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Results for “sample entropy”

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PubMed2005

The relationship between the flexibility of proteins and their conformational states on forming protein-protein complexes with an application to protein-protein docking.

We investigate the extent to which the conformational fluctuations of proteins in solution reflect the conformational changes that they undergo when they form binary protein-protein complexes. To do this, we study a set of 41 proteins that form such complexes and whose three-dimensional structures are known, both bound in the complex and unbound. We carry out molecular dynamics simulations of each protein, starting from the unbound structure, and analyze the resulting conformational fluctuations in trajectories of 5 ns in length, comparing with the structure in the complex. It is found that fluctuations take some parts of the molecules into regions of conformational space close to the bound state (or give information about it), but at no point in the simulation does each protein as whole sample the complete bound state. Subsequent use of conformations from a clustered MD ensemble in rigid-body docking is nevertheless partially successful when compared to docking the unbound conformations, as long as the unbound conformations are themselves included with the MD conformations and the whole globally rescored. For one key example where sub-domain motion is present, a ribonuclease inhibitor, principal components analysis of the MD was applied and was also able to produce conformations for docking that gave enhanced results compared to the unbound. The most significant finding is that core interface residues show a tendency to be less mobile (by size of fluctuation or entropy) than the rest of the surface even when the other binding partner is absent, and conversely the peripheral interface residues are more mobile. This surprising result, consistent across up to 40 of the 41 proteins, suggests different roles for these regions in protein recognition and binding, and suggests ways that docking algorithms could be improved by treating these regions differently in the docking process.

Cluster Analysis↗

PubMed2003

Complex haplotypic structure of the central MHC region flanking TNF in a West African population.

TNF polymorphisms have been associated with susceptibility to malaria and other infectious and inflammatory conditions. We investigated a sample of 150 West African chromosomes to determine linkage disequilibrium (LD) between 25 SNP markers located in an 80 kb segment of the MHC Class III region encompassing TNF and eight neighbouring genes. We observed 45 haplotypes, and 22 of them comprise 80% of the sample. The pattern of LD is remarkably patchy, such that many markers show no LD with adjacent markers but high LD with markers that are much further away. We introduce a method of examining the implications of LD data for disease association studies based on sample size considerations: this shows that certain TNF polymorphisms would be likely to yield positive associations if the true disease allele resided in LTA or BAT1. We conclude that detailed marker maps are needed to resolve the causal origin of disease associations observed at the TNF locus.

Adult↗

PubMed2004

Model for small-sample bias of free-energy calculations applied to Gaussian-distributed nonequilibrium work measurements.

We present a model for the bias of free-energy differences when determined using the nonequilibrium work (NEW) formalism due to Jarzynski. Input to the model is the distribution of work values underlying the NEW calculation, and the bias is estimated by assuming that all of the inaccuracy is incurred by failure to sample work values beyond a specific point in the tail of the distribution. The model is formulated considering both small- and large-sample NEW calculations. It is then applied to the study of bias for cases in which the work distribution is Gaussian. The model is shown to give an excellent description of the bias in situations where the bias is a more significant source of error than the sample variance. A scaling law is presented and it is shown that the bias as a function of sampling can be reduced to a single universal curve, approximately valid for all Gaussian work distributions. This result is used to formulate a simple criterion that can be applied to test if a NEW calculation is effectively free of bias. The criterion is shown to be effective even though it uses the measured (and perhaps biased) free energy as an input.

Chemistry, Physical↗

PubMed2000

Effects of genital tract inflammation on human immunodeficiency virus type 1 V3 populations in blood and semen.

