Heat flow measurements on a hydrothermally-active, slow-spreading ridge: The Escanaba Trough

Maximum heat flow measurements at three locations in the sediment-filled Escanaba Trough of the Gorda ridge exceed 1200 mW/m². At other ridge crests with thick sediment cover, heat flow values of this magnitude are accompanied by high temperature hydrothermal vent activity and massive sulfide deposition. A dredge haul from the southernmost high heat flow location recovered pyrrhotite, thereby confirming the presence of recent high temperature venting

Controlled drug delivery by means of drug :i onic polysaccharide interactions

The aim of the project was to investigate the potential of ionic polysaccharide/drug complexes as controlled release drug delivery systems. Two highly purified alginates from Laminaria hyperborea and Ascophyllum nodosum were characterised in terms of molecular weight, polydispersity and M:G ratio using gel permeation chromatography (GPC), low-speed sedimentation in the analytical ultracentrifuge and GPC combined with multi-angle laser light-scattering. Viscometric and nephelometric studies provided evidence that, above certain concentrations of propranolol, there was an interaction between propranolol and alginate in deionised water resulting in the formation of an insoluble complex, which dissociated in the presence of counter-ions, for example, sodium chloride. Binding studies were undertaken using equilibrium dialysis in order to quantify this interaction in the presence and absence of sodium chloride. These indicated that there was a one-to-one stoichiometric relationship between propranolol and the carboxyl group on each uronic acid reSidue of the alginate and that negative co-operativity was occurring, such that the binding of one propranolol molecule to the alginate made it more difficult for subsequent propranolol molecules to bind. The possible in-vacuo three-dimensional structure of the molecular complex was modelled using computational molecular modelling techniques. A freeze-dried complex of propranolol and alginate was prepared and characterised. In vitro investigations indicated that drug release from the complex (formulated as a suspension in deionised water or in isotonic glycerol solution) was delayed compared with release from a propranolol solution. The release of propranolol from the propranolol/ alginate complex was assessed in vivo using the anaesthetised rat as an animal model for nasal delivery. It was found that the rate of absorption of propranolol from the complex was much slower and was sustained over a greater period of time, compared with absorption from a propranolol solution. In addition, the bioavailability of the drug from the complex was comparable to that of the solution and to that of an intravenous dose carried out in rats by other workers (Hussain et al 1980b)

Controlled drug delivery by means of drug :i onic polysaccharide interactions

The aim of the project was to investigate the potential of ionic polysaccharide/drug complexes as controlled release drug delivery systems. Two highly purified alginates from Laminaria hyperborea and Ascophyllum nodosum were characterised in terms of molecular weight, polydispersity and M:G ratio using gel permeation chromatography (GPC), low-speed sedimentation in the analytical ultracentrifuge and GPC combined with multi-angle laser light-scattering. Viscometric and nephelometric studies provided evidence that, above certain concentrations of propranolol, there was an interaction between propranolol and alginate in deionised water resulting in the formation of an insoluble complex, which dissociated in the presence of counter-ions, for example, sodium chloride. Binding studies were undertaken using equilibrium dialysis in order to quantify this interaction in the presence and absence of sodium chloride. These indicated that there was a one-to-one stoichiometric relationship between propranolol and the carboxyl group on each uronic acid reSidue of the alginate and that negative co-operativity was occurring, such that the binding of one propranolol molecule to the alginate made it more difficult for subsequent propranolol molecules to bind. The possible in-vacuo three-dimensional structure of the molecular complex was modelled using computational molecular modelling techniques. A freeze-dried complex of propranolol and alginate was prepared and characterised. In vitro investigations indicated that drug release from the complex (formulated as a suspension in deionised water or in isotonic glycerol solution) was delayed compared with release from a propranolol solution. The release of propranolol from the propranolol/ alginate complex was assessed in vivo using the anaesthetised rat as an animal model for nasal delivery. It was found that the rate of absorption of propranolol from the complex was much slower and was sustained over a greater period of time, compared with absorption from a propranolol solution. In addition, the bioavailability of the drug from the complex was comparable to that of the solution and to that of an intravenous dose carried out in rats by other workers (Hussain et al 1980b)

Hypothalamic-Pituitary-Adrenal Axis Abnormalities in Response to Deletion of 11β-HSD1 is Strain-Dependent

