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BlogsPublished: 15 May 2019
5 Public Sector innovation champions
We've listed our top 5 public sector departments who are leading the way when it comes to new and innovative technology, along with what tech they're using.
With the arrival of Crown Commercial Service's Spark DPS, it looks like we'll be seeing a greater focus on innovation from government. So, whilst the arrival of Spark has got us thinking about future innovation, we thought we would dig out some examples of government bodies that already have their finger on the innovation pulse!
Arguably, one of the biggest champions of innovative technology in the public sector at the moment is the NHS. Possibly attributed to the stretched frontline of healthcare needing to find new streamlined and shared solutions, and also a focus on improving patient care.
This year they launched NHSX, an organisation tasked with moving forward digital transformation. Some seriously cool technology is currently in testing, including wearables, for health monitoring at home, and new ways to improve patients care (including Smart Homes for the elderly).
And, there's more on the way! NHS Digital have pledged £1m of funding for innovative uses of digital technology in adult social care for starters, as well as hoping to increase the use of AI within hospitals.
With the Home Office working alongside the DfT to seek novel ideas to shape the future of aviation and border security – announcing funding of £4.5m for it! – the Home Office are hard at work using innovative technology solutions. One example is their funding for proof of concept projects for knife detection technology in crowded places.
Last year they also announced they would be using AI to tackle extremist content being posted online and moved into crowd security applications too. Which is all part of their efforts to work more closely with the private sector to tackle UK security challenges with new ideas!
Another innovation champion in the public sector is the Ministry of Justice. Recently launching a secure digital ID application for employees and those working in the courts. Titled the 'professional-user access scheme', it's just one way the MoJ are using new ideas for service delivery.
They've also been pushing the use of video technology for their smaller civil cases, and have rolled out nationally new GPS tagging systems for offenders.
Department for Work and Pensions
As early as June last year, DWP highlighted their willingness to incorporate new and emerging technology into their service delivery, as they aim to make it all easier to use by the public. This includes machine learning, natural language processing and image processing – with a lot of AI solutions too!
They've stated that innovation should be at the heart of what the department does, championing new and exciting technologies. This includes bringing in AI to reduce benefits fraud and using blockchain technology alongside their mobile apps for benefit claimants.
Last but not least, HMRC were labelled as the government's leader in robotic automation (RA) technology by central gov themselves. They even set up an Automated Delivery Centre in 2016 and have had over 15 million RA transactions so far.
More recently, they've been pushing for the public to use Alexa and voice activated technology to deal with enquiries and transactions, and we could see a much bigger increase in using AI after Brexit, according to reports.
There you have it! This isn't an exhaustive list by any means, but these are exciting times for technology and innovation in government. We are patiently awaiting the government innovation strategy to see how else government is pledging its commitment to innovation.
Tags: Innovation, Spark
The opportunity for innovative tech in the public sector
We recently held our 'The opportunity for innovative tech in the public sector' webinar. Here's the recording in case you missed out!
5 examples of how IoT is improving government services
Many parts of society are already using IoT to improve and ease lives, but it seems universally agreed that the public sector haven't got involved. But is that true?


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Australia renews commitment to support Vietnam's economic reform
The Australian Government and the Vietnamese MIP jointly launched Aus4Reform – a four-year long programme to boost the productivity and competitiveness of Vietnam's economy, in Hanoi on December 13.
VNA Wednesday, December 13, 2017 18:27
NA leader pledges to support VN, Australia friendship organisations
Outcomes of VN, Australia PMs' talks announced
Australian Senate speaker delights at progress of ties with Vietnam
Australia supports manpower training at Tay Bac University
Tuesday, August 29, 2017 16:18
Australia – potential market for Vietnam goods
Wednesday, June 14, 2017 11:07
Vietnam hopes for sustainable economic ties with Australia
Australian Ambassador Craig Chittick speaks at the event (Source: courtesy of Australian Embassy in Vietnam)
Hanoi (VNA) - The Australian Government and the Vietnamese Ministry of Planning and Investment jointly launched Aus4Reform – a four-year long programme to boost the productivity and competitiveness of Vietnam's economy, in Hanoi on December 13.
