bluuebunny/crossref_metadata_2025 huggingface dataset:
Trans‐4‐hydroxy‐2‐hexenal is a neurotoxic product of docosahexaenoic (22:6; n‐3) acid oxidation
Authors: Long Eric K. , Murphy Tonya C. , Leiphon Laura J. , Watt John , Morrow Jason D. , Milne Ginger L. , Howard Jocelyn R. H. , Picklo Matthew J.
Published: March 2008

Lipid peroxidation of docosahexaenoic (22:6; n‐3) acid (DHA) is elevated in the CNS in patients with Alzheimer’s disease and in animal models of seizure and ethanol withdrawal. One product of DHA oxidation is trans‐4‐hydroxy‐2‐hexenal (HHE), a six carbon analog of the n‐6 fatty acid derived trans‐4‐hydroxy‐2‐nonenal (HNE). In this work, we studied the neurotoxic potential of HHE. HHE and HNE were toxic to primary cultures of cerebral cortical neurons with LD50’s of 23 and 18 μmol/L, respectively. Toxicity was prevented by the addition of thiol scavengers. HHE and HNE depleted neuronal GSH content identically with depletion observed with 10 μmol/L of either compound. Using an antibody raised against HHE–protein adducts, we show that HHE modified specific proteins of 75, 50, and 45 kDa in concentration‐ and time‐dependent manners. The time‐dependent formation of HHE differed from that of F4‐neuroprostanes following in vitro DHA oxidation likely as a result of the different oxidation pathways involved. Using purified mitochondrial aldehyde dehydrogenase ALDH5A, we found that HHE was oxidized 6.5‐fold less efficiently than HNE. Our data demonstrate that HHE and HNE have similarities but also differences in their neurotoxic mechanisms and metabolism.
Cytoskeletal protein carbonylation and degradation in experimental autoimmune encephalomyelitis
Authors: Smerjac Suzanne M. , Bizzozero Oscar A.
Published: March 2008

Protein carbonylation, the non‐enzymatic addition of aldehydes or ketones to specific amino acid residues, has been implicated in the pathophysiology of multiple sclerosis. In this study, we investigated whether protein carbonyls also accumulate in the spinal cord of Lewis rats with acute experimental autoimmune encephalomyelitis (EAE). Western blots analysis after derivatization with dinitrophenyl hydrazine (oxyblot) showed elevated protein carbonylation at the time of maximal clinical disability. During the same period glutathione levels were substantially reduced, suggesting a causal relationship between these two markers. In contrast, lipid peroxidation products accumulated in EAE spinal cord well before the appearance of neurological symptoms. Carbonyl staining was not restricted to inflammatory lesions but present throughout the spinal cord particularly in neuronal cell bodies and axons. By 2‐dimensional‐oxyblot, we identified several cytoskeletal proteins, including β‐actin, glial acidic fibrillary protein, and the neurofilament proteins as the major targets of carbonylation. These findings were confirmed by pull‐down experiments, which also showed an increase in the number of carbonylated β‐actin molecules and a decrease in that of oxidized neurofilament proteins in EAE. These data suggest the possibility that oxidation targets neurofilament proteins for degradation, which may contribute to axonal pathology observed in multiple sclerosis and EAE.
Serum‐ and glucocorticoid‐inducible kinase 1 enhances zif268 expression through the mediation of SRF and CREB1 associated with spatial memory formation
Authors: Tyan Shiaw‐Wei , Tsai Ming‐Chi , Lin Chien‐Ling , Ma Yun‐Li , Lee Eminy H. Y.
Published: March 2008

Serum‐ and glucocorticoid‐inducible kinase 1 (SGK1) has been shown to play an important role in spatial memory formation, but the molecular mechanism underlying this effect of SGK1 was not known. zif268 is an immediate early gene that is induced by water maze learning. To investigate the role of SGK1 in the regulation of zif268 expression, the dominant negative mutant of SGK1, SGK1 S422A, was infused to the hippocampal CA1 area of rats, and was found to decrease significantly the mRNA level of zif268 in both naïve animals and trained animals. SGK1 was also found to phosphorylate serum response factor (SRF) at Ser73, Ser75, and Ser99, and phosphorylate CREB1 at Ser133. Inhibition of SGK1 phosphorylation sites on SRF and CREB1 with alanine substitution significantly diminished SGK1‐enhanced zif268 expression in the promoter‐luciferase assay. SGK1 also phosphorylates Elk‐1 and SGK1 phosphorylation of Elk‐1 decreased the transcriptional activity of Elk‐1. But SGK1 phosphorylation of Elk‐1 did not affect SGK1‐enhanced zif268 expression. Moreover, the phosphorylation of SGK1 was increased in rat CA1 area after water maze learning, accompanied by increased phosphorylation of SRF at Ser99 and increased phosphorylation of CREB1 at Ser133. All these effects were antagonized by SGK1 S422A transfection. These results together suggest that SGK1 enhances zif268 expression through the mediation of SRF and CREB1, and these signaling pathways are associated with spatial memory formation in rats.
Gabapentin produces PKA‐dependent pre‐synaptic inhibition of GABAergic synaptic transmission in LC neurons following partial nerve injury in mice
Authors: Takasu Keiko , Ono Hideki , Tanabe Mitsuo
Published: March 2008