We have examined cell-free viral populations in the blood plasma and seminal plasma compartments of men infected with subtype C human immunodeficiency virus type 1 (HIV-1) using the V3-specific heteroduplex tracking assay (V3-HTA). We studied two cohorts of subjects who had visited either a sexually transmitted disease (STD) clinic for genital tract inflammation in the form of urethritis (n = 43) or a dermatology clinic (controls, n = 14) in Malawi. We have previously shown that the presence of urethritis is associated with an eightfold increase in virus load in the seminal plasma compartment (M. S. Cohen et al., Lancet 349:1868-1873, 1997). The purpose of this study was to determine whether genital tract inflammation and its treatment caused genetic instability in cell-free HIV-1 populations. In a cross-sectional analysis at study entry, three-fourths of the STD and control subjects had multiple V3 populations in their blood while 60% of the STD subjects and 79% of the control subjects had multiple V3 populations in their semen. Overall, one-fourth of all of the subjects showed discordance between results with blood and semen specimens when samples were compared for the presence and absence of subpopulations. When differences in the relative levels of abundance of bands were also taken into account, two-fifths of all of the subjects showed discordance between the compartments. Among the subset of subjects in whom multiple virus populations could be detected, half showed discordance between the compartments. There were no differences between STD and control cohorts for these comparisons of the compartments in this cross-sectional analysis at study entry. Longitudinal analysis of the viral populations from two separate clinic visits over 1 to 4 weeks showed that the complexity of each V3 population as measured by Shannon entropy was different in blood and semen at the two time points, indicating that the blood and semen constitute different compartments for HIV-1. The seminal plasma compartment was more dynamic than the blood plasma compartment for the STD subjects who were treated for urethritis, with changes being noted in the presence or absence of V3-HTA bands in the semen of 29% of these subjects but in the blood of only 9% of these subjects. However, the changes were generally small. Overall, our results suggest that 40% of male subjects show discordance between seminal and blood viral populations and that the complexity of each V3 population was different between the two compartments. Both of these results point to the partial independence of the seminal compartment as a viral niche within the body.

Base Sequence↗

PubMed1982

Measurement of plasma renin activity by a simple solid phase radioimmunoassay.

A solid phase RIA in which an antibody adsorbed onto polystyrene balls was developed to determine PRA. Complete inhibition of converting enzyme and angiotensinase during enzymatic reaction was achieved by phenyl methyl sulfonyl fluoride and EDTA combination. Pepstatin A was found to be an effective agent to block angiotensin I generation during the RIA, and the sample can be directly incubated at room temperature for RIA without any special treatment to inhibit renin activity. The intra- and interassay coefficients of variation (CV) were 5.5-6.9% and 3.7-8.2%, respectively. The recovery was 91.9-117% of added angiotensin I. The assay is sufficiently sensitive and reliable for routine use and correlates acceptably (r = 0.996) with an established RIA. The antibody-adsorbed balls were compared to the soluble antibody with respect to thermodynamic parameters. It was found that the apparent equilibrium constant of the antibody-adsorbed ball was reduced to approximately 1/2 sec of soluble antibody, which was predominately due to the decrease in unitary entropy change by adsorption.

Angiotensin I↗

PubMed1991

Informational and neural adaptation curves are asynchronous.

Norwich's entropy theory of perception (plus a few additional assumptions) suggests the existence of an "infromational adaptation curves" (change in stimulus equivocation with stimulus duration) for suprathreshold prothetic stimuli that is synchronous with the "neural adaptation curve" (change in firing rate with stimulus duration) observed for sensory neurons. Five experiments are reported in which informational adaptation curves were measured for auditory and visual stimuli by having subjects make absolute identifications of suprathreshold sound or light intenstiies of various durations. Information transmissions for the shortest duration stimuli (1 and 5 msec, respectively, for light and sound) were surprisingly large (small equivocations), indicating that intensity information is acquired very rapidly by the whole organism. The equations of entropy theory were fitted to adaptation data for peripheral sensory neurons (spiral ganglion cells and retinal ganglion cells) and were compared to the informational adaptation curves. It was found that informational adaptation occurred more rapidly than neural adaptation. That is, the two types of adaptation process are asynchronous. However, for both audition and vision, the total amount of information mediated by the adaptation process (channel capacity) was about the same for both types of processes (2.03 bits vs. 2.1 bits per stimulus for sound intensity; 1.3 vs. 2.0 bits per stimulus for light intensity). Faster acquisition could be accomplished in the whole organism through convergent neural circuits that increase sampling rate by pooling the samples taken by individual receptor systems.

