An investigation into the pathogenesis of vulvo-vaginal candidosis

OBJECTIVE: To monitor yeasts isolated from women during and between episodes of recurrent vulvo-vaginal candidosis (VVC) to determine whether vaginal relapse or re-infection occurred. METHODS:Women presenting at the genitourinary medicine clinic with signs and symptoms of VVC were recruited to the study (n = 121). A vaginal washing, high vaginal swab (HVS) and rectal swab were taken and the women treated with a single 500 mg clotrimazole pessary.Women were asked to re-attend after 1, 4, and 12 weeks, or when the VVC recurred, when vaginal washings and HVS were repeated. Candida isolates recovered were strain typed using the Ca3 probe and their similarity assessed. Antifungal susceptibility to fluconazole and clotrimazole were determined. RESULTS: Of the women recruited, 47 completed the study, either returning for four visits or suffering a recurrence during the study period. Of the 22 women who experienced recurrence, the same strain was responsible for the initial and recurrent episode in 17 women. For the remaining five women, four had strain replacement and one had a change of species. None of the isolates recovered from the women demonstrated resistance to either clotrimazole or fluconazole. CONCLUSIONS: Our findings support the theory of vaginal relapse and thus may support the use of more prolonged courses of antifungal therapy initially to increase the chances of eradication of the yeast

Controllable degradation kinetics of POSS nanoparticle-integrated poly(ε-caprolactone urea)urethane elastomers for tissue engineering applications.

Biodegradable elastomers are a popular choice for tissue engineering scaffolds, particularly in mechanically challenging settings (e.g. the skin). As the optimal rate of scaffold degradation depends on the tissue type to be regenerated, next-generation scaffolds must demonstrate tuneable degradation patterns. Previous investigations mainly focussed on the integration of more or less hydrolysable components to modulate degradation rates. In this study, however, the objective was to develop and synthesize a family of novel biodegradable polyurethanes (PUs) based on a poly(ε-caprolactone urea)urethane backbone integrating polyhedral oligomeric silsesquioxane (POSS-PCLU) with varying amounts of hard segments (24%, 28% and 33% (w/v)) in order to investigate the influence of hard segment chemistry on the degradation rate and profile. PUs lacking POSS nanoparticles served to prove the important function of POSS in maintaining the mechanical structures of the PU scaffolds before, during and after degradation. Mechanical testing of degraded samples revealed hard segment-dependent modulation of the materials' viscoelastic properties, which was attributable to (i) degradation-induced changes in the PU crystallinity and (ii) either the presence or absence of POSS. In conclusion, this study presents a facile method of controlling degradation profiles of PU scaffolds used in tissue engineering applications

NuSTAR Observations of the Black Hole GS 1354-645: Evidence of Rapid Black Hole Spin

We present the results of a NuSTAR study of the dynamically confirmed stellar-mass black hole GS 1354-645. The source was observed during its 2015 "hard" state outburst; we concentrate on spectra from two relatively bright phases. In the higher-flux observation, the broadband NuSTAR spectra reveal a clear, strong disk reflection spectrum, blurred by a degree that requires a black hole spin of a = cJ/GM^2 > 0.98 (1 sigma statistical limits only). The fits also require a high inclination: theta = 75(2) degrees. Strong "dips" are sometimes observed in the X-ray light curves of sources viewed at such an angle; these are absent, perhaps indicating that dips correspond to flared disk structures that only manifest at higher accretion rates. In the lower-flux observation, there is evidence of radial truncation of the thin accretion disk. We discuss these results in the context of spin in stellar-mass black holes, and inner accretion flow geometries at moderate accretion rates.Comment: Accepted for publication in ApJ Letter

Could magnetic properties be used to image a grouted rock volume?