We have previously demonstrated that gabapentin supraspinally activates the descending noradrenergic system to ameliorate pain hypersensitivity in mice with partial nerve ligation. To clarify the supraspinal mechanism of action of gabapentin, whole‐cell patch‐clamp recordings were performed on locus coeruleus (LC) neurons in brainstem slices prepared from mice after peripheral nerve injury or mice subjected to a sham‐operation, and the effects of gabapentin in the modulation of synaptic transmission were studied. Bath application of gabapentin (10, 30 and 100 μM) in a concentration‐dependent manner reduced the GABAAreceptor‐mediated inhibitory post‐synaptic currents (IPSCs) in slices prepared from partially nerve‐ligated mice, whereas glutamate‐mediated excitatory post‐synaptic currents were hardly affected. By contrast, gabapentin did not reduce IPSCs in slices taken from mice given a sham operation. Although gabapentin altered neither the amplitude nor the frequency of miniature IPSCs, it reduced IPSCs together with an increase in the paired‐pulse ratio, suggesting that gabapentin acts on the pre‐synaptic GABAergic nerve terminals in the LC. As the protein kinase A (PKA) inhibitor H‐89 but not the protein kinase C inhibitor chelerythrine abolished the inhibitory action of gabapentin on IPSCs, PKA‐mediated phosphorylation seems to be important for supraspinal gabapentin responsiveness in neuropathic conditions. Together, gabapentin generates PKA‐dependent pre‐synaptic inhibition of GABAergic synaptic transmission, and thereby removes the inhibitory influence on LC neurons only under neuropathic pain states. These findings provide crucial evidence of how supraspinally acting gabapentin recruits the descending noradrenergic system.
The Akt signaling pathway contributes to postconditioning’s protection against stroke; the protection is associated with the MAPK and PKC pathways
Authors: Gao Xuwen , Zhang Hanfeng , Takahashi Tetsuya , Hsieh Jason , Liao Janette , Steinberg Gary K. , Zhao Heng
Published: March 2008

We previously reported that ischemic postconditioning with a series of mechanical interruptions of reperfusion reduced infarct volume 2 days after focal ischemia in rats. Here, we extend this data by examining long‐term protection and exploring underlying mechanisms involving the Akt, mitogen‐activated protein kinase (MAPK) and protein kinase C (PKC) signaling pathways. Post‐conditioning reduced infarct and improved behavioral function assessed 30 days after stroke. Additionally, postconditioning increased levels of phosphorylated Akt (Ser473) as measured by western blot and Akt activity as measured by an in vitro kinase assay. Inhibiting Akt activity by a phosphoinositide 3‐kinase inhibitor, LY294002, enlarged infarct in postconditioned rats. Postconditioning did not affect protein levels of phosphorylated‐phosphatase and tensin homologue deleted on chromosome 10 or ‐phosphoinositide‐dependent protein kinase‐1 (molecules upstream of Akt) but did inhibit an increase in phosphorylated‐glycogen synthase kinase 3β, an Akt effector. In addition, postconditioning blocked β‐catenin phosphorylation subsequent to glycogen synthase kinase, but had no effect on total or non‐phosphorylated active β‐catenin protein levels. Furthermore, postconditioning inhibited increases in the amount of phosphorylated‐c‐Jun N‐terminal kinase and extracellular signal‐regulated kinase 1/2 in the MAPK pathway. Finally, postconditioning blocked death‐promoting δPKC cleavage and attenuated reduction in phosphorylation of survival‐promoting εPKC. In conclusion, our data suggest that postconditioning provides long‐term protection against stroke in rats. Additionally, we found that Akt activity contributes to postconditioning’s protection; furthermore, increases in εPKC activity, a survival‐promoting pathway, and reductions in MAPK and δPKC activity; two putative death‐promoting pathways correlate with postconditioning’s protection.
The TRPV1 receptor is associated with preferential stress in large dorsal root ganglion neurons in early diabetic sensory neuropathy
Authors: Hong Shuangsong , Agresta Laura , Guo Chunfang , Wiley John W.
Published: March 2008

Chronic diabetic neuropathy is associated with peripheral demyelination and degeneration of nerve fibers. The mechanism(s) underlying neuronal injury in diabetic sensory neuropathy remain poorly understood. Recently, we reported increased expression and function of transient receptor potential vanilloid 1 (TRPV1) in large dorsal root ganglion (DRG) neurons in diabetic sensory neuropathy. In this study, we examined the effects of TRPV1 activation on cell injury pathways in this subpopulation of neurons in the streptozotocin‐induced diabetic rat model. Large DRG neurons from diabetic (6–8 weeks) rats displayed increased oxidative stress and activation of cell injury markers compared with healthy controls. Capsaicin (CAP) treatment induced decreased labeling of MitoTracker Red and increased cytosolic cytochrome c and activation of caspase 3 in large neurons isolated from diabetic rats. CAP treatment also induced oxidative stress in large diabetic DRG neurons, which was blocked by pre‐treatment with caspase or calpain inhibitor. In addition, both μ‐calpain expression and calpain activity were significantly increased in DRG neurons from diabetic rats after CAP treatment. Treatment with capsazepine, a competitive TRPV1 antagonist, markedly reduced these abnormalities in vitro and prevented activation of cell injury in large DRG neurons in diabetic rats in vivo. These results suggest that activation of the TRPV1 receptor activates pathways associated with caspase‐dependent and calpain‐dependent stress in large DRG neurons in STZ‐diabetic rats. Activation of the TRPV1 receptor may contribute to preferential neuronal stress in large DRG neurons relatively early in diabetic sensory neuropathy.
MULTIANALYTICAL STUDY OF PALAEOLITHIC REINDEER ANTLER. DISCOVERY OF ANTLER TRACES IN LASCAUX PIGMENTS BY TEM*
Authors: CHADEFAUX CELINE , VIGNAUD COLETTE , MENU MICHEL , REICHE INA
Published: March 2008

