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Staphylococcus aureus pneumonia causes significant morbidity and mortality. Alpha-hemolysin (Hla), a pore-forming cytotoxin of S. aureus, has been identified through animal models of pneumonia as a critical virulence factor that induces lung injury. In spite of considerable molecular knowledge of how this cytotoxin injures the host, the precise host response to Hla in the context of infection remains poorly understood. We employed whole-genome expression profiling of infected lungs to define the host response to wild-type S. aureus compared with the response to an Hla-deficient isogenic mutant in experimental pneumonia. These data provide a complete expression profile at 4 and at 24 h postinfection, revealing a unique response to the toxin-expressing strain. Gene ontogeny analysis revealed significant differences in the extracellular matrix and cardiomyopathy pathways, both of which govern cellular interactions in the tissue microenvironment. Evaluation of individual transcript responses to Hla-secreting staphylococci was notable for upregulation of host cytokine and chemokine genes, including the p19 subunit of interleukin-23. Consistent with this observation, the cellular immune response to infection was characterized by a prominent Th17 response to the wild-type pathogen. These findings define specific host mRNA responses to Hla-producing S. aureus, coupling the pulmonary Th17 response to the secretion of this cytotoxin. Expression profiling to define the host response to a single virulence factor proved to be a valuable tool in identifying pathways for further investigation in S. aureus pneumonia. This approach may be broadly applicable to the study of bacterial toxins, defining host pathways that can be targeted to mitigate toxin-induced disease.
Staphylococcus aureus is a Gram-positive human pathogen that causes a considerable burden of disease characterized by a spectrum of illness ranging from mild skin infections to life-threatening infections such as sepsis, pneumonia, endocarditis, and osteomyelitis (47). Pneumonia due to S. aureus is one of the most common invasive forms of disease, carrying an associated mortality rate up to 50% (1, 24, 34, 39). The combination of high incidence, high pathogenicity, and frequent resistance to multiple antibiotics results in S. aureus being one of the most significant human pathogens.
S. aureus harbors a number of virulence factors, including several cytolytic, pore-forming toxins (19, 21). Among the best studied of these toxins is alpha-hemolysin (Hla), a secreted toxin that assembles into a membrane-perforating homoheptamer upon binding to its eukaryotic cellular receptor, ADAM10 (5, 36, 67). Hla induces pulmonary hypertension and inflammation in several animal models (52, 66) and has been demonstrated to be essential in the pathogenesis of lethal pneumonia in a murine model, causing widespread alveolar injury and concomitant epithelial barrier disruption (9, 10). Several studies shed light on the mechanism by which Hla induces inflammation and lung damage. Hla induces platelet-activating factor production in endothelial cells (25, 69, 70) and release of nitric oxide and inflammatory mediators from pulmonary epithelium-derived cells (64). The toxin also promotes cytokine release from macrophages (56) and induces cell death and cytokine release from monocytes (4). Cell death is triggered through the NLRP3-dependent program of cellular necrosis, resulting in the release of endogenous proinflammatory molecules (15); indeed, NLRP3−/− mice display reduced interleukin-1β (IL-1β) production in response to Hla and demonstrate more mild clinicopathologic features of S. aureus pneumonia (37). Hla has been shown to injure alveolar epithelial cells by upregulation of the enzymatic activity of the toxin receptor ADAM10, leading to E cadherin cleavage and disruption of the intercellular adherens junction that is essential for intact epithelial barrier function (30, 75). Conversely, innate host protection from the effects of Hla is accomplished through activation of type I interferon signaling, recently shown to be mediated by phospholipid scramblase 1 (PLSCR1)-induced mitigation of cellular ATP loss (46). Together, these studies indicate that Hla targets critical host defenses provided by both innate immune cells and the tissue barrier and highlight the complexity of the host response to the toxin.
Neutralization of key virulence factors is one approach to find effective preventative and therapeutic agents to combat staphylococcal infection; indeed, immunization and small-molecule strategies targeting Hla afford a high degree of protection against lethal pneumonia (11, 61, 62). Similarly, antivirulence strategies associated with reduced expression of Hla protect against disease (59, 60, 73). In the setting of bacterial toxin-induced disease, a viable alternative approach may be modulation of the host response to minimize the deleterious effects of intoxication. This strategy circumvents the challenges associated with pathogen-acquired resistance, especially to small-molecule-based therapies. We hypothesized that whole-genome transcriptional analysis of lung tissue infected with wild-type (WT) or Hla-negative (Hla−) S. aureus would allow us to pinpoint host signature responses during the course of infection that were specifically linked to the presence of the toxin. Such studies were anticipated to enhance our understanding of the host-pathogen interaction in S. aureus pneumonia and suggest avenues for disease modification.
Bacterial strains.Staphylococcus aureus Newman WT and its isogenic toxin-deficient mutant, designated Hla−, have been previously described (9, 10).
Mouse model of lung infection.Seven-week-old female C57BL/6J mice (Jackson Laboratories, Wilmington, MA) were inoculated via the intranasal route with either phosphate-buffered saline (PBS) or the S. aureus Newman or Hla− strain as described previously (9, 10). Following a 1:100 dilution of an overnight culture into fresh tryptic soy broth, the bacteria were grown with shaking at 37°C to an optical density of 0.5 at 660 nm. Culture aliquots (50 ml) were sedimented by centrifugation, and the bacteria were washed and resuspended in 1.0 to 1.5 ml of PBS. Animals utilized for microarray and transcription-based analyses received inocula ranging from 3 × 108 to 5 × 108 CFU, associated with clinical signs of severe lung disease. Animals utilized for T cell subset analyses received a sublethal inoculum of 1 × 108 CFU for initial infection, followed in 8 days by a second sublethal infection of 0.8 × 108 to 2 × 108 CFU and tissue harvesting at 24 h. Animals were anesthetized with ketamine and xylazine as previously described (49). After appropriate anesthesia was documented, 30 μl of the bacterial slurry was inoculated into the left nare and the animals were held upright for 1 min postinoculation. All animals were housed under standard conditions and provided food and water ad libitum. At time points of 4, 8, 12, or 24 h, animals underwent bronchoalveolar lavage fluid collection and were then sacrificed for removal of the lung tissue. All animal studies were performed in concordance with principles set forth by the Animal Welfare Act and the National Institutes of Health guidelines for the care and use of animals in biomedical research and were reviewed and approved by the University of Chicago Institutional Animal Care and Use Committee.
RNA isolation.Lung tissue was snap-frozen in liquid nitrogen and stored at −80°C. At the time of processing, total mouse lung RNA was isolated by directly solubilizing lung tissue in TRIzol LS reagent (Life Technologies) using a Brinkman Polytron tissue disrupter. RNA was then purified using an RNeasy purification kit according to the manufacturer's protocol (Qiagen). Approximately 10 μg of purified, total RNA was used for analyses.
Microarray data analysis.The microarray data analysis was performed using an Affymetrix GeneChip platform and Expression Analysis Manual protocols (Affymetrix Inc., Santa Clara, CA). Three mice were included for each condition. The signal intensity fluorescent images produced during Affymetrix GeneChip Mouse 430_2 array hybridizations were scanned using a Hewlett-Packard GeneArray G2500A scanner. We evaluated chip quality using GeneChip operating software (GCOS), dChip (43), and the affy package (6) in Bioconductor software. All RNA samples and chips used in this study passed established quality criteria (data not shown). The expression level of each probe set was summarized by the gcrma package in Bioconductor with GC robust multichip average (GCRMA) normalization (76). To identify differentially expressed genes, pairwise comparisons were conducted using the samr package (71) in Bioconductor. Only probe sets present (determined by the mas5calls function in the affy package in Bioconductor) in three replicates of at least one group were retained. The heat map, gene ontology biological process terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were generated using criteria of a false discovery rate (FDR) of <1% and a minimum of a 3-fold change between examined groups. The summary of the number of genes differentially regulated and tables of specific genes differing between S. aureus WT and Hla− infections, including the genes identified in the extracellular matrix (ECM) and cardiomyopathy pathways, were prepared using an FDR of <5% and a minimum of a 2-fold change. For probe sets with the same Entrez Gene or UniGene identifier, only the probe set with the lowest FDR or the highest fold changes in the gene list were included. We searched for any enriched KEGG (35) physiological pathways among the differential genes using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) (18, 29). A corrected P value of <0.05 (Fisher's exact test) after the Benjamini-Hochberg procedure (3) was used as the cutoff.
qRT-PCR analysis.Quantative reverse transcription-PCR (qRT-PCR) was performed with the two-step reaction protocol using SsoFast EvaGreen supermix (Bio-Rad Laboratories, Hercules, CA). First-strand cDNAs were synthesized using an iScript Select cDNA synthesis kit (Bio-Rad Laboratories, Hercules, CA) at 42°C for 70 min, followed by 85°C for 5 min and a hold at 4°C. Actin was used as the endogenous control. Primer sets used for the quantitative PCR analysis included IL1r2 (interleukin 1 receptor type II) forward (For; 5′-GTTTCTGCTTTCACCACTCCA-3′) and reverse (Rev; 5′-GAGTCCAATTTACTCCAGGTCAG-3′), Ccl11 (chemokine [C-C motif] ligand 11) For (5′-GAATCACCAACAACAGATGCAC-3′) and Rev (5′-ATCCTGGACCCACTTCTTCTT-3′), Sdc4 (syndecan 4) For (5′-GTCCCCGGAGAGTCGATTC-3′) and Rev (5′-GCACCAAGGGCTCAATCACTT-3′), Figf (c-fos-induced growth factor) For (5′-TCACGCTCAGCATCCCATC-3′) and Rev (5′-ACTTCTACGCATGTCTCTCTAGG-3′), Col5a2 (procollagen type V alpha 2) For (5′-ACAGGTGAAGTGGGATTCTCA-3′) and Rev (5′-CCATAGCACCCATTGGACCA-3′), Tgfb3 (transforming growth factor beta 3) For (5′-CAGGCCAGGGCAGTCAGAG-3′) and Rev (5′-ATTTCCAGCCTAGATCCTGCC-3′), IL-17A (interleukin-17A) For (5′-CTCCAGAAGGCCCTCAGACTAC-3′) and Rev (5′-AGCTTTCCCTCCGCATTGACACAG-3′), and Actin For (5′-TGGCATTGTTACCAACTGGGACG-3′) and Rev (5′-GCTTCTCTTTGATGTCACGCACG-3′). All qRT-PCR assays were carried out using primer sets from Integrated DNA Technologies. qRT-PCR parameters used were as follows: 95°C for 30 s and then 95°C for 5 s and 55°C for 5 s for 40 cycles. A melting curve was constructed for verification of the specificity of PCR products by increasing the temperature from 60 to 95°C in 0.5°C-step increments. PCR was performed with SsoFast EvaGreen supermix, using a CFX96 optical reaction module and C1000 thermal cycler (Bio-Rad Laboratories, Hercules, CA). The relative fold change in gene expression was calculated following actin normalization using the comparative threshold cycle (CT) method as described previously (45, 65). The mean value for the control mice was used to calculate the fold change for each experimental mouse.
Lung processing for flow cytometry.Mice were anesthetized and lungs were perfused with 6 ml PBS with 50 units/ml heparin injected through the right ventricle. Then, the lung was surgically excised and minced with sterile glass coverslips. The pieces were incubated in a shaker at 37°C for 30 min in complete Dulbecco modified Eagle medium (DMEM; Cellgro, Manassas, VA), 5% fetal bovine serum, 0.05 mM β-mercaptoethanol, 10 mM HEPES, 100 U/ml penicillin, and 100 μg/ml streptomycin with 146 U/ml collagenase I (Invitrogen, Carlsbad, CA). Samples were pipetted up and down 50 times to break up larger tissue sections, any remaining pieces of tissue were removed by straining the solution through a Nytex filter, and the cells in suspension were centrifuged and resuspended in complete DMEM. Cells were then resuspended in 44% Percoll (Sigma, St. Louis, MO) and spun in 44% and 66% Percoll gradients. Cells were collected at the interface of the two solutions. Live cell count was determined via trypan blue exclusion, and then the cells were divided for antibody staining and in vitro stimulation studies. For stimulation, cells were incubated overnight at 37°C in complete DMEM with IL-2 (20 U/ml) and then stimulated with phorbol myristate acetate (PMA; 20 ng/ml) plus ionomycin (400 ng/ml) for 6 h at 37°C, with brefeldin A (25 μg/ml) added for the final 2 h.
Flow cytometry.Prior to staining with antibodies, cells were washed and nonspecific antibody binding was blocked with anti-FcγR (2.4G2) antibodies. Surface staining antibodies included anti-CD3 allophycocyanin (APC) (clone 145-2c11; eBioscience, San Diego, CA) and anti-GR1 fluorescein isothiocyanate (clone 1A8; BD Biosciences Pharmingen, San Diego, CA). For intracellular staining, cells were first surface stained for 30 to 60 min and then fixed with 4% paraformaldehyde for 15 min and washed in permeabilization buffer (0.25% saponin in fluorescence-activated cell sorter buffer [0.2% bovine serum albumin and 0.012% sodium azide in PBS]), followed by intracellular staining for 60 min at 4°C. Intracellular antibodies were anti-IL-17A phycoerythrin (PE) antibody (clone eBio17B7) or isotype control antibody rat IgG2a PE (eBioscience, San Diego, CA). The samples were then washed and flow cytometric analysis was performed with an LSRII apparatus (BD Biosciences, Mountain View, CA). Data were analyzed with FlowJo software (Tree Star, Ashland, OR).
Data analysis and statistics.Data analysis and compilation were performed using Prism (version 5.0) software (GraphPad Software, San Diego, CA). Statistical analysis was performed using Student's t test, where a P value of <0.05 indicates a significant result.
Microarry data accession number.The microarray data obtained in this study have been deposited in the NCBI Gene Expression Omnibus (GEO) site (http://www.ncbi.nlm.nih.gov/geo/) under accession number GSE38053.
S. aureus Hla induces unique features of the host response to lung infection.To investigate the host response to Hla, we utilized an established mouse model of pneumonia in which 7-week-old C57BL/6J mice were infected intranasally with S. aureus Newman (9). In this model, lung injury is induced within the first 24 h postinfection, manifest as alveolar destruction, infiltration of large numbers of immune cells, especially neutrophils, and proliferation of S. aureus within the lung tissue. Mice infected with an Hla− variant of WT S. aureus demonstrate less severe lung inflammation, recovering from infection (9, 10). To first define the host transcriptional response to S. aureus pneumonia, we examined the gene expression profile in infected lung tissue using RNA prepared following infection with WT S. aureus and compared it to that in lung tissue following control treatment with PBS. Using the Affymetrix platform (Mouse Genome 430 [version 2.0] array) and a false discovery rate of <5% and requiring a minimum of a 2-fold change in gene expression, we identified 2,459 genes differentially expressed between WT-infected animals and the PBS controls (Table 1, top). A more pronounced effect was noted at the 24-h time point postinfection, wherein 7,306 genes were differentially expressed between WT-infected animals and control mice (Table 1, bottom). A total of 2,878 transcripts were upregulated, while 4,428 were downregulated at 24 h. Additional controls for these studies are shown in Table S1 in the supplemental material. Both WT S. aureus and the toxin-deficient strain induced a brisk host response to infection; at 4 h postinfection, the number of host genes with altered regulation was quantitatively similar (Table 1, top).
To understand the host cellular pathways impacted by S. aureus infection, gene ontology analysis was performed by comparison of the genes differentially expressed between WT- and Hla−-infected mice and PBS control-treated mice (FDR < 1% and fold change > 3). Prominent biological processes altered by infection with either strain included the immune response, defense response, inflammatory response, response to wounding, and chemotaxis (see Fig. S1 in the supplemental material), ontologies very consistent with those described in published studies of infectious lung damage in rodent models (42, 53, 58). Consistent with this finding, no specific host pathways were identified within 4 h of infection to be uniquely affected by the expression of Hla on the basis of gene ontogeny analysis (see Fig. S2 in the supplemental material).
Microarray analysis demonstrated 2,704 differentially regulated genes at 24 h postinfection by comparison of mice infected with the S. aureus Hla− strain and PBS control-treated mice (1,241 upregulated and 1,463 downregulated genes; Table 1, bottom), a number smaller than the 7,306 differentially regulated genes seen for WT. In contrast to the analysis at 4 h, a comparison of the host response to infection with WT S. aureus and the Hla− strain at 24 h revealed a large number of differentially regulated genes (Table 1, bottom), with the WT strain inducing upregulation of 540 genes and downregulation of 741 genes compared to the gene induction by the Hla− strain. Both quantitative and qualitative differences in gene regulation induced by these infecting strains are appreciated by heat map analysis (Fig. 1). Gene ontogeny analysis revealed three pathways that differ significantly between WT infection and Hla− infection at 24 h: dilated cardiomyopathy, ECM receptor interaction, and hypertrophic cardiomyopathy (Fig. 2). The ECM is made of macromolecules such as collagens and elastin, as well as proteoglycans such as hyaluronan, providing a scaffold that supports cells and tissue structure. The pathway is also very important for the response to injury, modulating activities such as cell proliferation, differentiation, migration, and adhesion (8, 33). As seen in Table S2 in the supplemental material, collagens, integrins, and syndecans are among the genes differentially regulated in the presence of the toxin.
A more detailed and comprehensive analysis of specific genes from many pathways, not only the three mentioned above, that exhibit differential regulation in the presence of Hla was performed, revealing genes that were upregulated (Table 2) or downregulated (Table 3) by greater than 6-fold in WT infection compared to Hla− infection. qRT-PCR analysis for a subset of genes was performed on lung RNA prepared from mice infected with either WT or Hla− S. aureus, validating the findings of the microarray (see Fig. S3 in the supplemental material).
Patterning of T cell response to S. aureus pneumonia by Hla.To appreciate the biological significance of microarray-based findings of differential host responses to Hla-expressing S. aureus, we chose to further examine the upregulated expression of IL-23 p19 observed in WT infection compared to Hla− infection (6.7-fold increase; Table 2). Production of IL-23 in the context of infection and autoimmunity has been linked to the differentiation of IL-17-producing CD4+ T helper cells, or a Th17 response (7). The secretion of IL-17 in the context of infection promotes the mobilization of neutrophils, augments cytokine production by epithelial cells, and maintains the integrity of the tight junction. Together, these responses enhance protective immunity to extracellular pathogens (16, 38, 51, 74). IL-17 is produced both by Th17 cells and by innate immune cells as part of the immediate host defense response to bacteria. These responses are of particular relevance at epithelial surfaces, key sites of human infection with S. aureus. Quantitative changes in the IL-23 p19 transcript were of considerable interest to us, given our prior studies of vaccine-mediated immunity to Hla and our ongoing efforts to define novel strategies by which to protect the host against toxin-mediated injury (11, 30). Th17 responses have been demonstrated to be important in the context of S. aureus skin infection (14, 55) and influenza virus coinfection (40). Th17-dominant responses have been suggested to play an important role in adaptive immunity to S. aureus (44) and have recently been highlighted to be a potential means by which to elicit vaccine-mediated immunity (68).
qRT-PCR for IL-23 p19 was performed on RNA harvested from lungs of mice infected with WT or Hla− S. aureus (or treated with PBS control) at four different time points. IL-23 p19 was upregulated more than 60-fold following infection with both WT and Hla− strains as early as 4 h after inoculation (Fig. 3). At 8, 12, and 24 h, however, WT infection was characterized by amplification and persistence of the IL-23 p19 transcriptional response greater than those obtained with Hla− infection (Fig. 3). Commensurate with these findings, the IL-17A transcriptional response was also greater in WT-infected mice than Hla−-infected mice at 24 h (see Fig. S4 in the supplemental material). These data indicate that the expression of IL-23 p19 is associated in part with the presence of Hla and suggest that the toxin may shape the nature of the host T cell response.
To examine the adaptive T cell immune response to S. aureus pneumonia, mice were infected with a sublethal dose of WT or Hla− S. aureus and allowed to recover. Eight days later, mice were reinfected with the same staphylococcal strain. The mice were then sacrificed at 24 h postinfection and lungs were harvested for cellular analysis. A fraction of the recovered cells was subjected to flow cytometric analysis of CD3 and GR1 expression to quantify T cell and neutrophil infiltration into the lung, respectively. Mice infected with WT S. aureus demonstrated an increased overall cell count in the lung compared to that for mice infected with the Hla− strain, consistent with our prior observations (Fig. 4A) (30). The absolute number of T cells and neutrophils was significantly higher in the WT infection than the Hla− infection (Fig. 4B and C). Given the initial finding that the IL-23 p19 transcript was markedly increased in mice infected with WT S. aureus compared to those infected with the Hla− strain, we examined the proportion of IL-17-positive (IL-17+) T cells as a subset of the CD3+ population. To facilitate these studies, harvested cells were plated overnight in the presence of IL-2, stimulated with PMA and ionomycin, and then analyzed for IL-17 expression. The absolute number of IL-17+ cells was higher in WT-infected mice (Fig. 5A to D), consistent with an overall increase in cell recovery. More importantly, the percentage of CD3+/IL-17+ cells was significantly higher in mice infected with WT S. aureus (Fig. 5E to H), suggesting that Hla expression in the context of staphylococcal pneumonia induces a qualitatively distinct T cell response, enhancing the generation of the Th17 population. Specificity of staining was confirmed by staining of lung cells from WT-infected mice with the isotype control antibodies (data not shown). Collectively, these data demonstrate that Hla is a strong inducer of Th17 cells during staphylococcal pneumonia.
We have used a whole-transcriptome approach as a tool to discern the impact of a single bacterial virulence factor on the host response to infection. S. aureus is unique among bacterial pathogens, given the multitude of organ systems and tissues that can be targeted during infection and the pleiotropic manifestations of disease apparent in different individuals. The wide array of virulence factors elaborated by S. aureus clearly patterns these diverse disease states. The pathological features of S. aureus pneumonia observed in animal model systems are intimately linked with the expression of Hla, providing a window of opportunity to dissect the host response to toxin exposure.
We observed that the general host response to both wild-type and toxin-deficient S. aureus is characterized by alterations in genes that regulate the biological processes of inflammation, defense, the immune response, wounding, and chemotaxis, extending earlier findings (2, 58). Specific alterations observed following expression with the Hla-expressing strain, however, serve to highlight the unique role of the toxin in host injury. Gene ontogeny analysis revealed that the extracellular matrix and cardiomyopathy pathways have significantly different regulation in the presence of Hla. These findings are consistent with several prior observations, namely, that staphylococcal isolates involved in necrotizing pneumonia display increased adhesion to extracellular matrix molecules (17) and that the Hla−–ADAM10 complex is associated with disruption of focal adhesions and intercellular adherens junction formation (30, 75). Future studies of the roles of differentially regulated genes in the ECM and cardiomyopathy pathways will likely lead to a more comprehensive understanding of the mechanisms of toxin-induced lung damage, perhaps also affording insight into the nascent mechanisms that underlie the host reparative response to injury.
The relevance of IL-17 to pulmonary infection has previously been established for Gram-negative bacteria (27, 28, 41, 77), and we have now examined IL-17 in the context of pneumonia due to a Gram-positive organism. Our focus on the Th17 response as a specific biological response pathway to intoxication was predicated on knowledge of the increased susceptibility of humans and mice lacking in this response to infection with S. aureus (48, 63), the association of Th17 cells with the host response to S. aureus (14, 23, 26, 31, 40), and the more recent findings from Niebuhr and colleagues that S. aureus Hla induced IL-17A in peripheral blood mononuclear cells and Th17 cells in the setting of atopic dermatitis (55).
Host recognition of staphylococcal cell wall components and bacterial lipopeptides leads to activation of Toll-like receptor (TLR) and Nod-like receptor (NLR) signaling on antigen-presenting cells such as monocytes and dendritic cells (12, 22, 23, 54, 72). These innate cellular responses pattern cytokine and chemokine production, immune cell recruitment, and the induction of the adaptive immune response. Collectively, these host responses clearly establish the balance between favorable immunologic clearance of the pathogen and deleterious immunopathology that contributes to host death in the setting of lung infection (2, 11, 15, 37, 50, 57, 72). Relevant to the current study, these early signaling events result in the production of IL-23, templating induction of the Th17 response (13, 20, 32, 51, 72).
The link between expression of Hla and the Th17 response observed in our studies may be accounted for by one of several molecular mechanisms. First, we have demonstrated previously that S. aureus recovery from the lungs of infected mice is reduced when the cellular action of Hla is antagonized during infection (11, 61, 62). In this context, the tissue bacterial load may emerge as a critical regulator of the host response. Infection with an Hla− S. aureus strain would be predicted to provide a lesser degree of innate immune stimulation by peptidoglycan and lipopeptides, dampening the magnitude or duration of the IL-23/IL-17 response. Indeed, we observed that the induction of IL-23 by WT and Hla− S. aureus was indiscernible at 4 h postinfection and then rapidly waned in response to the Hla− strain. Interestingly, a considerable number of staphylococci (≥5 × 106/lung) are still recovered at 24 h postinfection in the setting of Hla antagonism (11, 61, 62), suggesting that the nature of the host response may be determined within a relatively narrow window predicated on both the absolute burden of S. aureus in the tissue and the length of time over which the host is exposed.
As a second plausible mechanism, the direct actions of Hla on antigen-presenting cells may shape the host adaptive response. This may be accomplished by (i) stimulation of the NLRP3 inflammasome by the toxin (15, 37), (ii) enhanced inflammatory cytokine and/or chemokine production in response to lung epithelial injury caused by Hla (2, 11), or (iii) toxin-mediated cytolytic injury to innate antigen-presenting cells (4, 56). Deciphering between these possibilities will likely shed additional light on both the nature of the antistaphylococcal response and the role of Hla in patterning this response.
We have now extended previous studies by connecting the presence of a secreted cytotoxin to the pulmonary Th17 response in staphylococcal pneumonia. This emphasizes the importance of Hla in disease pathogenesis, most specifically, in contemplating the nature of the host immunologic response. Through these studies, we have demonstrated microarray technology and gene ontogeny analysis to be a powerful tool in the selective identification of toxin-responsive pathways, highlighting a number of toxin-induced cellular signatures for ongoing study. As Hla has emerged as a strategic target for vaccine and passive immunotherapy approaches to S. aureus disease, understanding how this toxin primes the host immune system is anticipated to inform the rational design of strategies capable of specifically enhancing the generation of adaptive immunity.
This work was supported by the Departments of Pathology, Pediatrics, and Microbiology at the University of Chicago and a grant from the National Institute of Allergy and Infectious Diseases to J.B.W. (grant AI097434). J.B.W. also acknowledges membership in and support from the Region V Great Lakes RCE (NIH award 2-U54-AI-057153).
We thank Jesse Williams and Anne Sperling for providing protocols and advice for flow cytometry experiments, Ting Wang for advice on qRT-PCR studies, Ryan Duggan and David Leclerc for flow cytometry expertise, and Georgia Sampedro for assistance with the preparation of figures.
- Received 14 April 2012.
- Returned for modification 10 May 2012.
- Accepted 14 June 2012.
- Accepted manuscript posted online 25 June 2012.
Supplemental material for this article may be found at http://dx.doi.org/10.1128/IAI.00191-12.
- Copyright © 2012, American Society for Microbiology. All Rights Reserved.