Adult↗

PubMed2006

Nocturnal growth hormone secretory dynamics are altered after resistance exercise: deconvolution analysis of 12-hour immunofunctional and immunoreactive isoforms.

To characterize the effects of daytime exercise on subsequent overnight growth hormone (GH) secretion and elimination dynamics, serum was sampled, and GH was measured every 10 min for 12 h (1800 to 0600) in a control (CON) condition and after a 50-set resistance exercise protocol (EX) from 1500 to 1700. GH was measured with a conventional immunoreactive (IR) and an immunofunctional (IF) assay, and values were analyzed via a multi-parameter deconvolution analysis. EX resulted in a higher overnight secretory burst frequency [CON: 7.6 (SD 2.4) < EX: 9.4 (2.2) bursts per 12 h, P = 0.005] but lower mean burst mass [CON: 9.2 (4.7) > EX: 6.0 (2.9) microg/l, P = 0.019] and secretory rate [CON: 0.68 (0.29) > EX: 0.48 (0.23) microg/l/min; P = 0.015; ANOVA main effect means presented]. Approximate entropy (ApEn) was greater after EX, indicating a less orderly GH release process than CON. The estimated half-life of IF GH was significantly lower than IR GH [IF: 15.3 (1.1) < IR 19.8 (1.6) min, P < 0.001] but similar between the CON and EX conditions (approximately 17 min). Despite the changes in secretory dynamics, 12-h mean and integrated GH concentrations were similar between conditions. The results suggest that although quantitatively similar total amounts of GH are secreted overnight in CON and EX conditions, resistance exercise alters the dynamics of secretion by attenuating burst mass and amplitude yet increasing burst frequency.

Adaptation, Physiological↗

PubMed2001

Growth hormone (GH) secretion in patients with an inactivating defect of the GH-releasing hormone (GHRH) receptor is pulsatile: evidence for a role for non-GHRH inputs into the generation of GH pulses.

GH secretion is regulated by the interaction of GHRH and somatostatin and is released in 10-20 pulses in each 24-h cycle. The exact roles in pulse generation played by somatostatin, GHRH, and the recently isolated GH-releasing peptide, Ghrelin, are not fully elucidated. To investigate the GHRH-mediated GH secretion in human, we investigated pulsatile, entropic, and 24-h rhythmic GH secretion in two young adults (male, 24 yr; female, 23 yr) from a Moroccan family with a novel inactivating defect of the GHRH receptor gene. Data were compared with values in age- and gender-matched controls. Plasma GH concentration were measured by a sensitive immunofluorometric assay, with a detection limit of 0.01 mU/L. All plasma GH concentrations in the female patient were measurable; in the male patient 30 of 145 samples were at or below the detection limit. GH secretion was pulsatile, with 21 and 23 secretory episodes/24 h in the male and female patients, respectively. The fraction of basal to total GH secretion was raised in both patients by 0.18 and 0.15, respectively. The total 24-h GH production rate was greatly diminished; in the male patient it was 6.9 mU/L (normal values for his age, 26--63 mU/L), and in the female patient it was 4.2 mU/L (normal values for her age, 96--390 mU/L). The nyctohemeral plasma GH rhythm was preserved (P < 0.001), with normal acrophases (0430 and 0218 h in the male and female, respectively). Approximate entropy was greatly elevated in both subjects (0.82 in the male and 1.17 in the female; upper normal values for age and gender, 0.24 and 0.59, respectively). Intravenous injection of 50 microg GHRH failed to increase the plasma GH concentration in both patients, but 100 microg GH-releasing peptide-2 elicited a definite increase (male patient, 0.13 to 1.74 mU/L; female patient, 0.29 to 0.87 mU/L). Both patients had a partial empty sella on magnetic resonance imaging scanning. In summary, the present studies in two patients with a profound loss of function mutation of the GHRH receptor favor the view that in the human the timing of GH pulses is primarily supervised by intermittent somatostatin withdrawal, and the amplitude of GH pulses is driven by GHRH. In addition, we infer that effectual GHRH input controls the GH cell mass and the orderliness of the secretory process.

Adult↗

PubMed2003

A thermodynamics-based estimation model for adsorption of organic compounds by carbonaceous materials in environmental sorbents.