Palaeolithic and modern reindeer antler were analysed using complementary techniques to evaluate the conservation state of bone material. X‐ray diffraction, FT‐IR spectroscopy, scanning electron microscopy (SEM–EDX) and transmission electron microscopy (TEM–EDX) as well as proton induced X‐ray and γ‐ray emission (PIXE–PIGE) at the particle accelerator AGLAE, C2RMF were applied. This study enabled us to define the chemical and structural features of ancient antler at the micro‐ and nanometre scale and compare them to those of other bone materials such as bone and ivory. Antler is richer in its organic fraction compared to bone and ivory. Its mineral fraction, carbonated hydroxylapatite, shows very specific crystal shapes at the nanometre scale. This specific property allowed us to recognize antler traces in pigment samples originating from rock art paintings in the Lascaux cave, Dordogne, southwestern France, Magdalenian period. Therefore, TEM–EDX is the technique of choice for characterizing antler traces in complex mixtures. In the paint material of Lascaux, antler seems most likely to be a pollutant introduced either by stirring the pigments in water with a piece of antler or by carving antler artefacts next to the preparation of paint material. However, it could eventually be used as a marker of paintings that were created contemporaneously.
Helicobacter pylori and Antrum Erosion‐Specific Gene Expression Patterns: The Discriminative Role of CXCL13 and VCAM1 Transcripts
Authors: Galamb Orsolya , Gyõrffy Balázs , Sipos Ferenc , Dinya Elek , Krenács Tibor , Berczi Lajos , Szõke Dominika , Spisák Sándor , Solymosi Norbert , Németh Anna Mária , Juhász Márk , Molnár Béla , Tulassay Zsolt
Published: March 2008

Background and Aims:  Chronic Helicobacter pylori infection affects approximately half of the world, leads to chronic gastritis and peptic ulceration, and is linked to gastric carcinoma. Our aims were to compare the gene expression profile (GEP) of H. pylori‐positive and H. pylori‐negative gastric erosions and adjacent mucosa to explain the possible role and response to H. pylori infection and to get erosion‐related mRNA expression patterns.

Methods:  Total RNA was extracted, amplified, and biotinylated from gastric biopsies of patients with H. pylori‐positive and H. pylori‐negative antrum erosions (ER) (8/8) and adjacent macroscopically normal mucosae (8/8). The GEP was evaluated using HGU133plus2.0 microarrays. Two independent normalizations (MAS5.0, RMA), PAM feature selection, hierarchical cluster analysis, and discriminant analysis were done. The expression of 14 genes was also measured by real‐time‐polymerase chain reaction. VCAM‐1 and CXCL13 immunohistochemistry (IHC) was done.

Results:  In H. pylori infection, significant overexpression of MHC class II antigen‐presenting genes, interleukin‐7 receptor, ubiquitin‐D, CXCR4, lactoferrin immune response‐related genes, CXCL‐2 and ‐13, CCL18 chemokine ligand, and VCAM‐1 genes were established. In erosive gastritis, increased proliferation (MET) and transport (UCP2, SCFD1, KPNA4) were found, while genes associated with adhesion (SIGLEC11), transcription regulation (ESRRG), and electron and ion transport (ACADM, CLIC6) were down‐regulated. Discriminant analysis successfully classified all samples into four groups (HP+ER–, HP+ER+, HP–ER+, HP–ER–) using a reduced gene set (20). Significant overexpression of VCAM‐1 and CXC13 protein was detected by IHC in HP+ samples (p < .05).

Conclusions:  Whole genomic microarray analysis yielded new H. pylori infection and erosion‐related gene expression changes. Discriminative genes can be used in mRNA‐based diagnostic classification of gastric biopsies.
NMR‐Based Metabonomics for Detection of Helicobacter pylori Infection in Gerbils: Which Is More Descriptive
Authors: Gao Xing X. , Ge Hui M. , Zheng Wei F. , Tan Ren X.
Published: March 2008

Background:  Helicobacter pylori, the human pathogenic gram‐negative microaerophilic bacterium, causes chronic gastric infection in more than half of the human population regardless of race. The infection of microbe is not yet controllable to pose a substantial public health impact and a growing social burden. The management of H. pylori infection primarily necessitates accurate and timely diagnosis at case level, on‐demand supervision of pathologic progression, and reliable evaluation of the impact of pharmacologic interventions on the patients’ population.

Methods:  The characterization of H. pylori infection on gerbils model was performed by metabolic profiling, employing 1H NMR spectroscopy compounding multivariate pattern recognition strategies. In the same manner, urine samples were individually collected from 10 gerbils infected with H. pylori GS13, and from 10 uninfected control animals equally accessible to feed and water.

Results:  The resultant metabolic profiles indicate that H. pylori infection disturbs carbohydrate metabolism to elevate the levels of α‐ and β‐glucose, and cis‐aconitate (a TCA cycle intermediate). In addition to the energy metabolism alteration, the colonization of H. pylori in gerbil stomach generates a remarkable deviation of amino acid metabolism as indicated by depletion of taurine and arginine, and elevation of proline and glutamine in the animal urine. Moreover, the H. pylori infection modifies the gut microbiota as highlighted by a range of microbial‐related metabolites such as indoxyl sulfate and hippurate.

