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71.
The study of pre-translational effects (ionization, tautomerization) and post-translational effects (methylation) of adenine and thymine has only recently been the focus of some studies. These effects can potentially help regulate gene expression as well as potentially disrupt normal gene function. Because of this wide array of roles, greater insight into these effects in deoxyribonucleic acids (DNA) are paramount. There has been considerable research of each phenomenon (tautomerization, methylation and ionization) individually. In this work, we attempt to shed light upon the pre-translational effects and post translational effects of adenine and thymine by investigating the electron affinities (EAs) and ionization potentials (IPs) of the major and minor tautomers and their methyl derivatives. We performed all calculations using the density functional theory (DFT) B3LYP functional accompanied with 6-311G(d,p), 6-311+G(d,p) and 6-311++G(df,pd) basis sets. Our results reveal that the thymine tautomer has a higher EA and IP than the adenine tautomers. The higher EA suggests that an electron that attaches to the AT base pair would predominately attach to the thymine instead of adenine. The higher IP would suggest that an electron that is removed from the AT base pair would be predominately removed from the adenine within the base pair. Understanding how tautomerization, ionization and methylation differences change effects, discourages, or promotes one another is lacking. In this work, we begin the steps of integrating these effects with one another, to gain a greater understanding of molecular changes in DNA bases. 相似文献
72.
73.
Noel M. Harrison Pat McDonnell Liam Mullins Niall Wilson Denis O’Mahoney Peter E. McHugh 《Biomechanics and modeling in mechanobiology》2013,12(2):225-241
Trabecular bone tissue failure can be considered as consisting of two stages: damage and fracture; however, most failure analyses of 3D high-resolution trabecular bone samples are confined to damage mechanisms only, that is, without fracture. This study aims to develop a computational model of trabecular bone consisting of an explicit representation of complete failure, incorporating damage criteria, fracture criteria, cohesive forces, asymmetry and large deformation capabilities. Following parameter studies on a test specimen, and experimental testing of bone sample to complete failure, the asymmetric critical tissue damage and fracture strains of ovine vertebral trabecular bone were calibrated and validated to be compression damage ?1.16 %, tension damage 0.69 %, compression fracture ?2.91 % and tension fracture 1.98 %. Ultimate strength and post–ultimate strength softening were captured by the computational model, and the failure of individual struts in bending and shear was also predicted. This modelling approach incorporated a cohesive parameter that provided a facility to calibrate ductile–brittle behaviour of bone tissue in this non-linear geometric and non-linear constitutive property analyses tool. Finally, the full accumulation of tissue damage and tissue fracture has been monitored from range of small magnitude (normal daily loading) through to specimen yielding, ultimate strength and post–ultimate strength softening. 相似文献
74.
Carla Manuela Abreu Ramesh Kumar Danielle Hamilton Andrew William Dawdy Kevin Creavin Sarah Eivers Karen Finn Jeremy Lynn Balsbaugh Rosemary O'Connor Patrick A. Kiely Jeffrey Shabanowitz Donald F. Hunt Muriel Grenon Noel Francis Lowndes 《PLoS genetics》2013,9(4)
The mediators of the DNA damage response (DDR) are highly phosphorylated by kinases that control cell proliferation, but little is known about the role of this regulation. Here we show that cell cycle phosphorylation of the prototypical DDR mediator Saccharomyces cerevisiae Rad9 depends on cyclin-dependent kinase (CDK) complexes. We find that a specific G2/M form of Cdc28 can phosphorylate in vitro the N-terminal region of Rad9 on nine consensus CDK phosphorylation sites. We show that the integrity of CDK consensus sites and the activity of Cdc28 are required for both the activation of the Chk1 checkpoint kinase and its interaction with Rad9. We have identified T125 and T143 as important residues in Rad9 for this Rad9/Chk1 interaction. Phosphorylation of T143 is the most important feature promoting Rad9/Chk1 interaction, while the much more abundant phosphorylation of the neighbouring T125 residue impedes the Rad9/Chk1 interaction. We suggest a novel model for Chk1 activation where Cdc28 regulates the constitutive interaction of Rad9 and Chk1. The Rad9/Chk1 complex is then recruited at sites of DNA damage where activation of Chk1 requires additional DDR–specific protein kinases. 相似文献
75.
