bluuebunny/crossref_metadata_2025 huggingface dataset:
Material testing for sustainable pavement foundation design
Authors: Lambert J. P. , Fleming P. R. , Frost M. W.
Published: April 2007

The current UK pavement foundation design process is based upon the California bearing ratio, coupled with a ‘method’ specification based on past experience and proven performance. This provides an empirical indicator of adequate performance but limits the use of materials. This in turn restricts the wider use of marginal and recycled/secondary aggregates necessary to achieve sustainability targets. Additionally there is a move towards analytically based pavement design, based upon the fundamental material performance properties of elastic stiffness and shear strength. Analytical design, combined with ‘performance’ specifications, potentially allows any materials that are ‘fit for purpose’. This approach requires field measurements to confirm that the assumed design performance is achieved; performance data for design are required before the materials are used to ensure confidence in their likely behaviour. A large-scale laboratory assessment test has been developed to measure the performance of coarse granular (capping) materials. The test utilises devices proposed to measure/check performance in the field, thus providing directly comparable results. This paper discusses the development of the laboratory performance test, its use and role in the wider context of the design process, and suggests areas where this test can help foster sustainable use of materials.
Seismic performance of inorganic polymer concrete joints
Authors: Brooke N. J. , Keyte L. M. , South W. , Ingham J. M. , Megget L. M.
Published: April 2007

Because of the large quantities of carbon dioxide released during cement production, the concrete industry is a major emitter of greenhouse gases worldwide. Inorganic polymer cement has the potential to replace Portland cement as a binder in concrete, which could reduce greenhouse gas emissions due to cement production by approximately 85%. This paper assesses the performance of three interior beam–column joints constructed using inorganic polymer concrete. The joints tested were designed using existing standards, and their performance was compared with the performance of a companion joint constructed from Portland cement concrete. Inorganic polymer concrete mixed at a precast concrete factory using conventional equipment was found to have predictable properties and to behave similarly to Portland cement concrete. Cyclic testing of beam–column joint subassemblies showed that the hysteretic, bond and energy dissipation characteristics of inorganic polymer concrete joints were identical to respective characteristics of Portland cement concrete joints. It was concluded from these results that inorganic polymer beam–column joints can be safely designed to resist earthquake-induced forces using existing New Zealand design standards.
Localized Attachment Loss in Pendred Syndrome: Incidental?
Authors: Sharma C.G. Dileep , Pradeep A.R.
Published: April 2007

Background: Pendred syndrome is a rare, inherited, autosomal recessive disorder with an iodine organification defect of thyroxin produced by the thyroid gland. Its clinical features include sensorineural hearing loss, classically congenital and prelingual, and goiter.

Methods: This is the first case report of Pendred syndrome in the dental literature with oral findings that include localized extensive attachment loss involving mandibular incisor teeth and idiopathic hypercementosis involving multiple teeth in addition to other oral manifestations, suggesting hypothyroidism‐like macroglossia and macrocheilia. Furthermore, serum alkaline phosphatase along with inorganic calcium and phosphate levels were also elevated. Peripheral neutrophil function test suggested a defective function of neutrophils.

Results: Management of the case included augmenting thyroxin supplementation, in consultation with an endocrinologist, and extraction of hopeless mandibular central incisors followed by placement of immediate transitional dentures.

Conclusion: A comprehensive medical history and systemic and laboratory evaluations should be considered a prerequisite to identify, manage, and report such rare conditions in routine clinical practice.
Two Human Hydroxyapatite‐Coated Dental Implants Retrieved After a 14‐Year Loading Period: A Histologic and Histomorphometric Case Report
Authors: Iezzi Giovanna , Scarano Antonio , Petrone Giovanna , Piattelli Adriano
Published: April 2007

Background: Controversy over the long‐term clinical effectiveness of hydroxyapatite (HA)‐coated dental implants still persists, despite numerous clinical studies documenting high survival rates. Concerns about the degradation of the coating over the years have been raised; it has been speculated that resorption of the HA could produce a space between the implant and the bone with a resultant mechanical instability.

Methods: Two HA‐coated implants were retrieved due to a fracture of the abutment screws after a loading period of 14 years and were treated to obtain thin ground sections for histologic evaluation.

Results: At low‐power magnification, it was possible to observe that the HA coating was in contact with mature bone. No gaps or connective fibrous tissue was found at the implant–bone interface. No epithelial downgrowth was present. No acute or chronic inflammatory cell infiltrate was present at the implant–bone interface. No foreign body reaction was present in the peri‐implant tissues. Some osteocytes were in direct contact with the coating. For implant 1, the percentage of bone–titanium contact was 25% ± 2.1%, and the percentage of bone–HA contact was 35% ± 1.4%. The total bone–implant contact was ∼60%. The HA coating appeared to be resorbed in 46% ± 3.2% of the implant perimeter, especially in the coronal portions of the implant. For implant 2, the mean percentage of bone–HA contact was 13% ± 1.8%, and the mean percentage of bone–titanium contact was 15% ± 2.3%. The total bone–implant contact was ∼28%. The HA coating appeared to be resorbed for a mean of 68% ± 4.1% of the implant perimeter, especially in the coronal portion of the implant.

