Animal-borne orthopoxviruses, like monkeypox, vaccinia and the closely related cowpox virus, are all capable of causing zoonotic infections in humans, representing a potential threat to human health. The disease caused by each virus differs in terms of symptoms and severity, but little is yet know about the reasons for these varying phenotypes. They may be explained by the unique repertoire of immune and host cell modulating factors encoded by each virus. In this study, we analysed the specific modulation of the host cell's gene expression profile by cowpox, monkeypox and vaccinia virus infection. We aimed to identify mechanisms that are either common to orthopoxvirus infection or specific to certain orthopoxvirus species, allowing a more detailed description of differences in virus-host cell interactions between individual orthopoxviruses. To this end, we analysed changes in host cell gene expression of HeLa cells in response to infection with cowpox, monkeypox and vaccinia virus, using whole-genome gene expression microarrays, and compared these to each other and to non-infected cells.
Despite a dominating non-responsiveness of cellular transcription towards orthopoxvirus infection, we could identify several clusters of infection-modulated genes. These clusters are either commonly regulated by orthopoxvirus infection or are uniquely regulated by infection with a specific orthopoxvirus, with major differences being observed in immune response genes. Most noticeable was an induction of genes involved in leukocyte migration and activation in cowpox and monkeypox virus-infected cells, which was not observed following vaccinia virus infection.
Despite their close genetic relationship, the expression profiles induced by infection with different orthopoxviruses vary significantly. It may be speculated that these differences at the cellular level contribute to the individual characteristics of cowpox, monkeypox and vaccinia virus infections in certain host species.
Viruses of the family Poxviridae are characterized by their large and complex virions, a double-stranded DNA genome of 130–375 kbp and the cytosol as the place of replication . As a family, poxviruses are able to infect both vertebrate and invertebrate hosts. Poxviruses of vertebrates are divided into ten genera . Out of these, especially the genus orthopoxvirus (OPV) contains several important pathogens of humans and animals, including some zoonotic members . After eradication of variola virus (VARV) , the most common OPV infections are caused today by monkeypox virus (MPXV), vaccinia virus (VACV) and cowpox virus (CPXV) . VACV is the prototype member of the OPV genus and the best-studied one. VACV served as vaccine during the smallpox eradication campaign and its virulence in man is generally low. However, several severe complications have been reported to occur after vaccination or laboratory-acquired exposition [5, 6]. Furthermore, researchers in Brazil have been reporting several cases of naturally occurring zoonotic VACV infections since 1999 [7–10]. Similar to VACV infections, human CPXV infections of healthy individuals are generally self-limiting and cause only localised skin lesions. However, severe generalised CPXV infections with lethal outcome have been reported in immunocompromised patients [11, 12]. In Europe and parts of northern and central Asia, endemic CPXV are the most common cause of human OPV infections . It is assumed that wild rodents serve as reservoir hosts for CPXV. However, transmission to various other species including several domestic and zoo animals has been reported, and of all OPV CPXV is suggested to possibly infect the widest range of host species . To date, no direct human-to-human transmission has been reported [13, 14]. In contrast to VACV and CPXV, MPXV causes a disease resembling smallpox in humans, but with milder morbidity and lower mortality rates . The severity of the disease depends on the geographic origin of the different MPXV strains, as virus isolates from Central Africa have been shown to be more virulent than those from Western Africa [16, 17]. MPXV was first described as an illness of captive zoo monkeys , and rodents are assumed to be the natural host .
Concerning the potential threat arising from VACV, MPXV and CPXV, a deepening of our knowledge about the mechanisms underlying differences in poxviral pathogenesis and species-specificity would allow greatly improved risk assessment.
Today, more than 100 OPV genomes have been fully sequenced. Therefore the unique arsenal of viral genes encoded by each virus is often known, and in several cases detailed information about viral gene functions is also available. However, current knowledge about corresponding events in the host cell and especially of the differences in host response towards infection and host modulation by these viruses is still limited. Several studies described the transcriptional host response towards infection of different cell types with VACV or closely related rabbitpox virus, either using microarrays or ultrahigh-throughput DNA sequencing for genome-wide transcriptome analysis [19–25]. These studies report that host genes are predominantly downregulated during infection, which may be due to an unspecific suppression of host mRNAs by VACV. The fewer cellular genes which are specifically induced by infection are supposed to play key roles in viral replication or host response to infection, respectively [19, 22, 25]. Especially mRNAs which are associated with the NF-κB cascade, apoptosis, signal transduction and ligand-mediated signalling were reported to be induced in response to VACV infection . Similarly, MPXV was described to cause a decrease in host mRNA levels, accompanied by an increase of fewer mRNAs following infection of MK2 cells . Besides these studies, which focused on analysis of the host response to infection by one specific virus, Rubins et al. directly compared how VACV and MPXV alter the gene expression programs in their hosts . However, to our knowledge, so far no study has investigated the transcriptional response of the host cell towards CPXV infection. As CPXV encodes several unique genes, not to be found in the VACV or MPXV genome, we decided to compare the way how these zoonotic poxviruses alter the gene expression of their host cells. We chose HeLa cells as a model system and characterized changes in the host transcriptional programs in response to infection with CPXV, MPXV or VACV, respectively, using microarrays representing the whole human genome. We aimed to identify mechanisms that are either common to OPV infection or to specific OPV species at the cellular level, allowing a more detailed description of differences in virus-host cell interactions between individual OPV.
HeLa cells were infected with either CPXV reference strain Brighton Red (BR), the highly pathogenic central African MPXV strain MSF-6  or the mouse-pathogenic VACV strain IHD-W . HeLa cells were chosen because of their high susceptibility towards OPV infection and because many fundamental studies on OPV biology and on host gene expression changes following infection have been performed with this cell line [19–21, 23, 25]. Cells were infected at a high multiplicity of infection of 5 plaque forming units (PFU) per cell to guarantee synchronous infection of all cells. Total RNA from infected and mock-infected control cells was isolated at 6 h post infection. This point of time was chosen to allow enough time for establishment of infection and progression to late viral gene expression but to avoid the risk of cell lysis and RNA degradation after completion of the first replication cycle [1, 24, 30]. Furthermore, previous studies described that specific gene activation in response to infection mainly occurs until 6 h post infection, while unspecific downregulation of genes prevails at later stages of infection [19, 23]. Therefore, we chose 6 h post infection to analyse the specific host cell modulation by CPXV, MPXV and VACV and to analyse differences in the cellular response towards these viruses. The successful infection of HeLa cells with all viruses and the uniform progression of infection were confirmed by immunofluorescence microscopy of cells infected in parallel. At 24 h post infection with each virus nearly all cells were infected and showed a pronounced cytopathic effect (data not shown). To verify that all viruses had uniformly proceeded from intermediate to late viral transcription at 6 h post infection, mRNA expression of the late transcription factor VLTF-1 (VACCP-G8R) and of the late 11 kDa virion core protein (VACCP-F17R) was confirmed via quantitative real-time PCR (data not shown).
Total RNA from infected and mock-infected control cells was used for cRNA microarray analysis of host cell transcription. All experiments were performed in duplicate using RNA samples from two independently infected cell cultures for each analysis. To compare the gene expression profiles, ratios were calculated by dividing the merged normalised signal intensities of infected samples by mock-control signal intensities. Genes that exhibited a fold change (FC) in gene expression ≥2 and signal intensities that were significantly above the background with p-values ≤0.01 were chosen for further analysis (see also Additional file 1).
At first, we compared the gene expression data of each virus-infected sample to the expression profile of the mock-infected HeLa cells to determine the relative modulation of cellular transcription induced by infection with CPXV, MPXV or VACV, respectively. As shown in Figure 1A, a majority of 96% of the assayed cellular transcripts remained unchanged after infection with either virus strain. Out of the 30,484 individual genes and transcripts assayed in total (using 41,000 probes), 1,027 (3.7%) transcripts in CPXV-infected cells, only 321 (1.1%) transcripts in MPXV-infected cells and 1,002 (3.3%) transcripts in VACV-infected cells showed expression changes larger than 2-fold after infection. Among the 1,027 CPXV-modulated transcripts, 660 (64.3%) were upregulated and only 367 downregulated. A similar distribution can be seen following MPXV infection which resulted in upregulation of 219 (68.2%) and downregulation of 102 transcripts. Likewise, VACV infection resulted in upregulation of 708 (70.7%) and downregulation of 294 transcripts. Taken together, these data show that an infection with CPXV, VACV and especially MPXV induces only marginal changes of the cellular gene expression profile at 6 h post infection.
Number of host mRNAs regulated by CPXV, MPXV or VACV infection. Shown are the numbers of cellular transcripts that exhibited expression changes larger than 2-fold after infection with each virus in two independent microarray experiments. Transcripts that were upregulated after infection in comparison to non-infected cells are shown in dark grey, transcripts that were downregulated in white (A). Intersections of transcript downregulation (B) or upregulation (C) in response to VACV, CPXV or MPXV infection are shown in the Venn diagram.
Despite of the fact that the number of host cell transcripts affected by CPXV and VACV infection was similar, the number of genes regulated by CPXV and VACV was only 330 (~33%) of approximately 1,000. Among the 321 host transcripts which are modulated by MPXV infection, 241 (75.1%) were also affected by CPXV but only 148 (46.1%) by VACV infection. Beyond that, by comparing all three data sets, we could identify a cluster of 133 transcripts whose expression is modulated after infection with each virus. Out of these, 96 transcripts (72.2%) were upregulated in all virus-infected samples and 37 were downregulated (Figure 1B, C). We applied a Gene Ontology (GO) term-based cluster analysis of these 133 transcripts to identify the biological processes in which the genes are involved. Analysis of gene set enrichment was used to identify statistically overrepresented processes. This analysis revealed that the most prominent group were genes involved in chromatin organisation, containing 50 of the 133 transcripts. Out of these, 46 belonged to the histone family of proteins. Increased detection of histone mRNAs following OPV infection has been described before to be an experimental artefact caused by de novo polyadenylation of these mRNAs by the viral poly(A) polymerase, resulting in their enhanced amplification and detection [22, 27]. Therefore histone mRNAs were excluded from further analysis, resulting in 87 genes which were regulated by infection with CPXV, MPXV as well as VACV. A comparison of the gene expression of these genes is shown in Additional file 2. Besides the histone family members, further functional clusters of transcripts were identified.
Cluster analysis of the 87 non-histone transcripts that were affected by all OPV tested revealed a statistically significant (Bonferroni-corrected group p-value = 1.1 × 10-5) overrepresentation of genes involved in inactivation of mitogen-activated protein kinase (MAPK) activity (DUSP5/6, SPRED1/2, SPRY2/4). All of these genes were upregulated in virus-infected cells and all of them are known to be induced following MAPK-ERK activation [31–35]. In this context, we could also observe a strong upregulation of the early growth-response gene EGR1 and a less pronounced upregulation of EGR2 by all three viruses. EGR1 upregulation via the MAPK-ERK pathway following VACV and CPXV infection has been described before by Silva et al. . Here we show a similar effect following MPXV infection as well. To further evaluate the general impact of OPV infection on biological processes of the infected cell, we examined potential enrichment of these 87 commonly affected genes in known canonical pathways, according to the KEGG pathway database. We could identify 12/87 genes which significantly mapped to two distinct pathways, the ErbB pathway with 5.75% of associated genes (AREG, CBLB, EREG, HBEGF, PRKCB; p = 1.6 × 10-3) and the JAK-STAT pathway with 4.52% of associated genes (CBLB, IL4R, LIF, SPRED1/2, SPRY2/4; p = 2.1 × 10-4). The ErbB signalling pathway comprises a family of receptor tyrosine kinases which are coupling the binding of extracellular growth factor ligands to intracellular signalling pathways such as the MAPK pathway. In this context, upregulation of the epidermal growth factor (EGF) family members EREG, AREG and HBEGF, respectively, may be seen as a trigger for enhanced MAPK-ERK signalling which itself results in upregulation of DUSP5/6, SPRED1/2, SPRY2/4 and EGR1/2, respectively, as a feedback mechanism. The induction of EGF family members and genes involved in regulation of MAPK activity by VACV, CPXV as well as MPXV is summarized in Table 1. Interestingly, only the immune-regulatory CBLB gene and the multifunctional PRKCB gene were downregulated by infection.
a Cluster and pathway analysis of the 87 non-histone transcripts that were affected by all OPV tested revealed a statistically significant overrepresentation of genes involved in inactivation of mitogen-activated protein kinase (MAPK) activity and growth factor signalling. Shown are gene expression changes of the identified genes at 6 h post infection in CPXV-, VACV- or MPXV-infected cells in comparison to mock-infected cells as average fold change (FC) values.
b Values that did not meet the analysis cut-off of an average FC ≥2.0 and p ≤0.05 are designated n.s. (not significant).
c Two values separated by a slash designate values obtained from two different probes on the microarray.
In contrast to these few commonly regulated genes, most infection-regulated genes differ from virus to virus. These differences were most prominent when comparing CPXV or MPXV to VACV infection. To this end, we attributed the enrichment of all genes to biological processes that were differentially regulated following infection in comparison to non-infected cells. This analysis again shows the common regulation of the MAP kinase pathway by all three viruses, but also highlights major differences in the gene clusters affected by CPXV, MPXV or VACV infection. All results are summarized in Table 2. In the case of CPXV infection we could identify 16 overrepresented clusters, including several genes encoding protein kinases, proteins mediating kinase activity and blood vessel development. However, this cluster also contained a significant overrepresentation of genes which can be involved in immune response-activating signal transduction such as Toll-like receptor signalling pathways. Notably, other significantly overrepresented groups were associated with immune system processes, too, such as regulation of leukocyte migration and myeloid cell differentiation.
a Overrepresented biological processes identified by GO clustering of the genes affected by CPXV, MPXV or VACV infection. Related terms were merged into functional groups to reduce redundancy, and the most significant term of the group was defined as group-leading term.
b The degree of connectivity between terms is calculated using κ statistics, and the calculated κ score is also used for defining functional groups. Shown are the identified overrepresented processes, the number of infection-regulated genes assigned to that process and the term p-values.
cn.a. = not applicable. Only term p-values are given if no grouping was done.
In the case of MPXV infection again an enrichment of genes involved in negative regulation of MAPK activity and negative regulation of intracellular protein kinase cascade was observed. Similar to CPXV infection, immunity-associated clusters were likewise overrepresented. This included the biological processes "cellular response to lipopolysaccharide" and "positive regulation of NF-κB transcription factor activity". Many of the regulated genes within either of these processes are also involved in positive regulation of leukocyte migration, Toll-like receptor signalling and chemotaxis.
In contrast, host genes modulated by VACV infection showed a significant overrepresentation only in four Gene Ontology (GO) terms. The most significantly affected biological process was negative regulation of intracellular protein kinase cascade and especially of the MAPK cascade. However, in comparison to CPXV and MPXV infection, no immune response-specific processes could be identified. Taken together, we could identify considerable differences concerning the expression of immunity-associated host genes which were significantly affected by CPXV and MPXV but not by VACV infection.
Infection with CPXV influenced the expression of 1,027 genes, 244 of which were represented in the KEGG pathway database, and 126 of these genes could be mapped to 21 significantly affected pathways (Figure 2). In the case of MPXV infection 104 genes were found in KEGG, and 35 of them could be mapped to pathways that met the criteria. Both after CPXV and MPXV infection a noticeable overrepresentation of immunity-related pathways was observed, along with a significant overrepresentation of genes mapping to pathways specific for certain infectious diseases. Interestingly, for the most part the disease-specific pathways which were affected by CPXV and MPXV infection describe infections caused by intracellular pathogens or inflammatory processes. For VACV-infected cells 191 out of 949 genes were found in KEGG. However, in sharp contrast to the numerous cellular pathways affected by CPXV or MPXV infection, only the ErbB signalling pathway was significantly affected by VACV infection. All significantly affected pathways are shown in Figure 2.
CPXV- and MPXV- but not VACV-modulated cellular pathways are involved in infectious diseases. Cellular pathways that were significantly affected by infection with CPXV, MPXV or VACV, respectively, as indicated by * (p ≤ 0.05) or ** (p ≤ 0.01). Along with pathways which describe general processes of the cell, we identified several immune system-specific pathways (A) and several pathways which are specific to certain diseases (B). P-values indicate the probability of random association between the genes in the data set and the canonical pathway. Abbreviations used in the figure: C-CR interaction = cytokine–cytokine receptor interaction; Transcr. misreg. in cancer = transcriptional misregulation in cancer.
Taken together, this shows the general importance of growth factor and MAPK signalling for OPV infection. Furthermore, the analysis highlighted that immune response-associated signalling pathways are highly affected by CPXV and MPXV, but not by VACV infection. Several genes which are affected by CPXV and MPXV infection were involved in disease-specific pathways. However, the majority of those genes also mapped to other, less pathogen-specific pathways like Toll-like and NOD-like receptor signalling pathways, phagosome, MAPK signalling and apoptosis pathways, albeit with a less significant enrichment.
We analysed enrichment of genes involved in immune system processes to further specify these results. To this end, we matched these genes against the GO immune system process database. We could identify an overrepresentation of genes involved in positive regulation of leukocyte migration (p = 1.2 × 10-2, 21.8%) and Toll-like receptor 2 signalling pathways (p = 4.9 × 10-2, 18.1%) after CPXV infection, and in positive regulation of leukocyte migration (p = 6 × 10-3, 12.7%) and TRIF-dependent Toll-like receptor signalling pathways (p = 5.9 × 10-3, 11.3%) after MPXV infection. No such overrepresentation could be detected among genes that showed regulation following VACV infection (data not shown).
A comparison of the changes in the host gene expression of immune response-affiliated genes, as defined by respective GO terms, showed several genes which were highly upregulated after CPXV or MPXV but not or only slightly upregulated after VACV infection. Especially following CPXV infection an upregulation of several inflammatory genes was observed. Furthermore, several genes encoding proteins which possess chemokine activity or are involved in positive regulation of leukocyte migration were induced by CPXV infection. This upregulation was similar for MPXV infection, but not or only weakly present following VACV infection. Additionally, we could observe a pronounced upregulation of several genes involved in leukocyte activation and positive regulation of leukocyte activation following CPXV infection, which could not be observed following VACV infection and only to a lesser extent following MPXV infection (Figure 3). The numbers of up- and downregulated genes which are associated with these GO terms are also shown in Table 3.
Modulation of immune response-associated genes by CPXV, MPXV or VACV infection. An overview of the changes in host gene expression patterns of immune response-associated genes induced by all three different OPV. Folds of change in gene expression in comparison to mock-infected cells are represented as gradient red and green colour representing low and high relative expression in the respective microarray (shown are 2 arrays per virus). Numbers indicate the log10 of the change fold values. GO term assignment of the respective genes is displayed by different colours. Red = "leukocyte activation", green = "regulation of leukocyte activation", blue = "leukocyte migration", magenta = "regulation of leukocyte migration", yellow = "human chemokine activity", turquoise = "inflammatory response". Only those genes are shown which had at least a 2-fold change in expression relative to the mock-infected control and for which the direction of regulation detected by both arrays was the same. Additionally, regulation in each selected gene differs by a factor of at least 2 between at least two of the samples.
Taken together, these data indicate that in contrast to VACV infection the regulation of immune response-associated genes by CPXV and MPXV infection may more likely indicate a pronounced antiviral immune response of the host cell than a process beneficial for viral replication. This is supported by the observed upregulation of many pro-inflammatory genes and especially chemokine genes following CPXV and MPXV infection.
In this study we applied a comparative analysis of changes of the host cell gene expression profile following infection with CPXV, MPXV or VACV, respectively. We addressed the question whether the different characteristics of each virus, especially the distinctive repertoire of host modulating factors encoded by each virus, may in part be reflected by different characteristics of the infected cells. OPV are well known to suppress the antiviral host defence, exploit the host cell machinery for reproduction and to inhibit or delay cell death. However, most of our knowledge about these mechanisms originates from studies using VACV. More recently, after the US outbreak in 2003, MPXV has come into focus [37, 38], but again, our knowledge about the differences in virus–host interactions between VACV and MPXV and even more so between VACV, MPXV and CPXV is still limited. In this study we investigated the host-cell transcriptome of CPXV-, MPXV- or VACV-infected cells to explore the different capabilities of each virus to interact with the host cell.
We found the host cell transcriptome to be mainly unaffected by poxviral infection, despite the major morphological changes induced by infection. Although this holds true for OPV infection in general, the impact of MPXV infection on the transcriptome seems to be uniquely low. This might indicate an even more elaborate "stealth" program than that performed by VACV or CPXV, allowing MPXV to especially well avoid the responses of the innate and adaptive immune systems to the developing infection. It would be interesting to investigate if this is true for MPXV infection in general, or if it might be a characteristic of the highly pathogenic central African MPXV strains in contrast to less pathogenic west African strains .
The data presented are in agreement with the results by Rubins et al. which show no general decline in cellular mRNAs after infection of HeLa cells with MPXV (Zaire strain) or VACV (Western Reserve strain) . In our study we could prove that the same was true for CPXV infection. Other studies describe that the cellular gene expression is generally suppressed in response to infection and that only few genes are specifically induced [19, 23, 26]. In our study, we found that more than two thirds of the few host cell transcripts which exhibited regulation in response to infection were upregulated at 6 h post infection. However, we cannot exclude the possibility of a more pronounced downnregulation of host cell genes at later stages of infection. Furthermore, in our study, only genes were taken into account that exhibited at least 2-fold change in gene expression, to set the focus on genes that exhibit stronger regulation. Therefore, a mild global downregulation of cellular genes which was below the cut-off value might have been neglected (see also Additional file 3). However, while repression of host genes by OPV is thought to be generalised and likely nonspecific, cellular genes which are induced by infection are of particular interest, as they are thought to play key roles in viral replication or host response to infection [19, 22, 25].
We found the infection-induced changes of the gene expression profiles of CPXV-, MPXV- and VACV-infected cells to be largely different. However, we could still identify several cellular transcripts which showed similar modulation after infection with each virus, the most significant one being histone mRNAs. An apparent induction of histone genes has been described previously in other studies [19–21, 26, 27]. However, this is thought to be an experimental artefact caused by de novo polyadenylation of the histone transcripts by the viral poly(A) polymerase, as histone mRNAs are the only mRNAs in eukaryotes that lack a poly(A) tail in general [22, 27]. This is supported by the fact that Yang et al. reported histone mRNAs to be overrepresented at 4 h post VACV infection even after poly(A)-specific mRNA isolation procedures . If this was the case, amplification of histone mRNAs from infected samples would be greatly enhanced by the poly(A)-dependent procedure we used. We therefore decided to exclude histone mRNAs from further analysis.
After exclusion of histone mRNAs, we could identify 87 cellular transcripts which seemed to be commonly modulated by OPV infection in general. Most noticeable was an apparent infection-induced upregulation of genes involved in inactivation of MAPK activity. The upregulated Sprouty (SPRY2/4) and Sprouty-related (SPRED1/2) proteins are known to be induced by growth factor receptor activation-mediated MAPK-ERK activation via Ras as a self-regulatory feedback inhibition mechanism [31–33]. Similarly, the upregulated DUSP5/6 and EGR1/2 genes are commonly induced as early response genes after activation of the MAPK-ERK signalling pathway and act as negative regulators of ERK phosphorylation [34, 35]. Therefore we suggest that the observed upregulation of genes involved in inactivation of MAPK activity may reflect a feedback mechanism towards virus-induced stimulation of MAPK-ERK activity, probably via an enhanced virus-induced signalling through EGF receptors. This theory is supported by the observed overrepresentation of components of the ErbB pathway among the commonly affected transcripts and by the upregulation of EGF family members following infection. Although modulation of the MAPK-ERK pathway seems to be a common effect of OPV infection, its importance differs from virus to virus. Silva et al. showed that inhibition of MEK/ERK signalling resulted in a significant decrease in VACV yield, but had no impact on CPXV replication [36, 39, 40]. The importance of MAPK-ERK signalling in the context of MPXV replication has not been addressed yet.
Despite these few commonly affected gene sets, major differences in the transcriptional response towards infection with CPXV, MPXV or VACV prevailed. Most interesting was an enrichment of genes involved in immunity-associated processes and pathways in CPXV- and MPXV-infected cells, which was strikingly absent following VACV infection. This included especially genes that are involved in leukocyte migration and Toll-like receptor signalling, which seemed to be affected by CPXV as well as by MPXV infection.
Interestingly, we could identify several pathways specific to certain infectious diseases to be affected by CPXV and MPXV infection. As most of these pathways were specific to infection by intracellular pathogens, this result may be explained by universal mechanisms of host modulation and inflammatory host response which could be affected alike by these diseases and by CPXV and MPXV.
A large proportion of the immunity-associated genes which were affected by CPXV and MPXV consisted of pro-inflammatory cytokine genes and genes involved in leukocyte chemotaxis or activation of immune cells. As most of these genes showed pronounced upregulation after CPXV and MPXV infection, this might reflect an inadequate subversion of the hosts' antiviral response. This may be supported by the fact that an induction of genes implicated in the immune response, e.g. IL6, could also be observed in response to attenuated modified VACV Ankara infection of HeLa cells  but not in response to non-attenuated VACV WR infection . Interestingly, an induction of pro-inflammatory cytokines and chemokines in response to CPXV and MPXV infection was observed by other studies as well. Increased IL8 gene expression following MPXV infection of MK2 cells was reported by Alkhalil et al. . And in vivo, strong secretion of IL-6, IL-8, and G-CSF or of IL-6, IL-8 and CCL-2, respectively, was observed following infection of cynomolgus macaques (Macaca fascicularis) with MPXV or CPXV, respectively [41–43].
To our knowledge, this study represents the first description of changes of the host cell gene expression program in response to infection with CPXV, a virus that is circulating in Europe as well as in parts of Asia and that displays some individual features in the genus OPV. While the host cell response towards VACV infection has been analysed in great detail by previous studies, we describe one of the first attempts to directly compare the impact of CPXV, MPXV and VACV on the gene expression profile of the host cell. We could show a major non-responsiveness of the transcriptional program of the host cell towards infection with all three viruses, which may be a sign of successful virostealth. In spite of this, we could also identify several genes which seemed to be affected by OPV infection in general or exhibited regulation by infection with a specific virus. By assigning these genes to certain biological processes or pathways, we could show that CPXV and MPXV infection induces several genes which are involved in immunity. This may indicate that CPXV and MPXV infection, but not VACV infection, induce a pronounced inflammatory response which may result in attraction of leukocytes. This leads to the question whether the induction of those genes is a part of the antiviral activity of the host or a process in benefit of infection as a mechanism that facilitates viral spread. The latter may be suggested by the important role which infected leukocytes are known to play in OPV dissemination across the body [27, 44]. It will be interesting to analyse the effect of different viral strains or cell types on the observed effects, especially concerning the large genetic diversity of different CPXV strains or of VACV strains from different geographical origin.
All cell lines were obtained from American Type Culture Collection (ATCC, Manassas, VA). HeLa cells (ATCC ID CCL-2) were cultivated in Eagle's minimal essential medium (EMEM) supplemented with 10% heat-inactivated foetal calf serum (FCS, PAA) and 2 mM of L-glutamine (PAA). Hep-2 cells (ATCC ID CCL-23) and Vero E6 cells (ATCC ID CRL-1586) were both cultured in Dulbecco's Modified Eagle Medium (DMEM) containing 10% FCS and 2 mM of L-glutamine. All cell lines were routinely screened for the absence of mycoplasma contamination.
VACV strain IHD-W (ATCC ID VR-1441, NCBI GenBank KC201194) and CPXV strain Brighton Red (ATCC ID VR-302; NCBI GenBank AF482758) were obtained from ATCC (ATCC, Manassas, VA). MPXV strain MSF-6 (sequence to be submitted soon), which was obtained from a fatally infected human in Congo, was kindly provided by Prof. Dr. Hermann Meyer (Institut für Mikrobiologie der Bundeswehr, München, Germany) . All viruses were propagated in Hep-2 cells and cell culture supernatants which were clarified by centrifugation were used as virus stocks. The titres of virus stocks were determined by plaque assay  in Vero E6 cells as described before  and were shown to be comparable for CPXV, VACV and MPXV. All virus stocks were screened for absence of mycoplasma contamination. For infection experiments, HeLa cells were grown in 25 cm2 cell culture flasks (Nunc) and incubated overnight before infection with each virus at a multiplicity of infection of 5 PFU/cell. Mock infections were performed using culture medium free of any virus. After adsorption of virus for 1 h at 37°C, the virus-containing medium or mock medium was removed and cells were washed twice with phosphate buffered saline (PBS) to reduce side effects caused by biological factors probably present in the inoculum. Afterwards, fresh culture medium was added. Cells were then incubated at 37°C until 6 h post infection. All infection experiments were performed in biosafety level 3 (S3) laboratories in accordance with the German legal regulations.
Total RNA was isolated using Trizol® Reagent (Invitrogen) as described in the manufacturer's protocol for adherent cells. RNA samples from two independently infected cell cultures were used for each analysis. Human total RNA quality and integrity were determined using the Agilent RNA 6000 Nano Kit on the Agilent 2100 Bioanalyzer (Agilent Technologies). RNA was quantified by measuring A260 nm on the ND-1000 Spectrophotometer (NanoDrop Technologies). Sample labelling was performed as detailed in the Agilent "One-Color Microarray-Based Gene Expression Analysis" protocol (version 5.7, part number G4140-90040). Briefly, 1 μg of each total RNA sample was used for the amplification and labelling step, using the Agilent Quick Amp Labeling Kit (Agilent Technologies) in the presence of cyanine 3-CTP. Yields of cRNA and the dye-incorporation rate were measured with the ND-1000 Spectrophotometer (NanoDrop Technologies).
The hybridisation procedure was performed according to the "One-Color Microarray-Based Gene Expression Analysis" protocol (Agilent Technologies, version 5.7, part number G4140-90040). Briefly, 1.65 μg of Cy3-labeled fragmented cRNA in hybridisation buffer was hybridised overnight (17 h, 65°C) to Agilent Whole Human Genome Oligo Microarrays 4 × 44 K, using Agilent's recommended hybridisation chamber and oven. Following hybridisation, the microarrays were washed once with the Agilent Gene Expression Wash Buffer 1 for 1 min at room temperature, followed by a second wash with preheated Agilent Gene Expression Wash Buffer 2 (37°C) for 1 min. The last washing step was performed with acetonitrile.
Fluorescence signals of the hybridised Agilent Microarrays were detected using Agilent's Microarray Scanner System (Agilent Technologies). The Agilent Feature Extraction Software (FES) 10.5.1.1 was used to read out and process the microarray image files. For determination of differential gene expression, FES-derived output data files were further analysed using the Rosetta Resolver gene expression data analysis system (Rosetta Biosoftware, Rosetta error model ). Ratios were calculated by dividing sample signal intensity through control signal intensity. The signal intensities from the single-experiment raw data lists were normalised by dividing the intensity values by their median. Putative candidate genes were selected based on a minimum fold change (FC) ≥2 and p-value ≤0.01. The calculation of merged ratios for replicate experiments was performed by calculating pair-wise log-ratios and log-ratio error and the subsequent combination to one ratio in an error-weighted averaging procedure. Data visualisation was done via generation of heat maps from the normalised signal intensity data using the software environment R (v2.15.0).
Analysis of enrichment of genes to certain canonical pathways was done using the software Cytoscape 2.8.2 in combination with the Cytoscape plugin ClueGO v1.4 [48, 49]. Enrichment analysis was based on terms provided by the KEGG databases (received 7th February 2012) . The probability of random association between the genes in the data set and the canonical pathway was calculated with a right-sided minimum likelihood test on the hypergeometric distribution using the Bonferroni correction of p-values. Pathways that were identified with statistical support of p-values ≤0.05 were taken into account. Due to the multitude of pathways which were identified by this method when analysing all differentially regulated genes, we decided to focus on significantly overrepresented terms. These were characterized by p-values ≤0.05, a ratio of ≥10% of term-annotated genes and a minimum of at least 4 genes per term.
Analysis of enrichment of genes to certain GO terms was also done using ClueGO. Enrichment analysis was based on terms provided by the GO (database file received 6th February 2012) . Again, we decided to focus on significantly overrepresented terms which were characterized by p-values ≤0.01, a ratio of ≥10% of term-annotated genes and a minimum of at least 6 genes per term. Furthermore, related terms were merged into functional groups and the most significant term of the group was defined as group leading term. The degree of connectivity between terms is calculated using κ statistics and the calculated κ score is also used for defining functional groups .
Microarray data have been submitted to the Gene Expression Omnibus (GEO) and can be searched using the record ID: GSE36854.
Daniel Bourquain, Piotr Wojtek Dabrowski contributed equally to this work.
The authors would like to thank Jung-Won Sim-Brandenburg and Jule Hinzmann for excellent technical assistance and Ursula Erikli for copy-editing. Furthermore, we would like to thank Prof. Dr. Hermann Meyer for providing the MPXV strain used in this work.
This research was supported by the Robert Koch Institute and by the German National Academic Foundation.
DB was responsible for design, conduct and completion of this work as well as for data analysis and writing of this manuscript. PWD was responsible for data processing and statistical analysis of microarray data. AN was the principal investigator and was primarily responsible for all aspects of research design and coordination and contributed to drafting the manuscript. All authors read and approved the final manuscript.


