New nonsteroidal androgen receptor modulators based on 4-(trifluoromethyl)-2(1H)-pyrrolidino[3,2-g] quinolinone

Typhoid fever is often associated with abnormal liver biochemical tests, but severe hepatic involvement with a clinical feature of acute hepatitis is a rare complication. There have been more than 150 cases of salmonella hepatitis reported from both developed and developing countries. The documented incidence varies widely from less than 1% to 26% patients with enteric fever. The possible associated factors for development of salmonella hepatitis are virulence of the organisms, delayed treatment and poor general health of the patients. The pathogenesis of severe hepatic involvement in salmonella infection may be multifactorial and includes endotoxin, local inflammatory and/or host immune reactions. Clinical jaundice in salmonella hepatitis usually occurs within the first 2 weeks of the febrile illness. Hepatomegaly and moderate elevation of transaminase levels are common findings. Extreme hepatic dysfunction with hepatic encephalopathy is a rare coexisting complication in salmonella hepatitis. A positive culture for salmonella from blood or stool is essential to differentiate salmonella hepatitis from other causes of acute hepatitis. Hepatic pathology is characterized by the presence of typhoid nodules with marked hyperplasia of reticuloendothelial cells. The prognosis is usually good as salmonella hepatitis responds well to a specific antibiotic therapy and juandice resolves with clinical improvement. The clinical course can be severe with a mortality rate as high as 20%, particularly with delayed treatment or in patients with other complications of salmonella infection. As enteric fever is a common infection, the recognition of salmonella hepatitis is of clinical importance.     

An atomic model of the outer layer of the bluetongue virus core derived from X-ray crystallography and electron cryomicroscopy

BACKGROUND: Bluetongue virus (BTV), which belongs to the Reoviridae family and orbivirus genus, is a non-enveloped, icosahedral, double-stranded RNA virus. Several protein layers enclose its genome; upon cell entry the outer layer is stripped away leaving a core, the surface of which is composed of VP7. The structure of the trimeric VP7 molecule has previously been determined using X-ray crystallography. The articulated VP7 subunit consists of two domains, one which is largely alpha-helical and the other, smaller domain, is a beta barrel with jelly-roll topology. The relative orientations of these two domains vary in different crystal forms. The structure of VP7 and the organizations of 780 subunits of this molecule in the core of virus is central to the assembly and function of BTV. RESULTS: A 23 A resolution map of the core, determined using electron cryomicroscopy (cryoEM) data, reveals that the 260 trimers of VP7 are organized on a rather precise T = 13 laevo icosahedral lattice, in accordance with the theory of quasi-equivalence. The VP7 layer occupies a shell that is between 260 A and 345 A from the centre of the core. Below this radius (230-260 A) lies the T = 1 layer of 120 molecules of VP3. By fitting the X-ray structure of an individual VP7 trimer onto the cryoEM BTV core structure, we have generated an atomic model of the VP7 layer of BTV. This demonstrates that one of the molecular structures seen in crystals of the isolated VP7 corresponds to the in vivo conformation of the molecule in the core. CONCLUSIONS: The beta-barrel domains of VP7 are external to the core and interact with protein in the outer layer of the mature virion. The lower, alpha-helical domains of VP7 interact with VP3 molecules which form the inner layer of the BTV core. Adjacent VP7 trimer-trimer interactions in the T = 13 layer are mediated principally through well-defined regions in the broader lower domains, to form a structure that conforms well with that expected from the theory of quasi-equivalence with no significant conformational changes within the individual trimers. The VP3 layer determines the particle size and forms a rather smooth surface upon which the two-dimensional lattice of VP7 trimers is laid down.     

