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On Air News Read for July 14, 2017
New Hampshire Attorney General Gordon MacDonald announced, yesterday, that his office, along with the Merrimack County Attorney’s Office, the Concord Police Department and the New Hampshire State Police, has begun a criminal investigation into St. Paul’s School in Concord. MacDonald said he launched the investigation in light of the report recently released by the school detailing sexual assaults of students by teachers and the exposure of student sexual conquest rituals, such as the “Senior Salute,” a practice which led to the highly publicized prosecution of Owen Labrie, a graduating St. Paul’s student in 2 0 1 5.
Another allegation of a sexual assault committed via a similar ritual reported last month is currently under investigation.
St. Paul’s: Trouble continues
The A G’s investigation will focus on whether school officials endangered the welfare of children. MacDonald also said the investigation will address any other crimes determined by the evidence and that he was confident that St. Paul’s would fully cooperate. Any person with information regarding criminal conduct at the school is urged to contact Investigator Mark Myrdek. (271-1263 or e-mail [email protected].) We have his contact information with this news read at Girard at Large dot com. We’ve also uploaded a copy of the report detailing the sexual misconduct of teachers against students and linked to the letter the school sent when releasing the report to parents and the community.
In my “hood” again
Hey, now I know why my wife was sending me text messages on Wednesday morning to tell me about the Manchester Police Department’sSWAT Team lobbing flash bombs into a house around the corner from ours. Turns out they were executing a search warrant in conjunction with the Hillsborough County Sheriff’s Department at 4 7 Linden Street. Once inside, they arrested fifty four year old Tony Pickard who lived there along fifty two year old Maurice Groulx. They also seized twenty eight point three grams of crystal meth, over fifteen hundred dollars in cash and more than twenty five hundred dollars of gold and silver. Pickard and Groulx were taken into custody on two separate warrants.
Bennett: WANTED
Who police didn’t find was fifty four year old Paul Bennett, who was also a target of the raid. Bennett, who wasn’t home at the time, has two outstanding drug related warrants for his arrest. If you know of Bennett’s whereabouts, please contact the Manchester Police Department at 6 6 8 8 7 1 1 or Manchester Crimeline, where you can provide an anonymous tip and be eligible for a cash reward, at 6 2 4 4 0 4 0.
We have Bennett’s picture and description with this news read at Girard at Large dot com. (Bennett is described as 5’05, 150 lbs. brown eyes and grey hair.)
News from our own backyard continues after this.
Ambrogi: Seeking 4th term
The Candidate Crawl to City Hall continues in the Queen City, albeit at a snail’s pace. Here are yesterday’s filings:
In Ward One, Sarah Ambrogi filed for reelection to the school board.
In Ward Two, Ryan Richman, of Fox Hollow Way, has thrown his hat into the ring for alderman, creating a primary for that seat in September.
In Ward Three, Phillip Harris, of Manchester St., filed for school board.
Freeman: Another try
In Ward Five, incumbent Lisa Freeman will run again for the school board.
Ward Seven had a flurry of activity as incumbent Alderman William P. Shea filed for a twelfth term and Brian Cole, of Howe St., filing to run against him.
In Ward Eight, former Alderman, State Senator and firefighter Betsy DeVries will again seek the ward’s aldermanic seat, creating a primary for the seat in September.
In Ward Nine, Michael Ricker, of Kenberma St., filed for alderman, creating a primary for that position as well. We’d been told he was going to run for school board, but…oh well. Nice to see another newcomer!
The filing period for all city offices, including ward moderator, ward clerk and ward selectman, closes a week from today, July 2 1st. We’ve posted the complete list of filings as of yesterday’s close of business with this news read at Girard at Large dot com.
Edwards: Good first filing
While we’re on the topic of elections, the campaign of Republican First District Congressional candidate Eddie Edwards announced it will report having raised more than one hundred twenty thousand for its first filing with the Federal Election Commission. Edwards’ consultant Derek Dufresne of RightVoter said more than eighty percent of the funds raised came from New Hampshire donors. Dufresne said the campaign was excited by the tally. Quote:
“Eddie is not a career politician, and donors are not giving to him as some sort of political payback, but rather they are supporting him because they believe in him and his message.”
Town Hall: No water
In case you’re wondering why Town Hall in Goffstown was closed yesterday afternoon, it’s because of a water outage. The outage also forced cancellation of the Planning Board’s meeting last night.
About The Author
Richard H. Girard is a well known and highly respected conservative public figure and opinion maker in southern New Hampshire. A native of Manchester, NH, Rich has devoted more than two decades to serving and educating the community about the critical issues in local politics and government. Rich’s diverse background includes running for and holding public office, providing leadership and management for other candidates’ political campaigns, extensive experience in the public and not-for-profit sectors, being sought as a political commentator by media outlets across the region, and having started and run three businesses, including this one. |
Setting priorities in prevention.
In the last few years prevention has again become the focus of attention because of various international developments such as the WHO strategy for Health for All by the year 2000. When resources are scarce, it is all the more important to set priorities. This applies to prevention as well as to curative care. In this paper, we describe a method for comparing prevention programmes with one another, using efficiency as the final parameter. To determine efficiency it is necessary to collect facts about a number of aspects of the health problems to be prevented: size of the health problem, degree of preventability, monetary and other costs involved and the probability that the prevention programme will cause changes in the overall pattern of morbidity and/or mortality. These aspects are discussed and some examples given. |
Introduction
============
Malaria remains an important public health problem despite persistent efforts for control and prevention. Disease related morbidity and mortality is the result of the parasite asexual cycle of red blood cell (RBC) invasion and intraerythrocytic replication, while disease transmission depends on a subset of parasites that escape this cycle and differentiate into gametocytes. Upon ingestion by a compatible mosquito vector, gametocytes embark on sexual reproduction and sporogonic development. Inside the mosquito midgut, male and female gametocytes rapidly produce gametes, which escape from the host cell membrane and fuse to form zygotes. Within hours, zygotes develop to motile ookinetes that escape the blood bolus-encasing peritrophic matrix and traverse the midgut epithelium. On the basal side of the epithelium, ookinetes develop to replicative oocysts where thousands of sporozoites are produced. Oocysts burst and sporozoites released into the hemocoel migrate to the salivary glands from where they are transmitted to a new host during a subsequent mosquito bite.
The gametocyte-to-ookinete-to-oocyst developmental transition is completed within the first 24 h in the mosquito midgut and is the most critical stage of the entire transmission cycle. The ingested parasite populations suffer substantial losses during this stage resulting in very few oocysts and in most cases, termination of transmission. This stage is therefore a good target of interventions aiming to control disease transmission (Aly and Matuschewski, [@b1]; Churcher *et al*., 2010; 2013[@b7],[@b8]; Griffin *et al*., [@b18]). However, the relatively small number of proteins that have been characterized to date with established functions in these stages does not permit comprehensive understanding of the molecular processes that control this transition stage, which could in turn inform the development of respective interventions. This is due to the rather complex regulatory mechanisms of gene expression, which hinder the identification of proteins and molecular mechanisms involved in these developmental processes.
Transcriptomic (Hayward *et al*., [@b20]; Mamoun *et al*., [@b37]; Bozdech *et al*., [@b5]; Le Roch *et al*., [@b34]; Hall *et al*., [@b19]; Silvestrini *et al*., [@b46]; Vontas *et al*., [@b52]; Xu *et al*., [@b55]; Young *et al*., [@b56]; Raibaud *et al*., [@b43]) and proteomic (Florens *et al*., [@b16]; Lasonder *et al*., 2002; 2008[@b32],[@b33]; Hall *et al*., [@b19]; Khan *et al*., [@b31]) studies, have revealed a key role of transcriptional regulation in *Plasmodium* biology. A relatively good correlation between transcript and protein temporal expression patterns has been revealed, which appears to generally apply also to late stages of the gametocyte-to-ookinete-to-oocyst developmental transition. Midgut invasion and transformation to oocyst are associated with transcripts specifically produced in the maturing zygote, e.g. the Circumsporozoite and TRAP-related protein (*CTRP*), chitinase (*CHT1*), secreted ookinete adhesive protein (*SOAP*), von Willebrand factor A domain-related protein (*WARP*) and others (Dessens *et al*., 1999; 2001; 2003[@b10],[@b11],[@b12]; Yuda *et al*., 1999a; 2001[@b57],[@b59]; Tomas *et al*., [@b50]; Kadota *et al*., [@b26]; Hirai *et al*., [@b21]; Ishino *et al*., [@b22]; Kariu *et al*., [@b29]; Siden-Kiamos *et al*., [@b45]; Ecker *et al*., [@b13]; Bushell *et al*., [@b6]). However, a temporal discontinuity between transcription and translation has also been observed as maternally inherited transcripts such as those encoding the major ookinete surface proteins P25 and P28 are expressed in female gametocytes but remain translationally repressed until after fertilization (Hall *et al*., [@b19]; Mair *et al*., 2006; 2010[@b35],[@b36]). Yet the example of the male inherited sporulation factor important for transmission that is transcribed and translated in male gametocytes but has a mutant phenotype manifested during the ookinete-to-oocyst transformation highlights the great complexity of the system (Bushell *et al*., [@b6]).
The principal aim of this study was to generate a comprehensive catalogue of genes that are transcriptionally regulated during *Plasmodium* development in the mosquito midgut. This data could be then used to guide future systematic approaches towards a better understanding of the gametocyte-to-ookinete-to-oocyst developmental transition. For this, we carried out a comprehensive transcriptional profiling of the developmental migration of the rodent malaria parasite *Plasmodium berghei in vivo* in the Afrotropical mosquito *Anopheles gambiae*, from midgut blood bolus stages to mature sporulating oocysts, using oligonucleotide DNA microarrays. We clustered the transcriptional profiles of genes showing regulation across the various time points and, guided by the profiles of already characterized genes, generated lists of genes putatively involved in parasite developmental programmes and interactions with the vector. To assess the functional relevance of our findings, we selected for targeted gene disruption and phenotypic characterization two genes with peak transcription 24 h post-infection (hpi). This analysis showed that disruption of either of the two genes compromises the capacity of parasites to infect the mosquito midgut. Our data provide new insights into gene expression during *Plasmodium* sexual and sporogonic development in the mosquito and identifies novel potential targets of malaria transmission blocking interventions.
Results
=======
Transcriptional profiling of *P. berghei* in the *A. gambiae* midgut
--------------------------------------------------------------------
We carried out three independent biological replicate infections of *A. gambiae* with the 259c12 line of *P. berghei* that constitutively expresses GFP (Franke-Fayard *et al*., [@b17]). For each replicate, RNA was prepared from 30--40 mosquito guts at six discrete time points post-infection; mixed asexual and sexual stages in the blood bolus (1 h), ookinete midgut invasion (24 h), early-stage oocysts (48 h), mid-stage oocysts (5 days), sporulating oocysts (10 days) and mature oocysts (13 days). Blood boluses were removed from 48 h guts to eliminate remnants of blood stage parasites.
To test the suitability of RNA samples, we performed three quality control assays. (i) We assessed the intensity of infection by examining the presence of oocysts in mosquito midguts at day 10. The average oocyst counts were 25.9, 32.1 and 40.7 in the three replicate infections respectively. (ii) As parasite developmental dynamics naturally fluctuate between infections, we carried out a quantitative real-time PCR (qRT-PCR) analysis of the *GFP* transcript levels in each of the time points and replicate infections. In each replicate, the GFP expression in each time point was referenced to the average GFP expression across all the time points. In all the replicates, the infection dynamics inferred from the *GFP* levels indeed resembled the expected parasite population dynamics in the mosquito midgut (Supporting Information [Fig. S1A](#sd1){ref-type="supplementary-material"}). (iii) We examined the expression of three stage-specific genes by qRT-PCR, including the gametocyte-specific *P28* gene, the zygote- and ookinete-specific *CTRP* gene and the sporozoite-specific circumsporozoite protein (*CSP*) gene. All the genes exhibited expected expression profiles (Supporting Information [Fig. S1B--D](#sd1){ref-type="supplementary-material"}).
We used the RNA samples in hybridizations of oligonucleotide DNA microarrays (Mair *et al*., [@b35]; Bushell *et al*., [@b6]). Our design involved hybridization of each of the RNA samples against a standard reference RNA that was a mixture of the RNA samples of each replicate infection, pooled according to the *GFP* expression as described in the 'Experimental procedures'. This design was chosen to ensure that all transcripts were represented in the reference sample.
Mapping of the oligonucleotide probes revealed that the microarrays encompassed 4284 of the 5164 genes predicted in the *P. berghei* genome according to the PlasmoDB 11.1 May 2014 release (i.e. 83% coverage). Of these, 3454 genes were identical to those included the original array design and were represented by the same probes, while 830 resulted from merging or splitting of genes between genebuilds and thus were represented by a different combination of probes. To preclude differential handling, the latter gene group was not considered further.
Data normalization and one-way analysis of variance (ANOVA) statistical tests on gene expression data following correction with the Benjamini-Hochberg hypergeometric test (see 'Experimental procedures') revealed that 1639 of 3454 genes exhibited statistically significant differential regulation between at least two of the time points (*P* ≤ 0.05; Supporting Information Table S1). Of these, 564 genes showed at least 0.8 log~2~-transformed fold difference between their minimum and maximum expression (Supporting Information Table S2). Clustering of the expression profiles of these 564 genes using a combination of self-organizing maps (SOM) and K-means clustering revealed the presence of a total of 12 co-expression clusters: six main clusters, of which four are divided into sub-clusters. These clusters together depicted the *P. berghei* developmental transcriptome in the mosquito midgut (Fig. [1](#fig01){ref-type="fig"} and Supporting Information Table S2). In support of our approach, genes with known developmental expression profiles were mapped in expected clusters and used to guide the annotation of the expression map.
{#fig01}
Characterization of developmental transcription profiles
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Genes exhibiting enriched expression in blood bolus stages (mixed asexual and sexual stages) are grouped into two highly populated co-expression clusters (CL1 and 2), together encompassing 381 genes (Fig. [1](#fig01){ref-type="fig"} and Supporting Information Table S2). CL1 is divided into five sub-clusters (CL1a-e), differentiated between them mainly based on the levels of differential regulation, together comprising 354 genes with transcript levels decreasing after 1 hpi. *MSP8* (Black *et al*., [@b4]) and *AMA1* (Narum and Thomas, [@b39]), the transcription factor *AP2-SP* (Yuda *et al*., [@b61]), the RNA helicase *DOZI* (Mair *et al*., [@b36]), *MTIP* (Bergman *et al*., [@b2]) and the calcium-dependent protein kinase *CDPK4* (Billker *et al*., [@b3]) belong to CL1. The master regulator of male-specific events during gametogenesis CDPK4 (as well as MTIP) is found in CL1e, which is characterized by an additional slightly increased expression during sporogony. Indeed, it was previously hypothesized that CDPK4 also has an unknown function during sporogony (Billker *et al*., [@b3]). Quantitative real-time PCR analysis confirmed the expression of *CDPK4* at 10 dpi (Supporting Information [Fig. S2](#sd1){ref-type="supplementary-material"}). CL2 contains 27 genes that are highly expressed in both 1 and 24 hpi, including the major zygote and ookinete surface proteins *P25* and *P28* (Paton *et al*., [@b41]).
CL3 is composed of two sub-clusters. CL3a is a tight cluster comprised of 21 genes exhibiting a sharp peak in transcript abundance at 24 hpi, suggesting enriched or specific expression in ookinetes (Fig. [1](#fig01){ref-type="fig"} and Supporting Information Table S2). Six of these genes have been previously implicated in mosquito midgut invasion, including *CTRP* (Dessens *et al*., [@b10]), *SOAP* (Dessens *et al*., [@b12]), *CHT1* (Dessens *et al*., [@b11]), *CDPK3* (Ishino *et al*., [@b22]), *WARP* (Yuda *et al*., [@b59]) and *PSOP2* (Ecker *et al*., [@b14]). Of the remaining 15 genes, five encode proteins bearing domains implicated in metabolic and housekeeping functions and 10 are of unknown function. Putative AP2-O transcription factor binding sites (Yuda *et al*., [@b60]) are found within a 1 kb region upstream of the open reading frames (ORFs) for 17 of these genes (Supporting Information Table S2), indicative of the ookinete specificity of this cluster.
CL3b is a small cluster that includes six previously uncharacterized genes showing increased expression at both 24 hpi and maturing oocysts. This cluster involves the *Plasmodium* perforin-like protein, PPLP4 (Ecker *et al*., [@b14]). Quantitative real-time PCR analysis confirmed expression of *PPLP4* in oocysts (Supporting Information [Fig. S2](#sd1){ref-type="supplementary-material"}).
Very little is known about the type of gene products required in the developing oocyst. Our analysis detected a large shift in gene expression as the ookinete transitions to oocyst. Genes exhibiting enriched expression in oocyst stages are grouped into three main clusters (CL4-6 in Fig. [1](#fig01){ref-type="fig"} and Supporting Information Table S2) together encompassing 155 genes.
CL4 is a highly populated cluster of 86 genes that are up-regulated as parasites develop from blood bolus stages to ookinete and to oocyst and retain their expression levels throughout oocyst development. CL4 is further divided into two sub-clusters, CL4a and CL4b, respectively, based on the level of differential regulation between the first three time points.
CL5 includes 30 genes with increasing expression throughout oocyst development. It includes the serine repeated antigen 5 (*SERA5*) gene that is essential for sporozoite egress from the oocyst (Aly and Matuschewski, [@b1]).
Finally, CL6 involves 39 genes exhibiting expression similar to those in CL5 but characterized by increased expression at 13 dpi. It involves *CSP* that is known to be expressed in sporozoites and be essential for their development (Ménard *et al*., [@b38]).
In addition to using genes with known expression profiles to validate the profiling, we used qRT-PCR for a number of genes to test the power of our approach in discovering novel genes with temporally regulated expression (Supporting Information [Fig. S2](#sd1){ref-type="supplementary-material"}). We carried out three new experimental replicate infections of *A. gambiae* mosquitoes with the 259c12 *P. berghei* line, and prepared RNA samples from the six time points using a protocol identical to that we used for the DNA microarray analysis. We examined the expression of 12 genes including seven novel genes, two known genes with newly detected expression in the oocyst stage, *CDPK4* and *PPLP4*, and the *P28*, *CTRP* and *CSP*; the latter three served as stage-specific controls (Supporting Information [Fig. S2](#sd1){ref-type="supplementary-material"}). The *GFP* transgene served as an internal reference for constitutive expression. An overall great consistency was observed between the DNA microarray and qRT-PCR expression profiles for all the genes tested. Minor relative quantitative differences are thought to be due to the different normalization methods and the different sets of probes/primes used in each approach.
Characterization of *GAMER* and *HADO*
--------------------------------------
We focused downstream analysis on genes putatively involved in ookinete development and transformation to oocyst, i.e. genes showing peak expression 24 hpi and included in CL3a and CL3b. Genes exhibiting *P25* and *P28*-like profiles, i.e. transcriptionally peak in ookinetes but are abundantly expressed also in blood bolus stages, and included in CL2, were not considered in the present study.
We prioritized for genetic characterization genes of which (i) orthologues exist in *P. falciparum* and *P. vivax*, (ii) gene models could indicate feasibility of targeted disruption by homologous recombination, including high-quality sequences for successful design of disruption vectors and sufficient distance from neighboring genes to preclude non-specific gene knockout and (iii) predicted protein domains did not hint at housekeeping functions. Here, we present the genetic and phenotypic characterization of two genes: PBANKA_122540 and PBANKA_060390, called *GAMER* and *HADO*, respectively, for reasons explained below.
The expression profiles of *GAMER* and *HADO* were confirmed by qRT-PCR (Fig. [2](#fig02){ref-type="fig"}A and B). We also examined the expression patterns of the two genes in early stages of sexual development using RT-PCR on purified *in vivo* and *in vitro* cultured parasite stage-specific populations (Fig. [2](#fig02){ref-type="fig"}C). The combination of these assays revealed that *GAMER* and *HADO* are expressed in gametocytes and further up-regulated in the zygote and ookinete. *HADO* shows paucity of expression throughout oocyst development whereas *GAMER* is re-expressed in a 13 day oocyst, presumably in sporozoites. Literature searches revealed that *GAMER* transcripts are down-regulated in gametocytes lacking CITH (CAR-I and fly Trailer hitch), the interacting partner of DOZI (Mair *et al*., [@b36]), while *HADO* transcripts are moderately enriched in gametocytes lacking DOZI (Mair *et al*., [@b35]). DOZI and CITH are repressors of maternally supplied mRNA important for ookinete development (Mair *et al*., [@b36]). Interestingly, putative *P. berghei* ookinete transcription factor AP2-O binding sites are found within 200--400 bp upstream of the predicted *GAMER* and *HADO* ORFs (Supporting Information Table S2).
{#fig02}
*GAMER* encodes a small 96 amino acid protein (10.7 kD) lacking recognizable domains, as revealed by both manual annotation and three-dimensional (3D) homology modelling. The deduced protein is conserved among plasmodia with 91%, 86%, 71%, 70% and 65% identity to *P. yoelii* PYYM_1228100, *P. chabaudi* PCHAS_122600, *P. knowlesi* PKH_011340, *P. vivax* PVX_093500 and *P. falciparum* PF3D7_1205200 respectively (Supporting Information [Fig. S3](#sd1){ref-type="supplementary-material"}). We produced rabbit polyclonal antibodies against the C-terminal peptide SEKAKELLRERGYVV (EP092419; 82--96 aa) of *P. berghei* GAMER. Western blot analysis of mixed blood stages, gametocytes and ookinetes confirmed that GAMER is a 10 kDa polypeptide specifically produced in ookinetes (Fig. [2](#fig02){ref-type="fig"}D). However, immunofluorescence assays (IFA) on *in vitro* purified (non-activated) gametocytes using GAMER antibodies revealed protein presence in the gametocyte cytoplasm, where it localizes to discrete foci possibly of vesicular nature (Fig. [2](#fig02){ref-type="fig"}F). IFA on purified ookinetes showed a diffused signal in the ookinete cytoplasm (data not shown).
*HADO* encodes a 379 amino acid protein (44.7 kD) that is also well conserved among plasmodia with 95%, 83%, 78%, 76% and 70% identity to PY05386, PF3D7_1205200, PCHAS_060570, PVX_084290 and PKH_130370 respectively (Supporting Information [Fig. S4](#sd1){ref-type="supplementary-material"}). Manual annotation and homology modelling analysis revealed that *HADO* encodes a haloacid dehalogenase (HAD) domain protein with structural similarity to the human magnesium-dependent phosphatase Mdp-1 (Supporting Information [Fig. S5](#sd1){ref-type="supplementary-material"}; Seifried *et al*., [@b44]). The name HADO was derived from HAD domain ookinete protein. The FDYDDTI motif of the HAD domain is conserved in all *Plasmodium* orthologues and the conserved 3D models suggest a putative DxDxT phosphatase with a very high probability (Supporting Information Figs S4 and S5). Western blot analysis using a rabbit polyclonal antibody raised against the C-terminal peptide VFPINFKDRNSIKNL (240--254 aa) of HADO identified a ∼ 45 kD protein expressed in ookinetes (Fig. [2](#fig02){ref-type="fig"}E), while preliminary data indicated low expression in purified gametocytes that was below threshold expression in mixed blood stages. IFA of *in vitro* purified ookinetes using the *P. berghei* HADO antibody revealed a distinctive cortical localization along the concave ookinete periphery (Fig. [2](#fig02){ref-type="fig"}G).
Generation and phenotypic analysis of *Δpbgamer* and *Δpbhado* mutant parasites
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*Plasmodium berghei* mutants were generated by replacing the entire *GAMER* and large parts of the *HADO*-coding regions with modified *Toxoplasma gondii* pyrimethamine resistance cassettes in the Pbc507 GFP-expressing parasite reference line (Janse *et al*., [@b24]; Supporting Information [Fig. S6A and B](#sd1){ref-type="supplementary-material"}). Integration of the disruption cassettes and disruption of each of the two genes in clonal parasite lines was verified by PCR (Supporting Information [Fig. S6C](#sd1){ref-type="supplementary-material"}) and Southern analysis of separated chromosomes and of digested genomic DNA (Supporting Information [Fig. S6D](#sd1){ref-type="supplementary-material"}). At least two clonal mutant lines per gene were generated from respective independent transfections and analysed as described below.
Phenotypic analysis revealed that both mutants exhibited normal development of asexual blood stages and mature gametocytes, while activation of male gametogenesis, as measured by the formation of exflagellation centres, was also normal in both mutants (Fig. [3](#fig03){ref-type="fig"}A--C). However, macrogamete to ookinete conversion was markedly reduced to 18% (*P* \< 0.0001) and 42% (*P* \< 0.01) for both *Δpbgamer* and *Δpbhado*, respectively, compared with 71.5% in *wt* parasites (Fig. [3](#fig03){ref-type="fig"}D). Both, *Δpbgamer* and *Δpbhado* macrogametes and ookinetes, albeit reduced in number, were morphologically normal and exhibited an expected surface distribution of P28 (Fig. [3](#fig03){ref-type="fig"}E).
{#fig03}
We assessed the ability of mutant parasites to develop to oocysts in both *A. gambiae* and *A. stephensi* mosquitoes that were fed on mice infected with each of these mutant or control *wt* parasites. Mice with a parasitaemia of 6--7% and gametocytaemia 1--2% were used for mosquito infections. The numbers of oocysts were determined 10 dpi. The results showed that, compared with *wt* controls at day 10 pi, oocyst numbers were significantly reduced in both *Δpbgamer* and *Δpbhado* mutants, reflecting prior gamete-to-ookinete developmental defects (Fig. [3](#fig03){ref-type="fig"}F and G and Supporting Information Table S3). The numbers of salivary gland sporozoites of the two mutants were also significantly reduced compared with *wt* controls respectively (Supporting Information Table S4). Mutant parasites that developed to normal oocysts and infect the salivary glands were able to be transmitted to the vertebrate host by both *A. gambiae* and *A. stephensi* mosquitoes as revealed by bite-back experiments at days 18 and 21 dpi using susceptible BL6/C56 recipient mice (Supporting Information Table S4).
GAMER is essential for gamete release
-------------------------------------
The detection of GAMER in gametocytes prompted us to investigate whether the effect of gene disruption in ookinete development is due to defects prior to or after fertilization by monitoring the exflagellation event at real time using time-lapse microscopy. The results showed that activated *Δpbgamer* male gametocytes produce morphologically normal and motile microgametes; however, the vast majority of them was unable to detach from the residual body of the gametocytes and remained attached to the exflagellation centres even 30 min post-activation (Fig. [4](#fig04){ref-type="fig"}A). This phenotype is consistent with a putative function of GAMER in male gametocytes. The name GAMER is therefore derived from GAMEte Release.
{#fig04}
We investigated further the *Δpbgamer* male gamete release phenotype through genetic crosses with *P. berghei* mutants producing fertile gametes of one sex but not the other. Indeed, genetic crosses with *Δpbs48/45*, which contribute fertile female but not male gametes, could not rescue the mutant phenotype (Fig. [4](#fig04){ref-type="fig"}B). Surprisingly, similar results were obtained when *Δpbgamer* was crossed to *Δpbs47*, which contribute fertile male but not female gametes, i.e. the mutant phenotype could not be rescued. These data indicated that *Δpbgamer* macrogametes are also defective, despite the apparently normal distribution of P28. It remains to be investigated whether GAMER is indeed involved in both male and female gametocyte release from the erythrocyte membrane. Equivalent results were obtained *in vivo*, in *A. gambiae* infected with *Δpbgamer* crossed with either *Δpbs47* or *Δpbs48/*45 respectively. Neither the male nor the female alleles alone could restore the oocyst numbers, confirming that the existence of functional forms of both parental alleles is essential for mosquito infection (Fig. [4](#fig04){ref-type="fig"}C and Supporting Information Table S6).
Discussion
==========
Malaria remains one of the most devastating diseases causing high morbidity and mortality despite persistent efforts for elimination. The inadequacy of current preventive measures can be largely attributed to the complex developmental life cycle of the malaria parasite in its human host and mosquito vector. Elucidation of the molecular mechanisms underlying parasite development and the interactions with its host and vector can provide fundamental insights into *Plasmodium* biology, which could eventually help in the design of novel disease elimination strategies.
Despite the wealth of transcriptome and proteome data on the asexual *Plasmodium* life cycle in the vertebrate host blood, mechanisms and molecules involved in vector stages of the life cycle remain poorly understood. Here, we report the profiling of the developmental transcriptomes of the rodent malaria parasite *P. berghei* in the midgut of the major African vector, *A. gambiae*, from blood bolus stages to mature oocysts in order to gain molecular insights into this critical phase of malaria transmission. This phase encompasses three major developmental processes: sexual reproduction (including gametogenesis and fertilization), meiotic development of the zygote/ookinete and vegetative growth of the oocyst via endomitotic replication. These processes are separated from each other by only few hours, while the transition between the latter two processes requires traversal of the mosquito midgut, a step that corresponds to the most critical population bottleneck of the entire parasite life cycle; more often than not, transmission is terminated at this very stage.
Our data provide new insights into the transcriptional programmes underpinning these developmental processes with a large number of genes found to be expressed between the various time points. These genes are grouped into distinct transcriptional programmes according to their expression profile, some of which operate during the various developmental processes, while others are involved in transition stages.
While epigenetic (Lopez-Rubio *et al*., [@b9001]) and post-transcriptional regulation (Mair *et al*., 2006; 2010[@b35],[@b36]) have emerged as significant regulatory mechanisms of gene expression, the AP2 protein family of transcriptional regulators is thought to be the fundamental machinery guiding gene expression throughout *Plasmodium* life cycle (Painter *et al*., [@b40]). AP2 proteins are shown to regulate the asexual to sexual life cycle switch (Kafsack *et al*., [@b27]; Sinha *et al*., [@b48]), the ookinete and sporozoite development in the vector (Yuda *et al*., 2009; 2010[@b60],[@b61]) and the sporozoite development in the host liver (Iwanaga *et al*., [@b23]). The AP2-O (Yuda *et al*., [@b60]) appears to be particularly relevant in understanding our data. It is specifically transcribed in the female *P. berghei* gametocyte, and its transcript that is translationally repressed in a DOZI-dependent manner becomes available for translation in the zygote/ookinete (Yuda *et al*., [@b60]). There, it drives the transcription of genes largely involved in midgut invasion including *CTRP*, *SOAP*, *CHT1*, *WARP*, *P25*, *P28*, *CDPK3* and *PSOPs* (Yuda *et al*., [@b60]).
A key objective of this work has been the molecular dissection of midgut invasion that coincides with the ookinete-to-oocyst developmental transition. Indeed, we detected a cluster of 21 genes (CL3) exhibiting a sharp peak in transcript abundance at 24 hpi, suggesting that these genes are substantially enriched or specifically expressed in midgut invading ookinetes, including *CTRP*, *SOAP*, *CHT1*, *WARP*, *CDPK3* and *PSOP2*. Putative AP2-O transcription factor binding sites (Yuda *et al*., [@b60]) are present in the upstream region of 21 of these 28 genes indicative of the ookinete specificity of this cluster. The phenotypic and functional characterization of *HADO* confirmed the functional identity of this cluster by revealing a new regulator of ookinete development. Therefore, CL3 appears to represent a classical example of AP2-O-regulated cluster, in which gene transcription is tightly linked to gene function.
*HADO* encodes a HAD domain phosphatase with a DxDxT catalytic motif, structurally similar to human Mdp-1 (Seifried *et al*., [@b44]). Proteins with this domain are known to be involved in the regulation of the actin dynamics through cofilin dephosphorylation. The distinctive cortical localization of HADO along the concave side of ookinetes supports the hypothesis that the protein may function in regulating the cellular actin dynamics, maybe towards carrying out or transitioning between specific movements types that take place during midgut invasion (Vlachou *et al*., [@b51]; Kan *et al*., [@b28]). Along these lines, it remains to be investigated whether *HADO* mutant parasites exhibit specific defects in ookinete motile behaviour. Nevertheless, HAD domain magnesium-dependent phosphatases are also known to play roles in lipid-associated cell signalling and metabolism, including Mdp-1, which functions to free proteins from glycation products. An alternative hypothesis for the function of HADO derives from the characterization of a DxDxT phosphatase in *Trypanosoma brucei*, which regulates differentiation in the tsetse fly via a glycosomal signalling pathway, activating major changes in parasite physiology that permit vector colonization (Szöőr *et al*., [@b49]).
The second gene we characterized in this study, *GAMER*, is found in CL3b that includes genes sharing transcriptional enrichment in ookinetes and midgut sporozoites. The function of GAMER in male gamete egress from the host erythrocyte together with our discovery that neither the male nor the female *GAMER* alleles can restore the mutant phenotype makes it likely that the protein is also involved in female gametocyte egress from host erythrocytes. Indeed, it has been suggested that both male and female gametocyte egress is governed by common mechanisms implicating PbMDV/PEG3 (Ponzi *et al*., [@b42]). This protein is involved in destabilization of the parasitophorous vacuole membrane, prior to erythrocyte membrane lysis in a yet unknown mechanism. Therefore, similarly to *GAMER*, both the male and the female *PbMDV/PEG3* alleles are required.
Parasite egress has been linked to gametocyte organelles (Wirth and Pradel, [@b53]). Both PbMDV/PEG3 and the gametocyte-specific protein Pfg377, which is also involved in egress of *P. falciparum* female gametes, are localized in osmiophilic bodies. Moreover, the perforin-like protein PPLP2 that also mediates gamete egress in both *P. falciparum* and *P. berghei* localizes in *P. falciparum* gametocyte vesicles other than Pfg377-positive osmiophilic bodies (Deligianni *et al*., [@b9]; Wirth *et al*., [@b54]). These data highlight the important and likely synergistic function of vesicles in gamete egress and are consistent with the putative function and vesicular localization of GAMER.
In sharp contrast to the small number and fine temporal regulation of genes in CL3 is the large number of genes expressed throughout the first 24 h in the mosquito midgut, which make CL1 and CL2, the expression of which progressively declines. This study was not designed to distinguish between sexual stage expression and asexual stage contamination in the blood bolus; however, previous *in vitro* studies in *P. falciparum* have shown that orthologues of the vast majority of genes in these clusters are already expressed in gametocytes and/or gametes (Florens *et al*., [@b16]; Lasonder *et al*., [@b32]), while some are also expressed in asexual stages (Le Roch *et al*., [@b34]). Together these data support the hypothesis that ookinete development is supported by at least two distinct transcriptional programmes: constitutive expression throughout sexual and meiotic development (CL1 and CL2) and transient expression in ookinetes (CL3). The second programme appears to be regulated mainly by AP2-O and includes genes linked to midgut invasion, some with confirmed localization in micronemes. Transcription of these genes appears to be initiated 8--10 h post-fertilization, and their expression remains active until the transformation to oocyst (Yuda *et al*., 1999b; 2001[@b58],[@b59]).
Commitment to sexual differentiation in the vertebrate host is mediated by significant changes in the transcriptional repertoire (Hall *et al*., [@b19]; Young *et al*., [@b56]), while asexual replication through schizogony is characterized by cyclical expression of distinct subsets of genes at each different stage (Mamoun *et al*., [@b37]; Bozdech *et al*., [@b5]). Here we show that the same is true for parasite development in the mosquito vector. The transition from the sexual, meiotic development in the mosquito midgut lumen to the asexual sporogonic development in the mosquito hemolymph is associated with a large shift in parasite transcriptional repertoire. At the same time, transcriptional activity in the oocyst seem to follow three main patterns, which in our assays appear to overlap significantly, perhaps because of asynchronous development of oocysts between, as well as within, mosquitoes. These patterns include the onset of oocyst development (CL4), maturation (CL5) and sporulation (CL6), and they may represent distinct transcriptional programmes.
The first of these programmes is very transient and presumably the most important with respect to perpetuation or termination of transmission. At this stage, the motile ookinete completes its meiotic division and transitions to a sessile stage, preparing for sporogony. The second programme concerns rapid vegetative growth through endomitotic replication and mirrors erythrocytic schizogony. It involves a large number of largely uncharacterized genes, which are predicted to be associated with general housekeeping processes such as transcription, translation, protein processing, signalling, cell cycle regulation, lipid metabolism, organelle transport and vesicle trafficking. This programme may be separated into smaller sub-programmes corresponding to the different stages of sporogony. The third programme includes genes expressed during late oocyst development, presumably involved in sporulation or sporozoite development and migration. This involves a cluster of 39 genes that alone cannot possibly support the function of sporozoites, including cell motility and other housekeeping processes. Therefore, we hypothesize that, like ookinetes, sporozoites are supported by at least two main programmes, a generic one that operates throughout oocyst development and a specific one that specifically operates during late sporogonic stages. Functional characterization of genes in these programmes will provide important insights into this late developmental phase in the vector, which is of high importance for transmission of the disease.
Experimental procedures
=======================
Ethics statement
----------------
This study was carried out in strict accordance with the United Kingdom Animals (Scientific Procedures) Act 1986. The protocols for maintenance of mosquitoes by blood feeding and for infection of mosquitoes with *P. berghei* by blood feeding on parasite-infected mice were approved and carried out under the UK Home Office License PLL70/7185 awarded in 2010. The procedures are of mild to moderate severity and the numbers of animals used are minimized by incorporation of the most economical protocols. Opportunities for reduction, refinement and replacement of animal experiments are constantly monitored, and new protocols are implemented following approval by the Imperial College London Ethical Review Committee.
Parasite cultivation and mosquito infections
--------------------------------------------
*Plasmodium berghei* strains ANKA 2.34 and non-gametocyte producer HPE cy1m50 cl1, the GFP-expressing reference lines, 259c12 (Franke-Fayard *et al*., [@b17]) and *507* (Janse *et al*., [@b24]) and the *Δpbs48/45* (RMgm-346) and *Δpbs47* (van Dijk *et al*., [@b9002]) mutant lines (kindly provided by Chris Janse) were used in this study. Parasite handling and purification were performed as described (Janse *et al*., [@b25]). *A. gambiae* Yaoundé and *A. stephensi* SD500 were reared and infected with *P. berghei* by direct feeding on infected mice with parasitaemia of 6--7% and gametocytaemia 1--2%, respectively, using standard protocols (Sinden, [@b47]).
DNA microarrays
---------------
The Agilent oligonucleotide *P. berghei* microarray platform is described previously (Bushell *et al*., [@b6]). Remapping of oligonucleotide probes on the latest *Plasmodium* genome assembly and annotation (PlasmoDB 11.1 May 2014) revealed coverage of 4284 of the 5164 predicted genes. Of these, 3454 genes were the same as in the original microarray design and represented by the same probes, while 830 genes resulted from merging or splitting of genes between the various genebuilds and were represented by a different combination of probes compared with the original probe combinations. The latter gene group was not considered further to preclude errors due to gene annotation problems.
For hybridizations, total RNA was extracted from 30--40 *A. gambiae* midguts infected with the 259c12 parasite line at 1 h, 24 h, 48 h and 5, 10 and 13 days (d) post-infection, from three replicate infections. The midguts were dissected in ice-cold phosphate-buffered saline (PBS) under a dissecting scope and immediately immersed in Trizol® reagent (Invitrogen). They were mechanically homogenized and total RNA was isolated according to the manufacturer\'s instructions under RNAse-free conditions. Total RNA was quantified using a NanoDrop® ND-1000 Spectrophotometer (Thermo Scientific) and stored at − 80°C.
A standard reference was generated for each replicate infection by pooling time point samples based on the GFP expression. Specifically, to calculate the proportional amount of total RNA of each time point to be contributed to the standard reference and ensure a more-or-less uniform representation of all the time points, the average GFP expression across time points was divided by the product of the GFP expression in that time point and the sum of GFP expression values in all the time points.
The standard reference was processed in parallel to and under the same conditions as the labelled RNA from each of the time points. Briefly, from each time point sample and the standard reference, 2 μg were used for generation and labelling of cRNA using the Agilent Low RNA Input Fluoresence Amplification Kit Protocol according to manufacturer\'s instructions. Two micrograms of Cy3 and Cy5 labelled cRNAs, from a time point sample and the standard reference, respectively, were mixed and competitively hybridized on the Agilent microarrays using the *in situ* Hybridisation Kit Plus according to the manufacturer\'s instructions.
The hybridized microarrays were scanned using the Gene-Pix 4000B scanner (Axon Instruments). Grid alignment, registering spot signal intensity, estimation of local backgrounds and manual inspection of spot quality were carried out using Gene-Pix Pro 6.1. Normalization of data was achieved using the linear regression method (Lowess) in GeneSpring GX 12.6 (Agilent Technologies).
Normalization of data was performed using the locally weighted linear regression method (Lowess) in GeneSpring GX 12.6 (Agilent Technologies). Significant transcriptional differences across infection stages were calculated using a one-way ANOVA with a *P*-value cut-off of 0.05, following correction with the Benjamini-Hochberg hypergeometric test. Co-expression analysis was carried out for genes exhibiting at least 0.8-fold change in the log~2~ scale between their minimum and maximum expression values using a combination of SOM and K-means analysis. Co-expression clusters were visualized using the Cluster software version 2.11 and Java Tree View software version 1.1.6 (Eisen *et al*., [@b15]).
Transcriptional profiling using qRT-PCR or RT-PCR
-------------------------------------------------
Total RNA was isolated from erythrocytic and sexual parasite stages and from infected mosquito midguts using the Trizol® reagent (Invitrogen). Gene-specific primers (Supporting Information Table S5) were designed using Primer3 (v. 0.4.0). Quantitative real-time PCR was carried out using SYBR-Green and the ABI Prism 7700 Sequence Detector (Applied Biosystems). *GAMER* and *HADO* transcript levels were normalized against transgenic *GFP* transcripts that provided an internal reference for the fluctuation in parasite numbers during development.
Generation of transgenic parasites
----------------------------------
Targeted disruption of *GAMER* and *HADO* was carried out by double homologous recombination in the *P. berghei* ANKA 2.34 or c507 genetic backgrounds as described (Janse *et al*., [@b25]). Briefly, 500--1000 bp regions upstream and downstream of each target gene were amplified from *P. berghei* genomic DNA using oligonucleotide primers carrying restriction enzyme sites: ApaI/HindIII for upstream and EcorI/BamHI for downstream regions (Supporting Information Table S5). PCR products were purified using a PCR purification kit (Qiagen) and cloned into the pBS-TgDHFR vector that encompasses polylinker sites flanking the modified *Toxoplasma gondii* dihydrofolate gene (*tgdhfr/ts*) conferring resistance to pyrimethamine (Dessens *et al*., [@b10]). Transfection of EcoRI/BamHI linearized disruption cassettes, selection of transgenic lines and limiting dilution cloning were carried out as previously described (Janse *et al*., [@b25]).
Genotypic analysis of transgenic parasites
------------------------------------------
*P. berghei* genomic DNA was prepared from transfected blood stage parasite populations. White blood cells were removed by filtration over CF-11 column (Whatman) and RBCs were lysed by incubation for 20 min on ice in 0.17 M ammonium chloride. Genomic DNA was extracted using DNeasy kit (Qiagen) and subjected to diagnostic PCR and Southern blot analysis to assess successful integration. For Southern blot analysis of transgenic lines, genomic DNA was digested with *HindIII* (*Δpbgamer*) or *EcoRV* (*Δpbhado*). Blots were hybridized with a PCR-generated probe recognizing a 500--1000 bp region of the mutants. Pulse field gel electrophoresis was performed on chromosomes derived from purified blood stage parasites and the blot was hybridized against a probe recognizing the HindIII/EcoRV digest *tgdhfr/ts* fragment obtained from the pBS-TgDHFR vector.
Exflagellation assays
---------------------
Equal parts of parasite-infected blood were mixed with ookinete culture medium as described (Bushell *et al*., [@b6]). Following 10 min incubation at room temperature, the number of exflagellation centres and total RBCs were counted and compared with the male gametocytaemia as determined by Giemsa-stained tail blood smears.
Macrogamete to ookinete conversion assays
-----------------------------------------
Macrogamete to ookinete conversion assay was carried out as described (Billker *et al*., [@b3]). Briefly, ookinete culture samples (0.1 mL) from a 24 h incubated culture were harvested at 500 g for 5 min. Pellets were resuspended in 0.1 mL ookinete medium and incubated with Cy3 labelled P28 antibody (1:100 dilution) for 10 min on ice. The conversion ratio was calculated from the total number of Cy3 positive ookinetes (crescent-shaped) divided by the total number of Cy3 positive macrogametes (spherical).
Statistics
----------
For statistical analysis of mosquito infection, *P*-values were calculated using the Mann--Whitney *U*-test. Statistical analysis for exflagellation and ookinete conversion assays was performed using a two tailed, unpaired Student\'s *t*-test with error bars representing the standard error of mean.
Imaging and enumeration of parasites
------------------------------------
Following mosquito infection and dissection, midguts were fixed in 4% formaldehyde (v/v) (16% methanol-free, ultrapure stock diluted in PBS, Polysciences Inc.) for 20 min at room temperature and washed three times for 10 min each in PBS. Fixed midguts were mounted in Vectashield® (VectorLabs) on glass slides under sealed coverslips. Oocyst numbers were counted at 10 dpi using fluorescence microscopy under ×10 magnification. Midgut and salivary gland sporozoite numbers were calculated from homogenates of 10 *P. berghei-*infected *A. stephensi* midguts or salivary glands at days 15 or 21 dpi respectively. The numbers of sporozoites per mosquito were calculated.
Transmission from mosquito to mouse
-----------------------------------
At least 30 *P. berghei-*infected mosquitoes were fed on anaesthetized C57BL/6 mice for 15 min at 18 and 21 dpi. Mice were allowed to recover and parasitaemia was monitored on days 5, 7, 10 and 14 following the recipient of potentially infective sporozoites by Giemsa-stained tail blood smears.
Genetic crosses
---------------
Genetic crosses between the *Δpbgamer* or *Δpbhado* and either male-deficient or female-deficient lines were carried out as described by infecting mice with different combinations of mutant parasites (Bushell *et al*., [@b6]). *A. gambiae* mosquitoes were infected by feeding on these mice.
Antibody production and detection
---------------------------------
Purified polyclonal peptide antibodies against GAMER and HADO were obtained from the pooled sera of two immunized rabbits (Eurogentec). α-PbGAMER (IgG19) targets the COOH-terminal peptide SEKAKELLRERGYVV (EP092419; 82--96 aa) and α-PbHADO (IgG21) targets the COOH-terminal peptide VFPINFKDRNSIKNL (EP092421; 240--254 aa). For Western blot analysis, samples of purified parasites were boiled under non-reducing or reducing conditions in SDS sample loading buffer, prior to 8% or 10% (for GAMER) SDS-PAGE protein fractionation. Immuno-detection by Western blot analysis was performed according to standard procedures using α-GAMER, α-HADO and α-TAT1 antibodies at 1:250, 1:100 and 1:1000 dilutions respectively. Secondary horse radish peroxidase (HRP) conjugated goat anti-rabbit IgG and goat anti-mouse IgG antibodies were used at 1:10 000 and 1:15 000 dilutions (Promega). For IFAs, purified inactivated gametocyte and ookinete pellets were re-suspended in PBS, smeared on glass slides and allowed to air dry prior to fixation in 4% paraformaldehyde in PBS for 10 min. Fixed parasites were then permeabilized with 0.2% Triton X-100 in PBS for 5 min. Following blocking, α-GAMER and α-HADO antibodies were used at 1:100 dilution, α-P28 antibody was used at 1:500 dilution. Secondary antibodies included the ALEXA FLUOR 488 goat anti-rabbit IgG and ALEXA FLUOR 647 goat anti-mouse antibodies (Molecular Probes) all used at 1:1500 dilutions. Images were acquired using a Leica SP5 MP confocal laser-scanning microscope. Images were analysed with the ImageJ software.
Homology modelling
------------------
Homology modelling was carried out using the homology/analogy recognition engine PHYRE2 (Kelley and Sternberg, [@b30]). HADO homology modelling (37% aa coverage) was generated based on the highest scoring template (PDB code IU70, 98% confidence) corresponding to the magnesium-dependent phosphatase 1. All structural figures were generated using PyMol (the PyMOL Molecular Graphics System, Version 1.3, Schrödinger LLC, Portland, USA (<http://www.pymol.org/>).
Phylogenetic analysis
---------------------
GAMER, HADO and their orthologous or homologous sequences were aligned using ClustalW2. BioEdit Sequence Alignment Editor was used for visualization of alignments.
We are grateful to Fotis C. Kafatos for supporting this work. We thank Hassan Yassine for helping with confocal imaging, Nikos Trasanidis for assistance with microarray analysis during revisions and Chryssa Taxiarchi for assistance with manuscript editing. We also thank the anonymous reviewers for their constructive comments that helped us to improve the manuscript. This work was largely funded by the Wellcome Trust grants GR077229/Z/05/Z and 093587/Z/10/Z. E.S.C.B was supported by a Wellcome Trust PhD studentship (PC3388). Lesser support was also received by the European Commission FP7 HEALTH-F3-2008-223736 Collaborative Project 'TransMalariaBloc' and the EVIMalaR Network of Excellence grant of the European Commission Framework Programme (FP7/2007--2013) under grant agreement N°242095.
Supporting information
======================
Additional Supporting Information may be found in the online version of this article at the publisher\'s web-site:
######
Gene expression in midgut samples used for the microarray experiments.
A. *GFP* transcript levels were monitored by qRT-PCR and normalized against the average GFP expression across all the time points and are presented in a logarithmic scale. The lowest value (2 dpi) is arbitrarily set at 10.
B--D. Quantitative real-time PCR analysis of *P28*, *CTRP* and *CSP* transcript levels. Values at all time points are normalized against *GFP* expression. In A--D, the mean expression values of three independent biological replicates are shown, with each time point assayed in duplicate. Error bars indicate standard error of the mean.
######
Comparison of the expression profiles of 12 genes obtained by DNA microarrays and real-time qRT-PCR. Quantitative real-time PCR data were obtained from three independent replicate infections of *A. gambiae* mosquitoes with the *P. berghei* 259c12 line, each assayed in two technical replicates. Mean fold regulation and standard errors of the mean (SEM) are shown. PlasmoDB Gene IDs are indicated.
######
Multiple sequence alignment of *Plasmodium* GAMERs. Sequence alignment of *P. berghei* GAMER (PbGAMER; PBANKA_122540) and its orthologues in *P. yoelii* (PyGAMER; PYYM_1228100); *P. chaubaudii* (PcGAMER; PCHAS_122600), *P. knowlesi* (PkGAMER; PKH_011340); *P. vivax* (PvGAMER; PVX_093500) and *P. falciparum* (PfGAMER; PF3D7_0805200). Coloured blocks outline the conserved among all species residues. Alignment was carried out using the ClustalW2; BioEdit Sequence Alignment Editor was used for visualization.
######
Multiple sequence alignment of *Plasmodium* HADOs. The putative HAD-like domain is marked by grey boundaries. This region shows high conservation among all the orthologues. The conserved residues involved in putative phosphor transfer catalysis are marked by red outlines and arrows. *P. berghei* (PbHADO; PBANKA_060390); *P. yoelii* (PyHADO; PY05386); *P. chaubadii* (PcHADO; PCHAS_060570), *P. knowlesi* (PkHADO; PKH_130370), *P. vivax* (PvHADO; PVX_084290) and *P. falciparum* (PfHADO; PF3D7_120520). Coloured blocks indicate residues conserved among all species. Alignment was carried out using the ClustalW2; BioEdit Sequence Alignment Editor was used for visualization.
######
Structural model of *Plasmodium* HADOs. 3D homology modelling of *P. berghei* HADO (PBANKA_060390) based on the magnesium-dependent phosphatase 1 (Mdp-1). The 3D model contains four conserved loops (grey) supported by a α/β (yellow and blue) core structure. The putative conserved residues aspartic (D), serine (S), arginine (R) and aspartic (D) on the conserved loops involved in the catalysis of phosphoryl transfer are shown in stick form. These residues are conserved in all the orthologues of HADO: *P. yoelii* (PY05386), *P. chaubadii* (PCHAS_0605700), *P. knowlesi* (PKH_130370), *P. vivax* (PVX_084290) and *P. falciparum* (PF3D7_120520).
######
Generation and genotypic analysis of *Δpbgamer and Δpbhado* mutant parasites. (A--C) Schematic representation of the native (wt) locus and the modified gene locus for each gene. Each disruption vector carries gene targeting sequences for *GAMER* (A) or *HADO* (B), which flank the pyrimethamine based selectable marker TgDHFR/TS. The pBS-TgDHFR/TS gene disruption vector is also presented for each gene in the middle. Integration of the ApaI/BamHI linearized vector results in replacement of the gene of interest. (C) Genotyping of *Δpbgamer* and *Δpbhado* mutant parasites by PCR-based analysis of the genomic DNA from *wt* and cloned parasites show that the *Δpbgamer* or *Δpbhado* locus is only present in each of the ko lines. (D) Southern blot analysis of genomic DNA from cloned and *wt* parasites digested with restriction enzymes. Successful integrations show a 3--4 kb band shift as a result of insertion of the TgDHFR/ts cassette into each respective locus.
######
*P. berghei* differentially regulated genes in the *A. gambiae* midgut. Genes exhibiting statistically significant differential regulation across the infections data, assessed using a one-way ANOVA following correction with the Benjamini-Hochberg hypergeometric test (*P* ≤ 0.05). The data are presented as log~2~-transformed signal intensity ratios of normalized *wt*-infected midguts vs. StR (standard reference). The expression data for 1639 genes are shown. Gene PlasmoDB IDs and functional annotation as well as *P. berghei* orthologues and their annotated gene description in other *Plasmodium* species are presented. Pb, *P. berghei*; Py, *P. yoelii*; Pc, *P. chabaudi*; Pk, *P. knowlesi*; Pv, *P. vivax*; Pf, *P. falciparum*; orth; orthologues.
######
Co-expression clusters of developmentally regulated *P. berghei* genes in the *A. gambiae* midguts. The table includes 564 differentially regulated *P. berghei* genes in the *A. gambiae* midgut (*P* ≤ 0.05) showing at least 0.8 log~2~-transformed fold difference between their minimum and maximum expression. They are presented according to their classification into 12 co-expression gene clusters (six main clusters, of which four are divided into sub-clusters). *P. berghei* proteomic and transcriptomic data of asexual blood stages, gametocytes, ookinetes, oocysts (day 9--12) and sporozoites (day 20--24) and orthologous *P. falciparum* proteomic and transcriptomic data from asexual blood stages, gametocytes/gametes, oocysts (days 7--8), oocyst derived sporozoites (days 13--14) and salivary gland derived sporozoites (days 18--22) are shown. AP2\_*cis* elements are presented for CL3. Gene PlasmoDB IDs and functional annotation as well as *P. berghei* orthologues and their annotated gene description in other *Plasmodium* species are also presented. Pb, *P. berghei*; Py, *P. yoelii*; Pk, Pc, *P. chabaudi*; *P. knowlesi*; Pv, *P. vivax*; Pf, *P. falciparum* (1) (Hall *et al*., 2005); (2) (Khan *et al*., 2005); (3) (Raibaud *et al*., 2006); (4) (Florens *et al*., 2002); (5) (Lasonder *et al*., 2002); (6) (Lasonder *et al*., 2008); (7) (Le Roch *et al*., 2003); (8) (Young *et al*., 2005).
