61 research outputs found
The contrasting chemical reactivity of potent isoelectronic iminopyridine and azopyridine osmium(ii) arene anticancer complexes
A wide variety of steric and electronic features can be incorporated into transition metal coordination complexes, offering the prospect of rationally-designed therapeutic agents with novel mechanisms of action. Here we compare the chemical reactivity and anticancer activity of organometallic OsII complexes [Os(η6-arene)(XY)Z]PF6 where arene = p-cymene or biphenyl, XY = N,NâČ-chelated phenyliminopyridine or phenylazopyridine derivatives, and Z = Cl or I. The X-ray crystal structure of [Os(η6-p-cym)(Impy-OH)I]PF6·0.5CH2Cl2·H2O (Impy-OH = 4-[(2-pyridinylmethylene)amino]-phenol) is reported. Like the azopyridine complexes we reported recently (Dalton Trans., 2011, 40, 10553â10562), some iminopyridine complexes are also potently active towards cancer cells (nanomolar IC50 values). However we show that, unlike the azopyridine complexes, the iminopyridine complexes can undergo aquation, bind to the nucleobase guanine, and oxidize coenzyme nicotine adenine dinucleotide (NADH). We report the first detection of an Os-hydride adduct in aqueous solution by 1H NMR (â4.2 ppm). Active iminopyridine complexes induced a dramatic increase in the levels of reactive oxygen species (ROS) in A549 lung cancer cells. The anticancer activity may therefore involve interference in the redox signalling pathways in cancer cells by a novel mechanism
Investigation of spectral interferences on the accuracy of broadband CW-NIRS tissue SO2 determination
An accurate SO2 prediction method for using broadband continuous-wave diffuse reflectance near infrared (NIR) spectroscopy is proposed. The method fitted the NIR spectra to a Taylor expansion attenuation model, and used the simulated annealing method to initialize the nonlinear least squares fit. This paper investigated the effect of potential spectral interferences that are likely to be encountered in clinical use, on SO2 prediction accuracy. The factors include the concentration of hemoglobin in blood, the volume of blood and volume of water in the tissue under the sensor, reduced scattering coefficient, ”s', of the muscle, fat thickness and the source-detector spacing. The SO2 prediction method was evaluated on simulated muscle spectra as well as on dual-dye phantoms which simulate the absorbance of oxygenated and deoxygenated hemoglobin
Water-loss dehydration and aging
This review defines water-loss and salt-loss dehydration. For older people serum osmolality appears the most appropriate gold standard for diagnosis of water-loss dehydration, but clear signs of early dehydration have not been developed. In older adults, lower muscle mass, reduced kidney function, physical and cognitive disabilities, blunted thirst, and polypharmacy all increase dehydration risk. Cross-sectional studies suggest a water-loss dehydration prevalence of 20-30% in this population. Water-loss dehydration is associated with higher mortality, morbidity and disability in older people, but evidence is still needed that this relationship is causal. There are a variety of ways we may be able to help older people reduce their risk of dehydration by recognising that they are not drinking enough, and being helped to drink more. Strategies to increase fluid intake in residential care homes include identifying and overcoming individual and institutional barriers to drinking, such as being worried about not reaching the toilet in time, physical inability to make or to reach drinks, and reduced social drinking and drinking pleasure. Research needs are discussed, some of which will be addressed by the FP7-funded NU-AGE (New dietary strategies addressing the specific needs of elderly population for a healthy ageing in Europe) trial
Vinyl sulfone-based ferrocenylation reagents: applications in conjugation and bioconjugation
The easy vinyl sulfone derivatization of ferrocene allows the preparation of some effective, versatile and valuable ferrocenylation reagents. The applicability of such compounds in conjugation and bioconjugation of amine and/or thiol containing molecules and biomolecules through Michael-type addition under mild conditions that preserve the biological function of the latter is described. The feasibility of the methodology is demonstrated by the preparation of a variety of conjugates and bioconjugates (ferrocenyl terminated dendrimers and ferroceneâsugar, ferroceneâcyclodextrin, ferroceneâpeptide and ferroceneâprotein conjugates).Financial support was provided by Ministerio de Ciencia e InnovaciĂłn (CTQ2011-29299-CO2-01)
Claiming the corner office: Female CEO careers and implications for leadership development
Drawing on evidence from a unique data set of inâdepth qualitative interviews with 12 female CEOs (and 139 male CEOs) of global corporations, we explore what enables some women to become CEOs. By drawing on our data from male and female CEOs, we set the scene by comparing the advice they would give to young women as they start their careers. We then focus the rest of our article on the experiences and career trajectory of the 12 female CEOs. We make three theoretical contributions: We identify, at the individual level, how women can take active ownership of their careers as part of a selfâacceptance process; how they can embrace gynandrous leadership as part of a selfâdevelopment process where both feminine and masculine leadership behaviors are embraced, with the feminine being dominant to help move beyond gender stereotypes, and finally, how they translate leadershipârather than combineâgenderâbased behaviors as part of a selfâmanagement process to develop their unique leadership style. For each of these theoretical contributions at the individual level, we also provide two practical recommendations for HR practice and policy, one relating to the intraorganizational context and the second having institutionalâlevel implications. We conclude by discussing implications for future research
Immunohistochemical assessment of cyclic guanosine monophosphate (cGMP) and soluble guanylate cyclase (sGC) within the rostral ventrolateral medulla
What can controllers and internal auditors do to support risk ownership?
Over the years, many organisations adopted several types of Three Lines models for optimising risk management coordination and control. According to these models, first line risk ownership is required for routinely applying risk management in all of the organisationâs activities, which seems highly underdeveloped. From an exploratory and development research, which builds on conventional risk management approaches, three pragmatic suggestions are derived: (1) simplifying risk management by asking three specific OUD-questions about Objectives, Uncertainties and what to Do, (2) clarification of objectives at all organisational levels, and (3) connecting responsibility for objectives to risk responsibility. Routinely applying these suggestions by second line controllers and third line internal auditors may support first line risk ownership
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