Prediction of mean skin temperature for use as a heat strain scale by introducing an equation for sweating efficiency

The present paper made the heat balance equation (HBE) for nude or minimally clad subjects a linear function of mean skin temperature (t _sk) by applying new equations for sweating efficiency (η _sw) and thermoregulatory sweat rate (S _wR). As the solution of the HBE, the equation predicting t _sk was derived and used for a heat strain scale of subjects. The η _sw was proportional to the reciprocal of S _w/E _max (S _w, sweat rate; E _max maximum evaporative capacity) and the S _wR was proportional to t _sk with a parameter of the sweating capacity of the subject. The errors of predicted t _sk from observations due to the approximation of η _sw were examined based on experimental data conducted on eight young male subjects. The value of errors of t _sk was ?0.10?±?0.42 °C (mean?±?sample standard deviation (SSD)). We aim to apply the predicted t _sk of a subject at a level of sweating capacity as a heat strain scale of a function of four environmental factors (dry- and wet-bulb temperatures, radiation, and air velocity) and three human factors (metabolic rate, sweating capacity, and clothing (≤0.2clo)).     

Development and validity of a universal empirical equation to predict skin surface temperature on thermal manikins

Clothing evaporative resistance is an important input in thermal comfort models. Thermal manikin tests give the most accurate and reliable evaporative resistance values for clothing. The calculation methods of clothing evaporative resistance require the sweating skin surface temperature (i.e., options 1 and 2). However, prevailing calculation methods of clothing evaporative resistance (i.e., options 3 and 4) are based on the controlled nude manikin surface temperature due to the sensory measurement difficulty. In order to overcome the difficulty of attaching temperature sensors to the wet skin surface and to enhance the calculation accuracy on evaporative resistance, we conducted an intensive skin study on a thermal manikin ‘Tore’. The relationship among the nude manikin surface temperature, the total heat loss and the wet skin surface temperature in three ambient conditions was investigated. A universal empirical equation to predict the wet skin surface temperature of a sweating thermal manikin was developed and validated on the manikin dressed in six different clothing ensembles. The skin surface temperature prediction equation in an ambient temperature range between 25.0 and 34.0 °C is T_sk=34.0–0.0132HL. It is demonstrated that the universal empirical equation is a good alternative to predicting the wet skin surface temperature and facilitates calculating the evaporative resistance of permeable clothing ensembles. Further studies on the validation of the empirical equation on different thermal manikins are needed however.     

Clothing insulation and temperature,layer and mass of clothing under comfortable environmental conditions

This study was designed to investigate the relationship between the microclimate temperature and clothing insulation (I_cl) under comfortable environmental conditions. In total, 20 subjects (13 women, 7 men) took part in this study. Four environmental temperatures were chosen: 14°C (to represent March/April), 25°C (May/June), 29°C (July/August), and 23°C (September/October). Wind speed (0.14ms^-1) and humidity (45%) were held constant. Clothing microclimate temperatures were measured at the chest (T_chest) and on the interscapular region (T_scapular). Clothing temperature of the innermost layer (T_innermost) was measured on this layer 30 mm above the centre of the left breast. Subjects were free to choose the clothing that offered them thermal comfort under each environmental condition. We found the following results. 1) All clothing factors except the number of lower clothing layers (L_lower), showed differences between the different environmental conditions (P<0.05). The ranges of T_chest were 31.6 to 33.5°C and 32.2 to 33.4°C in T_scapular. The range of T_innermost was 28.6 to 32.0°C. The range of the upper clothing layers (L_upper) and total clothing mass (M_total) was 1.1 to 3.2 layers and 473 to 1659 g respectively. The range of I_cl was 0.78 to 2.10 clo. 2) Post hoc analyses showed that analysis of T_innermost produced the same results as for that of I_cl. Likewise, the analysis of L_upper produced the same result as the analysis of the number of total layers (L_total) within an outfit. 3) Air temperature (t_a) had positive relationships with T_chest and T_scapular and with T_innermost but had inverse correlations with I_cl, M_total, L_upper and L_total. T_chest, T_scapular, and T_innermost increased as t_a rose. 4) I_cl had inverse relationships with T_chest and T_innermost, but positive relationships with M_total, L_upper and L_total. I_cl could be estimated by M_total, L_upper, and T_scapular using a multivariate linear regression model. 5) L_upper had positive relationships with I_cl and M_total, but L_lower did not. Subjects hardly changed L_lower under environmental comfort conditions between March and October. This indicates that each of the T_chest, M_total, and L_upper was a factor in predicting I_cl. T_innermost might also be a more influential factor than the clothing microclimate temperature.     

