bluuebunny/crossref_metadata_2025 huggingface dataset:
Mu opioid receptor and orexin/hypocretin mRNA levels in the lateral hypothalamus and striatum are enhanced by morphine withdrawal
Authors: Zhou Yan , Bendor Jacob , Hofmann Lauren , Randesi Matthew , Ho Ann , Kreek Mary Jeanne
Published: October 2006

In this study, we investigated the effects of acute morphine administration, chronic intermittent escalating-dose morphine administration and spontaneous withdrawal from chronic morphine on mRNA levels of mu opioid receptor (MOP-r), and the opioid peptides pro-opiomelanocortin (POMC) and preprodynorphin (ppDyn) in several key brain regions of the rat, associated with drug reward and motivated behaviors: lateral hypothalamus (lat.hyp), nucleus accumbens (NAc) core, amygdala, and caudate–putamen (CPu). There was no effect on MOP-r mRNA levels in these brain regions 30 min after either a single injection of morphine (10 mg/kg, i.p.) or chronic intermittent escalating-dose morphine (from 7.5 mg/kg per day on day 1 up to 120 mg/kg per day on day 10). Activation of the stress-responsive hypothalamic–pituitary–adrenal axis by 12 h withdrawal from chronic morphine was confirmed; both POMC mRNA levels in the anterior pituitary and plasma adrenocorticotropic hormone levels were significantly elevated. Under this withdrawal-related stress condition, there was an increase in MOP-r mRNA levels in the lat.hyp, NAc core, and CPu. Recent studies have demonstrated a novel role for the lat.hyp orexin (or hypocretin) activation in both drug-related positive rewarding, and withdrawal effects. Around 50% of lat.hyp orexin neurons express MOP-r. Therefore, we also examined the levels of lat.hyp orexin mRNA, and found them increased in morphine withdrawal, whereas there was no change in levels of the lat.hyp ppDyn mRNA, a gene coexpressed with the lat.hyp orexin. Our results show that there is an increase in MOP-r gene expression in a region-specific manner during morphine withdrawal, and support the hypothesis that increased lat.hyp orexin activity plays a role in morphine-withdrawal-related behaviors.
Adrenarche in the rat
Authors: Pignatelli Duarte , Xiao Fang , Gouveia Alexandra M , Ferreira Jorge G , Vinson Gavin P
Published: October 2006

Normal pubertal development in humans involves two distinct processes: maturation of adrenal androgen secretion (adrenarche) and activation of the hypothalamic–pituitary–gonadal axis (gonadarche). One factor thought to contribute to the adrenarche in man is increased adrenal 17-hydroxylase (CYP17) activity. In the rat, there is evidence for adrenal involvement in the initiation of puberty, but the adrenal glands of this species are generally thought to express CYP17 only very poorly at best. To further examine the nature of postnatal adrenal development in rat, plasma samples and adrenal tissues were taken from animals aged 2–90 days, circulating adrenal steroids assayed, and adrenal zones assessed quantitatively. A relative increase in zona reticularis, and peaks of circulating cortisol, androstenedione, and 17-OH-progesterone were observed around postnatal days 16–20, clearly before the development of the gonads, which begins at 30–35 days. Quantitative reverse transcriptase PCR confirmed a peak in mRNA coding for CYP17 in adrenal tissue from rats of similar age. The results suggest that the rat adrenal has the capacity to secrete steroids arising from 17-hydroxylation, and that this may contribute to a process similar to human adrenarche.
Dead Men Talking: Evidence of Post Death Contact and Continuing Bonds
Authors: Klugman Craig M.
Published: October 2006

Post Death Contact (PDC) is when a living individual feels that a person who is deceased is reaching out to connect with the living. Such experiences may be part of a model of grieving called Continuing Bonds. In order to further investigate the relationship between PDCs and the grieving process, a random telephone survey was developed to determine the ways in which PDCs are experienced in the United States. Most commonly, subjects reported PDCs that included dreams, sounds, feeling a presence, and having conversations.

The results suggest that experiencing PDCs may be a lifelong phenomenon and more widespread than previously thought.
Depressive Symptoms among Older Residents in Assisted Living Facilities
Authors: Jang Yuri , Bergman Elizabeth , Schonfeld Lawrence , Molinari Victor
Published: October 2006

Responding to the dramatic growth in Assisted Living Facilities (ALFs), the present study focused on mental health among older residents in ALFs. We assessed the effects of physical health constraints (chronic conditions, functional disability, and self-rated health) and psychosocial resources (social network, sense of mastery, religiosity, and attitude toward aging) on depressive symptoms. A sample of 150 residents ( Mage = 82.8, SD = 9.41) from 17 facilities in Florida was used for analyses. Higher levels of depressive symptoms were observed among older residents with a greater level of functional disability, poorer self-rated health, lower sense of mastery, less religiosity, and less positive attitude towards aging. In addition, the linkages between physical and mental health were modified by psychosocial resources. For older residents with more positive beliefs and attitudes (a higher sense of mastery, greater religiosity, and more positive attitudes toward aging), the adverse effects of functional disability or poorer self-rated health on depressive symptoms were attenuated. The protective roles of psychosocial resources against physical health constraints yield important implications for designing prevention and intervention strategies for the mental health of older populations in ALF settings.
Perceived Changes in Well-Being: The Role of Chronological Age, Target Age, and Type of Measure
Authors: Okun Morris A. , Dittburner Julie L. , Huff Barbara P.
Published: October 2006

