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Constitutive and barbital-induced expression of the Cyp6a2 allele of a high producer strain of CYP6A2 in the genetic background of a low producer strain.  


The levels of one or more cytochrome P450 (CYP) enzymes and the respective mRNAs are found to be higher in insecticide-resistant insects than in susceptible insects. To understand better how insects regulate the levels of CYPs, we examined the expression of the Cyp6a2 gene in various strains of Drosophila melanogaster. We also took a transgenic approach to understand the molecular mechanisms that are involved in strain variation of Cyp6a2 expression. RNA blot analysis showed that the constitutive expression of Cyp6a2 varies from strain to strain; the level of CYP6A2 mRNA is barely detectable in the underproducer ry506 strain, whereas it is very high in the overproducer 91-R and MHIII-D23 strains. The long terminal repeat (LTR) of mobile element 17.6 that is found in the 3' untranslated region (UTR) of the Cyp6a2 gene of some strains does not appear to have any role on the steady-state CYP6A2 mRNA level. We also found that the Cyp6a2 gene is inducible by barbital in 91-R, ry506 as well as 91-C, which carries an LTR insertion. To examine the genetic background of the underproducer ry506 strain with respect to Cyp6a2 expression, we transformed the ry506 strain with the Cyp6a2 allele of the overproducer 91-R strain (Cyp6a2-91 R) and measured the constitutive and barbital-induced expression of the Cyp6a2-91 R transgene in the transformed flies. The Cyp6a2-91 R transgene carrying 129 bp of DNA upstream of the ATG codon did not show any constitutive or barbital-induced expression in the ry506 host genome. However, transgenes with 1331 and 985 bp upstream DNA showed similar levels of constitutive expression that were higher than that of the endogenous Cyp6a2 gene of the ry506 host strain, but lower than the expression of the same gene in the 91-R strain. Both these transgenes, with 1331 and 985 bp upstream DNA, also showed induction with 0.1 M barbital. DNA sequence analysis revealed that in both 91-R and ry506, the upstream DNA between +1 and -985 bp contains a distal and a proximal group of three potential barbie boxes, i.e. cis-elements that are thought to be involved in barbiturate-mediated induction of CYP genes. Except for four bases located near the distal cluster of barbie boxes and two other bases, the base sequence of the upstream DNA is identical in ry506 and 91-R strains. These results suggest that the underproducer ry506 strain has the trans-regulatory factors to support constitutive and induced expression of the Cyp6a2-91 R allele carrying DNA between -129 and -1331 bp regions. Possible reasons for low constitutive expression of the endogenous Cyp6a2 gene and moderate level of expression of the Cyp6a2-91 R allele in the ry506 genetic background are discussed. PMID:9852951

Dombrowski, S M; Krishnan, R; Witte, M; Maitra, S; Diesing, C; Waters, L C; Ganguly, R



Freedom of Expression in the Original Constitution: A Bicentennial Review.  

ERIC Educational Resources Information Center

The original United States Constitution of 1787, specifically in the communication related provisions of Article 1, deals extensively with communication issues, and provides an illustration of the tensions that existed between freedom and suppression. Philosophically, there was support for freedom of expression while in real world events there was…

Kane, Peter E.


Constitutive expression of Botrytis aclada laccase in Pichia pastoris.  


The heterologous expression of laccases is important for their large-scale production and genetic engineering--a prerequisite for industrial application. Pichia pastoris is the preferred expression host for fungal laccases. The recently cloned laccase from the ascomycete Botrytis aclada (BaLac) has been efficiently expressed in P. pastoris under the control of the inducible alcohol oxidase (AOX1) promoter. In this study, we compare these results to the constitutive expression in the same organism using the glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter. The results show that the amounts of BaLac produced with the GAP system (517 mgL(-1)) and the AOX1 system (495 mgL(-1)) are comparable. The constitutive expression is, however, faster, and the specific activity of BaLac in the culture supernatant is higher (41.3 Umg(-1) GAP, 14.2 Umg(-1) AOX1). In microtiter plates, the constitutive expression provides a clear advantage due to easy manipulation (simple medium, no methanol feeding) and fast enzyme production (high-throughput screening assays can already be performed after 48 h). PMID:22705842

Kittl, Roman; Gonaus, Christoph; Pillei, Christian; Haltrich, Dietmar; Ludwig, Roland



Constitutive expression of Botrytis aclada laccase in Pichia pastoris  

PubMed Central

The heterologous expression of laccases is important for their large-scale production and genetic engineering—a prerequisite for industrial application. Pichia pastoris is the preferred expression host for fungal laccases. The recently cloned laccase from the ascomycete Botrytis aclada (BaLac) has been efficiently expressed in P. pastoris under the control of the inducible alcohol oxidase (AOX1) promoter. In this study, we compare these results to the constitutive expression in the same organism using the glyceraldehyde-3-phosphate dehydrogenase (GAP) promoter. The results show that the amounts of BaLac produced with the GAP system (517 mgL-1) and the AOX1 system (495 mgL-1) are comparable. The constitutive expression is, however, faster, and the specific activity of BaLac in the culture supernatant is higher (41.3 Umg-1 GAP, 14.2 Umg-1 AOX1). In microtiter plates, the constitutive expression provides a clear advantage due to easy manipulation (simple medium, no methanol feeding) and fast enzyme production (high-throughput screening assays can already be performed after 48 h). PMID:22705842

Kittl, Roman; Gonaus, Christoph; Pillei, Christian; Haltrich, Dietmar; Ludwig, Roland



NOX4 expression in human microglia leads to constitutive generation of reactive oxygen species and to constitutive IL-6 expression.  


Reactive oxygen species (ROS) generation by microglia is implicated in neuroinflammation and neurotoxicity, as well as in host defense, cell proliferation and excitatory amino acid release. Recent studies demonstrate that primary microglia preparations not only express the phagocyte NADPH oxidase NOX2, but also the NOX1 and NOX4 isoforms. Here we investigated the relationship between neuroinflammation and NOX isoform expression in the human microglia cell line clone 3 (HMC3). HMC3 cells are typical microglia, as suggested by the constitutive expression of Iba-1 and CD14, and IFN-gamma-induced expression of CD11b, CD68 and MHCII. However, the characteristics of NOX isoform expression and ROS generation by HMC3 cells were unexpected. RT-PCR demonstrated abundant expression of NOX4, but almost no NOX2 mRNA. ROS generation was constitutive and appeared predominantly intracellular, as superoxide was detected within intracellular vesicles, while the cell-permeable H(2)O(2) was found in the extracellular space. ROS generation by HMC3 was efficiently suppressed by siRNA directed against NOX4, but not by control siRNA. NOX4 suppression did not alter expression of the microglia-typical genes MHCII, CD68 and CD11b, nor did it affect the expression of iNOS, VEGF or TGF-beta. However, there was a marked decrease in IL-6 mRNA. Taken together, we demonstrate a constitutive NOX4-dependent ROS generation in a microglial cell line which leads to expression of IL-6 mRNA. The possibility that microglia could switch from tightly regulated NOX2-dependent ROS generation to constitutive NOX4-dependent ROS generation is of interest for the understanding of the role of microglia in maintaining the balance between neuroprotection and neuroinflammatory damage. PMID:20375612

Li, Bin; Bedard, Karen; Sorce, Silvia; Hinz, Boris; Dubois-Dauphin, Michel; Krause, Karl-Heinz



Constitutive \\  

Microsoft Academic Search

A dominant form of human congenital nightblindness is caused by a gly903asp (G90D) mutation in rhodopsin. G90D has been shown to activate the phototransduction cascade in the ab- sence of light in vitro. Such constitutive activity of G90D rho- dopsin in vivo would desensitize rod photoreceptors and lead to nightblindness. In contrast, other rhodopsin mutations typi- cally give rise to

Paul A. Sieving; Michael L. Fowler; Ronald A. Bush; Shigeki Machida; Peter D. Calvert; Daniel G. Green; Clint L. Makino; Christina L. McHenry



Downregulation of endothelial constitutive nitric oxide synthase expression by lipopolysaccharide.  


Lipopolysaccharide (LPS), a causal agent of sepsis, has been shown to induce systemic nitric oxide (NO) synthesis through complex mechanisms. However, the effect of LPS on endothelial cells is incompletely understood. To investigate the mechanism by which LPS influences the release of NO from endothelial cells, the effect of this compound on endothelial constitutive nitric oxide synthase (ecNOS) was studied in cultured bovine coronary venular endothelial cells. Western and Northern analyses showed that LPS decreased ecNOS expression at the protein and mRNA levels in a time-dependent and dose-responsive manner. Concurrent treatment of the endothelial cells with LPS and a transcription inhibitor, actinomycin D, resulted in decreased ecNOS mRNA within 8 hours. In contrast, treatment with actinomycin D had only a relatively insignificant effect on the ecNOS transcript level. This result suggests that the reduction of ecNOS by LPS resulted from an increased degradation rate of its transcript. PMID:8769085

Lu, J L; Schmiege, L M; Kuo, L; Liao, J C



Downregulation of Endothelial Constitutive Nitric Oxide Synthase Expression by Lipopolysaccharide  

Microsoft Academic Search

Lipopolysaccharide (LPS), a causal agent of sepsis, has been shown to induce systemic nitric oxide (NO) synthesis through complex mechanisms. However, the effect of LPS on endothelial cells is incompletely understood. To investigate the mechanism by which LPS influences the release of NO from endothelial cells, the effect of this compound on endothelial constitutive nitric oxide synthase (ecNOS) was studied

Jia-Ling Lu; Lorenz M. Schmiege; III; Lih Kuo; James C. Liao



Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda  

Microsoft Academic Search

BACKGROUND: Ayurveda is an ancient system of personalized medicine documented and practiced in India since 1500 B.C. According to this system an individual's basic constitution to a large extent determines predisposition and prognosis to diseases as well as therapy and life-style regime. Ayurveda describes seven broad constitution types (Prakritis) each with a varying degree of predisposition to different diseases. Amongst

Bhavana Prasher; Sapna Negi; Shilpi Aggarwal; Amit K Mandal; Tav P Sethi; Shailaja R Deshmukh; Sudha G Purohit; Shantanu Sengupta; Sangeeta Khanna; Farhan Mohammad; Gaurav Garg; Samir K Brahmachari; Mitali Mukerji



Cognitive impairments in adult mice with constitutive inactivation of RIP140 gene expression  

E-print Network

Cognitive impairments in adult mice with constitutive inactivation of RIP140 gene expression Kingdom. Running title: Behavioral phenotype of RIP140 -/- mice Keywords: RIP140, transcriptional regulator, learning and memory, behavioral phenotype Present address: Department of Biomedical Sciences

Paris-Sud XI, Université de


Cell cycle perturbation in a human hepatoblastoma cell line constitutively expressing Hepatitis C virus core protein  

Microsoft Academic Search

Summary. Hepatitis C virus (HCV) is one of the major causes of chronic liver disease with the potential for development of hepatocellular carcinoma (HCC). The core protein of HCV has been shown to modulate expression of various cellular genes and to influence a number of cellular functions. We investigated the effect of constitutively expressed HCV core protein on cell cycle

A. Ruggieri; M. Murdolo; T. Harada; T. Miyamura; M. Rapicetta



Gene Expression Regulation by Agonist-Independent Constitutive Signaling of Melanocortin-1 Receptor  

PubMed Central

Background Melanocortin-1 receptor (Mc1r), a key signaling receptor for melanogenesis, has been reported to mediate migration of B16F10 melanoma cells. Interestingly, this activity appears to be a part of the constitutive signaling of Mc1r. Methods We carried out small interfering RNA-mediated knock-down of Mc1r on murine melanoma B16F10 cells and performed microarray analysis to characterize changes in the gene expression profile. Results We isolated 22 and four genes whose expression decreased and increased, respectively, by 2.5-fold or higher as the result of Mc1r knock-down. Several down-regulated genes have been proposed to be involved in cell migration. Among these genes are several members of the chemokine gene family. Conclusion We provide a gene set for further functional analyses of Mc1r. The Mc1r target genes we present may be particularly relevant for understanding the ligand-independent activity of Mc1r. Further examination of the mode of action may lead to novel strategies in regulating the migration and metastasis of melanoma cells. PMID:25031891

Seong, Ikjoo



Defective neuromuscular synaptogenesis in mice expressing constitutively active ErbB2 in skeletal muscle fibers  

Microsoft Academic Search

We overexpressed a constitutively active form of the neuregulin receptor ErbB2 (CAErbB2) in skeletal muscle fibers in vivo and in vitro by tetracycline-inducible expression. Surprisingly, CAErbB2 expression during embryonic development was lethal and impaired synaptogenesis yielding a phenotype with loss of synaptic contacts, extensive axonal sprouting, and diffuse distribution of acetylcholine receptor (AChR) transcripts, reminiscent of agrin-deficient mice. CAErbB2 expression

Olga N. Ponomareva; Hualong Ma; Vita M. Vock; Elaine L. Ellerton; Susan E. Moody; Ramzi Dakour; Lewis A. Chodosh; Mendell Rimer



Simplified Vacuum Energy Expressions for Radial Backgrounds and Domain Walls  

E-print Network

We extend our previous results of simplified expressions for functional determinants for radial Schr\\"odinger operators to the computation of vacuum energy, or mass corrections, for static but spatially radial backgrounds, and for domain wall configurations. Our method is based on the zeta function approach to the Gel'fand-Yaglom theorem, suitably extended to higher dimensional systems on separable manifolds. We find new expressions that are easy to implement numerically, for both zero and nonzero temperature.

Gerald Dunne; Klaus Kirsten



Expression of constitutive nitric oxide synthase in rat and human gastrointestinal tract  

Microsoft Academic Search

The aim of this study was to determine the expression of constitutive NO synthases (ecNOS and bNOS) at the protein level in rat and human gastrointestinal tract. We established a quantitative Western blotting method for detection and quantification of ecNOS and bNOS in both species. Human gastric fundus was further analyzed by immunohistochemistry. EcNOS expression at the protein level could

H Fischer; J. C Becker; P Boknik; V Huber; H Lüss; J Neumann; W Schmitz; W Domschke; J Stachura; J. W Konturek



Constitutive homologous expression of phosphoglucomutase and transaldolase increases the metabolic flux of Fusarium oxysporum  

PubMed Central

Background Fusarium oxysporum is among the few filamentous fungi that have been reported of being able to directly ferment biomass to ethanol in a consolidated bioprocess. Understanding its metabolic pathways and their limitations can provide some insights on the genetic modifications required to enhance its growth and subsequent fermentation capability. In this study, we investigated the hypothesis reported previously that phosphoglucomutase and transaldolase are metabolic bottlenecks in the glycolysis and pentose phosphate pathway of the F. oxysporum metabolism. Results Both enzymes were homologously overexpressed in F. oxysporum F3 using the gpdA promoter of Aspergillus nidulans for constitutive expression. Transformants were screened for their phosphoglucomutase and transaldolase genes expression levels with northern blot. The selected transformant exhibited high mRNA levels for both genes, as well as higher specific activities of the corresponding enzymes, compared to the wild type. It also displayed more than 20 and 15% higher specific growth rate upon aerobic growth on glucose and xylose, respectively, as carbon sources and 30% higher biomass to xylose yield. The determination of the relative intracellular amino and non-amino organic acid concentrations at the end of growth on glucose revealed higher abundance of most determined metabolites between 1.5- and 3-times in the recombinant strain compared to the wild type. Lower abundance of the determined metabolites of the Krebs cycle and an 68-fold more glutamate were observed at the end of the cultivation, when xylose was used as carbon source. Conclusions Homologous overexpression of phosphoglucomutase and transaldolase in F. oxysporum was shown to enhance the growth characteristics of the strain in both xylose and glucose in aerobic conditions. The intracellular metabolites profile indicated how the changes in the metabolome could have resulted in the observed growth characteristics. PMID:24649884



Enhancement of Glucocorticoid Receptor-Mediated Gene Expression by Constitutively Active Heat  

E-print Network

the role of heat shock factor 1 (HSF1) in the stress potentiation of glucocorticoid receptor (GR) activity, we placed a constitutively active mutant of human HSF1 (hHSF1-E189) under the control of a doxycycline (DOX)-inducible vec- tor. In mouse L929 cells, DOX-induced expression of hHSF1-E189 correlated

Abraham, Nader G.


Constitutive Expression of the CIRCADIAN CLOCK ASSOCIATED 1 ( CCA1) Gene Disrupts Circadian Rhythms and Suppresses Its Own Expression  

Microsoft Academic Search

The CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) gene encodes a MYB-related transcription factor involved in the phytochrome induction of a light-harvesting chlorophyll a\\/b-protein (Lhcb) gene. Expression of the CCA1 gene is transiently induced by phytochrome and oscillates with a circadian rhythm. Constitutive expression of CCA1 protein in transgenic plants abolished the circadian rhythm of several genes with dramatically different phases. These

Zhi-Yong Wang; Elaine M. Tobin



An efficient plasmid vector for constitutive high-level expression of foreign genes in Escherichia coli.  


The levansucrase gene (lsrA) from Rahnella aquatilis was strongly expressed in a constitutive manner in Escherichia coli when cloned into a pBluescript KS-based pRL1CP plasmid vector. The native promoter upstream of lsrA and the lacZ promoter cooperatively enhanced the expression of lsrA to a level that was comparable to that of the T7 promoter, which is used in commercial pET expression vector system. A putative rho-independent transcription termination signal downstream of lsrA was crucial for gene expression. This plasmid vector also proved to be applicable for efficient expression of other foreign genes in E. coli. PMID:19214389

Seo, Jeong-Woo; Hong, Won-kyung; Rairakhwada, Dina; Seo, Pil-Soo; Choi, Min Ho; Song, Ki-Bang; Rhee, Sang-Ki; Kim, Chul Ho



Constitutive and Inducible Expression of B7 Family of Ligands by Human Airway Epithelial Cells  

Microsoft Academic Search

Activated T cells have been implicated in chronic rhinosinusitis (CRS) and asthma and physically interact with epithelial cells in the airways. We now report that human airway epithelial cells display significant constitutive cell-surfaceexpression of costimulatory ligands, B7-H1, B7-H2, B7-H3, and B7-DC. Expression of B7-H1 and B7-DC was selectively induced by stimulation of either BEAS2B or primary nasal epithelial cells (PNEC)

Jean Kim; Allen C. Myers; Lieping Chen; Drew M. Pardoll; Quynh-Ai Truong-Tran; John F. McDyer; Lowella Fortuno; Robert P. Schleimer



Constitutive expression of a chromosomal class A (BJM group 2) beta-lactamase in Xanthomonas campestris.  


Sequencing of the upstream region of the beta-lactamase gene from Xanthomonas campestris pv. campestris 11 (bla(XCC-1)) revealed the cognate ampR1 gene (289 amino acids, 31 kDa). It runs divergently from bla(XCC-1) with a 100-bp intergenic region (IG) containing partially overlapped promoters with structural features typical of the bla-ampR IG. The deduced AmpR1 protein shows significant identity in amino acid sequence and conserved motifs with AmpR proteins of other species, e.g., of Pseudomonas aeruginosa (58.2% amino acid identity). Results of insertional mutation, complementation tests, and beta-lactamase assays suggested that expression of bla(XCC-1) was constitutive and dependent on AmpR1. Four bla genes and two ampR genes are present in the fully sequenced X. campestris pv. campestris ATCC 33913 genome, with XCC3039 and XCC3040 considered the analogues of bla(XCC-1) and ampR1, respectively. An ampR1 homologue was detected by Southern hybridization in the ampicillin-resistant Xanthomonas strains, which appear to express beta-lactamase constitutively. Although the significance remains to be studied, constitutive expression of beta-lactamase by a widespread bacterial genus raises environmental concerns regarding the dissemination of resistance genes. PMID:14693541

Weng, Shu-Fen; Lin, Juey-Wen; Chen, Chih-Hung; Chen, Yih-Yuan; Tseng, Yi-Hsuan; Tseng, Yi-Hsiung



Constitutive expression of human keratin 14 gene in mouse lung induces premalignant lesions and squamous differentiation  

PubMed Central

Squamous cell carcinoma accounts for 20% of all human lung cancers and is strongly linked to cigarette smoking. It develops through premalignant changes that are characterized by high levels of keratin 14 (K14) expression in the airway epithelium and evolve through basal cell hyperplasia, squamous metaplasia and dysplasia to carcinoma in situ and invasive carcinoma. In order to explore the impact of K14 in the pulmonary epithelium that normally lacks both squamous differentiation and K14 expression, human keratin 14 gene hK14 was constitutively expressed in mouse airway progenitor cells using a mouse Clara cell specific 10 kDa protein (CC10) promoter. While the lungs of CC10-hK14 transgenic mice developed normally, we detected increased expression of K14 and the molecular markers of squamous differentiation program such as involucrin, loricrin, small proline-rich protein 1A, transglutaminase 1 and cholesterol sulfotransferase 2B1. In contrast, wild-type lungs were negative. Aging CC10-hK14 mice revealed multifocal airway cell hyperplasia, occasional squamous metaplasia and their lung tumors displayed evidence for multidirectional differentiation. We conclude that constitutive expression of hK14 initiates squamous differentiation program in the mouse lung, but fails to promote squamous maturation. Our study provides a novel model for assessing the mechanisms of premalignant lesions in vivo by modifying differentiation and proliferation of airway progenitor cells. PMID:18701433

Habib Dakir, EL; Feigenbaum, Lionel; Linnoila, R. Ilona



Constitutive expression of human keratin 14 gene in mouse lung induces premalignant lesions and squamous differentiation.  


Squamous cell carcinoma accounts for 20% of all human lung cancers and is strongly linked to cigarette smoking. It develops through premalignant changes that are characterized by high levels of keratin 14 (K14) expression in the airway epithelium and evolve through basal cell hyperplasia, squamous metaplasia and dysplasia to carcinoma in situ and invasive carcinoma. In order to explore the impact of K14 in the pulmonary epithelium that normally lacks both squamous differentiation and K14 expression, human keratin 14 gene hK14 was constitutively expressed in mouse airway progenitor cells using a mouse Clara cell specific 10 kDa protein (CC10) promoter. While the lungs of CC10-hK14 transgenic mice developed normally, we detected increased expression of K14 and the molecular markers of squamous differentiation program such as involucrin, loricrin, small proline-rich protein 1A, transglutaminase 1 and cholesterol sulfotransferase 2B1. In contrast, wild-type lungs were negative. Aging CC10-hK14 mice revealed multifocal airway cell hyperplasia, occasional squamous metaplasia and their lung tumors displayed evidence for multidirectional differentiation. We conclude that constitutive expression of hK14 initiates squamous differentiation program in the mouse lung, but fails to promote squamous maturation. Our study provides a novel model for assessing the mechanisms of premalignant lesions in vivo by modifying differentiation and proliferation of airway progenitor cells. PMID:18701433

Dakir, E L Habib; Feigenbaum, Lionel; Linnoila, R Ilona



CT-2576, an inhibitor of phospholipid signaling, suppresses constitutive and induced expression of human immunodeficiency virus.  

PubMed Central

Viruses such as human immunodeficiency virus (HIV) require cellular activation for expression. Cellular activation in lymphoid cells is associated with augmented accumulation of certain phosphatidic acid (PA) species derived from the hydrolysis of glycan phosphatidylinositol (GPI). This suggests that activation of a phospholipid pathway may play a role in initiation of viral replication. To test this hypothesis, we examined the effect of tat gene expression on the production of cellular PA species, as the Tat protein is essential for HIV expression and has been implicated in activating the expression of multiple host cellular genes. Expression of tat increased the expression of PA. We then tested whether synthetic inhibitors of PA metabolism would inhibit activation of the HIV long terminal repeat by Tat and tumor necrosis factor alpha (TNF-alpha). CT-2576 suppressed both PA generation induced by Tat and HIV long terminal repeat-directed gene expression in response to Tat or TNF-alpha at a posttranscriptional step. CT-2576 also inhibited constitutive as well as TNF-alpha- and interleukin 6-induced expression of HIV p24 antigen in chronically infected U1 cells and in peripheral blood lymphocytes acutely infected with a clinical isolate of HIV. Pharmacological inhibition of synthesis of selected PA species may therefore provide a therapeutic approach to suppression of HIV replication. Images Fig. 1 Fig. 3 Fig. 5 PMID:7761405

Leung, D W; Peterson, P K; Weeks, R; Gekker, G; Chao, C C; Kaplan, A H; Balantac, N; Tompkins, C; Underiner, G E; Bursten, S



Constitutive expression of small heat shock proteins in vegetative tissues of the resurrection plant Craterostigma plantagineum.  


Using antibodies raised against two sunflower small heat shock proteins (sHSPs), we have detected immunologically related proteins in unstressed vegetative tissues from the resurrection plant Craterostigma plantagineum. In whole plants, further accumulation of these polypeptides was induced by heat-shock or water-stress. In desiccation-intolerant Craterostigma callus tissue, we failed to detect sHSP-related polypeptides, but their expression, and the concurrent acquisition of desiccation tolerance was induced by exogenous abscisic acid (ABA) treatment. In untressed plants, the cross-reacting polypeptides were abundant in the roots and lower part of the shoots, where they showed homogeneous tissue-distributions. This constitutive expression is novel for vegetative tissues of higher plants, and resembles the expression patterns of sHSPs in desiccation-tolerant zygotic embryos and germinating seeds. PMID:8555452

Alamillo, J; Almoguera, C; Bartels, D; Jordano, J



Constitutive expression of transgenes encoding derivatives of the synthetic antimicrobial peptide BP100: impact on rice host plant fitness  

PubMed Central

Background The Biopeptide BP100 is a synthetic and strongly cationic ?-helical undecapeptide with high, specific antibacterial activity against economically important plant-pathogenic bacteria, and very low toxicity. It was selected from a library of synthetic peptides, along with other peptides with activities against relevant bacterial and fungal species. Expression of the BP100 series of peptides in plants is of major interest to establish disease-resistant plants and facilitate molecular farming. Specific challenges were the small length, peptide degradation by plant proteases and toxicity to the host plant. Here we approached the expression of the BP100 peptide series in plants using BP100 as a proof-of-concept. Results Our design considered up to three tandemly arranged BP100 units and peptide accumulation in the endoplasmic reticulum (ER), analyzing five BP100 derivatives. The ER retention sequence did not reduce the antimicrobial activity of chemically synthesized BP100 derivatives, making this strategy possible. Transformation with sequences encoding BP100 derivatives (bp100der) was over ten-fold less efficient than that of the hygromycin phosphotransferase (hptII) transgene. The BP100 direct tandems did not show higher antimicrobial activity than BP100, and genetically modified (GM) plants constitutively expressing them were not viable. In contrast, inverted repeats of BP100, whether or not elongated with a portion of a natural antimicrobial peptide (AMP), had higher antimicrobial activity, and fertile GM rice lines constitutively expressing bp100der were produced. These GM lines had increased resistance to the pathogens Dickeya chrysanthemi and Fusarium verticillioides, and tolerance to oxidative stress, with agronomic performance comparable to untransformed lines. Conclusions Constitutive expression of transgenes encoding short cationic ?-helical synthetic peptides can have a strong negative impact on rice fitness. However, GM plants expressing, for example, BP100 based on inverted repeats, have adequate agronomic performance and resistant phenotypes as a result of a complex equilibrium between bp100der toxicity to plant cells, antimicrobial activity and transgene-derived plant stress response. It is likely that these results can be extended to other peptides with similar characteristics. PMID:22947243



Distinct promoters mediate constitutive and inducible Bcl-XL expression in malignant lymphocytes.  


Bcl-X(L) is a Bcl-2-related survival protein that is essential for normal development. Bcl-X(L) expression is rapidly induced by a wide range of survival signals and many cancer cells constitutively express high levels. The Bcl-X gene has a complex organization with multiple promoters giving rise to RNAs with alternate 5' non-coding exons. Here we have investigated the mechanisms that control basal and induced expression of Bcl-X(L) in B-lymphoma cells. Antisense experiments demonstrated that Bcl-X(L) was essential for survival of Akata6 B-lymphoma cells. The levels of RNAs containing the IB Bcl-X non-coding exon, derived from the distal 1B promoter, correlated with basal expression of Bcl-X(L) in primary malignant B cells and this promoter was highly active in B-cell lines. The activity of this promoter was largely dependent on a single Ets binding site and Ets family proteins were bound at this promoter in intact cells. CD40 ligand (CD40L)-induced cell survival was associated with increased Bcl-X(L) expression and accumulation of exon IA-containing RNAs, derived from the proximal 1A promoter. Nuclear factor-kappaB (NF-kappaB) inhibition prevented induction of Bcl-X(L) protein and exon IA-containing RNAs by CD40L. Therefore, the distal Bcl-X 1B promoter plays a critical role in driving constitutive expression-mediated via Ets family proteins in malignant B cells, whereas NF-kappaB plays a central role in the induction of Bcl-X(L) in response to CD40 signalling via the proximal 1A promoter. PMID:16983335

Habens, F; Lapham, A S; Dallman, C L; Pickering, B M; Michels, J; Marcusson, E G; Johnson, P W M; Packham, G



Distinct gene-expression profiles characterize mammary tumors developed in transgenic mice expressing constitutively active and C-terminally truncated variants of STAT5  

PubMed Central

Background Stat5 is a latent transcription factor that regulates essential growth and survival functions in normal cells. Constitutive activity of Stat5 and the involvement of its C-terminally truncated variant have been implicated in blood cell malignancies and mammary or breast cancer. To distinguish the individual contributions of the Stat5 variants to mammary tumorigenesis, global gene-expression profiling was performed on transgenic STAT5-induced tumors. Results We identified 364 genes exhibiting differential expression in mammary tumors developed in transgenic mice expressing constitutively active STAT5 (STAT5ca) vs. its C-terminally truncated variant (STAT5?750). These genes mediate established Stat5 effects on cellular processes such as proliferation and cell death, as well as yet-unrelated homeostatic features, e.g. carbohydrate metabolism. A set of 14 genes linked STAT5?750 expression to the poorly differentiated carcinoma phenotype and STAT5ca to the highly differentiated papillary adenocarcinoma. Specifically affected genes exhibited differential expression in an individual tumor set vs. its counterpart and the intact mammary gland: 50 genes were specifically affected by STAT5ca, and 94% of these were downregulated, the latter involved in suppression of tumor suppressors and proliferation antagonistics. This substantial downregulation distinguishes the STAT5ca-induced tumorigenic consequences from the relatively equal effect of the STAT5?750 on gene expression, which included significant elevation in the expression of oncogenes and growth mediators. STAT5?750 mRNA expression was below detection levels in the tumors and the amount of STAT5ca transcript was not correlated with the expression of its specifically affected genes. Interestingly, we identified several groups of three to eight genes affected by a particular STAT5 variant with significant correlated expression at distinct locations in the clustergram. Conclusion The different gene-expression profiles in mammary tumors caused by the STAT5?750 and STAT5ca variants, corroborated by the absence of a direct link to transgenic STAT5 expression, imply distinct metabolic consequences for their oncogenic role which probably initiate early in tumor development. Tumorigenesis may involve induction of growth factor and oncogenes by STAT5?750 or suppression of tumor suppressors and growth antagonists by STAT5ca. The list of genes specifically affected by the STAT5 variants may provide a basis for the development of a marker set for their distinct oncogenic role. PMID:19450255

Eilon, Tali; Barash, Itamar



Conditional expression of constitutively active estrogen receptor {alpha} in chondrocytes impairs longitudinal bone growth in mice  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Conditional transgenic mice expressing constitutively active estrogen receptor {alpha} (caER{alpha}) in chondrocytes were developed. Black-Right-Pointing-Pointer Expression of caER{alpha} in chondrocytes impaired longitudinal bone growth in mice. Black-Right-Pointing-Pointer caER{alpha} affects chondrocyte proliferation and differentiation. Black-Right-Pointing-Pointer This mouse model is useful for understanding the physiological role of ER{alpha}in vivo. -- Abstract: Estrogen plays important roles in the regulation of chondrocyte proliferation and differentiation, which are essential steps for longitudinal bone growth; however, the mechanisms of estrogen action on chondrocytes have not been fully elucidated. In the present study, we generated conditional transgenic mice, designated as caER{alpha}{sup ColII}, expressing constitutively active mutant estrogen receptor (ER) {alpha} in chondrocytes, using the chondrocyte-specific type II collagen promoter-driven Cre transgenic mice. caER{alpha}{sup ColII} mice showed retardation in longitudinal growth, with short bone lengths. BrdU labeling showed reduced proliferation of hypertrophic chondrocytes in the proliferating layer of the growth plate of tibia in caER{alpha}{sup ColII} mice. In situ hybridization analysis of type X collagen revealed that the maturation of hypertrophic chondrocytes was impaired in caER{alpha}{sup ColII} mice. These results suggest that ER{alpha} is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo.

Ikeda, Kazuhiro [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan)] [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Tsukui, Tohru [Experimental Animal Laboratory, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan)] [Experimental Animal Laboratory, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Imazawa, Yukiko; Horie-Inoue, Kuniko [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan)] [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Inoue, Satoshi, E-mail: [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan) [Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan); Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan); Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo (Japan)



A minimal regulatory region maintains constitutive expression of the max gene.  

PubMed Central

Max is a basic helix-loop-helix/leucine zipper protein that forms heterodimers with the Myc family of proteins to promote cell growth and with the Mad/Mxi1 family of proteins to inhibit cell growth. The role of Max as the obligate binding partner for these two protein families necessitates the observed constitutive expression and relatively long half-life of the max mRNA under a variety of growth conditions. In this study, we have used the chicken max gene to map DNA elements maintaining max gene expression in vertebrate cells. We have identified a minimal regulatory region (MRR) that resides within 115 bp of the max translation initiation site and that possesses an overall structure typical of TATA-less promoters. Within the MRR are two consensus binding sites for Sp1, a ubiquitously expressed transcription factor that plays a role in the expression of many constitutive genes. Interestingly, we show that direct binding by Sp1 to these sites is not required for MRR-mediated transcription. Instead, the integrity of a 20-bp DNA element in the MRR is required for transcriptional activity, as is the interaction of this DNA element with a 90-kDa cellular protein. Our data suggest that it is the persistence of this 90-kDa protein in vertebrate cells which drives max gene expression, insulates the max promoter from the dramatic changes in transcription that accompany cell growth and development, and ensures that adequate levels of Max will be available to facilitate the function of the Myc, Mad, and Mxi1 families of proteins. PMID:9032230

Peters, M A; Sollenberger, K G; Kao, T L; Taparowsky, E J



Differential Expression of over 60 Chromosomal Genes in Escherichia coli by Constitutive Expression of MarA  

PubMed Central

In Escherichia coli, the MarA protein controls expression of multiple chromosomal genes affecting resistance to antibiotics and other environmental hazards. For a more-complete characterization of the mar regulon, duplicate macroarrays containing 4,290 open reading frames of the E. coli genome were hybridized to radiolabeled cDNA populations derived from mar-deleted and mar-expressing E. coli. Strains constitutively expressing MarA showed altered expression of more than 60 chromosomal genes: 76% showed increased expression and 24% showed decreased expression. Although some of the genes were already known to be MarA regulated, the majority were newly determined and belonged to a variety of functional groups. Some of the genes identified have been associated with iron transport and metabolism; other genes were previously known to be part of the soxRS regulon. Northern blot analysis of selected genes confirmed the results obtained with the macroarrays. The findings reveal that the mar locus mediates a global stress response involving one of the largest networks of genes described. PMID:10852879

Barbosa, Teresa M.; Levy, Stuart B.



Resistance to simian immunodeficiency virus low dose rectal challenge is associated with higher constitutive TRIM5? expression in PBMC  

PubMed Central

Background At least six host-encoded restriction factors (RFs), APOBEC3G, TRIM5?, tetherin, SAMHD1, schlafen 11, and Mx2 have now been shown to inhibit HIV and/or SIV replication in vitro. To determine their role in vivo in the resistance of macaques to mucosally-acquired SIV, we quantified both pre-exposure (basal) and post-exposure mRNA levels of these RFs, Mx1, and IFN? in PBMC, lymph nodes, and duodenum of rhesus macaques undergoing weekly low dose rectal exposures to the primary isolate, SIV/DeltaB670. Results Repetitive challenge divided the monkeys into two groups with respect to their susceptibility to infection: highly susceptible (2–3 challenges, 5 monkeys) and poorly susceptible (?6 challenges, 3 monkeys). Basal RF and Mx1 expression varied among the three tissues examined, with the lowest expression generally detected in duodenal tissues, and the highest observed in PBMC. The one exception was A3G whose basal expression was greatest in lymph nodes. Importantly, significantly higher basal expression of TRIM5? and Mx1 was observed in PBMC of animals more resistant to mucosal infection. Moreover, individual TRIM5? levels were stable throughout a year prior to infection. Post-exposure induction of these genes was also observed after virus appearance in plasma, with elevated levels in PBMC and duodenum transiently occurring 7–10 days post infection. They did not appear to have an effect on control of viremia. Interestingly, minimal to no induction was observed in the resistant animal that became an elite controller. Conclusions These results suggest that constitutively expressed TRIM5? appears to play a greater role in restricting mucosal transmission of SIV than that associated with type I interferon induction following virus entry. Surprisingly, this association was not observed with the other RFs. The higher basal expression of TRIM5? observed in PBMC than in duodenal tissues emphasizes the understated role of the second barrier to systemic infection involving the transport of virus from the mucosal compartment to the blood. Together, these observations provide a strong incentive for a more comprehensive examination of the intrinsic, variable control of constitutive expression of these genes in the sexual transmission of HIV. PMID:24884551



Mice constitutive for sex-limited protein (SLP) expression contain multiple Slp gene sequences.  


The murine fourth component of complement (C4) and sex-limited protein (Slp) are two closely related serum proteins whose structural genes map to the S region of H-2. Serum C4 levels vary as much as 20-fold between C4 high (C4H) and C4 low (C4L) strains, and Slp expression can be null (SlpO), limited to male mice of a subset of C4H strains (Slp+), or "constitutive" (SlpC), in which female as well as male mice express Slp. In this study, we compare, by genomic Southern blot analysis, the C4 and Slp genes from eight congenic inbred mouse strains representative of three distinct phenotypes: C4H, Slp+ (two strains), C4H, SlpO (two strains), C4H, SlpC (three strains), and C4L, SlpO (one strain). By using cDNA probes that recognize both C4 and Slp genes, and are derived from the extreme 5' and 3' ends of the mRNA as well as internal coding sequences, we find no evidence to suggest that strain-specific variations in the expression of C4 and Slp are due to gross deletions of major portions of the structural genes. In most cases, two distinct C4/Slp genes are detected; hybridization with C4- and Slp-specific probes indicate that one of these is C4 and the other is Slp. The three SlpC strains are exceptional: they carry at least four C4/Slp genes; one of these hybridizes to the C4-specific probe whereas the remaining genes hybridize to the Slp-specific probe. Hence, multiple duplication of a gene containing Slp sequences has occurred in certain strains of mice, and this is accompanied by constitutive expression of the Slp protein. PMID:3998475

Rosa, P A; Sepich, D S; Shreffler, D C; Ogata, R T



Constitutive expression of cell wall invertase genes increases grain yield and starch content in maize.  


Grain size, number and starch content are important determinants of grain yield and quality. One of the most important biological processes that determine these components is the carbon partitioning during the early grain filling, which requires the function of cell wall invertase. Here, we showed the constitutive expression of cell wall invertase-encoding gene from Arabidopsis, rice (Oryza sativa) or maize (Zea mays), driven by the cauliflower mosaic virus (CaMV) 35S promoter, all increased cell wall invertase activities in different tissues and organs, including leaves and developing seeds, and substantially improved grain yield up to 145.3% in transgenic maize plants as compared to the wild-type plants, an effect that was reproduced in our 2-year field trials at different locations. The dramatically increased grain yield is due to the enlarged ears with both enhanced grain size and grain number. Constitutive expression of the invertase-encoding gene also increased total starch content up to 20% in the transgenic kernels. Our results suggest that cell wall invertase gene can be genetically engineered to improve both grain yield and grain quality in crop plants. PMID:23926950

Li, Bei; Liu, Hua; Zhang, Yue; Kang, Tao; Zhang, Li; Tong, Jianhua; Xiao, Langtao; Zhang, Hongxia



Constitutive Expression of a High-Affinity Sulfate Transporter in Indian Mustard Affects Metal Tolerance and Accumulation  

E-print Network

Constitutive Expression of a High-Affinity Sulfate Transporter in Indian Mustard Affects Metal Terry, and Elizabeth A. H. Pilon-Smits* ABSTRACT The Stylosanthes hamata SHST1 gene encodes a high-affinity


Identification and refinement of two strong constitutive promoters for gene expression system of Schizosaccharomyces pombe.  


Fission yeast Schizosaccharomyces pombe shares various important properties with higher eukaryotes and is now considered a useful host for elevated production of mammalian proteins for medicinal applications. The full-length nmt1 promoter has been widely used as a strong promoter in S. pombe expression system. In the present study, the promoters of the eno101 and gpd3 genes in S. pombe were identified as strong constitutive promoters. For convenient applications in the plasmids of S. pombe, these promoters were refined to 276-bp eno and 273-bp gpd promoters by deleting undesired sequences and examining the expression of reporter genes including lacZ and xynA. Both the refined eno and gpd promoters provided approximately 1.5-fold higher expression of LacZ than nmt1 promoter. Furthermore, gene expression under the control of the eno or gpd promoter was not repressed by the components of YES medium while nmt1 promoter was inhibited by thiamine in yeast extract. Therefore, both eno and gpd promoters offer opportunities for efficient production of recombinant proteins by S. pombe in high cell-density fermentation. PMID:24452856

Wang, Hongcheng; Wang, Haiyang; Wang, Meng; Zhang, Lei; Wang, Ren; Mei, Yanzhen; Shao, Weilan



Electronic Supplemental Material Table 1: Examples of constitutively expressed novel traits of macroevolutionary  

E-print Network

) Pontia occidentalis (gray- veined white butterfly) Constitutive vernal wing phenotype Unpredictable cold Constitutive egg production Periods of ample larval nutrition [1,2] Pontia protodice (checkered white butterfly

Abouheif, Ehab


Expression of Constitutive Nitric Oxide Synthase Isoforms in Varicose Vein Wall; Preliminary Results  

PubMed Central

There are conflicting findings in literature about the structural changes of the primary varicose veins. NO (a potent vasodilatator) is synthesized by nitric oxide synthase (NOS). From 3 known NOS isoforms the two are constitutional: eNOS (endothelial NOS) and nNOS (neuronal NOS). 10 varicose and 10 control vein samples were processed by standard light microscopy and immuno-histochemica techniques using rabbit polyclonal antibodies against eNOS and nNOS. Antibodies expression was evaluated semiquantitatively and proved morphometrically by 2D-image analysis. total area of NOS isoforms expressions was determined by color analysis and color digital subtraction. The results showed discontinuous and significantly lower expression of both NOS isoforms the in the tunica media of varicose veins compared with the control group. For the statistical analysis the unpaired t-test was used. Our results suppose lower NO levels in varicose vein wall, deducing that varicose dilatation is due to other mechanism, and they contradict the results of previously published similar works. PMID:21748016

Haviarova, Zora; Janegova, Andrea; Janega, Pavel; Durdik, Stefan; Kovac, Peter; Stvrtinova, Viera; Mraz, Peter



Constitutive phosphorylation of the FOXO1 transcription factor in gastric cancer cells correlates with microvessel area and the expressions of angiogenesis-related molecules  

Microsoft Academic Search

Background  Although FOXO transcription factors may have an anti-angiogenic role, little is known about their role in tumor angiogenesis.\\u000a The present study was performed to investigate the correlation between the constitutive expression of phosphorylated FOXO1\\u000a (pFOXO1) and angiogenesis in gastric cancer.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Immunohistochemistry was performed on tissue array slides containing 272 gastric carcinoma specimens, and the correlations\\u000a between the cytoplasmic pFOXO1 expression

Sue Youn Kim; Jiyeon Yoon; Young San Ko; Mee Soo Chang; Jong-Wan Park; Hee Eun Lee; Min A Kim; Ji Hun Kim; Woo Ho Kim; Byung Lan Lee



Colonization of Transgenic Tobacco Constitutively Expressing Pathogenesis-Related Proteins by the Vesicular-Arbuscular Mycorrhizal Fungus Glomus mosseae  

PubMed Central

We studied the effect of constitutive expression of pathogenesis-related proteins (PRs) in tobacco plants on vesicular-arbuscular mycorrhiza. Tobacco lines genetically transformed to express various PRs constitutively under the control of the cauliflower mosaic virus 35S promoter of tobacco were examined. Immunoblot analysis and activity measurements demonstrated high levels of expression of the PRs in the root systems of the plants. Constitutive expression of the following acidic isoforms of tobacco PRs did not affect the time course or the final level of colonization by the vesicular-arbuscular mycorrhizal fungus Glomus mosseae: PR-1a, PR-3 (=PR-Q), PR-Q(prm1), PR-4, and PR-5. Similarly, constitutive expression of an acidic cucumber chitinase, of a basic tobacco chitinase with and without its vacuolar targeting peptide, of a basic (beta)-1,3-glucanase, and of combinations of PR-Q and PR-Q(prm1) or basic chitinase and basic (beta)-1,3-glucanase did not affect colonization by the mycorrhizal fungus. A delay of colonization by G. mosseae was observed in tobacco plants constitutively expressing the acidic isoform of tobacco PR-2, a protein with (beta)-1,3-glucanase activity. PMID:16535103

Vierheilig, H.; Alt, M.; Lange, J.; Gut-Rella, M.; Wiemken, A.; Boller, T.



Transcription factor ZBP-89 is required for STAT1 constitutive expression  

PubMed Central

IFN? is a pro-inflammatory cytokine that potentiates p53-independent apoptosis in a variety of cell types. STAT1 is the primary mediator of IFN? action. ZBP-89 is a transcription factor that binds to the G/C-rich elements and mediates p53-independent apoptosis. In this study, site-directed mutagenesis revealed that a G-rich element from +171 to +179 within the first intron of the STAT1 gene is critical for optimal STAT1 promoter activity. Electrophoretic mobility shift assays and promoter analysis revealed that ZBP-89 binds directly to this STAT1 G-rich element along with Sp1 and Sp3. Reduction of ZBP-89 with siRNA attenuated both basal and IFN?-induced STAT1 expression and subsequently diminished the activation of apoptotic markers, e.g. caspase-3 and PARP. Taken together, we conclude that ZBP-89 is required for constitutive STAT1 expression and in this way contributes to the ability of cells to be activated by IFN?. PMID:14654702

Bai, Longchuan; Merchant, Juanita L.



Constitutive Expression of Thermobifida fusca Thermostable Acetylxylan Esterase Gene in Pichia pastoris  

PubMed Central

A gene encoding the thermostable acetylxylan esterase (AXE) in Thermobifida fusca NTU22 was amplified by PCR, sequenced and cloned into the Pichia pastoris X-33 host strain using the vector pGAPZ?A, allowing constitutive expression and secretion of the protein. Recombinant expression resulted in high levels of extracellular AXE production, as high as 526 U/mL in the Hinton flask culture broth. The purified enzyme showed a single band at about 28 kDa by SDS-polyacrylamide gel electrophoresis after being treated with endo-?-N-acetylglycosaminidase H; this agrees with the predicted size based on the nucleotide sequence. About 70% of the original activity remained after heat treatment at 60 °C for three hours. The optimal pH and temperature of the purified enzyme were 8.0 and 60 °C, respectively. The properties of the purified AXE from the P. pastoris transformant are similar to those of the AXE from an E. coli transformant. PMID:21614198

Yang, Chao-Hsun; Lin, Kun-I; Chen, Gen-Hung; Chen, Yu-Fen; Chen, Cheng-Yu; Chen, Wei-Lin; Huang, Yu-Chun



Constitutive expression of a rhIL-2-HSA fusion protein in Pichia pastoris using glucose as carbon source.  


A constitutive expression vector for rhIL-2-HSA fusion protein production in yeast Pichia pastoris was constructed. The coding gene was placed in frame with the Saccharomyces cerevisiae ?-factor secretion signal sequence under the control of the GAP promoter. The recombinant plasmid pGAPZ?A-rhIL-2-HSA was integrated into the genome of the P. pastoris GS115. The effect of different carbon sources on rhIL-2-HSA fusion protein expression was evaluated in shaking flask cultures. We found that recombinant P. pastoris grew well and efficiently secreted rhIL-2-HSA fusion protein into the medium when using glucose as carbon source. To achieve higher production, the influence of initial pH and culture temperature was also evaluated. Fed-batch fermentation strategy using glucose as carbon source for constitutive expression of rhIL-2-HSA fusion protein was investigated in 5-L bioreactor and the expression level of rhIL-2-HSA could reach about 250 mg/L after 60-h fermentation. The rhIL-2-HSA fusion protein produced by this constitutive expression system was purified and exhibited a specific bioactivity of 1.040 × 10(6) IU/mg in vitro. This study described constitutive expression of rhIL-2-HSA fusion protein by P. pastoris and development of a simple high-cell density fermentation strategy for biologically active rhIL-2-HSA fusion protein using glucose as sole carbon source. PMID:23999737

Guan, Bo; Chen, Fengxiang; Lei, Jianyong; Li, Yunhua; Duan, Zuoying; Zhu, Ruiyu; Chen, Yun; Li, Huazhong; Jin, Jian



Altered Constitutive Expression of Fatty Acid-metabolizing Enzymes in Mice Lacking the Peroxisome Proliferator-activated  

E-print Network

Altered Constitutive Expression of Fatty Acid-metabolizing Enzymes in Mice Lacking the Peroxisome University School of Medicine, Matsumoto, Nagano 390, Japan Peroxisome proliferator-activated receptor (PPAR of peroxisomal and mitochondrial fatty acid metabolizing enzymes were deter- mined in the PPAR null mouse

Omiecinski, Curtis


Teaching Constitutional Issues with Scripted Trials: Search and Seizure, Freedom of Expression, and the Establishment Clause. Volume 1.  

ERIC Educational Resources Information Center

Intended for use by high school U.S. history and government teachers and students, these scripted trials and related materials are designed to help students develop an understanding about important ideas in the U.S. Constitution. The document focuses on three fundamental issues of the Bill of Rights: search and seizure, freedom of expression, and…

Leming, Robert S.; Vontz, Thomas S.



EPA Science Inventory

Constitutive expression of mRNAs for GROa, GROB, GROY, and MCP-1, belonging to the chemokine family of 8-10 kD cytokines with chemotactic properties for granulocytes and monocytes, has been identified in freshly isolated human nasal and bronchial epithelium, and in bronchoalveola...


Cell, Vol. 93, 12071217, June 26, 1998, Copyright 1998 by Cell Press Constitutive Expression of the CIRCADIAN CLOCK  

E-print Network

of the CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) Gene Disrupts Circadian Rhythms and Suppresses Its Own Expression in the phytochrome induction of a light-harvesting a circadian rhythm. These include movement of organs chlorophyll a with a circadian rhythm. Constitutive ex- processes such as respiration and photosynthesis, and pression of CCA1

Tobin, Elaine


Constitutive mRNA Expression of Various Glutathione S-Transferase Isoforms in Different Tissues of Mice  

Microsoft Academic Search

Glutathione S-transferase (Gst) enzymes are instrumental in protecting cellular macromolecules against electrophiles and products of oxidative stress. Of interest primarily to pharmacol- ogists and toxicologists is the ability of these enzymes to metabolize cancer chemotherapeutic drugs, insecticides, herbi- cides, and carcinogens. Thus, constitutive expression of Gsts might determine a tissue's ability to handle certain forms of chemical stress. In the

Tamara Raphael Knight; Supratim Choudhuri; Curtis D. Klaassen



Constitutive expression of the taurine transporter in a human colon carcinoma cell line.  