Clothing insulation as a biometeorological parameter during rest and exercise

A method of direct measurement of the heat and vapor transfer properties of clothing is described when worn in situ by human subjects during rest and exercise. Additional experimental observations were used to verify that a model for predicting F_pcl is reasonably accurate. From the thermal efficiency factor (F_cl), derived from _s and T_cl measurements, an effective value for I_clo can be determined and thus vapor permeation efficiency (F_pcl) can be predicted. A single coefficient () that characterizes the boundary environment over the skin surface is the ratio (hF_cl)/(h_eF_pcl) and is determined for any environment in terms of directly observed F_cl factor or clo value and relative air movement concerned. Ultimately,-factor may be used as a key biometeorological parameter to describe any heat balance condition graphically on a psychrometric chart. Its usefulness is also evident in prediction of the probable combination of operative temperature and humidity necessary for thermal acceptable zones, the limits for evaporative regulation, and the zone in which some degree of thermal regulatory failure can be expected.Presented at the Seventh International Biometeorological Congress, 17–23 August 1975, College Park, Maryland, USA.     

A comparison of galvanic skin conductance and skin wettedness as indicators of thermal discomfort during moderate and high metabolic rates

The relationship between local thermal comfort, local skin wettedness (w_local) and local galvanic skin conductance (GSC) in four body segments during two different exercise intensities was compared in 10 males. In a balanced order, participants walked at 35% VO_2max for 45 min (WALK) (29.0±1.9°C, 29.8±3.6% RH, no wind) in one test and in a separate test ran at 70% VO_2max for 45 min (RUN) (26.2±2.1°C, 31.1±7.0% RH, no wind). During both tests, participants wore a loose fitting 100% polyester long sleeve top and trouser ensemble with a low resistance to heat and vapour transfer (total thermal resistance of 0.154 m² K W⁻¹ and total water vapour resistance of 35.9 m² Pa W⁻¹). w_local, change from baseline in GSC (ΔGSC) and local thermal comfort were recorded every 5 min. The results suggest that both w_local and ΔGSC are strong predictors of thermal comfort during the WALK when sweat production is low and thermal discomfort minimal (r²>0.78 and r²>0.71, respectively). Interestingly, during the RUN w_local plateaued at ~0.6 to 0.8 due to the high sweat production, whilst ΔGSC gradually increased throughout the experiment. ΔGSC had a similar relationship with thermal comfort to w_local during the RUN (r²>0.95 and r²>0.94, respectively). Despite the strength of these relationships, the ability of w_local to predict local thermal comfort accurately dramatically reduces in the exponential part of the curve. In a situation of uncompensated heat stress such as high metabolic rate in hot climate, where sweat production is high, ΔGSC shows to be a better predictor of local thermal comfort than w_local. The w_local data shows regional differences in the threshold which triggers local discomfort during the WALK than RUN; lower values are found for upper arms (0.22±0.03 and 0.28 ±0.22) and upper legs (0.22±0.11 and 0.22±0.10), higher values for upper back (0.30±0.12 and 0.36 ±0.10) and chest (0.27±0.10 and 0.39 ±0.32), respectively. However, no regional differences in the threshold of discomfort are found in the ?GSC data. Instead, the data suggests that the degree of discomfort experienced appears to be related to the amount of sweat within and around the skin (as indirectly measured by ΔGSC) at each body site.     