######
Effect of *Δpbgamer* and *Δpbhado* mutants on oocyst development in *A. gambiae* and *A. stephensi* mosquitoes.
######
Effect of *Δpbgamer* and *Δpbhado* mutants on parasite development in *A. stephensi* and *A. gambiae* mosquitoes.
######
Primers for qRT-PCR, RT-PCR and generation of *Δpbgamer* and *Δpbhado* mutants.
######
Genetic crosses between *Δpbgamer* and female or male gamete-deficient mutants.
[^1]: These authors contributed equally to this work and are listed in alphabetical order.
|
Deciding about nursing home care in dementia: A conjoint analysis of how older people balance competing goals.
"Don't put me in a home" is a common preference of older people, but so too is "I don't want to be a burden on my family." These and other goals often conflict with each other when people have worsening dementia and the issue of possible nursing home admission arises. Community-dwelling older hospital patients were asked to imagine that they lived alone, had dementia and were experiencing increasing practical difficulties, and were presented with 11 possible "outcome packages." Conjoint analysis was used to investigate how participants ranked possible outcomes and traded-off between these factors: place of residence (home or nursing home), burden on their family, risk of harm and duration of life. Of 122 potential participants, 102 inpatients aged 65-80 years completed the study. Of these participants, 46 (46%) patients give the greatest weight to reducing the burden on their family, 39 (39%) to remaining at home, 11 (11%) to minimizing the risk of harm and five (5%) to maximizing the length of life. There were no significant clinical or demographic differences between these groups. There was a strong negative correlation (Spearman's rho -0.59, P < 0.0001) between importance scores for place of residence and for burden on family. There are important differences in how individual older people would balance the competing priorities of reducing the burden on their family and remaining at home in the event of developing dementia. Geriatr Gerontol Int 2017; 17: 2435-2440. |
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|
Safety and efficacy of AS-1 red blood cell use in neonates.
Many Regional Blood Centers are providing AS-1(Adsol preservative) red blood cells (RBCs) as a standard product because of the extended shelf life (42 days). The use of AS-1 RBCs is concerning in neonates because of high exposure to dextrose, adenine and mannitol. We conducted this study to evaluate the safety and efficacy of AS-1 RBC use in neonates. We assigned one unit of AS-1 RBCs to each infant for small volume transfusions (15 ml/kg) for the life of the unit (42 days). The study was conducted for one year. The infants under 1500 g were included in the study. We measured the pre- and post-transfusion hematocrit, post-transfusion serum sodium, potassium, glucose, bilirubin and blood pH. We compared the average number of transfusions per patient and average blood donor exposure per patient using AS-1 RBC to CPDA-1 packed red blood cells (PRBC) use, data available for prior year. We monitored the blood transfusion reactions during the study period. The hematocrit increased significantly from 30.1 +/- 4.6 pre-transfusion to 38.3 +/- 4.9 post-transfusion. The post-transfusion serum bilirubin, blood pH, serum potassium, sodium and glucose remained within the normal range. In spite of an increase in the number of average transfusions per patient with AS-1 RBC (6.67 +/- 5.1), the average donor exposure (1.8 +/- 1.1) remained less than two donors. There were not any transfusion reactions reported during the study. In conclusion, the use of AS-1 red blood cells is safe for small volume transfusions in neonates. |
A visitor looks at the faces of some of the victims of the Oklahoma City bombing at the Oklahoma National Memorial museum in Oklahoma City June 12, 2001, one day after the execution of Timothy McVeigh. (Photo by Joe Raedle/Getty Images) |
Q:
How can I shuffle an array/hash in Ruby?
For learning purposes, what is this called? Is the object being created an array or a hash?
stack_of_cards = []
This is how I'm filling it:
stack_of_cards << Card.new("A", "Spades", 1)
stack_of_cards << Card.new("2", "Spades", 2)
stack_of_cards << Card.new("3", "Spades", 3)
...
Here is my Card class:
class Card
attr_accessor :number, :suit, :value
def initialize(number, suit, value)
@number = number
@suit = suit
@value = value
end
def to_s
"#{@number} of #{@suit}"
end
end
I'd like to shuffle the elements in this array/hash (what is this called? :S)
Any suggestions?
A:
stack_of_cards.shuffle
It is an Array, see http://www.ruby-doc.org/core-1.8.7/classes/Array.html for more information.
I've written the functional form, which returns a new Array, and it's the new one that's shuffled. You can instead use:
stack_of_cards.shuffle!
...to shuffle the array in-place.
A:
If you want to shuffle a hash you can use something like this:
class Hash
def shuffle
Hash[self.to_a.sample(self.length)]
end
def shuffle!
self.replace(self.shuffle)
end
end
I've posted this answer since I always find this question if I search for "ruby shuffle hash".
|
Oneida Indian Nation leader Ray Halbritter says the Oneida and other tribes will launch a fund to buy uniforms to schools that drop nicknames offensive to Indians.
Halbritter already made the offer to Cooperstown High School, whose students recently voted to banish their "Redskins" nickname, to help buy the school new uniforms.
"In fact, to address this pervasive problem, the Oneida Nation is now working with Native American media outlets and other Indian nations to establish a fund that will help schools that follow in Cooperstown's footsteps to offset the cost of making similar transitions," Halbritter wrote in the New York Daily News.
Halbritter said there are 900 "ethnically insensitive" nicknames and mascots across the country at all levels of sport.
"The owners of professional sports franchises like the Cleveland Indians, the Atlanta Braves and the Washington Redskins continue to disrespect the heritage of Native American people with mascots and logos that insultingly portray aspects of our culture as a cheap cartoon -- and nothing more," Halbritter wrote. |
Jozef Stalin, paranoid dictator, mass murderer but a great drinker
Speaking of mean drunks, Jozef Stalin probably holds the record of having most people killed in the history of men. Experts estimated that the Soviet leader was responsible (direct or indirect) for the death of around 40 million people. Sure the health freaks are quick to point out that this was a result of his paranoia caused by his alcohol abuse. But the fact that they say it in their own language and not in German is also thanks to alcohol. For it was vodka and some good Georgian wines that made Stalin and Churchill allies. One night of hardcore drinking between the English and Soviet leader in the end caused the downfall of the third Reich.
Stalin was born in 1878 in Georgia under the name Jozef Vissarionovitsj Djugashvili. His father was an alcoholic who used to beat him. And if that wasn’t enough he also had a withered arm, a clubbed food and a face covered by small pox. Add the fact that he would never grow over 1.64 meters and you have proper material for the psychologists. His shortcomings only made him hungrier for power it seemed. And when he finally was in charge of the Soviet-Union he had everybody killed who he thought could ever take any of that power away from him. This basically meant he killed all the Soviet party big shots, their families and several millions more.
But his greatest act was probably a drunken night he had with the British leader Winston Churchill, who was a known heavy drinker himself, in 1942. Until that moment Churchill completely abhorred communism and everyone who had anything to do with it. A few years before he openly admired the Italian fascist leader Benito Mussulini, saying his line of politics could be a great way to stop the socialists. Needless to say this made dealing with Stalin not really easy. But all of this changed in August 1942 when Churchill was invited to a banquet in Moscow. The first meeting with Stalin by the British prime minister was archived as ‘Operation Bracelet’. History experts always pointed out that this meeting was a key point that made the Nazis lose the war. But it wasn’t till May 2013 that the National Archives revealed what actually went down when the two leaders met.
Sir Alec Cadogan, under-secretary at the foreign office, who accompanied Churchill explained in a letter what happened. At first the banquet seemed to turn into a disaster since Stalin’s demands were not to Churchill’s liking at all. In a last attempt to agree terms he asked for a meeting with just the two of them. At 01.00 in the morning Cadogan entered Stalins private room and saw the following scene: “There I found Winston and Stalin, and Molotov (Soviet minister of foreign affairs Vjatjeslav Molotov) who has joined them, sitting with a heavily-laden board between them: food of all kinds crowned by a sucking pig and innumerable bottles. What Stalin made me drink seemed pretty savage: Winston, who by that time was complaining of a slight headache, seemed wisely to be confining himself to a comparatively innocuous effervescent Caucasian red wine. Everyone seemed to be as merry as a marriage bell.”
After Cadogan’s arrival the party negotiations on an East-West alliance continued till 03.00 o’clock. As the British delegation was flying back at 04.15. On the way back Churchill was in a great mood, as Cadogan describes: “I think the two great men really made contact and got on terms. Certainly Winston was impressed and I think that feeling was reciprocated… Anyhow conditions have been established in which messages exchanged between the two will mean twice as much, or more, than they did before.”
It’s also good to know that drinking didn’t kill Stalin when he died in 1953, smoking did. But that makes sense since the two of them go so well together. There’s no doubt his regime was extremely tough, not in the last place to his own people, and it couldn’t have been easy to cooperate with a man like that. Probably even impossible if alcohol didn’t smoothen the deal. So at least ‘Father Stalin’ taught us one valuable lesson. |
The present invention relates to semiconductor devices, and more particularly to light emitting diodes mounted to a submount in a junction-down configuration.
GaN-based light emitting diodes (LEDs) typically comprise an insulating or semiconducting substrate such as SiC or sapphire on which a plurality of GaN-based epitaxial layers are deposited. The epitaxial layers comprise an active region having a p-n junction that emits light when energized. A typical LED is mounted substrate side down onto a submount, also called a package or lead frame (hereinafter referred to as a “submount”). FIG. 4 schematically illustrates a conventional LED having an n-type SiC substrate 10, an active region 12 comprising an n-GaN-based layer 14 and a p-GaN-based layer 16 grown on the substrate and patterned into a mesa. A metal p-electrode 18 is deposited on the p-GaN layer 16 and a wire bond connection 28 is made to a bond pad 20 on the p-electrode 18. An n-electrode 22 on the conductive substrate is attached to metallic submount 24 using a conductive epoxy 26. In the conventional process, the conductive epoxy 26 (usually silver epoxy) is deposited on the submount and the LED is pressed into the epoxy 26. The epoxy is then heat cured which causes it to harden, providing a stable and electrically conductive mount for the LED chip. A substantial amount of the light generated in the active region 12 may be transmitted into the substrate and absorbed by the epoxy 26.
Junction-down (or “flip-chip”) mounting of LEDs involves mounting the LED onto the submount substrate side up. Light is then extracted and emitted through the transparent substrate. Junction-down mounting may be an especially desirable technique for mounting SiC-based LEDs. Since SiC has a higher index of refraction than GaN, light generated in the active region does not internally reflect (i.e. reflect back into the GaN-based layers) at the GaN/SiC interface. Junction-down mounting of SiC-based LEDs may improve the effect of certain chip-shaping techniques known in the art. Junction-down packaging of SiC LEDs may have other benefits as well, such as improved heat dissipation, which may be desirable depending on the particular application for the chip.
One problem with junction-down mounting is illustrated in FIG. 5. Namely, when a chip is mounted junction-down on a conductive submount or package using conventional techniques, a conductive die attach material 26 is deposited on the chip and/or on the submount 24, and the chip is pressed into the submount 24. Alternatively, the conductive die attach material 26 may comprise a solder such as Sn or Au/Sn in which case the chip is bonded to the submount 24 by thermocompression bonding.
Thermocompression bonding is a technique whereby a device is mounted to a substrate or submount using heat and pressure, thereby creating a conductive bond between the device and the submount. Typically, a vacuum collet is used to pick up the device and physically place it in contact with a submount that is formed of a material with which the solder used may form an alloy. Once the device is in contact with the submount, force is applied to the device through the collet. Through a combination of heat and pressure, the solder becomes alloyed with the submount and the device is welded in place. In order to form such a bond, the device must include a metal pad layer made of a metal such as Sn that will form an alloy bond with the submount when heat and pressure are applied. Other metals and alloys having a sufficiently low melting point are Au/Sn, Pb/Sn, and Ag/Sn may be used. Some suitable submount materials are silver and gold.
Typical thermocompression processes utilize a minimum force of about 30 to 50 g to cause the die to become bonded to the submount. However, this force may cause some of the molten bond metal to squeeze out and form a shunt circuit between the n-type substrate and the submount around the p-n junction, degrading the device operation.
Accordingly, as illustrated in FIG. 5, the conductive die attach material 26 can squeeze out and make contact with the n-type layers 14 and 10 in the device, thereby forming a Schottky diode connection that short-circuits the p-n junction in the active region with predictably undesirable results. Thus, improvements in the design of LEDs may be desirable for improved junction-down mounting. |
Values in bitcoin and its rival cryptocurrencies sunk once again over the Black Friday weekend, bringing the market its lowest point since last September.
Bitcoin prices dipped below $4,000 (£3,110) per coin on Saturday morning, before reaching a low of $3,500 (£2,730) on Sunday, according to ranking website CoinMarketCap. Values for the digital coin were at about $3,900 (£3,040) as of 9.30am UK time on Monday.
Rival coins Ethereum and Ripple also took a tumble over the weekend, with their values this morning sitting at about $114 (£89) and $0.37 (£0.29) per coin respectively.
The market’s downturn over the past few days appears to be a continuation of the sell-off caused by the “hard fork” - a move whereby a cryptocurrency splits in two to form a new digital coin - in bitcoin’s sister virtual currency bitcoin cash two weeks ago, says Forbes.
However, while cryptocurrencies seem to be stuck in a continuous downward spiral, some investors believe the market could bounce back if greater “regulatory oversight” were introduced, the news site adds.
Herbert Sim, chief commercial officer at Singapore-based digital currency exchange Cryptology, told Forbes that “regulators need to put standards in place to separate the weeds from the roses in the cryptocurrency world” if the market is “to move forward and investor confidence to settle”.
“Having oversight of the cryptocurrency Wild West will legitimise, and subsequently stabilise the industry, which will allow it to reach the next step of maturity,” Sim said.
Can bitcoin bounce back next month?
Bitcoin has lost 80% of its value since peaking at nearly $20,000 (£15,590) in December 2017, which doesn’t bode well for the market.
However, Mati Greenspan, a senior marketing analyst at cryptocurrency trading site eToro, told the Daily Express that “it’s really impossible to know” where the digital currency is headed - and that he is still hopes there might be a “Santa Claus rally” before the year is out.
Pointing to the volatility of the market, he added: “[What] I’ve been saying from the beginning of the year, when people were asking for my end-year predictions, is that I can say with a 99% certainty bitcoin will be between $100 (£78) and $1m (£780m) on 31 December.” |
Q:
Looking for way to automate testing kshell app
I inherited a shell-script application that is a combination of kshell scripts, awk, and java programs. I have written JUnit tests for the java pieces.
Is there a good way to do something similar for the kshell scripts and awk programs?
I have considered using JUnit and System.exec() to call the scripts, but it seems like there should be a better way.
A:
I have found shUnit2 and will try that.
Update with the results of trying out shUnit
shUnit works as expected. Script files are written with test functions defined and then a call to shUnit.
Example:
#!/bin/sh
testFileCreated()
{
TESTFILE=/tmp/testfile.txt
# some code that creates the $TESTFILE
assertTrue 'Test file missing' "[ -s '${TESTFILE}' ]"
}
# load shunit2
. /path/to/shUnit/shunit2-2.1.5/src/shell/shunit2
Result
Ran 1 test.
OK
The 'OK' would be replaced with 'FAILED' if the file did not exist.
|
In Vancouver at the annual Ethereum Classic Summit on October 3, the Ethereum Foundation’s Virgil Griffith took to the stage to ruminate on the burgeoning friendship between two formerly bitter rivals: the communities of the Ethereum and Ethereum Classic blockchains.
The communities have reconciled their differences over the past year, as long-standing tensions ease and developers become more open to inter-blockchain collaboration. And that newfound friendship also brings benefits: as Ethereum inches ever closer to Ethereum 2.0, Ethereum Classic believers sense an opportunity to fill some of the void left by that upgrade.
Ethereum Classic is the original blockchain of the Ethereum network, which forked in 2016 to restore funds stolen in a $60 million hack. Ethereum Classic supporters have essentially clung onto the old network, and say the 2016 fork was a betrayal of the principle of “unstoppable” code. But now the communities are settling their differences.
To some, such as Ethereum Classic Cooperate staffer Yaz Khoury, collaboration with Ethereum will could bring in new recruits: Ethereum is set to transition from the miner-based Proof of Work algorithm to the less energy consumptive Proof of Stake algorithm. That could alienate scores of Ethereum miners, who believe it will hurt their business.
Others dream bigger, and predict that Ethereum Classic will eventually dwarf the Ethereum network entirely. Ethereum Classic Cooperative director Bob Summerwill, for instance, points to a spate of departures from the Ethereum community by developers who expressed fatigue at the long hours of unpaid, often thankless work.
The Ethereum Foundation declined to comment.
The blossoming friendship between the two networks began in 2018, at the EDCON conference in Toronto, when Ethereum Foundation Special Projects Director Virgil Griffith invited Anthony Lusardi, then head of the non-profit ETC cooperative, to attend the conference, as part of a broader drive for inclusivity. Lusardi gave a speech about interoperability.
“I think the Ethereum Foundation started to realize there was a benefit to working with other chains,” Lusardi said to Decrypt. The goal, he added, was about “exporting ETC politics to whoever will listen.”
The two communities are now working on a number of joint projects including a “peaceBridge,” funded partly by the Ethereum Foundation, that allows users to transact ether between chains. Likewise, some Ethereum and Ethereum Classic hardliners are coordinating resistance to a proposed upgrade, ProgPoW, which they allege was concocted by NVIDIA.
“There is a great opportunity for positive-sum collaboration between the Ethereum and Ethereum Classic communities,” said Terry Culver, the CEO of Ethereum Classic incubator ETC Labs. “They share values, and technical functionality. There is a complicated history, but there is a lot they can do together moving forward.”
Fork of his name
Ethereum Classic was born in July 2016, when some $60 million worth of ether was hacked from the world’s first “decentralized autonomous organization,” a leaderless, headless community built on the Ethereum network, in which thousands of participants had deposited millions of dollars of funds.
The hack came quick, and threw the dreamers involved into an immediate, ultimately devastating quandary: on a supposedly immutable, decentralized network, how could you help the victims of a hack? Could you simply reverse the transactions carrying the hacked funds?
To Summerwill, the answer was an absolute no. An obvious no. “My original reaction was ‘Of course we should not do anything,’” said the former Ethereum Foundation operative. But, “as that month developed, I could see that the majority of the community were in favor of intervention, and I came to understand the merits of both sides of the argument.”
But only one side prevailed. A majority of Ethereum developers voted to reverse the theft by engineering a hard fork, splitting the network and returning investors’ funds.
To the dissenters, the restoration gave the lie to the meaning of “unstoppable code.” “Immutability is the only reason we are in crypto,” said Khoury, the ETC Cooperative staffer. “It’s the Bitcoin model. The moment we abandon that and start bailing out the protocol, we become no different than traditional financial institutions.”
Thus Ethereum Classic was born, infused with an undisclosed investment from Digital Currency Group magnate Barry Silbert, and supported by the likes of Cardano co-founder Charles Hoskinson, Bloomberg Opinion columnist and Bitcoin maximalist Elaine Ou, and a group of pseudonymous contributors going by the name “arvicco”. The dissenters eschewed the post-DAO hard fork and continued on the old chain, letting the hacker get away with the theft. “It was about a week past the fork and ETC had a good resistance going,” recalled Lusardi.
And now, after years of relative stagnation, Ethereum Classicos believe they can do Ethereum one better. Khoury explains that he thinks Ethereum’s miners, hamstrung by the move to proof of stake, will shift their resources to Classic. There’s “no reason for them to mine a chain that can potentially be abandoned for a fresher new chain in Ethereum 2.0,” he said. “So the natural answer is Ethereum Classic. It’s technically the same as Ethereum 1.0, following the same technical roadmap.”
Similarly, he believes many developers of decentralized apps will feel stranded when Ethereum abandons the “Virtual Machine,” home to thousands of (often little-used) decentralized applications. Ethereum Classic makes a “great hedge” for those people, he said. “Yes, we would love that hash power,” agreed Summerwill, who nevertheless said the plot was less dastardly than it might appear to be. “ETC and ETH1 are kind of competitors, but ETC and ETH 2.0 are much more complementary.”
But Kristy-Leigh Minehan, a prominent miner, thinks it’s unlikely Ethereum miners will rush to Ethereum when proof of stake rolls out. While some of the more specialized ASIC miners will be forced to go to Ethereum Classic, she said, miners running adaptable GPUs will more likely quit Ethereum entirely and migrate to more liquid cryptocurrencies on blockchains like Grin and Beam.
“These ‘surges’ of miners swamping a new coin are never good,” she added. “Miners contribute heavily to the ‘sell’ liquidity for the coin. What is going to end up happening is miners—if they did switch to ETC all at once—would drown the exchanges in sell orders and push the price down.”
Lately, several prominent semi- and full departures have rocked the Ethereum community. Spankchain’s Ameen Soleimani announced last week that he was distancing himself from the protocol, after months of unpaid voluntary work left him exhausted. “I don't have enough ETH to justify [boosting Ethereum’s prospects] nor is anyone paying me to do it, so it's essentially volunteer work,” Soleimani tweeted. “I'm burnt tf out. It's not fun anymore.”
Lane Rettig, another developer, said he was stepping back for similar reasons earlier this month. Developer Afri Schoeden, meanwhile, formerly an Ethereum celebrity, defected to Ethereum Classic earlier this year.
Summerwill insisted in a Twitter thread that the Ethereum Classic community pays better, works better and coordinates better. Ethereum work, he argued, relies heavily on price swings.
That’s not to say the Ethereum Classic community and network are perfect by contrast. The sheer smallness of the network makes it an easy target for so-called 51 percent attacks, as happened earlier this year when some $1.1 million worth of fraudulent payments were made in a “reorg” (reorganization) of the network.
But despite this security threat and the lingering, simmering tensions, Ethereum Classic is still up and running, and the ETH-ETC bridge remains intact. “You could see it as being similar to the relationship between the British and the Americans,” said Summerwill. “At a certain point you get past ‘The War’ and can focus on common concerns, and be better for that.” Or perhaps the burgeoning “strategic friendship” will wind up more like the Molotov-Ribbentrop pact. |
Equality Betrayed: A Portrait Series
About This Photo
Hicham Kochman (aka Axiom)Artist, composer, and authorLille
“Those who do not live with this, this harassment, don’t understand what we are talking about. They don’t know what it generates in oneself, on the level of one’s feelings, to be designated, to be second tier, third tier, told you are nothing and to shut up. In this way they make you believe that you are nothing and no one. It’s a daily, ongoing form of humiliation. They [the police] are armed, so this danger exists daily and you are insulted daily.”
“My first experience of an identity check was when I was in my first year of law school. When I got home, I raced up the stairs and lay on my bed and cried and cried, without fully understanding why, but I cried without being able to stop. I realized that what I was learning was out of sync with reality.
I had always said to my close family that my skin color doesn’t exist, that it only exists for those that want to see it, but for me it doesn’t exist. My father raised me to think this way. But that day, I realized that something about me was different. I think that at that moment my faith as a ‘Dijonese’ citizen, my faith as a French citizen, disappeared, evaporated, dissolved.”
“I can tell you about my first identity check as if it occurred yesterday: the exact route we took, why we went to the city center and the manner in which the police spoke to us. I think it’s something that remains etched in one’s mind for life. We are a generation that grew up in war, not a war involving bombs, but one with the police. It’s not normal.
We don’t want to imagine a future in which we marry, have a house, and then have our children checked and go through the same things we have; it’s just not possible. It has to stop or it will lead to conflict.”
“When we walk in the city and we see the police, we feel unsafe. But there are other people for whom the police presence provides a sense ofsecurity. There are really two Frances. There is our France, the France of the poor suburbs, of immigrants, of persons of foreign origin, of the unemployed, and then there is the France of the others—those that feel reassured by police cars.
When the police check us, stories of police brutality run through our minds and we say to ourselves, ‘It could be me.’ The older we get, the more we think about that.”
“When you are checked in public, it creates a really unpleasant image. I wonder what passersby think, whether they really think that I committed a crime or that I really did something illegal, especially when the check occurs in the neighborhood where I work.
It’s especially the human effect it can have afterwards. An example that I find particularly striking is when I walk down the street and I passsomeone who shifts their bag to the other side—there is no mystery. I also try not to go to stores on Saturdays as I will likely be followed, be checked.”
“What people do not understand about these abusive controls is that it’s real violence for those who are targets. The feeling of being treated differently, that’s the first reckoning, the first awareness of a certain discrimination, of some difference, of a certain exclusion.
The influence and importance these police checks can have are very strong. Besides school and parents, they, the police, are the ones representing authority, and the checks can do a lot of damage to the perception young people have of authority. Trust is destroyed and distrust sets in. In addition, generalizing this, the police are the state, the police are the Republic, the nation. So the discriminatory policing damages one’s trust in institutions.”
“Because of the checks, at 20 we already thought like 40-year-olds. And that’s what I don’t want them to do to my son. I want my son to enjoy the time of his carefree days like other kids: to be full of dreams … I want my son to travel around the world; I don’t want him to be locked up inside himself because of identity checks that make him think that outside of his small neighborhood there is no life for him.”
“A police force that has the population against it cannot work, it is not possible. Constant identity checks are counterproductive; us police officers, as well as experts, academics, and people who observe us all say it. It has no rhyme or reason. We need to reverse course and allow only justified identity checks and not identity checks by the shovelful. The National Police needs to work with the public; police working against citizens is the world upside-down.”
“It is as if you did something wrong when the only thing wrong that you did was to be present. You feel that the simple fact of existing is a problem. When one hasn’t experienced this it is difficult to imagine the type of humiliation, to the point that it causes pain. There is even a feeling of humiliation when you are not checked yourself, but you know someone who is checked, even then it can cause pain. It’s something very intimate.”
Adji contrasts the excitement he felt when he first received the card that identified him as an elected official with the disillusionment of being singled out for an identity check.
“You think to yourself, ‘Ho la la, this card is a sign of my full belonging to the French Republic.’ And then ‘poof,’ when that moment comes of an identity check, a familiar memory immediately rises to the surface. You realize that while you belong to the Republic and you live in the Republic, you aren’t actually a full citizen. You are a second-class citizen. You are continually reminded that due to your face, due to your skin color, due to your appearance that you are not really from here—even when you are an elected official of the Republic.”
On the streets of Paris, a young black man can be six times as likely to be stopped and checked by the police as a young white man. For young males of Arab origin, the figure is even higher: They are at least eight times more likely to be stopped.
The French call it contrôle au faciès, which can be roughly translated as “being stopped because of the way you look.” It amounts to illegal discrimination.
But how does it feel? And what are the costs? In a new report, 13 young French people from minority communities talked to us about their experiences, together with two police officers who want things to change. Award-winning documentary photographer Ed Kashi took the pictures. |
using System;
using BizHawk.Emulation.Common;
using System.Collections.Generic;
namespace BizHawk.Emulation.Cores.Components.M6502
{
public partial class MOS6502X<TLink> : IDisassemblable
{
public string Disassemble(ushort pc, out int bytesToAdvance)
{
return MOS6502X.Disassemble(pc, out bytesToAdvance, _link.PeekMemory);
}
public string Cpu
{
get => "6502";
set
{
}
}
public string PCRegisterName => "PC";
public IEnumerable<string> AvailableCpus
{
get { yield return "6502"; }
}
public string Disassemble(MemoryDomain m, uint addr, out int length)
{
return MOS6502X.Disassemble((ushort)addr, out length, a => m.PeekByte((int)a));
}
}
public static class MOS6502X
{
private static ushort peeker_word(ushort address, Func<ushort, byte> peeker)
{
byte l = peeker(address);
byte h = peeker(++address);
return (ushort)((h << 8) | l);
}
/// <summary>
/// disassemble not from our own memory map, but from the supplied memory domain
/// </summary>
public static string Disassemble(ushort pc, out int bytesToAdvance, Func<ushort, byte> peeker)
{
byte op = peeker(pc);
switch (op)
{
case 0x00: bytesToAdvance = 1; return "BRK";
case 0x01: bytesToAdvance = 2; return $"ORA (${peeker(++pc):X2},X)";
case 0x04: bytesToAdvance = 2; return $"NOP ${peeker(++pc):X2}";
case 0x05: bytesToAdvance = 2; return $"ORA ${peeker(++pc):X2}";
case 0x06: bytesToAdvance = 2; return $"ASL ${peeker(++pc):X2}";
case 0x08: bytesToAdvance = 1; return "PHP";
case 0x09: bytesToAdvance = 2; return $"ORA #${peeker(++pc):X2}";
case 0x0A: bytesToAdvance = 1; return "ASL A";
case 0x0C: bytesToAdvance = 3; return $"NOP (${peeker_word(++pc, peeker):X4})";
case 0x0D: bytesToAdvance = 3; return $"ORA ${peeker_word(++pc, peeker):X4}";
case 0x0E: bytesToAdvance = 3; return $"ASL ${peeker_word(++pc, peeker):X4}";
case 0x10: bytesToAdvance = 2; return $"BPL ${pc + 2 + (sbyte)peeker(++pc):X4}";
case 0x11: bytesToAdvance = 2; return $"ORA (${peeker(++pc):X2}),Y *";
case 0x14: bytesToAdvance = 2; return $"NOP ${peeker(++pc):X2},X";
case 0x15: bytesToAdvance = 2; return $"ORA ${peeker(++pc):X2},X";
case 0x16: bytesToAdvance = 2; return $"ASL ${peeker(++pc):X2},X";
case 0x18: bytesToAdvance = 1; return "CLC";
case 0x19: bytesToAdvance = 3; return $"ORA ${peeker_word(++pc, peeker):X4},Y *";
case 0x1A: bytesToAdvance = 1; return "NOP";
case 0x1C: bytesToAdvance = 2; return $"NOP (${peeker(++pc):X2},X)";
case 0x1D: bytesToAdvance = 3; return $"ORA ${peeker_word(++pc, peeker):X4},X *";
case 0x1E: bytesToAdvance = 3; return $"ASL ${peeker_word(++pc, peeker):X4},X";
case 0x20: bytesToAdvance = 3; return $"JSR ${peeker_word(++pc, peeker):X4}";
case 0x21: bytesToAdvance = 2; return $"AND (${peeker(++pc):X2},X)";
case 0x24: bytesToAdvance = 2; return $"BIT ${peeker(++pc):X2}";
case 0x25: bytesToAdvance = 2; return $"AND ${peeker(++pc):X2}";
case 0x26: bytesToAdvance = 2; return $"ROL ${peeker(++pc):X2}";
case 0x28: bytesToAdvance = 1; return "PLP";
case 0x29: bytesToAdvance = 2; return $"AND #${peeker(++pc):X2}";
case 0x2A: bytesToAdvance = 1; return "ROL A";
case 0x2C: bytesToAdvance = 3; return $"BIT ${peeker_word(++pc, peeker):X4}";
case 0x2D: bytesToAdvance = 3; return $"AND ${peeker_word(++pc, peeker):X4}";
case 0x2E: bytesToAdvance = 3; return $"ROL ${peeker_word(++pc, peeker):X4}";
case 0x30: bytesToAdvance = 2; return $"BMI ${pc + 2 + (sbyte)peeker(++pc):X4}";
case 0x31: bytesToAdvance = 2; return $"AND (${peeker(++pc):X2}),Y *";
case 0x34: bytesToAdvance = 2; return $"NOP ${peeker(++pc):X2},X";
case 0x35: bytesToAdvance = 2; return $"AND ${peeker(++pc):X2},X";
case 0x36: bytesToAdvance = 2; return $"ROL ${peeker(++pc):X2},X";
case 0x38: bytesToAdvance = 1; return "SEC";
case 0x39: bytesToAdvance = 3; return $"AND ${peeker_word(++pc, peeker):X4},Y *";
case 0x3A: bytesToAdvance = 1; return "NOP";
case 0x3C: bytesToAdvance = 2; return $"NOP (${peeker(++pc):X2},X)";
case 0x3D: bytesToAdvance = 3; return $"AND ${peeker_word(++pc, peeker):X4},X *";
case 0x3E: bytesToAdvance = 3; return $"ROL ${peeker_word(++pc, peeker):X4},X";
case 0x40: bytesToAdvance = 1; return "RTI";
case 0x41: bytesToAdvance = 2; return $"EOR (${peeker(++pc):X2},X)";
case 0x44: bytesToAdvance = 2; return $"NOP ${peeker(++pc):X2}";
case 0x45: bytesToAdvance = 2; return $"EOR ${peeker(++pc):X2}";
case 0x46: bytesToAdvance = 2; return $"LSR ${peeker(++pc):X2}";
case 0x48: bytesToAdvance = 1; return "PHA";
case 0x49: bytesToAdvance = 2; return $"EOR #${peeker(++pc):X2}";
case 0x4A: bytesToAdvance = 1; return "LSR A";
case 0x4C: bytesToAdvance = 3; return $"JMP ${peeker_word(++pc, peeker):X4}";
case 0x4D: bytesToAdvance = 3; return $"EOR ${peeker_word(++pc, peeker):X4}";
case 0x4E: bytesToAdvance = 3; return $"LSR ${peeker_word(++pc, peeker):X4}";
case 0x50: bytesToAdvance = 2; return $"BVC ${pc + 2 + (sbyte)peeker(++pc):X4}";
case 0x51: bytesToAdvance = 2; return $"EOR (${peeker(++pc):X2}),Y *";
case 0x54: bytesToAdvance = 2; return $"NOP ${peeker(++pc):X2},X";
case 0x55: bytesToAdvance = 2; return $"EOR ${peeker(++pc):X2},X";
case 0x56: bytesToAdvance = 2; return $"LSR ${peeker(++pc):X2},X";
case 0x58: bytesToAdvance = 1; return "CLI";
case 0x59: bytesToAdvance = 3; return $"EOR ${peeker_word(++pc, peeker):X4},Y *";
case 0x5A: bytesToAdvance = 1; return "NOP";
case 0x5C: bytesToAdvance = 2; return $"NOP (${peeker(++pc):X2},X)";
case 0x5D: bytesToAdvance = 3; return $"EOR ${peeker_word(++pc, peeker):X4},X *";
case 0x5E: bytesToAdvance = 3; return $"LSR ${peeker_word(++pc, peeker):X4},X";
case 0x60: bytesToAdvance = 1; return "RTS";
case 0x61: bytesToAdvance = 2; return $"ADC (${peeker(++pc):X2},X)";
case 0x64: bytesToAdvance = 2; return $"NOP ${peeker(++pc):X2}";
case 0x65: bytesToAdvance = 2; return $"ADC ${peeker(++pc):X2}";
case 0x66: bytesToAdvance = 2; return $"ROR ${peeker(++pc):X2}";
case 0x68: bytesToAdvance = 1; return "PLA";
case 0x69: bytesToAdvance = 2; return $"ADC #${peeker(++pc):X2}";
case 0x6A: bytesToAdvance = 1; return "ROR A";
case 0x6C: bytesToAdvance = 3; return $"JMP (${peeker_word(++pc, peeker):X4})";
case 0x6D: bytesToAdvance = 3; return $"ADC ${peeker_word(++pc, peeker):X4}";
case 0x6E: bytesToAdvance = 3; return $"ROR ${peeker_word(++pc, peeker):X4}";
case 0x70: bytesToAdvance = 2; return $"BVS ${pc + 2 + (sbyte)peeker(++pc):X4}";
case 0x71: bytesToAdvance = 2; return $"ADC (${peeker(++pc):X2}),Y *";
case 0x74: bytesToAdvance = 2; return $"NOP ${peeker(++pc):X2},X";
case 0x75: bytesToAdvance = 2; return $"ADC ${peeker(++pc):X2},X";
case 0x76: bytesToAdvance = 2; return $"ROR ${peeker(++pc):X2},X";
case 0x78: bytesToAdvance = 1; return "SEI";
case 0x79: bytesToAdvance = 3; return $"ADC ${peeker_word(++pc, peeker):X4},Y *";
case 0x7A: bytesToAdvance = 1; return "NOP";
case 0x7C: bytesToAdvance = 2; return $"NOP (${peeker(++pc):X2},X)";
case 0x7D: bytesToAdvance = 3; return $"ADC ${peeker_word(++pc, peeker):X4},X *";
case 0x7E: bytesToAdvance = 3; return $"ROR ${peeker_word(++pc, peeker):X4},X";
case 0x80: bytesToAdvance = 2; return $"NOP #${peeker(++pc):X2}";
case 0x81: bytesToAdvance = 2; return $"STA (${peeker(++pc):X2},X)";
case 0x82: bytesToAdvance = 2; return $"NOP #${peeker(++pc):X2}";
case 0x84: bytesToAdvance = 2; return $"STY ${peeker(++pc):X2}";
case 0x85: bytesToAdvance = 2; return $"STA ${peeker(++pc):X2}";
case 0x86: bytesToAdvance = 2; return $"STX ${peeker(++pc):X2}";
case 0x88: bytesToAdvance = 1; return "DEY";
case 0x89: bytesToAdvance = 2; return $"NOP #${peeker(++pc):X2}";
case 0x8A: bytesToAdvance = 1; return "TXA";
case 0x8C: bytesToAdvance = 3; return $"STY ${peeker_word(++pc, peeker):X4}";
case 0x8D: bytesToAdvance = 3; return $"STA ${peeker_word(++pc, peeker):X4}";
case 0x8E: bytesToAdvance = 3; return $"STX ${peeker_word(++pc, peeker):X4}";
case 0x90: bytesToAdvance = 2; return $"BCC ${pc + 2 + (sbyte)peeker(++pc):X4}";
case 0x91: bytesToAdvance = 2; return $"STA (${peeker(++pc):X2}),Y";
case 0x94: bytesToAdvance = 2; return $"STY ${peeker(++pc):X2},X";
case 0x95: bytesToAdvance = 2; return $"STA ${peeker(++pc):X2},X";
case 0x96: bytesToAdvance = 2; return $"STX ${peeker(++pc):X2},Y";
case 0x98: bytesToAdvance = 1; return "TYA";
case 0x99: bytesToAdvance = 3; return $"STA ${peeker_word(++pc, peeker):X4},Y";
case 0x9A: bytesToAdvance = 1; return "TXS";
case 0x9D: bytesToAdvance = 3; return $"STA ${peeker_word(++pc, peeker):X4},X";
case 0xA0: bytesToAdvance = 2; return $"LDY #${peeker(++pc):X2}";
case 0xA1: bytesToAdvance = 2; return $"LDA (${peeker(++pc):X2},X)";
case 0xA2: bytesToAdvance = 2; return $"LDX #${peeker(++pc):X2}";
case 0xA4: bytesToAdvance = 2; return $"LDY ${peeker(++pc):X2}";
case 0xA5: bytesToAdvance = 2; return $"LDA ${peeker(++pc):X2}";
case 0xA6: bytesToAdvance = 2; return $"LDX ${peeker(++pc):X2}";
case 0xA8: bytesToAdvance = 1; return "TAY";
case 0xA9: bytesToAdvance = 2; return $"LDA #${peeker(++pc):X2}";
case 0xAA: bytesToAdvance = 1; return "TAX";
case 0xAC: bytesToAdvance = 3; return $"LDY ${peeker_word(++pc, peeker):X4}";
case 0xAD: bytesToAdvance = 3; return $"LDA ${peeker_word(++pc, peeker):X4}";
case 0xAE: bytesToAdvance = 3; return $"LDX ${peeker_word(++pc, peeker):X4}";
case 0xB0: bytesToAdvance = 2; return $"BCS ${pc + 2 + (sbyte)peeker(++pc):X4}";
case 0xB1: bytesToAdvance = 2; return $"LDA (${peeker(++pc):X2}),Y *";
case 0xB3: bytesToAdvance = 2; return $"LAX (${peeker(++pc):X2}),Y *";
case 0xB4: bytesToAdvance = 2; return $"LDY ${peeker(++pc):X2},X";
case 0xB5: bytesToAdvance = 2; return $"LDA ${peeker(++pc):X2},X";
case 0xB6: bytesToAdvance = 2; return $"LDX ${peeker(++pc):X2},Y";
case 0xB8: bytesToAdvance = 1; return "CLV";
case 0xB9: bytesToAdvance = 3; return $"LDA ${peeker_word(++pc, peeker):X4},Y *";
case 0xBA: bytesToAdvance = 1; return "TSX";
case 0xBC: bytesToAdvance = 3; return $"LDY ${peeker_word(++pc, peeker):X4},X *";
case 0xBD: bytesToAdvance = 3; return $"LDA ${peeker_word(++pc, peeker):X4},X *";
case 0xBE: bytesToAdvance = 3; return $"LDX ${peeker_word(++pc, peeker):X4},Y *";
case 0xC0: bytesToAdvance = 2; return $"CPY #${peeker(++pc):X2}";
case 0xC1: bytesToAdvance = 2; return $"CMP (${peeker(++pc):X2},X)";
case 0xC2: bytesToAdvance = 2; return $"NOP #${peeker(++pc):X2}";
case 0xC4: bytesToAdvance = 2; return $"CPY ${peeker(++pc):X2}";
case 0xC5: bytesToAdvance = 2; return $"CMP ${peeker(++pc):X2}";
case 0xC6: bytesToAdvance = 2; return $"DEC ${peeker(++pc):X2}";
case 0xC8: bytesToAdvance = 1; return "INY";
case 0xC9: bytesToAdvance = 2; return $"CMP #${peeker(++pc):X2}";
case 0xCA: bytesToAdvance = 1; return "DEX";
case 0xCB: bytesToAdvance = 2; return $"AXS ${peeker(++pc):X2}";
case 0xCC: bytesToAdvance = 3; return $"CPY ${peeker_word(++pc, peeker):X4}";
case 0xCD: bytesToAdvance = 3; return $"CMP ${peeker_word(++pc, peeker):X4}";
case 0xCE: bytesToAdvance = 3; return $"DEC ${peeker_word(++pc, peeker):X4}";
case 0xD0: bytesToAdvance = 2; return $"BNE ${pc + 2 + (sbyte)peeker(++pc):X4}";
case 0xD1: bytesToAdvance = 2; return $"CMP (${peeker(++pc):X2}),Y *";
case 0xD4: bytesToAdvance = 2; return $"NOP ${peeker(++pc):X2},X";
case 0xD5: bytesToAdvance = 2; return $"CMP ${peeker(++pc):X2},X";
case 0xD6: bytesToAdvance = 2; return $"DEC ${peeker(++pc):X2},X";
case 0xD8: bytesToAdvance = 1; return "CLD";
case 0xD9: bytesToAdvance = 3; return $"CMP ${peeker_word(++pc, peeker):X4},Y *";
case 0xDA: bytesToAdvance = 1; return "NOP";
case 0xDC: bytesToAdvance = 2; return $"NOP (${peeker(++pc):X2},X)";
case 0xDD: bytesToAdvance = 3; return $"CMP ${peeker_word(++pc, peeker):X4},X *";
case 0xDE: bytesToAdvance = 3; return $"DEC ${peeker_word(++pc, peeker):X4},X";
case 0xE0: bytesToAdvance = 2; return $"CPX #${peeker(++pc):X2}";
case 0xE1: bytesToAdvance = 2; return $"SBC (${peeker(++pc):X2},X)";
case 0xE2: bytesToAdvance = 2; return $"NOP #${peeker(++pc):X2}";
case 0xE4: bytesToAdvance = 2; return $"CPX ${peeker(++pc):X2}";
case 0xE5: bytesToAdvance = 2; return $"SBC ${peeker(++pc):X2}";
case 0xE6: bytesToAdvance = 2; return $"INC ${peeker(++pc):X2}";
case 0xE8: bytesToAdvance = 1; return "INX";
case 0xE9: bytesToAdvance = 2; return $"SBC #${peeker(++pc):X2}";
case 0xEA: bytesToAdvance = 1; return "NOP";
case 0xEC: bytesToAdvance = 3; return $"CPX ${peeker_word(++pc, peeker):X4}";
case 0xED: bytesToAdvance = 3; return $"SBC ${peeker_word(++pc, peeker):X4}";
case 0xEE: bytesToAdvance = 3; return $"INC ${peeker_word(++pc, peeker):X4}";
case 0xF0: bytesToAdvance = 2; return $"BEQ ${pc + 2 + (sbyte)peeker(++pc):X4}";
case 0xF1: bytesToAdvance = 2; return $"SBC (${peeker(++pc):X2}),Y *";
case 0xF4: bytesToAdvance = 2; return $"NOP ${peeker(++pc):X2},X";
case 0xF5: bytesToAdvance = 2; return $"SBC ${peeker(++pc):X2},X";
case 0xF6: bytesToAdvance = 2; return $"INC ${peeker(++pc):X2},X";
case 0xF8: bytesToAdvance = 1; return "SED";
case 0xF9: bytesToAdvance = 3; return $"SBC ${peeker_word(++pc, peeker):X4},Y *";
case 0xFA: bytesToAdvance = 1; return "NOP";
case 0xFC: bytesToAdvance = 2; return $"NOP (${peeker(++pc):X2},X)";
case 0xFD: bytesToAdvance = 3; return $"SBC ${peeker_word(++pc, peeker):X4},X *";
case 0xFE: bytesToAdvance = 3; return $"INC ${peeker_word(++pc, peeker):X4},X";
}
bytesToAdvance = 1;
return "???";
}
}
}
|
1. Field
The invention relates to the field of tire vulcanization moulds, and more particularly moulds of the segmented type.
2. Description of Related Art
A segmented mould comprises a number of separate parts which are brought together to delimit a quasi-toroidal mould cavity. In particular, a segmented mould has two lateral shells for molding the sidewalls of the tire, and a plurality of peripheral segments located between the shells for molding the tire tread. All these parts are brought together in an appropriate sequence of operations provided by a chosen mechanism. The green tire must be firmly applied and retained against the mould in order to produce a precise architecture and geometric dimensions and form the patterns of the tread.
In order to form the patterns of the tread, the segments of the mould comprise elements projecting from the radially inner surfaces of the segments, these elements forming a negative of the patterns to be molded on the tire tread.
To enable a single mould to be used to manufacture tires having tread patterns of different shapes, there is a known method, described for example in EP 0 523 958, for making a segment of the mould in a plurality of elements, namely a support block having a general shape defining the general curvature of the tire tread, and a plurality of lining elements applied to the support block and designed to form the patterns of the tire tread.
The lining element described in that document is produced by molding, for example by molding in steel. It is therefore a bulky, heavy element which is expensive to manufacture. |
Uncategorized
Each week we read dozens of transcripts from earnings calls and presentations as part of our investment process. Below is a weekly post which contains some of the most important quotes about the economy and industry trends from those transcripts. Click … Continued
Powell Brown – President and CEO Still a lot of capital in insurance In summary, there continues to be a lot of capital across the insurance market place. However the recent storms, fires and earthquakes may have implications on pricing … Continued
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This week we’re starting a new experiment. We’re going to try to run a weekly post each Monday to expand upon the quotes that we gather in our weekly digest. The weekly digest is intended to be an unbiased view … Continued
VCA Antech (WOOF) CFO Tom Fuller said the company is executing “So in recap, we have a great company and a wonderful, wonderful industry, demand is still very strong, consumer is getting strong, our economy is stable, and people just … Continued
Expeditors International (EXPD) is seeing the Chinese economy slow in real-time but says they are trying to making the transition to a consumer driven economy “Despite the general economic slowdown in China, it is still one of the fastest growing economies … Continued
UnitedHealth Group (UNH) CEO Stephen Hemsley said the company had its highest customer retention ratio in its history “UnitedHealth Group businesses have steadily strengthened over the last several years and this trend continued in the first quarter of 2016. Our … Continued
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Source: December 2015 Stanford Interview https://www.youtube.com/watch?v=cYN3ghAam14&list=PLnsTB8Q5VgnVzh1S-VMCXiuwJglk5AV–&index=19 Linkedin (LNKD) CEO Jeff Weiner said executive decision making ultimately drives the long term success or failure of a business “At the end of the day, I think one of the most important drivers of … Continued
Kevin Ozan — CFO Working to develop a national value platform “we are focused on working with our franchisees to develop a national value platform that will help have an everyday predictable value platform going forward. Those are the key … Continued |
import { actionCreators as ac, actionTypes as at } from "common/Actions.jsm";
import { ComponentPerfTimer } from "content-src/components/ComponentPerfTimer/ComponentPerfTimer";
import createMockRaf from "mock-raf";
import React from "react";
import { shallow } from "enzyme";
const perfSvc = {
mark() {},
getMostRecentAbsMarkStartByName() {},
};
let DEFAULT_PROPS = {
initialized: true,
rows: [],
id: "highlights",
dispatch() {},
perfSvc,
};
describe("<ComponentPerfTimer>", () => {
let mockRaf;
let sandbox;
let wrapper;
const InnerEl = () => <div>Inner Element</div>;
beforeEach(() => {
mockRaf = createMockRaf();
sandbox = sinon.createSandbox();
sandbox.stub(window, "requestAnimationFrame").callsFake(mockRaf.raf);
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
});
afterEach(() => {
sandbox.restore();
});
it("should render props.children", () => {
assert.ok(wrapper.contains(<InnerEl />));
});
describe("#constructor", () => {
beforeEach(() => {
sandbox.stub(ComponentPerfTimer.prototype, "_maybeSendBadStateEvent");
sandbox.stub(
ComponentPerfTimer.prototype,
"_ensureFirstRenderTsRecorded"
);
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>,
{ disableLifecycleMethods: true }
);
});
it("should have the correct defaults", () => {
const instance = wrapper.instance();
assert.isFalse(instance._reportMissingData);
assert.isFalse(instance._timestampHandled);
assert.isFalse(instance._recordedFirstRender);
});
});
describe("#render", () => {
beforeEach(() => {
sandbox.stub(DEFAULT_PROPS, "id").value("fake_section");
sandbox.stub(ComponentPerfTimer.prototype, "_maybeSendBadStateEvent");
sandbox.stub(
ComponentPerfTimer.prototype,
"_ensureFirstRenderTsRecorded"
);
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
});
it("should not call telemetry on sections that we don't want to record", () => {
const instance = wrapper.instance();
assert.notCalled(instance._maybeSendBadStateEvent);
assert.notCalled(instance._ensureFirstRenderTsRecorded);
});
});
describe("#_componentDidMount", () => {
it("should call _maybeSendPaintedEvent", () => {
const instance = wrapper.instance();
const stub = sandbox.stub(instance, "_maybeSendPaintedEvent");
instance.componentDidMount();
assert.calledOnce(stub);
});
it("should not call _maybeSendPaintedEvent if id not in RECORDED_SECTIONS", () => {
sandbox.stub(DEFAULT_PROPS, "id").value("topstories");
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
const instance = wrapper.instance();
const stub = sandbox.stub(instance, "_maybeSendPaintedEvent");
instance.componentDidMount();
assert.notCalled(stub);
});
});
describe("#_componentDidUpdate", () => {
it("should call _maybeSendPaintedEvent", () => {
const instance = wrapper.instance();
const maybeSendPaintStub = sandbox.stub(
instance,
"_maybeSendPaintedEvent"
);
instance.componentDidUpdate();
assert.calledOnce(maybeSendPaintStub);
});
it("should not call _maybeSendPaintedEvent if id not in RECORDED_SECTIONS", () => {
sandbox.stub(DEFAULT_PROPS, "id").value("topstories");
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
const instance = wrapper.instance();
const stub = sandbox.stub(instance, "_maybeSendPaintedEvent");
instance.componentDidUpdate();
assert.notCalled(stub);
});
});
describe("_ensureFirstRenderTsRecorded", () => {
let recordFirstRenderStub;
beforeEach(() => {
sandbox.stub(ComponentPerfTimer.prototype, "_maybeSendBadStateEvent");
recordFirstRenderStub = sandbox.stub(
ComponentPerfTimer.prototype,
"_ensureFirstRenderTsRecorded"
);
});
it("should set _recordedFirstRender", () => {
sandbox.stub(DEFAULT_PROPS, "initialized").value(false);
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
const instance = wrapper.instance();
assert.isFalse(instance._recordedFirstRender);
recordFirstRenderStub.callThrough();
instance._ensureFirstRenderTsRecorded();
assert.isTrue(instance._recordedFirstRender);
});
it("should mark first_render_ts", () => {
sandbox.stub(DEFAULT_PROPS, "initialized").value(false);
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
const instance = wrapper.instance();
const stub = sandbox.stub(perfSvc, "mark");
recordFirstRenderStub.callThrough();
instance._ensureFirstRenderTsRecorded();
assert.calledOnce(stub);
assert.calledWithExactly(stub, `${DEFAULT_PROPS.id}_first_render_ts`);
});
});
describe("#_maybeSendBadStateEvent", () => {
let sendBadStateStub;
beforeEach(() => {
sendBadStateStub = sandbox.stub(
ComponentPerfTimer.prototype,
"_maybeSendBadStateEvent"
);
sandbox.stub(
ComponentPerfTimer.prototype,
"_ensureFirstRenderTsRecorded"
);
});
it("should set this._reportMissingData=true when called with initialized === false", () => {
sandbox.stub(DEFAULT_PROPS, "initialized").value(false);
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
const instance = wrapper.instance();
assert.isFalse(instance._reportMissingData);
sendBadStateStub.callThrough();
instance._maybeSendBadStateEvent();
assert.isTrue(instance._reportMissingData);
});
it("should call _sendBadStateEvent if initialized & other metrics have been recorded", () => {
const instance = wrapper.instance();
const stub = sandbox.stub(instance, "_sendBadStateEvent");
instance._reportMissingData = true;
instance._timestampHandled = true;
instance._recordedFirstRender = true;
sendBadStateStub.callThrough();
instance._maybeSendBadStateEvent();
assert.calledOnce(stub);
assert.isFalse(instance._reportMissingData);
});
});
describe("#_maybeSendPaintedEvent", () => {
it("should call _sendPaintedEvent if props.initialized is true", () => {
sandbox.stub(DEFAULT_PROPS, "initialized").value(true);
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>,
{ disableLifecycleMethods: true }
);
const instance = wrapper.instance();
const stub = sandbox.stub(instance, "_afterFramePaint");
assert.isFalse(instance._timestampHandled);
instance._maybeSendPaintedEvent();
assert.calledOnce(stub);
assert.calledWithExactly(stub, instance._sendPaintedEvent);
assert.isTrue(wrapper.instance()._timestampHandled);
});
it("should not call _sendPaintedEvent if this._timestampHandled is true", () => {
const instance = wrapper.instance();
const spy = sinon.spy(instance, "_afterFramePaint");
instance._timestampHandled = true;
instance._maybeSendPaintedEvent();
spy.neverCalledWith(instance._sendPaintedEvent);
});
it("should not call _sendPaintedEvent if component not initialized", () => {
sandbox.stub(DEFAULT_PROPS, "initialized").value(false);
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
const instance = wrapper.instance();
const spy = sinon.spy(instance, "_afterFramePaint");
instance._maybeSendPaintedEvent();
spy.neverCalledWith(instance._sendPaintedEvent);
});
});
describe("#_afterFramePaint", () => {
it("should call callback after the requestAnimationFrame callback returns", () =>
new Promise(resolve => {
// Setting the callback to resolve is the test that it does finally get
// called at the correct time, after the event loop ticks again.
