bluuebunny/crossref_metadata_2025 huggingface dataset:
Autonomic Nervous System Activity and the State and Development of Obesity in Japanese School Children
Authors: Nagai Narumi , Matsumoto Tamaki , Kita Hiroko , Moritani Toshio
Published: April 2008

Objective: The autonomic nervous system (ANS) plays an important role in regulating energy expenditure and body fat content; however, the extent to which the ANS contributes to pediatric obesity remains inconclusive. The aim of this study was to evaluate whether sympathetic and/or the parasympathetic nerve activities were altered in an obese pediatric population. We further examined a physiological association between the duration of obesity and the sympatho‐vagal activities to scrutinize the nature of ANS alteration as a possible etiologic factor of childhood obesity.

Research Methods and Procedures: Forty‐two obese and 42 non‐obese healthy sedentary school children were carefully selected from 1080 participants initially recruited to this study. The two groups were matched in age, gender, and height. The clinical records of physical characteristics and development of the obese children were retrospectively reviewed to investigate the onset and progression of obesity. The ANS activities were assessed during a resting condition by means of heart rate variability power spectral analysis, which enables us to identify separate frequency components, i.e., total power (TP), low‐frequency (LF) power, and high‐frequency (HF) power. The spectral powers were then logarithmically transformed for statistical testing.

Results: The obese children demonstrated a significantly lower TP (6.77 ± 0.12 vs. 7.11 ± 0.04 ln ms2, p < 0.05), LF power (6.16 ± 0.12 vs. 6.42 ± 0.05 ln ms2, p < 0.05), and HF power (5.84 ± 0.15 vs. 6.34 ± 0.07 ln ms2, p < 0.01) compared with the non‐obese children. A partial correlation analysis revealed that the LF and HF powers among 42 obese children were negatively associated with the duration of obesity independent of age (LF: partial r = −0.55, p < 0.001; HF: partial r = −0.40, p < 0.01). The obese children were further subdivided into two groups based on the length of their obesity. All three spectral powers were significantly reduced in the obese group with obesity of >3 years (n = 18) compared to the group with obesity of <3 years.

Discussion: Our data indicate that obese children possess reduced sympathetic as well as parasympathetic nerve activities. Such autonomic depression, which is associated with the duration of obesity, could be a physiological factor promoting the state and development of obesity. These findings further imply that preventing and treating obesity beginning in the childhood years could be an urgent and crucial pediatric public health issue.
Getting Worse: The Stigmatization of Obese Children
Authors: Latner Janet D. , Stunkard Albert J.
Published: April 2008

Objective: The prevalence of childhood obesity more than doubled in the period from 1961 to 2001. We replicated a 1961 study of stigma in childhood obesity to see what effect this increased prevalence has had on this stigma.

Research Methods and Procedures: Participants included 458 5th‐ and 6th‐grade children attending upper‐middle and lower‐middle income U.S. public schools. Children ranked six drawings of same‐sex children with obesity, various disabilities, or no disability (“healthy”), in order of how well they liked each child.

Results: Children in both the present and the 1961 study liked the drawing of the obese child least. The obese child was liked significantly less in the present study than in 1961 [Kruskal‐Wallis H (1) = 130.53, p < 0.001]. Girls liked the obese child less than boys did [H (1) = 5.23, p < 0.02]. Children ranked the healthy child highest and significantly higher than in 1961 [H (1) = 245.40, p < 0.001]. The difference in liking between the healthy and obese child was currently 40.8% greater than in 1961.

Discussion: Stigmatization of obesity by children appears to have increased over the last 40 years.
The Estrogen Antagonist EM‐652 and Dehydroepiandrosterone Prevent Diet‐ and Ovariectomy‐Induced Obesity
Authors: Lemieux Christian , Picard Frédéric , Labrie Fernand , Richard Denis , Deshaies Yves
Published: April 2008

Objective: EM‐652 is a pure antiestrogen in human breast and uterine cancer cells that also reduces bone loss and plasma lipid levels in the rat. This study aimed to assess the ability of EM‐652, alone or with dehydroepiandrosterone (DHEA), to prevent obesity and related metabolic abnormalities induced by an obesity‐promoting diet and ovariectomy.

Research Methods and Procedures: Female rats were fed a high‐sucrose, high‐fat (HSHF) diet, were left intact or ovariectomized (OVX), and were treated with EM‐652, DHEA, or both for 20 days. Variables of energy balance and determinants of lipid metabolism and insulin sensitivity were assessed.

Results: The HSHF diet (vs. chow) and OVX both increased energy intake and gain, as well as energetic efficiency. Both EM‐652 and DHEA prevented diet‐ and OVX‐induced energy gain mainly by decreasing fat deposition, without being additive. The modest EM‐652‐induced increase in liver triglycerides of intact rats was prevented by its combination with DHEA. EM‐652, but not DHEA, decreased cholesterolemia. The HSHF diet and OVX reduced insulin sensitivity, an effect that was attenuated by EM‐652 and abrogated by DHEA and EM‐652+DHEA. Treatment with EM‐652, DHEA, or their combination abolished the diet‐ and OVX‐induced increase in adipose lipoprotein lipase activity that accompanied fat gain.

