bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatty acids and glucolipotoxicity in the pathogenesis of Type 2 diabetes
Authors: Cnop Miriam
Published: June 2008

The prevalence of Type 2 diabetes is increasing dramatically as a result of the obesity epidemic, and poses a major health and socio-economic burden. Type 2 diabetes develops in individuals who fail to compensate for insulin resistance by increasing pancreatic insulin secretion. This insulin deficiency results from pancreatic β-cell dysfunction and death. Western diets rich in saturated fats cause obesity and insulin resistance, and increase levels of circulating NEFAs [non-esterified (‘free’) fatty acids]. In addition, they contribute to β-cell failure in genetically predisposed individuals. NEFAs cause β-cell apoptosis and may thus contribute to progressive β-cell loss in Type 2 diabetes. The molecular pathways and regulators involved in NEFA-mediated β-cell dysfunction and apoptosis are beginning to be understood. We have identified ER (endoplasmic reticulum) stress as one of the molecular mechanisms implicated in NEFA-induced β-cell apoptosis. ER stress was also proposed as a mechanism linking high-fat-diet-induced obesity with insulin resistance. This cellular stress response may thus be a common molecular pathway for the two main causes of Type 2 diabetes, namely insulin resistance and β-cell loss. A better understanding of the molecular mechanisms contributing to pancreatic β-cell loss will pave the way for the development of novel and targeted approaches to prevent Type 2 diabetes.
Transdifferentiation of pancreatic ductal cells to endocrine β-cells
Authors: Bonner-Weir Susan , Inada Akari , Yatoh Shigeru , Li Wan-Chun , Aye Tandy , Toschi Elena , Sharma Arun
Published: June 2008

The regenerative process in the pancreas is of particular interest, since diabetes, whether Type 1 or Type 2, results from an inadequate amount of insulin-producing β-cells. Islet neogenesis, or the formation of new islets, seen as budding of hormone-positive cells from the ductal epithelium, has long been considered to be one of the mechanisms of normal islet growth after birth and in regeneration, and suggested the presence of pancreatic stem cells. Results from the rat regeneration model of partial pancreatectomy led us to hypothesize that differentiated pancreatic ductal cells were the pancreatic progenitors after birth, and that with replication they regressed to a less differentiated phenotype and then could differentiate to form new acini and islets. There are numerous supportive results for this hypothesis of neogenesis, including the ability of purified primary human ducts to form insulin-positive cells budding from ducts. However, to rigorously test this hypothesis, we took a direct approach of genetically marking ductal cells using CAII (carbonic anhydrase II) as a duct-cell-specific promoter to drive Cre recombinase in lineage-tracing experiments using the Cre-Lox system. We show that CAII-expressing pancreatic cells act as progenitors that give rise to both new islets and acini after birth and after injury (ductal ligation). This identification of a differentiated pancreatic cell type as an in vivo progenitor for all differentiated pancreatic cell types has implications for a potential expandable source for new islets for replenishment therapy for diabetes either in vivo or ex vivo.
Cytokinesis: the final stop for the chromosomal passengers
Authors: Carmena Mar
Published: June 2008

The CPC (chromosomal passenger complex) performs essential roles in the regulation and co-ordination of chromosomal and cytoskeletal events during mitosis and meiosis. The first functional analyses showed evidence of a role of the CPC in the regulation of cytokinesis. In this review, I summarize what we have learned since then about the role of the CPC in the late stages of mitosis and cytokinesis.
Control of the cytokinetic apparatus by flux of the Rho GTPases
Authors: Miller Ann L. , Dassow George von , Bement William M.
Published: June 2008

Cytokinesis in animal cells is powered by the cytokinetic apparatus, a ring of filamentous actin and myosin-2 that underlies the plasma membrane and closes between the separating chromosomes. Formation of the cytokinetic apparatus is at least partially dependent on the small GTPase, Rho. Similar to other small GTPases, Rho cycles between the active (GTP-bound) and inactive (GDP-bound) states. Because of this switch-like behaviour, Rho and other members of the Rho GTPase family, such as Rac and Cdc42, have long been thought to work in a manner such that their activation and inactivation are not tightly coupled. That is, a given Rho-dependent event, such as cytokinesis, has been thought to be initiated by activation of Rho, and then, many minutes later, terminated by inactivation of Rho. Here we discuss evidence suggesting that in fact Rho undergoes rapid movement through the GTPase cycle throughout the entire process of cytokinesis, and that this cycling is necessary for proper cytokinetic apparatus function.
Co-ordination of cytokinesis with chromosome segregation
Authors: Mendoza Manuel , Barral Yves
Published: June 2008

During anaphase, the spindle pulls the sister kinetochores apart until the sister chromatids are fully separated from each other. Subsequently, cytokinesis cleaves between the two separated chromosome masses to form two nucleated cells. Results from Schizosaccharomyces pombe suggested that cytokinesis and chromosome segregation are not co-ordinated with each other. However, recent studies indicate that, at least in budding yeast, a checkpoint called NoCut prevents abscission when spindle elongation is impaired, and might delay cytokinesis until all chromosomes are pulled out of the cleavage plane. Here, we discuss this possibility and summarize evidence suggesting that such a checkpoint is likely to be conserved in higher eukaryotes.
Membrane traffic and polarization of lipid domains during cytokinesis
Authors: Echard Arnaud
Published: June 2008

