bluuebunny/crossref_metadata_2025 huggingface dataset:
Brown fat UCP1 is not involved in the febrile and thermogenic responses to IL-1β in mice
Authors: Okamatsu-Ogura Yuko , Kitao Naoya , Kimura Kazuhiro , Saito Masayuki
Published: December 2006

The activity of brown adipose tissue (BAT), a site of nonshivering metabolic thermogenesis, has been reported to increase after interleukin (IL)-1β/lipopolysaccharide injection. To clarify the possible contribution of BAT thermogenesis to whole body febrile response, we investigated febrile and thermogenic response to IL-1β using mice deficient in uncoupling protein-1 (UCP1), a key molecule for BAT thermogenesis. In wild-type (WT) mice, IL-1β injection (5 μg/kg ip) increased body temperature (+1.82°C at 20 min), decreased physical activity (−37% at 1 h), and produced a slight and insignificant rise (+15% at 1 h) in oxygen consumption (V̇o2). V̇o2 dependent on metabolic thermogenesis (ΔV̇o2 thermogenesis) calculated by correcting the effect of physical activity was increased after IL-1β injection (726 ± 200 ml·h−1·kg−1 at 1 h). Almost the same responses were observed in UCP1-deficient mice, showing 638 ± 87 ml·h−1·kg−1 of ΔV̇o2 thermogenesis at 1 h. In contrast, CL316,243, a selective activator of BAT thermogenesis, increased body temperature, decreased physical activity, and produced a significant rise in V̇o2 in WT mice, showing 1,229 ± 35 ml·h−1·kg−1 of ΔV̇o2 thermogenesis at 1 h. These changes were not observed in UCP1-deficient mice. These results, conflicting with a previously proposed idea of a role of BAT in fever, suggest a minor contribution of BAT thermogenesis to IL-1β-induced fever. In support of this, we found no effect of IL-1β on triglyceride content and UCP1 mRNA level in BAT, in contrast with apparent effects of CL316,243.
Hyperphosphorylation of MEF2A in primary adipocytes correlates with downregulation of human GLUT4 gene promoter activity
Authors: Sparling David P. , Griesel Beth A. , Olson Ann Louise
Published: December 2006

GLUT4 promoter activity is regulated by hormonal, metabolic, and tissue-specific controls. This complicates the study of GLUT4 gene transcription, as no cell culture model adequately recapitulates these extracellular regulators. While investigating cultured primary adipocytes as a model system for GLUT4 transcription, we observed that GLUT4 mRNA was specifically and rapidly downregulated upon tissue dispersal. Downregulation of GLUT4 mRNA was mediated in part by loss of regulatory control by the trans-acting factors that control GLUT4 transcriptional activity [the myocyte enhancer factor 2 (MEF2) transcription factor family and the GLUT4 enhancer factor] and their cognate DNA binding sites in transgenic mice. The differences in GLUT4 transcription when whole adipose tissue and cell culture model systems are compared can be correlated to a posttranslational phosphorylation of the transcription factor MEF2A. The difference in the MEF2A phosphorylation state in whole tissue vs. isolated cells may provide a further basis for the development of an in vitro system that could recapitulate fully regulated GLUT4 promoter activity. Development of an in vitro system to reconstitute GLUT4 transcriptional regulation will further efforts to discern the molecular mechanisms that underlie GLUT4 expression.
Receiver Operating Characteristic (ROC) Analysis for Characterizing Synaptic Efficacy
Authors: Chance Frances S.
Published: December 2006

The role of background synaptic activity in cortical processing has recently received much attention. How do individual neurons extract information when embedded in a noisy background? When examining the impact of a synaptic input on postsynaptic firing, it is important to distinguish a change in overall firing probability from a true change in neuronal sensitivity to a particular input (synaptic efficacy) that corresponds to a change in detection performance. Here we study the impact of background synaptic input on neuronal sensitivity to individual synaptic inputs using receiver operating characteristic (ROC) analysis. We use the area under the ROC curve as a measure of synaptic efficacy, here defined as the ability of a postsynaptic action potential to identify a particular synaptic input event. An advantage of using ROC analysis to measure synaptic efficacy is that it provides a measure that is independent of postsynaptic firing rate. Furthermore, changes in mean excitation or inhibition, although affecting overall firing probability, do not modulate synaptic efficacy when measured in this way. Changes in overall conductance also affect firing probability but not this form of synaptic efficacy. Input noise, here defined as the variance of the input current, does modulate synaptic efficacy, however. This effect persists when the change in input variance is coupled with a change in conductance (as would result from changing background activity).
The Malignant Potential of Freshly Developed Colorectal Polyps According to Age
Authors: Yamaji Yutaka , Mitsushima Toru , Yoshida Haruhiko , Watabe Hirotsugu , Okamoto Makoto , Wada Ryoichi , Ikuma Hitoshi , Kawabe Takao , Omata Masao
Published: December 2006

Background: Although malignant colorectal neoplasms are found more frequently in older population, polyps found at one-time colonoscopy may be a mixture of lesions that developed at various earlier ages. Newly developed adenomas found at the follow-up colonoscopies will reflect the exact relation between malignant potential and the age of development of colorectal polyps.