// If it doesn't get called, this test will time out.
const callback = sandbox.spy(resolve);
const instance = wrapper.instance();
instance._afterFramePaint(callback);
assert.notCalled(callback);
mockRaf.step({ count: 1 });
}));
});
describe("#_sendBadStateEvent", () => {
it("should call perfSvc.mark", () => {
sandbox.spy(perfSvc, "mark");
const key = `${DEFAULT_PROPS.id}_data_ready_ts`;
wrapper.instance()._sendBadStateEvent();
assert.calledOnce(perfSvc.mark);
assert.calledWithExactly(perfSvc.mark, key);
});
it("should call compute the delta from first render to data ready", () => {
sandbox.stub(perfSvc, "getMostRecentAbsMarkStartByName");
wrapper
.instance()
._sendBadStateEvent(`${DEFAULT_PROPS.id}_data_ready_ts`);
assert.calledTwice(perfSvc.getMostRecentAbsMarkStartByName);
assert.calledWithExactly(
perfSvc.getMostRecentAbsMarkStartByName,
`${DEFAULT_PROPS.id}_data_ready_ts`
);
assert.calledWithExactly(
perfSvc.getMostRecentAbsMarkStartByName,
`${DEFAULT_PROPS.id}_first_render_ts`
);
});
it("should call dispatch SAVE_SESSION_PERF_DATA", () => {
sandbox
.stub(perfSvc, "getMostRecentAbsMarkStartByName")
.withArgs("highlights_first_render_ts")
.returns(0.5)
.withArgs("highlights_data_ready_ts")
.returns(3.2);
const dispatch = sandbox.spy(DEFAULT_PROPS, "dispatch");
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
wrapper.instance()._sendBadStateEvent();
assert.calledOnce(dispatch);
assert.calledWithExactly(
dispatch,
ac.OnlyToMain({
type: at.SAVE_SESSION_PERF_DATA,
data: { [`${DEFAULT_PROPS.id}_data_late_by_ms`]: 2 },
})
);
});
});
describe("#_sendPaintedEvent", () => {
beforeEach(() => {
sandbox.stub(ComponentPerfTimer.prototype, "_maybeSendBadStateEvent");
sandbox.stub(
ComponentPerfTimer.prototype,
"_ensureFirstRenderTsRecorded"
);
});
it("should not call mark with the wrong id", () => {
sandbox.stub(perfSvc, "mark");
sandbox.stub(DEFAULT_PROPS, "id").value("fake_id");
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
wrapper.instance()._sendPaintedEvent();
assert.notCalled(perfSvc.mark);
});
it("should call mark with the correct topsites", () => {
sandbox.stub(perfSvc, "mark");
sandbox.stub(DEFAULT_PROPS, "id").value("topsites");
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
wrapper.instance()._sendPaintedEvent();
assert.calledOnce(perfSvc.mark);
assert.calledWithExactly(perfSvc.mark, "topsites_first_painted_ts");
});
it("should not call getMostRecentAbsMarkStartByName if id!=topsites", () => {
sandbox.stub(perfSvc, "getMostRecentAbsMarkStartByName");
sandbox.stub(DEFAULT_PROPS, "id").value("fake_id");
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
wrapper.instance()._sendPaintedEvent();
assert.notCalled(perfSvc.getMostRecentAbsMarkStartByName);
});
it("should call getMostRecentAbsMarkStartByName for topsites", () => {
sandbox.stub(perfSvc, "getMostRecentAbsMarkStartByName");
sandbox.stub(DEFAULT_PROPS, "id").value("topsites");
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
wrapper.instance()._sendPaintedEvent();
assert.calledOnce(perfSvc.getMostRecentAbsMarkStartByName);
assert.calledWithExactly(
perfSvc.getMostRecentAbsMarkStartByName,
"topsites_first_painted_ts"
);
});
it("should dispatch SAVE_SESSION_PERF_DATA", () => {
sandbox.stub(perfSvc, "getMostRecentAbsMarkStartByName").returns(42);
sandbox.stub(DEFAULT_PROPS, "id").value("topsites");
const dispatch = sandbox.spy(DEFAULT_PROPS, "dispatch");
wrapper = shallow(
<ComponentPerfTimer {...DEFAULT_PROPS}>
<InnerEl />
</ComponentPerfTimer>
);
wrapper.instance()._sendPaintedEvent();
assert.calledOnce(dispatch);
assert.calledWithExactly(
dispatch,
ac.OnlyToMain({
type: at.SAVE_SESSION_PERF_DATA,
data: { topsites_first_painted_ts: 42 },
})
);
});
});
});
|
Trends in cerebral palsy among infants of very low birthweight (<1500 g) or born prematurely (<32 weeks) in 16 European centres: a database study.
The risk of cerebral palsy, the commonest physical disability of children in western Europe, is higher in infants of very low birthweight (VLBW)--those born weighing less than 1500 g--and those from multiple pregnancies than in infants of normal birthweight. An increasing proportion of infants from both of these groups survive into childhood. This paper describes changes in the frequency and distribution of cerebral palsy by sex and neurological subtype in infants with a birthweight below 1000 g and 1000-1499 g in the period 1980-96. A group of 16 European centres, Surveillance of Cerebral Palsy in Europe, agreed a standard definition of cerebral palsy and inclusion and exclusion criteria. Data for children with cerebral palsy born in the years 1980-96 were pooled. The data were analysed to describe the distribution and prevalence of cerebral palsy in VLBW infants. Prevalence trends were expressed as both per 1000 livebirths and per 1000 neonatal survivors. There were 1575 VLBW infants born with cerebral palsy; 414 (26%) were of birthweight less than 1000 g and 317 (20%) were from multiple pregnancies. 1426 (94%) had spastic cerebral palsy, which was unilateral (hemiplegic) in 336 (24%). The birth prevalence fell from 60.6 (99%CI 37.8-91.4) per 1000 liveborn VLBW infants in 1980 to 39.5 (28.6-53.0) per 1000 VLBW infants in 1996. This decline was related to a reduction in the frequency of bilateral spastic cerebral palsy among infants of birthweight 1000-1499 g. The frequency of cerebral palsy was higher in male than female babies in the group of birthweight 1000-1499 g (61.0 [53.8-68..2] vs 49.5 [42.8-56.2] per 1000 livebirths; p=0.0025) but not in the group of birthweight below 1000 g. These data from a large population base provide evidence that the prevalence of cerebral palsy in children of birthweight less than 1500 g has fallen, which has important implications for parents, health services, and society. |
Force.com and Apex Fundamentals for Developers
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Q:
Save canvas paths to SharedPreference and redraw on canvas when app is reopened
I have a custom view which I used to draw different sizes and image to a canvas. It's great. So every time I draw something I am adding those information to an actionList.
When the user exit the application, I am saving this actionList as string to sharedPreference. At the time the user reopens the app I am getting this data and use Gson to convert it back List previous_drawn_paths and update actionList with this.
When I do this I am getting segmentation fault, but there is data and memory reference. I have attached code and tombstone logcat as well.
DrawingView.java
public class DrawingView extends View {
public enum Type {
PATH,
TEXT,
STAMP;
}
/**
* Different type of draw
*/
public enum Mode {
DRAW,
ERASER,
TEXT,
STAMP;
}
/**
* Different Modes for Drawing
*/
public enum Drawer {
PEN,
LINE,
ELLIPSE;
}
/**
* Different Modes of Stamps
*/
public enum Stamper {
STAR,
THUMB;
}
private Context context = null;
private Canvas canvas = null;
private Bitmap bitmap = null;
private int width;
private int height;
private int historyPointer = 0;
private List<DrawingAction> previous_action_list = new ArrayList<>();
private String TAG = this.getClass().getCanonicalName();
public List<DrawingAction> getPrevious_action_list() {
return previous_action_list;
}
public void setPrevious_action_list(List<DrawingAction> previous_action_list) {
this.previous_action_list = previous_action_list;
updateHistoryPath();
}
/**
* Collection of different types of actions
*/
private List<DrawingAction> actionLists = new ArrayList<>();
public List<DrawingAction> getActionLists() {
return actionLists;
}
/**
* Flags for maintaining the states
*/
private boolean enabled = false;
private boolean isDown = false;
private Mode mode = Mode.DRAW;
private Drawer drawer = Drawer.PEN;
private Stamper stamper = Stamper.STAR;
private float startX = 0F;
private float startY = 0F;
private Paint drawPaint;
private Paint erasePaint;
private Paint textPaint;
private Bitmap starPaint;
private Bitmap thumbPaint;
public DrawingView(Context context) {
super(context);
this.setup(context);
}
public DrawingView(Context context, AttributeSet attrs) {
super(context, attrs);
this.setup(context);
}
public DrawingView(Context context, AttributeSet attrs, int defStyleAttr) {
super(context, attrs, defStyleAttr);
this.setup(context);
}
private void setup(Context context) {
this.context = context;
createDrawPaint();
createErasePaint();
createTextPaint();
createStamperPaint(context);
}
private void createDrawPaint() {
this.drawPaint = new Paint();
this.drawPaint.setAntiAlias(true);
this.drawPaint.setStyle(Paint.Style.STROKE);
this.drawPaint.setStrokeWidth(10F);
this.drawPaint.setStrokeCap(Paint.Cap.BUTT);
this.drawPaint.setStrokeJoin(Paint.Join.MITER);
this.drawPaint.setColor(Color.RED);
this.drawPaint.setAlpha(255);
}
private void createErasePaint() {
this.erasePaint = new Paint();
this.erasePaint.setColor(Color.WHITE);
this.erasePaint.setAlpha(255);
this.erasePaint.setAntiAlias(true);
this.erasePaint.setDither(true);
this.erasePaint.setStyle(Paint.Style.STROKE);
this.erasePaint.setStrokeJoin(Paint.Join.ROUND);
this.erasePaint.setStrokeCap(Paint.Cap.ROUND);
this.erasePaint.setStrokeWidth(10F);
}
private void createTextPaint() {
this.textPaint = new Paint();
this.textPaint.setAntiAlias(true);
this.textPaint.setStyle(Paint.Style.STROKE);
this.textPaint.setStrokeCap(Paint.Cap.BUTT);
this.textPaint.setStrokeJoin(Paint.Join.MITER);
this.textPaint.setTypeface(Typeface.DEFAULT);
this.textPaint.setTextSize(56F);
this.textPaint.setTextAlign(Paint.Align.RIGHT);
this.drawPaint.setColor(Color.RED);
this.textPaint.setStrokeWidth(0F);
}
private void createStamperPaint(Context context) {
this.starPaint = BitmapFactory.decodeResource(context.getResources(), R.mipmap.stamp_star);
this.thumbPaint = BitmapFactory.decodeResource(context.getResources(), R.mipmap.stamp_thumb);
}
private DrawingAction getCurrentAction() {
return this.actionLists.get(this.historyPointer-1);
}
private void drawText(DrawingAction action, Canvas canvas) {
String text = action.getText();
if((text == null) || (text.length() <= 0)) {
return;
}
float textX = action.getPositionX();
float textY = action.getPositionY();
Paint paintMeasureText = new Paint();
float textLength = paintMeasureText.measureText(text);
float lengthOfChar = textLength / (float) text.length();
float restWidth = this.canvas.getWidth() - textX; // text-align : right
int numChars = (lengthOfChar <= 0) ? 1 : (int) Math.floor((double) (restWidth / lengthOfChar)); // The number of characters at 1 line
int modNumChars = (numChars < 1) ? 1 : numChars;
float y = textY;
for (int i = 0, len = text.length(); i < len; i += modNumChars) {
String substring = "";
if ((i + modNumChars) < len) {
substring = text.substring(i, (i + modNumChars));
} else {
substring = text.substring(i, len);
}
//TODO: Adjust according to the font size
y += 56F;
canvas.drawText(substring, textX, y, this.textPaint);
}
}
private void updateHistory(DrawingAction action) {
if (this.historyPointer == this.actionLists.size()) {
this.actionLists.add(action);
Log.d(TAG,"history pointer update"+this.historyPointer);
this.historyPointer++;
} else {
// Removing the unused actions in history
this.actionLists.set(this.historyPointer, action);
this.historyPointer++;
for (int i = this.historyPointer, size = this.actionLists.size(); i < size; i++) {
this.actionLists.remove(this.historyPointer);
}
}
}
private void updateHistoryPath()
{
for(int index=0 ; index<previous_action_list.size(); index++)
{
Log.d(TAG,"adding canvas index from previous list"+index);
if (previous_action_list.get(index).getType()!=null)
{
updateHistory(new DrawingAction(previous_action_list.get(index).getType(),previous_action_list.get(index).getPath(),previous_action_list.get(index).getPaint()));
}
}
}
public boolean undo() {
if (this.historyPointer > 1) {
this.historyPointer--;
this.invalidate();
return true;
} else {
return false;
}
}
public boolean redo() {
if (this.historyPointer < this.actionLists.size()) {
this.historyPointer++;
this.invalidate();
return true;
} else {
return false;
}
}
@Override
protected void onDraw(Canvas canvas) {
super.onDraw(canvas);
canvas.drawColor(Color.TRANSPARENT);
if (this.bitmap != null) {
canvas.drawBitmap(this.bitmap, 0F, 0F, new Paint());
}
// this.historyPointer
for (int i = 0; i < this.historyPointer; i++) {
DrawingAction action = this.actionLists.get(i);
Type type = action.getType();
if(type == Type.PATH) {
canvas.drawPath(action.getPath(), action.getPaint());
Log.d("lingaraj","on draw history index"+i);
}
else if(type == Type.TEXT) {
this.drawText(action, canvas);
}
else if(type == Type.STAMP) {
Stamper stamper = action.getStamper();
if(stamper == Stamper.STAR) {
canvas.drawBitmap(this.starPaint, action.getPositionX(), action.getPositionY(), new Paint());
}
else if(stamper == Stamper.THUMB) {
canvas.drawBitmap(this.thumbPaint, action.getPositionX(), action.getPositionY(), new Paint());
}
}
}
this.canvas = canvas;
}
@Override
protected void onMeasure(int widthMeasureSpec, int heightMeasureSpec) {
int width = MeasureSpec.getSize(widthMeasureSpec);
int height = MeasureSpec.getSize(heightMeasureSpec);
setMeasuredDimension(width, height);
}
public void setCustomWidth(int width) {
this.width = width;
}
public int getCustomWidth() {
return this.width;
}
public void setCustomHeight(int height) {
this.height = height;
}
public int getCustomHeight() {
return this.height;
}
public void setEnabled(boolean enabled) {
this.enabled = enabled;
}
public boolean getEnabled() {
return this.enabled;
}
public void setMode(Mode mode) {
this.mode = mode;
}
public Mode getMode() {
return this.mode;
}
public void setDrawer(Drawer drawer) {
this.drawer = drawer;
this.mode = Mode.DRAW;
}
public void setStamper(Stamper stamper) {
this.stamper = stamper;
this.mode = Mode.STAMP;
}
public void setBitmap(Bitmap bitmap) {
this.bitmap = bitmap;
invalidate();
}
}
DrawingAction.java:
public class DrawingAction {
private DrawingView.Type type;
private Path path;
private Paint paint;
private String text;
private DrawingView.Stamper stamper;
private float positionX;
private float positionY;
public DrawingAction(DrawingView.Type type, Path path, Paint paint) {
this.type = type;
this.path = path;
this.paint = paint;
}
public DrawingAction(DrawingView.Type type, Path path, Paint paint, float positionX, float positionY) {
this.type = type;
this.path = path;
this.paint = paint;
this.positionX = positionX;
this.positionY = positionY;
}
public DrawingAction(DrawingView.Type type, String text, float positionX, float positionY) {
this.type = type;
this.text = text;
this.positionX = positionX;
this.positionY = positionY;
}
public DrawingAction(DrawingView.Type type, DrawingView.Stamper stamper, float positionX, float positionY) {
this.type = type;
this.stamper = stamper;
this.positionX = positionX;
this.positionY = positionY;
}
public DrawingView.Type getType() {
return type;
}
public Path getPath() {
return path;
}
public void setPath(Path path) {
this.path = path;
}
public Paint getPaint() {
return paint;
}
public void setPaint(Paint paint) {
this.paint = paint;
}
public String getText() {
return text;
}
public void setText(String text) {
this.text = text;
}
public DrawingView.Stamper getStamper() {
return stamper;
}
public void setStamper(DrawingView.Stamper stamper) {
this.stamper = stamper;
}
public float getPositionX() {
return positionX;
}
public void setPositionX(float positionX) {
this.positionX = positionX;
}
public float getPositionY() {
return positionY;
}
public void setPositionY(float positionY) {
this.positionY = positionY;
}
}
MainActivity.java:
public class MainActivity extends AppCompatActivity {
public static final String TAG = "Draw";
private DrawingView drawing;
private CanvasScroll scroll;
@Override
protected void onCreate(Bundle savedInstanceState) {
super.onCreate(savedInstanceState);
setContentView(R.layout.activity_correct);
drawing = (DrawingView) findViewById(R.id.canvasDrawing);
List<DrawingAction> drawing_action_list = new ArrayList<>();
drawing_action_list = stringToList(Settings.getCorrectionPath(getApplicationContext()));
disableScroll();
if (drawing_action_list.isEmpty())
{
Log.d(TAG,"Drawing action list empty previous path not drawn");
}
else
{
drawing.setPrevious_action_list(drawing_action_list);
Log.d(TAG,"Drawing action list previous path drawn on canvas");
}
}
logcat:
A/libc : Fatal signal 11 (SIGSEGV) at 0xb7bdb5a0 (code=1), thread 2064 (hourglass.drawing)
Tombstone:
backtrace:
--------- log /dev/log/main
08-20 02:39:00.584 2064 2064 D dalvikvm: Not late-enabling CheckJNI (already on)
08-20 02:39:00.664 2064 2064 W dalvikvm: VFY: unable to find class referenced in signature (Landroid/view/SearchEvent;)
08-20 02:39:00.664 2064 2064 I dalvikvm: Could not find method android.view.Window$Callback.onSearchRequested, referenced from method android.support.v7.view.WindowCallbackWrapper.onSearchRequested
08-20 02:39:00.664 2064 2064 W dalvikvm: VFY: unable to resolve interface method 19785: Landroid/view/Window$Callback;.onSearchRequested (Landroid/view/SearchEvent;)Z
08-20 02:39:00.664 2064 2064 D dalvikvm: VFY: replacing opcode 0x72 at 0x0002
08-20 02:39:00.664 2064 2064 I dalvikvm: Could not find method android.view.Window$Callback.onWindowStartingActionMode, referenced from method android.support.v7.view.WindowCallbackWrapper.onWindowStartingActionMode
08-20 02:39:00.664 2064 2064 W dalvikvm: VFY: unable to resolve interface method 19789: Landroid/view/Window$Callback;.onWindowStartingActionMode (Landroid/view/ActionMode$Callback;I)Landroid/view/ActionMode;
08-20 02:39:00.664 2064 2064 D dalvikvm: VFY: replacing opcode 0x72 at 0x0002
08-20 02:39:00.684 2064 2064 I dalvikvm: Could not find method android.content.res.TypedArray.getChangingConfigurations, referenced from method android.support.v7.widget.TintTypedArray.getChangingConfigurations
08-20 02:39:00.684 2064 2064 W dalvikvm: VFY: unable to resolve virtual method 448: Landroid/content/res/TypedArray;.getChangingConfigurations ()I
08-20 02:39:00.684 2064 2064 D dalvikvm: VFY: replacing opcode 0x6e at 0x0002
08-20 02:39:00.684 2064 2064 I dalvikvm: Could not find method android.content.res.TypedArray.getType, referenced from method android.support.v7.widget.TintTypedArray.getType
08-20 02:39:00.694 2064 2064 W dalvikvm: VFY: unable to resolve virtual method 470: Landroid/content/res/TypedArray;.getType (I)I
08-20 02:39:00.694 2064 2064 D dalvikvm: VFY: replacing opcode 0x6e at 0x0002
08-20 02:39:00.734 2064 2064 D dalvikvm: GC_FOR_ALLOC freed 240K, 9% free 3098K/3400K, paused 39ms, total 41ms
08-20 02:39:00.884 2064 2064 D dalvikvm: GC_FOR_ALLOC freed 9K, 9% free 3121K/3400K, paused 3ms, total 3ms
08-20 02:39:00.934 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 65.356MB for 65280012-byte allocation
08-20 02:39:00.954 2064 2072 D dalvikvm: GC_FOR_ALLOC freed <1K, 1% free 66870K/67152K, paused 16ms, total 16ms
08-20 02:39:01.254 2064 2064 D dalvikvm: GC_FOR_ALLOC freed 46K, 1% free 66909K/67164K, paused 4ms, total 5ms
08-20 02:39:01.264 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 75.718MB for 10825612-byte allocation
08-20 02:39:01.284 2064 2072 D dalvikvm: GC_FOR_ALLOC freed 2K, 1% free 77479K/77736K, paused 17ms, total 17ms
08-20 02:39:01.314 2064 2064 Din.co.hourglass.drawing.MainActivity: Original pixels3400/796
08-20 02:39:01.324 2064 2064 Din.co.hourglass.drawing.MainActivity: Scaled pixels1700/398
08-20 02:39:01.324 2064 2064 D dalvikvm: GC_FOR_ALLOC freed 1K, 1% free 77478K/77736K, paused 3ms, total 3ms
08-20 02:39:01.324 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 78.296MB for 2706412-byte allocation
08-20 02:39:01.344 2064 2072 D dalvikvm: GC_FOR_ALLOC freed <1K, 1% free 80121K/80380K, paused 15ms, total 15ms
08-20 02:39:01.374 2064 2064 D dalvikvm: GC_FOR_ALLOC freed 10572K, 14% free 69550K/80380K, paused 3ms, total 3ms
08-20 02:39:01.374 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 78.738MB for 11288012-byte allocation
08-20 02:39:01.424 2064 2064 D dalvikvm: GC_FOR_ALLOC freed <1K, 12% free 80573K/91404K, paused 2ms, total 2ms
08-20 02:39:01.424 2064 2064 Din.co.hourglass.drawing.MainActivity: Original pixels3400/830
08-20 02:39:01.424 2064 2064 Din.co.hourglass.drawing.MainActivity: Scaled pixels1700/415
08-20 02:39:01.424 2064 2064 D dalvikvm: GC_FOR_ALLOC freed <1K, 12% free 80573K/91404K, paused 3ms, total 3ms
08-20 02:39:01.434 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 81.429MB for 2822012-byte allocation
08-20 02:39:01.434 2064 2064 D dalvikvm: GC_FOR_ALLOC freed <1K, 9% free 83329K/91404K, paused 3ms, total 3ms
08-20 02:39:01.434 2064 2064 D dalvikvm: GC_FOR_ALLOC freed <1K, 9% free 83329K/91404K, paused 2ms, total 3ms
08-20 02:39:01.434 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 86.701MB for 5528412-byte allocation
08-20 02:39:01.444 2064 2064 D dalvikvm: GC_FOR_ALLOC freed <1K, 3% free 88728K/91404K, paused 2ms, total 2ms
08-20 02:39:01.484 2064 2064 D dalvikvm: GC_FOR_ALLOC freed 16422K, 4% free 72306K/75312K, paused 4ms, total 4ms
08-20 02:39:01.484 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 81.221MB for 11070412-byte allocation
08-20 02:39:01.534 2064 2064 D dalvikvm: GC_FOR_ALLOC freed <1K, 4% free 83117K/86124K, paused 10ms, total 10ms
08-20 02:39:01.534 2064 2064 Din.co.hourglass.drawing.MainActivity: Original pixels3400/814
08-20 02:39:01.534 2064 2064 Din.co.hourglass.drawing.MainActivity: Scaled pixels1700/407
08-20 02:39:01.544 2064 2064 D dalvikvm: GC_FOR_ALLOC freed <1K, 4% free 83117K/86124K, paused 8ms, total 8ms
08-20 02:39:01.544 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 83.861MB for 2767612-byte allocation
08-20 02:39:01.554 2064 2064 D dalvikvm: GC_FOR_ALLOC freed <1K, 1% free 85819K/86124K, paused 12ms, total 12ms
08-20 02:39:01.564 2064 2064 D dalvikvm: GC_FOR_ALLOC freed 10811K, 1% free 75008K/75312K, paused 2ms, total 3ms
08-20 02:39:01.564 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 81.215MB for 8296012-byte allocation
08-20 02:39:01.574 2064 2064 D dalvikvm: GC_FOR_ALLOC freed <1K, 1% free 83110K/83416K, paused 5ms, total 6ms
08-20 02:39:01.594 2064 2064 D dalvikvm: GC_FOR_ALLOC freed 8101K, 11% free 75009K/83416K, paused 4ms, total 4ms
08-20 02:39:01.594 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 77.350MB for 4243212-byte allocation
08-20 02:39:01.614 2064 2064 D dalvikvm: GC_FOR_ALLOC freed <1K, 6% free 79152K/83416K, paused 2ms, total 2ms
08-20 02:39:01.614 2064 2064 Din.co.hourglass.drawing.MainActivity: Original pixels3400/312
08-20 02:39:01.614 2064 2064 Din.co.hourglass.drawing.MainActivity: Scaled pixels1700/156
08-20 02:39:01.614 2064 2064 D dalvikvm: GC_FOR_ALLOC freed 4144K, 9% free 76045K/83416K, paused 2ms, total 3ms
08-20 02:39:01.614 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 83.239MB for 9356812-byte allocation
08-20 02:39:01.624 2064 2064 D dalvikvm: GC_FOR_ALLOC freed <1K, 8% free 85182K/92556K, paused 2ms, total 3ms
08-20 02:39:01.624 2064 2064 Din.co.hourglass.drawing.MainActivity: Bitmap Merged
08-20 02:39:01.714 2064 2064 D : HostConnection::get() New Host Connection established 0xb833f3c0, tid 2064
08-20 02:39:02.844 2064 2064 D dalvikvm: GC_FOR_ALLOC freed 18381K, 8% free 67150K/72492K, paused 3ms, total 8ms
08-20 02:39:02.844 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 77.371MB for 12312340-byte allocation
08-20 02:39:02.884 2064 2064 D dalvikvm: GC_FOR_ALLOC freed 8K, 7% free 79165K/84516K, paused 3ms, total 3ms
08-20 02:39:02.904 2064 2064 D lingaraj: adding canvas index from previous list0
08-20 02:39:02.904 2064 2064 D lingaraj: history pointer update0
08-20 02:39:02.904 2064 2064 D lingaraj: adding canvas index from previous list1
08-20 02:39:02.904 2064 2064 D lingaraj: history pointer update1
08-20 02:39:02.914 2064 2064 D Drawing: Drawing action list previous path drawn on canvas
08-20 02:39:03.074 2064 2064 D dalvikvm: GC_FOR_ALLOC freed 337K, 7% free 79264K/84516K, paused 3ms, total 4ms
08-20 02:39:03.074 2064 2064 I dalvikvm-heap: Grow heap (frag case) to 86.820MB for 9815116-byte allocation
08-20 02:39:03.084 2064 2064 D dalvikvm: GC_FOR_ALLOC freed <1K, 6% free 88849K/94104K, paused 2ms, total 3ms
08-20 02:39:03.084 2064 2064 F libc : Fatal signal 11 (SIGSEGV) at 0xb7bdb5a0 (code=1), thread 2064 (hourglass.drawing)
A:
The following is a working solution for saving paths and redrawing again, instead of imposing it on the Image and saving. In my case saved path is the problem not the paint object that i save.
PathPoint.Java
I am saving the co-ordinate of every action that was made by the user to this object and add it to a list in DrawingAction.java
public class PathPoint {
float startX;
float startY;
public float getStartX() {
return startX;
}
public void setStartX(float startX) {
this.startX = startX;
}
public float getStartY() {
return startY;
}
public void setStartY(float startY) {
this.startY = startY;
}
}
DrawingAction.java
Added the following piece of code to DrawingAction.java
private List<PathPoint> pts = new ArrayList<>();
public CorrectionView.Drawer getDrawer() {
return drawer;
}
public List<PathPoint> getPts() {
return pts;
}
public void setPts(List<PathPoint> pts) {
this.pts = pts;
}
public void addPts(PathPoint point)
{
this.pts.add(point);
//Adds touch co-ordinates to this list from Drawing View( on Touch Listener)
}
DrawingView.java
So In my DrawingView when the data is fectched from json, I am creating a fresh path and draw using the co_ordinates(PathPoint) from each actions. Thus I have able to achieve drawing from stored paths.
public void setPrevious_action_list(List<DrawingAction> previous_action_list) {
// updateActionListPath(previous_action_list);
this.previous_action_list = previous_action_list;
Path drawing_path;
for (DrawingAction action:previous_action_list)
{
drawing_path = new Path();
if (action.getType().equals(Type.PATH) && action.getDrawer().equals(Drawer.PEN) && action.getPts().size()>0)
{
//Setting starting path to path_point(0).startx and starty, if not set the points will be started from top corner.
drawing_path.moveTo(action.getPts().get(0).getStartX(),action.getPts().get(0).getStartY());
drawing_path.lineTo(action.getPts().get(0).getStartX(),action.getPts().get(0).getStartY());
drawing_path.moveTo(action.getPts().get(action.getPts(0).getStartX(),action.getPts().get(action.getPts(0).getStartY());
for (PathPoint path_point:action.getPts())
{
drawing_path.lineTo(path_point.getStartX(),path_point.getStartY());
}
action.setPath(drawing_path);
action.setPaint(this.drawPaint);
}
else if (action.getType().equals(Type.PATH) && action.getDrawer().equals(Drawer.LINE) && action.getPts().size()>0)
{
Log.d(TAG,"Using Line in setting action path");
drawing_path = new Path();
drawing_path.moveTo(action.getPts().get(0).getStartX(),action.getPts().get(0).getStartY());
for (PathPoint path_point:action.getPts())
{
drawing_path.lineTo(path_point.getStartX(),path_point.getStartY());
}
action.setPath(drawing_path);
action.setPaint(this.drawPaint);
}
else if (action.getType().equals(Type.PATH) && action.getDrawer().equals(Drawer.ELLIPSE) && action.getPts().size()>0)
{
if (action.getPts().size()==2)
{
drawing_path = new Path();
float start_x = action.getPts().get(0).getStartX();
float start_y = action.getPts().get(0).getStartY();
float end_x = action.getPts().get(1).getStartX();
float end_y = action.getPts().get(1).getStartY();
RectF rect = new RectF(start_x, start_y, end_x, end_y);
drawing_path.reset();
drawing_path.addOval(rect, Path.Direction.CCW);
action.setPath(drawing_path);
action.setPaint(this.drawPaint);
}
}
}
updateHistoryPath();
invalidate();
}
private void onActionMove(MotionEvent event) {
if (!isDown) {
return;
}
float x = event.getX();
float y = event.getY();
switch (this.mode) {
case DRAW:
DrawingAction drawing = this.getCurrentAction();
if(drawing.getType() == Type.PATH) {
Path path = drawing.getPath();
switch (this.drawer) {
case PEN:
path.lineTo(x, y);
PathPoint path_point = new PathPoint();
path_point.setStartX(x);
path_point.setStartY(y);
drawing.addPts(path_point);
drawing.setPath(path);
break;
case LINE:
path.reset();
path.moveTo(this.startX, this.startY);
path.lineTo(x, y);
// path_point = new PathPoint();
// path_point.setStartX(this.startX);
// path_point.setStartY(this.startY);
// drawing.addPts(path_point);
path_point = new PathPoint();
path_point.setStartX(x);
path_point.setStartY(y);
drawing.addPts(path_point);
drawing.setPath(path);
break;
case ELLIPSE:
RectF rect = new RectF(this.startX, this.startY, x, y);
path.reset();
path.addOval(rect, Path.Direction.CCW);
path_point =new PathPoint();
path_point.setStartY(this.startX);
path_point.setStartY(this.startY);
drawing.addPts(path_point);
path_point = new PathPoint();
path_point.setStartX(x);
path_point.setStartY(y);
drawing.addPts(path_point);
drawing.setPath(path);
break;
}
}
|
How To Keep Garden Tools Clean
Maintaining Garden Tools DoItYourself.comWhatever disinfectant method you choose, be sure to keep your tools clean and sharp. Lastly, if you don't regularly wear gardening gloves, be sure to wash your hands frequently when touching plants. Lastly, if you don't regularly wear gardening gloves, be sure to …... Clean and Dry Tools. Because most garden tools are exposed to dirt and moisture, this is the first place to start when it comes time for tool maintenance. Cleaning and drying your garden tools will keep them in good working order. For shovels, rakes and trowels that come in contact with soil, wash the dirt off with the strong spray from your hose. If the dirt is caked on, keep a brush nearby
Cleaning Garden Tools University of VermontLookin’ Sharp – How to Keep Your Garden Tools Clean and Sharpened (Video) May 3, 2009 by Genevieve 13 Comments Wrapping up our series on the hand tools we use most in gardening , I want to show you my favorite sharpening tool, the Speedy Sharp, and how to use it to sharpen your pruning shears and your soil knife or hori-hori :... 12/02/2014 · Jeyes Fluid can be used to clean garden tools with caked on mud and dirt. Take dirty tools and scrub them in diluted Jeyes Fluid. After a quick rinse with clean water your tools …
How to Clean Rusty Shovels Home Guides SF GateDrying, storing and cleaning your garden tools are very vital to keep your garden tools free from rust. However, it does not end there. Finding an However, it does not end there. Finding an awesome rust remover doesn’t put a stop to your rust problems. how to connect gamecom headphones to ps4 12/02/2014 · Jeyes Fluid can be used to clean garden tools with caked on mud and dirt. Take dirty tools and scrub them in diluted Jeyes Fluid. After a quick rinse with clean water your tools …
How to Clean Your Rusty Garden Tools 14 Steps wikiHowI admit it, I don't always remember to clean my garden tools when I'm done with them. Actually, I rarely remember! Unfortunately that means that as I get all my hand tools out for my spring gardening, that many of them are rusty. how to clean a wound after operation 1. Soak rusted items in vinegar for 3 hours, then scrub with a toothbrush. 2. Soak cleaned items in a solution of one part baking soda, two parts water for five minutes. 3. Rinse in water. Dry
How long can it take?
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Tools and equipment like secateurs, sheers, spades and even boots can spread disease. When pruning, always disinfect secateurs or pruners between specimens, using a solution no stronger than one part household bleach or tea tree oil to 10 parts water. Dip equipment into the solution for around 30 seconds. Use the same solution to keep your watering can clean, which needs a good scrub out every
Clean and Dry Tools. Because most garden tools are exposed to dirt and moisture, this is the first place to start when it comes time for tool maintenance. Cleaning and drying your garden tools will keep them in good working order. For shovels, rakes and trowels that come in contact with soil, wash the dirt off with the strong spray from your hose. If the dirt is caked on, keep a brush nearby
Keeping garden tools, such as shovels and spades, clean and sharp makes your job as a gardener easier. Not only can you count on your shovel to cut through the soil, but it will also last longer
To keep your tool blades sparkly and free of dust during hibernation, all you'll need is a little sand and oil. Follow these three easy steps to ensure your treasured tools will be in great shape for another season working the soil.
A new lubricant and water-repellant called Jig-A-Loo is a gardenerA?a‚¬a„?s dream product. Not only will it keep your tools from rusting or corroding when you accidently leave them out in the rain, but it will also prevent mud and other gunk from sticking to the tools and ruining them forever. |
---
abstract: 'We provide explicit sufficient conditions for a polynomial $f$ to be a sum of squares (s.o.s.), linear in the coefficients of $f$. All conditions are simple and provide an explicit description of a convex polyhedral subcone of the cone of s.o.s. polynomials of degree at most $2d$. We also provide a simple condition to ensure that $f$ is s.o.s., possibly after adding a constant.'
address: 'LAAS-CNRS and Institute of Mathematics, LAAS, 7 avenue du Colonel Roche, 31077 Toulouse cedex 4, France'
author:
- 'Jean B. Lasserre'
title: Sufficient conditions for a real polynomial to be a sum of squares
---
Introduction
============
The cone $\Sigma^2\subset\R[X]$ of real polynomials that are sum of squares (s.o.s.) and its subcone $\Sigma^2_d$ of s.o.s. of degree at most $2d$, play a fundamental role in many areas, and particularly in optimization; see for instance Lasserre [@lasserre1; @lasserre2], Parrilo [@parrilo] and Schweighofer [@markus]. When considered as a convex cone of a finite dimensional euclidean space, $\Sigma^2_d$ has a [*lifted semidefinite representation*]{} (such sets are called SDr sets in [@bental]). That is, $\Sigma^2_d$ is the projection of a convex cone of an euclidean space of higher dimension, defined in terms of the coefficients of the polynomial and additional variables (the “lifting”). However, so far there is no simple description of $\Sigma^2_d$ given [*directly*]{} in terms of the coefficients of the polynomial. For more details on SDr sets, the interested reader is referred to e.g. Ben Tal and Nemirovski [@bental], Helton and Vinnikov [@helton], Lewis et al. [@lewis].
Of course, one could use Tarski’s quantifier elimination to provide a description of $\Sigma^2_d$, solely in terms of the coefficients, but such a description is likely hopeless to be [*simple*]{}; in particular, it could be sensitive to the degree $d$. Therefore, a more reasonable goal is to search for simple descriptions of [*subsets*]{} (or [*subcones*]{}) of $\Sigma_d^2$ only. This is the purpose of this note in which we provide simple sufficient conditions for a polynomial $f\in\R[X]$ of degree at most $2d$, to be s.o.s. All conditions are expressed directly in terms of the coefficients $(f_\alpha)$, with no additional variable (i.e. with no lifting) and define a convex polyhedral subcone of $\Sigma^2_d$. Finally, we also provide a sufficient condition on the coefficients of highest degree to ensure that $f$ is s.o.s., possibly after adding a constant. All conditions stress the importance of the [*essential*]{} monomials $(X_i^{2k})$ which also play an important role for approximating nonnegative polynomials by s.o.s., as demonstrated in e.g. [@lasserre2; @lasserre-tim].
Conditions for being s.o.s.
===========================
For $\alpha\in\N^n$ let $\va:=\sum_{i=1}^n\vert\alpha_i\vert$. Let $\R[X]$ be the ring of real polynomials in the variables $X=(X_1,\ldots,X_n)$, and let $\R[X]_{2d}$ the vector space of real polynomials of degree at most $2d$, with canonical basis of monomials $(X^\alpha)=\{X^\alpha\::\:\alpha\in\N^n;\: \va\leq 2d\}$. Given a sequence $y=(y_\alpha)\subset\R$ indexed in the canonical basis $(X^\alpha)$, let $L_y:\R[X]_{2d}\to\,\R$ be the linear mapping $$f\,(=\sum_\alpha f_\alpha\,X^\alpha)\quad\mapsto\quad L_y(f)\,=\,\sum_{\alpha}f_\alpha\,y_\alpha,\quad f\in\R[X]_{2d},$$ and let $M_d(y)$ be the [*moment*]{} matrix with rows and columns indexed in $(X^\alpha)$, and defined by $$\label{moment}
M_d(y)(\alpha,\beta)\,:=\,L_y(X^{\alpha+\beta})\,=\,y_{\alpha+\beta},\qquad\alpha,\beta\in\N^n:\: \vert\alpha\vert,\vert\beta\vert\,\leq\,d.$$ Let the notation $M_d(y)\succeq0$ stand for $M_d(y)$ is positive semidefinite. It is clear that $$M_d(y)\,\succeq\, 0\quad\Longleftrightarrow\quad L_y(f^2)\geq\,0\quad\forall\,f\in\R[X]_d.$$ The set $\Sigma^2_d\subset\R[X]_{2d}$ of s.o.s. polynomials of degree at most $2d$ is a finite-dimensional convex cone, and $$\label{sos}
f\in\Sigma^2_d\quad\Longleftrightarrow\quad L_y(f)\,\geq\,0\quad
\forall \,y\:\mbox{ s.t. }M_d(y)\,\succeq\,0.$$
\[rem1\]
To prove that $L_y(f)\geq0$ for all $y$ such that $M_d(y)\succeq0$ it suffices to prove that $L_y(f)\geq0$ for all $y$ such that $M_d(y)\succeq0$ and $L_y(1)>0$ (and equivalently, by homogeneity, for all $y$ such that $M_d(y)\succeq0$ and $L_y(1)=1$).
Indeed, suppose that $L_y(f)\geq0$ for all $y$ such that $M_d(y)\succeq0$ and $L_y(1)>0$. Next, let $y$ be such that $M_d(y)\succeq0$ and $L_y(1)=0$. Fix $\epsilon>0$ arbitrary and let $y(\epsilon):=y+(\epsilon,0,\ldots,0)$ so that $L_{y(\epsilon)}(X^\alpha)=y_\alpha$ if $\alpha\neq0$ and $L_{y(\epsilon)}(1)=\epsilon >0$. Therefore $M_d(y(\epsilon))\succeq0$ (because $M_d(y)\succeq0$) and so $0\leq L_{y(\epsilon)}(f)=\epsilon f_0+L_y(f)$. As $\epsilon>0$ was arbitrary, letting $\epsilon\downarrow 0$ yields the desired result $L_y(f)\geq0$.
We first recall a preliminary result whose proof can be found in Lasserre and Netzer [@lasserre-tim].
\[lemma1\] With $d\geq1$, let $y=(y_\alpha)\subset\R$ be such that the moment matrix $M_d(y)$ defined in (\[moment\]) is positive semidefinite, and let $\tau_d:=\displaystyle\max_{i=1,\ldots,n}\,L_y(X_i^{2d})$. Then: $$\label{lemma1-1}
\vert L_y(X^\alpha)\vert\,\leq\,\max[\,L_y(1)\,,\,\tau_d\,],\qquad\forall\,\alpha\in\N^n:
\quad \va\leq 2d.$$
We next complement Lemma \[lemma1\].
\[lemma2\] Let $y=(y_\alpha)\subset\R$ be normalized with $y_0=L_y(1)=1$, and such that $M_d(y)\succeq0$. Let $\tau_d:=\displaystyle\max_{i=1,\ldots,n}\,L_y(X_i^{2d})$. Then: $$\label{lemma2-1}
\vert L_y(X^\alpha)\vert^{1/\vert\alpha\vert}\,\leq\,\tau_d^{1/2d},\qquad \forall\,\alpha\in\N^n:\:1\leq\vert\alpha\vert\,\leq\,2d.$$
For a proof see §\[proof-lemma2\].
Conditions for a polynomial to be s.o.s.
----------------------------------------
With $d\in\N$, let $\Gamma\subset\N^n$ be the set defined by: $$\label{setgamma}
\Gamma\,:=\,\{\:\alpha\in\N^n\::\:\va\leq 2d;\quad
\alpha=2\beta\quad\mbox{for some }\beta\in\N^n\}.$$ We now provide our first condition.
\[th1\] Let $f\in\R[X]_{2d}$ and write $f$ in the form $$\label{form}
f\,=\,f_0+\sum_{i=1}^nf_{i2d}\,X_i^{2d}\:+h,$$ where $h\in\R[X]_{2d}$ contains no essential monomial $X_i^{2d}$. If
$$\begin{aligned}
\label{th1-1}
f_0&\geq&\sum_{\alpha\not\in\Gamma}\,\vert f_\alpha\vert \quad-
\sum_{\alpha\in\Gamma}\min[0,f_\alpha]\\
\label{th1-2}
\min_{i=1,\ldots,n}\,f_{i2d}&\geq&
\sum_{\alpha\not\in\Gamma}\vert f_\alpha\vert\,\frac{\vert\alpha\vert}{2d}\quad-
\sum_{\alpha\in\Gamma}\min[0,f_\alpha]\,\frac{\vert\alpha\vert}{2d}\end{aligned}$$
then $f\in\Sigma^2_d$.
For a proof see §\[proof-th1\]. The sufficient conditions (\[th1-1\])-(\[th1-2\]) define a polyhedral convex cone in the euclidean space of coefficients $(f_\alpha)$ of polynomials $f\in\R[X]_{2d}$. This is because the functions, $$f\mapsto\displaystyle\min_{i=1,\ldots,n}f_{i2d}\,,\quad
f\mapsto\min[0,f_\alpha]\,,\quad
f\mapsto-\vert f_\alpha\vert,$$ are all piecewise linear and concave. The description (\[th1-1\])-(\[th1-2\]) of this convex polyhedral cone is [*explicit*]{} and given only in terms of the coefficients $(f_\alpha)$, i.e., with no lifting.\
Notice that (\[th1-1\])-(\[th1-2\]) together with $f_{i2d}=0$ for some $i$, implies $f_\alpha=0$ for all $\alpha\not\in\Gamma$, and $f_\alpha\geq0$ for all $\alpha\in\Gamma$, in which case $f$ is obviously s.o.s.\
Theorem \[th1\] is interesting when $f$ has a few non zero coefficients. When $f$ has a lot of non zero coefficients and contains the essential monomials $X_i^{2k}$ for all $k=1,\ldots,d$, all with positive coefficients, one provides the following alternative sufficient condition. With $k\leq d$, let $$\begin{aligned}
\label{setgammak1}
\Gamma^1_k&:=&\{\:\alpha\in\N^n\::\quad 2k-1\,\leq\,\va\,\leq\,2k\:\}\\
\label{setgammak2}
\Gamma^2_k&:=&\{\:\alpha\in\,\Gamma_k^1\::\quad
\alpha=2\beta\quad\mbox{for some }\beta\in\N^n\}.\end{aligned}$$
\[coro1\] Let $f\in\R[X]_{2d}$ and write $f$ in the form $$\label{newform}
f\,=\,f_0+h+\sum_{k=1}^d\sum_{i=1}^n\,f_{i2k}\,X_i^{2k},$$ where $h\in\R[X]_{2d}$ contains no essential monomial $X_i^{2k}$. If $$\begin{aligned}
\label{coro1-1}
\frac{f_0}{d}&\geq&\sum_{\alpha\in\Gamma^1_k\setminus\Gamma^2_k}\,\vert f_{\alpha}\vert \quad -
\sum_{\alpha\in\Gamma^2_k}\min[0,f_{\alpha}]\\
\label{coro1-2}
\min_{i=1,\ldots,n}\,f_{i2k}&\geq&
\sum_{\alpha\in\Gamma^1_k\setminus\Gamma^2_k}\vert f_\alpha\vert\,\frac{\vert\alpha\vert}{2k}\quad-
\sum_{\alpha\in\Gamma^2_k}\min[0,f_\alpha]\,\frac{\vert\alpha\vert}{2k}\end{aligned}$$ for all $k=1,\ldots,d$, then $f\in\,\Sigma^2_d$.
For a proof see §\[proof-coro1\]. Notice that (\[coro1-1\])-(\[coro1-2\]) together with $f_{i2k}=0$ for some $i$ and some $k\in\{1,\ldots d\}$, implies $f_\alpha=0$ for all $\alpha\in\Gamma^1_k\setminus\Gamma^2_k$, and $f_\alpha\geq0$ for all $\alpha\in\Gamma_2^k$.
Several variants of Corollary \[coro1\] can be derived; for instance, any other way to distribute the constant term $f_0$ as $\sum_{k=1}^d f_{0k}$ with $f_{0k}\neq f_0/d$, is valid and also provides another set of sufficient conditions. Consider also the case when $f$ can be written as $$f\,=\,f_0+h+\sum_{k\in\K}\,\sum_{i=1}^n\,f_{i2k}\,X_i^{2k},$$ where $\K:=\{k\,\in\,\{1,\ldots,d\}\::\:\min_{i=1,\ldots,n}f_{i2k}\,>0\}$, $d\in\K$, and $h\in\R[X]_{2d}$ contains no essential monomial $X_i^{2k}$, $k\in\K$. Then one may easily derive a set of sufficient conditions in the spirit of Corollary \[coro1\].\
Finally, one provides a simple condition for a polynomial to be s.o.s., possibly after adding a constant.
\[coro2\] Let $f\in\R[X]_{2d}$ and write $f$ in the form $$\label{newform2}
f\,=\,f_0+h+\sum_{i=1}^n\,f_{i2d}\,X_i^{2d},$$ where $h\in\R[X]$ contains no essential monomial $X_i^{2d}$. If $$\label{coro2-1}
\min_{i=1,\ldots,n}\,f_{i2d}\,>\,\sum_{\alpha\not\in\Gamma;\:\vert\alpha\vert=2d}
\vert f_\alpha\vert-
\sum_{\alpha\in\Gamma;\:\vert\alpha\vert=2d}\min[0,f_\alpha]$$ with $\Gamma$ as in (\[setgamma\]), then $f+M\in\Sigma^2_d$ for some $M\geq0$.
Let $-M:=\min\,[0,\,\inf_y \,\{L_y(f)\,:\, M_d(y)\succeq0;\,L_y(1)=1\}]$. We prove that $M<+\infty$. Assume that $M=+\infty$, and let $y^j$ be a minimizing sequence. One must have $\tau_{jd}:=\max_{i=1,\ldots,n} L_{y^j}(X_i^{2d})\to\infty$, as $j\to\infty$, otherwise if $\tau_{jd}$ is bounded by, say $\rho$, by Lemma \[lemma1\] one would have $\vert L_{y^j}(X^\alpha)\vert\leq \max[1,\rho]$ for all $\va\leq 2d$, and so $L_{y^j}(f)$ would be bounded, in contradiction with $L_{y^j}(f)\to-\infty$. But then from Lemma \[lemma2\], for sufficiently large $j$, one obtains the contradiction $$\begin{aligned}
0>\frac{L_{y^j}(f)}{\tau_{jd}}&\geq &
\min_{i=1,\ldots,n}\,f_{i2d}\quad-\sum_{\alpha\not\in\Gamma;\:\vert\alpha\vert=2d}\vert f_\alpha\vert\quad +\sum_{\alpha\in\Gamma;\:\vert\alpha\vert=2d}\min[0,f_\alpha]\\
&&-\sum_{0\leq\va<2d}\vert f_\alpha \vert\,\tau_{jd}^{(\va -2d)/2d}\,\geq0,\end{aligned}$$ where the last inequality follows from (\[coro2-1\]) and $\tau_{jd}^{(\va -2d)/2d}\to 0$ as $j\to\infty$.
Hence, $M<+\infty$ and so $L_y(f+M)\geq0$ for every $y$ with $M_d(y)\succeq0$, and $L_y(1)=1$ . But then, in view of Remark \[rem1\], $L_y(f+M)\geq0$ for all $y$ such that $M_d(y)\succeq0$, which in turn implies that $f+M$ is s.o.s.
In Theorem \[th1\], Corollary \[coro1\] and \[coro2\], it is worth noticing the crucial role played by the constant term and the essential monomials $(X_i^\alpha)$, as was already the case in [@lasserre2; @lasserre-tim] for approximating nonnegative polynomials by s.o.s.
Proofs
======
The proof of Lemma \[lemma2\] first requires the following auxiliary result.
\[lemma3\] Let $d\geq1$, and $y=(y_\alpha)\subset\R$ be such that the moment matrix $M_d(y)$ defined in (\[moment\]) is positive semidefinite, and let $\tau_d:=\displaystyle\max_{i=1,\ldots,n}\,L_y(X_i^{2d})$. Then: $L_y(X^{2\alpha})\,\leq\,\tau_d$ for all $\alpha\in\N^n$ with $\vert\alpha\vert=d$.
The proof is by induction on the number $n$ of variables. The case $n=1$ is trivial and the case $n=2$ is proved in Lasserre and Netzer [@lasserre-tim Lemma 4.2].
Let the claim be true for $k=1,\ldots,n-1$ and consider the case $n>2$. By the induction hypothesis, the claim is true for all $L_y\left(X^{2\alpha}\right)$, where $|\alpha| = d$ and $\alpha_{i}
=0$ for some $i$. Indeed, $L_y$ restricts to a linear form on the ring of polynomials with $n-1$ indeterminates and satisfies all the assumptions needed. So the induction hypothesis gives the boundedness of all those values $L_y\left(X^{2\alpha}\right)$.
Now take $L_y\left(X^{2\alpha}\right)$, where $|\alpha|=d $ and all $\alpha_{i} \geq 1$. With no loss of generality, assume $\alpha_{1}\leq \alpha_{2} \leq...\leq\alpha_{n}.$ Consider the two elements $$\gamma:=(2\alpha_{1},0,\alpha_{3}+\alpha_{2}-\alpha_{1},\alpha_{4},...,\alpha_{n})\in\N^{n} \mbox { and }$$ $$\gamma^{'}:=(0,2\alpha_{2},\alpha_{3}+\alpha_{1}-\alpha_{2},\alpha_{4},...,\alpha_{n})\in\N^{n}.$$ We have $|\gamma|=|\gamma^{'}|=d$ and $\gamma_{2}=\gamma^{'}_{1}=0$, and from what precedes, $$L_y(X^{2\gamma})\leq\tau_d\mbox{ and }
L_y(X^{2\gamma^{'}})\leq\tau_d.$$ As $M_d(y)\succeq0$, one also has $$L_y(X^{2\alpha})^{2}= L_y(X^{\gamma +\gamma^{'}})^{2}\leq
L_y(X^{2\gamma})\cdot L_y(X^{2\gamma^{'}}) \leq\tau_d^{2},$$ which yields the desired result $\vert L_y(X^{2\alpha})\vert\leq\tau_d$.