Growing evidence indicates that membrane traffic plays a crucial role during the late post-furrowing steps of cytokinesis in animal cells. Indeed, both endocytosis and exocytosis contribute to stabilizing the intercellular bridge that connects the daughter cells and to the final abscission in diverse organisms. The need for several intracellular transport routes probably reflects the complex events that occur during the late cytokinesis steps such as local remodelling of the plasma membrane composition, removal of components required for earlier steps of cytokinesis and membrane sealing that leads to daughter cell separation. In this mini-review, I will focus on recent evidence showing that endocytic pathways, such as the Rab35-regulated recycling pathway, contribute to the establishment of a PtdIns(4,5)P2 lipid domain at the intercellular bridge which is involved in the localization of cytoskeletal elements essential for the late steps of cytokinesis. Possible cross-talk between Rab35 and other endocytic pathways involved in cytokinesis are also discussed.
Girds ‘n’ cleeks o' cytokinesis: microtubule sticks and contractile hoops in cell division
Authors: Glover David M. , Capalbo Luisa , D'Avino Pier Paolo , Gatt Melanie K. , Savoian Matthew S. , Takeda Tetsuya
Published: June 2008

Microtubules maintain an intimate relationship with the rings of anillin, septins and actomyosin filaments throughout cytokinesis. In Drosophila, peripheral microtubules emanating from the spindle poles contact the equatorial cell cortex to deliver the signal that initiates formation of the cytokinetic furrow. Mutations that affect microtubule stability lead to ectopic furrowing because peripheral microtubules contact inappropriate cortical sites. The PAV-KLP (Pavarotti-kinesin-like protein)/RacGAP50C (where GAP is GTPase-activating protein) centralspindlin complex moves towards the plus ends of microtubules to reach the cell equator. When RacGAP50C is tethered to the cell membrane, furrowing initiates at multiple non-equatorial sites, indicating that mis-localization of this single molecule is sufficient to promote furrowing. Furrow formation and ingression requires RhoA activation by the RhoGEF (guanine-nucleotide-exchange factor) Pebble, which interacts with RacGAP50C. RacGAP50C also binds anillin, which associates with actin, myosin and septins. Thus RacGAP50C plays a pivotal role during furrow formation by activating RhoA and linking the peripheral microtubules with the nascent rings through its interaction with anillin.
Control of mitotic exit and cytokinesis by the APC/C
Authors: Lindon Catherine
Published: June 2008

Inactivation of key substrates by ubiquitin-mediated proteolysis controls the passage of cells through mitosis. The APC/C (anaphase-promoting complex/cyclosome) targets a large number of substrates for proteolysis during the final steps of mitosis and cytokinesis, but the significance of these targeting events, particularly in mammalian cells, is largely unknown. In this review, I summarize what is known about how the APC/C selects its targets during mitotic exit and review the evidence that substrate targeting after anaphase onset may be required for the correct execution of events at this time in the cell cycle.
The spindle position checkpoint: how to deal with spindle misalignment during asymmetric cell division in budding yeast
Authors: Fraschini Roberta , Venturetti Marianna , Chiroli Elena , Piatti Simonetta
Published: June 2008

During asymmetric cell division, spindle positioning is critical to ensure the unequal segregation of polarity factors and generate daughter cells with different sizes or fates. In budding yeast the boundary between mother and daughter cell resides at the bud neck, where cytokinesis takes place at the end of the cell cycle. Since budding and bud neck formation occur much earlier than bipolar spindle formation, spindle positioning is a finely regulated process. A surveillance device called the SPOC (spindle position checkpoint) oversees this process and delays mitotic exit and cytokinesis until the spindle is properly oriented along the division axis, thus ensuring genome stability.
The structural mechanics of cell division in Trypanosoma brucei
Authors: Vaughan Sue , Gull Keith
Published: June 2008

Undoubtedly, there are fundamental processes driving the structural mechanics of cell division in eukaryotic organisms that have been conserved throughout evolution and are being revealed by studies on organisms such as yeast and mammalian cells. Precision of structural mechanics of cytokinesis is however probably no better illustrated than in the protozoa. A dramatic example of this is the protozoan parasite Trypanosoma brucei, a unicellular flagellated parasite that causes a devastating disease (African sleeping sickness) across Sub-Saharan Africa in both man and animals. As trypanosomes migrate between and within a mammalian host and the tsetse vector, there are periods of cell proliferation and cell differentiation involving at least five morphologically distinct cell types. Much of the existing cytoskeleton remains intact during these processes, necessitating a very precise temporal and spatial duplication and segregation of the many single-copy organelles. This structural precision is aiding progress in understanding these processes as we apply the excellent reverse genetics and post-genomic technologies available in this system. Here we outline our current understanding of some of the structural aspects of cell division in this fascinating organism.
Cell division screens and dynamin
Authors: Bonner Mary Kate , Skop Ahna R.
Published: June 2008

