Characterization of a Reductively-Activated Elimination Pathway Relevant to the Biological Chemistry of the Kinamycins and Lomaiviticins

The lomaiviticins (1 and 2) and kinamycins (3–5) are bacterial metabolites with potent antimicrobial and antiproliferative activities. Herein we establish that 1–5 are capable of generating electrophilic acylfulvene intermediates (6) under mildly reducing conditions. These acylfulvenes 6 are formed by a multistep process comprising two-electron reduction and loss of dinitrogen to form an ortho-quinone methide, followed by elimination. Based on these studies, the structure of the product formed from 1 in DNA-cleavage assays is proposed (26). We also show that the bis(hydroxynaphthoquinone) substructures of the lomaiviticins activate the metabolites toward reduction. Finally, based on COMPARE and time-dependent cell response profiling analyses, we show that kinamycin C (4) and the monomeric lomaiviticin aglycon (24) operate by a mechanism of action that is distinct from simple diazofluorenes, such as 23

Determinants of health, health behaviours and demographic profile of patients attending an Australian university student-led osteopathy clinic.

BackgroundProfiles of health professions practice can inform pre-professional education, provide evidence to assist with interprofessional practice, and inform policy development. An understanding of the profile of patients seeking osteopathy care is emerging. Current research suggests that musculoskeletal presentations predominate with approximately one-third of patients presenting with co-morbid diseases. There is little data on these presentations in Australian osteopathy practice. This study aimed to describe the patient demographics, clinical presentations, health behaviours and determinants of health, including health literacy, of those attending for care at an Australian student-led osteopathy clinic.MethodsA convenience sample design was utilised where consecutive patients presenting for their initial consultation were invited to complete a health information questionnaire during 2016-2017. The questionnaire explored a range of health behaviours and the patient's health status. Data from the clinical records were also extracted to establish the presenting complaint, duration of the complaint and pertinent demographics. Descriptive statistics were generated for each variable.ResultsData were available for 1617 patients presenting for their initial consultation. The mean age of patients was 33.7 (±13.1) years with 55% (n = 887) identifying as female. Acute presentations predominated (n = 840, 52%), with presentations affecting the spine being the most common (57.8%). Most patients rated their health status as good to very good (75%). Approximately 7.5% of patients were identified as having low health literacy and 55.9% were currently suffering from one or more co-morbid presentations.ConclusionsThe demographic profile and presenting complaints of patients presenting to a student-led osteopathy clinic are largely consistent with other Australian private practice profiles. The current work also identified co-morbid presentations, and positive and negative health behaviours. Osteopaths may play a role in the management of, or referral for, these presentations where health behaviours require change, or management of co-morbid conditions is beyond the scope of practice. The increasing volume of patient profile literature globally suggests that osteopaths can play a substantial role in the management of musculoskeletal complaints. Further, osteopathy may play a role in screening determinants of health, and engage in multidisciplinary care to ensure those patients with co-morbid conditions or adverse health behaviours are managed appropriately

The Effect of Valve Cooling upon Maximum Permissible Engine Output as Limited by Knock

A Wright GR-1820-G200 cylinder was tested over a wide range of fuel-air ratios at maximum permissible power output as limited by knock with three different degrees of valve cooling. The valves used were stock valves (solid inlet valve and hollow sodium-cooled exhaust valve), hollow valves with no coolant, and hollow valves with flowing water as a coolant. Curves showing the variation in maximum permissible values of inlet-air pressure, indicated mean effective pressure, cylinder charge, and indicated specific fuel consumption with change in fuel-air ratio and valve cooling are shown. The use of valves cooled by a stream of water passing through their hollow interiors permitted indicated mean effective pressures 10 percent higher than the mean effective pressures permissible with stock valves when the engine was operated with fuel-air ratios from 0.055 to 0.065. Operation of the engine with lean mixtures with uncooled hollow valves resulted in power output below the output obtained with the stock valves. The data show an increase in maximum permissible indicated mean effective pressure due to cooling the valves, which averages only 2.1 percent with fuel-air ratios from 0.075 to 0.105

Radio haloes in nearby galaxies modelled with 1D cosmic-ray transport using SPINNAKER