This year's Ball, themed Puttin' on the Glitz, will take place on Saturday, March 23, 2019 at The Sugar Mill located in downtown New Orleans. The night will include a sensational silent auction filled with unique artwork, fine jewelry, vacation packages, sports memorabilia and much more. Nearly 40 restaurants will serve delectable offerings from their menus while live music fills the venue. We'll invite our patrons to have fun with our playful theme, even offering miniature golf as a featured area at the Ball. The evening will be elegant and full of southern charm.
A beacon of light and hope, Children's Hospital has been serving families of Louisiana and the Gulf Coast for over 60 years. From routine doctor visits to treating the sickest children and babies, Children's Hospital has remained on the forefront of pediatric medical care. We can't do it alone. Community support from events such as the Sugarplum Ball and partners like you help us to expand and advance our programs and services, purchase new technology and equipment and assist in funding life-saving research projects.
On the evening of Saturday, March 23, 2019, friends of Children's Hospital will come together at The Sugar Mill for the 38th annual Sugarplum Ball with one purpose: to help bring this innovative Simulation Center to Children's Hospital.
The center will house pediatric robots providing hands on learning in a variety of disciplines. Our healthcare providers will have the opportunity to hone their craft in critical lifesaving procedures such as heart and lung bypass (ECMO). A breakthrough in pediatric medical education, the simulators utilize dynamic facial expressions, movement and speech to mimic typical patient interactions. The creation of the new simulation center will allow healthcare providers to improve communication, refine critical thinking skills and enhance clinical training.
This exclusive party is available to sponsors $7,500 and above from 6 p.m. to 7 p.m.