Discussion: EM‐652 is an effective agent to prevent diet‐ and OVX‐induced obesity and its associated cardiovascular risk factors such as insulin resistance. The addition of DHEA prevents hepatic lipid accumulation and further ameliorates insulin sensitivity. The beneficial metabolic effects of such combined steroid therapy may, therefore, eventually prove to be clinically relevant.
Fetal Origins of Obesity
Authors: Oken Emily , Gillman Matthew W.
Published: April 2008

The worldwide epidemic of obesity continues unabated. Obesity is notoriously difficult to treat, and, thus, prevention is critical. A new paradigm for prevention, which evolved from the notion that environmental factors in utero may influence lifelong health, has emerged in recent years. A large number of epidemiological studies have demonstrated a direct relationship between birth weight and BMI attained in later life. Although the data are limited by lack of information on potential confounders, these associations seem robust. Possible mechanisms include lasting changes in proportions of fat and lean body mass, central nervous system appetite control, and pancreatic structure and function. Additionally, lower birth weight seems to be associated with later risk for central obesity, which also confers increased cardiovascular risk. This association may be mediated through changes in the hypothalamic pituitary axis, insulin secretion and sensing, and vascular responsiveness. The combination of lower birth weight and higher attained BMI is most strongly associated with later disease risk. We are faced with the seeming paradox of increased adiposity at both ends of the birth weight spectrum—higher BMI with higher birth weight and increased central obesity with lower birth weight. Future research on molecular genetics, intrauterine growth, growth trajectories after birth, and relationships of fat and lean mass will elucidate relationships between early life experiences and later body proportions. Prevention of obesity starting in childhood is critical and can have lifelong, perhaps multigenerational, impact.
Arg64β3‐Adrenoceptor Variant and the Components of Energy Expenditure
Authors: Walston Jeremy , Andersen Ross E. , Seibert Michael , Hilfiker Heather , Beamer Brock , Blumenthal Jacob , Poehlman Eric T.
Published: April 2008

Objective: To determineTrp64Argβ3‐adrenoceptor genotype‐specific differences in the components of energy expenditure.

Hypothesis: We hypothesized that resting metabolic rate (RMR) and physical activity levels would be lower and that thermic effect of feeding (TEF) would be higher in those with theArg64allele.

Research Methods and Procedures: RMR and TEF were measured by indirect calorimetry, physical activity by questionnaire, and total energy expenditure by the doubly labeled water method. Genotype‐specific measures were compared using ANOVA and analysis of covariance (ANCOVA).

Results: RMR inArg64homozygotes was significantly lower than inTrp64homozygotes [Arg64, 1373 ± 259 kcal/d (n= 15) vs.Trp64Arg, 1538 ± 238 kcal/d (n= 25) vs.Trp64, 1607 ± 290 kcal/d (n= 22);p< 0.01]. TEF was significantly higher inArg64homozygotes compared withTrp64homozygotes (Arg64, 359 ± 28 kcal/d;Trp64Arg, 322 ± 22 kcal/d; andTrp64, 279 ± 23 kcal/d;p< 0.05). No differences were identified between genotypes in physical activity or in total energy expenditure.

Discussion: Our results suggest that theArg64β3‐adrenoceptor allele contributes significantly to the genetic variability in both RMR and TEF.
A 45‐bp Insertion/Deletion Polymorphism of Uncoupling Protein 2 in Relation to Obesity in Tongans
Authors: Duarte Natalia L. , Colagiuri Stephen , Palu Taniela , Wang Xing Li , Wilcken David E.L.
Published: April 2008

We compared the current prevalence of increased BMI and type 2 diabetes in a representative group of Tongan subjects with measurements made in 1973, and we determined the distribution and possible interrelations with the UCP2 insertion/deletion (ins/del) polymorphism of these variables. We documented the BMI, glucose tolerance, and standard lipid variables in 1012 Tongan subjects (429 men and 583 women, ages 15 to 85 years) during 1998 and 2000 and compared the BMI findings with those of the 1973 survey. We also genotyped for the UCP2 ins/del polymorphism, assessed its association with obesity and type 2 diabetes, and compared its prevalence with those reported for other ethnic populations. The mean BMI ± SD was greatly increased in both men (30.2 ± 5.4 kg/m2) and women (33.8 ± 6.2 kg/m2), representing increases since 1973 of 11.9% and 19.4%, respectively. The genotype frequencies were 97% for the del/del genotype and 3% for the ins/del genotype; we found no ins/ins homozygotes. This distribution is strikingly different from those reported for white, South Indian, Pima Native‐American, and Asian populations (49 to 77% for del/del genotype). We conclude that there is a marked prevalence of obesity in Tonga, a prevalence that has increased since 1973. We also conclude that there is a unique, near‐uniform distribution of the UCP2 45‐bp ins/del polymorphism in Tongans. This may be the result of a founder effect and may be relevant to the prevalence of obesity and type 2 diabetes in Tonga.
Relationship of Insulin Sensitivity and Left Ventricular Mass in Uncomplicated Obesity
Authors: Iacobellis Gianluca , Ribaudo Maria Cristina , Zappaterreno Alessandra , Vecci Elio , Tiberti Claudio , Di Mario Umberto , Leonetti Frida
Published: April 2008

Objective: We studied uncomplicated obesity as a model to evaluate the influence of insulin sensitivity per se on left ventricular mass (LVM) and geometry.

Research Methods and Procedures: We selected 50 obese subjects (BMI > 30 kg/m2; 38 women and 12 men; mean age, 38.4 ± 10 years; BMI, 36.4 ± 10.5 kg/m2) with normal blood pressure, glucose tolerance, and plasmatic lipid levels. Thirty lean subjects formed the control group. Each subject underwent euglycemic insulin clamp (7 pmol/min per kg) to evaluate whole body glucose use (M index) and echocardiogram to calculate LVM and indexed LVM.