We present radio continuum maps of 12 nearby ($D\leq 27~\rm Mpc$), edge-on ($i\geq 76^{\circ}$), late-type spiral galaxies mostly at $1.4$ and 5 GHz, observed with the Australia Telescope Compact Array, Very Large Array, Westerbork Synthesis Radio Telescope, Effelsberg 100-m and Parkes 64-m telescopes. All galaxies show clear evidence of radio haloes, including the first detection in the Magellanic-type galaxy NGC 55. In 11 galaxies, we find a thin and a thick disc that can be better fitted by exponential rather than Gaussian functions. We fit our SPINNAKER (SPectral INdex Numerical Analysis of K(c)osmic-ray Electron Radio-emission) 1D cosmic-ray transport models to the vertical model profiles of the non-thermal intensity and to the non-thermal radio spectral index in the halo. We simultaneously fit for the advection speed (or diffusion coefficient) and magnetic field scale height. In the thick disc, the magnetic field scale heights range from 2 to 8 kpc with an average across the sample of $3.0\pm 1.7~\rm kpc$; they show no correlation with either star-formation rate (SFR), SFR surface density ($\Sigma_{\rm SFR}$) or rotation speed ($V_{\rm rot}$). The advection speeds range from 100 to $700~\rm km\,s^{-1}$ and display correlations of $V\propto \rm SFR^{0.36\pm 0.06}$ and $V\propto \Sigma_{\rm SFR}^{0.39\pm 0.09}$; they agree remarkably well with the escape velocities ($0.5\leq V/V_{\rm esc}\leq 2$), which can be explained by cosmic-ray driven winds. Radio haloes show the presence of disc winds in galaxies with $\Sigma_{\rm SFR} > 10^{-3}~\rm M_{\odot}\,yr^{-1}\,kpc^{-2}$ that extend over several kpc and are driven by processes related to the distributed star formation in the disc.Comment: 39 pages, 20 colour figures, 10 tables. Accepted by MNRA

Operating Temperatures of a Sodium-Cooled Exhaust Valve as Measured by a Thermocouple

A thermocouple was installed in the crown of a sodium-cooled exhaust valve. The valve was then tested in an air-cooled engine cylinder and valve temperatures under various engine operating conditions were determined. A temperature of 1337 F was observed at a fuel-air ratio of 0.064, a brake mean effective pressure of 179 pounds per square inch, and an engine speed of 2000 rpm. Fuel-air ratio was found to have a large influence on valve temperature, but cooling-air pressure and variation in spark advance had little effect. An increase in engine power by change of speed or mean effective pressure increased the valve temperature. It was found that the temperature of the rear spark-plug bushing was not a satisfactory indication of the temperature of the exhaust valve

A Mokken analysis of the literacy in musculoskeletal problems questionnaire.

BACKGROUND: Limited health literacy is known to impact on medication adherence, hospital readmission and potentially poorer health outcomes. The literature on the health literacy of those with musculoskeletal conditions suggests greater functional limitations and increased pain levels. There are a number of measures of health literacy. One that specifically relates to musculoskeletal complaints is the Literacy in Musculoskeletal Problems (LiMP) questionnaire. The LiMP contains 9 multiple choice items that cover anatomy, musculoskeletal conditions and the diagnosis of musculoskeletal complaints. The aim of the study was to evaluate the dimensionality and internal structure of the LiMP in patients attending for osteopathy care at a student-led clinic, as a potential measure of musculoskeletal health literacy. METHOD: Three hundred and sixty-one (n = 361) new patients attending the Victoria University Osteopathy Clinic completed the LiMP and a demographic and health information questionnaire prior to their initial consultation. Mokken scale analysis, a nonparametric item response theory approach, was used to evaluate the dimensionality and structure of the LiMP in this population, to ascertain whether the questionnaire was measuring a single latent construct - musculoskeletal health literacy. McDonald's omega and Cronbach's alpha were calculated as the reliability estimations. The relationship between the LiMP and a single item screen of health literacy was also undertaken. RESULTS: The 9 items on the LiMP did not form a Mokken scale and the reliability estimations were below an acceptable level (alpha and omega <0.45). LiMP items 5 and 8 were more likely to be answered correctly by those with higher health literacy (p < 0.05), however the effect sizes were small (<0.20). CONCLUSION: Calculation of a total score for the LiMP, as advocated by the original authors, is not supported based on data in the present study. Further research is required to explore the relationship of the LiMP items to demographic and clinical data, and to other broader measures of health literacy. Further research may also develop a health literacy measure that is specific to patients seeking manual therapy care for musculoskeletal complaints

Comparative Investigations of Social Context-Dependent Dominance in Captive Chimpanzees (Pan troglodytes) and Wild Tibetan Macaques (Macaca thibetana)

Theoretical definitions of dominance, how dominance is structured and organized in nature, and how dominance is measured have varied as investigators seek to classify and organize social systems in gregarious species. Given the variability in behavioral measures and statistical methods used to derive dominance rankings, we conducted a comparative analysis of dominance using existing statistical techniques to analyze dominance ranks, social context-dependent dominance structures, the reliability of statistical analyses, and rank predictability of dominance structures on other social behaviors. We investigated these topics using behavioral data from captive chimpanzees (Pan troglodytes) and wild Tibetan macaques (Macaca thibetana). We used a combination of all-occurrence, focal-animal, and instantaneous scan sampling to collect social, agonistic, and associative data from both species. We analyzed our data to derive dominance ranks, test rank reliability, and assess cross-context predictability using various statistical analyses. Our results indicate context-dependent dominance and individual social roles in the captive chimpanzee group, one broadly defined dominance structure in the Tibetan macaque group, and high within-context analysis reliability but little cross-context predictability. Overall, we suggest this approach is preferable over investigations of dominance where only a few behavioral metrics and statistical analyses are utilized with little consideration of rank reliability or cross-context predictability