The 6.5 million AUD programme will support the Government of Vietnam to achieve its targets for improving the business environment and move Vietnam towards a more market-based economy through assisting the development and implementation of economic policies, laws and institutions critical to helping Vietnam's economy meet its potential.
The initiative will also build linkages between Australian and Vietnamese institutions to share expertise and experience.
Australian Ambassador Craig Chittick said Vietnam has a long history of pursuing economic reform and Australia is proud to have offered our support throughout this process. "Economic reform is tough, but Australia will continue to support Vietnam on this journey," he said.
Australia's support will help Vietnam achieve its goal of one million new formal private enterprises by 2020, increase the percentage of women-led enterprises and accelerate the growth in private sector employment.
Aus4Reform brings together Vietnam's leading think-tanks and government agencies responsible for economic policy making and implementation, including the Central Institute of Economic Management (CIEM), Vietnam Competition and Consumer Agency (VCCA), the Institute of Policy and Strategy for Agriculture and Rural Development (IPSARD), Vietnam Chamber of Commerce and Industry (VCCI), the Party Central Committee's Economic Commission and the Economic Committee of the National Assembly.
The programme builds on the reform momentum achieved through previous Australia support including "Beyond WTO" and "Restructuring for a more Competitive Vietnam".-VNA
Australian Government Vietnamese Ministry of Planning and Investment Vietnam's economy Economic reform VCCI Vietnamplus Vietnam News Vietnam News Agency WTO National Assembly Related stories Australia
Reference exchange rate down 2 VND at week's beginning
The State Bank of Vietnam set the daily reference exchange rate at 23,155 VND/USD on January 20, down 2 VND from the last working day of previous week (January 17).
Tra Vinh farmers harvest mud crab for Tet, earn high profit
Farmers in the Mekong Delta province of Tra Vinh are entering the mud crab harvest for Tet (Lunar New Year) and earning a high profit of 30 - 35 million VND (1,300 - 1,500 USD) per hectare as demand is high for the coming holiday, which falls on January 25.

redpajama_set_name: RedPajamaCommonCrawl


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Interleukin-29 Binds to Melanoma Cells Inducing Jak-STAT Signal Transduction and Apoptosis
Kristan D. Guenterberg, Valerie P. Grignol, Ene T. Raig, Jason M. Zimmerer, Anthony N. Chan, Farriss M. Blaskovits, Gregory S. Young, Gerard J. Nuovo, Bethany L. Mundy, Gregory B. Lesinski and William E. Carson III
Kristan D. Guenterberg
Valerie P. Grignol
Ene T. Raig
Jason M. Zimmerer
Anthony N. Chan
Farriss M. Blaskovits
Gregory S. Young
Gerard J. Nuovo
Bethany L. Mundy
Gregory B. Lesinski
William E. Carson
DOI: 10.1158/1535-7163.MCT-09-0461 Published February 2010
Interleukin-29 (IL-29) is a member of the type III IFN family that has been shown to have antiviral activity and to inhibit cell growth. Melanoma cell lines were tested for expression of the IL-29 receptor (IL-29R) and their response to IL-29. Expression of IL-28R1 and IL-10R2, components of IL-29R, was evaluated using reverse transcription-PCR. A combination of immunoblot analysis and flow cytometry was used to evaluate IL-29–induced signal transduction. U133 Plus 2.0 Arrays and real-time PCR were used to evaluate gene expression. Apoptosis was measured using Annexin V/propridium iodide staining. In situ PCR for IL-29R was done on paraffin-embedded melanoma tumors. Both IL-28R1 and IL-10R2 were expressed on the A375, 1106 MEL, Hs294T, 18105 MEL, MEL 39, SK MEL 5, and F01 cell lines. Incubation of melanoma cell lines with IL-29 (10–1,000 ng/mL) led to phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT2. Microarray analysis and quantitative reverse transcription-PCR showed a marked increase in transcripts of IFN-regulated genes after treatment with IL-29. In the F01 cell line, bortezomib-induced and temozolomide-induced apoptosis was synergistically enhanced following the addition of IL-29. In situ PCR revealed that IL-10R2 and IL-28R1 were present in six of eight primary human melanoma tumors but not in benign nevi specimens. In conclusion, IL-29 receptors are expressed on the surface of human melanoma cell lines and patient samples, and treatment of these cell lines with IL-29 leads to signaling via the Jak-STAT pathway, the transcription of a unique set of genes, and apoptosis. Mol Cancer Ther; 9(2); 510–20
Interferon-lambda
IFN-α is commonly used in the treatment of malignant melanoma, both as an adjuvant to surgical resection and in the setting of advanced disease (1). This cytokine enhances the activity of immune effector cells while mediating antiproliferative and proapoptotic effects against tumor cells. The receptor for IFN-α is widely expressed on normal tissues and has been identified on tumor cell lines (2). The binding of IFN-α to its receptor results in the phosphorylation of Janus kinase 1 (Jak1) and tyrosine kinase 2 (Tyk2) on specific tyrosine residues. These phosphor-tyrosine residues provide docking sites for cytoplasmic transcription factors belonging to the signal transducer and activator of transcription (STAT) family of proteins. These STAT proteins (STAT1α, STAT2) are phosphorylated by the Janus kinases and subsequently form high-affinity DNA binding complexes that rapidly translocate to the cell nucleus to drive the expression of IFN-responsive genes (3, 4).
Interleukin-29 (IL-29), also known as IFN-λ, is a recently discovered cytokine of the type III IFN family (5, 6). It is thought to have biological properties similar to the type I IFNs. Unlike IFN-α, the receptor for IL-29 (IL-29R) is expressed on a limited number of normal cells, including dendritic cells, T cells, and intestinal epithelial cells. Leukemia cells and colon, prostate, pancreatic, lung, hepatoma, glioblastoma, and breast cancer cells have also been shown to express this receptor (6–12). In these reports IL-29 elicited signal transduction via activation of the Jak-STAT pathway, p-AKT, and the mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/ERK; refs. 5, 8, 9, 12, 13).
To date, the biological effects of IL-29 on human melanoma cells have not been investigated. Because this cytokine is postulated to have antitumor properties in other cancer cell lines (12, 14), the direct effects of IL-29 on melanoma cells were explored. In the present report, we characterize IL-29–induced signal transduction, gene expression, and apoptosis in melanoma cells. We also show that IL-29 can act in concert with other antitumor agents to enhance apoptosis of melanoma cells.
Cell Lines and Reagents
The A375, Hs294T, and SK MEL 5 human melanoma cell lines were purchased from the American Type Culture Collection. The 1106 MEL, 18105 MEL, MEL 39, F01, and 1174 MEL cell lines were a gift from Dr. Soldano Ferrone (Roswell Park Cancer Institute). IL-29 was obtained from ZymoGenetics. Cell lines were grown as previously described (15). Human natural killer (NK) cells were isolated directly from fresh peripheral blood leukopacks (American Red Cross) by a 25-min incubation with RossetteSep cocktail (Stem Cell Technologies) followed by Ficoll-paque (Sigma) density gradient centrifugation as previously described (16). NK cells were cultured in RPMI 1640 supplemented with 10% heat-inactivated pooled human AB serum (Sigma), 100 U/mL penicillin, 100 μg/mL streptomyocin, and 0.25 μg/mL amphotericin B (17).
Flow Cytometry of Tumor Cell Lines
Intracellular flow cytometry for phosphorylated STAT1 (P-STAT1) was done as previously described using alexafluor488-labeled antibodies (18). Briefly, total levels of Tyr701-P-STAT1 were measured by flow cytometry on a FACS Caliber (BD Bioscience). A minimum of 10,000 gated events were analyzed for each sample. Data were expressed as specific fluorescence (Fsp = Ft - Fb), where Ft represents the median value of total staining, and Fb represents the median value of background staining with an isotype control antibody (19, 20).