Results: Insulin‐resistant obese subjects had higher LVM, LVM/h2.7, LVM/body surface area, and LVM/fat‐free masskg (p = 0.001; p = <0.001 p = 0.001, and p = 0.04, respectively) than obese subjects with normal insulin sensitivity. Multivariate regression analysis showed that M index was the strongest independent correlate of LVM (r2 = 0.34; p = 0.03).

Discussion: Our findings showed that insulin resistance, in uncomplicated obesity, is associated with an increased LVM and precocious changes of left ventricular geometry, whereas preserved insulin sensitivity is not associated with increased LVM.
Association between Serum Leptin Levels and 24‐Hour Blood Pressure in Obese Women
Authors: Guagnano Maria T. , Manigrasso Maria R. , Ballone Enzo , Della Vecchia Rosanna , Riccioni Graziano , Marinopiccoli Marina , Nutini Michele , Sensi Sergio , Davì Giovanni
Published: April 2008

Objective: To assess the relationship between serum leptin and 24‐hour blood pressure (BP) in obese women, according to body fat distribution.

Research Methods and Procedures: A cross‐sectional study was carried out in a population of 70 nondiabetic, normotensive, obese women (40 with android and 30 with gynoid type of obesity) and 20 nonobese healthy women as a control group. All subjects underwent 24‐hour ambulatory BP monitoring. Blood samples were collected for serum leptin and plasma insulin measurements. Total cholesterol and high‐density lipoprotein cholesterol were also measured.

Results: Serum leptin levels were significantly higher in obese subjects than in controls, and they were more elevated in android obese women than in gynoid ones. Leptin levels were positively related to body mass index (BMI), insulin, and waist and hip circumferences in the android group. Among gynoid subjects, leptin levels showed positive associations with BMI and insulin. In women with android obesity, strong positive correlations (p < 0.001) were found between leptin levels and 24‐hour systolic BP (SBP), daytime SBP, nighttime SBP, 24‐hour diastolic BP (DBP), and daytime DBP. Multiple regression analyses, including age, insulin and leptin concentrations, BMI, and waist and hip circumferences on 24‐hour and daytime SBP and DBP, showed that only leptin levels contributed to the variability of BP.

Conclusions: Our study shows that serum leptin levels are directly related to 24‐hour BP levels in normotensive women with android fat distribution, independently of BMI.
Predictors of Weight Loss in Adults with Topiramate‐Treated Epilepsy
Authors: Ben‐Menachem Elinor , Axelsen Mette , Johanson Else Hellebö , Stagge Anna , Smith Ulf
Published: April 2008

Objective: We examined predictors of weight loss with topiramate, an anticonvulsant associated with weight loss in adults.

Research Methods and Procedures: In this uncontrolled, prospective clinical trial, topiramate was added to existing anticonvulsants in adults (40 to 110 kg) with partial‐onset seizures. Primary measurements were change from baseline weight after 3 months and 1 year in patients completing 1 year of topiramate treatment (N = 38). Physiological and metabolic measures were analyzed for correlation with weight loss during topiramate treatment.

Results: In patients who completed 1 year of topiramate treatment, baseline weight was reduced in 82% at 3 months and in 86% at 1 year. Mean body weight was reduced 3.0 kg (3.9% of baseline) at 3 months and 5.9 kg (7.3%) at 1 year. In obese patients [body mass index (BMI) ≥ 30 kg/m2], mean weight loss was 4.2 kg (4.3%) at 3 months and 10.9 kg (11.0%) at 1 year. Weight loss was primarily caused by reduction in body fat mass. For all patients, weight loss at 3 months correlated most strongly with reduced caloric intake (p = 0.02). At 1 year, caloric intake had returned to baseline levels; weight loss correlated most strongly with higher baseline BMI (p = 0.0007).

Discussion: Our results suggest that weight loss occurs in most adults treated with topiramate and is sustained for at least 1 year. Reduced caloric intake may account, in part, for weight loss during early treatment. The pattern of weight loss differs according to baseline BMI, with obese patients experiencing greater weight loss during continued therapy.
Gastric Electrical‐Stimulation Effects on Canine Gastric Emptying, Food Intake, and Body Weight
Authors: Xing JinHong , Brody Fredrick , Brodsky Jason , Rosen Michael , Larive Brett , Ponsky Jeffrey , Soffer Edy
Published: April 2008

Objective: It has been reported that electrical stimulation at the distal stomach can disrupt intrinsic gastric electrical activity and delay gastric emptying. Gastric dysrhythmia and impaired gastric emptying are associated with upper gastrointestinal symptoms and weight loss. The purpose of this study was to evaluate the effect of low‐frequency/long‐pulse gastric electrical stimulation (GES), at proximal and distal stomach, on canine gastric emptying, food intake, and body weight.

Research Methods and Procedures: Eight dogs were surgically implanted with four pairs of electrodes along the greater curvature and a gastric tube at the dependent part of the stomach. Liquid gastric emptying at baseline, during proximal and distal GES at 6 cycles per minute, was assessed first by a dye dilution technique. Proximal and distal GES were then randomly delivered during feeding for 10 consecutive days, and food intake and body weight were recorded daily.