The human colon carcinoma cell line HT-29, when grown to confluence, was found to take up taurine and accumulate it against a concentration gradient from a NaCl-containing uptake medium. Replacement of NaCl with choline chloride almost totally abolished the uptake. Taurine uptake was dependent not only on Na+ but also on Cl-, because other anions failed to support the uptake in the presence of Na+. The uptake process was specific for beta-amino acids such as taurine, hypotaurine, and beta-alanine. Apparently, a single transport system with a Michaelis-Menten constant of 10.6 +/- 0.3 microM was responsible for the uptake. Stoichiometric analyses revealed that the Na+:taurine coupling ratio was 2:1, whereas the Cl-:taurine coupling ratio was 1:1. Culture of the cells in the presence of taurine caused downregulation of the uptake system. These cells were also capable of accumulating beta-alanine against a concentration gradient in the presence of NaCl. Beta-Alanine uptake occurred via a single transport system with an apparent Michaelis-Menten constant of 36 +/- 2 microM. Taurine and beta-alanine exhibited mutual interaction during uptake. Kinetic experiments strongly suggested that a common transporter was responsible for the uptake of these two beta-amino acids. It is concluded that the HT-29 cells constitutively express the taurine transporter and that this cell line may be a suitable model for investigations of intestinal taurine transporter. PMID:1443137

Tiruppathi, C; Brandsch, M; Miyamoto, Y; Ganapathy, V; Leibach, F H



New Vectors for Chromosomal Integration Enable High-Level Constitutive or Inducible Magnetosome Expression of Fusion Proteins in Magnetospirillum gryphiswaldense  

PubMed Central

The alphaproteobacterium Magnetospirillum gryphiswaldense biomineralizes magnetosomes, which consist of monocrystalline magnetite cores enveloped by a phospholipid bilayer containing specific proteins. Magnetosomes represent magnetic nanoparticles with unprecedented magnetic and physicochemical characteristics. These make them potentially useful in a number of biotechnological and biomedical applications. Further functionalization can be achieved by expression of foreign proteins via genetic fusion to magnetosome anchor peptides. However, the available genetic tool set for strong and controlled protein expression in magnetotactic bacteria is very limited. Here, we describe versatile vectors for either inducible or high-level constitutive expression of proteins in M. gryphiswaldense. The combination of an engineered native PmamDC promoter with a codon-optimized egfp gene (Mag-egfp) resulted in an 8-fold increase in constitutive expression and in brighter fluorescence. We further demonstrate that the widely used Ptet promoter is functional and tunable in M. gryphiswaldense. Stable and uniform expression of the EGFP and ?-glucuronidase (GusA) reporters was achieved by single-copy chromosomal insertion via Tn5-mediated transposition. In addition, gene duplication by Mag-EGFP–EGFP fusions to MamC resulted in further increased magnetosome expression and fluorescence. Between 80 and 210 (for single MamC–Mag-EGFP) and 200 and 520 (for MamC–Mag-EGFP–EGFP) GFP copies were estimated to be expressed per individual magnetosome particle. PMID:24532068

Borg, Sarah; Hofmann, Julia; Pollithy, Anna; Lang, Claus



Hypoxia reduces constitutive and TNF-{alpha}-induced expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells  

SciTech Connect

Chronic hypoxia has been reported to be associated with macrophage infiltration in progressive forms of kidney disease. Here, we investigated the regulatory effects of hypoxia on constitutive and TNF-{alpha}-stimulated expression of monocyte chemoattractant protein-1 (MCP-1) in cultured human proximal renal tubular cells (HPTECs). Hypoxia reduced constitutive MCP-1 expression at the mRNA and protein levels in a time-dependent fashion for up to 48 h. Hypoxia also inhibited MCP-1 up-regulation by TNF-{alpha}. Treatment with actinomycin D showed that hypoxic down-regulation of MCP-1 expression resulted mainly from a decrease in the transcription but not the mRNA stability. Immunoblot and immunofluorescence analyses revealed that treatment with hypoxia or an iron chelator, desferrioxamine, induced nuclear accumulation of hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) in HPTECs. Desferrioxamine mimicked hypoxia in the reduction of MCP-1 expression. However, overexpression of a dominant negative form of HIF-1{alpha} did not abolish the hypoxia-induced reduction of MCP-1 expression in HPTECs. These results suggest that hypoxia is an important negative regulator of monocyte chemotaxis to the renal inflamed interstitium, by reducing MCP-1 expression partly via hypoxia-activated signals other than the HIF-1 pathway.

Li Xuan [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Kimura, Hideki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)]. E-mail:; Hirota, Kiichi [Department of Anesthesia, Tazuke Kofukai Medical Research Institute Kitano Hospital, Osaka (Japan); Department of Anesthesia, School of Medicine, Kyoto University, Kyoto (Japan); Sugimoto, Hidehiro [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Yoshida, Haruyoshi [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)



Field tolerance to fungal pathogens of Brassica napus constitutively expressing a chimeric chitinase gene  

SciTech Connect

Constitutive overexpression of a protein involved in plant defense mechanisms to disease is one of the strategies proposed to increase plant tolerance to fungal pathogens. A hybrid endochitinase gene under a constitutive promoter was introduced by Agrobacterium-mediated transformation into a winter-type oilseed rape (Brassica napus var. oleifera) inbred line. Progeny from transformed plants was challenged using three different fungal pathogens (Cylindrosporium concentricum, Phoma lingam, Sclerotinia sclerotiorum) in field trials at two different geographical locations. These plants exhibited an increased tolerance to disease as compared with the nontransgenic parental plants. 31 refs., 1 fig., 2 tabs.

Grison, R.; Grezes-Besset, B.; Lucante, N. [Rustica Prograin Genetique, Mondonville (France)] [and others] [Rustica Prograin Genetique, Mondonville (France); and others



Human Interleukin 113 Is Not Secreted From Hamster Fibroblasts When Expressed Constitutively From a Transfected cDNA  

Microsoft Academic Search

To understand the secretion and processing of interleukin-1 (IL-1), a Chinese hamster fibroblast cell line (R1610) was transfected with a human IL-113 cDNA under the control of the SV40 early promoter and linked to the gene for neomycin resistance. After selecting for transfected cells resistant to G418, two clones were found to constitutively express the IL-113 31-kD precursor which was

Peter R. Young; Daria J. Hazuda; Philip L. Simon



Revealing constitutively expressed resistance genes in Agrostis species using PCR-based motif-directed RNA fingerprinting.  


Agrostis species are mainly used in athletic fields and golf courses. Their integrity is maintained by fungicides, which makes the development of disease-resistance varieties a high priority. However, there is a lack of knowledge about resistance (R) genes and their use for genetic improvement in Agrostis species. The objective of this study was to identify and clone constitutively expressed cDNAs encoding R gene-like (RGL) sequences from three Agrostis species (colonial bentgrass (A. capillaris L.), creeping bentgrass (A. stolonifera L.) and velvet bentgrass (A. canina L.)) by PCR-based motif-directed RNA fingerprinting towards relatively conserved nucleotide binding site (NBS) domains. Sixty-one constitutively expressed cDNA sequences were identified and characterized. Sequence analysis of ESTs and probable translation products revealed that RGLs are highly conserved among these three Agrostis species. Fifteen of them were shown to share conserved motifs found in other plant disease resistance genes such as MLA13, Xa1, YR6, YR23 and RPP5. The molecular evolutionary forces, analysed using the Ka/Ks ratio, reflected purifying selection both on NBS and leucine-rich repeat (LRR) intervening regions of discovered RGL sequences in these species. This study presents, for the first time, isolation and characterization of constitutively expressed RGL sequences from Agrostis species revealing the presence of TNL (TIR-NBS-LRR) type R genes in monocot plants. The characterized RGLs will further enhance knowledge on the molecular evolution of the R gene family in grasses. PMID:17371611

Budak, Hikmet; Su, Senem; Ergen, Neslihan



Constitutive and cytokine-induced expression of human leukocyte antigens and cell adhesion molecules by human myotubes.  

PubMed Central

Understanding the immunobiology of muscle is relevant to muscular autoimmune diseases and to gene therapies based on myoblast transfer. We have investigated the constitutive and cytokine-induced intra- and extracellular expression of histocompatibility human leukocyte antigens (HLA) and cell adhesion molecules by multinucleated human myotubes using immunofluorescence microscopy. Myotubes constitutively expressed HLA class I but not HLA class II. Exposure to interferon-gamma, but not tumor necrosis factor-alpha, induced HLA-DR in the cytoplasm and on the surface membrane of approximately 40 to 95% of cultured myotubes. Surface expression was strongest in perinuclear membrane areas, and cytoplasmic expression was strongest at branching points and at the tips of myotubes. HLA-DP and HLA-DQ were not expressed in detectable amounts. Both interferon-gamma and tumor necrosis factor-alpha induced the intercellular adhesion molecule-1 (CD54) in the cytoplasm and on the surface of nearly all myotubes. The distribution of intercellular adhesion molecule-1 and HLA-DR was similar but not identical in double-positive myotubes. The leukocyte function-associated (LFA) adhesion molecules LFA-1 (CD11a/CD18), LFA-2 (CD2), and LFA-3 (CD58) could not be detected in the cytoplasm or on the surface. Our results indicate that cytokine-induced myotubes can participate in immune interactions with T lymphocytes. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8214008

Michaelis, D.; Goebels, N.; Hohlfeld, R.



Regulation of beta-glucuronidase synthesis in Escherichia coli K-12: constitutive mutants specifically derepressed for uidA expression.  


All methyl-beta-D-galacturonide-positive mutants isolated from Escherichia coli K-12 carry constitutive mutations for beta-glucuronidase (UID) synthesis. Most of these mutants are specific for UID synthesis and are distributed in three classes according to the derepression level of UID. Each specific mutant carries a mutation(s) near uidA, the structural gene for UID, at min 30.5 of the E. coli K-12 linkage map. The expression of UID synthesis in F-merodiploid strains carrying these mutations permits discrimination between dominant and recessive constitutivity over the wild-type allele. The first kind of mutation (dominant) should affect the operator site uidO of the structural gene uidA; the second type of mutation (recessive) should affect a regulatory gene, uidR, operating through a negative control. The isolation of mutants bearing at this locus superrepressed mutations, which can revert to produce a constitutive phenotype, confirms the occurrence of such a regulatory gene. The partially derepressed uidR mutants of the first class are normally inducible and remain constitutive at low temperature; their UID has the same thermal sensitivity as in the wild-type strains. The occurrence of similar regulatory gene mutants has been recently described in the lactose system (Shineberg, 1974). PMID:776933

Novel, M; Novel, G



Mast cell hyperplasia, B-cell malignancy, and intestinal inflammation in mice with conditional expression of a constitutively active kit.  


Signaling through the receptor tyrosine kinase kit controls proliferation and differentiation of hematopoietic precursor cells and mast cells. Somatic point mutations of the receptor that constitutively activate kit signaling are associated with mastocytosis and various hematopoietic malignancies. We generated a Cre/loxP-based bacterial artificial chromosome transgenic mouse model that allows conditional expression of a kit gene carrying the kitD814V mutation (the murine homolog of the most common mutation in human mastocytosis, kitD816V) driven by the kit promoter. Expression of the mutant kit in cells of adult mice, including hematopoietic precursors, caused severe mastocytosis with 100% penetrance at young age frequently associated with additional hematopoietic (mostly B lineage-derived) neoplasms and focal colitis. Restriction of transgene expression to mature mast cells resulted in a similar mast cell disease developing with slower kinetics. Embryonic expression led to a hyperproliferative dysregulation of the erythroid lineage with a high rate of perinatal lethality. In addition, most adult animals developed colitis associated with mucosal mast cell accumulation. Our findings demonstrate that the effects of constitutive kit signaling critically depend on the developmental stage and the state of differentiation of the cell hit by the gain-of-function mutation. PMID:21148330

Gerbaulet, Alexander; Wickenhauser, Claudia; Scholten, Julia; Peschke, Katrin; Drube, Sebastian; Horny, Hans-Peter; Kamradt, Thomas; Naumann, Ronald; Müller, Werner; Krieg, Thomas; Waskow, Claudia; Hartmann, Karin; Roers, Axel



SMYD2 is highly expressed in pediatric acute lymphoblastic leukemia and constitutes a bad prognostic factor.  


Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Although several clinical characteristics can be associated with worse prognosis, more robust biological markers still remains uncovered. SMYD2, a member of SMYD protein family, regulates the activity of several proteins through methylation. In this study, we performed quantitative real time PCR to compare the expression of SMYD2 in 83 pediatric ALL patients and non-neoplastic bone marrow samples (BMS). The study revealed that SMYD2 expression is altered in ALL BMS and its high expression was correlated with a bad prognosis. Moreover, we also revealed that SMYD2 expression level significantly decreases in patients that respond to chemotherapy treatment. PMID:24631370

Sakamoto, Luis Henrique Toshihiro; Andrade, Rosangela Vieira de; Felipe, Maria Sueli Soares; Motoyama, Andrea Barretto; Pittella Silva, Fabio



Constitutive IL-2 expression in HTLV-I-infected leukaemic T cell lines.  

PubMed Central

An IL-2 autocrine growth circuit has been proposed as a major mechanism in HTLV-I-related leukaemogenesis. We have developed a polymerase chain reaction combined with reverse transcription RT-PCR to detect IL-2 transcripts and a sensitive immunostaining method for IL-2 protein. Combination of these two methods with in situ hybridization demonstrated that most cells of the T cell line IARC 301.5, whose proliferation is stimulated by autocrine IL-2, constitutively synthesize IL-2. This pattern was also found in the HTLV-I T cell lines HUT, MT2 and C 8166/45, and in the HTLV-I-negative T cell lines Jurkat and HSB2 but not MOLT4. Four non-lymphoid cell lines and cultured fibroblasts were negative, in agreement with the T cell specificity of IL-2 synthesis. Hence, most T cell lines tested, whether HTLV-I-infected or not, constitutively synthesize IL-2, suggesting a possible common feature of leukaemic T cell lines. The presence of IL-2 transcript and protein in most cells of the reacting cell lines is consistent with an autocrine process possibly involved at some stage in acquiring growth autonomy. Images Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:1710547

Farcet, J P; Lebargy, F; Lavignac, C; Gaulard, P; Dautry, A; Gazzolo, L; Romeo, P H; Vainchenker, W



Glucocorticoids inhibit the expression of an inducible, but not the constitutive, nitric oxide synthase in vascular endothelial cells.  

PubMed Central

Vascular endothelial cells contain a constitutive nitric oxide (NO) synthase that is Ca2(+)-dependent. In addition, we have found that these cells express, after activation with interferon-gamma and lipopolysaccharide, an inducible Ca2(+)-independent NO synthase that is distinct from the constitutive enzyme. The generation of NO by this enzyme was detectable after a lag period of 2 hr, reached a maximum between 6 and 12 hr, and was maintained for the duration of the experiment (48 hr). The expression of the inducible NO synthase was inhibited by the protein synthesis inhibitor cycloheximide, a compound that had no direct effect on the activity of either of the two enzymes. Furthermore, hydrocortisone and dexamethasone, but not progesterone, inhibited the expression of the inducible enzyme, without directly affecting the activity of either enzyme, without directly affecting the activity of either enzyme. The effect of these steroids was inhibited in a concentration-dependent manner by cortexolone, a partial agonist of glucocorticoid receptors. Thus, the inhibition of the induction of an NO synthase by glucocorticoids is a receptor-mediated event involving the inhibition of the synthesis of mRNA for de novo synthesis of this enzyme. The induction of this NO synthase may contribute to the pathophysiology of immunologically based conditions. Furthermore, the inhibition of this induction by anti-inflammatory steroids may explain some of the therapeutic and adverse effects of these compounds. PMID:1702214

Radomski, M W; Palmer, R M; Moncada, S



Aberrant expression and constitutive activation of STAT3 in cervical carcinogenesis: implications in high-risk human papillomavirus infection  

Microsoft Academic Search

BACKGROUND: Recent observations indicate potential role of transcription factor STAT3 in cervical cancer development but its role specifically with respect to HPV infection is not known. Present study has been designed to investigate expression and activation of STAT3 in cervical precancer and cancer in relation to HPV infection during cervical carcinogenesis. Established cervical cancer cell lines and prospectively-collected cervical precancer

Shirish Shukla; Gauri Shishodia; Sutapa Mahata; Suresh Hedau; Arvind Pandey; Suresh Bhambhani; Swaraj Batra; Seemi F Basir; Bhudev C Das; Alok C Bharti



Sex steroid hormones regulate constitutive expression of Cyp2e1 in female mouse liver  

PubMed Central

CYP2E1 is of paramount toxicological significance because it metabolically activates a large number of low-molecular-weight toxicants and carcinogens. In this context, factors that interfere with Cyp2e1 regulation may critically affect xenobiotic toxicity and carcinogenicity. The aim of this study was to investigate the role of female steroid hormones in the regulation of CYP2E1, as estrogens and progesterone are the bases of contraceptives and hormonal replacement therapy in menopausal women. Interestingly, a fluctuation in the hepatic expression pattern of Cyp2e1 was revealed in the different phases of the estrous cycle of female mice, with higher Cyp2e1 expression at estrus (E) and lower at methestrus (ME), highly correlated with that in plasma gonadal hormone levels. Depletion of sex steroids by ovariectomy repressed Cyp2e1 expression to levels similar to those detected in males and cyclic females at ME. Hormonal supplementation brought Cyp2e1 expression back to levels detected at E. The role of progesterone appeared to be more prominent than that of 17?-estradiol. Progesterone-induced Cyp2e1 upregulation could be attributed to inactivation of the insulin/PI3K/Akt/FOXO1 signaling pathway. Tamoxifen, an anti-estrogen, repressed Cyp2e1 expression potentially via activation of the PI3K/Akt/FOXO1 and GH/STAT5b-linked pathways. The sex steroid hormone-related changes in hepatic Cyp2e1 expression were highly correlated with those observed in Hnf-1?, ?-catenin, and Srebp-1c. In conclusion, female steroid hormones are clearly involved in the regulation of CYP2E1, thus affecting the metabolism of a plethora of toxicants and carcinogenic agents, conditions that may trigger several pathologies or exacerbate the outcomes of various pathophysiological states. PMID:23548611

Cheng, Jie; Gonzalez, Frank J.



Constitutive expression of a celery mannitol dehydrogenase in tobacco enhances resistance to the mannitol-secreting  

E-print Network

, and its expression is induced by salicylic acid (SA), an inducer of many plant defense proteins. Mason Pharr1 and John D. Williamson1,Ã? 1 Department of Horticultural Science, and 2 Department of Botany previous observation that host plant extracts induce production and secretion of mannitol in the tobacco

Daub, Margaret


Constitutive expression of human keratin 14 gene in mouse lung induces premalignant lesions and squamous differentiation  

Microsoft Academic Search

Squamous cell carcinoma accounts for 20% of all human lung cancers and is strongly linked to cigarette smoking. It develops through premalignant changes that are characterized by high levels of keratin 14 (K14) expression in the airway epithelium and evolve through basal cell hyperplasia, squamous metaplasia and dysplasia to carcinoma in situ and invasive carcinoma. In order to explore the

EL Habib Dakir; Lionel Feigenbaum; R. Ilona


Antiviral specificity of the Solea senegalensis Mx protein constitutively expressed in CHSE-214 cells.  


Interferons play a key role in fish resistance to viral infections by inducing the expression of antiviral proteins, such as Mx. The aim of the present study was to test the antiviral activity of the Senegalese sole Mx protein (SsMx) against RNA and DNA viruses pathogenic to fish, i.e. the infectious pancreatic necrosis virus (IPNV, dsRNA), the viral haemorrhagic septicaemia virus (VHSV, ssRNA), and the European sheatfish virus (ESV, dsDNA), using a CHSE-214 cell clone expressing this antiviral protein. A strong inhibition of IPNV and VHSV replication was recorded in SsMx-expressing cells, as has been shown by the virus yield reduction and the decrease in the synthesis of the viral RNA encoding the polyprotein (for IPNV) and the nucleoprotein (for VHSV). The titres of these viruses replicating on SsMx-expressing cells were 100 times lower than those recorded on non-transfected cells. In contrast, SsMx did not inhibit ESV replication since no significant differences were observed regarding the virus yield or the major capsid protein gene transcription in transfected and non-transfected cells. PMID:22886190

Alvarez-Torres, Daniel; Garcia-Rosado, Esther; Fernandez-Trujillo, M Alejandra; Bejar, Julia; Alvarez, M Carmen; Borrego, Juan J; Alonso, M Carmen



Development and validation of four Leishmania species constitutively expressing GFP protein. A model for drug discovery and disease pathogenesis studies.  


Green fluorescent protein (GFP)-parasite transfectants have been widely used as a tool for studying disease pathogenesis in several protozoan models and their application in drug screening assays has increased rapidly. In the past decade, the expression of GFP has been established in several Leishmania species, mostly for in vitro studies. The current work reports generation of four transgenic parasites constitutively expressing GFP (Leishmania mexicana, Leishmania aethiopica, Leishmania tropica and Leishmania major) and their validation as a representative model of infection. This is the first report where stable expression of GFP has been achieved in L. aethiopica and L. tropica. Integration of GFP was accomplished through homologous recombination of the expression construct, pRib1.2?NEO?GFP downstream of the 18S rRNA promoter in all species. A homogeneous and high level expression of GFP was detected in both the promastigote and the intracellular amastigote stages. All transgenic species showed the same growth pattern, ability to infect mammalian host cells and sensitivity to reference drugs as their wild type counterparts. All four transgenic Leishmania are confirmed as models for in vitro and possibly in vivo infections and represent an ideal tool for medium throughput testing of compound libraries. PMID:24252638

Patel, Asha Parbhu; Deacon, Andrew; Getti, Giulia



Evaluation of constitutive iron reductase (AtFRO2) expression on mineral accumulation and distribution in soybean (Glycine max. L)  

PubMed Central

Iron is an important micronutrient in human and plant nutrition. Adequate iron nutrition during crop production is central for assuring appropriate iron concentrations in the harvestable organs, for human food or animal feed. The whole-plant movement of iron involves several processes, including the reduction of ferric to ferrous iron at several locations throughout the plant, prior to transmembrane trafficking of ferrous iron. In this study, soybean plants that constitutively expressed the AtFRO2 iron reductase gene were analyzed for leaf iron reductase activity, as well as the effect of this transgene’s expression on root, leaf, pod wall, and seed mineral concentrations. High Fe supply, in combination with the constitutive expression of AtFRO2, resulted in significantly higher concentrations of different minerals in roots (K, P, Zn, Ca, Ni, Mg, and Mo), pod walls (Fe, K, P, Cu, and Ni), leaves (Fe, P, Cu, Ca, Ni, and Mg) and seeds (Fe, Zn, Cu, and Ni). Leaf and pod wall iron concentrations increased as much as 500% in transgenic plants, while seed iron concentrations only increased by 10%, suggesting that factors other than leaf and pod wall reductase activity were limiting the translocation of iron to seeds. Protoplasts isolated from transgenic leaves had three-fold higher reductase activity than controls. Expression levels of the iron storage protein, ferritin, were higher in the transgenic leaves than in wild-type, suggesting that the excess iron may be stored as ferritin in the leaves and therefore unavailable for phloem loading and delivery to the seeds. Also, citrate and malate levels in the roots and leaves of transgenic plants were significantly higher than in wild-type, suggesting that organic acid production could be related to the increased accumulation of minerals in roots, leaves, and pod walls, but not in the seeds. All together, these results suggest a more ubiquitous role for the iron reductase in whole-plant mineral accumulation and distribution. PMID:24765096

Vasconcelos, Marta W.; Clemente, Thomas E.; Grusak, Michael A.



Higher constitutive IL15R? expression and lower IL-15 response threshold in coeliac disease patients  

PubMed Central

The IL-15 triggering effect of gliadin is not exclusive to coeliac disease (CD) patients, whereas the secondary response is CD specific. We have studied the expression of the IL-15 receptor, and the IL-15 response upon stimulation, in non-CD and CD patients, and the possible existence of a lower immunological threshold in the latter. Forty-two CD patients (20 on a gluten-containing diet, GCD, and 22 on gluten-free diet, GFD) and 24 non-CD healthy individuals were studied. IL15R? mRNA expression, and tissue characterization, were assayed in the duodenum. Biopsies from six CD patients on GFD and 10 non-CD individuals were studied in vitro using organ culture in basal conditions, as well as after IL-15 stimulation discarding basal IL-15 production. Secretion of immune mediators was measured in the culture supernatants. IL15R? mRNA expression was increased in CD patients, as compared with non-CD controls (on GFD P = 0·0334, on GCD P = 0·0062, respectively), and confirmed also by immunofluorescence. No differences were found between CD patients on GFD and on GCD. After in vitro IL-15 stimulation, IL15R? expression was only triggered in non-CD controls (P = 0·0313), though it remained increased in CD patients. Moreover, IL-15 induced a more intense immunological response in CD patients after triggering the production of both nitrites and IFN? (P = 0·0313, P = 0·0313, respectively). Gliadin-induced IL15 has a lower response threshold in CD patients, leading to the production of other immune mediators and the development of the intestinal lesion, and thus magnifying its effects within the CD intestine. PMID:18821940

Bernardo, D; Garrote, J A; Allegretti, Y; Leon, A; Gomez, E; Bermejo-Martin, J F; Calvo, C; Riestra, S; Fernandez-Salazar, L; Blanco-Quiros, A; Chirdo, F; Arranz, E



Construction of a constitutively expressed homo-fermentative pathway in Lactobacillus brevis.  


Lactobacillus brevis is a promising lactic acid producing strain that simultaneously utilizes glucose and xylose from lignocellulosic hydrolysate without carbon catabolic repression and inhibition. The production of by-products acetic acid and ethanol has been the major drawback of this strain. Two genes, pfkA (fructose-6-phosphate kinase [PFK]) and fbaA (fructose-1,6-biphosphate aldolase [FBA]), that encode the key enzymes of the EMP/glycolytic pathway from Lactobacillus rhamnosus, were fused to the downstream of the strong promoter P32 and expressed in L. brevis s3f4 as a strategy to minimize the formation of by-products. By expressing the two enzymes, a homo-fermentative pathway for lactic acid production was constructed. The lactic acid yields achieved from glucose in the transformants were 1.12 and 1.16 mol/mol, which is higher than that of the native strain (0.74 mol/mol). However, the lactic acid yield from xylose in the transformants stayed the same as that of the native strain. Enzyme assay indicated that the activity of the foreign protein FBA in the transformants was much higher than that of the native strains, but was ten times lower than that in L. rhamnosus. This result was consistent with the metabolic flux analysis, which indicated that the conversion efficiency of the expressed PFK and FBA was somewhat low. Less than 20 % of the carbons accumulated in the form of fructose-6-phosphate were converted into glyceraldehyde-3-phosphate (GAP) by the expressed PFK and FBA. Metabolic flux analysis also indicated that the enzyme phosphoketolase (XPK) played an important role in splitting the carbon flow from the pentose phosphate pathway to the phosphoketolase pathway. This study suggested that the lactic acid yield of L. brevis could be improved by constructing a homo-fermentative pathway. PMID:24728715

Guo, Wei; He, Ronglin; Ma, Lijuan; Jia, Wendi; Li, Demao; Chen, Shulin



Embryonal recombination and germline inheritance of recombined FRT loci mediated by constitutively expressed FLP in tobacco  

Microsoft Academic Search

FLP site-specific recombination has been shown in transgenic plants to excise DNA sequences between target FRT sites, and thereby activate transgenes in plants. In previous reports, crossing of tobacco plants expressing FLP recombinase\\u000a from a CaMV-35s promoter with plants containing the target FRT sites, hybrid plants with deletion sectors were generated, which were infrequently transmitted to progeny. In this report

David Gidoni; Moshe Bar; Baruch Leshem; Nehama Gilboa; Anahit Mett; Julia Feiler



are constitutively expressed in different structures of guinea pig skeletal muscle: implications for contractile function  

Microsoft Academic Search

The expression of NOS isoforms was studied in guinea pig skeletal muscle at the mRNA and protein level, and the effect of NO on contractile response was examined. Ribonuclease protection analyses demonstrated NOS I and NOS II mRNAs in diaphragm and gastrocnemius muscle. In Western blots, NOS I and NOS II immunoreacti'vities were found in the particulate but not the



Characterization of Constitutive Promoters for piggyBac Transposon-Mediated Stable Transgene Expression in Mesenchymal Stem Cells (MSCs)  

PubMed Central

Multipotent mesenchymal stem cells (MSCs) can undergo self-renewal and give rise to multi-lineages under given differentiation cues. It is frequently desirable to achieve a stable and high level of transgene expression in MSCs in order to elucidate possible molecular mechanisms through which MSC self-renewal and lineage commitment are regulated. Retroviral or lentiviral vector-mediated gene expression in MSCs usually decreases over time. Here, we choose to use the piggyBac transposon system and conduct a systematic comparison of six commonly-used constitutive promoters for their abilities to drive RFP or firefly luciferase expression in somatic HEK-293 cells and MSC iMEF cells. The analyzed promoters include three viral promoters (CMV, CMV-IVS, and SV40), one housekeeping gene promoter (UbC), and two composite promoters of viral and housekeeping gene promoters (hEFH and CAG-hEFH). CMV-derived promoters are shown to drive the highest transgene expression in HEK-293 cells, which is however significantly reduced in MSCs. Conversely, the composite promoter hEFH exhibits the highest transgene expression in MSCs whereas its promoter activity is modest in HEK-293 cells. The reduced transgene expression driven by CMV promoters in MSCs may be at least in part caused by DNA methylation, or to a lesser extent histone deacetlyation. However, the hEFH promoter is not significantly affected by these epigenetic modifications. Taken together, our results demonstrate that the hEFH composite promoter may be an ideal promoter to drive long-term and high level transgene expression using the piggyBac transposon vector in progenitor cells such as MSCs. PMID:24714676

Wen, Sheng; Zhang, Hongmei; Li, Yasha; Wang, Ning; Zhang, Wenwen; Yang, Ke; Wu, Ningning; Chen, Xian; Deng, Fang; Liao, Zhan; Zhang, Junhui; Zhang, Qian; Yan, Zhengjian; Liu, Wei; Zhang, Zhonglin; Ye, Jixing; Deng, Youlin; Zhou, Guolin; Luu, Hue H.; Haydon, Rex C.; Shi, Lewis L.; He, Tong-Chuan; Wei, Guanghui



De novo missense mutation in a constitutively expressed exon of the slow alpha-tropomyosin gene TPM3 associated with an atypical, sporadic case of nemaline myopathy  

Microsoft Academic Search

We describe an atypical case of nemaline myopathy with an unusual distribution of muscle weakness who presented at 14 years of age with kyphoscoliosis . In this patient, we demonstrate heterozygosity for a de novo CGT–CAT (Arg167His) mutation in a constitutively expressed exon (exon 5) of slow alpha-tropomyosin (TPM3). This is the first mutation identified in a constitutively expressed exon

H. J Durling; P Reilich; J Müller-Höcker; B Mendel; D Pongratz; C Wallgren-Pettersson; P Gunning; H Lochmüller; N. G Laing



Constitutive Expression of Human Telomerase Enhances the Proliferation Potential of Human Mesenchymal Stem Cells  

PubMed Central

Abstract Human mesenchymal stem cells (hMSCs) are highly desirable cells for bone engineering due to the inherent multipotent nature of the cells. Unfortunately, there is a high degree of variability, as primary hMSC cultures quickly undergo replicative senescence with loss of proliferative potential as they are continually propagated in cell culture. We sought to reduce the variability of these cells by insertion and expression of human telomerase reverse transcriptase (TERT) to immortalize the cell line. hMSCs were transduced with a lentivirus containing the human TERT gene. The resulting cell line has been propagated through more than 70 population-doubling level (PDL) to date and continues to grow exhibiting the characteristic fibroblastic hMSC phenotype. Expression of TERT mRNA and protein activity was confirmed in the TERT-transduced cells. Mock-transduced hMSCs had almost undetectable levels of TERT mRNA and protein activity and lost proliferation potential at PDL 14. The enhanced growth capacity of the hMSC TERT cells was due to increased cell proliferation and reduced cellular senescence rather than due to inhibition of apoptosis. The multipotent nature of the TERT cells was confirmed by differentiation toward the osteoblastic and adipogenic lineages in vitro. Osteoblastic differentiation was confirmed by both expression of alkaline phosphate and mineral deposition visualized by Alizarin Red staining. Adipogenic differentiation was confirmed by production of lipid droplets, which were detected by Oil Red-O staining. In summary, we have generated a stable hMSC line that can be continually propagated and retains both osteoblastic and adipogenic differentiation potential. PMID:23515239

Bischoff, David S.; Makhijani, Nalini S.



Expression of constitutively active guanylate cyclase in cardiomyocytes inhibits the hypertrophic effects of isoproterenol and aortic constriction on mouse hearts.  


Evidence from several rodent models has suggested that a reduction of either atrial natriuretic peptide or its receptor in the heart affects cardiac remodeling by promoting the onset of cardiac hypertrophy. The atrial natriuretic peptide receptor mediates signaling at least in part via the generation of intracellular cyclic GMP. To directly test whether accumulation of intracellular cyclic GMP conveys protection against cardiac hypertrophy, we engineered transgenic mice that overexpress a catalytic fragment of constitutively active guanylate cyclase domain of the atrial natriuretic peptide receptor in a cardiomyocyte-specific manner. Expression of the transgene increased the intracellular concentration of cyclic GMP specifically within cardiomyocytes and had no detectable effect on cardiac performance under basal conditions. However, expression of the transgene attenuated the effects of the pharmacologic hypertrophic agent isoproterenol on cardiac wall thickness and prevented the onset of the fetal gene expression program normally associated with cardiac hypertrophy. Likewise, expression of the transgene inhibited the hypertrophic effects of abdominal aortic constriction, since it abolished its effects on ventricular wall thickness and greatly attenuated its effects on cardiomyocyte size. Altogether, our results suggest that cyclic GMP is a cardioprotective agent against hypertrophy that acts via a direct local effect on cardiomyocytes. PMID:14500707

Zahabi, Ahmad; Picard, Sylvie; Fortin, Nadia; Reudelhuber, Timothy L; Deschepper, Christian F



Pmg-1 and pmg-2 constitute a novel family of KAP genes differentially expressed during skin and mammary gland development.  


The epidermis, by invagination of the undifferentiated ectodermal cells, gives rise to several distinct structures including hair, sebaceous, eccrine sweat and mammary glands. We have recently isolated a novel gene, pmg-1, expressed in the pubertal mouse mammary gland. While investigating its genomic structure, we identified a related gene in close proximity, which we have termed pmg-2. pmg-1 and pmg-2 are intron-less, are transcribed in opposite directions and are separated by a potential promoter region of 2.8 kb containing putative binding motifs for the developmental transcription factors Lef-1, Sox5 and D-STAT. pmg-1 and pmg-2 encode small proteins rich in G, S, F, Y and Q and contain characteristic repeats reminiscent of the keratin-associated proteins (KAPs). Both genes are expressed in growing hair follicles in skin as well as in sebaceous and eccrine sweat glands. Interestingly, expression is also detected in the mammary epithelium where it is limited to the onset of the pubertal growth phase and is independent of ovarian hormones. Their broad, developmentally controlled expression pattern, together with their unique amino acid composition, demonstrate that pmg-1 and pmg-2 constitute a novel KAP gene family participating in the differentiation of all epithelial cells forming the epidermal appendages. PMID:10446281

Kuhn, F; Lassing, C; Range, A; Mueller, M; Hunziker, T; Ziemiecki, A; Andres, A C



International Constitutional Law (ICL)  

NSDL National Science Digital Library

Hosted by the University of Wuerzburg (Germany), International Constitutional Law (ICL) provides English texts of constitutional documents and links to background information on over seventy countries. Documents are cross-referenced for comparison of constitutional provisions. Also featured are links to Constitutional Court sites, a Model Constitutional Code, a section on German Case Law, a comprehensive list of international organizations, and a strong collection of links to constitutional and international law and constitution sites. The material available at ICL is widely applicable to fields such as political science, international relations, or government, and could be very useful for research projects in both secondary and university classrooms.



Constitutive expression of yeast phospholipid biosynthetic genes by variants of Ino2 activator defective for interaction with Opi1 repressor.  


Regulated expression of structural genes involved in yeast phospholipid biosynthesis is mediated by inositol/choline-responsive element (ICRE) upstream motifs, bound by the heterodimeric activator complex Ino2 + Ino4. Gene repression occurs in the presence of sufficient inositol and choline, requiring an intact Opi1 repressor which binds to Ino2. For a better understanding of interactions among regulators, we mapped an 18 aa repressor interaction domain (RID, aa 118-135) within Ino2 necessary and sufficient for binding by Opi1. By alanine scanning mutagenesis of the entire RID we were able to identify nine residues critical for Opi1-dependent repression of Ino2 function. Consequently, the corresponding dominant Ino2 variants conferred constitutive expression of an ICRE-dependent reporter gene and were no longer inhibited even by overproduction of Opi1. Interestingly, Ino2 RID partially overlaps with transcriptional activation domain TAD2. As certain mutations exclusively affect repression while others affect both repression and activation, both functions of Ino2 can be functionally uncoupled. Correspondingly, we mapped the RID-binding activator interaction domain (AID, aa 321-380) at the C-terminus of Opi1 and introduced missense mutations at selected positions. An Opi1 variant simultaneously mutated at three highly conserved positions showed complete loss of repressor function, confirming RID-AID interaction as the crucial step of regulated expression of ICRE-dependent genes. PMID:15819625

Heyken, Willm-Thomas; Repenning, Antje; Kumme, Jacqueline; Schüller, Hans-Joachim



Constitutively Active PTH/PTHrP Receptor Specifically Expressed in Osteoblasts Enhances Bone Formation Induced by Bone Marrow Ablation  

PubMed Central

Bone is maintained by continuous bone formation by osteoblasts provided by proliferation and differentiation of osteoprogenitors. Parathyroid hormone (PTH) activates bone formation, but because of the complexity of cells in the osteoblast lineage, how these osteoprogenitors are regulated by PTH in vivo is incompletely understood. To elucidate how signals by PTH in differentiated osteoblasts regulate osteoprogenitors in vivo, we conducted bone marrow ablation using Col1a1-constitutively active PTH/PTHrP receptor (caPPR) transgenic mice. These mice express caPPR specifically in osteoblasts by using 2.3 kb Col1a1 promoter and showed higher trabecular bone volume under steady-state conditions. In contrast, after bone marrow ablation, stromal cells recruited from bone surface extensively proliferated in the marrow cavity in transgenic mice, compared to limited proliferation in wild-type mice. Whereas de novo bone formation was restricted to the ablated area in wild-type mice, the entire marrow cavity, including not only ablated area but also outside the ablated area, was filled with newly formed bone in transgenic mice. Bone mineral density was significantly increased after ablation in transgenic mice. Bone marrow cell culture in osteogenic medium revealed that alkaline phosphatase-positive area was markedly increased in the cells obtained from transgenic mice. Furthermore, mRNA expression of Wnt-signaling molecules such as LRP5, Wnt7b, and Wnt10b were upregulated after marrow ablation in bone marrow cells of transgenic mice. These results indicate that constitutive activation of PTH/PTHrP receptor in differentiated osteoblasts enhances bone marrow ablation-induced recruitment, proliferation, and differentiation of osteoprogenitors. PMID:21866553




Constitutive expression of ectopic c-Myc delays glucocorticoid-evoked apoptosis of human leukemic CEM-C7 cells  

PubMed Central

Sensitivity to glucocorticoid (GC)-evoked apoptosis in lymphoid cell lines correlates closely with GC-mediated suppression of c-Myc expression. To establish a functional role for c-Myc in GC-mediated apoptosis, we have stably expressed MycER™, the human c-Myc protein fused to the modified ligand-binding domain of the murine estrogen receptor ?, in GC-sensitive CEM-C7-14 cells. In CEM-C7-14 cells, MycER™ constitutively imparts c-Myc functions. Cells expressing MycER™ (C7-MycER™) exhibited a marked reduction in cell death after 72 h in 100 nM dexamethasone (Dex), with 10 – 20-fold more viable cells when compared to the parental CEM-C7-14 clone. General GC responsiveness was not compromised, as evidenced by Dex-mediated suppression of endogenous c-Myc and cyclin D3, and induction of c-Jun and the glucocorticoid receptor. MycER™ also blunted Dex-mediated upregulation of p27kip1 and suppression of the Myc target p53. In comparison to parental CEM-C7-14 cells, Dex-evoked DNA strand breaks were negligible and caspase activation was delayed, but the extent of G1 cell cycle arrest was similar in C7-MycER™ cells. Myc-ER™ did not result in permanent, complete resistance to GC however, and the GC-treated cells eventually died, indicative of redundant or interactive mechanisms in the GC-evoked lytic response of lymphoid cells. Our results emphasize the importance of c-Myc suppression in GC-evoked apoptosis of CEM-C7-14 cells. PMID:11498786

Medh, Rheem D; Wang, Aixia; Zhou, Feng; Thompson, E Brad



Genetic Background May Contribute to PAM50 Gene Expression Breast Cancer Subtype Assignments  

PubMed Central

Recent advances in genome wide transcriptional analysis have provided greater insights into the etiology and heterogeneity of breast cancer. Molecular signatures have been developed that stratify the conventional estrogen receptor positive or negative categories into subtypes that are associated with differing clinical outcomes. It is thought that the expression patterns of the molecular subtypes primarily reflect cell-of-origin or tumor driver mutations. In this study however, using a genetically engineered mouse mammary tumor model we demonstrate that the PAM50 subtype signature of tumors driven by a common oncogenic event can be significantly influenced by the genetic background on which the tumor arises. These results have important implications for interpretation of “snapshot” expression profiles, as well as suggesting that incorporation of genetic background effects may allow investigation into phenotypes not initially anticipated in individual mouse models of cancer. PMID:24015230

Hu, Ying; Bai, Ling; Geiger, Thomas; Goldberger, Natalie; Walker, Renard C.; Green, Jeffery E.; Wakefield, Lalage M.; Hunter, Kent W.



Memory for facial expression is influenced by the background music playing during study  

PubMed Central

The effect of the emotional quality of study-phase background music on subsequent recall for happy and sad facial expressions was investigated. Undergraduates (N = 48) viewed a series of line drawings depicting a happy or sad child in a variety of environments that were each accompanied by happy or sad music. Although memory for faces was very accurate, emotionally incongruent background music biased subsequent memory for facial expressions, increasing the likelihood that happy faces were recalled as sad when sad music was previously heard, and that sad faces were recalled as happy when happy music was previously heard. Overall, the results indicated that when recalling a scene, the emotional tone is set by an integration of stimulus features from several modalities. PMID:22956988

Woloszyn, Michael R.; Ewert, Laura



Genetic background may contribute to PAM50 gene expression breast cancer subtype assignments.  


Recent advances in genome wide transcriptional analysis have provided greater insights into the etiology and heterogeneity of breast cancer. Molecular signatures have been developed that stratify the conventional estrogen receptor positive or negative categories into subtypes that are associated with differing clinical outcomes. It is thought that the expression patterns of the molecular subtypes primarily reflect cell-of-origin or tumor driver mutations. In this study however, using a genetically engineered mouse mammary tumor model we demonstrate that the PAM50 subtype signature of tumors driven by a common oncogenic event can be significantly influenced by the genetic background on which the tumor arises. These results have important implications for interpretation of "snapshot" expression profiles, as well as suggesting that incorporation of genetic background effects may allow investigation into phenotypes not initially anticipated in individual mouse models of cancer. PMID:24015230

Hu, Ying; Bai, Ling; Geiger, Thomas; Goldberger, Natalie; Walker, Renard C; Green, Jeffery E; Wakefield, Lalage M; Hunter, Kent W



Ortho-aminoazotoluene activates mouse constitutive androstane receptor (mCAR) and increases expression of mCAR target genes  

SciTech Connect

2'-3-dimethyl-4-aminoazobenzene (ortho-aminoazotoluene, OAT) is an azo dye and a rodent carcinogen that has been evaluated by the International Agency for Research on Cancer (IARC) as a possible (class 2B) human carcinogen. Its mechanism of action remains unclear. We examined the role of the xenobiotic receptor Constitutive Androstane Receptor (CAR, NR1I3) as a mediator of the effects of OAT. We found that OAT increases mouse CAR (mCAR) transactivation in a dose-dependent manner. This effect is specific because another closely related azo dye, 3'-methyl-4-dimethyl-aminoazobenzene (3'MeDAB), did not activate mCAR. Real-time Q-PCR analysis in wild-type C57BL/6 mice revealed that OAT induces the hepatic mRNA expression of the following CAR target genes: Cyp2b10, Cyp2c29, Cyp3a11, Ugt1a1, Mrp4, Mrp2 and c-Myc. CAR-null (Car{sup -/-}) mice showed no increased expression of these genes following OAT treatment, demonstrating that CAR is required for their OAT dependent induction. The OAT-induced CAR-dependent increase of Cyp2b10 and c-Myc expression was confirmed by Western blotting. Immunohistochemistry analysis of wild-type and Car{sup -/-} livers showed that OAT did not acutely induce hepatocyte proliferation, but at much later time points showed an unexpected CAR-dependent proliferative response. These studies demonstrate that mCAR is an OAT xenosensor, and indicate that at least some of the biological effects of this compound are mediated by this nuclear receptor. - Highlights: > The azo dye and mouse carcinogen OAT is a very effective mCAR activator. > OAT increases mCAR transactivation in a dose-dependent manner. > OAT CAR-dependently increases the expression of a specific subset of CAR target genes. > OAT induces an unexpectedly deferred, but CAR-dependent hepatocyte proliferation.

Smetanina, Mariya A., E-mail: [Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030 (United States); Laboratory of Gene Expression Control, Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, prospekt Lavrentyeva 10, Novosibirsk 630090 (Russian Federation); Group of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, prospekt Lavrentyeva 8, Novosibirsk 630090 (Russian Federation); Pakharukova, Mariya Y. [Laboratory of Gene Expression Control, Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, prospekt Lavrentyeva 10, Novosibirsk 630090 (Russian Federation); Kurinna, Svitlana M. [Department of Biochemistry and Molecular Biology, Unit 1000, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030 (United States); Dong, Bingning; Hernandez, Juan P.; Moore, David D. [Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030 (United States); Merkulova, Tatyana I. [Laboratory of Gene Expression Control, Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, prospekt Lavrentyeva 10, Novosibirsk 630090 (Russian Federation)



Rabbit cardiac and skeletal myocytes differ in constitutive and inducible expression of the glucose-regulated protein GRP94.  

PubMed Central

The glucose-regulated protein GRP94 is a stress-inducible glycoprotein that is known to be constitutively and ubiquitously expressed in the endoplasmic reticulum of mammalian cells. From a rabbit heart cDNA library we isolated four overlapping clones coding for the rabbit homologue of GRP94 mRNA. Northern blot analysis shows that a 3200 nt mRNA species corresponding to GRP94 mRNA is detectable in several tissues and it is 5-fold more abundant in the heart than in the skeletal muscle. Hybridization analysis in situ shows that GRP94 mRNA accumulates in cardiac myocytes, whereas in skeletal muscles it is not detectable in myofibres. A monoclonal antibody raised by using a 35 kDa recombinant GRP94 polypeptide as immunogen detects a single reactive polypeptide of 94 kDa in a Western blot of liver and heart homogenates and does not react with skeletal muscle homogenates. Conversely, GRP94 mRNA and protein are detectable in both cardiac and skeletal muscle myocytes of fetal and neonatal rabbits. After 24 h of endotoxin administration to adult rabbits, GRP94 mRNA accumulation increases 3-fold in both heart and skeletal muscle and it is followed by a comparable increase in protein accumulation. However, hybridization and immunohistochemistry in situ do not reveal any change in the expression of GRP94 mRNA and protein in skeletal muscle myocytes after endotoxin treatment. Thus skeletal muscle fibres display a unique regulation of the GRP94 gene, which is up-regulated during perinatal development, whereas in the adult animal it is apparently silent and not responsive to endotoxin treatment. PMID:9601063

Vitadello, M; Colpo, P; Gorza, L



Regulation of the constitutive expression of the human CYP1A2 gene: cis elements and their interactions with proteins.  


Cytochrome P4501A2 (CYP1A2) is a member of the cytochrome P450 family that is involved in phase I drug metabolism in vertebrates. To understand how the constitutive expression of the human CYP1A2 gene is regulated, its 5' flanking region was analyzed. The promoter activity of a human CYP1A2 gene sequence [base pairs (bp) -3203 to +58 bp] was measured in transiently transfected HepG2 cells using fusion constructs containing the luciferase reporter gene. Using 5'-end deletion analysis, two functionally important cis elements, i.e., a proximal 42-bp DNA from bp -72 to bp -31 and a distal 259-bp DNA from bp -2352 to bp -2094, were identified. The proximal sequence (bp -72 to -31) contained CCAAT and GC boxes, with which well characterized transcription factors such as nuclear factor-1/CCAT transcription factor and simian virus 40 promoter factor-1 could interact. With regard to the 259-bp fragment (bp -2352 to bp -2094), gel mobility shift analyses with HepG2 nuclear lysates indicated high affinity, specific interactions of several trans-acting factors. Three protein binding sites within the 259-bp fragment were identified by DNase 1 footprinting analysis; these sites contained activator protein-1, nuclear factor-E1.7, and one-half hepatic nuclear factor-1 (HNF-1) binding consensus sequences. Only the region from bp -2124 to bp -2098, in which the HNF-1 binding site was located, was markedly protected by a HepG2 nuclear extract, compared with a MCF7 human breast cancer nuclear extract. These results suggested that the 259-bp DNA fragment contained positive regulator binding sites and HNF-1 could contribute to the liver-specific expression of human CYP1A2. PMID:7723729

Chung, I; Bresnick, E



Constitutive expression of a high-affinity sulfate transporter in Indian mustard affects metal tolerance and accumulation.  


The Stylosanthes hamata SHST1 gene encodes a high-affinity sulfate transporter located in the plasma membrane. In this study the S. hamata SHST1 gene was constitutively expressed in Indian mustard [Brassica juncea (L.) Czern.] to investigate its importance for tolerance and accumulation of various oxyanions that may be transported by SHST1 and for cadmium, which is detoxified by sulfur-rich compounds. The transgenic SHST1 lines SHST1-12C and SHST1-4C were compared with wild-type Indian mustard for tolerance and accumulation of arsenate, chromate, tungstate, vanadate, and cadmium. As seedlings the SHST1 plants accumulated significantly more Cd and W, and somewhat more Cr and V. The SHST1 seedlings were less tolerant to Cd, Mo, and V compared to wild-type plants. Mature SHST1 plants were less tolerant than wild-type plants to Cd and Cr. SHST1 plants accumulated significantly more Cd, Cr, and W in their roots than wild-type plants. In their shoots they accumulated significantly more Cr and somewhat more V and W. Shoot Cd accumulation was significantly lower than in wild-type, and As levels were somewhat reduced. Compared to wild-type plants, sulfur accumulation was enhanced in roots of SHST1 plants but not in shoots. Together these results suggest that SHST1 can facilitate uptake of other oxyanions in addition to sulfate and that SHST1 mediates uptake in roots rather than root-to-shoot translocation. Since SHST1 overexpression led to enhanced accumulation of Cr, Cd, V, and W, this approach shows some potential for phytoremediation, especially if it could be combined with the expression of a gene that confers enhanced metal translocation or tolerance. PMID:16585614

Lindblom, Stormy Dawn; Abdel-Ghany, Salah; Hanson, Brady R; Hwang, Seongbin; Terry, Norman; Pilon-Smits, Elizabeth A H



Constitutive expression of fluorescent protein by Aspergillus var. niger and Aspergillus carbonarius to monitor fungal colonization in maize plants.  


Aspergillus niger and Aspergillus carbonarius are two species in the Aspergillus section Nigri (black-spored aspergilli) frequently associated with peanut (Arachis hypogea), maize (Zea mays), and other plants as pathogens. These infections are symptomless and as such are major concerns since some black aspergilli produce important mycotoxins, ochratoxins A, and the fumonisins. To facilitate the study of the black aspergilli-maize interactions with maize during the early stages of infections, we developed a method that used the enhanced yellow fluorescent protein (eYFP) and the monomeric red fluorescent protein (mRFP1) to transform A. niger and A. carbonarius, respectively. The results were constitutive expressions of the fluorescent genes that were stable in the cytoplasms of hyphae and conidia under natural environmental conditions. The hyphal in planta distribution in 21-day-old seedlings of maize were similar wild type and transformants of A. niger and A. carbonarius. The in planta studies indicated that both wild type and transformants internally colonized leaf, stem and root tissues of maize seedlings, without any visible disease symptoms. Yellow and red fluorescent strains were capable of invading epidermal cells of maize roots intercellularly within the first 3 days after inoculation, but intracellular hyphal growth was more evident after 7 days of inoculation. We also tested the capacity of fluorescent transformants to produce ochratoxin A and the results with A. carbonarius showed that this transgenic strain produced similar concentrations of this secondary metabolite. This is the first report on the in planta expression of fluorescent proteins that should be useful to study the internal plant colonization patterns of two ochratoxigenic species in the Aspergillus section Nigri. PMID:23899775

Palencia, Edwin Rene; Glenn, Anthony Elbie; Hinton, Dorothy Mae; Bacon, Charles Wilson



Constitutional Possibilities  

Microsoft Academic Search

What are our constitutional possibilities? The importance of this question is illustrated by the striking breadth of recent discussions, ranging from the interpretation of the United States Constitution as a guarantee of fundamental economic equality and proposals to restore the lost constitution to arguments for the virtual abandonment of structural provisions of the Constitution of 1789. Such proposals are conventionally

Lawrence B. Solum



Constitutive expression of pathogenesis-related proteins PR-1, GRP, and PR-S in tobacco has no effect on virus infection.  

PubMed Central

Samsun NN tobacco cells were transformed with chimeric genes for pathogenesis-related (PR) proteins derived from genomic (PR-1a, GRP) or cDNA (PR-S) clones under the transcriptional control of the cauliflower mosaic virus 35S promoter. Regenerated plants were assayed by RNA and protein gel blotting, and plants showing high specific expression of the inserted genes were selected for self-pollination and seed formation. Inspection of second generation transformants showed that constitutive expression of PR-1a, GRP, and PR-S in tobacco in general does not have an effect on the phenotypic appearance of the plants or the expression of other endogenous PR genes. Furthermore, constitutive expression of the above genes does not affect the susceptibility of the plants to infection with tobacco mosaic virus or alfalfa mosaic virus. PMID:2535503

Linthorst, H J; Meuwissen, R L; Kauffmann, S; Bol, J F



Constitutive expression of a small heat-shock protein confers cellular thermotolerance and thermal protection to the photosynthetic apparatus in cyanobacteria  

Microsoft Academic Search

The role of a small heat-shock protein (Hsp) in the acquisition of thermotolerance in cyanobacteria was investigated. Synechococcus sp. PCC 7942 was transformed with an expression vector carrying the coding sequence of the hspA gene encoding a small heat-shock protein from Synechococcus vulcanus under the control of the tac promoter. The transformant which was shown to constitutively express HspA displayed

Hitoshi Nakamoto; Nobuaki Suzuki; Sanjit Kumer Roy



Functional ability of cytoskeletal ? - actin regulator to drive constitutive and ubiquitous expression of a fluorescent reporter throughout the life cycle of transgenic marine medaka Oryzias dancena  

Microsoft Academic Search

Marine medaka Oryzias dancena, a candidate model organism, represents many attractive merits as a material for experimental transgenesis and\\/or heterologous\\u000a expression assay particularly in the field of ecotoxicology and developmental biology. In this study, cytoskeletal ?-actin gene was characterized from O. dancena and the functional capability of its promoter to drive constitutive expression of foreign reporter protein was evaluated.\\u000a The

Young Sun Cho; Sang Yoon Lee; Youn Kyoung Kim; Dong Soo Kim; Yoon Kwon Nam


Problems related to the interpretation of autoradiographic data on gene expression using common constitutive transcripts as controls.  

PubMed Central

The 28S rRNA, a ribosomal RNA, and the ACTB and GAPD mRNAs, coding respectively for beta-actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), are frequently presented as controls of modulated gene expression. These transcripts were quantified by replicate slot-blot autoradiography and image analysis in mammary epithelial cells and fibroblasts from breast tissues. Each cell-type group comprised strains with different pathological backgrounds, growth rates, antigenic phenotypes and culture histories. The effects of a differentiating agent (cholera toxin) and/or a tumor promoter (12-O-tetradecanoyl-phorbol-13-acetate) were also examined. Despite the impression that visual examination of autoradiographs might create, image analysis suggests that 28S rRNA, ACTB and GAPD are substantially and independently influenced by the above biological factors and by the drugs. Therefore, these transcripts represent specifically regulated cellular activities and may not be taken as alternative indicators of the overall transcription rate or of the amount of material being examined. Instead, such nonspecific variation may be accurately measured and removed from quantitative data using a principal component function. A methodology that allows comparison of expression (or amplification) patterns between genes, between experiments or, even, between laboratories is presented with an example of quantification of transcripts related to cell-growth, differentiation, signaling and cancer. Images PMID:8367299

Spanakis, E



Constitutional Issues and Iowa.  

ERIC Educational Resources Information Center

Important constitutional issues are presented in a manner appropriate for use in the classroom. Case studies and events from the history of Iowa are used to illuminate the Constitution and Bill of Rights. Freedom of expression and students' rights are discussed in "The Black Armband Case"; free exercise of religion as won by the Iowa's Amish is…

Gore, Deborah, Ed.



Destabilizing Protein Polymorphisms in the Genetic Background Direct Phenotypic Expression of Mutant SOD1 Toxicity  

PubMed Central

Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS) cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation behavior and genetic interactions of mutant forms of SOD1. Expression of three structurally distinct SOD1 mutants in C. elegans muscle cells resulted in the appearance of heterogeneous populations of aggregates and was associated with only mild cellular dysfunction. However, introduction of destabilizing temperature-sensitive mutations into the genetic background strongly enhanced the toxicity of SOD1 mutants, resulting in exposure of several deleterious phenotypes at permissive conditions in a manner dependent on the specific SOD1 mutation. The nature of the observed phenotype was dependent on the temperature-sensitive mutation present, while its penetrance reflected the specific combination of temperature-sensitive and SOD1 mutations. Thus, the specific toxic phenotypes of conformational disease may not be simply due to misfolding/aggregation toxicity of the causative mutant proteins, but may be defined by their genetic interactions with cellular pathways harboring mildly destabilizing missense alleles. PMID:19266020

Gidalevitz, Tali; Krupinski, Thomas; Garcia, Susana; Morimoto, Richard I.



Strain background influences neurotoxicity and behavioral abnormalities in mice expressing the tetracycline transactivator  

PubMed Central

The tet-off system has been widely used to create transgenic models of neurological disorders including Alzheimer’s, Parkinson’s, Huntington’s, and prion disease. The utility of this system lies in the assumption that the tetracycline transactivator (TTA) acts as an inert control element and does not contribute to phenotypes under study. Here we report that neuronal expression of TTA can affect hippocampal cytoarchitecture and behavior in a strain-dependent manner. While studying neurodegeneration in two tet-off Alzheimer’s disease models, we unexpectedly discovered neuronal loss within the dentate gyrus of single transgenic TTA controls. Granule neurons appeared most sensitive to TTA exposure during postnatal development, and doxycycline treatment during this period was neuroprotective. TTA-induced degeneration could be rescued by moving the transgene onto a congenic C57BL/6J background, and recurred on re-introduction of either CBA or C3H/He backgrounds. Quantitative trait analysis of B6C3 F2 TTA mice identified a region on Chromosome 14 that contains a major modifier of the neurodegenerative phenotype. Although B6 mice were resistant to degeneration, they were not ideal for cognitive testing. F1 offspring of TTA C57BL/6J and 129X1/SvJ, FVB/NJ, or DBA/1J showed improved spatial learning, but TTA expression caused subtle differences in contextual fear conditioning on two of these backgrounds indicating that strain and genotype can interact independently under different behavioral settings. All model systems have limitations that should be recognized and mitigated where possible; our findings stress the importance of mapping the effects caused by TTA alone when working with tet-off models. PMID:22855807

Han, Harry J.; Allen, Carolyn C.; Buchovecky, Christie M.; Yetman, Michael J.; Born, Heather A.; Marin, Miguel A.; Rodgers, Shaefali P.; Song, Bryan J.; Lu, Hui-Chen; Justice, Monica J.; Probst, Frank J.; Jankowsky, Joanna L.



Constitutive CCND1/CDK2 activity substitutes for p53 loss, or MYC or oncogenic RAS expression in the transformation of human mammary epithelial cells.  


Cancer develops following the accumulation of genetic and epigenetic alterations that inactivate tumor suppressor genes and activate proto-oncogenes. Dysregulated cyclin-dependent kinase (CDK) activity has oncogenic potential in breast cancer due to its ability to inactivate key tumor suppressor networks and drive aberrant proliferation. Accumulation or over-expression of cyclin D1 (CCND1) occurs in a majority of breast cancers and over-expression of CCND1 leads to accumulation of activated CCND1/CDK2 complexes in breast cancer cells. We describe here the role of constitutively active CCND1/CDK2 complexes in human mammary epithelial cell (HMEC) transformation. A genetically-defined, stepwise HMEC transformation model was generated by inhibiting p16 and p53 with shRNA, and expressing exogenous MYC and mutant RAS. By replacing components of this model, we demonstrate that constitutive CCND1/CDK2 activity effectively confers anchorage independent growth by inhibiting p53 or replacing MYC or oncogenic RAS expression. These findings are consistent with several clinical observations of luminal breast cancer sub-types that show elevated CCND1 typically occurs in specimens that retain wild-type p53, do not amplify MYC, and contain no RAS mutations. Taken together, these data suggest that targeted inhibition of constitutive CCND1/CDK2 activity may enhance the effectiveness of current treatments for luminal breast cancer. PMID:23390492

Junk, Damian J; Cipriano, Rocky; Stampfer, Martha; Jackson, Mark W



Constitutive CCND1/CDK2 Activity Substitutes for p53 Loss, or MYC or Oncogenic RAS Expression in the Transformation of Human Mammary Epithelial Cells  

PubMed Central

Cancer develops following the accumulation of genetic and epigenetic alterations that inactivate tumor suppressor genes and activate proto-oncogenes. Dysregulated cyclin-dependent kinase (CDK) activity has oncogenic potential in breast cancer due to its ability to inactivate key tumor suppressor networks and drive aberrant proliferation. Accumulation or over-expression of cyclin D1 (CCND1) occurs in a majority of breast cancers and over-expression of CCND1 leads to accumulation of activated CCND1/CDK2 complexes in breast cancer cells. We describe here the role of constitutively active CCND1/CDK2 complexes in human mammary epithelial cell (HMEC) transformation. A genetically-defined, stepwise HMEC transformation model was generated by inhibiting p16 and p53 with shRNA, and expressing exogenous MYC and mutant RAS. By replacing components of this model, we demonstrate that constitutive CCND1/CDK2 activity effectively confers anchorage independent growth by inhibiting p53 or replacing MYC or oncogenic RAS expression. These findings are consistent with several clinical observations of luminal breast cancer sub-types that show elevated CCND1 typically occurs in specimens that retain wild-type p53, do not amplify MYC, and contain no RAS mutations. Taken together, these data suggest that targeted inhibition of constitutive CCND1/CDK2 activity may enhance the effectiveness of current treatments for luminal breast cancer. PMID:23390492

Junk, Damian J.; Cipriano, Rocky; Stampfer, Martha; Jackson, Mark W.



Constitutively active erythropoietin receptor expression in breast cancer cells promotes cellular proliferation and migration through a MAP-kinase dependent pathway  

SciTech Connect

The role of erythropoietin receptor (EpoR) expression in tumor cells and the potential of EpoR-mediated signaling to contribute to cellular proliferation and invasiveness require further characterization. To determine whether EpoR expression and activation in tumor cells modulates intracellular signal transduction to promote cellular proliferation and migration, we employed a novel experimental model using human breast cancer cells engineered to stably express a constitutively active EpoR-R129C variant. EpoR-R129C expression resulted in increased cellular proliferation and migration of breast cancer cells and these effects were associated with significantly increased Epo-induced phosphorylation of ERK1/2, AKT and c-Jun-NH2-kinase (SAPK/JNK) proteins. Expression of the constitutively active EpoR-R129C receptor promoted the proliferation and migration of breast cancer cells via activation of ERK- and SAPK/JNK-dependent signaling pathways, respectively. These findings suggest that EpoR over-expression and activation in breast cancer cells has the potential to contribute to tumor progression by promoting the proliferation and invasiveness of the neoplastic cells.

Fu Ping; Jiang Xiaohong [Department of Medicine, Hematology-Medical Oncology, Duke University Medical Center, DUMC Box 3912, Durham, NC 27710 (United States); Arcasoy, Murat O. [Department of Medicine, Hematology-Medical Oncology, Duke University Medical Center, DUMC Box 3912, Durham, NC 27710 (United States)], E-mail:



Antisense Suppression of a (+)-?-Cadinene Synthase Gene in Cotton Prevents the Induction of This Defense Response Gene during Bacterial Blight Infection But Not Its Constitutive Expression1[w  

PubMed Central

In cotton (Gossypium hirsutum) the enzyme (+)-?-cadinene synthase (CDNS) catalyzes the first committed step in the biosynthesis of cadinane-type sesquiterpenes, such as gossypol, that provide constitutive and inducible protection against pests and diseases. A cotton cDNA clone encoding CDNS (cdn1-C4) was isolated from developing embryos and functionally characterized. Southern analysis showed that CDNS genes belong to a large multigene family, of which five genomic clones were studied, including three pseudogenes and one gene that may represent another subfamily of CDNS. CDNS expression was shown to be induced in cotton infected with either the bacterial blight or verticillium wilt pathogens. Constructs for the constitutive or seed-specific antisense suppression of cdn1-C4 were introduced into cotton by Agrobacterium-mediated transformation. Gossypol levels were not reduced in the seeds of transformants with either construct, nor was the induction of CDNS expression affected in stems of the constitutive antisense plants infected with Verticillium dahliae Kleb. However, the induction of CDNS mRNA and protein in response to bacterial blight infection of cotyledons was completely blocked in the constitutive antisense plants. These results suggest that cdn1-C4 may be involved specifically in the bacterial blight response and that the CDNS multigene family comprises a complex set of genes differing in their temporal and spatial regulation and responsible for different branches of the cotton sesquiterpene pathway. PMID:15849309

Townsend, Belinda J.; Poole, Andrew; Blake, Christopher J.; Llewellyn, Danny J.



Constitutive expression of a fungal glucose oxidase gene in transgenic tobacco confers chilling tolerance through the activation of antioxidative defence system  

Microsoft Academic Search

Scientific evidences in the literature have shown that plants treated exogenously with micromole concentration of hydrogen\\u000a peroxide (H2O2) acquire abiotic stress tolerance potential, without substantial disturbances in the endogenous H2O2 pool. In this study, we enhanced the endogenous H2O2 content of tobacco (Nicotiana tabaccum L. cv. SR1) plants by the constitutive expression of a glucose oxidase (GO; EC gene

Subbiyan Maruthasalam; Yi Lun Liu; Ching Mei Sun; Pei Ying Chen; Chih Wen Yu; Pei Fang Lee; Chin Ho Lin



Constitutive expression of a cowpea trypsin inhibitor gene, CpTi , in transgenic rice plants confers resistance to two major rice insect pests  

Microsoft Academic Search

The gene encoding a cowpea trypsin inhibitor (CpTI), which confers insect resistance in trangenic tobacco, was introduced into rice. Expression of the CpTi gene driven by the constitutively active promoter of the rice actin 1 gene (Act1) leads to high-level accumulation of the CpTI protein in transgenic rice plants. Protein extracts from transgenic rice plants exhibit a strong inhibitory activity

Deping Xu; Qingzhong Xue; David McElroy; Yogesh Mawal; Vaughan A. Hilder; Ray Wu



Constitutive IDO expression in human cancer is sustained by an autocrine signaling loop involving IL-6, STAT3 and the AHR  

PubMed Central

Indoleamine-2,3-dioxygenase (IDO) inhibitors have entered clinical trials based on their ability to restore anti-tumor immunity in preclinical studies. However, the mechanisms leading to constitutive expression of IDO in human tumors are largely unknown. Here we analyzed the pathways mediating constitutive IDO expression in human cancer. IDO-positive tumor cells and tissues showed basal phosphorylation and acetylation of STAT3 as evidenced by western blotting and immunoprecipitation. Inhibition of IL-6 or STAT3 using siRNA and/or pharmacological inhibitors reduced IDO mRNA and protein expression as well as kynurenine formation. In turn, IDO enzymatic activity activated the AHR as shown by the induction of AHR target genes. IDO-mediated AHR activation induced IL-6 expression, while inhibition or knockdown of the AHR reduced IL-6 expression. IDO activity thus sustains its own expression via an autocrine AHR–IL-6–STAT3 signaling loop. Inhibition of the AHR–IL-6–STAT3 signaling loop restored T-cell proliferation in mixed leukocyte reactions performed in the presence of IDO-expressing human cancer cells. Identification of the IDO-AHR-IL-6-STAT3 signaling loop maintaining IDO expression in human cancers reveals novel therapeutic targets for the inhibition of this core pathway promoting immunosuppression of human cancers. The relevance of the IDO-AHR-IL-6-STAT3 transcriptional circuit is underscored by the finding that high expression of its members IDO, STAT3 and the AHR target gene CYP1B1 is associated with reduced relapse-free survival in lung cancer patients. PMID:24657910

Sahm, Felix; Rauschenbach, Katharina J.; Trump, Saskia; Winter, Marcus; Ott, Martina; Ochs, Katharina; Lutz, Christian; Liu, Xiangdong; Anastasov, Natasa; Lehmann, Irina; Hofer, Thomas; von Deimling, Andreas; Wick, Wolfgang; Platten, Michael



Constitutive Expression of a Transcription Termination Factor by a Repressed Prophage: Promoters for Transcribing the Phage HK022 nun Gene  

Microsoft Academic Search

Lysogens of phage HK022 are resistant to infection by phage l. Lambda resistance is caused by the action of the HK022 Nun protein, which prematurely terminates early l transcripts. We report here that transcription of the nun gene initiates at a constitutive prophage promoter, PNun, located just upstream of the protein coding sequence. The 5* end of the transcript was




Constitutional Displacement  

Microsoft Academic Search

This Article examines the intersection between territory and constitutional liberty. Territoriality, as defined by Robert Sack, is the attempt to affect, influence, or control people, phenomena, and relationships by delimiting and asserting control over a geographic area. Territoriality affects constitutional liberty in profound ways. These effects have been apparent in certain infamous historical episodes, including the territoriality of racial segregation,

Timothy Zick



Altered Constitutive Expression of Fatty Acid-metabolizing Enzymes in Mice Lacking the Peroxisome Proliferator-activated Receptor a (PPARa)  

Microsoft Academic Search

Peroxisome proliferator-activated receptor a (PPARa )i s a member of the steroid\\/nuclear receptor superfamily and mediates the biological and toxicological effects of peroxi- some proliferators. To determine the physiological role of PPARa in fatty acid metabolism, levels of peroxisomal and mitochondrial fatty acid metabolizing enzymes were deter- mined in the PPARa null mouse. Constitutive liver b-oxida- tion of the long

Toshifumi Aoyama; Jeffrey M. Peters; Nobuko Iritanii; Tamie Nakajima; Kenichi Furihata; Takashi Hashimoto; Frank J. Gonzalez



Growth suppression of human mast cells expressing constitutively active c-kit receptors by JNK inhibitor SP600125  

Microsoft Academic Search

Activation of c-jun N-terminal kinase (JNK) through c-kit-mediated phosphatidylinositol 3 (PI3) and Src kinase pathways plays an important role in cell proliferation and survival in mast cells. Gain-of-function mutations in c-kit are found in several human neoplasms. Constitutive activa- tion of c-kit has been observed in human mastocytosis and gastrointestinal stromal tumor. In the present study, we demonstrate that an

Bin Wang; Junichi Tsukada; Takehiro Higashi; Takamitsu Mizobe; Ai Matsuura; Fumihiko Mouri; Norifumi Sawamukai; Chisei Ra; Yoshiya Tanaka



Sorting of neutrophil-specific granule protein human cathelicidin, hCAP-18, when constitutively expressed in myeloid cells  

Microsoft Academic Search

Neutrophil granulocytes carry storage organelles, e.g., azurophil and specific granules. Poorly understood are the mechanisms for re- trieval from constitutive secretion followed by sort- ing for storage. Therefore, we asked whether the specific granule protein human cathelicidin (hCAP- 18) could be sorted for storage in other granules when the biosynthetic window is widened to allow this. We observed that hCAP-18

Elinor Bulow; Niklas Bengtsson; Jero Calafat; Urban Gullberg; Inge Olsson


Constitutive G s activation using a single-construct tetracycline-inducible expression system in embryonic stem cells and mice  

Microsoft Academic Search

Introduction  The controlled expression of many genes, including G-protein coupled receptors (GPCRs), is important for delineating gene\\u000a functions in complex model systems. Binary systems for inducible regulation of transgene expression are widely used in mice.\\u000a One system is the tTA\\/TRE expression system, composed of a tetracycline-dependent DNA binding factor and a separate tetracycline\\u000a operon. However, the requirement for two separate transgenes

Edward C Hsiao; Trieu D Nguyen; Jennifer K Ng; Mark J Scott; Wei Chun Chang; Hengameh Zahed; Bruce R Conklin



Expression of Constitutively Active Raf-1 in the Mitochondria Restores Antiapoptotic and Leukemogenic Potential of a Transformation-deficient BCR/ABL Mutant  

PubMed Central

The oncogenic BCR/ABL protein protects hematopoietic cells from apoptosis induced by growth factor deprivation, but the mechanisms are only partially understood. A BCR/ABL mutant lacking amino acids 176–426 in the BCR domain (p185?BCR) failed to protect interleukin 3–deprived 32Dcl3 myeloid precursor cells from apoptosis, although it possessed tyrosine kinase activity and was capable of activating the Ras-Raf-MAP kinase pathway. Compared to p185 wild-type transfectants, p185?BCR-transfected cells showed markedly reduced levels of Bcl-2 and expressed the hypophosphorylated, proapoptotic form of BAD. Bcl-2 expression in the mitochondrial fraction of p185?BCR cells was also markedly diminished and mitochondrial RAF was undetectable. In p185?BCR cells transfected with a mitochondria-targeted, constitutively active RAF (M-Raf) BAD was expressed in the hyperphosphorylated form and released from the mitochondria into the cytosol. p185?BCR/M-Raf–transfected cells were completely resistant to apoptosis induced by growth factor deprivation in vitro. Moreover, constitutive expression of dominant-negative M-Raf (K375W) enhanced the susceptibility of 32Dcl3 cells expressing wild-type BCR/ABL to apoptosis. In severe combined immunodeficiency (SCID) mice, p185?BCR/M-Raf double transfectants were leukemogenic, whereas cells expressing only p185?BCR showed no leukemogenic potential. Together, these data support the existence of a BCR/ABL-dependent pathway that leads to expression of an active RAF in the mitochondria and promotes antiapoptotic and leukemia-inducing effects of BCR/ABL. PMID:9625759

Salomoni, Paolo; Wasik, Mariusz A.; Riedel, Richard F.; Reiss, Krzysztof; Choi, John K.; Skorski, Tomasz; Calabretta, Bruno



Constitution Daily  

NSDL National Science Digital Library

Everyone could use a bit of the Constitution added to their daily lives, and this website more than delivers on its promise to deliver "smart conversation about the Constitution". Constitution Daily is an experimental blog edited by the National Constitution Center (NCC) in Philadelphia, and commentary here can include conversations about student privacy rights, the Second Amendment, and the activities of Congress. Visitors can click on the "Issues" section to dive into topic areas that include civility and privacy. After looking at each topic area, visitors can look at an interactive timeline that arranges comments, posts, and discussion on the subject. The site also contains some nice polls, and information about upcoming events at the NCC.


Constitutive expression and enzymatic activity of Tan protein in brain and epidermis of Ceratitis capitata and of Drosophila melanogaster wild-type and tan mutants.  


The present report shows a partial biochemical characterization and life cycle expression of N-?-alanyldopamine hydrolase (Tan protein) in Ceratitis capitata and Drosophila melanogaster. This enzyme catalyzes the hydrolysis of N-?-alanyldopamine (NBAD), the main tanning precursor of insect brown cuticles. It also plays an important role in the metabolism of brain neurotransmitters, recycling dopamine and histamine. In contrast to NBAD-synthase, Tan is expressed constitutively in epidermis and does not respond directly to microbial challenge. Immunodetection experiments showed the novel localization of NBAD-hydrolase in the embryo central neural system and in different regions of the adult brain, in addition to optic lobes. We sequenced and characterized Drosophila mutants tan¹ and tan³. The latter appears to be a mutant with normal expression in neural tissue but weak one in epidermis. PMID:21571070

Pérez, M M; Sabio, G; Badaracco, A; Quesada-Allué, L A



Regulation of Endothelial Constitutive Nitric Oxide Synthase Gene Expression in Endothelial Cells and In Vivo A Specific Vascular Action of Insulin  

Microsoft Academic Search

Background—The vasodilatory effect of insulin can be acute or increase with time from 1 to 7 hours, suggesting that insulin may enhance the expression of endothelial nitric oxide synthase (eNOS) in endothelial cells. The objective of the present study was to characterize the extent and signaling pathways by which insulin regulates the expression of eNOS in endothelial cells and vascular

Koji Kuboki; Zhen Y. Jiang; Noriko Takahara; Sung Woo Ha; Masahiko Igarashi; Teruaki Yamauchi; Edward P. Feener; Terrance P. Herbert; Christopher J. Rhodes; George L. King


High-risk human papillomaviruses repress constitutive kappa interferon transcription via E6 to prevent pathogen recognition receptor and antiviral-gene expression.  


Persistent infections with human papillomavirus type 16 (HPV16), HPV18, or HPV31 are necessary for the development of cervical cancer, implying that HPVs have evolved immunoevasive mechanisms. Recent global transcriptome analyses indicated that these HPV types downregulate the constitutive expression of interferon (IFN)-stimulated genes (ISGs), but the underlying mechanism is not well understood. Comparative analyses of ISG transcription in keratinocytes with complete HPV16, -18, and -31 genomes revealed that antiviral genes (IFIT1 and MX1), genes involved in IFN signaling (STAT1), proapoptotic genes (TRAIL and XAF1), and pathogen recognition receptors (TLR3, RIG-I, and MDA5) are inhibited to similar extents by HPV16, -18, and -31. The lower expression of pathogen receptors in HPV-positive cells correlated with a greatly impaired induction of IFN-? and also of IFN-?1, -2, and -3 upon receptor stimulation. IFN-? is constitutively expressed in normal keratinocytes and is strongly repressed by HPV16, -18, and -31. ISGs downregulated in HPV-positive cells can be reactivated by IFN-? expression. The viral E6 and E7 oncogenes are sufficient for IFN-? repression, with E6 being mainly responsible. E6 inhibits IFN-? transcription independently from binding to PDZ proteins. IFN-? expression can be activated in only one cell line by E6AP knockdown but can be activated in all tested HPV-positive cells by addition of a DNA methyltransferase inhibitor, suggesting that HPVs modulate DNA methylation. Taken together, these results suggest that carcinogenic HPVs target IFN-? by different pathways in keratinocytes to inhibit both antiviral ISGs and pathogen recognition receptors, which in turn reduces the expression of inducible IFNs. PMID:21849431

Reiser, Jeanette; Hurst, José; Voges, Maike; Krauss, Peter; Münch, Peter; Iftner, Thomas; Stubenrauch, Frank



Constitution Annotated  

NSDL National Science Digital Library

What exactly does the United States Constitution mean? It is subject, of course, to ongoing meditation, debate, argument, and interpretation. This useful site provides one lens of interpretation of the Constitution, based primarily on Supreme Court case law and legal analysis. Visitors can look over each section of the Constitution individually, including all of the articles and amendments. Additionally, the site contains a complete table of Supreme Court cases, along with those cases that have been overruled as well as proposed amendments that have not been ratified. Additionally, the site contains a gallery of significant primary source documents from American history. Interested users should not forget to download the helpful app that is also included here.



Molecular identication of phenylalanine ammonia-lyase as a substrate of a specic constitutively active Arabidopsis CDPK expressed  

E-print Network

of the phenylpropanoid pathway are en- doplasmic reticulum localised and evidence for this and con- sequent metabolic channelling of intermediates has been pre- sented [16]. Biochemical evidence has accumulated that con cloning and absolute identi¢cation. As an alternative approach a number of heterologously expressed

Sheen, Jen


Constitutive expression of a celery mannitol dehydrogenase in tobacco enhances resistance to the mannitol-secreting fungal pathogen Alternaria alternata  

Microsoft Academic Search

Summary Our previous observation that host plant extracts induce production and secretion of mannitol in the tobacco pathogen Alternaria alternata suggested that, like their animal counterparts, plant pathogenic fungi might produce the reactive oxygen quencher mannitol as a means of suppressing reactive oxygen- mediated plant defenses. The concurrent discovery that pathogen attack induced mannitol dehydrogenase (MTD) expression in the non-mannitol-containing

Dianne B. Jennings; Margaret E. Daub; D. Mason Pharr; John D. Williamson



Tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA is constitutively expressed in bovine, human normal, and osteoarthritic articular chondrocytes.  


Tissue inhibitors of metalloproteinases (TIMPs) inhibit the extracellular matrix (ECM) metalloproteinases (MMPs). To determine the source of TIMPs in synovial fluids of patients with osteoarthritis (OA), the ability of chondrocytes to express TIMP-2 and its regulation by agents found in inflammed joints was investigated. The constitutive TIMP-2 mRNA expression was demonstrated in chondrocytes from normal bovine, human OA and normal cartilage. The cross-hybridization of human and bovine TIMP-2 suggested its evolutionary conservation. Serum, IL-1, IL-6 and TGC-beta were unable to augment considerably the basal expression of TIMP-2 mRNA. TIMP-1 RNA expression in chondrocytes from human OA cartilage was elevated compared to non-OA chondrocytes, while TIMP-2 mRNA levels were similar in both. IL-1 beta, IL-6 and TGF-beta did not affect TIMP-2 expression but TGF-beta induced TIMP-1 mRNA in human OA chondrocytes. TIMP-2 and TIMP-1 are therefore differentially regulated in chondrocytes and the basal TIMP-2 levels may be needed for the cartilage ECM integrity. PMID:8655631

Zafarullah, M; Su, S; Martel-Pelletier, J; DiBattista, J A; Costello, B G; Stetler-Stevenson, W G; Pelletier, J P



The DNA puff BhB10-1 gene is differentially expressed in various tissues of Bradysia hygida late larvae and constitutively transcribed in transgenic Drosophila.  


We extended the characterization of the DNA puff BhB10-1 gene of Bradysia hygida by showing that, although its mRNA is detected only at the end of the fourth larval instar, BhB10-1 expression is not restricted to the salivary gland, the tissue in which this gene is amplified. Different amounts of BhB10-1 mRNA were detected in other larval tissues such as gut, Malpighian tubules, fat body, brain and cuticle, suggesting that this gene is expressed differentially in the various tissues analyzed. Analysis of transgenic Drosophila carrying the BhB10-1 transcription unit and flanking sequences revealed that the tested fragment promotes transcription in a constitutive manner. We suggest that either cis-regulatory elements are missing in the transgene or factors that temporally regulate the BhB10-1 gene in B. hygida are not conserved in Drosophila. PMID:11449302

Monesi, N; Sousa, J F; Paçó-Larson, M L



The protein kinase C agonist PEP005 increases NF-kappaB expression, induces differentiation and increases constitutive chemokine release by primary acute myeloid leukaemia cells.  


Acute myeloid leukaemia (AML) cells show constitutive release of several chemokines that occurs in three major clusters: (I) chemokine (C-C motif) ligand (CCL)2-4/chemokine (C-X-C motif) ligand (CXCL)1/8, (II) CCL5/CXCL9-11 and (III) CCL13/17/22/24/CXCL5. Ingenol-3-angelate (PEP005) is an activator of protein kinase C and has antileukaemic and immunostimulatory effects in AML. We investigated primary AML cells derived from 35 unselected patients and determined that PEP005 caused a dose-dependent increase in the release of chemokines from clusters I and II, including several T cell chemotactic chemokines. The release of granulocyte-macrophage colony-stimulating factor and hepatocyte growth factor was also increased. CCL2-4/CXCL1/8 release correlated with nuclear factor (NF)-kappaB expression in untreated AML cells, and PEP005-induced chemokine production was associated with further increases in the expression of the NF-kappaB subunits p50, p52 and p65. Increased DNA binding of NF-kappaB was observed during exposure to PEP005, and the specific NF-kappaB inhibitor BMS-345541 reduced constitutive chemokine release even in the presence of PEP005. Finally, PEP005 decreased expression of stem cell markers (CD117, CXCR4) and increased lineage-associated CD11b and CD14 expression. To conclude, PEP005 has a unique functional pharmacological profile in human AML. Previous studies have described proapoptotic and T cell stimulatory effects and the present study describes additional T cell chemotactic and differentiation-inducing effects. PMID:19388934

Olsnes, Astrid Marta; Ersvaer, Elisabeth; Ryningen, Anita; Paulsen, Kristin; Hampson, Peter; Lord, Janet M; Gjertsen, Bjørn Tore; Kristoffersen, Einar Klaeboe; Bruserud, Øystein



Constitutive expression of mustard annexin, AnnBj1 enhances abiotic stress tolerance and fiber quality in cotton under stress  

Microsoft Academic Search

Annexins belong to a multigene family of Ca2+ dependent, phospholipid and cytoskeleton binding proteins. They have been shown to be upregulated under various stress conditions.\\u000a We generated transgenic cotton plants expressing mustard annexin (AnnBj1), which showed enhanced tolerance towards different abiotic stress treatments like sodium chloride, mannitol, polyethylene\\u000a glycol and hydrogen peroxide. The tolerance to these treatments was associated with

Kesanakurti Divya; S. K. Jami; P. B. Kirti



Constitutive Smad signaling and Smad-dependent collagen gene expression in mouse embryonic fibroblasts lacking peroxisome proliferator-activated receptor-{gamma}  

SciTech Connect

Transforming growth factor-{beta} (TGF-{beta}), a potent inducer of collagen synthesis, is implicated in pathological fibrosis. Peroxisome proliferator-activated receptor-{gamma} (PPAR-{gamma}) is a nuclear hormone receptor that regulates adipogenesis and numerous other biological processes. Here, we demonstrate that collagen gene expression was markedly elevated in mouse embryonic fibroblasts (MEFs) lacking PPAR-{gamma} compared to heterozygous control MEFs. Treatment with the PPAR-{gamma} ligand 15d-PGJ{sub 2} failed to down-regulate collagen gene expression in PPAR-{gamma} null MEFs, whereas reconstitution of these cells with ectopic PPAR-{gamma} resulted in their normalization. Compared to control MEFs, PPAR-{gamma} null MEFs displayed elevated levels of the Type I TGF-{beta} receptor (T{beta}RI), and secreted more TGF-{beta}1 into the media. Furthermore, PPAR-{gamma} null MEFs showed constitutive phosphorylation of cellular Smad2 and Smad3, even in the absence of exogenous TGF-{beta}, which was abrogated by the ALK5 inhibitor SB431542. Constitutive Smad2/3 phosphorylation in PPAR-{gamma} null MEFs was associated with Smad3 binding to its cognate DNA recognition sequences, and interaction with coactivator p300 previously implicated in TGF-{beta} responses. Taken together, these results indicate that loss of PPAR-{gamma} in MEFs is associated with upregulation of collagen synthesis, and activation of intracellular Smad signal transduction, due, at least in part, to autocrine TGF-{beta} stimulation.

Ghosh, Asish K [Northwestern University Feinberg School of Medicine, Division of Rheumatology, 240 East Huron Street, Chicago, IL 60611 (United States)], E-mail:; Wei, Jun; Wu, Minghua [Northwestern University Feinberg School of Medicine, Division of Rheumatology, 240 East Huron Street, Chicago, IL 60611 (United States); Varga, John [Northwestern University Feinberg School of Medicine, Division of Rheumatology, 240 East Huron Street, Chicago, IL 60611 (United States)], E-mail:



Constitutive expression of the xylanase inhibitor TAXI-III delays Fusarium head blight symptoms in durum wheat transgenic plants.  


Cereals contain xylanase inhibitor (XI) proteins which inhibit microbial xylanases and are considered part of the defense mechanisms to counteract microbial pathogens. Nevertheless, in planta evidence for this role has not been reported yet. Therefore, we produced a number of transgenic plants constitutively overexpressing TAXI-III, a member of the TAXI type XI that is induced by pathogen infection. Results showed that TAXI-III endows the transgenic wheat with new inhibition capacities. We also showed that TAXI-III is correctly secreted into the apoplast and possesses the expected inhibition parameters against microbial xylanases. The new inhibition properties of the transgenic plants correlate with a significant delay of Fusarium head blight disease symptoms caused by Fusarium graminearum but do not significantly influence leaf spot symptoms caused by Bipolaris sorokiniana. We showed that this contrasting result can be due to the different capacity of TAXI-III to inhibit the xylanase activity of these two fungal pathogens. These results provide, for the first time, clear evidence in planta that XI are involved in plant defense against fungal pathogens and show the potential to manipulate TAXI-III accumulation to improve wheat resistance against F. graminearum. PMID:23945000

Moscetti, Ilaria; Tundo, Silvio; Janni, Michela; Sella, Luca; Gazzetti, Katia; Tauzin, Alexandra; Giardina, Thierry; Masci, Stefania; Favaron, Francesco; D'Ovidio, Renato



Constitutive Expression of HIF-? Plays a Major Role in Generation of Clear-cell Phenotype in Human Primary and Metastatic Renal Carcinoma.  


The extensive lipid accumulation occurring in clear-cell renal cell carcinoma (ccRCC) results in a clear-cell cytoplasm. Hypoxia-inducible factor ? (HIF-?) is constitutively expressed in many ccRCC and transcriptionally regulates >100 genes. In a recent breakthrough study, HIF-1? induced ccRCC in transgenic mice. On the basis of these findings, we developed a hypothesis that accounted for HIF-? generation of the clear-cell phenotype. The aim of the present study was to use immunohistochemical staining methods in tissue microarray to determine the extent to which the clear-cell phenotype coincided with HIF-? expression in primary and metastatic ccRCC. In addition, we studied whether the prolyl-hydroxylases (PHD2,3) play a role in promoting the elevated expression of HIF-? in tumor cells. The clear-cell phenotype was observed in all primary and metastatic cases of ccRCC examined. A total of 168 renal cell carcinomas were evaluated by immunohistochemical methods; 141 of the 168 (84%) tumors expressed HIF-? (HIF-1? and/or HIF-2?). In contrast, HIF-? was expressed in only 1 of the 23 (4%) non-ccRCCs. These data supported the hypothesis that in the majority of the tumors HIF-? expression overlapped with the clear-cell phenotype and was indicative of an HIF-?-mediated lipid accumulation. In a smaller percentage of ccRCC cases (16%), HIF-? was not detected in the tumor cells and suggested that lipid accumulation by HIF-?-lipid-independent process. PHD3 was undetectable in both primary and metastatic ccRCC cases. We concluded that the undetectable PHD3 could contribute to the higher HIF-? expression in ccRCC. PMID:25046225

Tóth, Károly; Chintala, Sreenivasulu; Rustum, Youcef M



The influence of caregiver singing and background music on vocally expressed emotions and moods in dementia care: A qualitative analysis  

Microsoft Academic Search

Background: Music and singing are considered to have a strong impact on human emotions. Such an effect has been demonstrated in caregiving contexts with dementia patients. Objectives: The aim of the study was to illuminate vocally expressed emotions and moods in the communication between caregivers and persons with severe dementia during morning care sessions. Design: Three types of caring sessions

Eva Gotell; Steven Brown; Sirkka-Liisa Ekman


Ectopic Expression of CsCTR1, a Cucumber CTR-Like Gene, Attenuates Constitutive Ethylene Signaling in an Arabidopsis ctr1-1 Mutant and Expression Pattern Analysis of CsCTR1 in Cucumber (Cucumis sativus)  

PubMed Central

The gaseous plant hormone ethylene regulates many aspects of plant growth, development and responses to the environment. Constitutive triple response 1 (CTR1) is a central regulator involved in the ethylene signal transduction pathway. To obtain a better understanding of this particular pathway in cucumber, the cDNA-encoding CTR1 (designated CsCTR1) was isolated from cucumber. A sequence alignment and phylogenetic analyses revealed that CsCTR1 has a high degree of homology with other plant CTR1 proteins. The ectopic expression of CsCTR1 in the Arabidopsis ctr1-1 mutant attenuates constitutive ethylene signaling of this mutant, suggesting that CsCTR1 indeed performs its function as negative regulator of the ethylene signaling pathway. CsCTR1 is constitutively expressed in all of the examined cucumber organs, including roots, stems, leaves, shoot apices, mature male and female flowers, as well as young fruits. CsCTR1 expression gradually declined during male flower development and increased during female flower development. Additionally, our results indicate that CsCTR1 can be induced in the roots, leaves and shoot apices by external ethylene. In conclusion, this study provides a basis for further studies on the role of CTR1 in the biological processes of cucumber and on the molecular mechanism of the cucumber ethylene signaling pathway. PMID:25226540

Bie, Beibei; Sun, Jin; Pan, Junsong; He, Huanle; Cai, Run



Constitutive expression of the SAP1 gene from willow (Salix discolor) causes early flowering in Arabidopsis thaliana.  


SAP1-1 and SAP1-2 were isolated from the male reproductive buds of willow (Salix discolor, clone S365). SAP1-1 differs from SAP1-2 based on a few nucleotide substitutions, but the sizes of their full-length cDNAs are identical. The deduced amino acid sequences of SAP1-1 and SAP1-2 were 98% similar and contain the same C-terminal amino acid motif "GYGA" like that of PTAP1-2 from Populus trichocarpa. The expression patterns of SAP1 in various parts of the male reproductive buds of S. discolor implicate this gene in the formation of the inflorescence meristems, bracts, and floral meristems. To characterize the functions of SAP1, we assessed Arabidopsis thaliana transformed with 35S: :SAP1-1. A total of 52 transgenic T1 lines were obtained, and a 3:1 segregation ratio was obtained in the T2 generation of each line. In the T3 generation, five homozygous transgenic lines were obtained, which were used for further analysis. Screening of transgenic lines was greatly facilitated by the detection of GFP expression starting with germinating seeds. Phenotypes of the homozygous transgenic lines included early flowering, conversion of inflorescence branches to solitary flowers, formation of terminal flowers, and formation of flowers with greater number of petals, stamens, and pistils. Northern analysis showed similar expression levels in all five lines. This study provides the first functional analysis of an APETALA1 (AP1)/SQUAMOSA (SQUA) homolog from a dioecious species and suggests that SAP1 is a homolog of the AP1/SQUA gene. PMID:16228224

Fernando, Danilo D; Zhang, Shiliang



Establishment of Stably Transfected Cells Constitutively Expressing the Full-Length and Truncated Antigenic Proteins of Two Genetically Distinct Mink Astroviruses  

PubMed Central

Astroviruses are becoming a growing concern in veterinary and public health. To date there are no registered vaccines against astrovirus-induced disease, mostly due to the difficulty to cultivate astroviruses to high titer for vaccine development using conventional techniques. As means to circumvent this drawback, we have developed stably transfected mink fetal cells and BHK21 cells constitutively expressing the full-length and truncated capsid proteins of two distinct genotypes of mink astrovirus. Protein expression in these stably transfected cells was demonstrated by strong signals as evaluated by in-situ PLA and IFA, and confirmed by Western blotting. The recombinant full-length and truncated proteins induced a high level of antibodies in mink, evaluated by ELISA, demonstrating their immunogenicity. In a challenge experiment in mink, a reduction in presentation clinical signs and virus shedding was observed in mink kits born from immunized females. The gene integration and protein expression were sustained through cell passage, showing that the used approach is robust and reliable for expression of functional capsid proteins for vaccine and diagnostic applications. PMID:24376619

Bidokhti, Mehdi R. M.; Ullman, Karin; Jensen, Trine H.; Chriel, Mariann; Mottahedin, Amin; Munir, Muhammad; Andersson, Anna Maria; Detournay, Olivier; Hammer, Anne Sofie; Baule, Claudia



Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH17 cytokine interleukin-22  

PubMed Central

Considerable functional heterogeneity within human natural killer (NK) cells has been revealed through the characterization of distinct NK-cell subsets. Accordingly, a small subset of CD56+NKp44+NK cells, termed NK-22 cells, was recently described within secondary lymphoid tissue (SLT) as IL-22? when resting, with a minor fraction of this population becoming IL-22+ when activated. Here we discover that the vast majority of stage 3 immature NK (iNK) cells in SLT constitutively and selectively express IL-22, a TH17 cytokine important for mucosal immunity, whereas earlier and later stages of NK developmental intermediates do not express IL-22. These iNK cells have a surface phenotype of CD34?CD117+CD161+CD94?, largely lack expression of NKp44 and CD56, and do not produce IFN-? or possess cytolytic activity. In summary, stage 3 iNK cells are highly enriched for IL-22 and IL-26 messenger RNA, and IL-22 protein production, but do not express IL-17A or IL-17F. PMID:19244159

Hughes, Tiffany; Becknell, Brian; McClory, Susan; Briercheck, Edward; Freud, Aharon G.; Zhang, Xiaoli; Mao, Hsiaoyin; Nuovo, Gerard; Yu, Jianhua



Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH 17 cytokine interleukin-22.  


Considerable functional heterogeneity within human natural killer (NK) cells has been revealed through the characterization of distinct NK-cell subsets. Accordingly, a small subset of CD56(+)NKp44(+)NK cells, termed NK-22 cells, was recently described within secondary lymphoid tissue (SLT) as IL-22(-) when resting, with a minor fraction of this population becoming IL-22(+) when activated. Here we discover that the vast majority of stage 3 immature NK (iNK) cells in SLT constitutively and selectively express IL-22, a T(H)17 cytokine important for mucosal immunity, whereas earlier and later stages of NK developmental intermediates do not express IL-22. These iNK cells have a surface phenotype of CD34(-)CD117(+)CD161(+)CD94(-), largely lack expression of NKp44 and CD56, and do not produce IFN-gamma or possess cytolytic activity. In summary, stage 3 iNK cells are highly enriched for IL-22 and IL-26 messenger RNA, and IL-22 protein production, but do not express IL-17A or IL-17F. PMID:19244159

Hughes, Tiffany; Becknell, Brian; McClory, Susan; Briercheck, Edward; Freud, Aharon G; Zhang, Xiaoli; Mao, Hsiaoyin; Nuovo, Gerard; Yu, Jianhua; Caligiuri, Michael A



Apoptosis is inversely related to necrosis and determines net growth in tumors bearing constitutively expressed myc, ras, and HPV oncogenes.  

PubMed Central

Immortalized rat fibroblasts were transfected with expression plasmids containing a mutated human Ha-ras (T24) oncogene, human c-myc, HPV 16 or 18 genomes, or combinations of these. Cell proliferation rates in vitro of the resulting 13 transformed lines were closely similar but apoptotic rates in vitro varied over a 60-fold range and correlated inversely with rates of population expansion in culture. To determine whether such differences in susceptibility to apoptosis affected the pattern of tumor growth in vivo, the transfected lines were injected subcutaneously into immunesuppressed mice producing fibrosarcomas in which prevalence of apoptosis and mitosis, extent of necrosis, and net growth rate were measured. Cell lines with high apoptotic rates in vitro tended to generate slowly growing tumors with high ratios of apoptosis to mitosis and little necrosis. The three most extreme examples of this phenotype all resulted from single transfections with c-myc. Lines with low apoptotic rates in vitro generated rapidly expanding tumors with high mitotic rates, extensive necrosis, and little apoptosis relative to mitosis, even in the compromised zone at the edge of necrotic regions. The four fastest-growing tumors all contained a T24-ras oncogene. The results suggest that oncogene expression determines intrinsic apoptotic rates and in this way may significantly influence the net growth rate and extent of necrosis in tumors. Images Figure 1 Figure 5 PMID:8178928

Arends, M. J.; McGregor, A. H.; Wyllie, A. H.



Increased Na+/Ca2+ Exchanger Expression/Activity Constitutes a Point of Inflection in the Progression to Heart Failure of Hypertensive Rats  

PubMed Central

Spontaneously hypertensive rat (SHR) constitutes a genetic model widely used to study the natural evolution of hypertensive heart disease. Ca2+-handling alterations are known to occur in SHR. However, the putative modifications of Ca2+-handling proteins during the progression to heart failure (HF) are not well established. Moreover, the role of apoptosis in SHR is controversial. We investigated intracellular Ca2+, Ca2+-handling proteins and apoptosis in SHR vs. control Wistar rats (W) from 3 to 15 months (mo). Changes associated with the transition to HF (i.e. lung edema and decrease in midwall fractional shortening), occurred at 15 mo in 38% of SHR (SHRF). In SHRF, twitch and caffeine-induced Ca2+ transients, significantly decreased relative to 6/9 mo and 15 mo without HF signs. This decrease occurred in association with a decrease in the time constant of caffeine-Ca2+ transient decay and an increase in Na+/Ca2+ exchanger (NCX) abundance (p<0.05) with no changes in SERCA2a expression/activity. An increased Ca2+-calmodulin-kinase II activity, associated with an enhancement of apoptosis (TUNEL and Bax/Bcl2) was observed in SHR relative to W from 3 to 15 mo. Conclusions: 1. Apoptosis is an early and persistent event that may contribute to hypertrophic remodeling but would not participate in the contractile impairment of SHRF. 2. The increase in NCX expression/activity, associated with an increase in Ca2+ efflux from the cell, constitutes a primary alteration of Ca2+-handling proteins in the evolution to HF. 3. No changes in SERCA2a expression/activity are observed when HF signs become evident. PMID:24781001

Rodriguez, Jesica S.; Velez Rueda, J. Omar; Salas, Margarita; Becerra, Romina; Di Carlo, Mariano N.; Said, Matilde; Vittone, Leticia; Rinaldi, Gustavo; Portiansky, Enrique L.; Mundina-Weilenmann, Cecilia; Palomeque, Julieta; Mattiazzi, Alicia



The TLR4 D299G and T399I SNPs Are Constitutively Active to Up-Regulate Expression of Trif-Dependent Genes  

PubMed Central

Dysregulated Toll-Like Receptor (TLR) signalling and genetic polymorphisms in these proteins are linked to many human diseases. We investigated TLR4 functional variants D299G and T399I to assess the impact on LPS-induced responsiveness in comparison to wild-type TLR4. The mechanism by which this occurs in unclear as these SNPs do not lie within the lipid A binding domain or dimerisation sites of the LPS-TLR4/MD2 receptor complexes. Transfection of TLR4D299G, TLR4T399I or TLR4D299G. T399I into HEK cells resulted in constitutive activation of an NF-?B reporter gene and a blunting of the LPS-induced reporter activation compared to WT-TLR4. Unstimulated human monocyte/macrophages, from patients with the D299G and T399I SNPs demonstrated a downregulation of many genes, particularly Tram/Trif signalling pathway constitutents compared to the TLR4 wild-type subjects supporting the concept of basal receptor activity. Monocyte/macrophages from carriers of the TLR4 D299G and T399I polymorphisms stimulated with LPS showed >6 fold lower levels of NF-?B and ?12 fold higher IFN-? gene expression levels compared to wild-type subjects (P<0.05; MWU test) and dramatically altered resultant cytokine profiles. We conclude that these TLR4 SNPs affect constitutive receptor activity which impacts on the hosts ability to respond to LPS challenge leading to a dysregulated sub-optimal immune response to infection. PMID:25365308

Hold, Georgina L.; Berry, Susan; Saunders, Karin A.; Drew, Janice; Mayer, Claus; Brookes, Heather; Gay, Nick J.; El-Omar, Emad M.; Bryant, Clare E.



Selection for low or high primary dormancy in Lolium rigidum Gaud seeds results in constitutive differences in stress protein expression and peroxidase activity  

PubMed Central

Seed dormancy in wild Lolium rigidum Gaud (annual ryegrass) populations is highly variable and not well characterized at the biochemical level. To identify some of the determinants of dormancy level in these seeds, the proteomes of subpopulations selected for low and high levels of primary dormancy were compared by two-dimensional polyacrylamide gel electrophoresis of extracts from mature, dry seeds. High-dormancy seeds showed higher expression of small heat shock proteins, enolase, and glyoxalase I than the low-dormancy seeds. The functional relevance of these differences in protein expression was confirmed by the fact that high-dormancy seeds were more tolerant to high temperatures imposed at imbibition and had consistently higher glyoxalase I activity over 0–42?d dark stratification. Higher expression of a putative glutathione peroxidase in low-dormancy seeds was not accompanied by higher activity, but these seeds had a slightly more oxidized glutathione pool and higher total peroxidase activity. Overall, these biochemical and physiological differences suggest that L. rigidum seeds selected for low dormancy are more prepared for rapid germination via peroxidase-mediated cell wall weakening, whilst seeds selected for high dormancy are constitutively prepared to survive environmental stresses, even in the absence of stress during seed development. PMID:20974739

Goggin, Danica E.; Powles, Stephen B.; Steadman, Kathryn J.



Constitutive Expression of Gs?(R201C) in Mice Produces a Heritable, Direct Replica of Human Fibrous Dysplasia Bone Pathology and Demonstrates Its Natural History.  


Fibrous dysplasia of bone (FD) is a crippling skeletal disease associated with postzygotic mutations (R201C, R201H) of the gene encoding the ? subunit of the stimulatory G protein, Gs. By causing a characteristic structural subversion of bone and bone marrow, the disease results in deformity, hypomineralization, and fracture of the affected bones, with severe morbidity arising in childhood or adolescence. Lack of inheritance of the disease in humans is thought to reflect embryonic lethality of germline-transmitted activating Gs? mutations, which would only survive through somatic mosaicism. We have generated multiple lines of mice that express Gs?(R201C) constitutively and develop an inherited, histopathologically exact replica of human FD. Robust transgene expression in neonatal and embryonic tissues and embryonic stem (ES) cells were associated with normal development of skeletal tissues and differentiation of skeletal cells. As in humans, FD lesions in mice developed only in the postnatal life; a defined spatial and temporal pattern characterized the onset and progression of lesions across the skeleton. In individual bones, lesions developed through a sequence of three distinct histopathological stages: a primary modeling phase defined by endosteal/medullary excess bone formation and normal resorption; a secondary phase, with excess, inappropriate remodeling; and a tertiary fibrous dysplastic phase, which reproduced a full-blown replica of the human bone pathology in mice of age ?1 year. Gs? mutations are sufficient to cause FD, and are per se compatible with germline transmission and normal embryonic development in mice. Our novel murine lines constitute the first model of FD. © 2014 American Society for Bone and Mineral Research. PMID:24764158

Saggio, Isabella; Remoli, Cristina; Spica, Emanuela; Cersosimo, Stefania; Sacchetti, Benedetto; Robey, Pamela G; Holmbeck, Kenn; Cumano, Ana; Boyde, Alan; Bianco, Paolo; Riminucci, Mara



Genetic background influences adaptation to cardiac hypertrophy and Ca2+ handling gene expression  

PubMed Central

Genetic variability has a profound effect on the development of cardiac hypertrophy in response to stress. Consequently, using a variety of inbred mouse strains with known genetic profiles may be powerful models for studying the response to cardiovascular stress. To explore this approach we looked at male C57BL/6J and 129/SvJ mice. Hemodynamic analyses of left ventricular pressures (LVPs) indicated significant differences in 129/SvJ and C57BL/6J mice that implied altered Ca2+ handling. Specifically, 129/SvJ mice demonstrated reduced rates of relaxation and insensitivity to dobutamine (Db). We hypothesized that altered expression of genes controlling the influx and efflux of Ca2+ from the sarcoplasmic reticulum (SR) was responsible and investigated the expression of several genes involved in maintaining the intracellular and sarcoluminal Ca2+ concentration using quantitative real-time PCR analyses (qRT-PCR). We observed significant differences in baseline gene expression as well as different responses in expression to isoproterenol (ISO) challenge. In untreated control animals, 129/SvJ mice expressed 1.68× more ryanodine receptor 2(Ryr2) mRNA than C57BL/6J mice but only 0.37× as much calsequestrin 2 (Casq2). After treatment with ISO, sarco(endo)plasmic reticulum Ca2+-ATPase(Serca2) expression was reduced nearly two-fold in 129/SvJ while expression in C57BL/6J was stable. Interestingly, ? (1) adrenergic receptor(Adrb1) expression was lower in 129/SvJ compared to C57BL/6J at baseline and lower in both strains after treatment. Metabolically, the brain isoform of creatine kinase (Ckb) was up-regulated in response to ISO in C57BL/6J but not in 129/SvJ. These data suggest that the two strains of mice regulate Ca2+ homeostasis via different mechanisms and may be useful in developing personalized therapies in human patients. PMID:23508205

Waters, Steve B.; Diak, Douglass M.; Zuckermann, Matthew; Goldspink, Paul H.; Leoni, Lara; Roman, Brian B.



Acetaminophen Modulates P-Glycoprotein Functional Expression at the Blood-Brain Barrier by a Constitutive Androstane Receptor-Dependent Mechanism  

PubMed Central

Effective pharmacologic treatment of pain with opioids requires that these drugs attain efficacious concentrations in the central nervous system (CNS). A primary determinant of CNS drug permeation is P-glycoprotein (P-gp), an endogenous blood-brain barrier (BBB) efflux transporter that is involved in brain-to-blood transport of opioid analgesics (i.e., morphine). Recently, the nuclear receptor constitutive androstane receptor (CAR) has been identified as a regulator of P-gp functional expression at the BBB. This is critical to pharmacotherapy of pain/inflammation, as patients are often administered acetaminophen (APAP), a CAR-activating ligand, in conjunction with an opioid. Our objective was to investigate, in vivo, the role of CAR in regulation of P-gp at the BBB. Following APAP treatment, P-gp protein expression was increased up to 1.4–1.6-fold in a concentration-dependent manner. Additionally, APAP increased P-gp transport of BODIPY-verapamil in freshly isolated rat brain capillaries. This APAP-induced increase in P-gp expression and activity was attenuated in the presence of CAR pathway inhibitor okadaic acid or transcriptional inhibitor actinomycin D, suggesting P-gp regulation is CAR-dependent. Furthermore, morphine brain accumulation was enhanced by P-gp inhibitors in APAP-treated animals, suggesting P-gp–mediated transport. A warm-water (50°C) tail-flick assay revealed a significant decrease in morphine analgesia in animals treated with morphine 3 or 6 hours after APAP treatment, as compared with animals treated concurrently. Taken together, our data imply that inclusion of APAP in a pain treatment regimen activates CAR at the BBB and increases P-gp functional expression, a clinically significant drug-drug interaction that modulates opioid analgesic efficacy. PMID:24019224

Thompson, Brandon J.; Sanchez-Covarrubias, Lucy; Zhang, Yifeng; Laracuente, Mei-Li; Vanderah, Todd W.; Ronaldson, Patrick T.; Davis, Thomas P.



Expression of mRNA encoding the macrophage colony-stimulating factor receptor (c-fms) is controlled by a constitutive promoter and tissue-specific transcription elongation.  

PubMed Central

The gene encoding the receptor for macrophage colony-stimulating factor 1 (CSF-1), the c-fms protooncogene, is selectively expressed in immature and mature mononuclear phagocytes and trophoblasts. Exon 1 is expressed only in trophoblasts. Isolation and sequencing of genomic DNA flanking exon 2 of the murine c-fms gene revealed a TATA-less promoter with significant homology to human c-fms. Reverse transcriptase primer extension analysis using exon 2 primers identified multiple clustered transcription initiation sites. Their position was confirmed by RNase protection. The same primer extension products were detected in equal abundance from macrophage or nonmacrophage sources of RNA. c-fms mRNA is acutely down-regulated in primary macrophages by CSF-1, bacterial lipopolysaccharide (LPS), and phorbol myristate acetate (PMA). Each of these agents reduced the abundance of c-fms RNA detectable by primer extension using an exon 3 primer without altering the abundance of presumptive short c-fms transcripts detected with exon 2 primers. Primer extension analysis with an intron 2 primer detected products at greater abundance in nonmacrophages. Templates detected with the intronic primer were induced in macrophages by LPS, PMA, and CSF-1, suggesting that each of the agents caused a shift from full-length c-fms mRNA production to production of unspliced, truncated transcripts. The c-fms promoter functioned constitutively in the RAW264 macrophage cell line, the B-cell line MOPC.31C, and several nonhematopoietic cell lines. Macrophage-specific expression and responsiveness to selective repression by LPS and PMA was achieved by the incorporation of intron 2 into the c-fms promoter-reporter construct. The results suggest that expression of the c-fms gene in macrophages is controlled by sequences in intron 2 that act by regulating transcription elongation. Images PMID:8497248

Yue, X; Favot, P; Dunn, T L; Cassady, A I; Hume, D A



The Constitution Community  

NSDL National Science Digital Library

A new addition to the National Archives and Records Administration (NARA) Digital Classroom site (see the November 18, 199 Scout Report for Social Sciences), the Constitution Community is a partnership between classroom teachers and education specialists from the NARA. Like other Digital Classroom projects, the Constitution Community offers sample lesson plans, correlated to the National History Standards, that make use of original documents and images from American history. In addition to the lesson plan, each also includes background information, a number of suggested teaching activities, and its connection to the US Constitution The lessons are grouped by eight historical eras, covering the American Revolution to the Great Depression to the Civil Rights Act. Highlights include The Growth of Regionalism, The Civil War as Photographed by Mathew Brady, FDR's First Inaugural Address: Declaring "War" on the Great Depression, and the Founding Documents of the Peace Corps.


Reduced expression of IL-12 p35 by SJL/J macrophages responding to Theiler's virus infection is associated with constitutive activation of IRF-3  

SciTech Connect

Macrophages responding to viral infections may contribute to autoimmune demyelinating diseases (ADD). Macrophages from ADD-susceptible SJL/J mice responding to Theiler's Virus (TMEV) infection, the TLR7 agonist loxoribine, or the TLR4 agonist-LPS expressed less IL-12 p35 but more IL-12/23 p40 and IFN-{beta} than macrophages from ADD-resistant B10.S mice. While expression of IRF-1 and -7 was similar between B10.S and SJL/J TMEV-infected macrophages, SJL/J but not B10.S macrophages exhibited constitutively active IRF-3. In contrast to overexpressed IRF-1, IRF-5, and IRF-7, which stimulated p35 promoter reporter activity, overexpressed IRF-3 repressed p35 promoter activity in response to TMEV infection, loxoribine, IFN-{gamma}/LPS, but not IFN-{gamma} alone. IRF-3 lessened but did not eliminate IRF-1-stimulated p35 promoter activity. Repression by IRF-3 required bp -172 to -122 of the p35 promoter. The data suggest that pre-activated IRF-3 is a major factor in the differences in IL-12 production between B10.S and SJL/J macrophages responding to TMEV.

Dahlberg, Angela [Department of Oral Biology and Nebraska Center for Virology, University of Nebraska Medical Center, 40th and Holdrege Sts., Lincoln, NE 68583-0740 (United States); Auble, Mark R. [Department of Oral Biology and Nebraska Center for Virology, University of Nebraska Medical Center, 40th and Holdrege Sts., Lincoln, NE 68583-0740 (United States); Petro, Thomas M. [Department of Oral Biology and Nebraska Center for Virology, University of Nebraska Medical Center, 40th and Holdrege Sts., Lincoln, NE 68583-0740 (United States)]. E-mail:



Construction and characterization of stable, constitutively expressed, chromosomal green and red fluorescent transcriptional fusions in the select agents, Bacillus anthracis, Yersinia pestis, Burkholderia mallei, and Burkholderia pseudomallei.  


Here, we constructed stable, chromosomal, constitutively expressed, green and red fluorescent protein (GFP and RFP) as reporters in the select agents, Bacillus anthracis, Yersinia pestis, Burkholderia mallei, and Burkholderia pseudomallei. Using bioinformatic approaches and other experimental analyses, we identified P0253 and P1 as potent promoters that drive the optimal expression of fluorescent reporters in single copy in B. anthracis and Burkholderia spp. as well as their surrogate strains, respectively. In comparison, Y. pestis and its surrogate strain need two chromosomal copies of cysZK promoter (P2cysZK) for optimal fluorescence. The P0253-, P2cysZK-, and P1-driven GFP and RFP fusions were first cloned into the vectors pRP1028, pUC18R6KT-mini-Tn7T-Km, pmini-Tn7-gat, or their derivatives. The resultant constructs were delivered into the respective surrogates and subsequently into the select agent strains. The chromosomal GFP- and RFP-tagged strains exhibited bright fluorescence at an exposure time of less than 200 msec and displayed the same virulence traits as their wild-type parental strains. The utility of the tagged strains was proven by the macrophage infection assays and lactate dehydrogenase release analysis. Such strains will be extremely useful in high-throughput screens for novel compounds that could either kill these organisms, or interfere with critical virulence processes in these important bioweapon agents and during infection of alveolar macrophages. PMID:25044501

Su, Shengchang; Bangar, Hansraj; Saldanha, Roland; Pemberton, Adin; Aronow, Bruce; Dean, Gary E; Lamkin, Thomas J; Hassett, Daniel J



Interleukin-22 binding protein (IL-22BP) is constitutively expressed by a subset of conventional dendritic cells and is strongly induced by retinoic acid.  


Interleukin-22 (IL-22) is mainly produced at barrier surfaces by T cells and innate lymphoid cells and is crucial to maintain epithelial integrity. However, dysregulated IL-22 action leads to deleterious inflammation and is involved in diseases such as psoriasis, intestinal inflammation, and cancer. IL-22 binding protein (IL-22BP) is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We show both in rats and mice that, in the steady state, the main source of IL-22BP is constituted by a subset of conventional dendritic cells (DCs) in lymphoid and non-lymphoid tissues. In mouse intestine, IL-22BP was specifically expressed in lamina propria CD103(+)CD11b(+) DC. In humans, IL-22BP was expressed in immature monocyte-derived DC and strongly induced by retinoic acid but dramatically reduced upon maturation. Our data suggest that a subset of immature DCs may actively participate in the regulation of IL-22 activity in the gut by producing high levels of IL-22BP. PMID:23653115

Martin, J C J; Bériou, G; Heslan, M; Chauvin, C; Utriainen, L; Aumeunier, A; Scott, C L; Mowat, A; Cerovic, V; Houston, S A; Leboeuf, M; Hubert, F X; Hémont, C; Merad, M; Milling, S; Josien, R



Quantitative Comparison of Constitutive Promoters in Human ES cells  

Microsoft Academic Search

BackgroundConstitutive promoters that ensure sustained and high level gene expression are basic research tools that have a wide range of applications, including studies of human embryology and drug discovery in human embryonic stem cells (hESCs). Numerous cellular\\/viral promoters that ensure sustained gene expression in various cell types have been identified but systematic comparison of their activities in hESCs is still

Karin Norrman; Yvonne Fischer; Blandine Bonnamy; Fredrik Wolfhagen Sand; Philippe Ravassard; Henrik Semb; David S. Milstone



Constitution, 15 August 1982.  


This document reprints major provisions of the 1982 Constitution of Equatorial Guinea. The Constitution calls for protection of the family as the basic building block of society. Foreigners are afforded the same civil rights as citizens and may seek asylum but may not exercise political rights. The Constitution guarantees equality before the law and prohibits discrimination based on ethnic background, race, sex, language, religion, filiation, political or other views, social origin, economic position, or birth. Women are afforded the same rights as men regardless of their marital status. The Constitution also guarantees citizens freedom to travel nationally and internationally and to choose a place of residence. Equatoguineans are also entitled to a standard of living that insures health, nutrition, education, clothing, housing, medical care, and necessary social services. The family policy contained in the Constitution protects all types of legal marriages equally and recognizes nonattachable and inalienable family patrimony. Children are protected from the time of conception, and all inhabitants are guaranteed a basic state education which is compulsory and free. Efforts are also being made to eradicate illiteracy. Women are insured training and promotion for their integration into the active life and development of the country, and farmers are guaranteed traditional ownership of the lands they possess, although the state retains the right of eminent domain. PMID:12346662



Constitutive expression of selected genes from the pentose phosphate and aromatic pathways increases the shikimic acid yield in high-glucose batch cultures of an Escherichia coli strain lacking PTS and pykF  

PubMed Central

Background During the last two decades many efforts have been directed towards obtaining efficient microbial processes for the production of shikimic acid (SA); however, feeding high amounts of substrate to increase the titer of this compound has invariably rendered low conversion yields, leaving room for improvement of the producing strains. In this work we report an alternative platform to overproduce SA in a laboratory-evolved Escherichia coli strain, based on plasmid-driven constitutive expression of six genes selected from the pentose phosphate and aromatic amino acid pathways, artificially arranged as an operon. Production strains also carried inactivated genes coding for phosphotransferase system components (ptsHIcrr), shikimate kinases I and II (aroK and aroL), pyruvate kinase I (pykF) and the lactose operon repressor (lacI). Results The strong and constitutive expression of the constructed operon permitted SA production from the beginning of the cultures, as evidenced in 1 L batch-mode fermentors starting with high concentrations of glucose and yeast extract. Inactivation of the pykF gene improved SA production under the evaluated conditions by increasing the titer, yield and productivity of this metabolite compared to the isogenic pykF+ strain. The best producing strain accumulated up to 43 g/L of SA in 30 h and relatively low concentrations of acetate and aromatic byproducts were detected, with SA accounting for 80% of the produced aromatic compounds. These results were consistent with high expression levels of the glycolytic pathway and synthetic operon genes from the beginning of fermentations, as revealed by transcriptomic analysis. Despite the consumption of 100 g/L of glucose, the yields on glucose of SA and of total aromatic compounds were about 50% and 60% of the theoretical maximum, respectively. The obtained yields and specific production and consumption rates proved to be constant with three different substrate concentrations. Conclusions The developed production system allowed continuous SA accumulation until glucose exhaustion and eliminated the requirement for culture inducers. The obtained SA titers and yields represent the highest reported values for a high-substrate batch process, postulating the strategy described in this report as an interesting alternative to the traditionally employed fed-batch processes for SA production. PMID:24079972



Altered methylation and expression of ER-associated degradation factors in long-term alcohol and constitutive ER stress-induced murine hepatic tumors  

PubMed Central

Mortality from liver cancer in humans is increasingly attributable to heavy or long-term alcohol consumption. The mechanisms by which alcohol exerts its carcinogenic effect are not well understood. In this study, the role of alcohol-induced endoplasmic reticulum (ER) stress response in liver cancer development was investigated using an animal model with a liver knockout (KO) of the chaperone BiP and under constitutive hepatic ER stress. Long-term alcohol and high fat diet feeding resulted in higher levels of serum alanine aminotransferase, impaired ER stress response, and higher incidence of liver tumor in older (aged 16 months) KO females than in either middle-aged (6 months) KOs or older (aged 16 months) wild type females. In the older KO females, stronger effects of the alcohol on methylation of CpG islands at promoter regions of genes involved in the ER-associated degradation (ERAD) were also detected. Altered expression of ERAD factors including derlin 3, Creld2 (cysteine-rich with epidermal growth factor-like domains 2), Herpud1 (homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member), Wfs1 (Wolfram syndrome gene), and Yod1 (deubiquitinating enzyme 1) was co-present with decreased proteasome activities, increased estrogen receptor ? variant (ER?36), and enhanced phosphorylations of ERK1/2 (extracellular signal-regulated protein kinases 1 and 2) and STAT3 (the signal transducers and activators of transcription) in the older KO female fed alcohol. Our results suggest that long-term alcohol consumption and aging may promote liver tumorigenesis in females through interfering with DNA methylation and expression of genes involved in the ERAD. PMID:24198826

Han, Hui; Hu, Jay; Lau, Mo Y.; Feng, Min; Petrovic, Lydia M.; Ji, Cheng



A Constitutive Expressed Phosphate Transporter, OsPht1;1, Modulates Phosphate Uptake and Translocation in Phosphate-Replete Rice1[W][OA  

PubMed Central

A number of phosphate (Pi) starvation- or mycorrhiza-regulated Pi transporters belonging to the Pht1 family have been functionally characterized in several plant species, whereas functions of the Pi transporters that are not regulated by changes in Pi supply are lacking. In this study, we show that rice (Oryza sativa) Pht1;1 (OsPT1), one of the 13 Pht1 Pi transporters in rice, was expressed abundantly and constitutively in various cell types of both roots and shoots. OsPT1 was able to complement the proton-coupled Pi transporter activities in a yeast mutant defective in Pi uptake. Transgenic plants of OsPT1 overexpression lines and RNA interference knockdown lines contained significantly higher and lower phosphorus concentrations, respectively, compared with the wild-type control in Pi-sufficient shoots. These responses of the transgenic plants to Pi supply were further confirmed by the changes in depolarization of root cell membrane potential, root hair occurrence, 33P uptake rate and transportation, as well as phosphorus accumulation in young leaves at Pi-sufficient levels. Furthermore, OsPT1 expression was strongly enhanced by the mutation of Phosphate Overaccumulator2 (OsPHO2) but not by Phosphate Starvation Response2, indicating that OsPT1 is involved in the OsPHO2-regulated Pi pathway. These results indicate that OsPT1 is a key member of the Pht1 family involved in Pi uptake and translocation in rice under Pi-replete conditions. PMID:22649273

Sun, Shubin; Gu, Mian; Cao, Yue; Huang, Xinpeng; Zhang, Xiao; Ai, Penghui; Zhao, Jianning; Fan, Xiaorong; Xu, Guohua



What Is a Constitution?  

ERIC Educational Resources Information Center

Provides a lesson plan designed to help students better understand the concept of a constitution, distinguish constitutional law from statutory law, and recognize examples of constitutional government. (BSR)

OAH Magazine of History, 1988



Constitutive Activation of the G-Protein Subunit G[alpha]s within Forebrain Neurons Causes PKA-Dependent Alterations in Fear Conditioning and Cortical "Arc" mRNA Expression  

ERIC Educational Resources Information Center

Memory formation requires cAMP signaling; thus, this cascade has been of great interest in the search for cognitive enhancers. Given that medications are administered long-term, we determined the effects of chronically increasing cAMP synthesis in the brain by expressing a constitutively active isoform of the G-protein subunit G[alpha]s…

Kelly, Michele P.; Cheung, York-Fong; Favilla, Christopher; Siegel, Steven J.; Kanes, Stephen J.; Houslay, Miles D.; Abel, Ted



Cloning of a novel constitutively expressed pectate lyase gene pelB from Fusarium solani f. sp. pisi (Nectria haematococca, mating type VI) and characterization of the gene product expressed in Pichia pastoris.  

PubMed Central

Since plant-pathogenic fungi must penetrate through pectinaceous layers of the host cell wall, pectin-degrading enzymes are thought to be important for pathogenesis. Antibodies prepared against a pectin-inducible pectate lyase (pectate lyase A [PLA]) produced by a phytopathogenic fungus, Fusarium solani f. sp. pisi (Nectria haematococca, mating type VI), was previously found to protect the host from infection. The gene (pelA) and its cDNA were cloned and sequenced. Here we report the isolation of a new pectate lyase gene, pelB, from a genomic library of F. solani f. sp. pisi with the pelA cDNA as the probe. A 2.6-kb DNA fragment containing pelB and its flanking regions was sequenced. The coding region of pelB was amplified by reverse transcription-mediated PCR, using total RNA isolated from F. solani pisi culture grown in the presence of glucose as the sole carbon source. The predicted open reading frame of pelB would encode a 25.6-kDa protein of 244 amino acids which has 65% amino acid sequence identity with PLA from F. solani f. sp. pisi but no significant homology with other pectinolytic enzymes. The first 16 amino acid residues at the N terminus appeared to be a signal peptide. The pelB cDNA was expressed in Pichia pastoris, yielding a pectate lyase B (PLB) which was found to be a glycoprotein of 29 kDa. PLB was purified to homogeneity by using a two-step procedure involving ammonium sulfate precipitation followed by Superdex G75 gel filtration chromatography. Purified PLB showed optimal lyase activity at pH 10.0. A rapid drop in the viscosity of the substrate and Mono Q anion-exchange chromatography of the products generated by the lyase showed that PLB cleaved polygalacturonate chains in an endo fashion. Western blotting (immunoblotting) with antibodies raised against PLA showed that PLB and PLA are immunologically related to each other. The 5' flanking regions of both pelA and pelB were translationally fused to the beta-glucuronidase gene and introduced into F. solani f. sp. pisi, and beta-glucuronidase activities of the transformants were measured. Expression of the marker gene by the transformants showed that pelA expression is induced by pectin and repressed by glucose, whereas expression of pelB is constitutive and is not subject to glucose repression. Reverse transcription-mediated PCR showed that both pelA and pelB are expressed when F. solani f. sp. pisi infects pea epicotyl. PMID:8522511

Guo, W; Gonzalez-Candelas, L; Kolattukudy, P E



Different strategies for reducing intestinal background radioactivity associated with imaging HSV1-tk expression using established radionucleoside probes.  


One limitation of HSV1-tk reporter positron emission tomography (PET) with nucleoside analogues is the high background radioactivity in the intestine. We hypothesized that endogenous expression of thymidine kinase in bacterial flora could phosphorylate and trap such radiotracers, contributing to the high radioactivity levels in the bowel, and therefore explored different strategies to increase fecal elimination of radiotracer. Intestinal radioactivity was assessed by in vivo microPET imaging and ex vivo tissue sampling following intravenous injection of 18F-FEAU, 124I-FIAU, or 18F-FHBG in a germ-free mouse strain. We also explored the use of an osmotic laxative agent and/or a 100% enzymatically hydrolyzed liquid diet. No significant differences in intestinal radioactivity were observed between germ-free and normal mice. 18F-FHBG-derived intestinal radioactivity levels were higher than those of 18F-FEAU and 124I-FIAU; the intestine to blood ratio was more than 20-fold higher for 18F-FHBG than for 18F-FEAU and 124I-FIAU. The combination of Peptamen and Nulytely lowered intestinal radioactivity levels and increased (2.2-fold) the HSV1-tk transduced xenograft to intestine ratio for 18F-FEAU. Intestinal bacteria in germ-free mice do not contribute to the high intestinal levels of radioactivity following injection of radionucleoside analogues. The combination of Peptamen and Nulytely increased radiotracer elimination by increasing bowel motility without inducing dehydration. PMID:20128998

Ruggiero, Alessandro; Brader, Peter; Serganova, Inna; Zanzonico, Pat; Cai, Shangde; Lipman, Neil S; Hricak, Hedvig; Blasberg, Ronald G




EPA Science Inventory

The survival of genetically altered Pseudomonas putida strains harboring an inducible plasmid, PRO101, or a constitutive plasmid, PRO103, was compared. hese plasmids encode for the degradation of 2,4-dichlorophenoxyacetate (TFD) to 2-chloromaleylacetate, and the maintenance of ei...



EPA Science Inventory

Survival of genetically altered Pseudonomas putida strains harboring an inducible plasmid, pRO101, or a constitutive plasmid, pRO103, was compared. hese plasmids encoded for the degradation of 2,4-dichlorophenoxyacetate (TFD) to 2-chloromaleylacetate, and the maintenance of eithe...


Amending the Constitution: Current Proposals.  

ERIC Educational Resources Information Center

Provides background information on four constitutional amendment proposals: (1) flag protection amendment; (2) school prayer amendment; (3) balanced-budget amendment; and (4) victim rights amendment. Evaluates each in terms of timeliness, the support base, and the strength of their opposition. Includes questions for discussion. (CMK)

Schechter, Stephen L.



The Constitutional Amendment Process  

ERIC Educational Resources Information Center

This article discusses the constitutional amendment process. Although the process is not described in great detail, Article V of the United States Constitution allows for and provides instruction on amending the Constitution. While the amendment process currently consists of six steps, the Constitution is nevertheless quite difficult to change.…

Chism, Kahlil



Liberal constitutionalism, constitutional liberalism and democracy  

Microsoft Academic Search

The tension that is often seen to exist between the ideals of liberalism and of democracy is examined in this paper in light\\u000a of the distinction between two liberal outlooks at constitutional regimes, namely, on the one side, a liberal constitutionalism that focuses on the need to provide institutional safeguards of individual liberty as private autonomy and, on the other

Viktor J. Vanberg



Constitutive and tissue-specific differential expression of the cryIA(b) gene in transgenic rice plants conferring resistance to rice insect pest  

Microsoft Academic Search

The truncated chimeric Bt gene, cryIA(b) of Bacillus thuringiensis, driven by two constitutive promoters, 35S from CaMV and Actin-1 from rice, and two tissue-specific promoters, pith tissue\\u000a and pepcarboxylase (PEPC) for green tissue from maize, was introduced into several varieties of rice (indica and japonica)\\u000a by microprojectile bombardment and protoplast systems. A total of 1800 putative transgenic Bt rice plants

K. Datta; A. Vasquez; J. Tu; L. Torrizo; M. F. Alam; N. Oliva; E. Abrigo; G. S. Khush; S. K. Datta



Gene expression profiling in C57BL\\/6J and A\\/J mouse inbred strains reveals gene networks specific for brain regions independent of genetic background  

Microsoft Academic Search

BACKGROUND: We performed gene expression profiling of the amygdala and hippocampus taken from inbred mouse strains C57BL\\/6J and A\\/J. The selected brain areas are implicated in neurobehavioral traits while these mouse strains are known to differ widely in behavior. Consequently, we hypothesized that comparing gene expression profiles for specific brain regions in these strains might provide insight into the molecular

Simone de Jong; Tova F Fuller; Esther Janson; Eric Strengman; Steve Horvath; Martien JH Kas; Roel A Ophoff



Functional evaluation of a novel constitutive promoter F1 of Bacillus pumilus, as a rice epiphytic strain, and construction of an efficient expression and secretion system under the control of F1.  


To establish a constitutive, high-efficiency expression and secretion system for Bacillus pumilus, the function of a promoter and the abilities of three signal peptides in B. pumilus DX01 were tested. F1, cloned from the rice epiphyte B. pumilus strain DX01, had strong transcription activity and was a vegetative-phase constitutive promoter. The signal sequences of Bacillus subtilis levansucrase (sacB) and subtilisin, as well as B. pumilus DX01 RNase signal sequence could drive the secretion of E. coli beta-lactamase from B. pumilus DX01 efficiently, among which the signal sequence of B. subtilis sacB was the most effective. Likewise, they could also direct the secretion of green fluorescence protein (GFP) from DX01. PMID:16799766

Sun, Xiaobo; Chen, Yunpeng; Wu, Cuirong; Yang, Guangxiao; Guo, Bin; Shen, Daleng




EPA Science Inventory

Altered sensitivity of the mouse fetus to impaired prostatic bud formation by dioxin: Influence of genetic background and null expression of TGF and EGF. Rasmussen, N.T., Lin T-M., Fenton, S.E., Abbott, B.D. and R.E. Peterson. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)...


Role of p53 in Regulating Constitutive and X-Radiation-Inducible CD95 Expression and Function in Carcinoma Cells1  

Microsoft Academic Search

The p53 tumor suppressor protein is known to regulate the expression of the CD95 (Fas\\/APO-1) death receptor in a small subset of normal cell types as well as in many cancer cell types. However, whether p53-depend- ent regulation of CD95 expression is consistently associated with increased susceptibility to CD95-mediated cell death is poorly understood. To ad- dress this issue, we

Michael A. Sheard; Stjepan Uldrijan; Borivoj Vojtesek


974. Constitutive Expression of a Mutated Form of CTLA4Ig after Gene Transfer Is Well Tolerated and Prevents Immune Responses Against an Immunogenic Transgene in Nonhuman Primates  

Microsoft Academic Search

rAAV-mediated gene transfer in skeletal muscle of large animal models can sustain long-term expression of transgene, but when applied to genetic diseases, the newly expressed therapeutic protein often induces a deleterious immune response. We investigated whether such immune response could be prevented by treatment with a mutant form of CTLA4Ig with higher affinity for B7 molecules (LEA29Y), known to induce

Alice Toromanoff; Marcelo Hill; Yan Cherel; Jack-Yves Deschamps; Olivier Gauthier; Bernard Vanhove; Fabienne Rolling; Philippe Moullier; Ignacio Anegon; Caroline Le Guiner



Thailand Draft Constitution  

NSDL National Science Digital Library

On Saturday, October 11 The King of Thailand signed a new constitution, Thailand's 16th. The new constitution is not popular among many Thai politicians, but others see it as a route to greater democracy in the country. Nation Multimedia Group, publishers of the Thai newspaper The Nation, have posted the full text of the constitution on their site.



Enforcing Constitutional Constraints  

Microsoft Academic Search

I examine the enforcement of constitutional constraintson government. Citizens must be able to identify and prevent(or correct) observed violations of the constitution to successfullyenforce constraints. Identification requires specialized knowledgenecessitating employment of experts in constitutional law. Collectiveaction and coordination problems can also plague constitutionalenforcement efforts. I argue that judicial review is a relativelyefficient enforcement mechanism which substantially mitigatesthese problems.

Daniel Sutter



Hateful Expression and First Amendment Values: Toward a Theory of Constitutional Constraint on Hate Speech at Colleges and Universities after R.A.V. v. St. Paul.  

ERIC Educational Resources Information Center

Discussion of hate speech on college campuses focuses on whether the concept of hate speech encompasses expression deserving full First Amendment protection and thus virtual immunity from college regulation. It is argued that the Supreme Court could sustain some form of hate-speech policy on campus based on precedent elsewhere. (MSE)

Hartman, Rhonda G.



Transposon-Mediated Alteration of TaMATE1B Expression in Wheat Confers Constitutive Citrate Efflux from Root Apices[W  

PubMed Central

The TaMATE1B gene (for multidrug and toxic compound extrusion) from wheat (Triticum aestivum) was isolated and shown to encode a citrate transporter that is located on the plasma membrane. TaMATE1B expression in roots was induced by iron deficiency but not by phosphorus deficiency or aluminum treatment. The coding region of TaMATE1B was identical in a genotype showing citrate efflux from root apices (cv Carazinho) to one that lacked citrate efflux (cv Egret). However, sequence upstream of the coding region differed between these two genotypes in two ways. The first difference was a single-nucleotide polymorphism located approximately 2 kb upstream from the start codon in cv Egret. The second difference was an 11.1-kb transposon-like element located 25 bp upstream of the start codon in cv Carazinho that was absent from cv Egret. The influence of these polymorphisms on TaMATE1B expression was investigated using fusions to green fluorescent protein expressed in transgenic lines of rice (Oryza sativa). Fluorescence measurements in roots of rice indicated that 1.5- and 2.3-kb regions upstream of TaMATE1B in cv Carazinho (which incorporated 3? regions of the transposon-like element) generated 20-fold greater expression in the apical 1 mm of root compared with the native promoter in cv Egret. By contrast, fluorescence in more mature tissues was similar in both cultivars. The presence of the single-nucleotide polymorphism alone consistently generated 2-fold greater fluorescence than the cv Egret promoter. We conclude that the transposon-like element in cv Carazinho extends TaMATE1B expression to the root apex, where it confers citrate efflux and enhanced aluminum tolerance. PMID:23204428

Tovkach, Andriy; Ryan, Peter R.; Richardson, Alan E.; Lewis, David C.; Rathjen, Tina M.; Ramesh, Sunita; Tyerman, Stephen D.; Delhaize, Emmanuel



Sex Differences in Constitutive Autophagy  

PubMed Central

Sex bias has been described nowadays in biomedical research on animal models, although sexual dimorphism has been confirmed widely under pathological and physiological conditions. The main objective of our work was to study the sex differences in constitutive autophagy in spinal cord and skeletal muscle tissue from wild type mice. To examine the influence of sex on autophagy, mRNA and proteins were extracted from male and female mice tissues. The expressions of microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (p62), markers to monitor autophagy, were analyzed at 40, 60, 90, and 120 days of age. We found significant sex differences in the expression of LC3 and p62 in both tissues at these ages. The results indicated that sex and tissue specific differences exist in constitutive autophagy. These data underlined the need to include both sexes in the experimental groups to minimize any sex bias. PMID:24719882

Olivan, Sara; Calvo, Ana Cristina; Manzano, Raquel; Zaragoza, Pilar



Efficient production of 1,3-propanediol from glycerol upon constitutive expression of the 1,3-propanediol oxidoreductase gene in engineered Klebsiella pneumoniae with elimination of by-product formation.  


In the present study, we developed an efficient method of 1,3-propanediol (1,3-PD) production from glycerol by genetic engineering of Klebsiella pneumoniae AK mutant strains. The proposed approach eliminated by-product formation and IPTG induction resulted in maximal production of 1,3-PD. A series of recombinant strains was designed to constitutively express the dhaB and/or dhaT genes, using the bacteriophage T5 P(DE20) promoter and the rho-independent transcription termination signal of the Rahnella aquatilis levansucrase gene. Among these strains, AK/pConT expressing dhaT alone gave the highest yield of 1,3-PD. Fed-batch fermentation resulted in efficient production of 1,3-PD from either pure or crude glycerol, without by-product formation. PMID:23361186

Oh, Baek-Rock; Seo, Jeong-Woo; Heo, Sun-Yeon; Luo, Lian Hua; Hong, Won-Kyung; Park, Don-Hee; Kim, Chul-Ho



Water deficits and heat shock effects on photosynthesis of a transgenic Arabidopsis thaliana constitutively expressing ABP9, a bZIP transcription factor  

Microsoft Academic Search

The effects of water deficits (WD), heat shock (HS), and both (HSWD) on photosynthetic carbon- and light-use efficiencies together with leaf ABA content, pigment composition and expressions of stress- and light harvesting-responsive genes were investigated in ABP9 (ABA-responsive-element (ABRE) binding pro- tein 9) transgenic Arabidopsis (5P2). WD, HS, and HSWD significantly decreased photosynthetic rate (A) and stomatal conductance (gs) in

Xia Zhang; Bernd Wollenweber; Dong Jiang; Fulai Liu; Jun Zhao



L-ascorbic acid represses constitutive activation of NF-kappaB and COX-2 expression in human acute myeloid leukemia, HL-60.  


There is increasing evidence that L-ascorbic acid (LAA) is selectively toxic to some types of cancer cells at pharmacological concentrations, functioning as a pro-oxidant rather than as an anti-oxidant. However, the molecular mechanisms by which LAA initiates cellular signaling leading to cell death are still unclear. In an effort to gain insight into these mechanisms, the effects of LAA on eukaryotic transcription nuclear factor NF-kappaB and cyclooxygenase-2 (COX-2) expression were investigated. In the present study, LAA suppressed DNA binding activity of NF-kappaB, composed of a p65/p50 heterodimer, through inhibition of degradation of inhibitory kappaB-alpha (IkappaB-alpha) and prevention of nuclear translocation of p65. The inhibitory effect of LAA on NF-kappaB activity was dependent upon glutathione levels in HL-60 cells, as well as generation of H2O2 but not superoxide anion. LAA also downregulated the expression of COX-2, which has a NF-kappaB binding site on its promoter, through repressing NF-kappaB DNA binding activity. Moreover, cotreatment of 1 microM arsenic trioxide (As2O3) with various concentrations of LAA enhanced an LAA-induced repression of NF-kappaB activity and COX-2 expression. In conclusion, our data suggest that LAA exerts its anti-tumor activity through downregulation of NF-kappaB activity and COX-2 expression, and these inhibitory effects can be enhanced by co-treatment with As2O3. PMID:15368354

Han, Seong-Su; Kim, Kihyun; Hahm, Eun-Ryeong; Lee, Sook J; Surh, Young-Joon; Park, Hye K; Kim, Won S; Jung, Chul W; Lee, Mark H; Park, Keunchil; Yang, Jung-Hyun; Yoon, Sung-Soo; Riordan, Neil H; Riordan, Hugh D; Kimler, Bruce F; Park, Chan H; Lee, Je-Ho; Park, Seyeon



Contesting the Constitution: The Constitutional Dialogues.  

ERIC Educational Resources Information Center

This historical dramatization, prepared for presentation at the 1985 Wyoming Chatauqua, contains three dialogues, set during the administration of President Thomas Jefferson and presenting the issues surrounding the drafting and ratification of the U.S. Constitution. The dialogues are designed to be presented in three segments to permit discussion…

Hilenski, Ferdinand Alexi


Dynamic Alternations in Cellular and Molecular Components during Blossom-End Rot Development in Tomatoes Expressing sCAX1, a Constitutively Active Ca2+/H+ Antiporter from Arabidopsis1[W][OA  

PubMed Central

Although calcium (Ca) concentration in cellular compartments has been suggested to be tightly regulated, Ca deficiency disorders such as blossom-end rot (BER) in tomato (Solanum lycopersicum) fruit may be induced by abnormal regulation of Ca partitioning and distribution in the cell. The objectives of this work were to analyze the effects of high expression of the constitutively functional Arabidopsis (Arabidopsis thaliana) Ca2+/H+ exchanger (sCAX1) tonoplast protein in tomato fruit on cellular Ca partitioning and distribution, membrane integrity, and the transcriptional profile of genes potentially involved in BER development. Wild-type and sCAX1-expressing tomato plants were grown in a greenhouse. Wild-type plants did not develop BER, whereas sCAX1-expressing plants reached 100% BER incidence at 15 d after pollination. The sCAX1-expressing fruit pericarp had higher total tissue and water-soluble Ca concentrations, lower apoplastic and cytosolic Ca concentrations, higher membrane leakage, and Ca accumulation in the vacuole of sCAX1-expressing cells. Microarray analysis of healthy sCAX1-expressing fruit tissue indicated down-regulation of genes potentially involved in BER development, such as genes involved in membrane structure and repair and cytoskeleton metabolism, as well as up-regulation of genes that may have limited BER damage expansion, such as genes coding for heat shock proteins, glutathione S-transferases, and peroxidases. The results indicate that the high expression of the sCAX1 gene reduces cytosolic and apoplastic Ca concentrations, affecting plasma membrane structure and leading to BER symptom development in the fruit tissue. PMID:21464475

Tonetto de Freitas, Sergio; Padda, Malkeet; Wu, Qingyu; Park, Sunghun; Mitcham, Elizabeth J.



Comprehensive genome-wide survey, genomic constitution and expression profiling of the NAC transcription factor family in foxtail millet (Setaria italica L.).  


The NAC proteins represent a major plant-specific transcription factor family that has established enormously diverse roles in various plant processes. Aided by the availability of complete genomes, several members of this family have been identified in Arabidopsis, rice, soybean and poplar. However, no comprehensive investigation has been presented for the recently sequenced, naturally stress tolerant crop, Setaria italica (foxtail millet) that is famed as a model crop for bioenergy research. In this study, we identified 147 putative NAC domain-encoding genes from foxtail millet by systematic sequence analysis and physically mapped them onto nine chromosomes. Genomic organization suggested that inter-chromosomal duplications may have been responsible for expansion of this gene family in foxtail millet. Phylogenetically, they were arranged into 11 distinct sub-families (I-XI), with duplicated genes fitting into one cluster and possessing conserved motif compositions. Comparative mapping with other grass species revealed some orthologous relationships and chromosomal rearrangements including duplication, inversion and deletion of genes. The evolutionary significance as duplication and divergence of NAC genes based on their amino acid substitution rates was understood. Expression profiling against various stresses and phytohormones provides novel insights into specific and/or overlapping expression patterns of SiNAC genes, which may be responsible for functional divergence among individual members in this crop. Further, we performed structure modeling and molecular simulation of a stress-responsive protein, SiNAC128, proffering an initial framework for understanding its molecular function. Taken together, this genome-wide identification and expression profiling unlocks new avenues for systematic functional analysis of novel NAC gene family candidates which may be applied for improvising stress adaption in plants. PMID:23691254

Puranik, Swati; Sahu, Pranav Pankaj; Mandal, Sambhu Nath; B, Venkata Suresh; Parida, Swarup Kumar; Prasad, Manoj



A Continuous Bovine Kidney Cell Line Constitutively Expressing Bovine ?V?6 Integrin Has Increased Susceptibility to Foot-and-Mouth Disease Virus  

PubMed Central

Foot-and-mouth disease (FMD) is a worldwide problem limiting the trade of animals and their products from affected countries. The rapid isolation, serotyping, and vaccine matching of FMD virus from disease outbreaks is critical for enabling the implementation of effective vaccination programs and to stop the spread of infection during outbreaks. Some primary cells have been shown to be highly susceptible to most strains of FMD virus (FMDV) but are difficult and expensive to prepare and maintain. Since the ?V?6 integrin is a principal receptor for FMDV, we transduced a bovine kidney cell line to stably express both the ?V and ?6 bovine integrin subunits. This stable cell line (LFBK-?V?6) showed ?6 expression and enhanced susceptibility to FMDV infection for ?100 cell passages. LFBK-?V?6 cells were highly sensitive for detecting all serotypes of FMDV from experimentally infected animals, including the porcinophilic FMDV strain O/TAW/97. In comparison to other cell types that are currently used for virus isolation, LFBK-?V?6 cells were more effective at detecting FMDV in clinical samples, supporting their use as a more sensitive tool for virus isolation. PMID:23515553

LaRocco, Michael; Kramer, Ed; Ahmed, Zaheer; Pacheco, Juan M.; Duque, Hernando; Baxt, Barry; Rodriguez, Luis L.



Constitutive expression of a miR319 gene alters plant development and enhances salt and drought tolerance in transgenic creeping bentgrass.  


MicroRNA319 (miR319) is one of the first characterized and conserved microRNA families in plants and has been demonstrated to target TCP (for TEOSINTE BRANCHED/CYCLOIDEA/PROLIFERATING CELL FACTORS [PCF]) genes encoding plant-specific transcription factors. MiR319 expression is regulated by environmental stimuli, suggesting its involvement in plant stress response, although experimental evidence is lacking and the underlying mechanism remains elusive. This study investigates the role that miR319 plays in the plant response to abiotic stress using transgenic creeping bentgrass (Agrostis stolonifera) overexpressing a rice (Oryza sativa) miR319 gene, Osa-miR319a. We found that transgenic plants overexpressing Osa-miR319a displayed morphological changes and exhibited enhanced drought and salt tolerance associated with increased leaf wax content and water retention but reduced sodium uptake. Gene expression analysis indicated that at least four putative miR319 target genes, AsPCF5, AsPCF6, AsPCF8, and AsTCP14, and a homolog of the rice NAC domain gene AsNAC60 were down-regulated in transgenic plants. Our results demonstrate that miR319 controls plant responses to drought and salinity stress. The enhanced abiotic stress tolerance in transgenic plants is related to significant down-regulation of miR319 target genes, implying their potential for use in the development of novel molecular strategies to genetically engineer crop species for enhanced resistance to environmental stress. PMID:23292790

Zhou, Man; Li, Dayong; Li, Zhigang; Hu, Qian; Yang, Chunhua; Zhu, Lihuang; Luo, Hong



The Constitution by Cell  

ERIC Educational Resources Information Center

On their visit to the National Archives Experience in Washington, D.C., students in Jenni Ashley and Gay Brock's U.S. history classes at the Potomac School in McLean, Virginia, participated in a pilot program called "The Constitution by Cell." Armed with their cell phones, a basic understanding of the Constitution, and a willingness to participate…

Greenhut, Stephanie; Jones, Megan



Interpreting the Constitution.  

ERIC Educational Resources Information Center

Discusses constitutional interpretations relating to capital punishment and protection of human dignity. Points out the document's effectiveness in creating a new society by adapting its principles to current problems and needs. Considers two views of the Constitution that lead to controversy over the legitimacy of judicial decisions. (PS)

Brennan, William J., Jr.



Nepal's Constitutional Process  

E-print Network

..........................................................................................................3 III. THE INTERIM CONSTITUTION............................................................................... 5 A. THE INTERIM CONSTITUTION DRAFTING COMMITTEE ...........................................................5 1. Process... representations directly to the ICDC. More than 1,400 written submissions and “easily 2,000 to 3,000” verbal submissions were received.53 All political parties made recommendations, as did various international and domestic organisations, with ethnic...

International Crisis Group



The Trypanosoma brucei DNA polymerase alpha core subunit gene is developmentally regulated and linked to a constitutively expressed open reading frame.  

PubMed Central

As an initial step towards the characterization of replicative DNA polymerases of trypanosomes, we have cloned, sequenced and examined the expression of the Trypanosoma (Trypanozoon) brucei brucei gene that encodes the DNA polymerase alpha catalytic core (pol alpha). The protein sequence contains the six conserved regions that have been recognized previously in eukaryotic and viral replicative DNA polymerases. In addition, we have identified a seventh region which appears to be conserved primarily in alpha-type DNA polymerases. The T.brucei DNA pol alpha core N-terminus is 123 and 129 amino acids smaller than that of the human and yeast homologue, respectively. The gene is separated by 386 bp from an upstream open reading frame (ORF) of 442 codons. Stable transcripts of the upstream sequence are detected in both dividing and non-dividing forms, while pol alpha transcripts are detected principally in dividing forms. Allelic copies of the T.brucei pol alpha region exhibit restriction site polymorphisms; one such sequence polymorphism affects the amino acid sequence of the T.brucei DNA pol alpha core. The T.brucei pol alpha region cross-hybridizes weakly with that of T.(Nannomonas) congolense and T.(Duttonella) vivax. Images PMID:1754381

Leegwater, P A; Strating, M; Murphy, N B; Kooy, R F; van der Vliet, P C; Overdulve, J P



Formation of self-assembled triple-layered rotavirus-like particles (tlRLPs) by constitutive co-expression of VP2, VP6, and VP7 in stably transfected high-five insect cell lines.  


In this study, stable high-five insect cell line constitutively expressing rotavirus (RV) VP2 was co-transfected with VP6 and VP7-recombinant plasmids. The presence of RV proteins in stably transfected high-five cells was verified by molecular and protein analyses. To yield self-assembled triple-layered RV-like particles (tlRLPs), a stable insect high-five cell line was generated to produce RV VP6 and VP7 besides VP2. Self-assembled tlRLPs were observed by transmission electron microscopy (TEM), and enzyme-linked immunosorbent assay (ELISA) was used to assess their antigenicity in vivo. The results suggest that the stable transfected high-five cells are able to generate tlRLPs with the efficient antigenicity. J. Med. Virol. 87: 102-111, 2015. © 2014 Wiley Periodicals, Inc. PMID:24797918

Shoja, Zabihollah; Tagliamonte, Maria; Jalilvand, Somayeh; Mollaei-Kandelous, Yaghoub; De Stradis, Angelo; Tornesello, Maria Lina; Buonaguro, Franco M; Buonaguro, Luigi



Kenya's New Constitution  

E-print Network

On 4 August 2010, Kenyans voted to adopt a new constitution, culminating a process that began as part of a resolution to the violent conflict that followed the December 2007 elections. By reducing executive power, devolving ...

Kramon, Eric


Purification from rat liver of a novel constitutively expressed member of the aldo-keto reductase 7 family that is widely distributed in extrahepatic tissues.  


Antiserum raised against human aflatoxin B(1) aldehyde reductase 1 (hAFAR1) has been used to identify a previously unrecognized rat aldo-keto reductase (AKR). This novel enzyme is designated rat aflatoxin B(1) aldehyde reductase 2 (rAFAR2) and it characteristically migrates faster during SDS/PAGE than does the archetypal ethoxyquin-inducible rAFAR protein (now called rAFAR1). Significantly, rAFAR2 is essentially unreactive with polyclonal antibodies raised against rAFAR1. Besides its distinct electrophoretic and immunochemical properties, rAFAR2 appears to be regulated differently from rAFAR1 as it is expressed in most rat tissues and does not appear to be induced by ethoxyquin. Multiple forms of rAFAR2 have been identified. Anion-exchange chromatography on Q-Sepharose, followed by adsorption chromatography on columns of Matrex Orange A and Cibacron Blue, have been employed to purify rAFAR2 from rat liver cytosol. The Q-Sepharose chromatography step resulted in the resolution of rAFAR2 into three peaks of AKR activity, two of which were purified and shown to be capable of catalysing the reduction of 2-carboxybenzaldehyde, succinic semialdehyde, 4-nitrobenzaldehyde and 9,10-phenathrenequinone. The two most highly purified rAFAR2-containing preparations eluted from the Cibacron Blue column were 91 and 98% homogeneous. Analysis of these by SDS/PAGE indicated that the least anionic (peak CBA5) comprised a polypeptide of 37.0 kDa, whereas the most anionic (peak CBA6) contained two closely migrating polypeptides of 36.8 and 37.0 kDa; by contrast, in the present study, rAFAR1 was estimated by SDS/PAGE to be composed of 38.0 kDa subunits. Final purification of the 37 kDa polypeptide in CBA5 and CBA6 was accomplished by reversed-phase HPLC. Partial proteolysis of the two preparations of the 37 kDa polypeptide with Staphylococcus aureus V8 protease yielded fragments of identical size, suggesting that they represent the product of a single gene. Furthermore, the peptide maps from CBA5 and CBA6 differed substantially from that yielded by rAFAR1, indicating that they are genetically distinct from the inducible reductase. A peptide generated by CNBr digestion of the 37 kDa polypeptide from CBA6 was shown by Edman degradation to share 88% sequence identity with residues Tyr(168)-Leu(183) of rAFAR1. This provides evidence that the rat protein identified by its cross-reactivity with anti-hAFAR1 serum is an additional member of the AKR7 family. PMID:10816434

Kelly, V P; Ireland, L S; Ellis, E M; Hayes, J D



Human & Constitutional Rights  

NSDL National Science Digital Library

The Arthur W. Diamond Law Library at Columbia Law School maintains this excellent resource for finding materials on human rights and constitutional rights. The metasite serves students, scholars, and practitioners as a portal to documents and Internet resources on international and domestic law related to human and constitutional rights. The information resources are divided into six sections: Country Reports, International Links, Regional Links, National Links, Documents, and Other Web Resources. Each section is clearly organized into neat lists or pop-up menus to ease navigation. Marylin Raisch -- the International, Comparative, and Foreign Law Librarian responsible for this metasite -- also provides a Hot Topics section, which posts information on current events related to human and constitutional rights.


National Constitution Center  

NSDL National Science Digital Library

On July 4, 2003, the new National Constitution Center will open in a brand new facility within Independence Historical Park in Philadelphia that will help it pursue its mission of "increasing public understanding of, and appreciation for, the Constitution, its history, and its contemporary relevance." Visitors will want to take the virtual tour available online, which moves through the building's Great Hall, the Kimmel Theatre (which will be used for museum orientation programs), the DeVos Exhibit Hall, and the rest of the building's different areas. As might be expected, the Web site has an online version of the complete Constitution (in English and Spanish), along with helpful educational resources such as lesson plans for grades K-12. The site is rounded out by information for visitors and a "Save the Bill of Rights!" educational game where students help recover the Bill of Rights by looking for clues in a series of graphic images depicting each right protected by this important document.


Explore the Constitution  

NSDL National Science Digital Library

If you type the words âÂÂU.S. Constitutionâ into Google, the search engine returns about 31 million results. ThatâÂÂs a lot of talk about a document written by a handful of scholar-politicians in an upstart republic more than 227 years ago. Yet less than a quarter of Americans have actually read the document. This site, hosted by the National Constitution Center, includes the United States Constitution in its entirety, divided clearly by Article and Amendment, and annotated with notes by the Annenberg Classroom. Perhaps best of all, you can browse the site by Issue. For instance, click on Abortion and explore how the Roe v. Wade Supreme Court ruling was based on Ninth and 14th Amendment rights.


Hyperbaric oxygen upregulates cochlear constitutive nitric oxide synthase  

PubMed Central

Background Hyperbaric oxygen therapy (HBOT) is a known adjuvant for treating ischemia-related inner ear diseases. Controversies still exist in the role of HBOT in cochlear diseases. Few studies to date have investigated the cellular changes that occur in inner ears after HBOT. Nitric oxide, which is synthesized by nitric oxide synthase (NOS), is an important signaling molecule in cochlear physiology and pathology. Here we investigated the effects of hyperbaric oxygen on eardrum morphology, cochlear function and expression of NOS isoforms in cochlear substructures after repetitive HBOT in guinea pigs. Results Minor changes in the eardrum were observed after repetitive HBOT, which did not result in a significant hearing threshold shift by tone burst auditory brainstem responses. A differential effect of HBOT on the expression of NOS isoforms was identified. Upregulation of constitutive NOS (nNOS and eNOS) was found in the substructures of the cochlea after HBOT, but inducible NOS was not found in normal or HBOT animals, as shown by immunohistochemistry. There was no obvious DNA fragmentation present in this HBOT animal model. Conclusions The present evidence indicates that the customary HBOT protocol may increase constitutive NOS expression but such upregulation did not cause cell death in the treated cochlea. The cochlear morphology and auditory function are consequently not changed through the protocol. PMID:21342510



Constitutions and Economic Policy  

Microsoft Academic Search

t the rare moments in history when a nation debates constitutional reform, the key issues often concern how the reforms might affect economic policy and economic performance. For example, Italy abandoned a system of pure proportional representation, where legislators were elected according to the proportions of the popular national vote received by their parties, and moved toward including ingredients of

Torsten Persson; Guido Tabellini



Religion under State Constitutions  

Microsoft Academic Search

State constitutional provisions concerning church and state differ in specificity and substance from the First Amendment's establish ment clause. In large part, these differences reflect the fact that the state provisions originated in concrete historical disputes. After the American colonies declared independence, conflict over established churches led states to adopt provisions safeguarding freedom of worship and prohibiting aid to religious

G. Alan Tarr



Gut microbiota, tight junction protein expression, intestinal resistance, bacterial translocation and mortality following cholestasis depend on the genetic background of the host  

PubMed Central

Failure of the intestinal barrier is a characteristic feature of cholestasis. We have previously observed higher mortality in C57BL/6J compared with A/J mice following common bile duct ligation (CBDL). We hypothesized the alteration in gut barrier function following cholestasis would vary by genetic background. Following one week of CBDL, jejunal TEER was significantly reduced in each ligated mouse compared with their sham counterparts; moreover, jejunal TEER was significantly lower in both sham and ligated C57BL/6J compared with sham and ligated A/J mice, respectively. Bacterial translocation to mesenteric lymph nodes was significantly increased in C57BL/6J mice vs. A/J mice. Four of 15 C57BL/6J mice were bacteremic; whereas, none of the 17 A/J mice were. Jejunal IFN-? mRNA expression was significantly elevated in C57BL/6J compared with A/J mice. Western blot analysis demonstrated a significant decrease in occludin protein expression in C57BL/6J compared with A/J mice following both sham operation and CBDL. Only C57BL/6J mice demonstrated a marked decrease in ZO-1 protein expression following CBDL compared with shams. Pyrosequencing of the 16S rRNA gene in fecal samples showed a dysbiosis only in C57BL/6J mice following CBDL when compared with shams. This study provides evidence of strain differences in gut microbiota, tight junction protein expression, intestinal resistance and bacterial translocation which supports the notion of a genetic predisposition to exaggerated injury following cholestasis. PMID:23652772

Alaish, Samuel M.; Smith, Alexis D.; Timmons, Jennifer; Greenspon, Jose; Eyvazzadeh, Daniel; Murphy, Ebony; Shea-Donahue, Terez; Cirimotich, Shana; Mongodin, Emmanuel; Zhao, Aiping; Fasano, Alessio; Nataro, James P.; Cross, Alan S



The Constitution in Other Lands.  

ERIC Educational Resources Information Center

Designed for classroom teaching, this document contains articles on the new constitutions of Japan, South Korea, and the Philippine Islands which were modeled in part on the U.S. Constitution. These countries' experiences with constitutional government are examined, and whether or not the U.S. Constitution can be a suitable model for other…

Bill of Rights in Action, 1987



Constitution Making the European Way  

Microsoft Academic Search

A growing branch of public choice goes under the heading of constitutional political economy. Under the constitutional political economy approach, the citizens write the constitution or contract creating the state, and then enter into a principal-agent relationship with those who fill the offices of the executive, legislative and judicial branches. Sovereignty in a constitutional democracy lies with the citizens. Although

Dennis C. Mueller



Conscience and the Constitution  

NSDL National Science Digital Library

This companion site to the PBS national broadcast December 2000, of "Conscience and the Constitution" examines the historical and moral issues surrounding the decision of a handful of Japanese to refuse to be drafted from their location in an American concentration camp in 1944. The site also looks at the history of the Japanese American Citizens League (JACL), an organization of first generation Japanese-Americans that not only supported the efforts of the US military to apprehend and relocate Japanese citizens, but opposed all efforts of individual Japanese-Americans to challenge the constitutionality of the government's actions. In addition to the thoughtful narration of the history and the controversy it continues to generate, the Website provides access to original documents of the parties involved, including letters and statements from the draft resisters, who eventually served more than two years hard labor, the columns of the journalist who supported their civil disobedience, and public statements and correspondence of the JACL. Some video portions of the broadcast are also available here in RealPlayer.


Ethics and constitutional government.  


The term ethics refers to a set of principles that govern acceptable, proper conduct. Attacks on the Constitution of the United States pose the most serious breach of ethics today. Our country was founded as a republic, not as a democracy. Our Founding Fathers' main concern was to protect citizens from the power of the federal government, so constitutionally, the central government has little or no authority over individual citizens except on federal property. One of the major problems today is the fact that we now have professional politicians. This is due in large part to the lure of financial gain from countless special interest groups. This would change under constitutional law because the federal budget would decrease drastically. Article 1 states that all legislative power is vested in Congress. Congress has only 18 enumerated powers, and almost half of these pertain to defense of the country. Many of our current problems are due to regulatory agencies that have become independent fiefdoms with unconstitutional legislative, as well as executive and judicial, powers. The regulatory agency most relevant to medicine, both clinical care and research, is the FDA. It is now obvious that its basic structure needs to be changed or abolished because its actions are identical to those inherent in authoritarian systems. Constructive change could come from Congress, but it would be most desirable if the Supreme Court would take the lead and reestablish the authority of the Constitution as the Supreme Law of the Land. The FDA's function could be limited to the determination of safety, but preferably its mission would be altered to that of product certification. Defenders of the current system claim that such a drastic change would be too dangerous and their prime example is thalidomide. But it is now known that the market has already solved that problem prior to the government-imposed sanctions. Realistically, market forces and their ramifications, including our legal system, provide the most effective methods of protecting the public from harmful drugs and devices. Fortunately, a model for miracles is available. It is New Zealand, which had become increasingly socialistic after WW II. As a result, they had become noncompetitive, and with the formation of the European Union, they lost their major market exports. In order to survive they made some astounding changes in the mid-1980s. They studied every agency that depended on government funding and transferred much of this work over to the private sector. They turned the remaining agencies into profit-making enterprises. These agencies had cost the government about $1 billion/year. Now, they produce about $1 billion in revenue and taxes. Without question, a return to constitutional government would be an invigorating stimulus to bioengineering research in the future. It would flourish. The eminence of this country did not develop from a strong central government. It is due to its absence, but we are rapidly reaching a point of no return. PMID:18298395

Albright, James A



Graduate Student Association Constitution Constitution of the Graduate Student Association  

E-print Network

of the Undergraduate Student Government Association. The Graduate Student Association, as developed and the University of Memphis in order to enhance intellectual development through faculty/student interactionGraduate Student Association Constitution Constitution of the Graduate Student Association

Dasgupta, Dipankar


The Molecular through Ecological Genetics of Abnormal Abdomen in Drosophila Mercatorum. V. Female Phenotypic Expression on Natural Genetic Backgrounds and in Natural Environments  

PubMed Central

The abnormal abdomen (aa) syndrome in Drosophila mercatorum depends on the presence of R1 inserts in a third or more of the X-linked 28S rDNA genes and the absence of selective underreplication of inserted repeats in polytene tissues that is controlled by an X-linked locus (ur) half a map unit from the rDNA complex. This syndrome affects both life history and morphology in the laboratory. Because abnormal morphologies are rarely encountered in nature, the purpose of this study is to see if the female life history traits are still affected under more natural genetic backgrounds and environmental conditions. Two outbred stocks were extracted from the natural population living near Kamuela, Hawaii: KaaX that has only X chromosomes with ur(aa) alleles, and K+X that has only ur(+) alleles. These two stocks have nonoverlapping distributions of insert proportions, indicating strong disequilibrium between the ur locus and the rDNA complex. The KaaX stock had almost no morphological penetrance of ur(aa), indicating that genetic background is important. KaaX expressed longer female egg-to-adult developmental times, increased early adult female fecundity, and decreased female adult longevity compared with K+X. By bagging natural rots of the cactus Opuntia megacantha near Kamuela, Hawaii, it was shown that egg-to-adult developmental time is slowed down by 0.92 days in females bearing ur(aa) alleles in nature, with no detectable slowdown in ur(aa) males. The bagged rot data also indicate that females bearing ur(aa) alleles have a strong fecundity advantage in nature under some ecological conditions but not others. PMID:8325484

Templeton, A. R.; Hollocher, H.; Johnston, J. S.



Constitution, 5 May 1989.  


This document contains provisions of Cambodia's Constitution of May 5, 1989. Article 7 gives men and women equal rights in marriage and the family, calls for monogamous marriages, and affords social protection to mothers and children. Article 8 guides parent-child relationships. The 14th article defines state property, and the 15th gives citizens full rights to own, use, and inherit land. The use of agricultural and forested land can only be changed with permission. Article 22 assigns educational responsibilities to the state, including free elementary education and a gradual expansion of higher education. Adult literacy classes are also promoted. Article 26 guarantees free medical consultations, and article 27 gives women a 90-day paid maternity leave. Breast-feeding women are also given special privileges. Article 33 guarantees the right to pay equity and to social security benefits. Article 36 grants the freedom to travel, the inviolability of homes, and privacy in correspondence of all types. PMID:12344287



Constitution, 5 October 1988.  


This document contains major provisions of the constitution adopted by Brazil on 5 October 1988. This constitution seeks to promote the welfare of all citizens without discrimination. The equality of all citizens is guaranteed, and the equal rights of women are specifically mentioned. Property rights are also guaranteed and defined. Female inmates are granted the right to remain with their children while breast feeding. Workers are guaranteed a minimum wage, a family allowance for dependents, maternity/paternity leave, specific incentives to protect the labor market for women, retirement benefits, free day care for preschool-age children, pay equity, and equal rights between tenured and sporadically employed workers. Agrarian reform provisions are given, including the authority to expropriate land. Social and economic policies to promote health are called for, and public health services are to be decentralized, to be integrated, and to foster community participation. Pension plan and social assistance provisions are outlined as are duties of the state in regard to education. The amount of money to be dedicated to education is set out, and a national educational plan is called for to achieve such goals as the eradication of illiteracy, the universalization of school attendance, the improvement of instruction, and the provision of vocational training. Specific measures are set out to protect and preserve the environment. Family policy deals with issues of marriage, the definition of a family, divorce, the right to family planning services, and the deterrence of domestic violence. Social protection provisions cover mothers and children, handicapped persons, and protection of minors. Finally, the customs and rights of Indians are protected, with special provisions given to protect land tenure and to protect the rights of Indians in water resource development and prospecting and mining activities. PMID:12344286



Constitutive Interoperability Amit K. Chopra  

E-print Network

]: Interoperability; I.2.11 [Artificial Intelligence]: Distributed artificial intelligence--Multiagent sys- tems of interoperability, constitutive and regulative. Constitutive interoperability takes into account solely the meaning of messages whereas regulative interoperability also takes into consideration mes- sage order, occurrence


Affirmative Duty and Constitutional Tort  

Microsoft Academic Search

The Constitution ordinarily places only negative restrictions on government and does not require affirmative acts to assist individuals. The statutory vehicle for most constitutional tort litigation, 42 U.S.C. section 1983, echoes this constitutional principle. It extends liability to \\

Michael L. Wells; Thomas A. Eaton



Constitutive models in LAME.  

SciTech Connect

The Library of Advanced Materials for Engineering (LAME) provides a common repository for constitutive models that can be used in computational solid mechanics codes. A number of models including both hypoelastic (rate) and hyperelastic (total strain) constitutive forms have been implemented in LAME. The structure and testing of LAME is described in Scherzinger and Hammerand ([3] and [4]). The purpose of the present report is to describe the material models which have already been implemented into LAME. The descriptions are designed to give useful information to both analysts and code developers. Thus far, 33 non-ITAR/non-CRADA protected material models have been incorporated. These include everything from the simple isotropic linear elastic models to a number of elastic-plastic models for metals to models for honeycomb, foams, potting epoxies and rubber. A complete description of each model is outside the scope of the current report. Rather, the aim here is to delineate the properties, state variables, functions, and methods for each model. However, a brief description of some of the constitutive details is provided for a number of the material models. Where appropriate, the SAND reports available for each model have been cited. Many models have state variable aliases for some or all of their state variables. These alias names can be used for outputting desired quantities. The state variable aliases available for results output have been listed in this report. However, not all models use these aliases. For those models, no state variable names are listed. Nevertheless, the number of state variables employed by each model is always given. Currently, there are four possible functions for a material model. This report lists which of these four methods are employed in each material model. As far as analysts are concerned, this information is included only for the awareness purposes. The analyst can take confidence in the fact that model has been properly implemented and the methods necessary for achieving accurate and efficient solutions have been incorporated. The most important method is the getStress function where the actual material model evaluation takes place. Obviously, all material models incorporate this function. The initialize function is included in most material models. The initialize function is called once at the beginning of an analysis and its primary purpose is to initialize the material state variables associated with the model. Many times, there is some information which can be set once per load step. For instance, we may have temperature dependent material properties in an analysis where temperature is prescribed. Instead of setting those parameters at each iteration in a time step, it is much more efficient to set them once per time step at the beginning of the step. These types of load step initializations are performed in the loadStepInit method. The final function used by many models is the pcElasticModuli method which changes the moduli that are to be used by the elastic preconditioner in Adagio. The moduli for the elastic preconditioner are set during the initialization of Adagio. Sometimes, better convergence can be achieved by changing these moduli for the elastic preconditioner. For instance, it typically helps to modify the preconditioner when the material model has temperature dependent moduli. For many material models, it is not necessary to change the values of the moduli that are set initially in the code. Hence, those models do not have pcElasticModuli functions. All four of these methods receive information from the matParams structure as described by Scherzinger and Hammerand.

Hammerand, Daniel Carl; Scherzinger, William Mark



The Constitution Project  

NSDL National Science Digital Library

Recently, The Constitution Project (TCP) started the bipartisan Task Force on Detainee Treatment. The purpose of TCP is to "bring the American people a comprehensive understanding of what is known and what may still be unknown about the past and current treatment of detainees by the U.S. government, as part of the counterterrorism policies of the Obama, Bush, and Clinton administrations." Visitors to their site can learn about their efforts to shed light on these various activities, and it is a good idea to take a quick look over their "Headline News" area to get started. Users should not miss the report "Principles for Government Data Mining", which can be found near the bottom of the homepage. This section is dedicated to looking into the threats to civil liberties posed by government data mining programs and recommends a series of reforms. Along with reading the report here, users can watch a webcast that features a panel of experts discussing the report's findings and future directions.


Natural resources - constitutional law  

SciTech Connect

New England Power Co. reaffirms Congressional authority under the commerce clause to regulate interstate trade in natural resources. The Supreme Court has consistently held that states cannot restrict to their own citizens the benefits of natural resources located within state boundaries. As a result, a state's control over such resources is largely limited to taxing their generation or extraction. New England Power Co. reiterates the Court's adamant stand against economic protectionism, especially when natural resources are concerned. Secondarily, this case establishes that Congressional consent to otherwise impermissible state regulation of interstate commerce must be express; the Court will not infer such consent. 29 references.

Jorgensen, C.L.



Expression of macrophage migration inhibitory factor in human glomerulonephritis  

Microsoft Academic Search

Expression of macrophage migration inhibitory factor in human glomerulonephritis.BackgroundWe have recently demonstrated that macrophage migration inhibitory factor (MIF) plays a pathogenic role in experimental glomerulonephritis (GN). The aim of the current study was to investigate MIF expression in human GN.MethodsMIF expression was examined by in situ hybridization and immunohistochemistry staining in 65 biopsies from a variety of glomerulonephridities.ResultsThere is constitutive

Hui Y Lan; Niansheng Yang; David J Nikolic-Paterson; Xue Q Yu; Wei Mu; Nicole M Isbel; Christine N Metz; Richard Bucala; Robert C Atkins



Explaining constitution-makers’ preferences: the cases of Estonia and the United States  

Microsoft Academic Search

This article is concerned with the effects of the kinds of framers involved in constitution-making on the content of constitutional\\u000a provisions proposed during the drafting process. It tests the hypotheses that predict framers’ constitutional preferences\\u000a on the basis of their institutional position, partisan background and constitutional expertise with two specific cases: the\\u000a Constitutional Assembly of Estonia (1991–1992) and the Federal

Ringa Raudla



Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice.  

PubMed Central

Mice that lack the Nrf2 basic-region leucine-zipper transcription factor are more sensitive than wild-type (WT) animals to the cytotoxic and genotoxic effects of foreign chemicals and oxidants. To determine the basis for the decrease in tolerance of the Nrf2 homozygous null mice to xenobiotics, enzyme assay, Western blotting and gene-specific real-time PCR (TaqMan) have been used to examine the extent to which hepatic expression of GSH-dependent enzymes is influenced by the transcription factor. The amounts of protein and mRNA for class Alpha, Mu and Pi glutathione S-transferases were compared between WT and Nrf2 knockout (KO) mice of both sexes under both constitutive and inducible conditions. Among the class Alpha and class Mu transferases, constitutive expression of Gsta1, Gsta2, Gstm1, Gstm2, Gstm3, Gstm4 and Gstm6 subunits was reduced in the livers of Nrf2 mutant mice to between 3% and 60% of that observed in WT mice. Induction of these subunits by butylated hydroxyanisole (BHA) was more marked in WT female mice than in WT male mice. TaqMan analyses showed the increase in transferase mRNA caused by BHA was attenuated in Nrf2(-/-) mice, with the effect being most apparent in the case of Gsta1, Gstm1 and Gstm3. Amongst class Pi transferase subunits, the constitutive hepatic level of mRNA for Gstp1 and Gstp2 was not substantially affected in the KO mice, but their induction by BHA was dependent on Nrf2; this was more obvious in female mutant mice than in male mice. Nrf2 KO mice exhibited reduced constitutive expression of the glutamate cysteine ligase catalytic subunit, and, to a lesser extent, the expression of glutamate cysteine ligase modifier subunit. Little variation was observed in the levels of glutathione synthase in the different mouse lines. Thus the increased sensitivity of Nrf2(-/-) mice to xenobiotics can be partly attributed to a loss in constitutive expression of multiple GSH-dependent enzymes, which causes a reduction in intrinsic detoxification capacity in the KO animal. These data also indicate that attenuated induction of GSH-dependent enzymes in Nrf2(-/-) mice probably accounts for their failure to adapt to chronic exposure to chemical and oxidative stress. PMID:11991805

Chanas, Simon A; Jiang, Qing; McMahon, Michael; McWalter, Gail K; McLellan, Lesley I; Elcombe, Clifford R; Henderson, Colin J; Wolf, C Roland; Moffat, Graeme J; Itoh, Ken; Yamamoto, Masayuki; Hayes, John D



Constitutional Change: A Case Study.  

ERIC Educational Resources Information Center

Presents a lesson for secondary students which teaches that the U.S. Constitution has changed in a variety of ways and that it has a direct effect upon the lives of citizens. Provides a worksheet and a lecture outline covering three methods of constitutional change and Supreme Court cases such as Dred Scott and Brown vs. Board of Education. (GEA)

Christofferson, Walter D.; Pergande, Donald J.



Microplane constitutive model for porous isotropic rocks  

NASA Astrophysics Data System (ADS)

The paper deals with constitutive modelling of contiguous rock located between rock joints. A fully explicit kinematically constrained microplane-type constitutive model for hardening and softening non-linear triaxial behaviour of isotropic porous rock is developed. The microplane framework, in which the constitutive relation is expressed in terms of stress and strain vectors rather than tensors, makes it possible to model various microstructural physical mechanisms associated with oriented internal surfaces, such as cracking, slip, friction and splitting of a particular orientation. Formulation of the constitutive relation is facilitated by the fact that it is decoupled from the tensorial invariance restrictions, which are satisfied automatically. In its basic features, the present model is similar to the recently developed microplane model M4 for concrete, but there are significant improvements and modifications. They include a realistic simulation of (1) the effects of pore collapse on the volume changes during triaxial loading and on the reduction of frictional strength, (2) recovery of frictional strength during shearing, and (3) the shear-enhanced compaction in triaxial tests, manifested by a deviation from the hydrostatic stress-strain curve. The model is calibrated by optimal fitting of extensive triaxial test data for Salem limestone, and good fits are demonstrated. Although these data do not cover the entire range of behaviour, credence in broad capabilities of the model is lend by its similarity to model M4 for concrete - an artificial rock. The model is intended for large explicit finite-element programs.

Baant, Zdenk P.; Zi, Goangseup



MAR Background Report MAR Background Report: The Revolution in Bahrain  

E-print Network

MAR Background Report MAR Background Report: The Revolution in Bahrain Unrest in Tunisia, Egypt forces. MAR data also reports that social services in Shi'a neighborhoods are inferior to those in Sunni of ethnic groups worldwide #12;MAR Background Report In Bahrain, the freedom of press and expression

Milchberg, Howard


Antisense Suppression of a (1)-d-Cadinene Synthase Gene in Cotton Prevents the Induction of This Defense Response Gene during Bacterial Blight Infection But Not Its Constitutive Expression1(w)  

Microsoft Academic Search

In cotton (Gossypium hirsutum) the enzyme (1)-d-cadinene synthase (CDNS) catalyzes the first committed step in the biosynthesis of cadinane-type sesquiterpenes, such as gossypol, that provide constitutive and inducible protection against pests and diseases. A cotton cDNA clone encoding CDNS (cdn1-C4) was isolated from developing embryos and functionally characterized. Southern analysis showed that CDNS genes belong to a large multigene family,

Belinda J. Townsend; Andrew Poole; Christopher J. Blake; Danny J. Llewellyn


Constitutive modeling of active polymers  

E-print Network

This thesis develops a three-dimensional constitutive model of active polymeric materials, including changes in material volume and properties due to actuation. Active polymers reversibly change shape, volume and/or material ...

Therkelsen, Scott V. (Scott Vincent), 1980-



Constitutive modeling for isotropic materials  

NASA Technical Reports Server (NTRS)

The unified constitutive theories for application to typical isotropic cast nickel base supperalloys used for air-cooled turbine blades were evaluated. The specific modeling aspects evaluated were: uniaxial, monotonic, cyclic, creep, relaxation, multiaxial, notch, and thermomechanical behavior. Further development of the constitutive theories to model thermal history effects, refinement of the material test procedures, evaluation of coating effects, and verification of the models in an alternate material will be accomplished in a follow-on for this base program.

Ramaswamy, V. G.; Vanstone, R. H.; Dame, L. T.; Laflen, J. H.



Politics of the 1945 Constitution:Democratization and Its Impact on Political Institutions in Indonesia  

Microsoft Academic Search

Introduction : Before 1998, no one could think about the amendment of the 1945 Constitution. The 1945 Constitution was a product of nationalist who had hard fought for independence from the Dutch colonization. This historical background made it the symbol of independence of the Indonesian nation. Thus, it has been considered as forbidden to touch contents of the 1945 Constitution

Koichi Kawamura



Phenotypic and histological expression of different genetic backgrounds in interactions between lettuce, wild Lactuca spp., L. sativa × L. serriola hybrids and Bremia lactucae  

Microsoft Academic Search

Phenotypic and histological responses of cultivated lettuce (Lactuca sativa) and wild relatives L. saligna, L.?virosa as well as interspecific crosses derived from L. sativa × L. serriola to two races of Bremia lactucae (CS2, CS9) were investigated. With the exception of L. sativa genotypes, all accessions and hybrids expressed incomplete or complete resistance to both pathogen races, with slight differences

Aleš Lebeda; Michaela Sedlá?ová; James Lynn; David A. C. Pink



The Level of Expression of ?-toxin by Different Strains of Clostridium perfringens is Dependent on Differences in Promoter Structure and Genetic Background  

Microsoft Academic Search

The control of expression of the ?-toxin gene (cpaorplc) ofClostridium perfringenshas been studied in three strains shown to have high (NCTC8237), intermediate (strain 13) and low (NCTC8533) phospholipase C activity in the culture supernatant. The phospholipase C activity was shown to be related tocpamRNA levels. Primer extension studies were performed to locate thecpapromoter regions in strains NCTC8237 and 13. Differences

Helen L. Bullifent; Anne Moir; Milena M. Awad; Paul T. Scott; Julian I. Rood; Richard W. Titball



Medroxyprogesterone Acetate Elevation of Nm23-H1 Metastasis Suppressor Expression in Hormone Receptor - Negative Breast Cancer  

Microsoft Academic Search

Background: Reestablishment of metastasis suppressor gene expression may constitute a therapeutic strategy for high- risk breast cancer patients. We previously showed that medroxyprogesterone acetate (MPA), a progestin that has been tested as treatment for advanced breast cancer, ele- vates expression of the Nm23-H1 metastasis suppressor gene in hormone receptor - negative metastatic human breast carcinoma cell lines in vitro via

Diane Palmieri; Douglas O. Halverson; Christine E. Horak; Massimiliano Salerno; Jennifer Johnson; W. Douglas Figg; Melinda Hollingshead; Stephen Hursting; David Berrigan; Seth M. Steinberg; Maria J. Merino; Patricia S. Steeg


Expression and Functional Roles of Angiopoietin-2 in Skeletal Muscles  

Microsoft Academic Search

BackgroundAngiopoietin-1 (ANGPT1) and angiopoietin-2 (ANGPT2) are angiogenesis factors that modulate endothelial cell differentiation, survival and stability. Recent studies have suggested that skeletal muscle precursor cells constitutively express ANGPT1 and adhere to recombinant ANGPT1 and ANGPT2 proteins. It remains unclear whether or not they also express ANGPT2, or if ANGPT2 regulates the myogenesis program of muscle precursors. In this study, ANGPT2

Mahroo Mofarrahi; Sabah N. A. Hussain



Investigations of Mechanisms of Drug-induced Changes in Gene Expression: W-Methylformamide-induced Changes in Synthesis of the Mr 72,000 Constitutive Heat Shock Protein during Commitment of HL60  

Microsoft Academic Search

HL-60 cells were treated with the differentiating agent iV-methylforma- mide and early changes in gene expression and protein content were investigated. Analysis of protein synthesis had previously shown an early (<12 In fall in the synthesis of M, 70.000 heat shock proteins (F. M. Richards, A. Watson, and J. A. Hickman. Cancer Res., 48: 6715-6720, 1988). The changes have now

Helen M. Beere; Richard I. Morimoto; John A. Hickman



Digital Media Design Students Constitution  

E-print Network

Digital Media Design Students Constitution ARTICLE I: ORGANIZATION'S NAME AND PURPOSE Section 1. Name The name of this organization is Digital Media Design Students (DMDS). Section 2: Purpose A. To promote, enhance and further develop educational and social achievements and interests in digital media. B

Jones, Michelle



E-print Network

CONSTITUTION Article I--NAME The Botany Club Article II--PURPOSE The Botany Club will foster--MEMBERSHIP Membership is open to all students, faculty, and staff that have an interest in Botany. Size is unlimited. We The Botany Club will elect a President, Vice President, and Treasurer once each year during the spring


The Constitution: A Resource Guide.  

ERIC Educational Resources Information Center

Presents a 234-item annotated bibliography of a wide variety of resources for teaching about the Constitution at all grade levels. The materials include: books; computer software; inspirational literature; teaching aids such as letters, memoirs, and diaries; teacher's handbooks; portraits and pictures; music, songbooks, and recordings; and…

Social Studies Review, 1987



The Constitution and the Corporation  

ERIC Educational Resources Information Center

Corporations wielding greater power than many states and some nations make decisions having far greater implications for communities than do the local laws governing those communities. It is speculated that the constitutional framers may have provided checks, balances and constraints for them as they did for government if their potential power had…

Henning, Joel F.



On Background Independence  

E-print Network

This paper concerns what Background Independence itself is (as opposed to some particular physical theory that is background independent). The notions presented mostly arose from a layer-by-layer analysis of the facets of the Problem of Time in Quantum Gravity. Part of this coincides with two relational postulates which are thus identified as classical precursors of two of the facets of the Problem of Time. These are furthemore tied to the forms of each of the GR Hamiltonian and momentum constraints. Other aspects of Background Independence include the algebraic closure of these constraints, expressing physics in terms of beables, foliation independence as implemented by refoliation invariance, the reconstruction of spacetime from space. The final picture is that Background Independence - a philosophically desirable and physically implementable feature for a theory to have - has the facets of the Problem of Time among its consequences. Thus these arise naturally and are problems to be resolved, as opposed to avoided `by making one's physics background-dependent in order not to have these problems'. This serves as a selection criterion that limits the use of a number of model arenas and physical theories.

Edward Anderson



Assessing the language skills of children from culturally and linguistically diverse backgrounds: the expressive vocabulary performance of Singaporean English-Mandarin bilingual pre-schoolers.  


Standardized language assessments such as the Clinical Evaluation of Language Fundamentals Pre-school 2 United Kingdom (CELF Preschool 2 UK) are often used in speech-language pathology clinics to determine if a child is at risk of language difficulties. Many of these assessments are designed and standardized for use with monolingual Standard English-speaking children. It is thus recommended that these assessments should only be used with the populations they were designed for; if not test bias might result. However, such tests are still selected and used in the clinics of many multicultural and multilinguistic communities (e.g., Singapore). This research aimed to explore the performance of 79 Singaporean English-Mandarin pre-school children on the Expressive Vocabulary (EV) sub-test of the CELF Preschool 2 UK and to determine if their performance on the EV sub-test accurately reflected their language abilities by comparing their performance on a local screening language assessment tool, the Singapore English Action Picture Test (SEAPT). Results showed that local children performed poorly as compared to their UK counterparts. Two plausible reasons for the findings are: (1) the sub-test elicited only a single measure in English which ignored the language abilities of these bilingual children in their second language; and (2) the presence of culturally and linguistically biased test items. PMID:22335605

Teoh, Wei Qin; Brebner, Chris; McCormack, Paul



Judicial Illumination of the Constitutional \\  

Microsoft Academic Search

Police brutality is one of the most serious and enduring human rights violations in the United States today. One means by which victims may seek redress is under 42 U.S.C. 1983, which provides a civil cause of action against state actors who deprive individuals of their constitutional rights. This Note examines 1983 litigation brought by post-arrest, pretrial detainees alleging the

Eamonn OHagan



Importance of genetic background for risk of relapse shown in altered prefrontal cortex gene expression during abstinence following chronic alcohol intoxication  

PubMed Central

Alcoholism is a relapsing disorder associated with excessive consumption after periods of abstinence. Neuroadaptations in brain structure, plasticity and gene expression occur with chronic intoxication but are poorly characterized. Here we report identification of pathways altered during abstinence in prefrontal cortex, a brain region associated with cognitive dysfunction and damage in alcoholics. To determine the influence of genetic differences, an animal model was employed with widely divergent responses to alcohol withdrawal, the Withdrawal Seizure-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) lines. Mice were chronically exposed to highly intoxicating concentrations of ethanol and withdrawn, then left abstinent for 21 days. Transcriptional profiling by microarray analyses identified a total of 562 genes as significantly altered during abstinence. Hierarchical cluster analysis revealed that the transcriptional response correlated with genotype/withdrawal phenotype rather than sex. Gene Ontology category overrepresentation analysis identified thyroid hormone metabolism, glutathione metabolism, axon guidance and DNA damage response as targeted classes of genes in low response WSR mice, with acetylation and histone deacetylase complex as highly dimorphic between WSR and WSP mice. Confirmation studies in WSR mice revealed both increased neurotoxicity by histopathologic examination and elevated T3 levels. Most importantly, relapse drinking was reduced by inhibition of thyroid hormone synthesis in dependent WSR mice compared to controls. These findings provide in vivo physiological and behavioral validation of the pathways identified. Combined, these results indicate a fundamentally distinct neuroadaptive response during abstinence in mice genetically selected for divergent withdrawal severity. Identification of pathways altered in abstinence may aid development of novel therapeutics for targeted treatment of relapse in abstinent alcoholics. PMID:21081154

Hashimoto, Joel G.; Forquer, Melissa R.; Tanchuck, Michelle A.; Finn, Deborah A.; Wiren, Kristine M.



Non-coplanar polychlorinated biphenyls (PCBs) are direct agonists for the human pregnane-X receptor and constitutive androstane receptor, and activate target gene expression in a tissue-specific manner  

SciTech Connect

The polychlorinated biphenyl group possesses high environmental persistence, leading to bioaccumulation and a number of adverse effects in mammals. Whilst coplanar PCBs elicit their toxic effects through agonism of the aryl hydrocarbon receptor; however, non-coplanar PCBs are not ligands for AhR, but may be ligands for members of the nuclear receptor family of proteins. To better understand the biological actions of non-coplanar PCBs, we have undertaken a systematic analysis of their ability to activate PXR and CAR-mediated effects. Cells were exposed to a range of non-coplanar PCBs (99, 138, 153, 180 and 194), or the coplanar PCB77: Direct activation of PXR and CAR was measured using a mammalian receptor activation assay in human liver cells, with rifampicin and CITCO used as positive controls ligands for PXR and CAR, respectively; activation of target gene expression was examined using reporter gene plasmids for CYP3A4 and MDR1 transfected into liver, intestine and lung cell lines. Several of the non-coplanar PCBs directly activated PXR and CAR, whilst the coplanar PCB77 did not. Non-coplanar PCBs were also able to activate PXR/CAR target gene expression in a substitution- and tissue-specific manner. Non-coplanar PCBs act as direct activators for the nuclear receptors PXR and CAR, and are able to elicit transcriptional activation of target genes in a substitution- and tissue-dependent manner. Chronic activation of PXR/CAR is linked to adverse effects and must be included in any risk assessment of PCBs. -- Highlights: ? Several Non-coplanar PCBs are able to directly activate both PXR and CAR in vitro. ? PCB153 is the most potent direct activator of PXR and CAR nuclear receptors. ? Non-coplanar PCB activation of CYP3A4/MDR1 reporter genes is structure-dependent. ? Non-coplanar PCB activate CYP3A4/MDR1 reporter genes in a tissue-dependent. ? PCB153 is the most potent activator of PXR/CAR target gene in all tissues.

Al-Salman, Fadheela; Plant, Nick, E-mail:



Constitutive Expression of Inter-?-inhibitor (I?I) Family Proteins and Tumor Necrosis Factor-stimulated Gene-6 (TSG-6) by Human Amniotic Membrane Epithelial and Stromal Cells Supporting Formation of the Heavy Chain-Hyaluronan (HC-HA) Complex*  

PubMed Central

Recently, we reported HC-HA, a covalent complex formed between heavy chains (HCs) of inter-?-inhibitor (I?I) and hyaluronan (HA) by the catalytic action of tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6), is responsible for human amniotic membrane (AM) anti-inflammatory, anti-scarring, and anti-angiogenic actions. At the present time, the only well characterized source of I?I is serum being produced by the liver. This study showed that AM epithelial and stromal cells and stromal matrix all stained positively for HA, HC 1, 2, and 3, bikunin, and TSG-6. TSG-6 mRNA and protein were constitutively expressed by cultured AM epithelial and stromal cells without being up-regulated by TNF. In serum-free conditions, these cells expressed I?I, leading to the formation of HC-HA complex that contained both HC1 and HC2. In contrast, only HC1 was found in the HC-HA complex purified from AM. Local production of I?I, the HC-TSG-6 intermediate complex, and HC-HA were abolished when cells were treated with siRNA to HC1, HC2, bikunin (all of which impair the biosynthesis of I?I), or TSG-6 but not to HC3. Collectively, these results indicate that AM is another tissue in addition to the liver to constitutively produce I?I and that the HC-HA complex made by this tissue is different from that found at inflammatory sites (e.g. in asthma and arthritis) and in the matrix of the cumulus oocyte complex. PMID:22351758

Zhang, Suzhen; He, Hua; Day, Anthony J.; Tseng, Scheffer C. G.



Cloning and functional characterization of an Arabidopsis nitrate transporter gene that encodes a constitutive component of low-affinity uptake.  

PubMed Central

The Arabidopsis CHL1 (AtNRT1) gene encodes an inducible component of low-affinity nitrate uptake, which necessitates a "two-component" model to account for the constitutive low-affinity uptake observed in physiological studies. Here, we report the cloning and characterization of a CHL1 homolog, AtNRT1:2 (originally named NTL1), with data to indicate that this gene encodes a constitutive component of low-affinity nitrate uptake. Transgenic plants expressing antisense AtNRT1:2 exhibited reduced nitrate-induced membrane depolarization and nitrate uptake activities in assays with 10 mM nitrate. Furthermore, transgenic plants expressing antisense AtNRT1:2 in the chl1-5 background exhibited an enhanced resistance to chlorate (7 mM as opposed to 2 mM for the chl1-5 mutant). Kinetic analysis of AtNRT1:2-injected Xenopus oocytes yielded a K(m) for nitrate of approximately 5.9 mM. In contrast to CHL1, AtNRT1:2 was constitutively expressed before and after nitrate exposure (it was repressed transiently only when the level of CHL1 mRNA started to increase significantly), and its mRNA was found primarily in root hairs and the epidermis in both young (root tips) and mature regions of roots. We conclude that low-affinity systems of nitrate uptake, like high-affinity systems, are composed of inducible and constitutive components and that with their distinct functions, they are part of an elaborate nitrate uptake network in Arabidopsis. PMID:10449574

Huang, N C; Liu, K H; Lo, H J; Tsay, Y F



Unborn children as constitutional persons.  


In Roe v. Wade, the state of Texas argued that "the fetus is a 'person' within the language and meaning of the Fourteenth Amendment." To which Justice Harry Blackmun responded, "If this suggestion of personhood is established, the appellant's case, of course, collapses, for the fetus' right to life would then be guaranteed specifically by the Amendment." However, Justice Blackmun then came to the conclusion "that the word 'person,' as used in the Fourteenth Amendment, does not include the unborn." In this article, it is argued that unborn children are indeed "persons" within the language and meaning of the Fourteenth and Fifth Amendments. As there is no constitutional text explicitly holding unborn children to be, or not to be, "persons," this argument will be based on the "historical understanding and practice, the structure of the Constitution, and thejurisprudence of [the Supreme] Court." Specifically, it is argued that the Constitution does not confer upon the federal government a specifically enumerated power to grant or deny "personhood" under the Fourteenth Amendment. Rather, the power to recognize or deny unborn children as the holders of rights and duties has been historically exercised by the states. The Roe opinion and other Supreme Court cases implicitly recognize this function of state sovereignty. The states did exercise this power and held unborn children to be persons under the property, tort, and criminal law of the several states at the time Roe was decided. As an effect of the unanimity of the states in holding unborn children to be persons under criminal, tort, and property law, the text of the Equal Protection Clause of the Fourteenth Amendment compels federal protection of unborn persons. Furthermore, to the extent Justice Blackmun examined the substantive law in these disciplines, his findings are clearly erroneous and as a whole amount to judicial error. Moreover, as a matter of procedure, according to the due process standards recognized in Fifth Amendment jurisprudence of the Supreme Court, Roe v. Wade should be held null and void as to the rights and interests of unborn persons. PMID:20443281

Roden, Gregory J



Written Constitution or None: Which Works Better?  

ERIC Educational Resources Information Center

Explores the differences between the U.S. Constitution and British constitutional law. Specifically examines the concept of the U.S. Bill of Rights in relation to the United Kingdom common law doctrine of parliamentary sovereignty. (BSR)

Cowen, Zelman



75 FR 57835 - Constitution Day and Citizenship Day, Constitution Week, 2010  

Federal Register 2010, 2011, 2012, 2013

...Day and Citizenship Day, Constitution Week, 2010 Proclamation 8563--National POW...Day and Citizenship Day, Constitution Week, 2010 By the President of the United States...Citizenship Day, and during Constitution Week, we commemorate the legacy passed...



Nongeometric fluxes as supergravity backgrounds  

SciTech Connect

We consider examples of D=4 string theory vacua which, although globally nongeometric, admit a local description in terms of D=10 supergravity backgrounds. We analyze such backgrounds and find that the supersymmetry spinors vary nontrivially along the internal manifold, reproducing the interpolating supergravity solutions found by Frey and Grana. Finally, we propose a simple, local expression for nongeometric fluxes in terms of the internal spinors of the compactification.

Marchesano, Fernando [ASC, Ludwig-Maximilians-Universitaet, Theresienstrasse 37, 80333 Munich (Germany); Schulgin, Waldemar [Max Planck Institut fuer Physik, Foehringer Ring 6, 80805 Munich (Germany)



A Darwinist View of the Living Constitution  

Microsoft Academic Search

The metaphor of a “living” Constitution imports terms from biology into law and, in the process, relies on biology for its meaning. A proper understanding of biology is therefore central to understanding the idea of “living” constitutionalism. Yet despite its rampant use by both opponents and proponents of living constitutionalism, and despite the current fervent debate over whether biology can

Scott Dodson



Notch Intracellular Domain Expression in Various Skin Fibroproliferative Diseases  

PubMed Central

Background The effects of the Notch signaling pathway in fibroproliferative skin diseases have not been fully elucidated. Objective The aim of this study was to investigate the expression of activated Notch signaling molecules in various skin fibroproliferative diseases. Methods Immunohistochemical analysis of Notch intracellular domain (NICD) expression in keloid, hypertrophic scar, morphea, dermatofibroma, and normal control skin specimens was performed, and the clinical characteristics of patients with various skin fibroproliferative diseases were analyzed. Results NICD was highly expressed in fibroblasts of keloids and moderately to highly expressed in hypertrophic scars and dermatofibromas, whereas low or no expression was detected in the fibroblasts of normal skin specimens and morpheas. NICD was constitutively expressed in keratinocytes, endothelial cells, and immune cells in normal skin specimens. Conclusion NICD was significantly expressed in human fibroproliferative skin disorders, especially keloids, suggesting that an activated Notch signaling pathway is involved in the pathogenesis of skin fibrosis. PMID:24966632

Kim, Jung-Eun; Lee, Joo-Hyun; Jeong, Kwan-Ho; Kim, Gyong Moon



Constitutional Amendment A: Prohibit Property Taxes for School Funding. Issue Memorandum 98-13.  

ERIC Educational Resources Information Center

This issue memorandum describes Constitutional Amendment A, an initiative in South Dakota that, if approved, would prohibit taxation of real property for school purposes. The report provides background information on Constitutional Amendment A, which reads as follows: "The legislature shall make such provision by general taxation as with the…

Becker, David


Constitutive expression of the machinery for programmed cell death  

Microsoft Academic Search

In the presence of cycloheximide (CHX) to inhibit protein synthesis, a high concentration of stau- rosporine (STS) induces almost all cells in explant cul- tures of 8\\/8 types of newborn mouse organs and 3\\/3 types of adult mouse organs to die with the characteris- tic features of apoptosis. Eggs and blastomeres also die in this way when treated with STS

M. Weil; M. D. Jacobson; H. S. R. Coles; T. J. Davies; R. L. Gardner; K. D. Raft; M. C. Raft



Expression of B7-H1 in Inflammatory Renal Tubular Epithelial Cells  

Microsoft Academic Search

Background: Renal tubular epithelial cells (TECs) function as antigen-presenting cells (APCs) as they constitutively express MHC-II molecules and have the capacity to present peptide antigen to T cells. Nevertheless, co-stimulatory signals provided by TECs for regulating T cell activation have not been fully characterized. We therefore investigated the expression of B7-H1, a member of the B7 superfamily, on TECs under

Yongwen Chen; Jingbo Zhang; Jingyi Li; Liyun Zou; Tingting Zhao; Yan Tang; Yuzhang Wu



Constitutive relations associated with the Mott-Smith distribution function  

USGS Publications Warehouse

It is shown that the distribution function assumed by Mott-Smith determines a unique relation between heat flux, stress, and fluid velocity given by q = (3/2)??u, i.e., it provides a constitutive relation for heat flux, and it also determines a simple expression for this ratio of third-order central moments Q = . These expressions allow the equation of transfer for c x2 to be cast in a form that yields a nonlinear constitutive relation for stress. The results obtained from the Mott-Smith ansatz are compared with the theory of Baganoff and Nathenson and results from a numerical solution of the Boltzmann equation for shock-wave structure obtained by Hicks and Yen.

Nathenson, M.; Baganoff, D.



Covariant constitutive relations and relativistic inhomogeneous plasmas  

SciTech Connect

The notion of a 2-point susceptibility kernel used to describe linear electromagnetic responses of dispersive continuous media in nonrelativistic phenomena is generalized to accommodate the constraints required of a causal formulation in spacetimes with background gravitational fields. In particular the concepts of spatial material inhomogeneity and temporal nonstationarity are formulated within a fully covariant spacetime framework. This framework is illustrated by recasting the Maxwell-Vlasov equations for a collisionless plasma in a form that exposes a 2-point electromagnetic susceptibility kernel in spacetime. This permits the establishment of a perturbative scheme for nonstationary inhomogeneous plasma configurations. Explicit formulae for the perturbed kernel are derived in both the presence and absence of gravitation using the general solution to the relativistic equations of motion of the plasma constituents. In the absence of gravitation this permits an analysis of collisionless damping in terms of a system of integral equations that reduce to standard Landau damping of Langmuir modes when the perturbation refers to a homogeneous stationary plasma configuration. It is concluded that constitutive modeling in terms of a 2-point susceptibility kernel in a covariant spacetime framework offers a natural extension of standard nonrelativistic descriptions of simple media and that its use for describing linear responses of more general dispersive media has wide applicability in relativistic plasma modeling.

Gratus, J.; Tucker, R. W. [Physics Department, Lancaster University, Lancaster, LA1 4YB (United Kingdom) and Cockcroft Institute, Daresbury Laboratory, Daresbury Science and Innovation Campus, Keckwick Lane, Daresbury, Warrington, Cheshire WA4 4AD (United Kingdom)



Classification of Sasang constitutional body types using immunostimulatory activities of constitution-specific herbal extracts in human primary immune cells.  


Sasang is a Korean traditional constitutional medicine in which individuals are classified into four constitutional types: Taeyangin, Soeumin, Taeumin, and Soyangin. However, the classification of each constitution is empirical and not scientific, and so it is difficult to consistently classify patients into these four constitutional types. Acanthopanacis cortex (AC; Taeyangin), Rehmanniae radix (RR; Soyangin), Ephedra herba (EH; Taeumin), and White ginseng (WG; Soeumin) are herbal medicines that are used to treat and prevent diseases associated with these four constitutions. Therefore, AC, RR, EH, and WG extracts (ACE, RRE, EHE, and WGE) were used as reference extracts to determine constitutional differences in the immunostimulatory activities of primary immune cells isolated from the blood of 15 volunteers. Cellular proliferation, nitric oxide (NO), tumor necrosis factor-? (TNF-?) protein production, TNF-? and interleukin-6, and inducible NO synthase mRNA expression were measured as the immunostimulatory parameters. The increase in cell proliferation of V2, V3, V8, V11, and V12 was highest in EHE-treated lymphocytes among the ACE-, RRE-, EHE- or WGE-treated lymphocytes, and increase in cellular proliferation of V4, V7, V13, V14, and V15 in RRE-treated lymphocytes was significantly better than the other three medicines. The cell proliferation of V1, V5, V6, V9, and V10 responded best to WGE among the four extracts. Results of cell proliferation and other immunostimulatory parameters showed similar trends in regard to individual differences. These extracts may be useful as reference extracts in the development of a rapid and dependable individual lymphocyte- or macrophage-based assay that aids in the Sasang constitutional classification. PMID:22870991

Choi, Jae-Ho; Chung, Mi Ja; Oh, Deog-Hwan



Constitutive models for impacted morsellised cortico-cancellous bone  

Microsoft Academic Search

Constitutive models are developed, based on the results of confined compression testing, to describe the visco-elastic, and non-linear elasto-plastic behaviour of morsellised cortico-cancellous bone (MCB). It is found that the elastic modulus, E of MCB can be expressed as a linear function of the applied pressure, p. E varied from 3 to 30N\\/mm2 for pressures up to 1N\\/mm2. The visco-elastic

Andrew Phillips; Pankaj Pankaj; Fraser May; Kenneth Taylor; Colin Howie; Asif Usmani



The constitution of cometary nuclei  

NASA Technical Reports Server (NTRS)

The nongravitational term in the expression for the total force acting on a comet is calculated, and an upper limit is obtained for the product of the radial nongravitational term times the radius times the square root of the albedo. This condition is satisfied for ten periodic comets with q no greater than 1.5 AU, and the activity of these comets is consistent with control by H2O ice. Some of the comets must be spotty to account for their low albedo values. The effect of cosmic rays on comets, leading to frosting of their surface, is discussed.

Whipple, F. L.



The E92K Melanocortin 1 Receptor Mutant Induces cAMP Production and Arrestin Recruitment but Not ERK Activity Indicating Biased Constitutive Signaling  

PubMed Central

Background The melanocortin 1 receptor (MC1R) constitutes a key regulator of melanism. Consequently, many naturally-occurring MC1R mutations are associated with a change in color. An example is the Glu-to-Lys substitution found at position II:20/2.60 in the top of transmembrane helix II which has been identified in melanic mice and several other species. This mutation induces a pronounced increase in MC1R constitutive activity suggesting a link between constitutive activity and melanism which is corroborated by the attenuation of ?-melanocyte stimulating hormone (?MSH) induced activation. However, the mechanism by which the mutation induces constitutive activity is currently not known. Methodology/Principal Findings Here we characterize the constitutive activity, cell surface expression and internalization of the mouse mutant, Mc1r E92K. As previously reported, only positively charged residues at position II:20/2.60 induced an increase in constitutive activity as measured by cAMP accumulation and CREB activation. Furthermore, the mutation induced a constitutive recruitment of ?-arrestin. This phenomenon is only observed in MC1R, however, as the equivalent mutations in MC2-5R had no effect on receptor signaling. Interestingly, the mutation did not induce constitutive ERK1/2 phosphorylation or increase the internalization rate indicating the constitutive activity to be biased. Finally, to identify regions of importance for the increased constitutive activity of Mc1r E92K, we employed a chimeric approach and identified G102 and L110 in the extracellular loop 1 to be selectively important for the constitutive activity as this, but not ?MSH-mediated activation, was abolished upon Ala substitution. Conclusions/Significance It is concluded that the E92K mutation induces an active conformation distinct from that induced by ?MSH and that the extracellular loop 1 is involved in maintaining this conformational state. In turn, the results suggest that in MC1R, which lacks an extracellular loop 2, the first extracellular loop may play a more prominent role during receptor activation than in general. PMID:21931793

Benned-Jensen, Tau; Mokrosinski, Jacek; Rosenkilde, Mette M.



FindLaw Constitutional Law Center  

NSDL National Science Digital Library

This offering from FindLaw (last discussed in the January 15, 1999 Scout Report) focuses on the US Constitution. The site is composed of two primary sections. The first offers an annotated Constitution, commentary on selected topics with links to key sections of the Constitution or The Federalist Papers, a history of the Constitution, and brief biographies of notable "Founding Fathers" and delegates to the Constitutional Convention. The second section highlights the Third Branch of government, with a history of the Supreme Court, landmark decisions regarding civil rights with the full opinions, a summary and analysis of the criminal law and procedure decisions of the October 1998 Supreme Court Term, and several links for current Supreme Court news and information. Both sections also feature a search engine. Additional resources at the site include a Town Hall section that explores Hot Topics (currently flag burning) and message boards on a wide variety of Constitutional issues.



Aberrant Expression and Mutation-Inducing Activity of AID in Human Lung Cancer  

Microsoft Academic Search

Background  Activation-induced cytidine deaminase (AID) is expressed in B lymphocytes and triggers antibody diversification. Recent reports\\u000a have indicated that the constitutive expression of AID in mice causes not only lymphomas, but also cancers of some organs\\u000a including the lung, prompting us to investigate the expression and effect of AID on human lung cancer.\\u000a \\u000a \\u000a \\u000a \\u000a Materials and Methods  We examined AID mRNA expression in

Kazuya Shinmura; Hisaki Igarashi; Masanori Goto; Hong Tao; Hidetaka Yamada; Shun Matsuura; Mari Tajima; Tomonari Matsuda; Arito Yamane; Kazuhito Funai; Masayuki Tanahashi; Hiroshi Niwa; Hiroshi Ogawa; Haruhiko Sugimura



Who, Where and When: The History & Constitution  

E-print Network

51 Science (1893-2000) 51 Social Sciences 52 Veterinary Medicine 53 #12;History and Constitution 6Who, Where and When: The History & Constitution of the University of Glasgow #12;#12;Compiled and Lesley Richmond, 2001 Published by University of Glasgow, G12 8QQ Typeset by Media Services, University

Mottram, Nigel


Naked Land Transfers and American Constitutional Development  

Microsoft Academic Search

The constitutional prohibition on naked land transfers, laws granting to B property that belonged to A, played a far greater role in American constitutional development than is generally realized. The Marshall and Taney Courts heard numerous cases in which government officials were accused of expropriating private property, typically by legislative oversight rather than by deliberate intent. When resolving these cases,

Mark A. Graber



World Studies through a Comparative Constitutional Prism.  