The goal of this study is to investigate whether perceived changes in one's well-being from the present to the future are related to chronological age, target age, and type of measure (psychological well-being versus life satisfaction). Young adults ( N = 114) rated their current well-being and their future well-being at one of three target ages (30, 50, or 70 years old) and middle-aged adults ( N = 51) rated their current well-being and future well-being at the target age of 70 years old. Future self-enhancement effects were observed on both measures of well-being for young adults and on life satisfaction for middle-aged adults. Future self-enhancement effects were greater for life satisfaction than for psychological well-being. One-way MANOVAs showed that there were chronological age differences but not target age differences in the magnitude of future self-enhancement effects for well-being. Future self-enhancement effects were larger for young adults than for middle-aged adults.
Meaning Reconstruction in the First Two Years of Bereavement: The Role of Sense-Making and Benefit-Finding
Authors: Holland Jason M. , Currier Joseph M. , Neimeyer Robert A.
Published: October 2006

Contemporary grief theories have highlighted the role of meaning-making in adaptation to bereavement, focusing on two major construals of meaning: making sense of the loss and finding benefit in the experience. The current investigation attempted a conceptual replication of the findings of Davis, Nolen-Hoeksema, and Larson (1998) that suggested that sense-making predicts adaptation to loss in the early period of bereavement, whereas benefit-finding primarily plays an ameliorative role as time progresses. To this end, an ethnically diverse sample of 1,022 recently bereaved college students completed the Inventory of Complicated Grief (ICG) as well as questions that assessed sense-making, benefit-finding, and the circumstances surrounding their losses. Results only partially replicated the findings of Davis and his colleagues, demonstrating that: 1) time since loss bore no relation to grief complications; 2) sense-making emerged as the most robust predictor of adjustment to bereavement; and 3) benefit finding interacted with sense making, with the fewest complications predicted when participants reported high sense, but low personal benefit, in the loss.
Loss of Resistin Improves Glucose Homeostasis in Leptin Deficiency
Authors: Qi Yong , Nie Zhenying , Lee Yun-Sik , Singhal Neel S. , Scherer Philipp E. , Lazar Mitchell A. , Ahima Rexford S.
Published: October 2006

Resistin levels are increased in obesity, and hyperresistinemia impairs glucose homeostasis in rodents. Here, we have determined the role of resistin in ob/ob mice that are obese and insulin resistant because of genetic deficiency of leptin. Loss of resistin increased obesity in ob/ob mice by further lowering the metabolic rate without affecting food intake. Nevertheless, resistin deficiency improved glucose tolerance and insulin sensitivity in these severely obese mice, largely by enhancing insulin-mediated glucose disposal in muscle and adipose tissue. In contrast, in C57BL/6J mice with diet-induced obesity but wild-type leptin alleles, resistin deficiency reduced hepatic glucose production and increased peripheral glucose uptake. Resistin deficiency enhanced Akt phosphorylation in muscle and liver and decreased suppressor of cytokine signaling-3 level in muscle, and these changes were reversed by resistin replacement. Together, these results provide strong support for an important role of resistin in insulin resistance and diabetes associated with genetic or diet-induced obesity.
Recognition of HLA Class I–Restricted β-Cell Epitopes in Type 1 Diabetes
Authors: Ouyang Qin , Standifer Nathan E. , Qin Huilian , Gottlieb Peter , Verchere C. Bruce , Nepom Gerald T. , Tan Rusung , Panagiotopoulos Constadina
Published: October 2006

Type 1 diabetes results from the autoimmune destruction of insulin-producing pancreatic β-cells by cytotoxic T-lymphocytes (CTLs). In humans, few β-cell epitopes have been reported, thereby limiting the study of β-cell–specific CTLs in type 1 diabetes. To identify additional epitopes, HLA class I peptide affinity algorithms were used to identify a panel of peptides derived from the β-cell proteins islet amyloid polypeptide (IAPP), islet-specific glucose-6-phosphatase catalytic subunit–related protein (IGRP), insulin, insulinoma-associated antigen 2 (IA-2), and phogrin that were predicted to bind HLA-A*0201. Peripheral blood mononuclear cells from 24 HLA-A*0201 recent-onset type 1 diabetic patients and 11 nondiabetic control subjects were evaluated for γ-interferon secretion in response to peptide stimulation in enzyme-linked immunospot assays. We identified peptides IAPP9-17, IGRP215-223, IGRP152-160, islet IA-2(172-180), and IA-2(482-490) as novel HLA-A*0201–restricted T-cell epitopes in type 1 diabetic patients. Interestingly, we observed a strong inverse correlation between the binding affinity of β-cell peptides to HLA-A*0201 and CTL responses against those peptides in recent-onset type 1 diabetic patients. In addition, we found that self-reactive CTLs with specificity for an insulin peptide are frequently present in healthy individuals. These data suggest that many β-cell epitopes are recognized by CTLs in recent-onset type 1 diabetic patients. These epitopes may be important in the pathogenesis of type 1 diabetes.
Poly(ADP-Ribose) Polymerase Inhibitors Ameliorate Nephropathy of Type 2 Diabetic Leprdb/dbMice
Authors: Szabó Csaba , Biser Alisha , Benkő Rita , Böttinger Erwin , Suszták Katalin
Published: October 2006