Multi-species compartment epidemic models, such as the multi-species susceptible–infectious–recovered (SIR) model, are extensions of the classic SIR models, which are used to explore the transient dynamics of pathogens that infect multiple hosts in a large population. In this article, we propose a dynamical Bayesian hierarchical SIR (HSIR) model, to capture the stochastic or random nature of an epidemic process in a multi-species SIR (with recovered becoming susceptible again) dynamical setting, under hidden mass balance constraints. We call this a Bayesian hierarchical multi-species SIR (MSIRB) model. Different from a classic multi-species SIR model (which we call MSIRC), our approach imposes mass balance on the underlying true counts rather than, improperly, on the noisy observations. Moreover, the MSIRB model can capture the discrete nature of, as well as uncertainties in, the epidemic process. 相似文献
76.
77.
The miniaturized wireless inertial measurement unit (IMU) technology and algorithms presented herein promote rapid and accurate predictions of the center-of-rotation (CoR) for ball/spherical joints. The algorithm improves upon existing IMU-based methods by directly utilizing the measured acceleration and angular velocity provided by the IMU to deduce the CoR in lieu of relying on error-prone velocity and position estimates. Results demonstrate that this new method resolves the position of the CoR to within a 3 mm sphere of the true CoR determined by a precision coordinate measuring machine. Such accuracy may render this method attractive for broad use in field, laboratory and clinical settings requiring non-invasive and rapid estimates of joint CoR. 相似文献
78.
William E. Schrank Blanca Skoda Paul Parsons Noel Roy 《Ocean Development & International Law》2013,44(4):357-390
The commercial fishery for northern cod off Newfoundland has been closed since 1992. Since then, the recreational “food fishery”; has also been closed, as have the fisheries for many additional cod and other groundfish stocks. The Newfoundland fisheries had been commercially unviable for many years before the closures. This article records the federal and provincial governments’ financial outlays (expenditures, transfer payments to individuals, subsidies, net equity purchases, and net loans) on the fishery during the decade following 1981. Special emphasis is placed on the cost of the financial restructuring of the industry in the mid‐1980s, net unemployment insurance payments, and social overhead capital expenditures. 相似文献
79.
Cleoni Alves Mendes de Lima Harrison Magdinier Gomes Maraníbia Aparecida Cardoso Oelemann Jesus Pais Ramos Paulo Cezar Caldas Carlos Eduardo Dias Campos Márcia Aparecida da Silva Pereira Fátima Fandinho Onofre Montes Maria do Socorro Calixto de Oliveira Philip Noel Suffys Maria Manuela da Fonseca Moura 《Memórias do Instituto Oswaldo Cruz》2013,108(4):457-462
The main cause of pulmonary tuberculosis (TB) is infection with
Mycobacterium tuberculosis (MTB). We aimed to evaluate the
contribution of nontuberculous mycobacteria (NTM) to pulmonary disease in
patients from the state of Rondônia using respiratory samples and
epidemiological data from TB cases. Mycobacterium isolates were identified using
a combination of conventional tests, polymerase chain reaction-based restriction
enzyme analysis of hsp65 gene and hsp65 gene
sequencing. Among the 1,812 cases suspected of having pulmonary TB, 444 yielded
bacterial cultures, including 369 cases positive for MTB and 75 cases positive
for NTM. Within the latter group, 14 species were identified as
Mycobacterium abscessus, Mycobacterium
avium, Mycobacterium fortuitum,
Mycobacterium intracellulare, Mycobacterium
gilvum, Mycobacterium gordonae,
Mycobacterium asiaticum, Mycobacterium
tusciae, Mycobacterium porcinum,
Mycobacterium novocastrense, Mycobacterium
simiae, Mycobacterium szulgai,
Mycobacterium phlei and Mycobacterium
holsaticum and 13 isolates could not be identified at the species
level. The majority of NTM cases were observed in Porto Velho and the relative
frequency of NTM compared with MTB was highest in Ji-Paraná. In approximately
half of the TB subjects with NTM, a second sample containing NTM was obtained,
confirming this as the disease-causing agent. The most frequently observed NTM
species were M. abscessus and M. avium and
because the former species is resistant to many antibiotics and displays
unsatisfactory cure rates, the implementation of rapid identification of
mycobacterium species is of considerable importance. 相似文献
80.
Xin Hu Milos Vujanac Noel Southall C. Erec Stebbins 《Bioorganic & medicinal chemistry letters》2013,23(4):1056-1062
The bacterial protein tyrosine phosphatase YopH is an essential virulence determinant in Yersinia pestis and a potential antibacterial drug target. Here we report our studies of screening for small molecule inhibitors of YopH using both high throughput and in silico approaches. The identified inhibitors represent a diversity of chemotypes and novel pTyr mimetics, providing a starting point for further development and fragment-based design of multi-site binding inhibitors. We demonstrate that the applications of high throughput and virtual screening, when guided by structural binding mode analysis, is an effective approach for identifying potent and selective inhibitors of YopH and other protein phosphatases for rational drug design. 相似文献