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text:
THIS WEEKS STORIES
EYE TV
On Cox
SUN VALLEY ASSOCIATES
Sun Valley Summer Symphony Gets New Identity
The new website was scheduled to go up at 5 this morning.
STORY AND PHOTOS BY KAREN BOSSICK
Call it the Sun Valley Music Festival from now on.
The Sun Valley Summer Symphony has officially changed its name, and that is expected to elevate the symphony's reputation around the nation and the world.
"The new name will help the Festival build its reputation," said Board President Sue Monson. "The community should be proud of the orchestra it has built over the last 35 years, and the Sun Valley Music Festival deserves to be counted among the great classical music festivals in the world, including Tanglewood, Ravinia, Salzburg and Lucerne."
Derek Dean, Margaret Hamamoto and Dan Drackett toast the new name.
Names can make all the difference, as Derek Dean discovered when he stepped into the role of executive director of the Sun Valley Summer Symphony a year ago.
"One of the first things I did was to google top classical music festivals and summer music festivals. Up came articles form the New York Times and New York Magazine and others, and nowhere was the Sun Valley Summer Symphony. I think part of the reason is that people don't know what this is," said Dean.
The name Sun Valley Summer Symphony sounds like a regional orchestra made up of musicians from Sun Valley, rather than musicians who represent the top orchestras in the United States and Canada, he said.
"They don't know this is actually a festival orchestra of the best musicians in the country," said Dean. "I'm hopeful calling ourselves a 'music festival' will put us in the same crowd as the Grand Teton Music Festival, which is similar to what we do and is on the list of top festivals.
Others cheering on the new name were Nils Ribi, John Evans, Lauren Jorgenson , Kim Gasenica and Stephanie Guzman.
"In some ways, the Sun Valley Summer Symphony has been a best kept secret," he added. "The locals and second homeowners know about us, but the name was seasonal and regional."
Dean announced the name change to symphony supporters Tuesday night at a cocktail reception held in the lobby of the symphony's Ketchum office.
"We believe the phrase 'music festival' represents what this organization is," he said. "It presents concerts not throughout the year but in winter and summer and it's comprised of musicians who make their living with other orchestras and who come together for festivals. I hope the Sun Valley Music Festival will take its place among the Salzburg Festival and others," he added.
The advent of the Winter Festival, which debuted in February, was the catalyst for the name change, said Dean. As Music Director Alasdair Neale noted, "If we plan to keep the winter festival permanent, we probably shouldn't call it a summer symphony."
Sun Valley's General Manager Tim Silva chatted with longtime arts supporter Richard Smooke.
The name change enables the organization to assemble musicians from its festival orchestra at different times in the year, no longer exclusively in the summer, said Dean.
"We will also continue to present programs of all sizes and formats as part of these festivals," he added. "As an example, this summer we will feature Jean-Yves Thibaudet and Gautier Capucon in a duo recital without orchestra. Calling ourselves a 'music festival' more accurately represents what we are and will continue to be."
Alasdair Neale said the name change takes the symphony back to its roots when it began as the Elkhorn Music Festival 35 years ago.
"With this change we reaffirm that we really are a music festival, more than a regional or seasonal symphony," he said. "I've been asked if this changes what we do. The short answer is no--it doesn't change the artistic direction. That's not to say we aren't always on the lookout for new ways to present what we do."
Carol O'Loughlin, Debra Levin and Leslie Silva were among those talking about the new name.
The new logo for the Sun Valley Music Festival features a French horn meant to evoke the notion of classical music. Mountains are outlined inside the horn.
The font's forms "are classic enough to speak to the quality and tradition of music making with strong pointed serifs reminiscent of Alasdair's coif but with smooth and gracious curves that invoke the soaring of the music," the designer said.
The symphony organization sent hundreds of photos of nature around Sun Valley in different seasons to the designer asking them to come up with the color palette that represents Sun Valley. What they came up with ranges from yellow goldens of fall to the red Idaho dogwood and will be rotated throughout the year, said Dean.
"It's perfect for the organization we have," Board Member Carol Nie said of the name change. "Our organization does such a variety of things from the summer festival to the winter festival and the music school. It's no longer a summer organization and it hasn't been for many, many years. Now, when we google 'music festivals' we'll probably see the Sun Valley Music Festival listed among them. And the 2019 season is going to be so brilliant I think it's going to be hard to find a space even on the lawn."
The Music Festival is making a number of other changes along with its name:
The first week of concerts in the summer, formerly known as the "In Focus" week, will be integrated fully into the Summer Concert Series.
Each concert will feature a Pre-Concert Chat on the lawn, which can also be accessed on mobile phones via live audio streaming. The big video screen will be live beginning with the first concert, as well, enabling lawn audiences to see, as well as hear the concerts.
All of the Music Festival's education programs will become part of its Music Institute. The institute will continue to offer both year-round programs, in partnership with the Blaine County School District, as well as intensive summer programs that run concurrent with the Summer Concert Series.
The Music Festival will have a new website, live today at www.svmusicfestival.org.
A LOOK AHEAD:
Tickets for the 2019 Gala featuring Branford Marsalis on Aug. 11 will go on sale to the public at 9 a.m. Wednesday, April 10. For more information, visit www.svmusicfestival.org.
~ Today's Topics ~
Dogs with Altitude
Sun Valley Wine Auction to Showcase a New Look at Vine and Dine
Campaign Aims to Cut Down on Deaths by Firearms
Advertising /Marketing /Public Relations
Inquiries Contact:
Leisa Hollister
leisahollister@gmail.com
The largest online daily news media service in the Wood River Valley. We are the community leader, publishing 7 days a week. Our publication features current news articles, feature stories, local sports articles/video content articles and the Eye On Sun Valley show 6 days a week on COX Channel 13. See our Kiosks around the Wood River Valley!
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redpajama_set_name: RedPajamaCommonCrawl


text:
Examiner's Answer
2275 Examiner's Answer [R-08.2017]
37 C.F.R. 41.39 Examiner's answer.
(a) Content of examiner's answer. The primary examiner may, within such time as may be directed by the Director, furnish a written answer to the appeal brief.
(1) An examiner's answer is deemed to incorporate all of the grounds of rejection set forth in the Office action from which the appeal is taken (as modified by any advisory action and pre-appeal brief conference decision), unless the examiner's answer expressly indicates that a ground of rejection has been withdrawn.
(2) An examiner's answer may include a new ground of rejection. For purposes of the examiner's answer, any rejection that relies upon any Evidence not relied upon in the Office action from which the appeal is taken (as modified by any advisory action) shall be designated by the primary examiner as a new ground of rejection. The examiner must obtain the approval of the Director to furnish an answer that includes a new ground of rejection.
(b) Appellant's response to new ground of rejection. If an examiner's answer contains a rejection designated as a new ground of rejection, appellant must within two months from the date of the examiner's answer exercise one of the following two options to avoid sua sponte dismissal of the appeal as to the claims subject to the new ground of rejection:
(1) Reopen prosecution. Request that prosecution be reopened before the primary examiner by filing a reply under § 1.111 of this title with or without amendment or submission of affidavits (§§ 1.130, 1.131 or 1.132 of this of this [sic] title) or other Evidence. Any amendment or submission of affidavits or other Evidence must be relevant to the new ground of rejection. A request that complies with this paragraph will be entered and the application or the patent under ex parte reexamination will be reconsidered by the examiner under the provisions of § 1.112 of this title. Any request that prosecution be reopened under this paragraph will be treated as a request to withdraw the appeal.
(2) Maintain appeal. Request that the appeal be maintained by filing a reply brief as set forth in § 41.41. Such a reply brief must address as set forth in § 41.37(c)(1)(iv) each new ground of rejection and should follow the other requirements of a brief as set forth in § 41.37(c). A reply brief may not be accompanied by any amendment, affidavit (§§ 1.130, 1.131 or 1.132 of this of this [sic] title) or other Evidence. If a reply brief filed pursuant to this section is accompanied by any amendment, affidavit or other Evidence, it shall be treated as a request that prosecution be reopened before the primary examiner under paragraph (b)(1) of this section.
(c) Extensions of time. Extensions of time under § 1.136(a) of this title for patent applications are not applicable to the time period set forth in this section. See § 1.136(b) of this title for extensions of time to reply for patent applications and § 1.550(c) of this title for extensions of time to reply for ex parte reexamination proceedings.
MPEP § 1207 through § 1207.05 relate to preparation of examiner's answers in appeals. The procedures covered in these sections apply to appeals in both patent applications and patents undergoing ex parte reexamination proceedings, except as provided for in this Chapter. For example, there is no requirement for pre-appeal conferences in reexamination proceedings but there is a requirement for panel review of the examiner's answer.
After receipt of a reply brief in compliance with 37 CFR 41.41 or the expiration of the time in which to file such a reply brief (37 CFR 41.35 ), jurisdiction over the appeal passes to the Board. Normally, the examiner does not need to acknowledge the reply brief and will not have an opportunity for further comment prior to a decision by the Board. However, the Board may remand the appeal to the examiner to furnish a substitute examiner's answer responsive to the remand or the Director may remand the proceeding under 37 CFR 41.35(c), such as where there has been a change of law that would require that a new ground of rejection be considered. See 37 CFR 41.50(a)(2) and MPEP § 1207.05 for information on substitute examiner's answer. A substitute examiner's answer is not permitted unless the reexamination proceeding has been remanded by the Board or Director for such purposes.