A model was developed to estimate Langmuir affinities for adsorption of low-polarity organic compounds from either water or air by carbonaceous sorbents. Sorption enthalpies and entropies provided the basic information for the description of sorption affinities in terms of the entropy of melting and either solubility in water or vapor pressure. For m-xylene, polycyclic aromatic hydrocarbons (PAHs) and chlorobenzenes on 10 different sorbents, 80% of the measured sorption affinities fall within a factor of four of the model estimates. Equations for the limiting distribution coefficients in terms of either octanol-air (K(OA)) or octanol-water partition (K(ow)) coefficients were derived from regressions of calculated affinities combined with an estimated relation between experimental Langmuir sorption capacities and K(ow). Estimated soot-water distribution coefficients were within a factor of three of measured data for polychlorobiphenyls (PCBs) and lower molecular weight PAHs on automotive soot samples and captured the dependence of PCB distribution coefficients on the extent of ortho substitution. For higher molecular weight PAHs, sorption was underestimated. For soot in sediment-water distribution coefficients of PAHs and PCBs, estimated values captured both the trend of measured data with K(ow) and the dependence on sorbate planarity. Tentative application to aerosol-air distribution explained the observed independence of distribution coefficient-K(OA) relations for PCBs on the extent of ortho substitution and suggested nonequilibrium conditions for PAHs in comparison with recent measurements.

Adsorption↗

PubMed2002

Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men.

The present clinical study compares the impact of low- and high-dose parenteral testosterone (T) supplementation on daily GH secretory patterns and serum IGF-I, IGFBP-1, and IGFBP-3 concentrations in healthy older (60-82 yr) and young (20-40 yr) men. To this end, we administered three consecutive weekly injections of randomly ordered saline and either a low (100 mg) or a high (200 mg) dose of testosterone enanthate im; namely, saline (n = 17, young and n = 16, older), a low dose (n = 8 young, n = 8 older) and a high dose (n = 9 young, and n = 8 older) of androgen. To monitor somatotropic-axis responses, blood was sampled every 10 min for 24 h for later chemiluminescence-based assay of serum GH, RIA of serum IGF-I, and immunoradiometric assay of serum IGFBP-1 and IGFBP-3 concentrations. Data were analyzed via a nested analysis of covariance statistical design. At baseline (saline injection), older, compared with young, men maintained: 1) similar serum total T, IGFBP-1, and IGFBP-3 but reduced IGF-I concentrations, namely, mean (+/- SEM) IGF-I 160 plus or minus 15 vs. 280 plus or minus 18 microg/liter, (P < 0.001); 2) reduced GH secretory burst mass (0.68 +/- 0.09 vs. 1.2 +/- 0.20 microg/liter, P = 0.031); 3) more disorderly GH release patterns (approximate entropy 0.501 +/- 0.058 vs. 0.288 +/- 0.021, P < 0.001); and 4) blunted 24-h rhythmic GH output (nyctohemeral amplitude 0.25 +/- 0.05 vs. 0.47 +/- 0.08 microg/liter, P = 0.025). Serum T concentrations (ng/dl) did not differ in the two age groups supplemented with either a low dose [550 +/- 50 (young) and 544 +/- 128 (older)] and high [1320 +/- 92 (young) and 1570 +/- 140 (older)] dose of T. The 100-mg dose of androgen exerted no detectable effect on GH secretion in either age cohort but increased the serum IGF-I concentration in young men by 20% (P = 0.00098). The 200-mg dose of T failed to alter daily GH production in young volunteers but in older men stimulated: 1) a 2.03-fold rise in the mean (24-h) serum GH concentration (P = 0.0053, compared with the response to saline); 2) a 1.20-fold increase in basal (nonpulsatile) GH production (P = 0.039); 3) a 2.15-fold amplification of GH secretory burst mass (P = 0.0020); 4) a 2.17-fold elevation of the Mesor of nyctohemeral GH output (P = 0.025); 5) a 1.79-fold enhancement in GH approximate entropy (P = 0.0003); and 6) a 40% increase in the fasting serum IGF-I concentration (P = 0.000005). Multivariate statistical analysis indicated that following high-dose T administration, the E2 increment significantly predicted the IGF-I increment in both age groups combined (P = 0.003); T dose positively forecast the serum total IGF-I concentration (P = 0.0031); and age and T dose jointly determined serum LH concentrations (P = 0.031). In summary, neither a physiological nor a pharmacological dose of T administered parenterally for 3 wk augments daily GH secretion in eugonadal young men. In contrast, a high dose of aromatizable androgen significantly amplifies 24-h basal, pulsatile, entropic, and nyctohemerally rhythmic GH production and elevates the serum IGF-I concentration in older men. The mechanistic basis for the foregoing age-related distinction in GH/IGF-I axis responsivity to T is not known.

