Growth, voluntary food intake and digestion in farmed temperate and tropical deer

Growth and voluntary feed intake (VFI) in grazing temperate farmed deer species are influenced by the feeding value of the forage and the stage of the deer's seasonal cycle. Liveweight gain (LWG) of growing red deer was greater when perennial ryegrass (0.80)/white clover (0.20) pasture was grazed at 10 cm than 5 cm surface height, but venison production by one year of age was still low. Chicory and red clover were of superior feeding value for deer than perennial ryegrass-based pastures, increasing LWG of young red and hybrid (0.25 elk; 0.75 red deer) deer during summer and autumn, due to higher VFI and to higher organic matter digestibility. Relative to perennial ryegrass, chicory disintegrated faster in the rumen, with very low rumination time and faster rumen outflow rates of liquid and particulate matter. Inputs of red clover and chicory substantially increased venison carcass weights at one year of age from grazing red and hybrid stags. In indoor pen feeding studies, red deer were shown to have a seasonal cycle of digestive function, with greater rumen mean retention time (MRT) and greater rates of rumen ammonia production in summer than in winter. It was deduced that the purpose of the digestive cycle was to maintain apparent digestibility constant as VFI increased during summer. Tropical sambar deer were also shown to have seasonal cycles in growth and VFI that were of reduced amplitude compared with red deer. Peak VFI and growth occurred in autumn and minimum VFI and growth occurred in spring. Feed conversion (kg DM eaten/kg LWG) was more efficient for sambar than for red deer, due to lower VFI and lower heat production, but there was no difference between species in digestive efficiency.     

Mechanism of irreversible inactivation of phosphomannose isomerases by silver ions and flamazine

Silver ions and silver-containing compounds have been used as topical antimicrobial agents in a variety of clinical situations. We have previously shown that the enzyme phosphomannose isomerase (PMI) is essential for the biosynthesis of Candida albicans cell walls. In this study, we find that PMI can be inhibited by silver ions. This process is shown to be irreversible, and is a two-step process, involving an intermediate complex with a dissociation constant, Ki, of 59 +/- 8 microM, and a maximum rate of inactivation of 0.25 +/- 0.04 min-1 in 50 mM Hepes buffer, pH 8.0 at 37 degrees C. The enzyme can be protected against this inactivation by the substrate mannose 6-phosphate, with a dissociation constant of 0.31 +/- 0.04 mM, close to its Km value. Flamazine (silver sulfadiazine) is a silver-containing antibiotic which is used clinically as a topical antimicrobial and antifungal agent. We compared the ability of silver sulfadiazine and two other silver-containing compounds to irreversibly inactivate C. albicans PMI. The addition of the organic moiety increased the affinity of the compounds, with silver sulfadiazine showing a Ki of 190 +/- 30 nM. In all cases, the maximum inhibition rate was similar, implying a similar rate-determining step. Silver sulfadiazine does not inhibit Escherichia coli PMI, and this suggests a role of the only free cysteine, Cys-150, in the inactivation process. To confirm this, we mutated this residue to alanine in C. albicans PMI. The resultant Cys150 --> Ala mutant protein showed similar Vm and Km values to the wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the proline-rich antigen of Coccidioides immitis as a vaccine candidate in mice

We have expressed the proline-rich antigen (PRA) from Coccidioides immitis in Escherichia coli and evaluated its potential as a vaccine candidate. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of the recombinant protein (rPRA) revealed two bands, which exhibited virtually identical primary amino acid sequences. T cells from rPRA-immunized BALB/c mice showed a significant in vitro proliferative response to rPRA. A small but statistically significant proliferative response was also induced by rPRA in T cells from mice immunized with whole-cell coccidioidal vaccines. BALB/c mice immunized with rPRA and challenged intraperitoneally with virulent C. immitis had a greatly reduced fungal burden in their lungs and spleens compared to unvaccinated mice. The number of organisms in the lungs was reduced 500-fold, and similar reductions were observed in the spleens of immunized mice. These studies support the continued development of rPRA as a candidate vaccine for prevention of coccidioidomycosis.     

An Overview of Next-Generation Androgen Receptor-Targeted Therapeutics in Development for the Treatment of Prostate Cancer

Traditional endocrine therapy for prostate cancer (PCa) has been directed at suppression of the androgen receptor (AR) signaling axis since Huggins et al. discovered that diethylstilbestrol (DES; an estrogen) produced chemical castration and PCa tumor regression. Androgen deprivation therapy (ADT) still remains the first-line PCa therapy. Insufficiency of ADT over time leads to castration-resistant PCa (CRPC) in which the AR axis is still active, despite castrate levels of circulating androgens. Despite the approval and use of multiple generations of competitive AR antagonists (antiandrogens), antiandrogen resistance emerges rapidly in CRPC due to several mechanisms, mostly converging in the AR axis. Recent evidence from multiple groups have defined noncompetitive or noncanonical direct binding sites on AR that can be targeted to inhibit the AR axis. This review discusses new developments in the PCa treatment paradigm that includes the next-generation molecules to noncanonical sites, proteolysis targeting chimera (PROTAC), or noncanonical N-terminal domain (NTD)-binding of selective AR degraders (SARDs). A few lead compounds targeting each of these novel noncanonical sites or with SARD activity are discussed. Many of these ligands are still in preclinical development, and a few early clinical leads have emerged, but successful late-stage clinical data are still lacking. The breadth and diversity of targets provide hope that optimized noncanonical inhibitors and/or SARDs will be able to overcome antiandrogen-resistant CRPC.     

