text:
Glioblastoma is the most common primary brain tumor in adults. Though a lot of research has been focused on this disease, the causes and pathogenesis of glioblastoma have not been indentified clearly.
We indentified 1,236 significantly differentially expressed genes, and 30 pathways enriched in the set of differentially expressed genes among 243 tumor and 11 normal samples. We also indentified 97 differentially expressed microRNAs among 240 tumor and 10 normal samples. 22 of which have been reported to affect glioblastoma and 50 of which were implicated in other cancers and brain diseases. We regressed gene expression on microRNA expression in 237 tumor tissues and 10 normal tissues comprehensively. We found two experimentally validated microRNA targets and 1,094 miRNA-target gene pairs in our datasets which were predicted by miRanda algorithm, 8 of the target genes were tumor suppressor genes and 3 were oncogenes. Further function analysis of target genes suggested that microRNAs most frequently targeted genes associated with Cell Signalling and Nervous System.
We investigated gene and microRNA Expression in Glioblastoma and gave a comprehensive function study of differential expressed gene and microRNA in glioblastoma patients. These findings gave important clues to study of the carcinogenic process in glioblastomas.
Glioblastoma Multiforme (GBM) is the most common and most aggressive type of primary brain tumor, accounting for 52% of all primary brain tumor cases and 20% of all intracranial tumors [1]. Primary GBM arise de novo, without any history of pre-existing lower-grade tumor, whereas secondary GBM have clinical, radiologic, or histopathologic evidence of malignant progression from pre-existing lower-grade tumor [2]. In the past two decades, the molecular mechanisms, genetics and paths to treatment of Glioblastoma have extensively been studied [3]. However, the causes and pathogenesis of glioblastoma have not been indentified clearly. With the continuing improvement of high-throughput genomic technologies, it is now feasible to survey human cancer genomes comprehensively. The Cancer Genome Atlas (TCGA) aims to catalogue and discover major cancer-causing genome alterations in large cohorts of human tumors through integrated multi-dimensional analyses [4]. Glioblastoma is the first cancer studied by TCGA. To identify the genetic alterations in glioblastoma, we investigated the expression profiles of gene and microRNA.
MicroRNAs (miRNAs) are single-stranded short coding RNA molecules of about 22 nucleotides in length, which usually repress gene expression by binding at the 3'UTR region of target gene [5]. The expressions of microRNAs are found to be highly different in organ development and tissue differentiation [6]. Moreover, many microRNAs have been found to associate with apoptosis and cancer, suggesting they function as oncogene or tumor suppressor gene [7]. In our study, we examined the expression levels of 470 human miRNAs in glioblastoma and indentify a group of microRNAs whose expression is significantly altered in this tumor. We also indentified the significantly altered gene expression and pathways related to glioblastoma.
All types of data were acquired from TCGA project [4] (http://cancergenome.nih.gov/dataportal/data/about/ webcite). Gene expression microarrays were performed on Affymetrix HT Human Genome U133 Array Plate Set by Massachusetts Institute of Technology (MIT). Level three data gave calls for genes per sample after Probeset-level and Gene-level Robust Multiarray Analysis (quantile normalization and background corrected) until the most recent update on Sep. 05, 2008. After calculation the average expression values for duplicated samples, finally 243 tumor tissue samples, 10 normal tissues and 1 cell line sample from glioblastomas patients were used for differential expression analysis. MicroRNA expression experiments were performed on Agilent 8 x 15KHuman microRNA-specific microarray by Universities of North Carolina (UNC). There are 534 microRNAs (470 human microRNAs) and 240 tumor tissue samples, 10 normal tissue samples available in level three data (after quantile normalization and batch adjusted) until the most recent update on Nov. 10, 2008. As it is very difficult to get the brain tissue samples from normal people, the control samples are all from the adjacent normal tissues of glioblastomas patients. Thus we focus on detecting the effect of somatic difference on disease, which is also a common approach in many other cancer studies. We used 254 samples for gene expression and pathway analysis, 250 samples for microRNA expression analysis, 247 samples common in microRNA and gene expression datasets for miRNA targets analysis.
Gene expression analysis
A total of 1,236 genes were identified to be significantly differentially expressed between tumour and normal tissues. The results were given in Additional file 1. To further investigate the function of these differentially expressed genes, we used DAVID [8,9], bioinformatics resources and pathway analysis [10] for systematic and integrative analysis of large gene lists. 1,221 of 1,236 differentially expressed genes had annotations in DAVID Functional Annotation Tools. We carried out gene set enrichment analysis to indentify the most enriched gene function annotation terms (GO terms) [11] in the list of 1,221 annotated differentially expressed genes. (See methods for details.) The top ten enriched GO terms in the list of differentially expressed genes were shown in Table 1, suggesting these genes were enriched in brain and mainly associated with Nervous system development and function. The detailed information, for example, genes which shared the GO terms was given in Additional file 1.
Table 1. The top ten GO terms most enriched in the differentially expressed gene list
Additional file 1. A total of 1236 genes were significantly differentially expressed by both T-test and Mann-Whitney Test after Bonferroni correction for multiple tests. The top 10 enriched GO terms and the first 2 significant GO terms clusters were given in sheet 2 and sheet 3, respectively.
Format: XLS Size: 228KB Download file
This file can be viewed with: Microsoft Excel Viewer
DAVID also could cluster similar functional GO terms together. The first two enriched GO term groups in the differentially expressed gene list were all the function terms relevant to brain and neuron. They were: 1) GOTERM Cellular Component including five terms: neuron projection, cell projection, dendrite, cell soma, and axon. 53 genes belong to this cluster including CDK5 , SNCG , UCHL1 , FREQ.
According to NCBI Entrez gene annotation [12], it was reported that the deregulation of gene CDK5 causes neuronal death and neurodegenerative diseases. Gene SNCG encodes a member of the synuclein family of proteins which are believed to be involved in the pathogenesis of neurodegenerative diseases. Mutations in this gene have also been associated with breast tumor development. Gene UCHL1 is specifically expressed in the neurons and in cells of the diffuse neuroendocrine system. Mutations in this gene may be associated with Parkinson disease. FREQ gene encodes calcium-binding proteins expressed predominantly in neurons. The protein encoded by this gene is associated with secretory granules and modulates synaptic transmission and synaptic plasticity. 2) GOTERM Biological Process including twenty one terms: synaptic transmission; transmission of nerve impulse; neurotransmitter secretion; regulated secretory pathway; generation of a signal involved in cell-cell signaling; regulation of neurotransmitter levels; neurological system process; cell-cell signaling; exocytosis; SNARE binding; secretory pathway and so on. A total of 336 genes belong to this cluster. The detailed information for this two GO term groups were given in Additional file 1.
Pathway analysis
We first used algorithm proposed in TAPPA (Topological Analysis of Pathway Phenotype Association) [10] for pathway analysis. The results revealed that 131 pathways were significantly associated with glioblastoma (Additional file 2). The 131 associated pathways belonged to 33 functional groups, among which Cell Signaling, Neuroscience, Immunology and Expression were the most enriched pathway groups. Glioma pathway was the only significant pathway in the cancer functional group with P-value= 5.75 × 10–7. Similar to the GO terms enrichment analysis, we used DAVID Functional Annotation Tools to indentify which pathways were most enriched in the list of differentially expressed genes. The 40 significant pathways were also given in Additional file 2. Cell Signaling, Signal Transduction, Apoptosis and Neuroscience were the most enriched pathway groups. A total of 30 significant pathways found by both methods were shown in Additional file 2. The detailed genes information involved in the over-represented pathways was also provided. Long-term potentiation(a Nervous System pathway) and Calcium signaling pathway(a Signal Transduction pathway), were the most significantly enriched pathways with p-value 2.62 × 10–8 and 3.26 × 10–8, respectively. There were 11significant Cell Signaling pathways, 4 significant Apoptosis pathways, 4 significant Signal Transduction pathways, 3 significant Immunology pathways, 3 significant Neuroscience pathways and 2 significant Nervous System pathways, (Some pathways may belong to different functional groups). The results suggested that the differentially expressed genes were most involved in signal, apoptosis and neuroscience pathways. Take long-term potentiation pathway as an example, Figure 1 show all the genes in this pathway, Hippocampal long-term potentiation (LTP) is a long-lasting increase in synaptic efficacy, is the molecular basis for learning and memory. 3 of the 71 genes in this pathway were significant over expressed genes and were highlighted in blue and 21 were under expressed and were highlighted in red. (One box in the figure may denote several genes)
Figure 1. Long term potentiation pathway Figure 1 shows all the genes in this pathway. Significant over expressed genes are highlighted in blue and under expressed genes in red.
Additional file 2. Three sheets gave the list of 131 significant pathways indentified by TAPPA method, the list of 40 significant pathways indentified by Fisher Exact Test and the list of 30 pathways shared by two methods, respectively.
Format: XLS Size: 72KB Download file
This file can be viewed with: Microsoft Excel Viewer
Analysis of differential expression of microRNA
A total of 97 microRNAs were significantly differentially expressed between tumor and normal tissues (Additional files 3). To examine whether these miRNAs were associated with glioblastoma, we used miR2Disease [13] to validate our results (Updated Date: Dec. 19, 2008). MiR2Disease provides a comprehensive literature reported resource of miRNA deregulation in various human diseases. From the data in miR2Disease, 81 of the 97 significant miRNAs have been reported to associate with 84 diseases, among them, 72 miRNAs are associated with 59 cancers and brain diseases. 22 of those miRNAs have been reported to induce glioblastoma/ glioblastoma multiforme(GBM)/neuroblastoma (NB) and the expression pattern of miRNA(up-regulated or down-regulated) in published literatures is exactly the same as that in our data. Table 2 gave the p-value, expression pattern, disease and references for the 22 miRNAs. We inferred that the other 50 miRNAs which were related to other cancers and brain diseases may also be important for carcinogenesis in brain. However, further experiment validations were required to confirm our results. Among the 97 significant miRNAs, 30 miRNAs were up-regulated and 67 were down-regulated.
Table 2. 22 MicroRNAs related to glioblastoma/ GBM/ Neuroblastoma
Additional file 3. A total of 97 microRNAs were significantly differentially expressed by both T-test and Mann-Whitney Test after Bonferroni correction for multiple tests.
Format: XLS Size: 33KB Download file
This file can be viewed with: Microsoft Excel Viewer
To further examine the function of those significant miRNAs, we need to find the target gene of miRNAs associated with glioblastomas. So we carried out the regression analysis for miRNA and gene expression.
The regulation of gene expression by microRNA
miRNA has been thought to promote degradation of target mRNA or suppress translation of corresponding protein by matching with mRNA in the 3'-UTR region[20-23]. There is no doubt that miRNAs perform various biological functions through regulation of gene expression. To reveal the mechanisms of how miRNA regulates gene expression in GBM, we identified target genes of miRNAs and constructed miRNA target networks. Since miRNAs repress the expression of its target gene, the first step was to test the inverse relationship between the expression profile of miRNA and that of its potential targets. To achieve this, we regressed the expression of target mRNA on the expression of miRNAs and select mRNA with significant negative regression coefficients as miRNA targets. P-value for declaring significant evidence of miRNA target was 1.00 × 10–4. The second step was to conduct sequence analysis which used sequence complementarities of miRNA and its target site to predict potential miRNA target genes. To achieve this, we use experimentally verified and predicted miRNA targets data from three miRNAs databases: miR2Disease[13], TarBase [24] and miRBase[25]. MiR2Disease (updated on Dec.19, 2008) and TarBase (updated on June, 2008) provided experimentally verified microRNA target genes. MiRBase predicted the target gene of miRNA by miRanda algorithm [26], where the predicted target genes and miRNAs could be downloaded directly (updated on: Oct.31, 2007).
We compiled 1,236 differentially expressed mRNAs and 97 differentially expressed miRNAs data in 237 tumor tissue sample and 10 normal tissue samples. We found two experimentally confirmed results. The literature reported that the in nasopharyngeal carcinomas underexpressed hsa-mir-29c (expression fold change (tumor/normal)=0.20) target overexpressed gene COL4A1(expression fold change(tumor/normal)=5.24) [27]. In our result, down-regulated hsa-mir-29c (differentially expressed P-value <5.11 × 10–12) targets over-expressed gene COL4A1 (differentially expressed P-value <3.58 × 10–6) with regression β = –389.02 and P= 1.35 × 10–8. We conclude that hsa-mir-29c is also an important miRNA in glioblastomas. Another experiment validated targets gene was LDOC1 targeted by has-miR-155[28]. The known oncogenic miRNA hsa-miR-155 can regulate a set of target genes including LDOC1, a regulator of apoptosis [29]. Our results showed that hsa-miR-155 was over-expressed (differentially expressed P-value <1.40 × 10–10) and targets under-expressed gene LDOC1 (differentially expressed P-value <1.085 × 10–31) with regression β = –196.77 and P= 4.00 × 10–15. We inferred that hsa-mir-155 could induce cancer through regulation of apoptosis gene LDOC1 in glioblastomas.
For predicted targets in miRBase, we found 1,094 matched miRNA-gene pairs including 70 miRNAs and 661 genes (Additional file 4). 44 down-regulated miRNAs target 202 overexpressed genes while 26 up-regulated microRNAs target 459 underexpressed genes. The up and down-regulated miRNA-gene pairs were shown in Figure 2 and Figure 3.
Figure 2. Up-regulated miRNA and their targets Figure 2 show the network of 26 up-regulated miRNAs and 459 under-expressed target genes.
Figure 3. Down-regulated miRNA and their targets Figure 3 shows the network of 44 down-regulated miRNAs and 202 over-expressed target genes.
Additional file 4. The 1,094 matched miRNA-gene pairs including 70 microRNAs and 661 genes predicted by both our results and miRanda algorithm.
Format: XLS Size: 127KB Download file
This file can be viewed with: Microsoft Excel Viewer
The 661 target genes were a subset of the 1236 significant differentially expressed genes. We examined which pathways were these genes enriched in and compared them with the previous results. 11 pathways were significant by fisher exact test in DAVID, 8 of which were the same as the pathways identified from the previous sections: Epithelial cell signaling in Helicobacter pylori infection,Cholera - Infection, Long-term potentiation, Calcium signaling pathway, Neurodegenerative Diseases, Long-term depression, Gap junction, Neuroactive ligand-receptor interaction. Three new enriched pathways include Amyotrophic lateral sclerosis (ALS), Alzheimer's disease, Wnt signaling pathway. These differentially expressed genes were also most involved in signal and neuroscience pathways.
To investigate the function of the 661 target genes, we searched the TSGDB [30] (a tumor suppressor gene database) and DNA-Tumor Suppressor and Oncogene Database [31] and we found eight tumor suppressor genes APC, TP53, BIN1, BTG1, CDK2AP1, LDOC1, RASSF1, WFDC1 and three oncogenes: MCF2, MPL, THRA.
According to NCBI Entrez gene annotation [12], APC encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It is also involved in other processes including cell migration and adhesion, transcriptional activation, and apoptosis. TP53 encodes tumor protein p53, which responds to diverse cellular stresses to regulate target genes that induce cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. BIN1 encodes several isoforms of a nucleocytoplasmic adaptor protein, one of which was initially identified as a MYC-interacting protein with features of a tumor suppressor. Isoforms that are expressed in the central nervous system may be involved in synaptic vesicle endocytosis and may interact with dynanim, synaptojanin, endophilin, and clathrin. LDOC1 is thought to regulate the transcriptional response mediated by the nuclear factor kappa B (NF-kappaB). The gene has been proposed as a tumor suppressor gene whose protein product may have an important role in the development and/or progression of some cancers. RASSF1 encoded protein was found to interact with DNA repair protein XPA. The protein was also shown to inhibit the accumulation of cyclin D1, and thus induce cell cycle arrest. WFDC1 gene is mapped to chromosome 16q24, an area of frequent loss of heterozygosity in many cancers. Owing to its location and a possible growth inhibitory property of its gene product, this gene is suggested to be a tumor suppressor gene. MCF2 is a member of a large family of GDP-GTP exchange factors that modulate the activity of small GTPases of the Rho family. Five-prime recombinations result in the loss of N-terminal codons, producing MCF2 variants with oncogenic potential.
To further investigate the function of target genes, we identified the miRNA targeted pathways by right-tail fisher exact test, which tested enrichment of pathways in the miRNA target gene set. A total of 83 pathways targeted by 94 miRNAs were listed in Additional file 5 after Bonferroni correction for multiple tests (p-values<1.00 × 10–4). Many of the pathways were targeted by more than one miRNA. We shown 29 pathways which were targeted by more than 10 miRNAs in Figure 4. Long-term potentiation (Nervous System pathway) was targeted by 79 (the most) miRNAs and Nitric Oxide Signalling (Signalling pathway) was targeted by 74 (the second most) miRNAs. We can see that the differentially expressed miRNAs most frequently targeted genes in Cell Signalling and Nervous System. The red bar gave the negative logarithm with 10 base of average p-value indicating the significance of enrichment of the pathway in the miRNA targets. The DNA replication pathway and the cell cycle pathway have the smallest average P-value 7.70 × 10–9 and the second smallest P- value 1.17 × 10–6. P-values of Long-term potentiation pathway (7.29 × 10–6) and Nitric Oxide Signalling pathway (9.99 × 10–6) were also small.
Figure 4. Down-regulated miRNA and their targets A total of 29 pathways which were targeted by more than 10 miRNAs were shown in Figure 4. The blue bar indicated that the pathway was targeted by the number of miRNAs. The red bar gave the negative logarithm to the base 10 of average P-value indicating the significance of enrichment of the pathway in miRNA targets.
Additional file 5. A total of 83 pathways targeted by 94 microRNAs were listed after Bonferroni correction for multiple tests.
Format: XLS Size: 198KB Download file
This file can be viewed with: Microsoft Excel Viewer
In this paper, we performed detailed analysis of differential expression of gene and miRNA between tumor tissues and normal brain tissues in glioblastomas. We also performed gene sets enrichment analysis to find the enriched GO terms and pathways. Most of the genes were enriched in Nervous system associated GO terms and Cell Signaling and Neuroscience associated pathways. 22 differentially expressed miRNAs were related to Glioblastoma multiforme or neuroblastoma. To study the regulation of gene expression by miRNA, we combined the sequence predicted miRNA targets in miRBase database, experiment validated miRNA targets in TarBase and miR2Disease database with our predictions from the gene and miRNA expression profiles and found 2 experiment validated targets and 1,094 predicted targets. Further function analysis of target genes suggests that miRNAs most frequently targeted genes in Cell Signalling and Nervous System. However, the number of normal tissues in the studies is small. More samples are needed for further investigation.
DAVID bioinformatics resources
The Database for Annotation, Visualization and Integrated Discovery (DAVID) provides a comprehensive set of functional annotation tools for investigators to understand biological meaning behind large list of genes [8,9] (http://david.abcc.ncifcrf.gov/ webcite). After inputting large gene lists, it automatically calculates and identifies enriched biological themes, particularly GO terms and pathways; discovers enriched functional-related gene groups and clusters redundant annotation terms. For any one GO terms, right tail modified Fisher Exact was used to determine whether the number of genes with this GO terms is enriched in the differentially expressed gene list compared to the number of genes with this GO terms in all the 19,439 genes on HG-U133A array(Background). For any one pathway, right tail modified Fisher Exact was used to determine whether the number of genes within this pathway is enriched in the differentially expressed gene list compared to the number of genes within all KEGG or Biocarta pathways. The smaller the p-value was, much more enriched in the GO terms or pathway than by random chance.
Pathway-based differential expression analysis
We used algorithm proposed in TAPPA (Topological Analysis of Pathway Phenotype Association) [10] for pathway analysis. It calculated a Pathway Connectivity Index for each pathway and then evaluates its correlation to the phenotype variation. Gene connections of 162 KEGG pathways with gene number higher than 8 were collected in that paper and used for PCI calculation. For those pathways with no edge connections collected, PCI would degenerate into the average of gene expression values. Totally 501 pathways from KEGG [32] and Biocarta [33] were assembled in our analysis. The p-value for declaring significance after Bonferroni correction for multiple tests was 1 × 10–4.
Statistical analysis
The differential expression of the gene and microRNA were tested by T-test and Mann-Whitney Test. The thresholds for declaring significance after Bonferroni correction for multiple tests were 4.15 × 10–6 and 9.36 × 10–5, for gene and miRNA respectively. Linear regression was used to investigate the relationships between miRNA and gene expressions. The linear model took its common form: where y is an n-by-1 vector of observations, such as gene expression. X is an n-by-p matrix of regressors, such as miRNA expression, β is a p-by-1 vector of parameters; known as regression coefficient and ε is an n-by-1 vector of random disturbances. Right-tail fisher exact test were used to test for the enriched Gene Ontology Terms, pathways in the datasets. Matlab code for T-Test, Mann-Whitney Test and linear regression was attached in Additional files 6.
Additional files 6. We have attached the Matlab code for T-Test, Mann-Whitney Test and linear regression in additional files 6
Format: TXT Size: 5KB Download file
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
HD was responsible for acquisition, analysis and interpretation of data and wrote the draft. HS, LL, XF did the statistical analysis and the programming. LJ and MX provided the administrative, technical and material support. MX participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.
We thank the Cancer Genome Atlas Research Network for providing data and the members of TCGA's External Scientific Committee and the Glioblastoma Disease Working Group (http://cancergenome.nih.gov/components/). Li Jin, Hua Dong and Hoicheong Siu are supported by grants from the National Outstanding Youth Science Foundation of China (30625016), National Science Foundation of China (30890034), Shanghai Commission of Science and Technology (04dz14003) and 863 Program (2007AA02Z312). Momiao Xiong and Li Luo are supported by Grant from National Institutes of Health NIAMS P01 AR052915-01A1, NIAMS P50 AR054144-01 CORT, HL74735, ES09912, and Grant from Hi-Tech Research and Development Program of China(863)(2007AA02Z300). Publication of this supplement was made possible with support from the International Society of Intelligent Biological Medicine (ISIBM).
This article has been published as part of BMC Genomics Volume 11 Supplement 3, 2010: The full contents of the supplement are available online at http://www.biomedcentral.com/1471-2164/11?issue=S3.
wikipedia[http://en.wikipedia.org/wiki/Glioblastoma_multiforme#Causes] webcite
Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A, Hahn WC, Ligon KL, Louis DN, Brennan C, et al.: Malignant astrocytic glioma: genetics, biology, and paths to treatment.
Genes Dev 2007, 21(21):2683-2710. PubMed Abstract | Publisher Full Text
Mischel PS, Nelson SF, Cloughesy TF: Molecular analysis of glioblastoma: pathway profiling and its implications for patient therapy.
Cancer Biol Ther 2003, 2(3):242-247. PubMed Abstract | Publisher Full Text
The Cancer Genome Atlas Research Network: Comprehensive genomic characterization defines human glioblastoma genes and core pathways.
Nature 2008, 455(7216):1061-1068. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Sassen S, Miska EA, Caldas C: MicroRNA: implications for cancer.
Virchows Arch 2008, 452(1):1-10. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Rosenfeld N, Aharonov R, Meiri E, Rosenwald S, Spector Y, Zepeniuk M, Benjamin H, Shabes N, Tabak S, Levy A, et al.: MicroRNAs accurately identify cancer tissue origin.
Nat Biotechnol 2008, 26(4):462-469. PubMed Abstract | Publisher Full Text
Lee YS, Dutta A: MicroRNAs in cancer.
Annu Rev Pathol 2009, 4:199-227. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Dennis G Jr., Sherman BT, Hosack DA, Yang J, Gao W, Lane HC, Lempicki RA: DAVID: Database for Annotation, Visualization, and Integrated Discovery.
Genome Biol 2003, 4(5):P3. PubMed Abstract | BioMed Central Full Text
Huang da W, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
Nat Protoc 2009, 4(1):44-57. PubMed Abstract | Publisher Full Text
Gao S, Wang X: TAPPA: topological analysis of pathway phenotype association.
Bioinformatics 2007, 23(22):3100-3102. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al.: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium.
Nat Genet 2000, 25(1):25-29. PubMed Abstract | Publisher Full Text
Maglott D, Ostell J, Pruitt KD, Tatusova T: Entrez Gene: gene-centered information at NCBI.
Nucleic Acids Res 2007, 35(Database issue):D26-31. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Jiang Q, Wang Y, Hao Y, Juan L, Teng M, Zhang X, Li M, Wang G, Liu Y: miR2Disease: a manually curated database for microRNA deregulation in human disease.
Nucleic Acids Res 2009, 37(Database issue):D98-104. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Ciafre SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG: Extensive modulation of a set of microRNAs in primary glioblastoma.
Biochem Biophys Res Commun 2005, 334(4):1351-1358. PubMed Abstract | Publisher Full Text
Chan JA, Krichevsky AM, Kosik KS: MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells.
Cancer Res 2005, 65(14):6029-6033. PubMed Abstract | Publisher Full Text
Silber J, Lim DA, Petritsch C, Persson AI, Maunakea AK, Yu M, Vandenberg SR, Ginzinger DG, James CD, Costello JF, et al.: miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells.
BMC Med 2008, 6:14. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text
Fontana L, Fiori ME, Albini S, Cifaldi L, Giovinazzi S, Forloni M, Boldrini R, Donfrancesco A, Federici V, Giacomini P, et al.: Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM.
PLoS ONE 2008, 3(5):e2236. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Schulte JH, Horn S, Otto T, Samans B, Heukamp LC, Eilers UC, Krause M, Astrahantseff K, Klein-Hitpass L, Buettner R, et al.: MYCN regulates oncogenic MicroRNAs in neuroblastoma.
Int J Cancer 2008, 122(3):699-704. PubMed Abstract | Publisher Full Text
Kefas B, Godlewski J, Comeau L, Li Y, Abounader R, Hawkinson M, Lee J, Fine H, Chiocca EA, Lawler S, et al.: microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma.
Cancer Res 2008, 68(10):3566-3572. PubMed Abstract | Publisher Full Text
Huang JC, Morris QD, Frey BJ: Bayesian inference of MicroRNA targets from sequence and expression data.
J Comput Biol 2007, 14(5):550-563. PubMed Abstract | Publisher Full Text
Huang JC, Babak T, Corson TW, Chua G, Khan S, Gallie BL, Hughes TR, Blencowe BJ, Frey BJ, Morris QD: Using expression profiling data to identify human microRNA targets.
Nat Methods 2007, 4(12):1045-1049. PubMed Abstract | Publisher Full Text
John B, Sander C, Marks DS: Prediction of human microRNA targets.
Methods Mol Biol 2006, 342:101-113. PubMed Abstract
Kuhn DE, Martin MM, Feldman DS, Terry AV Jr., Nuovo GJ, Elton TS: Experimental validation of miRNA targets.
Methods 2008, 44(1):47-54. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Sethupathy P, Corda B, Hatzigeorgiou AG: TarBase: A comprehensive database of experimentally supported animal microRNA targets.
RNA 2006, 12(2):192-197. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Griffiths-Jones S, Saini HK, van Dongen S, Enright AJ: miRBase: tools for microRNA genomics.
Nucleic Acids Res 2008, 36(Database issue):D154-158. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
John B, Enright AJ, Aravin A, Tuschl T, Sander C, Marks DS: Human MicroRNA targets.
PLoS Biol 2004, 2(11):e363. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Sengupta S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Cheng YJ, Chen CJ, Hildesheim A, Sugden B, Ahlquist P: MicroRNA 29c is down- regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins.
Proc Natl Acad Sci U S A 2008, 105(15):5874-5878. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Skalsky RL, Samols MA, Plaisance KB, Boss IW, Riva A, Lopez MC, Baker HV, Renne R: Kaposi's sarcoma-associated herpesvirus encodes an ortholog of miR-155.
J Virol 2007, 81(23):12836-12845. PubMed Abstract | Publisher Full Text | PubMed Central Full Text
Inoue M, Takahashi K, Niide O, Shibata M, Fukuzawa M, Ra C: LDOC1, a novel MZF-1-interacting protein, induces apoptosis.
FEBS Lett 2005, 579(3):604-608. PubMed Abstract | Publisher Full Text
Yang Y, Fu LM: TSGDB: a database system for tumor suppressor genes.
Bioinformatics 2003, 19(17):2311-2312. PubMed Abstract | Publisher Full Text
DNA- Tumor Suppressor and Oncogene Database[http://embryology.med.unsw.edu.au/dna/DNA10.htm] webcite
Hashimoto K, Goto S, Kawano S, Aoki-Kinoshita KF, Ueda N, Hamajima M, Kawasaki T, Kanehisa M: KEGG as a glycome informatics resource.
Glycobiology 2006, 16(5):63R-70R. PubMed Abstract | Publisher Full Text
Biocarta[http://www.biocarta.com/] webcite