Immunoblot Analysis
Lysates were prepared from melanoma cell lines stimulated with PBS or IL-29 and assayed for the expression of Jak-STAT and MAPK proteins by immunoblot as previously described (15, 19), with antibodies to p-AKT, p-ERK, pSAPK, poly(ADP-ribose) polymerase, and P-STAT1/2/3/5 (Cell Signaling Technology) or β-actin (Sigma).
Cytotoxicity Assays
Purified human NK cells were plated in 96-well V-bottom plates in 10% human AB medium supplemented with 10 to 1,000 ng/mL of IL-29 and incubated overnight at 37°C. 51Cr-labeled cells were added to wells at various effector:target ratios, and following a 4-h incubation at 37°C, supernatants were harvested for quantification of chromium release. Percentage of cell lysis was determined as previously described (21).
cRNA Preparation and Array Hybridization
Probe sets from U133 Plus 2.0 Arrays (Affymetrix), which query approximately 47,000 human transcripts, were used in these analyses. The cRNA was synthesized as suggested by Affymetrix. Following lysis of cells in TRIzol (Invitrogen), total RNA was isolated by RNeasy purification (Qiagen). cDNA was generated from 2 μg of total RNA using the Superscript Choice System according to the manufacturer's instructions (Invitrogen). Biotinylated cRNA was generated using the Bio Array High Yield RNA Transcript Labeling System (Enzo Life Sciences Inc.). The cRNA was purified using the RNeasy RNA purification kit. cRNA was fragmented according to the Affymetrix protocol, and the biotinylated cRNA was hybridized to microarrays. Raw data were collected with a GeneChip Scanner 3000 (Affymetrix; ref. 22).
PCR analysis was conducted to detect transcripts for IL-28R1 and IL-10R2 (the IL-29 receptor components). Briefly, total RNA was isolated using the RNeasy RNA Isolation Kit (Qiagen) and 2 μg of total cellular RNA was used as a template for reverse transcription-PCR (RT-PCR) with random hexamers (Invitrogen). The following primers were used for the PCR reaction: IL-10R2 F 5′ GGCTGAATT TGCAGATGAGCA 3′ and R 5′ GAAGACCGAGGCCAT GAGG 3′; IL-28R1 F 5′ ACCTATTTTGTGGCCTATCAGAGCT 3′ and R 5′ CGGCTCCACTTCAAAAAGGTAAT 3′. The amplification scheme used was as follows: 94°C for 5 min, then 35 cycles of 94°C for 45 s, 60°C for 45 s, and 72°C for 45 s, followed by 72°C for 7 min and then 4°C.
Real-time PCR was used to assess gene expression in melanoma cells that had been stimulated with either PBS or IL-29 (10–1,000 ng/mL) for 12 h. cDNA was prepared as described above and then used as a template for real-time PCR using predesigned primer/probe sets and TaqMan Universal PCR Master Mix (Applied Biosystems) according to the manufacturer's instructions. Real-time data were analyzed using the Sequence Detector software (version 2.2, Applied Biosystems).
Proliferation Assays and Evaluation of Apoptosis
Cell proliferation was measured using the MTT assay according to manufacturer's recommendations as previously described (23). Flow cytometric analysis of cells stained with Annexin V/propidium iodide staining was used to measure the percentage of apoptotic cells following various treatments (24).
In situ RT-PCR
Using the primers previously listed, seven benign nevi and eight melanoma lesions were tested for IL-10R2 and IL-28R1 mRNA expression using in situ RT-PCR (25, 26). Briefly, optimal protease digestion time was determined using nonspecific incorporation of the reporter nucleotide digoxigenin dUTP. Protease digestion was followed by overnight incubation in RNase-free DNase (10 U per sample; Boehringer Mannheim) and one-step RT PCR using the rTth system and digoxigenin dUTP. Following PCR, nitroblue tetrazolium and bromochloroindolyl phosphate were used to stain the tissue with nuclear fast red as the counterstain. Controls for the in situ PCR reaction included use of tissues negative for IL-28R1 and IL-10R2 (e.g., benign nevi and normal skin), omission of the primers (negative controls), and omission of the DNase step which yields an intense nuclear-based signal in all cell types. This is due to amplification of genomic DNA that has been exposed by the protease digestion step and serves as a positive control (25, 26). Images were taken with an Olympus DP-10 camera (Olympus) using a Nikon Labphotomat-2 microscope (Nikon) and adjusted with Adobe Photoshop CS4 (Adobe).