ധാതുശക്തി വര്‍ദ്ധിപ്പിക്കുന്നു. ബീജങ്ങളുടെ എണ്ണവും ഗുണവും കൂട്ടുന്നു.
എട്ട് വയസ്സിനു മുകളില് പ്രായമുള്ള ഏവര്‍ക്കും ഉപയോഗിക്കാവുന്ന കേശതൈലം.
തുടര്‍ച്ചയായ 30 ദിവസത്തെ ഉപയോഗം കൊണ്ട് പ്രമേഹരോഗം തീര്‍ത്തും ശമികുന്നു.
Shivaprasad shenoy, Managing director and chairman of Sunson group is a well known physician who practiced hereditary Auyrveda system of medicine and was well known in social spiritual and cultural field of Kannur, Kasaragod districts. In this modern scientific era, ayurveda acquired prominence among all kinds of people by the use of genuine and natural ingredients. Sunson provides an ayurvedic world of natural healing with 100% herbal, nature friendly, non-polluted and pure products.
Sunson herbals was established in the year of 1961 in an Indian village town Payyanur with the blessing of Shrimad Danwanthari Moorthi in order to serve the people suffering from diseases at different stage of life and community.
Nellikka Oil:A best medicine for anti ageing, for both skin&hair. and regular use gives good memory power.
പ്രമേഹരോഗം 10 ദിവസം കൊണ്ട് ശമിച്ചുതുടങ്ങുന്നു. തുടര്‍ച്ചയായ 30 ദിവസത്തെ ഉപയോഗം കൊണ്ട് പ്രമേഹരോഗം തീര്‍ത്തും ശമിച്ചതായികാണുന്നു.
Shri U. Surendra Shenoy (SURYAN) he was a renowned hereditary physician who practiced Auyrveda system of medicine and was well known in social spiritual and cultural field of Kannur, Kasaragod districts. In this modern scientific era, ayurveda acquired prominence among all kinds of people by the use of genuine and natural ingredients. Sunson provides an ayurvedic world of natural healing with 100% herbal, nature friendly, non-polluted and pure products. Sunson herbals was established in the year of 1961 in an Indian village town Payyanur with the blessing of Shrimad Danwanthari Moorthi in order to serve the people suffering from diseases at different stage of life and community.
A herbal water mix for all ages , especially for diabetes and weakness.
a new product from Sunson Herbals Products forReduce fat & cholesterol, increase urine output.
a new ayurvedic medicine from Sunson Herbals Products for sexual weakness,increase count & volume.