Proof of Lemma \[lemma2\] {#proof-lemma2}
-------------------------
The proof is by induction on $d$. Assume it is true for $k=1,\ldots,d$, and write $M_{d+1}(y)$ in the following block form below with appropriate matrices $V,U_i,V_i,S_i$:
-------------- -------------- --------------- ------------
$M_{d-2}(y)$ $U_1$ $U_2$ $V$
$U_1^T$ $S_{2d-2}$ $V_{2d-1}$ $V_{2d}$
$U_2^T$ $V_{2d-1}^T$ $S_{2d}$ $V_{2d+1}$
$V^T$ $V_{2d}^T$ $V_{2d+1}^T $ $S_{2d+2}$
-------------- -------------- --------------- ------------
When $d=1$, the blocks $M_{d-2}(y)$, and $U_1,U_2,U_1^T,U_2^T,V$ disappear.\
$\bullet$ The case $\vert\alpha\vert=2d+2$ is covered by Lemma \[lemma3\].\
$\bullet$ Consider an arbitrary $y_\alpha$ with $\vert\alpha\vert=2d$. From the definition of the moment matrix, one may choose a pair $(i,j)$ such that the position $(i,j)$ in the matrix $M_{d+1}(y)$ lies in the submatrix $V_{2d}$, and the corresponding entry is $y_\alpha$. From $M_{d+1}(y)\succeq0$, $$M_{d+1}(y)(i,i)\,M_{d+1}(y)(j,j)\,\geq\,y_\alpha^2,$$ As $M_{d+1}(y)(i,i)$ is an element $y_\beta$ of $S_{2d-2}$ with $\vert\beta\vert=2d-2$, invoking the induction hypothesis yields $M_{d+1}(y)(i,i)\leq \tau_d^{(2d-2)/2d}$. On the other hand, $M_{d+1}(y)(j,j)$ is a diagonal element $y_{2\beta}$ of $S_{2d+2}$ with $\vert\beta\vert=d+1$. From Lemma \[lemma3\], every diagonal element of $S_{2d+2}$ is dominated by $\tau_{d+1}$, and so $M_{d+1}(y)(j,j)\leq \tau_{d+1}$. Combining the two yields $$y_\alpha^2\,\leq\,\tau_d^{(d-1)/d}\tau_{d+1},\qquad\forall\,\alpha:\quad\va\,=\,2d.$$ Next, picking up the element $\alpha$ such that $y_\alpha=\tau_d$ one obtains $$\label{tau}
\tau_d^2\,\leq\,\tau_d^{1-1/d}\tau_{d+1}\quad\Rightarrow\quad
\tau_d^{1/d}\leq\tau_{d+1}^{1/(d+1)},$$ and so, $$y_\alpha^2\,\leq\,\tau_d^{(d-1)/d}\tau_{d+1}\,;\qquad
\vert y_\alpha\vert^{1/\vert\alpha\vert}\,\leq\,\tau_{d+1}^{1/(2d+2)},\quad\forall\,\alpha\::\:\va=2d.$$ $\bullet$ Next, consider an arbitrary $y_\alpha$ with $\va=2d+1$. Again, one may choose a pair $(i,j)$ such that the position $(i,j)$ in the matrix $M_{d+1}(y)$ lies in the submatrix $V_{2d+1}$, and the corresponding entry is $y_\alpha$. The entry $M_{d+1}(y)(i,i)$ corresponds to an element $y_{2\beta}$ of $S_{2d}$ with $\vert\beta\vert=d$, and so, by Lemma \[lemma3\], $M_{d+1}(y)(i,i)\leq\tau_d$; similarly the entry $M_{d+1}(y)(j,j)$ corresponds to an element $y_{2\beta}$ of $S_{2d+2}$ with $\vert\beta\vert=d+1$, and so, by Lemma \[lemma3\] again, $M_{d+1}(y)(j,j)\leq\tau_{d+1}$. From $M_{d+1}(y)\succeq0$, we obtain $$\tau_{d+1}\,\tau_d\,\geq\,M_{d+1}(y)(i,i)\,M_{d+1}(y)(j,j)\,\geq\,y_\alpha^2,$$ which, using (\[tau\]), yields $\vert y_\alpha\vert^{1/\vert\alpha\vert}=\vert y_\alpha\vert^{1/(2d+1)}
\leq \tau_{d+1}^{1/(2d+2)}$ for all $\alpha$ with $\va=2d+1$.
$\bullet$ Finally, for an arbitrary $y_\alpha$ with $1\leq\va<2d$, use the induction hypothesis $\vert y_\alpha\vert^{1/\vert\alpha\vert}\,\leq\,\tau_d^{1/2d}$ and (\[tau\]) to obtain $\vert y_\alpha\vert^{1/\va}\leq\tau_{d+1}^{1/2(d+1)}$. This argument is also valid for the case $\vert\alpha\vert=2d$, but this latter case was treated separately to obtain (\[tau\]).
It remains to prove that the induction hypothesis is true for $d=1$. This easily follows from the definition of the moment matrix $M_1(y)$. Indeed, with $\va=1$ one has $y_\alpha^2\leq y_{2\alpha}\leq\tau_1$ (as $L_y(1)=1$), so that $\vert y_\alpha\vert\leq \tau_1^{1/2}$ for all $\alpha$ with $\va=1$. With $\va=2$, say with $\alpha_i+\alpha_j=2$, one has $$\tau_1^2\,\geq\,L_y(X_i^2)\,L_y(X_j^2)\,\geq\,L_y(X_iX_j)^2\,=\,y_\alpha^2,$$ and so $\vert y_\alpha\vert\leq \tau_1$ for all $\alpha$ with $\va=2$. $\qed$
Proof of Theorem \[th1\] {#proof-th1}
------------------------
From (\[sos\]), it suffices to show that $L_y(f)\geq0$ for [*any*]{} $y$ such that $M_d(y)\succeq0$, and by Remark \[rem1\], we may and will assume that $L_y(1)=1$.
So let $y$ be such that $M_d(y)\succeq0$ with $L_y(1)=1$. Let $\tau_d$ be as in Lemma \[lemma1\] and consider the two cases $\tau_d\leq1$ and $\tau_d>1$.\
$\bullet$ The case $\tau_d\leq 1$. By Lemma \[lemma1\], $\vert L_y(X^\alpha)\vert\leq 1$ for all $\alpha\in\N^n$ with $\va \leq 2d$. Therefore, $$L_y(f)\:\geq\quad f_0\quad-\sum_{\alpha\not\in\Gamma}
\vert f_\alpha\vert\quad+\sum_{\alpha\in\Gamma}\min[0,f_\alpha]\quad\geq0,$$ where the last inequality follows from (\[th1-1\]).
$\bullet$ The case $\tau_d>1$. Recall that $L_y(1)=1$, and from Lemma \[lemma2\], one has $\vert L_y(X^\alpha)\vert^{1/\va}\leq\tau_d^{1/2d}$ for all $\alpha\in\N^n$ with $1\leq\va\leq 2d$. Therefore, $$\begin{aligned}
L_y(f)&\geq&f_0+(\min_{i=1,\ldots,n}f_{i2d})\,\tau_d\\
&&-\sum_{\alpha\not\in\Gamma}\vert f_\alpha\vert\,
\tau_d^{\va/2d}
+\sum_{\alpha\in\Gamma}\min[0,f_\alpha]\,\tau_d^{\va/2d}\end{aligned}$$ Consider the univariate polynomial $t\mapsto p(t)$, with $$p(t)=f_0+(\min_{i=1,\ldots,n}f_{i2d})\,t^{2d}-
\sum_{\alpha\not\in\Gamma}\vert f_\alpha\vert\,t^{\vert\alpha\vert}
+\sum_{\alpha\in\Gamma}\min[0,f_\alpha]\,
t^{\vert\alpha\vert},$$ and denote $p^{(k)}\in\R[X]$, its $k$-th derivative.
By (\[th1-2\]), $\displaystyle\min_{i=1,\ldots,n}f_{i2d}\geq0$ and so by (\[th1-1\]), $p(1)\geq0$. By (\[th1-2\]) again, $p'(1)\geq0$. In addition, with $1\leq k\leq 2d$, (\[th1-2\]) also implies $$\begin{aligned}
\min_{i=1,\ldots,n}f_{i2d}&\geq&
\sum_{\alpha\not\in\Gamma;\:\va\geq k}
\vert f_\alpha\vert
\frac{\vert\alpha\vert}{2d}\,\frac{(\vert\alpha\vert-1)}{2d-1}\,\cdots
\frac{(\vert\alpha\vert-(k-1))}{2d-(k-1)}\\
&&-
\sum_{\alpha\in\Gamma;\:\va\geq k}
\min[0,f_\alpha]
\frac{\vert\alpha\vert}{2d}\,\frac{(\vert\alpha\vert-1)}{2d-1}\,\cdots
\frac{(\vert\alpha\vert-(k-1))}{2d-(k-1)}\end{aligned}$$ because $\va-j\leq 2d-j$, for all $j=1,\ldots,k-1$, and so $$\begin{aligned}
\left(\prod_{j=0}^{k-1} (2d-j)\right)\min_{i=1,\ldots,n}f_{i2d}&\geq&
\sum_{\alpha\not\in\Gamma;\:\va\geq k}
\vert f_\alpha\vert\left(\prod_{j=0}^{k-1} (\va-j)\right)\\
&-&
\sum_{\alpha\in\Gamma;\:\va\geq k}
\min[0,f_\alpha]\,
\left(\prod_{j=0}^{k-1} (\va-j)\right),
\end{aligned}$$ which implies $p^{(k)}(1)\geq0$. Therefore, $p^{(k)}(1)\geq 0$ for all $k=0,1,\ldots,2d$, and so, as a special case of Budan-Fourier’s theorem, $p$ has no root in $(1,+\infty)$; see Basu et al [@basu Theor. 2.36]. Hence, $p\geq0$ on $(1,+\infty)$ and as $\tau_d>1$, $L_y(f)\geq p(\tau_d^{1/2d})\geq 0$. $\qed$
Proof of Corollary \[coro1\] {#proof-coro1}
----------------------------
Let $y$ be such that $M_d(y)\succeq0$. Again in view of Remark \[rem1\], we may and will assume that $L_y(1)=1$.
Then $L_y(f)\geq\displaystyle\sum_{k=1}^d A_k$, with $$\begin{aligned}
\label{sk}
A_k&:=&\frac{f_0}{d}+\sum_{i=1}^nf_{i2k}\,L_y(X_i^{2k})+
\sum_{\alpha\in\Gamma^2_k} \min[0,f_\alpha] \,L_y(X^\alpha) \\
\nonumber
&&-\sum_{\alpha\in\Gamma^1_k\setminus\Gamma^2_k} \vert f_\alpha\vert\, \vert L_y(X^\alpha)\vert,\qquad k=1,\ldots,d.\end{aligned}$$ Fix $k$ arbitrary in $\{1,\ldots,d\}$ and consider the moment matrix $M_k(y)\succeq0$, which is a submatrix of $M_d(y)$.
$\bullet$ Case $\tau_k\leq 1$. By Lemma \[lemma1\] applied to $M_k(y)$, $\vert L_y(X^\alpha)\vert\leq 1$ for all $\alpha\in\N^n$ with $\va \leq 2k$. Therefore, with $A_k$ as in (\[sk\]), $$A_k\,\geq\quad\frac{f_0}{d}\quad-\sum_{\alpha\in\Gamma^1_k\setminus\Gamma^2_k}
\vert f_\alpha\vert\quad+\sum_{\alpha\in\Gamma^2_k}\min[0,f_\alpha]\,\quad\geq0,$$ where the last inequality follows from (\[coro1-1\]).
$\bullet$ Case $\tau_k>1$. From Lemma \[lemma2\] applied to $M_k(y)$, $\vert L_y(X^\alpha)\vert^{1/\va}\leq\tau_k^{1/2k}$ for all $\alpha$ with $\va\leq 2k$. Therefore, $A_k\geq p_k(\tau_k^{1/2k})$, where $p_k\in\R[t]$, and $$p_k(t)=\frac{f_0}{d}+t^{2k}\left(\,\min_{i=1,\ldots,n}f_{i2k}+\sum_{\alpha\in\Gamma^2_k}\min[0,f_\alpha]\right)- \sum_{\alpha\in\Gamma^1_k\setminus\Gamma^2_k}\vert f_\alpha\vert\,t^{\vert\alpha\vert} .$$ As in the proof of Theorem \[th1\], but now using (\[coro1-1\])-(\[coro1-2\]), one has $p_k^{(j)}(1)\geq0$ for all $j=0,1,\ldots,2k$. As a particular case of Budan-Fourier’s theorem, $p_k$ has no root in $(1,+\infty)$; see Basu et al [@basu Theor. 2.36]. Therefore, $p_k\geq0$ on $(1,+\infty)$ which in turn implies $A_k\geq p_k(\tau_k^{1/2k})\geq0$ because $\tau_k>1$. Finally, $L_y(f)\geq\sum_{k=1}^dA_k\geq0$, as $A_k\geq0$ in both cases $\tau_k\leq1$ and $\tau_k>1$. $\qed$
[99]{}
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A. Ben-Tal, A. Nemirovski. *Lectures on Modern Convex Optimization*, SIAM, Philadelphia, 2001.
J.W. Helton, V. Vinnikov. *Linear matrix inequality representation of sets,* Technical report, Mathematic Dept., University of California at San Diego, USA, 2004. `arXiv:math.OC/0306180 v1`.
J.B. Lasserre. *Global optimization with polynomials and the problem of moments*, SIAM J. Optim. 11 (2001), 796–817.
J. B. Lasserre. *A sum of squares approximation of nonnegative polynomials*, SIAM J. Optim. 16 (2006), 751-765.
J.B. Lasserre, T. Netzer. *SOS approximation of nonnegative polynomial via simple high degree perturbations*, Math. Z. (2006), to appear.
A.S. Lewis, P. Parrilo, M.V. Ramana. *The Lax conjecture is true*, Proc. Am. Math. Soc. 133 (2005), 2495-2499.
P. A. Parrilo. *Semidefinite programming relaxations for semialgebraic problems*, Math. Progr. Ser. B 96 (2003), 293-320.
M. Schweighofer. *Optimization of polynomials on compact semialgebraic sets*, SIAM J. Optim. 15 (2005), 805-825.
|
Acting Defense Secretary urges allies to condemn Iran, join maritime security effort to protect Strait of Hormuz Mark Esper will return to Brussels in mid-July to brief NATO allies on Iran.
Acting Defense Secretary Mark Esper urged European allies on Thursday to publicly condemn Iran's actions and join a new U.S.-proposed maritime security effort to protect the Strait of Hormuz, after a series of attacks on tankers and the shoot down of a American drone in that strategic waterway. His comments come as Iran is expected to breach the agreed upon cap on its enriched uranium stockpile.
During a news conference at the NATO Defense Ministerial in Brussels, Esper said he asked allies to join a coalition of "like-minded countries" that would support freedom of navigation in the Strait of Hormuz through "broader maritime surveillance."
"And that should include air surveillance all the way up to a picket line of ships to help protect the international waterways and to include maybe even escorts," Esper said. "We have to flesh it out on our end, and we'll see what makes the most sense."
Esper, who stepped into the role of acting Pentagon chief only on Monday, also announced that he would return to Brussels in mid-July to give allies a more detailed briefing "on the history of this Iranian threat."
Secretary of State Mike Pompeo made a similar pitch for a maritime coalition to U.S. allies in the Middle East this week with the State Department dubbing the proposed mission the "Sentinel program." The project would include around 20 countries, Pompeo said on Monday.
But it's unknown if any countries in Europe or the Middle East have firmly committed to such a coalition. Saudi Arabia did not mention the idea in a readout of Pompeo's meeting with King Salman and Crown Prince Mohammed bin Salman, although the U.S. readout said they discussed "the need for stronger maritime security."
A senior State Department official described the coalition as military and commercial ships serving in an observer role in the Gulf with cameras and binoculars, but not actually escorting tankers.
Top administration officials have stressed the need for Asian nations, many of whom receive the vast majority of oil from the Gulf, to be part of an international response to Iran's aggression in the region. The topic is expected to come up at the G20 Summit in Japan this weekend.
At NATO, Esper reiterated that the U.S. does not seek war with Iran and wants to bring Tehran to the negotiating table -- an action Iranian leadership has so far refused, citing distrust of Washington and its tough sanctions on Tehran.
"Our strategy is at its core an economic and diplomatic one," Esper said, before adding that "no one should mistake restraint for weakness."
The NATO ministerial comes as Iran's Foreign Minister Javad Zarif tweeted that U.S. sanctions "aren't alternative to war; they ARE war," and that "negotiations and threats are mutually exclusive."
Last week, Iran vowed to breach the cap on its enriched uranium stockpile that was agreed to under the 2015 nuclear deal by Thursday. A spokesperson for the United Nation's nuclear agency, which monitors Iran's program, declined to comment to ABC News on whether Iran had done so. But an anonymous diplomat at the agency told Reuters that Iran hadn't reached the limit yet and was "more likely" to do so "at the weekend if they do it."
The U.S. has been criticized by European partners for exiting the nuclear deal with some blaming the U.S. sanctions for why Iran is lashing out. But Esper defended the U.S., saying the country was "by no means the instigator of recent tensions in the Strait of Hormuz."
"Iran's hostile actions are an international problem that affects many nations," he said, adding later, "We've had at least six ships attacked by Iran or its proxies. We've had mortar attacks into Saudi Arabia. We've had a cruise missile attack on Saudi Arabia. We of course had the shoot down of our unarmed aircraft in international airspace and the list goes on."
President Donald Trump has said he intends to nominate Esper to the role of defense secretary permanently. Esper previously served as Army Secretary and as a chief lobbyist for Raytheon. |
Donald Trump demanded on Friday that any deal to resolve the fate of young undocumented migrants must be paired with funding for a wall along the southern US border.
It was not immediately clear if Trump’s intervention would derail attempts to find a compromise on the issue, or negotiations over government funding.
Spokespeople for Democratic leaders said they looked forward to resuming “a serious negotiation” on immigration when Congress returns next week.
Trump tweeted his demand among a volley of similarly strident messages, the morning after he spoke to the New York Times in a surprise and wide-ranging interview that included remarks on immigration and Daca. Shortly after his morning tweets, he left his Mar-a-Lago resort in Florida for one of his golf courses.
There are about 700,000 so-called Dreamers, undocumented migrants brought to the US as children. In September. Trump announced that he was rescinding the Deferred Action for Childhood Arrivals program, or Daca, a policy implemented by Barack Obama in 2012 that allowed Dreamers to come out of the shadows to study and work legally in the US.
Trump placed the fate of the young immigrants squarely in the hands of Congress, giving lawmakers until 5 March to find a legislative solution.
On Friday, the president wrote: “The Democrats have been told, and fully understand, that there can be no Daca without the desperately needed WALL at the Southern Border and an END to the horrible Chain Migration & ridiculous Lottery System of Immigration etc. We must protect our Country at all cost!”
Trump staked a similar position in his New York Times interview: “I wouldn’t do a Daca plan without a wall. Because we need it. We see the drugs pouring into the country, we need the wall.”
“Chain migration”, referred to in Trump’s tweet, is a family-based immigration policy that allows naturalized citizens and certain immigrants to petition for relatives to come to the US. Trump also called for the elimination of the Diversity Visa Lottery, a state department program that helps citizens of countries with historically low rates of immigration to come to the US.
Trump has been vocal on both issues in the wake of terror attacks in New York.
Akayed Ullah, a 27-year-old from Bangladesh accused of detonating a bomb in a subway tunnel earlier this month, came to the US in 2011 on a visa available to relatives living in the country.
Sayfullo Saipov, a 29-year-old from Uzbekistan accused of killing eight people with a pickup truck on a bike path in October, was allowed into the country on a visa obtained through the lottery program in 2010.
“They take the worst people in the country, they put ‘em into the lottery, then they have a handful of bad, worse ones, and they put them out. ‘Oh, these are the people the United States…’” Trump said. “We’re gonna get rid of the lottery, and by the way, the Democrats agree with me on that. On chain migration, they pretty much agree with me.”
The wall, one of Trump’s central campaign promises and the centerpiece of his hardline immigration platform, is a non-starter for Democrats. The Senate minority leader, Chuck Schumer ,and House minority leader, Nancy Pelosi, are resolutely opposed to any immigration legislation or government funding plan that includes funding for a wall.
Democrats are, however, under increasing pressure to pass legislation that would permanently shield Dreamers from deportation.
Immigration advocates and liberal groups are furious with lawmakers who left Washington last week despite having promised to force a vote on the issue before the end of the year. Some groups have vowed to retaliate against Democrats who supported a spending bill to keep the federal government open that did not address the Dreamers issue.
A bipartisan group of senators are scrambling to find a compromise. Jeff Flake of Arizona, a Trump critic and Republican member of the working group who is a longtime proponent of immigration reform, has said that plan will receive a vote next month.
Pelosi and Schumer, along with the House speaker, Paul Ryan, and Senate majority leader, Mitch McConnell, are due to meet the White House chief of staff, John Kelly, on Wednesday to discuss the year’s priorities, including immigration, according to two sources familiar with the plans for meeting. |
Thursday, October 19, 2017
TrickBot's New Magic Trick ==> Sending SPAM
It has been a while since we had a blog from Arsh Arora, who is pursuing his Ph.D., which has kept him away from blogging for a bit. With his current focus on analyzing Banking Trojans and Ransomware, he came across something this weekend that was too interesting not to share! Take it away, Arsh!
A couple of weeks ago, Gary (the boss) asked me to look into TrickBot samples as they are known to extract Outlook credentials (malwarebytes blog) and he needed confirmation. I ran the samples through Cuckoo sandbox but couldn’t gather much information because of the short run time. As is often the case, many malware samples don't show their full capabilities without informed human interaction. Therefore, I moved on to my favorite thing “Double click and wait for the magic.”
First Stage – Extracting the Config File
During the first run, Clifford Wilson, a new malware researcher in our lab, helped in extracting some valuable indicators. In the initial stage, we found out that when testing the TrickBot binary:
The original binary launches a child process and then it gets replaced by a different binary that is downloaded. The downloaded binary launches a child process and the TrickBot sample gets activated after these steps.
When analyzing we found out that it launches several “svchost.exe,” it varies from 4 to 7 depending upon the time of your run.
Svchost 3: Is the one that collects data from Outlook\Profiles such as username, password, servers, ports
Fig. 2: Outlook exfiltration
Svchost 4: Scans the internet history to search for stored credentials
Svchost 5: Contain a list of random email ids, research is being to understand the use of those emails.
Confirmation of Svchost being launched by TrickBot binary
In order to confirm our hypothesis about the various svchost being launched by a single process and not more than one processes, researchers tested a different binary and found the results to be identical. We used Process Monitor to confirm the creation of "Svchost.exe" by the same process.
Fig. 3: Svchost Create Process
Config File : Svchost 2
adelaidebank[.]com[.]au
anzdirect[.]co[.]nz
anztransactive[.]anz[.]com
arabbank[.]com[.]au
asb[.]co[.]nz
bankcoop[.]ch
bankleumi[.]co[.]uk
bankline[.]natwest[.]com
bankline[.]rbs[.]com
bankofireland[.]com
bankofmelbourne[.]com[.]au
bankofscotland[.]co[.]uk
banksa[.]com[.]au
banksyd[.]com[.]au
bankwest[.]com[.]au
barclays[.]co[.]uk
barclays[.]com
barclayswealth[.]com
bcv[.]ch
bendigobank[.]com[.]au
beyondbank[.]com[.]au
bibplus[.]uobgroup[.]com
bizchannel[.]cimb[.]com
bmo[.]com
bmoharris[.]com
bnz[.]co[.]nz
boi-bol[.]com
boqspecialist[.]com[.]au
business[.]hsbc[.]co
cams[.]scotiabank[.]com
cibc[.]com
citibank[.]com[.]sg
citibusiness[.]citibank[.]com
coinbase[.]com
co-operativebank[.]co[.]uk
corp[.]westpac[.]co
corp[.]westpac[.]com
corpnet[.]lu
coutts[.]com
cua[.]com[.]au
danskebank[.]ie
defencebank[.]com[.]au
dev[.]bmo[.]com
ebanking[.]hsbc[.]co
ebanking[.]zugerkb[.]ch
fidunet[.]lu
flexipurchase[.]com
greater[.]com[.]au
gtb[.]unicredit[.]eu
harrisbank[.]com
heartland[.]co[.]nz
hsbc[.]com[.]au
humebank[.]com[.]au
hypovereinsbank[.]de
ib[.]boq[.]com
ib[.]kiwibank[.]co
icicibank[.]com
imb[.]com[.]au
internationalmoneytransfers[.]com[.]au
iombankibanking[.]com
kbc[.]ie
lloydsbank[.]co[.]uk
lloydsbank[.]com
lukb[.]ch
macquarie[.]com[.]au
maybank[.]com[.]sg
mebank[.]com[.]au
metrobankonline[.]co[.]uk
my[.]commbiz[.]commbank[.]au
mystate[.]com[.]au
nab[.]com[.]au
nationwide[.]co[.]uk
navyfederal[.]org
netteller[.]com[.]
newcastlepermanent[.]com[.]au
nwolb[.]com
ocbc[.]com
online[.]anz[.]com
online[.]lloydsbank[.]com
onlinebanking[.]iombank[.]com
onlinesbiglobal[.]com
postfinance[.]ch
qtmb[.]com[.]au
rabobank[.]co[.]nz
rabobank[.]com[.]au
rabodirect[.]co[.]nz
rabodirect[.]com[.]au
raiffeisendirect[.]ch
rbc[.]com
rbsdigital[.]com
rbsiibanking[.]com
ruralbank[.]com[.]au
salesforce[.]com
santander[.]co[.]uk
sbisyd[.]com[.]au
sbs[.]net[.]nz
scotiabank[.]com
secure[.]societegenerale[.]fr
secure[.]wellsfargo[.]com
standardchartered[.]com
standardchartered[.]com[.]sg
stgeorge[.]com[.]au
suncorpbank[.]com[.]au
tdcommercialbanking[.]com
tmbank[.]com[.]au
tsb[.]co[.]uk
tsbbank[.]co[.]nz
tsw[.]com[.]au
ubank[.]com[.]au
ubs[.]com
ulsterbankanytimebanking[.]co[.]uk
ulsterbankanytimebanking[.]ie
unicredit[.]it
unicreditbank[.]ba
unicreditbank[.]lu
unicreditbank[.]sk
unicreditbanking[.]net
unicreditcorporate[.]it
uobgroup[.]com
valiant[.]ch
wellsfargo[.]com
westpac[.]co[.]nz
westpac[.]com[.]au
This is the comprehensive list of all the unique financial institutions mentioned in the Svchost 2. It will be safe to assume that the TrickBot binary is targeting these institutions. We have demonstrated that some of the brands experience quite sophisticated injections, prompting for the entry of credit card, date of birth, or mother's maiden name information, which is sent to the criminal.
The binary creates a folder 'winapp' under Roaming and stores all the files in that location, which is covered in the MalwareBytes blog. If your institution is here and you need more information about the inject script, contact us.
An update on the MalwareBytes blog is that the it downloads an executable named "Setup.exe" under WinApp. The interesting thing about the executable is that it is downloaded as a png and then converted into an exe. The URLs the executable is downloaded are:
The downloaded files being converted into "Setup.exe" and can be found under the Roaming/WinApp directory.
Second Stage - Spam aka 'Pill Spam'
After the completion of initial analysis, there was a strange pattern observed when analyzed the Wireshark traffic with 'IMF' filter. Our network (10.0.2.15) was used as a server along with being a proxy. Our address was proxy for other messages coming from 208.84.244.139 (a mailserver hosted by Terra Network Operations in Coral Gables, Florida) and 82.208.6.144 (a mailserver in Prague, Czech Republic.) Also, our network was sending outbound spam.
Fig. 7: Wireshark capture with IMF filter
Outbound Spam
As can be seen in the figure 7, top 3 spam messages are outbound and are being sent from our network. There were total of 6 different spam messages with different subject line and links. The email is mentioned below:
Fig. 8: Email message
Following were some of the subjects and urls that were spammed.
Subject URL
Affordable-priced Brand Pilules
http://martinagebhardt[.]hu/w/1gox[.]php
Blue Pills easy-ordering
http://host[.]teignmouthfolk[.]co[.]uk/w/zxaj[.]php
Eromedications Wholesale
http://martinagebhardt[.]hu/w/1pyo[.]php
Great offers on Male Pills
http://host.bhannu[.]com/w/w10x[.]php
Here we sell Branded tablets
http://host[.]selfcateringintenerife[.]co[.]uk/w/l5fz[.]php
Online offers Branded pharmacueticals
http://host[.]iceskatemag[.]co[.]uk/w/lztg[.]php
When we visited these links they redirect to a counterfeit pill website featuring pain and anxiety medications such as Xanax, Tramadol, Ambien, Phentermine, and more. A depiction of the pill website with affiliate id is shown below.
Fig. 9: Redirect to a pill website with aff id
When we tried to analyze these weblinks individually, they contained a list of php under the 'w' directory. Last, when tree walked just to the domain it led to a dating/porn website.
Inbound Spam
As can be seen in the Figure 3, there is a significant amount of inbound traffic that seems to be different spam messages redirected through our machine. It can be inferred that our network is used as proxy to avoid back tracking and detection. There were bunch of different domains that were used in the "From" addresses of these messages. An example of one such message is:
From: Walmart
Reply-To: newsletters@walmart.com
To: Grazielle
Subject: =?UTF-8?Q?Huge_Clearance_savings_you_can=E2=80=99t_miss?=
The capture contained different messages from all the following domains mentioned below:
aggadi.com.br
aol.com
belissimacosmeticos.com.br
catcorlando.com
citrosuco.com.br
connect.match.com
uspoloassn.com
newsletter.coastalscents.com
email.modait.com.br
facebookmail.com
id.apple.com
itmae.com.br
limecrimemakeup.com
offers.dominos.com
pcpitstopmail.com
photojojo.com
pof.com
sigmabeauty.com
submamails.com
twitter.com
walmart.com
Credential Exchange
TrickBot displays a similar characteristic to the Kelihos Botnet , in a sense that it logs in to the mail server with the stolen credentials before it starts to send spam. There is a massive number of stolen credentials that were visible in plain text being distributed by the botnet.
Fig. 10: Stolen Credentials reconstructed in Network Miner
With these analysis, it is safe to assume that TrickBot is extremely tricky!! Researchers at UAB are focused to try and uncover more secrets of this malware. Will keep everyone posted with our new findings!!
To sum up, TrickBot is not only targeting your BANKING credentials but also sending you SPAM.
Monday, October 02, 2017
While many corporations have great spam filtering, quite a few small businesses and individuals still deal with a deluge of spam on a daily basis. For some time now, a particular group of criminals have been stealing your personal information by fraudulently offering "Gift Cards" to various things.
Just in the last day, we've seen Gift Card spam for Amazon, Discover, Target, and Walgreens.
Although it doesn't seem like it, none of these spam messages have anything to do with the sponsoring organization. There is also absolutely no chance that these spam messages will lead to you receiving a Gift Card, or anything else of value. So what is their purpose? These spam messages are sent to try to get you to provide personal information to criminals who enrich themselves by stealing your data and selling it to others.
In each case, after forwarding you through several intermediate places, you end up at a Survey, fraudulently branded to represent the spam campaign you clicked on. Note that ALREADY AT THIS POINT, the criminals have your email address, and know that you have an interest in the brand they have chosen. When you click on Amazon, the first time you touch the survey, you are revealing "My email address is (your email here) and I click on spam messages about Amazon!" (or Discover, or Target, or Walgreens...)
All of the surveys are exactly the same, although each is branded a bit differently and there are not just dozens but HUNDREDS of websites that have all been registered for these scammy surveys.
The Amazon survey and the Walgreens survey are on the website "powerclub .xyz" (created on 21SEP2017). The Discover survey is on "rewardsurveyscenter .com" (updated on 29AUG2017).
The Target survey is on "healthmarket .xyz" (created on 25SEP2017). All use a privacy service in the Cayman Islands to protect THEIR personal information while they steal yours!
We'll just look a bit more at the Discover one as an example. The survey consisted of seven questions, asking your gender, whether you had the Discover mobile app installed, whether you were happy with your FICO score, whether you thought your interest rate was too high, and some questions about customer service from Discover.
What is the point of the survey, since they have no intention of providing you with a gift card?
They want to be able to sell your contact information to other people, as is made plain in their privacy policy:
By the way, there IS no address for the Online Privacy Coordinator listed at the end of the Privacy Policy. Oops!
After completing the survey, instead of receiving a gift card, you have the opportunity to subscribe to one of several offers.
A Testostone Booster, a Skin Cream, a Garcinia Cambogia diet supplement, e-Cigarettes, or a "Male Enhancement" that promises to make you "Get Bigger, Last Longer, and Stay Harder." Sadly, the only thing anyone might actually want, the Apple iPad Pro, is "Out of Stock" (and always will be.)
The fine print, by the way, warns that if you take the free product, they will bill you at the full price every thirty days until you find a way to make them stop. And, similar to the Online Privacy Commissioner, there are few hints about what that telephone number may be. |
Q:
Facebook connect trouble
I've been struggeling with the facebook connect for a few days now, I'm only using the PHP SDK downloaded from facebook.
I first used some custom code, but after that failed I just copied the code on facebook, but this still fails.
Is there anything I do wrong? I've created an app on facebook, added the right domain (I get redirected correctly).
Once people login, this is the URL they get redirected to:
http://www.mysite.com/index.php?state=33e35654a84559d246c152ed10e8150b&code=AQBGxCMu4vgbw5HgU8EIoyq8rhuHaKvtJQR-VbPMVH8bd2JMIRcxojqJ-l7XrjIdG9TNN05el14Jv8isbHbUWj9so-CdhaEqj7tLR-Rj6-JaOTA7QErrpfN_0XQN1CGCmvmTL6ZtoUupgkVwkzq_CWDT9lSoDPvNHu2F67Jqlsi2DfQZGE1J7pDzujBoSoJhDhs#_=_
The code I copied from facebook:
<?
// Remember to copy files from the SDK's src/ directory to a
// directory in your application on the server, such as php-sdk/
require_once('classes/facebook/facebook.php');
$config = array(
'appId' => 'appID here',
'secret' => 'secret here',
);
$facebook = new Facebook($config);
$user_id = $facebook->getUser();
?>
<html>
<head></head>
<body>
<?
if($user_id) {
// We have a user ID, so probably a logged in user.
// If not, we'll get an exception, which we handle below.
try {
$user_profile = $facebook->api('/me','GET');
echo "Name: " . $user_profile['name'];
} catch(FacebookApiException $e) {
// If the user is logged out, you can have a
// user ID even though the access token is invalid.
// In this case, we'll get an exception, so we'll
// just ask the user to login again here.
$login_url = $facebook->getLoginUrl();
echo 'Please <a href="' . $login_url . '">login.</a>';
error_log($e->getType());
error_log($e->getMessage());
}
} else {
// No user, print a link for the user to login
$login_url = $facebook->getLoginUrl();
echo 'Please <a href="' . $login_url . '">login.</a>';
}
?>
</body>
</html>
A:
It turns out it had something to do with the certificate, after some looking around I found out that changing
if (curl_errno($ch) == 60) {
// CURLE_SSL_CACERT
to
if (curl_errno($ch) == 60 || curl_errno($ch) == 77) {
// CURLE_SSL_CACERT
solves the problem
|
/* -*- coding: utf-8 -*-
* ----------------------------------------------------------------------
* Copyright © 2012, RedJack, LLC.
* All rights reserved.
*
* Please see the COPYING file in this distribution for license
* details.
* ----------------------------------------------------------------------
*/
#include <dirent.h>
#include <errno.h>
#include <fcntl.h>
#include <string.h>
#include <sys/stat.h>
#include <sys/types.h>
#include <unistd.h>
#include "libcork/core/attributes.h"
#include "libcork/core/error.h"
#include "libcork/core/types.h"
#include "libcork/ds/buffer.h"
#include "libcork/helpers/errors.h"
#include "libcork/helpers/posix.h"
#include "libcork/os/files.h"
static int
cork_walk_one_directory(struct cork_dir_walker *w, struct cork_buffer *path,
size_t root_path_size)
{
DIR *dir = NULL;
struct dirent *entry;
size_t dir_path_size;
rip_check_posix(dir = opendir(path->buf));
cork_buffer_append(path, "/", 1);
dir_path_size = path->size;
errno = 0;
while ((entry = readdir(dir)) != NULL) {
struct stat info;
/* Skip the "." and ".." entries */
if (strcmp(entry->d_name, ".") == 0 ||
strcmp(entry->d_name, "..") == 0) {
continue;
}
/* Stat the directory entry */
cork_buffer_append_string(path, entry->d_name);
ei_check_posix(stat(path->buf, &info));
/* If the entry is a subdirectory, recurse into it. */
if (S_ISDIR(info.st_mode)) {
int rc = cork_dir_walker_enter_directory
(w, path->buf, path->buf + root_path_size,
path->buf + dir_path_size);
if (rc != CORK_SKIP_DIRECTORY) {
ei_check(cork_walk_one_directory(w, path, root_path_size));
ei_check(cork_dir_walker_leave_directory
(w, path->buf, path->buf + root_path_size,
path->buf + dir_path_size));
}
} else if (S_ISREG(info.st_mode)) {
ei_check(cork_dir_walker_file
(w, path->buf, path->buf + root_path_size,
path->buf + dir_path_size));
}
/* Remove this entry name from the path buffer. */
cork_buffer_truncate(path, dir_path_size);
/* We have to reset errno to 0 because of the ambiguous way
* readdir uses a return value of NULL. Other functions may
* return normally yet set errno to a non-zero value. dlopen
* on Mac OS X is an ogreish example. Since an error readdir
* is indicated by returning NULL and setting errno to indicate
* the error, then we need to reset it to zero before each call.
* We shall assume, perhaps to our great misery, that functions
* within this loop do proper error checking and act accordingly.
*/
errno = 0;
}
/* Check errno immediately after the while loop terminates */
if (CORK_UNLIKELY(errno != 0)) {
cork_system_error_set();
goto error;
}
/* Remove the trailing '/' from the path buffer. */
cork_buffer_truncate(path, dir_path_size - 1);
rii_check_posix(closedir(dir));
return 0;
error:
if (dir != NULL) {
rii_check_posix(closedir(dir));
}
return -1;
}
int
cork_walk_directory(const char *path, struct cork_dir_walker *w)
{
int rc;
char *p;
struct cork_buffer buf = CORK_BUFFER_INIT();
/* Seed the buffer with the directory's path, ensuring that there's no
* trailing '/' */
cork_buffer_append_string(&buf, path);
p = buf.buf;
while (p[buf.size-1] == '/') {
buf.size--;
p[buf.size] = '\0';
}
rc = cork_walk_one_directory(w, &buf, buf.size + 1);
cork_buffer_done(&buf);
return rc;
}
|
Contact Info
Welcome to BEST WESTERN PLUS Sonora Oaks
Stay at this Sonora, California hotel conveniently located at the junction of Highways 49,108, and 120 in the heart of Gold Country. Those in need of Yosemite lodging will not be disappointed at the BEST WESTERN PLUS Sonora Oaks Hotel and Conference Center!
Nestled under a grove of ancient oaks in the Columbia Historic Park area of the Sierra Foothills is the comfortable and accommodating BEST WESTERN PLUS Sonora Oaks Hotel and Conference Center. Guests will be a short distance from many landmarks and recreational attractions in the Sonora area, including the Sierra Railroad, Columbia State Park and Yosemite National Park. Hotel guests will also be near Dodge Ridge Ski Area and Leland Snow Park. We are the closest hotel to the Black Oak Casino.
The BEST WESTERN PLUS Sonora Oaks Hotel and Conference Center is a great Yosemite lodging choice while visiting the colorful city of Sonora and exploring the Mother Lode area. Hotel guests enjoy a daily complimentary continental breakfast, as well as a secluded outdoor swimming pool.
Our Yosemite hotel's conference center provides a forum for meetings or group events, with details attended to by a professional staff. Our unique meeting facilities can comfortably accommodate between 22 to160 guests. Make an online reservation today at this Best Western in Sonora, California! |
Continuous tepid blood cardioplegia can preserve coronary endothelium and ameliorate the occurrence of cardiomyocyte apoptosis.
In modern cardiac surgery, crystalloid or blood cardioplegic solutions have been used widely for myocardial protection; however, ischemia does occur during protection with intermittent infusion of cold crystalloid or blood cardioplegic solutions. The present study was designed to evaluate the effect of different cardioplegic methods on myocardial apoptosis and coronary endothelial injury after global ischemia, cardiopulmonary bypass (CPB), and reperfusion in anesthetized open-chest dogs. The dogs were classified into five groups to identify the injury of myocardium and coronary endothelium: group 1, normothermic CPB without cardiac arrest; group 2, hypothermic CPB with continuous tepid blood cardioplegia, and with cardiac arrest; group 3, hypothermic CPB with intermittent cold blood cardioplegia, and with cardiac arrest; group 4, hypothermic CPB with intermittent cold crystalloid cardioplegia, and with cardiac arrest; and group 5, sham-operated control group. During CPB, cardiac arrest was achieved with different cardioplegia solutions for 60 min, followed by reperfusion for 4 h before the myocardium and coronary arteries were harvested. Coronary arteries were harvested immediately and analyzed by scanning electron microscopy. Cardiomyocytic apoptosis was detected using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling, Western blot, and DNA ladder methods. Regardless of the detection method used, significantly higher percentages of apoptotic cardiomyocytes were found in group 3 and group 4 than in other groups. Expression of caspase-3 correlated with increased apoptosis. Scanning electron microscopy revealed severe endothelial injury of coronary arteries in group 3 and group 4. These results point to an important explanation for the difference in cardiac recovery after hypothermic ischemia and arrest with various cardioplegic solutions. |
Photorefractives are able to create real-time holograms through the interference of two or more laser beams within the photorefractive material. The hologram can take the form of a real or virtual image of an object or data, or, in the simplest case, form a diffraction grating. Generally, a diffraction grating is an optical component with a regular pattern, which splits and diffracts light into several beams travelling in different directions. The diffraction grating can be either in phase with the optical interference pattern or out of phase. When in phase, the diffraction grating behaves in the same way as any common diffraction grating, causing equal diffraction of each of the writing beams. However, if the diffraction grating is out of phase with respect to the optical interference pattern, power may be transferred from one or more beams to another. This well established technique is useful for amplifying weak signal beams and for coherently combining two or more beams into a single stronger laser beam.
Diffraction gratings within waveguide structures have previously been used as extremely sensitive optical sensors. The method relies on placing a diffraction grating (a Bragg grating) within a thin optical waveguide at the surface of a transparent substrate. The electric field component of the guided light is able to penetrate a very small distance beyond the confines of the waveguide surface into the surrounding environment. This surface electric field is often called the evanescent field. The propagation of the light within the surface waveguide is highly sensitive to any changes of the surface refractive index, even changes which occur within the evanescent field above the surface. The reflectivity and wavelength selectivity of the surface waveguide diffraction grating are therefore sensitive to any changes of the evanescent field. Materials which come into contact with (or very close to) the surface influence the effective surface refractive index and can be detected by monitoring changes in the optical properties of the embedded diffraction grating. Optical fibers and surface waveguides have both been used successfully for this application and the best devices are capable of detecting fifth decimal place changes in refractive index. Typical applications include biological sensors, refractive index measurement, and product and substance identification. |
[Iliac-femoral artery involvement in relapsing polychondritis].
A patient presenting a relapsing polychondritis with ruptured iliac arterial aneurysm and lower limbs arteritis is described. The analysis of the results compared with the literature's cases confirm the no response for surgical and medical treatments. |
#!/usr/bin/env python
import os
import shutil
import sys
import fileinput
from optparse import OptionParser
def sh(command):
return os.popen(command).read()
def bundle_path(binary_name):
return "%s.app" % binary_name
def bundle_name(binary_name):
return os.path.basename(bundle_path(binary_name))
def target_plist(binary_name):
return os.path.join(bundle_path(binary_name), 'Contents', 'Info.plist')
def target_directory(binary_name):
return os.path.join(bundle_path(binary_name), 'Contents', 'MacOS')
def target_binary(binary_name):
return os.path.join(target_directory(binary_name),
os.path.basename(binary_name))
def copy_bundle(binary_name):
if os.path.isdir(bundle_path(binary_name)):
shutil.rmtree(bundle_path(binary_name))
shutil.copytree(
os.path.join('TOOLS', 'osxbundle', bundle_name(binary_name)),
bundle_path(binary_name))
def copy_binary(binary_name):
shutil.copy(binary_name, target_binary(binary_name))
def apply_plist_template(plist_file, version):
for line in fileinput.input(plist_file, inplace=1):
print (line.rstrip().replace('${VERSION}', version))
def main():
version = sh("./version.sh --print").strip()
usage = "usage: %prog [options] arg"
parser = OptionParser(usage)
parser.add_option("-s", "--skip-deps", action="store_false", dest="deps",
default=True,
help="don't bundle the dependencies")
(options, args) = parser.parse_args()
if len(args) != 1:
parser.error("incorrect number of arguments")
else:
binary_name = args[0]
print("Creating Mac OS X application bundle (version: %s)..." % version)
print("> copying bundle skeleton")
copy_bundle(binary_name)
print("> copying binary")
copy_binary(binary_name)
print("> generating Info.plist")
apply_plist_template(target_plist(binary_name), version)
if options.deps:
print("> bundling dependencies")
sh(" ".join(["TOOLS/dylib-unhell.py", target_binary(binary_name)]))
print("done.")
if __name__ == "__main__":
main()
|
Keep the world’s best pet adoption platform running!
This is probably the nicest ask you’ll receive this tax time. It’s not our style to call you up and ask for money, to fill your mailbox with begging letters and branded pens, or to recruit an army of chuggers to stop you in the street. We run our donation drives on a shoestring to maximise the impact of your gifts - to keep the world’s best pet adoption platform running, and to help save the lives of thousands of rescue pets every month. Please take one minute to help keep PetRescue here for everyone who needs us. Thank you.
Hello there. It seems you like visiting PetRescue. That's great!
It's a little awkward to ask, but we need your help. We don’t invest huge amounts of funds and resources in fundraising. We’re a small but growing team of pet-loving techies who look at the big picture and create radical change that improves outcomes for rescue pets Australia-wide. We depend on donations, but only 0.05% of visitors to the PetRescue website give. If you donate just $3, less than the price of a morning coffee, you can help keep PetRescue thriving and free for everyone who needs it. Thank you.
John Bishop, PetRescue Co-Founder
It feels a little awkward to say this, but we need your help.
You’re probably thinking PetRescue will be fine if you don’t give anything today. Because someone else always gives, right? But only 0.05% of visitors to PetRescue donate. And here's the thing... If every pet lover using the website donated just $15 this tax time, in less than one week we'd raise enough funds to make sure we’re here for another year - helping more people like you and thousands more rescue pets in need. So, if PetRescue is useful to you, please take a moment to help. Thank you.
Give up just one cup to help rescue pets every month.
It only takes a minute, and as little as $3 a month (a very reasonably priced coffee), to give rescue pets the very best chance of finding the love and care they need for life.
Keep the world’s best pet adoption platform running!
It only takes a minute to help keep PetRescue running, thriving, growing and FREE for all humans and pets who need us.
Please select an amount (in AUD)
$3
$15
$25
$50
$100
Other ($)
I'd like to add to cover the transaction fees so you can keep 100% of my donation.
Not available for interstate adoption
Snow white
Stunningly pure
Female Domestic Medium Hair Cat
Not available for interstate adoption
Snow white is a stunning, beautiful, affectionate cat. Searching for her new forever home.
She was rescued a few weeks back , covered in ticks, fleas and starving. She never hesitated even in her malnourished state all she had to offer was love and affection.
Making herself right at home. Snow white spends her days playing, eating and snuggling with her baby sheep toy. When ever someone walks into the room she stands to attention, begging for hugs, pats and affection.
Snow white would make a lovely addition to any family.
Adoption details
All adoptions will need to fill in an adoption form in regard to the animal they are looking at.
This is a questionnaire filled with easy to answer questions to make sure you and the animal are suited for each other.
If you are eligible for a meet and greet someone will be in touch to organise.
Our aim is to find the perfect home aswell as making sure our animals suit their new owners so everyone is happy and has forever home they have desired. |
Dimitri Zenghelis
Climate economics
Dimitri Zenghelis is Co-Head Policy at the Grantham Research Institute at the LSE. In 2014 he was Acting Chief Economist for the Global Commission on the Economy and Climate. He was recently Senior Economic Advisor to Cisco’s long term innovation group and an Associate Fellow at the Royal Institute of International Affairs, Chatham House. Previously, he headed the Stern Review Team at the Office of Climate Change, London, and was a senior economist on the Stern Review on the Economics of Climate Change, commissioned by the then Chancellor Gordon Brown. Before working on climate change, Dimitri was Head of Economic Forecasting at HM Treasury. He has provided regular briefings to the Chancellor Gordon Brown and Prime Minister Tony Blair. He has also worked at Oxford Economics, the Institute of International Finance, Washington DC, and Tokai Bank Europe, London. |
Q:
Edimax EW-7811UN dongle drops connection on ubuntu laptop
I have an Edimax EW-7811UN WiFi dongle which I bought for a raspberry pi. I have not managed to get it to work so am testing on my laptop for easier fault finding and since I know the installation and wireless (with built in adaptor) is working fine.
If I disable the built in adaptor (wlan0) and enable and configure the USB Edimax adaptor (wlan2), it constantly tries to connect. Then it will sometimes manage but then immediately drop the connection and try again.
There is no MAC filtering on the router. Any other device works without any problems. I am using WPA2, if that makes a difference.
I have trawled the net and tried every fix of alternative drivers that I could find.. but still no luck. But most of these are for if it isn't recognised.
Any ideas?
A:
I have found a link to a page which appears to work on the laptop! Perhaps the key was to configure via wpa_supplicant.conf rather than through the GUI..?
Anyway, for anyone else having the same problem..
Now to try it on the rpi!
http://elinux.org/RPi_edimax_EW-7811Un
|
Q:
How to set up XFCE4 XKB plugin to remember settings over reboots?
Following this answer I've installed xfce - xfce4-xkb-plugin to indicate and switch keyboard layouts in XUbuntu. But it resets all the settings (languages I use and a switch layouts hotkey) every time I reboot. How to make it to remember?
A:
As the best previous answer appears to be commented afterwards by the user as not working anymore, I will give here an updated perfected version of a quite successful workaround. Sorry not to be able to provide a more scientific less empirical approach, I am not an advanced user, just had the luck to get what I want in this case and want to share this, maybe as a temporary patchwork. So, bare with me.
I use Xubuntu, maybe some instructions are limited to that.
My solution is this (my case is English-US as default, second French, third Romanian standard - replace accordingly):
Go to Setting Manager > Keyboard > Layout, and set the languages in the preferred order (delete them and add them in order to achieve this). Go to the properties of the xkb plugin and make the same settings in the same order with the same default language.
Open the file
$HOME/.config/xfce4/xfconf/xfce-perchannel-xml/keyboard-layout.xml
Edit it to look similar to this.
Open the file
$HOME/.config/xfce4/panel/xkb-plugin-##.rc
(replace ## with appropriate number).
Edit it to look similar to this.
Open the file
/etc/default/keyboard
(as root)
Edit it accordingly:
XKBMODEL="pc105"
XKBLAYOUT="us,fr,ro"
XKBVARIANT=",,std"
XKBOPTIONS="grp:alt_shift_toggle"
Maybe not all these are necessary to make it work, but just in case...
A:
This is a known bug. I use xfce in arch linux and what I do is edit the ~/.config/xfce4/panel/xkb-plugin-##.rc and add a new line or something and it works for some sessions. Another temporary fix may be what #31 suggests
1. Set the desired options in the plugin
2. Copy the ~/.config/xfce4/panel/xkb-plugin-##.rc to some other file e.g. ~/.config/xfce4/panel/goodxkb.rc
3. Add this command to a startup job:
sh -c "cp ~/.config/xfce4/panel/goodxkb.rc ~/.config/xfce4/panel/xkb-plugin-##.rc && pkill xkb"
(change the ## to your number)
The pkill part is crucial to reload the plugin and its config.
|
Adrenergic stimulation decreases osteoblast oxytocin synthesis.
Oxytocin (OT) regulates bone mass by inducing the differentiation of osteoblasts to a mature, mineralizing phenotype. We have shown recently that osteoblasts can synthesize OT. In view of known interactions between OT-ergic and adrenergic neurons in the central nervous system, we questioned whether the negative regulation of osteoblast differentiation by adrenergic nerves was mediated through its suppression of OT synthesis. We first confirmed that α(1b) and β(2) adrenergic receptors were expressed on both primary murine osteoblasts and MC3T3-E1 cells. We then showed that α(1) and β(2) adrenergic agonists downregulated OT synthesis, and that the effect of each agonist was reversed by its respective antagonist. The data suggest that the negative effects of adrenergic stimulation on bone mass could, in part, arise from decreased OT synthesis. |
Synthesis of poly(N-aminoethyl)acrylamide chelating fiber and properties of concentration and separation of noble metal ions from samples.
A new kind of poly(N-aminoethyl)acrylamide chelating fiber was synthesized from nitrilon (an acrylonitrile-based synthetic fiber) and used for the concentration and separation of traces of noble metal ions from solution. The results showed that 16-80 ng ml (1) of Au(III), Pt(IV), Pd(IV), Ir(IV), Ru(III) and Rh(III) can be quantitatively concentrated by the fiber up to a flow rate of 20 ml min (-1) at pH 3, and can be desorbed quantitatively with an eluting agent from the fiber column with recoveries of 96-100%. For a fiber reused 10 times, the recoveries of these ions were still over 94%, and a 100-1000 times excess of Fe(III), Al(III), Ca(II), Mg(II), Ni(II), Co(II), Cu(II) and Zn(II) caused no interference in the determination of these ions by inductively-coupled plasma atomic emission spectrometry. The capacities of the fiber for the analytes were in the range 0.80-2.62 mol g(-1), The relative standard deviation of the method was between 0.02% and 2.6%. Recoveries of a standard added to a real sample were 96.8-99.2%. The average error for the analysis by this method for a powder sample was 3.5%. The IR spectra of the analyte-bearing fiber showed that these ions coordinated to nitrogen sites in the fiber. |
Vandhaan Vendraan
Vanthaan Vendraan () is a 2011 Indian Tamil-language action crime comedy thriller film written and directed by R. Kannan that stars Jiiva, Nandha and Taapsee Pannu in the lead roles. Principal photography began on 27 August 2010, and the film released on 16 September 2011 to mixed reviews. The film was dubbed in Telugu as Vachadu Gelichadu.
Plot
The film opens to a school in a village where a boy recites a national anthem before all the staff and students of the school. Another boy is seen running to school as he is late. His teacher punishes him, while comparing him to the boy who recited earlier, who is revealed to be his younger half-brother. An enmity grows in the older brother as he is always compared to his younger brother. The younger brother burns the photo of the older brother's father as he was the reason for his defeat in the school's kabbadi match. In retaliation, the older brother throws the younger brother into a well. Watching him get drowned in the well, the older brother runs away from the village.
The film then opens to Mumbai, just a few years after the incident. The older brother grows up to become Ramana (Nandha), who is an underworld don doing smuggling business with the help of the local police and political support. He tries to kill Govardhan, who is a rival to him, but he fails. Arjun (Jiiva) tries to see him for many days but is not able to. Finally, with the help of Ramana's cook Delhi (Santhanam), he manages to see him and tells him about his life story. Arjun is a boxer and accidentally meets Anjana (Taapsee Pannu) while going to a boxing selection match. He could not attend the match because he spoils the miniature that Anjana was carrying for her interview the same day.
He helps her out and in turn, Anjana travels to Kerala to meet the person in charge of the boxing selection match so that Arjun can get a second chance. However, it turns out that Arjun has come with her to Kerala to express his love for her, which she does not reciprocate. Finally, she agrees on the condition, if her father (Raviprakash) agrees. When Arjun meets Anjana's father, he rejected Arjun's marriage proposal to his daughter before being accidentally shot and killed by Ramana when he tries to kill Govardhan. Anjana proposes a deal to Arjun that if he makes Ramana surrender to the police, she will marry him, which he accepts. Arjun has come to Ramana to make him surrender, but Ramana and his gang thrash Arjun and throw him out.
