colorectal cancer includes cancerous growths in the colon, rectum and appendix and affects around 30?000 people in England each year. Maximizing health benefits for patients with colorectal cancer requires consideration of costs and outcomes across the whole service. In an era of scarce healthcare resources, there is a need to consider not only whether technologies and services may be considered clinically effective, but also whether they are cost-effective, that is, whether they represent value for money for the health service. Through the development of a whole disease model, it is possible to evaluate the cost-effectiveness of a range of options for service development consistently within a common framework. Discrete event simulation has been used to model the complete colorectal cancer patient pathway from patient presentation through to referral and diagnosis, treatment, follow-up, potential recurrence, treatment of metastases and end-of-life care. This simulation model has been used to examine the potential cost-effectiveness of different options for change across the entire colorectal cancer pathway. This paper provides an empirical demonstration of the potential application of modelling entire disease areas to inform clinical policy and resource allocation decision-making. 相似文献
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Among Thurston maps (orientation-preserving, postcritically finite branched coverings of the 2-sphere to itself), those that arise as subdivision maps of a finite subdivision rule form a special family. For such maps, we investigate relationships between various notions of expansion—combinatorial, dynamical, algebraic, and coarse-geometric. 相似文献
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Short and Efficient Syntheses of Protoberberine Alkaloids using Palladium‐Catalyzed Enolate Arylation
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Alice E. Gatland Dr. Ben S. Pilgrim Dr. Panayiotis A. Procopiou Prof. Timothy J. Donohoe 《Angewandte Chemie (International ed. in English)》2014,53(52):14555-14558
A concise synthesis of the biologically active alkaloid berberine is reported, and a versatile palladium‐catalyzed enolate arylation is used to form the isoquinoline core. The overall yield of 50 % is a large improvement over the single, previous synthesis. By design, this modular route allows the rapid synthesis of other members of the protoberberine family (e.g., pseudocoptisine and palmatine) by substitution of the readily available aryl bromide and ketone coupling partners. Moreover, by combining enolate arylation with in situ functionalization, substituents can be rapidly and regioselectively introduced at the alkaloid C13 position, as demonstrated by the total synthesis of dehydrocorydaline. The avoidance of electrophilic aromatic substitution reactions to make the isoquinoline allows direct access to analogues possessing more varied electronic properties, such as the fluorine‐containing derivative synthesized here. 相似文献
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Gerardo Ochoa Corey D. Pilgrim Michele N. Martin Christopher A. Colla Peter Klavins Prof. Matthew P. Augustine Prof. William H. Casey 《Angewandte Chemie (International ed. in English)》2015,54(51):15444-15447
Nuclear spin relaxation rates of 2H and 139La in LaCl3+2H2O and La(ClO4)3+2H2O solutions were determined as a function of pressure in order to demonstrate a new NMR probe designed for solution spectroscopy at geochemical pressures. The 2H longitudinal relaxation rates (T1) vary linearly to 1.6 GPa, consistent with previous work at lower pressures. The 139La T1 values vary both with solution chemistry and pressure, but converge with pressure, suggesting that the combined effects of increased viscosity and enhanced rates of ligand exchange control relaxation. This simple NMR probe design allows experiments on aqueous solutions to pressures corresponding roughly to those at the base of the Earth’s continental crust. 相似文献
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Ararimeh Aiyejina Dhurjati Prasad Chakrabarti Angelus Pilgrim M.K.S. Sastry 《International Journal of Multiphase Flow》2011
The gelling of waxy crudes and the deposition of wax on the inner walls of subsea crude oil pipelines present a costly problem in the production and transportation of oil. The timely removal of deposited wax is required to address the reduction in flow rate that it causes, as well as to avoid the eventual loss of a pipeline in the event that it becomes completely clogged. In order to understand this problem and address it, significant research has been done on the mechanisms governing wax deposition in pipelines in order to model the process. Furthermore, methods of inhibiting the formation of wax on pipeline walls and of removing accumulated wax have been studied to find the most efficient and cost-effective means of maintaining pipelines prone to wax deposition. This paper seeks to review the current state of research into these areas, highlighting what is so far understood about the mechanisms guiding this wax deposition, and how this knowledge can be applied to modelling and providing solutions to this problem. 相似文献
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Dallanegra R Pilgrim BS Chaplin AB Donohoe TJ Weller AS 《Dalton transactions (Cambridge, England : 2003)》2011,40(25):6626-6628
The metal-promoted dehydrogenation of cyclic thioethers S(C(5)H(9))(R) (R = C(5)H(9), Ph) to give the corresponding cycloalkenes, S(C(5)H(7))(R), using the [Rh{Ph(2)P(CH(2))(3)PPh(2)}](+) fragment is reported. 相似文献