Head injury mechanisms and the concept of preventive management: a review and critical synthesis

Recent advances in head injury research have produced a plethora of useful data coupled with a paucity of conceptual integration across the four ways in which this research is pursued. These research orientations are the epidemiological, biomechanical, basic neuroscientific, and clinicopathologic/therapeutic (including rehabilitation). This overview of the history and current state of the art assumes that biomechanics is the basic science of causation in head injury research and when fully integrated with its counterparts, physiology and pathology, it can serve to overcome our conceptual handicaps. A paradigm integrating biomechanics; into the sequence of preventive, protective, acute therapeutic, and rehabilitative interventions will be described as the concept of preventive management. From this we derive the hypothesized claim that the exact biomechanics and the physiopathologic response at the time of injury (at the macroscopic and microscopic levels) determine the sequence of so-called secondary effects that are conceived as the inexorable delayed manifestations of the primary events and concomitant boundary conditions. Knowledge of these events will enable accurate predictions of the natural history and outcome of head injuries from observations carried out in the early acute phase. Examples to test this claim will be given with particular reference to the two types of traumatic brain injury (TBI) phenomenologically associated with disturbances of consciousness, the onset of which can be either immediate or delayed. The current economics and availability of computational power provide a significant opportunity for the development of selected experimental, physical, and simulated models of head injury on the basis of which the complex neurovascular and nonneural cellular and fluid elements of the nervous system may be accurately modeled. This approach will significantly improve the efficiency and quality of the essential biological and clinical observations and model experiments required to validate the theoretical methods and their predictions.     

Collisionless spin waves in normal and superfluid3He

Standing spin-wave modes in liquid³He have been studied by cw NMR at Larmor frequencies of 1, 2, and 4 MHz and pressures of 0, 6.3, and 12.3 bar. The spin waves, which produce peaks in the NMR line, are visible at temperatures below 5 mK at zero pressure. With the assumption of a slightly simplified sample shape and no transverse spin relaxation at the walls, the theory of Leggett fits the spin-wave frequencies in the normal liquid very well, giving a value of the Fermi liquid parameterF ₁ ^a =–0.6±0.2 at zero pressure. The width of some of the peaks is larger than expected from other determinations of the quasiparticle diffusion time _D . This could be due to wall relaxation or to deviations from the assumed sample geometry. In the superfluid A₁ and A phases, where the data cannot be fitted to existing theories, the spin-wave modes are shifted in frequency and suffer additional damping as the temperature is decreased. At still lower temperatures in the B phase an inversion of the spin-wave spectrum from one side of the NMR line to the other is observed, agreeing quantitatively with the predictions of the 1975 theory of Combescot.     

Solvent-free oxidation of benzyl alcohol with oxygen using zeolite-supported Au and Au–Pd catalysts

The oxidation of benzyl alcohol to benzaldehyde has been investigated in the absence of solvent using zeolite-supported Au and Au–Pd catalysts. Three zeolites were investigated, ZSM-5, zeolite β and zeolite Y, and these were contrasted with the titanoslicalite TS-1 and TiO₂ as supports. For the Au catalysts the best results are obtained with zeolite β as the support and the conversions were comparable or better than those observed with TiO₂ in terms of turn over frequencies. However, the selectivities observed with the acidic zeolites were lower than the non-acidic TS-1 and TiO₂. This is due to the subsequent reaction of benzaldehyde via acid catalysed reactions to give benzyl benzoate and its dibenzyl acetal, and, in some cases dibenzylether. Initial catalysts were evaluated with a gold loading of 2 wt% and increasing this to 4 wt% showed the expected increase in activity, indicating that there is scope to improve the performance of these catalysts. The most active catalysts were prepared by impregnation and catalysts prepared by deposition precipitation were considerably less active. Introduction of Pd into the catalyst improved the activity without significantly affecting the selectivity.     

Studies of lipoproteins and fatty acids in maternal and cord blood of two racial groups in Trinidad

The high mortality rate from coronary heart disease (CHD) among Indians compared to Negroes in Trinidad led us to test plasma lipid profiles to see whether dietary or genetic factors might be involved. There were no interracial differences in the composition of plasma cholesterol ester fatty acids of the tested women and neonates. This finding suggests that dietary fat does not account for the interracial difference in CHD, nor does the cause appear to be due to genetic differences in lipid profiles, as there was no significant difference between values for plasma triglycerides, total cholesterol, high density lipoprotein (HDL) cholesterol, apo-I, apo-II, apo B or cholesterol ester fatty acids in the cord blood of each racial group. Blood samples were collected from 69 nonpregnant and 71 postpartum, fasted Negro and Indian women. Also taken were 71 umbilical cord blood samples. The mean triglyceride level was significantly lower in the Negro nonpregnant and postpartum women than in the Indians. HDL cholesterol and apo-I values were lower in the Indian women. There were no significant differences in the total cholesterol and apo B measurements. The triglyceride values for postpartum women were higher than those of the nonpregnant Negroes and Indians (75% and 47%, respectively), whereas the total cholesterol and HDL cholesterol, apo A-I and apo A-II ranged from 9% to 29% higher in the postpartum women. Apo B was about 40% higher postpartum in both ethnic groups. The high CHD rate of Indians in Trinidad cannot be explained by dietary factors, plasma total cholesterol or fatty acid composition. However, the lower level of HDL cholesterol and plasma A-I could play a role in the higher CHD rate in Indians.     