Methods: The results of 44,065 follow-up colonoscopies on 11,912 subjects were analyzed. The proportion of invasive cancer or high-grade dysplasia among all neoplasms, “proportion of malignancy,” was evaluated in relation to age groups (young: <50 years old; middle: 50-59 years old; and old: ≥60 years old).

Results: At the follow-up colonoscopies, a total of 8,271 newly developed neoplasms were found, of which 41 (0.50%) lesions were malignant. The proportion of malignancy was 0.35%, 0.31%, and 1.07% in the young, middle, and old age groups, respectively (Ptrend = 0.002). This trend remained significant when stratified by the size of polyps. The proportion of malignancy was higher on the left-side colon than on the right-side colon, except in the old age group, where it was similar on either side. The proportion of malignancy at the follow-ups was not associated with the lesions found at the initial colonoscopies.

Conclusions: The development of malignant lesions in small sizes increased on the colon or rectum at older ages. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2418–21)
Prolonged Prevention of Squamous Cell Carcinoma of the Skin by Regular Sunscreen Use
Authors: van der Pols Jolieke C. , Williams Gail M. , Pandeya Nirmala , Logan Valerie , Green Adèle C.
Published: December 2006

Half of all cancers in the United States are skin cancers. We have previously shown in a 4.5-year randomized controlled trial in an Australian community that squamous cell carcinomas (SCC) but not basal cell carcinomas (BCC) can be prevented by regular sunscreen application to the head, neck, hands, and forearms. Since cessation of the trial, we have followed participants for a further 8 years to evaluate possible latency of preventive effect on BCCs and SCCs. After prolonged follow-up, BCC tumor rates tended to decrease but not significantly in people formerly randomized to daily sunscreen use compared with those not applying sunscreen daily. By contrast, corresponding SCC tumor rates were significantly decreased by almost 40% during the entire follow-up period (rate ratio, 0.62; 95% confidence interval, 0.38-0.99). Regular application of sunscreen has prolonged preventive effects on SCC but with no clear benefit in reducing BCC. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2546–8)
Family History of Cancer and the Risk of Renal Cell Cancer
Authors: Negri Eva , Foschi Roberto , Talamini Renato , Montella Maurizio , Ramazzotti Valerio , Dal Maso Luigino , Bosetti Cristina , Franceschi Silvia , Zucchetto Antonella , La Vecchia Carlo
Published: December 2006

Only scant information is available on the association between family history of kidney cancer and risk of renal cell cancer (RCC), particularly as concerns the variation of the risk according to sex, age, and type of relative or the association of family history of other cancers with RCC. We thus investigated the issue using data from a large multicentric case-control study conducted in Italy between 1992 and 2004 on 767 patients (494 men and 273 women) under age 80 years, with incident, histologically confirmed RCC, and 1,534 controls under age 80 years, admitted to hospital for a wide spectrum of acute, nonneoplastic conditions and frequency matched 2:1 to cases by center, sex, and age. Conditional logistic regression models, conditioned on center, sex, and age and adjusted for year of interview, smoking, body mass index, and number of brothers and sisters were used to estimate odds ratios (OR). Eighteen RCC and 8 controls reported a family history of kidney cancer in one first-degree relative [OR, 5.2; 95% confidence interval (95% CI), 2.2-12.2]. No significant heterogeneity emerged according to sex or age of the proband or of the affected relative, or smoking habits, body mass index, and history of hypertension of the proband. Although not significant, the OR was higher when the affected relative was a sibling (OR, 7.0; 95% CI, 1.8-27.7) rather than a parent or child (OR, 4.3; 95% CI, 1.5-12.9), as suggested from previous studies. The OR of RCC was also significantly elevated for a family history of prostate cancer (OR, 1.9), leukemias (OR, 2.2), or any cancer (OR, 1.5). (Cancer Epidemiol Biomarkers Prev 2006;15(12):2441–4)
The Importance of Cytologic Intrarater and Interrater Reproducibility: the Case of Ductal Lavage
Authors: Visvanathan Kala , Santor Deborah , Ali Syed Z. , Hong In Soon , Davidson Nancy E. , Helzlsouer Kathy J.
Published: December 2006

The reproducibility of a test result is a critical component of its clinical utility. Little information is available concerning the intrarater reproducibility of cytologic assessments. This study evaluated the reproducibility of cytologic interpretation of epithelial cells obtained from ductal lavage (DL), a minimally invasive method used to obtain sample cells from breast tissue. Two cytospin slides were made for each duct sampled. Slides with <10 cells were considered inadequate to make a diagnosis; the remaining slides were classified into mildly atypical, markedly atypical, and malignant cells. Each pair of slides were classified by the more serious diagnosis. DL samples from 100 ducts were independently blind-reviewed by two experienced cytopathologists. All abnormal slides and a random sample of normal slides and slides identified as inadequate for diagnosis (n = 43) were re-reviewed. The κ for intrarater agreement was 0.59 ± 0.10 for cytopathologist 1 and 0.33 ± 0.08 for cytopathologist 2. The κ for interrater agreement of slides from 100 ducts was 0.46 ± 0.07. The interrater agreement of the slides that were re-reviewed was κ = 0.27 ± 0.09. Fair to moderate intrarater and interrater agreement of DL cytology was observed. Low intrarater and interrater cytologic consistency may compromise the interpretation of clinical studies of DL. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2553–6)
Contractile Properties of Various Histaprodifen Derivatives in Guinea Pig Isolated Ileum and Trachea
Authors: Christophe B. , Carlier B. , Schunack W. , Chatelain P. , Peck M. , Massingham R.
Published: December 2006