Results: There was no significant difference in gastric emptying parameters among the various sessions. The mean daily food consumption was significantly reduced during both sessions of GES, resulting in significant immediate weight loss. Percentage weight loss was comparable between both sessions of GES.

Discussion: Short‐term GES significantly reduced canine food intake and weight. This effect may not be related to changes in gastric emptying. GES may have a potential role in the treatment of obesity.
Gender Differences in Shame in Patients with Binge‐Eating Disorder
Authors: Jambekar Sheila A. , Masheb Robin M. , Grilo Carlos M.
Published: April 2008

Objective: To examine the relationship between shame and the behavioral and attitudinal features of eating disorders in men and women diagnosed with binge‐eating disorder (BED).

Research Methods and Procedures: Participants were 188 consecutively evaluated adults (38 men and 150 women) who met Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria for BED. Participants were interviewed and completed a battery of measures assessing shame, behavioral and attitudinal features of eating disorders, and general psychological functioning.

Results: Shame did not differ significantly by gender and was not associated with BMI or binge‐eating frequency. Shame was significantly associated with the attitudinal features of eating disorders, even after controlling for levels of depression and self‐esteem. When considered separately by gender and controlling for depression and self‐esteem, shame was associated with body dissatisfaction in men and with weight concern in women.

Discussion: Men and women with BED, who presented for treatment, reported similar levels of shame. Overall, while shame was related to attitudinal features, the specific associations differed by gender. For men, shame was related to how dissatisfied they felt with their bodies, whereas for women, shame was associated with concerns about weight. Interestingly, shame was not related to BMI or binge‐eating frequency in men or women. These results provide preliminary support for self‐conscious emotions playing different roles in men and women with BED.
Assessment of Global Coronary Heart Disease Risk in Overweight and Obese African‐American Women
Authors: Patt Madhavi R. , Yanek Lisa R. , Moy Taryn F. , Becker Diane M.
Published: April 2008

Objective: To examine, with the use of national guidelines, coronary heart disease (CHD) risk with increasing BMI for primary prevention in urban African‐American women.

Research Methods and Procedures: Participants were recruited for CHD risk factor screening from 20 churches as part of a larger study of nutrition and fitness (Project Joy). All participants had a demographic, smoking and medical history assessment, and the following measurements were taken: weight, height, waist circumference, blood pressure, lipid levels, and glucose. Three methods of defining risk, the Framingham Point Scoring System, a count of risk factors, and the presence of the multiple metabolic syndrome, based on the National Cholesterol Education Program Adult Treatment Panel III Report and BMI classes established by the Clinical Guidelines, were used.

Results: A total of 396 women were eligible. Participants were 40 to 80 years of age and had marked excess prevalence of overweight and obesity (84%); 55% were obese. There was a linear increase in risk factors as BMI increased. Lipids did not differ significantly among BMI classifications. Seventeen percent of women had multiple metabolic syndrome. Eight percent and 16% of women in the normal and overweight BMI classes, respectively, had two or more modifiable risk factors. There was no difference in number of modifiable risk factors among the obese classes. The Framingham Point Scoring System assigned a <10% risk of a hard CHD event in 10 years to 97% of the women.

Discussion: National risk assessment guidelines for primary prevention of CHD may not be adequate for overweight and obese urban African‐American women and require further study.
Regional Fat Pad Growth and Cellularity in Obese Zucker Rats: Modulation by Caloric Restriction
Authors: Hausman Dorothy B. , Fine Jacqueline B. , Tagra Krishna , Fleming Shea S. , Martin Roy J. , DiGirolamo Mario
Published: April 2008

Objective: To investigate, in young obese male Zucker rats, the effects of chronic food restriction and subsequent refeeding on: 1) parameters of nonadipose and adipose growth, 2) regional adipose depot cellularity [fat cell volume (FCV) and number], and 3) circulating leptin levels.

Research Methods and Procedures: Obese (fa/fa) and lean (Fa/?) male Zucker rats were studied from age 5 to 19 weeks. After baseline food intake monitoring, 10 obese rats were subjected to 58 days of marked caloric restriction from ad libitum levels [obese‐restricted (OR)], followed by a return to ad libitum feeding for 22 days. Ten lean control rats and 10 obese control rats were fed ad libitum for the entire experiment. All rats were fed using a computer‐driven automated feeding system designed to mimic natural eating patterns.

Results: After food restriction, OR rats weighed significantly less than did lean and obese rats and showed a significant diminution in body and adipose growth as compared with obese rats. Relative adiposity was not different between obese and OR rats and was significantly higher than that of lean rats. The limitation in growth of the adipose tissue mass in OR rats was due mostly to suppression of fat cell proliferation because the mean FCV in each of the four depots was not affected. Serum leptin levels of OR and obese rats were not different from each other but were significantly higher than those of lean rats.

Discussion: Marked caloric restriction affects obese male Zucker rats in a manner different from that of nongenetic rodent models (i.e., Wistar rats). In comparison with the response to caloric deprivation of Wistar rats, these calorically restricted obese male Zucker rats appeared to defend their relative adiposity and mean FCV at the expense of fat cell number. These findings indicate that genetic and/or tissue‐specific controls override the general consequences of food restriction in this genetic model of obesity.
Chitosan Supplementation and Fecal Fat Excretion in Men
Authors: Gades Matthew D. , Stern Judith S.
Published: April 2008

Objective: Few weight loss supplements are clinically tested for efficacy, yet their proliferation continues. Chitosan‐based supplements are sold as fat trappers and fat magnets. They purportedly block fat absorption and cause weight loss without food restriction. We quantified the in vivo effect of a chitosan product on fat absorption.