Linear mixed effects models were used to compare the levels of phosphorylated STAT1 (as determined by flow cytometry) for the various doses of IL-29 for each of the cell lines. Linear mixed effects models were used to model the dose-response relationship for the IL-29 and bortezomib/temozolomide combination experiments. As each experiment was run in triplicate, a random effect was included for each of the replications allowing for correlation in the response. For the combination experiments, doses were considered as categorical variables and the error was assumed linear in log(E/(1-E)) where E represents the fraction of cells surviving. Synergy was assessed via interaction contrasts at specific dose combinations. In addition, interaction indices were calculated based on Loewe additivity (27) and the median effect equation of Chou and Talalay (28). An index value of 1 indicates additivity of the two agents, whereas a value <1 indicates synergism. Fisher's exact test was used to determine significance of IL-29R expression in melanomas as compared with benign nevi. Results were considered significant if P < 0.05.
Human Melanoma Cell Lines Express IL-29 Receptor Transcripts
The expression of IL-28R1 and IL-10R2 was evaluated by RT-PCR in a panel of eight human melanoma cell lines. Each of the eight cell lines expressed the IL-10R2 mRNA; however, expression of the IL-28R1 subunit was variable between cell lines and was absent in the 1174 MEL cell line (Fig. 1A). These results were confirmed via semiquantitative real-time PCR. This analysis confirmed that both receptors were expressed in all the cell lines except 1174 MEL, which showed no expression of IL-28R1, and SK MEL 5, which had very low expression of IL-28R1 (Fig. 1B). In addition, real-time PCR was used to evaluate the presence of IL-10R1 and IL-20R1, receptors coexpressed with IL-10R2. Both receptors were found to be present in all eight melanoma cell lines (data not shown).
Melanoma cell lines express components of the IL-29 receptor. A, mRNA expression of the IL-29 receptor (IL-10R2 and IL-28R1) was evaluated using RT-PCR. 18s was used as a housekeeping gene. B, mRNA levels were measured by real-time PCR for the expression of IL-10R2 and IL-28R1 on the same cell lines and expression was calculated relative to 18s. The graph depicts a representative experiment of n = 2. Columns, mean of triplicate wells; bars, SD.
IL-29 Induces Jak-STAT Signal Transduction in Melanoma Cells
Melanoma cell lines were stimulated with IL-29 and the activation of downstream signal transduction pathways was evaluated. Following stimulation of melanoma cell lines for 20 minutes with IL-29 (10–1,000 ng/mL), phosphorylation of STAT1 (at Tyr 701) and STAT2 (Tyr 690) was induced in all the cell lines tested that expressed both IL-29R components (Fig. 2A). IL-29–induced phosphorylation of STAT1 was confirmed using intracellular flow cytometry (Fig. 2B and C). STAT1 and STAT2 phosphorylation in response to IL-29 was variable across the individual melanoma cell lines. For example, the 1106 MEL cell line exhibited strong induction of P-STAT1 and P-STAT2 following IL-29 treatment, whereas the A375 cell line required high doses of IL-29 to elicit maximal phosphorylation of STAT1 and STAT2. There was a statistically significant increase in P-STAT1 signaling in the 1106 MEL (P = 0.0003), A375 (P = 0.0014), and F01 cell lines (P = 0.0379) following treatment with 1,000 ng/mL IL-29 as compared with media treatment. There was no significant increase in Jak-STAT signaling in the 1174 MEL cell line in response to any dose of IL-29, which is consistent with its lack of the IL-28R1.