Cell division is the most fundamental process in the development of all living organisms. The generation of cell diversity throughout development, the multiplication of cells during wound repair and the maintenance of stem cells in several tissues and organs all rely on proper progress through cell division. Historically, biochemical studies of cell division proved to be difficult, since mitosis is a moving target. The rapid and dynamic nature of mitosis means necessary proteins often exist in multiple isoforms and some for only brief moments during a particular stage in the cell cycle. The advent of proteomics and the introduction of stage-specific inhibitors have enabled the field to identify numerous factors required at distinct steps in the cell cycle. One such factor identified in many of these screens was the highly conserved protein dynamin. Dynamin, long known for its role in endocytosis, is also necessary for co-ordinating actin assembly at membranes. Our knowledge of its precise cell cycle function and upstream/downstream targets, however, is unclear. Our review will describe current knowledge regarding the impacts of several cell division screens and the multiple roles that dynamin may play during mitosis.
Endosome positioning during cytokinesis
Authors: Montagnac Guillaume , Chavrier Philippe
Published: June 2008

In mammalian cells, completion of cytokinesis relies on targeted delivery of recycling membranes to the midbody. At this step of mitosis, recycling endosomes are organized as clusters located at the mitotic spindle poles as well as at both sides of the midbody. However, the mechanism that controls endosome positioning during cytokinesis is not known. Here, we discuss the possible mechanisms that drive the formation of endosomal clusters and the importance of this process for the targeted delivery of recycling membranes to the midbody.
SUMO, hypoxia and the regulation of metabolism
Authors: Agbor Terence A. , Taylor Cormac T.
Published: June 2008

Post-translational modification is a critical event in the dynamic regulation of protein stability, location, structure, function, activity and interaction with other proteins and as such plays an important role in organism complexity. Over the last 10 years, the extensive and critical role of one such protein modification by SUMO (small ubiquitin-related modifier) has become apparent. The focus of this mini-review will be on recent reports of a possible functional role for the SUMO pathway in the adaptive cellular response to metabolic challenge, such as oxygen deprivation (hypoxia). Here, we will briefly review the evolving evidence for this pathway in the regulation of a number of metabolic regulators and discuss a possible role for SUMOylation in the regulation of basic metabolic function.
Development and implementation of split-GFP-based bimolecular fluorescence complementation (BiFC) assays in yeast
Authors: Barnard Emma , McFerran Neil V. , Trudgett Alan , Nelson John , Timson David J.
Published: June 2008

BiFC (bimolecular fluorescence complementation) is a tool for investigating interactions between proteins. Non-fluorescent fragments of, for example, GFP (green fluorescent protein) are fused to the interacting partners. The interaction brings the fragments together, which then fold, reassemble and fluoresce. This process can be carried out in living cells and provides information both on the interaction and its subcellular location. We have developed a split-GFP-based BiFC assay for use in the budding yeast Saccharomyces cerevisiae in which the modifications are carried out at the genomic level, thus resulting in the tagged yeast proteins being expressed at wild-type levels. The system is capable of detecting interactions in all subcellular compartments tested (the cytoplasm, mitochondria and nucleus) and makes a valuable addition to techniques for the investigation of protein–protein interactions in this model organism.
Substances that can change alternative splice-site selection
Authors: Sumanasekera Chiranthani , Watt David S. , Stamm Stefan
Published: June 2008

Alternative pre-mRNA splicing is an important element in eukaryotic gene expression, as most of the protein-coding genes use this process to generate multiple protein isoforms from a single gene. An increasing number of human diseases are now recognized to be caused by the selection of ‘wrong’ alternative exons. Research during the last few years identified a number of low–molecular-mass chemical substances that can change alternative exon usage. Most of these substances act by either blocking histone deacetylases or by interfering with the phosphorylation of splicing factors. How the remaining large number of these substances affect splicing is not yet fully understood. The emergence of these low-molecular-mass substances provides not only probes for studying alternative pre-mRNA splicing, but also opens the door to the possible harnessing of these compounds as drugs to control diseases caused by the selection of ‘wrong’ splice sites.
Recognition of nonsense mRNA: towards a unified model
Authors: Mühlemann Oliver
Published: June 2008

Among the different cellular surveillance mechanisms that ensure accurate gene expression, nonsense-mediated mRNA decay rapidly degrades mRNAs harbouring PTCs (premature translation-termination codons) and thereby prevents the accumulation of potentially deleterious proteins with C-terminal truncations. In the present article, I review recent data from yeast, fluitflies, nematode worms and human cells and endeavour to merge these results into a unified model for recognition of nonsense mRNA. According to this model, the distinction between translation termination at PTCs and at ‘normal’ termination codons relies on the physical distance between the terminating ribosome and PABP [poly(A)-binding protein]. Correct translation termination is promoted by a PABP-mediated signal to the terminating ribosome, whereas the absence of this signal leads to the assembly of an mRNA decay-promoting protein complex including the conserved NMD factors UPF (up-frameshift) 1–3.
Regulation of the ELAV target ewg: insights from an evolutionary perspective
Authors: Soller Matthias , Li Min , Haussmann Irmgard U.
Published: June 2008

