Inversed linear dichroism in F <em>K</em>-edge NEXAFS spectra of fluorinated planar aromatic molecules

et al.The symmetry and energy distribution of unoccupied molecular orbitals is addressed in this work by means of NEXAFS and density functional theory calculations for planar, fluorinated organic semiconductors (perfluorinated copper phthalocyanines and perfluoropentacene). We demonstrate how molecular orbitals with significant density of states on the fluorine atoms show different symmetry from those mainly located on C and N atoms. As a result, the angle-dependent linear dichroism in NEXAFS F K-edge spectra is inversed with respect to that in the C and N K-edges. In addition, the significant overlap in energy of π * and σ * orbitals throughout the F K-edge spectrum hampers its use for analysis of molecular orientations from angle-dependent NEXAFS measurements. © 2012 American Physical Society.J.E.O. and A.R. acknowledge funding from the Spanish MEC through Grants No. FIS2011-65702-C02-01, No. MAT2010-21156-C03-01, and No. PIB2010US-00652, and from the Basque Government through Grants No. IT-257-07 and No. IT-319-07. A.R. additionally acknowledges that financial support was provided by ACI-Promociona Grant No. ACI2009-1036 and the European Research Council Advanced Grant DYNamo (ERC-2010-AdG, Proposal No. 267374). A.S. acknowledges the support of the Research Funds of the University of Helsinki and the Academy of Finland through Contract No. 1127462, Centers of Excellence Program, and the National Graduate School in Materials Physics. J.M.G.L. acknowledges support from The Lundbeck Foundation’s Center for Atomic-Scale Materials Design and the Danish Center for Scientific Computing.Peer Reviewe

Maturation of mammalian H/ACA box snoRNAs: PAPD5-dependent adenylation and PARN-dependent trimming

Small nucleolar and small Cajal body RNAs (snoRNAs and scaRNAs) of the H/ACA box and C/D box type are generated by exonucleolytic shortening of longer precursors. Removal of the last few nucleotides at the 3' end is known to be a distinct step. We report that, in human cells, knock-down of the poly(A) specific ribonuclease (PARN), previously implicated only in mRNA metabolism, causes the accumulation of oligoadenylated processing intermediates of H/ACA box but not C/D box RNAs. In agreement with a role of PARN in snoRNA and scaRNA processing, the enzyme is concentrated in nucleoli and Cajal bodies. Oligo(A) tails are attached to a short stub of intron sequence remaining beyond the mature 3' end of the snoRNAs. The noncanonical poly(A) polymerase PAPD5 is responsible for addition of the oligo(A) tails. We suggest that deadenylation is coupled to clean 3' end trimming, which might serve to enhance snoRNA stability

Influence of a Transport Current on Magnetic Anisotropy in Gyrotropic Ferromagnets

Current-induced torques are commonly used to manipulate non-collinear magnetization configurations. In this article we discuss current-induced torques present in a certain class of collinear magnetic systems, relating them to current-induced changes in magnetic anisotropy energy. We present a quantitative estimate of their characteristics in uniform strained ferromagnetic (Ga,Mn)As.Comment: 12 pages, 8 figures; submitted to Phys. Rev.

Profiling a decade of information systems frontiers’ research

This article analyses the first ten years of research published in the Information Systems Frontiers (ISF) from 1999 to 2008. The analysis of the published material includes examining variables such as most productive authors, citation analysis, universities associated with the most publications, geographic diversity, authors’ backgrounds and research methods. The keyword analysis suggests that ISF research has evolved from establishing concepts and domain of information systems (IS), technology and management to contemporary issues such as outsourcing, web services and security. The analysis presented in this paper has identified intellectually significant studies that have contributed to the development and accumulation of intellectual wealth of ISF. The analysis has also identified authors published in other journals whose work largely shaped and guided the researchers published in ISF. This research has implications for researchers, journal editors, and research institutions

Importance of Ethnicity, CYP2B6 and ABCB1 Genotype for Efavirenz Pharmacokinetics and Treatment Outcomes: A Parallel-group Prospective Cohort Study in two sub-Saharan Africa Populations.

