The application of discriminant analysis and Machine Learning methods as tools to identify and classify compounds with potential as transdermal enhancers.

Discriminant analysis (DA) has previously been shown to allow the proposal of simple guidelines for the classification of 73 chemical enhancers of percutaneous absorption. Pugh et al. employed DA to classify such enhancers into simple categories, based on the physicochemical properties of the enhancer molecules (Pugh et al., 2005). While this approach provided a reasonable accuracy of classification it was unable to provide a consistently reliable estimate of enhancement ratio (ER, defined as the amount of hydrocortisone transferred after 24h, relative to control). Machine Learning methods, including Gaussian process (GP) regression, have recently been employed in the prediction of percutaneous absorption of exogenous chemicals (Moss et al., 2009; Lam et al., 2010; Sun et al., 2011). They have shown that they provide more accurate predictions of these phenomena. In this study several Machine Learning methods, including the K-nearest-neighbour (KNN) regression, single layer networks, radial basis function networks and the SVM classifier were applied to an enhancer dataset reported previously. The SMOTE sampling method was used to oversample chemical compounds with ER>10 in each training set in order to improve estimation of GP and KNN. Results show that models using five physicochemical descriptors exhibit better performance than those with three features. The best classification result was obtained by using the SVM method without dealing with imbalanced data. Following over-sampling, GP gives the best result. It correctly assigned 8 of the 12 "good" (ER>10) enhancers and 56 of the 59 "poor" enhancers (ER<10). Overall success rates were similar. However, the pharmaceutical advantages of the Machine Learning methods are that they can provide more accurate classification of enhancer type with fewer false-positive results and that, unlike discriminant analysis, they are able to make predictions of enhancer ability.

Measurement of the decay rate of single-frequency perturbations on blast waves.

To explore the validity of theories forwarded to explain the dynamics of hydrodynamic perturbations on high Mach number blast waves, we have studied the decay rate of perturbations on blast waves traveling through nitrogen gas. In our experiments, 1 kJ pulses from the Z-Beamlet laser at Sandia National Laboratories illuminated solid targets immersed in gas and created blast waves. The polytropic index implied by comparing experiment to theoretical predictions is compared to simulation results.

Normal exercise blood pressure response in African-American women with parental history of hypertension.

BACKGROUND: Genetic and environmental hypotheses may explain why normotensive persons at high risk of developing hypertension often exhibit greater cardiovascular reactivity to stressors than those at low risk. METHODS: Pearson's correlation was used to evaluate reproducibility and independent t test to compare the cardiovascular responses to 30 W of exercise of normotensive young adult African-American women with positive and negative parental histories (PH) of hypertension (PH, n = 23; PH, n = 20). RESULTS: Correlations were significant for duplicate measurements. The effects of PH on blood pressure measured at rest and during exercise were not statistically significant (P > 0.1). A nearly significant trend for greater resting (.-)VO(2) (P = 0.08) was detected in the PH than in the PH group (3.67 +/- 0.18 versus 3.26 +/- 0.14 mL/kg/min). CONCLUSION: A hyper-reactive blood pressure response to exercise, characteristic of the evolution of hypertension, may not be present among the normotensive female offspring of hypertensive African Americans. The significance of an 11% intergroup difference in the mean resting (.-)VO(2) observed in this study is unclear.

Demonstration of radiation symmetry control for inertial confinement fusion in double Z-pinch hohlraums.

Simulations of a double Z-pinch hohlraum, relevant to the high-yield inertial-confinement-fusion concept, predict that through geometry design the time-integrated P2 Legendre mode drive asymmetry can be systematically controlled from positive to negative coefficient values. Studying capsule elongation, recent experiments on Z confirm such control by varying the secondary hohlraum length. Since the experimental trend and optimum length are correctly modeled, confidence is gained in the simulation tools; the same tools predict capsule drive uniformity sufficient for high-yield fusion ignition.

Symmetric inertial-confinement-fusion-capsule implosions in a double-z-pinch-driven hohlraum.

An inertial-confinement-fusion (ICF) concept using two 60-MA Z pinches to drive a cylindrical hohlraum to 220 eV has been recently proposed. The first capsule implosions relevant to this concept have been performed at the same physical scale with a lower 20-MA current, yielding a 70+/-5 eV capsule drive. The capsule shell shape implies a polar radiation symmetry, the first high-accuracy measurement of this type in a pulsed-power-driven ICF configuration, within a factor of 1.6-4 of that required for scaling to ignition. The convergence ratio of 14-21 is to date the highest in any pulsed-power ICF system.

Physical activity and blood pressure responsiveness to the cold pressor test in normotensive young adult African-American males.

The aim of our study was to examine whether there is an association between blood pressure reactivity to the cold pressor test in African Americans who engaged in different levels of physical activity. We examined the systolic pressure, diastolic pressure, mean arterial blood pressure, heart rate, cardiac index, total peripheral resistance, and forearm blood flow during a two-minute cold pressor test in 15 aerobic, physically active and 15 physically inactive, normotensive young adult African-American males. Peak oxygen consumption varied as a function of physical activity, and was significantly higher in the physically active than in the physically inactive subjects (54.5 +/- 1.5 vs 36.8 +/- 0.7 ml kg(-1) min(-1)) (P<.05). During the cold pressor test, consisting of immersing the foot in ice water, the change in cardiovascular responses were similar between the physically active and the physically inactive groups. These results suggest that regular physical activity may not contribute to an attenuated blood pressure response to behavioral stress of the cold pressor test in normotensive young adult African-American males.

Effect of trap position, habitat, and height on the capture of pepper maggot flies (Diptera: Tephritidae).

Trapping results indicate that pepper maggot, Zonosemata electa (Say), flies occupy tree canopies adjacent to fields when not on host plants. Several in- and near-field trap positions were used to find a reliable monitoring system for adult pepper maggots. Traps baited with liquid ammonium hydroxide (Stills-style trap), hung in the canopy of trees on the edges of pepper fields, caught significantly more Z. electa flies than when positioned lower along the treeline or in the field. In a second experiment, significantly more pepper maggot flies were captured in sugar maples compared with choke cherry trees, which indicates a pest preference for certain nonhost habitats. The lowest trap height tested (2.1 m) failed to capture Z. electa flies in either tree species when the pest population level was low. These studies demonstrated that pepper maggot flies can be reliably detected with Stills-style traps positioned at approximately 6.4 m height within the canopy of sugar maple trees adjacent to pepper fields. Fruit oviposition scars also are useful site-specific indicators of pepper maggot presence/absence and may aid in determining if insecticide applications are necessary and in timing sprays.

Aerobic exercise attenuates blood pressure reactivity to cold pressor test in normotensive, young adult African-American women.

Exaggerated blood pressure reactivity to behavioral stress has been observed in the African-American population, and such a pressor response is believed to play a role in hypertension. Regular aerobic exercise has been shown to exert an anti-hypertensive effect, and this may alter the blood pressure hyperreactivity observed in African Americans. To test the hypothesis that aerobic exercise attenuates pressor reactivity in African Americans, we studied eight healthy aerobically-trained normotensive African-American females and five similar sedentary females. The stress stimuli consisted of the cold pressor test with the foot immersed in ice water for two minutes. The aerobic exercise training protocol consisted of six weeks of jogging at 60-70% of peak oxygen uptake (VO2peak), three days/week for 35 min/exercise session. Systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, heart rate, cardiac output, total peripheral resistance, and forearm blood flow were measured. Manifestation of a training effect was illustrated by a 24.1 +/- 0.2% increase in VO2peak (26.9 +/- 1.2 mL x kg(-1) min(-1) vs 35.4 +/- 1.6 mL x kg(-1) min(-1)) (P<.05). Within the exercise-trained group there was a 6.3 +/- .15% decrease in systolic pressure (129 +/- 4.6 mm Hg vs. 121 +/- 5.4 mm Hg) (P<.05), and a 5.0 +/- .05% decrement in mean arterial blood pressure (99 +/- 3.3 mm Hg vs 94 +/- 3.6 mm Hg) (P<.05) during the cold pressor test. Pressor reactivity to cold stress did not change in the untrained group. Measures of heart rate, cardiac output, total peripheral resistance, and forearm blood flow were unaltered during conditions of the cold pressor test. We conclude that aerobic exercise attenuates the blood pressure reactivity to behavioral stress in young, adult normotensive African-American females. A lifestyle change such as exercising may play a role in reducing the risk of hypertension in African-American women.

Hierarchical classification with a competitive evolutionary neural tree.

A new, dynamic, tree structured network, the Competitive Evolutionary Neural Tree (CENT) is introduced. The network is able to provide a hierarchical classification of unlabelled data sets. The main advantage that the CENT offers over other hierarchical competitive networks is its ability to self determine the number, and structure, of the competitive nodes in the network, without the need for externally set parameters. The network produces stable classificatory structures by halting its growth using locally calculated heuristics. The results of network simulations are presented over a range of data sets, including Anderson's IRIS data set. The CENT network demonstrates its ability to produce a representative hierarchical structure to classify a broad range of data sets.

Racial differences in minimum lower leg vascular resistance in normotensive young adults with positive and negative parental histories of hypertension.

OBJECTIVE: To determine whether peripheral hemodynamic differences exist in young adult normotensive African Americans and white Americans with a positive and negative parental history of hypertension. METHODS: The participants were healthy men of whom 13 were African Americans and nine white Americans with a positive parental history and 19 were African Americans and 13 white Americans with a negative parental history. Lower leg blood flows were obtained at rest and during reactive hyperemia. Lower leg minimum vascular resistance (Rmin) was computed from reactive hyperemic blood flow measured by venous occlusion plethysmography, and mean arterial blood pressure was determined by auscultation of the brachial artery. RESULTS: Resting blood flow and mean arterial pressure were similar in all groups. A significant race x parental history interaction effect was observed for lower leg Rmin. In the white men the lower leg Rmin was significantly greater in the positive than the negative parental group (P < 0.05). Lower leg Rmin was significantly greater in African Americans than in white men without a parental histoy (P < 0.05). Mean arterial blood pressure and heart rate were similar among the groups. CONCLUSIONS: This study demonstrates that lower leg Rmin is greater in young white men with a positive parental history of hypertension than those with a negative parental history. In African Americans with either positive or negative parental histories, lower leg Rmin is not different. This finding suggests that heredity may have a greater influence in white populations than in African Americans on the structural changes in resistance vessels. The study also suggests that African Americans have an earlier structural change in the resistance vessels compared with white people, regardless of a parental history of hypertension. This suggests that factors other than heredity are of importance in changing the structure of the resistance vessels.

Lower leg high-intensity resistance training and peripheral hemodynamic adaptations.

High-intensity resistance (HIR) training has been associated with muscle hypertrophy and decreased microvascular density that might produce a blood flow limitation. The effect of HIR training on lower leg maximal blood flow and minimum vascular resistance (Rmin) during reactive hyperemia were investigated in 7 healthy males. The gastrocnemius-soleus muscles of one leg were trained using maximal isokinetic concentric contractions for 4 weeks; the nontrained leg was the control. Lower leg blood flow was measured by venous occlusion plethysmography. Lower leg muscle volume was determined using magnetic resonance imaging. Peak isokinetic torque increased in both the trained (T) and nontrained (NT) legs (p < .05). Lower leg muscle volume increased by 2% in the T leg only (p < .05). In the T leg, maximal blood flow decreased and Rmin increased (p < .05); no hemodynamic change was detected in the NT leg. It is concluded that HIR training of the calf muscles is associated with a decrease in hyperemia-induced blood flow; thereby, indicating a blood flow limitation to the calf muscles.

Structure-activity relationships within a series of C(7)-substitutedoxyiminocephalosporins containing the C(3)-methylaminopyridiniumthiomethyl substituent. Synthesis and biological properties of BRL 57342 and some close analogues.

(6R,7R)-7-[2-(2-Amino-4-thiazolyl)-2-[(Z)-[(S)-carboxy(3,4- dihydroxyphenyl)methyl]oxyimino]acetamido]-3-(1-methylaminopyri dinium-4-thiomethyl)ceph-3-em-4-carboxylate sodium salt (BRL 57342, 1f) combines excellent in vitro antibacterial potency against Gram-positive and Gram-negative bacteria, including P. aeruginosa and Acinetobacter spp., with excellent stability to extended spectrum beta-lactamases. This potency is reflected in in vivo efficacy studies.

Synthesis and biological activity of 3-(N-substituted pyridinium-4-thiomethyl)-7 alpha-formamido cephalosporins.

The synthesis and antibacterial activity of a series of 3-(1-substituted pyridinium-4-thiomethyl)-7 alpha-formamido cephalosporins is described. All the derivatives showed good potency and stability to bacterial beta-lactamases. The antibacterial efficacy seen with the N-alkyl pyridinium substituents was enhanced by the introduction of a catecholic side chain at C-7 and by preparation of N-(substituted amino)pyridinium derivatives.

Synthesis and biological properties of some 3-[(N-substituted-amino)pyridinium-4-thiomethyl]-7-[2-(2-amino-thiazol- 4-yl)-2-(Z)-(methoxyimino)acetamido]ceph-3-em-4-carboxylates.

The synthesis and antibacterial activity of a series of beta-lactamase stable, broad spectrum 7-[2-(2-amino-thiazol-4-yl)-2-(Z)-(methoxyimino)acetamido]-cephalo sporins, characterised by a C-3-[N-(substituted-amino)pyridinium-4-thiomethyl] group, is described. Gram-positive and Gram-negative bacteria including extended spectrum beta-lactamase-producing strains were most susceptible to the N-amino- and N-methylamino derivatives (3a) and (3b); with the exception of Pseudomonas aeruginosa, (3b) was more active in vitro and in vivo than cefpirome or ceftazidime.

Evaluation of the Colin STBP-680 at rest and during exercise: an automated blood pressure monitor using R-wave gating.

The application of automated blood pressure measurement during exercise has been limited by inaccuracies introduced by the effects of accompanying motion and noise. We evaluated a newly developed automated blood pressure monitor for measuring exercise blood pressure (Colin STBP-680; Colin, San Antonio, Texas, USA). The STBP-680 uses acoustic transduction with the assistance of the electrocardiogram R-wave to trigger the sampling period for blood pressure measurement. The automated monitor readings were compared with simultaneous technician mercury sphygmomanometric readings in the same arm. Blood pressure was measured in 18 men at rest and during exercise at 40% VO2 peak, (low intensity), 70% VO2 peak (moderate intensity) and VO2 peak (high intensity) on the cycle ergometer. Mean(s.d.) systolic blood pressure difference between the automated monitor and mercury manometer readings at rest and during exercise at low, moderate and high work intensities were 3(0) mmHg, 3(2) mmHg, 1(1) mmHg, and 0(11) mmHg respectively (analysis of variance; P > 0.05). Resting diastolic blood pressure obtained with the STBP-680 was similar to the mercury manometer readings (78(10) versus 81(7) mmHg (P > 0.05). Exercise diastolic pressure at the low level of work intensity was almost identical between the automated monitor and mercury manometer readings (64(8) versus 65(10) mmHg (not significant)). Diastolic blood pressure readings between the STBP-680 and mercury manometer showed a greater difference at the moderate and high workloads (11 mmHg and 9 mmHg, respectively), but this difference was not significant (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of active and passive recovery on lactate removal and subsequent isokinetic muscle function.

The effect of active and passive recovery on the removal of accumulated blood lactate and subsequent muscle function were tested using five male subjects. The experimental protocol consisted of two exercise sessions performed on a mechanical brake cycle ergometer at 150% VO2max for 60 seconds. Termination of the supramaximal work bouts were followed by a 20 minutes active recovery period cycling at 30% VO2max and a 20 minutes passive recovery period sitting quietly. Following the recovery modes, isokinetic measures of peak torque, total work output and fatigue were evaluated in the dominant quadricep muscle group. During the control test, exercise performance was limited to that of isokinetic evaluation. The order of the experimental and control tests were randomly assigned. Postexercise blood lactate levels prior to the isokinetic muscle test were 9.2 and 9.1 mM during the active and passive recovery conditions respectively. Blood lactate concentration during the control test was .4 mM prior to the isokinetic muscle test. The rate of blood lactate disappearance was significantly greater during active recovery (3.5 mM) when compared with passive recovery (7.2 mM). Blood lactate concentration during the control test was significantly lower (.4 mM) in comparison to both active and passive lactate concentrations prior to the isokinetic muscle test. Despite significant differences in blood lactate between active and passive recovery conditions, there was no difference in isokinetic measures of maximal strength, work output and muscle fatigue between recovery modes. Further indication that lactate is unrelated to muscle function was the nonsignificant finding in muscle function between the control and experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Polymorphic phase behavior of lysophosphatidylethanolamine dispersions. A thermodynamic and spectroscopic characterization.

We have investigated the phase behavior of aqueous dispersions of a series of synthetic lysophosphatidylethanolamines as a function of the acyl chain length. Lysophosphatidylethanolamines exhibit phase polymorphism encompassing a well-ordered crystalline phase which may arise either from a metastable interdigitated lamellar gel phase or a metastable micellar phase. The time course of interconversion between these various phases have been outlined by observing the low temperature incubation time dependence of the calorimetric thermograms. We have determined differences in structure of these phases by Raman spectroscopy and 31P nuclear magnetic resonance spectroscopy. It appears that a principal contribution to this polymorphic phase behavior lies in the nature of headgroup hydration and headgroup-headgroup interactions.

Effects of dietary fish oil or pectin on blood pressure and lipid metabolism in the DOCA-salt hypertensive rat.

This study investigated the effects of diets containing fish oil or pectin on blood pressure and lipid metabolism in the deoxycorticosterone acetate (DOCA)-salt hypertensive rat. Three groups (8 rats/group) of unilaterally nephrectomized rats were fed for 21 d one of three purified diets: a) 8% fish oil + 2% safflower oil + 5% alpha cellulose (fish oil diet), b) 10% safflower oil + 5% pectin (pectin diet), or c) 10% safflower oil + 5% alpha cellulose (control diet). Each of the diets contained 6% NaCl and all rats received DOCA (30 mg/kg body wt, subcutaneously) twice weekly. Systolic blood pressure of rats fed fish oil was significantly lower (P less than 0.05) than that of rats fed the control diet; there was no significant difference between the pectin and control groups. Plasma renin activity and net sodium and potassium balances were similar among the three groups. Plasma total cholesterol, LDL cholesterol and HDL cholesterol were significantly lower (P less than 0.05) in the group fed the fish oil diet than in the group fed the control diet. Total, LDL and HDL cholesterol did not differ between rats fed the pectin and rats fed the control diet. Plasma triglyceride concentration did not differ among the three groups. Thus, dietary fish oil attenuated the development of DOCA-salt hypertension, unrelated to alterations of net sodium balance. Fish oil feeding also lowered total, LDL and HDL cholesterol, but did not alter the HDL/LDL ratio. In contrast, dietary pectin exerted no effect on blood pressure or lipid metabolism.