text:
Staff writers
The Bay Area air district declared toxic chemical levels were safe after Monday night's Chevron refinery fire in Richmond, so why did nearly 1,700 people rush to hospital emergency rooms complaining of stinging eyes, wheezing and difficulty breathing?
Experts note the tests analyzed chemicals in the air, but not the particulate matter -- soot -- that turns smoke black and can irritate the eyes, nose, throat and lungs.
"The fact that the laboratory results don't show much is reassuring, but that's not the whole story," said Dr. Wendel Brunner, public health director for Contra Costa County. "The tests that we were doing didn't really test for the particulate matter."
The plume of smoke rose 1,000 feet or higher and blew east into the Central Valley and the Sierra, dispersing along the way, said Eric Stevenson, director of technical services for the Bay Area Air Quality Management District.
As a result, most of the soot lifted above the community, he said.
But Brunner noted that winds "were quirky that night" and may have blown particulate matter through some neighborhoods before rising.
The air district tested for sulfur dioxide and hydrogen sulfide and found ordinary levels except for a small increase in sulfur dioxide in Martinez, but still well within safety standards, Stevenson said.
The air district also tested for 23 hydrocarbons as the fire burned and "there was nothing out of the ordinary that occurred," he said.
Many residents, however, say their experience was anything but ordinary.
"It felt like an asthma attack, and I haven't had one of those in years," said Jamisha Reames, 23, of Richmond. "I had to give my son a breathing treatment, and my newborn daughter was coughing a lot."
"I had tightness in my chest and a bad cough," said Charmagne Moore, 36, of San Pablo. "I didn't want to leave the house."
Moore visited the emergency department at Kaiser Permanente in Richmond on Tuesday and was prescribed two inhaled medicines, something she had never used before.
By midday on Wednesday, Doctors Medical Center in San Pablo estimated it had seen more than 600 people complaining of respiratory problems. Kaiser Permanente Richmond Medical Center said it had seen more than 900 people.
Some may have sought care to get documentation for filing a claim against Chevron, but health leaders said they believe many of the complaints were real.
"A lot of people were understandably anxious," Brunner said. "Fortunately, nobody was injured seriously enough to have to be admitted to the hospital."
The air district had instruments that measured particulate matter several miles away in Oakland, Vallejo and San Rafael and that turned up nothing out of the ordinary, Stevenson said.
Other equipment in San Pablo, a couple miles from the refinery, can also measure particulate matter, but the results from that will not be available for a week or two, he said.
Brunner noted that the San Pablo equipment is on an automatic schedule and would have begun monitoring at midnight, several hours after the fire began.
"So we are not going to have really good measures of the particulate matter," Brunner said. "The truth of the matter is we are not going to have good measures of what people were exposed to."
Although the level of toxic chemicals in the air remained well within safety standards, people can experience a cumulative effect from living in an area with industrial and diesel emissions, experts note.
Young children, the elderly and those who have chronic conditions may be more affected by low levels of exposure, said Stephen Zavestoski, an El Cerrito resident and professor of environmental studies at the University of San Francisco. "The cumulative effect of this really triggers people's emotions and their anger," he said.
People living in industrial areas such as North Richmond and West Oakland often contend with higher rates of diesel and other emissions, asthma hospitalizations, poverty and a lack of educational opportunities that can bring added stress and increase health problems, noted Alex Briscoe, director of the Alameda County Health Care Services Agency.
"It's not the exposure of this week," Briscoe said. 'It's the exposure over months and years and decades."
Staff writer Sean Maher contributed to this report. Sandy Kleffman covers health. Contact her at 925-943-8249. Follow her at Twitter.com/skleffman.

subset: commoncrawl


text:
Economics Professor Eric Hughson Installed as Freeberg Chair
Eric Hughson was recently installed as the Don and Lorraine Freeberg Professor of Economics and Finance at CMC. Hughson teaches in the Robert Day School of Economics and Finance, and is the director of the Financial Economics Institute. As part of the evening's program at the Marian Miner Cook Athenaeum, Hughson gave a talk on "Funding Constraints, Asset Volatility, Market Liquidity, and Financial Crises: Lessons from History." S. Brock Blomberg P'13, dean of the Robert Day School and the Peter Barker '70 Professor of Economics and George R. Roberts Fellow, presented Hughson with his medallion.
"The Freeberg Chair gave me the opportunity to come to CMC and work with great students," said Hughson. "I've enjoyed both my research and teaching interactions here very much."
Hughson earned his B.S. from the Massachusetts Institute of Technology, and his M.A. and Ph.D. from Carnegie Mellon University. Before joining the faculty of CMC, Hughson was an associate professor of finance at the University of Colorado, Boulder.
Hughson's research focuses on market microstructure, financial econometrics, and decision theory. He is a member of the American Finance Association and the American Economic Association, and is a referee for a number of research journals, including Journal of Banking and Finance, Review of Financial Studies, Canadian Journal of Economics, and American Economic Review. President Gann recognized Don and Lorraine Freeberg for their long-time support of the College, and presented them with a plaque of appreciation. Freeberg is a Life Trustee on the CMC Board of Trustees, and was a recipient of the Honorary Life Membership Award in CMCAA.
For more information on Professor Hughson, visit his profile page.


text:
Take a sneak peek at the new NIST.gov and let us know what you think!(Please note: some content may not be complete on the beta site.).
Draft Talking Points for
Phillip J. Bond,
Under Secretary of Commerce for Technology
Chief of Staff to the Secretary of Commerce
NIST Center for Neutron Research Recognition Event
5 August 2002
[Mr. Bond is introduced by NIST Director Arden Bement.]
The National Institute of Standards and Technology (NIST) is an agency of the U.S. Department of Commerce.
Privacy Policy / Security Notice / Accessibility Statement /
Disclaimer /
Freedom of Information Act (FOIA) /
Environmental Policy Statement /
No Fear Act Policy /
NIST Information Quality Standards /
Scientific Integrity Summary /
DOC Communications Policy
Date created: August 5, 2002 | Last updated: October 5, 2010
Contact: Webmaster


text:
'Insecure' Creator, Star Issa Rae on How Hannibal Buress Gave Her That First Big Break
TCA 2016: Executive producers of new HBO comedy discuss diversity, nudity and making history
TCA 2016: Executive producers of new HBO comedy discuss diversity, nudity and making history
From Louis C.K.'s Jack Russell Terrier protagonist to Kevin Hart as villainous bunny Snowball, there's a whole pack of Hollywood stars bringing Illumination Entertainment's animated movie to life
Danny Glover, Logan Marshall-Green and Martin Starr were added to the cast last week
"Are we a dysfunctional family? Epically," reads the caption
Comedy Central show returns on Feb. 17
The Paramount release opens on Dec. 25
The comedian's Comedy Central series "Why? With Hannibal Buress" premieres July 8
"I don't want to have a fancy shark costume, because I want people to be able to relate to me," the comedian says
Comedian Hannibal Buress hosts 19th annual event, streaming online May 19 at 9 a.m. ET
Other nominees for the program's 19th edition include Zach Galifianakis, Kevin Hart and Vice Media
The comedian will open the show and enforce the Webby's trademark five-word acceptance speech rule on May 18
"I get a lot of messages from people about it," Buress told Jimmy Kimmel
The "Believe" singer threw some punches of his own after jabs from Kevin Hart, Natasha Leggero, Snoop Dogg
The series has been picked up for eight episodes and will air in July
Athletes and hip-hop artists round out the star-studded, egg-throwing affair
The funnyman was carried away after the "attack" which was being filmed for an upcoming movie
"I don't know why it's so hard to believe women," says the comedian, "You to go Saudi Arabia and you need two women to testify against a man. Here you need 25"
"Washington is increasingly in a bubble much the same that a lot of people who live in Hollywood are in a bubble," comedian Lewis Black says on "Meet the Press"
Programming block will be anchored by "Lucas Bros. Moving Co." and "Stone Quackers"
"Marty is a very intimidating person. What he's doing is letting people know that if they fuck with his client, they're going to have a battle," civil litigator Howard Alperin tells TheWrap
Therese Serignese accuses the comedian of sexually assaulting her in 1976
Hollywood be warned: we live in a world where full transparency is the rule, not the exception
After "View" moderator Whoopi Goldberg asks why accuser Joan Tarshis didn't get a kit down, TheWrap uncovers the answer from experts in sexual assault cases
Showbiz fixers weigh in on the comedian's PR disaster, and say silence is golden
Projects with the entertainment icon will continue despite sexual assault victims' recent public statements
"Mr. Cosby does not intend to dignify these allegations with any comment" the comedian's attorney says Sunday
"The women victimized by Bill Cosby have been talking about his crimes for more than a decade. Why didn't our stories go viral?" Barbara Bowman writes
Syndicated daytime talker accused of having "cold feet" surrounding actor and comedian's appearance
The former "Saturday Night Live" writer and comedian reminded his audience that the "Cosby Show" patriarch has been accused of sexual assault


text:
a1 Columbia University firstname.lastname@example.com
The consensus view that all Roman money consisted of coins has been undermined in recent times and should be discarded. The inhabitants of the Roman Empire frequently and on a significant scale made payments by means of credit-money, creating a 'multiplier effect', which meant that in high classical times the Roman economy was not constricted, as is often supposed, by an inelastic money-supply. Yet the monetary system was not modern; rather it had its counterparts in such economies as those of seventeenth-and early eighteenth-century Britain.
Key Words:
* I warmly thank Jean Andreau, Jean-Jacques Aubert, Alessandra Casella, Marcello De Cecco, Richard Duncan-Jones, Martha Howell, Elio Lo Cascio, Paolo Malanima, and Peter Temin, who all read and criticized an earlier version of this paper with salutary effects. It is obviously not to be presumed that they agree with my conclusions. I am also extremely grateful to St John's College, Oxford, for the opportunities provided by a visiting fellowship.


text:
Open AccessThis article is
Notes: Multiple requests from the same IP address are counted as one view.
- freely available
- re-usable
Crystals 2012, 2(3), 1210-1221; doi:10.3390/cryst2031210
Electronic Structure of Cu(tmdt)2 Studied with First-Principles Calculations
1 Nanosystem Research Institute (NRI) "Research Initiative of Computational Sciences (RICS)", National Institute of Advanced Industrial Science and Technology (AIST), 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan 2 Japan Advanced Institute of Science and Technology (JAIST), 1-1 Asahidai, Nomi, Ishikawa923-1292, Japan
* Author to whom correspondence should be addressed.
Received: 13 April 2012 / Revised: 9 August 2012 / Accepted: 13 August 2012 / Published: 21 August 2012
(This article belongs to the Special Issue Molecular Conductors)
View Full-Text | Download PDF [2977 KB, uploaded 21 August 2012] | Browse Figures
AbstractWe have studied the electronic structure of Cu(tmdt)2, a material related to single-component molecular conductors, by first-principles calculations. The total energy calculations for several different magnetic configurations show that there is strong antiferromagnetic (AFM) exchange coupling along the crystal a-axis. The electronic structures are analyzed in terms of the molecular orbitals near the Fermi level of isolated Cu(tmdt)2 molecule. This analysis reveals that the system is characterized by the half-filled pdσ(−) band whose intermolecular hopping integrals have strong one-dimensionality along the crystal a-axis. As the exchange splitting of the band is larger than the band width, the basic mechanism of the AFM exchange coupling is the superexchange. It will also be shown that two more ligand orbitals which are fairly insensitive to magnetism are located near the Fermi level. Because of the presence of these orbitals, the present calculation predicts that Cu(tmdt)2 is metallic even in its AFM state, being inconsistent with the available experiment. Some comments will be made on the difference between Cu(tmdt)2 and Cu(dmdt)2.
Keywords: single-component molecular conductor; Cu(tmdt)2; electronic structure; first-principles calculation; antiferromagnetic state
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
Share & Cite This Article
MDPI and ACS Style
Ishibashi, S.; Terakura, K. Electronic Structure of Cu(tmdt)2 Studied with First-Principles Calculations. Crystals 2012, 2, 1210-1221.View more citation formats
AMA Style
Ishibashi S, Terakura K. Electronic Structure of Cu(tmdt)2 Studied with First-Principles Calculations. Crystals. 2012; 2(3):1210-1221.Chicago/Turabian Style
Ishibashi, Shoji; Terakura, Kiyoyuki. 2012. "Electronic Structure of Cu(tmdt)2 Studied with First-Principles Calculations." Crystals 2, no. 3: 1210-1221.
Find Other Styles
Related Articles
Article Metrics
Notes: Multiple requests from the same IP address are counted as one view.
For more information on the journal, click here
Comments[Return to top]
Crystals EISSN 2073-4352 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert


text:
4 Strategies for Structuring Productive Remote Teams: ow.ly/q67l303H0g0
As visual collaboration announcements about new products continue to hit the news it can be somewhat challenging to discern the technical jargon from the user benefit. Nearly all of these announcements refer back to some set of technical terms that may be lauded in the announcement but aren't fully explained. Below are some key terms and meanings that you might have seen recently. SVC – Scalable Video Coding: Up until now most major video conferencing manufacturers have built their solutions around AVC (Advanced Video Coding). Essentially AVC and SVC are formats of compression technology that allow high definition video to be sent across networks in an …Read more
Since most people have little to no understanding of legal jargon and legal processes they rely heavily on their attorney to handle things properly. Clients must place a significant amount of faith in their attorney; trusting that he knows what he is doing because it's impossible to check over his shoulder. For example, at the grocery store you can double check your bill to ensure you were not double charged for items; but how do you know if your lawyer filed the correct paperwork? Law firms rely heavily on building relationships by staying in touch with clients; and face-to-face communication is …Read more
IBM conducts a biannual study of global CEOs to determine the latest trends in global organizations. In a HBR chat, Saul Berman and Stephen Hasselmann discuss some of the findings from their recent study. If you have an hour to invest, the recording is well worth the time; otherwise the highlights are available here. The key takeaway from both the study and the chat is the value of connecting employees, partners and customers. Technology is changing rapidly and the advances that result are changing the business and economic landscape for most companies. We are more connected than ever and the most effective …Read more
Yesterday Polycom held a press event at NASDAQ to announce a bevy of products and offerings. This event was the culmination of several years of R&D and the announcements signaled Polycom's strategic direction for the next several years. Specifically, the announcements surrounded room and personal based video conferencing systems, as well as, new software based solutions and cloud offerings. Specific announcements included: Move to SVC Polycom is moving to an open source version of SVC (Scalable Video Coding). What is particular interesting about this is not only is Polycom gaining the feature benefits of SVC (1080p60, bandwidth scalability, etc), they are also offering up their …Read more
It's finally here, the Capstone class that completes the last semester of my MBA. In it, we break up into teams and play a computer simulated game where we compete against each other in a mock business world. At the beginning of the class our professor said, "I would suggest meeting in person, teams that meet over video historically haven't done very well." This slightly upset me since I work at a video company and truly believe that teams meeting over video can be just as effective as teams meeting in person. I thought to myself, challenge accepted, and set out …Read more
Technology can be quite fickle; it's amazing and life-saving when it works but frustrating and downright annoying when it doesn't. Whether the unit isn't powering on, sound isn't coming out of the speakers or the display is flashing some cryptic message; a support technician is just a phone call away to troubleshoot and diagnose the issue. The day of a help desk technician usually starts with a cup of coffee and a review of the ticketing queue. First up, are any new tickets that have been submitted and a quick review of the issues customers are having. Then, a review of …Read more
Last week Telework Exchange released "Fly Me to Your Room: Government Video Conferencing Collaboration Report." This report outlined the benefits of video conferencing and telecommuting that can be realized by the federal government. In the report, the authors interviewed 128 Federal employees in an attempt to understand the value of video within the government. As a prelude to this report, President Obama issued Executive Order 13589 in November of last year that promoted "efficient spending" and one of the key areas mention was Government travel. What's truly amazing about this is that the federal government spent $15 billion on travel in …Read more
We've all been there, in that meeting that just seems to drag. You can't help but look at your phone and think of all the better things you could be doing with your time. The longer you sit, the most frustrated you become as people get off topic and nothing actually seems to get accomplished. Instead of getting annoyed, stop and think, is this dreadful meeting actually your fault? While your initial response might be absolutely not, the more you think about it there's a slight possibility. Here's how: You Assume All Meetings Are a Waste of Time If you go into a …Read more
Football reigns supreme in our nation; whether it's the NFL, NCAA, High School or even little league. In many towns, Friday night games are the center of a town's social activity; and anyone involved with the winning touchdown is considered a hero. It's no wonder kids are gearing up to play almost as soon as they can walk. In fact, my nephew has been playing since he was four years old! Unfortunately, repeated hits to the head from high contact sports have spurred a concussion epidemic that spans from football, to hockey, to even wrestling. Multiple concussions can cause brain damage …Read more
With all the buzz around unified communications including new product releases, features, acquisitions and more, it's easy to forget the why of UC and how it can benefit an organization. In this series of posts we will examine some of the key areas of UC and what the business benefit can be. For part one click here. Now that we have examined what some of the key features of UC solutions are, it's important to understand who are the major players in the market and what solutions they offer. While many of these solutions have been on the market for …Read more


text:
Username or Email Address
(forgot?) Register
A comprehensive Flickr plugin that makes it easy to show off your images in style.
Download Version 0.1.9
If you know how to use it, all works as expected
RSS link for this plugin's reviews.
You must log in to submit a review. You can also log in or register using the form near the top of this page.


text:
New DVD
TCM Greatest Classic Films Collection - Comedy
- Summary
- Reviews / Ratings
- Photos
- Videos
- Events
Includes - A Night at the Opera (1935), MPAA Rating: NR Arsenic and Old Lace (1944), MPAA Rating: NR Father of the Bride (1950), MPAA Rating: NR The Long, Long Trailer (1954) A Night at the Opera Although some purists hold out for Duck Soup (1933), many Marx Brothers fans consider A Night at the Opera the team's best film. Immediately after the credits roll, we are introduced to Groucho Marx as penny-ante promoter Otis B. Driftwood. After a sumptuous dinner with a beautiful blonde at a fancy Milan restaurant, Driftwood tries to cadge another free meal from his wealthy patroness, Mrs. Claypool (Margaret Dumont). The dignified dowager complains that Driftwood had promised to get her into high society, but has done nothing so far. Otis B. counters by introducing Mrs. C to pompous opera entrepreneur Gottleib (Sig Rumann); all Mrs. Claypool has to do is invest several hundred thousand dollars in Gottleib's opera company, and her entree into society is in the bag. Contingent upon this plan is Driftwood's signing of Rodolfo Lassparri (Walter Woolf King), a self-important tenor. Backstage at the opera, Driftwood meets Fiorello (Chico Marx), who poses as a manager and offers to sell Driftwood the "world's greatest tenor"-not Lassparri, as Driftwood assumes, but Fiorello's pal Ricardo Baroni (Allan Jones). Instantly the two sharpsters try to draw up a contract ("The party of the first part shall hereafter be known as the party of the first part..."), which they proceed to tear up piece by piece whenever coming across a clause that displeases them (Driftwood: "That's a sanity clause"; Fiorello: "You no foola me. There ain't no Sanity Claus"). Having lost Lassparri to Gottleib, Driftwood sails back to America with Mrs. Claypool and the opera company. Gottleib arranges for Driftwood to get the tiniest, least accessible stateroom on the ship. Unpacking his trunk, Driftwood discovers that he's got to share his postage-stamp quarters with Ricardo Baroni, who has stowed away because he's in love with the opera troupe's leading lady Rosa (Kitty Carlisle). Also hiding out in Driftwood's trunk is Fiorello, who's come along because he's still Ricardo's manager, and the wacky Tomasso (Harpo Marx), Lassparri's former dresser, who has come along for the hell of it. Anxious to arrange a tete-a-tete with Mrs. Claypool in his stateroom, Otis finds out that his unwelcome guests won't leave until they're fed ("Do you have any stewed prunes? Well, give them some black coffee, that'll sober 'em up"). After ordering a huge dinner, Otis and his new friends are crowded even farther by a steady stream of intruders, including an engineer and his assistant, a cleaning lady, a manicurist, a girl looking for her Aunt Minnie, and a dozen waiters. The celebrated "stateroom scene" comes to a rollicking conclusion when Mrs. Claypool has the misfortune of opening the door. On the last night of the voyage, Fiorello, Tomasso and Ricardo sneak out of their stateroom to enjoy an impromptu ethnic festival in steerage. Ricardo sings, Fiorello "shoots the keys" on the piano, and Tomasso plays the film's theme song Alone on the harp. The stowaways are caught and thrown in the brig, but with Driftwood's help they escape. To avoid recapture, the stowaways don heavy beards and pose as three famed Russian aviators. After making a shambles of a public reception, the three reprobates hide out in Driftwood's New York apartment, where everyone conspires to drive an investigating detective (Robert Emmet O'Connor) crazy. Driftwood is fired from the opera company for associating with the stowaways, while Rosa is dismissed for refusing Lassparri's affections. In order to restore Rosa's job and put the deserving Ricardo in Lassparri's place during the opening performance of La Traviata, Driftwood, Fiorello and Tomasso concoct a scheme that will reduce the opera to comic chaos. The actual night at the opera in A Night at the Opera must be seen to be believed, but the spirit of the scene c
More Details
Released - Tuesday, November 3 , 2009
- Distributed by - Warner Home Video
- MPAA Rating - NR


text:
RadioShack Profit Rises 9% on Sales of Mobile Phones
RadioShack Corp., the consumer-electronics retailer, said second-quarter profit increased almost 9 percent, spurred by demand for mobile phones.
Net income advanced to $53 million, or 41 cents a share, from $48.8 million, or 39 cents, a year earlier, Fort Worth, Texas-based RadioShack said today in a statement. The earnings per share were in line with the average of 16 analyst estimates in a Bloomberg survey.
RadioShack, led by Chairman and Chief Executive Officer Julian Day, spent more on marketing and boosted inventories of mobile devices. U.S. stores' wireless sales including Sprint Nextel, T-Mobile and AT&T phones climbed 61 percent, blunting declines for digital converter boxes, netbooks, cameras and batteries.
Sales rose 4.7 percent to $1.01 billion, slightly less than the average analysts' projection of $1.02 billion. RadioShack climbed 61 cents, or 3 percent, to $20.80 at 4:02 p.m. in New York Stock Exchange composite trading. The shares have advanced 6.7 percent this year.
The company plans to expand a test selling wireless devices in kiosks at Target Corp., the second-largest U.S. discount retailer. Starting Aug. 15, it plans to set up Bullseye Mobile kiosks in most Target stores by mid-2011. The Minneapolis-based company operated 1,740 stores as of May 1.
Added Inventory
Inventory increased 12 percent to $646.2 million in the quarter, while selling, general and administrative expenses totaled $364.5 million, 8.6 percent higher than a year earlier. The company cut its full-year forecast for capital expenditures to $90 million to $110 million from as much as $120 million.
Three private equity firms have backed away from pursuing RadioShack, three people with knowledge of the plans said last week. TPG Capital plans to drop out of bidding for the retailer, a person briefed on the talks said at the time. Blackstone Group LP, which had weighed a joint offer with TPG, is not likely to pursue RadioShack on its own, said another person.
Bain Capital LLC, which had separately expressed interest, also has backed off, one person said last week. All three people asked not to be identified because the bidding process is private.