Conclusions:  These findings demonstrate that the 1H NMR‐based urine metabolic profiling is a promising technique capable of providing an accurate, noninvasive, and rapid diagnosis of H. pylori infection.
Is streamlined evaluation of children for epilepsy surgery possible?
Authors: Patil Shekhar G. , Cross J. Helen , Kling Chong W. , Boyd Stewart G. , Harkness William J. , Neville Brian G. R. , Scott Rod C.
Published: March 2008

Summary 

Background:The presurgical evaluation of children with intractable epilepsy includes evaluation by an experienced clinician, MRI, video EEG, and functional imaging techniques to localize seizure onset. However, the contributions of each investigation to surgical decision making has not been systematically assessed.

Method:Data used for decision on eligibility for surgery on 353 children was discussed at a presurgical multidisciplinary meeting and systematically recorded. The relationships between MRI, EEG, SPECT findings, and the probability of being offered epilepsy surgery were investigated retrospectively using a quick unbiased statistical tree (QUEST).

Results:Sixteen children were offered nonresective surgery. Of the remaining, 236 (70%) were offered resective surgery. The proportion of children with a localized lesion on MRI offered resective surgery was 92%[95% CI: 88 to 95%], and EEG telemetry did not modify decision making in this group (p < 0.001). In children with bilateral MRI changes or normal scan the probability of being offered resective surgery was 78% in those with localized ictal onset on EEG compared to 9% with nonlocalized EEG (p < 0.001). SPECT did not appear to systematically influence decision making in any group.

Conclusion:Children with medically intractable epilepsy and localized lesions on MRI may not necessarily need ictal EEG recordings or SPECT prior to offering resective surgery. More targeted use of EEG telemetry could allow more children with less obvious surgical targets to be investigated without increasing resources.
Understanding the Organization of Industrial Ecosystems
Authors: Ashton Weslynne
Published: March 2008

Industrial symbiosis (IS) has been used to describe the physical exchange and shared management of input and output materials by geographically proximate firms. Firms that engage in IS are said to belong to an industrial ecosystem. Symbiosis has been found to be motivated by economic considerations, such as lowering costs for waste disposal, as well as by environmental ones, such as accessing limited water supplies. Communication and trust among managers are thought to play important roles in exchanges; however, empirical studies have not been previously conducted. This study used social network analysis (SNA) to identify the prevalence of industrial symbiosis linkages in Barceloneta, Puerto Rico. The study quantified patterns in various relationships among firms and managers, including formal relations through supply chains, and informal ones through interpersonal interactions. SNA and statistical methods were used to explore how these ties correlate with observed industrial symbiosis activities. IS linkages were found to be less prevalent than product sales among firms and were concentrated among pharmaceutical firms at the core of the regional network. Trust among managers and position in the social hierarchy were found to be correlated with IS but not supply chain links. SNA was useful for examining the organization of different relationships in the industrial ecosystem, but contextual information is still needed to add meaning to its findings.
CAT Bonds and Other Risk‐Linked Securities: State of the Market and Recent Developments
Authors: Cummins J. David
Published: March 2008

Abstract

This article reviews the current status of the market for catastrophic risk (CAT) bonds and other risk‐linked securities. CAT bonds and other risk‐linked securities are innovative financial vehicles that have an important role to play in financing mega‐catastrophes and other types of losses. The vehicles are especially important because they access capital markets directly, exponentially expanding risk‐bearing capacity beyond the limited capital held by insurers and reinsurers. The CAT bond market has been growing steadily, with record amounts of risk capital raised in 2005, 2006, and 2007. CAT bond premia relative to expected losses covered by the bonds have declined by more than one‐third since 2001. CAT bonds now appear to be priced competitively with conventional catastrophe reinsurance and comparably rated corporate bonds. CAT bonds have grown to the extent that they now play a major role in completing the market for catastrophic‐risk finance and are spreading to other lines such as automobile insurance, life insurance, and annuities. CAT bonds are not expected to replace reinsurance but to complement the reinsurance market by providing additional risk‐bearing capacity. Other innovative financing mechanisms such as risk swaps, industry loss warranties, and sidecars also are expected to continue to play an important role in financing catastrophic risk.
Repair of Right Carotid Artery Pseudoaneurysm in a Patient with Hostile Aortic Arch through Left Ventricular Approach
Authors: HARJAI KISHORE J. , ANDERSON JOHN
Published: March 2008

We describe the case of an 81‐year‐old male who presented with a rapidly expanding neck hematoma from a common carotid artery pseudoaneurysm. Percutaneous repair using the right femoral artery approach was unsuccessful due to a hostile aortic arch. Using a small left thoracotomy and antegrade left ventricular access to the ascending aorta, a covered stent was successfully delivered at the site of the pseudoaneurysm. Our case provides proof‐of‐principle that complex carotid interventions can be performed expediently through a left ventricular approach in patients with hostile aortic arch.
NOTES ON THE GEOLOGY OF THE MACKENZIE DELTA
Authors: Kellaway G.A.
Published: March 2008

Little information has been published regarding the general geology of the Mackenzie Delta region. On the western side of the Delta bedrock appears to consist largely of Mesozoic sedimentary formations. Coal‐bearing rocks occur some 25 miles northwest of Aklavik and a six‐foot coal seam with almost vertical dip is worked at Moose River Coal Mine. A description of these workings is given.

The eastern side of the Delta shows some variety in its geology. Bedrock areas between Campbell Lake and Dolomite Lake are largely formed of dolomite and magnesian limestone. Dolomite, limestone and reddish slaty shale are seen on the north shore of Dolomite Lake and exposures of shaly material are seen on the east bank of the East Channel eight miles south of the entrance channel leading to Dolomite Lake.

