The evolution and arrest of a turbulent stratified oceanic bottom boundary layer over a slope: Upslope regime and pv dynamics

AbstractThe influence of a sloping bottom and stratification on the evolution of an oceanic bottom boundary layer (BBL) in the presence of a mean flow is explored. As a complement to an earlier study by Ruan et al. (https://doi.org/10.1175/JPO-D-18-0079.1) examining Ekman arrest in a downslope regime, this paper describes turbulence and BBL dynamics during Ekman arrest in the upslope regime. In the upslope regime, an enhanced stratification develops in response to the upslope Ekman transport and suppresses turbulence. Using a suite of large-eddy simulations, we show that the BBL evolution can be described in a self-similar framework based on a nondimensional number X/Xa. This nondimensional number is defined as the ratio between the lateral displacement of density surfaces across the slope X and a displacement Xa required for Ekman arrest; the latter can be predicted from external parameters. Additionally, the evolution of the depth-integrated potential vorticity is considered in both upslope and downslope regimes. The PV destruction rate in the downslope regime is found to be twice the production rate in the upslope regime, using the same definition for the bottom mixed layer thickness. It is shown that this asymmetry is associated with the depth scale over which turbulent stresses are active. These results are a step toward improving parameterizations of BBL properties and evolution over sloping topography in coarse-resolution ocean models.</jats:p

The evolution and arrest of a turbulent stratified oceanic bottom boundary layer over a slope: Downslope regime

AbstractThe dynamics of a stratified oceanic bottom boundary layer (BBL) over an insulating, sloping surface depend critically on the intersection of density surfaces with the bottom. For an imposed along-slope flow, the cross-slope Ekman transport advects density surfaces and generates a near-bottom geostrophic thermal wind shear that opposes the background flow. A limiting case occurs when a momentum balance is achieved between the Coriolis force and a restoring buoyancy force in response to the displacement of stratified fluid over the slope: this is known as Ekman arrest. However, the turbulent characteristics that accompany this adjustment have received less attention. We present two estimates to characterize the state of the BBL based on the mixed layer thickness: Ha and HL. The former characterizes the steady Ekman arrested state, and the latter characterizes a relaminarized state. The derivation of HL makes use of a newly defined slope Obukhov length Ls that characterizes the relative importance of shear production and cross-slope buoyancy advection. The value of Ha can be combined with the temporally evolving depth of the mixed layer H to form a nondimensional variable H/Ha that provides a similarity prediction of the BBL evolution across different turbulent regimes. The length scale Ls can also be used to obtain an expression for the wall stress when the BBL relaminarizes. We validate these relationships using output from a suite of three-dimensional large-eddy simulations. We conclude that the BBL reaches the relaminarized state before the steady Ekman arrested state. Calculating H/Ha and H/HL from measurements will provide information on the stage of oceanic BBL development being observed. These diagnostics may also help to improve numerical parameterizations of stratified BBL dynamics over sloping topography.</jats:p

Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.

Several studies have proposed that brain glutamate signaling abnormalities and glial pathology have a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn from post-mortem studies in which forebrain brain regions were examined. The locus coeruleus (LC) is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to have a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection (LCM) to selectively harvest LC tissue from post-mortem brains of MDD patients, patients with bipolar disorder (BPD) and from psychiatrically normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR (qPCR) and in situ hybridization (ISH). Our findings reveal multiple signaling pathway alterations in the LC of MDD but not BPD subjects. These include glutamate signaling genes, SLC1A2, SLC1A3 and GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: (1) are unique to MDD and distinguishable from BPD, and (2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions

Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

“The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

Feasibility study of a system for combined light dosimetry and interstitial photodynamic treatment of massive tumors

A system for the photodynamic laser treatment of massive tumors that employs multiple optical fibers to be inserted into the tumor mass is described. The light flux through the tumor can be assessed by use of the individual fibers both as transmitters and as receivers. With a computer model that describes the diffusive light propagation, optical dosimetry is under development, The system has been tested in an experimental animal tumor model in preparation for clinical work. Currently, delta-aminolevulinic acid is used as a sensitizer, activated by 635-nm radiation from a 2.0-W compact diode laser system. With the availability of future, highly selective drugs absorbing approximately 750 nm, larger tumor volumes should be treatable, and surrounding, sensitive normal tissue should be spared

Interstitial photodynamic therapy - diagnostic measurements and treatment in rat malignant experimental tumours