text:
IMCgp100 in Advanced Unresectable Melanoma
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Advanced Disease
Drug: IMCgp100 injection
Phase 0
|Study Type:
|Study Design:
|Primary Purpose: Treatment
|Official Title:
|A Phase 0, Exploratory Study of the Pharmacodynamics of a Single Intratumoral Dose of IMCgp100, a Monoclonal Receptor Anti-CD3 scFv Fusion Protein, in Subjects With Advanced Unresectable Melanoma
- Adverse Events as a Measure of Safety and Tolerability [ Designated as safety issue: Yes ]
To determin the safety and pharmacodynamic properties of single intratumoral doses of IMCgp100 in the setting of advanced unresectable melanoma.
Tumor Lesions, peripheral blood pre- and post-injection will be used to determine the safety and pharmacodynamic properties of single intratumoral doses of IMCgp100 in the setting of advanced unresectable melanoma
- Adverse events [ Designated as safety issue: Yes ]Will be used to determine the safety and tolerability of IMCgp100 at subtherapeutic doses.
- Vital signs [ Designated as safety issue: Yes ]will be used to determin the safety and tolerabiluty of IMCgp100 at subtherapeutic doses.
- PE examinations findings [ Designated as safety issue: Yes ]will be used to determin the safety and tolerability of IMCgp 100 at subtherapeutic doses.
- Periperal blood samples [ Designated as safety issue: Yes ]will be used to examine peripheral cytokine measurements as evidence of product immunoactivity and peripheral T and NK cell numbers, phenotype and activation marker status.
|Estimated Enrollment:
|Study Start Date:
|September 2010
|Study Completion Date:
|March 2012
|Primary Completion Date:
|March 2012 (Final data collection date for primary outcome measure)
Drug: IMCgp100 injection
This study will test the safety effect of a single dose of the investigational drug IMCgp100 when administered directly into the metastatic melanoma lesion in patients with advanced metastatic melanoma. IMCgp100 is a drug made up of two components. The first is the T cell receptor designed to bind specifically and tightly with protein found at high levels on the surface of melanoma cancer cells and second is an anti-CD3 fragment that is meant to bind to and activate the T cells. There will be two stage dose regimens each enrolling 3 patients. Stage 1 dose will 0.00017 mg IMCgp100 and Stage 2 dose will be 0.0017 mg IMCgp100. Inclusion Criteria: 1. Histologically confirmed dx of advanced unresectable melanoma not requiring immediate treatment and/or in a window between treatments 2. Two or more cutaneous or subcutaneous melanoma metastatic lesions 7 to 15 mm in at least one dimension and amenable to subsequent biopsy 3. Greater or equal to 18 years of age 4. ECOG PS 0-2 5.
Able to provide informed consent and willing to comply with protocol requirements 6. Female patients must not be of childbearing potential or must have negative serum pregnancy test 48 hours prior to receiving investigational drug 7. Male patients must agree to use reliable form of birth control throughout study 8. Must have adequate organ system function Exclusion Criteria: 1. Received any other chemo, immune, radiation or investigational therapy agents within 2 weeks prior to study treatment 2. Cutaneous metastasis that have received prior local therapy 3. Pregnant or breastfeeding 4.
History of autoimmune disease 5. Current treatment with steroid or other immunosuppresive meds 6. Active uncontrolled infection 7. Known HIV infection 8. Uncontrolled seizures 9. Known delayed wound healing 10. On full dose anticoagulation therapy.
|Ages Eligible for Study:
|18 Years and older (Adult, Senior)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Inclusion Criteria:
- 1. Histologically confirmed diagnosis of melanoma, with advanced unresectable disease not currently requiring immediate treatment and/or in a window between treatments.
- 2. Two or more cutaneous or subcutaneous melanoma metastatic lesions 7-15 mm in at least one dimension and amenable to subsequent biopsy.
- 3. Age 18 years
- 4. ECOG performance status 0-2
- 5. Able to understand and to provide written informed consent and willingness to comply with all protocol requirements;
- 6. Female patients who are not be of childbearing potential as documented by medical history (e.g., tubal ligation or hysterectomy), or be post menopausal with a minimum 1 year without menses or have a negative serum beta human chorionic gonadotropin (HGC) pregnancy test within 48 hours prior to receiving the intratumoral injection and agree to use an acceptable form of birth control, defined as abstinence or use of an intrauterine device (IUD), oral contraceptive, barrier and spermicide, or hormonal implant throughout the study period;
- 7. Male patients who must agree to use an acceptable form of birth control throughout the study period.
- 8. Adequate organ system function as evidenced by laboratory values: -Absolute neutrophil count (ANC) greater than or equal to 1.0 X 109/L -Hemoglobin greater than or equal to 9 g/dL -Platelets greater than or equal to 75 X 109/L -Total bilirubin less than or equal to 1.5 mg/dL -AST and ALT less than or equal to 2.5 X ULN ( 2.5 X ULN in the presence of liver metastasis.) -Creatinine less than or equal to 2 mg/dL -TSH within normal limits -INR/PT and PTT less than or equal to 1.3 X ULN
Exclusion Criteria:
- 1. Receive any chemotherapy, immunotherapy, radiation therapy, or other investigational agents (agents part of a research protocol or not approved by the FDA) within 2 weeks prior to injection. A minimum of 14 days is required between last therapy and injection on this study. In addition, any clinically significant drug-related toxicity should have recovered to grade 1 or less (excluding alopecia)
- 2. Patients without cutaneous or subcutaneous metastatic lesions;
- 3. Cutaneous metastases that have received prior local therapy, such as radiation or isolated limb perfusion.
- 4. Pregnancy or breastfeeding
- 5. History of autoimmune disease (excluding vitiligo or controlled thyroid disease) or immunodeficiency.
- 6. Current treatment with steroids (inhaled, topical or systemic) or other immunosuppressive medications within 2 weeks of injection;
- 7. Active uncontrolled infection;
- 8. Known HIV positivity;
- 9. Uncontrollable seizures;
- 10. Known delayed wound healing;
- 11. Full dose anticoagulation with heparin, warfarin, or any other anticoagulant within 2 weeks of injection ;
- 12. History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting, stroke or TIA within the past 24 weeks.;
- 13. Known hypersensitivity of IMCgp100 or any of its components (ie, Tween) ;
- 14. Class II, III, or IV heart failure as defined by the New York Heart Association;
- 15. Any psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
- 16. Any other condition that in the investigators opinion would jeopardize compliance with the protocol ;
Please refer to this study by its ClinicalTrials.gov identifier: NCT01209676
|United States, Pennsylvania
|Abramson Cancer Center of the University of Pennsylvania
|Philadelphia, Pennsylvania, United States, 19104
|Responsible Party:
|Abramson Cancer Center of the University of Pennsylvania
|ClinicalTrials.gov Identifier:
|NCT01209676 History of Changes
|Other Study ID Numbers:
|Study First Received:
|September 22, 2010
|Last Updated:
|February 25, 2013
|Health Authority:
|United States: Food and Drug Administration
Keywords provided by Abramson Cancer Center of the University of Pennsylvania:
Adult subjects with histologically confirmed diagnosis of melanoma, with advanced unresectable
disease not currently requiring treatment and/or in a window between treatments
Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
ClinicalTrials.gov processed this record on August 23, 2016


text:
(A) No drug may be dispensed on prescription unless a label is affixed to the container in which such drug is dispensed and such label includes:
(1) The name and address of the pharmacy as it appears on the terminal distributor of dangerous drugs license unless it is filled pursuant to a board-approved central filling operation, in which case the label shall bear the name and address of the originating pharmacy as it appears on the terminal distributor of dangerous drugs license;
(2) The full name of the patient for whom the drug is prescribed; or, if the patient is an animal, the full name of the owner and identification of the animal;
(3) The full name of the prescriber;
(4) Directions for use of the drug;
(5) The date of dispensing;
(6) Any cautions which may be required by federal or state law;
(7) The serial number of the prescription;
(8) The proprietary name, if any, or the generic name and the name of the distributor of the drug dispensed; and the strength, if more than one strength of the drug is marketed. The dispensing pharmacist may omit the name and strength of the drug only if the prescriber specifically requests omission in writing in the case of a written prescription, or verbally in the case of an orally transmitted prescription;
(9) The quantity of drug dispensed;
(10) If filled as part of a board-approved central filling operation, an identification of the pharmacy providing the drugs for the dispensing operation.
(B) The term "affix" means the prescription label must be attached or fastened to the container.
(C) At least the prescription number and the name of the patient must be placed on all prescription containers too small to bear a complete prescription label and dispensed in a container bearing a complete prescription label. The label bearing only the prescription number and the name of the patient does not need to be applied to any product whose function would be impaired by such a label. In all cases, a complete prescription label meeting the requirements of paragraph (A) of this rule must be applied to the container in which such product is dispensed.
(D) This rule does not apply to drugs which are dispensed for use by inpatients of an institutional facility whereby the drug is not in the possession of the ultimate user prior to administration. Such drugs shall be labeled in accordance with rule 4729-17-10 of the Administrative Code.
Five Year Review (FYR) Dates:
10/20/2015 and
Promulgated Under: 119.03
Statutory Authority: 3715.69, 3719.28, 4729.26
Rule Amplifies: 3715.64, 3719.01, 3719.08, 4729.01, 4729.27, 4729.28, 4729.37, 4729.38
Prior Effective Dates: 9/10/76, 8/1/84, 9/1/85, 7/1/91, 2/1/98, 3/1/99, 3/31/00, 1/1/10


text:
NEWBURGH — Safe Homes of Orange County received a $20,000 unrestricted grant toward its programs and services for survivors of domestic abuse.
The grant was one of 150 totaling $3 million presented by the Mary Kay Foundation in honor of Domestic Violence Awareness Month.
The money will be divided among three Safe Homes programs, according to Executive Director Kellyann Kostyal-Larrier: their language line, which provides translation of incoming calls; the Safe Pets Project, a new collaboration with the Warwick Valley Humane Society to temporarily place pets of abuse victims; and to help buy playground and laundry equipment for the agency's 17-bed shelter.
Safe Homes maintains a 24-hour hotline, which received 3,853 calls in 2012; provides advocacy and accompaniment for victims; and maintains liaisons with Orange County's Department of Social Services, Child Protective Services and District Attorney's Office, as well as local law enforcement agencies.
To learn more about Safe Homes, visit www.safehomesorangecounty.org/. The 24-hour hotline number is 562-5340 or toll-free at 888-503-4673 (HOPE).
Location, ST | website.com


text:
Mary Liz Curtin: Pay Well and Keep the Job Satisfying
How do you keep nonfamily, top executives of family-owned companies motivated, if they know they will never run the company?
Any company is run by a team, not just the person with the top title. Everybody, from the manager to those working the line, writing the code or running the registers, needs to be appreciated, compensated and acknowledged for his or her contributions, large and small. Executives are no different. Retaining top talent is a combination of paying well and keeping the job challenging and satisfying.
The chances of ascending to the very top are small, no matter who you are or where you work, but in a family business the problem is more than not getting the top job: The biggest issue is not that one loses the promotion but that the kid with the family name may not be qualified or have a sense of unearned entitlement. To keep your executives happy any promotion must be deserved, all employees must be respected and anyone related to the boss should work harder than everyone else.
It isn't always easy for the family, either, by the way. In a family shop, just being in line doesn't necessarily mean you will get the top job, as Prince Charles can tell you.
Mary Liz Curtin (@marylizcurtin) is the owner of Leon & Lulu, a destination lifestyle store in Detroit.


text:
Founding Father Of VC Linked To Madoff
By Tomio Geron
For months we've been wondering whether any venture capitalists are connected to Bernard Madoff's Ponzi scheme. Turns out, one of their founding fathers is linked to him.
Arthur Rock, one of the original Silicon Valley venture capitalists, invested with Bernard Madoff through five trusts, according to court records released Thursday. It is unclear whether Rock had invested in the alleged Ponzi scheme or rather in the broker-dealer business. Rock was traveling and could not be reached for comment Thursday.
Rock, 82 years old, is known for helping to start-up and finance some of the key companies that built Silicon Valley, including Fairchild Semiconductor, Intel Corp. and Apple Inc.
Rock is known for having introduced eight unhappy scientists from Shockley Labs to Sherman Fairchild in 1957. At the time Rock was an investment banker with Hayden Stone. The eight scientists were eager to jump ship from William Shockley, who had just won a Nobel Prize in physics for helping to invent the transistor.
Sherman Fairchild invested in the group, which became Fairchild Semiconductor, one of the key points in the development of what is now Silicon Valley.
One of the eight scientists, sometimes known as the "Traitorous Eight," was Eugene Kleiner who later founded Kleiner Perkins Caufield & Byers with Tom Perkins.
Later Rock —and Kleiner Perkins – would invest in Intel, which was itself started by former Fairchild founders.
Rock founded venture firms Davis & Rock with Thomas J. Davis Jr. in 1961, and Arthur Rock & Co. through which he would invest in a range of companies such as Apple, Scientific Data Systems, which was acquired by Xerox, and Teledyne.
Forbes listed Rock as having a net worth of $1.1 billion in 2008.
Our sister blog, Private Equity Beat, uncovered several private equity professionals on the Madoff client list.