Cross-Correlation Functions for a Neuronal Model

Cross-correlation functions, R_XY(t,τ), are obtained for a neuron model which is characterized by constant threshold θ, by resetting to resting level after an output, and by membrane potential U(t) which results from linear summation of excitatory postsynaptic potentials h(t). The results show that: (1) Near time lag τ = 0, R_XY(t,τ) = f_U [θ-h(τ), t + τ] {h′(τ) + E_U [u′(t + τ)]} for positive values of this quantity, where f_U(u,t) is the probability density function of U(t) and E_U [u′(t + τ)] is the mean value function of U′(t + τ). (2) Minima may appear in R_XY(t,τ) for a neuron subjected only to excitation. (3) For large τ, R_XY(t,τ) is given approximately by the convolution of the input autocorrelation function with the functional of point (1). (4) R_XY(t,τ) is a biased estimator of the shape of h(t), generally over-estimating both its time to peak and its rise time.     

Time spent in shade and its relationship with physiological factors of thermoregulation in three breeds of cattle

Time spent in shade by a group of 6 Brahman (B), 6 Shorthorn (S) and 6 Brahman × Hereford—Shorthorn cross (BX) steers was studied in an experimental shade-yard and subsequently at pasture. B sought shade least and S the most in both situations; the cooling effect of time spent in shade on S is reported. Time spent in shade was positively correlated with mean radiant temperature and solar radiation in both situation. The amount of time animals spent in shade in an experimental shade-yard was highly correlated with the amount of time spent in shade and in grazing at pasture.Mean values of rectal temperature (T_re), respiration rate (R_r), skin temperature ($\text{T}{}_{\mathrm{sk}}$) and sweating rate (S_r) measured immediately prior to release in the shade-yard were calculated. T_re and R_r were positively correlated with time spent in shade, both in the shade-yard and at pasture, and negatively correlated with time spent grazing. S_r was highly positively correlated with time spent in shade and negatively correlated with time spent grazing. The relative contribution of the physiological parameters to time spent in shade and grazing, were estimated by stepwise multiple regression models. R_r was the best predictor of the time spent in shade in both situations. The only significant improvement in variance accounted for was by the inclusion of S_r in the time spent in shade at pasture. T_re was the best predictor of grazing time and the variance accounted for by the model could not be significantly improved by inclusion of any other physiological factor measured.It is suggested that shade use and respiration rate could be simple and effective methods to select heat tolerant animals in the tropics. Both are easily measured over a wide range of situations and are better correlates of thermoregulatory behaviour than the other physiological factors measured.     

Thermal body patterns for healthy Brazilian adults (male and female)

The aim of this study was to establish the skin temperature (T_sk) thermal profile for the Brazilian population and to compare the differences between female and male Brazilian adults. A total of 117 female and 103 male were examined with a thermographic camera. The T_sk of 24 body regions of interest (ROI) were recorded and analyzed. Male T_sk results were compared to female and 10 ROI were evaluated with respect to the opposite side of the body (right vs. left) to identify the existence of significant contralateral T_sk differences (ΔT_sk). When compared right to left, the largest contralateral ΔT_sk was 0.3 °C. The female vs. male analysis yielded significant differences (p<0.05) in 13 of the 24 ROI. Thigh regions, both ventral and dorsal, had the highest ΔT_sk by sex (≈1.0 °C). T_sk percentile below P₅ or P₁₀ and over P₉₀ or P₉₅ may be used to characterize hypothermia and hyperthermia states, respectively. Thermal patterns and T_sk tables were established for Brazilian adult men and women for each ROI. There is a low T_sk variation between sides of the body and gender differences were only significant for some ROIs.     

On indicator dilution and perfusion heterogeneity: A stochastic model

Unidirectional extraction of a substrate S in the capillaries following the arterial injection of a bolus containing S and a reference tracer R is assumed to follow first-order kinetics. If C_R and C_S denote normalized venous effluent concentrations of R and S, respectively, let L(t)=ln[C_R(t)⧸C_S(t)]. We derive a formula which expresses the experimental L(t) data in terms of the mean μ(t) and variance of the transit times of those capillaries which are contributing indicators at each sample time t. We examine the information thus contained in the L data about capillary and noncapillary transit times under several kinematic assumptions. We show that if the capillary and noncapillary transit times are stochastically independent with frequency functions h_c(t) and h_av(t), respectively, then the shapes of the graphs of L(t) and μ(t) depend on the variances and skewnesses of h_c(t) and h_av(t). Specifically, let r₂ be the ratio of the variance of h_c(t) to the variance of h_av(t), and let r₃ be the ratio of skewnesses in the same order. Then the graph of μ(t) is concave downward if r₂⧸r₃ > 1, concave upward if r₂⧸r₃< 1, and linear if r₂⧸r₃ = 1. If the fraction of S extracted is not too large, L(t) has nearly the same shape as μ(t), and therefore, L(t) contains information about h_c(t) and h_av(t).     

