bluuebunny/crossref_metadata_2025 huggingface dataset:
Receptor activator NF κB ligand (RANKL) and osteoprotegerin (OPG) protein expression in periodontitis
Authors: Crotti Tania , Smith Malcolm D. , Hirsch Robert , Soukoulis Steven , Weedon Helen , Capone Maria , Ahern Michael J. , Haynes David
Published: November 2010

Objectives and background:  This study investigated the expression of key mediators that regulate differentiation of osteoclasts, receptor activator of nuclear factor κB ligand (RANKL), and its natural inhibitor, osteoprotegerin (OPG), in periodontitis. We aimed to compare the levels of the RANKL and OPG in the granulomatous tissue adjacent to areas of alveolar bone loss from patients with periodontitis to that present in tissue from patients without periodontitis. In addition, we aimed to determine the types of cells expressing these factors in these tissues and to demonstrate the expression of the osteoclastic markers, RANK and tartrate‐resistant acid phosphatase (TRAP), in periodontitis.

Materials and methods:  Frozen biopsy specimens were analysed using specific monoclonal antibodies and were evaluated by semiquantitative analysis and digital image analysis to compare levels of RANKL and OPG protein expression. Double labelling of frozen sections with antibodies to different cell lineage specific markers was used to determine the types of cells expressing these proteins. In situ hybridization was used to detect cells expressing RANK mRNA.

Results:  Semiquantitative image analysis demonstrated that significantly higher levels of RANKL protein (P < 0.05) were expressed in the periodontitis tissue. Conversely, OPG protein was significantly lower (P < 0.05) in the periodontitis tissues. RANKL protein was associated with lymphocytes and macrophages. OPG protein was associated with endothelial cells in both tissues. Many leukocytes expressing RANK mRNA and TRAP were observed in periodontitis tissues.

Conclusion:  The change in the levels of these key regulators of osteoclast differentiation may play a major role in the bone loss seen in periodontitis.
Growth hormone regulates osteogenic marker mRNA expression in human periodontal fibroblasts and alveolar bone‐derived cells
Authors: Haase H. R. , Ivanovski S. , Waters M. J. , Bartold P. M.
Published: November 2010

Background:  Growth hormone (GH) is a potent regulator of bone formation. The proposed mechanism of GH action is through the stimulation of osteogenic precursor cell proliferation and, following clonal expansion of these cells, promotion of differentiation along the osteogenic lineage.

Objectives:  We tested this hypothesis by studying the effects of GH on primary cell populations of human periodontal ligament cells (PLC) and alveolar bone cells (ABC), which contain a spectrum of osteogenic precursors.

Methods:  The cell populations were assessed for mineralization potential after long‐term culture in media containing β‐glycerophosphate and ascorbic acid, by the demonstration of mineral deposition by Von Kossa staining. The proliferative response of the cells to GH was determined over a 48‐h period using a crystal violet dye‐binding assay. The profile of the cells in terms of osteogenic marker expression was established using quantitative reverse transcriptase polymerase chain reaction (RT‐PCR) for alkaline phosphatase (ALP), osteopontin, osteocalcin, bone sialoprotein (BSP), as well as the bone morphogenetic proteins BMP‐2, BMP‐4 and BMP‐7.

Results:  As expected, a variety of responses were observed ranging from no mineralization in the PLC populations to dense mineralized deposition observed in one GH‐treated ABC population. Over a 48‐h period GH was found to be non‐mitogenic for all cell populations. Quantitative reverse transcriptase polymerase chain reaction (RT‐PCR) BSP mRNA expression correlated well with mineralizing potential of the cells. The change in the mRNA expression of the osteogenic markers was determined following GH treatment of the cells over a 48‐h period. GH caused an increase in ALP in most cell populations, and also in BMP expression in some cell populations. However a decrease in BSP, osteocalcin and osteopontin expression in the more highly differentiated cell populations was observed in response to GH.

Conclusion:  The response of the cells indicates that while long‐term treatment with GH may promote mineralization, short‐term treatment does not promote proliferation of osteoblast precursors nor induce expression of late osteogenic markers.
Immunohistochemical analysis of Th1/Th2 cytokine profiles and androgen receptor expression in the pathogenesis of nifedipine‐induced gingival overgrowth
Authors: Huang W‐T. , Lu H‐K. , Chou H‐H. , Kuo Mark Y. P.
Published: November 2010

Background:  Numerous studies have demonstrated that gingival overgrowth may be associated with androgen and cytokine expression in tissues.

Objectives:  The aim of this study was to compare the expression of androgen receptor‐presenting cells (AR+ cells) and Th1/Th2 cytokine [Th1: interleukin (IL)‐2, interferon‐γ (IFN‐γ); Th2: IL‐4, IL‐10, IL‐13] expression cells in tissue sections of patients with gingival overgrowth.

Materials and methods:  Tissue samples were collected from patients with healthy periodontium (H group), adult periodontitis (P group), surgically extracted teeth (S group), and nifedipine‐induced gingival overgrowth (NIGO group). The clinical periodontal parameters of pocket depth (PD), bleeding on probing (BOP), and plaque control record (PCR) were measured around selected sample teeth. Gingival biopsies were further processed by immunohistochemical staining method. The expressions of cells positive for AR, IL‐2, IFN‐γ, IL‐4, IL‐10, and IL‐13 were counted by predetermined semiquantitative methods.