We evaluated the importance of ethnicity and pharmacogenetic variations in determining efavirenz pharmacokinetics, auto-induction and immunological outcomes in two African populations. ART naïve HIV patients from Ethiopia (n = 285) and Tanzania (n = 209) were prospectively enrolled in parallel to start efavirenz based HAART. CD4+ cell counts were determined at baseline, 12, 24 and 48 weeks. Plasma and intracellular efavirenz and 8-hydroxyefvairenz concentrations were determined at week 4 and 16. Genotyping for common functional CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 variant alleles were done. Patient country, CYP2B6*6 and ABCB1 c.4036A>G (rs3842A>G) genotype were significant predictors of plasma and intracellular efavirenz concentration. CYP2B6*6 and ABCB1 c.4036A>G (rs3842) genotype were significantly associated with higher plasma efavirenz concentration and their allele frequencies were significantly higher in Tanzanians than Ethiopians. Tanzanians displayed significantly higher efavirenz plasma concentration at week 4 (p<0.0002) and week 16 (p = 0.006) compared to Ethiopians. Efavirenz plasma concentrations remained significantly higher in Tanzanians even after controlling for the effect of CYP2B6*6 and ABCB1 c.4036A>G genotype. Within country analyses indicated a significant decrease in the mean plasma efavirenz concentration by week 16 compared to week 4 in Tanzanians (p = 0.006), whereas no significant differences in plasma concentration over time was observed in Ethiopians (p = 0.84). Intracellular efavirenz concentration and patient country were significant predictors of CD4 gain during HAART. We report substantial differences in efavirenz pharmacokinetics, extent of auto-induction and immunologic recovery between Ethiopian and Tanzanian HIV patients, partly but not solely, due to pharmacogenetic variations. The observed inter-ethnic variations in efavirenz plasma exposure may possibly result in varying clinical treatment outcome or adverse event profiles between populations

Circulation of human influenza viruses and emergence of Oseltamivir-resistant A(H1N1) viruses in Cameroon, Central Africa

<p>Abstract</p> <p>Background</p> <p>While influenza surveillance has increased in most developing countries in the last few years, little influenza surveillance has been carried out in sub-Saharan Africa and no information is available in Central Africa. The objective of this study was to assess the prevalence of influenza viruses circulating in Yaounde, Cameroon and determine their antigenic and genetic characteristics.</p> <p>Methods</p> <p>Throat and/or nasal swabs were collected from November 2007 to October 2008 from outpatients with influenza-like illness (ILI) in Yaounde, Cameroon and analyzed by two different techniques: a one-step real time reverse transcription-polymerase chain reaction (RT-PCR) and virus isolation in MDCK cells. Typing and subtyping of virus isolates was performed by hemagglutination inhibition (HI), and viruses were sent to the WHO Collaborating Centre in London, UK for further characterization and analyses of antiviral resistance by enzyme inhibition assay and nucleotide sequencing.</p> <p>Results</p> <p>A total of 238 patients with ILI were sampled. During this period 70 (29%) samples were positive for influenza by RT-PCR, of which only 26 (11%) were positive by virus isolation. By HI assay, 20 of the 26 isolates were influenza type A (10 H3N2 and 10 H1N1) and 6 were influenza type B (2 B/Victoria/2/87 lineage and 4 B/Yagamata/16/88 lineage). Seven (70%) of the H1N1 isolates were shown to be resistant to oseltamivir due to a H275Y mutation.</p> <p>Conclusions</p> <p>This study confirmed the circulation of influenza A(H1N1), A(H3N2) and B viruses in the human population in Central Africa and describes the emergence of oseltamivir-resistant A(H1N1) viruses in Central Africa.</p

Left ventricular twist mechanics during incremental cycling and knee extension exercise in healthy men

Purpose: The objective of the present study was to investigate left ventricular (LV) twist mechanics in response to incremental cycling and isometric knee extension exercises. Methods: Twenty-six healthy male participants (age = 30.42 ± 6.17 years) were used to study peak twist mechanics at rest and during incremental semi-supine cycling at 30 and 60% work rate maximum (W) and during short duration (15 s contractions) isometric knee extension at 40 and 75% maximum voluntary contraction (MVC), using two-dimensional speckle tracking echocardiography. Results: Data presented as mean ± standard deviation or median (interquartile range). LV twist increased from rest to 30% W (13.21° ± 4.63° to 20.04° ± 4.76°, p  0.05), whilst twisting velocity increased (rest 89.15° ± 21.77° s to 75% MVC 124.32° ± 34.89° s, p  0.05) then increased from 40 to 75% MVC [−98.44 (43.54)° s to −138.42 (73.29)° s, p < 0.01]. Apical rotations and rotational velocities were greater than basal during all conditions and intensities (all p < 0.01). Conclusion: Cycling increased LV twist to 30% W which then remained unchanged thereafter, whereas twisting velocities showed further increases to greater intensities. A novel finding is that LV twist was unaffected by incremental knee extension, yet systolic and diastolic twisting velocities augmented with isometric exercise

Differences in Nevirapine Biotransformation as a Factor for its Sex-Dependent Dimorphic Profile of Adverse Drug Reactions

OBJECTIVES: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. METHODS: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. RESULTS: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. CONCLUSIONS: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity