Porometry, porosimetry, image analysis and void network modelling in the study of the pore-level properties of filters

We present fundamental and quantitative comparisons between the techniques of porometry (or flow permporometry), porosimetry, image analysis and void network modelling for seven types of filter, chosen to encompass the range of simple to complex void structure. They were metal, cellulose and glass fibre macro- and meso-porous filters of various types. The comparisons allow a general re-appraisal of the limitations of each technique for measuring void structures. Porometry is shown to give unrealistically narrow void size distributions, but the correct filtration characteristic when calibrated. Shielded mercury porosimetry can give the quaternary (sample-level anisotropic) characteristics of the void structure. The first derivative of a mercury porosimetry intrusion curve is shown to underestimate the large number of voids, but this error can be largely corrected by the use of a void network model. The model was also used to simulate the full filtration characteristic of each sample, which agreed with the manufacturer's filtration ratings. The model was validated through its correct a priori simulation of absolute gas permeabilities for track etch, cellulose nitrate and sintered powder filters. © 2011 Elsevier Ltd

Histone deacetylase inhibitors containing chiral heterocyclic capping groups

Histone deacetylase (HDAC) enzymes are one of the best characterised epigenetic targets; aberrant activity of one or more of the 11 zinc-dependent HDAC isoforms has been associated with many different cancers, as well as several other diseases. Some HDAC inhibitors have been proven to be efficacious in treating cancer; three are FDA approved for treating cutaneous T-cell lymphoma or multiple myeloma. Animal models of other diseases have shown that HDAC inhibitors have potential as therapeutic agents. However the clinical use of HDAC inhibitors is currently limited by toxicity and side effects, amongst other problems, possibly arising because the inhibitors are not isoform selective. This thesis focuses on attempts to synthesise novel HDAC inhibitors with increased isoform selectivity. A series of mocetinostat analogues substituted at the 4-poisition of the terminal 2-aminophenyl ring, was synthesised and tested for inhibition of HDAC isoforms, but no improvement over mocetinostat was found. Subsequently multiple series of compounds containing a chiral heterocycle, in place of the pyrimidine ring in mocetinostat, were prepared and evaluated against a selection of HDAC isoforms. The development of highly convergent methodology enabled the rapid synthesis of these chiral mocetinostat analogues. Several compounds were discovered that are more potent and selective inhibitors than mocetinostat against HDAC3. Those compounds containing a 2-amino-linked dihydrooxazole ring were the most potent, and in all cases the amino-linked heterocycle outperformed its thioetherlinked analogue. Mocetinostat and a novel chiral analogue were shown to be slow, tightbinding inhibitors of HDAC2 and HDAC3. Attempts were made to discover a novel zinc-binding group; a selection of potential bi-dentate zinc-chelating fragments was assayed and 8-hydroxyquinoline emerged as a promising candidate for HDAC8 inhibition. Accordingly some substituted 8-hydroxyquinolines were prepared in order to conduct a brief SAR study of the novel zinc-binding group, however no improvement on the unsubstituted 8-hydroxyquinoline was found

Potent and selective inhibitors of histone deacetylase-3 containing chiral oxazoline capping groups and a N-(2-Aminophenyl)-benzamide binding unit

A novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contains an oxazoline capping group and a N-(2-aminophenyl)-benzamide unit. Among several new inhibitors of this type exhibiting Class I selectivity and potent inhibition of HDAC3-NCoR2, in vitro assays for the inhibition of HDAC1, HDAC2, and HDAC3-NCoR2 by N-(2-aminophenyl)-benzamide 15k gave respective IC50 values of 80, 110, and 6 nM. Weak inhibition of all other HDAC isoforms (HDAC4, 5, 6, 7, and 9: IC50 > 100 000 nM; HDAC8: IC50 = 25 000 nM; HDAC10: IC50 > 4000 nM; HDAC11: IC50 > 2000 nM) confirmed the Class I selectivity of 15k. 2-Aminoimidazolinyl, 2-thioimidazolinyl, and 2-aminooxazolinyl units were shown to be effective replacements for the pyrimidine ring present in many other 2-(aminophenyl)-benzamides previously reported, but the 2-aminooxazolinyl unit was the most potent in inhibiting HDAC3-NCoR2. Many of the new HDAC inhibitors showed higher solubilities and lower binding to human serum albumin than that of Mocetinostat. Increases in histone H3K9 acetylation in the human cell lines U937 and PC-3 was observed for all three oxazolinyl inhibitors evaluated; those HDAC inhibitors also lowered cyclin E expression in U937 cells but not in PC-3 cells, indicating underlying differences in the mechanisms of action of the inhibitors on those two cell lines