We characterized the histamine H1 receptor agonism of various histaprodifen derivatives in guinea pig isolated ileum and trachea in comparison with histamine. Based on their affinity (calculated pKA values for ileum and trachea, respectively), the compounds were ranked as follows: suprahistaprodifen (8.31/8.08) > Nα-(4-phenylbutyl)histaprodifen (7.22/5.93) ≧ histamine (5.79/5.19) ≈ methylhistaprodifen (5.57/6.07). Based on their efficacy (calculated τ values for ileum and trachea, respectively), the compounds were ranked as follows: methylhistaprodifen (37.67/2.50) > histamine (5.64/1.80) > suprahistaprodifen (1.63/1.42) ≧ Nα-(4-phenylbutyl)histaprodifen (0.083/1.54). In the ileum, histamine and methylhistaprodifen showed a high histamine H1 receptor reserve while suprahistaprodifen and Nα-(4-phen-ylbutyl)histaprodifen are devoid of any histamine H1 receptor reserve. On the trachea, no histamine H1 receptor reserve was demonstrable with the four tested agonists. The kinetic of contraction/relaxation of the ileum was faster with histamine and methylhistaprodifen than with suprahistaprodifen and Nα-(4-phenylbutyl)histaprodifen. Histamine contracted the trachea faster than histaprodifen derivatives. Levocetirizine antagonized contractions induced by histamine and histaprodifen derivatives in both tissues. The differences observed in the calculated pA2 (7.60–8.29) and/or pD′2 values (6.28–7.90) depending on the tissue and/or the agonist are discussed.
What You Don't Know Can Hurt You: Investor-State Disputes and the Protection of the Environment in Developing Countries
Authors: Tienhaara Kyla
Published: December 2006

Recent years have seen a substantial increase in investor-state disputes. In many cases matters of public interest, including environmental regulations, are being tried. While it is crucial to assess the outcomes of investor-state disputes that involve matters of public policy, the procedures followed in investment arbitration make this difficult and, in some cases, impossible. This is relevant not only for researchers, but also crucially for regulators. This article focuses on how the lack of transparency in arbitration, and the lack of consistency of tribunal decisions, creates uncertainty for regulators. This uncertainty, when combined with the financial risk involved in proceeding to arbitration, may create situations in which the threat of an investment dispute is sufficient to convince a government to reverse, amend or fail to enforce an environmental regulation—a phenomenon referred to as regulatory chill. These issues are explored in an Indonesian case involving a dispute over mining contracts in protected forests.
Legal Stability and Claims of Change: The International Court's Treatment of Jus ad Bellum and Jus in Bello
Authors: Orakhelashvili Alexander
Published: December 2006

The post-Cold War era has witnessed a number of international conflicts and attendant claims that the law related to the use of force and armed conflicts has experienced significant changes in consequence of those events and processes. This has been argued extensively in terms of the conflicts of Iraq, Yugoslavia, or Afghanistan. The proof of legal change is, however, difficult to establish as it is subject to a high standard of proof and at the same time legal changes can damage the consistency and credibility of the system. As the International Court's consistent jurisprudence demonstrates, the argument of alleged legal changes in the legal regime governing armed conflicts is not based on consistent reasoning. This is explained by example in the Court's treatment of a number of fields, such as consent to the use of force, proof of the facts of the use of force, the law of self-defence and the law of belligerent occupation. The Court's consistent jurisprudence not only undermines the argument of legal change but also demonstrates that the legal position in this field maintains its separate existence in relation to power and politics. The strict application of legal norms is an inevitable requirement for a transparent legal system.
The Confessional Framework of Rule of Law Development: How to Offer Salvation to Willing Legal Subjects
Authors: Beard Jennifer
Published: December 2006

This article examines the theological underpinnings to rule of law development programmes. The article reveals the metaphysics of First World development practices in the Third World in order to suggest that international lawyers ought to consider carefully their approach to development practices. The article focuses in particular on rule of law development programmes and what has become known as the 'will to reform' dilemma amongst lawyers attempting to encourage changes in the legal cultures of programme recipients. The article examines how rule of law reforms constitute legal subjectivity at both the national and individual level and demonstrates how development, as a Western concept, enables these reforms to call the legal subject into being in the same way that the Word of God has been used to call Christian subjectivity into being with a promise.
Does the Influence of Oblate-Like Distortions in Larger Raindrops Make a Difference in Collection and Evaporation Parameterizations?
Authors: Straka Jerry M. , Gilmore Matthew S.
Published: December 2006

This note documents the results of more exact parameterizations for continuous-collection growth and evaporation against simpler traditional ones. Although the main focus is on improving research models, the research results also apply to high-resolution forecast models because the use of lookup tables can make the proposed evaporation, terminal velocity, and collection parameterizations as fast as or faster than proposed ones. It is shown that the older method of ignoring oblate-like distortions of shapes in raindrops, truncated at a maximum diameter of 8 mm, gives a solution like that including oblate-like distortions but only because of two large errors that nearly cancel. The biggest differences from the solutions using oblate-like distortions in shape arise from parameterizations that incorporate more exact approximations (e.g., sweep-out diameter) that are not combined with appropriately more exact approximations for other variables dependent on diameter (e.g., terminal velocity).
Debt and Deforestation
Authors: Culas Richard J.
Published: December 2006