Research Methods and Procedures: Participants (n = 15) consumed five meals per day for 12 days. Energy intake was not restricted. Participants consumed no supplements during a 4‐day control period and two capsules five times per day (4.5 g chitosan/d), 30 minutes before each meal, during a 4‐day supplement period. All feces were collected from days 2 to 12. Oral charcoal markers permitted division of the feces into two periods. The two fecal pools were analyzed for fat content.

Results: Participants were male, 26.3 ± 5.9 years old, BMI of 25.6 ± 2.3 kg/m2. Subjects consumed 133 ± 23 g of fat/d and 12.91 ± 1.79 MJ/d (3084 ± 427 kcal/d). Individual meals averaged 26.3 ± 9.3 g of fat. With chitosan supplementation at 10 capsules/day, fecal fat excretion increased by 1.1 ± 1.8 g/d (p = 0.02), from 6.1 ± 1.2 to 7.2 ± 1.8 g/d.

Discussion: The effect of chitosan on fat absorption is clinically negligible. Far from being a fat trapper, at 0.11 ± 0.18 g of fat trapped per 0.45‐g capsule or 1.1 g (9.9 kcal) fat trapped per day, this product would have no significant effect on energy balance. The fat trapping claims associated with chitosan are unsubstantiated.
attB site disruption in marine Actinomyces sp. M048 via DNA transformation of a site‐specific integration vector
Authors: Hou Yan‐Hua , Wang Quan‐Fu , Ding Ling , Li Fu‐Chao , Qin Song
Published: April 2008

An efficient conjugation method has been developed for the marine Actinomyces sp. isolate M048 to facilitate the genetic manipulation of the chandrananimycin biosynthesis gene cluster. A φC31‐derived integration vector pIJ8600 containing oriT and attP fragments was introduced into strain M048 by bi‐parental conjugation from Escherichia coli ET12567 to strain M048. Transformation efficiency was (6.38±0.41)×10−5 exconjugants per recipient spore. Analysis of eight exconjugants showed that the plasmid pIJ8600 was stably integrated at a single chromosomal site (attB) of the Actinomyces genome. The DNA sequence of the attB was cloned and shown to be conserved. The results of antimicrobial activity analysis indicated that the insertion of plasmid pIJ8600 seemed to affect the biosynthesis of antibiotics that could strongly inhibit the growth of E. coli and Mucor miehei (Tü284). HPLC–MS analysis of the extracts indicated that disruption of the attB site resulted in the complete abolition of chandrananimycin A–C production, proving the identity of the gene cluster. Instead of chandrananimycins, two bafilomycins were produced through disruption of the attB site from the chromosomal DNA of marine Actinomyces sp. M048.
Comparison of four methods for the purification and refolding of human interleukin‐2–mouse granulocyte/macrophage colony‐stimulating factor fusion protein
Authors: Wen Qian , Ma Li , Luo Wei , Zhou Ming‐Qian , He Dong , Lin Ying , Wu Zhen‐Qiang , He Xiao‐Wei , Wang Ju‐Fang , Wang Xiao‐Ning
Published: April 2008

The combination of IL‐2 (interleukin‐2) and GM‐CSF (granulocyte/macrophage colony‐stimulating factor) has been broadly studied in antitumour immune therapy, but its efficacy is uncertain. To better exert the activities of the two cytokines and study them in a mouse model, we have constructed a bifunctional protein, hIL‐2–mGM‐CSF (human IL‐2–mouse GM‐CSF), fused to a C‐terminal tag of six histidine residues (His6). The fusion protein was expressed in Escherichia coli as IBs (inclusion bodies). After extracting and clarifying the IBs, four methods of protein purification and refolding were compared in order to optimize the preparation technique. Of these methods, the best result was obtained with a four‐step process consisting of (1) purification with denaturing affinity chromatography, (2) followed by fully denaturing the protein with system conversion, (3) then refolding by isovolumetric ultrafiltration and (4) finally, purification by anion‐exchange chromatography. The purity of the hIL‐2–mGM‐CSF was approx. 95%, yielding approx. 20 mg of protein/l of culture. The fusion protein retained the natural activities of IL‐2 and GM‐CSF, with specific activities of 8.7×106 and 1.1×107 i.u./mg respectively. Flow‐cytometric analysis indicated that hIL‐2–mGM‐CSF could specifically bind to the corresponding receptor‐positive cells. The present study provides important preliminary information for studying the antitumour activity of hIL‐2–mGM‐CSF in vivo, which will facilitate future clinical research into the use of hIL‐2/hGM‐CSF in immune therapy.
Development of SCAR (sequence‐characterized amplified region) markers as a complementary tool for identification of ginger (Zingiber officinale Roscoe) from crude drugs and multicomponent formulations
Authors: Chavan Preeti , Warude Dnyaneshwar , Joshi Kalpana , Patwardhan Bhushan
Published: April 2008