Melanoma cell lines signal via the Jak-STAT pathway. A, the human melanoma cell lines 1106 MEL, A375, F01, and 1174 MEL cells were treated with IFN-α at 104 units/mL or IL-29 at 10, 100, or 1,000 ng/mL and evaluated by immunoblot analysis for P-STAT1/2/3/5. Membranes were probed with β-actin antibody as a loading control. Human melanoma cell lines 1106 MEL, A375, F01, and 1174 MEL were stimulated with increasing doses of IL-29 (0–1,000 ng/mL) for 30 min at 37°C and cells were evaluated for P-STAT1 by intracellular flow cytometry. Fluorescence data are presented as Fsp intensity of P-STAT1 staining (Fsp = Ft - Fb). B, representative histograms for a single experiment and (C) graph for all cell lines evaluated. Columns, mean from a single experiment; bars, SD. D, protein levels of pAKT, pERK, and pSAPK were measured by immunoblot analysis after no treatment (0), or treatment with phorbol 12-myristate 13-acetate (50 ng/mL), or IL-29 (10, 100, 1,000 ng/mL).
Basal phosphorylation of the STAT3 and STAT5 transcription factors is common in melanoma cell lines and is thought to contribute to the oncogenic phenotype (29–33). As expected, there was basal phosphorylation of STAT3 in all of the cell lines except for 1106 MEL (20). However, in contrast to stimulation with IFN-α, stimulation of cells with IL-29 did not lead to a further increase in P-STAT3 except in the 1106 MEL cell line. Phosphorylation of STAT5 in response to IL-29 treatment was also observed in the 1106 MEL and 1174 MEL cell lines. Although 1174 MEL lacks the IL-28R1 component it does express the IL-10R2 subunit. We hypothesize that the interaction of the IL-10R2 component and other cytokine receptor components such as IL-10R1 or IL-20R1 may have led to the increased phosphorylation of STAT5. The ability of IL-29 to modulate the activation of AKT, ERK, and stress-activated protein kinase/Jun-amino-terminal kinase (SAPK/JNK) was also investigated in this panel of melanoma cell lines. There was no activation of these pathways irrespective of the dose of IL-29 employed (Fig. 2D).
Microarray Analysis of IL-29–Induced Gene Expression
Microarray analysis was conducted to determine the transcriptional profile of melanoma cells following IL-29 stimulation. The 1106 MEL cell line was stimulated for 5 or 18 hours with IL-29 (10 and 1,000 ng/mL) or PBS (control). The predominant genes expressed in response to IL-29 stimulation were IFN-stimulated genes (ISG; e.g., Mx1, OAS, IFI27; Table 1). This is consistent with prior studies conducted in IL-29–stimulated somatic cells (34). The number of genes induced increased both with increasing dose of IL-29 and with increasing duration of treatment. At the 18-hour time point there was upregulation of 60 genes as compared with the 41 genes that were upregulated at the 5-hour time point. For example, in response to a 5-hour treatment with IL-29 at doses of 10 and 1,000 ng/mL expression of radical s-adenosyl methionine domain containing protein 2 (RSAD2) increased by 21.1- and 48.5-fold, respectively, as compared with 19.7- and 84.4-fold following an 18-hour treatment. In response to a 5-hour treatment with 10 and 1,000 ng/mL IL-29, expression of 2′-5′-oligoadenylate synthetase 2 (OAS2) increased by 5.3- and 11.3-fold, respectively, as compared with 27.9- and 64-fold at 18 hours. In addition, IL-29 induced the expression of multiple ISGs that regulate transcription and apoptosis (e.g., MX1, IFI6, IFITM1, Pric 285, TLX2, IRF9, and IRF7).
Genes upregulated in response to IL-29
IL-29–Induced IFN Stimulated Gene Expression
Real-time PCR was done on three melanoma cell lines to confirm the expression of genes that were most strongly induced by IL-29 on microarray analysis. There was a marked increase in the expression of IFI27, RSAD2, OAS1/2, DDX58, ISG15, IFI6, IFIT3, IFTM1, and Mx1 in response to 10 to 1,000 ng/ml IL-29 for the 1106 MEL, A375, and F01 cell lines (Fig. 3A and B). Based on previous studies showing that overexpression of SOCS-1 protein in neuroendocrine and hepatoma cells abrogates IL-29–induced Jak-STAT signaling (12, 13), the expression of SOCS genes was tested. SOCS-1 was upregulated 2.0-fold in the F01 cell line in response to IL-29 and SOCS-4 was downregulated by 0.5-fold. SOCS-6 was induced by 1.0- to 1.6-fold in all cell lines (Fig. 3B).