In this study, the feasibility to develop a detectable permeation grouting system is tested, based on the addition of magnetic materials to the grout, specifically, magnetite. A magnetic-based detection system is selected for development because unlike other previously trialled detection methods, magnetic fields are detectable over large distances within the subsurface, and importantly, attenuation of the magnetic field is not strongly dependent on the material properties of the surrounding rock. To test the conceptual feasibility of such a system, a finite element based numerical model is developed to simulate the magnetic field anomaly that can be achieved by the addition of magnetic materials to a cement grout. The model is verified against an analytical solution and then used to predict the magnetic field generated by a grouted cylinder of rock, assuming a fixed percentage of uniformly distributed magnetic minerals, and a central injection borehole. Two field trials are conducted to verify the detectable grouting concept, the first using a walkover survey that allowed mapping of the magnetic signal in 2D. The second is designed to mimic magnetic field measurements from a borehole monitoring array, with a single central magnetic grout block (representing the grout close to the injection point). Results of the two field trials show that the magnetic cement is detectable, even when the background magnetic noise within the surrounding soils/rocks is significant. A good agreement is obtained between the measured and the modelled magnetic anomaly. This research opens the door to the development of a ‘detectable’ magnetic grouting system, that can increase confidence in the integrity of grouted rock volumes and reduce the inefficiencies currently present in the grouting industry, enabling in-situ real-time optimisation of grouting campaigns

Occupation, colonialism, apartheid? A re-assessment of Israel’s practices in the occupied Palestinian territories under international law

This study was commissioned and coordinated by the Middle East Project (MEP) of the Democracy and Governance Programme, a research programme of the Human Sciences Research Council of South Africa. The genesis of this study was the suggestion made in January 2007 by Professor John Dugard, in his capacity as UN Special Rapporteur on the human rights situation in the occupied Palestinian territories, that Israel’s military occupation displays elements of colonialism and apartheid. The Human Sciences Research Council commissioned this study to scrutinise Professor Dugard’s hypothesis from the perspective of international law. Over a period of 15 months, the team of scholars engaged in extensive research, discussion, and rounds of lively debate through seven drafts. The result is the consensus represented in this report, offered here for public discussion. Constructive criticism is welcomed, in order that shortcomings in this document may be addressed in a future edition. Although this study is essentially a legal document, observations from other disciplines are encouraged

Identification of Genes Involved in Lipid Biosynthesis through de novo Transcriptome Assembly from Cocos nucifera Developing Endosperm

Cocos nucifera (coconut), a member of the Arecaceae family, is an economically important woody palm that is widely grown in tropical and subtropical regions. The coconut palm is well known for its ability to accumulate large amounts of oil, approximately 63% of the seed weight. Coconut oil varies significantly from other vegetable oils as it contains a high proportion of medium-chain fatty acids (MCFA; 85%). The unique composition of coconut oil raises interest in understanding how the coconut palm produces oil of a high saturated MCFA content, and if such an oil profile could be replicated via biotechnology interventions. Although some gene discovery work has been performed there is still a significant gap in the knowledge associated with coconut’s oil production pathways. In this study, a de novo transcriptome was assembled for developing coconut endosperm to identify genes involved in the synthesis of lipids, particularly triacylglycerol. Of particular interest were thioesterases, acyltransferases and oleosins because of their involvement in the processes of releasing fatty acids for assembly, esterification of fatty acids into glycerolipids and protecting oils from degradation, respectively. It is hypothesized that some of these genes may exhibit a strong substrate preference for MCFA and hence may assist the future development of vegetable oils with an enriched MCFA composition. In this study, we identified and confirmed functionality of five candidate genes from the gene families of interest. This study will benefit future work in areas of increasing vegetable oil production and the tailoring of oil fatty acid compositions

Impact of PNKP mutations associated with microcephaly, seizures and developmental delay on enzyme activity and DNA strand break repair

Microcephaly with early-onset, intractable seizures and developmental delay (MCSZ) is a hereditary disease caused by mutations in polynucleotide kinase/phosphatase (PNKP), a DNA strand break repair protein with DNA 5'-kinase and DNA 3'-phosphatase activity. To investigate the molecular basis of this disease, we examined the impact of MCSZ mutations on PNKP activity in vitro and in cells. Three of the four mutations currently associated with MCSZ greatly reduce or ablate DNA kinase activity of recombinant PNKP at 30°C (L176F, T424Gfs48X and exon15Δfs4X), but only one of these mutations reduces DNA phosphatase activity under the same conditions (L176F). The fourth mutation (E326K) has little impact on either DNA kinase or DNA phosphatase activity at 30°C, but is less stable than the wild-type enzyme at physiological temperature. Critically, all of the MCSZ mutations identified to date result in ∼10-fold reduced cellular levels of PNKP protein, and reduced rates of chromosomal DNA strand break repair. Together, these data suggest that all four known MCSZ mutations reduce the cellular stability and level of PNKP protein, with three mutations likely ablating cellular DNA 5'-kinase activity and all of the mutations greatly reducing cellular DNA 3'-phosphatase activity