text:
Please explain.
Lets take the example you gave before.......
Well now lets say this baby stays in your house for 16 years and gives birth to a second child, is the second child any more legitimately a member of your family (or nation). Now repeat this cycle about 10 times and you have the current American population. If you accept that analogy, then the whole of America still belongs to the native peoples.
If you accept that analogy, then the whole of America still belongs to the native peoples.
By Steve's analogy, it should. Unless you think that manifest destiny was right, in which case may the god that gave you the right to that pilfered land have mercy on your soul.
uh no... if you want to use that sort of logic than no one can be a citizen of any country.
Then correct your analogy to suit the reality of American ethnic composition. The United States was basically built on the first case--European "mothers" having their children on aboriginal lands and saying that the natives were responsible to provide land to their "new children." Right now, your analogy is entirely faulty, and I don't see any reason to contest an argument that is almost wholly fallacious. It's a bad argument even if I stretch the Principle of Charity to its absolute limit.
Then correct your analogy to suit the reality of American ethnic composition. The United States was basically built on the first case--European "mothers" having their children on aboriginal lands and saying that the natives were responsible to provide land to their "new children." Right now, your analogy is entirely faulty, and I don't see any reason to contest an argument that is almost wholly fallacious.
incorrect. Some of the land was taken unjustly but not all of the land. If you really want to be accurate you could say that the original states were stolen from England.
Also, the settlers who came to the New World did not ask the natives to provide for them. They bartered for some things and killed for others.
Why do you feel the "native americans" present when europeans arrived had a supreme claim to the lands they were living on?
Post edited by HMTKSteve on May 2010
Irrelevant. It's simple conquest doctrine; the conqueror absolutely cannot recognize the property rights of those conquered. If we did then we would have to give them everything we took and the property rights bestowed upon the European settlers would mean nothing.
Academically, it's nice to talk about the aboriginals, but as far as legal theory goes, they are pretty much irrelevant to modern rights.
No more than anyone else in the broad sense, I suppose, However, there are many people who are let in with the same or less, so while it's a point, it's not the strongest one, I think. If nothing else, I'm willing to work my arse off, and rather unwilling to take benefits like welfare even if I were able to, and there is no job that I consider beneath me - which is more than can be said for a not-insignificant number of people who do have US citizenship.
This is something I'm looking into. I could make ends meet on 20 hours a week, if I was careful, and supplemented my income with savings and such.
Depends what kinda crazy, not all crazy is good crazy.
That's a secondary option, if the primary options don't work out - I do have a Preliminary network that I've been working on already throughout the area I'll be moving to, and a few contacts in cities besides - I've exploited the Hackspace, noisebridge, 2600 and LAdead communities for that, and also been catching up with some old FA and other international friends.
Also, worse comes to worse, I can bust my ass and live off stand up comedy and entertaining gigs, and supplement it with some quasi-legal buying and selling - Last of all, I have a slowly expanding Acquisitions and Consulting business that I can legally register back home, simply do business under that name and possibly get a business visa, but again, I'll be busting my ass to make it work. Absolute worst case, I can run my business affairs back home from the states, and live off that, though the mechanics of transporting money into the country can be a little shady, I'm still looking into that.
Imagine that.
Post edited by HungryJoe on May 2010
HAHAHAHAHA! XD
Oh Joe... you just made my night.
My personal opinion is that it requires full jurisdictionbut the court does not agree with me.
Are you trying to insult me by pointing out that I do not agree with SCOTUS? If so it is a very lame attempt at an insult because most SCOTUS opinions are not unanimous, including this one.
I didn't agree with the Dread Scott decision and I'm glad it was eventually reversed. Are you going to insult me for not agreeing with that one?
Steve, if you'll look at the previous comments, you'll see that no one here agrees with you either. That's because, as usual, you haven't a clue as to what you're talking about. Furthermore, as usual, you don't understand that the lack of agreement you find on this board added to the lack of agreement with the Court (because you so obviously don't understand what you're talking about) is the substance of the joke. The joke is that (also as usual) no one who understands the concept you are trying to discuss agrees with you.
Are you really this clueless?
One thing I've realized is that it's not worth getting wound up over such things. Surely you didn't miss feelings of anger. Re-engaging with the forum was risky enough. If nobody agrees with him, why fall back into that harmful mindset? Been there, done that. Moved on and happy for it.
Both Relevant and to lighten the mood - "So You Want to Be an American: 5 Circles of Immigration Hell"
Wow. That was interesting. I can tell you that, based on my own experience, at least one other country out there is similar. Never underestimate Government red tape. It even holds back the workers. I've seen first hand that smart, motivated workers eventually leave. It's really a shame.
I didn't agree with the Dread Scott decision
Yarrrrrr.
I know that Australia, while we do have a pretty good level of bureaucracy, we're not quite that bad, though there are a fair few hoops to jump though. We're not exactly throwing the gates open, but even we're more chilled out than that.
However, to Temper her statements in that article, it's entirely possible that it was simply a run of bad luck that she had, rather than the process overall - though, of course, the opposite is just as likely(if not more likely) to be true.
Double Z
Start Handing Out Green Cards With Diplomas Via Forbes.com
The feds are suing Arizona over its unconstitutional immigration law.
The user comments on that page are kinda scary.
The federal agency has filed a lawsuit claiming the state has overstepped its authority, and that the law will lead to racial profiling and discrimination.
A preliminary injunction argues the Arizona law is unconstitutional, stating that "A state may not establish its own immigration policy or enforce state laws in a manner that interferes with the federal immigration laws."
So, why is there no mention of racial profiling in the complaint? How is AZ interfering with federal immigration laws? Why is the DOJ not suing Rhode Island over their immigration policy?
So, why is there no mention of racial profiling in the complaint?
Racial profiling is a concern, but the illegality of the law does not require this as a prerequisite for overturning it. The law is likely unconstitutional for a number of other reasons, primarily for the fact that it supercedes a federal law in a manner beyond the power vested into a state's government. It also makes contradictory requirements in enforcement due to its poor writing.
That aside, this law was and is nothing more than a pathetic attempt by local potentates to show their "tough stance on illegal immigration," which is really just a scapegoat down their for wider economic hardship.
What federal law does it supersede?
Missouri, Virginia and Rhode Island have identical laws to Arizona's immigration law
Missouri, Virginia and Rhode Island have identical laws to Arizona's immigration law
It's very telling that all of the links in this article that supposedly prove that "Missouri, Virginia and Rhode Island have identical laws to Arizona's immigration law" link back instead to the same source and the same author. The only time he gets close to using an actual source is when he states that "one of our contributors, M.K., says that Missouri law says thus and and so".
I'd say that without cites to the actual statutes in Missouri, Virginia, and Rhode Island along with a side-by side comparison to Arizona, the proposition that these states are identical to Arizona in this respect is a big fail. Try again.
Post edited by HungryJoe on July 2010
ILLEGAL IMMIGRATION CONTROL ORDER - RI
SCS SBs 348, 626 & 461 - MO
I'll let you google the rest...
Nine states (and the Mariana Islands) have Arizona's back
The amicus briefs point out that federal law already allows states to enforce immigration statutes. "While much of border enforcement is left to the federal government, federal law expressly allows states to arrest people who are not legally present in the United States. Arizona's law doesn't change any of this. That's why we are stunned that the government has sued Arizona," Virginia Attorney General Ken Cuccinelli said.
Missouri, Virginia, and Rhode Island certainly are huge avenues of daily immigration concerns, I'll grant you that. I mean, think of all the border crossings they have to worry about that would generate enforcement cases and SCOTUS appeals! True, they directly border places like Mexico, Canada, Lithuania, Iranizfghanizbackistan, Portugal, West Virginia, Antarctica -- all places with undesirable, evil, jorrrbs-stealing ruffians.
Guess what? When Arizona's law is ruled unconstitutional, any theoretically identical laws in other states would be, too.
Post edited by Jason on July 2010
So, why is there no mention of racial profiling in the complaint? How is AZ interfering with federal immigration laws? Why is the DOJ not suing Rhode Island over their immigration policy?Are you really going to fucking argue this case? I'll ask again: are you really, REALLY going to fucking do this?
That's the same question democrat governors are asking the administration.


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text:
Category: Events PULASKI COUNTY WASTE TIRE COLLECTION DAYS
March 10, 2015 by clackey
KET PRESS RELEASE:
Kentucky Life spotlights environmental efforts of Eastern Kentucky PRIDE
For Release: 2015-03-02 11:07:00
Kentucky Life digs in – literally – with volunteers from Eastern Kentucky PRIDE to clean up litter along Kentucky's Highway 27 in Pulaski County on the next episode of Kentucky Life. The special episode features a 30-minute spotlight on the work of Eastern Kentucky PRIDE (Personal Responsibility in a Desired Environment), which facilitates environmental clean-up and education efforts in a 42-county region of Eastern Kentucky. The episode airs Saturday, March 28 at 8/7 pm and Sunday, March 29 at 4/3 pm on KET and Monday, March 30 at 7/6 pm on KET2.
Launched in 1997 by Congressman Hal Rogers and the late Brig. Gen. James Bickford, Eastern Kentucky PRIDE encourages Kentucky citizens to take pride in protecting their environment and offers educational resources so they feel empowered to do so. The show follows volunteers during the 2013 Dale Hollow Lake Spring Cleanup in Cumberland County as well as along Highway 27 during the 2014 Cleansweep. It also tags along with students from McCreary County Middle School as they visit the London Regional Recycling Center and the Laurel Ridge Landfill, to emphasize the importance of recycling. Finally, the show stops by Russell County Middle School, where wetland ecologist Tom Biebighauser and RCMS teacher Jean Clement offer lessons in the school's wetland outdoor classroom. The episode includes interviews with Rogers; Tammie Wilson, PRIDE president/CEO; Jack Keeney, vice-chair of the PRIDE board of directors; Mark Davis, former PRIDE field representative; Calvin Saum, Breathitt County solid waste coordinator; and Ashley Bowman, Wolf County solid waste coordinator, among others. Kentucky Life is a KET production. Series producer is Brandon Wickey. This episode was produced by Matt Grimm. KET is Kentucky's largest classroom, serving more than one million people each week via television, online and mobile. Learn more about Kentucky's preeminent public media organization on Twitter @KET and facebook.com/KET and at KET.org.
Contact: Tom Martin
KET features PRIDE on special episode of Kentucky Life
« Friends of Lake Cumberland Cleanup September 25, 2021 |


text:
{-# LANGUAGE OverloadedStrings #-}
{-# LANGUAGE TupleSections #-}

module Y2018.Day04 (answer1, answer2) where

import           Data.Foldable

import           Text.Megaparsec
import           Text.Megaparsec.Char
import           Text.Megaparsec.Char.Lexer

import           Data.Function
import           Data.List
import qualified Data.Map.Strict               as Map
import           Data.Vector                    ( (//) )
import qualified Data.Vector                   as V
import           Data.Void
import           Data.Functor
import qualified Data.Text                     as Tx
import qualified Data.Text.IO                  as Tx.IO

import qualified Utils.Parser                  as U

answer1, answer2 :: IO ()
answer1 = do
  shifts <- getData
  let m@(mostId, mostVals) = maximumBy (compare `on` (V.sum . snd)) (guardStats shifts)
  print $ mostId * V.maxIndex mostVals

answer2 = do
  shifts <- getData
  let m@(mostId, mostVals) = maximumBy (compare `on` (V.maximum . snd)) (guardStats shifts)
  print $ mostId * V.maxIndex mostVals

data SleepStatus = Sleep | Awake deriving Show
data Date = Date
  { dY :: Int
  , dM :: Int
  , dD :: Int
  , dH :: Int
  , dMin :: Int
  }
  deriving (Show, Eq, Ord)

data Shift = Shift
  { sStart :: Date
  , sGuardId :: Int
  , sEvents :: [(Date, SleepStatus)]
  } deriving (Show)

-- | gives for each guard, a vector of the number of time asleep at minute m
guardStats :: [Shift] -> [(Int, V.Vector Int)]
guardStats shifts =
  let f m s = Map.insertWith (V.zipWith (+)) (sGuardId s) (timeAsleep s) m
      allGuards = Map.toList $ foldl' f Map.empty shifts
  in allGuards