Aged↗

PubMed2004

Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity.

Ghrelin plays a key role in the regulation of growth hormone secretion and energy homeostasis. Adiponectin is exclusively secreted by adipose tissue and is abundantly present in the circulation, with important effects on metabolism. We studied five lean and five obese young men [ages: 24.2 +/- 1.0 (lean) and 21.8 +/- 1.6 (obese) years (difference not significant); body mass indexes: 35.0 +/- 1.3 and 23.0 +/- 0.3 kg/m2 (P = 0.01)], sampled blood every 7 min over 24 h, and measured ghrelin, adiponectin, and leptin in 2,070 samples for a total of 6,210 data points. Circulating 24-h ghrelin showed significant ultradian fluctuations and an orderly pattern of release in lean and obese subjects with similar pulsatility characteristics. Plasma adiponectin concentrations were significantly lower in the obese group, with lower pulse height. In contrast to leptin, which is secreted in an orderly manner, the 24-h patterns of adiponectin were not significantly different from random in both the lean and obese groups. We show here that adipocytes can simultaneously secrete certain hormones, such as leptin, in patterns that are orderly, whereas other hormones, such as adiponectin, are secreted in patterns that appear to be random. The cross-approximate entropy statistic revealed pattern synchrony among ghrelin-leptin, ghrelin-adiponectin, and leptin-adiponectin hormone time series in the lean and obese subjects. Plasma ghrelin concentrations showed a nocturnal rise that exceeded the meal-associated increases in lean subjects, and this newly identified nocturnal rise was blunted in the obese. We suggest that the blunting of the nocturnal rise of ghrelin is a biological feature of human obesity.

Adipocytes↗

PubMedDate not supplied

Genomics and proteomics: the new millennium of drug discovery and development.

One of the most pressing issues facing the pharmaceutical and biotechnology industry is the tremendous dropout rate of lead drug candidates. Over the last two decades, several new genomic technologies have been developed in hopes of addressing the issues of target identification and lead candidate optimization. Gene expression microarray is one of these technologies and this review describes the four main formats, which are currently available: (a) cDNA; (b) oligonucleotide; (c) electrokinetic; and (d) fiberoptic. Many of these formats have been developed with the goal of screening large numbers of genes. Recently, a high-throughput array format has been developed where a large number of samples can be assayed using arrays in parallel. In addition, focusing on gene expression may be only one avenue in preventing lead candidate failure. Proteomics or the study of protein expression may also play a role. Two-dimensional polyacrylamide gel electrophoresis (2-DE) coupled with mass spectroscopy has been the most widely accepted format to study protein expression. However, protein microarrays are now being developed and modified to a high-throughput screening format. Examples of several gene and protein expression studies as they apply to drug discovery and development are reviewed. These studies often result in large data sets. Examples of how several statistical methods (principal components analysis [PCA], clustering methods, Shannon entropy, etc.) have been applied to these data sets are also described. These newer genomic and proteomic technologies and their analysis and visualization methods have the potential to make the drug discovery and development process less costly and more efficient by aiding to select better target and lead candidates.

Drug Industry↗

PubMed2004

Analysis of hepatitis C virus quasispecies transmission and evolution in patients infected through blood transfusion.