Further evidence and biological significance for non-random localization of the centromere on mammalian chromosomes

A further quantitative analysis of the localization of the centromere on chromosomes was made using 16,817 individual chromosomes obtained from 723 mammalian species. Centromeric position was expressed quantitatively by the size of short arms as per cent weight (S_w) relative to the X-containing haploid set. When the class interval of S_w was 0·1 instead of the previous 0·2 (Imai, 1975), the frequency distribution of S_w showed an uneven (W-shaped) pattern with two distinct antimodes lying at S_w 0·6 (reconfirmation) and 0·1 (new finding). Two hypotheses, that are not mutually exclusive, are proposed to explain the non-random distribution of centromere position. One is that there are three structurally different short arms consisting of (1) centromere, (2) constitutive heterochromatin (as determined by C-banding), and (3) euchromatin, each arm-type being approximately characterized by the size of short arms (S_w) as S_w < 0·1, 0·1 ? S_w ? 0·6 and S_w > 0·6. The other possibility is concerned with an “orthogenetical” change of chromosome morphologies. When the chromosomes with S_w < 0·1, 0·1 ? S_w ? 0·6 and S_w > 0·6 are denoted as telocentric (T), acrocentric (A), and meta-, submeta- and subtelocentric (M, SM & ST), it was suggested that the chromosome morphologies tend to change orthogenetically (in a statistical sense) from T to M, SM & ST via A-chromosomes by rearrangements such as tandem growth of constitutive heterochromatic, pericentric inversions, and centric fusions.     

Alkaloids of stem and rootbark of Tabernaemontana dichotoma

During chemical investigation for compounds possessing biological activity in the stem and rootbark of Tabernaemontana dichotoma, 22 alkaloids were isolated. Ten monomeric alkaloids were identified, viz. (?)-apparicine, coronaridine, 3-oxocoronaridine, 3-ketopropylcoronaridine, 19R-heyneanine, 3-ketopropyl-19R-heyneanine, ibogamine, isomethuenine, perivine and vobasine. Two of the monomeric alkaloids isolated were new, one was identified as 3,19R-oxidocoronaridine and the other one is not yet identified. The other ten alkaloids isolated were dimeric compounds, three were identified as tabernamine, voacamine and 3′R/S-hydroxyvoacamine. Five of the dimers were new alkaloids related to tabernamine and ervahanine type structures and identified as 3′R/S-hydroxytabernamine, 3′R/S-hydroxy-N₄-demethyltabernamine, N₄-demethyltabernamine and 3′R/S-hydroxy-N₄-demethytervahanine A and B. The remaining two alkaloids are partially characterized.     

Population dynamics of a thistle-feeding lady beetle Epilachna niponica (Coccinellidae: Epilachninae) in Kanazawa, Japan. 1. Adult demographic traits and population stability

 Population dynamics of a thistle-feeding univoltine lady beetle, Epilachna niponica Lewis (Coleoptera: Coccinellidae), was studied from 1996 to 1999 in Yuwaku, Kanazawa, Japan. The lady beetles often reached such a high density level that food was depleted. The Jolly–Seber method was used for adult marking, release, and recapture data to estimate population parameters of adult number, daily resident rate, longevity, reproductive rate (R, the number of new adults produced per overwintered adults), and survival rate of new adults to the reproductive seasons (S _w). These estimates were compared with those of the Asiu, Kutsuki (A and F), and Kyoto populations, which were previously studied with similar methods and have similar intensities. Asiu and Kutsuki F populations remained at a rather low density with a low R, while Kutsuki A and Kyoto populations reached a high density where food depletion occurred with a high R value. The Yuwaku population often reached a food-depleting level as in the Kutsuki A and Kyoto populations. It also shared the short life span of overwintered adults (13.5 days) of other high-density populations; however, it showed much shorter longevity of new adults (36.6 days), much lower R (1.0–2.5), and higher S _w (43%–53%). In some traits the Yuwaku population was similar to the Asiu population: low R, high S _w, and low population variability (SD of log densities; 0.103 and 0.115 for overwintered and new adults, respectively, which were lowest among the populations). Received: July 26, 2001 / Accepted: May 21, 2002     