text:
Metal and wood.
2 7/8"W x 7"H x 1 3/4"D
Scale: 1/12
Assembly Required:
No1/12 scale, also referred to as one-inch scale (or 1" scale), means 1 inch = 1 foot
This item is made well and is so worth the price. It exceded my expectations. I thought it would be smaller but it is a substantial piece of furniture for the kitchen.
miniatures.com is dedicated to bringing you quality items at the best prices, and
we stand behind our products 100 percent. Satisfaction guaranteed. If, for any reason,
you are not completely satisfied with your order from miniatures.com, simply return
it to us within 30 days. We are more than happy to exchange it or provide you with
a credit or refund.


text:
Housing charity worker suspended for 'homophobic' comments
Published by Anonymous for 24dash.com in Housing
Housing charity worker suspended for 'homophobic' comments
A housing charity worker was suspended after telling a colleague
about his Christian beliefs against homosexuality, it was revealed
David Booker, 44, was chatting about his faith with co-worker Fiona Vardy during a late shift at the hostel in Southampton, Hants on March 26.
He told her he was opposed to same-sex marriages and to homosexual clergy but denied being homophobic and said that he had homosexual friends.
The next evening, Mr Booker was suspended from his £19,000-a-year post as a hostel support worker with Society of St James where he has worked for the last four years.
His employers told him the action was taken for "events that happened last night".
On March 30 he received a formal suspension notice which alleged that he "seriously breached" the charity's code of conduct "by promoting your religious views which contained discriminatory comments regarding a person's sexual orientation...
"The action has been taken to safeguard both residents and staff" at the Southampton Street hostel.
Mr Booker, 44, a born-again Christian from Southampton, turned to the Christian Legal Centre (CLC) which instructed human rights lawyer Paul Diamond to represent him.
Andrea Minichiello Williams, barrister and director of CLC, said: "Mr Booker has been suspended since March 27 for two weeks pending investigation.
"No date has been set for the investigation and disciplinary hearing.
"This case shows that in today's politically correct, increasingly secularised society, even consenting reasonable discussion on religion between two employees is being twisted by employers to discriminate and silence the Christian voice and freedom of expression."
He said the charity English Churches House Group, which was recently taken over by Society of St James, was largely funded by churches throughout Hampshire whose followers would be "shocked at the attitude and action taken by a Christian organisation towards a Christian employee".
He added: "The Archbishop of Canterbury, as patron, has confirmed the Church's teaching on marriage, same-sex relationships and homosexuality and that is in the public domain.
"We are interested to know whether his patronage is now under threat under the charity's Culture and Diversity Code of Conduct."
Trevor Pickup, Society of St James chief executive, later confirmed that Mr Booker had been suspended.
"The investigation is still ongoing," he said.
"Once we have made a decision, if it is appropriate, further action will be taken. At this stage we are still investigating.
"We are housing vulnerable adults and we need to be very careful to demonstrate our respect to them and the integrity of our staff as well."
The Society welcomed talks with CLC which has not contacted it as yet, he said.
Council calls for residents' views on new homes
Login and comment using one of your accounts...


text:
By Appointment
Dr. George Barber joined Greenville College in the fall of 1999 as head men's basketball coach. Before coming to Greenville College, Barber served as an assistant coach at Bradley University and an administrative assistant at the University of Kentucky where he was a member of Rick Pitino's staff for the 1996 national championship team. Barber graduated from Asbury College in 1986 before completing a master's degree and doctorate at the University of Kentucky.
While at Greenville as head men's basketball coach, he has coached players which have received -
1 NCCAA Pete Maravich National Player of the Year Award
23 NCCAA All Region Awards
2 NCCAA All-American Award
19 SLIAC All-Conference Awards
2 SLIAC All-Defensive Team Awards
5 SLIAC Team Sportsmanship Awards
He is the longest tenured head men's basketball coach in Greenville College history and is second in all time coaching wins with 199 through 2014-15.
Head Men's Basketball Coach
Full Professor - Department of Kinesiology and Sport
NABC - National Association of Basketball Coaches (since 1995)
AAHPHERD - American Alliance for Health Physical Education Recreation and Dance (Since 1985)
Back to Basketball Coaching Staff


text:
My Dad was the foreman of the Pacific Telephone and Telegraph Company crew at Treasure Island at the time of the Golden Gate International Expo, enabling him to get passes for my sister Betty and me. What a great summer that was! There was so much to see and do.
To add to the atmosphere of the fair and the celebration of the opening of the Golden Gate and the San Francisco Oakland Bay Bridges, San Francisco took on a Western theme. The citizens had to dress in some type of cowboy gear. It was great fun for us catholic grammar school kids because we could wear cowboy stuff to school instead of our uniforms, cap pistols and all. By the way, that's how Levis jeans got so popular. Everybody bought some and really liked them after finding out how rugged and comfortable they were. The original Levi factory was on Valencia Street between 15th and 16th Streets. My dad thought the whole thing was silly and didn't join in until he was caught by the Keystone Cops on Market Street and put in Kangaroo Court, a wooden play jail on a trailer with a judge. What a burn up for him! He was fined and ordered to wear something western. He finally broke down and bought a neckerchief that he kept taking off and on.
Almost every major company had an exhibit at the fair. I saw television for the first time. They transmitted from the GE exhibit to the other end of the Island. There also were free outdoor shows with name performers. I remember my sister and several of her high school pals catching the first ferry in the morning to get good seats for Bing Crosby's show. It also featured most of the big bands like Jimmy and Tommy Dorsey, Glenn Miller, Benny Goodman, Harry James and Count Basie.
I saw it all, even Elsie the Cow, who was the trademark of The Borden Milk Company. Elsie was in a streamlined trailer, one side made of glass. Bing Crosby, Bob Hope and The Andrew Sisters also gave a free show but you couldn't get near that one. There was a show with a cast of hundreds called the Cavalcade of the Golden West. It was a history of the United States telling about driving the final stake for the trans-continental railroad with actual locomotives moving on the stage. It reenacted Custer's Last Stand with the Cavalry and Indians on horseback shooting their rifles. There also was Billy Rose's Aquacade featuring Esther Williams and Johnny Weissmuller, the Folies Bergere and a great Amusement Park at the north end of the Island.
The movie Alexander Graham Bell, starring Don Ameche and Henry Fonda as Mr. Watson had its west coast premier in 1939 on Treasure Island. My Mom and Dad had a photo, now missing, of Ameche, Fonda, the president and other officers of PT&T with my Dad in front of the theater before the premier. The Telephone Company had an exhibit in the Trade Building. One of our very close friends, Beverly Grubb the future Mrs. Jim Hagarty, was one of the hostesses there in 1940. She recently showed us a picture of her and the crew in front of the "Tower of the Sun." What a beauty she was and still is.
The Fair was originally built to become the San Francisco Oakland International Airport. The three permanent buildings on the south side of the island were to be the administration building and two hangers. Pan American Airlines' "China Clipper" was housed and took off from there. The inlet between Yerba Buena and Treasure Island was known as "Clipper Cove." The war came along and changed all that. "TI" (Treasure Island) became a Naval Base, the operations base for the Western Sea Frontier.
Matt O'Neil, Sacramento, CA
From SAN FRANCISCO'S LOST LANDMARKS, James R. Smith
Post a Follow-up:


text:
Take a sneak peek at the new NIST.gov and let us know what you think!
(Please note: some content may not be complete on the beta site.).
Project Brief
NIST Measurement Science and Engineering Research Grants
RECIPIENT: George Mason University, Fairfax, VA
Plans for cryptographic deployment on a wide variety of platforms, ranging from tiny RFID devices to busy Internet servers, are often derailed by the reality of inadequate software or hardware performance. Information regarding performance plays a critical role in standardization of cryptographic functions, and in selection of the preferred platforms, development tools, and hardware architectures for cryptography. Unfortunately, many evaluations of new cryptographic functions have biased performance testing, and even unbiased testing is often too limited to produce a true assessment of what performance can be expected in a variety of situations. In this project, the researchers will extend existing cryptographic benchmarking efforts into field-programmable gate arrays (FPGAs) and application-specific integrated circuits (ASICs), and develop a joint methodology and a single unified collaborative environment for benchmarking software, FPGA, and ASIC implementations of cryptography. The environment will be used to evaluate candidates submitted to NIST's SHA-3 contest for a new hash function standard, used as a basis for future secure digital signature schemes. The environment will be available to the entire cryptographic community, allowing researchers to fairly, comprehensively, and automatically compare their new cryptographic algorithms, hardware architectures, and optimization methods against previous work.
Public contact (for project information):
Chris LaPaille, 703-993-8860
Project Partners: Virginia Tech, University of Illinois at Chicago
NIST Program Office Contact:
Jason Boehm, 301-975-8678