ELAV (embryonic lethal abnormal visual system)/Hu family proteins are prototype RNA-binding proteins with binding preferences for AU-rich regions. Due to frequent occurrence of AU-rich motifs in introns and untranslated regions, it is poorly understood how gene-specific RNA-binding proteins, such as ELAV/Hu family members, recognize their complement of target RNAs in a complex cellular environment. The powerful genetic tools of Drosophila make the fruitfly an excellent model to study alternative mRNA processing in vivo in a developing organism. Recent sequencing of 12 Drosophila genomes will provide a novel resource to enhance our understanding of how gene-specific regulation of mRNA processing is achieved by ELAV/Hu family proteins.
Alternative splicing in plants
Authors: Simpson Craig G. , Lewandowska Dominika , Fuller John , Maronova Monika , Kalyna Maria , Davidson Diane , McNicol Jim , Raczynska Dorota , Jarmolowski Artur , Barta Andrea , Brown John W.S.
Published: June 2008

The impact of AS (alternative splicing) is well-recognized in animal systems as a key regulator of gene expression and proteome complexity. In plants, AS is of growing importance as more genes are found to undergo AS, but relatively little is known about the factors regulating AS or the consequences of AS on mRNA levels and protein function. We have established an accurate and reproducible RT (reverse transcription)–PCR system to analyse AS in multiple genes. Initial studies have identified new AS events confirming that current values for the frequency of AS in plants are likely to be underestimates.
The use of Affymetrix GeneChips as a tool for studying alternative forms of RNA
Authors: Harrison Andrew P. , Rowsell Joanna , Camargo Renata da Silva , Langdon William B. , Stalteri Maria , Upton Graham J.G. , Arteaga-Salas Jose M.
Published: June 2008

We are developing a computational pipeline to use surveys of Affymetrix GeneChips as a discovery tool for unravelling some of the biology associated with post-transcriptional processing of RNA. This work involves the integration of a number of bioinformatics resources, from comparing annotations to processing images to determining the structure of transcripts. The rapidly growing datasets of GeneChips available to the community puts us in a strong position to discover novel biology about post-transcriptional processing, and should enable us to determine the mechanisms by which some groups of genes make co-ordinated changes in their production of isoforms.
Nonsense-mediated mRNA decay
Authors: Wen Jikai , Brogna Saverio
Published: June 2008

Translation and mRNA decay are coupled processes; the link is most obvious in the case of NMD (nonsense-mediated mRNA decay). NMD is a mechanism that drastically reduces the level of mRNA harbouring PTCs (premature translation termination codons). The defining event in NMD is premature translation termination and the key question is: what distinguishes premature from normal translation termination? Surprisingly, in mammalian cells, PTC recognition is linked to pre-mRNA splicing. Here, we review the current understanding in view of recent developments.
Polyadenylation and degradation of mRNA in mammalian mitochondria: a missing link?
Authors: Bobrowicz Agnieszka J. , Lightowlers Robert N. , Chrzanowska-Lightowlers Zofia
Published: June 2008

mRNA turnover in human mitochondria, one of the key mechanisms governing mitochondrial gene expression, still presents an unsolved puzzle. The present article summarizes the current research on the mechanisms and enzymes that may be involved in that process.
Human papillomavirus type 16 late gene expression is regulated by cellular RNA processing factors in response to epithelial differentiation
Authors: Cumming Sarah A. , Cheun-Im Thanaporn , Milligan Stephen G. , Graham Sheila V.
Published: June 2008

HPV16 (human papillomavirus type 16) is a 7.9 kb double-stranded DNA virus that infects anogenital mucosal epithelia. In some rare cases, in women, infection can progress to cervical cancer. HPV16 gene expression is regulated through use of multiple promoters and alternative splicing and polyadenylation. The virus genome can be divided into an early and a late coding region. The late coding region contains the L1 and L2 genes. These encode the virus capsid proteins L1 and L2; protein expression is confined to the upper epithelial layers and is regulated post-transcriptionally in response to epithelial differentiation. A 79 nt RNA regulatory element, the LRE (late regulatory element), involved in this regulation is sited at the 3′-end of the L1 gene and extends into the late 3′-UTR (3′-untranslated region). This element represses late gene expression in differentiated epithelial cells and may activate it in differentiated cells. The present paper describes our current knowledge of LRE RNA–protein interaction and their possible functions.
Targeting of transcripts encoding membrane proteins in polarized epithelia: RNA–protein binding studies of the SGLT1 3′-UTR
Authors: Pedder Christopher M. , Ford Dianne , Hesketh John E.
Published: June 2008

mRNA stability, mRNA translation and spatial localization of mRNA species within a cell can be governed by signals in the 3′-UTR (3′-untranslated region). Local translation of proteins is essential for the development of many eukaryotic cell types, such as the Drosophila embryo, where the spatial and temporal localization of bicoid and gurken mRNAs, among others, is required to establish morphogen gradients. More recent studies have suggested that mRNA localization also occurs with transcripts coding for membrane-based or secreted proteins, and that localization at organelles such as the endoplasmic reticulum directs translation more efficiently to specific subdomains, so as to aid correct protein localization. In human epithelial cells, the mRNA coding for SGLT1 (sodium–glucose co-transporter 1), an apical membrane protein, has been shown to be localized apically in polarized cells. However, the nature of the signals and RNA-binding proteins involved are unknown. Ongoing work is aimed at identifying the localization signals in the SGLT1 3′-UTR and the corresponding binding proteins. Using a protein extract from polarized Caco-2 cells, both EMSAs (electrophoretic mobility-shift assays) and UV cross-linking assays have shown that a specific protein complex is formed with the first 300 bases of the 3′-UTR sequence. MFold predictions suggest that this region folds into a complex structure and ongoing studies using a series of strategic deletions are being carried out to identify the precise nature of the motif involved, particularly the role of the sequence or RNA secondary structure, as well as to identify the main proteins present within the complex. Such information will provide details of the post-transcriptional events that lead to apical localization of the SGLT1 transcript and may reveal mechanisms of more fundamental importance in the apical localization of proteins in polarized epithelia.
Coupling transcription to RNA processing via the p68 DEAD box RNA helicase androgen receptor co-activator in prostate cancer
Authors: Clark Emma L. , Fuller-Pace Frances V. , Elliott David J. , Robson Craig N.
Published: June 2008

The mechanisms involved in the transition from androgen-dependent to androgen-independent PCa (prostate cancer) remain largely undefined. The AR (androgen receptor) is an androgen-dependent transcription factor and is thought to play an important role in the development of both androgen-dependent and -independent prostatic malignancy. AR-mediated transcription is regulated by the binding of various cofactor proteins to the AR that facilitate transcriptional initiation and elongation. Elucidating the mechanisms by which cofactors regulate AR transcriptional activity may reveal the therapeutic potential of cofactors in PCa. Current models of gene expression indicate that transcription and RNA processing are tightly coupled. In this review, we discuss how the ATP-dependent DEAD box RNA helicase p68, which has established roles in transcription and RNA processing, may function as an ‘adaptor’ or coupling protein to facilitate cross-talk between transcription and RNA processing in AR-regulated genes by controlling the rate of transcriptional initiation/elongation.
Heat-shock protein gene polymorphisms and the risk of nephropathy in patients with Type 2 diabetes
Authors: Buraczynska Monika , Swatowski Andrzej , Buraczynska Kinga , Dragan Michal , Ksiazek Andrzej
Published: June 2008

HSPs (heat-shock proteins) are molecular chaperones synthesized under stress conditions, and are involved in renal cell survival and matrix remodelling in acute and chronic renal diseases. In the present study, we investigated whether the HSP70 gene polymorphisms affect susceptibility to DN (diabetic nephropathy) in patients with T2DM (Type 2 diabetes mellitus). The study group consisted of 452 patients with nephropathy. Two control subgroups involved 340 healthy individuals and 132 patients with T2DM lasting ≥10 years who were free of nephropathy. Subjects were genotyped for the HSP70-1 +190 G/C and −110 A/C, HSP70-2 +1267 A/G and HSP70-hom +2437 T/C polymorphisms by PCR, followed by digestion with restriction endonucleases. There were no statistically significant differences in genotype distribution between patients with T2DM with DN and controls for the HSP70-hom polymorphism. Significant differences were observed for HSP70-1 and HSP70-2 polymorphisms. CC homozygotes of the −110 and +190 HSP70-1 polymorphisms were more frequent in patients with T2DM with DN compared with healthy controls (22 compared with 6% and 15 compared with 6.5% respectively; P<0.01). The OR (odds ratio) for the risk allele was 2.17 [95% CI (confidence interval), 1.73–2.72] for the −110 A/C and 1.74 (95% CI, 1.40–2.15) for +190 G/C polymorphisms. A strong association with DN was found for the +1267 HSP70-2 polymorphism. The GG genotype and the G allele were associated with DN, with the OR for the G allele being 4.77 (95% CI, 3.81–5.96). All GG homozygotes in the patient group had higher LDL (low-density lipoprotein)-cholesterol levels than AA homozygotes (P<0.01), suggesting that the observed effect might be associated with this cardiovascular risk factor. These patients progressed faster to end-stage renal failure than those with other genotypes. In conclusion, our results indicate that the HSP70-1 and HSP70-2 polymorphisms are associated with renal complications in T2DM and may be useful in identifying patients with increased risk of DN.
Injury to rat carotid arteries causes time-dependent changes in gene expression in contralateral uninjured arteries
Authors: Forte Amalia , Finicelli Mauro , de Luca Pasquale , Nordström Ina , Onorati Francesco , Quarto Cesare , Santè Pasquale , Renzulli Attilio , Galderisi Umberto , Berrino Liberato , de Feo Marisa , Hellstrand Per , Rossi Francesco , Cotrufo Maurizio , Cascino Antonino , Cipollaro Marilena
Published: June 2008

Vascular surgery aimed at stenosis removal induces local reactions often leading to restenosis. Although extensive analysis has been focused on pathways activated in injured arteries, little attention has been devoted to associated systemic vascular reactions. The aim of the present study was to analyse changes occurring in contralateral uninjured rat carotid arteries in the acute phase following unilateral injury. WKY (Wistar–Kyoto) rats were subjected to unilateral carotid arteriotomy. Contralateral uninjured carotid arteries were harvested from 4 h to 7 days after injury. Carotid arteries were also harvested from sham-operated rats and uninjured rats. Carotid morphology and morphometry were examined. Affymetrix microarrays were used for differential analysis of gene expression. A subset of data was validated by real-time RT–PCR (reverse transcription–PCR) and verified at the protein level by Western blotting. A total of 1011 genes were differentially regulated in contralateral uninjured carotid arteries from 4 h to 7 days after arteriotomy (P<0.0001; fold change, ≥2) and were classified into 19 gene ontology functional categories. To a lesser extent, mRNA variations also occurred in carotid arteries of sham-operated rats. Among the changes, up-regulation of members of the RAS (renin–angiotensin system) was detected, with possible implications for vasocompensative mechanisms induced by arteriotomy. In particular, a selective increase in the 69 kDa isoform of the N-domain of ACE (angiotensin-converting enzyme), and not the classical somatic 195 kDa isoform, was observed in contralateral uninjured carotid arteries, suggesting that this 69 kDa isoenzyme could influence local AngII (angiotensin II) production. In conclusion, systemic reactions to injury occur in the vasculature, with potential clinical relevance, and suggest that caution is needed in the choice of controls during experimental design in vivo.
A guide to accurate measurement of diffusion using fluorescence correlation techniques with blinking quantum dot nanoparticle labels
Authors: Bachir Alexia I. , Kolin David L. , Heinze Katrin G. , Hebert Benedict , Wiseman Paul W.
Published: June 2008