Inter-individual differences in hypothalamic-pituitary-adrenal (HPA) axis activity underlie differential vulnerability to neuropsychiatric and metabolic disorders, although the basis of this variation is poorly understood. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has previously been shown to influence HPA axis activity. 129/MF1 mice null for 11β-HSD1 (129/MF1 HSD1−/−) have greatly increased adrenal gland size and altered HPA activity, consistent with reduced glucocorticoid negative feedback. On this background, concentrations of plasma corticosterone and adrenocorticotrophic hormone (ACTH) were elevated in unstressed mice, and showed a delayed return to baseline after stress in HSD1-null mice with reduced sensitivity to exogenous glucocorticoid feedback compared to same-background genetic controls. In the present study, we report that the genetic background can dramatically alter this pattern. By contrast to HSD1−/− mice on a 129/MF1 background, HSD1−/− mice congenic on a C57Bl/6J background have normal basal plasma corticosterone and ACTH concentrations and exhibit normal return to baseline of plasma corticosterone and ACTH concentrations after stress. Furthermore, in contrast to 129/MF1 HSD1−/− mice, C57Bl/6J HSD1−/− mice have increased glucocorticoid receptor expression in areas of the brain involved in glucocorticoid negative feedback (hippocampus and paraventricular nucleus), suggesting this may be a compensatory response to normalise feedback control of the HPA axis. In support of this hypothesis, C57Bl/6J HSD1−/− mice show increased sensitivity to dexamethasone-mediated suppression of peak corticosterone. Thus, although 11β-HSD1 appears to contribute to regulation of the HPA axis, the genetic background is crucial in governing the response to (and hence the consequences of) its loss. Similar variations in plasticity may underpin inter-individual differences in vulnerability to disorders associated with HPA axis dysregulation. They also indicate that 11β-HSD1 inhibition does not inevitably activate the HPA axis

The subresolution DaTSCAN phantom: a cost-effective, flexible alternative to traditional phantom technology

The Alderson striatal phantom is frequently used to assess I-FP-CIT (Ioflupane) image quality and to test semi-quantification software. However, its design is associated with a number of limitations, in particular: unrealistic image appearances and inflexibility. A new physical phantom approach is proposed on the basis of subresolution phantom technology. The design incorporates thin slabs of attenuating material generated through additive manufacturing, and paper sheets with radioactive ink patterns printed on their surface, created with a conventional inkjet printer. The paper sheets and attenuating slabs are interleaved before scanning. Use of thin layers ensures that they cannot be individually resolved on reconstructed images. An investigation was carried out to demonstrate the performance of such a phantom in producing simplified I-FP-CIT uptake patterns. Single photon emission computed tomography imaging was carried out on an assembled phantom designed to mimic a healthy patient. Striatal binding ratio results and linear striatal dimensions were calculated from the reconstructed data and compared with that of 22 clinical patients without evidence of Parkinsonian syndrome, determined from clinical follow-up. Striatal binding ratio results for the fully assembled phantom were: 3.1, 3.3, 2.9 and 2.6 for the right caudate, left caudate, right putamen and right caudate, respectively. All were within two SDs of results derived from a cohort of clinical patients. Medial-lateral and anterior-posterior dimensions of the simulated striata were also within the range of values seen in clinical data. This work provides the foundation for the generation of a range of more clinically realistic, physical phantoms

Anisotropic permeability in deterministic lateral displacement arrays

We uncover anisotropic permeability in microfluidic deterministic lateral displacement (DLD) arrays. A DLD array can achieve high-resolution bimodal size-based separation of microparticles, including bioparticles, such as cells. For an application with a given separation size, correct device operation requires that the flow remains at a fixed angle to the obstacle array. We demonstrate via experiments and lattice-Boltzmann simulations that subtle array design features cause anisotropic permeability. Anisotropic permeability indicates the microfluidic array's intrinsic tendency to induce an undesired lateral pressure gradient. This can cause an inclined flow and therefore local changes in the critical separation size. Thus, particle trajectories can become unpredictable and the device useless for the desired separation task. Anisotropy becomes severe for arrays with unequal axial and lateral gaps between obstacle posts and highly asymmetric post shapes. Furthermore, of the two equivalent array layouts employed with the DLD, the rotated-square layout does not display intrinsic anisotropy. We therefore recommend this layout over the easier-to-implement parallelogram layout. We provide additional guidelines for avoiding adverse effects of anisotropy on the DLD.Comment: 13 pages, 10 figures, 1 table, DLD, particle separation, microfluidics, anisotropic permeabilit