-- | minutes when the guard was asleep for the given shift?
timeAsleep :: Shift -> V.Vector Int
timeAsleep shifts =
  let updates = map (, 1) $ concat $ snd $ foldl' f ((0, Awake), []) $ sEvents shifts
      f ((prevMin, prevStatus), n) ev@(d, status) = case status of
        Sleep -> ((dMin d, status), n)
        Awake -> ((dMin d, status), [prevMin..dMin d-1] : n)
  in V.replicate 60 0 // updates

type Parser = Parsec Void Tx.Text

getData :: IO [Shift]
getData = do
  raw <- Tx.IO.readFile "data/2018/day04.txt"
  case parse dataParser "day04" raw of
    Left err -> error $ show err
    Right x -> pure x

dataParser :: Parser [Shift]
dataParser = do
  lines <- U.parseLines parseRawLine
  let sortedLines = sortOn rawDate lines
  pure $ foldl' foldShifts [] sortedLines
    where
      rawDate = either fst fst

type RawLine = (Either (Date, Int) (Date, SleepStatus))

foldShifts :: [Shift] -> RawLine -> [Shift]
foldShifts acc (Left (d, i)) = Shift d i [] : acc
foldShifts [] (Right _) = error "guard with no shift?"
foldShifts (s:acc) (Right ev) = addEvent ev s : acc
  where
    -- highly non optimal but shouldn't matter
    addEvent e s = s {sEvents = sEvents s <> [e]}

parseRawLine :: Parser RawLine
parseRawLine = try (Left <$> parseGuardLine) <|> Right <$> parseStatusLine

parseShift :: Parser Shift
parseShift = do
  (d, g) <- parseGuardLine
  Shift d g <$> parseStatuses

parseDate :: Parser Date
parseDate = Date
  <$ char '['
  <*> decimal
  <* char '-'
  <*> decimal
  <* char '-'
  <*> decimal
  <* char ' '
  <*> decimal
  <* char ':'
  <*> decimal
  <* char ']'

parseGuardLine :: Parser (Date, Int)
parseGuardLine = (,)
  <$> parseDate
  <* char ' '
  <*> parseGuard

parseGuard :: Parser Int
parseGuard = string "Guard #" *> decimal <* takeWhileP Nothing (/= '\n')

parseStatuses :: Parser [(Date, SleepStatus)]
parseStatuses = loop []
  where
    loop acc = do
      r <- try (U.isEOF *> fail "eof") <|> try (parseGuardLine $> Nothing) <|> (Just <$> parseStatusLine)
      case r of
        Nothing -> pure (reverse acc)
        Just s -> loop (s : acc)

parseStatusLine :: Parser (Date, SleepStatus)
parseStatusLine = (,)
  <$> parseDate
  <* char ' '
  <*> parseStatus

parseStatus :: Parser SleepStatus
parseStatus
  =   string "falls asleep" $> Sleep
  <|> string "wakes up" $> Awake

testShift1 = Shift
  (Date 1518 11 1 0 0)
  10
  [ (Date 1518 11 1 0 5, Sleep)
  , (Date 1518 11 1 0 25, Awake)
  , (Date 1518 11 1 0 30, Sleep)
  , (Date 1518 11 1 0 55, Awake)
  ]

redpajama_set_name: RedPajamaGithub


Rentplus has very strong relationships with local authorities and in particular those with aspirations for growth. The credibility of high-level financial backing offered by Rentplus means that affordable housing can be delivered quickly and in volume to realise strategic priorities.
Building new affordable homes will alleviate housing waiting lists and provide much-needed developments in regions across the country, as well as replenishing housing stock.
By utilising the Rentplus model, local authorities can benefit from a significant increase in the number of homes available at affordable rents. There is also the potential to add value to council-owned land through inclusion of the tenure.
Rentplus promotes mixed tenure developments and Rentplus villages to achieve a step change in delivery of affordable housing. We have a commitment to neighbourhood planning and establishing strong communities who will take pride in their homes and the local area. As properties will be managed by partner housing associations, let at affordable rents to tenants aspiring to home ownership, local authorities can be assured their strategic housing and economic priorities will be addressed.
These developments can also kick-start existing approvals which may have stalled due to the changing financial climate, as well as stimulating the local economy through new jobs, training opportunities and boosting the supply chain.
Using the Rentplus model will also allow local authorities to benefit from New Homes Bonuses.
We work in partnership with local authorities to agree scheme specific local lettings plans to ensure that the allocation of Rentplus homes assists the local authority to meet their housing responsibilities including housing people from the waiting list, enabling local people to stay in their communities and to support inward investment and local employment.
The first Rentplus scheme is at Persimmon's Palmerston Heights development in Plymouth.
There are 19 Rentplus homes, all of which are 2 and 3 bedroom houses. The first residents moved into the Rentplus homes in October 2016. Tamar Housing also procured six social rented homes on the same estate, enabling them to improve the cost effectiveness of services to their tenants.
Residents for the properties available for 5 years were taken from the help-to-buy waiting list. All had a local connection to Plymouth, were first time buyers with earnings under the shared ownership salary threshold.
The remaining homes, available for 10, 15 or 20 years, were allocated via Devon HomeChoice. The properties attracted huge interest with over 200 bids received in less than 24 hours.
The residents work a wide variety of jobs including retail (3), healthcare (3), manufacturing (8), administration roles (3), skilled trades including trainees (3), armed service (1) and domestic/catering (2). One household has an IVA whilst a further has a CCJ – both have been allocated homes with a 10 year purchase option, giving them ample time to clear their debts and be ready to apply for a mortgage with a good credit history.
The age range of the residents is from 25 to 47 years old. Of the 17 households, 9 do not currently have any savings and the remainder have savings of between £2,000 and £7,000.
The first residents moved into the Rentplus homes at Persimmon's Corelli estate in Sherborne in March 2016. Occupation was phased, with the last residents moving into their homes in August 2016.
There is a mix of families, couples, single parent families and single people in the properties.
All residents are working, either full-time, part-time or self-employed in a variety of roles across healthcare, education, hospitality/catering, construction, factories, retail transport, engineering, clerical, farmer, childcare, automotive.
Incomes range from £20,000 up to £65,000 at the top end; the majority of household income is in the median range of £25,000 – 35,000.
Lagan Homes, an SME builder, developed the Moorgate scheme of 19 stone-built homes in Lechlade-on-Thames in the Cotswolds. Rentplus has six properties comprising 2 x 2 bedroom homes, 3 x 3 bedroom homes and 1 x 4 bedroom home.
Our housing association partner, GreenSquare, invited applications for the homes using the Gloucestershire Homeseekers Choice-Based Lettings scheme. Four residents were allocated their homes through the CBL scheme; the remaining two were sourced through separate advertising.
The first residents moved into their homes in August 2016. All the households are couples with children; their age range is from 32 – 48 years old; the 4 bedroom home has been allocated the 20 year purchase option.
Gross incomes range from £25,000 to £61,000 per annum; two residents are self-employed whilst others are employed in the care sector, public sector and engineering. One household has a cleared CCJ and they are using the Rentplus rental period to build their credit history in advance of buying their home.
The first Rentplus scheme in Oxfordshire is Flanders Close, part of Mulberry Homes Stratton Park development in Bicester. This is also our first flatted scheme.
The Rentplus homes comprise 10 x 2 bedroom flats in a three-storey building; 60 expressions of interest were received when the flats were first advertised.
Our housing association partner is Harrow Churches Housing Association (HCHA). Cherwell District Council identified suitable households from their waiting list and passed their details to HCHA to allocate the properties to applicants based on their assessment of their circumstances.
The residents' ages range from 23 to 52 years old; two are self-employed with the remainder working in a range of occupations from the prison service, forestry service, social care, retail, logistics and hospitality. Incomes range from £13,320 to 52,200 per annum.
One tenant is disabled and ex-forces; another has learning difficulties whose his parents have established a trust fund for him which will purchase the property for him in five years' time. The Rentplus home gives him independence and a secure future and gives his parents peace of mind.
Rentplus has 20 homes on the Barratt Homes Saxon Fields development in Cullompton. The first ten residents moved in to their new homes in August 2017; future phases will be completed during 2018.
The 20 homes comprise 11 x two bed houses & 9 x three bed houses and are managed by our housing association partner Cornerstone.
Mid-Devon District Council requested that Cornerstone write to all 1500 applicants on their Home Choice list rather than inviting applications through the on-line system. In total, 136 expressions of interest were received for the 20 homes and 45 applications for the first 10 homes. Of these, the majority have moved from private rented homes, with seven applicants registered on Devon Home Choice.
The residents are aged between 26 and 38 years old and are employed working in a diverse range of occupations, including engineering, health & social care, NHS, construction, highways, catering and delivery. Their incomes range from £17,300 to £37,000, some have debt and all have savings.
Working with another local developer - J&M Homes Ltd - with a history of building smaller high quality homes, Rentplus has six properties on this small development in the South Hams district in Devon. Tamar Housing is the Rentplus partner housing association.
The six Rentplus homes comprise 2 x 1 bed flats and 4 x 2 bed houses. The residents moved in during July 2017 and all were allocated their homes via Devon HomeChoice.
One resident is self-employed, the remained are in full-time employment in a variety of occupations including from nursery nurse, NHS, double glazing and marine engineering. Their age ranges is from 20 – 53 years old and their incomes range from £12,000 to £24,000, reflecting the smaller size of these properties.
Get in touch today to see how Rentplus could help you provide more affordable housing.
Testimony from one of our registered provider partners is positive confirmation on how working in partnership with the Rentplus privately funded model adds real value to communities, and to the delivery of more affordable housing.
"Rentplus' affordable rent-to-buy homes give local households, often languishing in the lower bands of need, the opportunity to access good quality affordable housing managed and maintained by a registered provider. Low income families often have very few housing options and Rentplus offers an unique Rent, Save, Own product that gives more security than private rented accommodation at an affordable rent and a chance to move into home ownership following an agreed period of renting. Our Rentplus properties are allocated via choice based lettings and homes have been let to local households from bands B to E with priority given to those in existing social housing thereby freeing up homes for those in higher need. New communities of mixed tenure developments are enhanced by the inclusion of Rentplus due to the positivity and hope value of the tenants.
"In the East of England, we have a growing economy, and a really significant need for quality new housing to support that growth. Rentplus offers local authorities a new and realistic way to provide affordable housing in support of working people, with a route into home ownership. I look forward to seeing it used to accelerate development on major sites, and to supporting our market towns by attracting and retaining young families into those communities."
"I am really excited about the Rentplus housing product. I think it offers a fresh, desirable and complementary affordable housing option for hardworking local people to find a home in a place they want to live, at a price they can realistically afford.
"Rentplus...will work alongside the delivery of the council's traditional affordable housing supply, offering genuine additionality in supply.
"I believe that Rentplus provides a welcomed opportunity for lots of people who aspire to own their own home and, with support, can achieve home ownership rather than a life in expensive and insecure private-rented accommodation. Furthermore, it also provides a cost-effective alternative to shared ownership for households that do not have a deposit to purchase.
"We are pleased to be working with Rentplus to bring forward a new model of housing delivery aimed at supporting aspirant first time buyers as they struggle to find a home of their own.
"Rentplus is demonstrating its ability to secure ethical institutional funding into the provision of affordable housing. It has also adopted an exemplary approach to community engagement which is increasingly important as we work with local communities to make the case for new homes.
"Pioneers in delivering innovative affordable rent to buy housing for aspiring home owners. Tetlow King Planning are proud to be assisting Rentplus in making affordable home ownership a reality for many people who don't want to be caught in the spiral of renting in the unsecure private rented sector."
"Rentplus aligns well with national planning policies and guidance that seek to increase delivery of affordable housing (and growth in general), particularly paragraphs 47 and 50 of the NPPF. Rentplus cannot be defined as solely affordable rent or intermediate housing, as such a change to the NPPF definition would help to support new models such as this. LPAs preparing plans or making decisions on planning applications can integrate and support the provision of Rentplus affordable housing at their discretion, as many have done already (as have the HCA via a Short Form Agreement).
Right to Buy, Help to Buy and Starter Home products require applicants to have a deposit or to have the means to get a deposit together. If someone is currently in social rented property or the private rented sector and can't rely on a deposit from their parents, a viable solution for the 'missing middle' or 'generation rent' can be Rentplus. To help bring forward affordable products like this a step change in delivery is required capable of providing flexible tenures in response to changes in national policy.
Rentplus benefits from institutional investment and so is not reliant on subsidy or grant. Rentplus can be scaled up more quickly than traditional social housing delivered by LAs or RPs who are constrained by borrowing limits. The Rentplus village concept can provide affordable housing in the first or early phases or take on serviced sites and plots delivered directly with their own contractor partners. For products such as Rentplus to achieve the scalability desired changes are required to national policy and guidance to allow products such as this to help bring forward a step change in delivery, capable of filling and exceeding the gaps created by the proposed planning, housing and welfare reforms.
Rentplus is designed to be attractive to the private sector and acceptable to LAs and RPs. Rentplus' funders like the fact that the products are let on a 20 year FRI lease as it means they are regulated within the social housing sector and administered by RPs. The future strategy is to form a national network of small RPs to share best practice. In instances where an RP is likely to lose much of its stock the Rentplus product can offer a solution to continue delivery of pipeline stock by directly working with the respective RPs to identify a revised and appropriate tenure split. Rentplus would seek to work with smaller RPs and allow them to grow organically off- balance sheet, receiving a management fee from Rentplus for administering the Rentplus affordable units. The model is simpler to traditional affordable housing, RP partners would provide financial advisers to help tenants set up mini-cash ISAs and to demonstrate creditworthiness.