Conclusions: No acute or chronic inflammatory cell infiltrate was present in the peri‐implant tissues. No signs of coating infection, fatigue, or failure were observed in two specimens. The HA coating may not be susceptible to degradation or dissolution under long‐term function.
Favorable Periodontal Healing of 1‐Wall Infrabony Defects After Application of Calcium Phosphate Cement Wall Alone or in Combination With Enamel Matrix Derivative: A Pilot Study With Canine Mandibles
Authors: Shirakata Yoshinori , Yoshimoto Takehiko , Goto Hisanori , Yonamine Yutaka , Kadomatsu Hideshi , Miyamoto Motoharu , Nakamura Toshiaki , Hayashi Chie , Izumi Yuichi
Published: April 2007

Background: Although various periodontal regenerative therapies are used, their effects on non‐contained infrabony defects are unpredictable. Our previous studies showed that injectable, moldable, fast‐setting calcium phosphate cement (CPC) promoted histocompatible periodontal healing in 3‐wall intrabony defects. The present study evaluated healing patterns after surgical application of CPC walls with and without an enamel matrix derivative (EMD) in 1‐wall infrabony defects in dogs.

Methods: One‐wall infrabony defects (5 × 5 × 4 mm) were created surgically on the mesial and distal sides of bilateral mandibular fourth premolars in four beagle dogs. After elevating a full‐thickness flap, exposed root surfaces were planed thoroughly. The 16 defects were assigned randomly to one of the following experimental conditions: CPC, CPC+EMD, EMD, and open flap debridement (OFD). Ten weeks post‐surgery, the animals were sacrificed, and histologic specimens were prepared for histomorphometric evaluation.

Results: Defect sites treated with EMD only exhibited varying degrees of new cementum and new bone formation, whereas the OFD group presented only limited new cementum and bone formation. Defect sites where a CPC wall was implanted (CPC and CPC+EMD groups) revealed significantly greater regeneration of new bone and new cementum than in the EMD and OFD groups. No significant differences were observed between the CPC and CPC+EMD groups.

Conclusions: CPC walls with and without EMD promoted regeneration of alveolar bone and cementum in 1‐wall infrabony defects. Space and stable wound healing are believed to be crucial for periodontal regeneration in non‐contained infrabony defects.
Human Insulin Vesicle Dynamics During Pulsatile Secretion
Authors: Michael Darren J. , Xiong Wenyong , Geng Xuehui , Drain Peter , Chow Robert H.
Published: April 2007

In healthy individuals, plasma insulin levels oscillate in both fasting and fed states. Numerous studies of isolated pancreata and pancreatic islets support the hypothesis that insulin oscillations arise because the underlying rate of insulin secretion also oscillates; yet, insulin secretion has never been observed to oscillate in individual pancreatic β-cells. Using expressed fluorescent vesicle cargo proteins and total internal reflection fluorescence (TIRF) microscopy, we demonstrate that glucose stimulates human pancreatic β-cells to secrete insulin vesicles in short, coordinated bursts of ∼70 vesicles each. Randomization tests and spectral analysis confirmed that the temporal patterns of secretion were not random, instead exhibiting alternating periods of secretion and rest, recurring with statistically significant periods of 15–45 s. Although fluorescent vesicles arrived at the plasma membrane before, during, and after stimulation, their rate of arrival was significantly slower than their rate of secretion, so that their density near the plasma membrane dropped significantly during the cell's response. To study in greater detail the vesicle dynamics during cyclical bursts of secretion, we applied trains of depolarizations once a minute and performed simultaneous membrane capacitance measurements and TIRF imaging. Surprisingly, young fluorescent insulin vesicles contributed at least half of the vesicles secreted in response to a first train, even though young vesicles were vastly outnumbered by older, nonfluorescent vesicles. For subsequent trains, young insulin vesicles contributed progressively less to total secretion, whereas capacitance measurements revealed that total stimulated secretion did not decrease. These results suggest that in human pancreatic β-cells, young vesicles are secreted first, and only then are older vesicles recruited for secretion.
The Type and Frequency of Immunoregulatory CD4+ T-Cells Govern the Efficacy of Antigen-Specific Immunotherapy in Nonobese Diabetic Mice
Authors: Pop Shannon M. , Wong Carmen P. , He Qiuming , Wang Yaming , Wallet Mark A. , Goudy Kevin S. , Tisch Roland
Published: April 2007

Antigen-specific immunotherapy, an approach to selectively block autoimmune diabetes, generally declines in nonobese diabetic (NOD) mice as disease progresses. To define the parameters influencing the efficacy of antigen-specific immunotherapy once diabetes is established, plasmid DNA (pDNA) vaccination was used to suppress autoimmune-mediated destruction of syngeneic islet grafts in diabetic NOD recipients. pDNAs encoding a glutamic acid decarboxylase 65 (GAD65)-Ig molecule (pGAD65), interleukin (IL)-4 (pIL4), and IL-10 (pIL10) significantly delayed the onset of recurrent diabetes compared with pGAD65+pIL10-vaccinated recipients. Despite differences in efficacy, a similar frequency of GAD65-specific CD4+ T-cells secreting IL-4, IL-10, or interferon-γ were detected in mice treated with pGAD65+pIL4+pIL10 and pGAD65+pIL10. However, the frequency of FoxP3-expressing CD4+CD25+CD62Lhi T-cells was increased in the renal and pancreatic lymph nodes of diabetic recipients vaccinated with pGAD65+pIL4+pIL10. These immunoregulatory CD4+CD25+ T-cells (CD4+CD25+ Treg) exhibited enhanced in vivo and in vitro suppressor activity that partially was transforming growth factor-β dependent. Furthermore, duration of islet graft protection in pGAD65+pIL4+pIL10-vaccinated diabetic recipients correlated with the persistence of CD4+CD25+ Treg. These data demonstrate that the frequency and maintenance of FoxP3-expressing CD4+CD25+ Treg influence antigen-induced suppression of ongoing β-cell autoimmunity in diabetic recipients.
Loss of Stearoyl-CoA Desaturase-1 Improves Insulin Sensitivity in Lean Mice but Worsens Diabetes in Leptin-Deficient Obese Mice
Authors: Flowers Jessica B. , Rabaglia Mary E. , Schueler Kathryn L. , Flowers Matthew T. , Lan Hong , Keller Mark P. , Ntambi James M. , Attie Alan D.
Published: April 2007