The debt crisis of developing countries led to the widespread adoption of Structural Adjustment Programs (SAPs) during the 1980s. This article examines the hypothesis that heavy foreign debt causes a high rate of tropical deforestation mainly through the clearing of forestland for agricultural expansion. The article also reviews the possible causal links between debt, agricultural expansion and deforestation. Empirical evidence from tropical developing countries indicates that debt and deforestation are positively linked. The article concludes by suggesting that reducing the debt burden of developing countries can widen the opportunities for better environmental policies.
Spiritual Transformation, Relation and Radical Empathy: Core Components of the Ritual Healing Process
Authors: Koss-Chioino Joan D.
Published: December 2006

Based on studies of spirit healing, this article proposes a model of the process of ritual healing that is focused on the core components of spiritual transformation, relatedness and empathy. It describes the central role of spiritual transformation in healers from which emerges their capacity for relation and empathy. Many spirit healers, following a spiritual transformation, begin to exercise ‘radical empathy,’ in which individual differences between healer and sufferer are melded into one field of feeling and experience. The model is compared and contrasted with aspects of healing processes in some psychotherapeutic and analytic therapies. These comparisons are offered in the light of the growing interest in incorporating spirituality into psychological and medical treatments.A concluding section briefly explores some implications of aspects of the model of healing process that support the claim that it is widely applicable and identifies foundational components.
Generation of activation-specific human anti-αMβ2 single-chain antibodies as potential diagnostic tools and therapeutic agents
Authors: Eisenhardt Steffen U. , Schwarz Meike , Schallner Nils , Soosairajah Juliana , Bassler Nicole , Huang Dexing , Bode Christoph , Peter Karlheinz
Published: December 2006

The leukocyte integrin Mac-1 (αMβ2) plays a pivotal role in inflammation and host defense. Upon leukocyte activation, Mac-1 undergoes a conformational change exposing interaction sites for multiple ligands. We aimed to generate single-chain antibodies (scFv's) directed against activation-specific Mac-1 ligand-binding sites. Using human scFv phage libraries, we developed subtractive strategies with depletion of phages binding to nonactivated Mac-1 and selection of phages binding to activated Mac-1, using monocytes as well as CHO cells transfected with native or mutated, activated Mac-1. Three scFv clones demonstrated exclusive binding to activated Mac-1. Mac-1 binding of the ligands fibrinogen, heparin, and ICAM-1, but not C3bi, was inhibited. Using alanine substitutions, the paratope was identified within the heavy chain HCDR3s of the scFv's. The epitope was localized to Lys245-Arg261 of the αM I-domain. In a pilot study with septicemic patients, we provide initial support for the use of these scFv's as markers of monocyte activation and as potential diagnostic tools. Potential therapeutic use was tested in adhesion assays under static and flow conditions demonstrating the selective blockade of activated monocytes only. Furthermore, scFv HCDR3–derived peptides retain selectivity for the activated integrin, providing a unique template for the potential development of inhibitors that are specific for the activated Mac-1.
Cell-free production of scFv fusion proteins: an efficient approach for personalized lymphoma vaccines
Authors: Kanter Gregory , Yang Junhao , Voloshin Alexei , Levy Shoshana , Swartz James R. , Levy Ronald
Published: December 2006

The unique immunoglobulin (Ig) idiotype on the surface of each B-cell lymphoma represents an ideal tumor-specific antigen for use as a therapeutic vaccine. We have used an Escherichia coli—based, cell-free protein-expression system to produce a vaccine within hours of cloning the Ig genes from a B-cell tumor. We demonstrated that a fusion protein consisting of an idiotypic single chain Fv antibody fragment (scFv) linked to a cytokine (GM-CSF) or to an immunostimulatory peptide was an effective lymphoma vaccine. These vaccines elicited humoral immune responses against the native Ig protein displayed on the surface of a tumor and protected mice against tumor challenge with efficacy equal to that of the conventional Ig produced in a mammalian cell and chemically coupled to keyhole limpet hemocyanin. The cell-free E coli system offers a platform for rapidly generating individualized vaccines, thereby allowing much more efficient application in the clinic.
High precision multi-genome scale reannotation of enzyme function by EFICAz
Authors: Arakaki Adrian K , Tian Weidong , Skolnick Jeffrey
Published: December 2006

Background

The functional annotation of most genes in newly sequenced genomes is inferred from similarity to previously characterized sequences, an annotation strategy that often leads to erroneous assignments. We have performed a reannotation of 245 genomes using an updated version of EFICAz, a highly precise method for enzyme function prediction.

