Injected carrier profiles and consequent optical mode variations in semiconductor waveguides

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Nesfatin-1/NUCB2 as a Potential New Element of Sleep Regulation in Rats.

STUDY OBJECTIVES: Millions suffer from sleep disorders that often accompany severe illnesses such as major depression; a leading psychiatric disorder characterized by appetite and rapid eye movement sleep (REMS) abnormalities. Melanin-concentrating hormone (MCH) and nesfatin-1/NUCB2 (nesfatin) are strongly co - expressed in the hypothalamus and are involved both in food intake regulation and depression. Since MCH was recognized earlier as a hypnogenic factor, we analyzed the potential role of nesfatin on vigilance. DESIGN: We subjected rats to a 72 h-long REMS deprivation using the classic flower pot method, followed by a 3 h-long 'rebound sleep'. Nesfatin mRNA and protein expressions as well as neuronal activity (Fos) were measured by quantitative in situ hybridization technique, ELISA and immunohistochemistry, respectively, in 'deprived' and 'rebound' groups, relative to controls sacrificed at the same time. We also analyzed electroencephalogram of rats treated by intracerebroventricularly administered nesfatin-1, or saline. RESULTS: REMS deprivation downregulated the expression of nesfatin (mRNA and protein), however, enhanced REMS during 'rebound' reversed this to control levels. Additionally, increased transcriptional activity (Fos) was demonstrated in nesfatin neurons during 'rebound'. Centrally administered nesfatin-1 at light on reduced REMS and intermediate stage of sleep, while increased passive wake for several hours and also caused a short-term increase in light slow wave sleep. CONCLUSIONS: The data designate nesfatin as a potential new factor in sleep regulation, which fact can also be relevant in the better understanding of the role of nesfatin in the pathomechanism of depression

Combinations of QT-prolonging drugs: towards disentangling pharmacokinetic and pharmaco-dynamic effects in their potentially additive nature.

Background: Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug–drug interactions. Methods: In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other QTc-prolonging risk factors. We concurrently considered administered drug doses and pharmacokinetic interactions modulating drug clearance to calculate individual weights of relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we estimated individual drug exposure with these drugs and included this information as weights in weighted regression analyses. Results: Drugs attributing a ‘known’ risk for clinical consequences were associated with the largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with 95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for the ‘conditional’ risk class increased upon refinement with relative drug exposure and coadministration of a ‘known’ risk drug as a further risk factor. Conclusions: These observations indicate that indiscriminate combinations of QTc-prolonging drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation caused by drug combinations strongly depends on the nature of the combination partners and individual drug exposure. Concurrently, it stresses the value of the AZCERT classification also for the risk prediction of combination therapies with QT-prolonging drugs

CFD Analysis of Localised Crud Effects on the Flow of Coolant in Nuclear Rod Bundles

It has been suggested that crud deposits on a number of adjacent fuel rods might reduce coolant flow rates in associated sub-channels. Such reduced flow rates could then worsen thermal-hydraulic conditions, such as margin to saturated boiling, fuel surface temperature, and the DNB ratio. We report the results of a detailed computational fluid dynamics study of the flow pattern in a partially-crudded rod bundle. Values obviously depend on, for example, the thickness of crud assumed, but sub-channel flow rate reductions of ~10% were predicted by this analysis. However, this mass flow rate reduction was found to be more than offset by improved heat transfer induced by the relatively rough surface of the crud. Cladding temperatures were predicted to be essentially unchanged, and the DNBR was similarly little altered. We conclude that such flow reduction and diversion is not likely to be of concern

Atmospheric pressure vapour phase decomposition: a proof of principle

In the present work we demonstrated that the digestion of difficult matrices (high boiling petrochemical fractions and distillation bottoms) can be achieved by oxidation with nitric acid vapours at atmospheric pressure employing simple laboratory glassware. The application of this procedure as a digestion method prior to Total Reflection X Ray Fluorescence (TXRF) is presented, although the employment of other detection techniques may be foreseen. The method ensured a fast, less than half an hour, treatment time and detection limits in the range 20 \u2013 100 microg/kg for As, Bi, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, Zn, whereas higher values were obtained for Ba, Ca, K, P, Rh, Ti and V (0.3 \u2013 3 mg/kg). The potentialities and limitations of this procedure were discussed: the application to a broad range of matrices may be foreseen