Between Dolomite Lake and the southern end of the Caribou Hills bedrock is concealed beneath unconsolidated deposits covered by bush and muskeg. The deposits appear to consists largely of silt, clay and gravel, and wrap round and conceal the junction of the Caribou Hills formation with the underlying formations. The undulating and rather formless character of this tract of ground and the relation of the deposits to the bedrock at Dolomite Lake suggest that they are glacial drifts.

The Caribou Hills form the most striking feature on the east side of the Delta. They form a steep face or escarpment overlooking the East Channel and rise to their maximum height south of the Reindeer Station. Northwards their altitude gradually diminishes and they terminate against the tundra south‐east and the swamps of the Delta of Tununuk. The rocks consist of soft poorly consolidated silty clay, and fine silt and sand with some pebbly or gravelly sand capping the hills locally. Beds of lignite and very thin layers of ironstone were also seen and, where the lignite has been burned out reddened patches and bands appear on the steep hill slopes. The Caribou Hills formation recalls Tertiary lignite‐bearing formations described from other parts of Northern Canada and Alaska.

The bearing of these and other observations upon the history of the Mackenzie Delta is briefly discussed.
Population Size Estimation in a Two‐List Surveillance System with a Discrete Covariate
Authors: You Na , Xuan Mao Chang
Published: March 2008

Summary Capture–recapture methods are widely adopted to estimate sizes of populations of public health interest using information from surveillance systems. For a two‐list surveillance system with a discrete covariate, a population is divided into several subpopulations. A unified framework is proposed in which the logits of presence probabilities are decomposed into case effects and list effects. The estimators for the whole population and subpopulation sizes, their adjusted versions, and asymptotic standard errors admit closed‐form expressions. Asymptotic and bootstrap individual and simultaneous confidence intervals are easily constructed. Conditional likelihood ratio tests are used to select one from three possible models. Real examples are investigated.
A Two‐Stage Stepwise Estimation Procedure
Authors: Chen John T.
Published: March 2008

Summary This article proposes a two‐stage simultaneous confidence procedure for the comparisons of k pairs of population means, without using multiplicity adjustment of more than two populations. The proposed procedure can be broadly applied to parametric or nonparametric models. It is robust and versatile because its derivation only utilizes a partitioning approach in conjunction with a bivariate adjustment, without any assumption on the underlying distribution. To elucidate the application, the proposed procedure is intertwined with the estimation of the therapeutic window of a drug. It provides confidence limits for the efficacy and the toxicity of the effective doses, highest ineffective dose, safe doses, and lowest unsafe dose, simultaneously. Such estimation information facilitates follow‐up studies in clinical trials. As an illustrative example, the new procedure is applied to analyze a data set on molecular cancer therapeutics regarding the apoptotic killing effects of different chemical compounds on two leukemia cell lines.
Analyzing Complex Capture–Recapture Data in the Presence of Individual and Temporal Covariates and Model Uncertainty
Authors: King R. , Brooks S. P. , Coulson T.
Published: March 2008

Summary We consider the issue of analyzing complex ecological data in the presence of covariate information and model uncertainty. Several issues can arise when analyzing such data, not least the need to take into account where there are missing covariate values. This is most acutely observed in the presence of time‐varying covariates. We consider mark‐recapture‐recovery data, where the corresponding recapture probabilities are less than unity, so that individuals are not always observed at each capture event. This often leads to a large amount of missing time‐varying individual covariate information, because the covariate cannot usually be recorded if an individual is not observed. In addition, we address the problem of model selection over these covariates with missing data. We consider a Bayesian approach, where we are able to deal with large amounts of missing data, by essentially treating the missing values as auxiliary variables. This approach also allows a quantitative comparison of different models via posterior model probabilities, obtained via the reversible jump Markov chain Monte Carlo algorithm. To demonstrate this approach we analyze data relating to Soay sheep, which pose several statistical challenges in fully describing the intricacies of the system.
Evaluation of Residual Stress in a Multilayer Ceramic Capacitor and its Effect on Dielectric Behaviors Under Applied dc Bias Field
Authors: Yang Gang , Yue Zhenxing , Sun Tieyu , Jiang Wugui , Li Xiang , Li Longtu
Published: March 2008

The residual stress in a multilayer ceramic capacitor (MLCC) has been evaluated by two‐dimensional finite element simulation in combination with X‐ray diffraction measurement. It is shown that there is a compressive in‐plane stress in the active layers of the MLCC, which increases with increases in the number of dielectric layers when both dielectric layer thickness and electrode thickness are kept constant. A good order of magnitude agreement between the residual stresses obtained from two approaches is found. The ɛ–V response of the MLCC with different number of dielectric layers demonstrates that under a given or no applied field, the dielectric permittivity increases with increasing compressive stress. Additionally, under dc bias field, the higher the compressive in‐plane stress existing in the MLCC, the more significant the decrease of the dielectric permittivity. These results can be explained through a phenomenological thermodynamic model, including both elastic and electrostatic energy, based on the Ginsburg–Landau–Devonshire theory.
Aurivillius Phase Potassium Bismuth Titanate: K0.5Bi4.5Ti4O15
Authors: Wang Chun‐Ming , Wang Jin‐Feng
Published: March 2008