Forebrain-specific transgene rescue of 11β-HSD1 associates with impaired spatial memory and reduced hippocampal BDNF mRNA levels in aged 11β-HSD1 deficient mice

Mice lacking the intracellular glucocorticoid‐regenerating enzyme 11β‐hydroxysteroid dehydrogenase type 1 (11β‐HSD1) are protected from age‐related spatial memory deficits. 11β‐HSD1 is expressed predominantly in the brain, liver and adipose tissue. Reduced glucocorticoid levels in the brain in the absence of 11β‐HSD1 may underlie the improved memory in aged 11β‐HSD1 deficient mice. However, the improved glucose tolerance, insulin sensitisation and cardioprotective lipid profile associated with reduced peripheral glucocorticoid regeneration may potentially contribute to the cognitive phenotype of aged 11β‐HSD1 deficient mice. In the present study, transgenic mice with forebrain‐specific overexpression of 11β‐HSD1 (Tg) were intercrossed with global 11β‐HSD1 knockout mice (HSD1KO) to examine the influence of forebrain and peripheral 11β‐HSD1 activity on spatial memory in aged mice. Transgene‐mediated delivery of 11β‐HSD1 to the hippocampus and cortex of aged HSD1KO mice reversed the improved spatial memory retention in the Y‐maze but not spatial learning in the watermaze. Brain‐derived neurotrophic factor (BDNF) mRNA levels in the hippocampus of aged HSD1KO mice were increased compared to aged wild‐type mice. Rescue of forebrain 11β‐HSD1 reduced BDNF mRNA in aged HSD1KO mice to levels comparable to aged wild‐type mice. These findings indicate that 11β‐HSD1 regenerated glucocorticoids in the forebrain and decreased levels of BDNF mRNA in the hippocampus play a role in spatial memory deficits in aged wild‐type mice, although 11β‐HSD1 activity in peripheral tissues may also contribute to spatial learning impairments in aged mice

Dominion cartoon satire as trench culture narratives: complaints, endurance and stoicism

Although Dominion soldiers’ Great War field publications are relatively well known, the way troops created cartoon multi-panel formats in some of them has been neglected as a record of satirical social observation. Visual narrative humour provides a ‘bottom-up’ perspective for journalistic observations that in many cases capture the spirit of the army in terms of stoicism, buoyed by a culture of internal complaints. Troop concerns expressed in the early comic strips of Australians, Canadians, New Zealanders and British were similar. They shared a collective editorial purpose of morale boosting among the ranks through the use of everyday narratives that elevated the anti-heroism of the citizen soldier, portrayed as a transnational everyman in the service of empire. The regenerative value of disparagement humour provided a redefinition of courage as the very act of endurance on the Western Front

Reduced thymic output, cell cycle abnormalities, and increased apoptosis of T lymphocytes in patients with cartilage-hair hypoplasia

Producción CientíficaBackground: Cartilage-hair hypoplasia (CHH) is characterized by metaphyseal dysplasia, bone marrow failure, increased risk of malignancies, and a variable degree of immunodeficiency. CHH is caused by mutations in the RNA component of the mitochondrial RNA processing (RMRP) endoribonuclease gene, which is involved in ribosomal assembly, telomere function, and cell cycle control. Objectives: We aimed to define thymic output and characterize immune function in a cohort of patients with molecularly defined CHH with and without associated clinical immunodeficiency. Methods: We studied the distribution of B and T lymphocytes (including recent thymic emigrants), in vitro lymphocyte proliferation, cell cycle, and apoptosis in 18 patients with CHH compared with controls. Results: Patients with CHH have a markedly reduced number of recent thymic emigrants, and their peripheral T cells show defects in cell cycle control and display increased apoptosis, resulting in poor proliferation on activation. Conclusion: These data confirm that RMRP mutations result in significant defects of cell-mediated immunity and provide a link between the cellular phenotype and the immunodeficiency in CH