BACKGROUND & AIMS: Studies on hepatitis C virus (HCV) quasispecies dynamics in the natural course of infection are rare owing to difficulties in obtaining samples from the early phase of infection. METHODS: We studied 15 patients from the Transfusion-Transmitted Viruses Study who seroconverted to anti-HCV after receiving infected blood. Follow-up serum samples were collected every 2-3 weeks for 6 months, at 10 months, and at 11-16 years. Viral quasispecies in the second envelope hypervariable region 1 (E2/HVR1) and 5' untranslated region (5'UTR) were analyzed with single-strand conformation polymorphism (SSCP) and heteroduplex mobility assay (HMA). RESULTS: Seven patients cleared infection within 7-24 weeks (mean, 14.0 wk) and 3 patients eventually became anti-HCV negative. In 6 patients with resolving hepatitis the SSCP band pattern remained stable, whereas in one patient minor changes appeared before clearance. In contrast, in all 8 patients progressing to chronicity, major changes in the E2/HVR1 quasispecies developed at 8-22 weeks (mean, 13.1 wk). Shannon entropy and medium mobility shift values derived from HMA gels remained stable in patients with resolving hepatitis but changed in those who developed chronic infection. Only 2 patients showed minor changes in 5'UTR. A decrease in E2/HVR1 complexity at the time of transmission (bottleneck) was found in 5 patients altogether. CONCLUSIONS: Changes in E2/HVR1 quasispecies 8-22 weeks after infection, likely caused by mounting immune pressure, were predictive of ensuing chronic infection, whereas stability was associated with resolution. Our study also showed that composition of HCV quasispecies may be preserved during transmission from host to host.

Adult↗

PubMed2005

Predicting failure using conditioning on damage history: demonstration on percolation and hierarchical fiber bundles.

We formulate the problem of probabilistic predictions of global failure in the simplest possible model based on site percolation and on one of the simplest models of time-dependent rupture, a hierarchical fiber bundle model. We show that conditioning the predictions on the knowledge of the current degree of damage (occupancy density p or number and size of cracks) and on some information on the largest cluster improves significantly the prediction accuracy, in particular by allowing one to identify those realizations which have anomalously low or large clusters (cracks). We quantify the prediction gains using two measures, the relative specific information gain (which is the variation of entropy obtained by adding new information) and the root mean square of the prediction errors over a large ensemble of realizations. The bulk of our simulations have been obtained with the two-dimensional site percolation model on a lattice of size L x L=20 x 20 and hold true for other lattice sizes. For the hierarchical fiber bundle model, conditioning the measures of damage on the information of the location and size of the largest crack extends significantly the critical region and the prediction skills. These examples illustrate how ongoing damage can be used as a revelation of both the realization-dependent preexisting heterogeneity and the damage scenario undertaken by each specific sample.

Journal Article↗

PubMed1995

Variability analysis of the T-cell receptors using three variability indexes.

In the absence of a three-dimensional structure for TCR molecules, several attempts to identify their hypervariable regions by variability methods have been made; this subjects is still troublesome. In this paper three different variability indexes were used: (i) the Kabat index, which is the classical measure of sequence variability, (ii) the modified Kabat index, successfully used in the beta-chain of T-cell receptors and (iii) an information-theoretical entropy concept, recently proposed as an improved measure of the variability. In order to identify the hypervariable regions in the TCR sequences, a Fourier filtering was applied on each variability profile. Results show that the three variability indexes have distinct resolutions for different levels of variability. Thus, the simultaneous use of these indexes compensates for the deficiency of any one of them in estimating variability. Applying the Fourier filtering, it is found that the hypervariable regions here identified, roughly coincide with the defined CDR-2 and CDR-3 in TCR by analogy with Ig. However, no hypervariable in the CDR-1 of alpha- and beta-chains was found. The study on the influence of sample size in variability analysis, indicates that results are independent of the sample size. Considering current structural models of TCR-peptide-MHC interaction, one can suggest that the low-variability characteristics of these regions is inherently related to the interaction with relatively conserved region on the alpha-helices of MHC.

Amino Acid Sequence↗

PubMed1997

Differential molar heat capacities to test ideal solubility estimations.