Dynamic behaviour of viologen-activated nanostructured TiO2: correlation between kinetics of charging and coloration

The dynamic response of viologen-activated nanostructured titanium dioxide has been studied by means of electrical and electro-optical measurements. We show that the state of charge of the semiconductor network is the key factor mediating between the electrode potential and colouration of viologen. Theoretically, we relate the electrode potential to the statistics of occupancy of both TiO₂ nanoparticles and oxidized viologen molecules attached to the surface, on the assumption of quasi-equilibrium of Fermi levels in these contacting phases. Experimentally, we determine the statistical function from steady-state measurements (electrochemical impedance spectroscopy) of the capacitance of the semiconductor film. From this understanding we explain the main features that correlate the simultaneous voltammetry and transmittance responses. Finally, the redox process of viologen is resolved separately from the TiO₂ response by means of transmittance data.     

Studies of cyclic and linear poly(dimethyl siloxanes): 5. Diffusion behaviour in dilute solution

The diffusion coefficients of cyclic and linear oligomeric and polymeric dimethyl siloxanes, containing number-average numbers of skeletal bonds in the range $\text{6 <}\text{n}\text{?}{}_{\mathrm{n}}\text{< 650}$, have been measured in toluene solution at 298K. Impermeable diffusion behaviour was observed for all the siloxanes studied, in agreement with previous findings for ethylene oxide and hexamethylene oxide oligomers and polymers. The ratio of the friction coefficients $\text{f}{}_{\mathrm{r}}\text{f}{}_{\mathrm{l}}$ for the ring (r) and linear (l) dimethyl siloxanes was found to be $\text{8}\text{3κ}$ (within the limits of experimental error) over the whole range of molecular weights studied. Values of the expansion factor α_f for the linear poly(dimethyl siloxanes) (obtained from the diffusion measurements) were found to be approximately equal to the corresponding values for α_η (found previously by viscometric studies) for small values of the excluded volume parameter z; and α_f was larger than α_η for large z, as predicted by first-order perturbation theory. Mean-square radii of gyration 〈s²_G〉 were calculated from the diffusion data for both cyclic and linear poly(dimethyl siloxanes) assuming Gaussian statistics, and found to be in good agreement with the corresponding values obtained by neutron scattering. However, the values of 〈s²_G,l〉 for the short chain poly(dimethyl siloxanes) did not agree with the corresponding values of 〈s²_O,l〉, calculated using the rotational isomeric state model of Flory, Crescenzi and Mark. This discrepancy is thought to arise from deviations from Gaussian behaviour, and considerably better agreement between experiment and theory was achieved by using appropriate values of a function ψ_l(x), which relates radii of gyration and impermeable hydrodynamic diffusion radii.     

Solvent-free oxidation of benzyl alcohol using titania-supported gold–palladium catalysts: Effect of Au–Pd ratio on catalytic performance

The oxidation of benzyl alcohol with molecular oxygen under solvent-free conditions has been investigated using a range of titania-supported Au–Pd alloy catalysts to examine the effect of the Au–Pd ratio on the conversion and selectivity. The catalysts have been compared at high reaction temperature (160 °C) as well as at 100 °C, to determine the effect on selectivity since at lower reaction temperature the range of by-products that are formed are limited. Under these conditions the 2.5 wt.% Au–2.5 wt.% Pd/TiO₂ was found to be the most active catalyst, whereas the Au/TiO₂ catalyst demonstrated the highest selectivity to benzaldehyde. Toluene, formed via either a hydrogen transfer process or an oxygen transfer process, was observed as a major by-product under these forcing conditions.