Anjana pesters Arjun, as he is taking a long time to make Ramana surrender. In order to speed things up, Arjun demolishes Ramana's smuggling business and leaks about him to the press. Ramana's business is sealed by the police, and they plan an encounter for Ramana. Since all this happened because of Arjun, a fight ensues between both of them where Arjun is stabbed fatally by Ramana at the end. Delhi comes in and reveals to Ramana that Arjun is the latter's younger brother whom he threw in the well in their childhood. It is also revealed that what he told him about Anjana and her revenge for her father's death was all a fake and imaginative story so that Ramana will have compassion for their love, as Ramana's love was a failure. Arjun has thought Ramana would succumb to Arjun's plea and surrender to the police so that he would escape from the police's encounter and he can return to their family.
Ramana realizes himself and surrenders to the police, but not before admitting Arjun in a hospital, saving his life. Arjun goes back to his home and reunites with his family. Ramana writes to his family in a letter, while he is in jail, promising them that he will come back and will be more responsible from now. His parents were touched by this. Ramana is set to be married to a girl his family set him up with. In the end, a girl identical to Arjun's imaginative and fake girlfriend, Anjana meets Arjun similar to their meeting in Arjun's imaginative and fake story.
The film ends with a happy note that is THE LOVE IN HIS IMAGINATION BECOMES TRUE......
Cast
Jiiva as Arjun
Nandha as Ramana
Taapsee Pannu as Anjana
Rahman as Mumbai Commissioner
Santhanam as Delhi
John Vijay as Training Coach
Sapan Saran as Ramana's lover
Malavika Avinash as Arjun and Ramana's mother
Raviprakash as Anjana's father
Sree Raam as Young Ramana
Azhagam Perumal
Kamala Krishnaswamy
Rachana Maurya as item number
Production
Reports had claimed that the plot was based on the American film Going the Distance, which was denied by Kannan. The scenes were shot in Sri Sivasubramaniya Nadar College of Engineering with all lead roles. Later Tamannaah was replaced by Taapsee in the film.
Critical reception
The film opened to mixed and negative reviews. The critic from Sify rated the film as "average" citing that "the key problem with the film is its script and narration", whilst describing Thaman's music as the "major plus point". Behindwoods gave 2.5 out of 5 with a verdict: "Fairly entertaining with an unexpected twist".
Soundtrack
The soundtrack was composed by Thaman. The soundtrack launch was held on 21 July 2011 at Sathyam Cinemas which was attended by several prominent celebrities. The soundtrack received mixed reviews. Behindwoods.com gave a score of two and a half stars out of five and deemed the album as a "Decorous effort by Thamman", further citing "Vandhaan Vendraan has some promising tracks that urge music lovers to hear them over and again. With couple of songs ‘Anjana’ and ‘Kanchana Mala’ turning to be cherry-picks, rest of the songs might gain the attention with the visuals."
References
External links
Category:Tamil-language films
Category:Indian films
Category:Films set in Mumbai
Category:2010s crime thriller films
Category:Indian crime thriller films
Category:2011 films
Category:2010s Tamil-language films
Category:Films shot in Mumbai
Category:Indian nonlinear narrative films
Category:Tamil film scores by S. Thaman
Category:Indian gangster films
Category:Films featuring an item number |
Over the next three years, a new state early-childhood-workforce plan aims to fill some of those holes, in part through alternative pathways like the training offered by Mile High. But experts agree the task is formidable.
In Colorado, the dearth of well-trained child-care and preschool teachers has worsened in recent years even as evidence mounts that quality caregivers play a critical role in setting kids up for long-term success.
Christi Chadwick, who heads the Transforming Colorado’s Early Childhood Workforce project at the nonprofit Early Milestones Colorado, said the state’s population growth, stagnant wages in the field, and more demanding worker qualification have exacerbated the problem. It’s particularly acute for community child-care providers, which can’t usually pay preschool teachers as much as school districts do.
“The compensation is a challenge,” Chadwick said. “If we’re going to ever professionalize the field, we have to think of how we have our teachers on par with those in elementary education.”
Experts say many child-care workers back into the profession—following a twisting path that may not include any formal training on how to work with little kids.
Some come in with only high-school diplomas, some with associates degrees, and some with bachelor’s degrees, though often in unrelated subjects.
Take Muna, a 24-year-old participant in the recent Mile High training. She holds a bachelor’s degree in international affairs from the University of Colorado Boulder and has held jobs working with adult refugees and teaching high-school girls in Saudi Arabia.
Until eight months ago when she became a staff aide at Mile High’s center in the Lowry neighborhood, Muna had never worked with young children.
Staff aides are entry-level workers who make about $12 an hour. They allow Mile High to meet staff-child ratio requirements, but under state rules, can’t be left alone with children.
Muna, who asked that her last name not be used, is exactly the kind of person Harris wants to nudge up the career ladder with the new training program.
“We want to push them out of staff aide. We want them to be teacher assistants,” Harris said, noting that a pay bump comes with the promotion.
Mile High is among a variety of organizations that offer the training, which leads to a credential called the Child Development Associate. Mile High staff can take the course for free as long as they commit to stay for a year. Employees at other Denver-area centers can participate for a fee. Harris said one of Mile High’s next steps will be to offer the training in Spanish.
For Muna, the course was mainly a way to learn the ropes of a profession she’s found both fulfilling and unfamiliar.
“I felt like I really didn’t know anything,” she said. “I didn’t want to be making mistakes or doing anything wrong.” |
Green coffee beans are coffee beans that have not yet been roasted. The roasting process of coffee beans reduces amounts of the chemical chlorogenic acid. This roasting process seems to destroy some of the healthy, natural chemicals in the beans. Therefore, green coffee beans have a higher level of chlorogenic acid compared to regular, roasted coffee beans. Chlorogenic acid in green coffee is associated to having health benefits for heart disease, diabetes, weight loss, and others.
Some research shows green coffee may help with weight loss. Studies suggest that it can reduce the absorption of carbohydrates from the digestive tract, which lowers blood sugar and insulin spikes.
In a study presented at the 243rd National Meeting & Exposition of the American Chemical Society (ACS), the world's largest scientific society, Joe Vinson, Ph.D., and colleagues described how a group of overweight or obese people who consumed a fraction of an ounce of ground green coffee beans each day lost about 10 percent of their body weight. "Based on our results, taking multiple capsules of green coffee extract a day -- while eating a low-fat, healthful diet and exercising regularly -- appears to be a safe, effective, inexpensive way to lose weight," Vinson said at the ACS meeting. He is with the University of Scranton in Pennsylvania. |
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The night Hillary Clinton lost the White House, Amanda Litman cried so hard she threw up.
In Atlanta, as the returns rolled in, Traci Feit Love faced a question from her anguished 8-year-old daughter: “Now what do we do?”
Across the country, in the heart of Silicon Valley, Rita Bosworth wondered the same thing.
The three never met, never spoke, never communicated in any fashion. But in the days and weeks that followed, they became common threads in a sprawling patchwork: the angry and politically aggrieved who — with no help from politicians, political parties or any formal campaign structure — have joined to fight President Trump and his policies.
From her Brooklyn apartment, the 27-year-old Litman co-founded a group called Run For Something, which encourages people under age 35 to do just that. Thousands have signed up, many of them political novices.
Love, a 40-year-old attorney, took to Facebook and virtually overnight created Lawyers for Good Government, now a coast-to-coast army of legal experts battling Trump on issues such as immigration and a ban on travelers from six Muslim-majority countries.
Bosworth, 38, helped start a network that steers donors and activists in Democratic-leaning states like California toward legislative contests in more Republican redoubts, on the theory that their actions can have a greater impact where resources are scarce.
The “idea is to build a pipeline of candidates and create incubators for policy that can eventually take the national stage,” said Bosworth, who plans to leave her job as a San Jose public defender soon to work full time for her organization, the Sister District Project (as in “sister cities”).
It’s not a Bernie thing or a Hillary thing or an Obama thing. It’s about speaking with one voice. Alex Wall, Democratic communications strategist
Powered by social media and fired by deep antagonism, Bosworth and others have produced a movement seemingly without precedent: artists, doctors, lawyers, scientists, software engineers and others organizing themselves to seek elected office, flood congressional town hall meetings and agitate on a broad range of issues.
Their numbers are unknowable; for many, a good part of the appeal of the do-it-yourself movements is the lack of rigid structure or top-down management.
But seemingly every week brings a new group with new designs: academics giving advice, librarians raising their voices, quilters taking up their sewing needles.
It turns out Trump, a president loathed by Democrats, is a far greater spur to liberal activism than the revered Barack Obama, a former community organizer who hoped to inspire a wave of officeholders and Democratic idealists. Instead, he presided over the hollowing-out of his party.
“In November last year, being a politician was the last thing I would have ever, ever, ever intended to do,” said Kellen Squire, a 32-year-old emergency room nurse in central Virginia, who, helped by Litman’s group, is waging an uphill fight for a seat in the state House of Delegates. “But I saw whatever was going to come down the pike was going to be so jacked up, I wasn’t going to just take it. I had to stand up, yell, scream and holler.”
Not all of the incipient energy is being directed toward the electoral arena.
A group calling itself the Resistance Media Collective has assembled 200 animators, graphic designers, videographers and other volunteers to live-stream anti-Trump protests and produce materials such as a cartoon brochure titled “A Preparedness Guide for Undocumented Families.”
Its tips, in English and Spanish, include finding a U.S. citizen to act as a child’s legal guardian and advice on navigating the court system. “Our goal, very very simply, is to amplify the resistance,” said Kathryn Jones, 48, a former actress in New York City and one of the group’s leaders.
Much of the effort is aimed at revivifying a Democratic Party that lost hundreds of gubernatorial, congressional and legislative seats under Obama, slumping to its weakest position in decades.
But many involved have purposely kept their distance from the national party and also tried to steer clear of lingering resentments over who backed Clinton or Bernie Sanders in 2016.
“It’s not a Bernie thing or a Hillary thing or an Obama thing,” said Alex Wall, a Democratic communications strategist and one of dozens of volunteers working together to help the anti-Trump opposition hone its message and broaden its reach on Facebook, Twitter and other social media. “It’s about speaking with one voice.”
Party leaders say they welcome the freelancing. “We’re all united in the same message,” said Sabrina Singh, a spokeswoman for the Democratic National Committee. “We want to elect Democrats that reflect our values and the values of the states they’re running in.”
Amanda Litman pitches Run For Something to an audience of prospective candidates and donors at a house party in Brooklyn Heights. (Mark Z. Barabak / Los Angeles Times)
Litman, a product of the Washington, D.C., suburbs, started walking precincts in Virginia as a 16-year-old. She went from Obama’s political operation to directing Clinton’s 2016 email program. After her queasy election night, she binged on Netflix and traveled to Costa Rica, where she devoured a history of Emily’s List, the Democratic group that promotes women running for office.
She contemplated a life away from campaigns. During an interview with a New York publishing house, however, she found her thoughts drifting to the imagined horrors of a Trump presidency and passively watching from the sidelines.
“That just seemed pathetic,” she said, as she headed to her office for the day, a table and chair at a Lower Manhattan wine bar renting work space in the off hours.
Running up her credit cards and digging into savings, Litman worked with Democratic consultant Ross Morales Rocketto, the husband of a Clinton campaign co-worker, to launch Run For Something. Their idea was to tap thousands of political contacts and share that knowledge base with a fresh generation of candidates.
They launched on Inauguration Day, and within a week 500 people had visited their website and expressed interest. The number, Litman said, has since climbed to more than 10,000.
The most common question — what should I run for? — is easily answered, she told about 20 potential donors and candidates gathered beneath a leafy canopy at a backyard party in New York’s Brooklyn Heights. Decide the problem you want solved and the best place to do so, she said.
For many, that means local offices, such as school boards and city councils, which are easier to win than seats in Congress, and where results can be more immediate than in gridlocked Washington. “They’re affordable,” Litman said, as though peddling a line of practical footwear, “and so, so, so important.”
Candidates who pass a screening — they must be Democratic-leaning, personable and committed to the time and effort a campaign requires — are offered a buffet of free advice from political pros: how to file for office, write a news release, design a website.
Heather Ward, 21, a recent college graduate running for a school board seat outside Philadelphia, was counseled on door-to-door canvassing: Polish a crisp message; leave a note if no one’s home. With guidance from her tutor, who helped run Clinton’s North Carolina campaign, she finished atop a field of four candidates and reached the November runoff.
Like any start-up, there’s a freedom that comes with low overhead and minimal expectations. No fat cat donors to appease, no anxious incumbents to allay, so the group can look beyond a single election cycle.
The hope, of course, is to win wherever and whenever possible, Litman said, but more important is grooming a stable of newcomers who can step up years from now to run for governor or U.S. Senate.
Or, she posited, the ultimate post-Trump fantasy: “A 2032 presidential candidate who started with us.”
mark.barabak@latimes.com
@markzbarabak on Twitter
ALSO
There’s only one Trump — that’s a key challenge for Democrats targeting GOP seats in 2018
Europe’s once-positive worldview of U.S. slips under Trump
What happens when scientists leave their labs to experiment with politics?
These Democrats feel guilty for sitting out the 2016 election, and they aren’t waiting to register voters for the midterms
Billionaire Tom Steyer at a crossroad: Run for California governor or go after Trump? |
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<!ENTITY Ctr_combrelstop "Stop & genindlæs: kombinér knapper på værktøjslinje">
<!ENTITY Ctr_stoprel1 "Vigtigt: placér genindlæs efter stop!">
<!ENTITY Ctr_panelmenucol "Panelmenu-pop-op'er: alternativ baggrundsfarve">
<!ENTITY Ctr_hideprivmask "Privat browsing: skjul maskeindikator">
<!ENTITY Ctr_navsmallicons "Små ikoner">
<!ENTITY Ctr_navlargeicons "Store ikoner">
<!ENTITY Ctr_nbisizedelay0 "Indledende forsinkelse ved opstart af browser">
<!ENTITY Ctr_nbisizedelay "ms (1000 ms = 1 sekund)">
<!ENTITY Ctr_findbar "Findlinje">
<!ENTITY Ctr_findbar_hws "Luk findlinje ved rulning af side">
<!ENTITY Ctr_findbar_width "Findboksenes bredde: ">
<!ENTITY Ctr_findbarpos "Findlinjernes placering">
<!ENTITY Ctr_findbar_def "Bunden (standard)">
<!ENTITY Ctr_findbar_top "Toppen">
<!ENTITY Ctr_findbar_topa "Toppen (alternativ rækkefølge på indhold)">
<!ENTITY Ctr_findbar_bota "Bunden (alternativ rækkefølge på indhold)">
<!ENTITY Ctr_nav_txt_ico0 "Vis kun ikoner (standard)">
<!ENTITY Ctr_nav_txt_ico1 "Vis store ikoner">
<!ENTITY Ctr_nav_txt_ico2 "Vis ikoner og tekst">
<!ENTITY Ctr_nav_txt_ico3 "Vis kun tekst">
<!ENTITY Ctr_nav_txt_exp "Klassik-attributter (eksperimentel):">
<!ENTITY Ctr_iat_notf_vt "Udeluk lodrette værktøjslinjer">
<!ENTITY Ctr_cpanelmenus "Panelmenu-pop-op'er (bogmærker, historik, osv.): kompakt visning">
<!ENTITY Ctr_hidezoomres "Zoom-knapper på værktøjslinje: skjul zoom-nulstil-knapper">
<!ENTITY Ctr_alt_newtabp "Nyt faneblad-side (about:newtab): alternativt udseende">
<!ENTITY Ctr_nosnippets "Startside (about:home): skjul snippets">
<!ENTITY Ctr_search_ui "Søg">
<!ENTITY Ctr_ctroldsearch "Gamle søgning">
<!ENTITY Ctr_ctroldsearchd "Not compatible to other search add-ons!">
<!ENTITY Ctr_ctroldsearchc "Ryd søgeboks efter søgning">
<!ENTITY Ctr_ctroldsearchr "Fald tilbage til første søgetjeneste i liste, efter søgning">
<!ENTITY Ctr_ctrosearchdel "forsinkelse">
<!ENTITY Ctr_search_oit "Åbn søgning i nyt faneblad">
<!ENTITY Ctr_osearch_meoit "Mellemklik: søg i nyt 'forgrundsfaneblad'">
<!ENTITY Ctr_osearch_meoit1 "Search engine">
<!ENTITY Ctr_osearch_meoit2 "Search glass">
<!ENTITY Ctr_osearch_iwidth "Automatisk justering af pop-op-bredde">
<!ENTITY Ctr_osearch_cwidth "Brugerdefineret bredde for søge-pop-op'er">
<!ENTITY Ctr_osearch_dm "Lille rullegardinsmenu-pil">
<!ENTITY Ctr_addonmanager "Tilføjelseshåndtering">
<!ENTITY Ctr_alt_addonsp "'Mere info'-side: alternativ rækkefølge">
<!ENTITY Ctr_am_showrecup "Vis altid kategorien 'Seneste opdateringer'">
<!ENTITY Ctr_alt_addonsm "Alternativt udseende">
<!ENTITY Ctr_am_nowarning "Tilføjelseslister: skjul advarsler">
<!ENTITY Ctr_am_compact "Tilføjelseslister: kompakt visning">
<!ENTITY Ctr_am_compact2 "Kompakt udseende +">
<!ENTITY Ctr_am_highlight "Tilføjelseslister: fremhæv element når der peges">
<!ENTITY Ctr_am_buticons "Tilføjelseslister: erstat knap-etiketter med ikoner">
<!ENTITY Ctr_am_hovshowb "Tilføjelseslister: vis kun knapper når der peges">
<!ENTITY Ctr_addonversion "Tilføjelseslister: vis tilføjelsesversion">
<!ENTITY Ctr_xpinstallui "Gamle tilføjelser-installationsvindue">
<!ENTITY Ctr_bmbutton "Bogmærker-menuknap">
<!ENTITY Ctr_hiderecentbm "Bogmærkers pop-op: skjul senest tilførte bogmærker">
<!ENTITY Ctr_hideeditbm "Bogmærkers stjerne: skjul pop-op (hvis side ikke er bogmærket)">
<!ENTITY Ctr_oldplacesbut "Bogmærkepunkter og -mapper på værktøjslinje: gammelt udseende">
<!ENTITY Ctr_dl_pm_drop "Download-knappanel: vis rullegardinsmenu-pil">
<!ENTITY Ctr_bmbutpanelm "Pop-op: panelmenu udseende">
<!ENTITY Ctr_bmbunsortbm "Pop-op: 'Usorterede bogmærker'-menu">
<!ENTITY Ctr_bmbunsortbm2 "Menu over bogmærker">
<!ENTITY Ctr_bmbviewbmsb "Pop-op: vis 'Vis bogmærker i sidepanel'">
<!ENTITY Ctr_bmbviewbmtb "Pop-op: vis 'Vis bogmærkelinjen'">
<!ENTITY Ctr_bmbutnotb "Popup: hide 'Bookmarks Toolbar' menu">
<!ENTITY Ctr_bmbnounsort "Pop-op: skjul 'Usorterede bogmærker'">
<!ENTITY Ctr_bmbutclpopup "Popup: only show 'Bookmark this page' and bookmarks">
<!ENTITY Ctr_bmbutnotext "Skjul etiket på bogmærkelinje">
<!ENTITY Ctr_skipprintpr "Udskriv-knap: spring vis udskrift over">
<!ENTITY Ctr_tbconmenu "Værktøjslinjens genvejsmenu: skjul 'flyt til menu', 'fjern fra værktøjslinje', 'genindlæs/bogmærk alle faneblade' og 'fortryd lukning af faneblade">
<!ENTITY Ctr_noresizerxp "Skjul tilpasning af størrelse (Windows XP)">
<!ENTITY Ctr_extraurlkeycb "Åbn yderligere adresselinje (Cmd/Ctrl+">
<!ENTITY Ctr_pmhidelabels "Hovedpanelmenu-pop-op: skjul mærkater på knapper">
<!ENTITY Ctr_menupopupscr "Menu-pop-op'er: vis rullepaneler i stedet for rullepile">
<!ENTITY Ctr_closegeneral "Generelle luk-ikoner">
<!ENTITY Ctr_tabsep_def "Standard fanebladsseparatorer">
<!ENTITY Ctr_fxmockup "&brandShortName; model">
<!ENTITY Ctr_tabmokcolor "Hvid farve til fanebladsknapper (luk, nyt, grupper, list alle)">
<!ENTITY Ctr_tabmokcolor2 "Hvid farve og sort skygge til tekst på faneblade som ikke er aktive">
<!ENTITY Ctr_tabmokcolor4 "Hvid farve til tomme prikkede faneblad-favicon">
<!ENTITY Ctr_navthrobber1 "Klik på aktivitetsindikatoren åbner følgende URL i et nyt faneblad:">
<!ENTITY Ctr_navthrobber2 "Tilføj URL eller lad være tom">
<!ENTITY Ctr_anewtaburl "Nyt faneblad-URL-side">
<!ENTITY Ctr_anewtaburlcb "Brugerdefineret nyt faneblad-URL-side (standard: 'about:newtab')">
<!ENTITY Ctr_anewtaburlpcb "Brugerdefineret privat nyt faneblad side url (standard: 'about:privatebrowsing')">
<!ENTITY Ctr_anewtaburlpf "Focus location bar after loading">
<!ENTITY Ctr_tab_tf_info1 "Farvenavne, heks-koder, rgb(a), og hsl(a) værdier er understøttet.">
<!ENTITY Ctr_tab_tf_info2 "Indtastede værdier valideres ikke!">
<!ENTITY Ctr_tabact_t "Markeret">
<!ENTITY Ctr_tabhov_t "Der peges på">
<!ENTITY Ctr_tabnor_t "Standard">
<!ENTITY Ctr_tabpen_t "Ikke indlæst">
<!ENTITY Ctr_tabunr_t "Ikke læst">
<!ENTITY Ctr_ntab_t "Nyt faneblad">
<!ENTITY Ctr_customsqtab1 "Baggrund">
<!ENTITY Ctr_ctext "Tekst">
<!ENTITY Ctr_ctextsh "Tekstskygge">
<!ENTITY Ctr_tabnor "Standard faneblad">
<!ENTITY Ctr_tabhov "Faneblad der peges på">
<!ENTITY Ctr_tabact "Markeret faneblad">
<!ENTITY Ctr_tabpen "Ikke indlæst faneblad">
<!ENTITY Ctr_tabunr "Ikke læst faneblad">
<!ENTITY Ctr_ntabnor "Standard nyt faneblad">
<!ENTITY Ctr_ntabhov "Nyt faneblad der peges på">
<!ENTITY Ctr_bold "Fed">
<!ENTITY Ctr_italic "Kursiv">
<!ENTITY Ctr_underlined "Understreget">
<!ENTITY Ctr_notabhov "Aktiveret indstillinger overstyrer 'Der peges på'-indstillinger">
<!ENTITY Ctr_tablowopa "Reducér fanebladets synlighed">
<!ENTITY Ctr_tabc_act_tb "Baggrundsfarve på værktøjslinjer">
<!ENTITY Ctr_urlbar "Adresselinje">
<!ENTITY Ctr_starinurl "Stjerne-knap">
<!ENTITY Ctr_starinurlinfo "Standard bogmærker-menuknap skjules">
<!ENTITY Ctr_feedinurl "RSS feed-knap">
<!ENTITY Ctr_hideurelstop "Skjul knapperne 'Stop & genindlæs'">
<!ENTITY Ctr_hideurelstop2 "Vis altid 'gå'-knap">
<!ENTITY Ctr_hideurlgo "Skjul 'gå'-knap">
<!ENTITY Ctr_hideurlsrg "Skjul 'genindlæs-, stop & gå'-knapseparatorer & mellemrum">
<!ENTITY Ctr_urlbardropm "Flyt rullegardinsmenu-pilen til den sidst mulige placering">
<!ENTITY Ctr_urlbardropm2 "Rullegardinsmenu-pil altid synlig">
<!ENTITY Ctr_altreaderico "Alternative 'Læser'-ikoner">
<!ENTITY Ctr_hideurlzoom "Skjul zoom-knap (hvis den er der)">
<!ENTITY Ctr_urlbardark "Dark background color">
<!ENTITY Ctr_hideprbutton "Skjul notifikationsikonet når en pop-op blokeres">
<!ENTITY Ctr_locsearchbw10 "Reducér adresselinjers og søgelinjers højde (eksperimentel)">
<!ENTITY Ctr_urlbar_ib "Knappen Identitet for websted">
<!ENTITY Ctr_ib_nohovcolor "Vis ikke grå farve når der peges">
<!ENTITY Ctr_ib_graycolor "Grå farve for ukendt identitet og 'about:'-sider">
<!ENTITY Ctr_verifiedcolors "Knapfarver for bekræftede websteder, sikre og ikke-sikre forbindelser">
<!ENTITY Ctr_ibinfoico "Erstat 'i'-ikon med globe-ikon">
<!ENTITY Ctr_ibinfoico2 "Skjul 'i'-ikon (hvis det er muligt)">
<!ENTITY Ctr_iblabels "Skjul etiketter">
<!ENTITY Ctr_faviconurl "Favicon: nuværende webstedsikon">
<!ENTITY Ctr_padlock "Hængelås ikon for sikre forbindelser">
<!ENTITY Ctr_padlock_hid "skjul">
<!ENTITY Ctr_padlock_def "standard">
<!ENTITY Ctr_padlock_cla "klassik">
<!ENTITY Ctr_padlock_mod "moderne">
<!ENTITY Ctr_padlock_ext "'&brandShortName;'-ikon for gyldige 'about'-sider">
<!ENTITY Ctr_icopageinfo "Favicon/globe/'i'-ikon: 'klik' åbner 'sideoplysninger-vindue'">
<!ENTITY Ctr_lbsbsize "Brugerdefineret brede">
<!ENTITY Ctr_searchbar "Søgelinje">
<!ENTITY Ctr_autocomplete "Autofuldfør-pop-op">
<!ENTITY Ctr_altautocompl "Alternativt udseende">
<!ENTITY Ctr_autocompl_it "Fjern 'Søg med...'- og 'Besøg'-punkter (hvis de er der)">
<!ENTITY Ctr_acompl_search "Vis søgetjenester">
<!ENTITY Ctr_autocompl_hl "Fremhæv fundet tekst">
<!ENTITY Ctr_autocompl_rhl "Aero-farver for fremhævede resultater">
<!ENTITY Ctr_autocompl_not "Skjul sidetitel">
<!ENTITY Ctr_autocompl_sep "Vis separator mellem resultater">
<!ENTITY Ctr_urlbar_uc "Deaktivér 'samlede autofuldfør'-funktion">
<!ENTITY Ctr_lbsugresi "Deaktivér højdegrænse">
<!ENTITY Ctr_cresultshcb "Brugerdefineret højde grænse: ">
<!ENTITY Ctr_lbsugres "Antal resultater">
<!ENTITY Ctr_lbsbradius "Brugerdefineret kantafrundning">
<!ENTITY Ctr_menubar_items "Placering af menupunkter">
<!ENTITY Ctr_extrabar "Yderligere værktøjslinjer">
<!ENTITY Ctr_extrabar0 "Yderligere værktøjslinje(r)">
<!ENTITY Ctr_extrabar1 "Yderligere værktøjslinje">
<!ENTITY Ctr_extrabarinfo "Skifte mellem 'faneblade øverst' og 'faneblade skal ikke være øverst' ændre tilfældigt på rækkefølgen af yderligere værktøjslinjer. &brandShortName; skal genstartes for at løse dette problem.">
<!ENTITY Ctr_invicons "Omvendte farver på ikoner">
<!ENTITY Ctr_menubar "Menulinje">
<!ENTITY Ctr_tabstoolbar "Fanebladslinje">
<!ENTITY Ctr_navbar "Navigationslinje">
<!ENTITY Ctr_bookbar "Bogmærkelinje">
<!ENTITY Ctr_notoolbar "Skjul (vis ikke menupunkter)">
<!ENTITY Ctr_mbarforceleft "Første element">
<!ENTITY Ctr_mbarforceright "Sidste element">
<!ENTITY Ctr_toolbars "Værktøjslinjer">
<!ENTITY Ctr_dblclnewtab "Dobbeltklik på værktøjslinje åbner et nyt faneblad">
<!ENTITY Ctr_dblclnewtabdes "Ikke egnet til alle komplette temaer når Windows-titellinje er aktiv.">
<!ENTITY Ctr_hidetbwot "Skjul fanebladslinjen når der kun er ét faneblad">
<!ENTITY Ctr_hidetbwote "Reducér forsinkelse ved skjul under opstart">
<!ENTITY Ctr_hidetbwote_i "Kan give fejl på fanebladenes værktøjslinje">
<!ENTITY Ctr_hidetbwote2 "Juster automatisk titellinje mellemrum">
<!ENTITY Ctr_notabfog "Fjern baggrundståge (Windows AeroGlass/8)">
<!ENTITY Ctr_notabbg "Fjern baggrundsfarve (Windows AeroGlass/8)">
<!ENTITY Ctr_hightabpos "Reducér mellemrum over værktøjslinje (hvis det er muligt)">
<!ENTITY Ctr_showalltabsb "Vis altid knappen 'alle faneblade'">
<!ENTITY Ctr_alttabstb "Alternativ baggrundsfarve">
<!ENTITY Ctr_alttabstb2 "I maksimeret tilstand (faneblade øverst)">
<!ENTITY Ctr_altmenubar "Tilføj baggrundsfarve (OS titellinje)">
<!ENTITY Ctr_altmenubarpos "alternativ placering">
<!ENTITY Ctr_altmenubarpos2 "Under &brandShortName;-titellinje">
<!ENTITY Ctr_menubarnofog "Fjern baggrundsfarve/tåge (Windows AeroGlass/8)">
<!ENTITY Ctr_aerocolors "Blå Aero-farver til værktøjslinjer (og faneblade)">
<!ENTITY Ctr_aerocolorsg "Grå-blå Aero-farver">
<!ENTITY Ctr_transpttbw10 "Titel-/menu-/fanebladsværktøjslinje: fjern baggrundsfarve">
<!ENTITY Ctr_transpttbew10 "Yderligere tweaks til nogle OS-temaer">
<!ENTITY Ctr_transptcw10 "Skjul standard OS min/maks/luk-knapper">
<!ENTITY Ctr_hidenavbar "Skjul værktøjslinje">
<!ENTITY Ctr_navbarpad "Yderligere venstre- og højre mellemrum">
<!ENTITY Ctr_navbarpad_l "Venstre:">
<!ENTITY Ctr_navbarpad_r "Højre:">
<!ENTITY Ctr_nobookbarbg "Fjern baggrundsfarve">
<!ENTITY Ctr_bookbarfs "I fuldskærmstilstand">
<!ENTITY Ctr_nonavbarbg "Fjern baggrundsfarve">
<!ENTITY Ctr_nonavbarbg1 "Denne tilføjelses yderligere værktøjslinjer og andre værktøjslinjer i toppen påvirkes.">
<!ENTITY Ctr_nonavbarbg2 "Alle værktøjslinjer i 'Beyond Australis'-tilføjelsens 'Slim Chrome' påvirkes.">
<!ENTITY Ctr_nonavborder "Tilføj kant på værktøjslinjen">
<!ENTITY Ctr_nonavtbborder "Øverste værktøjslinjer: fjern kanten på værktøjslinje">
<!ENTITY Ctr_toptb_oldpad "Øverste værktøjslinjer: gammel venstre- og højre margen">
<!ENTITY Ctr_hidesbclose "Sidepaneler: skjul luk-knap">
<!ENTITY Ctr_hidesidebardm "Sidepaneler: hide dropmarker">
<!ENTITY Ctr_comp_sbheader "Sidepaneler: compact header">
<!ENTITY Ctr_notextshadow "Værktøjslinjer: skjul skygge for tekst på værktøjslinje og faneblade">
<!ENTITY Ctr_chevronfix "Navigationslinje: skjul dobbelt-pil på værktøjslinjernes slutning">
<!ENTITY Ctr_tbsep_winc "Øverste værktøjslinjer: yderligere separatorer for værktøjslinje">
<!ENTITY Ctr_closeabarbut "Tilføjelseslinje: skjul luk-knap">
<!ENTITY Ctr_highaddonsbar "Større">
<!ENTITY Ctr_lessaddonsbar "Mindre">
<!ENTITY Ctr_addonbarfs "I fuldskærmstilstand">
<!ENTITY Ctr_tabthrobber "Standard indlæsningsbillede">
<!ENTITY Ctr_bmanimation "Animation på stjerne ved bogmærkning">
<!ENTITY Ctr_pananimation "Animation ved åbning af panel">
<!ENTITY Ctr_tabanimation "Animation ved lukning/åbning af faneblad">
<!ENTITY Ctr_dlanimation "Animation ved 'Filhentning notifikation'">
<!ENTITY Ctr_uianimation "General ui animations">
<!ENTITY Ctr_fsanimation "Fuldskærmsanimationer">
<!ENTITY Ctr_fsaduration "Fuldskærmsanimationer for HTML5-indhold">
<!ENTITY Ctr_findbarhl "Findbar: animate result highlighting">
<!ENTITY Ctr_toolsitem "Menupunkt i værktøjslinje">
<!ENTITY Ctr_appmenuitem "Menupunkt i programknappermenu">
<!ENTITY Ctr_contextitem "Menupunkt i værktøjslinje genvejsmenu">
<!ENTITY Ctr_puictrbutton "Knap i hovedpanelmenu">
<!ENTITY Ctr_otherctroptns "Andre indstillinger">
<!ENTITY Ctr_cuibotbuttons "Ekstra knapper i 'Tilpas'-tilstand">
<!ENTITY Ctr_nodevtheme "Forhindre 'Developer Edition'-tema i at blive aktiveret">
<!ENTITY Ctr_experttweaks "Avanceret">
<!ENTITY Ctr_fx34loop "Deaktivér denne indstilling for at fjerne funktionen 'opkald og samtaler'.">
<!ENTITY Ctr_fx38pocket "Deaktivér denne indstilling for at deaktivere funktionen 'Pocket' og for at fjerne dens knap fra værktøjslinjerne.">
<!ENTITY Ctr_fx38pocket2 "Bemærk: flyttes Pocket-knappen til 'Flere værktøjer og funktioner'-området i 'Tilpas'-tilstand før denne indstilling deaktiveres, vil det også fjerne 'Pocket'-relaterede poster fra Bogmærker- og Læser-menu-pop-op'er.">
<!ENTITY Ctr_e_loop "Hello/opkald og samtale/Loop">
<!ENTITY Ctr_e_readermode "Læsertilstand">
<!ENTITY Ctr_e_geolocation "Positionstjeneste">
<!ENTITY Ctr_e_pocket "Pocket">
<!ENTITY Ctr_e_tabsaudioico "Lydafspilningsikon på faneblade">
<!ENTITY Ctr_e_containertab "Indeholdende faneblade">
<!ENTITY Ctr_e_flyweb "Flyweb">
<!ENTITY Ctr_e_resfprinting "Anti fingerprinting protection">
<!ENTITY Ctr_e_oldfontgfx "Old font rendering">
<!ENTITY Ctr_pw_settings "Indstillinger">
<!ENTITY Ctr_pw_set_reset "Gendan standard">
<!ENTITY Ctr_pw_set_predef "Klassisk-opsætning">
<!ENTITY Ctr_pw_set_preaus "&brandShortName;-opsætning">
<!ENTITY Ctr_pw_set_export "Eksportér indstillinger">
<!ENTITY Ctr_pw_set_import "Importér indstillinger">
<!ENTITY Ctr_pw_set_syncon "Føj til Sync">
<!ENTITY Ctr_pw_set_syncoff "Fjern fra Sync">
<!ENTITY Ctr_pw_set_impexp "Preferences containing a 'about:config >> ...' description are default browser preferences and do not get exported or imported!">
<!ENTITY Ctr_special_font "Indstillinger til baggrundsfarve gælder kun til standard tema!">
<!ENTITY Ctr_special_info "Nogle indstillinger giver måske ikke altid synlige ændringer">
<!ENTITY Ctr_special_info2 "Tredjeparts temaer registreret! Nogle indstillinger virker ikke med tredjeparts temaer!">
<!ENTITY Ctr_special_acr "Rapportér kun problemer gennem officielle support-kanaler og ikke ved brug af 'Add-on Compatibility Reporter'!">
<!ENTITY Ctr_support "Support">
<!ENTITY Ctr_support_forum1 "MozillaZine (engelsk forum)">
<!ENTITY Ctr_support_forum2 "Camp Firefox (tysk forum)">
<!ENTITY Ctr_github_issues "Rapportér problem på Github">
<!ENTITY Ctr_newversion "Latest CTR version">
<!ENTITY Ctr_newversion2 "Latest CTR beta">
<!ENTITY Ctr_addon-bar.accesskey "A">
<!ENTITY appMenuGettingStarted.label "I gang">
<!ENTITY goCmd.label "Gå">
<!ENTITY Ctr_showfx57pcomp "Emphasize 'Firefox 57+' compatible CTR options">
<!ENTITY Ctr_showfx57pcomp1 "Green - possible with userChrome.css or userContent.css">
<!ENTITY Ctr_showfx57pcomp2 "Blue - possible by default">
<!ENTITY Ctr_showfx57pcomp3 "Yellow - possible with WebExtensions">
<!ENTITY Ctr_showfx57pcomp4 "Orange - not needed anymore">
<!ENTITY Ctr_showfx57pcomp5 "Red - not possible anymore">
<!ENTITY Ctr_menu_restart.label "Genstart">
<!ENTITY Ctr_restartapp "Vis 'Genstart' i &brandShortName;-menu og Filer-menu">
<!ENTITY Ctr_restartapp2 "Vis 'Genstart' i hovedpanelmenu">
<!ENTITY Ctr_contextfind "Show 'Find' and 'Find Again' in toolbars context menu">
<!ENTITY Ctr_ctrnewinv "Understreg nye indstillinger for nuværende &brandShortName; version">
<!ENTITY Ctr_cssoverride "Custom css code">
<!ENTITY Ctr_cssoverride2 "Css code will not be checked for errors!">
<!ENTITY Ctr_openInCurrentTab "Åbn inputs i nuværende faneblad">
<!ENTITY Ctr_openInNewTab "Åbn inputs i et nyt faneblad">
<!ENTITY Ctr_openInNewWindow "Åbn inputs i et nyt vindue">
<!-- Old search default browser labels -->
<!ENTITY Ctr_engineManager_label "Manage Search Engines...">
<!ENTITY Ctr_searchEndCap_label "Search">
<!-- For page context entries. Have to be adjusted for every locale! -->
<!ENTITY backCmd.accesskey "T">
<!ENTITY forwardCmd.accesskey "F">
<!ENTITY reloadCmd.accesskey "G">
<!ENTITY stopCmd.accesskey "S">
<!ENTITY bookmarkPageCmd2.accesskey "b">
<!-- Fallback entities. Do not change! -->
<!ENTITY openCmd.commandkey "">
<!ENTITY urlbar.accesskey "">
<!ENTITY urlbar.placeholder2 ""> |
Meghan Markle and Prince Harry are officially married. Though the entire royal family reportedly adores the former Suits actress, the couple has had to make a few changes to adjust to the new expectations that come with their married life. Prince Harry’s grandmother, Queen Elizabeth II, wants the couple to stop doing one non-royal thing immediately (No. 10). You also won’t believe what Prince Harry and Meghan Markle can’t call each other when out in public (No. 12).
2. Advice from seasoned pros
These four are getting closer and closer. | Chris Jackson/Getty Images
Since her life has changed drastically and she made the move to the U.K. to be with Prince Harry, Markle has learned a lot about being royal. Luckily, she lived steps away from Prince William and Duchess Kate. She’s been able to grow close to them, even bonding with their two children, Prince George and Princess Charlotte.
After having to go through royal training herself, Duchess Kate has been a helpful resource for Markle as she learns to navigate her new royal life. Prince William has also reportedly made himself available as a resource for Markle if she ever has any questions or needs help with something.
Next: This was once out of the question for royals.
3. Overlooking a royal no-no
Queen Elizabeth II has given the couple her official approval. | Oli Scarff-WPA Pool/Getty Images
My Lords, I declare My Consent to a Contract of Matrimony between My Most Dearly Beloved Grandson Prince Henry Charles Albert David of Wales and Rachel Meghan Markle, which Consent I am causing to be signified under the Great Seal and to be entered in the Books of the Privy Council.
This is super modern because Markle is a divorcee, which would have been a major no-no a few decades ago. Also, how cute is Harry being the queen’s “most dearly beloved grandson”?
A royal insider told Women’s Day, “Meghan is such a warm person, but being a royal is very different to being a celebrity, and Meghan still has a lot to learn.”
Next: The infamous royal rules and protocols
5. Say no to selfies
Fans won’t be able to snap selfies with Meghan or Prince Harry. | Chris Jackson/Getty Images
Harry and Markle also have to limit themselves when it comes to selfies, per royal protocol and the queen’s personal preference. Markle has already gotten ahead of herself by deleting all of her social media accounts. It’s probably been pretty helpful since royals are absolutely forbidden to take selfies. (Apparently, that’s peasant behavior.)
Next: The new royal could actually be fined for doing one thing in public.
6. Always keep your composure
Like the queen, Meghan Markle must always look fresh and not tired or fatigued. | Ben Birchall/WPA Pool/Getty Images
Long trips, tiresome speeches, and dull events are all on Markle’s royal calendar. However, she must always be careful to mask her exhaustion. In fact, if the former actress yawns in public, she’s actually going to be penalized. She’s also not supposed to gasp or frown.
We suppose the Northwestern alum should start trying to act as robotic as possible.
7. Maintain distance
The royal couple will be avoiding photos during their celebratory nights out. | Chris J Ratcliffe/Getty Images
8. The appropriate way to wear a tiara
She’ll have the honor of donning a tiara just like Queen Elizabeth. | Michael Ukas/ Pool /Getty Images
When we think of Markle’s princess lessons, we like to imagine her walking around Buckingham Palace with a stack of books balanced on her head, but we’ve probably seen too many movies. Markle is now officially allowed to wear a tiara, but the glittering diamond incrusted crowns must be worn properly.
Modern royals wear their tiaras pushed back slightly away from the top of their heads and at a 45-degree angle. How regal.
Next: Learning to greet commoners
9. A swift hello
She’ll even have to improve her wave. | Oli Scarff/AFP/Getty Images
We’d imagine that constantly waving your hand at the public would make anyone tiresome, but as a royal, it’s just part of life.
Zarife Hardy, the founder of the Australian School of Etiquette explained, “She’ll obviously be taught more on the royal wave, it’s a bit gregarious right now and needs to be more fine-tuned. And also just that art of meeting and greeting. Looking someone in the eye, a nice firm handshake, no more than two pumps and a lovely warm smile.
Next: The one thing the queen no longer wants the couple to do
10. Stop the PDA
Though the queen adores her grandson and his new bride, she’s not too pleased about one aspect of their relationship. The super cute duo are extremely loving and affectionate in public, but that is a massive royal taboo.
An insider revealed to Women’s Day, “Being affectionate just comes naturally to Harry and Meghan, but it’s totally against royal protocol. The Queen isn’t thrilled about it at all, and word is she summoned Harry to the palace to remind him what’s expected of a royal. All the hand-holding just isn’t the royal way at all.”
Next: More surprising royal etiquette rules Markle has to follow.
11. The right way to sit
They must sit with their legs together. | Phil Noble-WPA Pool/Getty Images
You’ll never see a royal crossing their knees — especially royal women. They must always sit with their legs together. And, if they must cross something, they can cross their ankles.
That said, they can also angle their legs to the side. Kate Middleton’s go-to position incorporates all three aspects and has even been coined “the duchess slant” by Beaumont Etiquette.
Next: You’ll never hear this in public.
12. No nicknames
Meghan Markle and Prince Harry | Matt Dunham – WPA Pool/Getty Images
Notice how we never hear Prince William call the Duchess of Cambridge Kate? That’s because the royal family doesn’t have nicknames — at least, publicly they don’t. When referring to his wife in a public matter, he always calls her Catherine.
Next: The queen requires this upon first introduction.
13. How to address the Queen
Address her as “your majesty.” | Chris Jackson/Getty Images
After that, she goes by “ma’am.” In addition, male members of the royal family are addressed as “your royal highness,” followed by “sir,” and female members are addressed as “your royal highness,” followed by “ma’am.”
Next: A strict dress code
14. Adhere to the royal dress code
The royal family has a strict dress code policy — one that should never be broken. As a rule of thumb, all members of the royal family must dress modestly. Markle doesn’t appear to have any problem looking modest and royal.
Next: When the queen stops doing this, everyone stops.
15. Everyone stops eating when the queen does
Follow the queen’s lead. | Sharon Smith/AFP/Getty Images
No matter who you are or where you are seated, the queen has control of all dinners, including when everyone is finished eating. As soon as she stops, so must everyone else.
Next: There are even rules for how to walk.
16. Rank dictates walking order
The royals are supposed to go first, but it’s also polite to let women lead. | Chris Jackson/Getty Images
While royals are always accompanied by their spouses, it’s tradition for the royals to walk a few steps ahead. That said, it is also proper etiquette to let the woman lead. While the queen always walks slightly ahead of Prince Philip, Prince Harry often allows Meghan Markle to lead the way.
By royal family standard, the queen follows proper suit, but that doesn’t mean Harry is in the wrong. It’s still considered polite to let the lady lead — royal, or not.
Next: Royals even have to learn a certain way to walk.
17. A specific way to descend stairs
Women must keep their chins in line with the ground. | Nicolas Maeterlinck/AFP/Getty Images
Descending stairs in a ball gown and heels can be a recipe for disaster. Luckily, members of the royal family are trained to walk down stairs with poise. For added stability, men typically put a hand out for their spouses.
That said, women must descend stairs in a specific manner. The royal family protocol is to keep their hands at their sides and the chin in line with the ground. They may use the banister for stability but cannot grab onto it. Instead, they place their hand gently on it and point their toes toward it as they walk. Who knew walking down a flight of stairs could be so complicated?
Next: Royals don’t need to ask permission to do this.
18. Don’t ask to be excused
Just get up and go. | Lewis Whyld/WPA Pool/Getty Images
When dining, the royal family doesn’t ask permission to be excused from the table, and they certainly don’t make a fuss about it. Instead, they simply say, “excuse me,” and get up and go. |
I see five ladies here. The daughter that mother used to be; the inner girl of mother, the present mother, the present daughter, and the mother she will be.Then... what means "time" if a fraction of a second captures 50 years?
They two represent the force of love going from each one to the other, for walk to a future that they saw in the past and their quest in their actual moment, when mother learn to teach how to advance to that future and the daughter learns how to be a mother who protects against internal and external ghosts.This made me remember a love song lyrics that goes something like "...I love you because on the street, elbow to elbow, we're much more than two..." And in black and white, it's a timeless razon.
Again, what is time...?
Maybe the only definition of time, with sense, is " time is this very moment that I live". Beyond that, everything is speech.
And, for me, it's a proof the real power is clearly owned: the tuft of a beloved little lady retracts any blurred menace, (and certainly exposure time was the same for both). The second man I see there, blurred too, is myself, when I don't get inner peace.
About Me
Paris reached out and grabbed me when I was 8 years old and it only took me 40 years to actually get there! I love Paris, its people, its architecture and all of France. This is a photo blog about Paris and occasionally other places in the world. |
Q:
Update trigger issue throwing errors on IF statements
I have created a trigger, basically what I want it to do is update or insert a record to another table.
Two table I have got:
MVF_Transport_Register: Main table
MVF_Transport_Acc: table trigger need to update.
When a record is updated on the Main table, I want to the trigger to check if that records exists on the MVF_Transport_Acc.
If it does only update the Record_status column.
If the record is not in MVF_Transport_Acc then insert the new record.
This is what I have written but I am getting the following error when trying to deploy it:
Msg 156, Level 15, State 1, Procedure UpdateTransport_TEST1, Line 36
Incorrect syntax near the keyword 'END'.
Here's the trigger:
SET ANSI_NULLS ON
GO
SET QUOTED_IDENTIFIER ON
GO
ALTER TRIGGER [dbo].[UpdateTransport_TEST1]
ON [dbo].[MVF_Transport_Register]
AFTER UPDATE
AS
IF UPDATE (Record_Status)
BEGIN
IF (i.Order_No=c.Order_No )
UPDATE c
set Record_Status=i.Record_Status
FROM dbo.MVF_Transport_Acc AS c
JOIN inserted as i
ON i.Order_No = c.Order_No
JOIN deleted as d
ON i.Order_No=d.Order_No
OR (i.Record_Status <> d.Record_Status)
WHERE (i.Record_Status = 'CONFIRMED' OR
i.Record_Status = 'AMENDED') AND (i.Price > 0)
ELSE
INSERT into dbo.MVF_Transport_Acc
([Order_No], [Record_Status], [Notes], [Transport_Supplier], [Surcharge], [Vendor_No], [Pallets], [Amend_Pallets],[Price], [Input_Date], [Amend_Price], [Transport_Invoice_No],[Transport_Job_No], [Amend_Date], [Report_Price],
[Return_Price], [Report_Date])
SELECT i.[Order_No], i.[Record_Status], i.[Notes], i.[Transport_Supplier], i.[Surcharge], i.[Vendor_No], i.[Pallets], i.[Amend_Pallets],i.[Price], i.[Input_Date], i.[Amend_Price], i.[Transport_Invoice_No],i.[Transport_Job_No], i.[Amend_Date], i.[Report_Price],
i.[Return_Price], i.[Report_Date]
FROM [dbo].[MVF_Transport_Register] c
INNER JOIN inserted i on
c.Order_No = i.Order_No
WHERE (i.Record_Status = 'CONFIRMED' OR
i.Record_Status = 'AMENDED') AND (i.Price > 0)
END IF
END
A:
This logic seems wrong to me, but I think you have it way more complicated than it needs to be:
ALTER TRIGGER [dbo].[UpdateTransport_TEST1]
ON [dbo].[MVF_Transport_Register]
AFTER UPDATE
AS
BEGIN
UPDATE c
SET c.Record_Status = i.Record_status
FROM dbo.MVF_Transport_Acc AS c
INNER JOIN inserted AS i
ON c.Order_No = i.Order_No
AND c.Record_Status <> i.Record_Status
WHERE i.Record_Status IN ('CONFIRMED', 'AMENDED')
AND i.Price > 0;
IF @@ROWCOUNT = 0
BEGIN
INSERT dbo.MVF_Transport_Acc
([Order_No], [Record_Status], [Notes], [Transport_Supplier],
[Surcharge], [Vendor_No], [Pallets], [Amend_Pallets],[Price],
[Input_Date], [Amend_Price], [Transport_Invoice_No],[Transport_Job_No],
[Amend_Date], [Report_Price], [Return_Price], [Report_Date])
SELECT i.[Order_No], i.[Record_Status], i.[Notes], i.[Transport_Supplier],
i.[Surcharge], i.[Vendor_No], i.[Pallets], i.[Amend_Pallets],
i.[Price], i.[Input_Date], i.[Amend_Price], i.[Transport_Invoice_No],
i.[Transport_Job_No], i.[Amend_Date], i.[Report_Price],
i.[Return_Price], i.[Report_Date]
FROM inserted AS i
WHERE i.Record_Status IN ('CONFIRMED', 'AMENDED')
AND i.Price > 0;
END
END
GO
I still feel like that logic is incomplete for some reason.
|
#7 Davenport Rugby travels to St. Charles, MO to take on #3 Lindenwood Rugby for the Charles Labry Memorial Shield in a D1A Mid-South showdown.
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Optogenetic Medicine: Synthetic Therapeutic Solutions Precision-Guided by Light.
Gene- and cell-based therapies are well recognized as central pillars of next-generation medicine, but controllability remains a critical issue for clinical applications. In this context, optogenetics is opening up exciting new opportunities for precision-guided medicine by using illumination with light of appropriate intensity and wavelength as a trigger signal to achieve pinpoint spatiotemporal control of cellular activities, such as transgene expression. In this review, we highlight recent advances in optogenetics, focusing on devices for biomedical applications. We introduce the construction and applications of optogenetic-based biomedical tools to treat neurological diseases, diabetes, heart diseases, and cancer, as well as bioelectronic implants that combine light-interfaced electronic devices and optogenetic systems into portable personalized precision bioelectronic medical tools. Optogenetics-based technology promises the capability to achieve traceless, remotely controlled precision dosing of an enormous range of therapeutic outputs. Finally, we discuss the prospects for optogenetic medicine, as well as some emerging challenges. |
Zurayids
The Zurayids (بنو زريع, Banū Zuraiʿ), were a Yamite Hamdani dynasty based in Yemen in the time between 1083 and 1174. The centre of its power was Aden. The Zurayids suffered the same fate as the Hamdanid sultans, the Sulaymanids and the Mahdids, since their lands were taken over by the Ayyubids, and they themselves were liquidated. They were a Shia Ismaili dynasty that followed the Fatimid Caliphs based in Egypt. They were also Hafizi Ismaili as opposed to the Taiyabi Ismaili.
The Sulayhid connection
The Zurayid dynasty had a strong affiliation with Sulayhids, starting with Ismaili Hamdani common origin, vassalage & eventually intermarriage with the last Sulyahid Queen.
Ismaili Hamdani common origin
Both the Sulayhid & Zurayid dynasties were founded by Ismaili Hamdani religious dais, who preached Ismailism with the support of the Fatimid Caliphate (at that time encompassing North Africa, Sicily & parts of the Levant), they were also tribally affiliated with Hamdan, competing with the Sunni Himyarite dynasties & rising Zaydi state in Sa'ada, this Ismaili connection eventually lead to the demise of the Hamdani Ismaili dynasties, as they were replaced by the Sunni & Zaydi dynasties, forcing the Hamdan clans to convert to Zaydi or Sunni sects (with the exception of the Haraz & Najran Ismaili enclaves).
Vassals of the Sulayhids
About the history of the dynasty we have only insufficient information. What we know mostly derives from the twelfth-century chronicle of 'Umara, who had personal contacts with the last princes. According to his account, the Sulayhid ruler Ali al-Sulayhi (d. 1066 or 1081) subdued the important port Aden which was ruled by the Banu Ma'n, in 1062. This family were also masters of Lahij, Abyan, Shihr and Hadramawt. The Himyarite clan of Banu Ma'n paid tribute until the death of Ali and then declared their independence. However, Ali's son Al-Mukarram Ahmad immediately invested Aden and put an end to the rule of the family. Instead, two brothers called Al-Abbas and Al-Msaod, sons of Al-Karam, were summoned. The brothers were placed in power in 1083 and shared the governmental affairs between them. Al-Abbas resided in Ta'kar and took care of the trade with the interior, while Al-Msaod resided in the castle al-Khadra and handled shipping. About 100,000 dinars were paid in tribute each year to al-Mukarram.
Marriage & absorbing the Sulayhid dynasty
After taking control of coastal Southern Arabia (Taiz to Dhofar), King Muhammad bin Saba married the last Sulayhid Queen Arwa Al-Sughra & by effect inherited the remaining Sulayhid possessions, Zurayid control remained direct in Central, South Yemen & nominal in Northern Yemen until the dynasty was ended by the Ayyubid expansion.
Rule in Aden & Lahj
Al-Abbas died in 1084. His son Zuray, who gave the dynasty its name, proceeded to rule together with his uncle Al-Msaod. They took part in the Sulayhid leader al-Mufaddal's campaign against the Najahid capital Zabid and were both killed during the siege (1110). Their respective sons ceased to pay tribute to the Sulayhid queen Arwa al-Sulayhi. They were worsted by a Sulayhid expedition but queen Arwa agreed to reduce the tribute by half, to 50,000 dinars per year. The Zurayids again failed to pay and were once again forced to yield to the might of the Sulayhids, but this time the annual tribute from the incomes of Aden was reduced to 25,000. Later on they ceased to pay even that since Sulayhid power was on the wane. After 1110 the Zurayids thus led a more than 60 years long independent rule in the city, bolstered by the international trade. The chronicles mention luxury goods such as textiles, perfume and porcelain, coming from places like North Africa, Egypt, Iraq, Oman, Kirman and China. After the demise of queen Arwa al-Sulayhi in 1138, the Fatimids in Cairo kept a representation in Aden, adding further prestige to the Zurayids.
The two dynasties
The descendants of the brothers Al-Abbās and Al-Msaod lived in severe rivalry with each other. Due to that the constellations of power often shifted. The two lines met in open warfare in 1138. Ali bin Abi Al-Gharat bin Al-Msaod faction was defeated by his kinsman Saba bin Abi Saud and were pushed out of Aden; Ali will later be killed in the battle of Za'za' in Lahij in 1150, displacing them out of Lahij. The victor Saba's sons likewise had a falling-out. But the rivalries also motivated ambitions for expansion.
Zurayid Expansion
After the defeat of Al-Msaod branch, The Zurayid sphere of power stretched from Taiz to Dhofar. A decade later the ruler Muhammad bin Saba bought a number of important Sulayhid fortresses and towns & married the last Sulayhid Queen effectively inheriting all Sulayhid possessions. Among them were Dhū Jibla, al-Takar, Ibb and Ḥabb. Muhammad bin Saba died in 1153, and his son and successor Imran in 1166. Both were praised by their contemporary 'Umara as able and amicable rulers. Imran left three small sons. Affairs were henceforth taken care of by the wazir Yāsir bin Bilāl, son of a freedman, who was characterized as brave, virtuous and generous.
Mahdid & Ayyubid Sunni pressure
A new aggressive Sunni dynasty in Zabid, the Mahdids, besieged Aden in 1164. In the face of the acute threat, the Zurayids sought assistance from fellow Hamdanid sultan of San'a. Together the allies were able to utterly defeat the Mahdid ruler Abd an-Nabi in 1173. Immediately after these events, however, an Ayyubid expedition under prince Turan Shah was dispatched against southern Arabia. When the Ayyubids conquered Aden on 22 June 1174 the rule of the Zurayids ended. Yāsir bin Bilāl, who still attended the affairs of the state, fled the city but was betrayed and turned over to Turan Shah who executed him in 1175.
The End of the Zurayid Dynasty
During the first two decades of Ayyubid over-lordship Zurayid influence (remnants of Zurayid-Sulayhid dynasties) surfaced in the highlands enclaves, until it, too, was eventually suppressed in about 1193 with the surrender of the Damloa castle in Southwestern Yemen.
List of rulers
Al-Msaod line - Coastal possessions
Al-Msaod bin Al-Karam Al-Zurayi (1083-1110)
Abi Al-Gharat bin Al-Msaod (1110-?)
Muhammad bin Abi Al-Gharat bin Al-Msaod (?-?)
Ali bin Muhammad bin Abi Al-Gharat bin Al-Msaod (?-1150)
Al-Abbas line - Inland Possessions
Al-Abbas bin Al-Karam Al-Zurayi (1083-1084)
Zuray bin Al-Abbas (1084-1110)
Abi Saud bin Zuray (1110-?)
Saba bin Abi Saud bin Zuray (?-1138)
Ali Al-A'azz bin Saba (1138-1139)
Muhammad bin Saba (1139-1153) "expansion into Central Yemen"
Imran Muhammad bin Saba (1153-1166)
Muhammad bin Imran Muhammad bin Saba (1166-1174)
Abi Saud bin Imran Muhammad bin Saba (1166-1174)
See also
History of Yemen
Islamic history of Yemen
Ismailism
References
Literature
H.C. Kay, Yaman: Its early medieval history, London 1892, https://archive.org/stream/yamanitsearlymed00umar#page/n5/mode/2up
G. Rex Smith: "Politische Geschichte des islamischen Jemen bis zur ersten türkischen Invasion". In: Werner Daum: Jemen. Umschau-Verlag, Frankfurt am Main 1987, , pp. 136–154.
G. Rex Smith, The Ayyubids and early Rasulids in the Yemen, Vols. I-II, London: Gibb Memorial Trust 1974-1978.
Category:Islamic history of Yemen
Category:Shia dynasties
Category:Arab dynasties
Category:Banu Hamdan
Category:Vassal rulers of the Fatimid Caliphate |
Q:
How does one set the RAM and CPU parameters for java programs running in an anaconda environment?
In a standard Linux environment with java installed, I can run the any java program using the command:
java -jar path/to/picard.jar
Where picard is an example of a java program.
I can also specify how many CPU threads or RAM the JVM should use using this way:
java -XX:ParallelGCThreads=5 -Xms900m -jar path/to/program.jar
That JVM will get 5 threads and and 900 MB of RAM.
All quite straight forward.
However, when I run java programs in an anaconda (conda) environment, which has it's own installation of java, I can run the software simply by typing it:
picard
How do I pass the resource parameters to anaconda? What are the default parameters?
A:
My solution is to first, find where Conda installed Picard within your environment and then give a full path to picard.jar while passing memory arguments to java:
java -Xms4G -jar path_to/picard.jar [your_picard_command]
|
Messenger RNA expression of podocyte-associated molecules in the urinary sediment of patients with diabetic nephropathy.
Podocyte loss plays an important role in the pathogenesis of diabetic nephropathy. We hypothesize that messenger RNA expression of podocyte-associated molecules in urinary sediment may provide important clinical information in patients with diabetic nephropathy. We studied 21 patients with biopsy-proven diabetic nephropathy and 9 healthy controls. The mRNA expression of nephrin, podocin, synaptopodin, Wilms' tumor-1 (WT-1) and alpha-actinin-4 in urinary sediment were measured by real-time quantitative polymerase chain reaction. The degree of histological damage was quantified by morphometric analysis. Patients were then followed for an average of 25.63 +/- 10.76 months. The rate of glomerular filtration rate (GFR) decline was calculated by the least-square regression. There were significant differences in nephrin, podocin, synaptopodin, alpha-actinin-4 (p < 0.01 for all comparisons) and WT-1 (p = 0.028) expression between patients and normal controls. Urinary nephrin expression was significantly correlated with proteinuria (r = 0.502, p = 0.020); urinary synaptopodin was significantly correlated with proteinuria (r = 0.585, p = 0.005), serum creatinine (r = 0.516, p = 0.017) and estimated GFR (r = -0.560, p = 0.008), and urinary WT-1 expression was significantly correlated with the degree of tubulointerstitial fibrosis (r = 0.558, p = 0.009). There was no significant correlation between GFR decline and urinary expression of target genes. Urinary mRNA expressions of nephrin, podocin, synaptopodin, WT-1 and alpha-actinin-4 are higher in patients with diabetic nephropathy than in normal controls. Urinary nephrin and synaptopodin expressions are correlated with baseline clinical parameters such as proteinuria or renal function, while WT-1 expression is related to the degree of histological damage. Our results suggest that urinary mRNA expression of podocyte-associated molecules may be used for risk stratification of diabetic nephropathy. |
CLOT x NikeLab Air VaporMax Set to Restock
The CLOT x NikeLab VaporMax made its debut late-July 2017 to select European retailers and exclusively at a pop-up shop in Los Angeles, California.
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Good news for those still looking to cop a pair. Today, CLOT has announced on Instagram that they’ll be restocking the popular Red Nike Air VaporMax. Although they didn’t give much details on when/how they’ll be re-releasign the collab, but they did note that more info will be coming soon.
While its unlikely for these to appear on Nike.com, you can expect the restock to become available via Clot online and at their upcoming pop-up shop in LA. Stay tuned for more details. |
est to -2/3 in -17.09128, 5, 3, -2/9?
-2/9
What is the closest to 2 in -155/3, -5, 0?
0
What is the closest to -6/13 in 1/4, -7, 3/41, -2/11, -0.11, -0.71?
-0.71
Which is the nearest to 0.1? (a) 0.4 (b) 2/9 (c) -414 (d) -0.69
b
What is the nearest to 0.2 in 86, -0.02, -1/7, 0.1, -2/349?
0.1
What is the nearest to 0 in 0.3, 0.2, 0.0231, 14/75, 1/4?
0.0231
What is the closest to -3 in 1/8, -33, 5, 0.03?
0.03
What is the closest to -5.1 in 10, -2/25, 104?
-2/25
What is the closest to 159 in 2, 3/2, -0.4, 14906?
2
What is the closest to 2/5 in 2/7, -1/8, -2, 2/12683?
2/7
What is the closest to -0.1 in -4/7, 0.2, -4962, -0.05, -1?
-0.05
Which is the nearest to 1? (a) -1960 (b) 3/44 (c) 0.02
b
Which is the nearest to -1/4? (a) -27 (b) 5 (c) 0.418 (d) 1/74
d
What is the closest to 1 in -7, -1/3, -3/5, 1692619, -1?
-1/3
Which is the closest to -1? (a) 1/105 (b) -2/7 (c) -0.2 (d) 60354 (e) 5
b
Which is the closest to -3? (a) -4 (b) -453 (c) -5 (d) -6/11 (e) -0.25
a
What is the closest to 2/17 in 1/39615, -1/2, -3/5?
1/39615
Which is the nearest to -1337? (a) -4 (b) -2/11 (c) 33 (d) 2
a
What is the closest to 5183 in -34, -12, 2/17?
2/17
Which is the nearest to 0? (a) 4/3 (b) 0.75 (c) 0.5 (d) -3 (e) -1.63 (f) 2/21
f
What is the nearest to 2 in 6, -3/2, 0.244158, -7?
0.244158
Which is the closest to 11/5? (a) 1/3 (b) -0.3 (c) 1/6 (d) -0.1 (e) -5 (f) -290
a
Which is the nearest to -0.1? (a) 6288 (b) -16 (c) -0.03 (d) 1
c
What is the closest to -1/7 in -16, 0, 865?
0
Which is the nearest to -2? (a) -24 (b) 2/7 (c) -306555
b
Which is the nearest to -0.1? (a) 2/45 (b) -3 (c) 1 (d) 1622/281
a
What is the closest to -0.3 in -607.7, 6, 3/14?
3/14
What is the closest to 1/2 in 28, 2/755, -0.3?
2/755
What is the closest to -4250 in -4, 0.4, -3, 17, 9?
-4
What is the nearest to -0.2 in -2/21, 2/117, -1/2, 6, 47/5?
-2/21
Which is the closest to -2/27? (a) -0.07 (b) 13/3 (c) 49 (d) 237
a
What is the closest to 0.1 in -60, -673/6, 2?
2
What is the closest to -2/105 in 0.4, -14, 2112, -5, 0.22?
0.22
What is the nearest to -1.47 in -501/8, -1, -0.1, 0.4?
-1
Which is the nearest to 37? (a) -0.2 (b) 36143 (c) 0.55 (d) 0.2
c
Which is the closest to 0.1? (a) 0.209 (b) 141 (c) -2/11 (d) 5 (e) 0.27 (f) -3
a
Which is the nearest to 0? (a) 3/2 (b) 4 (c) 3766063
a
What is the nearest to 3 in -0.0402, -3, -232?
-0.0402
What is the closest to 0.3 in -0.079, 3, -0.1, 67?
-0.079
What is the closest to 0.1 in 21/5, -0.1, 0.05, -13.45?
0.05
Which is the nearest to -49? (a) -8 (b) 0.13 (c) -0.9 (d) 193 (e) 4
a
What is the closest to -1 in -6, 44, -1.45, -0.4?
-1.45
What is the nearest to 1 in -0.2, 3646, 4, -2/15, 2/11?
2/11
What is the closest to -0.04 in -0.1, 2/17, 132, 658/3, 6/11?
-0.1
Which is the nearest to 2503? (a) -0.24 (b) -4 (c) -1/2
a
What is the nearest to 30 in 3, 2/3, 5, 0.073, 2, -35?
5
What is the nearest to -0.2 in -2/7, -1629/733, 7?
-2/7
What is the closest to 0.01 in -0.0221, -5, -8/3, 3?
-0.0221
Which is the closest to -71/6? (a) -8 (b) -3/4 (c) -1/7 (d) -2/7
a
What is the nearest to 0.36 in -1/3, 7, 1/8520?
1/8520
Which is the nearest to -5? (a) -0.8 (b) -4 (c) -49/130 (d) -3 (e) -2/7 (f) 0.2
b
Which is the nearest to 62? (a) -2/5 (b) 65 (c) 0.09 (d) 2/13 (e) -400 (f) -0.5
b
What is the nearest to -6 in -1/4, 5, 0, -379, 413?
-1/4
What is the closest to 0.2 in 3, 1, 215, -3.7, -9?
1
What is the closest to 0.6 in 0, 3, 5, 541?
0
What is the nearest to -0.1 in 0.4, 172, 2, 0.1, 0.04?
0.04
Which is the closest to 20? (a) -1 (b) -1497/22 (c) 4 (d) -5
c
Which is the closest to -1/13? (a) -23 (b) -1/9 (c) 0.4 (d) -3/4 (e) 38
b
Which is the nearest to -27? (a) -4/3 (b) 159 (c) -4 (d) -0.18
c
Which is the nearest to -0.02? (a) -2 (b) -0.3 (c) -63 (d) 1/707 (e) 4 (f) 3
d
What is the closest to -4 in -1/3, 1596, -4, -16?
-4
Which is the nearest to 113? (a) -0.01 (b) -20 (c) -2/9 (d) -162
a
What is the nearest to 483 in -0.3, -4, 2, 2/17, -25/6?
2
Which is the closest to 10379? (a) -1 (b) -0.5 (c) -35.9
b
Which is the nearest to 1/3? (a) -38 (b) -0.4 (c) 2/15 (d) -19/5 (e) 1
c
Which is the closest to 4/7? (a) -0.2 (b) 0.2 (c) -538 (d) -7
b
What is the nearest to 835 in 3/7, -10, -55?
3/7
What is the nearest to 1 in 4, 2/3, 0.5247, 0.5, -1/10?
2/3
Which is the closest to -15839.6? (a) -2 (b) -0.9 (c) -3 (d) -0.1 (e) 2
c
Which is the closest to -0.033? (a) 2/15 (b) -4500 (c) 5 (d) -4 (e) -5
a
Which is the nearest to -1? (a) 4774.3 (b) -0.4 (c) -0.7
c
Which is the closest to 0? (a) 1/4 (b) 10 (c) 0 (d) -0.4061 (e) 4/5
c
Which is the closest to -3.66? (a) 2 (b) 4 (c) 341 (d) 1/9 (e) -3
e
Which is the nearest to -328? (a) -0.3 (b) -6 (c) -134
c
Which is the nearest to 21? (a) 0 (b) -5 (c) 438/49
c
What is the nearest to 8/5 in -0.4, -5, -0.3, 1277, 11?
-0.3
What is the closest to -0.6 in 0.23, -0.5, 344, 0.4?
-0.5
Which is the closest to -0.0246? (a) -1.9 (b) 2 (c) -1/5 (d) 15 (e) 0
e
Which is the nearest to 1? (a) -215 (b) 14 (c) -16.5 (d) 3/7
d
Which is the nearest to -48? (a) 10.26 (b) -0.029 (c) -1 (d) -5
d
What is the closest to -5 in 0.4, 507, 0.8, -1.3, 0?
-1.3
Which is the nearest to -1? (a) 11 (b) 1/4 (c) -1 (d) -285 (e) -0.61
c
What is the nearest to 837.9 in 12.2, -2, 3?
12.2
What is the closest to 1 in 6/7, -1017, 1.23?
6/7
Which is the closest to 1? (a) -10 (b) -2 (c) -8 (d) 1 (e) 0 (f) -13/3
d
What is the closest to 55 in 16, 0.1, -1/6, -51/2, 38/5?
16
What is the closest to -0.89 in 3, -21, 8, 1, -3/17?
-3/17
Which is the closest to -0.1? (a) -4/7 (b) -3/31 (c) 4/59 (d) -3 (e) -0.2
b
What is the closest to -0.05 in -3, 45608, -7, 2/7?
2/7
What is the nearest to 0.22 in 0.72, -2/575, -4/3, -0.1?
-2/575
What is the nearest to 3.4 in 1, 0.1, -1, 2/7, -0.05, -468?
1
What is the closest to 0 in 2, 135739, 4/7?
4/7
Which is the closest to -0.2? (a) -1 (b) 2/859 (c) 0.1 (d) 1 (e) 52
b
Which is the nearest to 1709? (a) -0.4 (b) -3/7 (c) 165/4
c
Which is the closest to -2? (a) 2.6 (b) -0.026 (c) 0.09 (d) -0.4 (e) 7/2
d
What is the closest to 16 in 220, -6/11, 140?
-6/11
Which is the closest to -2? (a) 1 (b) 3 (c) 0.13 (d) -1 (e) 2.8 (f) 0.4
d
Which is the closest to 42971? (a) -10 (b) 2 (c) 12
c
Which is the closest to 141396? (a) -0.04 (b) 1/6 (c) 1/2 (d) 1 (e) -0.24
d
What is the nearest to 23/11 in 0.46, 3/4, -3/2, 60?
3/4
Which is the nearest to -93? (a) 1 (b) 2/11 (c) 2.86
b
What is the closest to 3 in -2, -253, 2.5, -9, -1/109?
2.5
What is the closest to 0.1 in 0.025, 5, -344/3, -310/3, -1/7, 4?
0.025
Which is the nearest to 2/75? (a) -1572 (b) 0 (c) 2/17 (d) 1
b
What is the closest to -1735 in 42, -24, 5?
-24
Which is the nearest to 2/9? (a) -0.4 (b) -0.32 (c) 2 (d) 4 (e) -1/79 (f) 62
e
Which is the closest to -27? (a) -81 (b) 0.3 (c) 2 (d) -1/11
d
What is the closest to 4869 in -0.63, 0.4, 1, -1?
1
What is the closest to -6 in -14.3, -4, 718/3?
-4
Which is the closest to 3/2? (a) -746 (b) -0.04 (c) 3/2 (d) 2 (e) -1/4
c
Which is the nearest to 5? (a) -39.47 (b) -3 (c) -0.01
c
What is the nearest to 4.03 in 2/11, -112, -0.1?
2/11
What is the nearest to -3/40 in 1/7, 73, -3, -4, -0.2?
-0.2
What is the nearest to -0.0675 in 0, -1/2, -2/15, -0.13, -1/4, 0.4?
-0.13
What is the nearest to -2 in 5.5, 193, 3, -1/4, 0.0746?
-1/4
Which is the nearest to 1/4? (a) -4.9 (b) -3 (c) 0.2 (d) -1 (e) -5.03
c
What is the closest to -2 in -0.1, 2/13, 12895, -3310?
-0.1
What is the nearest to 0.3 in -0.13144, 0.3, -1/2, -0.3?
0.3
What is the closest to 0 in 1/30448, 8, -1/6, 9, 3/5, 1?
1/30448
What is the nearest to 26.062 in -3/7, 2/213, -3?
2/213
What is the nearest to -0.2 in 54, 49, -1/5, -3, 4/3?
-1/5
Which is the nearest to 0.3? (a) 1/11 (b) 13/15097 (c) 1/3 (d) 4
c
Which is the closest to -2/5? (a) -2.13 (b) -4 (c) 1 (d) 1.1
c
Which is the closest to -2? (a) -1736 (b) -258 (c) 2 (d) -4
d
What is the closest to -1/3 in 29780, -1/3, -1, 2, -55, 4?
-1/3
What is the closest to 1 in -124, -1/6, 5, 2, -1, 3.5?
2
What is the closest to 0 in 3/185, 1/42, 503?
3/185
Which is the closest to -62? (a) 1 (b) -5/4 (c) 4/11 (d) -3 (e) - |
In Australia an individual or corporation can be declared a vexatious litigant for repeatedly using the legal system solely to harrass or subdue an adversary. They are then (permanently) banned from pursuing any further civil court actions. |
Swimming at the 2008 Summer Olympics – Women's 200 metre breaststroke
The women's 200 metre breaststroke event at the 2008 Olympic Games took place on 13–15 August at the Beijing National Aquatics Center in Beijing, China.
U.S. swimmer Rebecca Soni pulled away over the final lap to capture gold and set a new world record of 2:20.22. Australia's world record holder and top favorite Leisel Jones enjoyed a strong lead in the first 100 metres, but ended up only with a silver in 2:22.05, almost two seconds behind Soni. Meanwhile, Sara Nordenstam earned Norway's second Olympic medal in swimming, as she powered home with a bronze in a European record of 2:23.02.
Austria's Mirna Jukić finished outside the medals in fourth place at 2:23.24, while Russia's Yuliya Yefimova set a national record of 2:23.76 to hold off Canada's Annamay Pierse (2:23.77) for a fifth spot by a hundredth of a second (0.01). Japanese duo Rie Kaneto (2:25.14) and Megumi Taneda (2:25.23) closed out the field.
Notable swimmers failed to reach the top 8 final, featuring Germany's Anne Poleska, bronze medalist in Athens four years earlier. Competing at her fourth Olympics, defending champion Amanda Beard placed eighteenth in 2:27.70, but missed the semifinals by 0.42 seconds.
Earlier in the prelims, Soni posted a top-seeded time of 2:22.17 to lead the heats, cutting off Beard's Olympic record by exactly two-tenths of a second (0.20).
Records
Prior to this competition, the existing world and Olympic records were as follows.
The following new world and Olympic records were set during this competition.
Results
Heats
Semifinals
Semifinal 1
Semifinal 2
Final
References
External links
Official Olympic Report
Women's breaststroke 200 metre
Category:2008 in women's swimming
Category:Women's events at the 2008 Summer Olympics |
That's a bad idea. Windows automatically detects the number of cores and can use 256 at once. If Windows doesn't use all 8 cores under load situations, that's a BIOS issue. Intel Core iX and Xeon 5500 CPUs disable cores to save power and turn them back on
when needed. This however requires BIOS and operating system support. Using the BIOS, power capping can be forced to do all kinds of funny things, though. Usually you'll find relevant options there.
You shouldn't change the kernel options from the defaults, that may have funny results. If for whatever reason those options were set, there should have been a reason for it, even if unchacked is the default.
That's a bad idea. Windows automatically detects the number of cores and can use 256 at once. If Windows doesn't use all 8 cores under load situations, that's a BIOS issue. Intel Core iX and Xeon 5500 CPUs disable cores to save power and turn them back on
when needed. This however requires BIOS and operating system support. Using the BIOS, power capping can be forced to do all kinds of funny things, though. Usually you'll find relevant options there.
You shouldn't change the kernel options from the defaults, that may have funny results. If for whatever reason those options were set, there should have been a reason for it, even if unchacked is the default.
Thanks for the tip Dovella, but that suggestion is for boot time only. I was wondering about normal execution after boot. And they were already unchecked from the beginning, I did not change that.
I would like to reiterate that I find all my cores work to full capacity when the CPU gets busy, so Windows is doing things right already. I was merely curious why Windows chose to keep some specific cores idle. For example, in Ubuntu under very light load,
I find that 2 cores are being used at any given time, and it cycles in a round-robin manner.
Thanks for the tip Dovella, but that suggestion is for boot time only. I was wondering about normal execution after boot. And they were already unchecked from the beginning, I did not change that.
I would like to reiterate that I find all my cores work to full capacity when the CPU gets busy, so Windows is doing things right already. I was merely curious why Windows chose to keep some specific cores idle. For example, in Ubuntu under very light load,
I find that 2 cores are being used at any given time, and it cycles in a round-robin manner.
Well... as mentioned before Windows might do core parking. This means that the cores are shut down and power is saved. In my opinion that's an ideal behaviour because why would you keep all cores powered up if you only need a subset of them because of not
much really going on?
Thanks for the tip Dovella, but that suggestion is for boot time only. I was wondering about normal execution after boot. And they were already unchecked from the beginning, I did not change that.
I would like to reiterate that I find all my cores work to full capacity when the CPU gets busy, so Windows is doing things right already. I was merely curious why Windows chose to keep some specific cores idle. For example, in Ubuntu under very light load,
I find that 2 cores are being used at any given time, and it cycles in a round-robin manner.
no, sorry, perhaps I expressed myself badly.This is a bug in Windows 7
FWIW. 64-bit is nothing but a pain to me. No silverlight on 64 IE for one. Had IE back button issues until just the other day a SP seemed to fix it . Drivers lag behind and not as tested as the more popular 32. Other strange print and pdf issues can pop up with apps like QB and more. I would just change back to win7 32 if it was not so much work at this point. I want to love it, but just do not see where it helps me in any way.
If you want to stress your system, throw video encoding at it. It is one of the few things that will pretty much always stress a system. I have a Core2Quad at home and a i7 at work, it is one of the few things that spikes my processor now a days.
@staceyw: really? I've been on x64 Win7 builds since it was in beta, I run x64 builds for most apps and stuff works great. I will say older hardware tends to not have x64 drivers however.
Only real driver issue I had was a driver from a USB wifi adapter that was pretty old. While I'm not thrilled when it effects me, I do understand when hardware makers do stuff like that. There is a cost for making and supporting. |
/*
* Copyright (C) 2014 Apple Inc. All rights reserved.
*
* Redistribution and use in source and binary forms, with or without
* modification, are permitted provided that the following conditions
* are met:
* 1. Redistributions of source code must retain the above copyright
* notice, this list of conditions and the following disclaimer.
* 2. Redistributions in binary form must reproduce the above copyright
* notice, this list of conditions and the following disclaimer in the
* documentation and/or other materials provided with the distribution.
*
* THIS SOFTWARE IS PROVIDED BY APPLE INC. AND ITS CONTRIBUTORS ``AS IS''
* AND ANY EXPRESS OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO,
* THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR
* PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL APPLE INC. OR ITS CONTRIBUTORS
* BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR
* CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF
* SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS
* INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN
* CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE)
* ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED OF
* THE POSSIBILITY OF SUCH DAMAGE.
*/
#ifndef CDMSession_h
#define CDMSession_h
#if ENABLE(ENCRYPTED_MEDIA_V2)
#include <runtime/Uint8Array.h>
#include <wtf/Forward.h>
#include <wtf/PassRefPtr.h>
#include <wtf/text/WTFString.h>
namespace WebCore {
class CDMSessionClient {
public:
virtual ~CDMSessionClient() { };
virtual void sendMessage(Uint8Array*, String destinationURL) = 0;
enum {
MediaKeyErrorUnknown = 1,
MediaKeyErrorClient,
MediaKeyErrorService,
MediaKeyErrorOutput,
MediaKeyErrorHardwareChange,
MediaKeyErrorDomain,
};
typedef unsigned short MediaKeyErrorCode;
virtual void sendError(MediaKeyErrorCode, uint32_t systemCode) = 0;
virtual String mediaKeysStorageDirectory() const = 0;
};
enum CDMSessionType {
CDMSessionTypeUnknown,
CDMSessionTypeClearKey,
CDMSessionTypeAVFoundationObjC,
CDMSessionTypeAVStreamSession,
CDMSessionTypeAVContentKeySession,
};
class CDMSession {
public:
CDMSession() { }
virtual ~CDMSession() { }
virtual CDMSessionType type() { return CDMSessionTypeUnknown; }
virtual void setClient(CDMSessionClient*) = 0;
virtual const String& sessionId() const = 0;
virtual RefPtr<Uint8Array> generateKeyRequest(const String& mimeType, Uint8Array* initData, String& destinationURL, unsigned short& errorCode, uint32_t& systemCode) = 0;
virtual void releaseKeys() = 0;
virtual bool update(Uint8Array*, RefPtr<Uint8Array>& nextMessage, unsigned short& errorCode, uint32_t& systemCode) = 0;
virtual RefPtr<ArrayBuffer> cachedKeyForKeyID(const String&) const { return nullptr; }
};
}
#endif // ENABLE(ENCRYPTED_MEDIA_V2)
#endif // CDMSession_h
|
Kristen Wiig is one of the brightest stars to ever emerge from Saturday Night Live. She’s uniquely versatile, unfailingly funny, and has been a dominant force in the comedy landscape for nearly a decade now. She also has broken incredible ground for women in comedy. The success of her 2011 film, Bridesmaids, blew through Hollywood’s comedy glass ceiling and paved a path for comediennes like Melissa McCarthy to become superstars in their own right.
That said, Wiig’s legacy at Saturday Night Live might be a little more complicated than it appears. Wiig’s gargantuan talent might have inadvertently pushed other performers down and made it nigh on impossible for Saturday Night Live to foster new female talent in the years she was there.
Saturday Night Live has always been a strange place for women in comedy. On one hand, the very first person cast for the show was the luminous Gilda Radner. Along with Jane Curtin and Larraine Newman, Radner helped establish a space for women on Saturday Night Live where they were on equal ground as their male counterparts. And considering they were working alongside such legends as Chevy Chase, Dan Aykroyd, John Belushi, and Bill Murray, that was no small feat. Over the years, though, women have also encountered some serious resistance on the show; Julia Louis-Dreyfus and Janeane Garofalo are just two of the female performers who had infamously difficult times at the show. When Tina Fey became the show’s first female head writer, she made it a point to work with the other women on the show in a supportive and collaborative manner, and since her tenure, it seems obvious that women do best on Saturday Night Live when they champion each other.
When Wiig joined the cast of Saturday Night Live in 2005, Tina Fey was still the head writer. Fey, along with Amy Poehler, Rachel Dratch, and Maya Rudolph, had worked to usher in a Golden Era for female performers on the variety show. Those four women were fond of working together in pairs and teams and making each other look great. Their comedy was often based on satire, interpersonal relationships, and shrewd social commentary.
As Dratch, Rudolph, Fey, and Poehler all left the show, Wiig became the most visible female cast member. In an interesting twist, though, at times it felt like she was the only female on the show. During this era, Lorne Michaels hired a slew of talented female comics—including Casey Wilson, Michaela Watkins, Nasim Pedrad, and Jenny Slate—but none of them ever seemed to totally gel with the cast. Or, more specifically, none of them gelled with Wiig.
Kristen Wiig liked to do character-based sketches on SNL wherein she would play someone with an outlandish character quirk — constant one-upmanship, an obsession with Target, a violent inability to keep a secret, having tiny hands, etc. — who would bulldoze through the scene and make almost every other character feel uncomfortable. These characters are usually either obsessed with being center stage or just naturally take the spotlight away from everyone else. It’s a very specific style of comedy that’s unabashedly Wiig, and that doesn’t require a huge amount of collaborative effort from the other players. Everyone else is there to play it more or less straight so that Wiig’s wackiness seems even more pronounced.
Now, it’s not Wiig’s responsibility as an artist to also be a mentor. It was never on her to pull Casey Wilson or Abby Elliott aside and say, “Hey, let’s write a sketch together.” However, it is fascinating to me that when she did collaborate on the show, it was often with the male performers like Fred Armisen (“Garth and Kat”), Jason Sudeikis (“Two A-Holes”), and Bill Hader.
It’s also noteworthy that she hasn’t really worked with either Fey or Poehler since they left Studio 8H. She’s got a cameo in Date Night, but that’s kind of it. She never guest-starred on 30 Rock or Parks and Recreation, and the only female SNL alumni in Bridesmaids are Rudolph (who was a Groundling with Wiig) and two women from earlier eras: Nancy Walls and Melanie Hutsell. Then again, perhaps there’s nothing gendered about Wiig’s choices. Maybe it all just comes down to who her friends are, and if so, it appears (to an outsider) that she was better at making friends with women from the Groundlings and the dudes on the show than she ever was with her female SNL castmates.
Since Wiig left Saturday Night Live, a new generation of female comedians has flourished on the show. Vanessa Bayer, Kate McKinnon, Cecily Strong, Aidy Bryant, Leslie Jones, and Sasheer Zamata routinely steal the show and spark the cultural conversation (arguably more so than any of their male castmember contemporaries), but you have to wonder if they would have thrived as well in Wiig’s shadow. As much as Kristen Wiig represents how well women can do in comedy, her own towering talents (and very singular style of sketch comedy) left little room for her female contemporaries to shine.
[Where to Stream Saturday Night Live]
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Mughal-e-Azam (musical)
Mughal-e-Azam () is a Broadway-style musical based on the 1960 Bollywood film of the same name, directed by K. Asif and produced by Shapoorji Pallonji. The musical was directed by Feroz Abbas Khan and produced by Shapoorji Pallonji Group.
Based on the love story between Mughal Prince Salim and courtesan Anarkali, Mughal-e-Azam portrays the conflict faced by Mughal Emperor Akbar: his responsibility towards the future of his empire and his duty as the father of a beloved son.
It was the first large-scale Indian Broadway-style musical, and was in production for ten months. The show was well received by critics in the media and entertainment industry. In 2017, it won seven out of the fourteen BroadwayWorld India Awards including Best Play, Best Director, and Best Costume Design.
Plot
In the era of the Mughals, Emperor Akbar's desire of a son is fulfilled when his wife, Jodhabai, gives birth to Salim, who grows up to be a spoiled brat filled with disrespect and self-indulgence. Consequently, he's sent off to war in Akbar's army and returns as a reformed person with perseverance and discipline fourteen years later. Salim, now a young man, falls in love with Anarkali, a lowly courtesan. Bahar, a dancer who covets the love of the Prince, is filled with jealousy upon discovering the secret affair and exposes it to Akbar. The emperor, full of royal pride, vehemently disapproves of the relationship and imprisons Anarkali, which leads Salim to declare an open rebellion against him. The war between father and son changes the lives of everyone in the empire threatening the foundations of the Mughal rule in India.
Background
The 1960 K. Asif film was inspired by a play called Anarkali, written in Lahore in 1922 by dramatist Imtiaz Ali Taj. Feroz Abbas Khan had wanted to recreate the film onstage since he saw the black-and-white film re-released in colour in 2004. In a 2017 interview, Khan said he hadn't wanted to do an imitation of Asif’s Mughal-e-Azam, but rather "pay a tribute to K. Asif sahab". For him, the play was “an interpretation; carrying the legacy forward in a different medium.” Prior to Mughal-e-Azam, Khan was known for minimalistic productions like Tumhari Amrita, and as a director, he wanted to do something entirely different. Inspired by Mughal-e-Azam, he approached Shapoorji Pallonji Group to get the stage rights. The current CEO and director of Shapoorji Pallonji Group, Deepesh Salgia, agreed on the condition that the play kept up the tradition of the film and provided creative consultancy for the production.
According to Salgia, after the colourisation of the original black-and-white movie, the company was looking for new ways to promote the film. The musical retained Naushad’s soundtrack and Shakeel Badayuni’s lyrics from the original film, along with two newly composed songs. The songs are sung live by the singers on stage to a pre-recorded orchestral and choral score. The play is in both the Urdu and Hindi languages, with LED screens displaying English subtitles of the dialogue.
Production
The technical team included Drama Desk Award-winning light designer David Lander; Emmy-nominated John Narun for projection design, who has previously worked on Madonna’s concerts and productions at Radio City Music Hall in New York; and production designer Neil Patel, a recipient of the Obie Award and Helen Hayes Award, who recreated the design of Emperor Akbar’s Sheesh Mahal (mirror hall) on set. Bollywood designer Manish Malhotra designed over 550 costumes and choreographer Mayuri Upadhya recreated the dance sequences from the film for the play.
Cast
Mughal-e-Azam recruited a cast and crew of over 350 people, including 30 classically trained Kathak dancers who had been living and training in Mumbai for three months. Since the lead actresses had to both sing and dance simultaneously, two actresses — Neha Sargam and Priyanka Barve — played the part of Anarkali alternatively. Theatre actors Nissar Khan, Syed Shahab Ali, and Dhanveer Singh played the parts of Akbar and Salim respectively. The part of Jodha Bai was played by Sonal Jha Rajesh jais & Tareeq Ahmed Khan played part of Sangtarash/Narrator,and Palvi Jaswal essayed the role of Suraiya. Durjan Singh was portrayed by Chirag Garg and Amit Pathak alternatively.
Reception
The premiere public shows of the musical were held at the Jamshed Bhabha Theatre. The musical had 57 shows in Mumbai, and one successful season in Delhi. The premiere of the musical in Delhi was attended by Union Finance Minister Arun Jaitley, Information and Broadcasting and Textiles Minister Smriti Irani, Nitin Gadkari, and Jyotiraditya Scindia. Bollywood actresses Rekha and Hema Malini, and directors Karan Johar, Ashutosh Gowariker, and Gurinder Chadha attended the last show of the musical at the Jamshed Bhabha Theatre in Mumbai.
In her review of the Broadway-style musical, Eshita Bhargava of the Indian Express called it “an audio-visual extravaganza that will be a joy to behold”. Rishi Kapoor, a Bollywood actor and the grandson of actor Prithviraj Kapoor who played the role of Mughal emperor Akbar in the original film, tweeted “I don't have enough of adjectives to describe it. This will play forever.” Karan Johar, Bollywood director and actor, tweeted “Mughal-e-Azam, the musical play, was a spectacular throwback to the legendary film; the team and director Feroz Khan have excelled themselves.” The Quint called it “Indian theatre’s coming of age”, “succeeding in giving the audience its own, new set of timeless memories”. In her theatre review of The Times of India, Purvaja Sawant stated “the live performances of 'Mughal-e-Azam's hit songs transport you back to a nostalgic era, one you don't want to come out of.”
Awards
Mughal-e-Azam: The Musical won seven trophies, including the Best Indian Play, at the Broadway World India Awards 2017.
References
Category:2016 musicals
Category:Indian musicals
Category:Musicals based on films |
Q:
How can create 80x86 emulator?
I've found an emulator for 80x86 created by using Java,
and I want know, how I can create an emulator 80x86 by Java?
where I can found tutorials and documentation?
etc ...
Thanks very much!
A:
It seems you're talking about JPC. You can download its source code; hopefully it will be well-documented and -commented. You could also try asking for documentation in its source forge support forums.
A:
The 8086 has a pretty complicated architecture. For your first forays into writing emulators, I'd suggest a much simpler 8-bit chip such as the 8090/8085 family. I once wrote an simulator for the 8080 in FORTRAN in about a week, complete with assembler, debugger etc.
The way an emulator works is pretty simple - you have an array representing memory, which you fill with the correct machine code or your program. You then walk through this memory interpreting the machine code at the simulated programming counter as you go, and adjusting the program counter according to the opcode being executed. To do this you will need the spec of the processor, and a reasonably good understanding of assembly/machine code, and the processor architecture.
|
Cape CBD crime rate drops by half
May 31 2001 at 09:40pm
By Ashley Smith
The crime rate in Cape Town's Central Business District was slashed by up to 46 percent in the first four months of this year since the implementation of a city improvement district in November last year.
This was announced by Michael Farr, chief executive officer of The Cape Town Partnership, who released the figures hours after Safety and Security Minister Steve Tshwete lifted the government's moratorium on crime statistics yesterday.
The Cape Town Partnership is a Section 21 company in which business and the Cape Town unicity are stakeholders. On November 1 last year it implemented a city improvement district in the central business district, dividing it into nine precincts or sectors.
Property owners in the area pay 9,5 percent more rates to top up existing municipal services like cleansing, security and marketing of the city.
The figures, compiled for the partnership by the city's Community Patrol Board, under which police reservists patrolling the streets fall, show crime on the Foreshore is down by 46 percent compared to the first three months of last year.
This reflects a significant drop in crimes like assault, shop-lifting, drunkenness, housebreaking, robbery and possession of stolen property.
According to Farr, so-called petty offences like gambling, riotous behaviour and drinking in public made up 95% of crime in the city centre and serious ones involving a threat to life, like robbery and assault, only 5%.
Unicity mayor Peter Marais said he was grateful for the reduction in crime levels.
"We will deliver on our promise to make Cape Town a living hell for criminals. We have started in the city centre, but we will take the fight to the suburbs and end by cornering them in the heart of Bishop Lavis and Manenberg," he said.
Marais said the unicity was in the process of training 500 community police officers to guard the city. There were also plans to spend R8 million on expanding the city's closed-circuit television camera system and - with the police, provincial government and the department of justice - to open eight new municipal courts for R8m more to enforce by-laws.
Farr said the statistics showed that the city centre had turned the corner in the fight against crime as a result of the cameras, more visible policing, mounted and foot patrols by community patrol officers and private security companies.
The city's closed-circuit cameras, monitored from a control room on the Foreshore, and supported by city improvement security officers, is seen as one of the principal reasons for crime levels declining.
The city improvement district employs 129 municipal and eight mounted patrol officers in the different precincts. Another 40 community police officers are provided by the unicity.
Farr said there were moves to extend the city improvement district to peripheral areas like Sea Point, Camps Bay, Oranjezicht and Higgovale.
He said statistics for the first three months of last year compared to this year in the nine precincts of the CBD were:
Sector one (bounded by the Heerengracht, Hans Strydom Ave, the Buitengracht and Table Bay Boulevard) showed a decrease of 46 percent.
Sector two (the Heerengracht, Table Bay Boulevard, Oswald Pirow and Old Marine Drive): down 15 percent.
Sector three (Adderley, Strand and Long streets and Hans Strydom Ave): up 8 percent. |
Primary and secondary liver malignancies are the most frequent cause of death in oncologic patients, the only potential curative treatment is surgical resection. In patients with colorectal liver metastases, only 10 to 30% are considered for a resection ([August *et al*, 1985](#bib1){ref-type="other"}; [Schlag *et al*, 1991](#bib21){ref-type="other"}); in patients with an isolated liver involvement, 20 to 40% ([Lorenz *et al*, 1997](#bib15){ref-type="other"}). If resection is not possible, then improved quality of life through maximal control of liver lesions must be the goal. Treatment options include systemic or regional chemotherapy, transarterial chemoembolization, percutaneous ethanol injections, laser-induced interstitial thermotherapy, cryotherapy and radio-frequency ablation.
As a palliative treatment with lower side effects regional chemotherapy seems to provide higher local drug concentrations, higher response rates, and less systemic toxicity compared to systemic application ([Collins, 1984](#bib5){ref-type="other"}; [Rougier *et al*, 1992](#bib20){ref-type="other"}; [Venook, 1997](#bib24){ref-type="other"}). Direct intratumoural percutaneous injections deliver even higher drug concentrations to selective sites, are minimally invasive, and effectively produce necrosis ([Curley *et al*, 1995](#bib6){ref-type="other"}). A novel injectable gel has been developed containing cisplatin as the chemotherapeutic and epinephrine as the vasoconstricting agent. This allows high drug concentrations to the treatment site and a slow dispersion to the surrounding tissues, thus reducing systemic exposure. In preclinical studies, conventional chemotherapeutic agents such as cisplatin, fluorouracil, or vinblastine administered intratumourally in the gel formulation enhanced drug retention and increased antitumoural efficacy ([Curley *et al*, 1995](#bib6){ref-type="other"}). Injectable gels have been used to treat various spontaneous tumours in veterinary patients and human malignancies such as basal and squamous cell carcinomas and accessible solid tumours of various histologic types ([Miller *et al*, 1997](#bib16){ref-type="other"}; [Burris *et al*, 1998](#bib2){ref-type="other"}). A recent french study showed development of therapy-induced necrosis after percutaneous intratumoural injections of mitoxantrone in primary and secondary liver malignancies ([Farrés *et al*, 1998](#bib8){ref-type="other"}).
MATERIALS AND METHODS
=====================
This study is part of a multicentre, open-label, phase II trial on the safety and efficacy of percutaneous intratumoural administration of Cisplatin/epinephrine (CDDP/epi) injectable gel in patients with hepatic metastases of colorectal cancer and patients with unresectable primary hepatocellular carcinoma. The investigational agent, CDDP/epi gel (IntraDose® Injectable Gel, Matrix Pharmaceutical, Inc., Fremont, CA, USA) is an injectable, biodegradable, viscous gel composed of cisplatin (CDDP, 4 mg ml^−1^); the vasoconstrictor, epinephrine (epi, 0.1 mg ml^−1^ to a maximum of 1 mg per injection); a protein carrier matrix (purified bovine collagen, 2 mg ml^−1^) as a gellant; and other inactive excipients as buffering and osmotic agents. The components are mixed within 2 h of use. The IntraDose® gel has a gelatinous consistency at room temperature and can flow through a 19.5-gauge needle for direct percutaneous injection in the liver tumour.
Patients
--------
Seventeen patients were included, nine patients with unresectable hepatocellular carcinoma (HCC) and eight patients with unresectable colorectal liver metastases (CRLM). Seventeen CRLM in eight patients were treated with an average of 5.1 injections per patient (range 1--8) and in nine patients with HCC 13 lesions were treated with an average of 3.1 injections (range 1--4). The number of injections depended on parameters such as tumour size and general condition of the patient. The average patient age was 67.1 years (range 39--79 years), 13 patients were male, four female. All patients had previously undergone other oncologic treatments before entering the study. One patient with HCC had prior chemoembolization for seperate lesion, all patients with colorectal metastases had received systemic chemotherapy with 5-Fluorouracil and folinic acid and three patients had undergone liver resection. All patients had either progressive or recurrent disease after previous treatment.
The study is open to adult patients with up to three intrahepatic biopsy proven tumours (HCC or metastases of colorectal carcinoma) with no extrahepatic spread, Karnofsky Performance Status should be 40 or more and the laboratory results have to be within ranges defined by protocol. Coronary artery disease, history of gastro-oesophageal varices, encephalopathy or bleeding from liver tumours as well as known hypersensitivity to one of the ingredients of the gel or radiographic contrast agents were exclusion criteria. Patients signed a written informed consent proven by the local ethics committee.
Study design
------------
Prior to treatment patients had a complete history, physical examination, laboratory studies and helical contrast-enhanced computed tomography (CT) scans. Treatment consisted of up to 4 weekly percutaneous intratumoural administrations of IntraDose® gel with up to 10 ml gel (=40 mg Cisplatin) at each treatment session. A second cycle of four treatments could follow the first at the discretion of the investigator. Contrast-enhanced helical CT scans were performed at 2 weeks, 2 months and 6 months after each treatment cycle. After 6 months patients were followed at 3 month intervals by visits or telephone calls.
Injection technique
-------------------
Before each treatment, patients are hydrated with intravenous infusions of 500--1000 ml of saline, 0.9% sodium chloride solution. After a plain CT scan the intrahepatic administration of IntraDose® gel was performed under local anaesthesia. To allow a safe lesion localization and homogeneous distribution of the gel throughout the whole tumour volume, several localizations of the needle tip are required in most cases. For this a computer-generated guidance system (CARE® Vision CT, Siemens, Erlangen, Germany) which made nearly online visualization possible was used (see [Figure 1](#fig1){ref-type="fig"}Figure 1Visualization of the injection procedure in a hepatic metastasis (open arrows) shown in segment 5 using the CARE vision CT programme. Note the needle placed centrally in the tumour (arrow). ) ([Froelich *et al*, 1997](#bib9){ref-type="other"}). A 19.5-gauge stainless steel puncture needle with six side holes at the tip to support the distribution of the gel was utilized (SOMATEX®, Berlin, Germany). Blood pressure and heart rate were monitored during the treatment procedure. Afterwards the patient had 6 h bed rest.
Imaging procedures
------------------
Hepatic lesions were evaluated via unenhanced and contrast-enhanced CT studies performed with a helical CT scanner (SOMATOM Plus 4®, Siemens AG, Erlangen, Germany). Continuous 5-mm-slice acquisition was used. After the unenhanced CT images were obtained, 120 ml of a non-ionic contrast agent (Ultravist 370®, Schering AG, Berlin, Germany) was administered. The contrast-enhanced helical CT scans were obtained in three phases with the indicated volume, flow, and time delay parameters: arterial phase (volume, 120 ml; flow, 2.5 ml s^−1^; time delay, 20 s); portal venous phase (120 ml, 2.5 ml s^−1^, 70 s); and venous equilibrium phase (120 ml, 2.5 ml s^−1^, 300 s). Image reconstruction parameters included 5-mm slice thickness; 7.5 mm per second feed/rotation, and 5 mm increment.
Quantitative analysis
---------------------
Quantitative analyses were performed using the region-of-interest (ROI) technique to determine viable tumour volume and volume of tumour necrosis in the CT scans. The tumour/necrosis areas were marked manually on each CT slice at the CT console, then the volumes were calculated using also the slice thickness. This is one of the most accurate means to determine volumes in CT. Tissues enhanced with contrast media were assumed to be viable and unenhanced tissue nonviable or necrotic. Tumour size, viable tumour volume, and tumour necrosis were assessed before treatment, 2 weeks, 2 and 6 months after treatment then at 3-month intervals.
RESULTS
=======
Pretherapeutic initial volumetric CT imaging revealed a mean tumour volume per patient of 91.3 ml in colorectal metastases (range 2--125 ml, median 107 ml) and 31.4 ml in HCC (range 1--113 ml, median 16 ml). Measurements of pretherapeutic tumour necrosis in the contrast enhanced studies resulted in a mean value of 13.9 ml for the group of metastases and in 0.4 ml for the group of HCC, the measurements of viable tumour resulted in 77.4 ml for the metastases and 29.2 ml for HCC. After intratumoural drug application quantitative CT evaluation revealed an increase of necrosis in contrast to the initial studies in all patients. Mean necrotic volume 2 weeks after the final treatment resulted in a decrease in viable tumour revealed to be 68.3 ml for metastases (tumour/necrosis volume: 176.4/108.1 ml) and 14.5 ml for HCC (tumour/necrosis volume: 41.8/27.3 ml). However viable tumour at Month 2 control showed a progression again especially for the CRLM to mean 103 ml (tumour/necrosis volume: 219/116 ml) and for the HCC to 21.6 ml (tumour/necrosis volume: 42/ 20.4 ml) (see [Figure 2](#fig2){ref-type="fig"}Figure 2Volumetric measurements of viable tumour volumes before treatment (screen) and 2 weeks and 2 months after last treatment. ). Statistical calculations using the Student *t*-test did show that the increase of necrosis after therapy for the HCC is statistically significant (*P*=0.001/0.003 after 2 weeks/2 months with a 95% confidence interval), the change of tumour volume is not significant (*P*=0.65). Although vital tumour in HCC decreased from 29.2 to 14.5 ml this change is not statistically significant (*P*=0.3). In the group of CRLM a significant increase in necrosis (*P*=0.001/0.002 after 2 week/2 months) but also in tumour volume (*P*=0.05) was found. Also as in HCC the decrease in vital tumour was not significant (*P*=0.44 after 2 months).
Evaluable for efficacy were seven patients with colorectal metastases and eight patients with HCC. One patient with colorectal metastasis withdrew from treatment after the first injection, in one patient with HCC and progressive liver cirrhosis treatment was discontinued after one injection due to worsening laboratory values.
The CT scans revealed a variety of tissue changes in the peripheral area of the tumour/necrosis. In colorectal metastases, the hypodense areas were larger in comparison to the initial tumour volume and showed an inhomogeneous contrast enhancement and poorly defined margins. The HCC nodules generally developed a more sharply defined necrosis and no contrast enhancement in the peripheral areas. If the follow up control scans did not show signs of remaining tumour activity, these changes were attributed to oedema and peritumoral reactions. In addition, remaining vessels with a relevant perfusion rate could be detected next to the treated region in the arterial phase of the CT scan.
The CT-Fluoroscopy supported an easy and safe performance of the injections. Complications due to intravascular or intrabiliary injections, significant bleeding or a pneumothorax were not observed. The modified treatment needle permitted adequate distribution of the gel within the tumour, although a better visualization of the gel would be desirable. Small tumours with a volume of a few ml could be reached without complications. For example, a HCC nodule of initially 3 ml showed complete necrosis after four injections without signs of tumour viability both in the 6 month follow-up CT scan and later studies. In the [Figures 3a--c](#fig3){ref-type="fig"}Figure 3(**a**) 69-year-old patient with histopathologically proven HCC in segment 5/8. Pretreatment CT scan on the left side, lesion identified with decreased attenuation values. CT scan 2 weeks after the fourth/last treatment with IntraDose® gel. Segment 5/8 reveals an irregular area of necrosis that developed after treatment (arrows). Both scans portal venous phase. (**b**) MRI scan (T2-weighted) 2 years after treatment, The lesion is still detectable but has not changed in size, the patient is in a good clinical condition. and [4a,b](#fig4){ref-type="fig"}Figure 4A 55-year-old patient with colorectal metastases to the liver. (**a**) Pretreatment CT scan in segment 8 (portal venous phase). (**b**) CT scan (portal venous phase) at 8 weeks after the pretreatment evaluation and 2 weeks after the fourth treatment. Increased tumour necrosis is evident after treatment. , examples of treated tumours are shown.
Clinical follow up
------------------
In the patients with liver metastases, CT-evaluation revealed local tumour control in only three patients with a total of four lesions (local tumour control rate 26%). In six patients (75%), new intrahepatic tumours were detected. Local tumour control was defined as complete inactivity of the treated lesions in the 3 and 6 month follow-up scans. Of the eight patients in the HCC group local tumour control rate was 70%. Three patients developed new HCC manifestations (43%). Two patients with worsening liver function and interrupted treatment were not included in the evaluation for local tumour control rate. At this time all eight patients with colorectal metastases and seven of the nine HCC patients died as a result of their disease. During the period for the determination of the control rates only one patient with HCC received another anti-tumour therapy (chemoembolization), no systemic chemotherapy was administered.
The survival rates were calculated with the Kaplan--Meier method. The overall cumulative survival for all 17 patients included was 13.15 months (median 10.17 months; mean 95% Confidence interval 9.25--17.06 months). The survival of the eight patients with CRM was 14.48 months of the nine patients with HCC, 14.11 months. This data can only show a tendency since the number of patients is very small.
Clinical effects: tolerance, side effects
-----------------------------------------
Overall the treatment procedure was well tolerated. During and immediately after injection the patients suffered from transient local pain (76%), an increase in blood pressure, and heart palpitations during injection (24%) and sweating or shoulder pain (each 30%). Nausea and vomiting were initially seen in 53%, but could be reduced with pretherapeutic infusion of cortisone (Merck, Darmstadt, Germany) and ondansetron (Glaxo Wellcome, Bad Oldesloe, Germany). Clinical signs of cisplatin-induced toxicity like nephrotoxicity, peripheral neurotoxicity or ototoxicity did not occur. Laboratory results were obtained before every treatment and evaluation and did not show major toxicity (for toxicity see [Table 1](#tbl1){ref-type="table"}Table 1Toxicity criteria (NCCOG/NCI) (North Central Cooperative Oncology Group/National Cancer Institute, 1991) ). Transient elevation of alkaline phosphatase, transaminases and a slight decrease in haemoglobin and lymphocytes could be detected in some patients but never with therapeutic consequences. One patient with hepatitis induced Child-Pugh B classified liver cirrhosis (total bilirubin initially 3.4 mg dl^−1^) died due to liver failure (increasing bilirubin results 10 days after the first treatment). Another patient with Child-Pugh B classified liver cirrhosis (total bilirubin initially 4.1 mg dl^−1^) showed increasing bilirubin values resulting in termination of treatment. Therefore a connection between the worsening liver function and treatment must be considered. The death was assessed as a serious adverse event.