ERIC Educational Resources Information Center

Emphasizes the importance of understanding the development of democracy around the world by comparative study of constitutions. Uses the development of the Japanese constitution after World War II as a case study. Describes the work of the team appointed by General Douglas MacArthur and the significance of the clause guaranteeing equal rights for…

Robinson, Donald



The Meaning of Religion: A Constitutional Perspective.  

ERIC Educational Resources Information Center

The problems of formulating a legal definition of religion as used in the U.S. Constitution may be traced through the Supreme Court's interpretation of the word. According to the U.S. Constitution, religious tests cannot be required for any office or public trust under the central government. The Bill of Rights states that the national government…

Lilly, Edward R.


The Intelligence Function And the Constitution  

Microsoft Academic Search

Strategic intelligence is requisite to national security. But fitting an intelligence function, with its ancillary covert action and counterintelligence activities, into the U.S. constitutional framework is an enduring and perhaps unsolvable problem. Conduct of the government's clandestine operations overseas is an executive function requiring extraordinary secrecy. Yet the Constitution requires that the president share with Congress decisions about intelligence policy,

Harry Howe Ransom



Contragate, Covert Action, and the Constitution.  

ERIC Educational Resources Information Center

The "Iran-Contragate" hearings were indicative of serious constitutional crisis. Analyzes and disputes following three defenses used by President Reagan to justify his actions in affair: he did not know or approve; it was not a violation of law; and his authority over foreign affairs is given in war powers clause of the Constitution--Congress…

Ratner, Michael



Ratification of European Union Constitution Hits a Roadblock  

NSDL National Science Digital Library

This past week, the ratification of the European Union's constitution met with some resistance as voters in both the Netherlands and France both voted "no" to approving the document. Some analysts have suggested that this rejection of the constitution is indicative of the fact that there is an increasing unease about the process of unification more generally in various countries across the continent. Pundits and analysts also agreed that there was no one defining reason why voters rejected the constitution. In France, those voting "no" seemed to range from those on the far right to the far left, and interestingly enough, included a large proportion of young people. It is worth noting that a number of opponents (particularly those on the political left) of ratification continue to make the claim that the constitution promotes a type of unencumbered capitalism that is akin to the type of socioeconomic mode of governance practiced in the United Kingdom and the United States. It will be sometime before the full impact of this recent development is understood, but it is certainly a story that is worthy of a closer look. The first link will take users to coverage of the ongoing EU Constitution process offered by the Voice of America from this past Monday. The second link will take visitors to a fine news piece from the Guardian that provides some insight into the recent rejection of the EU Constitution by Dutch voters. The third link leads to an article from Deutsche Welle that discusses the implications of these latest developments in Europe. The fourth link leads to a very thorough set of analyses of the ratification process as reported by National Public Radio. From this main page, visitors can also learn about the history of the EU Constitution and read some essential background material about the document. The fifth link, offered by the BBC, provides a quick introduction to the Constitution, along with providing a link to the full text of the document. The final link leads to the homepage of the Historical Archives of the European Union, where visitors can review primary documents related to the EU's development and also learn about utilizing their various collections.


How Does Astronomy Constitute A Learning Community?  

NASA Astrophysics Data System (ADS)

This study was conducted in Turkey within an interdisciplinary project called "From a windowless home to a skyscraper: Let's build a home". It was realized through collaboration between a public university and a private high school. Researchers from Physics Education Department and volunteer teachers from high school, each studying on a different discipline, and volunteer high school students, all from an urban area of the country, conducted the project in a rural small town with resident secondary school students. It was implemented on the basis of history, through the use of different fields such as science, mathematics, geography, art, handcraft, architecture, engineering and astronomy in August 2008. The purpose of this study was to present the effect of the astronomical activities involved in the project. These implementations constructed a scientific and social base for the framework of astronomical activities of IYA2009, including building an amateur observatory. Since today's people are not so much acquainted with the issues of space and astronomy as much as the people of Antiquity, we attached special importance to the efforts in this field. The project, proceeded by a preparatory and informative period, involved night sky observation, initially with naked eye, followed by observation through telescope. Not only the students but also countless people, old or young, participated in our work in the field of astronomy. It provided a chance for all the people participating in or connected to the project to discover the sky. Astronomical activities aroused curiosity among students and the community and made a difference by inducing an awareness of the sky. The participants of the study had completely different social and cultural backgrounds, and this study removed all these differences bringing them together under the overarching astronomical and historical aspect. Moreover the community revealed all the characteristics that constitute a learning community.

Dogan, Yasemin; Sengul, R.; Unat, O.; Aknil, A.; Gurel, Z.



76 FR 58705 - Constitution Day and Citizenship Day, Constitution Week, 2011  

Federal Register 2010, 2011, 2012, 2013

...Constitution Day and Citizenship Day, Constitution Week, 2011 Proclamation 8715--National Employer Support of the Guard and Reserve Week, 2011 Proclamation 8716--National Farm Safety and Health Week, 2011 Proclamation 8717--National...



Documents from the Continental Congress and the Constitutional Convention  

NSDL National Science Digital Library

The Library of Congress American Memory Project has been producing high-quality digital collections for a decade, and one of their first projects has recently been updated and is worthy of a second (or first) look. This particular collection brings together a number of documents, including dozens of broadsides related to the work of the Continental Congress, dating from 1774 to 1788. The majority of these items contain extracts of the journals of Congress, resolutions, proclamations, treaties, and other congressional proceedings. Other documents in the collection include early printed versions of the United States Constitution and the Declaration of Independence. Those persons who are seeking a bit more background information will want to take a look at two timelines that cover related events from the 1764 Sugar Act to the official ratification of the Constitution in 1788. Finally, the site also contains a nice essay titled âÂÂTo Form a More Perfect Union.âÂÂ.


Constitutive equations for meeting elevated-temperature-design needs  

SciTech Connect

Constitutive equations for representing the inelastic behavior of structural alloys at temperatures in the creep regime are discussed from the viewpoint of advances made over the past decade. An emphasis is placed on the progress that has been made in meeting the needs of the program whose design process is based in part on a design-by-inelastic-analysis approach. In particular, the constitutive equations that have been put into place for current use in design analyses are discussed along with some material behavior background information. Equations representing short-term plastic and long-term creep behaviors are considered. Trends towards establishing improved equations for use in the future are also described. Progress relating to fundamentals of continuum mechanics, physical modeling, phenomenological modeling, and implementation is addressed.

Pugh, C.E.; Robinson, D.N.



Closing in on the constitution of consciousness  

PubMed Central

The science of consciousness is a nascent and thriving field of research that is founded on identifying the minimally sufficient neural correlates of consciousness. However, I have argued that it is the neural constitution of consciousness that science seeks to understand and that there are no evident strategies for distinguishing the correlates and constitution of (phenomenal) consciousness. Here I review this correlation/constitution distinction problem and challenge the existing foundations of consciousness science. I present the main analyses from a longer paper in press on this issue, focusing on recording, inhibition, stimulation, and combined inhibition/stimulation strategies, including proposal of the Jenga analogy to illustrate why identifying the minimally sufficient neural correlates of consciousness should not be considered the ultimate target of consciousness science. Thereafter I suggest that while combined inhibition and stimulation strategies might identify some constitutive neural activities—indeed minimally sufficient constitutive neural activities—such strategies fail to identify the whole neural constitution of consciousness and thus the correlation/constitution distinction problem is not fully solved. Various clarifications, potential objections and related scientific and philosophical issues are also discussed and I conclude by proposing new foundational claims for consciousness science.

Miller, Steven M.




EPA Science Inventory

Pseudomonas cepacia G4 expresses a unique toluene ortho-monooxygenase (Tom) that enables it to degrade toluene and trichloroethylene (TCE). ransposon mutants of G4 have been isolated that constitutively express Tom. wo fixed-film bioreactor designs were investigated for the explo...


Constitutively active UVR8 photoreceptor variant in Arabidopsis.  


Arabidopsis thaliana UV RESISTANCE LOCUS 8 (UVR8) is a UV-B photoreceptor that initiates photomorphogenic responses underlying acclimation and UV-B tolerance in plants. UVR8 is a homodimer in its ground state, and UV-B exposure results in its instantaneous monomerization followed by interaction with CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1), a major factor in UV-B signaling. UV-B photoreception by UVR8 is based on intrinsic tryptophan aromatic amino acid residues, with tryptophan-285 as the main chromophore. We generated transgenic plants expressing UVR8 with a single amino acid change of tryptophan-285 to alanine. UVR8(W285A) appears monomeric and shows UV-B-independent interaction with COP1. Phenotypically, the plants expressing UVR8(W285A) exhibit constitutive photomorphogenesis associated with constitutive activation of target genes, elevated levels of anthocyanins, and enhanced, acclimation-independent UV-B tolerance. Moreover, we have identified COP1, REPRESSOR OF UV-B PHOTOMORPHOGENESIS 1 and 2 (RUP1 and RUP2), and the SUPPRESSOR OF PHYA-105 (SPA) family as proteins copurifying with UVR8(W285A). Whereas COP1, RUP1, and RUP2 are known to directly interact with UVR8, we show that SPA1 interacts with UVR8 indirectly through COP1. We conclude that UVR8(W285A) is a constitutively active UVR8 photoreceptor variant in Arabidopsis, as is consistent with the crucial importance of monomer formation and COP1 binding for UVR8 activity. PMID:24277841

Heijde, Marc; Binkert, Melanie; Yin, Ruohe; Ares-Orpel, Florence; Rizzini, Luca; Van De Slijke, Eveline; Persiau, Geert; Nolf, Jonah; Gevaert, Kris; De Jaeger, Geert; Ulm, Roman



FOXO1 Binds to the TAU5 Motif and Inhibits Constitutively Active Androgen Receptor Splice Variants  

PubMed Central

BACKGROUND Aberrant activation of the androgen receptor (AR) is a major factor highly relevant to castration-resistant progression of prostate cancer (PCa). FOXO1, a key downstream effector of PTEN, inhibits androgen-independent activation of the AR. However, the underlying mechanism remains elusive. METHODS The inhibitory effect of FOXO1 on full-length and constitutively active splice variants of the AR was examined by luciferase reporter assays and real-time reverse transcription polymerase chain reaction (RT-qPCR). In vitro protein binding assays and western blot analyses were used to determine the regions in FOXO1 and AR responsible for their interaction. RESULTS We found that a putative transcription repression domain in the NH2-terminus of FOXO1 is dispensable for FOXO1 inhibition of the AR. In vitro protein binding assays showed that FOXO1 binds to the transcription activation unit 5 (TAU5) motif in the AR NH2-terminal domain (NTD), a region required for recruitment of p160 activators including SRC-1. Ectopic expression of SRC-1 augmented transcriptional activity of some, but not all AR splice variants examined. Forced expression of FOXO1 blocked the effect of SRC-1 on AR variants’ transcriptional activity by decreasing the binding of SRC-1 to the AR NTD. Ectopic expression of FOXO1 inhibited expression of endogenous genes activated primarily by alternatively spliced AR variants in human castration-resistant PCa 22Rv1 cells. CONCLUSIONS FOXO1 binds to the TAU5 motif in the AR NTD and inhibits ligand-independent activation of AR splice variants, suggesting the PTEN/FOXO1 pathway as a potential therapeutic target for inhibition of aberrant AR activation and castration-resistant PCa growth. PMID:23389878

Bohrer, Laura R.; Liu, Ping; Zhong, Jian; Pan, Yunqian; Angstman, James; Brand, Lucas J.; Dehm, Scott M.; Huang, Haojie



[Constitution and nutrition. III: On the constitution and nutrition of the Germans in early history].  


This documentation is part of an inquiry about constitution and nutrition in Germany since early history. In this documentation, authorities of antiquity and modern researches about constitution and nutrition in early Teutonic history were collected and then possible influences of nutrition of that period on constitution of early Teutons were analysed. The early Teutons were characterised by great and strong stature, tendence to dolichocephalie and were of spectacular vigour. Their food was characterised by vitality and growth stimulating ingredients (like milk, meat, barley, oats, millet), but with differences in quantity in course of the year. A comparisation between nutrition and constitution of early Teutons shows a connection among typical patterns of early-Teuton-constitution and these nutrition. Differences in constitution to the southern neighbours, Celts and Romans, were not so marked, that constitutional changes in Germany, especially in southern Germany, in the middle ages can be explained by mixed race. PMID:3552852

Wurm, H



Teaching with Documents: Ratification of the Constitution.  

ERIC Educational Resources Information Center

Briefly reviews the history surrounding the ratification of the U.S. Constitution. Presents a facsimile of Delaware's 200 year-old ratification document and suggests six activities for its use with secondary level students. (JDH)

Gray, Leslie; Burroughs, Wynell



Inelastic constitutive equations for complex flows  

Microsoft Academic Search

A new class of inelastic constitutive equations is presented and discussed. In addition to the rate-of-strain tensor, the stress is assumed to depend also on the relative-rate-of-rotation tensor, a frame-indifferent quantity that brings information about the nature of the flow. The material functions predicted by these constitutive equations are given for simple shear and uniaxial extension. A special case of

Paulo R. Souza Mendes; Mahesh Padmanabhan; L. E. Scriven; Christopher W. Macosko



Cosmic Microwave Background Tutorials  

NSDL National Science Digital Library

Probing whether space is curved or flat, cosmologists have been searching for clues in ripples in the universe's microwave background left from the big bang. These tutorials explain the cosmic microwave background for neophytes, as well as more advanced readers.

Hu, Wayne



Rate constitutive theories for ordered thermofluids  

NASA Astrophysics Data System (ADS)

The paper considers developments of constitutive theories in Eulerian description for compressible as well as incompressible ordered homogeneous and isotropic thermofluids in which the deviatoric Cauchy stress tensor and the heat vector are functions of density, temperature, temperature gradient, and the convected time derivatives of the strain tensors of up to a desired order. The fluids described by these constitutive theories are called ordered thermofluids due to the fact that the constitutive theories for the deviatoric Cauchy stress tensor and heat vector are dependent on the convected time derivatives of the strain tensor up to a desired order, the highest order of the convected time derivative of the strain tensor in the argument tensors defines the `order of the fluid'. The admissibility requirement necessitates that the constitutive theories for the stress tensor and heat vector satisfy conservation laws, hence, in addition to conservation of mass, balance of momenta, and conservation of energy, the second law of thermodynamics, that is, Clausius-Duhem inequality must also be satisfied by the constitutive theories or be used in their derivations. If we decompose the total Cauchy stress tensor into equilibrium and deviatoric components, then Clausius-Duhem inequality and Helmholtz free energy density can be used to determine the equilibrium stress in terms of thermodynamic pressure for compressible fluids and in terms of mechanical pressure for incompressible fluids, but the second law of thermodynamics provides no mechanism for deriving the constitutive theories for the deviatoric Cauchy stress tensor. In the development of the constitutive theories in Eulerian description, the covariant and contravariant convected coordinate systems, and Jaumann measures are natural choices. Furthermore, the mathematical models for fluids require Eulerian description in which material point displacements are not measurable. This precludes the use of displacement gradients, that is, strain measures, in the development of the constitutive theories. It is shown that compatible conjugate pairs of convected time derivatives of the deviatoric Cauchy stress and strain measures in co-, contravariant, and Jaumann bases in conjunction with the theory of generators and invariants provide a general mathematical framework for the development of constitutive theories for ordered thermofluids in Eulerian description. This framework has a foundation based on the basic principles and axioms of continuum mechanics but the resulting constitutive theories for the deviatoric Cauchy stress tensor must satisfy the condition of positive work expanded, a requirement resulting from the entropy inequality. The paper presents a general theory of constitutive equations for ordered thermofluids which is then specialized, assuming first-order thermofluids, to obtain the commonly used constitutive theories for compressible and incompressible generalized Newtonian and Newtonian fluids. It is demonstrated that the constitutive theories for ordered thermofluids of all orders are indeed rate constitutive theories. We have intentionally used the term `thermofluids' as opposed to `thermoviscous fluids' due to the fact that the constitutive theories presented here describe a broader group of fluids than Newtonian and generalized Newtonian fluids that are commonly referred as thermoviscous fluids.

Surana, K. S.; Nunez, D.; Reddy, J. N.; Romkes, A.



Building Background Knowledge  

ERIC Educational Resources Information Center

This article make a case for the importance of background knowledge in children's comprehension. It suggests that differences in background knowledge may account for differences in understanding text for low- and middle-income children. It then describes strategies for building background knowledge in the age of common core standards.

Neuman, Susan B.; Kaefer, Tanya; Pinkham, Ashley



Spectral response of benthic diatoms with different sediment backgrounds  

Microsoft Academic Search

Remote sensing of terrestrial vegetation uses a wide range of vegetation indices (VIs) to monitor plant characteristics, but these indices can be very sensitive to canopy background reflectance. This study investigated background influences on VIs applied to intertidal microphytobenthos, using a synthetic spectral library constituted by a spectral combination of three contrasting types of sediment (sand, fine sand, and mud)

Laurent Barillé; Jean-Luc Mouget; Vona Méléder; Philippe Rosa; Bruno Jesus



Gravitational wave background from coalescing compact stars in eccentric orbits  

Microsoft Academic Search

Gravitational wave background produced by a stationary coalescing population of binary neutron stars in the Galaxy is calculated. This background is found to constitute a confusion limit within the LISA frequency band up to a limiting frequency nulim~10-3 Hz, leaving the frequency window ~10-3-10-2 Hz open for the potential detection of cosmological stochastic GW. .

A. G. Kuranov; V. B. Ignatiev; K. A. Postnov; M. E. Prokhorov



Generation of transgenic wheat (Triticum aestivum L.) for constitutive accumulation of an Aspergillus phytase  

Microsoft Academic Search

The Aspergillus niger phytase-encoding gene (phyA) has been constitutively expressed in wheat. Transgenic wheat lines were generated by microprojectile bombardment of immature embryos, using the bar-Bialaphos selection system. The bar and the phyA gene expression were controlled by the maize ubiquitin-1 promoter. To ensure secretion and glycosylation of the microbial phytase, an expression cassette was designed (Ubi-SP-Phy) where an a-amylase

Henrik Brinch-Pedersen; Annette Olesen; Søren K. Rasmussen; Preben B. Holm



Constitutional Rights of Children. Prepared for the Subcommittee on the Constitution of the Committee on the Judiciary, United States Senate, by the American Law Division, Congressional Research Service of the Library of Congress.  

ERIC Educational Resources Information Center

This paper reviews the rights of children as defined by the Constitution of the United States and summarizes a series of Supreme Court decisions which have defined the protections afforded to children by the Constitution. A short historical overview of the legal status of children is provided as background for the report. It is suggested that the…

Library of Congress, Washington, DC. Congressional Research Service.


Generalized constitutive relations for metamaterials based on the quasi-static Lorentz theory  

Microsoft Academic Search

This paper presents a method of calculating the elements of the generalized matrix representation of the macroscopic constitutive relations for a three-dimensional (3-D) array of non-magnetic inclusions with arbitrary shape. The derivation is based on the quasi-static Lorentz theory and the inclusions are represented by electric and magnetic dipole moments. The 6×6 constitutive relation matrix is expressed in terms of

Akira Ishimaru; Seung-Woo Lee; Yasuo Kuga; Vikram Jandhyala



Sakhalin tender background detailed  

Microsoft Academic Search

This paper reports that on Jan. 27, 1992, the committee constituted by order of the Russian government of Dec. 23, 1991, and headed by V.I. Danilov-Danilyan, the Russian Federation's Minister for Ecology and Natural Resources, assessed the results of a tender announced in May 1991. The tender was for foreign companies to submit feasibility studies for exploration and development of




Folate receptor-? constitutes a marker for human proinflammatory monocytes.  


Activated macrophages are commonly involved in the pathogenesis of inflammatory and autoimmune diseases and have been frequently reported to overexpress FR-?. Although FR-targeted therapies aimed at eliminating activated macrophages have shown promise for treating inflammatory diseases, little work has been performed to evaluate whether other hematopoietic cells might also express FR-?. Analysis of peripheral blood cells with a mAb to human FR-? reveals that only monocytes express FR-?. Molecular characterization of these circulating monocytes further demonstrates that solely the classic/proinflammatory subset (CD14(high)CD16(-)) expresses the FR and that only CD14(high)CD16(-) FR-?(+) monocytes also display the ability to bind folate-linked molecules. Confirmation that this subset of monocytes indeed constitutes the proinflammatory subpopulation was obtained by demonstrating coexpression of FR-? with other proinflammatory markers, including CCR2 and HLA-DR. Synovial monocytes from the joints of patients with RA were also shown to express FR-?. As inhibition of the chemotaxis of proinflammatory monocytes into sites of inflammation has been explored frequently as a means of controlling autoimmune diseases, demonstration that FR-? is uniquely expressed on this proinflammatory subpopulation offers a new strategy to suppress migration of inflammatory monocytes into sites of inflammation. PMID:25015955

Shen, Jiayin; Hilgenbrink, Andrew R; Xia, Wei; Feng, Yang; Dimitrov, Dimiter S; Lockwood, Michael B; Amato, Robert J; Low, Philip S



Constitutional trisomy 8 mosaicism as a model for epigenetic studies of aneuploidy  

PubMed Central

Background To investigate epigenetic patterns associated with aneuploidy we used constitutional trisomy 8 mosaicism (CT8M) as a model, enabling analyses of single cell clones, harboring either trisomy or disomy 8, from the same patient; this circumvents any bias introduced by using cells from unrelated, healthy individuals as controls. We profiled gene and miRNA expression as well as genome-wide and promoter specific DNA methylation and hydroxymethylation patterns in trisomic and disomic fibroblasts, using microarrays and methylated DNA immunoprecipitation. Results Trisomy 8-positive fibroblasts displayed a characteristic expression and methylation phenotype distinct from disomic fibroblasts, with the majority (65%) of chromosome 8 genes in the trisomic cells being overexpressed. However, 69% of all deregulated genes and non-coding RNAs were not located on this chromosome. Pathway analysis of the deregulated genes revealed that cancer, genetic disorder, and hematopoiesis were top ranked. The trisomy 8-positive cells displayed depletion of 5-hydroxymethylcytosine and global hypomethylation of gene-poor regions on chromosome 8, thus partly mimicking the inactivated X chromosome in females. Conclusions Trisomy 8 affects genes situated also on other chromosomes which, in cooperation with the observed chromosome 8 gene dosage effect, has an impact on the clinical features of CT8M, as demonstrated by the pathway analysis revealing key features that might explain the increased incidence of hematologic malignancies in CT8M patients. Furthermore, we hypothesize that the general depletion of hydroxymethylation and global hypomethylation of chromosome 8 may be unrelated to gene expression regulation, instead being associated with a general mechanism of chromatin processing and compartmentalization of additional chromosomes. PMID:23816241



Establishment of a quantitative PCR system for discriminating chitinase-like proteins: catalytically inactive breast regression protein-39 and Ym1 are constitutive genes in mouse lung  

PubMed Central

Background Mice and humans produce chitinase-like proteins (CLPs), which are highly homologous to chitinases but lack chitinolytic activity. Mice express primarily three CLPs, including breast regression protein-39 (BRP-39) [chitinase 3-like-1 (Chi3l1) or 38-kDa glycoprotein (gp38k)], Ym1 (Chi3l3) and Ym2 (Chi3l4). Recently, CLPs have attracted considerable attention due to their increased expression in a number of pathological conditions, including asthma, allergies, rheumatoid arthritis and malignant tumors. Although the exact functions of CLPs are largely unknown, the significance of their increased expression levels during pathophysiological states needs to be determined. The quantification of BRP-39, Ym1 and Ym2 is an important step in gaining insight into the in vivo regulation of the CLPs. Methods We constructed a standard DNA for quantitative real-time PCR (qPCR) by containing three CLPs target fragments and five reference genes cDNA in a one-to-one ratio. We evaluated this system by analyzing the eight target cDNA sequences. Tissue cDNAs obtained by reverse transcription from total RNA from four embryonic stages and eight adult tissues were analyzed using the qPCR system with the standard DNA. Results We established a qPCR system detecting CLPs and comparing their expression levels with those of five reference genes using the same scale in mouse tissues. We found that BRP-39 and Ym1 were abundant in the mouse lung, whereas Ym2 mRNA was abundant in the stomach, followed by lung. The expression levels of BRP-39 and Ym1 in the mouse lung were higher than those of two active chitinases and were comparable to glyceraldehyde-3-phosphate dehydrogenase, a housekeeping gene which is constitutively expressed in all tissues. Conclusion Our results indicate that catalytically inactive BRP-39 and Ym1 are constitutive genes in normal mouse lung. PMID:25294623



The European constitution project from the perspective of constitutional political economy  

Microsoft Academic Search

Three topics of a European constitution are discussed. First, basic arguments from constitutional political economy that aim at restricting representatives’ potential misuse of powers in a European Union with extended competencies are summarized. Since a European demos does not yet exist, an extension of competencies of the European Parliament is not sufficient in order to legitimate political decisions at the

Lars P. Feld



Background Check Presentation  

E-print Network

·July 1, 2012 ­ The UNM Division of Human Resources engaged in an RFP process to identify a NationalBackground Check Presentation Kim Herron-Singleton, Recruitment & UNMTemps Services Manager #12 check website to include BC and FP processes and resources · New background check request e-mail box

New Mexico, University of


A constitutive model for partially saturated soils  

Microsoft Academic Search

The Paper presents a constitutive model for describing the stress-strain behaviour of partially saturated soils. The model is formulated within the framework of hardening plasticity using two iode- pendent sets of stress variables: the excess of total stress over air pressure and the suction. The mode1 is able to represent, in a consistent and unified manner, many of the fundamental




Quantum interference distinguishes between constitutional isomers.  


Matter waves, as introduced by de Broglie in 1923 (L. de Broglie, Nature, 1923, 112, 540), are a fundamental quantum phenomenon, describing the delocalized center of mass motion of massive bodies and we show here their sensitivity to the molecular structure of constitutional isomers. PMID:20458383

Tüxen, Jens; Gerlich, Stefan; Eibenberger, Sandra; Arndt, Markus; Mayor, Marcel



Employee drug testing: A constitutional perspective  

Microsoft Academic Search

The proliferation of employee drug testing by federal and state governments and by private sector employers acting pursuant to governmental directives has led to a steadily growing number of lawsuits raising constitutional challenges to such testing. Most of these cases have been based on the Fourth Amendment's prohibition of unreasonable searches and seizures. In 1989, the Supreme Court addressed the

Thomas H. Christopher



Social Work Students' Society Constitution November 2005  

E-print Network

Social Work Students' Society Constitution ­ November 2005 Preamble The Social Work Students operating out of the University of Regina's Faculty of Social Work. Mission The SWSS exists as a venue for social work students to gather and pursue common goals and interests. The SWSS shall have as an over

Argerami, Martin


Crushed-salt constitutive model update  

SciTech Connect

Modifications to the constitutive model used to describe the deformation of crushed salt are presented in this report. Two mechanisms--dislocation creep and grain boundary diffusional pressure solutioning--defined previously but used separately are combined to form the basis for the constitutive model governing the deformation of crushed salt. The constitutive model is generalized to represent three-dimensional states of stress. New creep consolidation tests are combined with an existing database that includes hydrostatic consolidation and shear consolidation tests conducted on Waste Isolation Pilot Plant and southeastern New Mexico salt to determine material parameters for the constitutive model. Nonlinear least-squares model fitting to data from the shear consolidation tests and a combination of the shear and hydrostatic consolidation tests produced two sets of material parameter values for the model. The change in material parameter values from test group to test group indicates the empirical nature of the model but demonstrates improvement over earlier work with the previous models. Key improvements are the ability to capture lateral strain reversal and better resolve parameter values. To demonstrate the predictive capability of the model, each parameter value set was used to predict each of the tests in the database. Based on the fitting statistics and the ability of the model to predict the test data, the model appears to capture the creep consolidation behavior of crushed salt quite well.

Callahan, G.D.; Loken, M.C.; Mellegard, K.D. [RE/SPEC Inc., Rapid City, SD (United States); Hansen, F.D. [Sandia National Labs., Albuquerque, NM (United States)



Constitutive laws, tensorial invariance and chocolate cake  

NASA Astrophysics Data System (ADS)

Although constitutive modeling is a well-established branch of mathematics which has found wide industrial application, geophysicists often do not take full advantage of its known results. We present a synopsis of the theory of constitutive modeling, couched in terms of the ‘simple material’, which has been extensively studied and is complex enough to include most of the correct models proposed to describe the behavior of geological materials. Critical in the development of the theory are various invariance requirements, the principal ones being coordinate invariance, peer group invariance (isotropy), and frame-indifference. Each places distinet restrictions on constitutive equations. A noncomprehensive list of properly invariant and commonly used constitutive equations is given. To exemplify use of the equations, we consider two problems in detail: steady extension, which models the commonly performed constant strain rate triaxial test, and simple shearing. We note that each test is so restricted kinematically that only the most trivial aspects of material behavior are manifested in these tests, no matter how complex the material. Furthermore, the results of one test do not generally determine the results of the other.

Rundle, John B.; Passman, S. L.



Constituting Friendship in Talk and Metatalk.  

ERIC Educational Resources Information Center

Sets forth a relational perspective on developing friendships. Examines talk in and about children's friendships to test the assumption that conversation constitutes and structures friendships. Found that discourse patterns appeared in particular configurations of expectations (where the model of friendship is forming) and behavior (where the…

Yingling, Julie



Geographical Gerontology: The constitution of a discipline  

Microsoft Academic Search

Health and healthcare have always been central considerations in geographical gerontology. This paper reviews progress in this part of the field over the past decade (1995–2006) and also looks to the future. It demonstrates how geographical gerontology is currently constituted of multiple fields of empirical interest studied by multiple academic disciplines. Specifically, the continuation and development of traditional perspectives on

Gavin J. Andrews; Malcolm Cutchin; Kevin McCracken; David R. Phillips; Janine Wiles




E-print Network

responsibility to participate in governance of the College, including the establishment of College educational that pertain to the educational interests of the College as a whole. Among these are: (1) educational policy (2CONSTITUTION AND BYLAWS RULES OF ORDER AND STANDING RULES FOR THE COLLEGE OF ENGINEERING

Lee, Dongwon


School Choice and State Constitutions' Religion Clauses  

ERIC Educational Resources Information Center

After the U.S. Supreme Court's decision in "Zelman v. Simmons-Harris," only state religion clauses represent a potential constitutional bar to the inclusion of religious options in properly designed school choice programs. The two most significant are compelled support clauses and Blaine Amendments. Both are frequently misinterpreted by state…

Komer, Richard D.



Ordered Rate Constitutive Theories in Eulerian Description  

E-print Network

derivatives of upto orders n and m of the strain and stress tensors (i.e. rates) in their respective bases. Thus, there are many possibilities for various rate theories depending upon the choices of the dependent variables in the constitutive theories...

Nunez, Daniel



Celebrating the Constitution: A Bicentennial Retrospective.  

ERIC Educational Resources Information Center

This commemorative document was published to celebrate the Bicentennial of the signing of the U.S. Constitution and to pay tribute to the bicentennial celebration efforts of the U.S. National Archives and Records Administration staff. The included articles are: (1) "Introduction: A Celebration at the National Archives" (F. Burke); (2) "The Odyssey…

Walch, Timothy G., Ed.



Fetal pain, abortion, viability, and the Constitution.  


In early 2010, the Nebraska state legislature passed a new abortion restricting law asserting a new, compelling state interest in preventing fetal pain. In this article, we review existing constitutional abortion doctrine and note difficulties presented by persistent legal attention to a socially derived viability construct. We then offer a substantive biological, ethical, and legal critique of the new fetal pain rationale. PMID:21561518

Cohen, I Glenn; Sayeed, Sadath



Public health and the Australian Constitution.  


The powers vested in the Commonwealth Government by the Constitution contain the basis of much public health law in Australia. Yet this is not often recognised; public health law is generally, and historically, seen as the states' responsibility. This article surveys the broad range of constitutional powers that the Commonwealth Government can rely upon to make public health laws. It considers areas of power specified in the Constitution, such as those with respect to external affairs and corporations. Decisions of the High Court have interpreted the various heads of power very broadly and have significantly enhanced the potential of the Commonwealth to pass detailed and far-reaching public health law. To this fact must be added the taxation arrangements in Australia and, with these, the very extensive control that the Commonwealth can exercise through its monopoly of major taxation sources. Its power to make financial arrangements can tie dependent states into specific policies (including public health policies) as a condition of the grants made to them. However, these broad powers may be limited in some important respects: the High Court is increasingly identifying rights and freedoms in the Constitution that may increasingly bring both state and Commonwealth public health law under challenge. Despite this possibility, the Commonwealth may prove to be our most significant source of public health law, and public health policy makers should recognise the full potential of its power to make such laws. PMID:7626674

Reynolds, C



Our Forgotten Constitution: A Bicentennial Comment  

Microsoft Academic Search

This is a story about the Constitution that begins with some rather shocking facts: The parchment that all of us-practitioners, judges, scholars- have been using for the last century as the definitive copy of the supreme law of the land, is not. The handwritten, handsigned document enshrined in the National Archives and reprinted everywhere was never ratified by \\

Akhil Reed Amar



Guy Verhofstadt The new European Constitution  

E-print Network

Guy Verhofstadt The new European Constitution from Laeken to Rome Humboldt-Reden zu Europa 25. November 2003 #12;,,Humboldt-Reden zu Europa" In der Reihe Humboldt-Reden zu Europa sprechen ehemalige und Europa 5 ISSN 1618-4858 (Printausgabe) ISSN 1618-4866 (Onlineausgabe) ISBN 3

Röder, Beate


Constituting women’s subjectivity in Cyberspace  

Microsoft Academic Search

This study looks critically at how Foucault’s notion of subject formation unfolds within the matrix of power: a dynamic complex of force relations permeating society. Moreover, it elucidates how a singular subject is constituted in its interaction with the Internet. Foucault analyses our contemporary system of power as a pastoral regime where the responsibilities of government extend from institutions to

M. Pileggi; C. M. Stewart; Gisela Gil-Egui



Viscoelastic constitutive law in large deformations  

Microsoft Academic Search

Traction tests on soft tissues show that the shape of the stress–strain curves depends on the strain rate at which the tests are performed. Many of the constitutive models that have been proposed fail to properly consider the effect of the strain rate when large deformations are encountered. In the present study, a framework based on elastic and viscous potentials

D. P. Pioletti; L. R. Rakotomanana; J.-F. Benvenuti; P.-F. Leyvraz



Application of symbolic computations to the constitutive modeling of structural materials  

NASA Technical Reports Server (NTRS)

In applications involving elevated temperatures, the derivation of mathematical expressions (constitutive equations) describing the material behavior can be quite time consuming, involved and error-prone. Therefore intelligent application of symbolic systems to faciliate this tedious process can be of significant benefit. Presented here is a problem oriented, self contained symbolic expert system, named SDICE, which is capable of efficiently deriving potential based constitutive models in analytical form. This package, running under DOE MACSYMA, has the following features: (1) potential differentiation (chain rule), (2) tensor computations (utilizing index notation) including both algebraic and calculus; (3) efficient solution of sparse systems of equations; (4) automatic expression substitution and simplification; (5) back substitution of invariant and tensorial relations; (6) the ability to form the Jacobian and Hessian matrix; and (7) a relational data base. Limited aspects of invariant theory were also incorporated into SDICE due to the utilization of potentials as a starting point and the desire for these potentials to be frame invariant (objective). The uniqueness of SDICE resides in its ability to manipulate expressions in a general yet pre-defined order and simplify expressions so as to limit expression growth. Results are displayed, when applicable, utilizing index notation. SDICE was designed to aid and complement the human constitutive model developer. A number of examples are utilized to illustrate the various features contained within SDICE. It is expected that this symbolic package can and will provide a significant incentive to the development of new constitutive theories.

Arnold, Steven M.; Tan, H. Q.; Dong, X.



Background stratospheric aerosol layer  

SciTech Connect

Balloonborne aerosol particle counter measurements are used in studying the stratospheric sulfate layer at Laramie, Wyoming, during 1978 and 1979, a 2-year volcanically quiescent period in which the layer appears to have been in a near equilibrium background state. Subtracting the background aerosol concentration from data obtained during an earlier volcanically active period indicates that the actual decay rate of volcanic aerosol is over 30% faster than one would obtain without this correction. At background, the aerosol size distribution is found to remain remarkably constant between the tropopause and an altitude of approx.25 km, with a sudden transition to a distribution dominated by smaller particles above this altitude. The observations, in some respects, compare favorably with equilibrium one-dimensional stratospheric aerosol models and thus to some extent support the concept of relatively inert tropospheric sulfurous gases, such as carbonyl sulfide and carbon disulfide, as the main background stratospheric aerosol sulfur source. Models which incorporate sulfur chemistry are apparently not able to predict the observed variation of particle size with altitude. The 2-year background period is not long enough in itself to establish long-term trends. The eruption of Mt. St. Helens in May 1980 has considerably disrupted the background stratospheric aerosol which will probably not recover for several years. A comparison of the 1978--79 observations with Junge's original measurements made some 20 years earlier, also during a period void of volcanic perturbations, does not preclude a long-term increase in the background stratospheric aerosol level.

Hofmann, D.J.; Rosen, J.M.



Constitutive Somatostatin Receptor Subtype 2 Activity Attenuates GH Synthesis  

PubMed Central

Somatostatin signals predominantly through somatostatin receptor (SSTR) subtype 2 to attenuate GH release. However, the independent role of the receptor in regulating GH synthesis is unclear. Because we had previously demonstrated constitutive SSTR2 activity in mouse corticotrophs, we now analyzed GH regulation in rat pituitary somatotroph (GC) tumor cells, which express SSTR2 exclusively and are devoid of endogenous somatostatin ligand. We demonstrate that moderately stable SSTR2 overexpression (GpSSTR2WT cells) was associated with decreased GH promoter activity, GH mRNA, and hormone levels compared with those of control transfectants (GpCon cells). In contrast, levels of GH mRNA and peptide and GH promoter activity were unchanged in GpSSTR2DRY stable transfectants moderately expressing DRY motif mutated SSTR2 (R140A). GpSSTR2DRY did not exhibit an enhanced octreotide response as did GpSSTR2WT cells; however, both SSTR2WT-enhanced yellow fluorescent protein (eYFP) and SSTR2DRY-eYFP internalized on octreotide treatment. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, increased GH synthesis in wild-type GC cells and primary pituitary cultures. GpSSTR2WT cells induced GH synthesis more strongly on SAHA treatment, evident by both higher GH peptide and mRNA levels compared with the moderate but similar GH increase observed in GpCon and GpSSTR2DRY cells. In vivo SAHA also increased GH release from GpSSTR2WT but not from control xenografts. Endogenous rat GH promoter chromatin immunoprecipitation showed decreased baseline acetylation of the GH promoter with exacerbated acetylation after SAHA treatment in GpSSTR2WT compared with that of either GpSSTR2DRY or control cells, the latter 2 transfectants exhibiting similar GH promoter acetylation levels. In conclusion, modestly increased SSTR2 expression constitutively decreases GH synthesis, an effect partially mediated by GH promoter histone deacetylation. PMID:23696564

Ben-Shlomo, Anat; Pichurin, Oxana; Khalafi, Ramtin; Zhou, Cuiqi; Chesnokova, Vera; Ren, Song-Guang; Liu, Ning-Ai



Diffuse Background Radiation  

E-print Network

A new determination of the upper limit to the cosmic diffuse background radiation, at ~110 nm, of 300 photons s-1 cm-2 sr-1 nm-1, is placed in the context of diffuse background measurements across the entire electromagnetic spectrum, including new optical, infrared, visible, and gamma-ray background measurements. The possibility that observed excess diffuse visible radiation is due to redshifted cosmological Lyman alpha recomination radiation is explored. Also, a new standard of units for the display of spectra is advocated.

Richard C. Henry



The GLAST Background Model  

SciTech Connect

In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles that would affect the LAT. In addition to the well-known components of the cosmic radiation, we included splash and reentrant components of protons, electrons (e+ and e-) from 10 MeV and beyond as well as the albedo gamma rays produced by cosmic ray interactions with the atmosphere. We made estimates of the irreducible background components produced by positrons and hadrons interacting in the multilayered micrometeorite shield and spacecraft surrounding the LAT and note that because the orbital debris has increased, the shielding required and hence the background are larger than were present in EGRET. Improvements to the model are currently being made to include the east-west effect.

Ormes, J. F. [University of Denver (United States); Atwood, W. [University of California at Santa Cruz (United States); Burnett, T. [University of Washington (United States); Grove, E. [Naval Research Laboratory (United States); Longo, F. [Instituto Nazionale di Fisica Nucleare (INFN)-Pisa (Italy); McEnery, J.; Ritz, S. [NASA Goddard Space Flight Center (United States); Mizuno, T. [Hiroshima University (Japan)



The GLAST Background Model  

SciTech Connect

In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles that would affect the LAT. In addition to the well-known components of the cosmic radiation, we included splash and reentrant components of protons, electrons (e+ and e-) from 10 MeV and beyond as well as the albedo gamma rays produced by cosmic ray interactions with the atmosphere. We made estimates of the irreducible background components produced by positrons and hadrons interacting in the multilayered micrometeorite shield and spacecraft surrounding the LAT and note that because the orbital debris has increased, the shielding required and hence the background are larger than were present in EGRET. Improvements to the model are currently being made to include the east-west effect.

Ormes, J.F.; /Denver U.; Atwood, W.; /UC, Santa Cruz; Burnett, T.; /Washington U., Seattle; Grove, E.; /Naval Research Lab, Wash., D.C.; Longo, F.; /INFN, Pisa; McEnery, J.; /NASA, Goddard; Mizuno, T.; /Hiroshima U.; Ritz, S.; /NASA, Goddard



The Cosmic Background Radiation  

E-print Network

We summarise the current status of cosmic microwave background spectrum and anisotropy measurements, and their theoretical interpretation. This is the update of the mini-review for the 1997 web-version of the Review of Particle Properties.

George Smoot; Douglas Scott



Introduction 1 Background 1  

E-print Network

squirrel (Sciurus carolinensis). The grey squirrel was introduced to Britain in the late 19 th century populations in Northern Ireland. Background The red squirrel (Sciurus vulgaris) was once ubiquitous


Background Studies for EXIST  

NASA Technical Reports Server (NTRS)

We present results from a study of the trapped proton and electron background for several orbital inclinations and altitudes. This study includes time dependent effects. In addition we describe a 3 component cosmic background model developed at the University of Southampton, UK. The three components are cosmic diffuse gamma rays, atmospheric albedo gamma rays, and cosmic ray protons. We present examples of how this model was applied to BATSE and discuss its application to EXIST.

Wilson, Colleen A.; Pendleton, G. N.; Fishman, G. J.



Mechanism of constitution liquid film migration  

SciTech Connect

Liquid film migration (LFM) in liquid phase sintering classically involves a large metastable liquid volume adjacent to solid, and migration occurs at an isolated solid-liquid (S-L) interface. Constitutional liquid film migration (CLFM), discovered in alloy 718, has major characteristics similar to those of LFM, except that the metastable liquid is from the constitutional liquation of precipitates on the grain boundary. The similarity between LFM and CLFM has led to the theory that coherency lattice strain responsible for LFM is also responsible for CLFM. The coherency strain hypothesis was tested in this study by evaluating whether the Hillert model of LFM would also apply for CLFM. Experimental results of CLFM in alloy 718 showed that migration velocity followed the trend predicted by the Hillert model. This indicates that the coherency strain hypothesis of LFM also applies for CLFM and that the coherency lattice strain responsible for LFM is also the driving force for CLFM.




Isolation and characterization of oil palm constitutive promoter derived from ubiquitin extension protein (uep1) gene.  


The ubiquitin extension protein (uep1) gene was identified as a constitutively expressed gene in oil palm. We have isolated and characterized the 5' region of the oil palm uep1 gene, which contains an 828 bp sequence upstream of the uep1 translational start site. Construction of a pUEP1 transformation vector, which contains gusA reporter gene under the control of uep1 promoter, was carried out for functional analysis of the promoter through transient expression studies. It was found that the 5' region of uep1 functions as a constitutive promoter in oil palm and could drive GUS expression in all tissues tested, including embryogenic calli, embryoid, immature embryo, young leaflet from mature palm, green leaf, mesocarp and meristematic tissues (shoot tip). This promoter could also be used in dicot systems as it was demonstrated to be capable of driving gusA gene expression in tobacco. PMID:20123048

Masura, Subhi Siti; Parveez, Ghulam Kadir Ahmad; Ismail, Ismanizan



1?Constitutional Amendments: “Materializing” Organizational Communication  

Microsoft Academic Search

This essay aims to “materialize” organizational communication in three senses. First, we seek to make the field of study bearing this name more tangible for North American management scholars, such that recognition and engagement become common. To do so, we trace the development of the field’s major contribution thus far: the communication?as?constitutive principle, which highlights how communication generates defining realities

Karen Lee Ashcraft; Timothy R. Kuhn; François Cooren



Mood-Congruent Cognitions Constitute Mood Experience  

Microsoft Academic Search

Three studies tested the assumption of a dispositional theory of moods that mood-related cognitions constitute essential parts of the phenomenal mood experience. In Study 1, after a hot- versus a cold-, sad-, or angry-mood induction, participants reported their momentary moods and their momentary mood-related cognitions. Self-reported moods and mood-related cognitions changed in a strictly parallel fashion in all mood induction

Matthias Siemer



Unified viscoplastic constitutive equations and their applications  

NASA Technical Reports Server (NTRS)

Unified constitutive equations for time- and temperature-dependent metallic plastic deformation have been applied in FEM simulations of forming processes; increasingly powerful computational tools and physical models are being used to numerically model complex engineering problems. Once confidence has been gained through adequate verification, these numerical models will increasingly replace experimental models. Attention is presently given to the contributions made by physical metallurgy, continuum mechanics, and computational mechanics.

Lindholm, U. S.



Practical constitutive model for soil liquefaction  

Microsoft Academic Search

A practical constitutive model is presented that incorporates shear-induced effects in both loading and unloading as well as rotation effects. It is developed within a classical plasticity approach com- bined with a multi-laminate model. A multi-laminate model uses many mobilized planes, but the proposed model has only two mobilized planes; a maximum shear stress plane, and a horizontal plane. The

S.-S. Park; P. M. Byrne


Rapid implementation of advanced constitutive models  

NASA Astrophysics Data System (ADS)

This paper presents a methodology based on the NICE integration scheme [1, 2] for simple and rapid numerical implementation of a class of plasticity constitutive models. In this regard, an algorithm is purposely developed for the implementation of newly developed advanced constitutive models into explicit finite element framework. The methodology follows the organization of the problem state variables into an extended form, which allows the constitutive models' equations to be organized in such a way, that the algorithm can be optionally extended with minimal effort to integrate also evolution equations related to a description of other specific phenomena, such as damage, distortional hardening, phase transitions, degradation etc. To confirm simplicity of the program implementation, computational robustness, effectiveness and improved accuracy of the implemented integration algorithm, a deep drawing simulation of the cylindrical cup is considered as the case study, performed in ABAQUS/Explicit. As a fairly complex considered model, the YLD2004-18p model [3, 4] is first implemented via external subroutine VUMAT. Further, to give additional proof of the simplicity of the proposed methodology, a combination of the YLD2004-18p model and Gurson-Tvergaard-Needleman model (GTN) is considered. As demonstrated, the implementation is really obtained in a very simple way.

Starman, Bojan; Halilovi?, Miroslav; Vrh, Marko; Štok, Boris



A constitutive mechanical model for energetic materials  

SciTech Connect

Cookoff modeling of energetic materials has traditionally addressed reactive heat flow with the goal of defining the onset of runaway combustion behavior. Current modeling efforts are now aimed toward predicting the violence of the event. Combined thermal, chemical, and mechanical response must be modeled, since confinement results in pressure buildup which can breach confinement or enhance gas-phase combustion rates leading to runaway combustion behavior. Thermally induced stresses can also cause gaps which inhibit heat flow. These mechanical effects must also be included in cookoff modeling. A new reactive elastic-plastic constitutive model for micromechanical response has been developed which represents a stress-strain relation for reacting materials such as explosives, propellants, pyrotechnics, or burning foams. This micromechanical model is based on bubble mechanics. A local force balance, with mass continuity constraints, forms the basis of the constitutive model requiring input of temperature and reacted fraction. This constitutive material model has been incorporated into a quasistatic mechanics code, SANTOS. To provide temperature and reacted gas fraction, the thermal-chemical solver, XCHEM, has been coupled to SANTOS. This paper summarizes the development of the micromechanical model with material property estimates for conventional energetic materials. This study shows that large pressures can arise from small reacted fractions which implies that cookoff modeling must consider the strong interaction between thermochemistry and mechanics.

Hobbs, M.L.; Baer, M.R.; Gross, R.J.



Comparison of Gut Microbiota between Sasang Constitutions  

PubMed Central

The Sasang constitutional medicine has long been applied to diagnose and treat patients with various diseases. Studies have been conducted for establishment of scientific evidence supporting Sasang Constitutional (SC) diagnosis. Recent human microbiome studies have demonstrated individual variations of gut microbiota which can be dependent on lifestyle and health conditions. We hypothesized that gut microbial similarities and discrepancies may exist across SC types. We compared the difference of gut microbiota among three constitutions (So-Yang, So-Eum, and Tae-Eum), along with the investigation of anthropometric and biochemical parameters. Firmicutes and Bacteroidetes were predominant phyla in all SC types. The median plot analysis suggested that Firmicutes and Bacteroidetes appeared more abundant in SE and TE, respectively, in the male subjects of 20–29 years old. At the genus level, Bifidobacterium and Bacteroides manifested the difference between SE and TE types. For anthropometry, body weight, body mass index, and waist circumference of the TE type were significantly higher than those of the other types. Overall, findings indicated a possible link between SC types and gut microbiota within a narrow age range. Further investigations are deemed necessary to elucidate the influences of age, gender, and other factors in the context of SC types and gut microbiota. PMID:24454486

Bae, Hyo Sang; Lim, Chi-yeon; Kim, Mi Jeong; Seo, Jae-gu; Kim, Jong Yeol; Kim, Jai-eun



Constitutive modeling for isotropic materials (HOST)  

NASA Technical Reports Server (NTRS)

The results of the first year of work on a program to validate unified constitutive models for isotropic materials utilized in high temperature regions of gas turbine engines and to demonstrate their usefulness in computing stress-strain-time-temperature histories in complex three-dimensional structural components. The unified theories combine all inelastic strain-rate components in a single term avoiding, for example, treating plasticity and creep as separate response phenomena. An extensive review of existing unified theories is given and numerical methods for integrating these stiff time-temperature-dependent constitutive equations are discussed. Two particular models, those developed by Bodner and Partom and by Walker, were selected for more detailed development and evaluation against experimental tensile, creep and cyclic strain tests on specimens of a cast nickel base alloy, B19000+Hf. Initial results comparing computed and test results for tensile and cyclic straining for temperature from ambient to 982 C and strain rates from 10(exp-7) 10(exp-3) s(exp-1) are given. Some preliminary date correlations are presented also for highly non-proportional biaxial loading which demonstrate an increase in biaxial cyclic hardening rate over uniaxial or proportional loading conditions. Initial work has begun on the implementation of both constitutive models in the MARC finite element computer code.

Lindholm, Ulric S.; Chan, Kwai S.; Bodner, S. R.; Weber, R. M.; Walker, K. P.; Cassenti, B. N.



A constitutive theory for rigid polyurethane foam  

SciTech Connect

Rigid, closed-cell, polyurethane foam consists of interconnected polyurethane plates which form cells. When this foam is compressed, it exhibits an initial elastic regime which is followed by a plateau regime in which the load required to compress the foam remains nearly constant. In the plateau regime, cell walls are damaged and large permanent volume changes are generated. As additional load is applied, cell walls are compressed against neighboring cell walls, and the stiffness of the foam increases and approaches a value equal to that of solid polyurethane. When the foam is loaded in tension, the cell walls are damaged and the foam fractures. A constitutive theory for rigid polyurethane foam has been developed. This theory is based on a decomposition of the foam into two parts: a skeleton and a nonlinear elastic continuum in parallel. The skeleton accounts for the foam behavior in the elastic and plateau regimes and is described using a coupled plasticity with continuum damage theory. The nonlinear elastic continuum accounts for the lock-up of the foam due to internal gas pressure and cell wall interactions. This new constitutive theory has been implemented in both static and dynamic finite element codes. Numerical simulations performed using the new constitutive theory are presented.