Results

Based on our three-field EC number predictions, we have obtained lower-bound estimates for the average enzyme content in Archaea (29%), Bacteria (30%) and Eukarya (18%). Most annotations added in KEGG from 2005 to 2006 agree with EFICAz predictions made in 2005. The coverage of EFICAz predictions is significantly higher than that of KEGG, especially for eukaryotes. Thousands of our novel predictions correspond to hypothetical proteins. We have identified a subset of 64 hypothetical proteins with low sequence identity to EFICAz training enzymes, whose biochemical functions have been recently characterized and find that in 96% (84%) of the cases we correctly identified their three-field (four-field) EC numbers. For two of the 64 hypothetical proteins: PA1167 from Pseudomonas aeruginosa, an alginate lyase (EC 4.2.2.3) and Rv1700 of Mycobacterium tuberculosis H37Rv, an ADP-ribose diphosphatase (EC 3.6.1.13), we have detected annotation lag of more than two years in databases. Two examples are presented where EFICAz predictions act as hypothesis generators for understanding the functional roles of hypothetical proteins: FLJ11151, a human protein overexpressed in cancer that EFICAz identifies as an endopolyphosphatase (EC 3.6.1.10), and MW0119, a protein of Staphylococcus aureus strain MW2 that we propose as candidate virulence factor based on its EFICAz predicted activity, sphingomyelin phosphodiesterase (EC 3.1.4.12).

Conclusion

Our results suggest that we have generated enzyme function annotations of high precision and recall. These predictions can be mined and correlated with other information sources to generate biologically significant hypotheses and can be useful for comparative genome analysis and automated metabolic pathway reconstruction.
Dealing with missing data in a multi-question depression scale: a comparison of imputation methods
Authors: Shrive Fiona M , Stuart Heather , Quan Hude , Ghali William A
Published: December 2006

Background

Missing data present a challenge to many research projects. The problem is often pronounced in studies utilizing self-report scales, and literature addressing different strategies for dealing with missing data in such circumstances is scarce. The objective of this study was to compare six different imputation techniques for dealing with missing data in the Zung Self-reported Depression scale (SDS).

Methods

1580 participants from a surgical outcomes study completed the SDS. The SDS is a 20 question scale that respondents complete by circling a value of 1 to 4 for each question. The sum of the responses is calculated and respondents are classified as exhibiting depressive symptoms when their total score is over 40. Missing values were simulated by randomly selecting questions whose values were then deleted (a missing completely at random simulation). Additionally, a missing at random and missing not at random simulation were completed. Six imputation methods were then considered; 1) multiple imputation, 2) single regression, 3) individual mean, 4) overall mean, 5) participant's preceding response, and 6) random selection of a value from 1 to 4. For each method, the imputed mean SDS score and standard deviation were compared to the population statistics. The Spearman correlation coefficient, percent misclassified and the Kappa statistic were also calculated.

Results

When 10% of values are missing, all the imputation methods except random selection produce Kappa statistics greater than 0.80 indicating 'near perfect' agreement. MI produces the most valid imputed values with a high Kappa statistic (0.89), although both single regression and individual mean imputation also produced favorable results. As the percent of missing information increased to 30%, or when unbalanced missing data were introduced, MI maintained a high Kappa statistic. The individual mean and single regression method produced Kappas in the 'substantial agreement' range (0.76 and 0.74 respectively).

Conclusion

Multiple imputation is the most accurate method for dealing with missing data in most of the missind data scenarios we assessed for the SDS. Imputing the individual's mean is also an appropriate and simple method for dealing with missing data that may be more interpretable to the majority of medical readers. Researchers should consider conducting methodological assessments such as this one when confronted with missing data. The optimal method should balance validity, ease of interpretability for readers, and analysis expertise of the research team.
Serum Retinol-Binding Protein 4 Is Reduced after Weight Loss in Morbidly Obese Subjects
Authors: Haider Dominik G. , Schindler Karin , Prager Gerhard , Bohdjalian Arthur , Luger Anton , Wolzt Michael , Ludvik Bernhard
Published: December 2006

Context: Administration of retinol-binding protein 4 (RBP-4) impairs insulin sensitivity in animals, and elevated serum concentrations have been associated with insulin resistance in humans.

Objective: We have studied whether weight loss influences RBP-4.

Patients and Methods: Fasting serum concentrations of RBP-4 were measured before and 6 months after gastric banding surgery in 33 morbidly obese patients aged 40 ± 11 yr with a body mass index (BMI) of 46 ± 5 kg/m2. Fourteen healthy subjects aged 29 ± 5 yr with a BMI less than 25 kg/m2 served as controls. To characterize the association of weight loss with central and peripheral appetite regulation, the signaling protein agouti-related protein (AGRP), the orexigenic hormone ghrelin, and its recently identified antagonist obestatin were determined.

Results: At baseline, RBP-4 levels were markedly higher in obese than in lean subjects (2.7 ± 0.5 vs. 0.9 ± 0.5 μg/ml; P < 0.001). In contrast, AGRP and obestatin were lower in obese subjects compared with lean controls (all P < 0.001). Six months after gastric banding, BMI was reduced to 40 ± 5 kg/m2, RBP-4 was reduced to 2.0 ± 0.7 μg/ml, AGRP increased from 1.8 ± 1.1 to 3.4 ± 1.1 ng/ml, ghrelin increased from 93 ± 58 to 131 ± 70 pg/ml, and obestatin increased from 131 ± 52 to 173 ± 35 pg/ml (all P < 0.05). Individual changes of RBP-4 were associated with changes of BMI (r = 0.72), the homeostasis model assessment insulin resistance-index (r = 0.53), and total cholesterol (r = 0.42, for all P < 0.05).