DISCUSSION
==========
In order to increase the therapeutic index of the drugs, regional treatments for primary and secondary liver tumours are in use. Regional drug infusion parameters, like the hepatic extraction and the regional blood flow, are influencing the pharmacokinetic properties. The collagen matrix gel mixed with cisplatin and epinephrine alters both these factors. It maintains the cisplatin at high concentrations in the treated tumour and so induces an increased cellular extraction of the drug. Further, it reduces the blood flow in the region of the tumour by three factors: the vasoconstriction caused by the epinephrine which is added to the collagen and the cisplatin, the compression of the tumour vessels by the increasing intratumoural pressure following injection and by occlusion of tumour vessels by collagen matrix gel infiltrating into tumour vascular spaces ([Davidson *et al*, 1995](#bib7){ref-type="other"}).
Preclinical studies indicated that via the local application of the IntraDose® gel 20 to 30 times and higher intratumoural cytostatic concentrations can be achieved compared to systemic application.
The antitumourous effect is thought to be due to the combination of substances as epinephrine gel alone did show rapid tumour recurrence in veterinary trials, and addition of epinephrine to the Cisplatin gel showed an improvement of the effect.
Additionally pretherapeutical hydratation of the patient is expected to further reduce systemic toxicity ([Hayes *et al*, 1977](#bib11){ref-type="other"}). [Curley *et al* (1995)](#bib6){ref-type="other"} are reporting on the induction of a significant tumour necrosis and reduction in tumour volume in lesions as large as 12 cm in diameter in human liver malignancies. No cisplatin-related toxicity was reported, the treatments were well tolerated with a transient pain at the injection site and in the liver from stretching the liver capsule ([Curley *et al*, 1995](#bib6){ref-type="other"}). These published data are offering the basis for our *in vivo* studies.
The effects of percutaneous intratumoural administration of Intradose® gel have to be compared with systemic chemotherapy and other local treatments such as local ethanol instillation, chemoembolization and arterial chemo perfusion as well as to no treatment.
The comparative analysis of our data shows that CT-guided intratumoural injection of CDDP/epi gel has induced a statistic significant increase in necrosis in both groups. However, the local effectiveness based on the rate of local recurrences was higher in patients with HCC *vs* the patients with metastases, in HCC local tumour control was 70% and in CRLM only 26%. The response in CRLM is comparable with these after systemic chemotherapy which mainly remains below 30% ([Kemeny *et al*, 1993](#bib12){ref-type="other"}). For the HCC our results are comparable to these after chemoembolization or hepatic arterial infusion, a response of 30--60% after TACE ([Takayasu *et al*, 1989](#bib23){ref-type="other"}; [GTCH 1995](#bib10){ref-type="other"}; [Colella *et al*, 1998](#bib4){ref-type="other"}) and 40--50% after HAI ([Carr, 1996](#bib3){ref-type="other"}; [Patt *et al*, 1997](#bib18){ref-type="other"}) is reported. Here complications due to hepatobiliary toxicity may occur, especially in cirrhotic patients when the liver function is reduced ([Ravoet *et al*, 1993](#bib19){ref-type="other"}; [Kemeny, 1995](#bib13){ref-type="other"}). However complete necrosis of 80--90% can be reached with percutaneous ethanol injection in small HCC ([Livraghi *et al*, 1999](#bib14){ref-type="other"}).
An efficient and innovative treatment for malignant liver tumours -- metastases and HCC -- in patients with unresectable lesions is MR-guided laser-induced thermotherapy (LITT). This minimally invasive, locoregional technique results in a reliable local tumour control rate of more than 95% in lesions ⩽40 mm in diameter ([Vogl *et al*, 1998](#bib25){ref-type="other"}). Similar to LITT percutaneous radiofrequency (RF) ablation is another ablative method used to induce thermal coagulation of tumour tissue. Both are competitive methods to surgical resection and should not be responded to in detail in this work.
The different results in both groups might be due on the one hand to the different morphology and growth pattern in the HCC nodules. These tumours are regularly encapsulated and have a lower degree of peritumoural spread; thus, the intratumoural pressure after injection may be higher in HCC and may result in a more homogeneous distribution of the drug. On the other hand the group of patients with CRLM had a more palliative character reflected in the high number of patients that developed new intrahepatic metastases.
The survival data has to be judged carefully since the number of patients is relatively low in our study. But an advantage in survival can be seen to emerge in contrast to no treatment, in the CRLM mean survival with 14.6 months is higher than the 7.5 months reported by [Stangl *et al* (1994)](#bib22){ref-type="other"} in a large German study on patients with CRLM receiving no treatment. The survival in HCC is approximately similar than with only palliative treament ([Okuda *et al*, 1985](#bib17){ref-type="other"}).
Further trials are continuing to assess the influence of IntraDose® gel on increased survival of patients with non-resectable liver cancers. A second objective is to establish the optimum tumour size criteria for treatable lesions. Also randomized and combined trials with systemic chemotherapy or chemoembolization are planned.
Conclusion
----------
In summary, direct intratumoural injection of CDDP/epi injectable gel is a feasible and well tolerated method without major toxicity and results in the development of a relevant necrosis in malignant liver tumours. For HCC, a higher local therapy control rate compared to colorectal metastases was seen.
|
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Revive! has announced its first foray into the world of motorsport by sponsoring the Pirtek Racing team in the 2012 British Touring Car Championship (BTCC).
The cosmetic smart repair franchise will have its red and black branding on the car bumper.
Pirtek is racing one of only eight new generation touring cars (NGTC) on the circuit. It's brand new NGTC – spec Honda Civic with a Neal Brown engine, the same as the Honda Works team car, and will be driven by 24-year-old Andrew Jordan.
Hopes are high for Jordan who placed fifth during the recent BTCC media day. His debut BTCC season was in 2008 and he made BTCC history by being the youngest ever driver to qualify on pole position. Last year he had one race win, six podiums and four independent wins driving as an independent under the Pirtek banner.
Mark Llewellyn, Managing Director of Revive!, said: “We've worked hard to drive up the image of cosmetic smart repair within the automotive industry. Quality is the key word for us – we run a very professional network of highly skilled technicians and we wanted to link up with a team that shares our commitment to excellence and striving for the best results. We’re excited about Pirtek’s new generation touring car and are impressed by Andrew Jordan’s enthusiasm and ambition. It's a great opportunity for the Revive! branding to be seen throughout the 2012 season, and we wish Pirtek and Andrew every success.”
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derma e® Supports Vitamin Angels at Sprouts Farmers Market Stores
derma e®, the pioneer of vitamin-rich, high-performance antioxidant skincare products, announced today that it will continue its mission to improve the health of children in need worldwide by participating in Sprouts Farmers Market’s August Back to School Campaign in support of non-profit, Vitamin Angels.
SIMI VALLEY, Calif., (August 1, 2014) - (PressReleasePoint) -derma e®, the pioneer of vitamin-rich, high-performance antioxidant skincare products, announced today that it will continue its mission to improve the health of children in need worldwide by participating in Sprouts Farmers Market’s August Back to School Campaign in support of non-profit, Vitamin Angels. Sprouts is a healthy grocery store providing fresh, natural and organic foods and body care products at great prices.
In August, derma e® will donate 25 cents for every one of the following Hydrating products purchased: derma e® Hydrating Cleanser, Hydrating Mist, Hydrating Serum, Hydrating Day Crème, Hydrating Night Crème and Hydrating Eye Crème. All it takes is 25 cents for Vitamin Angels to give one child the lifesaving vitamins he or she needs for an entire year.
“It is an honor to participate in this event,” says Jennifer Norman Vice President of Marketing for derma e®. “By working with Vitamin Angels and Sprouts, both compassionate companies that share our passion for health and wellness, we are making a significant impact by helping others all over the world live healthier, more fulfilling lives.”
Nearly one third of the world’s children under the age of five are deficient in vitamin A, leaving them with compromised immune systems that are unable to fight off illnesses including measles and respiratory infections. In 2013, Vitamin Angels distributed vitamin A to 30 million children in about 45 countries. Just one dose of vitamin A twice a year, at a cost of 25 cents per child, can reduce the risk of early signs of blindness caused by vitamin A deficiency by 68% and child mortality rates by 24%.
ABOUT DERMA E® HYDRATING PRODUCTS
derma e® Hydrating line with Hyaluronic Acid deeply moisturizes and plumps skin to diminish the signs of visible aging such as fine lines and wrinkles. Rich in nature’s “moisture magnet” Hyaluronic Acid, plus vitamins and botanicals, these formulas help replenish hydration and vital nutrients for a healthy, youthful glow.
ABOUT DERMA E®
Family owned and operated for 30 years, derma e® has pioneered the development of vitamin-rich, high-performance antioxidant skincare solutions. The award-winning line features over 80 products that are free of parabens, phthalates, mineral oil and petrolatum. derma e® products are cruelty-free and 100 percent vegan. Manufacturing and operations are offset 100 percent by wind power. derma e® can be found in over 8,000 retail outlets across the U.S. with additional distribution in 25 countries internationally and on www.dermae.com. For more information, visit www.dermae.com, call (800) 933-9344, follow on Facebook at derma e® Natural Bodycare or Twitter @derma_e. |
Sen. Kamala Harris Kamala HarrisButtigieg stands in as Pence for Harris's debate practice First presidential debate to cover coronavirus, Supreme Court Harris joins women's voter mobilization event also featuring Pelosi, Gloria Steinem, Jane Fonda MORE (D-Calif.) is fundraising for her presidential campaign off former Rep. Beto O'Rourke Beto O'RourkeJimmy Carter says his son smoked pot with Willie Nelson on White House roof O'Rourke endorses Kennedy for Senate: 'A champion for the values we're most proud of' 2020 Democrats do convention Zoom call MORE's (D-Texas) announcement that he is also entering the 2020 race.
In a Thursday campaign email with the subject line "Beto O'Rourke," the California senator noted the "record number of Democrats" in the race and said she looks forward to debating her opponents, including O'Rourke.
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“We are facing something unprecedented: a record number of Democrats — including a record number of women and people of color — are running for President. This is greatly encouraging for the future of our country, but there is still a long path ahead of us," she said in the email.
“I look forward to engaging in substantive debates with each of these candidates, including the newest to join the race today, Beto O’Rourke — and ultimately selecting a Democratic nominee who will take on and beat Donald Trump Donald John TrumpOmar fires back at Trump over rally remarks: 'This is my country' Pelosi: Trump hurrying to fill SCOTUS seat so he can repeal ObamaCare Trump mocks Biden appearance, mask use ahead of first debate MORE in November of 2020," Harris added.
Harris said to run a winning campaign her team will "have to cut through the noise of this crowded primary and share our message with as many voters as possible."
"That’s why I am planning to spend as much time as possible out on the campaign trail, meeting with communities across the country, listening to the issues affecting them," she said.
Earlier Thursday, O'Rourke officially entered the 2020 Democratic primary race, saying in a video announcing his candidacy that "this is a defining moment of truth for this country and every single one of us."
He is entering a crowded field that, in addition to Harris, includes Sens. Bernie Sanders Bernie SandersButtigieg stands in as Pence for Harris's debate practice Bernie Sanders warns of 'nightmare scenario' if Trump refuses election results Harris joins women's voter mobilization event also featuring Pelosi, Gloria Steinem, Jane Fonda MORE (I-Vt.), Amy Klobuchar Amy KlobucharSocial media platforms put muscle into National Voter Registration Day Battle lines drawn on precedent in Supreme Court fight Sunday shows - Ruth Bader Ginsburg's death dominates MORE (D-Minn.), Cory Booker Cory Anthony BookerBipartisan praise pours in after Ginsburg's death DHS opens probe into allegations at Georgia ICE facility Democratic lawmakers call for an investigation into allegations of medical neglect at Georgia ICE facility MORE (D-N.J.), Elizabeth Warren Elizabeth WarrenHarris joins women's voter mobilization event also featuring Pelosi, Gloria Steinem, Jane Fonda Judd Gregg: The Kamala threat — the Californiaization of America GOP set to release controversial Biden report MORE (D-Mass.) and Kirsten Gillibrand Kirsten GillibrandSunday shows preview: Justice Ginsburg dies, sparking partisan battle over vacancy before election Suburban moms are going to decide the 2020 election Jon Stewart urges Congress to help veterans exposed to burn pits MORE (D-N.Y.).
Former Vice President Joe Biden Joe BidenOmar fires back at Trump over rally remarks: 'This is my country' Trump mocks Biden appearance, mask use ahead of first debate Trump attacks Omar for criticizing US: 'How did you do where you came from?' MORE is also expected to jump into the race. |
1. Field of the Invention
The present invention is related to a health consulting system; more specifically, the present invention is related to a knowledge-based personal intelligent health consulting system that guides a user to identify symptoms leading to possible diseases and provides relevant health information.
2. The Prior Arts
Nowadays, people often relied on Internet as the most instant, convenient, and reliable source of information when encountering health related problems. Although a vast amount of information can be obtained with ease, most health related information, whether regarding description of symptoms or diseases, is very profession-oriented. That is to say, for the general public, it is extremely mind-consuming and substantially difficult to obtain accurate and useful information due to lack of in-depth understanding of medical knowledge.
Certain healthcare advisory systems can be found on the internet, yet, for most conventional systems, information are presented in a subjective written manner. Since not all users are of medical related background and cannot provide precise description of their condition verbally, it is very unlikely for them to readily comprehend the information requested by those conventional systems and let alone fully utilize the information eventually received. Furthermore, those conventional systems usually inquire users' health related data via unilateral questionnaires. Without interactive and eliciting scenarios, this type of conventional systems cannot provide its users with intelligent, accurate, and appropriate healthcare consultation.
These setbacks of the conventional systems significantly reduce the users' willingness to seek personalized health consultation and, consequently, increase the risk of critical illnesses and the burden on healthcare resources. Thus, for the purposes of providing fast and accurate healthcare consultations and promoting awareness of personal healthcare, it is of urgent necessity for the development of an interactive, user-friendly, and knowledge-based system or method. |
PROVO — Just around 100 players took the practice field at BYU on Wednesday, although one of the most notable players there was dressed in plain clothes. Cougar junior receiver Neil Pau'u, who was charged with a DUI in the offseason, was there with his teammates throughout practice despite not participating in it or any fall practices to come.
BYU head coach Kalani Sitake clarified Pau'u's status to the media as part of his post-practice interview.
"I love him to death. He's on the team, he's on the roster, but he's not participating in fall camp because he's not going to play this fall," Sitake said. "He's going to redshirt and be a junior for us next year. But he's in school and he's on the team."
Pau’u pleaded not guilty to DUI, a class B misdemeanor, and not guilty to interference with a traffic control device, a class C misdemeanor, in Provo City Justice Court, according to court documents stemming from his June 8 arrest.
A 6-foot-4, 220-pound native of Santa Ana, California, Pau’u caught 18 passes for 216 yards and one touchdown last season as a sophomore. He started in three games for the Cougars and played in 13.
Pau'u was viewed as a likely heavy contributor out of spring practices, but his contribution will now wait until 2020 as he works through his legal troubles.
Neil Pau'u is the younger brother of former BYU linebacker Butch Pau'u and played for Servite High School in Anaheim, California prior to accepting an offer to play for the Cougars. |
Philippine Drug Enforcement Agency (PDEA) chief Director General Aaron Aquino was seen partying with the sacked second-highest official of the agency and a dismissed police officer linked to the P11-billion worth of “shabu” allegedly smuggled into the country.
In a photo released by the Senate Blue Ribbon Committee during a hearing on Thursday regarding the alleged shabu shipment, Aquino was seen at the birthday party of former Deputy Director General for Administration Ismael Fajardo. Dismissed Senior Supt. Eduardo Acierto, who is also being linked to the shipment, is also in the photo.
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Senator Richard Gordon, Blue Ribbon committee chairman, said the photo was taken on September 3. The magnetic lifters said to have contained the illegal drugs were found in a warehouse in GMA, Cavite on August 9.
READ: 1 ton of shabu worth P6.8B eludes PDEA, PNP
On September 27, Aquino announced in a hearing at the House of Representatives that he relieved Fajardo on September 15. He reportedly said that an investigation showed that Fajardo, Acierto and former Customs intelligence officer Jimmy Guban had knowledge of the shipment.
READ: PDEA exec fired over ‘knowledge’ on ‘smuggled’ P6.8B shabu – Aquino
But while the involvement of Acierto and Fajardo might have not been established yet before the holding of that party, Gordon said Aquino should have already put them under suspicion.
“I am not saying Aaron Aquino should [be involved]. He has to explain why he is pleasing with these people and why he is making all these statements while an investigation is going on na bumababa ang [price] ng drugs, bumabaha ang drugs,” Gordon told reporters.
“That’s very unfortunate eh, ‘yung mga pictures na ganyan, especially when there is a big investigation ongoing, or after a big, big drug bust has occurred,” he said.
Gordon, however, clarified he is not suspecting Aquino and just questioning his presence in the event. He said he would have confronted the PDEA chief if he was in the Senate hearing.
Aquino missed the hearing since he is in Dubai, United Arab Emirates to attend the 87th International Police Organization General Assembly. /jpv
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“The median household income in 2015 was $56,515, which the average healthcare CEO made in less than a day.”
(COMMONDREAMS) — While the Senate GOP’s plan to repeal the Affordable Care Act (ACA) has been denounced as potentially devastating to the poor, the sick, women, people of color, children, and those with pre-existing conditions, a new analysis published Monday finds that no matter what happens, the CEOs of large healthcare companies are likely to continue living lavishly.
Since the Affordable Care Act (ACA) passed in 2010, the “CEOs of 70 of the largest U.S. healthcare companies cumulatively have earned $9.8 billion,” according to a report by Axios‘s Bob Herman.
Herman goes on to add that the CEOs’ earnings “far outstrip[ped] the wage growth of nearly all Americans.”
“The richest year [for healthcare CEOs] was 2015, when 70 healthcare CEOs collectively made $2 billion,” Herman notes. “That was an average of about $28.5 million per CEO and a median of about $17.3 million per CEO. The median household income in 2015 was $56,515, which the average healthcare CEO made in less than a day.”
John Martin, former CEO of the pharma giant Gilead Sciences, topped Axios‘s list: he pulled in $863 million in the “ACA era.”
CEOs of 70 of the largest US health care companies have earned $9.8 billion in the seven years since ACA was passed https://t.co/1VBAavfiWZ pic.twitter.com/aeXbUmtW4j — Axios (@axios) July 24, 2017
Despite President Donald Trump’s repeated insistence that Obamacare has been a “nightmare” and that the entire system is collapsing, Herman observes, “The ACA has not hurt the healthcare industry. Stock prices have boomed, and CEOs took home nearly 11 percent more money on average every year since 2010.” And the Senate GOP’s alternative, which Trump has enthusiastically endorsed, would likely be a further boon to industry executives, who would stand to benefit from the bill’s massive tax cuts for the wealthy.
Axios‘s analysis focused on 70 of the largest publicly traded healthcare companies—including some of the largest insurance and pharmaceutical companies—in the United States.
Perhaps the most consequential component of healthcare CEO pay, Herman observes, is the fact that “a gigantic portion of what CEOs make comes in the form of vested stock, and those incentives drive their decision-making.”
This means that CEOs are incentivized not to take actions that would benefit the healthcare system overall, but rather to “inflate stock prices” using methods “such as repurchasing shares or issuing dividends to shareholders.”
Such moves lead to higher salaries for CEOs, but not to widely shared benefits.
“Stock-heavy pay,” Herman concludes, “drives CEOs to do the exact opposite of their buzzword-laden goals of creating a ‘patient-centered’ health system that focuses on ‘value.'”
Some commentators portrayed the analysis as both indicative of the fundamental injustice at the heart of the for-profit insurance model and proof of the need for Medicare for All.
The central healthcare initiative of the Dem Party is a policy that effectively subsidizes the pay of these execs https://t.co/briYBbU5EG — David Sirota (@davidsirota) July 24, 2017
But how could we possibly afford a Medicare for all system? https://t.co/jynH0yollk pic.twitter.com/rIY8mRSlAa — Billy Gendell (@billygendell) July 24, 2017
By Jake Johnson / Creative Commons / Common Dreams / Report a typo
This article was chosen for republication based on the interest of our readers. Anti-Media republishes stories from a number of other independent news sources. The views expressed in this article are the author’s own and do not reflect Anti-Media editorial policy. |
What is Soft Links and Hard Links in Linux File System
This short post explains what links are and the difference between symbolic (soft) and hard links. A link is a mechanism that allows several filenames to refer to a single file on disk. There are two kinds of links:1. hard links.
2. symbolic (soft) links.
Hard Links
– A hard link associates two (or more) filenames with an inode.
– Hard links all share the same disk data blocks while functioning as independent directory entries.
– Hard links may not span disk partitions, since inode numbers are only unique within a given device.
Symbolic Links
– A symbolic link is a special file type which points to another file.
– The contents of this special file is the name of the file that it points to.
– Symbolic links are created by the “ln -s“” command.
– Once a file which is pointed to by a symbolic link is deleted, the link still points to it, leaving a hanging link.
– You can use the find command to locate symbolic links:
# find ./* -type l -ls
Examples
1. Consider a file ‘example’ to which there is a hard link ‘hlink’ and a symbolic link ‘slink’. Check the contents of the directory for the file ‘example’: |
Hudák is second official candidate for head of Supreme Court
Supreme Court Justice and former state secretary of the Justice Ministry Daniel Hudák is another candidate for the top post at the Supreme Court (SC).
Supreme Court Justice and former state secretary of the Justice Ministry Daniel Hudák is another candidate for the top post at the Supreme Court (SC).
Hudák is the second candidate for this post, after Daniela Švecová. Hudák was proposed by justices of the SC, the office of the Judicial Council confirmed for the SITA newswire.
Daniela Švecová was the first candidate nominated to run for the post of Supreme Court’s chairperson, proposed by the Trnava Regional Court. Švecová was a vice-chair of the Supreme Court and currently is the chair of one of the panels of its civil-rights college.
The head of the SC will be elected on the very last possible day, September 16, and the location was recently changed from the municipality of Spišské Hanušovce in the east of Slovakia to the Slovak capital. The date was set by former head of the Judicial Council Štefan Harabin shortly before his term expired, while the location proposed by him, Spišské Hanušovce, was changed by the newly-elected vice-head of the Judicial Council Ján Vanko.
The previous attempt to elect a new SC head on May 19 was unsuccessful, as none of the three candidates – outgoing chair Štefan Harabin, Jana Bajánková and Zuzana Ďurišová – received enough votes. None of them can compete in this round, though if nobody is elected on September 16, they can run again in a third round of balloting. The Supreme Court is now temporarily led by its vice-chair Jarmila Urbancová.
On September 16, the SC head will be elected for the first time separately from the position of Judicial Council’s head, as on September 1, these two positions will be separated due to an amendment to the Constitution, SITA wrote.
(Source: SITA)Compiled by Zuzana Vilikovská from press reportsThe Slovak Spectator cannot vouch for the accuracy of the information presented in its Flash News postings.
THE THREE members of a military helicopter MI-17 crew were training winching up people into helicopter with the help of a rope not practicing landings, when they crashed on July 28 afternoon near Prešov.
Another police officer convicted for corruption was released by the appellate senate chaired by Štefan Harabin with the argument that the police inspectorate that investigated his case is unlawful. The former… |
/*
* Licensed to Elasticsearch under one or more contributor
* license agreements. See the NOTICE file distributed with
* this work for additional information regarding copyright
* ownership. Elasticsearch licenses this file to you under
* the Apache License, Version 2.0 (the "License"); you may
* not use this file except in compliance with the License.
* You may obtain a copy of the License at
*
* http://www.apache.org/licenses/LICENSE-2.0
*
* Unless required by applicable law or agreed to in writing,
* software distributed under the License is distributed on an
* "AS IS" BASIS, WITHOUT WARRANTIES OR CONDITIONS OF ANY
* KIND, either express or implied. See the License for the
* specific language governing permissions and limitations
* under the License.
*/
package org.elasticsearch.index.reindex;
import org.elasticsearch.action.get.GetResponse;
import org.elasticsearch.action.index.IndexRequestBuilder;
import org.elasticsearch.index.engine.VersionConflictEngineException;
import java.util.concurrent.TimeUnit;
import java.util.concurrent.atomic.AtomicBoolean;
import java.util.concurrent.atomic.AtomicReference;
import static org.apache.lucene.util.TestUtil.randomSimpleString;
import static org.elasticsearch.action.support.WriteRequest.RefreshPolicy.IMMEDIATE;
import static org.hamcrest.Matchers.either;
import static org.hamcrest.Matchers.equalTo;
/**
* Mutates a document while update-by-query-ing it and asserts that the mutation
* always sticks. Update-by-query should never revert documents.
*/
public class UpdateByQueryWhileModifyingTests extends ReindexTestCase {
private static final int MAX_MUTATIONS = 50;
private static final int MAX_ATTEMPTS = 50;
public void testUpdateWhileReindexing() throws Exception {
AtomicReference<String> value = new AtomicReference<>(randomSimpleString(random()));
indexRandom(true, client().prepareIndex("test", "test", "test").setSource("test", value.get()));
AtomicReference<Exception> failure = new AtomicReference<>();
AtomicBoolean keepUpdating = new AtomicBoolean(true);
Thread updater = new Thread(() -> {
while (keepUpdating.get()) {
try {
BulkByScrollResponse response = updateByQuery().source("test").refresh(true).abortOnVersionConflict(false).get();
assertThat(response, matcher().updated(either(equalTo(0L)).or(equalTo(1L)))
.versionConflicts(either(equalTo(0L)).or(equalTo(1L))));
} catch (Exception e) {
failure.set(e);
}
}
});
updater.start();
try {
for (int i = 0; i < MAX_MUTATIONS; i++) {
GetResponse get = client().prepareGet("test", "test", "test").get();
assertEquals(value.get(), get.getSource().get("test"));
value.set(randomSimpleString(random()));
IndexRequestBuilder index = client().prepareIndex("test", "test", "test").setSource("test", value.get())
.setRefreshPolicy(IMMEDIATE);
/*
* Update by query increments the version number so concurrent
* indexes might get version conflict exceptions so we just
* blindly retry.
*/
int attempts = 0;
while (true) {
attempts++;
try {
index.setVersion(get.getVersion()).get();
break;
} catch (VersionConflictEngineException e) {
if (attempts >= MAX_ATTEMPTS) {
throw new RuntimeException(
"Failed to index after [" + MAX_ATTEMPTS + "] attempts. Too many version conflicts!");
}
logger.info("Caught expected version conflict trying to perform mutation number [{}] with version [{}] "
+ "on attempt [{}]. Retrying.", i, get.getVersion(), attempts);
get = client().prepareGet("test", "test", "test").get();
}
}
}
} finally {
keepUpdating.set(false);
updater.join(TimeUnit.SECONDS.toMillis(10));
if (failure.get() != null) {
throw new RuntimeException(failure.get());
}
}
}
}
|
Effective Targeted Delivery of RNA-based Vaccines and Therapeutics: RNA-based vaccines and therapeutics have emerged as great promise for HIV prevention and treatment, respectively. However, many obstacles still need to be overcome, in particular RNA instability, manufacturing problems, and clinically relevant delivery mechanisms of RNA into target cells. The primary objective is to develop improved platform technologies for the delivery of RNA into specific cells and tissues to improve the efficacy of HIV vaccines or therapeutics. To enhance the efficacy of traditional HIV vaccines and therapeutics, combinations of cytokines, adjuvants, broadly neutralizing monoclonal antibodies, immune checkpoint inhibitors, etc. can also be co-delivered in mRNA form. |
Q:
Does the use of Tor makes additional encryption unnecessary?
I know Tor uses encryption to guarantee anonymity, but I if wish to guarantee the privacy of my conversations should I use an additional layer of encryption?
Can my home router or ISP intercept Tor packets and see its contents?
A:
Yes, additional security is necessary. No, your home router or ISP can't intercept the packets.
But then why is additional security still necessary?
If you decide to use Tor for being anonymous but still use personal information then your data will be safe from your PC till the last hop within the Tor network, but the endpoint can monitor your traffic if he wants to. Simply because he no longer has to send stuff over the Tor network, so your data will have been decrypted at that point such that it is no longer encrypted when sent again. That's why you should still use HTTPS instead of HTTP if you want your data to arrive securely at its final destination.
What if a ISP decides to fake responses to Tor traffic?
This is not possible as a public / private key encryption is being used, see the comment thread.
A:
When reading the Wikipedia article about Tor I found this
You see that the last link is unencrypted. So an additional layer of encryption seems to be necessary.
That's not the case when using TorChat because it uses end-to-end encryption
|
The World Health Organization has faced fierce backlash after telling people to replace butter and lard with 'healthier' oils in the New Year.
A leading cardiologist today said he was 'shocked and disturbed' by the advice, which the UN agency listed as a tip to prolong people's lives.
Butter has been demonised for decades over its saturated fat content – but an array of evidence is beginning to prove it can be healthy.
Dr Aseem Malhotra, an NHS consultant cardiologist, has now called on the WHO to review and update its guidance 'as a matter of urgency'.
Dr Aseem Malhotra is an avid supporter of saturated fats, which he thinks have been wrongly demonised since the 1970s
He told MailOnline: 'I'm frankly both shocked and disturbed that the WHO are giving incorrect and non-evidence based advice on fat.
'In my view, asking people to replace butter or lard with industrial seed oils such as corn, sunflower, soybean or safflower will continue to cause harm to public health.
'These oils, being particularly high in omega 6 fatty acids, are pro-inflammatory and can be toxic when heated for common frying purposes.'
Dr Malhotra pointed to studies which have linked heating up vegetable oils to a group of chemicals associated with cancer, heart disease and dementia.
Research in 2015 found heating the oils produces levels of aldehydes far higher than the WHO's own recommended safe levels.
But the organisation now suggests using these oils instead of butter or animal fat, which tests have shown produce fewer chemicals but are linked to heart disease.
Dr Malhotra added: 'Conversely, natural fats found in nutritious foods such as butter, full-fat yoghurt and cheese can be very much part of a healthy diet.
'I call on the WHO to review the evidence and update their guidance [on telling people to avoid butter and lard] as a matter of urgency.'
Dr Malhotra instead urged the WHO to focus on encouraging people to avoid consuming too much food that is ultra-processed.
The WHO published its 'Five tips for a healthy diet this New Year' last week. It is currently the first story featured on its homepage.
Butter has been demonised for decades over its saturated fat content - but an array of evidence is beginning to prove it can be healthy
THE ROW OVER SATURATED FATS Saturated fats have been demonised since the 1970s after a major study linked them to high levels of 'bad' cholesterol (LDL). Several trials have since added fuel to the fire, by bolstering the link between the fat - found in butter - and boosted cholesterol levels. The type of fat has also been linked to dementia, by blocking the blood flow to the brain, and cancer as it contains oestrogen which fuels tumour growth. But confusion over the safety of saturated fat has intensified in recent years, amid studies that have shown the fat can actually boost 'good' cholesterol levels (HDL). Advertisement
The article also tells people to eat a variety of food and cut back on salt, limit sugar intake and avoid drinking too much alcohol.
Under its tip on swapping out certain fats, it said: 'We all need some fat in our diet, but eating too much – especially the wrong kinds – increases risks of obesity, heart disease and stroke.
'Replace butter, lard and ghee with healthier oils such as soybean, canola (rapeseed), corn, safflower and sunflower.'
The WHO advice added: 'Whatever your New Year's Resolution, a healthy and balanced diet will provide many benefits into 2019 and beyond.
'What we eat and drink can affect… how likely we are to develop health problems later in life, including obesity, heart disease, diabetes and different types of cancer.
'The exact ingredients of a healthy diet will depend on different factors like how old and how active we are, as well as the kinds of foods available in the communities where we live.
'But across cultures, there are some common food tips for helping us lead healthier, longer lives.'
The WHO told MailOnline that its stance on telling people to replace butter would not change – despite the criticism.
Saturated fats have been demonised since the 1970s after a major study linked them to high levels of 'bad' cholesterol (LDL).
Several trials have since added fuel to the fire by bolstering the link between cholesterol levels and the type of fat which is found in butter.
The fat has also been linked to dementia, by blocking the blood flow to the brain, and cancer, as it contains oestrogen which fuels tumour growth.
But confusion over the safety of saturated fat has intensified in recent years, with studies showing it can actually boost 'good' cholesterol levels (HDL).
Dr Malhotra, who describes himself as one of Britain's most influential cardiologists on his own website, has a history of defending saturated fats.
He argues that cutting saturated fat from diets has led it to be replaced with sugar and carbohydrates, which are fueling obesity.
In a scathing video recorded for MailOnline in August, he slammed a Harvard professor who claimed coconut oil is poison as talking 'unscientific nonsense'.
The founder of campaign group Action on Sugar, Dr Malhotra alleged he was the victim of 'dirty tricks' by Public Health England back in September.
He co-authored a book last year, called The Pioppi Diet, which contradicts the healthy eating advice offered by the Government body.
Labour's deputy leader Tom Watson has credited the diet – which saw him add butter to his coffee – for helping him lose 7st (98lbs/44kg). |
This is the Debian GNU/Linux prepackaged version of util-linux.
This package was put together by Guy Maor <maor@debian.org> and later
maintained by Sean 'Shaleh' Perry <shaleh@debian.org>, and Adrian Bunk
<bunk@stusta.de>.
The current maintainer is LaMont Jones <lamont@debian.org>.
See also: git://git.debian.org/~lamont/util-linux.git
It was downloaded from:
ftp://ftp.us.kernel.org/pub/linux/utils/util-linux-ng/
Upstream maintainers include:
Maintainer: Karel Zak <kzak@redhat.com>
Past Maintainer: Adrian Bunk <bunk@fs.tum.de>
Past Maintainer: Andries Brouwer <aeb@cwi.nl>
See also /usr/share/doc/util-linux/AUTHORS
Copyright:
A variety of people and entities, as befits the nature of the package.
See the individual sources for exact copyright holder information.
License:
The project doesn't use same license for all code. There is code with:
* GPLv2+ (GNU General Public License version 2, or any later version)
* GPLv2 (GNU General Public License version 2)
* BSD with advertising
* Public Domain
Please, check source code for more details. A license is usually at the start
of each source file.
Anything lacking an explicit license may be redistributed under the terms
of the GNU GPL Version 2 or later found on Debian systems in the file
/usr/share/common-licenses/GPL
|
Taking a scientific approach to design, researchers from Harvard University and Massachusetts Institute of Technology are offering a new take on that debate. The same design elements that attract so much criticism, they report, can also make a visualization more memorable. |
Natural, non-toxic lip products that also perform beautifully? I’ve got the list! These all-natural lipsticks, lip stains, lip glosses, and lip tints are as good for you as they are gorgeous.
Fun fact: the average woman eats 4 pounds of lip product in her lifetime!
Yowza that’s a lot of lippies.
And guess what? Some actually estimate it to be closer to 7 pounds.
Now this is just a little teeny bit concerning given everything we know about the very loosely regulated American cosmetics industry. Need a reminder? Well it’s basically the Wild Wild West — companies are allowed to use all but 30 banned ingredients (in contrast, the EU has banned over 1200 ingredients) in our skincare and beauty products without first doing adequate testing to prove safety. And so a lot of unhealthy chemicals are used in products, and eventually applied to our skin, where they’re then absorbed into our bloodstream.
And with lip products, exposure is even more direct since we’re actually ingesting (i.e. eating!) them.
So of course, we better make sure our lipsticks, stains, glosses, and tints are all-natural and non-toxic!
As a lippie lover (there’s usually at least 4 in my purse at any given time) I’ve tried so many natural lipsticks, lip stains, and lip tints over the years — far too many to count!
Some have flopped while others are quickly became surefire favorites.
I promise you that when it comes to natural skincare and beauty products, you don’t have to sacrifice performance for safety! Each of my favorites performs like an absolute dream, providing gorgeous color and leaving lips soft and kissable… just without the unhealthy chemicals.
10 Gorgeous Non-Toxic Lip Picks: Natural Lipsticks, Stains, Glosses, and Tints
The Best Natural Lipsticks
My absolute favorite! So moisturizing and super silky. I have both Rose and Scarlet. Though “sheer” they are very pigmented and buildable, with a glossy finish. They can be worn alone for a bold look or layered with balm for subtle color. Plus they have a yummy vanilla scent.
A beautiful full-coverage lipstick option. These are more long-lasting than the Beautycounter lip sheers, with a thicker formula that stays put quite well. I have the Raspberry color and love it!
These lipsticks are made with a base of antioxidant-rich (hence the “anti-aging” part of their name) pomegranate oil — so luxurious! And because of this, they provide amazing moisture and don’t dry your lips out.
The Best Natural Lip Stains
These are really just the coolest ever — their “all-natural formula reacts and adjusts to your own chemistry for an irresistible shade that flatters your skin tone.” They look so light but then magically transform to a much deeper, more vibrant color once on the lips. They give a long-lasting stain with a glossy finish, and have a slight strawberry scent that’s really lovely. I have the Pink and Red colors and love them both.
THIS! I’m so in love. It on like a gloss but provides all-day color. It’s a vibrant deep pink color that I think would suit most skin tones. More so than the Jane Iredale lip stains, I am able to really define my lip shape with this stain. I apply one coat, let it sit for a few minutes, then wash what remains and either repeat the process for deeper color or apply a balm or sheer color on top for lighter coverage.
Gotta love a multi-purpose product! If you’re looking for a great option for lips and cheeks, this is it. Comes in a variety of beautiful shades (I have “Scandal”). It’s definitely more subtle and doesn’t last as long as the other two options, but a very different type of product.
The Best Natural Lip Glosses
I was never really into lip glosses very much (I tend to prefer a more matte finish) but this was like a gateway drug for me. A gateway lip gloss, if you will. A great option if you want a sheer, subtle pop of color with that high-gloss shine. I have the color “Fig” and adore it — it’s an especially great color for fall and winter.
If you’re looking for a lip gloss that packs a huge pop of color, this is it. In fact, I’m not really totally sure if it’s a highly pigmented gloss or a glossy lipstick… either way, it’s the perfect marriage between the two! Also, it smells and tastes delicious — yes, like caramel!
The Best Natural Lip Tints
These are not full-coverage lipsticks, but vibrant tinted balms. The Cherry ColorBalm is one of my must-haves for everyday wear. It’s a beautiful color perfect for work and play.
Another everyday favorite of mine. Don’t let the word “tint” fool you — these are very pigmented! I layer them with balm for subtle color, but applied alone they give a bold color and stain-like effect. The Cranberry color is a super vibrant red while Sugar Plum is a more natural mauvey red.
Do you have a favorite non-toxic lip pick that isn’t on my list?
Please share with us in the comments! |
Q:
Get an item from Datagrid.Items collection in wpf c#
I have a datagrid with some items in it and I need to get them to convert to DataRowView but can't seem to find a way to get each item individually out of the collection.
My code:
for (int i = 0; i < DataGrid1.Items.Count; i++)
{
var test = DataGrid1.Items[i];
DataRowView row = (DataRowView)test;
}
I would imagine DataGrid1.Items[i] would get me the item itself but only gets System.Windows.Controls.SelectedItemCollection
Or am I missing something?
A:
Apparently the problem was with how I was adding items into the DataGrid. I was adding them from another DataGrid and since I was using
DataGrid1.Items.Add(Datagrid.SelectedItems);
All the items in the DataGrid where ItemCollections themselfs that's why selecting an Item from that DataGrid would return an ItemCollection.
The DataGrid looks the same no matter if the items added are actual items or item collections.
So changing how I add items to
DataGrid1.Items.Add(Datagrid.SelectedItems[0]);
Added items themselfs and not collections to the seconds DataGrid and that way they can be accessed with the code I used in the question.
I'll leave this here in case somebody runs into a similar kind of a problem.
|
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Randall Delgado Has Some Fun on The Twitter and Other Bullets
If you came to the Bullets to escape the Ryan Dempster Saga (I’ve been wanting to call it the Ryan Dempster Hostage Crisis, but (1) that doesn’t seem quite fair or accurate, and (2) it seems kind of insensitive to, like, actual hostage situations, which are quite bad), I must apologize to you for what follows …
I’ve had Randall Delgado’s Twitter feed open in a tab for three days now, because I’m a huge loser (in case you’ve been in a bunker, Delgado is the 22-year-old Braves pitcher for whom the Cubs had an agreement to trade Ryan Dempster). There wasn’t much to see, until … OMG! Last night Randall Delgado tweeted “Abt go to Chicago.” Dempster accepted the deal! It’s going to happen! Hooray! Er, well, not sure about that. In the same tweet, Delgado – for whom English is a second language, so be kind – he said “Nothing happened.” In the immediately previous tweet, he said “in the way to my home.” He followed the Chicago tweet with “i’m still in Atlanta,” and “They don’t did a trade.” So, is there anything there? Probably not. But I’ll concede this – I can’t think of a reason Delgado would be headed to Chicago for reasons unrelated to the Cubs. He’s currently on the Braves’ AAA roster in Gwinnett, and they don’t play anywhere near Illinois. The Braves have an off-day today, and then host the Phillies in Atlanta. Given the off-day, I’ll allow the reasonable speculation that a reason for Delgado to go to Chicago would be for a physical. That’s not unreasonable of you. And maybe Delgado quickly realized that his “nothing happened” admonition didn’t make sense to folks when he said he was going to Chicago, so he said there was no trade. It’s possible. But it’s also possible that string of tweets has nothing to do with anything, or is Delgado screwing with folks in his second language. In sum: I really wouldn’t put too much into this. (UPDATE: Indeed, check out BN’er Omar’s comment below, which is a pretty darn good interpretation. Like I said: I really don’t think there’s anything here.)
Ryan Dempster, on his dugout “tantrum” (seriously, he shoved a cooler and threw a Gatorade bottle – it was so not a big deal), which he conceded was in response to being pulled from the game before he felt he should have been (though he later added that he was also upset that he gave up the lead): “No, I’m OK – I’m fine. I’m allowed to be upset. I respect [Sveum] a lot. It’s his decision. That doesn’t mean I have to be happy about it. At the end of the day, he has to do what’s best for the ballclub, and I have nothing but respect for that. I’m just a competitor and want to stay out there and pitch.”
Remember when Dale Sveum made Alfonso Soriano drop his bat size a bit, and then Soriano went off on a tear? Well, Sveum isn’t willing to claim the credit. “He only went down half an ounce,” Sveum said. “I haven’t talked to him about it. He might have gone back up, for all I know. All I know is since that day, he’s been one of the more productive players in all of Major League Baseball.”
A site note: Since time immemorial (ok, since last year), and time there is very big news in the Cubs world, the volume of comments here increases exponentially. Most new commenters are genuine Cubs fans, who just want to share their thoughts about the team they love. Most comments are totally fine, even if there is … an adjustment period to feeling out what the community here is like. Some folks, however, just want to be raging jerks. This is not a problem unique to BN, or heck, to the Internet. It’s an unfortunate part of life. I encourage you to ignore those folks, because they’ll be gone soon, one way or another. When you really sit back and look, they are an extraordinarily small percentage of the participants around here. And, as for you regulars, just know that your participation in – and efforts to preserve – this community are not unnoticed by me. You’re good people, and thoughtful Cubs fans. I appreciate it, and, more importantly, I enjoy being a part of it.
Disclaimer
In addition to news, Bleacher Nation publishes both rumor and opinion, as well as information reported by other sources. Information on Bleacher Nation may contain errors or inaccuracies, though we try to avoid them. Links to content and the quotation of material from other news sources are not the responsibility of Bleacher Nation. Photos used are the property of Bleacher Nation, are used under a license with Getty Images, are used with permission, are fair use, or are believed to be in the public domain. Legitimate requests to remove copyrighted photos not in the public domain will be honored promptly. Comments by third parties are neither sponsored or endorsed by Bleacher Nation.
Bleacher Nation Privacy Policy and Terms of Use. Bleacher Nation is a private media site, and it is not affiliated in any way with Major League Baseball or the Chicago Cubs. Neither MLB nor the Chicago Cubs have endorsed, supported, directed, or participated in the creation of the content at this site, or in the creation of the site itself. It's just a media site that happens to cover MLB and the Chicago Cubs.
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# Colors (Horizon Dark)
colors:
# Primary colors
primary:
background: '0x1c1e26'
foreground: '0xe0e0e0'
# Normal colors
normal:
black: '0x16161c'
red: '0xe95678'
green: '0x29d398'
yellow: '0xfab795'
blue: '0x26bbd9'
magenta: '0xee64ac'
cyan: '0x59e1e3'
white: '0xd5d8da'
# Bright colors
bright:
black: '0x5b5858'
red: '0xec6a88'
green: '0x3fdaa4'
yellow: '0xfbc3a7'
blue: '0x3fc4de'
magenta: '0xf075b5'
cyan: '0x6be4e6'
white: '0xd5d8da'
|
1. Technical Field
The present disclosure relates to an all-in-one computer audio system.
2. Description of Related Art
With the development of all-in-one computers, uses of the all-in-one computer is increasing. One use of the all-in-one computer is as an independent display for other equipment. When a conventional all-in-one computer is only used as a display, there is no independent audio circuit in the conventional all-in-one computer to response to the equipment, thus, the conventional all-in-one computer can not function as a display with audio function. |
Evaluation of the use of self-reported facial flushing and ethanol patch test for ALDH2 genotypes.
It is generally assumed that subjects with ALDH2*1/1 do not exhibit flushing symptoms after alcohol intake, but recent studies have revealed discordance in ALDH2 genotypes with self-reported facial flushing and the ethanol patch test. We evaluated the reliability of a facial flushing questionnaire and the ethanol patch test in 495 Japanese volunteers. Genomic DNA was extracted from peripheral blood samples and amplified by polymerase chain reaction (PCR) to detect ALDH2 polymorphisms as reported previously. The subjects were classified by the presence or absence of facial flushing using a questionnaire. Ethanol patch tests were performed using the previously described method. Each subject's alcohol consumption was established through a questionnaire. In each gender, there was a high frequency of facial flushing and positive ethanol patch tests in ALDH2*1/1 subjects. Alcohol consumption was not significantly different between ALDH2*1/1 subjects with positive and negative results. However, alcohol consumption in the positive ALDH2*1/1 group was significantly higher than that of ALDH2*1/2 subjects in both tests, indicating that the positive results may lead to variance with ALDH2*1/1. Most of the ALDH2*1/2 subjects exhibited facial flushing and a positive patch test. Meanwhile, 100% in the ALDH2*2/2 group exhibited positive results. There was no significant gender difference in either facial flushing or ethanol patch test reactions. In addition, the frequency of both male and female ALDH2*1/1 subjects with positive flushing and ethanol patch test reactions increased roughly in proportion to drinking frequency, but no significant differences were observed between them. Consequently, the general use of self-reported facial flushing or ethanol patch tests instead of ALDH2 genotyping should be carefully handled for genetic association studies of drinking behavior and alcohol-related diseases. |
Renal T-cell lymphoma with cerebral metastasis in a dog with chronic canine ehrlichiosis.
A renal T-cell lymphoma with exclusive cerebral metastasis was diagnosed in a 5-year-old Staffordshire bull terrier bitch euthanased for aggression. This is the first recorded case of primary renal lymphoma in a dog. Immune suppression, due to chronic canine monocytic ehrlichiosis, may account for the unusual primary site and metastatic pattern of the tumour. |
/**
* Copyright (c) 2017-present, Facebook, Inc.
* All rights reserved.
*
* This source code is licensed under the BSD-style license found in the
* LICENSE file in the root directory of this source tree. An additional grant
* of patent rights can be found in the PATENTS file in the same directory.
*/
const path = require("path");
const cluster = require("cluster");
const os = require("os");
const chalk = require("chalk");
const sqlite3 = require("sqlite3");
const db = new sqlite3.Database(path.resolve(__dirname, "..", "overnight.sqlite"));
if (cluster.isMaster) {
console.log(`Master ${chalk.cyan(process.pid)} started`);
db.run(
`create table fuzz_error (
seed text,
code text,
expected_error bool,
expected text,
actual_error bool,
actual text
)`,
error => {
if (error) throw error;
db.close();
masterMain();
}
);
function masterMain() {
const aliveWorkers = new Map();
// Fork workers.
const cpus = os.cpus().length;
for (let i = 0; i < cpus; i++) {
forkWorker();
}
// Restart workers when they die.
cluster.on("exit", (worker, code, signal) => {
const pid = chalk.cyan(worker.process.pid);
const error = chalk.red(signal || code);
console.log(`Worker ${pid} died (${error}). Restarting...`);
forkWorker();
});
// Creates a new worker
function forkWorker() {
const worker = cluster.fork();
markWorkerAlive(worker);
worker.on("message", message => {
if (worker.isDead()) return;
if (message === "ping") markWorkerAlive(worker);
});
}
// Marks a worker as alive. We kill workers after 10 minutes of inactivity
// since the worker might be stuck in an infinite loop. Or might be trying
// to shrink a really large test case.
function markWorkerAlive(worker) {
// Clear the old timeout
if (aliveWorkers.has(worker)) {
clearTimeout(aliveWorkers.get(worker));
}
// Create a new timeout
const timeoutId = setTimeout(() => {
const pid = chalk.cyan(worker.process.pid);
console.log(`Haven’t heard from worker ${pid} in 10 minutes. Killing...`);
// Hard kill since we suspect the process is in an infinite loop so the
// process can’t receive an IPC message.
process.kill(worker.process.pid, "SIGKILL");
aliveWorkers.delete(worker);
}, 1000 * 60 * 10);
aliveWorkers.set(worker, timeoutId);
}
}
} else {
console.log(`Worker ${chalk.cyan(process.pid)} started`);
// Make the reporter a noop.
require("./report").reportTestFinish = () => {};
const { check } = require("testcheck");
const { executeNormal, executePrepack } = require("./execute");
const { prepackWorks } = require("./property");
const insert = db.prepare(`insert into fuzz_error values (?, ?, ?, ?, ?, ?)`);
loop();
function loop() {
process.send("ping");
const test = check(prepackWorks, { numTests: Infinity, maxSize: 200 });
process.send("ping");
console.log(`Worker ${chalk.cyan(process.pid)} found a failing test case`);
// Add all the failing test cases to the database.
test.shrunk.smallest.forEach((code, i) => {
const expected = executeNormal(code);
const actual = executePrepack(code);
insert.run(
test.seed.toString(),
code,
expected.error,
expected.error ? expected.value.stack : JSON.stringify(expected.value),
actual.error,
actual.error ? actual.value.stack : JSON.stringify(actual.value),
error => {
if (error) throw error;
loop();
}
);
});
}
}
|
Q:
Outlier detection using recursive curve fitting and error elimination
Is there any way to do anomaly detection in dataset using recursive curve fitting and removing points having the most mean square error with respect to the curve, upto an acceptable threshold?
I am using the scipy.optimize.curve_fit function for python 2.7, and I need to work with python preferably.
A:
You are most probably speaking about recursive regression (which is quite easy in Matlab). For python, try and use the scipy.optimize.curve_fit.
For a simple 3 degree polynomial fit, this would work based on numpy.polyfit and poly1d.
import numpy as np
import matplotlib.pyplot as plt
points = np.array([(1, 1), (2, 4), (3, 1), (9, 3)])
# get x and y vectors
x = points[:,0]
y = points[:,1]
# calculate polynomial
z = np.polyfit(x, y, 3)
f = np.poly1d(z)
# calculate new x's and y's
x_new = np.linspace(x[0], x[-1], 50)
y_new = f(x_new)
plt.plot(x,y,'o', x_new, y_new)
plt.xlim([x[0]-1, x[-1] + 1 ])
plt.show()
|
Just an up-date from Zero Hedge. add to that the suicide rate of farmers is double that of veterans, and the average age of a farmer is 63. My opinion, when the farms go down – the guns will come up. As I said, with food we can solve virtually any problem, without – none. No food = No United States. Cut the supply chain and no enemy can survive. The Just in Time Delivery system is simple to collapse. There is only 1 solution, and that one is being ignored.
Solution & Analysis of Soviet Situation Below the Fold.
The solution is
To create a critical mass of small sustainable farms throughout the country, thus removing the dependability on Just in Time Delivery and rebuilding Americas regional Food Sheds. This creates a minimum amount of food produced to sustain life within 30 miles of regional populations centers. 80-20 Rule. 20% is produced locally.
To create the Sustainable Farms requires a Change of Paradigm in investment physiology for Americans.
I can only think of 2 ways,
1) get the billionaires involved (for a few reasons)
2) change the tax law. That should be possible with an Executive Order and in 1 day. Which means both you and I are trying to influence Trump. The US already has a structure to do this – just look at the Corn Ethanol structure. Billions from the private sector went into this field of production. Yes it is a disaster from the energy side. But the investors are making a profit because of tax structure put in by Bush Sr.
If we change the tax structure so an investment in a Sustainable Farm yields a competitive ROI for the Investors by tax write offs, then we will see a huge amount invested by the private sector throughout the country. Simply define what qualifies as “Sustainable Farm” to qualify for the tax write-off.
We can design the Sustainable Farm so it can withstand an EMP and grid down event (and other major Threats) and continues to produce food when the country is in crisis. Simple to do, and I have done the design. We have the technology, so it is simply getting the money to invest.
So we create a National Sustainable Food Grid using the tax system.
One more point. It is obvious the US Dollar has to be devalued at some point. If we can get the tax law changed first, then we get investors to exchange strong Dollars for Sustainable Food Production Equipment & Facilities while the dollar is still strong. When the dollar revalues, the tax write offs become moot – but we have created a food production safety net.
If we have food and sustainable food production, we can withstand an EMP, a Financial Collapse, a Pandemic, a Cyber Attack, ect. as our regional centers are protected.
With Food we can solve virtually all problems. So let us create the structure to guarantee food production.
Also needed are removal of administrative barriers by the FDA, EPA, BLM, IRS, ect. (Bush’s henchmen)
All of this takes time and we do not have it. It looks like we have 3 to 4 years before something happens.
Create the Short Term Solution, then create the Long Term solution.
The “End Around” is an EO from the President creating the short term solution.
We can take all existing farms (Big & Small) and make the 80% Sustainable in less then 6 months with proper investment.
This seems to be a battle between Corporate Fascism and true Capitalism. We want to get the production of food back into the hands of the people.
Soviet Peaceful Collapse
Why was the Soviet Collapse peaceful? 300 million people and within 1 week there was no Federal government, no currency, no guidance, no pensions, ect. Nobody had a game plan. Disorganized peaceful chaos.
There seems to be some reasons
1) There was never a society fear of starvation. While shipping collapsed, and the kolkhoz farm system collapsed, there was food. Local kolkhoz where relatively small and regionally located. And most slowly died, so they still produced for a while.
2) the collapse happened in November, so the harvest was already in for the year. So they had food storage which gave time for the restart.
3) The west convinced Yeltsin (G-24 grants) to back the Soviet Ruble for 2 years until new currencies where put in place. So there was a exchange system that continued, although it had staggering inflation.