Adaptation of Drosophila to temperature: Heat-shock proteins and survival in Drosophila melanogaster

Two stocks of Drosophila melanogaster, one sensitive (6.5% survival) and one resistant (76.24%) to heat shock (40°C/25 min) were derived through indirect selection [1]. Genetic analysis of heat-sensitive and heat-resistant lines we had selected revealed that the survival rate is chiefly determined by cytoplasmic inheritance but also depends to some extent on the nucleus [1]. The ability of the fly to survive thermal stress was found to have an excellent correlation with the kinetics of protein synthesis in ovaries or glands subjected to heat treatment. The incorporation rate of ³⁵S-methionine into proteins was found to be higher for strains exhibiting higher survival (R₁, R₁S₁) than for strains with a lesser ability (S₁, S₁ R₁) to survive heat shock. Moreover, the intensity of labeling of the proteins synthesized and especially of the hsps (heat-shock proteins) after the heat shock is higher in the R₁ and R₁S₁ stocks than in the S₁ and S₁R₁ stocks. This convergence between survival and the cellular level of hsps (both manipulated by selection) bears on the physiological significance of these proteins which seems to participate in the control of the survival as an additive component.     

Improved predictive ability of climate–human–behaviour interactions with modifications to the COMFA outdoor energy budget model

The purpose of this paper is to implement current and novel research techniques in human energy budget estimations to give more accurate and efficient application of models by a variety of users. Using the COMFA model, the conditioning level of an individual is incorporated into overall energy budget predictions, giving more realistic estimations of the metabolism experienced at various fitness levels. Through the use of VO₂ reserve estimates, errors are found when an elite athlete is modelled as an unconditioned or a conditioned individual, giving budgets underpredicted significantly by −173 and −123 W m⁻², respectively. Such underprediction can result in critical errors regarding heat stress, particularly in highly motivated individuals; thus this revision is critical for athletic individuals. A further improvement in the COMFA model involves improved adaptation of clothing insulation (I _cl), as well clothing non-uniformity, with changing air temperature (T _a) and metabolic activity (M _act). Equivalent T _a values (for I _cl estimation) are calculated in order to lower the I _cl value with increasing M _act at equal T _a. Furthermore, threshold T _a values are calculated to predict the point at which an individual will change from a uniform I _cl to a segmented I _cl (full ensemble to shorts and a T-shirt). Lastly, improved relative velocity (v _r) estimates were found with a refined equation accounting for the degree angle of wind to body movement. Differences between the original and improved v _r equations increased with higher wind and activity speeds, and as the wind to body angle moved away from 90°. Under moderate microclimate conditions, and wind from behind a person, the convective heat loss and skin temperature estimates were 47 W m⁻² and 1.7°C higher when using the improved v _r equation. These model revisions improve the applicability and usability of the COMFA energy budget model for subjects performing physical activity in outdoor environments. Application is possible for other similar energy budget models, and within various urban and rural environments.     

Enantioselectivity and stereoselectivity in the reactions of the enantiomers of the platinum complex [PtCl2(ahaz)] (ahaz = 3(R)- or 3(S)-aminohexahydroazepine) with DNA

The platinum-DNA adduct profile formed by the R- and S-enantiomers of [PtCl₂(ahaz)] (ahaz = 3(R)-aminohexahydroazepine or 3(S)-aminohexahydroazepine) on reaction with salmon sperm DNA were characterised using HPLC and GFAAS (graphite furnace atomic absorption spectrometry) analyses. At a platinum to nucleotide ratio (R_t) equalling 0.05, the R-enantiomer forms a substantially larger amount (approximately 60%) of monofunctional adducts than the S-enantiomer (less than 35%). Fewer intrastrand GpG adducts are formed by the R-enantiomer (approximately 21%) than the S-enantiomer (approximately 37%). For both enantiomers, two isomeric GpG adducts, corresponding to the different orientations of the primary amine of ahaz ligand with respect to the O6 atom of the 5′ guanine, were observed in the ratios of 1:1.3 and 1:4.3 for the R- and S-enantiomers, respectively. The reasons for this enantioselectivity and stereoselectivity are discussed.     