Conclusion: Reductions in circulating RBP-4 may contribute to improved insulin resistance in morbidly obese subjects after weight loss. This is accompanied by favorable changes in appetite-regulating hormones, which might support the sustained weight loss after obesity surgery.
Predisposition for de Novo Gene Aberrations in the Offspring of Mothers with a Duplicated CYP21A2 Gene
Authors: Baumgartner-Parzer S. M. , Fischer G. , Vierhapper H.
Published: December 2006

Context: Although CYP21A2 de novo mutations are assumed to account for 1 to 2% of congenital adrenal hyperplasia (CAH) alleles and CYP21 genotyping has been done worldwide, there are only a few well-documented cases of CYP21A2 de novo mutations. The majority of these are deletions resulting from unequal crossings over owing to misalignment of homologous chromosomes during meiosis. Whereas so far, only heterozygous deletions of the CYP21A1P pseudogene were seen as premutations for de novo aberrations, the present report addresses such a predisposing role for parental duplicated CYP21A2 genes.

Subjects and Methods: As part of routine diagnostic procedures, CYP21 genotyping has been performed in two unrelated female CAH index patients and in their clinically asymptomatic parents and siblings.

Results: Both patients have inherited the paternal Intron2splice mutation and have harbored a de novo gene aberration (large deletion and I271N/exon 4) on their maternal haplotype. Surprisingly, both mothers were carriers of rare duplicated CYP21A2 haplotypes carrying CAH alleles, which were not detected in the daughters. Among 133 CAH alleles that were detected in patients and that could be traced to the respective family members by genotyping, these two de novo aberrations (representing 1.5% of 133 traced CAH alleles) were the only ones identified.

Conclusion: Because both de novo CYP21A2 gene aberrations so far identified in our laboratory occurred in the gametes of mothers carrying rare duplicated CYP21A2 haplotypes, we hypothesize that duplicated CYP21A2 genes could predispose for de novo mutations in the offspring, which is of relevance for prenatal CYP21 genotyping and genetic counseling.
Sumoylation dynamics during keratinocyte differentiation
Authors: Deyrieux Adeline F. , Rosas-Acosta Germán , Ozbun Michelle A. , Wilson Van G.
Published: December 2006

SUMO modification regulates the activity of numerous transcription factors that have a direct role in cell-cycle progression, apoptosis, cellular proliferation, and development, but its role in differentiation processes is less clear. Keratinocyte differentiation requires the coordinated activation of a series of transcription factors, and as several crucial keratinocyte transcription factors are known to be SUMO substrates, we investigated the role of sumoylation in keratinocyte differentiation. In a human keratinocyte cell line model (HaCaT cells), Ca2+-induced differentiation led to the transient and coordinated transcriptional activation of the genes encoding crucial sumoylation system components, including SAE1, SAE2, Ubc9, SENP1, Miz-1 (PIASxβ), SUMO2 and SUMO3. The increased gene expression resulted in higher levels of the respective proteins and changes in the pattern of sumoylated substrate proteins during the differentiation process. Similarly to the HaCaT results, stratified human foreskin keratinocytes showed an upregulation of Ubc9 in the suprabasal layers. Abrogation of sumoylation by Gam1 expression severely disrupted normal HaCaT differentiation, consistent with an important role for sumoylation in the proper progression of this biological process.
Inhibition of autoignition and combustion rate for n-heptane homogeneous charge compression ignition combustion by methanol additive
Authors: Xingcai Lu , Yuchun Hou , Linlin Zu , Zhen Huang
Published: December 2006

This paper investigated the effects of methanol additive on autoignition and combustion rate of homogeneous charge compression ignition (HCCI) combustion using n-heptane. n-Heptane and 10–40 per cent (v/v) methanol/n-heptane blend fuels were injected into the intake port. The combustion characteristics and emissions of HCCI combustion for different methanol/n-heptane blend fuels at 1800r/min were recorded and analysed. The results show that the ignition timing of low- and high-temperature reaction is delayed and the maximum heat release during the low-temperature stage decreases with the increase in methanol addition in n-heptane. Sequentially, both the maximum and minimum accepted equivalence ratio increase, but the maximum engine load could not be further expanded beyond 40 per cent and above methanol/n-heptane fuels. For 20 and 30 per cent methanol/ n-heptane blend fuels, the combustion phasing of the high-temperature reaction occurs between -5-5° CA ATDC (crank angle after top dead centre) and the combustion events accomplished during the expanding stroke. With regard to the emissions, 10 and 20 per cent methanol addition shows little effect on CO and HC emissions, but substantially increases for 30 and 40 per cent methanol/n-heptane blend fuels. NOx emissions are greatly lowered for all fuels.
Optimization of multi-stage (booster) compression systems with waste heat recovery
Authors: Söylemez M. S.
Published: December 2006

This paper presents a thermo-economic optimization technique yielding simple algebraic formulae for estimating the optimum heat-exchanger effectiveness and the number of stages of multi-stage (booster) gas-compression system with waste heat recovery applications. An economic analysis method is used together with thermal analysis to set up a mathematical model for the multi-variable thermo-economic optimization of multi-stage compressors.
Sliding mode control with perturbation compensation for a class of uncertain systems
Authors: Tai Tsang-Li
Published: December 2006