The activation of the poly(ADP-ribose) polymerase (PARP) plays an important role in the pathophysiology of various diseases associated with oxidative stress. We found increased amounts of poly(ADP) ribosylated proteins in diabetic kidneys of Leprdb/db (BKsJ) mice, suggesting increased PARP activity. Therefore, we examined the effects of two structurally unrelated PARP inhibitors (INO-1001 and PJ-34) on the development of diabetic nephropathy of Leprdb/db (BKsJ) mice, an experimental model of type 2 diabetes. INO-1001 and PJ-34 were administered in the drinking water to Leprdb/db mice. Both INO-1001 and PJ-34 treatment ameliorated diabetes-induced albumin excretion and mesangial expansion, which are hallmarks of diabetic nephropathy. PARP inhibitors decreased diabetes-induced podocyte depletion in vivo and blocked hyperglycemia-induced podocyte apoptosis in vitro. High glucose treatment of podocytes in vitro led to an early increase of poly(ADP) ribosylated modified protein levels. Reactive oxygen species (ROS) generation appears to be a downstream target of hyperglycemia-induced PARP activation, as PARP inhibitors blocked the hyperglycemia-induced ROS generation in podocytes. INO-1001 and PJ-34 also normalized the hyperglycemia-induced mitochondrial depolarization. PARP blockade by INO-1001 and PJ-34 prevented hyperglycemia-induced nuclear factor-κB (NFκB) activation of podocytes, and it was made evident by the inhibitor of κBα phosphorylation and NFκB p50 nuclear translocation. Our results indicate that hyperglycemia-induced PARP activation plays an important role in the pathogenesis of glomerulopathy associated with type 2 diabetes and could serve as a novel therapeutic target.
Attenuation of Insulin-Evoked Responses in Brain Networks Controlling Appetite and Reward in Insulin Resistance
Authors: Anthony Karen , Reed Laurence J. , Dunn Joel T. , Bingham Emma , Hopkins David , Marsden Paul K. , Amiel Stephanie A.
Published: October 2006

The rising prevalence of obesity and type 2 diabetes is a global challenge. A possible mechanism linking insulin resistance and weight gain would be attenuation of insulin-evoked responses in brain areas relevant to eating in systemic insulin resistance. We measured brain glucose metabolism, using [18F]fluorodeoxyglucose positron emission tomography, in seven insulin-sensitive (homeostasis model assessment of insulin resistance [HOMA-IR] = 1.3) and seven insulin-resistant (HOMA-IR = 6.3) men, during suppression of endogenous insulin by somatostatin, with and without an insulin infusion that elevated insulin to 24.6 ± 5.2 and 23.2 ± 5.8 mU/l (P = 0.76), concentrations similar to fasting levels of the resistant subjects and approximately threefold above those of the insulin-sensitive subjects. Insulin-evoked change in global cerebral metabolic rate for glucose was reduced in insulin resistance (+7 vs. +17.4%, P = 0.033). Insulin was associated with increased metabolism in ventral striatum and prefrontal cortex and with decreased metabolism in right amygdala/hippocampus and cerebellar vermis (P < 0.001), relative to global brain. Insulin’s effect was less in ventral striatum and prefrontal cortex in the insulin-resistant subjects (mean ± SD for right ventral striatum 3.2 ± 3.9 vs. 7.7 ± 1.7, P = 0.017). We conclude that brain insulin resistance exists in peripheral insulin resistance, especially in regions subserving appetite and reward. Diminishing the link be-tween control of food intake and energy balance may contribute to development of obesity in insulin resistance.
Imaging Islets Labeled With Magnetic Nanoparticles at 1.5 Tesla
Authors: Tai Joo Ho , Foster Paula , Rosales Alma , Feng Biao , Hasilo Craig , Martinez Violetta , Ramadan Soha , Snir Jonatan , Melling C.W. James , Dhanvantari Savita , Rutt Brian , White David J.G.
Published: October 2006

We have developed a magnetic resonance imaging (MRI) technique for imaging Feridex (superparamagnetic iron oxide [SPIO])-labeled islets of Langerhans using a standard clinical 1.5-Tesla (T) scanner and employing steady-state acquisition imaging sequence (3DFIESTA). Both porcine and rat islets were labeled with SPIO by a transfection technique using a combination of poly-l-lysine and electroporation. Electron microscopy demonstrated presence of SPIO particles within the individual islet cells, including β-cells and particles trapped between cell membranes. Our labeling method produced a transfection rate of 860 pg to 3.4 ng iron per islet, dependent on the size of the islet. The labeling procedure did not disrupt either the function or viability of the islets. In vitro 3DFIESTA magnetic resonance images of single-labeled islets corresponded with their optical images. In vivo T2*-weighted scan using 1.5 T detected as few as 200 SPIO-labeled islets transplanted under rat kidney capsule, which correlated with immunohistochemistry of the transplant for insulin and iron. Ex vivo 3DFIESTA images of kidneys containing 200, 800 or 2,000 SPIO-labeled islet isografts showed good correlation between signal loss and increasing numbers of islets. These data provide evidence that islets can be labeled with SPIO and imaged using clinically available 1.5- T MRI.
Common Variants in the ENPP1 Gene Are Not Reproducibly Associated With Diabetes or Obesity
Authors: Lyon Helen N. , Florez Jose C. , Bersaglieri Todd , Saxena Richa , Winckler Wendy , Almgren Peter , Lindblad Ulf , Tuomi Tiinamaija , Gaudet Daniel , Zhu Xiaofeng , Cooper Richard , Ardlie Kristin G. , Daly Mark J. , Altshuler David , Groop Leif , Hirschhorn Joel N.
Published: October 2006