Neilsen, M.K. [Sandia National Labs., Albuquerque, NM (United States); Krieg, R.D. [Tennessee Univ., Knoxville, TN (United States). Dept. of Engineering Science and Mechanics; Schreyer, H.L. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Mechanical Engineering



Sakhalin tender background detailed  

SciTech Connect

This paper reports that on Jan. 27, 1992, the committee constituted by order of the Russian government of Dec. 23, 1991, and headed by V.I. Danilov-Danilyan, the Russian Federation's Minister for Ecology and Natural Resources, assessed the results of a tender announced in May 1991. The tender was for foreign companies to submit feasibility studies for exploration and development of oil and gas on the continental shelf off Sakhalin Island. The announced winner was the MMM group consisting of McDermott International Inc., Marathon Oil Co., and Mitsui and Co. Ltd. In its decision the governmental tender committee (GTC) begged to differ from V. Fedorov, governor of the Territory of Sakhalin, in whose opinion the U.S.-Japanese combine of Exxon Corp.-Sakhalin Oil Development Co. (Sodeco) should have been pronounced winner at the bidding's end. GTC's decision also ran counter to the verdict by a panel of experts constituted by decision of the Examining Council under the Chairman of the Russian Government on Dec. 3, 1991, and headed by F. Salmanov, first deputy Minister of Geology of the U.S.S.R.

Konoplyanik, A. (Russian Federation Ministry for Fuels and Energy (SU))



Constitutional thinness and anorexia nervosa: a possible misdiagnosis?  


Clinical and biological aspects of restrictive anorexia nervosa (R-AN) are well documented. More than 10,000 articles since 1911 and more than 600 in 2013 have addressed R-AN psychiatric, somatic, and biological aspects. Genetic background, ineffectiveness of appetite regulating hormones on refeeding process, bone loss, and place of amenorrhea in the definition are widely discussed and reviewed. Oppositely, constitutional thinness (CT) is an almost unknown entity. Only 32 articles have been published on this topic since 1953. Similar symptoms associating low body mass index, low fat, and bone mass are reported in both CT and R-AN subjects. Conversely, menses are preserved in CT women and almost the entire hormonal profile is normal, except for leptin and PYY. The aim of the present review is to alert the clinician on the confusing clinical presentation of these two situations, a potential source of misdiagnosis, especially since R-AN definition has changed in DSM5. PMID:25368605

Estour, Bruno; Galusca, Bogdan; Germain, Natacha



Constitutional Thinness and Anorexia Nervosa: A Possible Misdiagnosis?  

PubMed Central

Clinical and biological aspects of restrictive anorexia nervosa (R-AN) are well documented. More than 10,000 articles since 1911 and more than 600 in 2013 have addressed R-AN psychiatric, somatic, and biological aspects. Genetic background, ineffectiveness of appetite regulating hormones on refeeding process, bone loss, and place of amenorrhea in the definition are widely discussed and reviewed. Oppositely, constitutional thinness (CT) is an almost unknown entity. Only 32 articles have been published on this topic since 1953. Similar symptoms associating low body mass index, low fat, and bone mass are reported in both CT and R-AN subjects. Conversely, menses are preserved in CT women and almost the entire hormonal profile is normal, except for leptin and PYY. The aim of the present review is to alert the clinician on the confusing clinical presentation of these two situations, a potential source of misdiagnosis, especially since R-AN definition has changed in DSM5. PMID:25368605

Estour, Bruno; Galusca, Bogdan; Germain, Natacha



Search, Seizure, and Privacy. Exploring the Constitution Series.  

ERIC Educational Resources Information Center

This book, part of the "Exploring the Constitution Series," provides a basic introduction to important areas of constitutional law. Each volume contains a general introduction to a particular constitutional issue combined with excerpts from significant Supreme Court decisions in that area. The text of the Constitution, a chronological listing of…

McWhirter, Darien A., Ed.


Constitutionalism and the Presidency in the Russian Federation  

Microsoft Academic Search

The general tendency for post-Communist states has been to adopt strong or `thick' constitutions. This article explains the kind of constitutionalization which will achieve strong constitutional protection. The Russian Federation has chosen to adopt a strong presidential regime together with a potentially `thick' constitution which gives far-reaching human rights protection and constitutionalization possibilities. The result is a rather thin constitution,

Anders Fogelklou



Discrete-Source Backgrounds in Cosmology  

NASA Astrophysics Data System (ADS)

Cosmological backgrounds can be decomposed into a component originating from diffuse emission, and one produced by a collection of discrete sources. The object of the present thesis is the study of the properties of the discrete component and the exploration of several of its cosmological applications. In chapter 1, an overview of the study of discrete-source backgrounds is presented. In addition, a description of the cosmic X-ray and radio-source backgrounds, of the effect of gravitational lensing by clusters, and of the Sunyaev-Zel'dovich effect is provided. The soft X-Ray Background is now known to originate primarily from discrete sources. In chapter 2, we study the two-point correlation function between the X-Ray Background and galaxy catalogs, and develop a direct two-dimensional formalism to interpret its angular dependence. This allows us to measure the mean X-ray flux of optical galaxies and to probe faint diffuse X-ray emission. Gravitational lensing can affect extragalactic backgrounds by altering the apparent density and flux distributions of their constituting sources. In chapter 3, the effect of gravitational lensing by clusters of galaxies on the X-Ray background is discussed. By considering the particular case of the cluster A1689, we show that the lensing-induced depletion in the number of detectable sources should be observable by the future X-ray mission AXAF. In chapter 4, we show that gravitational lensing causes a systematic deficit in the residual intensity of the radio-source background, after subtraction of detectable sources. If not corrected for, this can lead to an overestimation of the Sunyaev-Zel'dovich temperature decrement in the Cosmic Microwave Background, and to an underestimation of subsequent determination of the Hubble constant. Conclusions and natural extensions of this thesis are summarized in chapter 5.

Refregier, Alexandre



Rumex acetosa Y chromosomes: constitutive or facultative heterochromatin?  


Condensed Y chromosomes in Rumex acetosa L. root-tip nuclei were studied using 5-azaC treatment and immunohistochemical detection of methylated histones. Although Y chromosomes were decondensed within root meristem in vivo, they became condensed and heteropycnotic in roots cultured in vitro. 5-azacytidine (5-azaC) treatment of cultured roots caused transitional dispersion of their Y chromosome bodies, but 7 days after removal of the drug from the culture medium, Y heterochromatin recondensed and again became visible. The response of Rumex sex chromatin to 5-azaC was compared with that of condensed segments of pericentromeric heterochromatin in Rhoeo spathacea (Sw.) Steam roots. It was shown that Rhoeo chromocentres, composed of AT-rich constitutive heterochromatin, did not undergo decondensation after 5-azaC treatment. The Y-bodies observed within male nuclei of R. acetosa were globally enriched with H3 histone, demethylated at lysine 4 and methylated at lysine 9. This is the first report of histone tail-modification in condensed sex chromatin in plants. Our results suggest that the interphase condensation of Y chromosomes in Rumex is facultative rather than constitutive. Furthermore, the observed response of Y-bodies to 5-azaC may result indirectly from demethylation and the subsequent altered expression of unknown genes controlling tissue-specific Y-inactivation as opposed to the global demethylation of Y-chromosome DNA. PMID:16201317

Mosio?ek, Magdalena; Pasierbek, Pawe?; Malarz, Janusz; Mo?, Maria; Joachimiak, Andrzej J



Constitutive models for impacted morsellised cortico-cancellous bone.  


Constitutive models are developed, based on the results of confined compression testing, to describe the visco-elastic, and non-linear elasto-plastic behaviour of morsellised cortico-cancellous bone (MCB). It is found that the elastic modulus, E of MCB can be expressed as a linear function of the applied pressure, p. E varied from 3 to 30N/mm(2) for pressures up to 1N/mm(2). The visco-elastic behaviour of MCB can be described using a fourth-order Prony series. The plastic behaviour of MCB can be described using a Drucker Prager Cap (DPC) yield criterion, in which consolidation behaviour is described using an exponential function. The developed relationships allow MCB to be included in a realistic manner in finite element models, for example of the acetabular construct, following revision hip arthroplasty, carried out using the Slooff-Ling impaction grafting technique. PMID:16309740

Phillips, Andrew; Pankaj, Pankaj; May, Fraser; Taylor, Kenneth; Howie, Colin; Usmani, Asif



The symbolic constitution of addiction: language, alienation, ambivalence.  


The author offers an articulation of addiction, via existential-phenomenology and Lacanian psychoanalysis, where it is argued that the addicted subject is constituted via a symbolic structuring evolving from societal practices, laws and the effects of language. Language carries a heritage, which bears on the knowledge and practices of designated subjects and practitioners of that discourse. Addiction, as one particular form of embodied existence and knowledgeable practice, finds expression through the speech and habits of the addict. Addiction, it is argued, is symbolically saturated with ambivalence and alienation. Also the addict is described as the complete modern technocratic subject, consumed by the ideology of consumption. The clinical implications are briefly explored where it is noted that two major approaches to addiction, namely 12-step fellowships and motivational interviewing, both attend to language as a critical component of their treatment approach. PMID:22199180

Kemp, Ryan



Cosmological Gravitational Wave Backgrounds  

E-print Network

An overview is presented of possible cosmologically distant sources of gravitational wave backgrounds, especially those which might produce detectable backgrounds in the LISA band between 0.1 and 100 mHz. Examples considered here include inflation-amplified vacuum fluctuations in inflaton and graviton fields, bubble collisions in first-order phase transitions, Goldstone modes of classical self-ordering scalars, and cosmic strings and other gauge defects. Characteristic scales and basic mechanisms are reviewed and spectra are estimated for each of these sources. The unique impact of a LISA detection on fundamental physics and cosmology is discussed.

Craig J. Hogan



Supersymmetric heterotic string backgrounds  

E-print Network

We present the main features of the solution of the gravitino and dilatino Killing spinor equations derived in hep-th/0510176 and hep-th/0703143 which have led to the classification of geometric types of all type I backgrounds. We then apply these results to the supersymmetric backgrounds of the heterotic string. In particular, we solve the gaugino Killing spinor equation together with the other two Killing spinor equations of the theory. We also use our results to classify all supersymmetry conditions of ten-dimensional gauge theory.

Ulf Gran; George Papadopoulos; Diederik Roest



A constitutive law for dense granular flows  

E-print Network

A continuum description of granular flows would be of considerable help in predicting natural geophysical hazards or in designing industrial processes. However, the constitutive equations for dry granular flows, which govern how the material moves under shear, are still a matter of debate. One difficulty is that grains can behave like a solid (in a sand pile), a liquid (when poured from a silo) or a gas (when strongly agitated). For the two extreme regimes, constitutive equations have been proposed based on kinetic theory for collisional rapid flows, and soil mechanics for slow plastic flows. However, the intermediate dense regime, where the granular material flows like a liquid, still lacks a unified view and has motivated many studies over the past decade. The main characteristics of granular liquids are: a yield criterion (a critical shear stress below which flow is not possible) and a complex dependence on shear rate when flowing. In this sense, granular matter shares similarities with classical visco-plastic fluids such as Bingham fluids. Here we propose a new constitutive relation for dense granular flows, inspired by this analogy and recent numerical and experimental work. We then test our three-dimensional (3D) model through experiments on granular flows on a pile between rough sidewalls, in which a complex 3D flow pattern develops. We show that, without any fitting parameter, the model gives quantitative predictions for the flow shape and velocity profiles. Our results support the idea that a simple visco-plastic approach can quantitatively capture granular flow properties, and could serve as a basic tool for modelling more complex flows in geophysical or industrial applications.

Pierre Jop; Yoël Forterre; Olivier Pouliquen



Cosmic background radiation  

Microsoft Academic Search

We summarise the current status of cosmic microwave background spectrum and\\u000aanisotropy measurements, and their theoretical interpretation. This is the\\u000aupdate of the mini-review for the 1997 web-version of the Review of Particle\\u000aProperties.

George Smoot; Douglas Scott



INDIAN BACKGROUNDS Patuxent Wildlife  

E-print Network

of Sport Fisheries and Wildlife Circular 138 #12;#12;INDIAN BACKGROUNDS of the Patuxent Wildlife Research of the Interior Fish and Wildlife Service Bureau of Sport Fisheries and Wildlife Circular 138 #12; Exhibit the Indian hunted with spear and arrow to supply the necessities of life--food, clothing, and shelter


PANDEMIC INFLUENZA background briefing  

E-print Network

PANDEMIC INFLUENZA background briefing Biomedicine Forum 5 November 2008 compiled by David Evans, Dave Carr, David Lynn and Phil Green Transmission electron micrograph of Influenza A virus (Wellcome influenza!' Page 2 #12;Consequences of an influenza pandemic THE PANDEMIC THREAT DEATH If the next pandemic

Rambaut, Andrew


Local microwave background radiation  

E-print Network

An inquiry on a possible local origin for the Microwave Background Radiation is made. Thermal MBR photons are contained in a system called {\\it magnetic bottle} which is due to Earth magnetic field and solar wind particles, mostly electrons. Observational tests are anticipated.

Domingos S. L. Soares



David Smith Academic background  

E-print Network

David Smith Academic background Ph.D. in Mathematics (Algebra), Université de Sherbrooke, Canada project program (I. Assem, F. Bergeron, C. Reutenauer, D. Smith) $132,000 ($44,000 per year for 3 years. Schiffler and D. Smith, Friezes, strings and cluster variables, to appear in Glasgow Mathematcal Journal. 2


Native American Constitution and Law Digitization Project  

NSDL National Science Digital Library

A cooperative effort from the University of Oklahoma Law Center, the National Indian Law Library (NILL), and Native American tribes, this site offers access to the full texts of selected legal documents. Among these are Constitutions, Tribal Codes, Charters, Indian Land Titles, and summaries of recent US Supreme Court cases that have involved or affected Native Americans. At present, the Project provides only about 30 documents total, but scholars and users with an interest in Native American legal issues will want to monitor the site.


Numerically abnormal chromosome constitutions in humans  

SciTech Connect

Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.




Reflection and transmission matrices at a free-space-chiral interface based on the invariant constitutive relations for gyrotropic media and the Drude-Born-Federov constitutive relations.  


The expressions for the linear and cross-polarized reflection and transmission coefficients based on the invariant gyrotropic constitutive relations and the Drude-Born-Federov constitutive relations are compared. A physical interpretation for the first-order terms in the gyrotropic parameter and the chiral parameter is presented for normal and oblique angles of incidence. The analytical expressions for the linear cross-polarized or circular-like polarized reflection coefficients are proportional to the product of the gyrotropic measure, the tangent squared of the angle of refraction in the host medium, the round trip transmission coefficients for the horizontally and vertically polarized waves, and the polarization dependent reflection coefficients for a perfectly conducting mirror. These analytical results are consistent with the observed enhancement of the differential circular reflection for near-grazing incidence. PMID:19649118

Bahar, Ezekiel



Gauging the cosmic microwave background  

SciTech Connect

We provide a new derivation of the anisotropies of the cosmic microwave background (CMB), and find an exact expression that can be readily expanded perturbatively. Close attention is paid to gauge issues, with the motivation to examine the effect of super-Hubble modes on the CMB. We calculate a transfer function that encodes the behavior of the dipole, and examine its long-wavelength behavior. We show that contributions to the dipole from adiabatic super-Hubble modes are strongly suppressed, even in the presence of a cosmological constant, contrary to claims in the literature. We also introduce a naturally defined CMB monopole, which exhibits closely analogous long-wavelength behavior. We discuss the geometrical origin of this super-Hubble suppression, pointing out that it is a simple reflection of adiabaticity, and hence argue that it will occur regardless of the matter content.

Zibin, J. P.; Scott, Douglas [Department of Physics and Astronomy, University of British Columbia, Vancouver, British Columbia, V6T 1Z1 (Canada)



Deleterious background selection with recombination  

SciTech Connect

An analytic expression for the expected nucleotide diversity is obtained for a neutral locus in a region with deleterious mutation and recombination. Our analytic results are used to predict levels of variation for the entire third chromosome of Drosophila melanogaster. The predictions are consistent with the low levels of variation that have been observed at loci near the centromeres of the third chromosome of D. melanogaster. However, the low levels of variation observed near the tips of this chromosome are not predicted using currently available estimates of the deleterious mutation rate and of selection coefficients. If considerably smaller selection coefficients are assumed, the low observed levels of variation at the tips of the third chromosome are consistent with the background selection model. 33 refs., 4 figs., 1 tab.

Hudson, R.R. [Univ. of California, Irvine, CA (United States); Kaplan, N.L. [National Institute of Environmental Health Sciences, Research Triangle Park, NC (United States)



Gauging the cosmic microwave background  

E-print Network

We provide a new derivation of the anisotropies of the cosmic microwave background (CMB), and find an exact expression that can be readily expanded perturbatively. Close attention is paid to gauge issues, with the motivation to examine the effect of super-Hubble modes on the CMB. We calculate a transfer function that encodes the behaviour of the dipole, and examine its long-wavelength behaviour. We show that contributions to the dipole from adiabatic super-Hubble modes are strongly suppressed, even in the presence of a cosmological constant, contrary to claims in the literature. We also introduce a naturally defined CMB monopole, which exhibits closely analogous long-wavelength behaviour. We discuss the geometrical origin of this super-Hubble suppression, pointing out that it is a simple reflection of adiabaticity, and hence argue that it will occur regardless of the matter content.

J. P. Zibin; Douglas Scott



Enhanced Expression of CXCL13 in Human Helicobacter pylori Associated Gastritis  

Microsoft Academic Search

Background and Aims  Chemokine CXC ligand 13 (CXCL13) and CXC receptor type 5 (CXCR5) are constitutively expressed in tertiary lymphoid follicles\\u000a where the CXCL13\\/CXCR5 system regulates B lymphocytes homing. In this study, we sought to examine CXCL13 expression in the\\u000a H. pylori-infected and -uninfected gastric mucosa and to elucidate the implication in the pathogenesis of HAG in humans.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Using endoscopic biopsies

Yujiro NakashimaHajime; Hajime Isomoto; Kayoko Matsushima; Akira Yoshida; Toshiyuki Nakayama; Masaaki Nakayama; Junzo Hisatsune; Tatsuki Ichikawa; Fuminao Takeshima; Tomayoshi Hayashi; Kazuhiko Nakao; Toshiya Hirayama; Shigeru Kohno


Gravitational wave background from coalescing compact stars in eccentric orbits  

Microsoft Academic Search

Stochastic gravitational wave background produced by a stationary coalescing population of binary neutron stars in the Galaxy is calculated. This background is found to constitute a confusion limit within the LISA frequency band up to a limiting frequency of nulim~10-3Hz, leaving the frequency window ~10-3-10-2Hz open for the potential detection of cosmological stochastic GWs and of signals involving massive black

V. B. Ignatiev; A. G. Kuranov; K. A. Postnov; M. E. Prokhorov



Constitutively active phosphatase inhibitor-1 improves cardiac contractility in young mice but is deleterious after catecholaminergic stress and with aging  

PubMed Central

Phosphatase inhibitor-1 (I-1) is a distal amplifier element of ?-adrenergic signaling that functions by preventing dephosphorylation of downstream targets. I-1 is downregulated in human failing hearts, while overexpression of a constitutively active mutant form (I-1c) reverses contractile dysfunction in mouse failing hearts, suggesting that I-1c may be a candidate for gene therapy. We generated mice with conditional cardiomyocyte-restricted expression of I-1c (referred to herein as dTGI-1c mice) on an I-1–deficient background. Young adult dTGI-1c mice exhibited enhanced cardiac contractility but exaggerated contractile dysfunction and ventricular dilation upon catecholamine infusion. Telemetric ECG recordings revealed typical catecholamine-induced ventricular tachycardia and sudden death. Doxycycline feeding switched off expression of cardiomyocyte-restricted I-1c and reversed all abnormalities. Hearts from dTGI-1c mice showed hyperphosphorylation of phospholamban and the ryanodine receptor, and this was associated with an increased number of catecholamine-induced Ca2+ sparks in isolated myocytes. Aged dTGI-1c mice spontaneously developed a cardiomyopathic phenotype. These data were confirmed in a second independent transgenic mouse line, expressing a full-length I-1 mutant that could not be phosphorylated and thereby inactivated by PKC-? (I-1S67A). In conclusion, conditional expression of I-1c or I-1S67A enhanced steady-state phosphorylation of 2 key Ca2+-regulating sarcoplasmic reticulum enzymes. This was associated with increased contractile function in young animals but also with arrhythmias and cardiomyopathy after adrenergic stress and with aging. These data should be considered in the development of novel therapies for heart failure. PMID:20071777

Wittkopper, Katrin; Fabritz, Larissa; Neef, Stefan; Ort, Katharina R.; Grefe, Clemens; Unsold, Bernhard; Kirchhof, Paulus; Maier, Lars S.; Hasenfuss, Gerd; Dobrev, Dobromir; Eschenhagen, Thomas; El-Armouche, Ali



Microstructural Constitutive Model of Active Coronary Media  

PubMed Central

Although vascular smooth muscle cells (VSMCs) are pivotal in physiology and pathology, there is a lack of detailed morphological data on these cells. The objective of this study was to determine dimensions (width and length) and orientation of swine coronary VSMCs and to develop a microstructural constitutive model of active media. The dimensions, spatial aspect ratio and orientation angle of VSMCs measured at zero-stress state were found to follow continuous normal (or bimodal normal) distributions. The VSMCs aligned off circumferential direction of blood vessels with symmetrical polar angles 18.7°±10.9°, and the local VSMC deformation was affine with tissue-level deformation. A microstructure-based active constitutive model was developed to predict the biaxial vasoactivity of coronary media, based on experimental measurements of geometrical and deformation features of VSMCs. The results revealed that the axial active response of blood vessels is associated with multi-axial contraction as well as oblique VSMC arrangement. The present morphological data base is essential for developing accurate structural models and is seminal for understanding the biomechanics of muscular vessels. PMID:23859656

Chen, Huan; Luo, Tong; Zhao, Xuefeng; Lu, Xiao; Huo, Yunlong; Kassab, Ghassan S.



Constitutional moments in governing science and technology.  


Scholars in science and technology studies (STS) have recently been called upon to advise governments on the design of procedures for public engagement. Any such instrumental function should be carried out consistently with STS's interpretive and normative obligations as a social science discipline. This article illustrates how such threefold integration can be achieved by reviewing current US participatory politics against a 70-year backdrop of tacit constitutional developments in governing science and technology. Two broad cycles of constitutional adjustment are discerned: the first enlarging the scope of state action as well as public participation, with liberalized rules of access and sympathetic judicial review; the second cutting back on the role of the state, fostering the rise of an academic-industrial complex for technology transfer, and privatizing value debates through increasing delegation to professional ethicists. New rules for public engagement in the United Sates should take account of these historical developments and seek to counteract some of the anti-democratic tendencies observable in recent decades. PMID:21879357

Jasanoff, Sheila



Constitutive modeling for isotropic materials (HOST)  

NASA Technical Reports Server (NTRS)

This report presents the results of the second year of work on a problem which is part of the NASA HOST Program. Its goals are: (1) to develop and validate unified constitutive models for isotropic materials, and (2) to demonstrate their usefulness for structural analyses of hot section components of gas turbine engines. The unified models selected for development and evaluation are that of Bodner-Partom and Walker. For model evaluation purposes, a large constitutive data base is generated for a B1900 + Hf alloy by performing uniaxial tensile, creep, cyclic, stress relation, and thermomechanical fatigue (TMF) tests as well as biaxial (tension/torsion) tests under proportional and nonproportional loading over a wide range of strain rates and temperatures. Systematic approaches for evaluating material constants from a small subset of the data base are developed. Correlations of the uniaxial and biaxial tests data with the theories of Bodner-Partom and Walker are performed to establish the accuracy, range of applicability, and integability of the models. Both models are implemented in the MARC finite element computer code and used for TMF analyses. Benchmark notch round experiments are conducted and the results compared with finite-element analyses using the MARC code and the Walker model.

Lindholm, U. S.; Chan, K. S.; Bodner, S. R.; Weber, R. M.; Walker, K. P.; Cassenti, B. N.



Computer simulation of the mathematical modeling involved in constitutive equation development: Via symbolic computations  

NASA Technical Reports Server (NTRS)

Development of new material models for describing the high temperature constitutive behavior of real materials represents an important area of research in engineering disciplines. Derivation of mathematical expressions (constitutive equations) which describe this high temperature material behavior can be quite time consuming, involved and error prone; thus intelligent application of symbolic systems to facilitate this tedious process can be of significant benefit. A computerized procedure (SDICE) capable of efficiently deriving potential based constitutive models, in analytical form is presented. This package, running under MACSYMA, has the following features: partial differentiation, tensor computations, automatic grouping and labeling of common factors, expression substitution and simplification, back substitution of invariant and tensorial relations and a relational data base. Also limited aspects of invariant theory were incorporated into SDICE due to the utilization of potentials as a starting point and the desire for these potentials to be frame invariant (objective). Finally not only calculation of flow and/or evolutionary laws were accomplished but also the determination of history independent nonphysical coefficients in terms of physically measurable parameters, e.g., Young's modulus, was achieved. The uniqueness of SDICE resides in its ability to manipulate expressions in a general yet predefined order and simplify expressions so as to limit expression growth. Results are displayed when applicable utilizing index notation.

Arnold, S. M.; Tan, H. Q.; Dong, X.



Gravitational wave background from rotating neutron stars  

NASA Astrophysics Data System (ADS)

The background of gravitational waves produced by the ensemble of rotating neutron stars (which includes pulsars, magnetars, and gravitars) is investigated. A formula for ?(f) (a function that is commonly used to quantify the background, and is directly related to its energy density) is derived, without making the usual assumption that each radiating system evolves on a short time scale compared to the Hubble time; the time evolution of the systems since their formation until the present day is properly taken into account. Moreover, the formula allows one to distinguish the different parts of the background: the unresolvable (which forms a stochastic background or confusion noise, since the waveforms composing it cannot be either individually observed or subtracted out of the data of a detector) and the resolvable. Several estimations of the background are obtained, for different assumptions on the parameters that characterize neutron stars and their population. In particular, different initial spin period distributions lead to very different results. For one of the models, with slow initial spins, the detection of the background by present or planned detectors can be rejected. However, other models do predict the detection of the background, that would be unresolvable, by the future ground-based gravitational wave detector ET. A robust upper limit for the background of rotating neutron stars is obtained; it does not exceed the detection threshold of two cross-correlated Advanced LIGO interferometers. If gravitars exist and constitute more than a few percent of the neutron star population, then they produce an unresolvable background that could be detected by ET. Under the most reasonable assumptions on the parameters characterizing a neutron star, the background is too faint to be detected. Previous papers have suggested neutron star models in which large magnetic fields (like the ones that characterize magnetars) induce big deformations in the star, which produce a stronger emission of gravitational radiation. Considering the most optimistic (in terms of the detection of gravitational waves) of these models, an upper limit for the background produced by magnetars is obtained; it could be detected by ET, but not by BBO or DECIGO. Simple approximate formulas to characterize both the total and the unresolvable backgrounds are given for the ensemble of rotating neutron stars, and, for completion, also for the ensemble of binary star systems.

Rosado, Pablo A.



A theory of the Earth's background free oscillations  

Microsoft Academic Search

It has recently been established that the Earth's free oscillations are continuously excited by phenomena other than earthquakes and that these oscillations constitute the background noise in the normal mode band at quiet sites. On the basis of evidence that the excitation source is at or just above the Earth's surface, a normal mode theory of the Earth's free oscillations

Yoshio Fukao; Kiwamu Nishida; Naoki Suda; Kazunari Nawa; Naoki Kobayashi



A constitutively active cryptochrome in Drosophila melanogaster.  


Light-activated cryptochrome (CRY) regulates circadian photoresponses in Drosophila melanogaster. Removing the carboxy (C) terminus to create CRYDelta produces, in yeast, a light-independent, constitutively active form. Here we show that flies overexpressing CRYDelta have a longer free-running period of locomotor activity, as well as altered cycling kinetics of the clock proteins timeless (TIM) and period (PER). Moreover, at the cellular level, they show a reduction in the level of TIM and in the nuclear localization of TIM and PER in two significant clusters of behavioral pacemaker cells: the large and the small ventral lateral neurons (LN(v)s). These effects are similar to those seen in wild-type flies under continuous light and suggest a regulatory role for the C terminus of CRY on the photosensitive, photolyase-like part of the protein. PMID:15258584

Dissel, Stephane; Codd, Veryan; Fedic, Robert; Garner, Karen J; Costa, Rodolfo; Kyriacou, Charalambos P; Rosato, Ezio



Constitutive Models for Shape Memory Alloy Polycrystals  

NASA Technical Reports Server (NTRS)

Shape memory alloys (SMA) exhibiting the superelastic or one-way effects can produce large recoverable strains upon application of a stress. In single crystals this stress and resulting strain are very orientation dependent. We show experimental stress/strain curves for a Ni-Al single crystal for various loading orientations. Also shown are model predictions; the open and closed circles indicate recoverable strains obtained at various stages in the transformation process. Because of the strong orientation dependence of shape memory properties, crystallographic texture can be expected to play an important role in the mechanical behavior of polycrystalline SMA. It is desirable to formulate a constitutive model to better understand and exploit the unique properties of SMA.

Comstock, R. J., Jr.; Somerday, M.; Wert, J. A.



What constitutes a nursing practical skill?  


Practical nursing skills ensure patients' physical comfort, hygiene, and safe medical treatment. The learning, performance, or significance of nursing practical skills are seldom a theme in theoretical and philosophical debate or the topic of research within nursing. This might be due to a long-standing behavioristic tradition in nursing of viewing nursing practical skills in a simplistic way, only as correctly sequenced motor movement. The purpose of this article is to bring forth an argument for a broader understanding of the constitution of nursing practical skills. This argument is substantiated by a review of past and present conceptualizations of nursing practical skills as well as by philosophical reflections on the value of practical skills in the nursing profession. Nursing practical skills embrace dimensions of performance, intention, and nursing "disciplined" understanding. PMID:11512159

Bjørk, I T



Rotational and constitutional dynamics of caged supramolecules  

PubMed Central

The confinement of molecular species in nanoscale environments leads to intriguing dynamic phenomena. Notably, the organization and rotational motions of individual molecules were controlled by carefully designed, fully supramolecular host architectures. Here we use an open 2D coordination network on a smooth metal surface to steer the self-assembly of discrete trimeric guest units, identified as noncovalently bound dynamers. Each caged chiral supramolecule performs concerted, chirality-preserving rotary motions within the template honeycomb pore, which are visualized and quantitatively analyzed using temperature-controlled scanning tunneling microscopy. Furthermore, with higher thermal energies, a constitutional system dynamics appears, which is revealed by monitoring repetitive switching events of the confined supramolecules’ chirality signature, reflecting decay and reassembly of the caged units. PMID:21098303

Kühne, Dirk; Klappenberger, Florian; Krenner, Wolfgang; Klyatskaya, Svetlana; Ruben, Mario; Barth, Johannes V.



A continuum constitutive model for amorphous metallic materials  

E-print Network

A finite-deformation, Coulomb-Mohr type constitutive theory for the elastic-viscoplastic response of pressure-sensitive and plastically-dilatant isotropic materials has been developed. The constitutive model has been ...

Su, Cheng, Ph. D. Massachusetts Institute of Technology



The Constitutional Origins of the President's Foreign Affairs Power  

E-print Network

from a lesser degree of scrutiny than other constitutional subjects. Few scholars have addressed the original source of authority and legitimacy of the Constitution—its ratification—as a means of determining whether the modern presidency continues...

Thoma, Oliver



Close view of the Constitution Avenue elevation to show arched ...  

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Close view of the Constitution Avenue elevation to show arched gateways and pedimented pavilion ("Commerce and Communication" sculpted pediment) - Interstate Commerce Commission, Constitution Avenue between Twelfth and Fourteenth streets, Washington, District of Columbia, DC


The Iron Line Background  

E-print Network

We investigate the presence of iron line emission among faint X-ray sources identified in the 1Ms Chandra Deep Field South and in the 2Ms Chandra Deep Field North. Individual source spectra are stacked in seven redshift bins over the range z=0.5-4. We find that iron line emission is an ubiquitous property of X-ray sources up to z~3. The measured line strengths are in good agreement with those expected by simple pre-Chandra estimates based on X-ray background synthesis models. The average rest frame equivalent width of the iron line does not show significant changes with redshift.

Marcella Brusa; Roberto Gilli; Andrea Comastri



POLYFLOW theoretical background  

NASA Astrophysics Data System (ADS)

In the scope of the 1990-04 lecture series on computational fluid dynamics, a finite element program is described. POLYFLOW was designed for the analysis of industrial processes dominated by nonlinear viscous phenomena and viscoelastic effects. It is based on the general principles of continuum mechanics, together with phenomenological or kinetic theoretical models for describing the rheological behavior of the fluid. The theoretical background, necessary to understand the models, and numerical techniques used in POLYFLOW, are provided. The governing equations, their finite element formulations and the solution procedures are summarized.

Crochet, M. J.


The Environmental Estrogen, Nonylphenol, Activates the Constitutive Androstane Receptor  

PubMed Central

Nonylphenol (NP) and its parent compounds, the nonylphenol ethoxylates are some of the most prevalent chemicals found in U.S. waterways. NP is also resistant to biodegradation and is a known environmental estrogen, which makes NP a chemical of concern. Our data show that NP also activates the constitutive androstane receptor (CAR), an orphan nuclear receptor important in the induction of detoxification enzymes, including the P450s. Transactivation assays demonstrate that NP increases murine CAR (mCAR) transcriptional activity, and NP treatment can overcome the inhibitory effects of the inverse agonist, androstanol, on mCAR activation. Treatment of wild-type (CAR +/+) mice with NP at 50 or 75 mg/kg/day increases Cyp2b protein expression in a dose-dependent manner as demonstrated by Western blotting, and was confirmed by quantitative reverse transcription–PCR of Cyp2b10 transcript levels. CAR-null (CAR ?/?) mice show no increased expression of Cyp2b following NP treatment, indicating that CAR is required for NP-mediated Cyp2b induction. In addition, NP increases the translocation of CAR into the nucleus, which is the key step in the commencement of CAR's transcriptional activity. NP also induced CYP2B6 in primary human hepatocytes, and increased Cyp2b10 messenger RNA and protein expression in humanized CAR mice, indicating that NP is an activator of human CAR as well. In conclusion, NP is a CAR activator, and this was demonstrated in vitro with transactivation assays and in vivo with transgenic CAR mouse models. PMID:17483497

Hernandez, Juan P.; Huang, Wendong; Chapman, Laura M.; Chua, Steven; Moore, David D.; Baldwin, William S.




E-print Network

for the individual beyond the classroom, laboratory, and library; 2. To provide and develop an environment and programs pertinent to the intellectual, social, cultural, recreational, and personal development identity or expression. #12;ARTICLE IV - RECALL AND REVERSAL: The Lory Student Center Governing Board


The Separation of Church and State. Exploring the Constitution Series.  

ERIC Educational Resources Information Center

This textbook on the separation of church and state continues the "Exploring the Constitution Series," which introduces important areas of constitutional law. Intended to serve either as a reference work, a supplement to a standard textbook, or as the textbook for a course, this volume covers the constitutional issues of prayer in public schools,…

McWhirter, Darien A.


Application of linear viscoelastic differential constitutive equation in ABAQUS  

Microsoft Academic Search

There are a number of ways to describe the rheological behavior of rock and soil, in which the establishment of differential constitutive equations is intuitive, and convenient for application. The paper sets out how the linear viscoelastic differential constitutive equations applied in ABAQUS. Using Laplace transform, three commonly used differential constitutive equations are derived into prony series forms for the

Kong Juan; Yuan Ju-yun



A multi-dimensional constitutive model for shape memory alloys  

Microsoft Academic Search

This paper presents a multi-dimensional thermomechanical constitutive model for shape memory alloys (SMAs). This constitutive relation is based upon a combination of both micromechanics and macromechanics. The martensite fraction is introduced as a variable in this model to reflect the martensitic transformation that determines the unique characteristics of shape memory alloys. This constitutive relation can be used to study the

C. Liang; C. A. Rogers



Same-Sex Marriage in South Africa: A Constitutional Possibility  

Microsoft Academic Search

The South African Constitution is unlike any other in the world in terms of its inclusion of sexual orientation. The Constitutional Court has taken a clear position in interpreting the Bill of Rights and implementing its goal of protecting individuals and groups from discrimination. The Sodomy, Immigration, and Spousal Benefits Cases demonstrate that the Constitutional Court recognizes that homosexuals have

Mary P. Byrn



Sacrifice and Sacred Honor: Why the Constitution is a \\  

Microsoft Academic Search

Most legal scholars and elected officials embrace the popular cliché that “the Constitution is not a suicide pact.” Typically, those commentators extol the “Constitution of necessity,” the supposition that Government, essentially the Executive, may take any action—may abridge or deny any fundamental right—to alleviate a sufficiently serious national security threat. The “Constitution of necessity” is wrong. This Article explains that

Peter Brandon Bayer



Frederick Douglass Changed My Mind about the Constitution  

ERIC Educational Resources Information Center

Frederick Douglass dramatically and publicly changed his own mind about the Constitution. Like Frederick Douglass, the author had originally viewed the Constitution as pro-slavery. Yet a close look at Douglass's writings revealed a Constitution that empowered the federal government to abolish slavery.

Oakes, James



Recent Developments in Russian Constitutional and Administrative Law  

Microsoft Academic Search

This article is a brief sketch of recent development of the doctrine and practice in Russian constitutional and administrative law. The focus is made on the controversial issues of state organization and status of individuals, as well as the realization of legal principles established by the Constitution of the Russian Federation in 1993.\\u000aThe Constitution of the Russian Federation adopted

Sergey A. Belov



On the treatment of non-solvable implicit constitutive relations in solid mechanics  

NASA Astrophysics Data System (ADS)

We report results concerning the treatment of elastic bodies described by implicit constitutive relations which are not solvable, in the sense of expressing the stresses as functions of the strains or vice versa. Motivated by the theory of generalized hyperelastic materials, which applies also to polyatomic crystals, the field equations to be solved for a body described by a non-solvable implicit constitutive relation in the above sense are lied down. In addition to the momentum equation, auxiliary variables come into play. These variables are accompanied by an equation governing them. We specialize to the case of an isotropic constitutive relation and give some conditions in order for a broad subclass of an isotropic body to be a generalized material. Then, we lay down the field equations for such a body.

Sfyris, D.; Bustamante, R.



Enhancing activity of N-glycosylation for constitutive proteins secretions in non-polarized cells  

SciTech Connect

Several fusion proteins of mouse Interleukins (mILs) and the enhanced green fluorescent protein (EGFP) were expressed in fibroblast and epithelial cells. Among these proteins, the mIL-31 derivative was the most efficiently secreted into the medium in a N-glycosylation-dependent manner. From the analysis of deletion mutants, the minimal structure for constitutive secretions consisted of a signal peptide and N-glycosylation. Introduction of the signal sequence from mIL-31 to human p53 protein failed to secrete the products, but further addition of the N-glycosylation site resulted in constitutive secretion of biologically active p53 protein into the medium in the N-glycosylated form. In this report, we showed the importance of N-glycosylation for constitutive protein secretions, especially using non-polarized cells.

Akiyama, Nobutake, E-mail: [Department of Molecular Immunology, Institute of DNA medicine, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan)] [Department of Molecular Immunology, Institute of DNA medicine, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan); Ohno, Yuji [Department of Pharmacology, Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan)] [Department of Pharmacology, Jikei University School of Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan); Fukuda, Takahiro [Division of Neuropathology, Dept. of Neuroscience, Research Center of Medical Science, The Jikei Univ. Schl. Med., 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461 (Japan)] [Division of Neuropathology, Dept. of Neuroscience, Research Center of Medical Science, The Jikei Univ. Schl. Med., 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105-8461 (Japan); Manome, Yosinobu [Department of Molecular Cell Biology, Institute of DNA medicine, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan)] [Department of Molecular Cell Biology, Institute of DNA medicine, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan); Saito, Saburo [Department of Molecular Immunology, Institute of DNA medicine, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan)] [Department of Molecular Immunology, Institute of DNA medicine, Jikei University, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8461 (Japan)



Constitutive Theory Developed for Monolithic Ceramic Materials  

NASA Technical Reports Server (NTRS)

With the increasing use of advanced ceramic materials in high-temperature structural applications such as advanced heat engine components, the need arises to accurately predict thermomechanical behavior that is inherently time-dependent and that is hereditary in the sense that the current behavior depends not only on current conditions but also on the material's thermomechanical history. Most current analytical life prediction methods for both subcritical crack growth and creep models use elastic stress fields to predict the time-dependent reliability response of components subjected to elevated service temperatures. Inelastic response at high temperatures has been well documented in the materials science literature for these material systems, but this issue has been ignored by the engineering design community. From a design engineer's perspective, it is imperative to emphasize that accurate predictions of time-dependent reliability demand accurate stress field information. Ceramic materials exhibit different time-dependent behavior in tension and compression. Thus, inelastic deformation models for ceramics must be constructed in a fashion that admits both sensitivity to hydrostatic stress and differing behavior in tension and compression. A number of constitutive theories for materials that exhibit sensitivity to the hydrostatic component of stress have been proposed that characterize deformation using time-independent classical plasticity as a foundation. However, none of these theories allow different behavior in tension and compression. In addition, these theories are somewhat lacking in that they are unable to capture the creep, relaxation, and rate-sensitive phenomena exhibited by ceramic materials at high temperatures. The objective of this effort at the NASA Lewis Research Center has been to formulate a macroscopic continuum theory that captures these time-dependent phenomena. Specifically, the effort has focused on inelastic deformation behavior associated with these service conditions by developing a multiaxial viscoplastic constitutive model that accounts for time-dependent hereditary material deformation (such as creep and stress relaxation) in monolithic structural ceramics. Using continuum principles of engineering mechanics, we derived the complete viscoplastic theory from a scalar dissipative potential function.

Janosik, Lesley A.



Constitutive Relation in Transitional Granular Flows  

NASA Technical Reports Server (NTRS)

To study the constitutive behavior of granular materials, the presence of gravity is detrimental. Although empirical relations have been obtained for engineering designs to control granular flows on Earth, it is not known how well these Earthbound relations can be used in another gravity field. Fundamental understanding must be derived to reliably design for granular flows in space exploration. There are two extremes of granular flows of which significant amount of knowledge is available. One deals with a dense and quasi-static situation where the deformation rate nearly vanishes. The other deals with dilute and rapidly fluctuating grain velocities where particle inertia dominates. This project, funded by the NASA Microgravity Fluid Physics Program, aims to study this transitional regime via physical experiments and computer simulations. A conceptual model has been established as described below. There are two natural time scales in a granular flow. One is the travel time between two consecutive collisions and the other is the duration of a collision contact. At a very low shear-rate, the shear-induced particle velocity is low. Hence the travel time between collisions is longer than the contact time between colliding particles. Binary collisions prevail. As the shear-rate increases, the traveling time between collisions reduces and the probability of multiple collisions goes up. These particle groups disperse shortly after and new groups form. When shear-rate is further increased, clusters grow in size due to an increasing chance for free particles to join before groups have the time to disperse. The maximum cluster size may depend on the global concentration and material properties. As the solid concentration approaches zero, the cluster size goes to one particle diameter. The maximum possible cluster size under any condition is the container size, provided that the shear flow is inside a container. The critical shear-rates that dictate the initiation of the multiple contacts, and the size and lifetime of the collision clusters, are functions of the concentration also. A 'regime' theory has been proposed by Babic et al. This theory suggested that both the solid concentration, C, and the non-dimensional shear-rate, B, are important in determining the regimes of the granular constitutive law. Additional information is included in the original extended abstract.

Shen, Hayley H.; Hanes, Daniel M.; Jenkins, James T.



Cosmic Microwave Background Polarization  

E-print Network

Cosmic microwave background (CMB) anisotropy is our richest source of cosmological information; the standard cosmological model was largely established thanks to study of the temperature anisotropies. By the end of the decade, the Planck satellite will close this important chapter and move us deeper into the new frontier of polarization measurements. Numerous ground--based and balloon--borne experiments are already forging into this new territory. Besides providing new and independent information on the primordial density perturbations and cosmological parameters, polarization measurements offer the potential to detect primordial gravity waves, constrain dark energy and measure the neutrino mass scale. A vigorous experimental program is underway worldwide and heading towards a new satellite mission dedicated to CMB polarization.

James G. Bartlett



[Consequences of the judgment of the Federal Constitutional Court on the fighting dog problem].  


The Federal Constitutional Court decided with its "Dangerous dog-judgment" about the constitutional complaint of 53 dog breeders on the federal act combating dangerous dogs. This judgment was a so-called Pyrrhic Victory for the appellants. The Court declared the legislative competence of the federal level in this issue for null and void. But the statutory prohibition for breeding Pitbull-Terrier-, American Staffordshire-Terrier-, Staffordshire-Bullterrier-, Bullterrier-races and cross breeding out of this dogs will be governed in police laws by the Laender finally. The Standing Conference of the Ministers for Internal Affairs declared an appropriate recommendation. The use of the category "race" was refused by experts in discussions as completely wrong and not acceptable. But the Federal Constitutional Court reasons that the legislator can use the category "race" within his scope of evaluation and prognostication in accordance with the Constitution for the ban of import of dangerous dogs. The Court demands--because of the weak data background - that the legislator monitors the legislation, to adjust it according to current developments. The Constitutional Court creates with the judgment "dangerous dogs" legal certainty. The jurisprudence of the administrative courts of the Laender and of the Federal Administrative Court based on the category "race" was approved as well as the police laws of the Laender dealing with dangerous dogs. PMID:15847070

Hülsenbusch, M



Constitutive Modeling of Magnesium Alloy Sheets  

SciTech Connect

Magnesium alloy sheets have unique mechanical properties: high in-plane anisotropy/asymmetry of yield stress and hardening response, which have not been thoroughly studied. The unusual mechanical behavior of magnesium alloys has been understood by the limited symmetry crystal structure of h.c.p metals and thus by deformation twinning. In this paper, the phenomenological continuum plasticity models considering the unusual plastic behavior of magnesium alloy sheet were developed for a finite element analysis. A new hardening law based on two-surface model was developed to consider the general stress-strain response of metal sheets such as Bauschinger effect, transient behavior and the unusual asymmetry. Three deformation modes observed during the continuous tension/compression tests were mathematically formulated with simplified relations between the state of deformation and their histories. In terms of the anisotropy and asymmetry of the initial yield stress, the Drucker-Prager's pressure dependent yield surface was modified to include the anisotropy of magnesium alloys. Also, characterization procedures of material parameters for the constitutive equations were presented and finally the correlation of simulation with measurements was performed to validate the proposed theory.

Lee, M. G.; Piao, K.; Wagoner, R. H. [Department of Materials Science and Engineering, 2041 College Road, Ohio State University, Columbus, OH 43210 (United States); Lee, J. K. [Department of Mechanical Engineering, Scott Laboratory, 201 West 19th Avenue, Ohio State University, Columbus, OH 43210 (United States); Chung, K. [School of Materials Science and Engineering, Intelligent Textile System Research Center, Seoul National University, 56-1, Shinlim-Dong, Kwanak-Ku, Seoul 151-742 (Korea, Republic of); Kim, H. Y. [Division of Mechanical Engineering and Mechatronics, Kangwon National University, 192-1 Hyoja 2-Dong, Chunchon, Gangwon-Do, 200-701 (Korea, Republic of)



A Constitutive Equation for Stratospheric Balloon Materials  

NASA Technical Reports Server (NTRS)

The selection of a suitable material for use as a reliable stratospheric balloon gas barrier and structural component is based on a variety of properties. Due to a more desirable combination of properties, the low density polyethylene that has been used for the last half century has been replaced during the last decade by linear low density polyethylene (LLDPE). This paper describes the effort to characterize the time dependent properties of a 38 micron coextrusion of LLDPE. The nonlinear viscoelastic constitutive equation presented may be used to accurately describe the creep and/or relaxation of this film when subjected to a biaxial state of stress, such as might be required for an extended balloon flight. Recent laboratory data have been used to mod@ an existing model of LLDPE to account for differences caused by the coextrusion process. The new model will facilitate structural design optimization and reliability assessment, and may be further utilized as a predictive tool to benefit in-flight operations. Current structural analysis tech&ques based on linear elastic properties have predicted stresses in excess of those which would actually exist.

Rand, J. L.; Sterling, W. J.



Geographical Gerontology: the constitution of a discipline.  


Health and healthcare have always been central considerations in geographical gerontology. This paper reviews progress in this part of the field over the past decade (1995-2006) and also looks to the future. It demonstrates how geographical gerontology is currently constituted of multiple fields of empirical interest studied by multiple academic disciplines. Specifically, the continuation and development of traditional perspectives on older population health--in terms of dynamics, distributions and movements--are traced, as well as emerging post-modern perspectives and qualitative approaches that sensitively investigate the complex relationships between older people and the varied places within which they live and are cared for. Mirroring theoretical developments and diversity in the social sciences, the future research challenges that lie ahead will involve the articulation of varied and often hidden cultural practices and social processes, and hitherto taken-for-granted--as well as new--social and spatial relations, between older people, health and place. If however geographical gerontology is to meet these challenges most effectively, there has to be greater collaboration and communication within and between its constituent disciplines and diverse empirical areas. This will help it become recognized to a greater degree as a distinct discipline. PMID:17459544

Andrews, Gavin J; Cutchin, Malcolm; McCracken, Kevin; Phillips, David R; Wiles, Janine



Health Care for Micronesians and Constitutional Rights  

PubMed Central

Under the Compacts of Free Association (COFA), people from the Freely Associated States — the Republic of Palau (ROP), the Republic of the Marshall Islands (RMI), and the Federated States of Micronesia (FSM) — have been migrating to the United States in increasing numbers. In 1996, Congress passed broad welfare reform (Personal Responsibility and Work Opportunity Reconciliation Act) which limited certain federal benefits previously available to COFA migrants, including Medicaid benefits. Prior to July 2010, the State of Hawai‘i had continued to include COFA migrants under its state-funded Medicaid program. In the face of budget constraints, the State removed these people from its Medicaid rolls. A challenge on the legal basis of the denial of equal protection of the laws, ie, the Fourteenth Amendment to the US Constitution, was successful in reinstating health care to the COFA migrants in December 2010. From the health worker's perspective, regardless of various social justice arguments that may have been marshaled in favor of delivering health care to the people, it was an appeal to the judicial system that succeeded. From the attorney's perspective, the legal victories are potentially limited to the four walls of the courtroom without community involvement and related social justice movements. Together, the authors propose that in order to better address the issue of health care access for Micronesian peoples, we must work together, as health and legal advocates, to define a more robust vision of both systems that includes reconciliation and community engagement. PMID:22235150

Shek, Dina



Constitutive modeling for single crystal superalloys  

NASA Technical Reports Server (NTRS)

The inelastic response of single crystal gamma/gamma prime superalloys is quite different from the behavior of polycrystalline nickel base superalloys. Upto a critical temperature the yield stress of single crystal alloys is a function of the material orientation relative to the direction of the applied stress and the material exhibits significant tension/compression asymmetry. This behavior is primarily due to slip on the octahedral slip system. Above the critical temperature there is a sharp drop in the yield stress, cube slip becomes more predominant and the tension/compression asymmetry is reduced. Similar orientation and tension/compression asymmetry is observed in creep and secondary creep above the critical temperature is inferred to occur by octahedral slip. There are two exceptions to this behavior. First, loading near the (111) orientation exhibits cube slip at all temperatures, and; second, loading near the (001) orientation produces only octahedral slip at all temperatures. The constitutive model is based on separating the total global strain into elastic and inelastic components. This model is developed and briefly discussed.

Stouffer, D. C.; Jayaraman, N.; Sheh, M.; Alden, D.



Elastic-Plastic Constitutive Equation of WC-Co Cemented Carbides with Anisotropic Damage  

SciTech Connect

Elastic-plastic constitutive equation of WC-Co cemented carbides with anisotropic damage is proposed to predict a precise service life of cold forging tools. A 2nd rank symmetric tensor damage tensor is introduced in order to express the stress unilaterality; a salient difference in uniaxial behavior between tension and compression. The conventional framework of irreversible thermodynamics is used to derive the constitutive equation. The Gibbs potential is formulated as a function of stress, damage tensor, isotropic hardening variable and kinematic hardening variable. The elastic-damage constitutive equation, conjugate forces of damage, isotropic hardening and kinematic hardening variable is derived from the potential. For the kinematic hardening variable, the superposition of three kinematic hardening laws is employed in order to improve the cyclic behavior of the material. For the evolution equation of the damage tensor, the damage is assumed to progress by fracture of the Co matrix - WC particle interface and by the mechanism of fatigue, i.e. the accumulation of microscopic plastic strain in matrix and particles. By using the constitutive equations, calculation of uniaxial tensile and compressive test is performed and the results are compared with the experimental ones in the literature. Furthermore, finite element analysis on cold forward extrusion was carried out, in which the proposed constitutive equation was employed as die insert material.