The lipogenic gene stearoyl-CoA desaturase (SCD)1 appears to be a promising new target for obesity-related diabetes, as mice deficient in this enzyme are resistant to diet- and leptin deficiency–induced obesity. The BTBR mouse strain replicates many features of insulin resistance found in humans with excess visceral adiposity. Using the hyperinsulinemic-euglycemic clamp technique, we determined that insulin sensitivity was improved in heart, soleus muscle, adipose tissue, and liver of BTBR SCD1-deficient mice. We next determined whether SCD1 deficiency could prevent diabetes in leptin-deficient BTBR mice. Loss of SCD1 in leptinob/ob mice unexpectedly accelerated the progression to severe diabetes; 6-week fasting glucose increased ∼70%. In response to a glucose challenge, Scd1−/− leptinob/ob mice had insufficient insulin secretion, resulting in glucose intolerance. A morphologically distinct class of islets isolated from the Scd1−/− leptinob/ob mice had reduced insulin content and increased triglycerides, free fatty acids, esterified cholesterol, and free cholesterol and also a much higher content of saturated fatty acids. We believe the accumulation of lipid is due to an upregulation of lipoprotein lipase (20-fold) and Cd36 (167-fold) and downregulation of lipid oxidation genes in this class of islets. Therefore, although loss of Scd1 has beneficial effects on adiposity, this benefit may come at the expense of β-cells, resulting in an increased risk of diabetes.
A Functional Variant of the Adipocyte Glycerol Channel Aquaporin 7 Gene Is Associated With Obesity and Related Metabolic Abnormalities
Authors: Prudente Sabrina , Flex Elisabetta , Morini Eleonora , Turchi Federica , Capponi Daria , De Cosmo Salvatore , Tassi Vittorio , Guida Valentina , Avogaro Angelo , Folli Franco , Maiani Francesca , Frittitta Lucia , Dallapiccola Bruno , Trischitta Vincenzo
Published: April 2007

Aquaporin 7 (AQP7), the gateway protein controlling glycerol release, has recently emerged as a modulator of adipocyte metabolism. AQP7 knockout mice develop obesity and hyperglycemia. The contribution of AQP7 to these abnormalities in humans is unknown. We examined whether common single nucleotide polymorphisms (SNPs) in the AQP7 gene modulate the risk of obesity and related abnormalities. Among several SNPs we identified, A-953G in the AQP7 promoter was associated with type 2 diabetes in 977 (530 female/447 male) Caucasians: odds ratio for XG (i.e., AG+GG) versus AA individuals was 1.36 (95% CI 1.01–1.84), P = 0.04. This finding was entirely due to the association among females (1.8 [1.2–2.6], P = 0.004), which was no longer significant when adjusted for BMI. In fact, BMI was higher in XG than in AA females (30.8 ± 6.6 vs. 28.9 ± 5.2, P = 0.002). This association was confirmed in independent case-control study (n = 299 female subjects) for morbid obesity (1.66 [1.01–2.74], P = 0.04). Luciferase and mobility shift assays showed that, compared with −953A, the −953G promoter had reduced transcriptional activity (P = 0.001) and impaired ability to bind CCAAT/enhancer binding protein (C/EBP)β transcription factor (P = 0.01). Finally, AQP7 expression in adipose tissue decreased from AA to AG to GG individuals (P = 0.036). These data strongly suggest that AQP7 downregulation is pathogenic for obesity and/or type 2 diabetes.
Early-Life Stress and the Development of Obesity and Insulin Resistance in Juvenile Bonnet Macaques
Authors: Kaufman Daniel , Banerji Mary Ann , Shorman Igor , Smith Eric L.P. , Coplan Jeremy D. , Rosenblum Leonard A. , Kral John G.
Published: April 2007

Stress is a risk factor for chronic illnesses such as obesity, type 2 diabetes, and hypertension and has been postulated to cause the metabolic syndrome via perturbation of the hypothalamo-pituitary-adrenal (HPA) axis. In our model of early-life stress (variable foraging demand [VFD]), food insecurity is imposed on monkey mothers for 16 weeks beginning when their nursing offspring are 3–5 months of age. Under VFD, food availability is never restricted, and the infant's growth is unaffected. VFD rearing does, however, cause a range of neurobiological abnormalities, including dysregulation of the HPA axis, manifested in abnormal cerebrospinal fluid cortisol and corticotropin-releasing factor levels. We previously reported spontaneous occurrence of metabolic syndrome in 14% of normally reared peripubertal bonnet macaques given ad libitum access to standard monkey chow. Here, we show that compared with normally reared monkeys, peripubertal VFD juveniles exhibit greater weight, BMI, abdominal circumference, and glucagon-like peptide-1 and decreased glucose disposal rates during hyperinsulinemic-euglycemic clamps. Our data suggest that early-life stress during a critical period of neuro development can result in the peripubertal emergence of obesity and insulin resistance.
Adiponectin-Induced Endothelial Nitric Oxide Synthase Activation and Nitric Oxide Production Are Mediated by APPL1 in Endothelial Cells
Authors: Cheng Kenneth K.Y. , Lam Karen S.L. , Wang Yu , Huang Yu , Carling David , Wu Donghai , Wong Chiwai , Xu Aimin
Published: April 2007

Adiponectin protects the vascular system partly through stimulation of endothelial nitric oxide (NO) production and endothelium-dependent vasodilation. The current study investigated the role of two recently identified adiponectin receptors, AdipoR1 and -R2, and their downstream effectors in mediating the endothelium actions of adiponectin. In human umbilical vein endothelial cells, adiponectin-induced phosphorylation of endothelial NO synthase (eNOS) at Ser1177 and NO production were abrogated when expression of AdipoR1 and -R2 were simultaneously suppressed. Proteomic analysis demonstrated that the cytoplasmic tails of both AdipoR1 and -R2 interacted with APPL1, an adaptor protein that contains a PH (pleckstrin homology) domain, a PTB (phosphotyrosine-binding) domain, and a Leucine zipper motif. Suppression of APPL1 expression by RNA interference significantly attenuated adiponectin-induced phosphorylation of AMP-activated protein kinase (AMPK) at Thr172 and eNOS at Ser1177, and the complex formation between eNOS and heat shock protein 90, resulting in a marked reduction of NO production. Adenovirus-mediated overexpression of a constitutively active version of AMPK reversed these changes. In db/db diabetic mice, both APPL1 expression and adiponectin-induced vasodilation were significantly decreased compared with their lean littermates. Taken together, these results suggest that APPL1 acts as a common downstream effector of AdipoR1 and -R2, mediating adiponectin-evoked endothelial NO production and endothelium-dependent vasodilation.
Caspase Inhibitor Therapy Enhances Marginal Mass Islet Graft Survival and Preserves Long-Term Function in Islet Transplantation
Authors: Emamaullee Juliet A. , Stanton Laura , Schur Colleen , Shapiro A.M. James
Published: April 2007

Islet transplantation can provide insulin independence in patients with type 1 diabetes, but islets derived from two or more donors are often required. A significant fraction of the functional islet mass is lost to apoptosis in the immediate posttransplant period. The caspase inhibitor N-benzyloxycabonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD-FMK) has been used therapeutically to prevent apoptosis in experimental animal models of ischemic injury, autoimmunity, and degenerative disease. In the current study, zVAD-FMK therapy was examined in a syngeneic islet transplant model to determine whether caspase inhibition could improve survival of transplanted islets. zVAD-FMK therapy significantly improved marginal islet mass function in renal subcapsular transplantation, where 90% of zVAD-FMK–treated mice became euglycemic with 250 islets, versus 27% of the control animals (P < 0.001). The benefit of zVAD-FMK therapy was further demonstrated after intraportal transplantation, where 75% of zVAD-FMK–treated animals established euglycemia with only 500 islets, and all of the controls remained severely diabetic (P < 0.001). zVAD-FMK pretreatment of isolated islets in the absence of systemic therapy resulted in no significant benefit compared with controls. Long-term follow-up of transplanted animals beyond 1 year posttransplant using glucose tolerance tests confirmed that a short course of zVAD-FMK therapy could prevent metabolic dysfunction of islet grafts over time. In addition, short-term zVAD-FMK treatment significantly reduced posttransplant apoptosis in islet grafts and resulted in preservation of graft insulin reserve over time. Our data suggest that caspase inhibitor therapy will reduce the islet mass required in clinical islet transplantation, perhaps to a level that would routinely allow for insulin independence after single-donor infusion.
Lineage Tracing Evidence for In Vitro Dedifferentiation but Rare Proliferation of Mouse Pancreatic β-Cells
Authors: Weinberg Noa , Ouziel-Yahalom Limor , Knoller Sarah , Efrat Shimon , Dor Yuval
Published: April 2007

Understanding and manipulating pancreatic β-cell proliferation is a major challenge for pancreas biology and diabetes therapy. Recent studies have raised the possibility that human β-cells can undergo dedifferentiation and give rise to highly proliferative mesenchymal cells, which retain the potential to redifferentiate into β-cells. To directly test whether cultured β-cells dedifferentiate, we applied genetic lineage tracing in mice. Differentiated β-cells were heritably labeled using the Cre-lox system, and their fate in culture was followed. We provide evidence that mouse β-cells can undergo dedifferentiation in vitro into an insulin-, pdx1-, and glut2-negative state. However, dedifferentiated β-cells only rarely proliferate under standard culture conditions and are eventually eliminated from cultures. Thus, the predominant mesenchymal cells seen in cultures of mouse islets are not of a β-cell origin.
Direct Free Fatty Acid Uptake Into Human Adipocytes In Vivo
Authors: Shadid Samyah , Koutsari Christina , Jensen Michael D.
Published: April 2007

We sought to assess whether direct uptake of circulating free fatty acids (FFAs) by adipocytes occurs in vivo in overnight postabsorptive humans and, if so, whether there are regional differences in uptake between lean and obese women and men. We used bolus injections of radiolabeled FFA tracers followed by carefully timed adipose tissue biopsies. First, we validated a method to measure direct adipocyte FFA uptake and then quantitated this process using the modified methods in normal-weight postabsorptive men and women. We then used a continuous infusion of radiolabeled FFA to measure direct and indirect (VLDL) regional adipose tissue uptake in obese men and women. Direct FFA uptake was greater in women than men: 8.2 ± 0.6 vs. 4.0 ± 0.5% (P < 0.0001) of FFAs were taken up by subcutaneous adipose tissue, respectively. Abdominal subcutaneous fat took up FFAs more avidly than femoral fat in men, but this did not occur in women. Similar sex and regional difference were found to occur in obese women and men. Gene expression of fatty acid transporters was greater in abdominal than femoral fat in men (P < 0.05) but not in women (P = 0.80). We observed sex- and site-specific recycling of circulating FFAs into subcutaneous fat. This is a novel FFA disposal pathway that may also play a role in the development or maintenance of body fat distribution. Regional variations in facilitated fatty acid transport may contribute to this process.
Transcription Factor 7-Like 2 (TCF7L2) Is Associated With Gestational Diabetes Mellitus and Interacts With Adiposity to Alter Insulin Secretion in Mexican Americans
Authors: Watanabe Richard M. , Allayee Hooman , Xiang Anny H. , Trigo Enrique , Hartiala Jaana , Lawrence Jean M. , Buchanan Thomas A.
Published: April 2007

OBJECTIVE— Variation in transcription factor 7-like 2 (TCF7L2) gene has been shown to be associated with type 2 diabetes and diabetes-related quantitative traits. We examined variation in a 0.1-Mb region surrounding marker DG10S478 for association with diabetes-related quantitative traits in 132 Mexican-American families of a proband with previous gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS— Study participants were phenotyped by an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test and by a dual-energy X-ray absorptiometry scan for percentage of body fat. Of the 42 tag single nucleotide polymorphisms (SNPs) genotyped, 15 were identified.

RESULTS— On univariate analysis, none of the SNPs showed association with diabetes-related quantitative traits. However, rs12255372 showed association with 30′ Δinsulin (OGTT 30′ min fasting insulin) in an interaction with percentage of body fat (Bonferroni-corrected P = 0.027). The effect of adiposity to increase 30′ Δinsulin was greater in subjects with the T allele. This interaction was not associated with acute insulin response to intravenous glucose. rs12255372 also showed an association with β-cell compensation for insulin resistance based on 30′ Δinsulin in an interaction with percentage of body fat (Bonferroni-corrected P = 0.014). rs12255372 was also associated with GDM (odds ratio [OR] 2.49 [95% CI 1.17–5.31]; P = 0.018) in our case-control sample.

CONCLUSIONS— We conclude that variation in TCF7L2 is associated with GDM and interacts with adiposity to alter insulin secretion in Mexican Americans. Our observations partly explain the increased ORs observed in previous associated studies when analyses were restricted to lean subjects and the variability in quantitative trait association results.
A Mutation in the TMD0-L0 Region of Sulfonylurea Receptor-1 (L225P) Causes Permanent Neonatal Diabetes Mellitus (PNDM)
Authors: Masia Ricard , De Leon Diva D. , MacMullen Courtney , McKnight Heather , Stanley Charles A. , Nichols Colin G.
Published: April 2007

OBJECTIVE—We sought to examine the molecular mechanisms underlying permanenent neonatal diabetes mellitus (PNDM) in a patient with a heterozygous de novo L225P mutation in the L0 region of the sulfonylurea receptor (SUR)1, the regulatory subunit of the pancreatic ATP-sensitive K+ channel (KATP channel).

RESEARCH DESIGN AND METHODS—The effects of L225P on the properties of recombinant KATP channels in transfected COS cells were assessed by patch-clamp experiments on excised membrane patches and by macroscopic Rb-flux experiments in intact cells.

RESULTS—L225P-containing KATP channels were significantly more active in the intact cell than in wild-type channels. In excised membrane patches, L225P increased channel sensitivity to stimulatory Mg nucleotides without altering intrinsic gating or channel inhibition by ATP in the absence of Mg2+. The effects of L225P were abolished by SUR1 mutations that prevent nucleotide hydrolysis at the nucleotide binding folds. L225P did not alter channel inhibition by sulfonylurea drugs, and, consistent with this, the patient responded to treatment with oral sulfonylureas.

CONCLUSIONS—L225P underlies KATP channel overactivity and PNDM by specifically increasing Mg-nucleotide stimulation of the channel, consistent with recent reports of mechanistically similar PNDM-causing mutations in SUR1. The mutation does not affect sulfonylurea sensitivity, and the patient is successfully treated with sulfonylureas.
The End of American Environmentalism?
Authors: Devall Bill
Published: April 2007

The death of American environmentalism has recently been proclaimed by some commentators (Schellenberger and Nordhaus 2005). Such declarations tend to be limiting because they fail to explore and evaluate the historical context of international, national, and regional social forces and social changes that shaped the American environmental movement over the past century. In this essay, I propose to explore the important question of the decline of American environmentalism within the context of a recurring theme pursued by the American movement: the protection of places wherein we dwell. David Brower has called this the practice of Conservation, Preservation, and Restoration, or CPR (Brower 1995).
Environmental Realism: From Apologetics to Substance
Authors: Murphy Raymond
Published: April 2007

This article assesses the cornucopian theory of the mastery of plastic nature. Serious deficiencies are found, especially the theory's complacent faith in economic rationality and its underestimation of nature's capacity for unexpected emergent disturbances. Conclusions about the real state of the world and realistic expectations for the future must take into account not only present trends, but also the findings of research into disasters and societies that have collapsed. Learning from the analysis of such discontinuities and breaking points will help to avoid simplistic presumptions of safety based on extrapolating time-series trends of present well-being in wealthy societies into the distant future. It is precisely disaster research and studies of collapsed societies that can teach us about failures of foresight concerning nature's dynamics, about the material consequences of such errors, about the uncertainties involved in foreseeing nature's emergent dynamics, and about social barriers to learning from the prompts of nature. Although apologetics for business-as-usual, full-steam-ahead practices that masquerade as realism should be rejected, a deeper realism that has learned to expect the unexpected from nature is necessary. Such a critical realist perspective for investigating prompts from nature has been elaborated in this article.
Diphenylamine‐Substituted Cruciform Oligo(phenylene vinylene): Enhanced One‐ and Two‐Photon Excited Fluorescence in the Solid State
Authors: He F. , Tian L. L. , Tian X. Y. , Xu H. , Wang Y. H. , Xie W. J. , Hanif M. , Xia J. L. , Shen F. Z. , Yang B. , Li F. , Ma Y. G. , Yang Y. Q. , Shen J. C.
Published: April 2007

1,4‐di(4′‐N,N‐diphenylaminostyryl)benzene (DPA‐DSB) is a well known compound with a large two‐photon absorption (TPA) section and strong fluorescence in solution. However, the ease with which it crystallizes results in the formation of discontinuous crystalline phases during vacuum deposition processes, thereby greatly limiting its applicability in solid‐state devices. A cruciform dimer of DPA‐DSB, 2,5,2′,5′‐tetra(4′‐N,N‐diphenylaminostyryl)biphenyl (DPA‐TSB) is reported, wherein two DPA‐DSB molecules are linked through a central biphenyl bond. The DPA‐TSB molecules take on a cruciform configuration because of the steric crowding around the central biphenyl core, which has the effect of efficiently suppressing crystalline and intermolecular interactions. The neat DPA‐TSB solid shows strong green–blue fluorescence because of both steady‐state absorption as well as TPA. The DPA‐TSB solid exhibits a photoluminescence (PL) efficiency (ηsolid) of 29 % and a solid‐state two‐photon action cross section (δηsolid) of 954 GM (1 GM = 1 × 10–50 cm4 s photon–1 molecule–1), which is much greater than for the model compound DPA‐DSB (ηsolid = 16 % and δηsolid = 150 GM, where δ is the TPA cross section and η is the fluorescence quantum yield). Based on its high PL efficiency, good film‐forming ability, and strong TPA, DPA‐TSB seems to be a good candidate for applications in solid‐state optical devices.
UV‐vis‐Induced Vitrification of a Molecular Crystal
Authors: Naito T. , Sugawara H. , Inabe T. , Kitajima Y. , Miyamoto T. , Niimi H. , Asakura K.
Published: April 2007

A charge‐transfer complex of 2,5‐dimethyl‐N,N′‐dicyanoquinonediimine (DM) with silver (crystalline Ag(DM)2, defined as α) is irreversibly transformed by UV‐vis illumination. Depending on the illumination conditions, three new types of solids (defined as γ, δ, and ϵ) with different structural and physical properties are obtained and examined by a variety of analytical techniques, including solid‐state, high‐resolution, cross‐polarization magic angle spinning (CP‐MAS)13C NMR, elemental analysis (EA), mass spectrometry (MS), X‐ray absorption fine structure (XAFS), and powder X‐ray diffraction (XRD). The CP‐MAS, EA, MS, and XAFS results indicate that compound γ is a glass state of Ag(DM)2. The transformation from crystalline (α) to amorphous (γ) solid Ag(DM)2is an irreversible exothermic glass transition (glass‐transition temperature 155.2 °C; ΔH = –126.8 kJ mol–1), which implies that the glass form is thermodynamically more stable than the crystalline form. Compound δ (Ag(DM)1.5) consists of silver nanoparticles (diameter (7 ± 2) nm ) dispersed in a glassy matrix of neutral DM molecules. The N–CN–Ag coordination bonds of the α form are not maintained in the δ form. Decomposition of α by intense illumination results in a white solid (ϵ), identified as being composed of silver nanoparticles (diameter (60 ± 10) nm). Physical and spectroscopic (XAFS) measurements, together with XRD analysis, indicate that the silver nanoparticles in both δ and ϵ are crystalline with lattice parameters similar to bulk silver; however, the magnetic susceptibilities differ from bulk silver.
Inside Front Cover: Anti‐Lotus Effect for Nanostructuring at the Leidenfrost Temperature (Adv. Mater. 9/2007)
Authors: Elbahri M. , Paretkar D. , Hirmas K. , Jebril S. , Adelung R.
Published: April 2007

The scanning electron microscopy image (tilted, colored) shown on the inside cover depicts a ring of zinc oxide particles. This ring was obtained from a droplet of a highly diluted solution of zinc acetate by overheating on a 250°C hot silicon substrate, a method reported by Rainer Adelung and co‐workers on p. 1262. The overheating creates an explosion, which results in a spray of microscale droplets that form many rings similar to the one shown over a macroscopic substrate surface.
β‐Amyloid is a substrate of autophagy in sporadic inclusion body myositis
Authors: Lünemann Jan D. , Schmidt Jens , Schmid Dorothee , Barthel Konstanze , Wrede Arne , Dalakas Marinos C. , Münz Christian
Published: April 2007

Objective

Sporadic Inclusion Body Myositis (sIBM) is the most common acquired muscle disease in patients above 50 years of age. Apart from inflammation in the skeletal muscle, overexpression of amyloid precursor protein (APP) and intracellular accumulation of its proteolytic fragment β‐amyloid play a central role in the pathogenesis of sIBM. In neurodegenerative disorders, similar aggregations of aberrant proteins have recently been shown to be susceptible to autophagic degradation. Therefore, we analyzed macroautophagy of APP in human muscle cell lines and sIBM muscle biopsies.

Methods

Colocalization of APP with the essential autophagy protein Atg8/LC3, which associates with preautophagosomal and autophagosomal membranes via lipidation, was analyzed in the CCL‐136 muscle cell line and muscle biopsies by immunofluorescence. While APP was visualized with specific antibodies in the muscle cell line and in tissue sections. Atg8/LC3 localization was analyzed after GFP‐Atg8/LC3 transfection or with an Atg8/LC3 specific antiserum, respectively.

Results

We demonstrate here that Atg8/LC3 colocalizes with APP in cultured human muscle cells. In addition, APP/β‐amyloid‐containing autophagosomes can be observed at increased frequency in muscle fibers of sIBM muscle biopsies, but not in non‐myopathic muscle or non‐vacuolated myopathic controls. APP/β‐amyloid and Atg8/LC3 double‐positive compartments were almost exclusively observed in degenerating muscle fibers of the type II (fast‐twitching) and were in part associated with overexpression of major histocompatibility complex (MHC) class I and II on myofibers and invasion by CD4+ and CD8+ cells.

Interpretation

These findings indicate that APP/β‐amyloid is targeted for lysosomal degradation via macroautophagy and suggest that the autophagy pathway should be explored for its potential therapeutic merit in sIBM. Ann Neurol 2007;61:476–483
The complex relation between genotype and phenotype in motor neuron disease
Authors: Cañete‐Soler Rafaela , Schlaepfer William W.
Published: April 2007

The success in mapping genetic loci and identifying mutant genes in familial neurodegenerative disease has outpaced our ability to understand the linkage between genotype and phenotype of disease. The results have led to a backlog of genetic information with limited clarification of underlying disease mechanisms. A major dilemma is how mutations in widely expressed proteins lead to degeneration or dysfunction of small subsets of neurons. The problem raises fundamental questions as to the nature and interrelation of pathways that maintain the homeostasis of differentiated neurons. The issue also bears on the pathogenesis of sporadic forms of disease and prospective efficacy of therapeutic applications. This review examines the problem as it relates to motor neuron disease. Ann Neurol 2007
Pathological TDP‐43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations
Authors: Mackenzie Ian R. A. , Bigio Eileen H. , Ince Paul G. , Geser Felix , Neumann Manuela , Cairns Nigel J. , Kwong Linda K. , Forman Mark S. , Ravits John , Stewart Heather , Eisen Andrew , McClusky Leo , Kretzschmar Hans A. , Monoranu Camelia M. , Highley J. Robin , Kirby Janine , Siddique Teepu , Shaw Pamela J. , Lee Virginia M‐Y. , Trojanowski John Q.
Published: April 2007

Objective

Amyotrophic lateral sclerosis (ALS) is a common, fatal motor neuron disorder with no effective treatment. Approximately 10% of cases are familial ALS (FALS), and the most common genetic abnormality is superoxide dismutase‐1 (SOD1) mutations. Most ALS research in the past decade has focused on the neurotoxicity of mutant SOD1, and this knowledge has directed therapeutic strategies. We recently identified TDP‐43 as the major pathological protein in sporadic ALS. In this study, we investigated TDP‐43 in a larger series of ALS cases (n = 111), including familial cases with and without SOD1 mutations.

Methods

Ubiquitin and TDP‐43 immunohistochemistry was performed on postmortem tissue from sporadic ALS (n = 59), ALS with SOD1 mutations (n = 15), SOD‐1–negative FALS (n = 11), and ALS with dementia (n = 26). Biochemical analysis was performed on representative cases from each group.

Results

All cases of sporadic ALS, ALS with dementia, and SOD1‐negative FALS had neuronal and glial inclusions that were immunoreactive for both ubiquitin and TDP‐43. Cases with SOD1 mutations had ubiquitin‐positive neuronal inclusions; however, no cases were immunoreactive for TDP‐43. Biochemical analysis of postmortem tissue from sporadic ALS and SOD1‐negative FALS demonstrated pathological forms of TDP‐43 that were absent in cases with SOD1 mutations.

Interpretation

These findings implicate pathological TDP‐43 in the pathogenesis of sporadic ALS. In contrast, the absence of pathological TDP‐43 in cases with SOD1 mutations implies that motor neuron degeneration in these cases may result from a different mechanism, and that cases with SOD1 mutations may not be the familial counterpart of sporadic ALS. Ann Neurol 2007;61:427–434
Aluminum(III) complexes containing O,O chelating ligand
Authors: Dostál Libor , Jambor Roman , Císařová Ivana , Merna Jan , Holeček Jaroslav
Published: April 2007

The stoichiometric reactions of trimethylaluminum with 2,6‐(MeOCH2)2C6H3OH (LH) revealed compounds L3Al (1) and L2AlMe (2). On the other hand reaction of 1 equiv. of LH with trimethylaluminum did not lead to the formation of complex LAlMe2 (3), rather 2 together with Me3Al were observed as a result of a disproportionation of 3. Compounds 1 and 2 were characterized by elemental analysis, 1H and 13C NMR spectroscopy and in the case of 1 by X‐ray diffraction. Derivative 2 underwent transmetalation with Ph3SnOH, giving LSnPh3 (4) as the result of a migration of ligand L from the aluminum to the tin atom. The identity of 4 was established by elemental analysis, 1H, 13C and 119Sn NMR spectroscopy and 1H, 119Sn HMBC experiments. The system 2 and B(C6F5)3 in a 1:1 molar ratio was shown to be active in the polymerization of propylene oxide and ε‐caprolactone. Copyright © 2007 John Wiley & Sons, Ltd.
Application of FTIR spectroscopy for structural characterization of ternary poly(acrylic acid)–metal–poly(vinyl pyrrolidone) complexes
Authors: Moharram M. A. , Khafagi M. G.
Published: April 2007