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Faculty Advisor
Deskins, N Aaron
The purpose of this paper is to investigate the decomposition of several aromatic, tar compounds over a Pt (111) surface. Density functional theory is used for the modeling. Atomic adsorption energies are found and used to find reaction energies in agreement with other works. A favorable reaction pathway for the dehydrogenation reaction of benzene to dehydrobenzyne is calculated, as well as the dehydrogenation reaction pathway for naphthalene.
Worcester Polytechnic Institute
Date Accepted
April 2011
Chemical Engineering
Project Type
Major Qualifying Project
Copyright Statement
All authors have granted to WPI a nonexclusive royalty-free license to distribute copies of the work, subject to other agreements. Copyright is held by the author or authors, with all rights reserved, unless otherwise noted.
Advisor Department
Chemical Engineering

subset: commoncrawl


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Large Proton-Affinity Enhancements Triggered by Noncovalent Interactions
The proton affinity (PA) of the hydroxyl group of a series of compounds YHxOH (x=0–3; Y=Li, Na, Be, Mg, B, Al, Si, P, S, Cl, H) always increases on interaction with Lewis bases (LB=NH3, H2CNH, HCN) according to electronic structure calculations at the G4 level of theory. The LB:YHxOH complexes experience enhancements of PA from 24.8 to 304.8 kJ mol−1 for the OH group with respect to the free compounds. This enhancement is related to the ability of these YHxOH compounds, acting as Lewis acids, to form noncovalent interactions of different kinds. Interestingly, weakly interacting systems can give rise to PA enhancements equal to or even larger than those of strongly interacting systems, as observed in the halogen-bonded complex H2CNH⋅⋅⋅ClOH, whereby the free compound (PA=642.4 kJ mol−1) is transformed into a base (PA=947.2 kJ mol−1) that is stronger than pyridine.


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This week HigherEdMe is 2 years-old. We feel that our core matchmaking platform service has just been released. But it's already been 730 days!
Let's compare what the team has achieved since our first anniversary.
Thanks for many posts and advertising on social networks, we convinced more students to join our platform so they can receive study abroad opportunities from recruiters. We have now students from 174 countries. 30% are from Asia, 30% from Africa, 30% from Americas, 10% from Europe.
International Student Recruiters
Thanks to a specific exportation grant from Région Bourgogne Franche-Comté, HigherEdMe could participate and present its platform to many international recruiters and officers during EAIE in Liverpool and Seville, NAFSA in Los Angeles and APAIE in Kaohsiung. With our sales team, we grew our contacts from 1.000 to more than 3.000 international education professionals. Now the platform counts more than 250 users instead of 120.
Above : map of HEI users oct 2016
Above : map of HEI users oct 2017
Recruiters are now covering many regions of the globe.
Now it's matching
Having more student wishes and more recruiters and adding alerts and auto-replies, the platform started to do what it was built for: connecting recruiters with prospective students. We went from 450 connection requests to more than 6.500. Finally, we just have reached 1.000 accepted contacts. It means than more than one thousand students gave their mobile phone and email to the recruiters. First feedback from our best users show enrollments, which is the ultimate goal of the platform.
Are we still a startup?
Our turnover is the one of a young startup, we reinvest every penny in technology, just like the last motivation analysis algorithm we have developed. We still need to grow our reputation to collect more students and universities to make more matching and give a better UX.
Serving our customers to become profitable is our objective, keeping our values is our priority.
So the answer is yes. We are still a startup, needing every possible support !


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Fair Park 80th Anniversary Celebration
Fair Park will celebrate the 80th anniversary of the Centennial Exposition this summer with a four-day festival filled with fun and engaging activities for the entire family to commemorate one of the city's greatest treasures and historic landmarks.
The event will include a concert performance from the Dallas Symphony Orchestra; jazz from local musicians; featured performances from Brave Combo, the Quebe Sisters and The Mavericks; games on the Midway; free Ferris Wheel and Tower rides; kids activities; fireworks; a memorable exhibit highlighting the park's history; a wine stroll throughout the park; a Speakeasy party, and more.
In conjunction with the celebration, Fair Park will open a new children's play area featuring a carousel, playground equipment and community visioning area, inspiring everyone to look ahead at the future of the park.


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Friday, September 5, 2014
Film Review: The Identical
It's satisfying family entertainment, similar to most made-for-TV Hallmark-type films. Not boring, but a bit slow, finding its worth in its heart. Fans of "When the Game Stands Stall," "Amazing Grace" and other faith-inspired films will thoroughly enjoy.
The story follows twin brothers separated at birth, one set apart for God and the other destined to follow the path of the troubled celebrity. Neither knows the other exists, but when their musical talents cross paths in unexpected ways, it sets one brother on an inspiring and hopeful path.
The Identical is now playing in theatres.
Posted by Wheeler Reviews at 7:21 AM
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Pexels - CC0 License As a parent, you want your child's birthday to be memorable. However, that doesn't mean you can always afford to spend thousands on a lavish party. Thankfully, you don't have to. While it might require extra work, it is possible to stick to a budget without putting a limit on your little one's fun. You may even be able to create an event better than the … [Read more...]
Reasons You May Be Having a Hard Time Getting the Kids to Sleep
Try as you may, you can't seem to get your kids to calm down and get to bed. They seem to have a never-ending supply of energy that keeps them going for hours after you've tucked them in. Before you can have a moment to yourself they're barging in the room asking for one thing or another, or screaming at the top of their lungs from their bedroom down the hall. You're at the … [Read more...]


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Free shipping on orders over $40
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Gray Malin is an internationally renowned fine art photographer and New York Times best-selling author whose work combines the spirit of travel, adventure, luxury, and artistry.
Featuring Gray's best-selling fine art photography, this porcelain catch-all tray is both the perfect decorative object for your home and the perfect host or hostess gift. Made of porcelain with gold edges, each catch-all tray comes in signature Gray Malin packaging.
- 2 Piece Gift Box with Window
- Gilded Tray Edges
- 7.25 x 4.75", 184 x 121 mm
Explore more from the Gray Malin Collection
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Pretty tray; however, it is tiny.
Pretty tray; however, it is tiny.


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Cattle feeding and packer profit margins both declined last week as cash cattle prices were modestly lower. Cattle feeders eared $31 per head, $68 less than the previous week, while packer margins dipped $8 per head to $137, according to the Sterling Beef Profit Tracker. Cash cattle prices were $118.30, about 60 cents per cwt. lower.
The beef cutout was nearly steady at $211.38. The cost of finishing a steer last week was calculated at $1,590, which is $59 higher than the previous week and $8 higher than the same week a year ago. The Beef and Pork Profit Trackers are calculated by Sterling Marketing Inc., Vale, Ore.
A year ago cattle feeders were earning an average of $60 per head. Feeder cattle represent 71% of the cost of finishing a steer compared with 73% a year ago.
Farrow-to-finish pork producers saw their margins slip $6 to average losses of $26 per head. Lean carcass prices traded at $48.24 per cwt., $2.9 per cwt. lower than the previous week, and $4.69 lower than a month ago. A year ago pork producer margins were at breakeven. Pork packer margins averaged a profit of $43 per head last week.
Sterling Marketing president John Nalivka projects cash profit margins for cow-calf producers in 2018 will average $162 per cow. That would be steady compared to the $164 estimated average profit for 2017. Estimated average cow-calf margins were $176 in 2016, and $438 per cow in 2015.
For feedyards, Nalivka projects an average profit of $21 per head in 2018, which would be $160 less than the average of $181 per head in 2017. Nalivka expects packer margins to average about $168 per head in 2018, up from $120 in 2017.
For farrow-to-finish pork producers, Nalivka projects 2018 profit margins will average a profit of $2.50 per head in 2018, compared to profits of $21 in 2017. Pork packers are projected to earn $19 per head in 2018, down from $25 profit per head in 2017.


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Little Bear Height Chart
This is a cute height chart showing a little teddy bear interacting in different activities.
With a large yellow sun at the top, this is a sweet accessory to chart your child's growth.
Made of wood. It has a keyhole fixing on the back of the chart
Size: 9.5 cm x 99.5 cm


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You can pay online with a credit card securely via PayPal or for large orders a bank wire can be made and this information will be included in our reply if you send an email. Items are in stock and will usually ship-out in 1 – 3 working days from payment receipt.
Choose from three different test kit options below
Part # FT-1 Premium test kits are priced @ USD 5.95 per unit – sold in lots of 5 units
1 x premium packaged kit = 1 x 120 ml / 4 oz test bottle
– 1 x pair nitrile gloves– 1 x water detection agent – 1 x A4 instructions.
This kit has point of sale style clear PVC display box with hang tab.
Part FT-Premium test kits @ $5.95 per kit x 5 units = Total Price $29.75
Part # FT-Combo = FT-1 + FT-BUG @ USD 17.95 per unit
1 x 120 ml / 4 oz test bottle – 1 x water detection agent – 1 x dip-slide bug kit (with red spot technology)
– 1 x pair nitrile gloves – 1 x specimen label – 1 x A4 instructions in clear PVC box with hang tab.
This kit has point of sale style clear PVC display box with hang tab.
Part # FT-Water
1 x test kit = 1 capsule of water detection agent in vial. Kits packaged in plastic storage box. You can order minimum of 20 test units.
Part FT-Water 20 = 30 test kits @ $3.15 per kit = Total Price $63.00
Part FT-Water 30 = 30 test kits @ $2.75 per kit = Total Price $82.50
Part FT-Water 50 = 50 test kits @ $2.50 per kit = Total Price $125.00
Part FT-Water 75 = 75 test kits @ $2.25 per kit = Total Price $168.75
Part FT-Water 100 = 100 test kits @ $1.95 per kit = Total Price $195.00
NB – The key integral water and bacterial detection components contained in these test kits are made in the USA, Germany and /or the UK.
Other non-key parts of the kits like gloves, bottles, decals and packaging are sourced from Asia. This ensures high quality components and the best overall price for the kits.
For a written quote we need the following details in the email.
→ items required including part numbers
→ quantities amount – NB due to very low profit per unit on part # FT-1 Premium our minimum quantity order is 5 units for these kits
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Above not including post by standard or express postage or we can ship on your FEDEX, DHL or TNT account if you provide the details. Some orders may qualify for free shipping. You can email us for a quote if your order is large and we will provide our best price on the day.
Send us an email from the form below & we will email you a quote or answer your questions.