text:
MMSD Collaborates with MDAs on Mining Roadmap
Nigeria Mining Cadastre Office > News > MMSD Collaborates with MDAs on Mining Roadmap
The Ministry of Mines and Steel Development in furtherance of its plan to sensitise all stakeholders in the mining sector on key elements of the mining Roadmap, on Wednesday, held a forum on Mining Roadmap Synergy/Linkages Consultations with Ministries, Departments and Agencies (MDAS), in conjunction with the Mining Implementation and Strategy Team (MIST).
The aim of the forum is to introduce the components of the Roadmap to the different MDAS and collaborate with them on the areas of synergy and linkages to ensure full implementation of the roadmap for national economic growth.
The Permanent Secretary, Ministry of Mines and Steel Development speaking through his Representative, the Director of Human Resource Management, Alhaji Sanusi Ashiru, commended the MIST on sensitising stakeholders in the industry on the Roadmap and urged them to do more to actualise the implementation of the document to achieve its desired objectives.
He said the outcome of the synergy and linkages between the Ministry and MDAS would further enhance activities in the minerals value chain (MVC).
In his opening remarks, the Chairman of MIST, Professor Gbenga Okunlola, stated that MIST was inaugurated in December, 2016 to assist the Ministry in ensuring that the implementation elements embedded in the Roadmap are delivered against the respective timelines.
He said that MIST has organised four series of the sensitisation forum at different locations across the country. The first was held in Abuja for the Ministry's key staff, the second in Lagos for industrial key players which witnessed the attendance of the Minister alongside the Economic Summit Group, a forum with community and mining operators was held in Jos, while the fourth is on invitation to roadmap synergy/linkages consultations with MDAS in Abuja.
The invited MDAs include Ministries of Science and Technology, Environment, Foreign Affairs, Power, Works and Housing, Water Resources, Budget and National Planning among others.
Categories : News


Those mourning the Loot Cave in Destiny being nerfed, there's always the newly discovered farming point in the Rocketyard.
I say newly discovered because PS4 Trophies just posted a video about it, and since I have yet to play Destiny, I've no idea if this is a known farming point or not. I'm just trying to help out. Don't make fun of me.
See how it works in the video below. Thanks, Joystiq.


Louis Farrakhan Speech At Nipsey Hussle Funeral "We All Need To Come Together"
Re: Louis Farrakhan Speech At Nipsey Hussle Funeral "We All Need To Come Together"
Snoop Dogg Incredible Speech At Nipsey Hussle Funeral "He Changed The World"
I live-streamed some of Nipsey's service when it happened. I caught Battlecat DJing at the very end as he was carried out, and I thought the pastor before that made an inspirational and fitting speech.
I couldn't believe just how many people were lining the route his hearse was taking through south LA, there were so many. I thought it was disrespectful of people to be approaching his hearse and taking pictures of his coffin in the back, but unfortunately this seems to be peoples mentality these days.


text:
Fields of Law
Antitrust & Competition Law
Digitalization & Data Protection
Policy & Regulation
In-House Management
Legal Privilege
About ECLA
ECLA – from past to present
ECLA
ECLA history
From past to present
The European Company Lawyers Association (ECLA) is the umbrella organization for 19 company lawyers' associations in Europe. It represents the common interests of European company lawyers.
The history of ECLA is closely linked to the increasing relevance of legal departments in companies. Legal departments were first established in companies more or less at the same time in the US and Europe. The construction of railways, the formation of large insurance groups and utility companies from the 19th century onwards were accompanied by the need for professional legal advice, which became a prerequisite for handling problems arising from a plethora of new rules and regulations.
Europe: A special case
A difference soon became apparent between the New and the Old World. In Europe, the legal status of the company lawyer varies from country to country. In the Netherlands, Germany and Great Britain, in-house lawyers are admitted to the national bar association or similar professional associations (such as the Law Society). This is not permitted by law in Belgium, France and Italy. For this reason, Belgian in-house lawyers took the initiative in 1980 and reached beyond their national borders to establish contact with similar organizations in the Netherlands, England, Wales, Germany, Italy and France. This was the first step towards an exchange of experience on best practices and legal issues, particularly with regard to international business and the European legislation that impacted the activities of their respective companies.
In 1983, ECLA was founded in Belgium as a private, non-profit international association. John Boyd was appointed the first Secretary General. The A M. & S. case in 1982 was a significant factor in the founding of the Association. The case addressed the legal status of the confidentiality of lawyers' correspondence in European competition proceedings, among other issues. The European Court of Justice ruled at the time that the attorney-client privilege did not apply to company lawyers in the same way.
In September 1984, Prof. Dr. Walter Kolvenbach was appointed the first ECLA President. The author of the fundamental work The Company Legal Department held office until October 1987, during which time he dealt extensively with the question of how to achieve recognition throughout Europe for the profession of the company lawyer. Under the chairmanship of Barry O'Meara (October 1987 to May 1990), cooperation between the various European organizations was increased and enhanced. This did not only apply to cooperation at a scientific-research level, but also regarding discussions on the various ethical principles concerning professional practice, which vary from country to country, taking into account the harmonized rules on deontology.
The tasks
For this reason, it was decided to re-establish ECLA in Brussels as a scientifically-oriented international association governed by Belgian law. The association was officially recognized pursuant to a Royal Decree on 25 June 1990. The tasks of ECLA were laid down in the articles of association adopted in 1990 as follows:
Representation of its members at the international level, especially in Europe.
Establishment of centers for study and documentation, and the designation of contact persons to improve the exchange of professional information between members.
Organization of meetings, conferences or seminars relating to legal matters.
Promotion of legal research.
ECLA's articles of association provide for two governing bodies: the General Assembly, which is composed of one representative from each member organization, and the Executive Board, which consists of one nominated director from each member organization. The members' meetings are held once a year, at the latest six months after the beginning of the year. The board meets twice a year. In 2010, the articles of association were amended. It now provides for a General Assembly that meets twice a year, as well as an Executive Board elected by the General Assembly and consisting of the President, one or more Vice-Presidents, a Secretary and a Treasurer. The General Assembly also elects an internal auditor. The current President is US-citizen Jonathan Marsh, who is the International General Counsel at TOTAL Marketing Services in Paris.
Since its foundation, the number of ECLA members has grown continuously. It now includes company lawyers' associations in 19 countries. Until now, the members' meetings have been held regularly by the respective member organizations in their own countries. In order to manage the activities of ECLA, the Executive Board is endowed with all powers not reserved for the General Assembly. The current administrative activities of the association are subject to the managing director.
The beginning of a new era
At the beginning of this year, ECLA and the dfv media group entered into a service partnership. As part of this cooperation, the dfv media group provides media, networking, association and lobbying services to ECLA. The new offices of ECLA Association Services SPRL opened in April 2018 and are managed by managing directors Marcus M. Schmitt and Dr. Michael Henning, managing partner of dfv Association Services GmbH. In addition to his function as managing director of the dfv media group, Sönke Reimers also serves as a managing director of ECLA Association Services SPRL.
Comment or question? Don't hesitate to contact: feedback@inhouse-legal.eu
Europe must undergo profound reform to succeed in the digital, globalized age
Company lawyers as Ambassadors
A new cybersecurity regime brings enhanced agencies, reporting obligations
"Being that close to the business is just that much more exciting"
CJEU Decision reinforces the value of LPP
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