Soil CO2 efflux and soil carbon balance of a tropical rubber plantation

Natural rubber is a valuable source of income in many tropical countries and rubber trees are increasingly planted in tropical areas, where they contribute to land-use changes that impact the global carbon cycle. However, little is known about the carbon balance of these plantations. We studied the soil carbon balance of a 15-year-old rubber plantation in Thailand and we specifically explored the seasonal dynamic of soil CO₂ efflux (F _S) in relation to seasonal changes in soil water content (W _S) and soil temperature (T _S), assessed the partitioning of F _S between autotrophic (R _A) and heterotrophic (R _H) sources in a root trenching experiment and estimated the contribution of aboveground and belowground carbon inputs to the soil carbon budget. A multiplicative model combining both T _S and W _S explained 58 % of the seasonal variation of F _S. Annual soil CO₂ efflux averaged 1.88 kg C m^?2 year^?1 between May 2009 and April 2011 and R _A and R _H accounted for respectively 63 and 37 % of F _S, after corrections of F _S measured on trenched plots for root decomposition and for difference in soil water content. The 4-year average annual aboveground litterfall was 0.53 kg C m^?2 year^?1 while a conservative estimate of belowground carbon input into the soil was much lower (0.17 kg C m^?2 year^?1). Our results highlighted that belowground processes (root and rhizomicrobial respiration and the heterotrophic respiration related to belowground carbon input into the soil) have a larger contribution to soil CO₂ efflux (72 %) than aboveground litter decomposition.     

Effects of bee venom melittin on the order and dynamics of dimyristoylphosphatidylcholine unilamellar and multilamellar vesicles

The effects of bee venom melittin on the order and dynamics of dimyristoylphosphatidylcholine unilamellar and multilamellar vesicles at a protein-to-lipid molar ratio of 1:60 have been investigated by employing the techniques of nanosecond emission anisotropy with 1,6-diphenyl-1,3,5-hexatriene as the fluorescent probe, enhancement by polar groups of the weakly allowed 0-0 vibronic transition in the fluorescence spectrum of pyrene, and Raman spectroscopy. The emission anisotropy results, which are found to be consistent with the wobble-in-cone model, show that the protein induces an increase in the order parameter, S, of the acyl chains of unilamellar vesicles below, at, and above their phase transition temperature, T_t, and it decreases strongly the diffusion rate, D_w, only below T_t. On the other hand, for multilamellar vesicles, the protein induces a decrease in S only at T_t and does not affect D_w. These effects are consistent with the observed changes in the degree of enhancement of the 0-0 vibronic transition of pyrene. Moreover, the protein broadens the thermal transition profile of multilamellar vesicles but sharpens dramatically that of unilamellar vesicles and fuses them without changing significantly the T_t in either case. On the other hand, the Raman data detect a decrease in the inter- and intramolecular order of the acyl chains of multilamellar vesicles below T_t and a decrease of only the former above T_t. This disparity between the Raman and the nanosecond emission anisotropy data is discussed in terms of differences in the time scales of the two techniques and in the state of aggregation of the lipid-bound melittin. The data for the enhancement of the 0-0 vibronic transition of pyrene suggest that, for a melittin-to-lipid ratio of 1:60, the size or structure of channels formed in the bilayer by melittin does not allow the penetration of a neutral molecule the size of pyrene deeply into the bilayer.     