An Aurivillius phase bismuth layer‐structured compound potassium bismuth titanate is synthesized using conventional solid‐state processing. It was found that the range of sintering temperature for the potassium bismuth titanate is very narrow. Phase analysis was performed by X‐ray diffraction, and microstructural morphology was assessed by scanning electron microscopy. The Curie temperature TC, piezoelectric coefficient d33, and mechanical quality factor Qm (kp mode) of the dense potassium bismuth titanate were found to be 555°C, 21.2 pC/N, and 1602, respectively. Dielectric spectroscopy showed that potassium bismuth titanate possesses stable high‐temperature dielectric properties.
Preparation of Aluminum Oxynitride by Nitridation of a Precursor Derived from Aluminum–Glycine Gel and the Effects of the Presence of Europium
Authors: Kikkawa Shinichi , Hatta Naoya , Takeda Takashi
Published: March 2008

Spinel‐type AlON, Al2.75□0.25O3.74N0.26, was obtained by ammonia nitridation of an oxide precursor prepared by peptizing a glycine gel with aluminum nitrate. To achieve crystallization, the nitrided product had to be annealed at 1500°C for 10 min in flowing nitrogen. The use of glycine instead of citric acid was important for obtaining a white product without residual carbon. A similar preparation method was used for adding small amounts of europium below 10 mol%. A strong blue emission was observed for products ranging from 0.5 to 3.0 mol% Eu doping. The product with 0.5 mol% doping had a maximum emission intensity at 400 nm for an excitation of 254 nm. The products with 1 and 3 mol% doping showed double maxima at 475 and 520 nm. These three emissions were due to the presence of divalent europium in the EuAl12O19 magnetoplumbite‐like aluminum oxynitride impurity mixed with the AlON spinel major phase. The 1 mol% Eu‐doped product exhibited expanded hexagonal lattice parameters (a=0.5591 and c=2.236 nm) compared with the values for EuAl12O19 magnetoplumbite itself, observed in the 7.7 mol%‐doped product without any strong emission. The above spectrum change was discussed in relation to the coordination around Eu2+.
Nanocrystalline Yttria‐Stabilized Zirconia Fibers from Plant Fibers and their Polymer Composites
Authors: Das Rabindra N. , Nad Sanjukta , Pramanik Panchanan
Published: March 2008

Nanocrystalline zirconia–8‐mol% yttria (yttria‐stabilized zirconia (YSZ): ZrO2–8‐m% Y2O3) fibers have been prepared from aqueous poly vinyl alcohol (PVA)–zirconium oxy nitrate solution and jute (plant fiber). Soluble Zr and Y ions in PVA solution formed a uniform coating on the surface of jute once it dried completely. Slow hydrolysis of zirconium ion with ammonium hydroxide deposited zirconium hydroxide on the jute surface. Decomposition of the dried zirconium hydroxide‐coated jute at high temperature (1200°C/2 h) resulted in the formation of single‐phase, nanocrystalline cubic‐YSZ with the corresponding average X‐ray crystallite size 30–35 nm. Heat‐treated fibers have been characterized by X‐ray diffraction and scanning electron microscopy. We also prepared polymer composites by incorporating chopped, ground YSZ fibers into epoxy matrix and investigated polymer/fiber interface by transmission electron microscopy analysis.
Simulation of the Stress‐Assisted Densification Behavior of a Powder Compact: Effect of Constitutive Laws
Authors: Camacho‐Montes Héctor , García‐Casillas Perla Elvia , Rodríguez‐Ramos Reinaldo , Fuentes‐Montero María Elena , Fuentes‐Cobas Luis Edmundo
Published: March 2008

The densification of powders with linear and nonlinear viscous behavior (Scherer and Riedel models) and with power‐law‐deformation (Khun–McMeeking) behavior was studied under hot pressing and sintering forging conditions. Several numerical experiments, designated cases in this work, were performed to study the effect of (i) the uniaxial stress exerted by the piston and (ii) the rate of the uniaxial stress. The stress state was calculated using the finite‐element program ANSYS for each case. Considering the mesoscopic behavior of the powders, densification rates were obtained. The similarities and differences between predictions from the three constitutive models are highlighted. The relationship between the constitutive behavior and the most effective stress state is one of the focuses of this study. For example, we show that under constant stress loading, hot pressing more effectively promotes densification than sinter forging for constitutive behaviors that do not follow the power‐law creep. In general, as expected, the increase of uniaxial applied stress and piston velocity favored densification. However, the increase in densification depends strongly on the constitutive law.
Formation Process of Calcium‐α SiAlON Hollow Balls Composed of Nanosized Particles by Carbothermal Reduction–Nitridation
Authors: Hotta Mikinori , Tatami Junichi , Komeya Katsutoshi , Zhang Cheng , Meguro Takeshi , Terner Mark R. , Cheng Yi‐Bing
Published: March 2008

Carbothermal reduction–nitridation (CRN) of SiO2–Al2O3–CaO powders was performed under various firing conditions to investigate the formation process of Ca‐α sialon hollow balls composed of nanosized particles. Scanning electron microscopy and transmission electron microscopy observations of the samples obtained at different firing temperatures confirmed that solid spherical particles were formed at the early stage of the reaction, and nanosized particles were subsequently produced on the surface of these solid balls. From X‐ray diffraction and energy‐dispersive spectrometry analyses, it was found that the solid balls initially formed at 1450°C were mainly amorphous and contained Si, Al, Ca, O, and a small amount of N. Further nitridation at 1450°C gradually converted the solid balls into Ca‐α sialon hollow balls over time. The results revealed that the formation of Ca‐α sialon hollow balls depends on the formation of solid balls from the Si–Al–Ca–O liquid phase at the initial stage of the CRN process.
Populations and Emission Properties of the 5I6 and 5I7 Levels in Ho3+ Doped into PbO–Bi2O3–Ga2O3 Glasses
Authors: Heo Jong , Kim Kee Youn , Kwon Yong Kon
Published: March 2008