Zingiber officinale Roscoe (common or culinary ginger) is an official drug in Ayurvedic, Indian herbal, Chinese, Japanese, African and British Pharmacopoeias. The objective of the present study was to develop DNA‐based markers that can be applied for the identification and differentiation of the commercially important plant Z. officinale Roscoe from the closely related species Zingiber zerumbet (pinecone, bitter or ‘shampoo’ ginger) and Zingiber cassumunar [cassumunar or plai (Thai) ginger]. The rhizomes of the other two Zingiber species used in the present study are morphologically similar to that of Z. officinale Roscoe and can be used as its adulterants or contaminants. Various methods, including macroscopy, microscopy and chemoprofiling, have been reported for the quality control of crude ginger and its products. These methods are reported to have limitations in distinguishing Z. officinale from closely related species. Hence, newer complementary methods for correct identification of ginger are useful. In the present study, RAPD (random amplification of polymorphic DNA) analysis was used to identify putative species‐specific amplicons for Z. officinale. These were further cloned and sequenced to develop SCAR (sequence‐characterized amplified region) markers. The developed SCAR markers were tested in several non‐Zingiber species commonly used in ginger‐containing formulations. One of the markers, P3, was found to be specific for Z. officinale and was successfully applied for detection of Z. officinale from Trikatu, a multicomponent formulation.
A six-dimensional H2–H2 potential energy surface for bound state spectroscopy
Authors: Hinde Robert J.
Published: April 2008

We present a six-dimensional potential energy surface for the (H2)2 dimer based on coupled-cluster electronic structure calculations employing large atom-centered Gaussian basis sets and a small set of midbond functions at the dimer’s center of mass. The surface is intended to describe accurately the bound and quasibound states of the dimers (H2)2, (D2)2, and H2–D2 that correlate with H2 or D2 monomers in the rovibrational levels (v,j)=(0,0), (0,2), (1,0), and (1,2). We employ a close-coupled approach to compute the energies of these bound and quasibound dimer states using our potential energy surface, and compare the computed energies for infrared and Raman transitions involving these states with experimentally measured transition energies. We use four of the experimentally measured dimer transition energies to make two empirical adjustments to theab initio potential energy surface; the adjusted surface gives computed transition energies for 56 experimentally observed transitions that agree with experiment to within 0.036cm−1. For 26 of the 56 transitions, the agreement between the computed and measured transition energies is within the quoted experimental uncertainty. Finally, we use our potential energy surface to predict the energies of another 34 not-yet-observed infrared and Raman transitions for the three dimers.
Molecular dynamics simulation of phase separating binary liquids in cylindrical Couette flow
Authors: Thakre Amol K. , Padding J. T. , den Otter W. K. , Briels W. J.
Published: April 2008

We use molecular dynamics simulations to study phase separation of a 50:50 (by volume) fluid mixture in a confined and curved (Taylor–Couette) geometry, consisting of two concentric cylinders. The inner cylinder may be rotated to achieve a shear flow. In nonsheared systems we observe that, for all cases under consideration, the final equilibrium state has a stacked structure. Depending on the lowest free energy in the geometry the stack may be either flat, with its normal in the z direction, or curved, with its normal in the r or θ direction. In sheared systems we make several observations. First, when starting from a prearranged stacked structure, we find that sheared gradient and vorticity stacks retain their character for the durations of the simulation, even when another configuration is preferred (as found when starting from a randomly mixed configuration). This slow transition to another configuration is attributed to a large free energy barrier between the two states. In case of stacks with a normal in the gradient direction, we find interesting interfacial waves moving with a prescribed angular velocity in the flow direction. Because such a wave is not observed in simulations with a flat geometry at similar shear rates, the curvature of the wall is an essential ingredient of this phenomenon. Second, when starting from a randomly mixed configuration, stacks are also observed, with an orientation that depends on the applied shear rate. Such transitions to other orientations are similar to observations in microphase separated diblock copolymer melts. At higher shear rates complex patterns emerge, accompanied by deviations from a homogeneous flow profile. The transition from steady stacks to complex patterns takes place around a shear rate 1/τdv, where τdv is the crossover time from diffusive to viscous dominated growth of phase-separated domains, as measured in equilibrium simulations.
Explicitly correlated RMP2 for high-spin open-shell reference states
Authors: Knizia Gerald , Werner Hans-Joachim
Published: April 2008

We present an explicitly correlated version of the high-spin open-shell RMP2 method. The theory is derived in a unitarily invariant form, which is suitable for the insertion of local approximations. It is demonstrated that the rapid basis set convergence of closed-shell MP2-F12 is also achieved in RMP2-F12, and similar Ansätze and approximations can be employed. All integrals are computed using efficient density fitting approximations, and many-electron integrals are avoided using resolution of the identity approximations. The performance of the method is demonstrated by benchmark calculations on a large set of ionization potentials, electron affinities and atomization energies. Using triple-zeta basis sets RMP2-F12 yields results that are closer to the basis set limit than standard RMP2 with augmented quintuple-zeta basis sets for all properties. Different variants of perturbative corrections for the open-shell Hartree–Fock treatment are described and tested.
Development of residual stress in sol-gel derived Pb(Zr,Ti)O3 films: An experimental study
Authors: Corkovic S. , Whatmore R. W. , Zhang Q.
Published: April 2008