Hayakawa, Kunio; Nakamura, Tamotsu; Tanaka, Shigekazu [Department of Mechanical Engineering, Shizuoka University, 3-5-1 Johoku, Hamamatsu 432-8561 (Japan)



Bioelectrical impedance phase angle in constitutionally lean females, ballet dancers and patients with anorexia nervosa  

Microsoft Academic Search

Background\\/objective:Several articles have described body composition in anorexia nervosa, whereas little is known about this issue in underweight ballet dancers and constitutionally lean females. The main aim of this study was to assess whether phase angle (a bioimpedance variable related to body cell mass) differs according to the type of underweight in female adolescents and young women.Subjects\\/methods:Skinfold thicknesses and bioimpedance

M Marra; A Caldara; C Montagnese; E De Filippo; F Pasanisi; F Contaldo; L Scalfi



A micromorphic model for monolayer hexagonal boron nitride with determined constitutive constants by phonon dispersions  

NASA Astrophysics Data System (ADS)

A two dimensional (2D) micromorphic model is developed for monolayer hexagonal boron nitride (h-BN). Theoretical expressions of phonon dispersions for 2D crystals are derived based on the simplified governing equations of specialized three dimensional micromorphic crystals. The constitutive constants of governing equations of the h-BN micromorphic model are determined, which is performed by fitting the available phonon dispersions data of experimental measurements and first-principles calculations with our theoretical expressions. The obtained Young's modulus and Poisson's ratio of h-BN are comparable with the results of ab initio calculations and inelastic x-ray scattering experiments, thus the constitutive relations of the h-BN model are verified, which also indicates that mechanical properties of monolayer h-BN could be characterized by our 2D micromorphic model.

Zhang, Bin; Yang, Gang



Tetraethylammonium block of water flux in Aquaporin1 channels expressed in kidney thin limbs of Henle's loop and a kidney-derived cell line  

Microsoft Academic Search

BACKGROUND: Aquaporin-1 (AQP1) channels are constitutively active water channels that allow rapid transmembrane osmotic water flux, and also serve as cyclic-GMP-gated ion channels. Tetraethylammonium chloride (TEA; 0.05 to 10 mM) was shown previously to inhibit the osmotic water permeability of human AQP1 channels expressed in Xenopus oocytes. The purpose of the present study was to determine if TEA blocks osmotic

Andrea J Yool; Olga H Brokl; Thomas L Pannabecker; William H Dantzler; W Daniel Stamer



Origin of compaction bands: Anti-cracking or constitutive instability?  

NASA Astrophysics Data System (ADS)

Based on the theoretical analysis and finite-difference simulations, we study the onset and evolution of tabular compaction bands. In numerical models the bands are initiated as constitutive instabilities resulting from the deformation bifurcation. Then some bands are dying, while others continue to evolve accumulating the inelastic deformation/damage and compressive stress at their tips. The stress concentration/increase, however, does not exceed 0.1% of the background value. Starting from some stage, the bands begin to propagate similarly to cracks. At the next stage the propagation slows down simultaneously with the beginning of bands' thickening that occurs due to incorporation of not yet compacted material at the band flanks. The response of the already compacted "core" part of the band becomes mostly elastic. Then the propagation practically stops and the bands undergo only the heterogeneous thickening, maximal in the middle of the band and reducing toward its tips. This scenario obtained directly in the models (without any specific hypotheses about the propagation mechanism) appears more complicated than what can be expected from the linear elastic fracture mechanics (anti-crack) model. The band propagation distance is proportional to the initial (resulted from the bifurcation) band length that in turn is proportional to the hardening modulus and theoretically can reach infinity.

Chemenda, Alexandre I.



The normative constitution of professional power.  


This article concerns the manner in which we think and talk about power in health care policy and regulation, and the political and social practices allied with that discourse. I assert that in health care policy and practice we speak of and live within the era of countervailing power. In this language and practice power is a force exercised by one actor to enforce its will against another actor against whom power is exerted. I contend that this language inculcates an individual and social passivity in which citizens rely upon various types of representatives to constitute health care for them in a manner in which they do not and cannot participate. However, this language of power and the political and social practice with which it is associated is merely a contingent, historical product. I claim that an alternative discourse of power is possible, in which power consists of the social interactions in which all of us mutually participate but no one of us can control. Power in this sense is participatory by nature, and because no one is in control, it makes no sense to relegate tasks to specialized, nonparticipatory domains. This alternative discourse of power, therefore, might call forth participatory practices in health care and a concomitant diminution of specialization and expansion of the public sphere. The result would be to blur the lines separating politics from everyday interaction, politics from economy, professionals from patients, and insurers from insureds. Participation would mean much more than casting a vote or writing a check but would also include the mutual sharing of time and energy in the tasks that need to be done: long-term and short-term care, practices of prevention, caring for the chronically ill, and monitoring bureaucratic and professional activities. PMID:9057126

Frankford, D M



A Proposed Three-Dimensional Constitutive Model for Shape Memory Alloys  

Microsoft Academic Search

The shape memory alloy (SMA) stress-strain response associated with martensitic twinning hysteresis and austenite-martensite\\/martensite-austenite superelasticity is modeled using constitutive equations. Compared to the modeling work done on viscoelastic and viscoplastic be havior, this has been an area of limited study. The equations which are presented here express the growth of inelastic strain in a rate-type formulation similar to viscoplastic laws.

E. J. Graesser; F. A. Cozzarelli



Constitutive Activation of Stat3 Signaling Confers Resistance to Apoptosis in Human U266 Myeloma Cells  

Microsoft Academic Search

Interleukin 6 (IL-6) is the major survival factor for myeloma tumor cells and induces signaling through the STAT proteins. We report that one STAT family member, Stat3, is constitutively activated in bone marrow mononuclear cells from patients with multiple myeloma and in the IL-6-dependent human myeloma cell line U266. Moreover, U266 cells are inherently resistant to Fas-mediated apoptosis and express

Robyn Catlett-Falcone; Terry H Landowski; Marc M Oshiro; James Turkson; Alexander Levitzki; Rocco Savino; Gennaro Ciliberto; Lynn Moscinski; Jose Luis Fernández-Luna; Gabriel Nuñez; William S Dalton; Richard Jove



Chromatin-Dependent Cooperativity between Constitutive and Inducible Activation Domains in CREB  

Microsoft Academic Search

The cyclic AMP (cAMP)-responsive factor CREB induces target gene expression via constitutive (Q2) and inducible (KID, for kinase-inducible domain) activation domains that function synergistically in response to cellular signals. KID stimulates transcription via a phospho (Ser133)-dependent interaction with the coacti- vator paralogs CREB binding protein and p300, whereas Q2 recruits the TFIID complex via a direct associ- ation with hTAFII130.




Ethanol inducible expression of a mesophilic cellulase avoids adverse effects on plant development  

PubMed Central

Background Plant-produced biomass-degrading enzymes are promising tools for the processing of lignocellulose to fermentable sugars. A major limitation of in planta production is that high-level expression of such enzymes could potentially affect the structure and integrity of the plant cell wall and negatively influence plant growth and development. Results Here, we evaluate the impact on tobacco plant development of constitutive versus alcohol-inducible expression of the endoglucanase TrCel5A from the mesophilic fungus Trichoderma reesei. Using this system, we are able to demonstrate that constitutive expression of the enzyme, controlled by the doubled Cauliflower Mosaic Virus promoter, leads to lower cellulose content of the plant combined with severe effects on plant growth. However, using an alcohol-inducible expression of the endoglucanase in the plant leaves, we achieved similar enzymatic expression levels with no changes in the crystalline cellulose content. Conclusion We were able to produce significant amounts of cellulase in the plant leaves without detrimental effects to plant development. These results demonstrate the potential feasibility of an inducible expression system for producing biomass degrading enzymes in plants. PMID:23587418



Molecular pharmacological phenotyping of EBI2. An orphan seven-transmembrane receptor with constitutive activity.  


Epstein-Barr virus (EBV)-induced receptor 2 (EBI2) is an orphan seven-transmembrane (7TM) receptor originally identified as the most up-regulated gene (>200-fold) in EBV-infected cells. Here we show that EBI2 signals with constitutive activity through Galpha(i) as determined by a receptor-mediated inhibition of forskolin-induced cAMP production and an induction of the serum response element-driven transcriptional activity in a pertussis toxin-sensitive manner. Galpha(s) and Galpha(q) were not activated constitutively as determined by the lack of cAMP production, the lack of inositol phosphate turnover, and the lack of activities of the transcription factors: cAMP response element-binding protein and nuclear factor-kappaB. Immunohistochemistry and confocal microscopy of FLAG- and green fluorescent protein-tagged EBI2 revealed cell-surface expression. A putative N-terminal truncated version of EBI2, delta4-EBI2, showed similar expression and signaling through Galpha(i) as full-length EBI2. By using a 32P-labeled EBI2 probe we found a very high expression in lymphoid tissue (spleen and lymph node) and peripheral blood mononuclear cells and a high expression in lung tissue. Real-time PCR of EBV-infected cells showed high expression of EBI2 during latent and lytic infection, in contrast to the EBV-encoded 7TM receptor BILF1, which was induced during lytic infection. EBI2 clustered with the orphan GPR18 by alignment analysis as well as by close proximity in the chromosomal region 13q32.3. Based on the constitutive signaling and cellular expression pattern of EBI2, it is suggested that it may function in conjunction with BILF1 in the reprogramming of the cell during EBV infection. PMID:16540462

Rosenkilde, Mette M; Benned-Jensen, Tau; Andersen, Helene; Holst, Peter J; Kledal, Thomas N; Lüttichau, Hans R; Larsen, Jørgen K; Christensen, Jan P; Schwartz, Thue W



First Federal Appeals Court finds anti-violence law constitutional.  


In a unanimous decision issued on February 13, (1995) a three-judge panel of the U.S. Court of Appeals for the Fourth Circuit upheld the dismissal of two anti-choice challenges to the Freedom of Access to Clinic Entrances Act (FACE). The first mid-level federal bench to rule on FACE's validity, the appeals court held that the law "strikes a balance among competing rights holders. It protects those who seek or provide reproductive health services without suppressing robust debate about abortion. Those opposed to abortion or any other reproductive health service retain the freedom to express their deeply-held moral or religious views in a peaceful, non-obstructive way." In mid-June of last year in American Life League v. Reno, U.S. District Court Judge Leonie Brinkema in Alexandria, Virginia, found that FACE did not violate abortion opponents' First Amendment rights. In open court the next month, Judge Brinkema dismissed Woodall v. Reno, which was filed by an abortion opponent in concert with Concerned Women for America. The cases were consolidated on appeal. Attorneys for the plaintiffs have indicated that they will seek U.S. Supreme Court review. Every other federal court to rule on FACE since its May 1994 enactment has also found the measure constitutional. PMID:12346135



Dual action of oestrogens on the mouse constitutive androstane receptor.  

PubMed Central

mCAR (mouse constitutive androstane receptor; NR1I3) controls the expression of cytochrome P450 as well as other enzymes involved in drug and steroid metabolism. The high basal activity of mCAR can be modulated by inhibitory steroids related to androstenol and by activating xenobiotic chemicals such as 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene and chlorpromazine. The ability of oestrogens and some other xenobiotics to activate mCAR is not clear. In the present study, co-transfection assays in HEK-293 cells indicated that oestrogens varied in their efficacy to activate mCAR, depending on variation at the steroid D-ring and position of hydroxy groups. In general, oestrogens were weaker activators of mCAR than 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene and chlorpromazine. Also, the induction of CYP2B10 mRNA by oestrogens was less pronounced in mouse primary hepatocytes. Yeast two-hybrid assays indicated that, unlike androstenol and the established activators, oestrogens attracted both nuclear receptor co-repressors and co-activators to the mCAR ligand-binding domain, thus limiting the extent of mCAR activation. This novel dual action is not limited to oestrogens, but is shared by some xenobiotic CYP2B inducers such as clotrimazole and methoxychlor. These findings offer an alternative explanation for the recently suggested nuclear activation step of mCAR. PMID:12948398

Makinen, Janne; Reinisalo, Mika; Niemi, Kaisa; Viitala, Pirkko; Jyrkkarinne, Johanna; Chung, Hinfan; Pelkonen, Olavi; Honkakoski, Paavo



Unlike for Human Monocytes after LPS Activation, Release of TNF-? by THP-1 Cells Is Produced by a TACE Catalytically Different from Constitutive TACE  

PubMed Central

Background Tumor necrosis factor-alpha (TNF-?) is a pro-inflammatory cytokine today identified as a key mediator of several chronic inflammatory diseases. TNF-?, initially synthesized as a membrane-anchored precursor (pro-TNF-?), is processed by proteolytic cleavage to generate the secreted mature form. TNF-? converting enzyme (TACE) is currently the first and single protease described as responsible for the inducible release of soluble TNF-?. Methodology/Principal Findings Here, we demonstrated the presence on THP-1 cells as on human monocytes of a constitutive proteolytical activity able to cleave pro-TNF-?. Revelation of the cell surface TACE protein expression confirmed that the observed catalytic activity is due to TACE. However, further studies using effective and innovative TNF-? inhibitors, as well as a highly selective TACE inhibitor, support the presence of a catalytically different sheddase activity on LPS activated THP-1 cells. It appears that this catalytically different TACE protease activity might have a significant contribution to TNF-? release in LPS activated THP-1 cells, by contrast to human monocytes where the TACE activity remains catalytically unchanged even after LPS activation. Conclusions/Significance On the surface of LPS activated THP-1 cells we identified a releasing TNF-? activity, catalytically different from the sheddase activity observed on human monocytes from healthy donors. This catalytically-modified TACE activity is different from the constitutive shedding activity and appears only upon stimulation by LPS. PMID:22479555

Moreira-Tabaka, Helena; Peluso, Jean; Vonesch, Jean-Luc; Hentsch, Didier; Kessler, Pascal; Reimund, Jean-Marie; Dumont, Serge; Muller, Christian D.



The Aryl Hydrocarbon Receptor Is Constitutively Active in Advanced Prostate Cancer Cells  

PubMed Central

Background Distant prostate cancers are commonly hormone refractory and exhibit increased growth no longer inhibited by androgen deprivation therapy. Understanding all molecular mechanisms contributing to uncontrolled growth is important to obtain effective treatment strategies for hormone refractory prostate cancers (HRPC). The aryl hydrocarbon receptor (AhR) affects a number of biological processes including cell growth and differentiation. Several studies have revealed that exogenous AhR ligands inhibit cellular proliferation but recent evidence suggests AhR may possess intrinsic functions that promote cellular proliferation in the absence of exogenous ligands. Methods/Results qRT-PCR and western blot analysis was used to determine AhR mRNA and protein expression in hormone sensitive LNCaP cells as well as hormone refractory DU145, PC3 and PC3M prostate cancer cell lines. LNCaP cells express AhR mRNA and protein at a much lower level than the hormone refractory cell models. Cellular fractionation and immunocytochemistry revealed nuclear localization of AhR in the established hormone refractory cell lines while LNCaP cells are devoid of nuclear AhR protein. qRT-PCR analysis used to assess basal CYP1B1 levels and a xenobiotic responsive element binding assay confirmed ligand independent transcriptional activity of AhR in DU145, PC3 and PC3M cells. Basal CYP1B1 levels were decreased by treatment with specific AhR inhibitor, CH223191. An in vitro growth assay revealed that CH223191 inhibited growth of DU145, PC3 and PC3M cells in an androgen depleted environment. Immunohistochemical staining of prostate cancer tissues revealed increased nuclear localization of AhR in grade 2 and grade 3 cancers compared to the well differentiated grade 1 cancers. Conclusions Together, these results show that AhR is constitutively active in advanced prostate cancer cell lines that model hormone refractory prostate cancer. Chemical ablation of AhR signaling can reduce the growth of advanced prostate cancer cells, an effect not achieved with androgen receptor inhibitors or growth in androgen depleted media. PMID:24755659

Richmond, Oliver; Ghotbaddini, Maryam; Allen, Cidney; Walker, Alice; Zahir, Shokouh; Powell, Joann B.



Integrable Background Geometries  

NASA Astrophysics Data System (ADS)

This work has its origins in an attempt to describe systematically the integrable geometries and gauge theories in dimensions one to four related to twistor theory. In each such dimension, there is a nondegenerate integrable geometric structure, governed by a nonlinear integrable differential equation, and each solution of this equation determines a background geometry on which, for any Lie group G, an integrable gauge theory is defined. In four dimensions, the geometry is selfdual conformal geometry and the gauge theory is selfdual Yang-Mills theory, while the lower-dimensional structures are nondegenerate (i.e., non-null) reductions of this. Any solution of the gauge theory on a k-dimensional geometry, such that the gauge group H acts transitively on an ?-manifold, determines a (k+?)-dimensional geometry (k+??4) fibering over the k-dimensional geometry with H as a structure group. In the case of an ?-dimensional group H acting on itself by the regular representation, all (k+?)-dimensional geometries with symmetry group H are locally obtained in this way. This framework unifies and extends known results about dimensional reductions of selfdual conformal geometry and the selfdual Yang-Mills equation, and provides a rich supply of constructive methods. In one dimension, generalized Nahm equations provide a uniform description of four pole isomonodromic deformation problems, and may be related to the {SU}(?) Toda and dKP equations via a hodograph transformation. In two dimensions, the {Diff}(S^1) Hitchin equation is shown to be equivalent to the hyperCR Einstein-Weyl equation, while the {SDiff}(?^2) Hitchin equation leads to a Euclidean analogue of Plebanski's heavenly equations. In three and four dimensions, the constructions of this paper help to organize the huge range of examples of Einstein-Weyl and selfdual spaces in the literature, as well as providing some new ! ones. The nondegenerate reductions have a long ancestry. More ! recently , degenerate or null reductions have attracted increased interest. Two of these reductions and their gauge theories (arguably, the two most significant) are also described.

Calderbank, David M. J.



MAR Background Report MAR Background Report: Indigenous Protest in Brazil  

E-print Network

MAR Background Report MAR Background Report: Indigenous Protest in Brazil Hundreds of indigenous. According to MAR data, several violent incidents against landowners, miners and others have been observed groups worldwide #12;MAR Background Report About the Minorities at Risk Project The Minorities at Risk

Milchberg, Howard


The ethical foundations of constitutional order: A conventionalist perspective  

Microsoft Academic Search

This paper presents a conventionalist or modified contractarian perspective on constitutional and legal theory as a platform\\u000a from which to address five important questions about the connections between critical morality and constitutional order. It\\u000a finds that natural law and critical morality are inappropriately linked to constitutions and laws, but that there is nonetheless\\u000a a clear moral dimension to all law.

Noel B. Reynolds



The dietary terpene lupeol targets colorectal cancer cells with constitutively active Wnt/?-catenin signaling  

PubMed Central

Scope Aberrant activation of the Wingless-type mouse mammary tumor virus integration site family (Wnt)/?-catenin signaling pathway is the most common modification, and often considered, a hallmark of colorectal cancer (CRC). Typically in this pathway the ?-catenin translocates from the cytoplasm to the nucleus, where it functions as a transcription regulator of several genes that support tumor formation and progression. Thus, any agent that could attenuate the translocation of ?-catenin could be extremely valuable against CRC, especially the tumors that exhibit constitutively active Wnt/?-catenin signaling. Methods & Results Using human CRC cells that exhibit differential expression of Wnt/?-catenin signaling, we demonstrate that treatment of CRC cells with dietary triterpene lupeol results in a dose dependent i) decrease in cell viability, ii) induction of apoptosis, iii) decrease in colonogenic potential, iv) decrease in ?-catenin transcriptional activity, and v) decrease in the expression of Wnt target genes. Most importantly lupeol was observed to inhibit the translocation of ?-catenin from the cytoplasm to the nucleus. Importantly, all these effects of lupeol were restricted to cells that harbor constitutively active Wnt/?-catenin signaling while negligible effects were observed in cells that lack constitutively active Wnt/?-catenin signaling. Further, we also demonstrate that inhibition of Wnt signaling in cells with constitutive active Wnt/?-catenin results in loss of lupeol efficacy while inducing Wnt signaling sensitizes the cells to inhibitory effects of lupeol. Conclusions In summary, our data strongly advocate the efficacy of lupeol against CRC cells that exhibit constitutively active Wnt/?-catenin signaling. PMID:23836602

Tarapore, Rohinton S.; Siddiqui, Imtiaz A.; Adhami, Vaqar M.; Spiegelman, Vladimir S.; Mukhtar, Hasan



Generation of Cre Transgenic Mice with Postnatal RPE-Specific Ocular Expression  

PubMed Central

Purpose. To generate and characterize a constitutively active, RPE-specific, cre-expressing transgenic mouse line. This line can be used to create RPE-specific knockouts by crossing with mice harboring loxP-flanked (floxed) genes. Methods. A transgene construct was assembled with the BEST1 promoter driving cre expression. Transgenic mice were generated on a C57BL/6 background. Cre expression was assessed by immunofluorescence and Western blot analysis. Cre enzymatic activity was tested by crossing to three lines with floxed DNA regions and detecting deletion of the intervening sequences or through histochemical detection of lacZ activity. Potential cre-mediated toxicity was assessed by retinal histology up to 24 months of age and by electroretinography. Results. The BEST1-cre line with expression in the highest percentage of RPE cells displayed a patchy mosaic expression pattern, with 50% to 90% of RPE cells expressing cre. In mice outcrossed to a mixed B6/129 background, expression was consistently found in 90% of RPE cells. Within the eye, only the RPE cells were immunoreactive with an anti-cre antibody. Maximum cre expression quantified by Western blot analysis occurred at P28. Crosses with three lines containing floxed sequences revealed RPE-specific cre activity in the eye and extraocular expression limited to the testes. Histology and electroretinography showed no cre-mediated RPE toxicity. Conclusions. This BEST1-cre transgenic line enables generation of RPE-specific knockout mice. The mosaic expression pattern provides an internal control; the non–cre-expressing RPE cells continue to express the floxed genes. These mice should facilitate study of the multifunctional RPE and the generation of mouse models of human retinal disease. PMID:21212186

Iacovelli, Jared; Zhao, Chen; Wolkow, Natalie; Veldman, Peter; Gollomp, Kandace; Ojha, Pallavi; Lukinova, Nina; King, Ayala; Feiner, Leonard; Esumi, Noriko; Zack, Donald J.; Pierce, Eric A.; Vollrath, Douglas



Nonlinear Constitutive Relations for High Temperature Application, 1984  

NASA Technical Reports Server (NTRS)

Nonlinear constitutive relations for high temperature applications were discussed. The state of the art in nonlinear constitutive modeling of high temperature materials was reviewed and the need for future research and development efforts in this area was identified. Considerable research efforts are urgently needed in the development of nonlinear constitutive relations for high temperature applications prompted by recent advances in high temperature materials technology and new demands on material and component performance. Topics discussed include: constitutive modeling, numerical methods, material testing, and structural applications.



Background issues for defensive interceptors.  

National Technical Information Service (NTIS)

Mean nuclear backgrounds are large, but are arguably amenable to frame-to-frame subtraction. Striated backgrounds on the sensors for defensive interceptors could, however, cause clutter leak-through, which could make detection and track difficult. Nominal...

G. H. Canavan



Internal and External Radioactive Backgrounds  

E-print Network

Chapter 3 Internal and External Radioactive Backgrounds New physics is often discovered by pushing of the low energies involved. There are many radioactive elements that have decays at lower energies which;Chapter 3: Internal and External Radioactive Backgrounds 104 the rate of background. High-energy neutrino


REPORT NO. 5 background material  

E-print Network

REPORT NO. 5 background material for the development of radiation protection standards July 1964 Staff Report of the FEDERAL RADIATION COUNCIL #12;REPORT NO. 5 background material for the development INTRODUCTION This report contains background material used in the development of guidance for Federal agencies


Isolation and characterization of an oil palm constitutive promoter derived from a translationally control tumor protein (TCTP) gene.  


We have characterized an oil palm (Elaeis guineensis Jacq.) constitutive promoter that is derived from a translationally control tumor protein (TCTP) gene. The TCTP promoter was fused transcriptionally with the gusA reporter gene and transferred to monocot and dicot systems in order to study its regulatory role in a transient expression study. It was found that the 5' region of TCTP was capable of driving the gusA expression in all the oil palm tissues tested, including immature embryo, embryogenic callus, embryoid, young leaflet from mature palm, green leaf, mesocarp and stem. It could also be used in dicot systems as it was also capable of driving gusA expression in tobacco leaves. The results indicate that the TCTP promoter could be used for the production of recombinant proteins that require constitutive expression in the plant system. PMID:21549610

Masura, Subhi Siti; Parveez, Ghulam Kadir Ahmad; Ti, Leslie Low Eng



Cyanobacterial psbA families in Anabaena and Synechocystis encode trace, constitutive and UVB-induced D1 isoforms  

Microsoft Academic Search

Cyanobacteria cope with UVB induced photoinhibition of Photosystem II by regulating multiple psbA genes to boost the expression of D1 protein (in Synechocystis sp. PCC6803), or to exchange the constitutive D1:1 protein to an alternate D1:2 isoform (in Synechococcus sp. PCC7942). To define more general patterns of cyanobacterial psbA expression, we applied moderately photoinhibitory UVB to Anabaena sp. PCC7120 and

Cosmin I. Sicora; Sarah E. Appleton; Christopher M. Brown; Jonathon Chung; Jillian Chandler; Amanda M. Cockshutt; Imre Vass; Douglas A. Campbell



The Long History of State Constitutions and American Tort Law  

Microsoft Academic Search

In the modern tort reform movement that dates to the mid-1970s, courts have struck down a number of reform statutes as unconstitutional under state constitutions. Commentators on all sides have treated these decisions as a new phenomenon in American law. In fact, American tort law has developed for over a century in the shadow of state (and occasionally federal) constitutional

John F. Witt



On minimal representations for constitutive equations of anisotropic elastic materials  

Microsoft Academic Search

The problem of determining minimal representations for anisotropic elastic constitutive equations is proposed and investigated. For elastic constitutive equations in any given case of anisotropy, it is shown that there exist generating sets consisting of six generators and such generating sets are minimal in all possible generating sets. This fact implies that most of the established results for representations of

Heng Xiao



Simplifications and Comparisons of Shape Memory Alloy Constitutive Models  

Microsoft Academic Search

Here we will present a simplification of the form of one popular shape memory alloy (SMA) constitutive model. This simplification allows a more compact written form and hence easier calculations with the one-dimensional SMA constitutive law first developed by Tanaka, later modified by Liang and Rogers, and again by Brinson. In addition, a new derivation of the model will be

L. C. Brinson; M. S. Huang



One-Dimensional Thermomechanical Constitutive Relations for Shape Memory Materials  

Microsoft Academic Search

The use of the thermoelastic martensitic transformation and its reverse transformation has recently been proposed and demonstrated for several active control ap plications. However, the present constitutive models have lacked several important funda mental concepts that are essential for many of the proposed intelligent material system ap plications such as shape memory hybrid composites.A complete, unified, one-dimensional constitutive model of

C. Liang; C. A. Rogers



Do we understand the physics in the constitutive equation?  

Microsoft Academic Search

Summary The failure of some careful attempts to provide numerical solutions of the equations for non-Newtonian flow suggests to us some inadequacies of the constitutive equations. (After all no one would doubt the validity of the conservation of mass and momentum.) To understand the physics in the constitutive equation, and thence to correct its undesirable features, it is helpful to

J. M. Rallison; E. J. Hinch



Law and Terror in the Age of Colonial Constitution Making  

Microsoft Academic Search

In this exploration into the close relation between terror and law, I attempt first to show that the relation between terror and law is not a simple question of relating violence to law, but to the very process of constitution making. Second, laws relating to terror may or may not find a formal place in the constitution, but this relation

Ranabir Samaddar




E-print Network

AND JEEYEON N. PLOHR Abstract. We examine the approximations made in using Hooke's law as a constitutive equations for the stress involve new terms in addition to the traditional Hooke's law terms. These new terms), the constitutive relations (1.3) and (1.4), which embody the incremental form of Hooke's law, are only approximate


Teaching about the Constitutional Rights of Students. ERIC Digest.  

ERIC Educational Resources Information Center

This ERIC digest presents a rationale for teaching students about their rights and responsibilities as citizens under the U.S. Constitution. Social studies teachers have a special role in shaping the lives of young citizens and influencing whether students become politically involved adults. Specific constitutional rights such as the right of a…

Gottlieb, Stephen S.



E-print Network

AFRICAN AMERICAN AFFINITY GROUP ARTICLES OF THE CONSTITUTION & BYLAWS Date: May 22, 2012 African-American Affinity Group #12;AFRICAN AMERICAN AFFINITY GROUP ARTICLES OF THE CONSTITUTION - 2 - Revised and accepted is the "African -American Affinity Group" (AAAG). ARTICLE II � MISSION SECTION 1 The African-American Affinity


Constitutional Review and Democratic Consolidation: A Literature Review  

Microsoft Academic Search

This paper reviews the literature on the prevalence of constitutional review across the world, and particularly in emerging democracies, during the last two decades. Two major questions should be addressed in this regard. First, why has the judiciary been empowered and what factors affect judicial activism? Second, does constitutional review ensure an effective self-enforcing function? In sum, the literature shows

Yasushi Hazama




Microsoft Academic Search

The intenal structures of the moon, Mars, Venus, and Mercury are ; examined in the light of what is known about the constitution of the earth. A ; review of the seismic determination of the elastic constitution of the earth's ; mantie, using results on the stability of silicates at high pressures, leads to ; the following interpretation: the rapid

Gordon J. F. MacDonald



Constitutions for Local Collective Action and Institutional Interdependence  

Microsoft Academic Search

Collective action can take place at a plurality of levels. It has to be based on a constitution which defines the basic rules of interaction. Here, we are concerned with the problem of the constitutional setting of “bottom-up” formal institutions with a “club” nature. The pressure to improve the efficiency of services pushes local administrations to co-ordinate to produce public

Stefano Solari



Some Problems of Church and State in the Weimar Constitution  

Microsoft Academic Search

Because the United States was a comparatively new nation when its constitution was drafted, it could in many areas—among which church and state is one of the most important—embark upon a revolutionary political and social experiment without having to clear away the debris left by previous builders. The compromises crystalized in the Weimar constitution, on the other hand, represented but

Jan Ginter Deutsch



Reciprocity and the hidden constitution of world trade  

Microsoft Academic Search

In common descriptions of the world trading system, MFN and national treatment embody the principle of non-discrimination. Reciprocity is mostly regarded as a remnant of mercantilist trade policy. This paper argues that reciprocity is the more fundamental constitutional rule, because it reflects the unanimity principle enabling countries to identify Pareto-improving changes of trade policy. I reconstruct the implicit constitution of

Carsten Herrmann-Pillath



A unifying framework for watershed thermodynamics: constitutive relationships  

Microsoft Academic Search

The balance equations for mass and momentum, averaged over the scale of a watershed entity, need to be supplemented with constitutive equations relating flow velocities, pressure potential differences, as well as mass and force exchanges within and across the boundaries of a watershed. In this paper, the procedure for the derivation of such constitutive relationships is described in detail. This

Paolo Reggiani; S. Majid Hassanizadeh; Murugesu Sivapalan; William G. Gray



Equality: Constitutional Update. Bar/School Partnership Programs Series.  

ERIC Educational Resources Information Center

The second in a special four-part series of law-school partnership handbooks on constitutional themes, this document focuses on equality. "Equality--the Forgotten Word" (J. A. Hughes) discusses what has been considered the U.S. Constitution's one flaw, its failure to abolish slavery, and the remedy to that flaw, the Fourteenth Amendment. The issue…

American Bar Association, Chicago, IL. Special Committee on Youth Education for Citizenship.


Equality v. Liberty v. Pluralism: Latinos in American Constitutional Law.  

ERIC Educational Resources Information Center

This paper examines how U.S. courts, particularly the Supreme Court, have applied constitutional law principles to Latino communities and individuals in three areas: public education, the status of Puerto Rico, and jury selection. Consistent with traditional views of American society as biracial (black and white), constitutional law discussions…

Soltero, Carlos R.


Constraining fault constitutive behavior with slip and stress heterogeneity  

E-print Network

Constraining fault constitutive behavior with slip and stress heterogeneity B. T. Aagaard1 and T. H and postshear stress on a fault can be used to constrain fault constitutive behavior beyond that required on a vertical, planar strike-slip fault show that the conditions that lead to slip heterogeneity remain in place

Greer, Julia R.


High strain rate constitutive equation for aluminium metal matrix composites  

SciTech Connect

In this paper, high strain rate constitutive equations are presented for two different types of Al Metal Matrix Composite materials. Simple dynamic compression test results in conjunction with a numerical technique are used to determine the constants of this equation. For comparison, tests were also conducted on pure aluminum. Finally, some important issues relevant to the constitutive models for MMC are outlined.

Hamouda, A.M.S.; Hashmi, M.S.J. [Dublin City Univ. (Ireland). Advance Materials Processing Centre



The Constitutionality of School Choice in New Hampshire  

ERIC Educational Resources Information Center

Does a "school choice" program, under which state funds are disbursed on a neutral basis to parents in the form of a voucher to defray the cost of sending their children to a school of their choice, run afoul of the Establishment Clause of the First Amendment to the United States Constitution, or of the New Hampshire Constitution? No. A school…

Douglas, Charles G., III; Komer, Richard D.



The Quicksands of Originalism: Interpreting Minnesota’s Constitutional Past  

Microsoft Academic Search

There are several varieties of the “originalist” school of constitutional thought, but all subscribe in one degree or another to the belief that a constitutional clause should be interpreted according to its original meaning or the original intent of its authors. That original understanding or intent can be discerned from the text of the clause, the history of its drafting

Douglas A. Hedin



Dead or Alive: Originalism as Popular Constitutionalism in Heller  

Microsoft Academic Search

The Court's announcement in 2008 that the Second Amendment, ratified in 1791, protects an individual's right to bear arms against federal gun control regulation was long awaited by many, long feared by others. What produced this ruling and what might it reveal about the character of our constitutional order? For many, constitutional law changed because the Court interpreted the Second

Reva B Siegel



Constitutive camalexin production and environmental stress response variation in Arabidopsis populations from the Iberian Peninsula.  


Optimal defense theory predicts that induction of defensive secondary metabolites in plants will be inversely correlated with constitutive expression of those compounds. Here, we asked whether camalexin, an important defense against fungal and bacterial pathogens, support this prediction in structured natural populations of Arabidopsis thaliana from the Iberian Peninsula. In common garden experiments, we found that genotypes from the VIE population constitutively hyper-accumulated camalexin. Camalexin concentrations were not induced significantly when plants were exposed to a temperature of 10°C for 48h. However, they were induced when plants were exposed to 48h of infection by the virulent bacterial pathogen, Pseudomonas syringae pv. tomato DC3000. Genotypes from the VIE population with the hyper-accumulation of camalexin were significantly more resistant to bacterial growth. Induction of camalexin was negatively correlated with constitutive camalexin concentrations following log transformation and two different corrections for autocorrelation, thus supporting the tradeoff predicted by optimal defense theory. Constitutive overexpression of camalexin was not explained by the only known natural genetic polymorphism at the Accelerated Cell Death 6, ACD6, locus. Collectively, the results support an important role of camalexin in defense against P. syringae as well as significant structured variation in defense levels within wild populations. PMID:25017162

Zhang, Nana; Lariviere, Andy; Tonsor, Stephen J; Traw, M Brian



Upholding Indigenous Freedoms of Religion and Medicine: Peyotists at the 1906-1908 Oklahoma Constitutional Convention and First Legislature  

ERIC Educational Resources Information Center

In the five hundred years of European and American globalization of the world, seldom have Indigenous peoples been invited to a constitutional convention and first legislature to express their perspectives and concerns. Rarely in the five-hundred-year history of the European and American colonization of the world were the rights of the Indigenous…

Wiedman, Dennis



Constitutive properties of adult mammalian cardiac muscle cells  

NASA Technical Reports Server (NTRS)

BACKGROUND: The purpose of this study was to determine whether changes in the constitutive properties of the cardiac muscle cell play a causative role in the development of diastolic dysfunction. METHODS AND RESULTS: Cardiocytes from normal and pressure-hypertrophied cats were embedded in an agarose gel, placed on a stretching device, and subjected to a change in stress (sigma), and resultant changes in cell strain (epsilon) were measured. These measurements were used to examine the passive elastic spring, viscous damping, and myofilament activation. The passive elastic spring was assessed in protocol A by increasing the sigma on the agarose gel at a constant rate to define the cardiocyte sigma-versus-epsilon relationship. Viscous damping was assessed in protocol B from the loop area between the cardiocyte sigma-versus-epsilon relationship during an increase and then a decrease in sigma. In both protocols, myofilament activation was minimized by a reduction in [Ca2+]i. Myofilament activation effects were assessed in protocol C by defining cardiocyte sigma versus epsilon during an increase in sigma with physiological [Ca2+]i. In protocol A, the cardiocyte sigma-versus-epsilon relationship was similar in normal and hypertrophied cells. In protocol B, the loop area was greater in hypertrophied than normal cardiocytes. In protocol C, the sigma-versus-epsilon relation in hypertrophied cardiocytes was shifted to the left compared with normal cells. CONCLUSIONS: Changes in viscous damping and myofilament activation in combination may cause pressure-hypertrophied cardiocytes to resist changes in shape during diastole and contribute to diastolic dysfunction.

Zile, M. R.; Richardson, K.; Cowles, M. K.; Buckley, J. M.; Koide, M.; Cowles, B. A.; Gharpuray, V.; Cooper, G. 4th



Examining costs of induced and constitutive immune investment in Tenebrio molitor.  


Central to the conceptual basis of ecological immunity is the notion that immune effector systems are costly to produce, run, and/or maintain. Using the mealworm beetle, Tenebrio molitor, as a model we investigated two aspects of the costs of innate immunity. We conducted an experiment designed to identify the cost of an induced immune response, and the cost of constitutive investment in immunity, as well as potential interactions. The immune traits under consideration were the encapsulation response and prophylactic cuticular melanization, which are mechanistically linked by the melanin-producing phenoloxidase cascade. If immunity is costly, we predicted reduced longevity and/or fecundity as a consequence of investment in either immune trait. We found a measurable longevity cost associated with producing an inducible immune response (encapsulation). In contrast to other studies, this cost was expressed under ad libitum feeding conditions. We found no measurable costs for constitutive investment in immunity (prophylactic investment in cuticular colour). PMID:14635919

Armitage, S A O; Thompson, J J W; Rolff, J; Siva-Jothy, M T



Visual framework for development and use of constitutive models  

NASA Astrophysics Data System (ADS)

Advanced constitutive relations are used in geotechnical engineering to capture measured soil and rock behaviour in the laboratory, and in numerical models to represent the material response. These constitutive relations have traditionally been difficult to use, understand, and develop except by a limited number of specialists. This paper describes a framework for transforming the representation of constitutive relations, as well as stress and strain quantities from a series of mathematical equations and matrix quantities to multidimensional geometric/visual objects in a dynamic interactive colour-rich display environment. The paper proposes a shift in current approaches to the development of constitutive equations and their use in numerical simulations by taking advantage of rapid advancements in information technology and computer graphics. A novel interactive visualization development and learning environment for material constitutive relations referred to as VizCoRe is presented. Visualization examples of two constitutive relations, the linear elastic with von Mises failure criteria and the Modified Cam Clay (MCC) are shown. These include two- and three-dimensional renderings of stress states and paths and yield and failure surfaces. In addition, the environment allows for the visualization of the implicit integration algorithm used for the numerical integration of both constitutive models.

Hashash, Youssef M. A.; Wotring, Donald C.; I-Chiang Yao, John; Lee, Jung-Suk; Fu, Qingwei



Accommodating Ontologies to Biological Reality--Top-Level Categories of Cumulative-Constitutively Organized Material Entities  

PubMed Central

Background The Basic Formal Ontology (BFO) is a top-level formal foundational ontology for the biomedical domain. It has been developed with the purpose to serve as an ontologically consistent template for top-level categories of application oriented and domain reference ontologies within the Open Biological and Biomedical Ontologies Foundry (OBO). BFO is important for enabling OBO ontologies to facilitate in reliably communicating and managing data and metadata within and across biomedical databases. Following its intended single inheritance policy, BFO's three top-level categories of material entity (i.e. ‘object’, ‘fiat object part’, ‘object aggregate’) must be exhaustive and mutually disjoint. We have shown elsewhere that for accommodating all types of constitutively organized material entities, BFO must be extended by additional categories of material entity. Methodology/Principal Findings Unfortunately, most biomedical material entities are cumulative-constitutively organized. We show that even the extended BFO does not exhaustively cover cumulative-constitutively organized material entities. We provide examples from biology and everyday life that demonstrate the necessity for ‘portion of matter’ as another material building block. This implies the necessity for further extending BFO by ‘portion of matter’ as well as three additional categories that possess portions of matter as aggregate components. These extensions are necessary if the basic assumption that all parts that share the same granularity level exhaustively sum to the whole should also apply to cumulative-constitutively organized material entities. By suggesting a notion of granular representation we provide a way to maintain the single inheritance principle when dealing with cumulative-constitutively organized material entities. Conclusions/Significance We suggest to extend BFO to incorporate additional categories of material entity and to rearrange its top-level material entity taxonomy. With these additions and the notion of granular representation, BFO would exhaustively cover all top-level types of material entities that application oriented ontologies may use as templates, while still maintaining the single inheritance principle. PMID:22253856

Vogt, Lars; Grobe, Peter; Quast, Bjorn; Bartolomaeus, Thomas




E-print Network

Obligate intracellular bacteria commonly have much reduced genome sizes compared to their nearest free-living relatives. One reason for this is reductive evolution: the loss of genes rendered non-essential due to the intracellular habitat. This can occur because of the presence of orthologous genes in the host, combined with the ability of the bacteria to import the protein or metabolite products of the host genes. In this article we take a look at three such bacteria whose genomes have been fully sequenced. Buchnera is an endosymbiont of the pea aphid, Acyrthosiphon pisum, the relationship between these two organisms being so essential that neither can reproduce in the absence of the other. Rickettsia prowazekii is the causative agent of louse-borne typhus in humans and Mycobacterium leprae infection of humans leads to leprosy. Both of these human pathogens have fastidious growth requirements, which has made them very difficult to

Comp Funct Genom; Jo Wixon



E-print Network

OCA is a group of autosomal recessive disorders characterized by hypopigmentation and abnormalities related to ocular development. Mutations in genes regulating melanin-biosynthesis cause four classical types of OCA (OCA 1-4). The clinical spectrum of OCA often depends on the pigmentation threshold of a patient, highlighting the importance of ethnic- specific SNPs. We aimed to understand the molecular bases of OCA in India, where it is one of the four major causes of childhood blindness. Materials and methods Blood samples were collected from OCA patients and family members, mostly from eastern and southern India. Seven pigmentation related genes were screened for variations. Relevant non-synonymous changes in tyrosinase (TYR) were functionally validated. Eighteen SNPs from three OCA genes were genotyped in 552 normal individuals covering various ethnic groups of India. Results Our data suggest that defects in TYR cause albinism in 58 % (36/62) of the cases [1] (and unpublished data; see Figure 1). Functional assays with missense mutations proved that none of mutants are enzymatically active and are retained in the endoplasmic reticulum [1]. Screening of the remaining cases (43%) revealed OCA2 to be the second common locus followed by SLC45A2 [2] (Figure 1). Evaluation of SNPs in TYR, OCA2 and SLC45A2 in normal population suggested definitive bias for some of the SNPs towards specific populations.

Kunal Ray; Mainak Sengupta; Moumita Chaki; Maitreyee Mondal; Swapan Samanta



Extensive evidence has demonstrated that 24-hour dietary recalls provide the highest quality, least biased dietary data. Traditional 24-hour recalls, however, are expensive and impractical for large-scale research because they rely on trained interviewers and multiple administrations to estimate usual intakes. As a result, researchers often make use of food frequency questionnaires, which are less expensive but contain substantial error.



E-print Network

This Provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. Embryonic diapause in humans: time to consider?

Grazyna E Ptak; Jacek A Modlinski; Grazyna E Ptak; Jacek A Modlinski; Pasqualino Loi




The discovery that proteins and peptides are "leaked" by tumors into clinically accessible bodily fluids such as blood has led to the possibility of diagnosing cancer at an early stage or monitoring response to treatment by collecting these fluids and testing for the presence of cancer-related biomarkers. Prostate-specific antigen (PSA) and cancer antigen 125 (CA-125) are examples of blood-borne cancer protein biomarkers that are currently being used in the clinic.


PD-L1 Expression Is Increased in a Subset of Basal Type Breast Cancer Cells  

PubMed Central

Background Tumor cells express programmed death ligand 1 (PD-L1) and is a key immune evasion mechanism. PD-L1 expression in multiple breast cancer cell lines was evaluated to identify intrinsic differences that affect their potential for immune evasion. Methods PD-L1 expression was analyzed in six breast cancer cell lines: AU565&MCF7 (luminal), BT20&HCC1143 (basal A), MDA231&HCC38 (basal B). Surface and intracellular PD-L1 expression +/? interferon ? for 48 hours was measured by flow cytometry. PD-L1 gene expression data for all breast cancer cell lines in the Comprehensive Cell Line Encyclopedia (CCLE) was analyzed. Correlation between PD-L1 levels and clinicopathologic parameters was analyzed within Oncomine datasets. A tissue microarray containing 61 invasive breast cancer primary tumor cores was stained for PD-L1 expression and analyzed. Results Basal breast cancer cells constitutively express the highest levels of PD-L1. All cell lines increased PD-L1 expression with interferon ?, but basal B cells (MDA-231 and HCC38) demonstrated the largest increases. There were no differences in protein localization between cell lines. In the CCLE data, basal cell lines demonstrated higher mean PD-L1 expression compared to luminal cell lines. High PD-L1 expressing basal cell lines over-express genes involved in invasion, proliferation, and chemoresistance compared to low PD-L1 basal cell lines. High PD-L1 basal cell lines had lower expression of IRF2BP2 and higher STAT1 levels compared to low PD-L1 expressing cell lines. Within Oncomine datasets PDL1 mRNA levels were higher in basal type tumors. The TMA analysis demonstrated that lymph node positive cases had higher levels of PD-L1 protein expression compared to lymph node negative cases. Conclusions Basal type breast cancer (especially basal B) express greater levels of PD-L1 constitutively and with IFN ?. High PD-L1 basal cells over-express genes involved in invasion, motility, and chemoresistance. Targeting PD-L1 may enhance eradication of aggressive breast cancer cells by the immune system. PMID:24551119

Soliman, Hatem; Khalil, Farah; Antonia, Scott



Constitutive and blood meal-induced trypsin genes in Lutzomyia longipalpis.  


Trypsins constitute some of the most abundant midgut digestive proteases expressed by hematophagous insects upon blood feeding. In addition to their role in the digestion of the blood meal, these proteases also have been implicated in the ability of certain pathogens to infect their natural vector. In sand flies, digestive proteases including trypsins were associated with early killing of Leishmania and are believed to play a role in the species-specificity dictating sand fly vectorial capacity. Our group is involved in studies of midgut digestive proteases in the sand fly Lutzomyia longipalpis, the principal vector of visceral leishmaniasis in Brazil. Here we report on the identification of two cDNAs, Lltryp1 and Lltryp2, which code for putative midgut trypsins in L. longipalpis. Analyses of RNA abundance using semi-quantitative RT-PCR show a different pattern of expression between the two genes. Lltryp1 expression remains undetected until blood feeding and reaches a peak at 12 h post-blood meal (PBM), returning to pre-blood meal levels at 72 h PBM. Additionally, Lltryp1 expression is undetected during larval development. Lltryp2, on the other hand, is constitutively expressed as high levels in the non-blood fed female, but is reduced upon blood feeding. At the end of the digestive cycle, Lltryp2 regains its pre-blood meal levels. This cDNA also is present in all developmental stages and in adult males. This pattern of expression is reminiscent of what is seen in mosquitoes and Old World sand flies, but has characteristics that are unique to L. longipalpis. PMID:17879236

Telleria, Erich Loza; Pitaluga, André Nóbrega; Ortigão-Farias, João Ramalho; de Araújo, Adriana Pereira Oliveira; Ramalho-Ortigão, José Marcelo; Traub-Cseko, Yara Maria



NIK is involved in constitutive activation of the alternative NF-{kappa}B pathway and proliferation of pancreatic cancer cells  

SciTech Connect

Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-{kappa}B is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-{kappa}B activation. Here, we show that the alternative pathway is constitutively activated and NF-{kappa}B-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer.

Nishina, Takashi [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)] [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamaguchi, Noritaka [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan) [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan); Gohda, Jin [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)] [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Semba, Kentaro [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan) [Consolidated Research Institute for Advanced Science and Medical Care, Waseda University, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041 (Japan); Department of Life Science and Medical Bio-science, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480 (Japan); Inoue, Jun-ichiro, E-mail: [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)] [Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan)



Preubiquitinated chimeric ErbB2 is constitutively endocytosed and subsequently degraded in lysosomes  

SciTech Connect

The oncoprotein ErbB2 is endocytosis-deficient, probably due to its interaction with Heat shock protein 90. We previously demonstrated that clathrin-dependent endocytosis of ErbB2 is induced upon incubation of cells with Ansamycin derivatives, such as geldanamycin and its derivative 17-AAG. Furthermore, we have previously demonstrated that a preubiquitinated chimeric EGFR (EGFR-Ub{sub 4}) is constitutively endocytosed in a clathrin-dependent manner. We now demonstrate that also an ErbB2-Ub{sub 4} chimera is endocytosed constitutively and clathrin-dependently. Upon expression, the ErbB2-Ub{sub 4} was further ubiquitinated, and by Western blotting, we demonstrated the formation of both Lys48-linked and Lys63-linked polyubiquitin chains. ErbB2-Ub{sub 4} was constitutively internalized and eventually sorted to late endosomes and lysosomes where the fusion protein was degraded. ErbB2-Ub{sub 4} was not cleaved prior to internalization. Interestingly, over-expression of Ubiquitin Interaction Motif-containing dominant negative fragments of the clathrin adaptor proteins epsin1 and Eps15 negatively affected endocytosis of ErbB2. Altogether, this argues that ubiquitination is sufficient to induce clathrin-mediated endocytosis and lysosomal degradation of the otherwise plasma membrane localized ErbB2. Also, it appears that C-terminal cleavage is not required for endocytosis. -- Highlights: ? A chimera containing ErbB2 and a tetra-Ubiquitin chain internalizes constitutively. ? Receptor fragmentation is not required for endocytosis of ErbB2. ? Ubiquitination is sufficient to induce endocytosis and degradation of ErbB2. ? ErbB2-Ub4 is internalized clathrin-dependently.

Vuong, Tram Thu [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway)] [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Berger, Christian [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway)] [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway); Bertelsen, Vibeke; Rødland, Marianne Skeie [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway)] [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Stang, Espen [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway)] [Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway); Madshus, Inger Helene, E-mail: [Institute of Clinical Medicine, University of Oslo, Rikshospitalet, 0027 Oslo (Norway); Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. Box 4950 Nydalen, 0424 Oslo (Norway)



LC3, an autophagosome marker, is expressed on oligodendrocytes in Nasu-Hakola disease brains  

PubMed Central

Background Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder characterized by sclerosing leukoencephalopathy and multifocal bone cysts, caused by a loss-of-function mutation of either DAP12 or TREM2. TREM2 and DAP12 constitute a receptor/adaptor signaling complex expressed exclusively on osteoclasts, dendritic cells, macrophages, and microglia. Neuropathologically, NHD exhibits profound loss of myelin and accumulation of axonal spheroids, accompanied by intense gliosis accentuated in the white matter of the frontal and temporal lobes. At present, the molecular mechanism responsible for development of leukoencephalopathy in NHD brains remains totally unknown. Methods By immunohistochemistry, we studied the expression of microtubule-associated protein 1 light chain 3 (LC3), an autophagosome marker, in 5 NHD and 12 control brains. Results In all NHD brains, Nogo-A-positive, CNPase-positive oligodendrocytes surviving in the non-demyelinated white matter intensely expressed LC3. They also expressed ubiquitin, ubiquilin-1, and histone deacetylase 6 (HDAC6) but did not express Beclin 1 or sequestosome 1 (p62). Substantial numbers of axonal spheroids were also labeled with LC3 in NHD brains. In contrast, none of oligodendrocytes expressed LC3 in control brains. Furthermore, surviving oligodendrocytes located at the demyelinated lesion edge of multiple sclerosis (MS) did not express LC3, whereas infiltrating Iba1-positive macrophages and microglia intensely expressed LC3 in MS lesions. Conclusions These results propose a novel hypothesis that aberrant regulation of autophagy might induce oligodendrogliopathy causative of leukoencephalopathy in NHD brains. PMID:24886140