Fluctuation-based fluorescence correlation techniques are widely used to study dynamics of fluorophore labeled biomolecules in cells. Semiconductor quantum dots (QDs) have been developed as bright and photostable fluorescent probes for various biological applications. However, the fluorescence intermittency of QDs, commonly referred to as “blinking”, is believed to complicate quantitative correlation spectroscopy measurements of transport properties, as it is an additional source of fluctuations that contribute on a wide range of time scales. The QD blinking fluctuations obey power-law distributions so there is no single characteristic fluctuation time for this phenomenon. Consequently, it is highly challenging to separate fluorescence blinking fluctuations from those due to transport dynamics. Here, we quantify the bias introduced by QD blinking in transport measurements made using fluctuation methods. Using computer simulated image time series of diffusing point emitters with set “on” and “off” time emission characteristics, we show that blinking results in a systematic overestimation of the diffusion coefficients measured with correlation analysis when a simple diffusion model is used to fit the time correlation decays. The relative error depends on the inherent blinking power-law statistics, the sampling rate relative to the characteristic diffusion time and blinking times, and the total number of images in the time series. This systematic error can be significant; moreover, it can often go unnoticed in common transport model fits of experimental data. We propose an alternative fitting model that incorporates blinking and improves the accuracy of the recovered diffusion coefficients. We also show how to completely eliminate the bias by applying k-space image correlation spectroscopy, which completely separates the diffusion and blinking dynamics, and allows the simultaneous recovery of accurate diffusion coefficients and QD blinking probability distribution function exponents.
Cell compressibility studies utilizing noncontact hydrostatic pressure measurements on single living cells in a microchamber
Authors: Lin L. A. G. , Liu A. Q. , Yu Y. F. , Zhang C. , Lim C. S. , Ng S. H. , Yap P. H. , Gao H. J.
Published: June 2008

A micro-optical-fluidic system (MOFS), which integrates a force generating device and an optical detector, is designed to measure the bulk modulus of a single living cell in real time under a controlled hydrostatic pressure. In this design, the accuracy of the bulk modulus measurement is improved because neither the force generating device nor the optical detector needs to be in contact with the cells. The MOFS device has been used to investigate the mechanotransduction of THP-1 human acute monocytic leukemia cells and the effects of the toxin lipopolysaccharide and colchicine on various properties of these cells.
The role of plasma elongation on the linear damping of zonal flows
Authors: Angelino P. , Garbet X. , Villard L. , Bottino A. , Jolliet S. , Ghendrih Ph. , Grandgirard V. , McMillan B. F. , Sarazin Y. , Dif-Pradalier G. , Tran T. M.
Published: June 2008

Drift wave turbulence is known to self-organize to form axisymmetric macroscopic flows. The basic mechanism for macroscopic flow generation is called inverse energy cascade. Essentially, it is an energy transfer from the short wavelengths to the long wavelengths in the turbulent spectrum due to nonlinear interactions. A class of macroscopic flows, the poloidally symmetric zonal flows, is widely recognized as a key constituent in nearly all cases and regimes of microturbulence, also because of the realization that zonal flows are a critical agent of self-regulation for turbulent transport. In tokamaks and other toroidal magnetic confinement systems, axisymmetric flows exist in two branches, a zero frequency branch and a finite frequency branch, named Geodesic Acoustic Modes (GAMs). The finite frequency is due to the geodesic curvature of the magnetic field. There is a growing body of evidence that suggests strong GAM activity in most devices. Theoretical investigation of the GAMs is still an open field of research. Part of the difficulty of modelling the GAMs stems from the requirement of running global codes. Another issue is that one cannot determine a simple one to one relation between turbulence stabilization and GAM activity. This paper focuses on the study of ion temperature gradient turbulence in realistic tokamak magnetohydrodynamic equilibria. Analytical and numerical analyses are applied to the study of geometrical effects on zonal flows oscillations. Results are shown on the effects of the plasma elongation on the GAM amplitude and frequency and on the zonal flow residual amplitude.
A predictive wall model for large-eddy simulation based on optimal control techniques
Authors: Templeton Jeremy A. , Wang Meng , Moin Parviz
Published: June 2008