Relating near-Earth observations of an interplanetary coronal mass ejection to the conditions at its site of origin in the solar corona

A halo coronal mass ejection (CME) was detected on January 20, 2004. We use solar remote sensing data (SOHO, Culgoora) and near-Earth in situ data (Cluster) to identify the CME source event and show that it was a long duration flare in which a magnetic flux rope was ejected, carrying overlying coronal arcade material along with it. We demonstrate that signatures of both the arcade material and the flux rope material are clearly identifiable in the Cluster and ACE data, indicating that the magnetic field orientations changed little as the material traveled to the Earth, and that the methods we used to infer coronal magnetic field configurations are effective

Coronal jets, magnetic topologies, and the production of interplanetary electron streams

We investigate the acceleration source of the impulsive solar energetic particle (SEP) events on 2007 January 24. Combining the in situ electron measurements and remote-sensing solar observations, as well as the calculated magnetic fields obtained from a potential-field source-surface model, we demonstrate that the jets associated with the hard X-ray flares and type-III radio bursts, rather than the slow and partial coronal mass ejections, are closely related to the production of interplanetary electron streams. The jets, originated from the well-connected active region (AR 10939) whose magnetic polarity structure favors the eruption, are observed to be forming in a coronal site, extending to a few solar radii, and having a good temporal correlation with the electron solar release. The open-field lines near the jet site are rooted in a negative polarity, along which energetic particles escape from the flaring AR to the near-Earth space, consistent with the in situ electron pitch angle distribution. The analysis enables us to propose a coronal magnetic topology relating the impulsive SEP events to their solar source

Skyrmions in a ferromagnetic Bose-Einstein condensate

The recently realized multicomponent Bose-Einstein condensates provide opportunities to explore the rich physics brought about by the spin degrees of freedom. For instance, we can study spin waves and phase separation, macroscopic quantum tunneling, Rabi oscillations, the coupling between spin gradients and superfluid flow, squeezed spin states, vortices and other topological excitations. Theoretically, there have been already some studies of the ground-state properties of these systems and their line-like vortex excitations. In analogy with nuclear physics or the quantum Hall effect, we explore here the possibility of observing point-like topological excitations or skyrmions. These are nontrivial spin textures that in principle can exist in a spinor Bose-Einstein condensate. In particular, we investigate the stability of skyrmions in a fictitious spin-1/2 condensate of Rb87 atoms. We find that skyrmions can exist in this case only as a metastable state, but with a lifetime of the order of, or even longer than, the typical lifetime of the condensate itself. In addition to determining the size and the lifetime of the skyrmion, we also present its spin texture and finally briefly consider its dynamical properties.Comment: 4 pages (REVtex), 3 PDF figures. See also cond-mat/000237