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- Home/
- Car Rental France/
- Car Rental Chambery Aix - Airport
Car Hire in 3 Easy Steps
Compare cheap car rental Chambery Aix - Airport, (CMF), France (FR)
Feel the freedom of movement on a trip by car in France - car rental Voglans, FR provides the best support using the cheapest prices. In case you prefer road trips on and on anywhere you want, then cheap Voglans car rentals gives you a marvelous chance to get places in France which will astonish anyone with their loveliness and also welcoming warmness. Our services compare cheapest car rental prices in Voglans, FR and get the cheapest costs for you personally. The best with the cheapest prices!
Car rental Voglans Reservation
To be able to have a successful reserving of chosen car, you must be twenty one and have a legitimate driver license as well as main plastic card. While traveling you're also required to carry the passport (or even nationwide Identification card for European Union individuals). Car Rental 24H FR, Voglans will provide you with fast along with convenient support - book your automobile from any part of the world. To get a successful reservation ensure that you carry the next documentation to the front desk of Car Rental 24H Chambery Aix - Airport, (CMF), France (FR):
- The confirmation voucher.
- Your current driver license.
- A current credit card in the person's name, with adequate provisions to your deposit.
- If you need to add additional drivers to the agreement, all drivers must be present at the counter and provide his or her driver license.
- Sometimes you may be also asked for additional identification papers such as a latest electricity bill or another form of invoice to confirm a current address.
Benefits of Auto Assortment
For individuals who like touring around rural villages with genuine province houses and also relaxing movement of lifestyle, and anyone who has conferences in fantastic towns, Car Rental 24H FR, Voglans provides most affordable prices with the best money saving deals. French railways have been in a fantastic condition; however, you can't get pleasure from true independence of movement using them. Car rental Voglans features a great selection of cars that you can select from. In choosing a car, think about your own personal likes along with the number of individuals traveling. We've got autos from mini to SUV or perhaps vans of different class to satisfy each demand of the clients. Choose the best option together with great quality as well as lowest prices.
Insurance Kinds
In order to care for possible incidents that could happen to our customers throughout car rental use, car rental Voglans provides following kinds of insurance:
- Loss Damage Waiver (LDW) - limits your current liability for the excessive amount in case there is injury.
- Personal Accident Insurance - handles health care costs in case there is injuries.
- Personal Effects Coverage - covers expenditures of theft as well as loss in car rental items.
- Vehicle Theft Waiver - limits your current liability on the excessive amount in the case of thievery of the vehicle.
In the event of accidents on the road, most of each of our costs include Break down assistance that will take care of the clientele at any time and anywhere.
Genuine Taste of France
Driving throughout France may bring anyone remarkable memories and also amazing impressions that can fill every heart with the finest feelings you've had. It really is difficult not to love France you'll also find a chance to encounter that kind of affection simply by driving with car rental Voglans, FR.
There are several paths that you can use on your trip through the most well-known points of interest of France. You are able to tour throughout the coast of Southern France: enjoy lunch time at the village of Aigues-Mortes, drive from Montpellier to Arles, which runs over the Camargues with well-known wild white horses from the Camargues. Wonderful Arles and Marseille can wow anyone with excellent shorelines and delightful structures, throughout Nice, St. Tropez along with Cannes you may get good portion of sophistication and elegance. Don't forget to go to wonderful casinos of Monte Carlo as well|.
It's also possible to travel through Provence together with Arles, Avignon and Salon-de-Provence that are rich in vineyards. Decide on any one of them and proceed with your journey in the Pont du Gard, which is an excellent location for an open-air picnic. Hitting the major areas, go Montpellier-Avignon-Marseille-Arles-Montpellier and have a car trip of your life.
From Bordeaux to Biarritz you have couple of paths with outdoor camping sights, best seaside down the Atlantic ocean, world-famous Lourdes and much more. As well as you've got to experience the path Paris-Chartres-Le Mans-Rennes-Caen-Rouen-Paris. You can enjoy all of these routes, or you are interested in only one city, whatever the case is Car Rental 24H Chambery Aix - Airport, (CMF), France (FR) will give you a safe visit even for the most discerning customers.


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Celkon Mobile Service Center in Ghazipur
Celkon Mobile Service Center in Ghazipur, Uttar Pradesh – Address, Contact Number are listed below. If you have any problem with your Celkon mobile, kindly contact the service center officials. There is 1 Celkon authorized mobile service center in Ghazipur
List of Celkon Authorized Mobile Service Centers in Ghazipur:
Celkon mobile service center in Kachtari Road, Ghazipur
Name: ASHUTOSH COMMUNICATION
Address: Kachtari Road, Near Head Post Office, Ghazipur
City: Ghazipur
State: Uttar Pradesh
Pincode: 233001
Contact Person: Mr. Ashutosh Singh
Contact Number 1: 9415261224
Contact Number 2: 5482220873
Email: firstname.lastname@example.com
Working Hours: 10:00 AM to 6:00 PM
Working Days: Monday to Saturday [Sunday Holiday]
* Call the Celkon Service Center before planning your visit, to ensure that the service center address is correct and is open for service.
** Please comment below if you find any of the above information incorrect, we will fix it immediately. Thanks in advance


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Toronto-based marblemedia, Aboriginal programming producer Big Soul Productions and Canada's Aboriginal Peoples Television Network (APTN) are collaborating with Mike the Knight creator Alexander Bar to develop the new animated preschool series Snow Joe.
Snow Joe, set in Snowflake Peak in the Mackenzie Mountains, follows a young Aboriginal boy who dreams of becoming a hero like the ones he hears about in his grandfather's stories. Along with his pals, Buddy and Nina, he embarks on adventures with the help of "hero gear," which is essentially a costume that helps each character embody the qualities of their spirit animal. Joe, for instance, dons a wolf-like hoodie that makes him feel more brave.
marblemedia's interactive division will develop online and mobile elements to extend the brand online. Its partner company Distribution360 is handling international TV, interactive and format sales for the series.
marblemedia first began looking for potential Snow Joe partners when it shopped the series at MIPCOM in 2011.
From Playback Online with files from Lana Castleman


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228 Vote
In the mirror of others (part 2)
From a perspective of ethical perfection, to see ourselves in the mirrors of others is to take everything that emanates from them (actions, words, behaviour, etc.) as means to better know ourselves. Such was the general conclusion reached by Sandrine Duplessis in the first part of her inquiry. In this second part, the author gives us a few pointers as to how to concretely put this into practice.Read more


text: SAVING VINYL CITYwith BOILING POINT, ROB MAHLUM, and THE NAYMES Thursday, August 28, 2014 at 7:00pm$8.00 advance$10.00door18+Venue: First Avenue7th St Entry Info TabsPerformersPerformer: SAVING VINYL CITY FACEBOOKTWITTERSOUNDCLOUDREVERBNATIONSaving Vinyl City is a five piece, all good looking, band featuring instruments that range from strings all the way to brass. Every show is wild, fun, and energetic with heavy amounts of crowd participation. SVC plays original music but also likes to put their own spin on the songs they cover making every song and show they perform very unique. Read more about SAVING VINYL CITY Special GuestsSpecial Guests: BOILING POINT FACEBOOKTWITTERWEBSITEMYSPACEPassionate vocals and memorable guitar hooks set Boiling Point apart from the status quo. More importantly, what keeps people coming back is the band's emotional depth and willingness to be real with their fans through their songs, their live performances and their life's example. Boiling Point's music harnesses the fun, exciting parts of life, but isnot afraid to explore the deeply challenging parts. Energetic songs like "Miss Everything Zen" and "Try" mix with emotionally raw and haunting songs like "Symphony of It All" and "Rules of the Broken." Read more about BOILING POINT ROB MAHLUM FACEBOOKTWITTERSOUNDCLOUDYOUTUBESinger/Songwriter based out of Minneapolis, Minnesota. Read more about ROB MAHLUM THE NAYMES FACEBOOKTWITTERREVERBNATIONThe Naymes are that fresh sounding Rock N' Roll group, who's paving the way to that radiating 'Rick n' Rack' sound. Read more about THE NAYMES


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Eva Bouwman-van Gelder
E-mail: email@example.com
Since 2010 I also work for the educational institute Stivako as manager of education, where I am involved with adapting existing learning material to the changing needs in the market and the development of new learning materials as a result of new developments in the market. I am also a point of contact for companies looking for in-company training opportunities and I make sure that the required course material is developed and tailored for this purpose.
I am certified to use the Personal Profile Analysis (PPA) by Thomas International. This tool is used within Stivako as a very practical tool for coaching managers and employees in companies, or in the recruitment and selection of (own) staff. Furthermore, we use this tool in the training activities within Stivako, for the students in the various courses and training as part of their personal development and sustainable employability.
The PPA tool is a practical tool to use to give advice on career and guidance and in the context of sustainable employability of people in companies. I also give presentations on these subjects; sustainable employability and the use of the PPA tool.
At the Hotel School The Hague, Hospitality Business School, I completed my education with a Bachelor's degree in Business Administration in 1990. In this management training, I studied the various aspects of business such as marketing, organization of production, HR and other entrepreneurial subjects. After 15 years gaining experience within the hospitality sector, including the conference and event industry, I ended up in the printmedia industry.


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Multi-Omics Hub Updates: December 2017
Multi-Omics Hub The Multi-omics hub currently features the epigenetics group and the microbiome portal. The 2017 UW Epigenetics Symposium held Oct 5 at the Waisman Center was organized by the WID Epigenetics faculty Denu, Lewis, Sridharan and Zhong. The morning session featured talks on neuro-epigenetics, and the afternoon showcased short talks focused on latest methods, an open discussion of future efforts, and poster presentations from trainees. The major topics of discussion …
The Microbiome Hub: Enabling a Biological Revolution at UW–Madison
The Microbiome Hub will provide the means for researchers in diverse fields at UW-Madison, who have no training in microbiology or bioinformatics, to routinely examine the microbiome in their studies.


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Wednesday, January 26, the Council of Bishops of the AME Church has assigned the Right Reverend Frank Madison Reid III as the Presiding Prelate of the Third Episcopal District effective immediately under the provisions of the Discipline governing Episcopal Vacancies (page 171).
Bishop Reid succeeds Senior Bishop McKinley Young who died on Wednesday, January 16.
The Third District encompasses the states of Ohio, West Virginia and the Western part of Pennsylvania. Bishop Reid is married to Episcopal Supervisor Marlaa Reid and currently serves as the Ecumenical Officer. He will maintain both assignments until the 2020 General Conference.
Please continue to pray for the Young family, the Reid family and the Third Episcopal District during this season of transition.
Photo credit: Derek Anderson
Source: thechristianrecorder.com


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Essential oils have become one of the most popular natural remedies to help with sleep and relaxation. With BedJet's aromatherapy diffuser kit, you can enjoy your favorite essential oils for sleep and relaxation and freshen your sheets at the same time.
What Are Essential Oils?
If you're brand new to essential oils, here's some helpful info. Essential Oils are naturally extracted oils from plants — typically from the plant's roots, stems, leaves, flowers, or fruits. They retain the natural smell, or "essence," of the plant they are extracted from. Many people purchase and use essential oils for aromatherapy.
BedJet and Essential Oils for Sleep
To accommodate the growing number of essential oil enthusiasts, we've included an Aromatherapy Kit with every BedJet unit. It's super simple to use! Just add your favorite essential oil scents to the Aromatherapy Kit's foam strips and use the clip to attach it to the BedJet air nozzle. Turn the BedJet on and get instantly refreshed and wonderful smelling sheets.
In case you're new to essential oils and need some suggestions to try with your BedJet, here's a list of essential oil scents commonly associated with relaxation, calmness, and stress relief. They're some of our BedJet owners' favorite choices for relaxation at bedtime.
The Best Essential Oils for Sleep
People who enjoy aromatherapy before bed most frequently choose essential oils with these scents:
- Lavender — Lavender is the most widely used essential oil for sleep. Lavender may help treat mild versions of insomnia and many people who use it have mentioned it helps with anxiety. This scent has been known to lower blood pressure, heart rate, and skin temperature - all of which will aid in better sleep.
- Valerian — Typically taken as a sleep supplement or found in herbal teas, this essential oil has been proven to help relieve symptoms of both insomnia and menopause. The scent is calming and has been linked to improving overall sleep quality.
- Vanilla — Although on the sweeter side, this scent has proven to be a source of relaxation and stress relief for many people. Vanilla essential oils typically reduce hyperactivity, relax the nervous system, and lower blood pressure. It can also help relieve anxiety and depression while relaxing you at the same time.
- Jasmine — With a sweet floral scent, jasmine improves sleep quality and reduces restlessness. By reducing your need to toss and turn throughout the night, use of a jasmine essential oil will help increase your daytime alertness.
- Sandalwood — With a rich, earthy scent, sandalwood has been directly linked to feelings of relaxation and anxiety relief. Research has shown this scent to be effective in easing symptoms of anxiety. It has also been shown to reduce wakefulness throughout the night.
Other Ways to Use Essential Oils for Sleep
In addition to using the BedJet Aromatherapy Kit, here are some of the most common:
- Apply oil directly on your body (typically on pressure points, like your wrists or behind your ears)
- Spray oil on your pillow from spray bottle
- Mix oil with baking soda or Epsom salt and add to a hot bath before bedtime
- Use an essential oil fin your bedroom
Got questions about BedJet? We're happy to help. Call us at (401) 404–5250 to speak to a real human being or email us at firstname.lastname@example.com. Sign up for our VIP list and follow us elsewhere on the web to get the latest BedJet deals, promos and news!


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Bolid 1.0 Responsive News Magazine and Blog Theme
Sale Page: http://themeforest.net/item/bolid-responsive-news-magazine-and-blog-theme/4361177
Product Price: $45
You must be an active subscriber to download this file. Please Subscribe or Login.
Bolid is new responsive theme for magzines with modular and flexible homepage. Bolid is built for heavy-content websites, but it is suitable for all bloggers!
This theme comes with many cool features as sliders and carousels widgets, modular featured sections and flexible layout and possibility to manage color schemes, responsivity settings.
There are also 50+ advanced shortcodes with Shortcode Generator support, support for post formats and much more!
Main theme features:
- Advanced theme admin panel,
- Unlimited color schemes,
- Modular Homepage (using Homepage widgets),
- News Ticker,
- Single posts jQuery sliders,
- Blog template,
- Posts formats: Standard, Audio, Video, Gallery, Quote, Link, Image,
- Font selector/custom typography – 53 fonts available (hand-picked web-safe fonts and Google webfonts),
- Font Awesome integration,
- WP-PostRating integration,
- Video Thumbnails integration,
- Jetpack support (Social Comments, Email Subscription, Share buttons)
- 2 Custom Menus – with icons,
- jQuery sliders – Galleries,
- Shortcode generator (including layout shortcodes),
- Unlimited dynamic featured sections in Sidebars and Footer,
- Logo and favicon upload,
- Google Analytics Input,
- Custom Footer,
- Sidebar tabs (latest, popular, random posts + list of tags),
- Translation ready,
- WordPress 3.5 + ready,
- Smooth tabless design.


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Death Race (Video 2022) Action-Thriller rated r film.
- Oliver Swaby as Ken Simmons/Frankenstein, former thief now he's lead role from John Gibson.
- Josue Sanchez Ebanks as Jensen Ames (uncredited; voice calls)
- Jason Hydes as Brett \ Frankenstein (opening scene)
- Miguel Amador as 14k, former serial killer and joins death race.
- Harvey Swaby as Mikey; Ken's deceased brother he died from bank with gun shot.
- Luis Amador as 14k's brother (uncredited) he was deceased also.


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- Username
Thor Odinson
- ...
Thor was once a reckless boy, knowing nothing of the error of his ways, only headstrong with a vision of being the future king. He became a great warrior for Asgard as he aged, fighting many glorious battles, and defeating many ancient foes. A true son of Odin, favored by many. However, those glories would come to an end. After endangering the very lives of his own friends, the all-father, as punishment for committing such a reckless deed, a near crime, banished him to Midgard, relieving him of his title and all his powers—
—leaving him a broken man.
A kindly group of humans, though after incapacitating him, gave him a place to stay for the period of time he would spend there. Word reached his ears of something that he presumed to be Mjolnir, his hammer that followed him through the Bifrost. Determined to retrieve it, he enlisted the help of the human Jane to give him transport to the crash site. He launched an assault on the facility that had surrounded his hammer in a valiant effort to reclaim what was his, but once reaching it, he was greeted with a sad truth. After years of using the weapon as his own…
He would no longer be able to lift it.
Without it or his powers, he was mortal.
In custody, his brother Loki gave him the news of their father's timely passing, Thor's spirits were broken even further when he was told that he could never return to Asgard; to his friends, his family, his home.
Now accepting the state of being stripped of his godly powers and relations, Thor resigned himself to live a normal life on Midgard, where he would correct himself of the mistakes he had made before.
But still, danger sought him out, The Destroyer arriving from Asgard in search of one thing: To end Thor's life.
But in death, there is also hope.
"Whoever holds this hammer, if he be worthy,
shall possess the power of Thor."
The selfless act of allowing the giant to slay him had restored him to life, and bestowed upon him again, his right as The God of Thunder.
Once the destroyer was defeated, he, Lady Sif, and the Warriors Three traveled back to Asgard where he defeated Loki, at two costs; returning to Midgard, and what he believed to be his brother's life. But to spite all of that, he was a changed man, and now allied with The Avengers, he seeks to change to universe for the better.


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Commitment To Waste
Committed To Reducing Waste
LAND Leather is strongly committed to responsibly managing it's footprint on the world.The raw hides used by our tanneries and for our leather goods are the by-products that have been discarded from the food industry in production of meat for human consumption. Our hides are all individually inspected prior to cutting and we have committed ourselves to keeping a watchful eye on the excess waste of each hide. We get the most out of each hide by using scrap leather pieces to make smaller leather goods. This aides us in our commitment of reducing waste on every level.
Our Tanning Methods
We have also recently committed ourselves to changing the methods in which our hides are tanned. Previously, 80% of our hides were tanned in the chrome method, meaning heavy and harsh chemicals were used when producing these hides. As of 2017 we have begun to convert the tanning method of our hides to the more eco-friendly and bio-degradable vegetable tanning method which uses natural vegetable tannins and various tree bark types to give a leather hide it's wonderful finish.
We continue to make daily strides in the impact we have on the environment.


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Since you are reading this, it means you are familiar with weighted blankets. However, you don't feel like you know enough, which is why you want to know more about them. For starters, weighted blanket benefits both kids and adults. Perhaps you've heard how young ones with symptoms of autism spectrum can take advantage of the blanket to relax, while people who have insomnia are most likely going to sleep better with it. But the one reality you should know is that there are many other benefits weighted blankets have for adults like you, and this is what we're going to talk about in this post.
1 – Weighted blankets for grown-ups help those with sensory processing disorder.
Experts describe a sensory processing disorder as a traffic jam on your brain. It means that when information gets in, it feels like your brain suddenly clogs with lots of data inside. As a result, you may likely suffer from a meltdown or anxiety. Both kids and adults may suffer from it. There is proof that with a weighted blanket, the brain benefits from a calming effect, thereby averting the possibility of a sensory processing disorder.
2 – Weighted blankets contribute to the reduction or even the elimination of anxiety.
Another proof of the effectiveness of a weighted blanket is its ability to help people who suffer from anxiety eliminate the condition or at least minimise its effects. The reason why it is possible is that using a weighted blanket emulates that of getting a firm yet gentle hug from another person. We all know what a hug gives us. Most people will feel better and calm when someone hugs them tight.
3 – A weighted blanket combats the effects of stress.
It is no secret that many people including you, experience stress occasionally. There are moments when the stress level goes up so high that some people get consumed by it. The truth is you can get rid of it by having a good night sleep. With the help of weighted blankets for grown-ups, you achieve maximum relaxation while you sleep, thereby allowing your mind to calm itself down and eliminate the stress.
4 – A weighted blanket reduces or gets rid of the early symptoms of restless leg syndrome.
You probably haven't heard of it, but many people suffer from a weird condition called the restless leg syndrome. You have it when you feel a tingling or creepy sensation on your legs. Since the condition usually manifests at night, it often results to restlessness and insomnia. The feeling of having to move your legs constantly is something you can eliminate if you start using weighted blankets when you sleep at night.
Generally, since weighted blankets are primarily used in bedtime, you will benefit from them if you are someone who has trouble sleeping for whatever reason.


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The 2018 Australian Grand Prix. How to be a winner?Mar 25, 2018 Sebastian Vettel Taisiya Lavi
|How to be a winner?
How important is a win for the F1 driver?
What is the secret of Sebastian Vettel's success?
Why Vettel won Australian GP? Formula 1 driver Sebastian Vettel's way of a win.
The day before, there was difficult to believe that Sebastian Vettel will perform above the 2nd place. The confidence strong and bold Lewis Hamilton was stunning. Look at how confident he was smiling. All were convinced to prove who is who in this year in 1st. GP will be a miracle. What is this miracle? What helps man to succeed in spite of prying eyes?
1. He thought about himself.
Despite journalist's and fans' pressure, Scuderia Ferrari F1 teams' driver was so focused, that barely flashed a smile at the press conference. It became clear that he was thinking about 1st. place since 1st. interview.
Only winning was in Sebastian Vettel's mind.
Journalist: "can you and Ferrari find the speed to beat this guy over a whole season this year?" Sebastian Vettel: "We don't have the answer now. We try. ... I don't think it's the plan but I'm very confident that we're not using four engines this weekend, so we don't need to worry now". (Formula1.com)
And then Rolex Australian Grand Prix results in qualification.
1. Lewis Hamilton (Mercedes)
2. Kimi Raikkonen (Ferrari)
3. Sebastian Vettel (Ferrari)
All complete information and full version Australian F1 Grand Prix events, see on www.imf1fan.com
All complete information and full version Australian F1 Grand Prix events, see on www.imf1fan.com
Therefore, never pay attention to your competitors, think about yourself, about what is important to you. So, doing it also, as Sebastian Vettel did on GP
2. He was left alone and he did what he had to do.
Throughout the weekend, S. Vettel exactly knew what he had to do. Even he didn't say it out loud, great F1 driver just knew. It is not important, he isn't the first in qualifications, as isn't important he didn't take the first position on first turn corner of Australian autodrome. The Formula 1 driver just knew that is necessary for him. look at his interview after the race.
Only 'wipe the smile off his (L. Hamilton) face'. And he did that, So, always do listening to yourself inner voice. He will tell you how to succeed and come to victory under the first number
3. Who cares what anyone else says!
Now there are many rumors about the Haas F1 Team and that sabotage. First of all. It didn't make any sense. Secondly. Haas F1's team was very fast, that's true. There is more truth in Haas F1'team force than in all rumors.It will not matter what anybody says. Don't pay attention to other people's speculation and rumors, and Lady luck will hear you and all your hard work.
|The 2018 Australian Grand Prix
The safety car had become the point in Australian Grand Prix, it was a miracle for Sebastian Vettel. However, I agree that all of these wouldn't have happened if Vettel didn't t follow his strong win way. Now, tell me, how important is winning?
Did someone ever tell you that one moment can change the lives of other people? Do you remember Sergio Marchionne words and senses before Formula 1 racing starts? Look it for now.
"There could have been no better starting for Ferrari in this Championship,...." - Sergio Marchionne
"There could have been no better starting for Ferrari in this Championship,...." - Sergio Marchionne
|The 2018 Australian Grand Prix
Victory is important for every driver, for every man, every human. Small or big, it doesn't matter. Achievement leads to others! However, you need to work on yourself to win. I heartily congratulate Sebastian Vettel. He deserves this ovation.


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HCS Convergence Agreement
Following a year of intensive work, the HCS Convergence Working Group announced in Bangkok that they have reached agreement on convergence between the HCSA and HCS+ approaches. The Group has agreed on a single, coherent set of principles for implementation of companies' commitments to "no deforestation" in their palm oil operations and supply chains. The members of the Group worked together constructively to develop recommendations that provide a roadmap forward for addressing the issues that remain in a collaborative and integrated way.
Please click HCS Convergence Agreement to view the full agreement
The agreement outlines:
Fundamental elements of the converged methodology that protects HCS forests, HCV areas and peatlands, including forest stratification and decision-making in "young regenerating forest" within fragmented landscapes, the role of carbon and robust implementation of FPIC and other social requirements;
The intention for functional and institutional integration of HCS with the HCV Resource Network; and
A roadmap for resolving outstanding issues through a collaborative process.
The recommendations will be incorporated into the revised HCSA Toolkit and the members of the Group are committed to further the implementation of these recommendations and to address the important remaining issues through their engagement in the HCSA Steering Group. In addition, the agreement will be reflected in the policies and positions of the organizations endorsing this agreement and the revised HCSA toolkit will be implemented by the companies when it is issued in early 2017.
High Carbon Stock Study
In 2014, the Sustainable Palm Oil Manifesto, of which Sime Darby Plantation is a signatory, commissioned the High Carbon Stock (HCS) Science Study, which was aimed at clearly defining what constitutes a HCS forest, and establish HCS thresholds that takes into account not only environmental concerns but also socio-economic and political factors in developing and emerging economies. The HCS Science Study, which is supported by a wide range of stakeholders worldwide, has proposed HCS+ as a guide for oil palm growers to develop plantations that are carbon neutral, conflict-free, transparent and equitable to all stakeholders.
French - Étude de cas au Gabon – La méthodologie HCS+ testée sur le terrain
Chinese - 技术委员会独立报告 – 延伸摘要
French - Rapport indépendant du Comité technique – Résumé détaillé
Indonesian - Laporan Independen Komite Teknik – Ringkasan Lengkap
Spanish - Informe Independiente del Comité Técnico - Resumen ampliado
- Consulting Report 1- Review of forest inventory methods for estimating biomass carbon stocks
- Consulting Report 2 - Mapping tropical forest biomass: Synthesis of ground and remote sensing inventory
- Consulting Report 3 - Review of aboveground biomass estimation techniques
- Consulting Report 4 - Dynamics of carbon in disturbed tropical forests and plantations
- Consulting Report 5 - Practical guidance on locating and delineating peatlands and other organic soils in the tropics
- Consulting Report 6 - Practical guidance on how to estimate soil carbon stocks and soil greenhouse gas emissions following tropical forest conversion on mineral soil
- Consulting Report 7 - Review of global literature on the application of remote sensing for delineation and stratification of tropical forest ecosystems
- Consulting Report 8 - Review of global literature on the use of LiDAR technology for the assessment of aboveground biomass and carbon stocks at different spatial scales
- Consulting Report 9 - Synthesis of the state of the art of aboveground biomass estimation using remote sensing
- Consulting Report 10 - Overview of existing regulatory mechanisms and relevant actors
- Consulting Report 11 - Respecting rights and securing livelihoods in conserving 'High Carbon Stock' forests
- Consulting Report 11 - Menghormati hak dan mengamankan mata pencaharian dalam melestarikan hutan 'Stok Karbon Tinggi'
- Consulting Report 12 - The Felda case study
- Consulting Report 13 - Nigeria: A smallholder case study
- Consulting Report 14 - High Carbon Stock (HCS) and the socio-economics of palm oil: Towards improving the sustainability of the palm oil sector in Indonesia
- Consulting Report 15 - The economic impacts of palm oil in Indonesia
- Consulting Report 16 - Indonesian oil palm smallholders and high carbon stock: considerations to avoid errors of the past
- Consulting Report 17 - Palm oil in Liberia : missed opportunities and second chances


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1. Select your dates and number of guests
2. Click on Calculate.
|Sagrada Familia
|8 People
|Single beds
|Double beds
|Double Sofa-bed
This is a lovely small house at 2 minutes from Sagrada familia monument. In a traditional and quiet catalan street where you can park your car front of the house if you need to. There is 4 rooms. You can access to the terrace with the lift or by stairs. Which is also the perfect place to enjoy a sunny breackfast. This house will make you enjoy the cultural and quality area of Sagrada Familia. Lots of tasty restaurants cultural activities. Perfect for parents with children or group of friends older than 28 years old. The house is about 145 m and features Lift and Private Parking 25 . Transportation near the apartment Bus and Metro Sagrada Familia. This house in Barcelona can house up to 8 persons in 4 bedrooms with 4 single beds and 2 double beds. The house has 2 full bathrooms. The kitchen is fully equipped with Dishwasher Microwave Coffee maker Electrical cooker Kettle Oven Fridge Fridge/ freezer and Vitroceramic cooktop. For your comfort the house is equipped with Iron Hair dryer TV DVD Air conditioning Heating Internet Washing-machine and Tumble dryer. The house has handicap accessibility.
Check ins are from 1pm to 8pm. The check in before 1pm is not possible as checks out are realized at 11am and then the property has to be cleaned. Check ins after 8pm have an extra charge of 30 and after midnight an extra cost of 50 and 10 per additional hour. (For example: 1am = 60). Sundays and bank holidays, there is an extra cost of 30. The outstanding rental has to be paid in cash upon arrival. Please have the exact amount.


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Tanto si tuviste una experiencia estelar como si crees que hay margen de mejora, por favor cuéntanoslo. Valoramos tu experiencia en uBreakiFix por encima de todo. ¡Queremos conocer tu opinión!
I had to go in and call multiple days in order to actually get it fixed which only took one day
Outstanding service! All stars
Very courteous, professional and knowledgeable and the price was the lowest anywhere in town.
good work, fast turn around, even got a loaner phone while mine was in the shop.
Amazing, great service I highly recommend.
diagnosis was fast but we had to call our wireless carrier due to motherboard issue
Great service. Very fast
Repaired exactly what I needed, within the time frame promised, and was cheaper than I expected!
Great service. Very fast
Fast, professional and polite.
Was much better than other plav
Great service. Prompt response.


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What is a landing page?
A landing page is the first impression that a potential customer gets after clicking on a link to your site, typically through paid advertising. They are typically used to collect signups for your service or mailing list. SimplyCast offers a landing page application that will help you collect leads and monitor the effectiveness of your advertising campaign. You can find out more by visiting the landing page application details page.