The FTIR spectroscopic technique was used in the study of ternary polymer–metal complexes containing two polyelectrolytes of opposite charge and metal ions. The structure of the ternary (PAA‐Fe3+‐PVP) complexes was examined by following the changes in their infrared spectra. It was found that the shapes of the absorption bands of the resultant compounds are influenced by the presence of Fe3+. According to this result it was suggested that two types of structure which differ in the composition are formed, one of which results from the coordination of Fe3+ with PAA‐PVP complex and the other is due to the formation of Fe3+ polycarboxylate. Comparison between the spectrum of PAA‐PVP complex and those of the compounds resulted from the reaction between the two opposite charged electrolytes, PAA and PVP and each of the divalent metal chlorides NiCl2, CoCl2, CuCl2, and ZnCl2) led to the conclusion that a reaction took place between the divalent transition metal chlorides and the extent of reaction depends on the nature of metal ions and PAA‐PVP complex. The FTIR spectra of the precipitate resulted from the mixtures of PAA‐PVP and Ni(NO3)2 or Sr(NO3)2 were investigated. It was noted that the addition of Ni(NO3)2 or Sr(NO3)2 to the mixture of the electrolytes of PAA and PVP provoked appreciable changes in the characteristic spectral features of the complex resulting from the interaction of the metal ions with the polymer–polymer complex. The FTIR spectra of the precipitate resulted from the reaction between CeCl3, ErCl3, and LaCl3 were also investigated. It was concluded that a reaction took place between the rare earth metals and the PPC. This means that ternary polymer–metal–polymer complexes were formed. The extent of changes in the spectral features differs from metal to metal according to the nature of metal ions. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
DSC study on the effect of cure reagents on the lignin base epoxy cure reaction
Authors: Sun Hongguang , Sun Gang , Lv Hong , Liu Yu , Zhao Binyuan , Zhu Na , Hu Keao
Published: April 2007

The cure reactions of liquid lignin base epoxy resin (LEPL) with three different curing agents, viz., methylhexahydrophthalic anhydride, maleic anhydride, and 2‐methyl‐4‐methylimidazole (EMI‐2,4), were investigated by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry. Cure kinetics was evaluated using the multiple heating rate Kissinger method. The reactivities of the three curing agents were compared based on kinetics results obtained by DSC. FTIR spectra of these curing systems were also studied. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007
Dyeing of polylactide fibers in supercritical carbon dioxide
Authors: Wen Huibing , Dai Jin Jin
Published: April 2007

Polylactide (PLA) fibers were dyed with Disperse Blue 79 in supercritical carbon dioxide (SC‐CO2). The effects of dyeing conditions such as the temperature, pressure, and time on the dyeing and mechanical properties were discussed in comparison with those in water. A major advantage of dyeing PLA in SC‐CO2 over dyeing PLA in an aqueous medium was its much better retention of the fiber strength. The loss of the breaking strength of PLA dyed in SC‐CO2 at 120°C for 60 min was 9.22% versus a 44.66% loss in aqueous dyeing at the same temperature. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Graft copolymerization of methacrylic acid onto xanthan gum by Fe2+/H2O2 redox initiator
Authors: Kumar Rajesh , Srivastava Arti , Behari Kunj
Published: April 2007

The graft copolymer of xanthan gum with methacrylic acid was synthesized in inert atmosphere by using Fentos reagent as a redox initiator. The effect of reaction conditions on grafting parameters [G(%), E(%), C(%), A(%), H(%), and Rg] was investigated. Similar trend was observed on increasing the concentration of ferrous ion and hydrogen peroxide from 4.0 to 20.0 × 10−3 mol dm−3 and 2.5 to 10 × 10−3 mol dm−3 respectively, i.e., initially grafting parameters increased and after a certain range of concentration grafting parameters showed decreasing trend. Hydrogen ion shows influenced result i.e., small increment of concentration in hydrogen ion presents much increment in percent of grafting. It was observed that the [G(%), E(%), C(%), A(%), and Rg] increased upto 6.67 × 10−2 mol dm−3 concentration of methacylic acid after that it decreased. Maximum G(%) was obtained at minimum concentration of xanthan gum i.e., at 40 × 10−2 g dm−3. The optimum temperature and time duration of reaction for maximum percentage of grafting were found to be 45°C and 150 min respectively. Thermogravimetric analysis showed that the xanthan gum‐g‐methacrylic acid is thermally more stable than pure gum. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Involvement of renal tubular toll‐like receptor 9 in the development of tubulointerstitial injury in systemic lupus
Authors: Benigni Ariela , Caroli Cristina , Longaretti Lorena , Gagliardini Elena , Zoja Carla , Galbusera Miriam , Moioli Daniela , Romagnani Paola , Tincani Angela , Andreoli Laura , Remuzzi Giuseppe
Published: April 2007

Objective

Toll‐like receptor 9 (TLR‐9), a receptor for CpG DNA, has been implicated in the activation of immune cells in lupus. We undertook this study to determine whether the expression of TLR‐9 in resident renal cells in lupus nephritis is related to the development of tubulointerstitial injury.

Methods

TLR‐9 was analyzed in selectively retrieved renal tissue from (NZB × NZW)F1 mice at different stages of disease by laser capture microdissection combined with real‐time quantitative reverse transcriptase–polymerase chain reaction, and in renal biopsy specimens from lupus nephritis patients by immunohistochemistry. We investigated for the molecular component responsible for TLR‐9 activation by cultured proximal tubular cells in serum from patients with lupus.

Results

Renal tissue from NZB × NZW mice displayed robust TLR‐9 expression localized to proximal tubular cells. TLR‐9 levels correlated with proteinuria and tubulointerstitial injury to the extent that a cyclin‐dependent kinase inhibitor, while reducing proteinuria and renal structural damage, prevented tubular TLR‐9 generation in lupus mice. Consistently, exaggerated TLR‐9 staining was found in proximal tubular cells of lupus patients, which correlated with tubulointerstitial damage. DNA‐containing immune complexes purified from sera of patients with lupus induced TLR‐9 in cultured proximal tubular cells. This was prevented by CCGG‐rich short oligonucleotides, specific antagonists of CpG DNA, indicating that the DNA component of immune complexes was required for TLR‐9 stimulation.

Conclusion

These findings suggest that tubular TLR‐9 activation has a pathogenetic role in tubulointerstitial inflammation and damage in experimental and human lupus nephritis, and they indicate a novel target for future therapies.