Emission properties of PbO–Bi2O3–Ga2O3 glasses doped with Ho3+ were investigated for fiber‐optic amplification at the 1.18 μm wavelength region. When the glasses were doped with Ho3+ ions only, there was a weak emission at 1.18 μm with a lifetime of ∼200 μs. However, when Yb3+ ions were codoped, the lifetime of the 1.18 μm emission increased to 630 μs together with a significant increase in intensity. A similar enhancement in the intensity and lifetimes was realized for the 2.05 μm emission. These effects are due to energy transfer from the Yb3+:2F5/2 to the Ho3+:5I6 level. Devitrification of the ternary PbO–Bi2O3–Ga2O3 glasses was efficiently suppressed by adding 10 mol% GeO2. Optimum Ho3+ concentration was ∼0.4 mol%, whereas Yb3+ ions can be added up to the solubility limit.
Characterization of Defect Structure in Acceptor‐Modified Piezoelectric Ceramics by Multifrequency and Multipulse Electron Paramagnetic Resonance Spectroscopy
Authors: Eichel Rüdiger‐A.
Published: March 2008

The defect chemistry in the vicinity aliovalent acceptor‐type transition‐metal functional centers in piezoelectric perovskite oxides is characterized by means of multifrequency and multipulse electron paramagnetic resonance spectroscopy, assisted by density‐functional theory calculations. The focus is on the formation of charged

and neutral

defect dipoles, which are discussed causing internal bias fields, as well as isovalent manganese substitutes. Based on this nanoscale characterization of the defect structure, its impact on macroscopic material properties is discussed.
In vitro characterization of three‐dimensional scaffolds seeded with human bone marrow stromal cells for tissue engineered growth of bone: mission impossible? A methodological approach
Authors: Materna Thomas , Rolf Hans J. , Napp Johanna , Schulz Jutta , Gelinsky Michael , Schliephake Henning
Published: March 2008

Aims: The aim of the present report was to evaluate current methods of in vitro analysis of three‐dimensional (3D) scaffolds seeded with human bone marrow stromal cells (hBMSCs) from six bone marrow aspirates for tissue engineered growth of bone.

Methods: A series of experiments was conducted to compare methods of cell expansion and to validate analysis of proliferation and differentiation of hBMSCs in long term cultures of up to 40 days in 3D scaffolds of calcium carbonate (CaCO3) and mineralized collagen. Proliferation within the seeded scaffolds was monitored using cell counting, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide (MTT), neutral red (NR) and DNA fluorescence assays and compared with empty controls. Differentiation was assessed by means of ELISA for osteocalcin (OC) and real time PCR for OC and collagen I (Coll I).

Results: The results showed that the scaffold differed in seeding efficacy (CaCO3: 53.3%, min. Coll.: 83.3%). The precise identification of the number of cells in biomaterials by MTT, NR and DNA assays was problematic, as MTT and NR assay overestimated the number of cells, whereas DNA assay grossly underestimated the number of cells on the scaffolds. Monitoring of changes over time may be biased by unspecific material‐dependent background activity that has to be taken into account. Identification of osteogenic differentiation is not reliable by identifying osteogenic markers such as OC in the supernatant but has to be done on the transcriptional level.

Conclusions: It is concluded that monitoring of in vitro procedures for the construction of biohybrid scaffolds requires more emphasis in order to make the cell based approach a reliable treatment option in tissue engineering.
Effective treatment and prophylaxis of hyperuricemia and impaired renal function in tumor lysis syndrome with low doses of rasburicase
Authors: Hummel Margit , Reiter Sebastian , Adam Katja , Hehlmann Ruediger , Buchheidt Dieter
Published: March 2008

Background:  Tumor lysis syndrome (TLS) is a complication that can cause renal failure by precipitation of uric acid (UA) and phosphate crystals in renal tubules. Rasburicase proved to be effective in rapidly reducing UA levels. Costs of rasburicase average up to 4500€. To assess if lower doses of rasburicase are effective, we treated patients with lower doses than recommended.

Patients and methods:  Fifty patients received rasburicase for prophylaxis (n = 8) or treatment (n = 42) of TLS. The median age was 67 yr (16–88), 21 were female. The majority of patients (n = 46) had hematologic malignancies (acute leukemia, 14; lymphoma, 26; myeloproliferative/myelodysplastic syndromes, 6) and four had solid tumors. Creatinine levels were increased in 42 patients.

Results:  Baseline median UA and creatinine levels were 856.5 μmol/L (339–1659.5 μmol/L) and 192.7 μmol/L (65.4–761.1 μmol/L), respectively. Patients received between one and eight doses of rasburicase, the median total dose was 0.049 mg/kg. UA levels were lowered by 83%. After rasburicase treatment, median serum UA and creatinine levels were 160.6 μmol/L (5.9–779.2 μmol/L) and 111.4 μmol/L (46.9–610 μmol/L), respectively. Treatment costs were reduced by 96.8%.

Conclusions:  Low doses of rasburicase are effective and cost‐saving for prophylaxis and treatment of TLS. Application of an initial dose of 3–4.5 mg of rasburicase and subsequently dosage as needed, depending on UA levels, is feasible.
High serum YKL‐40 concentration is associated with severe bone disease in newly diagnosed multiple myeloma patients
Authors: Mylin Anne K. , Abildgaard Niels , Johansen Julia S. , Andersen Niels F. , Heickendorff Lene , Standal Therese , Gimsing Peter , Knudsen Lene M.
Published: March 2008

Objectives:  In multiple myeloma (MM) YKL‐40 is present in the bone marrow microenvironment and is suggested to play a role in remodelling of the extracellular matrix. Here, the association between serum YKL‐40 and severity of bone disease in MM is investigated.