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DADOS - DAta Driven Outcome System
Orthopaedic patient reported outcomes, registries, quality improvement and value based care ALL IN ONE solution
Orthopaedic Educational Videos for You
Review orthopaedic educational videos or share your own with the community...
Review Orthopaedic Programs & Apps
Review orthopaedic programs & apps to help build the community...
Trusted Patient Education for You
Provide your patients with trusted educational materials to help them make informed decisions about orthopaedic bone and joint conditions...
ORTHOREADER - Staying up to date. Your way!
Stop performing the same searches weekly or cluttering your inbox with table of content alerts to stay up to date on your subspecialty
Find Trusted Orthopaedic Information
Communication strategy may help ease patient concerns regarding diagnostic uncertainty
- Category: Editors Choice
A study published online in the International Journal for Quality in Health Care suggests that the way diagnostic uncertainty is communicated may affect patient perceptions of trust and physician competence.
- Details
Children's Hospital of Philadelphia Medical Student Research Opportunity 2018
- Category: Job Opportunities
The Benjamin Fox Orthopedic Research Scholar Award promotes clinical research by giving extraordinary U.S. medical students the opportunity to investigate pertinent topics in clinical orthopedic research at The Children's Hospital of Philadelphia (CHOP). This funded "year-out" scholar program is unique because it was specifically designed for students who are interested in pursuing a career in orthopedic surgery. The successful candidate will dedicate a year to clinical research with CHOP orthopedic surgeons before either the third or fourth year of medical school.
- Details
Is Sciatic Pain Destroying Your Daily Life? Try out These 10 Foods to Fight Back
- Category: Spine
That terrible pain radiating down your leg or that intense, sharp, lower pain may be sciatica. Sciatic pain is a widespread condition that can indeed destroy your everyday life.
- Details
Joint Replacement Awareness Day
- Category: Webcasts
LIVE ONLINE EVENTApril 14, 2018, 10am PSTJoint Replacement Awareness Day® is the first-ever, online educational event for people suffering from joint pain and considering, planning, or having had hip or knee replacement surgery.
- Details
6th World Congress on Controversies, Debates & Consensus in Bone, Muscle & Joint Diseases (BMJD)
- Category: Meetings
The 6th BMJD Congress will address the most burning questions in the field of Rheumatoid Arthritis, Inflammatory Arthritis, Osteoarthritis, Spondyloarthropathy, Lupus, and more.
- Details
Radiography Study Day
- Category: CME Courses
Neck, Shoulders, Knees and Toes ... the journey beyond A&E ... A Radiography Study Day from the Orthopaedic Institute, to be held at the Robert Jones & Agnes Hunt Orthopaedic Hospital NHS Trust, Oswestry Shropshire SY10 7AG on Saturday 3rd March 2018
- Details
Contract Negotiation Strategies Webinar for Orthopedic Surgeons
- Category: Webcasts
Join the webinar for better #reimbursement from your insurance networks. 50+ Year experienced healthcare veteran Michele Carter Graham of BillingParadise meets you virtually on January 10 2018 at 1: 30 P.M EST to unveil the #contractnegotiation strategies for #orthopedists, orthopedic practices and surgery centers.
- Details
AJRR announces new educational blog
- Category: Editors Choice
The American Joint Replacement Registry (AJRR)—an initiative of AAOS—is now offering a free educational blog to help improve orthopaedic care through the collection, analysis, and reporting of hip and knee arthroplasty data.
- Details
How well do those involved in high school sports understand concussion?
- Category: Editors Choice
Data from a study published in the December issue of the journal Mayo Clinic Proceedings suggest knowledge gaps regarding concussion among individuals involved with high school sports.
- Details
Calcium and vitamin D supplements may not reduce risk of fracture for older adults
- Category: Editors Choice
Data from a study published in The Journal of the American Medical Association suggest that use of calcium or vitamin D supplements may not be associated with a reduction in risk of fracture for older adults.
- Details
Orthogate Education Forums
Ask questions and get advice from fellow medical students and residents who know what you're going through...
Join in a discussion or start a new one!
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From leading impact orthopaedic journals, to orthopaedic websites you follow, you can browse, read, and share favorite orthopaedic content, presented in a streamlined format and delivered to you -.ORTHOREADER.
Orthopaedic Web Links
Orthopaedic Web Links - Comprehensive directory of orthopedics, orthopedic surgery & trauma. Search for orthopaedic surgeons, implants, equipment and resources on back pain, broken bones, other orthopaedic conditions.
Find a physiotherapy clinic in Canada with MyPhysiotherapy.ca. Simple. Quick. Effective.


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Suffolk University Success Story
Suffolk University, located in the heart of downtown Boston, serves a diverse student population of about 6,500 across three schools. Over the years, Suffolk has continued to expand its use of CBORD's campus card solutions, implementing additional features and modules to meet changing requirements. These solutions have enabled Suffolk to manage its growing campus services program successfully, yet there was an important function still being handled manually.
"We had a standalone access control system that didn't integrate fully with Odyssey," Mikhail explains. "There was a custom bridge built by the Odyssey team to update the standalone access control periodically. It was a lot of work to get that going at the beginning of every semester. We would have to enter information for students by hand and create their access manually."
The university needed a solution that would both eliminate the time-consuming manual processes and provide one cohesive solution, with one point of contact, for hardware and software.
"We wanted to move away from the environment where the locks and readers are provided by one company and the software is provided by another company," Mikhail comments. "When issues came up, there was confusion about which company to contact. We wanted to eliminate all of that."


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Peacock Alley
Pubs and Bars with Restaurants
Enjoy an exciting look into the Victorian past of the Waldorf Astoria Edinburgh - The Caledonian, inside one of the most magnificent tea rooms in the world. Guests can take in the sight of the historic Caledonian station clock that's placed in homage to the old railway station concourse and ticket office, which were formerly located beneath the hotel. Peacock Alley, with its effortless grandeur and legendary service that's synonymous with Waldorf Astoria, is the perfect venue in which to indulge in a superb afternoon tea of freshly cut sandwiches, a selection of sumptuous cakes and pastries, and warm, freshly baked scones. Customers are invited to relax while taking in the stunning surroundings of the Waldorf Astoria Edinburgh's lobby lounge


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The third run in the PKO Gdynia Grand Prix series, the best running event in Poland which consists of four 10 km runs: Birthday Run with PKO BP (February), European Run with PKO BP (May), Midsummer Night Run with PKO BP (June) and Independence Day Run with PKO BP (11 November).
The Midsummer Run organized on the occasion of the Swietojanska street festival is a real treat for physical activity enthusiasts. The race starts precisely at 23:59, which has already become part of the Midsummer's Eve tradition in Gdynia. Thousands of runners tightly fill the city's streets, proving that running is a trend for almost everyone, regardless of sex or age.
More information:


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Company Products
Company Services
Founded in 1999, «BURINTEKH», Scientific and production enterprise, limited liability company continues as the leading Russian developer and manufacturer of high-quality competitive tools for well drilling and workover operations.
«BURINTEKH», Ltd provides a wide range of oilfield services in complex or separately.
The Company operates in 28 regions of the Russian Federation.
Our Products are exported to CIS countries, Middle East, North Africa and Europe.
Company has Integrated Quality Management System in compliance with
This section contains company news.
We are always glad to see people in our team who can solve extraordinary tasks, manage changes and achieve results. We appreciate such qualities as creativity, educability, commitment to professional development and focus on results.
Official customer feedbacks on product performance and service quality.
Achieved performance records by utilizing our products.
Our articles published in various magazines and newspapers.
Find out more about our Products and Services.
IADC Classification for Roller Cone, PDC, Diamond Bits and Core Heads.
Labor Safety Policy, Environmental Policy, Anti-alcohol and Counter-drugs Policy.
This section contains company safety management standards.
Rational Environmental Management
Enterprise management pays special attention to ecological aspect of manufacturing, stands for rational exploitation of natural resources.
Main principle of control over provision labor safety is regular checks conducted by managers of different level of management.
Company Contacts
Catalogs & Broshures
On September 18 the annual Scientific and Practical Conference organized by «BURINTEKH», Ltd took place in Ufa. Representatives of Russian and foreign companies took part in the conference.
During the conference the next representations were listened to:
«Comparative analysis of using Bits in conditions of Orenburg Drilling Company, LLC»
Deputy Head of Technology, Pavel Archibasov;
«The application of rock destruction tools while drilling deep and ultra deep wells»
Chief Engineer, Efim Oksenoid;
«Stages of PDC bits implementation in Surgut Drilling Department-2»
Deputy Chief Technologist of Surgut Drilling Department-2, Igor Bagrarev;
«Innovations in Cementing and Workover operations»
General Director, Vladimir Samsonenko;
«Coiled tubing technologies of workover operations»
General Director, Almas Khamidullin;
«The application of nanotechnological methods for drilling fluid parameters managing»
Head of Well Cementing and Completion Laboratory, Zarif Sharafutdinov;
«Experience in bits selection for Karaduk field conditions in Kazakhstan»
«BURINTEKH», Ltd
Project Manager of Marketing and Production Development Department, Dmitry Palamarchuk;
«Inhibiting ability of aqueous solutions of salts»
«BURINTEKH», Ltd
Laboratory Engineer of Drlling Fluids Department, Alexey Khristenko;
«High-tech drilling fluid «SKIF» of «BURINTEKH», Ltd.»
«BURINTEKH», Ltd
Laboratory Engineer of Drlling Fluids Department, Alexey Khristenko;
«Perspectives of PDC Bits application for drilling medium hard and hard formations»
«BURINTEKH», Ltd
«Design and application of coring equipment of «BURINTEKH», Ltd.»
«BURINTEKH», Ltd
Head of DTDC Sector, Sergei Golovkin;
«Time reduction of well construction utilizing special tools»
«BURINTEKH», Ltd
«Experience in production and runnig jars of «BURINTEKH», Ltd.»
«BURINTEKH», Ltd


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The Asheville Home Builders Association is currently seeking qualified applicants to apply for the position of Executive Officer. Responsibilities include overall strategic operation and management of budgets, programs, activities and affairs of the association with a focus on growth of current programs and services. Click Here to reference complete job posting and position description.
Interested and qualified candidates must submit a letter of interest and a confidential resume via email to the attention of: AHBA Search Committee at email@example.com. Applications are being accepted now through October 15, 2018.
View Related AHBA Staff Announcement Here.


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12/26-The diet culture of aborigines:Leaf of Piper betel
Recently, environmental protection becomes a global common target, in order to avoid environment from chemical destroy, there are a lot people start to plant vegetable by themselves. Amis live in east of Taiwan, they call themselves as "grass-having" ethnic, they have a lot wild vegetable, thus, develop a unique culture. Nowadays, the Amis wild vegetable develop to the tasty food in fancy restaurant.