The common missense single nucleotide polymorphism (SNP) K121Q in the ectoenzyme nucleotide pyrophosphate phosphodiesterase (ENPP1) gene has recently been associated with type 2 diabetes in Italian, U.S., and South-Asian populations. A three-SNP haplotype, including K121Q, has also been associated with obesity and type 2 diabetes in French and Austrian populations. We set out to confirm these findings in several large samples. We genotyped the haplotype K121Q (rs1044498), rs1799774, and rs7754561 in 8,676 individuals of European ancestry with and without type 2 diabetes, in 1,900 obese and 930 lean individuals of European ancestry from the U.S. and Poland, and in 1,101 African-American individuals. Neither the K121Q missense polymorphism nor the putative risk haplotype were significantly associated with type 2 diabetes or BMI. Two SNPs showed suggestive evidence of association in a meta-analysis of our European ancestry samples. These SNPs were rs7754561 with type 2 diabetes (odds ratio for the G-allele, 0.85 [95% CI 0.78–0.92], P = 0.00003) and rs1799774 with BMI (homozygotes of the delT-allele, 0.6 [0.42–0.88], P = 0.007). However, these findings are not supported by other studies. We did not observe a reproducible association between these three ENPP1 variants and BMI or type 2 diabetes.
Modular Activation of Nuclear Factor-κB Transcriptional Programs in Human Diabetic Nephropathy
Authors: Schmid Holger , Boucherot Anissa , Yasuda Yoshinari , Henger Anna , Brunner Bodo , Eichinger Felix , Nitsche Almut , Kiss Eva , Bleich Markus , Gröne Hermann-Josef , Nelson Peter J. , Schlöndorff Detlef , Cohen Clemens D. , Kretzler Matthias ,   for the European Renal cDNA Bank (ERCB) Consortium
Published: October 2006

Diabetic nephropathy (DN) is the leading cause of end-stage renal failure and a major risk factor for cardiovascular mortality in diabetic patients. To evaluate the multiple pathogenetic factors implicated in DN, unbiased mRNA expression screening of tubulointerstitial compartments of human renal biopsies was combined with hypothesis-driven pathway analysis. Expression fingerprints obtained from biopsies with histological diagnosis of DN (n = 13) and from control subjects (pretransplant kidney donors [n = 7] and minimal change disease [n = 4]) allowed us to segregate the biopsies by disease state and stage by the specific expression signatures. Functional categorization showed regulation of genes linked to inflammation in progressive DN. Pathway mapping of nuclear factor-κB (NF-κB), a master transcriptional switch in inflammation, segregated progressive from mild DN and control subjects by showing upregulation of 54 of 138 known NF-κB targets. The promoter regions of regulated NF-κB targets were analyzed using ModelInspector, and the NF-κB module NFKB_IRFF_01 was found to be specifically enriched in progressive disease. Using this module, the induction of eight NFKB_IRFF_01–dependant genes was correctly predicted in progressive DN (B2M, CCL5/RANTES, CXCL10/IP10, EDN1, HLA-A, HLA-B, IFNB1, and VCAM1). The identification of a specific NF-κB promoter module activated in the inflammatory stress response of progressive DN has helped to characterize upstream pathways as potential targets for the treatment of progressive renal diseases such as DN.
Endothelial Nitric Oxide Synthase–Dependent Tyrosine Nitration of Prostacyclin Synthase in Diabetes In Vivo
Authors: Nie Hong , Wu Ji-liang , Zhang Miao , Xu Jian , Zou Ming-Hui
Published: October 2006

There is evidence that reactive nitrogen species are implicated in diabetic vascular complications, but their sources and targets remain largely unidentified. In the present study, we aimed to study the roles of endothelial nitric oxide synthase (eNOS) in diabetes. Exposure of isolated bovine coronary arteries to high glucose (30 mmol/l d-glucose) but not to osmotic control mannitol (30 mmol/l) switched angiotensin II–stimulated prostacyclin (PGI2)-dependent relaxation into a persistent vasoconstriction that was sensitive to either indomethacin, a cyclooxygenase inhibitor, or SQ29548, a selective thromboxane receptor antagonist. In parallel, high glucose, but not mannitol, significantly increased superoxide and 3-nitrotyrosine in PGI2 synthase (PGIS). Concurrent administration of polyethylene-glycolated superoxide dismutase (SOD), l-nitroarginine methyl ester, or sepiapterin not only reversed the effects of high glucose on both angiotensin II–induced relaxation and PGI2 release but also abolished high-glucose–enhanced PGIS nitration, as well as its association with eNOS. Furthermore, diabetes significantly suppressed PGIS activity in parallel with increased superoxide and PGIS nitration in the aortas of diabetic C57BL6 mice but had less effect in diabetic mice either lacking eNOS or overexpressing human SOD (hSOD+/+), suggesting an eNOS-dependent PGIS nitration in vivo. We conclude that diabetes increases PGIS nitration in vivo, likely via dysfunctional eNOS.
A Kir6.2 Mutation Causing Neonatal Diabetes Impairs Electrical Activity and Insulin Secretion From INS-1 β-Cells
Authors: Tarasov Andrei I. , Welters Hannah J. , Senkel Sabine , Ryffel Gerhart U. , Hattersley Andrew T. , Morgan Noel G. , Ashcroft Frances M.
Published: October 2006