Methods:  Serum YKL‐40 was measured in 34 MM patients at diagnosis. Bone disease was assessed by radiography and biochemical markers of bone metabolism. Patients were treated with conventional chemotherapy and followed for up to 30 months.

Results:  Patients with a serum YKL‐40 elevated above the age specific reference range (56%) had a higher total X‐ray score (P = 0.003) and higher levels of the markers of bone resorption serum C‐terminal telopeptide of collagen type I (P = 0.003), urine pyridinoline (P = 0.04) and urine deoxypyridinoline (P = 0.002), while the levels of urine N‐terminal telopeptide of collagen type I (NTX‐1) and the markers of bone formation equalled those seen in patients with a normal serum YKL‐40. Serum YKL‐40 level (β = 7.6; P = 0.002) and urine NTX‐1 (log2) (β = 3.5; P = 0.006) were independent predictors of total X‐ray score at diagnosis. Patients with elevated serum YKL‐40 at diagnosis had shorter time to first osteolytic event compared to patients with normal serum YKL‐40 (12 months vs. not reached; Log rank test: P = 0.03).

Conclusions:  Newly diagnosed MM patients with elevated serum concentrations of YKL‐40 have more severe bone destruction including increased bone resorptive activity and shorter time to progression of bone disease. At this point, a potential role for YKL‐40 in myeloma‐related bone disease must be considered.
Endothelial cells do not express GSTA1: potential relevance to busulfan‐mediated endothelial damage during haematopoietic stem cell transplantation
Authors: Vassord Camille , Lapouméroulie Claudine , Koumaravelou Kailasam , Srivastava Alok , Krishnamoorthy Rajagopal
Published: March 2008

Busulfan‐mediated endothelial damage is believed to be a common mechanism in a variety of vascular disorders that occur during haematopoietic stem cell transplantation. The alkylating capacity of busulfan is compromised in vivo by enzymatic conjugation with glutathione, principally catalysed by glutathione S‐transferase alpha (GST alpha). We investigated whether the susceptibility of endothelial cells to busulfan‐mediated damage is related to their intrinsic deficiency in GST alpha expression. We tested for the expression of GST alpha mRNA by real‐time quantitative PCR and the GST protein by enzyme‐linked immunosorbent assay in various independently derived endothelial cell types (human bone marrow‐derived endothelial cell line and endothelial cells from human vein umbilical cord ) and in a control hepatic cell line, HepG2. We demonstrate that endothelial cells, contrary to hepatic cells do not express GST alpha either at mRNA or protein levels and hence are potentially susceptible to busulfan‐mediated cytotoxic damage.
C/EBPα identifies differentiating preadipocytes around hair follicles in foetal and neonatal rat and mouse skin
Authors: Wojciechowicz Kamila , Markiewicz Ewa , Jahoda Colin A. B.
Published: March 2008

Abstract:  Previous studies have described a close anatomical association between hair follicles and subcutaneous adipocytes, yet little is known about the developmental origin of this preadipocyte population. Many transcription factors controlling adipogenesis in cell culture have been described; however, the molecular events governing the process of adipogenesis in rodent skin in vivo are largely unknown. In this study, we investigated the onset and progression of adipocyte differentiation in the skin of foetal and newborn rats and mice. We first analysed the temporo‐spatial expression pattern of the transcription factor C/EBPα, a key player in adipocyte differentiation. Oil red O staining was then used to identify the presence of lipid within mature adipocytes in the same skin samples. In both species, nuclear staining of C/EBPα was first seen in cells around and below the bases of fully formed hair follicles in foetal dermis between 2 and 3 days before birth. Over time, increasing numbers of cells became labelled with C/EBPα, predominantly located between, rather than below, the hair follicles. Oil red O staining followed exactly the same pattern seen with the C/EBPα antibody, but with a delay of 12–24 h, and histomorphometry showed that the C/EBPα labelled cells matured into lipid filled adipocytes. These data show that C/EBPα is a useful developmental marker of preadipocytes in vivo. The close developmental association and physical proximity between the lower follicle and surrounding preadipocytes leads us to postulate that follicles control local adipogenic events, via signalling or by contributing to the preadipocyte pool.
Exosome Function: From Tumor Immunology to Pathogen Biology
Authors: Schorey Jeffrey S. , Bhatnagar Sanchita
Published: March 2008

Exosomes are the newest family member of ‘bioactive vesicles’ that function to promote intercellular communication. Exosomes are derived from the fusion of multivesicular bodies with the plasma membrane and extracellular release of the intraluminal vesicles. Recent studies have focused on the biogenesis and composition of exosomes as well as regulation of exosome release. Exosomes have been shown to be released by cells of hematopoietic and non‐hematopoietic origin, yet their function remains enigmatic. Much of the prior work has focused on exosomes as a source of tumor antigens and in presentation of tumor antigens to T cells. However, new studies have shown that exosomes might also promote cell‐to‐cell spread of infectious agents. Moreover, exosomes isolated from cells infected with various intracellular pathogens, including Mycobacterium tuberculosis and Toxoplasma gondii, have been shown to contain microbial components and can promote antigen presentation and macrophage activation, suggesting that exosomes may function in immune surveillance. In this review, we summarize our understanding of exosome biogenesis but focus primarily on new insights into exosome function. We also discuss their possible use as disease biomarkers and vaccine candidates.