In this study, a perturbation compensator is introduced in the sliding mode control (SMC) through a function of the prespecified sliding function, which is capable of estimating the lumped uncertainty and external disturbance with a known bandwidth. The approaches are designed to ensure a stable attraction and to attenuate the perturbation, which can be determined through the frequency domain analysis. Furthermore, an upper bound on the perturbation estimating error can be obtained based on the designed parameters, which depend on the bandwidth of the perturbation and the resonant frequency of the proposed estimator. Owing to the fact that the gain margin at zero frequency is infinity, the constant load disturbance can be estimated exactly. Combining the estimator with the sliding mode control method not only drastically reduces the gain of the discontinuous control term as compared with a conventional sliding mode control scheme but also achieves a chattering alleviated performance. In contrast to the SMC, the switching action is then performed in the bandwidth of the proposed compensator. For a disturbance-free system, this scheme not only establishes the sliding condition but also directly specifies the dynamic characteristics of the controlled system during the reaching stage, in which a discontinuous term is not needed. Experimental studies for the design of a turntable spindle servo system are conducted to illustrate its feasibility and effectiveness.
Bond Length Contraction in Zinc-Triad Complexes Ligated by Hydrotris(pyrazolyl)borate: [M(Cl){HB(3,5-iPr2pz)3}] (M = ZnII, CdII, and HgII)
Authors: Fujisawa Kiyoshi , Matsunaga Yuki , Ibi Naoko , Amir Nagina , Miyashita Yoshitaro , Okamoto Ken-ichi
Published: December 2006

Bond length contraction in zinc-triad chloro complexes, which were characterized by X-ray crystallography and metal–halogen stretching frequency, is reported.
Facile Three-Component Synthesis of Substituted Quinolines Catalyzed by Iridium(III) Complex
Authors: Nakajima Takayuki , Inada Takashi , Igarashi Takeyuki , Sekioka Tadashi , Shimizu Isao
Published: December 2006

A convenient and efficient synthesis of substituted quinolines via a simple one-pot reaction of an aniline, an aromatic aldehyde, and an enolizable aliphatic aldehyde in the presence of the iridium catalyst [IrCl2H(cod)]2 under oxygen as an oxidant was developed. The reaction proceeds with Mannich-type imine formation followed by nucleophilic addition to give β-amino aldehydes. Dehydrative cyclization takes place to give dihydroquinoline, which is then dehydrogenated by aerobic oxidation to give 2-aryl-3-alkylquinolines. Dialkylquinolines were obtained by the reaction with anilines and aliphatic aldehydes in good yields.
Preparation of Seven-Membered Carbocycles Using Ring-Closing Metathesis Reaction and Application to Syntheses of Tormesol and Cyathane Skeleton
Authors: Nakashima Katsuyuki , Fujisaki Norihiro , Inoue Kosuke , Minami Atsushi , Nagaya Chisako , Sono Masakazu , Tori Motoo
Published: December 2006

Various precursors were synthesized and were reacted with the Grubbs reagent as well as the second generation Grubbs reagent to cyclize them into seven-membered carbocycles with di- or tri-substituted double bonds. These reactions were used to synthesize (−)-tormesol, which is an enantiomer of sphenolobane-type diterpene that was isolated from Halimium viscosum, and a basic skeleton of cyathane-type diterpene.
Aromatic C–H Borylation Catalyzed by Hydrotris(pyrazolyl)borate Complexes of Rhodium and Iridium
Authors: Murata Miki , Odajima Hiroki , Watanabe Shinji , Masuda Yuzuru
Published: December 2006

Dehydrogenative coupling of 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (pinacolborane) with arenes occurred in good yield in the presence of a catalytic amount of [Rh(TpMe2)(cod)] (TpMe2 = hydrotris(3,5-dimethylpyrazolyl)borate, cod = 1,5-cyclooctadiene), [Ir(Tp)(cod)] (Tp = hydrotris(pyrazolyl)borate), and related (pyrazolyl)borate complexes. The catalytic activity was strongly affected by substituents on the pyrazolyl rings.
Controlled Particle Size and Size Distribution of Co–Al Layered Double Hydroxide via the Hydrothermal Urea Method in Aqueous Alcohols
Authors: Kayano Mihoko , Ogawa Makoto
Published: December 2006

Hexagonal platy particles of CoII and AlIII layered double hydroxide were precipitated from homogeneous solutions via urea hydrolysis under hydrothermal conditions. The particle sizes and size distribution were successfully controlled by adding alcohols to the starting mixture.
Reconsideration of the Winner-Take-All Hypothesis: Complex Networks and Local Bias
Authors: Lee Eocman , Lee Jeho , Lee Jongseok
Published: December 2006

The literature on network effects has popularized a hypothesis that competition between incompatible technologies results in the “winner-take-all” outcome. For the survival of the firm in this sort of competition, the installed base has been emphasized. We argue that the validity of this hypothesis depends on how customers interact with one another (e.g., if they exchange advice or files). In some interaction networks, customers influenced by their acquaintances may adopt a lagging technology even when a lead technology has built a large installed base. The presence of such a local bias facilitates the persistence of incompatibilities. When local bias cannot be sustained in other interaction networks, one technology corners the market. Our study suggests that overemphasizing the installed base, while ignoring network structure, could mislead practitioners.
The Effect of Service Experiences over Time on a Supplier’s Retention of Business Customers
Authors: Bolton Ruth N. , Lemon Katherine N. , Bramlett Matthew D.
Published: December 2006