ATP-sensitive K+ channels (KATP channels) couple β-cell metabolism to electrical activity and thereby play an essential role in the control of insulin secretion. Gain-of-function mutations in Kir6.2 (KCNJ11), the pore-forming subunit of this channel, cause neonatal diabetes. We investigated the effect of the most common neonatal diabetes mutation (R201H) on β-cell electrical activity and insulin secretion by stable transfection in the INS-1 cell line. Expression was regulated by placing the gene under the control of a tetracycline promoter. Transfection with wild-type Kir6.2 had no effect on the ATP sensitivity of the KATP channel, whole-cell KATP current magnitude, or insulin secretion. However, induction of Kir6.2-R201H expression strongly reduced KATP channel ATP sensitivity (the half-maximal inhibitory concentration increased from ∼20 μmol/l to ∼2 mmol/l), and the metabolic substrate methyl succinate failed to close KATP channels or stimulate electrical activity and insulin secretion. Thus, these results directly demonstrate that Kir6.2 mutations prevent electrical activity and insulin release from INS-1 cells by increasing the KATP current and hyperpolarizing the β-cell membrane. This is consistent with the ability of the R201H mutation to cause neonatal diabetes in patients. The relationship between KATP current and the membrane potential reveals that very small changes in current amplitude are sufficient to prevent hormone secretion.
TCF7L2 Variation Predicts Hyperglycemia Incidence in a French General Population
Authors: Cauchi Stéphane , Meyre David , Choquet Hélène , Dina Christian , Born Catherine , Marre Michel , Balkau Beverley , Froguel Philippe ,   for the DESIR Study Group
Published: October 2006

Recently, case-control studies demonstrated that a TCF7L2 (transcription factor 7–like 2 gene) noncoding variant (rs7903146 T at-risk allele) was strongly associated with an increased risk of type 2 diabetes. However, the predictive value of this marker in a nonselected general population remains unknown. In this study, our aim was to assess the contribution of this variant to the prevalence and incidence of hyperglycemia (type 2 diabetes and impaired fasting glucose) and insulin regulation in a 9-year prospective study of 4,976 middle-aged participants in the French DESIR (Data from an Epidemiological Study on the Insulin Resistance Syndrome) cohort. Our data support previous studies associating the T at-risk allele with a higher prevalence of hyperglycemia at baseline (P = 0.049) and a higher incidence of hyperglycemia after 9 years of follow-up (P = 0.014). The population-attributable risk to develop hyperglycemia due to the T at-risk allele was estimated to be 10.4% at the end of the prospective study. The most likely inheritance model was found to be additive (P = 0.002) rather than deviating from linearity (P = 0.098). An increase in the incidence of hyperglycemia was confirmed by survival analyses among C/C, C/T, and T/T carriers during the 9 years of follow-up (P = 0.028 by log-rank test). Interestingly, in control individuals, there was weak evidence of association of the T at-risk allele with reduced fasting insulin levels and insulin secretion index (homeostasis model assessment of β-cell function) in control individuals. We conclude that the TCF7L2 T at-risk allele variation (rs7903146) predicts hyperglycemia incidence in a general French population, possibly through a deleterious effect on insulin secretion.
Intensive Insulin Therapy in Mixed Medical/Surgical Intensive Care Units
Authors: Van den Berghe Greet , Wilmer Alexander , Milants Ilse , Wouters Pieter J. , Bouckaert Bernard , Bruyninckx Frans , Bouillon Roger , Schetz Miet
Published: October 2006

Intensive insulin therapy (IIT) improves the outcome of prolonged critically ill patients, but concerns remain regarding potential harm and the optimal blood glucose level. These questions were addressed using the pooled dataset of two randomized controlled trials. Independent of parenteral glucose load, IIT reduced mortality from 23.6 to 20.4% in the intention-to-treat group (n = 2,748; P = 0.04) and from 37.9 to 30.1% among long stayers (n = 1,389; P = 0.002), with no difference among short stayers (8.9 vs. 10.4%; n = 1,359; P = 0.4). Compared with blood glucose of 110–150 mg/dl, mortality was higher with blood glucose >150 mg/dl (odds ratio 1.38 [95% CI 1.10–1.75]; P = 0.007) and lower with <110 mg/dl (0.77 [0.61–0.96]; P = 0.02). Only patients with diabetes (n = 407) showed no survival benefit of IIT. Prevention of kidney injury and critical illness polyneuropathy required blood glucose strictly <110 mg/day, but this level carried the highest risk of hypoglycemia. Within 24 h of hypoglycemia, three patients in the conventional and one in the IIT group died (P = 0.0004) without difference in hospital mortality. No new neurological problems occurred in survivors who experienced hypoglycemia in intensive care units (ICUs). We conclude that IIT reduces mortality of all medical/surgical ICU patients, except those with a prior history of diabetes, and does not cause harm. A blood glucose target <110 mg/day was most effective but also carried the highest risk of hypoglycemia.
Coupled membrane process applied to fruit juice concentration
Authors: Koroknai B. , Gubicza L. , Bélafi-Bakó K.
Published: October 2006

A coupled membrane process of membrane distillation and osmotic evaporation, where the solutions were thermostated separately at different temperatures, was developed. Enhanced water flux was obtained since the total driving force of the coupled process was higher than the sum of the driving forces of single processes. Apple, raspberry, sour cherry, red, and black currant juices were concentrated by the novel, mild technique.
Production of process water using integrated membrane processes
Authors: Karakulski K. , Gryta M. , Sasim M.
Published: October 2006

Application of ultrafiltration, nanofiltration, reverse osmosis, membrane distillation, and integrated membrane processes for the preparation of process water from natural water or industrial effluents was investigated. A two-stage reverse osmosis plant enabled almost complete removal of solutes from the feed water. High-purity water was prepared using the membrane distillation. However, during this process a rapid membrane fouling and permeate flux decline was observed when the tap water was used as a feed. The precipitation of deposit in the modules was limited by the separation of sparingly soluble salts from the feed water in the nanofiltration. The combined reverse osmosis—membrane distillation process prevented the formation of salt deposits on the membranes employed for the membrane distillation. Ultrafiltration was found to be very effective removing trace amounts of oil from the feed water. Then the ultrafiltration permeate was used for feeding of the remaining membrane modules resulting in the total removal of oil residue contamination. The ultrafiltration allowed producing process water directly from the industrial effluents containing petroleum derivatives.
Kinetics of pyrolysis and properties of carbon black from a scrap tire
Authors: Koreňová Z. , Juma M. , Annus J. , Markoš J. , Jelemenský L’.
Published: October 2006