A recently developed multiple fibre system for treating malignant tumours with interstitial photodynamic therapy was used in studies on rats with colon adenocarcinoma inoculated into the muscles of the hind legs. The animals were intraperitonially administrated delta -aminolevulinic acid (ALA), which is metabolised to protoporphyrin IX (PpIX) in the tissue. The treatment system consists of a laser light source, a beam-splitting system dividing the light into three or six output fibres and a dosimetry programme calculating the optimal fibre position within the tumour as well as the treatment time needed to obtain a given threshold value of the light dose. One aim of the study was to compare the treatment outcome with the modelled dosimetry predictions. Tumour reduction was examined three days post treatment. A volume decrease was found in 85\% of the treated tumours. The mean volume reduction was 44\%, with one tumour completely disappearing. Histopathological examination three days post treatment showed substantial necrotic parts which, however, to a smaller extent were present also for non-treated tumours. These results indicated that the tumours have been under treated and the light dose has to be increased. Measurements of the build-up and photo-induced bleaching of PpIX using laser-induced fluorescence were also performed during the experiments

An experimental and numerical investigation of chevron fin structures in serpentine minichannel heat sinks

Water-cooled micro/minichannel heat sinks are an important component in managing the temperature of electronic components, particularly where high density of heat rejection is required. This study examines the potential to decrease the thermal resistance and enhance convective heat transfer of a serpentine heat exchanger, by introducing chevron fins which create secondary flow paths. This novel design is found to significantly reduce both the pressure drop across the heat exchanger and the total thermal resistance by up to 60% and 10%, respectively, and enhance the average Nusselt number by 15%. A three-dimensional conjugate heat transfer model is developed and validated against experimental measurements, before being used to carry out a parametric study involving the chevron oblique angle, secondary channel width and heat flux. The design of the serpentine minichannel with chevron fins is then optimised in terms of the minichannel width, minichannel number and chevron oblique angle. A 50 point Optimal Latin Hypercubes (OLHC) Design of Experiment (DoE) is constructed within the design variable space, using a permutation genetic algorithm, and accurate metamodels built using a Radial Basis Function (RBF) approach. A Pareto front is constructed which enables designers to explore appropriate compromises between designs with low pressure drop and those with low thermal resistance

Relationship between quality of life and psychopathological profile: data from an observational study in children with ADHD

Although ADHD significantly affects the quality of life (QoL) of patients and their families, QoL in children with ADHD has rarely been investigated in association with psychopathological profile, and the relationship remains unclear. The open-label OBSEER study evaluated the effectiveness and tolerability of Equasym XL®, a modified-release methylphenidate, in routine care of children and adolescents (aged 6–17 years) with ADHD. At baseline, questionnaires assessing psychopathological profile (Strengths and Difficulties Questionnaire, SDQ; parental ratings) and QoL (KINDL; parent, child or adolescent versions) were completed; QoL was reassessed at final visit. We analysed the relationship between psychopathology and parent/patient-rated QoL in ADHD at baseline. Data from 721 consecutively referred children and adolescents were analysed. QoL was similarly low from parent and self-ratings and independent of severity on the SDQ subscale hyperactivity/inattention. Self-ratings indicated that additional conduct disorder was associated with further reduction in QoL. Similarly, children with high scores from parent and adolescent ratings on the SDQ subscale conduct problems had reduced QoL on some KINDL subscales. Adolescents with ADHD not receiving medication at baseline reported lower QoL than those already on medication. Results show that children and adolescents with ADHD have low QoL, independent of core symptom severity. Additional conduct problems may further impact QoL negatively, while ADHD medication use may show a trend towards improved QoL. Not all psychopathological problems associated with ADHD affect QoL similarly. As parents appear to have a less critical view of QoL compared with children’s self-ratings, both parent and child ratings should be included in clinical assessments

Synthesis and Anti-Mycobacterium tuberculosis Activity of Imidazo[2,1-b][1,3]oxazine Derivatives against Multidrug-Resistant Strains

The emergence of multidrug-resistant strains of M. tuberculosis has raised concerns due to the greater difficulties in patient treatment and higher mortality rates. Herein, we revisited the 2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine scaffold and identified potent new carbamate derivatives having MIC90 values of 0.18–1.63 μM against Mtb H37Rv. Compounds 47–49, 51–53, and 55 exhibited remarkable activity against a panel of clinical isolates, displaying MIC90 values below 0.5 μM. In Mtb-infected macrophages, several compounds demonstrated a 1-log greater reduction in mycobacterial burden than rifampicin and pretomanid. The compounds tested did not exhibit significant cytotoxicity against three cell lines or any toxicity to Galleria mellonella. Furthermore, the imidazo[2,1-b][1,3]oxazine derivatives did not show substantial activity against other bacteria or fungi. Finally, molecular docking studies revealed that the new compounds could interact with the deazaflavin-dependent nitroreductase (Ddn) in a similar manner to pretomanid. Collectively, our findings highlight the chemical universe of imidazo[2,1-b][1,3]oxazines and their promising potential against MDR-TB