Improvements of enzyme activity and enantioselectivity in lipase-catalyzed alcoholysis of (R,S)-azolides

With Candida antarctica lipase B (CALB)-catalyzed alcoholysis of (R,S)-naproxenyl 1,2,4-triazolide at the optimal conditions (i.e. anhydrous MTBE as the solvent, and methanol as the acyl acceptor at 45 °C) as the model system, the enzyme enantioselectivity in terms of V_R/V_S = 105.8 and specific activity for the fast-reacting (R)-azolide V_R/(E_t) = 0.979 mmol/(h g) were greatly improved in comparison with V_R/V_S = 8.0 and V_R/(E_t) = 0.113 mmol/(h g) of using (R,S)-naproxenyl 2,2,2-trifluoroethyl ester as the substrate. The resolution strategy was successfully extended to other (R,S)-profenyl 1,2,4-triazolides and lipases from Candida rugosa (Lipase MY) and Carica papaya (CPL) having opposite enantioselectivity to CALB. Moreover, the kinetic constants were estimated, compared with those obtained via hydrolysis, and employed for modeling time-course conversions of (R,S)-naproxenyl 1,2,4-triazolide in anhydrous MTBE. The advantages of easy substrate preparation, high enzyme reactivity and enantioselectivity, as well as easy product separation from the remaining substrate via reactive extraction demonstrate merits of using (R,S)-azolides but not the corresponding esters for the alcoholytic resolution.     

Synthesis and antimalarial evaluation of a screening library based on a tetrahydroanthraquinone natural product scaffold

As part of a research program aimed at discovering new antimalarial leads from Australian macrofungi a unique fungi-derived prefractionated library was screened against a chloroquine-sensitive Plasmodium falciparum line (3D7) using a radiometric growth inhibition assay. A library fraction derived from a Cortinarius species displayed promising antimalarial activity. UV-guided fractionation on the CH₂Cl₂/MeOH extract from this fungus resulted in the isolation of four known compounds: (1S,3R)-austrocortirubin (1), (1S,3S)-austrocortirubin (2), 1-deoxyaustrocortirubin (3), and austrocortinin (4). Compound 2 was used as a natural product scaffold in the parallel solution-phase synthesis of a small library of N-substituted tetrahydroanthraquinones (5–15). All compounds (1–15) were tested in vitro against P. falciparum 3D7 parasites and (1S,3S)-austrocortirubin (2), the major fungal constituent, was shown to be the most active compound with an IC₅₀ of 1.9 μM. This compound displayed moderate cytotoxicity against neonatal foreskin fibroblast (NFF) cells with an IC₅₀ of 15.6 μM.     

An active site-directed, irreversible inactivation of yeast hexokinase by (R,S)2,3-epoxypropyl beta-D-glucopyranoside

(1) Only (R,S)2′,3′-epoxypropyl β-d-glucopyranoside of the complete series of mono (R,S)2′.3′-epoxypropyl ethers and glycosides of d-glucopyranose significantly inactivated yeast hexokinase.(2) (R,S)2′,3′-Epoxypropyl β-d-glucopyranoside inactivates yeast hexokinase in the absence of MgATP^2?, The rate of inactivation is unaffected by MgATP^2?.(3) The rate of inactivation of hexokinase with (R,S)2′,3′-epoxypropyl β-d-ilucopyranoside was much greater when hexokinase was present in a monomeric form than when it was present in a dimeric form.(4) (R,S)2′,3′-Epoxypropyl β-d-glucopyranoside has a high K_t (0.38 M) and at a saturating concentrarion, the first order rate constant for the inactivation of monomeric hexokinase is 8.3 · 10^?4 sec.(5) d-Glucose protects against this inactivation and this was used to derive a dissocistion constant of 0.21 mM for d-glucose in the absence of MgATP^2?.(6) The alkylation of yeast hexokinase by (R,S)2′,3′-epoxypropyl β-d-gluco-pyranoside was not specific to the active site. When the concentration of (R,S)2′,3′-epoxypropyl β-d-glucopyranoside was 50 mM two thiol groups outside the active site were also alkylated.(7) The reaction between 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) and yeast hexokinase was examined in detail. Two thiol groups per monomer (mol. wt. 50000) reacted with a second order rate constant of 27 1 mole^?1 sec^?1. A third thiol group reacted more slowly with a second-order rate constant of 1.6 1 mole^?1 sec^?1 and a fourth thiol group reacted very slowly with inactivation of the enzyme. Tue second-order rate constant in this case was 0.1 1 mole^?1 sec^?1.