Residual stresses develop in the sol-gel-derived ferroelectric thin films during the transformation of the metal-organic gel to the metal oxide upon thermal treatment and due to the thermal and elastic mismatch between the Pb(Zrx,Ti1−x)O3 (PZT) film and the substrate materials during cooling. In this study, residual stresses were determined using the wafer curvature method after the deposition of multilayer PZT film on platinized (100) silicon wafers. A multilayer model for stress analysis was used to calculate the residual stress in PZT films of three different compositions: x=0.4, x=0.52, and x=0.6. Orientation dependent residual stresses were found in compositions containing the tetragonal phase, with x=0.4 and x=0.52. Depending on the fraction of (100) orientated domains low compressive or low tensile stress was found in Pb(Zr0.4Ti0.6)O3 (PZT 40∕60). Higher residual stress was found in PZT films consisting of only rhombohedral crystallographic structure (PZT 60∕40) while the residual stress in PZT films with morphotropic boundary composition (PZT 52∕48) was significantly dependent on the film orientation and the phase composition and could range from 17to90MPa. The effect of the film orientation on residual stress was found to be a function of the anisotropic thermal expansion coefficient of PZT. The contribution of the thermal and elastic properties of materials to the total wafer curvature was investigated and discussed. Finally, the residual stress results calculated with the four layer model were compared to the results calculated using the Stoney equation.
Linear absorbance of the pheophorbide-a butanediamine dendrimer P4 in solution: Computational studies using a mixed quantum classical methodology
Authors: Zhu Hui , May Volkhard , Röder Beate , Renger Thomas
Published: April 2008

The linear absorbance of a particular chromophore complex P4 dissolved in ethanol is computed. P4 is formed by a butanediamine dendrimer to which four pheophorbide-a molecules are covalently linked. The computations utilize a mixed quantum classical methodology and different approximations are compared. The electronic states of the P4 chromophores which form Frenkel excitons in the excited states are treated quantum mechanically, whereas the intramolecular, intermolecular, as well as solvent coordinates are described classically. The computations use an improved exciton model, where the charge and transition densities of the chromophores are described by atomic partial charges, derived from a fit of the respective ab initio electrostatic potentials. Room temperature molecular dynamics simulations of all nuclear coordinates result in a time-dependent exciton model. It includes modulations of chromophore excitation energies due to charge density coupling between all chromophores as well as between the chromophores and solvent molecules, and, finally, modulations of the interchromophore excitonic couplings. The different approximations to the absorbance agree rather well. In particular, they confirm the reliability of adiabatic excitonic states which energies and oscillator strengths are altered by the overall temporal evolution of P4 conformations. The fluctuations of solute-solvent interactions have a significantly larger effect on the absorbance broadening than the excitonic couplings but cannot completely explain the measured spectrum. The additional account for intrachromophore vibrations overcomes this discrepancy.
Monte Carlo free energy calculations using electronic structure methods
Authors: Matusek Daniel R. , Osborne Sébastien , St-Amant Alain
Published: April 2008

The molecular mechanics-based importance sampling function (MMBIF) algorithm [R. Iftimie, D. Salahub, D. Wei, and J. Schofield, J. Chem. Phys. 113, 4852 (2000)] is extended to incorporate semiempirical electronic structure methods in the secondary Markov chain, creating a fully quantum mechanical Monte Carlo sampling method for simulations of reactive chemical systems which, unlike the MMBIF algorithm, does not require the generation of a system-specific force field. The algorithm is applied to calculating the potential of mean force for the isomerization reaction of HCN using thermodynamic integration. Constraints are implemented in the sampling using a modification of the SHAKE algorithm, including that of a fixed, arbitrary reaction coordinate. Simulation results show that sampling efficiency with the semiempirical secondary potential is often comparable in quality to force fields constructed using the methods suggested in the original MMBIF work. The semiempirical based importance sampling method presented here is a useful alternative to MMBIF sampling as it can be applied to systems for which no suitable MM force field can be constructed.
Deformation mechanisms and damage in α-alumina under hypervelocity impact loading
Authors: Zhang Cheng , Kalia Rajiv K. , Nakano Aiichiro , Vashishta Priya , Branicio Paulo S.
Published: April 2008

Deformation mechanisms in α-alumina under hypervelocity impact are investigated using molecular dynamics simulations containing 540×106 atoms. A cylindrical projectile impacting normal to the (0001) surface at 18km∕s generates large temperature and pressure gradients around the impact face, and consequently local amorphization of the substrate in a surrounding hemispherical region is produced. Away from the impact face, a wide range of deformations emerge and disappear as a function of time under the influence of local stress fields, e.g., basal and pyramidal slips and basal and rhombohedral twins, all of which show good agreement with the experimental and theoretical results. New deformation modes are observed, such as twins along {01¯11}, which propagate at a roughly constant speed of 8km∕s and nucleate a large amount of defects where subsequent fractures initiate. The relation between deformation patterns and local stress levels is investigated. During unloading, we observe that microcracks nucleate extensively at the intersections of previous deformations within an hourglass-shaped volume that connects top and bottom free surfaces. From the simulation, the fracture toughness of alumina is estimated to be 2.0±0.5MPa√m. The substrate eventually fails along the surface of the hourglass region during spallation when clusters of substrate material are ejected from both free surfaces.
Fluctuation theorem and mesoscopic chemical clocks
Authors: Andrieux David , Gaspard Pierre
Published: April 2008

The fluctuation theorems for dissipation and the currents are applied to the stochastic version of the reversible Brusselator model of nonequilibrium oscillating reactions. It is verified that the symmetry of these theorems holds far from equilibrium in the regimes of noisy oscillations. Moreover, the fluctuation theorem for the currents is also verified for a truncated Brusselator model.
Diffusion-influenced reactions of particles with several active sites
Authors: Ivanov Konstantin L. , Lukzen Nikita N.
Published: April 2008