The JCMT Legacy Survey of the Gould Belt: Mapping 13CO and C 18O in Orion A

The Gould Belt Legacy Survey will map star-forming regions within 500 pc, using Heterodyne Array Receiver Programme (HARP), Submillimetre Common-User Bolometer Array 2 (SCUBA-2) and Polarimeter 2 (POL-2) on the James Clerk Maxwell Telescope (JCMT). This paper describes HARP observations of the J= 3 → 2 transitions of 13CO and C18O towards Orion A. The 15 arcsec resolution observations cover 5 pc of the Orion filament, including OMC 1 (including BN–KL and Orion bar), OMC 2/3 and OMC 4, and allow a comparative study of the molecular gas properties throughout the star-forming cloud. The filament shows a velocity gradient of ∼1 km s−1 pc−1 between OMC 1, 2 and 3, and high-velocity emission is detected in both isotopologues. The Orion Nebula and Bar have the largest masses and linewidths, and dominate the mass and energetics of the high-velocity material. Compact, spatially resolved emission from CH3CN, 13CH3OH, SO, HCOOCH3, CH3CHO and CH3OCHO is detected towards the Orion Hot Core. The cloud is warm, with a median excitation temperature of ∼24 K; the Orion Bar has the highest excitation temperature gas, at >80 K. The C18O excitation temperature correlates well with the dust temperature (to within 40 per cent). The C18O emission is optically thin, and the 13CO emission is marginally optically thick; despite its high mass, OMC 1 shows the lowest opacities. A virial analysis indicates that Orion A is too massive for thermal or turbulent support, but is consistent with a model of a filamentary cloud that is threaded by helical magnetic fields. The variation of physical conditions across the cloud is reflected in the physical characteristics of the dust cores. We find similar core properties between starless and protostellar cores, but variations in core properties with position in the filament. The OMC 1 cores have the highest velocity dispersions and masses, followed by OMC 2/3 and OMC 4. The differing fragmentation of these cores may explain why OMC 1 has formed clusters of high-mass stars, whereas OMC 4 produces fewer, predominantly low-mass stars

Strong environment X genotype interactions determine the fitness costs of antibiotic resistance in vitro and in an insect model of infection (article)

This is the author accepted manuscript. The final version is available from the American Society for Microbiology via the DOI in this record.The dataset associated with this article is located in ORE at: https://doi.org/10.24378/exe.2503The acquisition of antibiotic resistance commonly imposes fitness costs, a reduction in the fitness of bacteria in the absence of drugs. These costs have been primarily quantified using in vitro experiments and a small number of in vivo studies in mice, and it is commonly assumed that these diverse methods are consistent. Here, we used an insect model of infection to compare the fitness costs of antibiotic resistance in vivo relative to in vitro conditions. Experiments explored diverse mechanisms of resistance in a Gram-positive pathogen, Bacillus thuringiensis, and a Gram-negative intestinal symbiont, Enterobacter cloacae. Rifampicin resistance in B. thuringiensis showed fitness costs that were typically elevated in vivo, although these were modulated by genotype-environment interactions. In contrast, resistance to cefotaxime via de-repression of AmpC β-lactamase in E. cloacae resulted in undetectable costs in vivo or in vitro, while spontaneous resistance to nalidixic acid, and carriage of the IncP plasmid RP4, imposed costs that increased in vivo. Overall, fitness costs in vitro were a poor predictor of fitness costs in vivo because of strong genotype environment interactions throughout this study. Insect infections provide a cheap and accessible means of assessing fitness consequences of resistance mutations, data that is important to understand the evolution and spread of resistance. This study emphasizes that the fitness costs imposed by particular mutations or different modes of resistance are extremely variable, and that only a subset of these mutations are likely to be prevalent outside of the laboratory.Medical Research Council (MRC

Viral Hepatitis and Rapid Diagnostic Test Based Screening for HBsAg in HIV-infected Patients in Rural Tanzania.

\ud \ud Co-infection with hepatitis B virus (HBV) is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg) before initiation of combination antiretroviral therapy (cART) is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV) infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania. Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO) in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA. Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32-47), 169/272 (63%) subjects were females and median CD4+ count was 250 cells/µL (IQR 97-439). HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2-13.0%) subjects. Of these, 7/25 (28%) were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8-99.6%) and specificity at 100% (95% CI, 98.9-100%). Antibodies to HCV (anti-HCV) were found in 10/272 (3.7%, 95% CI 2.0-6.4%) of patients. This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa