bluuebunny/crossref_metadata_2025 huggingface dataset:
SPONTANEOUS POLARIZATION IN UNCONVENTIONAL Ta2O5 DIELECTRIC CERAMICS BY LASER SINTERING
Authors: JI LINGFEI , JIANG YIJIAN
Published: May 2011

Spontaneous polarization was found in Ta2O5 dielectric ceramics prepared by laser sintering technique. After heat corrosion, 90° and 180° domains in the ceramics was observed by field emission scanning electron micrographs. The crystal structure of the laser-sintered ceramics at RT was determined as monoclinic phase, which indicates the lattice distortion existed in the ceramics. The variation of O-Ta-O bending vibration mode was deduced from the variation of phonon mode at the low wave-number (57 cm-1 and 250 cm-1). The enhancement of effective electric field for tantalum atoms due to the lattice distortion was determined by calculation of charge distribution coefficients. The distortion of crystal structure due to the phase transformation from higher symmetric orthorhombic phase to lower symmetric monoclinic phase explained spontaneous polarization in the laser-sintered Ta2O5 ceramics.
INFLUENCE OF CaF2–4LiF ADDITIVE ON SINTERING AND ENERGY STORAGE PERFORMANCE OF SrTiO3 CERAMICS
Authors: LI YIQIU , LIU HANXING , ZHAO GUANGHUI , XU JING , CUI YUNJIANG , CAO MINGHE , HAO HUA , YU ZHIYONG
Published: May 2011

The CaF2–4LiF additive was added into SrTiO3 ceramics in order to decrease the sintering temperature for compact pulse power application. The crystalline structure, microstructure and energy storage performance of sintered ceramics were studied. Incorporating CaF2–4LiF additive to SrTiO3 ceramics contributes to a notably enhancement of the energy storage density. The great enhancement in energy storage density occurred due to the notable increase in breakdown strength and the refinement of microstructure. With 2 at% additive, the samples exhibited an average breakdown strength of 31.8 kV/mm, and an energy storage density of 1.212 J/cm3 which is about 1.4 times higher than pure SrTiO3 .
Characteristics of La2O3- and Al2O3-Capped HfO2 Dielectric Metal–Oxide–Semiconductor Field-Effect Transistors Fabricated on (110)-Oriented Silicon Substrates
Authors: Iijima Ryosuke , Edge Lisa F. , Bruley John , Paruchuri Vamsi , Takayanagi Mariko
Published: May 2011

The influence of the crystal orientation difference between (100) and (110) silicon substrates on characteristics of La2O3- and Al2O3-capped HfO2 dielectric metal–oxide–semiconductor field-effect transistors has been investigated. We observed that the equivalent oxide thickness of the capped devices varies according to the crystal orientation, indicating that the two substrates are not equal in the gate stack scalability within a sub-nanometer regime. We found that the mobility dependency on the crystal orientation is reduced by additional scattering associated with the capping films, suggesting the difficulty to derive maximum benefit from an inherent difference in the mobility depending on the crystal orientation.
Organic Electrodes Consisting of Dianthratetrathiafulvalene and Fullerene and Their Application in Organic Field Effect Transistors
Authors: Kato Takuji , Origuchi Chikako , Shinoda Masato , Adachi Chihaya
Published: May 2011

A double layer of dianthratetrathiafulvalene (DATTF) and fullerene (C60) on an n++-Si wafer pretreated with n-octyltrichlorosilane exhibited a high electrical conductivity of σ= 0.12 S/cm and was used as source–drain electrodes in organic field effect transistors (OFETs). A simplified OFET device architecture composed of an organic semiconducting active layer and an organic electrode layer was easily fabricated by successive vacuum deposition of organic donor and acceptor layers. It was confirmed that this device configuration is applicable for both p- and n-type FET operation.
Reverse-Tilt-Domain Boundary Wall in a Polymer-Encapsulated Flexible Liquid Crystal Display
Authors: Kim Sun-Kyoung , Lee Ji-Hoon
Published: May 2011

A reverse-tilt-domain boundary wall in a polymer-encapsulated nematic liquid crystal was examined. A boundary wall in which the liquid crystal director was nearly planar midway through the wall was formed during UV polymerization; it remained stable even though the liquid crystal molecules in neighboring domains are nearly vertically aligned. The formation of the boundary wall was found to be suppressed by the oblique irradiation with linearly polarized UV light.
Power Dependent Micro-Photoluminescence of Green-InGaN/GaN Multiple Quantum Wells
Authors: Yim Sang-Youp , Kim Joon Heon , Jeong Mun Seok , Park Seung-Han , Lee Jongmin
Published: May 2011

We report the excitation-power-dependent micro-photoluminescence (micro-PL) of green-InGaN/GaN multiple quantum wells grown on a sapphire substrate. By using a micro-PL imaging technique based on laser scanning confocal microscopy, bright luminescent centers emitting blue, green, and yellow bands were clearly resolved at a low excitation power. With increasing power, in addition, the strong blue-shift of PL bands from all luminescent centers was observed, with a much stronger blue-shift for initial yellow band. We show that the band-tail filling model qualitatively agrees well with our microscopic study revealing the origin of apparent bandwidth-narrowing in macroscopic ensemble PL spectra.
Highly Scalable Vertical Channel Phase Change Random Access Memory
Authors: Kim Kyung Soo , Lee Jongho , Cho Il Hwan
Published: May 2011

A novel vertical channel phase change random access memory (PCRAM) for application in high-density PCRAM technology with high scalability and small unselected cell current is proposed. The channel of the select transistor and the phase change material are integrated in a vertical structure. A side wall process for the self-aligned phase change material is suggested and memory operation is verified by three-dimensional (3D) device simulation. In addition, memory characteristics are compared for different types of select metal–oxide–semiconductor field-effect transistor (MOSFET).
Counteracting effect of TRPC1-associated Ca2+influx on TNF-α-induced COX-2-dependent prostaglandin E2production in human colonic myofibroblasts
Authors: Hai Lin , Kawarabayashi Yasuhiro , Imai Yuko , Honda Akira , Inoue Ryuji
Published: May 2011

TNF-α-NF-κB signaling plays a central role in inflammation, apoptosis, and neoplasia. One major consequence of this signaling in the gut is increased production of prostaglandin E2(PGE2) via cyclooxygenase-2 (COX-2) induction in myofibroblasts, which has been reported to be dependent on Ca2+. In this study, we explored a potential role of canonical transient receptor potential (TRPC) proteins in this Ca2+-mediated signaling using a human colonic myofibroblast cell line CCD-18Co. In CCD-18Co cell, treatment with TNF-α greatly enhanced Ca2+influx induced by store depletion along with increased cell-surface expression of TRPC1 protein (but not of the other TRPC isoforms) and induction of a Gd3+-sensitive nonselective cationic conductance. Selective inhibition of TRPC1 expression by small interfering RNA (siRNA) or functionally effective TRPC1 antibody targeting the near-pore region of TRPC1 (T1E3) antagonized the enhancement of store-dependent Ca2+influx by TNF-α, whereas potentiated TNF-α induced PGE2production. Overexpression of TRPC1 in CCD-18Co produced opposite consequences. Inhibitors of NF-κB (curcumin, SN-50) attenuated TNF-α-induced enhancement of TRPC1 expression, store-dependent Ca2+influx, and COX-2-dependent PGE2production. In contrast, inhibition of calcineurin-nuclear factor of activated T-cell proteins (NFAT) signaling by FK506 or NFAT Activation Inhibitor III enhanced the PGE2production without affecting TRPC1 expression and the Ca2+influx. Finally, the suppression of store-dependent Ca2+influx by T1E3 antibody or siRNA knockdown significantly facilitated TNF-α-induced NF-κB nuclear translocation. In aggregate, these results strongly suggest that, in colonic myofibroblasts, NF-κB and NFAT serve as important positive and negative transcriptional regulators of TNF-α-induced COX-2-dependent PGE2production, respectively, at the downstream of TRPC1-associated Ca2+influx.
cAMP-guanine exchange factor protection from bile acid-induced hepatocyte apoptosis involves glycogen synthase kinase regulation of c-Jun NH2-terminal kinase
Authors: Johnston A. , Ponzetti K. , Anwer M. S. , Webster C. R. L.
Published: May 2011

Cholestatic liver disorders are accompanied by the hepatic accumulation of cytotoxic bile acids that induce cell death. Increases in cAMP protect hepatocytes from bile acid-induced apoptosis by a cAMP-guanine exchange factor (cAMP-GEF)/phosphoinositide-3-kinase (PI3K)/Akt pathway. The aim of these studies was to identify the downstream substrate in this pathway and to determine at what level in the apoptotic cascade cytoprotection occurs. Since inhibitory phosphorylation of glycogen synthase kinase-3 (GSK) occurs downstream of PI3K/Akt and this phosphorylation has been implicated in cell survival, we conducted studies to determine whether GSK was downstream in cAMP-GEF/PI3K/Akt-mediated cytoprotection. Our results show that treatment of hepatocytes with the cAMP-GEF-specific analog, 4-(4-chlorophenylthio)-2′- O-methyladenosine-3′,5′-cAMP, results in PI3K-dependent phosphorylation of GSK. Direct chemical inhibition of GSK in rat hepatocytes or human HUH7-NTCP cells with several structurally and functionally distinct inhibitors including bromoindirubin-3′-oxime (BIO), maleimides (SB216763, SB415286), thiadiazolidine derivatives, and LiCl attenuates apoptosis induced by glycochenodeoxycholate (GCDC). In addition, genetic silencing of the GSK β isoform with small interfering RNA attenuates GCDC apoptosis in HUH7-NTCP cells. Adenoviral inhibition of the Rap1 blocks both cAMP-GEF-mediated cytoprotection against GCDC-induced apoptosis and Akt/GSK3β phosphorylation. GCDC-induced phosphorylation of the proapoptotic kinase, c-Jun NH2-terminal kinase (JNK) is inhibited by GSK inhibition or cAMP-GEF activation. GCDC-induced apoptosis is accompanied by phosphorylation of the endoplasmic reticulum stress markers pIEF2α and IRE-1, and pretreatment with the cAMP-GEF analog or GSK inhibitors prevents this phosphorylation. Collectively, our results support the presence of a cAMP/cAMP-GEF/Rap1/PI3K/Akt/GSKβ survival pathway in hepatocytes that inhibits bile acid-induced JNK phosphorylation.
Catalase overexpression in aortic smooth muscle prevents pathological mechanical changes underlying abdominal aortic aneurysm formation
Authors: Maiellaro-Rafferty Kathryn , Weiss Daiana , Joseph Giji , Wan William , Gleason Rudolph L. , Taylor W. Robert
Published: May 2011

The causality of the associations between cellular and mechanical mechanisms of abdominal aortic aneurysm (AAA) formation has not been completely defined. Because reactive oxygen species are established mediators of AAA growth and remodeling, our objective was to investigate oxidative stress-induced alterations in aortic biomechanics and microstructure during subclinical AAA development. We investigated the mechanisms of AAA in an angiotensin II (ANG II) infusion model of AAA in apolipoprotein E-deficient (apoE−/−) mice that overexpress catalase in vascular smooth muscle cells (apoE−/−xTgSMC-Cat). At baseline, aortas from apoE−/−xTgSMC-Cat exhibited increased stiffness and the microstructure was characterized by 50% more collagen content and less elastin fragmentation. ANG II treatment for 7 days in apoE−/− mice altered the transmural distribution of suprarenal aortic circumferential strain (quantified by opening angle, which increased from 130 ± 1° at baseline to 198 ± 8° after 7 days of ANG II treatment) without obvious changes in the aortic microstructure. No differences in aortic mechanical behavior or suprarenal opening angle were observed in apoE−/−xTgSMC-Cat after 7 days of ANG II treatment. These data suggest that at the earliest stages of AAA development H2O2 is functionally important and is involved in the control of local variations in remodeling across the vessel wall. They further suggest that reduced elastin integrity at baseline may predispose the abdominal aorta to aneurysmal mechanical remodeling.
AMPKα2deficiency uncovers time dependency in the regulation of contraction-induced palmitate and glucose uptake in mouse muscle
Authors: Abbott Marcia J. , Bogachus Lindsey D. , Turcotte Lorraine P.
Published: May 2011

AMP-activated protein kinase (AMPK) is a fuel sensor in skeletal muscle with multiple downstream signaling targets that may be triggered by increases in intracellular Ca2+concentration ([Ca2+]). The purpose of this study was to determine whether increases in intracellular [Ca2+] induced by caffeine act solely via AMPKα2and whether AMPKα2is essential to increase glucose uptake, fatty acid (FA) uptake, and FA oxidation in contracting skeletal muscle. Hindlimbs from wild-type (WT) or AMPKα2dominant-negative (DN) transgene mice were perfused during rest ( n = 11), treatment with 3 mM caffeine ( n = 10), or muscle contraction ( n = 11). Time-dependent effects on glucose and FA uptake were uncovered throughout the 20-min muscle contraction perfusion period ( P < 0.05). Glucose uptake rates did not increase in DN mice during muscle contraction until the last 5 min of the protocol ( P < 0.05). FA uptake rates were elevated at the onset of muscle contraction and diminished by the end of the protocol in DN mice ( P < 0.05). FA oxidation rates were abolished in the DN mice during muscle contraction ( P < 0.05). The DN transgene had no effect on caffeine-induced FA uptake and oxidation ( P > 0.05). Glucose uptake rates were blunted in caffeine-treated DN mice ( P < 0.05). The DN transgene resulted in a greater use of intramuscular triglycerides as a fuel source during muscle contraction. The DN transgene did not alter caffeine- or contraction-mediated changes in the phosphorylation of Ca2+/calmodulin-dependent protein kinase I or ERK1/2 ( P > 0.05). These data suggest that AMPKα2is involved in the regulation of substrate uptake in a time-dependent manner in contracting muscle but is not necessary for regulation of FA uptake and oxidation during caffeine treatment.
Relaxin regulates vascular wall remodeling and passive mechanical properties in mice
Authors: Debrah Dan O. , Debrah Julianna E. , Haney Jamie L. , McGuane Jonathan T. , Sacks Michael S. , Conrad Kirk P. , Shroff Sanjeev G.
Published: May 2011

Administration of recombinant human relaxin (rhRLX) to conscious rats increases global arterial compliance, and small renal arteries (SRA) isolated from these rats demonstrate increased passive compliance. Here we characterize relaxin-induced vascular remodeling and examine its functional relevance. SRA and external iliac arteries (EIA) were examined in rhRLX-treated (1.0 μg/h for 5 days) and relaxin knockout mice. Arterial geometric remodeling and compositional remodeling were quantified using immunohistochemical and biochemical techniques. Vascular mechanical properties were quantified using an ex vivo preparation wherein pressure-diameter data were obtained at various axial lengths. Compared with vehicle-treated mice, SRA from rhRLX-treated mice showed outward geometric remodeling (increased unstressed wall area and wall-to-lumen area ratio), increased smooth muscle cell (SMC) density, reduction in collagen-to-total protein ratio, and unchanged elastin-to-tissue dry weight ratio. Compared with wild-type mice, relaxin knockout mice exhibited the opposite pattern: decreased unstressed wall area and wall-to-lumen area ratio, decreased SMC density, and increased collagen-to-total protein ratio. Although tissue biaxial strain energy of SRA was not different between rhRLX- and vehicle-treated groups at low-to-physiological circumferential and axial strains, it was lower for the rhRLX-treated group at the highest circumferential strain. In contrast to SRA, relaxin administration was not associated with any vascular remodeling or changes in passive mechanics of EIA. Thus relaxin induces both geometric and compositional remodeling in vessel-specific manner. Relaxin-induced geometric remodeling of SRA is responsible for the increase in passive compliance under low-to-physiological levels of circumferential and axial strains, and compositional remodeling becomes functionally relevant only under high circumferential strain.
Differential responses of targeted lung redox enzymes to rat exposure to 60 or 85% oxygen
Authors: Gan Zhuohui , Roerig David L. , Clough Anne V. , Audi Said H.
Published: May 2011

Rat exposure to 60% O2(hyper-60) or 85% O2(hyper-85) for 7 days confers susceptibility or tolerance, respectively, of the otherwise lethal effects of exposure to 100% O2. The objective of this study was to determine whether activities of the antioxidant cytosolic enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and mitochondrial complex III are differentially altered in hyper-60 and hyper-85 lungs. Duroquinone (DQ), an NQO1 substrate, or its hydroquinone (DQH2), a complex III substrate, was infused into the arterial inflow of isolated, perfused lungs, and the venous efflux rates of DQH2and DQ were measured. Based on inhibitor effects and kinetic modeling, capacities of NQO1-mediated DQ reduction ( Vmax1) and complex III-mediated DQH2oxidation ( Vmax2) increased by ∼140 and ∼180% in hyper-85 lungs, respectively, compared with rates in lungs of rats exposed to room air (normoxic). In hyper-60 lungs, Vmax1increased by ∼80%, with no effect on Vmax2. Additional studies revealed that mitochondrial complex I activity in hyper-60 and hyper-85 lung tissue homogenates was ∼50% lower than in normoxic lung homogenates, whereas mitochondrial complex IV activity was ∼90% higher in only hyper-85 lung tissue homogenates. Thus NQO1 activity increased in both hyper-60 and hyper-85 lungs, whereas complex III activity increased in hyper-85 lungs only. This increase, along with the increase in complex IV activity, may counter the effects the depression in complex I activity might have on tissue mitochondrial function and/or reactive oxygen species production and may be important to the tolerance of 100% O2observed in hyper-85 rats.
Integrated, Genome-Wide Screening for Hypomethylated Oncogenes in Salivary Gland Adenoid Cystic Carcinoma
Authors: Shao Chunbo , Sun Wenyue , Tan Marietta , Glazer Chad A. , Bhan Sheetal , Zhong Xiaoli , Fakhry Carole , Sharma Rajni , Westra William H. , Hoque Mohammad O. , Moskaluk Christopher A. , Sidransky David , Califano Joseph A. , Ha Patrick K.
Published: May 2011

Purpose: Salivary gland adenoid cystic carcinoma (ACC) is a rare malignancy that is poorly understood. To look for relevant oncogene candidates under the control of promoter methylation, an integrated, genome-wide screen was conducted.

Experimental Design: Global demethylation of normal salivary gland cell strains using 5-aza-2′-deoxycytidine (5-aza-dC) and trichostatin A (TSA), followed by expression array analysis was conducted. ACC-specific expression profiling was generated using expression microarray analysis of primary ACC and normal samples. Next, the two profiles were integrated to identify a subset of genes for further validation of promoter demethylation in ACC versus normal. Finally, promising candidates were further validated for mRNA, protein, and promoter methylation levels in larger ACC cohorts. Functional validation was then conducted in cancer cell lines.

Results: We found 159 genes that were significantly re-expressed after 5-aza-dC/TSA treatment and overexpressed in ACC. After initial validation, eight candidates showed hypomethylation in ACC: AQP1, CECR1, C1QR1, CTAG2, P53AIP1, TDRD12, BEX1, and DYNLT3. Aquaporin 1 (AQP1) showed the most significant hypomethylation and was further validated. AQP1 hypomethylation in ACC was confirmed with two independent cohorts. Of note, there was significant overexpression of AQP1 in both mRNA and protein in the paraffin-embedded ACC cohort. Furthermore, AQP1 was upregulated in 5-aza-dC/TSA–treated SACC83. Finally, AQP1 promoted cell proliferation and colony formation in SACC83.

Conclusions: Our integrated, genome-wide screening method proved to be an effective strategy for detecting novel oncogenes in ACC. AQP1 is a promising oncogene candidate for ACC and is transcriptionally regulated by promoter hypomethylation. Clin Cancer Res; 17(13); 4320–30. ©2011 AACR.
Expression Signatures of the Lipid-Based Akt Inhibitors Phosphatidylinositol Ether Lipid Analogues in NSCLC Cells
Authors: Zhang Chunyu , Elkahloun Abdel G. , Liao Hongling , Delaney Shannon , Saber Barbara , Morrow Betsy , Prendergast George C. , Hollander M. Christine , Gills Joell J. , Dennis Phillip A.
Published: May 2011

Activation of the serine/threonine kinase Akt contributes to the formation, maintenance, and therapeutic resistance of cancer, which is driving development of compounds that inhibit Akt. Phosphatidylinositol ether lipid analogues (PIA) are analogues of the products of phosphoinositide-3-kinase (PI3K) that inhibit Akt activation, translocation, and the proliferation of a broad spectrum of cancer cell types. To gain insight into the mechanism of PIAs, time-dependent transcriptional profiling of five active PIAs and the PI3K inhibitor LY294002 (LY) was conducted in non–small cell lung carcinoma cells using high-density oligonucleotide arrays. Gene ontology analysis revealed that genes involved in apoptosis, wounding response, and angiogenesis were upregulated by PIAs, whereas genes involved in DNA replication, repair, and mitosis were suppressed. Genes that exhibited early differential expression were partitioned into three groups; those induced by PIAs only (DUSP1, KLF6, CENTD2, BHLHB2, and PREX1), those commonly induced by PIAs and LY (TRIB1, KLF2, RHOB, and CDKN1A), and those commonly suppressed by PIAs and LY (IGFBP3, PCNA, PRIM1, MCM3, and HSPA1B). Increased expression of the tumor suppressors RHOB (RhoB), KLF6 (COPEB), and CDKN1A (p21Cip1/Waf1) was validated as an Akt-independent effect that contributed to PIA-induced cytotoxicity. Despite some overlap with LY, active PIAs have a distinct expression signature that contributes to their enhanced cytotoxicity. Mol Cancer Ther; 10(7); 1137–48. ©2011 AACR.
NFBD1/MDC1 Regulates Cav1 and Cav2 Independently of DNA Damage and p53
Authors: Wilson Kathleen A. , Colavito Sierra A. , Schulz Vincent , Wakefield Patricia Heffernan , Sessa William , Tuck David , Stern David F.
Published: May 2011

NFBD1/MDC1 is involved in DNA damage checkpoint signaling and DNA repair. NFBD1 binds to the chromatin component γH2AX at sites of DNA damage, causing amplification of ataxia telangiectasia-mutated gene (ATM) pathway signaling and recruitment of DNA repair factors. Residues 508–995 of NFBD1 possess transactivation activity, suggesting a possible role of NFBD1 in transcription. Furthermore, NFBD1 influences p53-mediated transcription in response to adriamycin. We sought to determine the role of NFBD1 in ionizing radiation (IR)–responsive transcription and if NFBD1 influences transcription independently of p53.

Using microarray analysis, we identified genes altered upon NFBD1 knockdown. Surprisingly, most NFBD1 regulated genes are regulated in both the absence and presence of IR, thus pointing toward a novel function for NFBD1 outside of the DNA damage response. Furthermore, NFBD1 knockdown regulated genes mostly independent of p53 knockdown. These genes are involved in pathways including focal adhesion signaling, carbohydrate metabolism, and insulin signaling.

We found that CAV1 and CAV2 mRNA and protein levels are reduced by both NFBD1 knockdown and knockout independently of IR and p53. NFBD1-depleted cells exhibit some similar phenotypes to Cav1-depleted cells. Furthermore, like Cav1-depletion, NFBD1 shRNA increases Erk phosphorylation. Thus, Cav1 could act as a mediator of the DNA-damage independent effects of NFBD1 in mitogenic signaling. Mol Cancer Res; 9(6); 766–81. ©2011 AACR.
Does a More Specified Version of the HoNOS (Health of the Nation Outcome Scales) Increase Psychometric Properties of the Inventory?
Authors: Andreas Sylke , Rabung Sven , Mestel Robert , Koch Uwe , Hausberg Maria , Schulz Holger
Published: May 2011

Background: The Health of the Nation Outcome Scales (HoNOS) is a clinician-rated instrument for the differentiated measurement of severity in patients with mental disorder. Item 8 of the instrument, assessing ‘Other mental and behavioral problems’, is particularly relevant for patients with affective disorders, anxiety disorders, and eating and personality disorders. However, some studies have shown that the scale possesses unsatisfactory psychometric properties. The objective of the present study was therefore to validate the psychometric properties of a more specified version of the HoNOS-D item 8. Methods: The instrument’s reliability and validity were tested using a large, representative, clinical sample of patients with mental disorders (study 1: n = 1,918 and n = 1,357). Additional tests of reliability and criterion validity were performed using a further clinical sample of patients with mental disorders (study 2: N = 55). Results: The extended version of the HoNOS provides a differentiated picture of additional problem areas for the patient. Although inter-rater reliability indicates a need for more detailed instructions, the problem areas of item 8 proved on the whole to be suitable for measuring the extent and severity of mental problems that are present in addition to the primary problem. Conclusion: In order to make the extended assessment of the HoNOS useful for clinical routine practice, a supplemental glossary is needed.
Activation of the ERK1/2 Mitogen-Activated Protein Kinase Cascade by Dentin Matrix Protein 1 Promotes Osteoblast Differentiation
Authors: Eapen Asha , Ramachandran Amsaveni , Pratap Jitesh , George Anne
Published: May 2011

DMP1 has been shown to play many roles in osteogenesis. We recently demonstrated that calcium-mediated stress kinase activation by DMP1 leads to osteoblast differentiation. In this study we demonstrate that DMP1 can also activate the extracellular signal-regulated kinase (ERK)-MAPK pathway. This activation was mediated through the RGD integrin-binding domain in DMP1. Further, we demonstrate that Runx2, an essential transcription factor, is stimulated by the ERK-MAPK pathway.
Antennal-Lobe Organization in Desert Ants of the Genus Cataglyphis
Authors: Stieb Sara Mae , Kelber Christina , Wehner Rüdiger , Rössler Wolfgang
Published: May 2011

Desert ants of the genus Cataglyphis possess remarkable visual navigation capabilities. Although Cataglyphis species lack a trail pheromone system, Cataglyphis fortis employs olfactory cues for detecting nest and food sites. To investigate potential adaptations in primary olfactory centers of the brain of C. fortis, we analyzed olfactory glomeruli (odor processing units) in their antennal lobes and compared them to glomeruli in different Cataglyphis species. Using confocal imaging and 3D reconstruction, we analyzed the number, size and spatial arrangement of olfactory glomeruli in C. fortis, C.albicans, C.bicolor, C.rubra, and C.noda. Workers of all Cataglyphis species have smaller numbers of glomeruli (198–249) compared to those previously found in olfactory-guided ants. Analyses in 2 species of Formica – a genus closely related to Cataglyphis – revealed substantially higher numbers of olfactory glomeruli (c. 370), which is likely to reflect the importance of olfaction in these wood ant species. Comparisons between Cataglyphis species revealed 2 special features in C. fortis. First, with c. 198 C. fortis has the lowest number of glomeruli compared to all other species. Second, a conspicuously enlarged glomerulus is located close to the antennal nerve entrance. Males of C. fortis possess a significantly smaller number of glomeruli (c. 150) compared to female workers and queens. A prominent male-specific macroglomerulus likely to be involved in sex pheromone communication occupies a position different from that of the enlarged glomerulus in females. The behavioral significance of the enlarged glomerulus in female workers remains elusive. The fact that C. fortis inhabits microhabitats (salt pans) that are avoided by all other Cataglyphis species suggests that extreme ecological conditions may not only have resulted in adaptations of visual capabilities, but also in specializations of the olfactory system.
Neuronal Responses to Looming Objects in the Superior Colliculus of the Cat
Authors: Liu Yong-Jun , Wang Qian , Li Bing
Published: May 2011

The superior colliculus (SC) in the mammalian mesencephalon is involved in avoidance or escape behaviors, but little is known about the response properties of collicular neurons to an object approaching on a collision course towards the animal. The present study identified two classes of looming-sensitive neurons, rho and eta cells, in the SC of the cat, but did not find any tau cell, which has been observed in the pigeon tectofugal pathway. The looming responses were characterized by distinct firing patterns, in which the neuronal discharge steadily increased as the object was approaching, and peaked approximately at the time of collision (rho cell) or some time earlier (eta cell). The response onset time of both rho and eta cells was linearly related to the square root of the diameter/velocity ratio of looming objects; whereas for eta cells, the response peak time was linearly related to the diameter/velocity ratio. The receptive fields of these collicular cells were composed of an excitatory center and a suppressive surround, but the occurrence and development of neuronal responses to looming stimuli were independent of the receptive-field organization. Although the cell number was relatively small in the deep layers of the SC, the proportion of looming-sensitive neurons was close to that in the superficial layers. These results suggest that a population of collicular cells is involved in signaling impending collision of a looming object with the animal and the neural mechanisms underlying the collision avoidance behaviors are to some extent conservative across species from insects to mammals.
A Detailed Cardiovascular Characterization of Obesity Without the Metabolic Syndrome
Authors: Lind Lars , Siegbahn Agneta , Ingelsson Erik , Sundström Johan , Ärnlöv Johan
Published: May 2011

Objective—

Although obesity without metabolic disturbances has been regarded as harmless, we have recently shown that obese subjects without the metabolic syndrome (MetS) has an increased risk of cardiovascular (CV) disorders and mortality during long-term follow-up. To investigate the basis for that increased risk, we studied the impact of obesity without MetS on multiple markers of subclinical CV disease.

Methods and Results—

At age 70, 1016 subjects were investigated in the Prospective Investigation of the Vasculature in Uppsala Seniors study. According to body mass index (BMI)/MetS status, they were categorized as normal weight (BMI <25 kg/m
2
) without MetS (National Cholesterol Education Program criteria, n=319), normal weight with MetS (n=19), overweight (BMI 25 to 29.9 kg/m
2
) without MetS (n=333), overweight with MetS (n=94), obese (BMI ≥30 kg/m
2
) without MetS (n=102), and obese with MetS (n=118). Several different measurements of endothelial reactivity, arterial compliance (plethysmography and ultrasound), carotid artery atherosclerosis, and echocardiography were performed, and 7 markers of coagulation/fibrinolysis were measured. Subjects with obesity without MetS showed impaired vasoreactivity, a more echolucent carotid artery wall, increased left ventricular mass and function together with impaired coagulation/fibrinolysis compared with normal-weight subjects without the MetS (
P
<0.05 to 0.001). The majority of these disturbances were also seen in overweight subjects without the MetS.

Conclusion—

In contrast to some previous studies, our data do not support that obesity without MetS is a benign condition, because obesity without MetS was associated with impairments in multiple markers of subclinical CV disease. This was also the case for overweight subjects without the MetS.
Hepatic Steatosis, Obesity, and the Metabolic Syndrome Are Independently and Additively Associated With Increased Systemic Inflammation
Authors: Ndumele Chiadi E. , Nasir Khurram , Conceiçao Raquel D. , Carvalho Jose A.M. , Blumenthal Roger S. , Santos Raul D.
Published: May 2011

Objective—

The goal of this study was to assess the independent and collective associations of hepatic steatosis, obesity, and the metabolic syndrome with elevated high-sensitivity C-reactive protein (hs-CRP) levels.

Methods and Results—

We evaluated 2388 individuals without clinical cardiovascular disease between December 2004 and December 2006. Hepatic steatosis was diagnosed by ultrasound, and the metabolic syndrome was defined using National Heart, Lung, and Blood Institute criteria. The cut point of ≥3 mg/L was used to define high hs-CRP. Multivariate logistic regression was used to assess the independent and collective associations of hepatic steatosis, obesity, and the metabolic syndrome with high hs-CRP. Steatosis was detected in 32% of participants, 23% met criteria for metabolic syndrome, and 17% were obese. After multivariate regression, hepatic steatosis (odds ratio [OR] 2.07; 95% CI 1.68 to 2.56), obesity (OR 3.00; 95% CI 2.39 to 3.80), and the metabolic syndrome (2.39; 95% CI 1.88 to 3.04) were all independently associated with high hs-CRP. Combinations of these factors were associated with an additive increase in the odds of high hs-CRP, with individuals with 1, 2, and 3 factors having ORs for high hs-CRP of 1.92 (1.49 to 2.48), 3.38 (2.50 to 4.57), and 4.53 (3.23 to 6.35), respectively.

Conclusion—

Hepatic steatosis, obesity, and the metabolic syndrome are independently and additively associated with increased odds of high hs-CRP levels.
Pannexin1 Regulates α1-Adrenergic Receptor– Mediated Vasoconstriction
Authors: Billaud Marie , Lohman Alexander W. , Straub Adam C. , Looft-Wilson Robin , Johnstone Scott R. , Araj Christina A. , Best Angela K. , Chekeni Faraaz B. , Ravichandran Kodi S. , Penuela Silvia , Laird Dale W. , Isakson Brant E.
Published: May 2011

Rationale:

The coordination of vascular smooth muscle cell constriction plays an important role in vascular function, such as regulation of blood pressure; however, the mechanism responsible for vascular smooth muscle cell communication is not clear in the resistance vasculature. Pannexins (Panx) are purine-releasing channels permeable to the vasoconstrictor ATP and thus may play a role in the coordination of vascular smooth muscle cell constriction.

Objective:

We investigated the role of pannexins in phenylephrine- and KCl-mediated constriction of resistance arteries.

Methods and Results:

Western blot, immunohistochemistry, and immunogold labeling coupled to scanning and transmission electron microscopy revealed the presence of Panx1 but not Panx2 or Panx3 in thoracodorsal resistance arteries. Functionally, the contractile response of pressurized thoracodorsal resistance arteries to phenylephrine was decreased significantly by multiple Panx inhibitors (mefloquine, probenecid, and
10
Panx1), ectonucleotidase (apyrase), and purinergic receptor inhibitors (suramin and reactive blue-2). Electroporation of thoracodorsal resistance arteries with either Panx1-green fluorescent protein or Panx1 small interfering RNA showed enhanced and decreased constriction, respectively, in response to phenylephrine. Lastly, the Panx inhibitors did not alter constriction in response to KCl. This result is consistent with coimmunoprecipitation experiments from thoracodorsal resistance arteries, which suggested an association between Panx1 and α1D-adrenergic receptor.

Conclusions:

Our data demonstrate for the first time a key role for Panx1 in resistance arteries by contributing to the coordination of vascular smooth muscle cell constriction and possibly to the regulation of blood pressure.
Beta 2 Microglobulin and the Risk for Cardiovascular Events in Patients With Asymptomatic Carotid Atherosclerosis
Authors: Amighi Jasmin , Hoke Matthias , Mlekusch Wolfgang , Schlager Oliver , Exner Markus , Haumer Markus , Pernicka Elisabeth , Koppensteiner Renate , Minar Erich , Rumpold Helmut , Schillinger Martin , Wagner Oswald
Published: May 2011

Background and Purpose—

Atherosclerosis is a chronic inflammatory disease. Ongoing inflammation is associated with elevated levels of beta 2 microglobulin (B2M). We investigated B2M levels in a large cohort of patients with carotid atherosclerosis for the occurrence of major adverse cardiovascular events.

Methods—

One thousand five of 1286 consecutive, neurologically asymptomatic patients with carotid atherosclerosis were followed for a median of 3 years (interquartile range, 2.5 to 3.5) for the occurrence of major adverse cardiovascular events, a composite of myocardial infarction, percutaneous coronary intervention, coronary bypass graft, stroke, and death.

Results—

We recorded 359 major cardiovascular events in 271 (27%) patients. B2M was significantly associated with the occurrence of major adverse cardiovascular events. With increasing quartiles of B2M, the adjusted hazard ratios were 1.19 (95% CI, 0.81 to 1.73), 1.51 (95% CI, 1.05 to 2.18), and 1.88 (95% CI, 1.26 to 2.79) compared with the lowest quartile, respectively (
P
<0.001). Adjusted hazard ratios for the occurrence of death, myocardial infarction, and stroke for increasing quartiles of B2M were 1.25 (95% CI, 0.92 to 1.70), 1.52 (95% CI, 1.12 to 2.06), and 1.62 (95% CI, 1.16 to 2.67) compared with the lowest quartile, respectively (
P
<0.001). Through statistical estimation of improvement in risk stratification, addition of B2M to baseline risk factors improved the risk stratification for major cardiovascular events, at least as much as high-sensitivity C-reactive protein or even better.

Conclusions—

B2M was independently and significantly associated with adverse cardiovascular outcome in patients with prevalent asymptomatic carotid atherosclerosis.
Phosphatidylinositol-3-Kinase Gamma Plays a Central Role in Blood–Brain Barrier Dysfunction in Acute Experimental Stroke
Authors: Jin Rong , Song Zifang , Yu Shiyong , Piazza Abigail , Nanda Anil , Penninger Josef M. , Granger D. Neil , Li Guohong
Published: May 2011

Background and Purpose—

Phosphoinositide 3-kinase (PI3K)-γ is linked to inflammation and oxidative stress. This study was conducted to investigate the role of the PI3Kγ in the blood–brain barrier dysfunction and brain damage induced by focal cerebral ischemia/reperfusion.

Methods—

Wild-type and PI3Kγ knockout mice were subjected to middle cerebral artery occlusion (60 minutes) followed by reperfusion. Evans blue leakage, brain edema, infarct volumes, and neurological deficits were examined. Oxidative stress, neutrophil infiltration, and matrix metallopeptidase-9 were assessed. Activation of nuclear factor-κB and expression of proinflammatory and pro-oxidative genes were studied.

Results—

PI3Kγ deficiency significantly reduced blood–brain barrier permeability and brain edema formation, which were time-dependently correlated with preventing the degradation of the tight junction protein, claudin-5, and the basal lamina protein, collagen IV, and the phosphorylation of myosin light chain in brain microvessels. PI3Kγ deficiency suppressed ischemia/reperfusion-induced nuclear factor-κB p65 (Ser536) phosphorylation and the expression of the pro-oxidant enzyme NADPH oxidase (Nox1, Nox2, and Nox4) and proinflammatory adhesion molecules (E- and P-selectin, intercellular adhesion molecule-1) at different time points. These molecular changes were associated with significant inhibition of oxidative stress (superoxide production and malondialdehyde content), neutrophil infiltration, and matrix metallopeptidase-9 expression/activity in PI3Kγ knockout mice. Eventually, PI3Kγ deficiency significantly reduced infarct volumes and neurological scores at 24 hours after ischemia/reperfusion.

Conclusions—

Our results provide the first direct demonstration that PI3Kγ plays a significant role in ischemia/reperfusion-induced blood–brain barrier disruption and brain damage. Future studies need to explore PI3Kγ as a potential target for stroke therapy.
Using Administrative Databases to Calculate Framingham Scores Within a Large Health Care Organization
Authors: Ekundayo Olaniyi James , Vassar Stefanie D. , Williams Linda S. , Bravata Dawn M. , Cheng Eric M.
Published: May 2011

Background and Purpose—

Framingham calculators are typically implemented in 1-on-1 settings to determine if a patient is at high risk for development of cardiovascular disease in the next 10 years. Because health care administrative datasets are including more clinical information, we explored how well administrative data-derived Framingham scores could identify persons who would have stroke develop in the next year.

Methods—

Using a nested case-control design, we compared all 313 persons who had a first-time stroke at 5 Veterans Administration Medical Centers with a random sample of 25 361 persons who did not have a first-time stroke in 2008. We compared Framingham scores and risk using administrative data available at the end of 2007.