This paper examines the link between a supplier’s marketing and service operations and its business customers’ subsequent repatronage behavior. We develop a dynamic model of service contract renewal for an individual firm, at the contract level, recognizing interdependencies among service contract renewal decisions due to the firm’s purchase of multiple contracts from the same supplier. The decision to renew a service contract is modeled as a function of service quality and price, where service quality is measured by the supplier’s service operations metrics over time. By incorporating longitudinal data about the supplier’s service operations, this study investigates how average service levels, variability in service levels (especially extreme outcomes), and timing of service delivery influence firms’ service contract renewal decisions. The study context is support services for high-technology systems in business markets in Germany and the United Kingdom, where service operations metrics over time typically have skewed distributions. Firm behavior is represented by a binary choice model at the contract level, estimated as a binary response model with a complementary log-log link function incorporating random intercepts. The study shows that a firm that has a few extremely favorable experiences for a given service contract is more likely to subsequently renew that service contract, after controlling for average service levels. Firms weigh recent experiences (i.e., within the past year)—rather than earlier experiences—when deciding whether or not to renew, so the timing of service experiences may be critical to the survival of buyer-seller relationships. Overall, the study suggests that models of customer retention should incorporate the extent, variability, and timing of a supplier’s service delivery over time at the contract/product level.
The Influence of Acid Treatment on the Composition of Bentonite
Authors: Vuković Zorica , Milutonović Aleksandra , Rožić Ljiljana , Rosić Aleksandra , Nedić Zoran , Jovanović Dušan
Published: December 2006

Bentonite from the ‘Bogovina’ coal mine in Serbia, was characterized. The influence of acid treatment on its composition, as well as mathematical descriptions of this influence are reported. The purpose of this work was to correlate the concentration of the acid used for the treatment with the resulting bentonite composition. X-ray diffraction (XRD), infrared spectroscopy and quantitative chemical analysis were employed to define the changes caused by acid treatment.

The contents of all the cations, except Si, decreased exponentially with increasing concentration of the HCl used for the treatment of the bentonite. This approach was tested on previously published data and was shown to be valid.

The basal reflections of smectite decreased gradually and eventually disappeared after intense treatment, while the other reflections remained in the XRD patterns of all the samples, but decreased slightly with increasing acid strength. In addition, the amount of X-ray amorphous matter formed increased rapidly with increasing acid concentration up to 4.5 M. With further increase in the acid strength, the amount of X-ray amorphous matter remained virtually constant.
Ti-Pillared Clays: Synthesis and General Characterization
Authors: Romero Amaya , Dorado Fernando , Asencio Isaac , García Prado Belen , Valverde José Luis
Published: December 2006

This review is concerned with the synthesis and physical-chemical characteristics of a specific type of modified clay material: Ti-PILCs. The two general synthetic procedures and the main problems associated with the scale-up synthesis of these pillared materials are discussed in detail. The general characteristics of Ti-PILCs in terms of basal spacing, pillar homogeneity, surface area, microporosity, mesoporosity, pore size and distribution, thermal resistance and acidity are discussed in depth. Likewise, the most important synthesis parameters that have a clear and marked influence on the final characteristics of the materials are summarized.
Insulin resistance and enhanced protein glycation in men with prehypertension
Authors: Sathiyapriya Viswanathan , Nandeesha Hanumanthappa , Bobby Zachariah , Pavithran Purushothaman , Selvaraj Nambiar , Rattina Dasse Nadaradjan
Published: December 2006

Clin Chem Lab Med 2006;44:1457–61.
Recent advances in physiological calcium homeostasis / Neuere Forschungsergebnisse zur physiologischen Kalziumhomöostase
Authors: Ramasamy Indra
Published: December 2006

A constant extracellular Ca2+ concentration is required for numerous physiological functions at tissue and cellular levels. This suggests that minor changes in Ca2+ will be corrected by appropriate homeostatic systems. The system regulating Ca2+ homeostasis involves several organs and hormones. The former are mainly the kidneys, skeleton, intestine and the parathyroid glands. The latter comprise, amongst others, the parathyroid hormone, vitamin D and calcitonin. Progress has recently been made in the identification and characterisation of Ca2+ transport proteins CaT1 and ECaC and this has provided new insights into the molecular mechanisms of Ca2+ transport in cells. The G-protein coupled calcium-sensing receptor, responsible for the exquisite ability of the parathyroid gland to respond to small changes in serum Ca2+ concentration was discovered about a decade ago. Research has focussed on the molecular mechanisms determining the serum levels of 1,25(OH)2D3, and on the transcriptional activity of the vitamin D receptor. The aim of recent work has been to elucidate the mechanisms and the intracellular signalling pathways by which parathyroid hormone, vitamin D and calcitonin affect Ca2+ homeostasis. This article summarises recent advances in the understanding and the molecular basis of physiological Ca2+ homeostasis.