Optimal Sensor Networks for Area Monitoring Using Rotating and Beam Sensors

We consider the problem of monitoring the Euclidean plane using rotating sensors with detection sectors and beam sensors. We assume that intruders can appear anywhere at any time and move arbitrarily fast, and may have full knowledge of the sensor network. We require that such intruders be detected within a finite amount of time. We give an optimal network for this problem consisting of a combination of rotating sensors of angle 0 and beam sensors that uses the minimum number of both types of sensors. We show a trade-off between the density of beam sensors needed and the angle of the detection sector of the rotating sensors. Secondly, we give a family of sensor networks using only rotating sensors for the same problem, that demonstrate a trade-off between the detection time and the density of rotating sensors used. We show that the density of rotating sensors required in this case can be significantly reduced by increasing the angle of detection sectors. Finally, we show that our results on the infinite plane can be used to derive sensor networks that monitor some finite regions using a density of sensors that is asymptotically the same, or close to that of the infinite plane case.     

Corrosion resistance of phosphate coatings obtained by cathodic electrochemical treatment: Role of anode–graphite versus steel

The formation of phosphate coatings by cathodic electrochemical treatment using graphite and steel anodes and evaluation of their corrosion resistance is addressed in this paper. The type of anode used, graphite/steel, has an obvious influence on the composition of the coating, resulting in zinc–zinc phosphate composite coating with graphite anode and zinc–iron alloy–zinc phosphate–zinc–iron phosphate composite coating with steel anode. The corrosion resistance of the coating is found to be a function of the composition of the coating. The deposition of zinc/zinc–iron alloy along with the zinc phosphate/zinc and zinc–iron phosphate using graphite/steel anodes has caused a cathodic shift in the E_corr compared to uncoated mild steel substrates. The i_corr values of these coatings is very high. EIS studies reveal that zinc/zinc–iron alloy dissolution is the predominant reaction during the initial stages of immersion. Subsequently, the formation of zinc and iron corrosion products imparts resistance to the charge transfer process and increases the corrosion resistance with increase in immersion time. The corrosion products formed might consist of oxides and hydroxychlorides of zinc and iron. The study suggests that cathodic electrochemical treatment could be effectively utilized to impart the desirable characteristics of the coating by choosing appropriate anode materials, bath composition and operating conditions.     

Time resolved study of oriented crystallisation of poly(lactic acid) during rapid tensile deformation

Poly(l-lactic acid) with 4% d-lactic acid comonomer has been drawn in the amorphous state at 80, 90, 100, 110 and 120 °C at an extension rate of 4 s⁻¹ while simultaneously recording WAXS and SAXS patterns at intervals of 0.12 s. At 80, 90 and 100 °C, crystallisation is very rapid (1-4 s⁻¹) and follows a first order transformation process to give highly oriented crystals. SAXS patterns were barely detectable at these temperatures despite fractional crystallinity of ∼0.2. At 110 and 120 °C, crystallisation was very slow (∼0.01 s⁻¹) and gave rise to crystals with a lower degree of orientation. After eventual crystallisation at 120 °C, a two-point SAXS pattern develops with narrow lateral spread, suggesting ‘shish kebab’ morphology. When the 80 °C drawn sample was annealed at 120 °C, a strong four point SAXS pattern develops. The change in drawing and crystallisation behaviour at higher draw temperature is attributed to the onset of chain retraction relaxation processes. The WAXS fibre pattern after annealing shows sampling on intermediate layer lines that is consistent with the α crystal form with a 10₃ helix. However, prior to annealing, sampling indicates a different, less defined helical configuration.     

Particle-fluid heat transfer and dispersion in fluidised beds

The dynamic response of a gas fluidised bed has been measured for a range of particle sizes of lead glass ballotini and a range of particle Reynolds numbers. A dispersion model has been formulated that includes the effects of gas and particle mixing, fluid-to-particle heat transfer and intraparticle thermal conductivity, and the dynamic thermal response in theory has been found by solving the partial differential equations in the Laplace transform domain. The coefficient of thermal dispersion, the particle-to-fluid heat transfer coefficient and the intraparticle thermal conductivity have been found for the experimental response by non-linear regression. The coefficient of axial dispersion was found to be large and the particle to fluid heat transfer coefficients agreed with an established correlation for fixed and fluidised beds. The intraparticle thermal conductivity agreed with literature values for lead glass, the estimates showed no trend with flowrate, and the standard deviation of the estimate was three times smaller than the deviation found from similar experiments in fixed beds.