text:
MT. PLEASANT, S.C. - The College of Charleston men's tennis team extended its Southern Conference win streak to three-straight matches with a 4-3 decision over Appalachian State on Saturday afternoon at the CofC Tennis Center at Patriots Point.
Freshman Zack Lewis (Richmond, Ky.) clinched the dual match as he led 6-4 in the first set and 3-0 in the second set, before ASU's Matt Saltgaver had to retire due to injury.
The Cougars (5-6, 3-2 SoCon) won two of the three doubles matches versus the Mountaineers (3-8, 1-1 SoCon) to take the early 1-0 momentum going into singles play.
Lewis and sophomore Alon Faiman (Ramat Hasharon, Israel) claimed an 8-6 victory over the No. 3 doubles tandem of Steve Karendal and Steve Lake from ASU, while junior Crescente Lesser (Santiago, Chile) and sophomore Sebastian Lopez (Medellin, Colombia) clinched the doubles point by a count of 8-4 over Jen-Willem Kleynhans and Andrew McKinnon on court two.
Freshman Josh Record (Tallahassee, Fla.) saw a start in the singles lineup and put the Cougars up 2-0 on the scoreboard with a straight-set win over Steve Lake, 6-3, 6-2, at the No. 6 line.
Junior Brice Allanic (Colombes, France) used a love first set and 6-4 second set to defeat ASU's Sebastien King at the top of the order to position Lewis for the eventual match clincher.
"We are dealing with some health issues right now, but the best part of our team is that everyone is versatile and mentally tough," CofC Head Coach Jay Bruner said. "We were able to play through some things and bring new guys in today. (Freshman) Josh Record played awesome at No. 6 singles and Brice (Allanic) played a complete match at No. 1. We played well in every spot in the lineup, even in the matches we didn't win today. Our guys were tested by App State and I think the team is looking good. We are finding some rhythm in our doubles and the guys are working through things in singles."
CofC will have a quick two-day turnaround as it travels to Georgia Southern on Monday, March 18 at 2 p.m. (ET) in Statesboro, Ga. The match at Mercer on Sunday was cancelled.
"We will play another tough conference school in Georgia Southern on Monday," Bruner said. "This is a tough schedule and we will see what we are made of. We are coming together as a team and finding a way to win four points in each of our matches."
March 16, 2013
CofC Tennis Center at Patriots Point
at Mt. Pleasant, S.C.
Attendance: 55
No. 1 - Brice Allanic (CofC) def. Sebastien King (ASU), 6-0, 6-4.
No. 2 - Steve Karendal (ASU) def. Sebastian Lopez (CofC), 6-2, 4-6, 1-0 (7).
No. 3 - Zach Bost (ASU) def. Charlie Ghriskey (CofC), 4-6, 6-2, 1-0 (8).
No. 4 - Andrew McKinnon (ASU) def. Alon Faiman (CofC), 6-7, 2-3, retired.
No. 5 - Zack Lewis (CofC) def. Matt Saltsgaver (ASU), 6-4, 3-0, retired.
No. 6 - Josh Record (CofC) def. Steve Lake (ASU), 6-3, 6-2.
No. 1 - Zach Bost-Sebastien King (ASU) def. Brice Allanic-Charlie Ghriskey (CofC), 8-6.
No. 2 - Crescente Lesser-Sebastian Lopez (CofC) def. Jen-Willem Kleynhans-Andrew McKinnon (ASU), 8-4.
No. 3 - Alon Faiman-Zack Lewis (CofC) def. Steve Karendal-Steve Lake (ASU), 8-6.
Doubles: 1, 3, 2
Singles: 6, 1, 5*, 4, 2, 3


text:
The Life and Opinions of Tristram Shandy, Gentleman
by Laurence Sterne
The Life and Opinions of Tristram Shandy, Gentleman Book 3, Chapter 34 Summary
- TS compares Mr. Shandy's picking up an idea to a man who picks up an apple and, as a result, lays claim to the apple (dropping a reference to John Locke's ideas of ownership).
- He's a greedy little bugger who thinks his opinions are solely his property. And Mr. Shandy has some pretty strong ideas about noses, as well as every single book ever written on the subject.
- And here's good place for Tristram to give Uncle Toby some love.


text:
Top Definition
A member of the opposite sex, ussualy a female who entices you into thinking you have a chance. Almost always ends with you having blueballs and feelings of sorrow, resentment and bitterness.
A girl who works at a local pizza parlor in Berwyn, IL.
A girl who works at a local pizza parlor in Berwyn, IL.
Shit yo, that girl was mad down with me, shes ready for something, oh shit, nm, shes got a man, fuck, what a tease.
Stephanie K
Stephanie K
লিখেছেন- Snax 27 de ডিসেম্বার de 2004
Trending Now
Can you define these popular missing words?
A girl who knows she's wanted... but just wants to play with the guy's head. ;)
Damn straight she's a tease... & good at it too.
লিখেছেন- Not Jen 1 de ডিসেম্বার de 2003
A girl who likes to flirt a lot without the intention of giving it up to you.
She's such a TEASE..
লিখেছেন- Joshiro007 21 de ফেব্রুয়ারি de 2003
A girl who looks good and knows guys want her but only plays with their mind
David thought Brenda was gonna give him some but she left right when he got all hard..... he got teased.
লিখেছেন- Princess*B* 13 de সেপ্টেমবার de 2004
A girl that sexually excites a boy but leaves him with out sexual stimulation; a girl that acts interested in another boy just to seduce him.
I know this one girl Jenny, man, she gave her boyfriend blue balls so bad... she got on top of him all wet, then left him hanging... she's the definition of a tease.
লিখেছেন- OMG_its_amyyyy 18 de অগাস্ট de 2005
A girl who flirts with you, with no intention of giving it up
Jessica promised me booty but wouldn't let me get any. What a fucking tease!
লিখেছেন- RED_aLeRt 7 de এপ্রিল de 2004
A girl who makes you think you are getting but knows you arent.
A girl who will show you the window dressing but wont let you in the store!
Similar to a bitch but even less willing although might be friendlier.
A girl who will show you the window dressing but wont let you in the store!
Similar to a bitch but even less willing although might be friendlier.
I dated a girl who wanted to go skinny dipping but didnt want to have sex.
লিখেছেন- Cheerleader Fucker 25 de অগাস্ট de 2004


text:
Comments no longer part of stories
October 1, 2013 - Art Smith
For the last several years readers have been able to comment on most stories that appear on NewsandSentinel.com.
We started the comments to give readers a place to share their views on news stories. Since 2008 readers have left more than 30,000 comments on stories. We had hoped they would stay on topic and discuss in a rationally way what was being reported.
Most people on our site use a variety of pseudonyms when leaving comments. It would seem that because of this many felt they could disregard common decency and act like online bullies.
Name calling of people quoted in the stories, insulting of fellow posters, the attempted use of foul language — none of it should happen, and it will not happen here.
So today the comments on stories are gone.
We still want to hear what you have to say; we just want to hear it in the form of a letter to the editor. Letters to the editors reach all our readers, including those in print, online and on mobile devices. Letters to the editor can be submitted online; in fact you can submit one at this link. Our goal is to turn those who commented online into letter to the editor writers.
You can still tell everyone what you think, the only difference is now, they will know who you are.


text:
As the Maine Sunday Telegram highlights Maine's 2009 conservation accomplishments, a working group is completing a pitch for federal funding of conservation in that state's North Woods.
From the Maine Sunday Telegram:
What began with low expectations and uncertainty about the economy ended as a big year for land conservation in Maine, with tens of thousands of acres of farmland, forest and lakefronts permanently preserved statewide in 2009, according to conservation advocates.
The deals range from landscape-scale purchases in the North Woods to strategic protection efforts in the more populated southern part of the state.
(That story was written before TPL announced the conservation of 10,000 acres at Stowe Mountain and Robinson Peak this morning.)
One impetus to these conservation accomplishments may have been the "green lining" in the current real estate downturn, which we have blogged on before, most recently here.
In York, for example, a coalition of land trusts raised more than $3 million and preserved the 151-acre Highland Farm, a tract of fields and forest habitat near the York River estuary and a pond that supplies drinking water to three communities.
The farm had long ago been identified as one of the last large undeveloped coastal tracts in the region. But when it was put on the auction block in 2003, a developer beat out conservationists and bought it, said Wolfe Tone, state director for the Trust for Public Land in Maine.
The developer submitted plans for 38 building lots on the property and already had permits to begin the first phase before agreeing to sell to conservationists.
"We got another run at it, and we turned it right around," Tone said. "He was going to go ahead (and build) if we didn't get it."
In Maine's North Woods, conservation successes have developed from coalition-building between conservationists, forestry interests, and local residents; and a story this morning in the Bangor Daily News highlights such coalition-building as key to possible federal funding for North Woods conservation.
After months of discussion and several promising meetings with Obama administration officials, a working group is completing a pitch for federal funding for "landscape-scale" conservation in Maine's North Woods that would also strengthen the state's forest products industry.
Last summer during a visit to Maine, U.S. Interior Secretary Kenneth Salazar expressed interest in hearing suggestions about how the federal government could help Maine preserve large swaths of forestland.
But Salazar made clear that any proposal would need a broad base of support that includes landowners and industry.
The story suggests that federal conservation in the North Woods will probably not take the form of a big national park, such as has been proposed by advocates over the last few years.
"At its heart, this is a proposal to maintain a sustainably managed forest landscape, which continues to produce wood products and protects ecological values, while maintaining and improving recreational opportunities," reads a draft outline of the report.
What the Great Maine Forest Initiative is not proposing, coalition members and state officials insist, is a national park, a national forest or any other significant expansion of public lands in Maine.
Suggestions for another national park in Maine are "a no-starter with me," Gov. John Baldacci said this week. "I am proud of Maine's leadership and what we have been able to do on our own … We would be using federal dollars, and the attraction of the federal government is the opportunity to have conservation on a landscape scale."
The proposal calls for working with landowners to protect land largely through conservation easements. Some "special places," such as old-growth forests or areas with particular value from a recreational or ecological standpoint, could be purchased from willing property owners with the help of federal dollars.
The goal is "to protect anywhere from 500,000 to 2 million acres of working forests in the largest unfragmented forest east of the Mississippi River" and may serve as a model for funding other working-forest conservation.


text:
Motor Coach and Tour Bus Operators
Following is a list of Motor Coach and Tour Bus Operators who offer trips to the Hudson Valley Garlic Festival. If you are a Motor Coach or Tour Bus Operator and want to be listed on this page, please visit our contact page.
Horizon Tours CT
Phone: 800-314-8687
email: firstname.lastname@example.com
Wade Tours & Travel797 Burdeck St Schenectady, NY 12306 - 518-355-6767 ext 22
First Student Charter Center
Book a Charter:


text:
- Report: #1072303
Report - Rebuttal - Arbitrate
Complaint Review: Cemal gunbil
Cemal gunbil22 uria st Santa barbra, California USA
Cemal gunbil Cemal gunbil Cemal gunbil sells money at 300 percent last I heard that's loan sharking Santa barbra California
Ripoff Report
About you?
Ripoff Report
A business' first
line of defense
on the Internet.
If your business is
willing to make a
commitment to
customer satisfaction
Click here now..
Does your business have a bad reputation?
Fix it the right way.
Corporate Advocacy Program™
Cemal gunbil and his crew sell money at 300 percent wtf they turned me down for a loan because I wouldn't pay the piper
This report was posted on Ripoff Report on 08/01/2013 09:05 PM and is a permanent record located here: http://www.ripoffreport.com/r/Cemal-gunbil/Santa-barbra-California-90210/Cemal-gunbil-Cemal-gunbil-Cemal-gunbil-sells-money-at-300-percent-last-I-heard-thats-loa-1072303. The posting time indicated is Arizona local time. Arizona does not observe daylight savings so the post time may be Mountain or Pacific depending on the time of year.
Ripoff Report has an exclusive license to this report. It may not be copied without the written permission of Ripoff Report.
Click Here to read other Ripoff Reports on Cemal gunbil
If you would like to see more Rip-off Reports on this company/individual, search here:Search Tips
In order to assure the best results in your search:
- Keep the name short & simple, and try different variations of the name.
- Do not include ".com", "S", "Inc.", "Corp", or "LLC" at the end of the Company name.
- Use only the first/main part of a name to get best results.
- Only search one name at a time if Company has many AKA's.
Advertisers above have met our
strict standards for business conduct.