Wall models for large-eddy simulation (LES) based on optimal control theory have so far been nonpredictive due to the need to prescribe a known mean velocity profile to the controller. In this study, LES is coupled with a near-wall Reynolds-averaged Navier–Stokes (RANS) model that provides a target velocity for the cost function. For the wall model to be accurate and robust, the LES and RANS must not only be tied together via the controller but directly coupled to each other through boundary conditions. The method proves to be accurate and robust over a wide range of Reynolds numbers in a plane channel flow. It is shown that the control reacts only locally in all spatial directions, justifying the current control formulation and suggesting directions for future model development. Further, instantaneous velocity fields of the coarse LES indicate that the dynamics of the near-wall flow are very dependent on the computational grid, demonstrating that a control strategy is required in addition to physical reasoning for wall modeling.
Numerical study of incompressible fluid dynamics with nonuniform density by the immersed boundary method
Authors: Kim Yongsam , Peskin Charles S.
Published: June 2008

We apply the immersed boundary method to the dynamics of an incompressible fluid with a nonuniform density. In order to take into account both the inertial and gravitational effects of the variable density, the penalty immersed boundary (pIB) method is used [Y. Kim and C. S. Peskin, Phys. Fluids 19, 053103 (2007)]. Incompressible fluid motion with a nonuniform density has been extensively explored both experimentally and computationally. We show that the pIB method is a robust and efficient numerical tool for the simulation of fluids with variable density by conducting computations of some example problems: The falling of a heavier fluid surrounded by a lighter fluid and the Rayleigh–Taylor instabilities in two dimensions and three dimensions and the dynamic stabilization of the Rayleigh–Taylor instability.
Digital in-line holography of dusty plasmas
Authors: Kroll M. , Harms S. , Block D. , Piel A.
Published: June 2008

A digital in-line holography (DIH) approach for the instantaneous measurement of the three-dimensional positions of micrometer sized particles in a radio frequency gas discharge is presented. The applicability of this method to a strongly coupled dusty plasma is demonstrated. The performance of DIH is benchmarked and special attention is paid to its spatial and temporal resolution.
Characterization of Lewis acid sites on the (100) surface of β-AlF3: Ab initio calculations of NH3 adsorption
Authors: Bailey C. L. , Wander A. , Mukhopadhyay S. , Searle B. G. , Harrison N. M.
Published: June 2008

The current study employs hybrid-exchange density functional theory to show that the Lewis base, NH3, binds to the β-AlF3 (100) surface with a binding energy (BE) of up to −1.96eV per molecule. This is characteristic of a strong Lewis acid. The binding of NH3 to the surface is predominately due to electrostatic interactions. There is only a small charge transfer from the NH3 molecule to the surface. The BE as a function of coverage is computed and used to develop a lattice Monte Carlo model which is used to predict the temperature programed desorption (TPD) spectrum. Comparison with experimental TPD studies of NH3 from β-AlF3 strongly suggests that these structural models and binding mechanisms are good approximations to those that occur on real AlF3 surfaces.
An optical NMR spectrometer for Larmor-beat detection and high-resolution POWER NMR
Authors: Kempf J. G. , Marohn J. A. , Carson P. J. , Shykind D. A. , Hwang J. Y. , Miller M. A. , Weitekamp D. P.
Published: June 2008

Optical nuclear magnetic resonance (ONMR) is a powerful probe of electronic properties in III-V semiconductors. Larmor-beat detection (LBD) is a sensitivity optimized, time-domain NMR version of optical detection based on the Hanle effect. Combining LBD ONMR with the line-narrowing method of POWER (perturbations observed with enhanced resolution) NMR further enables atomically detailed views of local electronic features in III-Vs. POWER NMR spectra display the distribution of resonance shifts or line splittings introduced by a perturbation, such as optical excitation or application of an electric field, that is synchronized with a NMR multiple-pulse time-suspension sequence. Meanwhile, ONMR provides the requisite sensitivity and spatial selectivity to isolate local signals within macroscopic samples. Optical NMR, LBD, and the POWER method each introduce unique demands on instrumentation. Here, we detail the design and implementation of our system, including cryogenic, optical, and radio-frequency components. The result is a flexible, low-cost system with important applications in semiconductor electronics and spin physics. We also demonstrate the performance of our systems with high-resolution ONMR spectra of an epitaxial AlGaAs∕GaAs heterojunction. NMR linewidths down to 4.1Hz full width at half maximum were obtained, a 103-fold resolution enhancement relative any previous optically detected NMR experiment.
Complementary inverter circuits based on p-SnO2 and n-In2O3 thin film transistors
Authors: Dhananjay  , Chu Chih-Wei , Ou Chun-Wei , Wu Meng-Chyi , Ho Zhong-Yo , Ho Kuo-Chuan , Lee Shih-Wei
Published: June 2008

Thin film transistors (TFTs) of indium oxide (In2O3) and tin oxide (SnO2) were fabricated on SiO2 gate dielectric using reactive evaporation process. Structural investigation of the films revealed that In2O3 films were polycrystalline in nature with preferred (222) orientation and SnO2 films exhibited amorphous nature. The x-ray photoelectric spectroscopy measurements suggest that SnO2 films were oxygen rich and presume mixed oxidation states of Sn, namely Sn2+ and Sn4+. While the In2O3 based TFTs possess n-type channel conduction, SnO2 based TFTs exhibited anomalous p-type conductivity. Integration of these n- and p-type devices resulted in complementary inverter with a gain of 11.
ac hopping admittance in spinel manganate negative temperature coefficient thermistor electroceramics
Authors: Schmidt Rainer , Brinkman Andrew W.
Published: June 2008

In this work, the ac admittance of a thick film nickel manganate spinel negative temperature coefficient thermistor ceramic system containing a glass phase is investigated. The dominating relaxation process is a grain boundary (GB) effect and has been investigated comprehensively. We present double-logarithmic plots of the specific admittance σ′ vs ω and (σ′/σdc) vs ω, and specific impedance z′ vs −z″/ω and [(ρdc/z′)−1] vs ω, in order to characterize GB charge transport. Using the complex admittance notation (σ∗), an unusually low Jonscher exponent of frequency ∼0.007 was obtained and the GB relaxation displayed close to ideal behavior.
Temperature sensitivity (T) of tensile-strained GaAsP/(AlGa)As double-barrier separate confinement heterostructure laser diodes for 800 nm band
Authors: Maląg Andrzej , Dąbrowska Elżbieta , Grodecki Kacper
Published: June 2008

The temperature sensitivity of the double-barrier separate confinement heterostructure (DBSCH) laser diodes (LDs), intended for high-power, low vertical beam divergence emission, was shown to be somewhat lower than that of the large optical cavity (LOC) devices of similar beam divergences. For the lowest beam divergences, it still remains considerably high, resulting in low characteristic temperatures T0 not exceeding 80 K in the LDs of the vertical beam divergences below 15°. In this work, the decrease in the T0 values of such tensile-strained GaAsP/(AlGa)As DBSCH LDs has been found primarily due to an increased, thermally activated occupation of the heavy-hole subband and, to a minor degree, occupation of the second quantum level, both giving rise to transitions that do not contribute to the optical gain. This is caused by the higher and more temperature-dependent at-threshold band filling for devices of reduced confinement factor (Γ) aimed at achieving low beam divergence. This phenomenon seems to be common for all the tensile-strained LDs and acts in addition to other mechanisms that decrease the T0, such as the carrier escape from a quantum well to surrounding layers. However, in DBSCH LDs no carrier escape has been detected, presumably because of their thin waveguide layers. This can explain the somewhat higher T0 values of these devices when compared to their LOC counterparts.
Surface hydrogenation of silicon nanocrystallites during pulsed laser ablation of silicon target in hydrogen background gas
Authors: Umezu Ikurou , Takata Masatoshi , Sugimura Akira
Published: June 2008

The surface hydrogenated silicon nanocrystallites can be prepared by pulsed laser ablation of a silicon target in hydrogen background gas. Formation processes of the surface Si–H bonds were found by correlation between the surface structure of the deposited nanocrystal film and the time- and space-resolved spectra of plume emission during the deposition. A precursor of the hydrogenation is SiH species created in blast-wave stage by collision between ejected Si species and background hydrogen gas. Results of plume diagnostics indicate that the spatial or temporal separation between Si and SiH species is not an origin of the formation of the surface hydrogenated Si nanocrystallite. It is concluded that the correlation between the thermal stability of the Si–H bond and the temperature variation of the formed nanoparticle during the deposition is important for the formation of the chemical bonding on the surface.
Hole transport in blue and white emitting polymers
Authors: Parshin Mikhail A. , Ollevier Jeroen , Van der Auweraer Mark , de Kok Margreet M. , Nicolai Herman T. , Hof André J. , Blom Paul W. M.
Published: June 2008

Hole transport in a blue emitting polyspirobifluorene polymer and in a white emitting polymer consisting of a polyspirobifluorene backbone and two dyes (green and red) was studied. The hole mobility was measured using the time-of-flight method as a function of the electric field and temperature in the range 105−106 V/cm and 285−335 K, respectively. The observed temperature and electric field dependence of the hole mobility was analyzed in the framework of the Bässler disorder model. Also, steady-state current-voltage characteristics were measured over a wide range of electric fields and temperatures and the hole mobility was determined. Our measurements have shown that the hole mobility in the white emitting polymer is the same as in the blue emitting polymer. The performed disorder model analysis gives the same values for the effective energetic disorder (115 meV) and for the positional disorder (1.85) for both polymers. Therefore, we have concluded that the added green and red dyes do not act as hole traps as they have no influence on the hole mobility. It can therefore be concluded that their highest occupied molecular orbital (HOMO) levels are aligned with the HOMO level of the polyspirobifluorene backbone.
Crystallization properties of ultrathin phase change films
Authors: Raoux Simone , Jordan-Sweet Jean L. , Kellock Andrew J.
Published: June 2008

The crystallization behavior of ultrathin phase change films was studied using time-resolved x-ray diffraction (XRD). Thin films of variable thickness between 1 and 50nm of the phase change materials Ge2Sb2Te5 (GST), N-doped GST, Ge15Sb85, Sb2Te, and Ag- and In-doped Sb2Te were heated in a He atmosphere, and the intensity of the diffracted x-ray peaks was recorded. It was found for all materials that the crystallization temperature increases as the film thickness is reduced below 10nm. The increase depends on the material and can be as high as 200°C for the thinnest films. The thinnest films that show XRD peaks are 2nm for GST and N-GST, 1.5nm for Sb2Te and AgIn-Sb2Te, and 1.3nm for GeSb. This scaling behavior is very promising for the application of phase change materials to solid-state memory technology.