The pyrolysis of rubber from the sidewall and tread of a passenger car tire was carried out in a nitrogen flow at a wide range of final temperatures. Derivative thermogravimetric analysis (DTG) was applied to examine the kinetics at the different process conditions of completed pyrolysis. Two characteristic stages were observed in the DTG curves. The first stage corresponded to the decomposition of processing oil, plastifier, and additives, whereas the rubber polymer was decomposed in the second stage. Several properties of the carbon black formed by the pyrolysis such as ash content, specific surface area, and pore size distribution were determined. A change of the internal structure of the rubber particle in the meso-and macroregions of the pore size was observed.
Multiple steady states in a CSTR with total condenser: Comparison of equilibrium and nonequilibrium models
Authors: Švandová Z. , Markoš J. , Jelemenský L’.
Published: October 2006

Comparison of equilibrium and nonequilibrium models of a CSTR with total condenser focused on the multiple steady states and dynamic behaviour was carried out. The steady-state behaviour of the model system, MTBE synthesis from methanol and isobutene in a reactive distillation column, was studied in terms of the input parameters, i. e. feed flow rate of methanol or butenes, reflux ratio, and mass of catalyst. The dynamic behaviour of the system during the start-up was investigated and perturbations of manipulated variables were found to cause transitions between the parallel steady states.
Safety analysis and risk identification for a tubular reactor using the HAZOP methodology
Authors: Labovský J. , Jelemenský L’. , Markoš J.
Published: October 2006

A model approach to Hazard and Operability (HAZOP) analysis is presented based on the mathematical modeling of a process unit where both the steady-state analysis, including the analysis of the steady states multiplicity and stability, and the dynamic simulation are used. Heterogeneous tubular reactor for the ethylene oxide production from ethylene and oxygen was chosen to identify potential hazards for real system. The computer code DYNHAZ was developed consisting of a process simulator and a generator of the HAZOP algorithm.
Isolation and identification of anthraquinones of Caloplaca cerina and Cassia tora
Authors: Manojlović I. , Bogdanović-Dusanović G. , Gritsanapan W. , Manojlović N.
Published: October 2006

Five hydroxyanthraquinone derivatives physcion, emodin, fallacinal, teloschistin, and 1,3-dimethoxy-8-hydroxy-6-methyl-9,10-anthraquinone were isolated from the lichen Caloplaca cerina growing in Serbia. Three anthraquinone derivatives, namely physcion, emodin, and rhein were isolated and identified from the Thai medicinal plant Cassia tora.
Adaptive noise reduction using numerically stable fast recursive least squares algorithm
Authors: Ykhlef Farid , Arezki Madjid , Guessoum Abderezzak , Berkani Daoud
Published: October 2006

This paper is concerned with adaptive noise reduction based on the fast recursive least squares (FRLS) algorithm. It is well known that the fast recursive least squares (FRLS) algorithm suffers from numerical instability when operating under the effects of finite precision arithmetic. Several numerical solutions of stabilization were proposed in the case of stationary signals. In this work a new version of a numerically stable FRLS algorithm (NS‐FRLS) is proposed. The stability characteristics of this new stabilized algorithm are analysed. The analysis is based on a linear model for the errors in the states of the adaptive filter. Experimental results confirm the merits of adaptive filtering with the NS‐FRLS algorithm over optimum filtering using the solution provided by Wiener–Hopf equations. Copyright © 2006 John Wiley & Sons, Ltd.
Soft computing techniques in the design of a navigation, guidance and control system for an autonomous underwater vehicle
Authors: Loebis D. , Naeem W. , Sutton R. , Chudley J. , Tetlow S.
Published: October 2006

This paper discusses the navigation, guidance and control (NGC) of theHammerheadautonomous underwater vehicle (AUV). The navigation system is based on the integrated use of the global positioning system (GPS) and several inertial navigation system (INS) sensors. A simple Kalman filter (SKF) and an extended Kalman filter (EKF) are proposed to be used subsequently to fuse the data from the INS sensors and to integrate them with that of the GPS. This paper highlights the use of soft computing techniques, with an emphasis on fuzzy logic and genetic algorithms (GAs), both in single‐ and multiobjective modes to the adaptation of the initial statistical assumption of both the SKF and EKF caused by possible changes in sensor noise characteristics. It will be shown how the adaptation made by the proposed techniques is able to enhance the accuracy of the navigation system and hence it is considered as a major contribution of this particular study in relation to AUV technology.

The guidance and control system is based on a model predictive controller (MPC). The conventional MPC assumes a quadratic cost function and an optimization method such as quadratic programming (QP) to determine the optimum input to the process. For vehicle implementation, two modifications are proposed to the standard MPC problem. The first involves the replacement of the conventional optimizer with a GA in single objective mode whilst the quadratic cost function is replaced by a fuzzy performance index. The advantages of both schemes are outlined and simulation results are presented to evaluate the performance of the proposed techniques. Copyright © 2006 John Wiley & Sons, Ltd.
The 5‐HTTLPR s/s genotype at the serotonin transporter gene (SLC6A4) increases the risk for depression in a large cohort of primary care attendees: The PREDICT‐gene study
Authors: Cervilla Jorge A. , Rivera Margarita , Molina Esther , Torres‐González Francisco , Bellón Juan A. , Moreno Berta , de Dios Luna Juan , Lorente José A. , de Diego‐Otero Yolanda , King Michael , Nazareth Irwin , Gutiérrez Blanca ,   PREDICT Study Core Group
Published: October 2006