4) 90% of former Soviets had a Datcha that could produce up to 70% of the families yearly food. We would know this as a Victory Garden. 20 years later my mother-in-law at the age of 80 still farms her datcha. That also means 90% of the people had skills to grow food.
5) The majority of people believed life would get exponentially better. Life during the Soviet period was extremely tough, so many thought they were at the bottom and freedom was now here and life would get better.
6) There was not any destructive forces trying to create revolution.
Compare that to America now. If we have a collapse, no food, no food storage, no food production, no food delivery, no currency. Life will exponential and physiologically get much worse (not including 30% are on meds). And doubtful there will be any temporary solution for a collapsed dollar so what will we use as an exchange system?
Oh, and one other thing you should be aware of. When the Soviet Union collapsed it meant the Soviet Corporation over the 18 countries collapsed. Everything owned by the Corporation was up for grabs. Possession being 9/10ths of the law. Who owned the Soviet Nuclear Weapons if the old owner no longer existed?
Ukraine then became the 3rd most powerful Nuclear power in the world. That was a real “Change the Underwear day”. Russia and the US responded and bought back the weapons, well rumored most where bought back.
And of course the Rothschilds and Rockefellers sent in money to buy up assets cheap. Look who funded Khodorkovsky. It was corporate raiding on a continent size.
There are 2 other Large Unions similar to the Soviet Union. That is the European Union, and the Union of States – ie United States. It looks like it would behoove corporate raiding families to cause the collapse of these Unions as their assets would be up for grabs, while everybody else is in chaos.
So a big question. Who owns the United States Nuclear arsenal? If the US Corporation sitting over the 50 states collapses, who will own the nukes? The US military will no longer exist, so who will control?
Would that mean that if some nukes where in California than Gov Jerry Brown (or his predecessor) would control them? That could be a “Change the Underwear day”.
Just something to think about.
It gives a good reason to change the investment paradigm on Sustainable Small Farms. |
Cloning and sequencing of an intronless mouse S-adenosylmethionine decarboxylase gene coding for a functional enzyme strongly expressed in the liver.
A genomic clone for a mouse S-adenosylmethionine decarboxylase (AdoMetDC) gene was isolated from a cosmid library. Surprisingly, the gene proved to be intronless. With the exception of three base substitutions (changing 2 amino acids in the deduced protein), the 1002-nucleotide sequence of the open reading frame was identical to that of mouse AdoMetDC cDNA. Moreover, the gene contained a poly(dA) tract at the 3' end and was flanked by 13-base pair direct repeats. Our findings suggest that this gene has arisen by retroposition, in which a fully processed AdoMetDC mRNA has been reverse transcribed into a DNA copy and inserted into the genome. By polymerase chain reaction, we positively identified the intronless gene in the mouse genome, and, by primer extension analysis, we proved the gene to be functional. Thus, its transcripts were found in many cell lines and tissues of the mouse and were particularly abundant in the liver. When the open reading frame of the intronless gene was expressed in Escherichia coli HT551, a strain with no AdoMetDC activity, it was found to encode a 38-kDa protein, corresponding to AdoMetDC proenzyme. Although the change of methionine 70 to isoleucine was close to the cleavage site at serine 68, this protein underwent proenzyme processing, generating a 31-kDa alpha subunit and an 8-kDa beta subunit. Importantly, the protein encoded by the intronless gene was functional, i.e. it catalyzed the decarboxylation of S-adenosylmethionine, and its specific activity was comparable with that of recombinant human AdoMetDC purified according to the same procedure. |
Siri Worm
Siri Worm (born 20 April 1992) is a Dutch football defender who plays for FA WSL club Tottenham Hotspur and the senior Netherlands women's national football team.
Playing career
Club
FC Twente
Worm emerged from the youth academy of FC Twente. After several seasons as a reserve or utility player, she secured a place in the team at left back during the 2012–13 season, during which FC Twente were league champions and qualified for the UEFA Women's Champions League. FC Twente qualified for the Champions League 3 more times during Worm's tenure with the club.
Everton
Worm transferred to Everton in July 2017, part of a double transfer with teammate Marthe Munsterman.
Tottenham Hotspur
Following their promotion to the Women's Super League, in July 2019 Worm was announced as one of seven new Tottenham Hotspur signings.
International
She was the captain of the Dutch Under-19 national team in the 2010 and 2011 U-19 European Championships.
In October 2012 coach Roger Reijners called Worm up to the senior national team, as a replacement for the injured Petra Hogewoning. She won her first cap on 25 November 2012, in a 2–0 friendly win over Wales.
Worm was named in the Netherlands squad for UEFA Women's Euro 2013 in Sweden. She made a substitute appearance in the 1–0 defeat to Norway, replacing established left back Claudia van den Heiligenberg for the last 30 minutes. In April 2019, Worm was named as one of seven players on the Netherlands' standby list for the 2019 FIFA Women's World Cup.
International goals
Scores and results list the Netherlands goal tally first.
Honours
Club
FC Twente
Eredivisie (2): 2010–11, 2015–16
BeNe League (2): 2012–13, 2013–14
KNVB Women's Cup (1): 2014–15
International
Dutch Senior Team
Algarve Cup: 2018
References
External links
Profile at Onsoranje.nl (in Dutch)
Profile at onsorange.nl
Profile at vrouwenvoetbalnederland.nl (in Dutch)
Category:1992 births
Category:Living people
Category:People from Doetinchem
Category:Dutch women's footballers
Category:Netherlands women's international footballers
Category:Dutch expatriate footballers
Category:Expatriate women's footballers in England
Category:Dutch expatriate sportspeople in England
Category:Eredivisie (women) players
Category:FA Women's Super League players
Category:FC Twente (women) players
Category:Everton L.F.C. players
Category:Women's association football defenders
Category:Tottenham Hotspur F.C. Women players
Category:Dutch expatriate women's footballers |
{"files"=>["https://ndownloader.figshare.com/files/1495599"], "description"=>"<p>Each row represents a digital multicell along a study lineage. Circles signify propagule-eligible germ cells. Squares signify propagule-ineligible cells. Color intensity represents the number of mutagenic functions performed by propagule-eligible cells (blue) and propagule-ineligible cells (red). Within this lineage, the ancestral multicell began with all the cells in a pristine state. After (<b>a</b>), the propagule-eligible cells evolved to perform a variety of mutagenic functions and then to segregate their workload, thus producing pseudo-somatic cells (<b>b</b>). Eventually, these pseudo-somatic cells became ineligible to be used as propagules. At this point, they became true somatic cells (<b>c</b>). After this point, the somatic cells continued to perform mutagenic functions at a high level, while the germ cells remained quiescent. The mean propagule-eligible workload is correlated with the number of mutations that would be passed on to an offspring digital multicell. Notably, when germ–soma differentiation occurred (<b>c</b>), the mean propagule-eligible workload decreased, thus protecting the multicell's propagule from mutational damage.</p>", "links"=>[], "tags"=>["Evolutionary biology", "evolutionary theory", "evolutionary", "trajectory"], "article_id"=>1024986, "categories"=>["Biological Sciences"], "users"=>["Heather J. Goldsby", "David B. Knoester", "Charles Ofria", "Benjamin Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001858.g003", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_evolutionary_trajectory_of_an_example_digital_multicell_/1024986", "title"=>"The evolutionary trajectory of an example digital multicell.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-13 03:09:44"}
{"files"=>["https://ndownloader.figshare.com/files/1495594"], "description"=>"<p>Each histogram depicts the results for a specified FML with values ranging from 0.0 to 0.075 per-site probability. Each bar specifies the number of replicates (out of 30) that evolved a given proportion of propagule-ineligible cells. The vertical dashed line is the mean. In the absence of mutagenic effects (FML = 0.0) or at very high levels, propagule-ineligible cells failed to become abundant. At intermediate FMLs, peaking at 0.00075, propagule-ineligible cells evolved. Notably, these propagule-ineligible cells perform a disproportionately large amount of the mutagenic work of the multicell (e.g., propagule-ineligible cells within the 0.000075 and 0.00075 treatments evolved to perform 88.67% and 99.01% of the mutagenic work, respectively). Thus, we consider these propagule-ineligible cells to be soma.</p>", "links"=>[], "tags"=>["Evolutionary biology", "evolutionary theory", "mutagenic", "functions", "somatic"], "article_id"=>1024981, "categories"=>["Biological Sciences"], "users"=>["Heather J. Goldsby", "David B. Knoester", "Charles Ofria", "Benjamin Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001858.g002", "stats"=>{"downloads"=>5, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_mutagenic_functions_on_the_evolution_of_somatic_cells_/1024981", "title"=>"The effect of mutagenic functions on the evolution of somatic cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-13 03:09:44"}
{"files"=>["https://ndownloader.figshare.com/files/1495601"], "description"=>"<p>Over evolutionary time (<b>A</b>), a digital multicell evolves to consume resources more rapidly when young (resources consumed 0–1,000 updates of its lifetime; red line; circles) and relatively much more slowly when old (ratio of resources consumed late within its lifetime [9,000–10,000 updates], as compared with early in its lifetime [0–1,000 updates], blue line; triangles). The black dashed vertical line is the time point at which propagule-ineligible cells evolved. (<b>B</b>) At the beginning of the evolutionary run (the first step along the line of descent), the resource acquisition rate of a digital multicell remains constant throughout its lifetime (0–10,000 updates). (<b>C</b>) At the end of the evolutionary run (the final step along the line of descent), the resource acquisition rate of a digital multicell sharply decreases throughout its lifetime (0–10,000 updates). These results demonstrate antagonistic pleiotropy between resource consumption early in life and aging later in life.</p>", "links"=>[], "tags"=>["Evolutionary biology", "evolutionary theory", "multicell", "aging", "evolutionary"], "article_id"=>1024988, "categories"=>["Biological Sciences"], "users"=>["Heather J. Goldsby", "David B. Knoester", "Charles Ofria", "Benjamin Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001858.g004", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Measurements_of_digital_multicell_aging_over_evolutionary_time_/1024988", "title"=>"Measurements of digital multicell aging over evolutionary time.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-13 03:09:44"}
{"files"=>["https://ndownloader.figshare.com/files/1495607", "https://ndownloader.figshare.com/files/1495608", "https://ndownloader.figshare.com/files/1495609", "https://ndownloader.figshare.com/files/1495610", "https://ndownloader.figshare.com/files/1495611", "https://ndownloader.figshare.com/files/1495612", "https://ndownloader.figshare.com/files/1495613", "https://ndownloader.figshare.com/files/1495614", "https://ndownloader.figshare.com/files/1495615", "https://ndownloader.figshare.com/files/1495616", "https://ndownloader.figshare.com/files/1495617", "https://ndownloader.figshare.com/files/1495618"], "description"=>"<div><p>Reproductive division of labor is a hallmark of multicellular organisms. However, the evolutionary pressures that give rise to delineated germ and somatic cells remain unclear. Here we propose a hypothesis that the mutagenic consequences associated with performing metabolic work favor such differentiation. We present evidence in support of this hypothesis gathered using a computational form of experimental evolution. Our digital organisms begin each experiment as undifferentiated multicellular individuals, and can evolve computational functions that improve their rate of reproduction. When such functions are associated with moderate mutagenic effects, we observe the evolution of reproductive division of labor within our multicellular organisms. Specifically, a fraction of the cells remove themselves from consideration as propagules for multicellular offspring, while simultaneously performing a disproportionately large amount of mutagenic work, and are thus classified as soma. As a consequence, other cells are able to take on the role of germ, remaining quiescent and thus protecting their genetic information. We analyze the lineages of multicellular organisms that successfully differentiate and discover that they display unforeseen evolutionary trajectories: cells first exhibit developmental patterns that concentrate metabolic work into a subset of germ cells (which we call “pseudo-somatic cells”) and later evolve to eliminate the reproductive potential of these cells and thus convert them to actual soma. We also demonstrate that the evolution of somatic cells enables phenotypic strategies that are otherwise not easily accessible to undifferentiated organisms, though expression of these new phenotypic traits typically includes negative side effects such as aging.</p></div>", "links"=>[], "tags"=>["Evolutionary biology", "evolutionary theory", "evolutionary", "somatic", "cells"], "article_id"=>1024993, "categories"=>["Biological Sciences"], "users"=>["Heather J. Goldsby", "David B. Knoester", "Charles Ofria", "Benjamin Kerr"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001858.s001", "https://dx.doi.org/10.1371/journal.pbio.1001858.s002", "https://dx.doi.org/10.1371/journal.pbio.1001858.s003", "https://dx.doi.org/10.1371/journal.pbio.1001858.s004", "https://dx.doi.org/10.1371/journal.pbio.1001858.s005", "https://dx.doi.org/10.1371/journal.pbio.1001858.s006", "https://dx.doi.org/10.1371/journal.pbio.1001858.s007", "https://dx.doi.org/10.1371/journal.pbio.1001858.s008", "https://dx.doi.org/10.1371/journal.pbio.1001858.s009", "https://dx.doi.org/10.1371/journal.pbio.1001858.s010", "https://dx.doi.org/10.1371/journal.pbio.1001858.s011", "https://dx.doi.org/10.1371/journal.pbio.1001858.s012"], "stats"=>{"downloads"=>11, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Evolutionary_Origin_of_Somatic_Cells_under_the_Dirty_Work_Hypothesis_/1024993", "title"=>"The Evolutionary Origin of Somatic Cells under the Dirty Work Hypothesis", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-05-13 03:09:44"}
{"files"=>["https://ndownloader.figshare.com/files/1495591"], "description"=>"<p>Cells are either propagule-eligible (circles) or propagule-ineligible (squares). Deeper shades of color represent increased execution of mutagenic functions and, thus, accumulation of mutations in propagule-eligible cells (blue) and propagule-ineligible cells (red). Each cell contains a genetic program that guides its execution; a genome segment encoding one particular computational function (NOT) is shown. The last two depicted lines of the genome demonstrate how simple instructions can be used to evolve phenotypically plastic cells. In particular, the second to last line (<i>if_less</i>) specifies that the next instruction (<i>block_propagation</i>) should be executed only if the value in the <i>BX</i> register (e.g., 10001110100…) is less than the value in the <i>CX</i> register (e.g., 11110111111…). In this case, because the value in <i>BX</i> is indeed less than the value in <i>CX</i>, the <i>block_propagation</i> instruction is executed and thus the cell enters the propagule-ineligible state. However, if the values in the registers were different, then the cell could have remained eligible to be used as a propagule.</p>", "links"=>[], "tags"=>["Evolutionary biology", "evolutionary theory", "consisting", "multicells", "contains", "25"], "article_id"=>1024978, "categories"=>["Biological Sciences"], "users"=>["Heather J. Goldsby", "David B. Knoester", "Charles Ofria", "Benjamin Kerr"], "doi"=>"https://dx.doi.org/10.1371/journal.pbio.1001858.g001", "stats"=>{"downloads"=>5, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_World_consisting_of_digital_multicells_that_each_contains_up_to_25_cells_/1024978", "title"=>"World consisting of digital multicells that each contains up to 25 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-05-13 03:09:44"} |
1. Field of the Invention
The present invention relates generally to the field of data transmission, and more particularly to a method and apparatus for control of a transverter or transceiver by a modem in a wireless modem termination system.
2. Description of the Related Art
The customer side of a Point to Multi-point wireless system includes an RF Front End Transceiver or Transverter (the terms are used interchangeably herein) and a Wireless Modem Unit (WMU), which might be implemented as one unit or as separated units connected by an RF Cable. The transceiver is implemented on the Downstream path as a Low Noise Amplifier (LNA) and Down Converter (DC), and on the Upstream path as an Up Converter (UC) and Power Amplifier (PA) for the transmitted signal. The physical layer of the WMU includes a Modulator for the transmitted signal, a Demodulator for the received signal and a MAC layer to control both of them and also for controlling the Transceiver.
In the prior art systems, there is a need to control some parameters of the transceiver by the WMU. There is also a need to establish a control signal by the WMU, which will be decoded simply by the transceiver, and will not interfere with RX and IX signals. The following parameters should therefore be controlled: 1) Power Amplifier On/Off: 2) Upstream and downstream gain control: 3) Upstream and downstream frequency control 4) Transverter reference control oscillator control 5) Antenna Diversity Control |
Introduction {#Sec1}
============
Optimal treatment of locally advanced and lymph node-positive (cN1 or pN1) adenocarcinoma of the prostate has not yet been determined. There is abundant evidence gained from phase III studies that a substantial number of patients with locally advanced prostate cancer (PCa) derive a survival benefit from the combination of radiation and hormonal therapy \[[@CR1]--[@CR4]\]. Randomized trials of elective nodal irradiation of the pelvic lymph nodes in N0 men have not been shown to confer a survival benefit in similar patients \[[@CR5], [@CR6]\]. Therefore, the most appropriate treatment for men with clinically positive pelvic nodes, cN1 (or cN+), is an area of active controversy. The experience from extended lymphadenectomy suggests that for a subgroup of patients with limited positive pelvic lymph nodes, pN1, irradiation of the pelvic lymphatic structures could translate into long-lasting disease control \[[@CR7], [@CR8]\]. Similarly, there is emerging retrospective and prospective data that definitive radiation therapy and androgen deprivation therapy (ADT) in cN+ may be more beneficial than ADT alone \[[@CR9]--[@CR14]\].
In the present study we investigated the 5-year outcomes of patients with locally advanced and/or with N+ prostate cancer undergoing intensity modulated radiotherapy (IMRT) combined with long-term androgen deprivation therapy (ADT).
Patients and methods {#Sec2}
====================
Cohort characteristics {#Sec3}
----------------------
This study concerns consecutively treated patients treated with IMRT (*n* = 138) to the prostate, seminal vesicles and pelvic nodal basins and/or clinical positive nodal disease who had at least a 5-years of follow-up. Two patients were excluded from the survival analyses due to missing lymph node status. Only patients with less than 3 positive lymph nodes were eligible. The protocol was approved by the Ethics Committee of the Health Region South/East of Norway. All patients gave written consent.
Nodal sampling and N+ criteria {#Sec4}
------------------------------
In addition to the anatomical grading using the TNM/UICC stage classification \[[@CR15]\], the inclusion criteria were: age \< 75 years, no previous invasive cancer, initial PCa diagnosis made during the last 6 months, pN + M0 or a calculated N+ risk = \> 15 % using the Memorial Sloan-Kettering Cancer Center nomogram \[[@CR16]\] and prognostic high-risk disease defined by D'Amico's classification \[[@CR17]\]. During the recruitment period from 2004 to 2010 a trend towards radiographic N-assessment by magnetic resonance imaging (MRI) was seen due to low yield in the dissected lymph nodes obtained mainly from the obturator region when applying standard lymphadenectomy \[[@CR18]\].
IMRT planning and delivery {#Sec5}
--------------------------
The delineation of the clinical target volume (CTV) and organs at risk has been described in detail previously \[[@CR19]\]. Briefly, the CTV for the pelvic nodes was delineated by contouring a 0.7 cm radial area around the pelvic iliac vessels and adding a 2 mm margin to obtain a planning target volume (PTV). The medial portion of the presacral nodal area was left out in the delineation of lymph nodes, aiming to spare the recto-sigmoid, otherwise the contouring was per the recommendations attainable by the Radiation Therapy Oncology Group Web site ([www.rtog.org](http://www.rtog.org)).
The rectum was contoured from the anus to the rectosigmoid flexure. In the approved IMRT protocol predefined protocol-stated dose constraints to the OARs were mandatory. The use of 3D-conformal radiation therapy (CRT) and IMRT in prostate cancer permits dose escalation strategies with improved sparing of normal tissue.
The inverse planning software in Oncentra Masterplan (Nucletron, Veenendal, The Netherlands) was applied during the pilot phase of the study, and after 2006 the inverse planning software Konrad obtained from MRC Systems (MRC Systems GmbH, Heidelberg, Germany) was applied. Treatment plans were generated by seven coplanar fields to the delineated pelvic structures up to a total dose of 50 Gy encompassing the prostate, seminal vesicles and nodal basins (target volumes; PTV) by use of 15-MV photon beams. Radiation to the boost volume (24 Gy to the seminal vesicles and the prostate for T3b; 24 Gy to the prostate alone for ≤ T3a) was done by a four-field box technique. No attempt for dose escalation to N+ patients was included in this protocol. Patients were instructed to empty the rectum and keep the bladder filled during the course of radiotherapy. In the optimized plan the prescribed radiation dose was set equal to the mean dose of the ITV according to the International Commision on Radiation Units and Measurements Reports 62 (ICRU Report 62, [www.icru.org](http://www.icru.org)). Image guided patient set-up and irradiation was performed by daily field matching on bony landmarks for the majority of patients and on three implanted fiducial markers (Goldlock III, BeamPoint AB, Stockholm, Sweden) in 30 patients.
Androgen deprivation therapy (ADT) {#Sec6}
----------------------------------
All patients started neo-adjuvant ADT 6 months prior to IMRT, and this treatment was continued to a maximum of 2.5 years in some patients with pN+ and a very high-risk profile (Table [1](#Tab1){ref-type="table"}). We applied a 3-months depot injection with gosereline (Zoladex® 10.8 mg sc). As prophylaxis against flare-ups, bicalutamide 50 mg × 1 orally was given for 30 days, beginning 1 week prior to first injection of gosereline.Table 1Demographic, disease, and treatment characteristicsCharacteristicLymph node positive (*n* = 58)Lymph node negative (*n* = 78)*P*-valueMedian age at diagnosis (range), yrs66.7 (50.9 -- 76.8)67.4 (48.3 -- 79.1)0.03Mode of detection, *n* (%)0.17 Symptomatic25 (43)25 (32) Screening33 (57)53 (68)Median PSA (range), ng/mL24.4 (1.8 -- 109.0)26.0 (2.9 -- 109.0)0.26Gleason sum, *n* (%)0.21 3 + 33 (5)1 (1) 3 + 410 (17)8 (10) 4 + 313 (22)22 (28) 4 + 423 (40)29 (37) 4 + 55 (9)16 (21) 5 + 43 (5)2 (3) 5 + 51 (2)0 (0)Clinical stage, *n* (%)0.58 T1b1 (2)0 (0) T1c1 (2)6 (8) T2a3 (3)1 (1) T2b3 (5)4 (5) T2c3 (5)3 (4) T3a23 (40)32 (41) T3b23 (40)30 (38) T41 (2)2 (3)Median duration of ADT (range), months40.3 (11.9 -- 54.4)28.7 (9.0 -- 60.2)\<0.001Abbreviations: prostate-specific antigen (*PSA*)
Survivorship procedure {#Sec7}
----------------------
Patients were regularly seen in the outpatient clinic at 3--4 month intervals the first 2 years, and then every 6 months for the next 3 years. Routine history and physical exam was performed including blood samples with PSA and testosterone.
Physician-rated toxicity at 36 months {#Sec8}
-------------------------------------
Consecutively reported side effects or dysfunction on erectile potency, urinary, and bowel function were rated by one physician (WL) at regular intervals during follow-up. Grading of gastrointestinal and kidney-bladder side effects was done by the International Toxicity/RTOG morbidity grading scale \[[@CR20]\] Patients' self-rating side effects have been published previously \[[@CR21]\], but here we only report the prevalence of Grade 2 or more toxicity observed during the study period.
Statistical analysis {#Sec9}
--------------------
Primary endpoints of our study included biochemical failure-free survival (BFFS), relapse-free survival (RFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Biochemical failure was defined in accordance with the Radiation Therapy Oncology Group -- Association of Therapeutic Radiation Oncology (RTOG-ASTRO) Phoenix Consensus Conference definition. Relapse-free survival included local-regional or distant recurrence, as diagnosed by clinical exam, imaging, and/or biopsy. Death due to prostate cancer was defined as death in a patient with a documented history of hormone-refractory metastatic prostate cancer, evidence of a rising PSA at last follow-up visit, and no other obvious cause of death. Additionally, death certificates were cross-referenced to confirm cause of death. Patients who were alive were censored at last follow-up. For the purpose of calculating BFFS, patients without biochemical failure were censored at time of last PSA measurement. Survival endpoints were measured from the first day of initiation of ADT.
Differences in patient and treatment characteristics were compared between patients with and without radiologic and/or pathologic lymph node involvement using the *χ*^2^ test. Thresholds for categorical variables were defined in accordance with the literature. Univariate and multivariable Cox proportional hazards models were constructed for all survival endpoints. Hazard ratios for the associations between potential prognostic factors and survival endpoints were analyzed. Multivariable models adjusted for age at diagnosis, pre-treatment PSA, biopsy Gleason score, clinical stage, lymph node involvement, and duration of administration of ADT. Duration of ADT was calculated as the difference between the start and end dates of ADT administration, except when patients experienced biochemical failure, clinical recurrence, or death prior to completion of the originally prescribed course of ADT. In these cases, duration of ADT was calculated as the difference between the event date and start date of ADT. For each survival endpoint, backwards elimination was used to identify which covariates to include in the final multivariable model, using a threshold of *P*-value of 0.25 to make this determination. Additionally, Kaplan-Meier survival curves were constructed for all survival endpoints, with stratification by lymph node status and comparison of patient subsets using the log-rank test. Survival estimates at specific time points were derived from life tables.
Throughout the analysis, two-sided significance testing was used, and a *P*-value of 0.05 was considered statistically significant. All statistical analyses were performed with Stata software (Stata/IC10.0).
Results {#Sec10}
=======
Demographic, tumor, and treatment characteristics are detailed in Table [1](#Tab1){ref-type="table"}. The proportion of men with at least one high-risk factor (T3a or PSA \>20 ng/mL or Gleason 8--10) or T3b-T4, Gleason grade 5 or two or more risk factors (very high-risk) were 25 and 75 %, respectively. Radiologic and/or pathologic lymph node evaluation was positive for 71 patients (51 %). Men with lymph node involvement were younger and more likely to receive a duration of ADT that was greater than 28 months, as compared to men without lymph node involvement (both *p* \< 0.05). Mode of detection, initial PSA level, Gleason score, and clinical stage did not differ based on lymph node status.
Median follow-up of this cohort was 4.9 years (range: 0.9--11.1 years). Of the 136 men in the cohort who underwent combination treatment, 40 patients (29 %) experienced biochemical failure during the study period, and 34 patients (25 %) developed clinical relapse, including 15 patients (11 %) with distant metastases, 15 patients (11 %) with local-regional disease, and 4 patients (3 %) with concurrent distant and local-regional disease at time of relapse. In total, 18 patients (15 %) died during the follow-up period, including 8 patients (6 %) who died due to prostate cancer and 10 patients (7 %) who died from other causes.
For the entire cohort, the 5-year BFFS and 5-year RFS were 71.4 and 76.2 % respectively. The 5-year PCSS and 5-year OS were 94.5 and 89.0 % respectively (Fig. [1](#Fig1){ref-type="fig"}). Figure [2](#Fig2){ref-type="fig"} displays Kaplan-Meier estimates for survival endpoints, stratified by the presence of lymph node involvement. Men with lymph node positive disease experienced similar 5-year BFFS (*p* = 0.08), 5-year RFS (*p* = 0.07), and 5-year PCSS (*p* = 0.66), to those without pelvic nodal involvement. Interestingly, men with lymph node involvement experienced improved 5-year OS, as compared to men without lymph node involvement (96.5 % vs. 78.3 %, *p* = 0.03).Fig. 1Kaplan-Meier survival estimates for **a** biochemical failure-free survival, **b** relapse-free survival, **c** prostate cancer-specific survival, and **d** overall survival for overall cohortFig. 2Kaplan-Meier survival estimates for **a** biochemical failure-free survival, **b** relapse-free survival, **c** prostate cancer-specific survival, and **d** overall survival, stratified by lymph node status. Red curves represent men with radiologic and/or pathologic lymph node involvement. Blue curves represent men without lymph node involvement
On univariate analysis, a higher Gleason score was associated with inferior BFFS (*p* = 0.001) and inferior RFS (*p* = 0.001), but was not associated with either PCSS or OS (Additional file [1](#MOESM1){ref-type="media"}: Table S1). Additionally, a higher clinical stage was associated with inferior BFFS (*p* = 0.03) and inferior RFS (*p* = 0.05), but not with PCSS or OS. Interestingly, while lymph node involvement was not associated with BFFS, RFS or PCSS, it was associated with improved OS (*p* = 0.03). A duration of ADT greater than 28 months was also associated with improved PCSS (*p* = 0.03) and improved OS (*p* \< 0.001) on univariate analysis.
Table [2](#Tab2){ref-type="table"} details adjusted hazard ratios for the covariates included in the multivariable model, displaying results for covariates with a *p*-value of ≤0.10. A Gleason sum of 9 or 10 was associated with inferior BFFS (*p* = 0.001), RFS (*p* \< 0.001), and OS (*p* = 0.005), and had a borderline statistically significant association with PCSS (*p* = 0.07). Additionally, a duration of ADT greater than 28 months had a statistically significant association with improved PCSS (*p* = 0.02) and improved OS (*p* = 0.001). Lymph node involvement was not associated with any of the survival endpoints on multivariate analysis.Table 2Multivariate Cox proportional hazards analysis for associations between covariates and survival endpointsCovariateHazard ratio (95 % confidence interval)*P*-value*Biochemical failure-free survival*Gleason sum 9 or 103.33 (1.62 -- 6.85)0.001Clinical stage T3b/T42.17 (1.11 -- 4.22)0.02*Relapse-free survival*Gleason sum 9 or 104.43 (2.14 -- 9.14)\<0.001*Prostate cancer-specific survival*Gleason sum 9 or 104.13 (0.87 -- 19.58)0.07Duration of ADT ≥28 months0.20 (0.05 -- 0.81)0.02*Overall survival*Age ≥65 years3.57 (1.00 -- 12.82)0.05Gleason 4 + 317.26 (1.11 -- 268.69)0.04Gleason 4 + 414.67 (1.07 -- 200.81)0.04Gleason sum 9 or 1070.11 (3.49 -- 1407.99)0.005Duration of ADT ≥28 months0.15 (0.05 -- 0.44)0.001Multivariable models adjusted for age at diagnosis, pre-treatment PSA, biopsy Gleason score, clinical stage, lymph node involvement, and duration of administration of ADTAbbreviations: androgen deprivation therapy (*ADT*)Threshold of *p* \< 0.25 was used to exclude covariates from the final multivariable model, using backwards elimination
Maximum genitourinary and gastrointestinal toxicities are shown in Table [3](#Tab3){ref-type="table"}. During the follow-up period, urinary frequency and urinary urgency were the most common grade 2 or higher genitourinary toxicities experienced by patients, with 10 % of patients experiencing grade 3 frequency and 11 % of patients experiencing grade 3 urgency. The most common grade 2 gastrointestinal toxicities were fecal urgency and blood in the stool, but grade 3 gastrointestinal toxicities were rare overall.Table 3Prevalence of RTOG grade 2 or higher genitourinary or gastrointestinal toxicityRTOG Grade 2 toxicityRTOG Grade 3 toxicityGU-tract, *N* (%) Hematuria2 (1)1 (\<1) Urinary retention6 (4)2 (1) Urinary frequency49 (36)14 (10) Dysuria5 (4)2 (1) Urinary urgency63 (46)15 (11) Urinary leakage5 (4)1 (\<1)GI-tract, *N* (%) Fecal urgency37 (27)2 (1) Blood in stool17 (13)0 (0) Loose stools10 (7)1 (\<1) Fecal incontinence10 (7)1 (\<1)Abbreviations: Genitourinary (*GU*), Gastrointestinal (*GI*)
Discussion {#Sec11}
==========
In our study of locally advanced and N+ men with prostate cancer, we found a low risk for prostate-specific mortality (\<6 %) during a median of 4.9-years of follow-up, but moderate biochemical and/or clinical relapse with combined treatment of pelvic IMRT and ADT for the entire cohort. This agrees with the efficacy of combination treatment as shown in pivotal phase III trials for locally advanced PCa \[[@CR1]--[@CR4]\].
Our results in a cohort where 51 % of men were N+ are very favorable at 5 years when compared to the aforementioned phase III trials for locally advanced, but predominantly N0 PCa, On multivariable analysis, we did not find nodal involvement to be prognostic. Furthermore, in our cohort we found an interesting observation whereby men with N+ had an improved overall survival compared to patients without lymph node involvement. In the latter, duration of ADT was an independent predictor for survival. We did identify Gleason sum of 9--10 as a universally independent poor prognostic factor for all our clinical endpoints. However, long-term duration of ADT, greater than 28 months, was found to be an independent favorable prognostic factor for PSCC and OS. This last finding is in agreement with level 1 evidence from several randomized trials \[[@CR1], [@CR3], [@CR4], [@CR22]\] that long-term/life-long ADT should be applied in men with locally advanced PCa who are treated with radiotherapy.
Until recently, N+ has been synonymous with M1 disease, with most men being treated routinely with indefinite ADT alone and no local therapy. However, patients with M1 disease have a deleterious 5 year relative survival of 35 % underpinned by the latest report of the Norwegian Cancer Registry ([www.kreftregisteret.no](http://www.kreftregisteret.no)). All of the prospective radiotherapy trials that recruited men with locally advanced PCa involved none or a minority of N+ patients (\<5 %). Recently population based studies have suggested that the addition of local therapy in the N1 setting can have profound effects on survival \[[@CR13], [@CR14], [@CR23]\]. Specifically, the addition of radiation to cN1 patients has suggested these patients may enjoy long-term disease control \[[@CR24]\]. However, the optimal duration of ADT in men with N1 disease who receive combined radiotherapy and ADT is unknown. Longer-term ADT, but not indefinite ADT, was able to overcome the prognostic significance of N+ status in our cohort (Table [3](#Tab3){ref-type="table"}). Our data suggests that indefinite ADT may not be needed for limited N1 patients when combined with radiotherapy. In addition, dose escalation exceeding 50 Gy to cN1 pelvic lymph nodes not approached in our protocol may translate in long-lasting disease control.
Our study population consists of patients with aggressive tumors. Micrometastatic disease at diagnosis not detected by today's staging methods in these patients could have been associated with early relapse \[[@CR25]\]. However, rare detection of disseminated tumor cells in the bone marrow (data not shown) and limiting eligibility to \< 3 positive LNs supports our assumption that patients included in this study were not out of range for curatively intended treatment. Moreover, in these patients a major aim is to achieve local control by eradication of the primary tumor with combined treatment and thereby preventing re-seeding of tumor cells \[[@CR26]\].
Involving additional pelvic structures into the prostate irradiation fields increases the possibility for toxicity. The prevalence of grade 2 to 3 GI and or GU toxicity was moderate and mainly related to urgency. The rare event of grade 3 rectal bleeding might be due to early referring of patients to laser coagulation or hyperbaric oxygenation as a coping strategy. Our recently published patient self-reported results showed only a moderate increase of GI/GU side-effects not affecting overall QoL \[[@CR19], [@CR21]\]. Many of the men on this trial where treated before strict measures for daily image guidance were institutionalized, such as the use of fiducial markers in combination with Cone-Beam-CT. Such a patient set-up verification procedure allows a reduction of the treatment margins related to organ motion and set-up uncertainties, and a reduction in toxicity can thereby be expected. In addition, strategies addressing systemic treatments with a lower toxicity profile such as therapeutic cancer vaccines or novel class of androgen receptor inhibitors substituting partly ADT should be investigated \[[@CR27], [@CR28]\].
Strengths and limitations {#Sec12}
-------------------------
Our study limitations include retrospective analyses and the lack of randomization. Still, the similar work-up regimen and homogeneous treatment applications in this cohort of men with locally advanced PCa and/or N1 disease generated some interesting findings which are clinically meaningful in the wake of future results from randomized trials in this risk group.
Conclusion {#Sec13}
==========
Men with locally advanced and/or N1 prostate cancer have favorable outcomes following combined radiation and ADT and this can be achieved with low levels of toxicity when using IMRT to pelvic structures.
Additional file {#Sec14}
===============
Additional file 1: Table S1.Univariate Cox proportional hazards analysis for associations between covariates and survival endpoints. (DOC 48 kb)
Wolfgang Lilleby and Amol Narrang contributed equally to this work.
**Competing interests**
The authors declare that they have no competing interests.
**Authors' contribution**
WL outlined the protocol, carried out patients' inclusion and data collection, participated in analysis and helped drafting the manuscript. AN performed the data analysis and drafted the manuscript. PT participated in the data analysis and drafted the manuscript. AS, GT and KR included patients. KH performed the radiologic staging of all patients included. VL reviewed all histologic specimen and KE participated in writing the protocol and drafted the manuscript. All authors approved the final version of the manuscript.
The generous support of the study by grants from the Olav Raagholt and Gerd Meidel Foundation and the Prostate Cancer Foundation-Norway is highly appreciated. We also thank our study nurse Melanie-Birte Schulz for her superb coordination of the follow-up and patient's care.
|
Treatment of Ruptured Intracranial Aneurysms Using the Woven EndoBridge Device: A Two-Center Experience.
The Woven EndoBridge (WEB) device is a new treatment modality developed for broad-necked unruptured intracranial aneurysms (IAs) but shows potential for the treatment of ruptured IAs as well. Our aim was to describe 6-month aneurysm obliteration rates, clinical outcomes, and procedure-related complications after WEB treatment for ruptured IAs from 2 academic centers. We conducted a retrospective observational study, including all consecutive patients treated with the WEB device (WEB single layer and single-layer sphere) for a ruptured IA causing acute subarachnoid hemorrhage between 2014 (start of use) and 2017. Primary outcome was angiographic aneurysm obliteration (Beaujon Occlusion Scale Score) rate. Secondary outcomes were early re-bleedings, complications, and patient outcome (death and modified Rankin Scale). A total of 33 patients with ruptured IAs were treated 0-4 days from IA rupture. Of 27 survivors, 6-month angiographic follow-up was available for 26 patients, of whom 81% showed complete occlusion. Of the 27 survivors, 24 patients (89%) had a favorable neurologic outcome at 6 months after subarachnoid hemorrhage. Two aneurysms were retreated (8% of all). There was 1 fatal procedure-related complication. No early aneurysm re-bleedings were noted. For anatomically suitable ruptured IAs, WEB device treatment seems to be safe and results in acceptable occlusion rates. Still, larger studies with long-term results are needed before recommendations can be made. |
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Sort 1, 161, -65, -5, -4, 0 in decreasing order.
161, 1, 0, -4, -5, -65
Sort 3, 1, -789, 29, -12, 4.
-789, -12, 1, 3, 4, 29
Put 9, -53, 0.4, 1/3, -4, 93/13 in increasing order.
-53, -4, 1/3, 0.4, 93/13, 9
Sort 3, 17.7, -0.2, -1, 5, 1/2, 0.4.
-1, -0.2, 0.4, 1/2, 3, 5, 17.7
Put 1198, 0, 2, -5, 43, -3 in descending order.
1198, 43, 2, 0, -3, -5
Sort 1/404, 1.61, -8, 0.07.
-8, 1/404, 0.07, 1.61
Put 4, 138, 9375/28 in descending order.
9375/28, 138, 4
Sort -128197, 11, -4.
-128197, -4, 11
Sort -27, -1, 8, -3113.
-3113, -27, -1, 8
Put -1, -3114, 0, -279 in decreasing order.
0, -1, -279, -3114
Sort -2, -10502, 1521 in decreasing order.
1521, -2, -10502
Put 5, 0.06, -2, 3, -9/55, -5 in decreasing order.
5, 3, 0.06, -9/55, -2, -5
Sort -5, -2395, -1, -13, 4 in ascending order.
-2395, -13, -5, -1, 4
Sort -1, -5, -139, -59, -3, -1/3 in ascending order.
-139, -59, -5, -3, -1, -1/3
Put 328, -145, -303 in decreasing order.
328, -145, -303
Sort 0.03, 0, 3, -2, 3.6, -0.01, 29 in descending order.
29, 3.6, 3, 0.03, 0, -0.01, -2
Put 22, 6, -2, 1, -3, -8, 1268 in descending order.
1268, 22, 6, 1, -2, -3, -8
Sort -1/8, -2, -65707.
-65707, -2, -1/8
Sort 5, 10, -5, 13981, 2.
-5, 2, 5, 10, 13981
Put -2, -2279, 2/13, 25 in increasing order.
-2279, -2, 2/13, 25
Put 6, -1, 26, -1516 in increasing order.
-1516, -1, 6, 26
Sort 1/8, -2368, -2, -9, -0.5 in descending order.
1/8, -0.5, -2, -9, -2368
Put 20, 23, 10, -74, -2 in descending order.
23, 20, 10, -2, -74
Sort -0.07, -6.3, -67, 0.6, 4, 0 in decreasing order.
4, 0.6, 0, -0.07, -6.3, -67
Put -5, 25, 11, 5, 1, -31 in ascending order.
-31, -5, 1, 5, 11, 25
Sort -29828, 0, -408.
-29828, -408, 0
Sort -2/458075, 2.78, 0.
-2/458075, 0, 2.78
Put 1, -46, -5, -73, 39, 5 in increasing order.
-73, -46, -5, 1, 5, 39
Sort -1/7, -481, 12 in decreasing order.
12, -1/7, -481
Sort 0, 7070, 1073 in descending order.
7070, 1073, 0
Sort 2, -3, 59, 5, 12694 in descending order.
12694, 59, 5, 2, -3
Sort -1/12, 11/217, -0.05, -3/4 in increasing order.
-3/4, -1/12, -0.05, 11/217
Sort -0.03, 60, -2, 16/5, 1, 4/5.
-2, -0.03, 4/5, 1, 16/5, 60
Sort -5, 1313, 17, 0, 3 in descending order.
1313, 17, 3, 0, -5
Sort 55, -18, 1/2, 0.5317 in decreasing order.
55, 0.5317, 1/2, -18
Put 28741, -187, -5, 4 in descending order.
28741, 4, -5, -187
Sort -14, -253466, 4.
-253466, -14, 4
Sort 222, 92, 3, 12, 11.
3, 11, 12, 92, 222
Put 3, -4, -57.617 in decreasing order.
3, -4, -57.617
Put -2.5, 16666, -5/14 in increasing order.
-2.5, -5/14, 16666
Put 3, -264299, 18 in ascending order.
-264299, 3, 18
Sort -2, 3, 73, 1, -4, 22, -3 in descending order.
73, 22, 3, 1, -2, -3, -4
Put -24, 1, 6, -4, -34, -1 in decreasing order.
6, 1, -1, -4, -24, -34
Sort 2479, -32, -6.
-32, -6, 2479
Put 3, -13, 0, -1, 2, -86, 26 in descending order.
26, 3, 2, 0, -1, -13, -86
Sort 7005, -1, -2, 5, 170 in increasing order.
-2, -1, 5, 170, 7005
Sort 5, 114.6, -100, 1, -0.02 in decreasing order.
114.6, 5, 1, -0.02, -100
Sort 208095994, 2, 4 in decreasing order.
208095994, 4, 2
Sort 2, -6, 0, 11, -2, -15299.
-15299, -6, -2, 0, 2, 11
Put -2, 4, 1, 1/25, -2/5, 1/55 in descending order.
4, 1, 1/25, 1/55, -2/5, -2
Sort 3/7, 0.025, 1/215, -5, -27.2.
-27.2, -5, 1/215, 0.025, 3/7
Sort 4, -2/93, -405.3, -1/4 in descending order.
4, -2/93, -1/4, -405.3
Put -0.1, 1.7, 1/5, 3/2, 100, -5/6 in descending order.
100, 1.7, 3/2, 1/5, -0.1, -5/6
Sort 4, 3, 62.976775 in increasing order.
3, 4, 62.976775
Put 104, -0.26, -4, 2/11, -0.2 in increasing order.
-4, -0.26, -0.2, 2/11, 104
Sort -1771, 2/9, -21, -142 in descending order.
2/9, -21, -142, -1771
Sort 46822/97, 0.01, 5 in increasing order.
0.01, 5, 46822/97
Sort 87, -132, -9, -2, -3 in ascending order.
-132, -9, -3, -2, 87
Sort 35, 31, -3, 2, 4, -190.
-190, -3, 2, 4, 31, 35
Sort 1, -2, 301102, -3, 15, -4 in increasing order.
-4, -3, -2, 1, 15, 301102
Put -29, 17, 14, 3, 5, 1, -4 in decreasing order.
17, 14, 5, 3, 1, -4, -29
Sort -8/1237, -91/24, 1 in descending order.
1, -8/1237, -91/24
Sort 1, 2, 98, -12, 3, -4 in descending order.
98, 3, 2, 1, -4, -12
Sort -0.5, 1.1, 0.41, -8/15, 1/33 in descending order.
1.1, 0.41, 1/33, -0.5, -8/15
Put 2, 12, 0, -4, -2768, -10, -2 in increasing order.
-2768, -10, -4, -2, 0, 2, 12
Put 21, 105, 13, 4, -5, -6 in descending order.
105, 21, 13, 4, -5, -6
Put 4, -87, -72, 4335 in decreasing order.
4335, 4, -72, -87
Sort 83, 686, -7 in increasing order.
-7, 83, 686
Put 278/5, -125, -501 in ascending order.
-501, -125, 278/5
Put 0, -1, 5, -9.054754 in decreasing order.
5, 0, -1, -9.054754
Sort 12, 1, 67, -12, -3 in descending order.
67, 12, 1, -3, -12
Sort -1165, 169, -2, -3 in descending order.
169, -2, -3, -1165
Put 4/3, 16.56, 5/9412, 1 in increasing order.
5/9412, 1, 4/3, 16.56
Sort 5, -5025, 3, 1, -19 in decreasing order.
5, 3, 1, -19, -5025
Sort 5, 0, 2, 9, 1, 4, 212 in increasing order.
0, 1, 2, 4, 5, 9, 212
Sort -13, 1, 2, -5, 4, -6, 15.
-13, -6, -5, 1, 2, 4, 15
Put -4.1, 2, 4, -233, -4, 0.03 in decreasing order.
4, 2, 0.03, -4, -4.1, -233
Put 4/21, -3, 425593 in increasing order.
-3, 4/21, 425593
Sort 9384, 81, -53 in increasing order.
-53, 81, 9384
Sort -7, -8, 82819.
-8, -7, 82819
Sort 2, -118, -60, 0, -4, 7 in decreasing order.
7, 2, 0, -4, -60, -118
Sort 2, -6/19, -4, 8, -5, -2.8 in decreasing order.
8, 2, -6/19, -2.8, -4, -5
Sort -0.202, 0.5, 5867.7.
-0.202, 0.5, 5867.7
Sort -3, 2377, 5, -5, 9, 2 in ascending order.
-5, -3, 2, 5, 9, 2377
Put 7661, 4, -1, 2, -35, -27 in descending order.
7661, 4, 2, -1, -27, -35
Sort -52, 6, 25, 4, 558 in ascending order.
-52, 4, 6, 25, 558
Put -2, -1/5, 0, 168331, 1, -3/7 in descending order.
168331, 1, 0, -1/5, -3/7, -2
Sort 95, -165, -2, 3/11, 0.2, 3 in descending order.
95, 3, 3/11, 0.2, -2, -165
Sort 79, 14, -35658 in decreasing order.
79, 14, -35658
Put -2, 17134, 115 in descending order.
17134, 115, -2
Put -2257, 0.4, 1/4, -24/7, -8/3 in increasing order.
-2257, -24/7, -8/3, 1/4, 0.4
Sort -4, -8, 4, -2, 5, 688, -5 in descending order.
688, 5, 4, -2, -4, -5, -8
Sort 0.3, 4, 116, -0.5, 36.9, -1/24.
-0.5, -1/24, 0.3, 4, 36.9, 116
Sort -819, -55581, 3, -2.
-55581, -819, -2, 3
Sort -24690, -5, 78 in increasing order.
-24690, -5, 78
Sort 0.3, 2, -14, -382, -2 in ascending order.
-382, -14, -2, 0.3, 2
Put 0, 5, -27906, 17 in descending order.
17, 5, 0, -27906
Put 4, 1, 258308 in decreasing order.
258308, 4, 1
Sort 6315067, -7/2, 4 in descending order.
6315067, 4, -7/2
Sort -3, -1934, 32, -15.
-1934, -15, -3, 32
Sort 1, 4, -1, -11, -4, 168.
-11, -4, -1, 1, 4, 168
Sort 13, 11, -164, 52, 16 in decreasing order.
52, 16, 13, 11, -164
Sort 3, 1, 0.06, 9057 in decreasing order.
9057, 3, 1, 0.06
Put 1, -37, -30, -2, -92 in descending order.
1, -2, -30, -37, -92
Sort -18252, -10, 1/4, 2/93, -0.5.
-18252, -10, -0.5, 2/93, 1/4
Sort 16, -68928, 2.
-68928, 2, 16
Sort -897, -16, 2, -4 in descending order.
2, -4, -16, -897
Sort 446, 4, 506, -3, -29 in ascending order.
-29, -3, 4, 446, 506
Sort -12112, 3, 2, -5, 1, -1, -2 in decreasing order.
3, 2, 1, -1, -2, -5, -12112
Put 26, -29, 3, 169/15, 0.1 in increasing order.
-29, 0.1, 3, 169/15, 26
Put -833, 3/4, 0, -0.09645 in descending order.
3/4, 0, -0.09645, -833
Sort -49, 0, -0.2, 4, 1, -3, -8.
-49, -8, -3, -0.2, 0, 1, 4
Put 3, -95, 26, -3, 0, -2, 2 in descending order.
26, 3, 2, 0, -2, -3, -95
Put 532, 3, -23 in increasing order.
-23, 3, 532
Put -0.002070588, 1/7, -3 in decreasing order.
1/7, -0.002070588, -3
Sort -372652, -3, -8, 16.
-372652, -8, -3, 16
Sort 0, 167, -2, 16, -34, 4, 3 in decreasing order.
167, 16, 4, 3, 0, -2, -34
Sort 4, 19, 1, -3, -4, 40, 0 in decreasing order.
40, 19, 4, 1, 0, -3, -4
Sort 0, 50, 4, -2, 1151, -5, 9.
-5, -2, 0, 4, 9, 50, 1151
Sort 10, 49, 5, -1, 6, -15, -68.
-68, -15, -1, 5, 6, 10, 49
Sort -0.66, 3.9, -43, -24.7 in increasing order.
-43, -24.7, -0.66, 3.9
Sort -16, 62, 3, 600, -4, 1 in decreasing order.
600, 62, 3, 1, -4, -16
Sort -30, 9, 37051.
-30, 9, 37051
Put -3/4, |
Trim as much fat as possible from the roast and slice the meat across the grain into 1⁄4-inch slices. Season the slices well with salt and pepper (go easy on the salt if using canned broth).
Heat 1 tablespoon of the oil in a skillet over medium-high heat and sear the meat, a few slices at a time, until nicely browned on both sides. Transfer to a plate as they are done.
Reduce the heat to medium-low; if the meat has released a lot of liquid, let it cook until the skillet is nearly dry but not in danger of scorching. Add the remaining 3 tablespoons oil and the onions and cook, stirring and turning with a long fork, until the onions are soft and lightly browned, about 10 minutes.
Push the onions to one side of the pan and stir in the flour. Cook, stirring and scraping the pan, until the flour mixture turns a medium brown; keep an eye on the onions so they do not burn.
Add the stock, ale, vinegar, and accumulated juices from the meat plate to the pan and stir everything together.
Bring to a simmer, cook until any lumps of roux are dissolved, and season to taste.
Spoon a little of the sauce mixture into the bottom of a covered baking dish. Arrange the beef slices in the dish, then top with the onions and sauce, bay leaf and thyme.
Cover and bake 2 hours. Taste the sauce for balance, and add a little sugar if the sauce is on the bitter side. If the meat is not yet fork-tender, continue baking for another 1⁄2 hour or so.
Let the stew stand for a few minutes out of the oven, then skim off any excess fat around the edges. Or refrigerate it for up to several days and remove any hardened fat before reheating in a low oven.
Yield
Serves 6
Notes
The instructions here call for a heavy skillet for the stovetop cooking steps and another covered casserole dish for slow cooking in the oven. If you have a suitable covered pan that can go straight from the stovetop to the oven (an enameled cast-iron Dutch oven, a deep, stainless-lined sauté pan or some type of flameproof earthenware), you can do everything in that one pan, nestling the browned beef slices into the sauce and onion mixture before baking.
Good to know
Probably the most famous dish cooked with beer is carbonnade flamande, beef slices stewed Flemish style in beer with an ample amount of sliced onions made sweet by slow braising. Just as coq au vin can be cooked with whatever wine is at hand, carbonnade can in theory be made in many different “flavors” by varying the beer. In northern France near the Belgian border, the beer is mainly reddish, fruity ale. At least one authentic Flemish version would be made with one of that region’s tart-flavored wheat beers, such as lambic or gueuze. In search of a West Coast version of this dish (carbonnade cascadienne?), I have made this dish with various West Coast beers, from hefeweizen (which makes a tasty but rather pale stew, especially with a little extra vinegar) to a brown ale like Lost Coast Downtown Brown (my favorite for both flavor and deep brown color) to porter and stout. Feel free to experiment, but watch out for highly hopped ales, or the stew can come out too bitter.
Which beer should I drink with this?
It’s hard to go wrong serving the same beer you cook with, but you can also serve something with more hop bitterness than would be good in the dish. |
Q:
Spring MVC AngularJS No mapping found
I've been following the tutorial for integrating Spring Security with AngularJS, but it uses Spring Boot. I can get the tutorial examples working, but I need my app to run as a regular MVC application under Tomcat.
The problem is getting the application to route to the index.html page for the initial view. The only mappings I have in the controllers are the REST calls I want to receive from Angular, but I can't seem to get the application to go to the index page. Spring Boot does this automatically, but I'm going to run this as a web app under Tomcat. Trying to go there directly causes a 'No mapping found' error.
I'm using Java configuration and have the antMatchers, etc as described in the tutorial.
A:
Here are a few entries in my config classes to make this happen.
@Override
protected void configure(HttpSecurity http) throws Exception {
http.authorizeRequests()
.antMatchers("/index.html", "/home.html", "/login.html", "/").permitAll()
.antMatchers("/css/**").permitAll()
.antMatchers("/js/**").permitAll()
.antMatchers(HttpMethod.POST, "/user").permitAll().anyRequest()
.authenticated().and()
.csrf()
.csrfTokenRepository(csrfTokenRepository()).and()
.addFilterAfter(csrfHeaderFilter(), CsrfFilter.class);
if ("true".equals(System.getProperty("httpsOnly"))) {
LOGGER.info("launching the application in HTTPS-only mode");
http.requiresChannel().anyRequest().requiresSecure();
}
}
@Configuration
@EnableWebMvc
@ComponentScan("com.mygroupnotifier.controller")
public class ServletContextConfig extends WebMvcConfigurerAdapter {
@Override
public void addResourceHandlers(ResourceHandlerRegistry registry) {
registry.addResourceHandler("/css/**").addResourceLocations("/resources/static/css/");
registry.addResourceHandler("/js/**").addResourceLocations("/resources/static/js/");
registry.addResourceHandler("/*.html").addResourceLocations("/resources/static/");
}
@Override
public void addViewControllers(ViewControllerRegistry registry) {
registry.addViewController("/").setViewName("forward:/index.html");
}
}
As usual the most difficult part of this is getting the leading and ending / on the classes and the html files.
|
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