PURPOSE: Calculation of the ideal solubility of a crystalline solute in a liquid solvent requires knowledge of the difference in the molar heat capacity at constant pressure of the solid and the supercooled liquid forms of the solute, delta Cp. Since this parameter is not usually known, two assumptions have been used to simplify the expression. The first is that delta Cp can be considered equal to zero; the alternate assumption is that the molar entropy of fusion, delta Sf, is an estimate of delta Cp. Reports claiming the superiority of one assumption over the other, on the basis of calculations done using experimentally determined parameters, have appeared in the literature. The validity of the assumptions in predicting the ideal solubility of five structurally unrelated compounds of pharmaceutical interest, with melting points in the range 420 to 470 K, was evaluated in this study. METHODS: Solid and liquid heat capacities of each compound near its melting point were determined using differential scanning calorimetry. Linear equations describing the heat capacities were extrapolated to the melting point to generate the differential molar heat capacity. RESULTS: Linear data were obtained for both crystal and liquid heat capacities of sample and test compounds. For each sample, ideal solubility at 298 K was calculated and compared to the two estimates generated using literature equations based on the differential molar heat capacity assumptions. CONCLUSIONS: For the compounds studied, delta Cp was not negligible and was closer to delta Sf than to zero. However, neither of the two assumptions was valid for accurately estimating the ideal solubility as given by the full equation.

Calorimetry, Differential Scanning↗

PubMed2005

The dynamics of growth hormone (GH) secretion in adult cancer survivors with severe GH deficiency acquired after brain irradiation in childhood for nonpituitary brain tumors: evidence for preserved pulsatility and diurnal variation with increased secretory disorderliness.

Dynamics of GH secretion in patients with GH deficiency due to radiation damage of the hypothalamic-pituitary (h-p) axis acquired in childhood has rarely been studied. Thus, we used a sensitive chemiluminescence GH assay to analyze 24-h GH profiles (20-min sampling) from 10 adult cancer survivors with severe GH deficiency acquired after brain irradiation in childhood for nonpituitary brain tumors. An age- and sex-matched control group of 30 normal healthy volunteers, eight of whom were matched for body mass index with the patients, were also studied. Cluster analysis with gender-specific comparisons revealed a significant reduction (P < 0.05) in all amplitude-related measurements [profile mean GH levels or area under curve for GH, absolute (maximum) GH peak height, mean peak height, and mean pulse area] in patients. No differences were observed in frequency-related measurements (pulse frequency, pulse duration, and interpulse interval). Pulsatile secretion was relatively more attenuated than basal secretion in patients, and approximate entropy (ApEn) scores were significantly (P < 0.05) elevated, suggesting more disordered GH secretion. Radiation inflicts quantitative damage to the h-p axis, leading to amplitude-dependent dampening of GH secretion with relative preservation of nonpulsatile secretion. Qualitative perturbation in hypothalamic control of GH release is evident by the increase in ApEn values reflecting more disordered GH secretion. The integrity of the h-p axis and GH neuroregulation is fundamentally preserved in irradiated GH-deficient patients with a GH secretory pattern similar to that observed in normal subjects and those with GH deficiency due to other etiologies.

Adolescent↗

PubMed2006

Effect of molecular chirality on racemate stability: alpha-amino acids with nonpolar R groups.

A racemate of two opposite and resolvable enantiomers is generally assumed to be more stable than the corresponding conglomerate. Demonstrating this structure-stability relation, however, has proved difficult owing to a sampling bias (data available only for systems whose racemates are stable enough to exist) and a possible kinetic bias (racemates may be easier to crystallize than conglomerates from racemic media). As a new approach to studying the relation, we determined how the relative stability of the conglomerate and the racemate changes with the molecule's degree of chirality in a series of alpha-amino acids with nonpolar R groups. We found that the excess energy of the conglomerate over the racemate, (E(C) - E(R)), increases with the size of the R group, a measure of the molecule's chirality. If valid in general, this relation demonstrates a tendency for chiral molecules to form racemates rather than conglomerates. Because of the entropy effect on crystal stability, however, the excess free energy of the conglomerate over the racemate, (G(C) - G(R)), shows no simple relation with the degree of chirality at the temperatures of study (-3 to 180 degrees C).

Amino Acids↗