Previous reports and meta‐analyses have yielded inconclusive results as to whether the s/s genotype at the 5‐HTTLPR serotonin transporter polymorphism confers increased risk for depression. We tested the association between s/s genotype and depression in a large cohort (n = 737) of Spanish primary care consecutive attendees participating in a European study on predictors for depression in primary care (PREDICT study). Participants were administered the Composite International Diagnostic Interview (CIDI) depression subscale allowing diagnoses using ICD‐10 criteria for depressive episodes. Participants were genotyped to establish 5HTTLPR genotype. Both univariable and multivariable associations between the s/s genotype and depression were tested twice using two different depressive outcomes (ICD‐10 depressive episode and ICD‐10 severe depressive episode). We found an association between the s/s genotype and both depressive outcomes that was independent of age, sex, family history of psychological problems among first degree relatives and presence of comorbid generalized anxiety disorder. When comparing s/s homozygous versus the rest, the adjusted odds ratio for any ICD‐10 depressive episode and for severe ICD‐10 depressive episode were 1.50 (95% CI: 1.0–2.2; P = 0.045) and 1.79 (95% CI: 1.1–2.8; P = 0.016), respectively. The association was significantly stronger with increasing severity of depression (χ2 for linear association=6.1; P = 0.013) suggesting a dose‐dependent relationship. Our results are consistent with previous reports suggesting a small but independent effect by the s/s 5‐HTTLPR genotype increasing the risk for depression. © 2006 Wiley‐Liss, Inc.
Histological development and dynamic expression of Bmp2–6 mRNAs in the embryonic and postnatal mousecranial base
Authors: Kettunen Päivi , Nie Xuguang , Kvinnsland Inger Hals , Luukko Keijo
Published: October 2006

The cranial base is formed by endochondral ossification and is characterized by the presence of the synchondrosis growth centers. The aim of this study was to describe the histological development of the mouse midsagittal cranial base area from embryonic day 10 (E10) to the postnatal age of 2 months. The Bmp family of signaling molecules serves important functions in embryo and bone development and may therefore play a significant role in the early formation of the cranial base. To investigate this, we analyzed the mRNA pattern of expression of Bmp2–6 in the mouse cranial base from E10 to 5 days postnatally using radioactive in situ hybridization. We found that the formation of the mouse cranial base corresponds to that of rat and proceeds in a caudorostral sequence. Moreover, all Bmps studied showed distinct and overlapping developmentally regulated expression domains. Bmp2, Bmp5, and Bmp6 were expressed in the early mesenchymal condensations. Later, Bmp2, Bmp3, Bmp4, and Bmp5 were detected in the perichondrium and in the adjacent mesenchyme. Subsequently, Bmp2 and Bmp6 expressions were confined to hypertrophic chondrocytes, while Bmp3, Bmp4, and Bmp5 were expressed in the osteoblasts of the trabecular bone and bone collar. Interestingly, Bmp3 was uniquely expressed postnatally in the resting zone of the synchondrosis growth center, suggesting a role in the regulation of cranial base growth. These results suggest that Bmp signaling may serve specific and synergistic functions at different key stages of cranial base development and growth. Anat Rec Part A, 2006. © 2006 Wiley‐Liss, Inc.
Environmental awakening in the Swedish pulp and paper industry: pollution resistance and firm responses in the Early 20th century
Authors: Söderholm Kristina
Published: October 2006

The purpose of this article is to analyse in what way a conflict in the early 20th century (1904–1911) over a Swedish pulp mill's emissions into air and water impacted on the technology choices and strategies of the mill. The article also analyses what characterized the company's other responses to the complaints, in the form of counter‐arguments, as well as engagement of experts. The access to information about the deliberations at the mill's board meetings is very rare in historical studies of company behaviour in relation to the environment, and provides us with a unique opportunity to comprehend in what way business strategies were developed during the course of the conflict. Technology choices are often characterized by the search for knowledge that enables a company to employ existing but not yet developed technical potentials, rather than choices between known technical solutions. We emphasize that this is particularly evident in a case where a company is forced to alter its technology in order to solve previously unknown environmental problems. In spite of a persistent search, the mill did not find any ready‐made technological solutions to the environmental problems faced and was therefore forced to engage scientific expertise and even initiate basic scientific research. In 1911, the Swedish Supreme Administrative Court ordered the mill to undertake a number of pollution abatement investments. Interestingly – and partly in line with the so‐called Porter hypothesis – the long‐run economics of these investments turned out to be more favourable than anticipated prior to the verdict. Copyright © 2006 John Wiley & Sons, Ltd and ERP Environment.
Race as stigma: positioning the stigmatized as agents, not objects
Authors: Howarth Caroline
Published: October 2006

Using material from three qualitative studies into the social and psychological consequences of racism, this paper explores the insights gained from conceptualizing race as stigma. Not only does this shed light on the construction and contestation of racism in the lives of the research participants, the material presented raises important issues for a social psychology of stigma more generally. These include an assessment of the embodiment of stigma, the ideological construction of stigma within particular histories, the impact of stigma on identity and the ways in which we collectively contest and resist stigma. While acknowledging how stigma, particularly the stigma of race, acts to deny humanity, agency and liberty, I illustrate how stigma is collectively constructed, institutionalized and resisted in social and political relations. I conclude that a crucial part of the psychology of stigma must be a focus on the possibilities for communities to contest and transform representations and practices that stigmatize; that is, we need to explore the possibilities and conditions for stigmatized communities as agents and not (only) as objects or victims of stigma. Copyright © 2006 John Wiley & Sons, Ltd.
Haemolytic Activity and Adjuvant Effect of Notoginsenoside K from the Roots of Panax notoginseng
Authors: Qin Feng , Ye Yi‐Ping , Sun Hong‐Xiang
Published: October 2006

