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AbstractIntroductionMaterials and MethodsResultsDiscussionConclusionsAcknowledgmentsReferencesCopyright
Kenneth S. Ramos, Vilius Stribinskis, Marlene C. Steffen, Adrian Nanez, Diego Montoya-Durango, Qiang He, "Albumin-Like Proteins Are Critical Regulators of Vascular Redox Signaling", Oxidative Medicine and Cellular Longevity, vol. 2013, Article ID 628615, 10 pages, 2013. https://doi.org/10.1155/2013/628615
Albumin-Like Proteins Are Critical Regulators of Vascular Redox Signaling
Kenneth S. Ramos,1 Vilius Stribinskis,1 Marlene C. Steffen,1 Adrian Nanez,1 Diego Montoya-Durango,1 and Qiang He1
1Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, 580 South Preston Street, Louisville, KY 40202, USA
Academic Editor: Swaran J. S. Flora
Received30 Oct 2012
Accepted20 Dec 2012
Published05 Feb 2013
This laboratory previously identified an albumin-like protein (denoted as p70) as a component of the macromolecular complex assembled within the 5′-regulatory region of redox-sensitive genes in vascular smooth muscle cells (vSMCs). Here we show that p70 is present in the cytosolic and nuclear compartments of vSMCs and dynamically responsive to redox status. Intense cytoplasmic and perinuclear staining, coupled with enhanced nuclear localization, was observed in vSMCs, but not HepG2 cells, treated with benzo(a)pyrene (BaP), H2O2, or N-acetylcysteine, agents known to modulate redox status. 3′ RACE indicated that p70 is not generated as a product of endogenous gene expression, but rather taken up from the extracellular compartment. While p70 was undetectable in cells grown for 24 hours under serum-free conditions, cell-associated, acid-resistant albumin was detected 30 min after the addition of exogenous albumin. vSMCs incubated at 4°C with 100 μg/mL unlabeled BSA and 10 μg/mL FITC-BSA for 60 minutes and switched to 37°C to examine temperature-sensitive label uptake showed punctate structures throughout the cell consistent with albumin internalization at the higher temperature. Albumin was found to influence redox-signaling, as evidenced by modulation of cyp1a1 gsta1 and Ha-ras gene inducibility. Together, these results implicate albumin and albumin-like proteins as critical regulators of vascular redox signaling.
Aerobic organisms are continually subjected to endogenous and exogenous stressors that regulate redox homeostasis. As part of the adaptive response to oxidative insults, aerobes have evolved a variety of proteins that sense changes in redox homeostasis and convey signals to the nucleus to regulate gene expression. One prominent redox sensing mechanism involves the activation of a cis-acting regulatory element known as the antioxidant response element (ARE). ARE sequences are present in the 5′ UTR of genes involved in redox homeostasis [1, 2], growth regulation [3, 4], and drug metabolism [5, 6]. The transcriptional response mediated through AREs is complex and varies according to cell type, gene context, and chemical specificity [7]. AREs are regulated by polycyclic aromatic hydrocarbons, such as benzo(a)pyrene (BaP), phenolic antioxidants such as tert-butyl hydroquinone (tBHQ), or direct oxidants, such as H2O2 [7].
Redox signaling is of utmost importance in vascular cells where reactive oxygen species function as signaling molecules regulating important aspects of vascular physiology and where tight control of oxidative metabolism is essential for the preservation of structural and functional integrity. Multiple signal transduction cascades including NF-κB, ERK1/2, AP-1, and ARE have been characterized as critical elements of regulatory control within the vascular wall. vSMCs play a central role in the regulation of vascular redox signaling as evidenced by their involvement in the regulation of matrix metalloproteinases, paracrine regulation of endothelial function, and expression of proinflammatory molecules with strong atherogenic effects. Therefore, the study of vascular redox signaling is essential to advancements in our understanding of molecular vascular cell biology and modalities for therapeutic intervention to effectively prevent atherogenesis.
In efforts to characterize the molecular response to oxidative stress in vascular smooth muscle cells (vSMCs), we have focused on characterization of the multiprotein complex assembled on redox-regulated genes. Several ARE interacting proteins have been identified in vSMCs, including the Cap"n"Collar (CNC) proteins, Nrf1 and Nrf2, and c-Jun, and aryl hydrocarbon receptor (AHR), small Maf proteins, and AP3 [8]. ARE binding proteins belong to the leucine zipper family of transcription factors and dimerize with similar or related proteins to mediate gene activation or repression. Itoh et al. [9] first described a repression mechanism in response to electrophilic stress involving Nrf2 and Kelch-associated protein-1 (Keap-1). Addition of prooxidants overcomes this negative interaction and activates ARE-regulated transcription. Keap-1 is a homologue of the Drosophila actin-binding protein Kelch, a relationship consistent with the interactions of Nrf2 and Keap-1 with the actin framework in response to redox stress.
A p70 albumin-like protein was identified as a novel component of the redox sensing protein machinery of vSMCs [8]. BLAST analysis of this protein established homology to Bach2 and to several zinc-finger proteins containing homeodomains. Three domains of 100% homology are shared between albumin-like proteins and Bach2, suggesting that these structural features may be relevant to redox signaling. Bach2 possesses CNC and Broad-Complex, Tramtrack, and Bric-a-Brac (BTB) domains known to be critical for interaction with ARE sequences [10]. The BTB motif is also involved in regulation of Nrf2 interactions with other transcriptional regulatory proteins, such as N-CoR and SMART [11]. Bach2 is known to associate with Maf proteins via the CNC motif to participate in transcriptional control [12]. BTB proteins often contain Kelch domains that mediate interactions with the cytoskeleton; a relationship consistent with our previous finding that actin participates in ARE signaling [8]. Hoshino et al. [13] have suggested that oxidative stress abolishes nuclear export of Bach2, thus, implicating nuclear accumulation of this protein in a redox signaling. The involvement of albumin-like proteins in transcriptional control is best exemplified by the role of vitamin D binding protein (DBP) in sterol binding and activation of vitamin-D-regulated transcription [14]. Of special note is the finding that albumin and DBP share homologous patterns of disulfide bridge formation and protein folding [15].
On the basis of the above findings we hypothesized that p70 is involved in redox signaling in vSMCs. Evidence is presented here that p70 is dynamically regulated by oxidative stress and that its intracellular localization is dependent upon extracellular protein uptake. The translocation of p70 from the cytosolic to nuclear compartment is involved in redox regulation of vascular gene expression.
Cell culture and chemical treatment: cultures of C57/BL6 mouse aortic vSMCs were grown in Media 199, HepG2, and HEK293 cells in Eagle's Minimum Essential Medium and COS7 in RPMI 1640 supplemented with 10% fetal bovine serum (FBS). For chemical treatments, cells were challenged with either BaP or H2O2 at 37°C and 5% CO2 for various times and concentrations as noted. In studies to determine if albumin is taken up from the extracellular medium, cells were incubated in serum-free ExCell 293 medium to deplete endogenous albumin-like protein stores.
Protein extraction: cultures were rinsed twice with prewarmed PBS and harvested by scraping plates with Buffer A (20 mM HEPES—pH 7.6; 1.5 mM MgCl2; 0.2 mM EDTA; 10% glycerol; 0.5 mM DTT; Complete Mini (Roche) protease inhibitor cocktail) and placed on ice for 10 minutes. Cells were dounce-homogenized and centrifuged at 14,000 g for 20 minutes and supernatant (cytosol) collected and stored at −80°C. The nuclear pellet was redissolved in buffer B (20 mM HEPES—pH 7.6; 420 mM NaCl; 1.5 mM MgCl2; 0.2 mM EDTA; 25% glycerol; 0.5 mM DTT; Complete Mini (Roche) protease inhibitor cocktail), incubated on ice for 1 hour, and supernatant collected after centrifugation at 14,000 g for 20 minutes.
Anti-p70 polyclonal antibody production: female rabbits were purchased from Harlen Laboratories and immunized with a KLH-conjugated 17-mer peptide corresponding to the N-terminus of albumin-like protein. The sequence used for immunization corresponds to the N-terminus of the albumin-like protein identified previously [8] and extended based on resequencing of the originally described 12-mer peptide. After sufficient amounts immunoglobulin was detected by ELISA titers, animals were bled and crude polyclonal serum collected.
Western analysis and immunofluorescence microscopy: for western analysis, cytosolic and nuclear protein extracts were electrophoresed on 4–12% gradient polyacrylamide gels as described previously [8]. Immunofluorescence detection was carried out as described in [16]. Briefly, vSMCs were seeded at a density 43 cells/mm2 in 10 cm dishes containing super frost/plus microscope slides (Fisher). Cultures were preincubated for 1 hr with N-acetyl-cysteine (0.5 mM) prior to challenge with 0.3 or 3 μM BaP or vehicle for 3 hours. Cells were fixed in cold acetone/methanol and p70 was visualized by immunofluorescence. Nuclei were counterstained with Dapi or phalloidin 568 (Molecular Probes). Cover slips were mounted using Prolong Antifade (Molecular Probes) and slides were kept in chambers with desiccant at 4°C. Twenty images per slide per antibody were captured from ~400 cells in triplicate experiments. Images were filtered based on intensity and size to quantify positive events using the Zeiss Axiovision Rel 4.3 image analysis software and processed for analyses.
p70 cloning: 3′ RACE approach was used to clone p70 cDNA. Total RNA was isolated from vSMCs, mouse or rat liver or 11-day mouse embryos using TRIzol (Invitrogen). RNA samples were treated with DNAse I (DNA-free kit, Ambion) and 0.25 μg RNA reverse transcribed in 20 μL with SuperScript II (Invitrogen) using an oligo (dT17) anchored with specific oligo GACTCGAGTCGACATCGA(dT17). The products of the reverse transcription reaction (2 μL) were amplified using 3′-PCR primers, GACTCGAGTCGACATCGA and specific primers designed against the amino-terminal coding sequence of mice (CGCCCATCGGTATAATGAT), rat (GCCCATCGGTTTAAGGAC), or mice and rat (GAAGCACACAAGAGTGAG) albumin. In complementary experiments, 15 degenerate oligonucleotides were designed to amplify the p70 amino-terminal coding sequence (primer sequences available upon request) and annealed at 49–51°C for 15 sec, depending on the primer, extended at 68°C (1 kb/min), and subjected to variable numbers of cycles following denaturation at 94°C (15 sec).
Albumin uptake assays: the assays were essentially done as described by Siddiqui et al., 2004 [17]. Briefly, vSMCs were grown to subconfluence on either glass cover slips in 6-well culture plates or culture slide chambers in DMEM with 10% FBS. Prior to the assay, cells were grown for 24 hours in ExCell 293 medium to starve for albumin. The cells were washed with either cold growth medium or PBS in some experiments and incubated with ExCell 293 made with 100 μg/mL unlabeled BSA and 10 μg/mL FITC-BSA for 60 minutes at 4°C for the binding. It is well established that at this temperature albumin internalization does not occur. After 60 min plates were placed in the CO2 incubator at 37°C incubator and at different time points, plates were removed, put on ice, and washed with ice-cold PBS; 100 mM Na-Ac, pH 2.5, and 150 mM NaCl (to remove cell surface albumin); and with 100 mM Na-phosphate at pH 7.4 (to restore the pH to neutral). The antifade agent in glycerol 5% was added to the mounting medium to reduce photobleaching. Fluorescence of cells was monitored using FITC filter to visualize the internalized albumin. DAPI staining was used to stain nuclear and mitochondrial DNA. Images were visualized using a Zeiss Axiovert inverted fluorescence microscope.
Statistical Analysis. The significance of findings was calculated at the using Students t-test or nonparametric Wilcoxon rank test.
3.1. Compartmentalization of p70 in vSMCs
Female rabbits were immunized with a KLH-conjugated 17-mer peptide corresponding to the N-terminus of p70 to generate an affinity purified polyclonal antibody. A 70-kDa protein was detected in cytosolic extracts of vSMCs and this response was enhanced in cells challenged with chemical oxidants (Figures 1(a) and 1(b)). Cytosolic p70 signal decreased as a function of time under both control and oxidant-stimulated conditions, suggesting that the stability and/or intracellular localization of this protein is subject to regulation in vSMCs. A 30 kDa immunoreactive protein was also detected by the p70 antibody, but signal intensity remained unchanged as a function of time or chemical treatment indicating that this protein is not likely involved in redox signaling. The specificity of the antibody was confirmed in studies showing that incubation of anti-p70 antiserum with 1, 5, or 10 μg p70 17-mer peptide completely neutralized the immunoreactive signal (not shown). p70 was selectively enriched in the nucleus of BaP- or peroxide-treated vSMCs (Figures 2(a) and 2(b)), indicating that redox stress regulates intracellular localization of this protein. Nuclear detection was seen shortly after oxidant treatment, as evidenced by marked signal increases as early as 0.5 hr that lasted for 1–3 hr. Regulation of p70 compartmentalization exhibited cell-type specificity since cytosolic or nuclear expression was unchanged in HepG2 cells treated with BaP (not shown). To further evaluate the compartmentalization of p70, immunofluorescence measurements were carried out in cells challenged with oxidants in the presence or absence of N-acetylcysteine, a modulator of redox status in vSMCs [18]. Cytoplasmic and perinuclear staining was observed under basal conditions in vSMCs (Figures 3(a) and 3(b)). As reported earlier, treatment with BaP (0.3 or 3 μM) for 3 hr enhanced nuclear localization of p70 (Figure 3(c)), while pretreatment with 0.5 mM N-acetylcysteine enhanced nuclear localization of p70 and selectively neutralized the response elicited by 3 μM BaP. Collectively, these findings confirm that modulation of redox homeostasis by cellular oxidants and antioxidants modulates intracellular compartmentalization of p70 and induces transient nuclear localization in vSMCs.
p70 expression in the cytosolic compartment of vascular smooth muscle cells—time-course and oxidant treatment. Panel (a) shows that mouse vSMCs were treated with 3 μM BaP or vehicle (DMSO) for 0.5 or 3 hr. Duplicate cell samples were processed for reproducibility. Panel (b) shows vSMCs were treated with 50 μM H2O2 or vehicle (ddH2O) for 0.5 and 3 hr. p70 expression was normalized against p35, a cellular protein recognized specifically by the antibody but not involved in the cellular response to oxidative stress. Densitometric values denote the average of duplicate samples from 3 independent experiments.
p70 Expression in the nuclear compartment of vascular smooth muscle cells—time-course and oxidant treatment. Panel (a) shows that vSMCs were treated with 3 μM BaP or vehicle (DMSO) for 0.5–48 hr. Panel (b) shows vSMCs were treated with 50 μM H2O2 or vehicle (ddH2O) for 0.5–36 hr as above. Densitometric values denote the average for each time and treatment in 3 independent experiments.
Immunofluorescence localization of p70 in vascular smooth muscle cells. vSMCs were treated with vehicle or 0.3 or 3 μM BaP for 3 hr and then processed for immunofluorescence detection as described in Section 2. Panel (a)—morphometric analysis of total immunofluorescence signal before and after filtration for cellular signal. Panel (b)—morphometric analysis of total immunofluorescence signal before and after filtration for nuclear signal. Panel (c)—the interaction with N-acetylcysteine was examined in experiments where cultures were pretreated with 0.5 mM N-acetylcysteine and then challenged with 0.3 or 3 μM BaP or DMSO. Similar results were seen in 3 independent experiments.
3.2. p70 Cloning Efforts
The N-terminal 17 amino acid sequence of p70 is different from that of mouse albumin by two amino acids, but identical to rat albumin (Figure 4(a)). Therefore, experiments were conducted to determine if the p70 antibody recognizes mouse and/or rat albumin. Total protein was isolated from mouse vSMCs, rat or mouse liver extracts, and processed for western analysis. The p70 antibody had considerably lower affinity to mouse albumin compared to rat (Figure 4(b)), consistent with differences in the amino acid composition of the peptide sequence between mouse albumin and p70. Surprisingly, signal intensity of p70 in vSMCs extracts was comparable to that from rat liver, suggesting that p70 is different from mouse albumin. On the basis of these findings, we set out to determine if p70 is expressed in vivo or is limited to in vitro growth of cells in culture. A 3′ RACE approach was used to clone p70 cDNA. Considering the extensive amino acid sequence homology between mouse and rat albumin mRNAs, two specific oligonucleotides were designed to amplify a region homologous to both species. cDNAs were obtained from total RNA isolated from vSMCs, or rat and mouse liver using oligo(dT) anchored with specific oligonucleotide. In the second round of PCR, we used specific oligonucleotides and the anchor oligonucleotide to prime second strand DNA synthesis of all cDNAs obtained from RNAs with poly(A) tail. A specific PCR product was obtained from RNA isolated from rat liver, which corresponded to rat albumin, as determined by sequencing (data not shown). However, no specific product was amplified using RNA from vSMCs. In contrast, we obtained albumin cDNA from both rat and mouse with oligonucleotide recognizing both mRNAs. These controls indicate high specificity of the RT-PCR assay. No specific product was amplified using either oligonucleotide with two different RNA preparations from vSMCs. Although any other gene known to be specifically expressed in vSMCs, such as calponin and vSMC -actin, was amplified (data not shown). Therefore, we speculated that p70 codon usage might be different from that of rat and mouse albumin. To address this question, we designed 15 different degenerate oligonucleotides according to the coding capacity of p70 N-terminus and repeated the PCR. There was no specific product amplified with different RNA preparations from either vSMCs or 11-day mouse embryo (data not shown). We used RNA isolated from mouse embryos, because expression of p70, although low, can be detected by western analysis (data not shown). Therefore, we concluded that p70 is not a product of endogenous gene expression in vSMCs.
Structural correlates of p70. Panel (a)—Comparison of amino-termini (amino acids 25–44) sequences in different albumin proteins and p70. hALB, human; bALB, bovine; mALB, mouse; rALB, rat albumin. X, unidentified amino acid in p70. Conserved amino acids are in bold. Panel (b)—affinity of p70 antibody to proteins in cell extracts obtained from mouse vSMCs or rat and mouse livers. Different amounts of extracts were fractionated and probed with p70 antibody to ascertain relative protein abundance. Similar results were seen in 2 independent experiments.
3.3. Cellular Uptake of p70
The amino acid sequence of p70 matches cleaved albumin at its amino terminus suggesting that p70 is taken up by cells following appropriate signals. To determine if vSMCs internalize albumin present in the growth medium, vSMCs were grown in the absence or presence of serum in ExCell 293 medium and processed for Western analysis. Figure 5(a) demonstrates that p70 immunoreactivity is not detected in ExCell medium for 24 h, in different cell lines (vSMCs, Hek 293, and COS7), but is detected when cells are grown in medium supplemented with FBS. The level of p70 in COS7 cells is low compared to other cell types. It has been demonstrated that uptake of albumin by vascular endothelial and lung epithelial cells is mediated by TGF- receptor, and COS7 cells express neither TGF-βI nor TGF- II receptors and therefore have compromised uptake of exogenous albumin [17]. The observation that COS7 cells have low levels of p70 suggests that vSMCs and HEK 293 cells internalize p70 from the medium, and that this internalization may be dependent on TGF-β receptors. Of interest was the finding that p30 immunoreactivity was retained under conditions where extracellular albumin uptake from the extracellular medium was inhibited.
Cellular expression of p70. Panel (a)—p70 is not detected in vascular smooth muscle cells, HEK293, or Cos-7 cells after growth in serum-free medium. vSMCs, HEK293, and COS7 cells were grown either in the presence of serum (DMEM plus serum) or in serum-free medium (ExCell) and cellular extracts analyzed by western blotting using p70 antibody. FBS (extreme right lane) served as a positive control. Panel (b)—detection of p70 and BSA in vascular smooth muscle cells. Cell-associated albumin can be detected with p70 antibodies upon albumin addition for 30 min. Similar results were seen in 2 independent experiments.
Next, we sought to determine if external albumin is internalized by vSMCs. Cells were incubated for 24 hr in serum-free ExCell 293 medium to starve the cells for albumin and then switched to ExCell 293 medium containing 2.5 mg/mL BSA, the amount of albumin present in the medium when cells grown are grown in the presence of 10% FBS. Figure 5(b) demonstrates that p70 is not detectable in vSMCs grown under serum-free conditions for 24 hr. Following acidic washes to remove nonspecifically bound albumin, cell-associated albumin was detected as early as 30 min after addition of albumin to the medium. FITC-labeled albumin was then used to distinguish between surface bound and internalized albumin. Figure 6 shows specific surface association of extracellular albumin when cells are incubated with FITC albumin for 1 hr at 4°C. The fluorescence pattern shifted to an intracellular punctuate pattern upon incubation of the cells at 37°C, indicating that a temperature-sensitive mechanism participates in compartmentalization of cellular albumin. Together, these findings indicate that surface-associated albumin is actively internalized by vSMCs and that regulatory mechanisms exist that modulate albumin mobilization across cellular membranes.
Albumin uptake in vascular smooth muscle cells. Cell-internalized FITC albumin was visualized after removing the external FITC-albumin as described in Section 2. Cell accumulated albumin shows punctate staining. DAPI staining denotes the nucleus. Similar results were seen in 3 different experiments.
To examine the involvement of p70 in redox signaling, we compared the inducibility of cyp1a1 by BaP in vSMCs grown in serum-free medium before and after addition of bovine albumin (Figure 7(a)). Cyp1a1 is a member of the large superfamily of cytochromes P450 (CYPs) encoding for heme-containing monooxygenases involved in the hydroxylation of steroids and xenobiotics [18]. This gene is not expressed under constitutive conditions, but markedly induced by ligands of the aryl hydrocarbon receptor (AHR), a basic helix-loop-helix transcription factor involved in stress signaling in vSMCs. Reciprocal interactions between AHR and redox signaling have been documented, such that activation of the redox machinery inhibits cyp1a1 inducibility via oxidative modification of cysteine residues within the transactivation domain of redox-regulated transcriptional regulators [18, 19]. Thus, our approach enabled us to simultaneously examine the integrity of AHR and redox signaling as a function of albumin uptake. The expression of cyp1a1 in vSMCs was determined by RT-PCR before and after addition of BSA (2.5 mg/mL), a concentration that is representative of that achieved with 10% FBS. As expected, no cyp1a1 expression was detected in the absence of inducer under any experimental condition examined (Figure 7(a)). BaP challenge induced cyp1a1 in the presence or absence of serum, but gene induction was markedly enhanced in the absence of albumin. Next, we evaluated the inducibility profiles of nqo1, gsta1, and H-ras, vSMC genes known to be regulated via redox signaling through the activation/repression of AREs [3, 7, 8, 18]. No changes in the constitutive or inducible expression of nqo1 were observed in the presence or absence of albumin. In marked contrast, albumin repressed constitutive expression of gsta1 and failed to support inducibility of the gsta1 gene by 3 μM BaP. For Ha-ras, albumin inhibited both constitutive and inducible expression of the gene. These findings are consistent with the involvement of albumin in the assembly of macromolecular complexes that interact specifically with AREs in the regulatory region of target genes [8]. Together, these findings implicate a dynamic system in vSMCs responsible for intracellular localization of albumin under conditions of oxidative stress, and the association of albumin with transcription factors that modulate the adaptive cellular responses to oxidative stress.
Regulation of gene inducibility in vascular smooth muscle by albumin. vSMCs were grown in the presence of serum (DMEM plus serum), or in serum-free medium (ExCell 293). Panel (a) shows patterns of cyp1a1 inducibility by BaP in the presence or absence of extracellular albumin, ExCell 293 was supplemented with BSA (100 μg/mL) for and then challenged with BaP (3 μM) or vehicle (DMSO) for 24 hr. Total RNA was analyzed for cyp1a1 gene expression by RT-PCR and gel-electrophoresis. DNA ladder in basepairs (bp) was loaded at the extreme right. Similar profiles were seen in 4 independent experiments. Panel (b) shows patterns of redox regulated expression for NQO1, GSTA1 and Ha-ras in the presence or absence of extracellular albumin and BaP. Samples were processed as described above. Similar profiles were seen in 3 independent experiments.
p70 was first identified as an albumin-like protein within the macromolecular protein complex assembled on the AREs of redox-regulated genes [8]. A role for p70 as a signal transducer is consistent with the ability of other albumin-like proteins, such as DBP to bind sterols to convey transcriptional signals to the nucleus [14]. DBP is positioned on chromosome 4 in close proximity to chemokines and is believed to participate in redox-regulated inflammatory signaling [20]. Interestingly, a 70 kDa albumin-like protein has been described in the cornea that is modulated by oxidative stress [21]. BLAST analysis of p70 has shown homology to Bach2, a protein containing CNC and BTB domains that participate in the regulation of ARE signaling [10, 14, 22]. Cantin et al., 2000 [23], have shown that albumin modulates NF-κB activation and cellular GSH levels. Furthermore, serum albumin has been shown to modulate vSMC energy metabolism in carotid artery strips where extracellular albumin is taken up and broken down into byproducts that stimulate oxygen consumption and augment glucose oxidation [24].
An earlier report identified an albumin-like protein as the melanoma associated antigen, B700. B700-like molecules are produced by melanomas of murine, human, swine, and hamster origin [25–33]. The primary structure and biochemical functions of B700, as well as its in vivo metabolic fate, are largely unknown. B700 can be detected on the cell surface as well as the intracellular compartment in various murine cell lines [29]. Despite a significant homology to the mammalian serum albumins, monoclonal antibodies produced by eight different rat hybridoma cell lines against the melanoma-specific B700 antigen cross-react only with murine albumin [27]. The fact that both murine and human melanoma cells produce B700 antigen which is recognized by murine albumin antibodies suggests the presence of a murine-type albumin in human melanoma. Surprisingly, BLAST search retrieved a human clone which is completely homologous to the rat albumin (accession number AX430341). To date, no linkage between p70 and B700 has been established. Our inability to clone a mouse albumin-like protein in vSMCs using 3′ RACE suggests that either a unique gene product is not expressed in vSMCs or that an mRNA encoding p70 lacks a conventional polyA tail. The results of our studies, however, indicate that a more likely possibility is that extracellular albumin as well as other albumin-like proteins are taken up by vSMCs from the extracellular compartment and engaged in intracellular signaling. Within this context, previous studies have shown that colon, kidney, and lung epithelial cell, as well as vascular endothelial cells take up albumin [34]. Acute exposure of human proximal tubular epithelial cells to albumin induces IL-8 gene and protein expression in a time and dose-dependent manner and stimulates IL-8 secretion [34]. These investigators also demonstrated translocation of NF-κB into the nucleus after exposure to human albumin, as well as enhanced production of reactive oxygen species.
The nuclear localization of p70 following oxidative stress coupled to the modulation of redox-sensitive gene expression strongly implicates albumin as a key participant in redox signaling in vSMCs. Although a 30 kDa protein was consistently detected in vSMCs, the localization of this protein was not dependent upon chemical oxidant treatment, suggesting that its involvement in p70 redox biology is unlikely. Albumin acts as a powerful antioxidant in cell culture [35], and is known to bind, sequester and stabilize a variety of unstable molecular species [36]. This acidic, soluble protein has both high-affinity and secondary binding sites and optimizes the roles that fatty acids, metals, disulfides, and other molecules in cellular metabolism [37–40]. Vascular endothelial cells undergo albumin endocytosis using TGF-β receptor, and activation of the receptor stimulates endocytosis which results in TGF-βRII signaling leading to Smad2 phosphorylation and Smad4 translocation to the nucleus [17]. In addition, albumin endocytosis induces phosphorylation of p38 MAPK resulting in activation of endothelial proliferation and reduction of endothelial apoptosis [41].
5. Conclusions and Clinical Implications
This study implicates albumin and albumin-like proteins in the regulation of redox signaling in vSMCs. These proteins are present in the macromolecular complex assembled within the 5′-regulatory region of redox-sensitive genes and appear to be dynamically responsive to changes in redox status following internalization into vSMCs from the extracellular compartment via temperature-sensitive transport mechanisms. Future studies are required to determine if the ability of albumin and albumin-like proteins to repress ARE signaling involves solely regulation of macromolecular protein assembly during transactivation of redox-regulated genes, or redox sensing via molecular interactions between cysteine residues and chemical electrophiles. Collectively, these findings raise important questions about the cellular and molecular mechanisms responsible for the clinical effectiveness of albumin, not only in the restoration of oncotic pressure, but also in the management of patients with hypovolemia, shock, burns, surgery or trauma, cardiopulmonary bypass, acute respiratory distress syndrome, and hemodialysis. The present study suggests that the antioxidant mechanism of these proteins may warrant further investigation.
This work was supported in part by ES04849, ES017274, and ES014443 to K. S. Ramos. The technical contributions of Mr. Mark Holderman during the early stages of the project and the assistance of Dr. Hong Gao with image processing are gratefully acknowledged.
Y. Li and A. K. Jaiswal, "Regulation of human NAD(P)H: quinone oxidoreductase gene: role of AP1 binding site contained within human antioxidant response element," Journal of Biological Chemistry, vol. 267, no. 21, pp. 15097–15104, 1992. View at: Google Scholar
Y. H. Chen and K. S. Ramos, "A CCAAT/enhancer-binding protein site within antioxidant/electrophile response element along with CREB-binding protein participate in the negative regulation of rat GST-Ya, gene in vascular smooth muscle cells," Journal of Biological Chemistry, vol. 275, no. 35, pp. 27366–27376, 2000. View at: Publisher Site | Google Scholar
J. K. Kerzee and K. S. Ramos, "Activation of c-Ha-ras by benzo(a)pyrene in vascular smooth muscle cells involves redox stress and aryl hydrocarbon receptor," Molecular Pharmacology, vol. 58, no. 1, pp. 152–158, 2000. View at: Google Scholar
C. R. Partridge, Q. He, M. Brun, and K. S. Ramos, "Genetic networks of cooperative redox regulation of osteopontin," Matrix Biology, vol. 27, no. 5, pp. 462–474, 2008. View at: Publisher Site | Google Scholar
S. Liu and C. B. Pickett, "The rat liver glutathione S-transferase Ya subunit gene: characterization of the binding properties of a nuclear protein from HepG2 cells that has high affinity for the antioxidant response element," Biochemistry, vol. 35, no. 35, pp. 11517–11521, 1996. View at: Publisher Site | Google Scholar
T. Satoh, S. Saitoh, M. Hosaka, and K. Kosaka, "Simple ortho- and para-hydroquinones as compounds neuroprotective against oxidative stress in a manner associated with specific transcriptional activation," Biochemical and Biophysical Research Communications, vol. 379, no. 2, pp. 537–541, 2009. View at: Publisher Site | Google Scholar
K. P. Miller and K. S. Ramos, "Molecular mechanisms of environmental atherogenesis," in Atherosclerosis and Oxidant Stress, J. L. Holzman, Ed., chapter 8, pp. 161–211, Springer, New York, NY, USA, 2007. View at: Google Scholar
M. T. Holderman, K. P. Miller, L. J. Dangott, and K. S. Ramos, "Identification of albumin precursor protein, phi AP3, and α-smooth muscle actin as novel components of redox sensing machinery in vascular smooth muscle cells," Molecular Pharmacology, vol. 61, no. 5, pp. 1174–1183, 2002. View at: Publisher Site | Google Scholar
K. Itoh, N. Wakabayashi, Y. Katoh et al., "Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain," Genes and Development, vol. 13, no. 1, pp. 76–86, 1999. View at: Google Scholar
T. Nguyen, H. C. Huang, and C. B. Pickett, "Transcriptional regulation of the antioxidant response element. Activation by Nrf2 and repression by MafK," Journal of Biological Chemistry, vol. 275, no. 20, pp. 15466–15473, 2000. View at: Publisher Site | Google Scholar
K. D. Huynh and V. J. Bardwell, "The BCL-6 POZ domain and other POZ domains interact with the co-repressors N-CoR and SMRT," Oncogene, vol. 17, no. 19, pp. 2473–2484, 1998. View at: Google Scholar
K. Igarashi, H. Hoshino, A. Muto, N. Suwabe, S. Nishikawa, H. Nakauchi et al., "Identification of Bach2 as a B-cell-specific partner for small maf proteins that negatively regulate the immunoglobulin heavy chain gene 3' enhancer," Journal of Biological Chemistry, vol. 273, pp. 11783–11790, 1998. View at: Google Scholar
H. Hoshino, A. Kobayashi, M. Yoshida et al., "Oxidative stress abolishes leptomycin B-sensitive nuclear export of transcription repressor Bach2 that counteracts activation of Maf recognition element," Journal of Biological Chemistry, vol. 275, no. 20, pp. 15370–15376, 2000. View at: Publisher Site | Google Scholar
P. N. MacDonald, T. A. Baudino, H. Tokumaru, D. R. Dowd, and C. Zhang, "Vitamin D receptor and nuclear receptor coactivators: crucial interactions in vitamin D-mediated transcription," Steroids, vol. 66, no. 3–5, pp. 171–176, 2001. View at: Publisher Site | Google Scholar
I. Bogaerts, C. Verboven, A. Rabijns, E. Waelkens, H. Van Baelen, and C. De Ranter, "Purification, crystallization and preliminary X-ray investigation of the complex of human vitamin D binding protein and rabbit muscle actin," Acta Crystallographica Section D, vol. 57, no. 5, pp. 740–742, 2001. View at: Publisher Site | Google Scholar
H. Falahatpisheh, A. Nanez, D. Montoya-Durango, Y. Qian, E. Tiffany-Castiglioni, and K. S. Ramos, "Activation profiles of HSPA5 during the glomerular mesangial cell stress response to chemical injury," Cell Stress and Chaperones, vol. 12, no. 3, pp. 209–218, 2007. View at: Publisher Site | Google Scholar
S. S. Siddiqui, Z. K. Siddiqui, and A. B. Malik, "Albumin endocytosis in endothelial cells induces TGF-β receptor II signaling," American Journal of Physiology-Lung Cellular and Molecular Physiology, vol. 286, no. 5, pp. L1016–L1026, 2004. View at: Publisher Site | Google Scholar
J. K. Kerzee and K. S. Ramos, "Constitutive and inducible expression of Cyp1a1 and Cyp1b1 in vascular smooth muscle cells: role of the Ahr bHLH/PAS transcription factor," Circulation Research, vol. 89, no. 7, pp. 573–582, 2001. View at: Google Scholar
R. Barouki and Y. Morel, "Repression of cytochrome P450 1A1 gene expression by oxidative stress: mechanisms and biological implications," Biochemical Pharmacology, vol. 61, no. 5, pp. 511–516, 2001. View at: Publisher Site | Google Scholar
N. Yamamoto and V. R. Naraparaju, "Role of vitamin D3-binding protein in activation of mouse macrophages," Journal of Immunology, vol. 157, no. 4, pp. 1744–1749, 1996. View at: Google Scholar
L. Zhu and R. K. Crouch, "Albumin in the cornea is oxidized by hydrogen peroxide," Cornea, vol. 11, no. 6, pp. 567–572, 1992. View at: Publisher Site | Google Scholar
J. Jeyapaul and A. K. Jaiswal, "Nrf2 and c-Jun regulation of antioxidant response element (ARE)-mediated expression and induction of γ-glutamylcysteine synthetase heavy subunit gene," Biochemical Pharmacology, vol. 59, no. 11, pp. 1433–1439, 2000. View at: Publisher Site | Google Scholar
A. M. Cantin, B. Paquette, M. Richter, and P. Larivée, "Albumin-mediated regulation of cellular glutathione and nuclear factor kappa B activation," American Journal of Respiratory and Critical Care Medicine, vol. 162, no. 4, pp. 1539–1546, 2000. View at: Google Scholar
J. T. Barron, L. Gu, E. R. Rodriguez, and J. E. Parrillo, "Effect of serum albumin on vascular smooth muscle metabolism," Biochimica et Biophysica Acta, vol. 1459, no. 1, pp. 35–48, 2000. View at: Publisher Site | Google Scholar
C. Bennett and K. B. Cooke, "Further characterization of a melanoma-specific protein from human urine," British Journal of Cancer, vol. 41, no. 5, pp. 734–744, 1980. View at: Google Scholar
J. J. Marchalonis, C. Schwabe, D. M. Gersten, and V. J. Hearing, "Amino-terminal variation in melanoma antigens," Biochemical and Biophysical Research Communications, vol. 121, no. 1, pp. 196–202, 1984. View at: Google Scholar
Y. Tomita, P. M. Montague, and V. J. Hearing, "Monoclonal antibody production to a B16 melanoma associated antigen," International Journal of Cancer, vol. 35, no. 4, pp. 543–547, 1985. View at: Google Scholar
V. J. Hearing, D. M. Gersten, and P. M. Montague, "Murine melanoma-specific tumor rejection activity elicited by a purified, melanoma-associated antigen," Journal of Immunology, vol. 137, no. 1, pp. 379–384, 1986. View at: Google Scholar
D. M. Gertsen, D. Moody, W. D. Vieira, L. W. Law, and V. J. Hearing, "Production of monoclonal antibodies against the B700 murine melanoma antigen and their antimetastatic properties," Biochimica et Biophysica Acta, vol. 1138, no. 2, pp. 109–114, 1992. View at: Publisher Site | Google Scholar
N. K. Farzaneh, T. L. Walden Jr., V. J. Hearing, and D. M. Gersten, "B700, a melanoma-specific antigen, catalyzes metabolism of prostaglandin E2," International Journal of Cancer, vol. 45, no. 1, pp. 104–108, 1990. View at: Publisher Site | Google Scholar
N. K. Farzaneh, T. L. Walden, V. J. Hearing, and D. M. Gersten, "Comparison of the metabolic fate and tissue distribution of B700, an albumin-like melanoma-specific antigen with serum albumin in normal and tumor-bearing mice," International Journal of Biochemistry, vol. 23, no. 12, pp. 1385–1391, 1991. View at: Google Scholar
N. K. Farzaneh, T. L. Walden, V. J. Hearing, and D. M. Gersten, "B700, an albumin-like melanoma-specific antigen, is a vitamin D binding protein," European Journal of Cancer, vol. 27, no. 9, pp. 1158–1162, 1991. View at: Publisher Site | Google Scholar
A. A. Karelin, M. M. Phylippova, Y. E. Blishchenko et al., "Albumin-like glycoprotein from human fetal tissue," Biochemistry and Molecular Biology International, vol. 33, no. 1, pp. 73–80, 1994. View at: Google Scholar
S. Tang, J. C. K. Leung, K. Abe et al., "Albumin stimulates interleukin-8 expression in proximal tubular epithelial cells in vitro and in vivo," Journal of Clinical Investigation, vol. 111, no. 4, pp. 515–527, 2003. View at: Publisher Site | Google Scholar
M. Roche, P. Rondeau, N. R. Singh, E. Tarnus, and E. Bourdon, "The antioxidant properties of serum albumin," FEBS Letters, vol. 582, no. 13, pp. 1783–1787, 2008. View at: Publisher Site | Google Scholar
M. Fasano, S. Curry, E. Terreno et al., "The extraordinary ligand binding properties of human serum albumin," IUBMB Life, vol. 57, no. 12, pp. 787–796, 2005. View at: Publisher Site | Google Scholar
J. S. Koh, W. Lieberthal, S. Heydrick, and J. S. Levine, "Lysophosphatidic acid is a major serum noncytokine survival factor for murine macrophages which acts via the phosphatidylinositol 3-kinase signaling pathway," Journal of Clinical Investigation, vol. 102, no. 4, pp. 716–727, 1998. View at: Google Scholar
J. Lu, A. J. Stewart, P. J. Sadler, T. J. T. Pinheiro, and C. A. Blindauer, "Albumin as a zinc carrier: properties of its high-affinity zinc-binding site," Biochemical Society Transactions, vol. 36, no. 6, pp. 1317–1321, 2008. View at: Publisher Site | Google Scholar
A. Maczurek, K. Hager, M. Kenklies et al., "Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer's disease," Advanced Drug Delivery Reviews, vol. 60, no. 13-14, pp. 1463–1470, 2008. View at: Publisher Site | Google Scholar
A. Saifer and L. Goldman, "The free fatty acids bound to human serum albumin," Journal of Lipid Research, vol. 2, pp. 268–270, 1961. View at: Google Scholar
S. S. Siddiqui, Z. K. Siddiqui, S. Uddin, R. D. Minshall, and A. B. Malik, "p38 MAPK activation coupled to endocytosis is a determinant of endothelial monolayer integrity," American Journal of Physiology-Lung Cellular and Molecular Physiology, vol. 292, no. 1, pp. L114–L124, 2007. View at: Publisher Site | Google Scholar
Copyright © 2013 Kenneth S. Ramos et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


text:
Triaenodes gazella is een schietmot uit de familie Leptoceridae. De soort komt voor in het Oriëntaals gebied.

Schietmot uit het Oriëntaals gebied
Leptoceridae

redpajama_set_name: RedPajamaWikipedia


text:
Q: Estimating the $n^{th}$ prime $p_n$ in terms of $n$ for $n$ large From the prime number theorem we know that for $n$ large ,
$n=\pi(p_n)\sim\frac{p_n}{\log p_n}$
$\implies \log n \sim \log(p_n)-\log\log p_n \ \ -(i)$
Now $p_n \sim n\log p_n$.
Some calculations with primes between $10000$ and $100000$ makes me feel $p_n \sim n\log n$ holds. To prove this I'd have to show $\lim_{n\rightarrow \infty}\frac{\log \log p_n}{log n}=0$ .So that by $(i)$ I'd be done.
Can someone tell me if my intuition is correct and if so how to prove the step I'm stuck at.Thanks in advance.

A: $$\pi(x) \sim \frac{x}{\log x}$$
gives
$$\pi(x)\log \pi(x) \sim \frac{x}{\log x}\log (\frac{x}{\log x}) \sim x$$
letting $x=p_n$ gives your result
$$n \log n \sim p_n$$

redpajama_set_name: RedPajamaStackExchange


text:
John William Miles (21 June 1817 – 5 November 1878) was a British Conservative politician and briefly MP.

Miles was elected MP for Bristol at a by-election in April 1868. His election was soon declared void on 25 June 1868 due to "bribery and personation" and the findings saw the writ for the seat suspended until November. At the ensuing general election, Miles again stood for parliament but was unsuccessful.

Miles was the third son of former Bristol MP Philip Jones Miles and was educated at both Eton College and Oxford University. During his life, he was also a Justice of the Peace and Deputy Lieutenant of Herefordshire. He died unmarried in 1878.

References

External links

1817 births
1878 deaths
Deputy Lieutenants of Herefordshire
UK MPs 1865–1868
Conservative Party (UK) MPs for English constituencies
People educated at Eton College
Alumni of the University of Oxford


text:
The Scout Report for Business & Economics - October 7, 1999
The target audience of the new Scout Report for Business & Economics is faculty, students, staff, and librarians in business and economics. Each biweekly issue offers a selective collection of Internet resources covering topics in the field that have been chosen by librarians and content specialists in the given area of study.
The Scout Report for Business & Economics is also provided via email once every two weeks. Subscription information is included at the bottom of each issue.
W-2 Child Support Evaluation project: Initial findings
The Economic and Social Impacts of Electronic Commerce: Preliminary Findings and Research Agenda
What Caused Asia's Economic and Currency Crisis and Its Global Contagion?
World Bank Annual Report 1999
World Economic Outlook (WEO) -- IMF
Society for Electronic Commerce and Rights Management
Business Basics for the Workplace
Silicon Valley Companies Database
Fed in Print: An Index to Federal Reserve Economic Research
Business Research at Florida Gulf Coast University
Encyclopedia of the New Economy
Business-to-Business auctions -- Inc. Online
Ad Critic
Annual Review of Football Finance
Federal Reserve Bank Board of Governors (FRB BOG)
Bureau of Economic Analysis (BEA)
Bureau of Labor Statistics (BLS)
United States Department of Agriculture (USDA)
NetAid Concert to Relieve World from Poverty
W-2 Child Support Evaluation project: Initial findings [.pdf, 379K]
http://www.ssc.wisc.edu/irp/all.pdf
The Institute for Research on Poverty offers this 118-page report on their initial findings on Wisconsin Works's effects on child support. Wisconsin Works (W-2) was implemented in September 1997 as a replacement for Aid to Families with Dependent Children (AFDC). All participants in the program are required to work in order to get cash assistance. The report is divided into five chapters, including an introduction to W-2; the child support policy changes that took place as part of the program; early outcomes of the program including child support, income, and government cost; and a summary. The study charts the relative successes and failures of the program to this point. [EM][DC]
[Back to Contents]
The Economic and Social Impacts of Electronic Commerce: Preliminary Findings and Research Agenda [.pdf]
http://www.oecd.org/subject/e_commerce/summary.htm
Electronic Commerce has been in existence for little more than three years, but due to its enormous capacity to affect "economic activities and social environments," it has already had a huge impact on retail, finance, and communications, representing 30 percent of GDP. This 156-page report from the Organisation for Economic Co-operation and Development examines the past and potential impact that e-commerce promises to have on business and the economy. The report is broken into five chapters, which need to be downloaded separately, including "Growth of electronic commerce: present and potential," "Electronic commerce, jobs and skills," and "Societal implications of electronic commerce," each with its own set of charts and graphs. A report summary is also included. [EM]
http://www.stern.nyu.edu/~nroubini/asia/AsiaHomepage.htm
Created and maintained by Nouriel Roubini, Associate Professor of Economics and International Business, Stern School of Business at New York University, as well as Senior Advisor to the Under Secretary for International Affairs for the US Treasury Department, this comprehensive collection of online resources is dedicated to the Asian Economic Crisis. While the organization of the site could be tighter, there is a wealth of information here dating from 1997 to the present and covering topics from Brazil and Latin America to "G-7 Macroeconomic Issues, Policy Coordination and Target Zone Controversies." The site also includes basic readings on the Asian Crisis, recent articles on a variety of related issues, working papers and publications, and electronic mailing lists. This site is vital to anyone interested in the Asian Economic Crisis. [EM]
http://www.worldbank.org/html/extpb/annrep/
"Fiscal year 1999 (FY99) was a year of continued -- and formidable -- challenges," begins the World Bank Annual Report 1999. It goes on to list the financial crises in Brazil, Asia, and Russia and the natural disasters that struck the Caribbean, Asia, and Central America. And through it all, the World Bank was there. This report charts global economic progress and explains the World Bank's involvement in many aspects of the world economy. Broken into smaller reports, World Bank's annual report looks at the surprising rise of poverty, the issues surrounding Y2K and banking assistance, and the progress in anti-corruption efforts, among other issues. Also included are letters from the chairman, highlights, and summaries of improved projects. [EM]
World Economic Outlook (WEO) -- IMF [.pdf]
http://www.imf.org/external/pubs/ft/weo/1999/02/index.htm
This semi-annual comprehensive survey of the outlook of the world economy, from the staff of the International Monetary Fund, looks at world economic developments and future prospects. WEO considers the challenges of global adjustments in areas including the Middle East, Asia, and Europe, as well as the emerging market economies. Each chapter needs to be downloaded separately in .pdf format. This report also links to the new WEO Database. [EM]
http://www.ecarm.org/
Started in 1998 as a daily mailing list, The Society for Electronic Commerce and Rights Management (ECARM), (mailing list reviewed in the February 6. 1998 Scout Report) has grown into a not-for-profit agency focused on "the fostering and enabling of Electronic Commerce and Rights Management" by creating an online community; providing educational material by way of its mailing list, discussion groups, and links; and conducting research and analysis. Interested visitors may sign up for the mailing or discussion lists, view the current issue of the quarterly E*Journal, or read the weekly cartoon "eKarma." [EM]
http://www2.conferenceboard.ca/busbasics/en/wbcont.htm
This interactive workbook, from the Conference Board of Canada, aims to help its users understand basic business concepts. The introduction includes a quick quiz to test your business knowledge. Each chapter illustrates its points by following the progress of Newco Inc, a fictional company that serves as a case study. The site also contains charts and graphs, and workbook sections where users can record their own thoughts and ideas. [EM]
http://www.mercurycenter.com/svtech/companies/db/
Created by Mercury Center, this database offers financial information and company background for the 150 largest publicly traded companies in Silicon Valley. Silicon Valley is defined as the cities of Santa Cruz and Santa Clara, as well as the southern sections of San Mateo and Alameda counties. The database is searchable by company name, stock symbol, 1997 sales, industry type, product, and location. Clear, detailed instructions will help users best use the database. The search results link to company homepages and charted stock prices. [EM]
http://www.frbsf.org/system/fedinprint/
The Federal Reserve Bank of San Francisco presents this database of federal reserve economic research. Search the database by criteria including bank, publication name, keyword, or title. Also included are several handy search tips to help users navigate this system. [EM]
http://library.fgcu.edu/Subjects/Business/bushome.htm
The Florida Gulf Coast University (FGCU) Library has gathered a large collection of online business resources. The site is divided into two main sections. Business Guides, which contains topics such as Banking, Market Research, and Company Information, features bibliographies of print materials found at FGCU. If users scroll down to the end of each topic section, however, they will find a collection of partially annotated online resources. The second section, Internet Guides, is divided by resource types including Internet Business Libraries, Annual Reports, Working Papers, and Business Search Engines. Entries into this category are also partially annotated. [EM]
http://hotwired.lycos.com/special/ene/
From "Adhocracy" to "Zero-sum," HotWired and Anderson Consulting have published a comprehensive encyclopedia of terms, with definitions, and uses in business contexts. Words and phrases are organized in alphabetical order. A short introduction to the New Economy is also included. [EM]
http://www.inc.com/articles/details/0,,ART13544_CNT53,00.html
Online auctions are increasing in popularity among Internet-using consumers, and now businesses are beginning to participate, auctioning everything from conference tables to 100-pound rolls of bubble wrap. This article, from Inc. Online, looks at the advantages that auctioning online offers businesses. Also included is a list of sites where businesses may want to conduct auctions, as well as sites to get the tools needed for businesses to conduct their own auctions. [EM]
Ad Critic [Quicktime]
http://www.adcritic.com/
Ad Critic strives to enter every television advertisement into its database of online commercials, which can be downloaded for free and viewed with QuickTime. A complete list of advertisements is indexed by company and by ad title. There are, however, also indexes of newly added ads, most-downloaded ads, movie trailers, and music found in ads, making it easier for users to search for a new or favorite advertisement. Ad Critic includes a section on advertising news and commentary and provides services for advertising agencies including online market research and detailed viewer statistics. [EM]
Annual Review of Football Finance [.pdf]
http://www.deloitte.co.uk/news/arff99.htm
From the London offices of Deloitte and Touche, this report looks at the economy surrounding the English Professional Football Clubs. A synopsis of the report is immediately available, but interested users must complete a free registration form before viewing the full report, which may be downloaded in .pdf format. The report includes a synopsis of highlights, a review of football finances, and supplemental articles including "Football in the City: The Impact of Flotation," "The 'Gap': Premier League/Football League Divides," and "European Leagues." [EM]
http://www.hoovers.com/
Hoover's Online (first reviewed in the September 29, 1995 Scout Report) has been updated. It now includes information on about 50,000 companies, more than 3,000 links to news sources in its news library, and listings of weekly IPOs. Hoover's strives to be the comprehensive Website for business professionals. [EM]
(For links to additional current awareness on tables of contents, abstracts, preprints, new books, data, conferences, etc., visit the The Scout Report for Business & Economics Current Awareness Metapage: http://scout.cs.wisc.edu/report/bus-econ/metapage/).
Federal Reserve System:
FRB Cleveland Economic Research Working Papers [.pdf]
http://www.clev.frb.org/Research/workpaper/1999/index.htm
Social Security's Treatment of Postwar Americans: How Bad Can It Get?
http://www.clev.frb.org/Research/workpaper/1999/Wp9912.pdf
Optimal Monetary Policy in a Small Open Economy: A General Equilibrium Analysis
Timing and Real Indeterminacy in Monetary Models
Protection for Whom? Creditor Conflicts in Bankruptcy
Wage Adjustments: A Break from the Past
Banking and Commerce: A Liquidity Approach
FRB Dallas Economic Research Working Papers [.pdf]
http://www.dallasfed.org/htm/pubs/erpapers.html
Has Monetary Policy Become Less Effective?
http://www.dallasfed.org/htm/pubs/pdfs/erpapers/99_04.pdf
Core Inflation: A Review of Some Conceptual Issues
FRB Kansas City Research Working Papers [.pdf]
http://www.kc.frb.org/publicat/reswkpap/rwp99.htm
Do the Spreads Between the E/P Ratio and Interest Rates Contain Information on Future Equity Market Movements?
http://www.kc.frb.org/publicat/reswkpap/PDF/rwp99-03.pdf
FRB Minneapolis Staff Reports [.pdf]
http://research.mpls.frb.fed.us/research/sr/
Threats to Industry Survival and Labor Productivity: World Iron-Ore Markets in the 1980's
http://research.mpls.frb.fed.us/research/sr/sr263.pdf
FRB Philadelphia Working Papers [.pdf]
http://www.phil.frb.org/page.asp?page=workpapers99
Postwar Trends in Metropolitan Employment Growth: Decentralization and Deconcentration
http://www.phil.frb.org/files/wps/1999/wp99-10.pdf
Measuring Housing Services Inflation
http://www.phil.frb.org/files/wps/1999/wp99-9.pdf
A Welfare Comparison of Pre- and Post-WWII Business Cycles: Some Implications for the Role of Postwar Macroeconomic Policies
What Explains the Dramatic Changes in Cost and Profit Performance of the U.S.
Banking Industry?
FRB Richmond Working Papers [.pdf]
http://www.rich.frb.org/wpapers/
Does State-Dependent Pricing Imply Coordination Failure?
http://www.rich.frb.org/wpapers/pdfs/wp99-5.pdf
FRB San Francisco Working Papers [.pdf]
http://www.frbsf.org/econrsrch/workingp/index.html
Eurosystem Monetary Targeting: Lessons from U.S. Data
http://www.frbsf.org/econrsrch/workingp/wp99-13.pdf
Market Evidence on the Opaqueness of Banking Firms' Assets
Hidden Cost Reductions in Bank Mergers: Accounting for More Productive Banks
Heat Waves, Meteor Showers, and Trading Volume: An Analysis of Volatility Spillovers in the U.S. Treasury Market
Optimal Indicators of Socioeconomic Status for Health Research
Other Institutions:
World Bank Domestic Finance and Capital Markets Working Papers [.pdf]
http://www.worldbank.org/html/dec/Publications/Workpapers/domfincapmkts.html
Market Discipline and Financial Safety Net Design
http://www.worldbank.org/html/dec/Publications/Workpapers/wps2000series/wps2183/wps2183.pdf
Fiscal Adjustment and Contingent Government Liabilities: Case Studies of the Czech Republic and Macedonia
Fiscal Risks and the Quality of Fiscal Adjustment in Hungary
The Distributional Consequences of Monetary Policy: Evidence from Malaysia
Bank of International Settlements Basel Committee on Banking Supervision Publications [.pdf]
http://www.bis.org/publ/pub_list.htm#BS
Year 2000 Cross-Border Communications between Supervisors during the Millennium Period
http://www.bis.org/publ/bcbs59.pdf
Gathering Year 2000 Information from Financial Institutions: Recommendations for Supervisors
Performance of Models-Based Capital Charges for Market Risk: 1 July-31 December 1998
Enhancing corporate governance in banking organisations
Sound Practices for Loan Accounting and Disclosure
Principles for the Management of Credit Risk
Best Practices for Credit Risk Disclosure
Supervisory Guidance for Managing Settlement Risk in Foreign Exchange Transactions
Intra-Group Transactions and Exposures and Risk Concentrations Principles
http://www.bis.org/publ/bcbs51.htm
A new capital adequacy framework
Organisation for Economic Co-operation and Development (OECD) Working Papers
http://www.oecd.org/eco/wp/onlinewp.htm
The use of financial market indicators by monetary authorities
http://www.olis.oecd.org/olis/1999doc.nsf/5f293a526e52eb79c125675a00318d4c/235b0823c8b7e736c12567ed004236bb/$FILE/09E98895.ENG
Institute for International Economics Working Papers [.pdf]
http://www.iie.com/CATALOG/WP/1999/wp99.htm
Hazards and Precautions: Tales of International Finance
http://www.iie.com/CATALOG/WP/1999/99-11.pdf
Wharton Financial Institutions Center Working Papers [.pdf]
http://wrdsenet.wharton.upenn.edu/fic/wfic/papers/99.html
At Last the Internationalization of Retail Banking? The Case of the Spanish Banks in Latin America
http://wrdsenet.wharton.upenn.edu/fic/wfic/papers/99/9941.pdf
A Single-Server Queue with Markov Modulated Service Times
Managing Learning and Turnover in Employee Staffing
The Incentive Effects of No Fault Automobile Insurance
Stockholm School of Economics Working Paper Series in Economics and Finance [.pdf]
http://swopec.hhs.se/hastef/
Income-Related Inequality in Life-Years and Quality-Adjusted Life-Years
http://swopec.hhs.se/hastef/papers/hastef0334.pdf
The Dynamics of Capital Structure
Efficient estimation of price adjustment coefficients
Likelihood-Based Inference in Multivariate Panel Cointegration Models
FRB Atlanta Economic Review
http://209.239.32.240/publica/eco-rev/rev_abs/3rd99.html
FRB Chicago AgLetter [.pdf]
http://www.frbchi.org/pubs-speech/publications/periodicals/aglet/agaug99.pdf
FRB Dallas Houston Business [.pdf]
http://www.dallasfed.org/htm/pubs/pdfs/houston/hb99_09.pdf
FRB Minneapolis The Region
http://woodrow.mpls.frb.fed.us/pubs/region/99-09/index.html
FRB New York Current Issues in Economics and Finance [.pdf]
http://www.ny.frb.org/rmaghome/curr_iss/ci5-13.pdf
FRB San Francisco Economic Research
http://www.frbsf.org/econrsrch/wklyltr/wklyltr99/el99-30.html
FRB St. Louis International Economic Trends [.pdf]
http://www.stls.frb.org/docs/publications/iet/iet.pdf
The third quarterly installment of Economic Review from FRB Atlanta includes the articles "What Do Asset Prices Tell Us about the Future?," "The Banking Sector Rescue in Mexico," and "The Design of Wholesale Payments Networks: The Importance of Incentives." FRB Chicago's Ag Letter features a report on farmland values and credit conditions. The September 1999 issue of FRB Dallas's Houston Business contains the article "Insights from Several Corners of the Houston Economy." The Region is a quarterly publication from FRB Minneapolis; the September issue looks at the criteria for choosing Nobel Prize winners in Economics and the funding of minorities's start-up businesses, and contains an interview with Edward W. Kelley. The latest issue of Current Issues in Economics and Finance analyses the growth and stability of the US economy. The October 8, 1999 issue of Economic Research from FRB San Francisco focuses on depreciations and recessions. The featured articled in FRB St. Louis's International Economic Trends examines trade relations between Canada and the US. [EM]
International Monetary Fund Finance and Development
http://www.imf.org/external/pubs/ft/fandd/1999/09/index.htm
The September 1999 issue of Finance and Development from the IMF features several articles on Financial Architecture including "Reforming the International Financial Architecture," "The Case Against Benign Neglect of Exchange Rate Stability," and "Moderating Fluctuations in Capital Flows to Emerging Market Economies." Also included are comprehensive reports on commodity prices, the international monetary system, and the financial situation in Asia. [EM]
Bank for International Settlements (BIS)
BIS Review [.pdf]
http://www.bis.org/review/index.htm
Recently released articles and speeches from the BIS Review include president of the European Central Bank, Willem Duisenberg's September 10, 1999 speech stabilizing the price of the euro, the remarks of Robert W. Ferguson, a member of the Federal Reserve System Board of Governors, on the impact of information technology on productivity growth, and a speech on the role of the South African Reserve Bank "in the economic integration in the South African Development Community," given by Tio Mboweni, Governor of the South African Reserve Bank, at the University of Pretoria. [EM]
American Enterprise Institute for Public Policy Research
http://www.aei.org/eo/eo10962.htm
The October 1999 issue of Economic Outlook features the topic "What Should Central Banks Do?" It examines the role of central banking at the end of the twentieth century. [EM]
http://worldbank.org/aftdr/findings/english/find136.htm
Issue number 136 of The World Bank Group's Findings examines the Ghana Microfinance Institution (MFI) Action Research Network, which connects organizations interested in providing financial services with Ghana's poor. [EM]
Baker & Taylor Latest Books in Business -- October 1999
http://www.baker-taylor.com/Academia/M10/UBBS/ubbs17.html
Baker & Taylor Latest Books in Economics -- October 1999
Baker & Taylor lists business and economics books published in October 1999. [EM]
Econbase -- Elsevier
http://www.elsevier.nl/homepage/sae/econbase/menu.sht
The abstracts and tables of contents for the following journals are now available online: Japan and the World Economy (Vol 11, No 3), Journal of Economic Psychology (Vol 20, No 3), Regional Science and Urban Economics (Vol 29, No 5), International Journal of Forecasting (Vol 15, No 4), Journal of Financial Markets (Vol 2, No 3), Journal of Policy Modelling (Vol 21, No 4), and Land Use Policy (Vol 15, No 4). [EM]
Inomics Conference Calls:
Email Conference Alert
http://www.inomics.com/query/alert
Conference Search
http://www.inomics.com/query/conf_search
The economics research service Inomics (described in the June 18, 1998 Scout Report for Business & Economics) includes a conference alert service. Interested parties may specify their interests and receive email notifications of up-coming events, or they may search the Inomics conference database by date, geographic location, or JEL classification. [EM]
Conferences with Econometric Interest
http://www.eur.nl/few/ei/links/#conferences
The Royal Economics Society's Econometrics Journal site lists conferences in econometrics at this Econometric Links section. [EM]
European Business History Association (EBHA) Bordeaux 2000
http://www.univ-tlse1.fr/EBHA2000/
Hosted by the University of Bordeaux Political Sciences Institute, the EBHA conference will take place September 14-15, 2000. The featured topic is "Firms Committed to Internationalisation, Worldwide Expansion or Globalisation (19th- 20th century)." The Website is available in English and French. [EM]
Job Openings from The Chronicle of Higher Education
Job Openings in Economics
http://chronicle.com/free/jobs/faculty/sscience/econ/links.htm
Job Openings in Business and Management
http://chronicle.com/free/jobs/faculty/professional/business/links.htm
Job Openings for Economists (JOE)
http://www.eco.utexas.edu/joe/joe/
Inomics: Job Openings for Economists
http://www.inomics.com/query/job_search
US Reserve Assets and Foreign Official Assets Held at Federal Reserve Banks
http://www.bog.frb.fed.us/releases/bulletin/pagea51.pdf
This monthly statistical release from the Federal Reserve Board of Governors examines the US Reserve Assets and foreign official assets that are held at FRBs. This report displays the past eight months's activities, measured by millions of dollars, in each of these two sectors. [EM]
"Household Income at Record High; Poverty Declines in 1998, Census Bureau Reports"
http://www.census.gov/Press-Release/www/1999/cb99-188.html
This press release from the US Census Bureau announces that the number of Americans living under the poverty level dropped to 12.7 percent in 1998. This marks the fourth year in a row in which the median household income has risen. This report breaks the data down demographically and highlights some of the more inclusive findings. [EM]
Gross Domestic Product: Second Quarter 1999 (Final) Corporate Profits: Second Quarter 1999 (Revised)
http://www.bea.doc.gov/bea/newsrel/gdp299f.htm
According the revised estimates of the Commerce Department's Bureau of Economic Analysis, real gross domestic product increased at an annual rate of 1.6 percent in the second quarter of 1999. Real personal consumption expenditures only increased 4.8 percent, 1.9 percent less than the first quarter. Real exports of foods and services increased 4.9 percent in the second quarter, as compared to 5.1 in the first quarter. [EM]
Mass Layoffs (Monthly)
http://stats.bls.gov/news.release/mmls.toc.htm
This news release from the Bureau of Labor Statistics examines layoffs in the US. The report looks at layoffs in July 1999, with tables including mass layoff events and initial claimants for unemployment, industry distribution, and state distribution. The report is linked to data on local area unemployment statistics. [EM]
1999 Agency Reports/ Schedule
http://www.usda.gov/news/calindex.htm
USDA summarizes its report releases from various sources (the Economic Research Service, the National Agricultural Statistics Service, the Foreign Agricultural Service, and the World Agricultural Outlook Board) at this calendar site. Notable data for October 1999 include a summary of the new publication Floriculture and Environmental Horticulture from the Economic Research Service, US Department of Agriculture. [EM]
1) NetAid Official Site
http://www.netaid.org/
2) Cisco's NetAid Website
http://www.cisco.com/netaid/
3) The Complete Guide to the NetAid Concert
http://www.aloud.com/festivals/netaid.shtml
4) "Flashy launch for antipoverty Web site" -- CNet
http://news.cnet.com/news/0-1005-200-114484.html
5) "All-star cast at NetAid launch" -- BBC
http://news2.thls.bbc.co.uk/hi/english/world/newsid%5F441000/441545.stm
6) "Cisco: Net Will Be a Great Equalizer" -- PC World
http://www.pcworld.com:80/pcwtoday/article/0,1510,13070,00.html
7) "U.N. brings war on poverty online" -- ZDNet
http://www.zdnet.com/zdnn/stories/news/0,4586,2331067,00.html
8) "Bytes for the Hungry" -- ABCNews.com
http://abcnews.go.com/sections/tech/DailyNews/netaid990921.html
In one of the most bizarre collaborations in digital history, Cisco Systems has teamed up with the United Nations to bring the world NetAid, a day-long musical charity event designed to help rid the world of poverty and promote world peace. On Saturday, October 9, 1999, a host of recording artists ranging from Busta Rhymes, Sting, the reunited Eurythmics, and David Bowie will be performing simultaneous concerts in New York City, London, and Geneva. The event will be broadcast free worldwide by television, radio, and most notably, in Webcast form, in hopes to bring recognition and money to five social action causes, including relieving the world's poorest countries from debt. World-renown rock musicians Bono and Wyclef Jean have organized the event with the help of LiveAid producer Harvey Goldsmith, and David Goldberg and Don Mischer, who together produced The Opening & Closing Ceremonies for the 1996 Centennial Olympic Games. NetAid's mission is "to harness this power [of the World Wide Web] and use the Internet as a medium of social and economic change." After the concert, NetAid hopes to inspire people to continue to strive to make the world a better place through the millennium. The NetAid Website asks users to sign a petition to end world debt and make a donation to NetAid. This week's In the News looks at this online happening through the following eight resources containing news, information, and official sites about this upcoming event.
The NetAid Official Site (1) is a one-stop Website for news, information, Real Audio clips of the official NetAid theme song, and explanations of NetAid philosophies, as well as a place to download streaming video of the event during the broadcast and to donate to the United Nations Development Programme. Cisco's NetAid Website (2) focuses on the technology, people, and ideas behind the event. Aloud.com's The Complete Guide to the NetAid Concert (3) looks at the event from a strictly entertainment perspective with ticket and netcast information. Both CNet (4) and the BBC (5) examine support for the event from US President Bill Clinton, UK Prime Minister Tony Blair, UN Secretary General Kofi Annan, and former President of South Africa Nelson Mandela, including their presence at the launching of the NetAid Website. PC World's coverage of the upcoming event (6) considers Cisco's role in NetAid, and how the company sees NetAid as an example of the ways in which a Website can be used as a forum for social, economic, and political action. ZDNet (7) covers NetAid's strategies to end world poverty and compares NetAid to large-scale media events in the past 20 years. ABCNews's article "Bytes for the Hungry" (8) examines the technology used to bring NetAid in to every computer-user's home. [EM]
Scout Report for Business & Economics Subscription Instructions
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Internet Scout team member information
The Scout Report for Business & Economics
Brought to You by the Internet Scout Project
The Scout Report for Business & Economics is published every other Thursday by the Internet Scout Project, located in the University of Wisconsin-Madison's Department of Computer Sciences.
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Below are the copyright statements to be included when reproducing annotations from The Scout Report for Business & Economics.
From The Scout Report for Business & Economics, Copyright Internet Scout Project 1994-1999. http://scout.cs.wisc.edu/
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redpajama_set_name: RedPajamaCommonCrawl


A boutique 22-storey building, offering a mix of exclusive studio, 1, 2 & 3-bedroom residences crafted by the award-winning design team, FJMT.
A perfect combination of world-class architecture and stunning interiors that will set a new standard of living in the heart of the Parramatta CBD.
Your new home offering a vibrant lifestyle where transport, dining and entertainment are at your door step.
Gourmet kitchens with SMEG appliances and stone bench tops.
Open-air private residents' swimming pool and gymnasium on Level 1.
Large apartments all with built-in studies or media nooks.
Submit your details to receive more information, or to book an appointment at our Display Suite and view the actual finishes.
Your registration has been received and one of our sales agents will be in contact with you shortly.
You are now subscribed to news and updates about Charlie Parker.


text:
NORA FRIEDRICHS
"Nora Friedrichs gave us a scintillating Blonde. The voice has the lightness of cotton candy with an attractive vibrato and an easy top."
operatraveller.com
Winner of the Stella Maris Singing Competition and praised by Das Opernglas for her 'radiant coloratura', German soprano Nora Friedrichs was a member of the Oper Frankfurt studio from 2013 to 2015.
Highlights of the 2019/20 season included her debut at the Elbphilharmonie Hamburg and her role and house debut at Nationaltheater Mannheim, singing the role of Eurydike in Orpheus in der Unterwelt by J. Offenbach.
Season 2016/17 saw her debuting in two exciting roles: in November 2016 Nora made her role-debut as Queen of the Night with the Berliner Staatsoper Unter den Linden, and in May 2017 she sang the role of Fiakermilli (Arabella) with Oper Frankfurt.
Season 2017/18 saw her debuting at the prestigious Semperoper Dresden where she sang the role of Blonde in Entführung aus dem Serail as well as her house-debut at the Deutsche Oper am Rhein, singing Fiakermilli in Arabella.
Until 2019, the soprano was a member of the ensemble of Komische Oper Berlin where she was singing many important roles including Le feu / nightingale in L'enfant et les sortilèges, Blonde in Entführung aus dem Serail, Königin der Nacht in Die Zauberflöte, La Fèe in Cendrillon.
"Mit sehr witzig und treffsicher gesetzten Spitzentönen schließlich spielt die Sopranistin Nora Friedrichs in der Arie der Adele aus Strauss" "Fledermaus" die lebenshungrige Unschuld vom Lande."
© 2019 by Nora Friedrichs


There are many places on your home that can benefit from exterior railings. From the patio where family barbecues happen to the upper story porch on your home. Chances are you've seen many of the railing systems that are used on these areas. In fact, there are basically on a few styles that the majority of home owners choose today simply because they don't realize some better, much better, is out there. Getting exterior railings on your home doesn't need to be a one size fits all, but a custom railing solution that makes your home look great.


text:
Emory Students Apologize for Racially Insensitive Television Broadcast
Filed in Campus Racial Incidents on January 3, 2013
Students at Emory University apologized for a segment of a parody television broadcast called the "Dooley Show." The segment focused on the current Supreme Court case concerning the race-sensitive affirmative action admissions program at the University of Texas. In the satirical segment, viewers were asked to help identify students who "shouldn't be here and are only at the school because of affirmative action." The segment went on to make references to lynching, tarring and feathering, and cross burnings.
In a statement, the producers of the program wrote, "We would like to apologize for the segment that recently caused so much hurt, pain, and anger in the Emory community. The segment was poorly written and in poor taste. We were not aware of the pain the segment would cause, the wounds existing on our campus it would open, or the dialogue it would recall. We, too are members of the Emory community, and are deeply ashamed and sincerely sorry for all the pain and hurt our words have caused within it."
Related: Emory University
CommonSenseRules says:
Privilege — regardless of its sources — never has had to police itself. There is no evidence to suggest that it ever will. In today's environment the dominant class operates under the beliefs that: 1) so long as one does not use the N-word publicly, then no one should take offense; 2) if I wasn't around during slavery/Jim Crow, why do I get criticized?; and 3) if YOU were offended by X, then YOU need to get over being so sensitive.
Forget history; this isn't about yesteryear. Do not be misled by the contemporary plaudits bestowed on a select few. Emory's systemic practices of race-, class-, and Christian-based denigrations are alive and well.
P.S. I have not overlooked queers and other 'others'. They just aren't the focus of this latest outrage.


text:
Pacsirta è un film del 1963 diretto da László Ranódy. Tra gli interpreti, alcuni dei nomi più noti della cinematografia ungherese; il film, in concorso a Cannes 1964, si portò a casa il premio per il miglior attore vinto da Antal Páger ex aequo con Saro Urzì per Sedotta e abbandonata.

Trama

Produzione
Il film fu prodotto dalla Hunnia Filmgyár.

Riconoscimenti
Nel 1964, fu presentato in concorso al 17º Festival di Cannes, dove Antal Páger vinse il premio per la miglior interpretazione maschile.

Note

Collegamenti esterni

Film drammatici


Sub: – Establishment of ICT Enabled "Skills Lab" at Your Esteemed NGO.
By 2026, 64.8 per cent Indian population will be in the bracket of working group. As against this demographic dividend, we might have a shortage of skilled people- engineers (6 lakh), graduates (39 lakh) and vocationally trained personnel (7 lakh), according to CII report on linking skills to jobs. In addition, we might fall short of the target of skilling 500 million people by 2022. One should also consider that the country has set for itself monumental goals such as 'Make in India', 'Digital India', 'Smart Cities' to name a few and the ground reality suggests that we do not have enough skilled people to execute it effectively. In view of this, it is understandable that 'Skill India' is an official government program.
Like China, we wish to emerge as the manufacturing hub of the world. However, the manufacturing sector is pegged at 16% in terms of its share in GDP in comparison to China's 29%. At our ambitious best, we could set the target of raising it from 16% to 25% in short term. 'Make in India', 'Digital India' etc are manifestations of this aspiration. For this to translate into reality, we need to empower a whole generation of youth with high end skills and advanced competencies which can match the competitiveness of China and other countries.
To cater to the national skills development requirements of 'Skill India', Station-e has envisaged the concept of 'Skills Lab' which can be established at COUNCIL FOR TECHNICAL EDUCATION. When it comes to teaching-learning of skills, classroom culture of theoretical discussions may not prove to be adequate and effective in imparting the right skills to the youth. Therefore, we have developed a futuristic 'Skills Lab' that categorically focuses on imparting skills to the learners through activity based learning and advanced technology. Learning skills is about 'doing' something in real life situations and hence we have evolved course modules that provide ample simulation of real life situations and sufficient practice for the skills to become internalized as second nature. Secondly, technology if appropriately employed can play a vital role in skilling people.
In sync with this, 'Skills Lab' is a 'lab' equipped with next generation technology for various skills such as Communicative English, Computing Skills, Vedic Mathematics, Leadership Skills, Team Work, Goal Setting, Interview Skills, Group Discussion, Resume Building and other life and soft skills to be imparted, learnt, monitored and measured. 'Skills Lab' has the potential to draw the learners into 'putting skills into practice' and 'measuring' their own 'skills development' through the tech tools at their disposal in the lab. 'Skills Lab' is also the most suitable model of skills development implementation as it presents a model that provides 'quantification' of skills development through technological tools and 'demonstrable' skills enhancement which is measurable against any criteria.
'Skills Lab' is a revolution in the making. It is an idea whose time has come. It is also a mass model as it can be scaled up to the national level with meticulous precision to address the need of 'Skill, Scale, Speed'. It can be modified as per the diverse requirements of the different institutions, regions, and segments of learners. 'Skills Lab' can be a transformational system to supplement the core education practices and take the quality benchmark to the next level.
We are confident that the synergy efforts of both of us could empower the youth of the country to meet the challenges ahead.
Station-e Info Services Pvt. Ltd.