The main concern of the present work is consideration of sterically specific liquid-phase reactions in the case where one of the reactants has several active sites. In kinematic approximation we derived compact formulas for partial rate constants of individual active sites. Reaction rates are expressed via the kinetic rate constants and convolutions of the free Green functions over reaction zones. These results are valid for arbitrary geometry of reactants and active sites. Effects of mutual influence of the active sites were studied, their simple estimate was proposed.
Cooperativity between two types of hydrogen bond in H3C–HCN–HCN and H3C–HNC–HNC complexes
Authors: Li Qingzhong , An Xiulin , Luan Feng , Li Wenzuo , Gong Baoan , Cheng Jianbo , Sun Jiazhong
Published: April 2008

Hydrogen-bonded clusters, H3C–HCN, HCN–HCN, H3C–HCN–HCN, H3C–HNC, HNC–HNC, and H3C–HNC–HNC, have been studied by using ab initio calculations. The optimized structures, harmonic vibrational frequencies, and interaction energies are calculated at the MP2 level with aug-cc-pVTZ basis set. The cooperative effects in the properties of these complexes are investigated quantitatively. A cooperativity contribution of around 10% relative to the total interaction energy was found in the H3C–HCN–HCN complex. In the case of H3C–HNC–HNC complex, the cooperativity contribution is about 15%. The cooperativity contribution in the single-electron hydrogen bond is larger than that in the hydrogen bond of HCN–HCN and HNC–HNC complexes. NMR chemical shifts, charge transfers, and topological parameters also support such conclusions.
Coalescence of two viscoelastic droplets connected by a string
Authors: Yang Jianmao , Xu Yuanze
Published: April 2008

A new type of coalescence of viscoelastic droplets is described and analyzed. A viscoelastic drop of polyisobutene (PIB) containing high molar mass PIB (HPIB), suspended in polydimethylsiloxane, is separated into two droplets connected by a string, which is called “bead-string-bead” (BSB), through repeated elongation and relaxation in a four-roll mill rheometer. Upon flow cessation, the two drops are pulled to approach each other by the string and eventually coalesce. This process exhibits interesting features: The string remains stable like a rod without capillary breakup; the string length and the merging force decay exponentially with time; the string diameter may not change significantly through the approach. The string in BSB is more stable than that of the capillary thinning process of beads on string in jet or fixed-end rheometer. These phenomena are modeled based on the force balance of the viscoelasticity of HPIB systems, viscous drag, and the Laplace force. The model prediction agrees with the experimental observation reasonably well, revealing the viscoelastic nature of the coalescence of two droplets. The characteristic time of drop approach is comparable to that of the pulling stress decay. The condition of keeping a constant diameter in BSB approach creates a status where both drop approach and stress decay exponentially with the same characteristic time, which is comparable to the material relaxation time. This case allows the model to analyze the relationships between critical string diameter and the material parameter as well as the process parameters and to discuss the microscopic images of the BSB process.
Nonadiabatic couplings from time-dependent density functional theory. II. Successes and challenges of the pseudopotential approximation
Authors: Hu Chunping , Hirai Hirotoshi , Sugino Osamu
Published: April 2008

We present extensive calculations of nonadiabatic couplings (NACs) between the electronically ground and excited states of molecules, using time-dependent density functional theory (TDDFT) within (modified) linear response [C. Hu et al. J. Chem. Phys. 127, 064103 (2007)]. Our approach is implemented in the pseudopotential framework, with the consideration of nonlinear core corrections. The features of either the ordinary Jahn–Teller conical intersections in X3 (X=Li, Na, K, Cu, Ag, Au) trimers, or the elliptic Jahn–Teller conical intersections in NaH2, have been well reproduced. In particular, anticipated results for the H–H2 collision near the avoided crossing are obtained, showing appealing improvement over the first, real-time, TDDFT calculation. The other important type of intersections, Renner–Teller glancing intersection, has also been studied for several typical molecular systems (BH2, AlH2, CH2+, SiH2+), giving results in reasonable agreement with the theoretical model. Despite these successes, it is found that for some systems, including both Jahn–Teller and Renner–Teller systems, the pseudopotential scheme might give inaccurate results for some NAC components on nonhydrogen atoms. By trying different construction schemes of pseudopotentials, e.g., using local pseudopotentials, the results of NACs are found scheme-dependent and show improvement for some cases. Since there is much freedom in constructing ab initio nonlocal pseudopotentials, our findings on TDDFT calculation of NACs in the pseudopotential scheme might be helpful to give clues for constructing more “realistic” pseudopotentials.
Monte Carlo simulations of thermodynamic and structural properties of Mie(14,7) fluids
Authors: Nasrabad Afshin Eskandari
Published: April 2008

The vapor-liquid phase envelope of Mie(14,7) fluids is determined by the Gibbs ensemble Monte Carlo (MC) simulation technique. The NVT-MC simulation method is then utilized to compute the equation of state and the pair correlation function over a wide range of densities and temperatures. The effective diameters are calculated via the virial minimization method and the results are applied as the repulsion-attraction splitting distance within the generic van der Waals (GvdW) theory to compute the mean free volume. The density and temperature dependence of these parameters are studied and discussed. The results for the effective diameter, and the GvdW parameters are fitted to analytical functions of density and temperature. An examination of the results for the fluid phase equilibria of argon shows excellent agreement with empirical data for the densities of the coexisting phases, the vapor pressure, and the critical point. The computed free volumes are used to compute the diffusion coefficient of argon and the results are compared with experimental data.