Notoginsenoside K (1), a saponin isolated from the roots of Panax notoginseng (Burk.) F. H. Chen, was evaluated for its haemolytic activity and adjuvant potential on specific antibody and cellular response to ovalbumin (OVA) in mice. Compound 1 showed a slight haemolytic effect, its concentration inducing 50% of the maximum haemolysis (HD50 value) being 318±13 μg/ml, on a 0.5% suspension of red blood cells. Compound 1 significantly increased the concanavalin A (Con A)‐, lipopolysaccharide (LPS)‐, and OVA‐induced splenocyte proliferation in OVA‐immunized mice (P<0.05, P<0.01, or P<0.001). The OVA‐specific serum IgG, IgG1, and IgG2b antibody levels were also significantly enhanced by 1, especially at a dose of 25 μg compared to an OVA control group (P<0.001). Moreover, the enhancing effect of 1 on the OVA‐specific IgG2b antibody responses to OVA in mice was more significant than that of Alum (AlOH gel; P<0.01). These results suggest that 1 exhibits a slight haemolytic activity and a significant adjuvant effect on specific antibody and cellular response against OVA in mice.
Low serum albumin levels and liver metastasis are powerful prognostic markers for survival in patients with carcinomas of unknown primary site
Authors: Seve Pascal , Ray‐Coquard Isabelle , Trillet‐Lenoir Veronique , Sawyer Michael , Hanson John , Broussolle Christiane , Negrier Sylvie , Dumontet Charles , Mackey John R.
Published: October 2006

BACKGROUND.

The authors investigated how lymphopenia and low serum albumin levels correlate with the prognosis of patients with carcinoma of unknown primary (CUP).

METHODS.

Univariate and multivariate prognostic factor analyses were conducted in a population of 317 consecutive patients with CUP who were evaluated at the Cross Cancer Institute of Edmonton, Alberta, Canada, from 1998 to 2004.

RESULTS.

The results from multivariate analysis showed that patients who had a performance status ≥2 (using the World Health Organization scale), a high overall comorbidity score (on the Adult Comorbidity Evaluation 27), liver metastasis, elevated serum lactate dehydrogenase (LDH) levels, lymphopenia (defined as an absolute lymphocyte count ≥0.7 × 109/L), and low serum albumin levels had a worse prognosis. Based on the observation that the presence of liver metastasis and low serum albumin levels were the most powerful adverse prognostic factors, a classification scheme was delineated that took those 2 variables into account. A group of good‐risk patients (no liver metastasis and normal serum albumin levels) and a group of poor‐risk patients (liver metastasis and/or low serum albumin levels) were identified with median survivals of 371 days and 103 days, respectively (P < .0001). This classification was validated further in an independent data set of 124 patients who were evaluated at 2 French cancer centers: Among those patients, the median survival was 378 days in the good‐risk group and 90 days in the poor‐risk group (P < .0001). The new prognostic model substantially outperformed the previous standard prognostic model, which was based on performance status and serum LDH levels.

CONCLUSIONS.

Lymphopenia and low serum albumin levels were identified as 2 new independent markers of prognosis in patients with CUP. Although the authors confirmed the validity of the previous prognostic model, they developed and validated a more powerful, simple model based on the 2 most powerful adverse prognostic factors: liver metastasis and low serum albumin levels. These findings were confirmed in an independent cohort of patients with CUP, and consideration of the authors' improved prognostic model for survival of patients with CUP is warranted. Cancer 2006. © 2006 American Cancer Society.
Function‐in‐layout: a demonstration with bio‐inspired hyperacuity chip
Authors: Mozsáry András , Chung Jen‐Feng , Roska Tamás
Published: October 2006

Below 100 nm a new scenario is emerging in VLSI design: floorplanning and function are inherently interrelated. Using mainly local connectivity, wire delay and crosstalk problems are eliminated. A new design methodology is proposed, called function‐in‐layout, that possesses: regular layout, mainly local connectivity, functional ‘parasitics’. A bio‐inspired demonstration is presented, a hyperacuity chip, with 30 ps time difference detection using 0.35 mm complementary metal‐oxide semiconductor (CMOS) technology. Copyright © 2006 John Wiley & Sons, Ltd.
Fully nonlinear oscillator noise analysis: an oscillator with no asymptotic phase
Authors: Demir Alper
Published: October 2006

Oscillators exist in many systems. Detailed and correct characterization and comprehension of noise in autonomous systems such as oscillators is of utmost importance. Previous approaches to oscillator noise analysis are based on some kind of perturbation analysis, some linear and some nonlinear. However, the derivations of the equations for perturbation analysis are all based on information that is produced by a linearization of the oscillator equations around the periodic steady‐state solution, where it is assumed that the oscillator is orbitally stable and it has the so‐called asymptotic phase property. In this paper, we first discuss these notions from a qualitative perspective, and demonstrate that the asymptotic phase property is crucial in validating all of the previous approaches. We then present the case of a simple oscillator that is orbitally stable but without asymptotic phase, for which previous approaches fail. We then present a fully nonlinear noise analysis of this oscillator. We derive and compute nonlinear, non‐stationary and non‐Gaussian stochastic characterizations for both amplitude and phase noise. We arrive at results that are distinctly different when compared with the ones obtained previously for oscillators with asymptotic phase. We compare and verify our analytical results against extensive Monte Carlo simulations. Copyright © 2006 John Wiley & Sons, Ltd.