Results—

Stroke patients had higher risk profile than controls: older age, higher systolic blood pressure and total cholesterol, more likely to have diabetes, cardiovascular disease, left ventricular hypertrophy, and more likely to use treatment for blood pressure (
P
<0.05). The mean Framingham generalized cardiovascular disease score (18.0 versus 14.5) as well as the mean Framingham stroke-specific score (13.2 versus 10.2) was higher for stroke cases than controls (both
P
<0.0001). The c-statistic for the generalized cardiovascular disease score was 0.68 (95% CI, 0.65–0.70) and for the stroke score was 0.64 (95% CI, 0.62–0.67).

Conclusions—

Persons who had a stroke develop in the next year had a worse Framingham risk profile, as determined by administrative data. Future studies should examine how to improve the stroke predictive tools and to identify the appropriate populations and uses for applying stroke risk predictive tools.
Understanding Reasons for Delay in Seeking Acute Stroke Care in an Underserved Urban Population
Authors: Hsia Amie W. , Castle Amanda , Wing Jeffrey J. , Edwards Dorothy F. , Brown Nina C. , Higgins Tara M. , Wallace Jasmine L. , Koslosky Sara S. , Gibbons M. Chris , Sánchez Brisa N. , Fokar Ali , Shara Nawar , Morgenstern Lewis B. , Kidwell Chelsea S.
Published: May 2011

Background and Purpose—

Few patients arrive early enough at hospitals to be eligible for emergent stroke treatment. There may be barriers specific to underserved, urban populations that need to be identified before effective educational interventions to reduce delay times can be developed.

Methods—

A survey of respondents' likely action in a hypothetical stroke situation was given to 253 community volunteers in the catchment areas of a large urban community hospital. Concurrently, 100 structured interviews were conducted in the same hospital with patients with acute stroke or a proxy.

Results—

In this predominantly urban, black population, if faced with a hypothetical stroke, 89% of community volunteers surveyed said they would call 911 first, and few felt any of the suggested potential barriers applied to them. However, only 12% of patients with stroke interviewed actually called 911 first (OR, 63.9; 95% CI, 29.5 to 138.2). Instead, 75% called a relative/friend. Eighty-nine percent of patients with stroke reported significant delay in seeking medical attention, and almost half said the reason for the delay was thinking the symptoms were not serious and/or they would self-resolve. For those arriving by ambulance, only 25% did so because they thought it would be faster, whereas 35% cited having no other transportation options.

Conclusions—

In this predominantly black urban population, although 89% of community volunteers report the intent of calling 911 during a stroke, only 12% of actual patients with stroke did so. Further research is needed to determine and conquer the barriers between behavioral intent and actual behavior to call 911 for witnessed stroke.
Trigger Factors and Their Attributable Risk for Rupture of Intracranial Aneurysms
Authors: Vlak Monique H.M. , Rinkel Gabriel J.E. , Greebe Paut , van der Bom Johanna G. , Algra Ale
Published: May 2011

Background and Purpose—

Little is known about activities that trigger rupture of an intracranial aneurysm. Knowledge on what triggers aneurysmal rupture increases insight into the pathophysiology and facilitates development of prevention strategies. We therefore aimed to identify and quantify trigger factors for aneurysmal rupture and to gain insight into the pathophysiology.

Methods—

During a 3-year period, 250 patients with aneurysmal subarachnoid hemorrhage completed a structured questionnaire regarding exposure to 30 potential trigger factors in the period soon before subarachnoid hemorrhage (hazard period) and for usual frequency and intensity of exposure. We assessed relative risks (RR) of rupture after exposure to triggers with the case-crossover design comparing exposure in the hazard period with the usual frequency of exposure. Additionally, we calculated population-attributable risks.

Results—

Eight triggers increased the risk for subarachnoid hemorrhage: coffee consumption (RR, 1.7; 95% CI, 1.2–2.4), cola consumption (RR, 3.4; 95% CI,1.5–7.9), anger (RR, 6.3; 95% CI, 4.6–25), startling (RR, 23.3; 95% CI, 4.2–128), straining for defecation (RR, 7.3; 95% CI, 2.9–19), sexual intercourse (RR, 11.2; 95% CI, 5.3–24), nose blowing (RR, 2.4; 95% CI, 1.3–4.5), and vigorous physical exercise (RR, 2.4; 95% CI, 1.2–4.2). The highest population-attributable risks were found for coffee consumption (10.6%) and vigorous physical exercise (7.9%).

Conclusions—

We identified and quantified 8 trigger factors for aneurysmal rupture. All triggers induce a sudden and short increase in blood pressure, which seems a possible common cause for aneurysmal rupture. Some triggers are modifiable, and further studies should assess whether reduction of exposure to these factors or measures preventing sudden increase in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm.
Neural Associative Memory with Optimal Bayesian Learning
Authors: Knoblauch Andreas
Published: May 2011

Neural associative memories are perceptron-like single-layer networks with fast synaptic learning typically storing discrete associations between pairs of neural activity patterns. Previous work optimized the memory capacity for various models of synaptic learning: linear Hopfield-type rules, the Willshaw model employing binary synapses, or the BCPNN rule of Lansner and Ekeberg, for example. Here I show that all of these previous models are limit cases of a general optimal model where synaptic learning is determined by probabilistic Bayesian considerations. Asymptotically, for large networks and very sparse neuron activity, the Bayesian model becomes identical to an inhibitory implementation of the Willshaw and BCPNN-type models. For less sparse patterns, the Bayesian model becomes identical to Hopfield-type networks employing the covariance rule. For intermediate sparseness or finite networks, the optimal Bayesian learning rule differs from the previous models and can significantly improve memory performance. I also provide a unified analytical framework to determine memory capacity at a given output noise level that links approaches based on mutual information, Hamming distance, and signal-to-noise ratio.