text:
About MSD Capital
Overview MSD Platform Mission Statement Business Principles Risk Management
Overview Public, Private & Special Situation Investments Partnership Investments Group
MSD Platform
Public, Private & Special Situation Investments
Partnership Investments Group
Douglas Londal
Mr. Londal is the Head of MSD's Private Capital Group. He joined MSD Capital in September 2015 as a Partner to lead its Private Capital Group. Prior to joining MSD, Mr. Londal was the President and COO of New Mountain Capital, LLC, an alternative asset management firm with over $15 billion of assets under management. Mr. Londal joined New Mountain in 2004 when the firm had one private equity fund and $770 million of AUM. He helped grow New Mountain to $15 billion of AUM by 2014 and into three separate businesses, including private equity, a long/short hedge fund and a publicly-traded debt BDC (NYSE:NMFC).
Prior to joining New Mountain, Mr. Londal spent 14 years at Goldman, Sachs & Co. He was a Managing Director in the Principal Investment Area and, among other positions, served as Co-Head of the U.S. Merchant Banking business and Co-Head of U.S. Mezzanine business. Mr. Londal has been directly involved in investing over $10 billion in private equity and mezzanine transactions valued at over $20 billion. He has served on over 20 "for-profit" boards of directors (public and private) in roles including chairman and lead director, as well as chair of several audit and compensation committees.
Mr. Londal received his B.A. in Economics from the University of Michigan and his M.B.A. from the University of Chicago Graduate School of Business.
New York CitySanta MonicaWest Palm Beach
© 2020 MSD Capital L.P. All Rights Reserved. Submissions Policy Terms of Use Privacy Policy


text:
Q: Test presence of javascript code/snippet with rspec capybara (Rails 4) I'd like to create a test to make sure my third party tools (js scripts) are present (for example, to make sure nobody in the team removed it by accident!)
Here are 2 javascript third party tool that are loaded on my homepage view whose presence i'd like to test:
<script type="text/javascript">
var clicky_site_ids = clicky_site_ids || [];
xxxxxxxxxxxxxxxxxxxxxxxxx
(function() {
  var s = document.createElement('script');
  s.type = 'text/javascript';
  s.async = true;
  s.src = '//static.getclicky.com/js';
  ( document.getElementsByTagName('head')[0] || document.getElementsByTagName('body')[0] ).appendChild( s );
})();
</script>

<script src="//src.melvinize.io/r.js"></script>

Here are my rspec test (I'm using Capybara with webkit driver)
describe "third party tools are present inside source code", js: true do

    it 'should have js trackings' do
      visit(root_path)
      all('script').find { |s| s[:src].match /getclicky\.js$/ }.should_not be_nil
      all('script').find ("//static.getclicky.com/js").should_not be_nil

      all('script').find ("//src.melvinize.io/r.js").should_not be_nil
    end

  end

My test does not work as it always pass (!), but I'm a rookie with this kind of tests using regular expressions and I'm not even sure that's the right way to do it.


text:
Adjudicated Pedophile Brett Kimberlin Impotently Accuses me of Unauthorized Practice of Law
Or "Brett Kimberlin Goes the Full Schmalfeldt"
Brett's fail is much funnier in 3D!
This is the latest post in what I half-jokingly call The Kimberlin Saga®. If you are new to the story, that's okay! Not everyone reads my blog. The short version is that convicted terrorist Brett Kimberlin has been harassing me for over three years, his worst conduct being when he attempted to frame me for a crime. I recognize that this might sound like an incredible claim, but I provide video and documentary evidence of that fact; in other words, you don't have to believe my word. You only have to believe your eyes. Indeed, he sued me for saying this and lost on the issue of truth. And more recently when his wife came to us claiming that this convicted terrorist had threatened her harm, we tried to help her leave him, and for that, he sued myself, John Hoge, Robert Stacy McCain and Ali Akbar for helping his wife and for calling him a pedophile. He lost on the issue of truth. He is also suing Hoge, Akbar, Dan Backer, DB Capital Strategies, Patrick "Patterico" Frey, Mandy Nagy (who is significantly incapacitated by a stroke), Lee Stranahan, the National Bloggers Club, and others alleging that we are all in conspiracy to defame him because we reported factually about the spate of SWATtings committed against myself, Frey, Erickson and others. So, if you are new to the story, go to this page and you'll be able to catch up on what has been happening.
Now in the last two posts, I discussed Kimberlin v. Walker, et al., and Kimberlin v. National Bloggers Club (II), and I have discussed other cases in the past. One case I don't remember discussing at all, is Kimberlin v. Hunton and Williams, et al. That's largely because I am not a party in it, and not generally involved in that case, but my friend John Hoge is and he has been discussing it regularly at his blog, here. He calls it "RICO II," sometimes humorously adding "Electric Boogalo" to riff off the movie "Breakin' 2: Electric Boogalo" which is more famous for its title than anything else.
How to explain this suit? Well, the short version is this. Longtime readers know that Brett Kimberlin believes that there was a vast conspiracy against him called in shorthand "Team Themis" that involves the U.S. Chamber of Commerce, the FBI and I think the CIA. No word on whether the Templars are involved, too. Anyway, this suit is about that pile of crazy... and then he threw in some random unrelated state-law tort claims against John Hoge and Bill Nickless. The insertion of Mr. Hoge seems largely to be related to his anger at John for having won a peace order hearing the week before Brett filed this. He filed this dumb lawsuit literally the same week that Judge Hazel dismissed all RICO claims (and most other claims in Kimberlin v. National Bloggers Club (I). You can read that opinion here. And guess who got the new RICO case? Judge Hazel. It's like legal whack-a-mole.
Posted by A.W. at 2:01 PM 3 comments:
Adjudicated Pedophile Brett Kimberlin Impotently Pleads for a Stay of Execution
"He is an impotent little wannabe lawyer, isn't he?"
"Yeah, what a loser!"
"This is good popcorn."
Now, dear reader, the last two posts on Brett Kimberlin (here and here) have been instances where a lot of catch up was needed. I had to go back months in time to tell you what is happening. This time, we can build off of events in, well, those last two posts.
For those just catching up, I am going to do a recap, sort of a "last time on Lost," moment.
To briefly recap, Brett first had a case against me that we call Kimberlin v. Walker, et al. Basically it revolved primarily (but not exclusively) around allegations that Brett is a pedophile and issues like criminal charges that arose from that. We went to trial on defamation and false light and won that case for the most substantive reason possible: truth. Which means that from now on, Brett is not allowed to claim anyone has defamed him or placed him in a false light by calling him a pedophile at least as of August 12, 2014, even one that has practiced it in the past. In my last post I discussed how he attempted to appeal his loss in that case and lost that appeal.
Posted by A.W. at 10:50 PM 1 comment:
Appellate Court Affirms Brett Kimberlin's Status as an Adjudicated Pedophile
Or: "Catching Up with Kimberlin v. Walker, et. al."
With a headline like that, you know you
will need popcorn!
The headline, here, is that Brett Kimberlin has lost his latest appeal of his lawsuit involving charges that he is a pedophile. This is the same case that David Weigel wrote about in the Daily Beast. And you can see where I wrote in the immediate aftermath of that victory in the lower court here and here. To explain how we get there, however, is going to take a while. Bluntly, I don't write posts trying to chase the lastest breaking news. I try to give you thoughtful analysis you can read for a while and this post is no exception. If you read every embedded document, you are looking at around 300 pages of text by my best estimate. So there's nothing wrong with saving it for when you really have a long time to read.
Let's start with a quick background about the case. The short version is that in 2013, Brett Kimberlin's wife, Tetyana Kimberlin, separated from her husband and came to myself and John Hoge for help. She told us that Brett Kimberlin had seduced her when she was fourteen years old in Ukraine, that he brought her to America when she was fifteen and carried on a sexual relationship in violation of Maryland law (because she was below the relevant age of consent), and various other horribles. This lined up with other evidence that suggested Brett was a pedophile. She ended up filing charges based on that crime, but at some point reversed course and stopped cooperating as a witness, causing those charges to be dropped. Brett sue me and several of my friends (John Hoge, Robert Stacy McCain, Ali Akbar and two persons who allegedly wrote as KimberlnUnmasked) for alleged stalking and harassment (which is not a cause of action in Maryland), malicious prosecution, malicious use of process, intentional infliction of emotional distress, defamation and false light. First, we won a grant of summary judgment in our favor on all but the defamation and false light claims. Then we won a judgment (what is called a directed verdict in most states) at trial on the issue of false light or defamation, because Brett literally had no evidence that anything we said was false. In other words, he thought he could get up there, prove we said bad things about him and then rest his case, or he wanted the court to accept that argument. He has now lost that argument, twice.


Limping along with that hair?
Home/Hair, Haircare, Limp hair, Perms, Texturizing/Limping along with that hair?
If you are one of those people who has been cursed with fine, limp hair, I have some help for you.
Limp, fine hair is one of the hardest problems to address in my world behind the chair. Genetics, medical conditions, medications, styling, and stress, can all factor in to what may be causing this to occur. If you have suffered with this condition most of your life, you are pretty safe to rule out the last four and realize that it is time to make lemonade out of those lemons. Here are my best tips to help you turn your limp locks into voluminous waves.
Let it get dirty. Sounds contrary huh? Shampooing everyday is hard on the hair. Try instead to use a dry shampoo for one or preferably two days. There are a number on the market that are wonderful. Here is a link to a short list of the ones I have tested.
Avoid "volume" shampoos. I know, crazy huh? Actually, most "volume" shampoos work so well because they strip the oil. Years ago when I was educating with a manufacturer, we did strip tests on hair with various shampoos, and the OTC "volume" shampoos actually "permed" the hair we wrapped around rods – permanently!
Use a light conditioner. One of the most important things about the conditioner you are using is that it stays far, far away from your scalp. Your scalp does not need the conditioning, just the ends, and very lightly at that.
Don't comb while wet. Your baby fine hair is so fragile when it is wet! Use a wide tooth pick or comb and GENTLY get through the ends. Avoid vigorous towel drying. Instead, gently squeeze the excess moisture from your ends with a towel wrapped around the hair.
Style with TLC. Wash your hair the night before and allow to air-dry. The next day, mist your hair slightly to create the style you want with your blow-dryer on low. Instead of blow-drying it right out of the gate. Use a curling iron or flat iron on this type of hair for a rare occasion only. Consider investing in some good old fashion hot curlers, they are coming back into style again.
Professional Color. Not only can a stylist see the back of your head and exactly how close to get to the previously colored hair without overlapping, we also use products that are much safer and gentler on your hair. Over-the-counter hair dyes contain harsh chemicals and metals that can further damage already fragile hair.
Create an illusion. Use hair powder to disguise not only the roots and dry them out between shampoos, but to help create the illusion of more hair. Here is a short list from last week's tip of the best powder shampoos that double as scalp coverage and create a fuller look for you.
Consider getting a texture wave. Unlike the perms of the 80's, these texture creating waves are done on much larger rods and use gentler chemicals. This option should only be considered if you have strong enough hair that has not been weakened by a high lift color. Consult your professional for recommendations on this.
or however you would like to help them out!


Product Meaning:When choosing a ring that represents and celebrates the love you share, lots of things come into play. The three-stone ring can hold more and different meaning than the traditional solitaire, and has the ability to tell a story. Many couples choose this ring because to them, the three stones represent "past, present and future." Alternately, the ring can symbolize "friendship, love and fidelity." If you are a couple who wants to have deeper, more personal meaning in your engagement ring choice, the three-stone engagement ring just may be for you.
Best Engagement Rings on Italo,Browse fine designed engagement rings for women with low price from Italo jewelry.Picking Italo engagement rings here will be a wise choice.