Results:  Our results indicated that AR, IL‐2, IFN‐γ, IL‐4, IL‐10, and IL‐13 were intensively expressed in the nuclei of inflammatory cells and fibroblasts of gingival connective tissue. Stronger expressions of AR, IL‐2, and IFN‐γ were found in the NIGO group. The AR+ cells/0.01 mm2 in gingival fibroblasts were significantly higher in the NIGO group (80.2 ± 10.7) than those of the periodontitis group (52.5 ± 11.8) and control group (37.4 ± 11.3) (P < 0.05). The cytokine expression of the NIGO group showed a trend towards Th1‐type expression (IL‐2; P = 0.0001). In the surgically extracted tooth group, a stronger expression of Th2‐type cytokine (IL‐4, Il‐10, IL‐13; P < 0.05) was found in inflammatory cells. In a comparison of the IL‐2/IL‐4‐labeled cell ratio of the four groups, a descending sequence was discovered as NIGO group (0.92 ± 0.97) > H group (0.81 ± 0.61) > P group (0.77 ± 0.82) > S group (0.58 ± 1.77).

Conclusions:  Our data support the following: (i) taking nifedipine may elevate the expression of AR in susceptible oral tissue, e.g. gingiva; (ii) the cytokine profile of T‐cells in NIGO tissue indicates a trend preferentially towards Th1 activity; and (iii) elevation of AR expression cells and prominent Th1 cytokine‐labeled cells are two significant factors in the pathogenesis of NIGO.
Gingival crevicular fluid collagenase‐2 (MMP‐8) test stick for chair‐side monitoring of periodontitis
Authors: Mäntylä Päivi , Stenman Mathias , Kinane Denis F. , Tikanoja Sari , Luoto Hanne , Salo Tuula , Sorsa Timo
Published: November 2010

Background: A rapid chair‐side test based on the immunological detection of elevated levels of collagenase‐2 (matrix metalloproteinase‐8, MMP‐8) in gingival crevicular fluid (GCF) was developed to identify and monitor the course and treatment of adult periodontitis.

Methods: MMP‐8 was determined in GCF from periodontitis (11 patients, 90 sites), gingivitis (10 patients, 58 sites) and healthy control (8 patients, 59 sites) sites (i) by a test stick incorporating monoclonal antibodies to two epitopes on MMP‐8 and (ii) by measuring MMP‐8 concentration by a quantitative immunofluorometric assay. Patients with adult periodontitis were treated by scaling and root planing (SRP) and received oral hygiene instructions. GCF MMP‐8 testing and clinical measurements were done before and after SRP.

Results: MMP‐8 GCF levels and chair‐side test differentiated periodontitis from gingivitis and healthy control sites. MMP‐8 GCF levels > 1 mg/l and positive chair‐side test identified especially severe periodontitis sites. A positive and negative test stick result, the outcome of which was rapidly detectable in 5 mins, in GCF correlated well with MMP‐8 immunofluorometric assay analysis from the collected GCF samples and the severity of periodontitis. Scaling and root planing reduced the MMP‐8 levels in severe periodontitis sites with positive MMP‐8 test and gingival probing pocket depth (PD) > 5 mm before treatment. The test stick result and the quantitative assay were discrepant in only 18 of the 207 sites tested, thus agreement was very good (κ = 0.81). With a threshold of 1 mg/l MMP‐8 activity the chair‐side test provided a sensitivity of 0.83 and specificity of 0.96 (n = 207).

Conclusion: The MMP‐8 test can be used to differentiate periodontitis from gingivitis and healthy sites as well as to monitor treatment of periodontitis. A reduction in GCF MMP‐8 levels and a change in test stick result provide a means to optimize patient control during maintenance of periodontal treatment.
Bone turnover markers in serum and periodontal microenvironments
Authors: Wilson A. N. , Schmid M. J. , Marx D. B. , Reinhardt R. A.
Published: November 2010

Background:  Periodontitis is characterized by altered bone turnover, but local measurements are difficult.

Objectives:  The objective of this study was to develop a method to measure multiple markers of bone turnover from single samples collected at various bone surfaces of the periodontium, and to test the ratios of these markers against more traditional serum and gingival crevicular fluid (GCF) samples.

Materials and methods:  Fourteen subjects with untreated periodontitis were recruited for sampling serum, GCF (from sites ≥ 5 mm probing depth that bled on probing) and washes of periodontal bone surfaces (adjacent interproximal, vestibular cortical and trabecular bone) with a novel irrigating device. All samples were analyzed for osteocalcin (OC, bone turnover marker; RIA), cross‐linked N‐telopeptide of type I collagen (NTx, bone resorption marker; ELISA) and albumin (Alb, serum protein; ELISA). Results were reported as ratios: OC/NTx to determine relative bone turnover, and OC/Alb or NTx/Alb to determine local OC or NTx production.

Results:  The OC/NTx ratio was significantly higher (p ≤ 0.05) in serum vs. GCF (OC undetectable), interproximal bone and cortical vestibular bone, but significantly lower than in trabecular vestibular bone. The OC/Alb ratio for serum was also statistically lower than for vestibular trabecular bone. The NTx/Alb ratio for serum was statistically lower than for GCF and all the bone wash test sites. The results indicated considerable local production of both OC and NTx.

Conclusions:  This system demonstrated that multiple markers of bone turnover can be harvested by irrigation from periodontal bone microenvironments. Bone turnover profiles from periodontal bone surfaces and GCF differed from systemic bone turnover profiles (serum) and may be valuable in tracking site‐specific responses to disease or treatment.
Chromatin regulators as capacitors of interspecies variations in gene expression
Authors: Tirosh Itay , Reikhav Sharon , Sigal Nadejda , Assia Yael , Barkai Naama
Published: November 2010

Gene expression varies widely between closely related species and strains, yet the genetic basis of most differences is still unknown. Several studies suggested that chromatin regulators have a key role in generating expression diversity, predicting a reduction in the interspecies differences on deletion of genes that influence chromatin structure or modifications. To examine this, we compared the genome‐wide expression profiles of two closely related yeast species following the individual deletions of eight chromatin regulators and one transcription factor. In all cases, regulator deletions increased, rather than decreased, the expression differences between the species, revealing hidden genetic variability that was masked in the wild‐type backgrounds. This effect was not observed for individual deletions of 11 enzymes involved in central metabolic pathways. The buffered variations were associated with trans differences, as revealed by allele‐specific profiling of the interspecific hybrids. Our results support the idea that regulatory proteins serve as capacitors that buffer gene expression against hidden genetic variability.
The Molecular In Silico Dissection of Cancer using TCLASS and its Application in the Identification of the Tissue of Origin of *Cancers of Unknown Primary Site*
Authors: Ayoubi Torik
Published: November 2010

Traditional cancer diagnosis relies on a combination of clinical and histo-pathological data. In many cases, however, the morphology of in particular metastatic cancer is not discriminative enough for correct diagnosis. In addition, the morphology of tumor cells do not provide information on aberrant molecular pathways that may be used to specifically target the tumor like the application of Herceptin to breast cancers with amplification in the ERBB2 gene. With the completion of the human genome project, molecular pathology has dramatically increased its arsenal of novel molecular biomarkers that can be used to determine the phenotype of tumors. Gene expression profiling using high-density microarray technology is an extremely powerful tool to comprehensively characterize the tumor phenotype. We have developed TCLASS® a multi-class tumor classifier that interprets gene expression microarray data and allows the identification of the primary site of Cancers of Unknown Promary site (CUP). The classifier is implemented as a web-based tool and is an extremely simple and straightforward approach for molecular characterization of tumor samples. We are currently looking for collaborations with clinicians with access to fresh frozen CUP samples to further validate the tool in a clinical context. Alternatively, CEL files of CUP samples analyzed with Affynetrix 133 Plus 2.0 arrays can also be directly analyzed using TCLASS.
InterPro Curation: Integrating Predictive Protein Signatures Into Biological Hierarchies
Authors: Burge Sarah
Published: November 2010

InterPro is an integrated database of predictive protein signatures used for the classification and automatic annotation of proteins and genomes. As InterPro curators, we are responsible for assimilating information from our member databases and communicating it to our end users in a way that adds value to each individual signature. We categorise signatures according to their type (for example, Family, Domain or Repeat) and annotate entries with links to other databases, abstracts and protein matches.The InterPro database also identifies relationships between entries. For example, signatures at a general Family level are related to more specific subfamilies through a Parent/Child relationship. Families may also Contain individual Domains. In this manner, we aim to build up a hierarchy of InterPro entries that correctly represents relationships between biological families and domains. Users may then easily identify related proteins and signatures as the InterPro database attempts to map out biological hierarchies. Here we discuss InterPro relations, the criteria for their formation and how they may be useful to users. We will also discuss the challenges of representing biological hierarchies when automating relationship formation and the role manual curation plays in ensuring that we accurately represent biological networks.
Temporal trends in annual water yields from the Mackenzie, Saskatchewan-Nelson, Churchill, and Missouri-Mississippi River watersheds in western and northern Canada
Authors: Rayne Sierra , Forest Kaya
Published: November 2010

Historical temporal trends in annual water yields were examined at 109 hydrometric monitoring stations in the Mackenzie, Saskatchewan-Nelson, Churchill, and Missouri-Mississippi River watersheds from the western Canadian provinces of Alberta, Saskatchewan, and northeastern British Columbia, as well as the Northwest Territories and the eastern portion of the Yukon territory. Effective drainage areas range in size from 325 to 1,680,000 (mean=65,600; median=9,300) km^2^, with associated hydrometric record lengths ranging between 18 and 97 (mean=41; median=38) years. Approximately three-quarters of the stations have no significant trend in average annual flow, with about equal numbers of stations exhibiting significant temporal increases or decreases in annual water yields. Southwestern Alberta and the southwestern Northwest Territories contain small clusters of stations with increasing water yield trends; clusters of decreasing water yield trends are primarily located in central and southern Alberta. The co-location of regions with clusters of both increasing and decreasing trends, or increasing/decreasing and no trends, complicates generalizing broader scale trends in annual water yields across these regions of Canada. No bias in the trend directions appears evident with either watershed size or the length of the hydrometric record.
Introduction to N-Heterocyclic Carbenes: Synthesis and Stereoelectronic Parameters
Authors: Jahnke Mareike C. , Ekkehardt Hahn F.
Published: November 2010

N-Heterocyclic carbenes (NHCs) are cyclic compounds containing a divalent carbon atom bound to at least one nitrogen atom within the heterocycle. Variation of the size of the carbene ring, the substituents on the nitrogen atoms or the additional atoms within the heterocycle lead to an array of different NHCs exhibiting a broad range of electronic properties. Their ability to act as donors and the resulting stable bounds to most transition metals make them excellent ligands in coordination chemistry. In addition, free NHCs have found applications as organocatalysts in metal free chemical transformations. In this Chapter synthetic procedures leading to different NHCs and important structural and electronic features of this class of compounds are discussed.
Computational Studies on the Reactivity of Transition Metal Complexes Featuring N-Heterocyclic Carbene Ligands
Authors: Häller L. Jonas L. , Macgregor Stuart A. , Panetier Julien A.
Published: November 2010

Computational studies on the reactivity of transition metal complexes featuring N-heterocyclic carbene (NHC) ligands are reviewed. Reactions involving the direct participation of NHC ligands are first considered, including reductive elimination, migratory insertion and cyclometallation. Subsequent sections survey processes where NHC ligands act as spectator ligands, in particular those where their electronic and steric characteristics impact on reactivity. Small molecule activation is discussed, as well as the extensive studies on the behaviour of Grubbs' 2nd generation metathesis catalyst and related species.
NHC–Iron, Ruthenium and Osmium Complexes in Catalysis
Authors: Delaude Lionel , Demonceau Albert
Published: November 2010

In this Chapter, the catalytic applications of organometallic species —either pre-formed or generated in situ— based on Group 8 transition metals and N-heterocyclic carbene (NHC) ligands are surveyed. Thus far, only a few reports on the use of NHC–Fe complexes in organic catalysis are available, although significant work has been reported in the related field of biocatalysis. Contrastingly, the chemistry of NHC–Ru complexes has reached an unprecedented level of maturity, thanks to the relentless research efforts thrown into the development of olefin metathesis catalysts. Other carbon skeletal transformations based on NHC–Ru promoters include cyclopropanation, allylation, or cycloisomerisation reactions. Lastly, with only two reports to date concerning olefin metathesis and transfer hydrogenation, NHC–Os-based catalysis can hardly be considered anything else than a curiosity.
NHC–Nickel and Platinum Complexes in Catalysis
Authors: Fort Yves , Comoy Corinne
Published: November 2010

This Chapter summarizes the recent impact that the use of N-heterocyclic carbene (NHC) ligands in the field of Ni- and Pt-mediated processes.

This family of ligands have allowed for the development of novel nickel-based catalysts of increased reactivity and selectivity compared to previous Ni-phosphine reagents. These NHC–Ni reagents are active in hydrogenation, hydrogen transfer properties and C–S or C–F bond activation. Conversely, they efficiently catalyze arythiolation, hydrothiolation and cross-coupling reactions as well as different cross-couplings, cycloadditions of alkynes or isomerization of vinylcyclopropanes.

On the other hand, NHC–Pt analogues have been less studied for catalytic applications. Regioselective and/or asymmetric hydroboration as well as hydrosilylation constitute the two most areas of research for these species.
Oxidation Reactions with NHC–Metal Complexes
Authors: Podhajsky Susanne M. , Sigman Matthew S.
Published: November 2010

An overview of oxidative reactions promoted by N-heterocyclic carbene (NHC) metal complexes is presented. Rather than attempting to provide a comprehensive review, key systems and recent developments are laid out, with special attention given to mechanistic aspects. Specifically, O2 activation by metal carbene complexes is covered, followed by alcohol oxidation, Wacker-type reactions and oxidative cleavage of alkenes, and alkane as well as arene oxidations proceeding via C–H activation.
Reduction Reactions with NHC-bearing Complexes
Authors: Çetinkaya Bekir
Published: November 2010

This Chapter summaries the studies conducted on the reduction of multiple-bonded organic compounds in the presence of NHC–metal complexes as homogeneous catalysts. The following reactions have been examined: hydrogenation, transfer hydrogenation, hydrosilylation and hydroboration. Reports of the application of hydrosilylation and hydroboration in the synthesis of complex organic molecules and via subsequent cleavage of Si−C or B−C bonds are also discussed.
N-Heterocyclic Carbenes as Organic Catalysts
Authors: Chiang Pei-Chen , Bode* Jeffrey W.
Published: November 2010

The synthetic utility of azolium salts as catalysts was thought to be limited to the generation of acyl anion equivalents for use in benzoin and Stetter reactions. The discovery, in 2004, of new catalysts, substrates, and reaction manifolds has ignited a new generation of reactions that fall under the general rubrik of N-heterocyclic carbene (NHC) catalyzed reactions. These powerful new processes include the catalytic generation of activated carboxylates for α-functionalized aldehydes, enantioselective annulations via catalytically generated ester enolate equivalents, and the NHC-catalyzed generation of formal homoenolate equivalents. The history of these new reactions and an overview of the reactions, their substrate scope, and mechanistic pathways are summarized in this Chapter.
Drug Discovery by DNA-encoded Libraries
Authors: Li Yizhou , Zhu Zheng , Li Xiaoyu
Published: November 2010

In the past decade, drug discovery has been plagued by the lack of tools capable of exploring the vast chemical space to interrogate all the available drug targets in order to treat diseases more effectively. In the past decade, DNA-encoded library has emerged as one of the unique approaches to address this issue by incorporating Nature's evolutional strategy in discovery of small molecule functions. A variety of drug discovery platforms based on this approach have been created in pharmaceutical companies. In this chapter, we will first discuss the fundamental mechanisms underlying DNA-encoded library; and in the second half, we will discuss the variations and industrialization of this technology, and its potential to become one of the indispensable tool in modern drug discovery.
The natural history of chronic hepatitis B
Authors: Lai C.‐L. , Yuen M.‐F.
Published: November 2010

Summary.  The natural history of chronic hepatitis B is dependent on the age of acquiring the hepatitis B infection. Those who are infected at adolescence or adulthood (including most of the Caucasians) tend to have stable disease after hepatitis B e antigen seroconversion with normal serum alanine aminotransaminase (ALT) and hepatitis B virus (HBV) DNA levels <105 copies/mL (20 000 IU/mL). In contrast, those who are infected at birth or early childhood (including the majority of the world’s hepatitis B carriers, i.e. Asians) have a prolonged immune tolerance phase followed by a prolonged immune clearance phase. A proportion of these patients have progressive disease after HBeAg seroconversion with HBV DNA <104 copies/mL (<2000 IU/mL) and ALT between 0.5 and 2× upper limit of normal. Core promoter mutations may play a part in the development of cirrhosis‐related complications. However, continuing viral replication, even at a relatively low level of <104 copies/mL (<2000 IU/mL), is probably the most important factor for the development of complications.
Melatonin binding sites in estrogen receptor‐positive cells derived from human endometrial cancer
Authors: Kobayashi Yoichi , Itoh Masanori T. , Kondo Haruhiro , Okuma Yoshiaki , Sato Sojiro , Kanishi Yosuke , Hamada Naomi , Kiguchi Kazushige , Ishizuka Bunpei
Published: November 2010

Abstract:Our previous work showed that melatonin (N‐acetyl‐5‐methoxytryptamine) inhibits proliferation of the human endometrial cancer cell line, Ishikawa, which is estrogen receptor‐positive. The aim of the present study was to determine whether Ishikawa cells possess membrane melatonin receptors. Binding of the radioligand 2‐[125I]‐iodomelatonin to membrane preparations obtained from Ishikawa cells was detectable, saturable and stable. Scatchard analysis revealed that the dissociation constant (Kd) of the binding sites was 179.0 pm(similar to that of the MT2 [Mel1b] melatonin receptor subtype), and that the concentration (Bmax) of the binding sites was 12.9 fmol/mg protein. Luzindole, a selective MT2 melatonin receptor antagonist, significantly suppressed binding of 2‐[125I]‐iodomelatonin at all concentrations tested (10−8to 10−4 m). These results suggest that the MT2 melatonin receptor subtype is present in the membranes of Ishikawa cells, and that the antiproliferative effect of melatonin on Ishikawa cells is mediated via the MT2 receptor. This may have implications for the use of melatonin in endometrial cancer therapy.
Ta clustering and microstructural evolution in the A1 to L1Fe52PtX(Ta1−X) phase transformation
Authors: Means D. , Wang B. , Thompson G. B.
Published: November 2010

A series of Fe52Pt48,Fe52.3Pt46.3Ta1.4 and Fe52Pt40.7Ta7.3 thin films were sputter deposited and subsequently annealed at 550 and 750 °C for 30 min. The as-deposited films, which adopted the A1 phase, had a change from a predominate (111) fiber texture to (200) with the Ta additions. This has been explained in terms of the competition between the surface energy and strain energy. Annealing at 550 °C facilitated the L10 order in Fe52Pt48 and Fe52.3Pt46.3Ta1.4. Upon annealing at 750 °C, all three composition films phase transformed into L10. Atom probe tomography revealed nanoscale clustering in the annealed Ta containing films. The formation of these clusters appeared to be a necessary initial step to allow the L10 ordering reaction to occur but clustering in of itself is not sufficient for order. For the Fe52Pt40.7Ta7.3 film, the Ta must be depleted within the matrix to a sufficient level to allow the binary Fe–Pt to order. For the Fe52.3Pt46.3Ta1.4 film, these clusters were qualitatively observed within the grains at 550 °C and in the grain boundaries at 750 °C. The Fe52Pt40.7Ta7.3 film had clusters within and near grain boundaries. The clustering in the grain boundaries deterred grain growth through a Zener-based pinning mechanism.
Grain orientation of Y2O3–Si3N4 thin-film on the power-handling of InGaAs/AlAsSb ultrafast all-optical cross-phase modulators
Authors: Lim C. G.
Published: November 2010

Grain orientation is known to yield high thermal conductivity oriented yttrium silicon oxynitride (Y2O3–Si3N4). However, the anisotropic thermal conductivity of oriented Y2O3–Si3N4 in the stacking direction falls below that of nonoriented Y2O3–Si3N4 and Si3N4 at temperatures above 280 K and 630 K, respectively. Hence, it is unclear will grain orientation actually lead to better heat diffusions from the InGaAs/AlAsSb ultrafast all-optical cross-phase modulators or any other semiconductor devices to the oriented Y2O3–Si3N4 thin-film. To probe into this, the heat diffusion in an InGaAs/AlAsSb ultrafast all-optical cross-phase modulator whereby nonoriented and oriented Y2O3–Si3N4 thin-films are used as the heat-spreader is performed. Analysis shows that grain orientation in Y2O3–Si3N4 thin-film reduces the thermal resistance at the device-film interface through reduced void density, and leads to a marginally better heat diffusion in the device compared to nonoriented Y2O3–Si3N4 thin-film. Consequently, oriented Y2O3–Si3N4 thin-film heat-spreader improves the power-handling of the InGaAs/AlAsSb ultrafast all-optical cross-phase modulator by ∼0.46–∼1.8 times of the original value compared to ∼0.36–∼1.75 times of the original value for the case of nonoriented Y2O3–Si3N4 thin-film heat-spreader.
Magnetic and microstructural properties of Cu-doped FePt-Zr/MgO multilayer films
Authors: Jung Jun Ho , Kim Kisoo , Lee Seong-Rae , Jeung Won Young
Published: November 2010

The magnetic and microstructural properties of Zr-doped FePt/MgO and Cu-doped FePt-Zr/MgO nanocomposite films were investigated. The samples exhibited out-of-plane anisotropy after annealing for only 5 min and their grain growth was restrained by Zr doping. The Cu-doped FePt-Zr/MgO films showed an increased tendency to grow with the (001) texture on the MgO (200) layer, because of the increase in the a-lattice parameter of L10 Cu-doped FePt (002), which decreased the lattice mismatch with the MgO (200) layers. The Curie temperature decreases by about 145 K owing to the effects of Cu doing. Although the addition of Cu reduces the perpendicular magnetic anisotropy and the ability to restrain the grain growth, the addition of both Zr and Cu had a complementary effect on the magnetic and microstructural properties of FePt.
Intermittent sound generation and its control in a free-shear flow
Authors: Cavalieri André V. G. , Jordan Peter , Gervais Yves , Wei Mingjun , Freund Jonathan B.
Published: November 2010

Comparisons are made between direct numerical simulations (DNS) of uncontrolled and optimally noise-controlled two-dimensional mixing layers in order to identify the physical mechanism responsible for the noise reduction. The analysis is carried out in the time domain to identify events that are significant in sound generation and which are acted upon by the control. Results show that a triple vortex interaction in the uncontrolled mixing layer radiates high-amplitude pressure waves to the far acoustic field; the elimination of this triple merging accounts for 70% of the noise reduction accomplished by a body force control applied normal to the shear layer. The effect of this control is shown to comprise vertical acceleration of vortical structures; the acceleration, whose action on the structures is convected across the control volume, leads to changes in their relative convection velocities and a consequent regularization of their evolution, which prevents the triple merger. Analysis of a longer time series for the DNS of the uncontrolled mixing layer using a wavelet transform identifies several similar intermittent, noisy events. The sound production mechanism associated with such noisy events can be understood in terms of cancellation disruption in a noncompact source region, such as described by a retarded-potential formalism. This shows that acoustic analogies formulated from the perspective of quadrupole acoustic sources are, in principle, useful for the modeling of such events. However, this study also illustrates the extent to which time-averaged statistical analysis of sound producing flows can mask the most important source activity, suggesting that intermittency should be explicitly modeled in sound prediction methodologies.
Interfacial slippage of inorganic electronic materials on plastic substrates
Authors: Dai Longchao , Feng Xue , Liu Bin , Fang Daining
Published: November 2010

The stretchable and flexible electronics with the structure of inorganic films on plastic substrate has recently attracted an increasing interest. Interfacial failure inevitably occurs when the structure is subject to repeated bending or stretching in application. An analysis is presented in this letter on the slipping failure mechanism for the interface between inorganic film and plastic substrate. The critical radius of system curvature for the slipping crack propagation on its interface is obtained to analyze the bendability of the structure, which can provide the design guideline and characterization method to determine the interface fracture toughness of slipping failure.
Thermophoresis of axially and fore-and-aft symmetric aerosol particles
Authors: Chang Yu C. , Keh Huan J.
Published: November 2010

The thermophoretic motion of an aerosol particle of revolution with fore-and-aft symmetry in a uniformly prescribed temperature gradient normal to its axis of revolution is studied theoretically. The Knudsen number is assumed to be small so that the fluid flow is described by a continuum model. A method of distribution of a set of spherical singularities along the axis of revolution within a prolate particle or on the fundamental plane within an oblate particle is used to find the general solutions for the temperature and fluid velocity fields. The temperature jump and fluid slip conditions at the particle surface are satisfied by applying a boundary collocation technique to these general solutions to determine the unknown coefficients. The thermophoretic velocity of the particle is calculated with good convergence behavior for various cases, and the agreement between our results and the available analytical solutions is very good. It is found that the normalized thermophoretic velocity of a prolate or oblate spheroid perpendicular to its axis of revolution decreases monotonically with an increase in its axial-to-radial aspect ratio. For most practical cases of a spheroid with a specified aspect ratio, its thermophoretic mobility is not a monotonic function of its relative thermal conductivity. For the general problem of a particle with axial and fore-and-aft symmetry undergoing thermophoresis in a temperature gradient oriented arbitrarily with respect to its axis of revolution, the solution of the particle velocity can be obtained as a superposition of the solution obtained previously for the axisymmetric motion of the particle and the current result.
Permeation measurements and modeling of highly defective Al2O3 thin films grown by atomic layer deposition on polymers
Authors: Carcia P. F. , McLean R. S. , Reilly M. H.
Published: November 2010

We measured the thickness and temperature dependence of moisture permeation in highly defective (10–20 at. % hydrogen) Al2O3 thin films grown by atomic layer deposition on polymer substrates. We found that when films were grown at higher temperature or were thicker, independent of growth temperature, they were better moisture barriers. We determined the threshold thickness for measurement-limited barrier performance to be 7.5 nm for growth at 100 °C compared to 9.6 nm at 50 °C. We explained the permeability of these highly defective films with a new model, which relates moisture permeability to a critical density of defects and not due to pinholes.
In vivo and simultaneous multimodal imaging: Integrated multiplex coherent anti-Stokes Raman scattering and two-photon microscopy
Authors: Li Dong , Zheng Wei , Zeng Yan , Qu Jianan Y.
Published: November 2010

Simultaneous multimodal imaging is critical for in vivo study of biological dynamic processes and clinical applications. In this study, we demonstrate a multimodal nonlinear optical (NLO) microscopy of the capability to simultaneously produce images of multiplex coherent anti-Stokes Raman scattering (M-CARS), two-photon excitation fluorescence, and second harmonic generation in living biological systems. The excitation sources are a femtosecond Ti:sapphire laser and a broadband supercontinuum generated from a photonic crystal fiber. The simultaneously excited multiple NLO signals were recorded by using a time- and wavelength-resolved detection technique. In M-CARS imaging, the nonresonant background is effectively reduced by using a simple background subtraction method.
Effects of oxidation on surface chemical states and barrier height of AlGaN/GaN heterostructures
Authors: Higashiwaki Masataka , Chowdhury Srabanti , Swenson Brian L. , Mishra Umesh K.
Published: November 2010

The effects of oxidation on the surface structure and chemical bonding states of AlGaN/GaN heterostructures were investigated using x-ray photoelectron spectroscopy (XPS). In comparing Al 2p core-level XPS spectra among as-grown and annealed samples, we found that Al atoms on the surface were highly oxidized after rapid thermal annealing (RTA) at high temperature; not only in an O2 but also in an N2 gas atmosphere. The Al oxidation level was almost identical for the samples annealed at 800 °C, irrespective of the annealing atmosphere and time; yet there was a strong dependence on the annealing temperature. The dependence of surface barrier height on the annealing condition is associated with Al oxidation behavior. Before the RTA, the barrier height increased together with the AlGaN thickness, indicating an unpinned Fermi level and the existence of low-density and distributed surface donor states. After the high-temperature RTA, however, the height is maintained at a certain value, regardless of the thickness, due to Fermi level pinning by high-density donor states. These results can be explained by the formation of two types of oxide structures providing different types of donor states.
Targeted insertion of cysteine by decoding UGA codons with mammalian selenocysteine machinery
Authors: Xu Xue-Ming , Turanov Anton A. , Carlson Bradley A. , Yoo Min-Hyuk , Everley Robert A. , Nandakumar Renu , Sorokina Irina , Gygi Steven P. , Gladyshev Vadim N. , Hatfield Dolph L.
Published: November 2010

Cysteine (Cys) is inserted into proteins in response to UGC and UGU codons. Herein, we show that supplementation of mammalian cells with thiophosphate led to targeted insertion of Cys at the UGA codon of thioredoxin reductase 1 (TR1). This Cys was synthesized by selenocysteine (Sec) synthase on tRNA
[Ser]Sec
and its insertion was dependent on the Sec insertion sequence element in the 3′UTR of TR1 mRNA. The substrate for this reaction, thiophosphate, was synthesized by selenophosphate synthetase 2 from ATP and sulfide and reacted with phosphoseryl-tRNA
[Ser]Sec
to generate Cys-tRNA
[Ser]Sec
. Cys was inserted in vivo at UGA codons in natural mammalian TRs, and this process was regulated by dietary selenium and availability of thiophosphate. Cys occurred at 10% of the Sec levels in liver TR1 of mice maintained on a diet with normal amounts of selenium and at 50% in liver TR1 of mice maintained on a selenium deficient diet. These data reveal a novel Sec machinery-based mechanism for biosynthesis and insertion of Cys into protein at UGA codons and suggest new biological functions for thiophosphate and sulfide in mammals.
Amygdala regulates risk of predation in rats foraging in a dynamic fear environment
Authors: Choi June-Seek , Kim Jeansok J.
Published: November 2010

In a natural environment, foragers constantly face the risk of encountering predators. Fear is a defensive mechanism evolved to protect animals from danger by balancing the animals’ needs for primary resources with the risk of predation, and the amygdala is implicated in mediating fear responses. However, the functions of fear and amygdala in foraging behavior are not well characterized because of the technical difficulty in quantifying prey–predator interaction with real (unpredictable) predators. Thus, the present study investigated the rat's foraging behavior in a seminaturalistic environment when confronted with a predator-like robot programmed to surge toward the animal seeking food. Rats initially fled into the nest and froze (demonstrating fear) and then cautiously approached and seized the food as a function of decreasing nest−food and increasing food−robot distances. The likelihood of procuring food increased and decreased via lesioning/inactivating and disinhibiting the amygdala, respectively. These results indicate that the amygdala bidirectionally regulates risk behavior in rats foraging in a dynamic fear environment.
α-Dystrobrevin-1 recruits α-catulin to the α1D-adrenergic receptor/dystrophin-associated protein complex signalosome
Authors: Lyssand John S. , Whiting Jennifer L. , Lee Kyung-Soon , Kastl Ryan , Wacker Jennifer L. , Bruchas Michael R. , Miyatake Mayumi , Langeberg Lorene K. , Chavkin Charles , Scott John D. , Gardner Richard G. , Adams Marvin E. , Hague Chris
Published: November 2010

α1D-Adrenergic receptors (ARs) are key regulators of cardiovascular system function that increase blood pressure and promote vascular remodeling. Unfortunately, little information exists about the signaling pathways used by this important G protein-coupled receptor (GPCR). We recently discovered that α1D-ARs form a “signalosome” with multiple members of the dystrophin-associated protein complex (DAPC) to become functionally expressed at the plasma membrane and bind ligands. However, the molecular mechanism by which the DAPC imparts functionality to the α1D-AR signalosome remains a mystery. To test the hypothesis that previously unidentified molecules are recruited to the α1D-AR signalosome, we performed an extensive proteomic analysis on each member of the DAPC. Bioinformatic analysis of our proteomic data sets detected a common interacting protein of relatively unknown function, α-catulin. Coimmunoprecipitation and blot overlay assays indicate that α-catulin is directly recruited to the α1D-AR signalosome by the C-terminal domain of α-dystrobrevin-1 and not the closely related splice variant α-dystrobrevin-2. Proteomic and biochemical analysis revealed that α-catulin supersensitizes α1D-AR functional responses by recruiting effector molecules to the signalosome. Taken together, our study implicates α-catulin as a unique regulator of GPCR signaling and represents a unique expansion of the intricate and continually evolving array of GPCR signaling networks.
Self-organization, condensation, and annihilation of topological vortices and antivortices in a multiferroic
Authors: Chae S. C. , Horibe Y. , Jeong D. Y. , Rodan S. , Lee N. , Cheong S.-W.
Published: November 2010

The interaction among topological defects can induce novel phenomena such as disclination pairs in liquid crystals and superconducting vortex lattices. Nanoscale topological vortices with swirling ferroelectric, magnetic, and structural antiphase relationships were found in multiferroic h-YMnO
3
. Herein, we report the discovery of intriguing, but seemingly irregular configurations of a zoo of topological vortices and antivortices. These configurations can be neatly analyzed in terms of graph theory and reflect the nature of self-organized criticality in complexity phenomena. External stimuli such as chemistry-driven or electric poling can induce the condensation and eventual annihilation of topological vortex–antivortex pairs.
Microbial excavation of solid carbonates powered by P-type ATPase-mediated transcellular Ca
2+
transport
Authors: Garcia-Pichel Ferran , Ramírez-Reinat Edgardo , Gao Qunjie
Published: November 2010

Some microbes, among them a few species of cyanobacteria, are able to excavate carbonate minerals, from limestone to biogenic carbonates, including coral reefs, in a bioerosive activity that directly links biological and geological parts of the global carbon cycle. The physiological mechanisms that enable such endolithic cyanobacteria to bore, however, remain unknown. In fact, their boring constitutes a geochemical paradox, in that photoautotrophic metabolism will tend to precipitate carbonates, not dissolve them. We developed a stable microbe/mineral boring system based on a cyanobacterial isolate, strain BC008, with which to study the process of microbial excavation directly in the laboratory. Measurements of boring into calcite under different light regimes, and an analysis of photopigment content and photosynthetic rates along boring filaments, helped us reject mechanisms based on the spatial or temporal separation of alkali versus Acid-generating metabolism (i.e., photosynthesis and respiration). Instead, extracellular Ca
2+
imaging of boring cultures in vivo showed that BC008 was able to take up Ca
2+
at the excavation front, decreasing the local extracellular ion activity product of calcium carbonate enough to promote spontaneous dissolution there. Intracellular Ca
2+
was then transported away along the multicellular cyanobacterial trichomes and excreted at the distal borehole opening into the external medium. Inhibition assays and gene expression analyses indicate that the uptake and transport was driven by P-type Ca
2+
-ATPases. We believe such a chemically simple and biologically sophisticated mechanism for boring to be unparalleled among bacteria.
Inhibition of Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) signaling in the striatum reverts motor symptoms associated with
l
-dopa–induced dyskinesia
Authors: Fasano Stefania , Bezard Erwan , D'Antoni Angela , Francardo Veronica , Indrigo Marzia , Qin Li , Doveró Sandra , Cerovic Milica , Cenci M. Angela , Brambilla Riccardo
Published: November 2010

l
-dopa–induced dyskinesia (LID) is a common debilitating complication of dopamine replacement therapy in Parkinson's disease. Recent evidence suggests that LID may be linked causally to a hyperactivation of the Ras–ERK signaling cascade in the basal ganglia. We set out to determine whether specific targeting of Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1), a brain-specific activator of the Ras–ERK pathway, may provide a therapy for LID. On the rodent abnormal involuntary movements scale, Ras-GRF1–deficient mice were significantly resistant to the development of dyskinesia during chronic
l
-dopa treatment. Furthermore, in a nonhuman primate model of LID, lentiviral vectors expressing dominant negative forms of Ras-GRF1 caused a dramatic reversion of dyskinesia severity leaving intact the therapeutic effect of
l
-dopa. These data reveal the central role of Ras-GRF1 in governing striatal adaptations to dopamine replacement therapy and validate a viable treatment for LID based on intracellular signaling modulation.