IL-29 induces transcription and protein expression of IFN-stimulated genes. Transcript levels of various genes were measured using real-time PCR analysis after the treatment of 1106 MEL, A375, and F01 human melanoma cell lines with IL-29 at 10 to 1,000 ng/mL for 12 h (A) or 1,000 ng/mL for 12 h (B). Columns, mean from three separate experiments; bars, SD.
IL-29 Does Not Enhance NK Cell Cytotoxicity against Melanoma Target Cells
Because immune effector cells are known to express IL-28R1 and IL-10R2 and respond to IL-29, we postulated that this cytokine could potentially prime NK cells to mediate enhanced lysis of tumor cells. To test this hypothesis, NK cells were treated overnight with IL-29 and tested for their ability to lyse a panel of three melanoma tumor cell lines in a standard 4-hour 51Cr release assay. IL-29 did not enhance NK cytotoxic activity in this setting, despite the fact that NK cells were found to express both IL-10R2 and IL-28R1 and to induce Jak-STAT signal transduction (data not shown). Similar results were found with IL-29–treated peripheral blood mononuclear cells against the F01 cell line. In addition, melanoma cells pretreated with 1,000 ng/mL of IL-29 exhibited no change in their susceptibility to NK cell–mediated cytotoxicity (data not shown).
IL-29–Induced Apoptosis of Melanoma Cells Is Enhanced in the Presence of Bortezomib (a Proteasome Inhibitor) or Temozolomide
There was no change in the proliferation of melanoma cell lines following a 24- to 72-hour treatment with IL-29 (10–1,000 ng/mL) as assessed by either the MTT or [H3]thymidine incorporation methods (data not shown). The ability of IL-29 to induce apoptosis was next assessed in the F01 melanoma cell line. Flow cytometric analysis by Annexin V/propidium iodide staining revealed a dose-dependent increase in apoptosis in response to 48-hour treatment with IL-29 (Fig. 4A). Based on previous work showing that proteasome inhibition could enhance the proapoptotic effects of IFN-α in melanoma cells (24), the apoptosis of F01 cells was measured following treatment with IL-29 in combination with bortezomib. As expected, IL-29–induced apoptosis was enhanced following exposure to bortezomib (Fig. 4B). Chou and Talalay interaction indices were calculated for the combination of IL-29 and bortezomib (index values = 0.36–1.03). At the 20 nmol/L dose of bortezomib this combination induced synergistic apoptosis of F01 cells which was statistically significant (P < 0.018 for all dose levels). For example, IL-29 at 10 ng/mL induced 8.8% apoptosis and bortezomib at 20 nmol/L induced 50% apoptosis, whereas the combination caused apoptosis in 83% of the cells. Apoptosis was enhanced in response to these treatment combinations as confirmed by immunoblot analysis for the presence of cleaved poly(ADP-ribose) polymerase (Fig. 4C). A similar synergistic apoptotic effect was observed following treatment of F01 cells with temozolomide plus IL-29 (Fig. 4D). Synergistic apoptosis occurred with IL-29 at concentrations of 100 and 1,000 ng/mL at all doses of temozolomide (all interaction contrast P values <0.003, interaction indices = 0.003–0.18). For example, single-agent IL-29 at 1,000 ng/mL caused 15.2% apoptosis and single-agent temozolomide at 150 μmol/L caused 15.7% apoptosis. The combination resulted in 52.2% apoptosis, which was greater than the combined effects of both agents. Marginally significant synergy took place in response to IL-29 at 10 ng/mL and temozolomide at 50, 100, and 150 μmol/L (all interaction contrast P values <0.056, interaction indices = 0.03–0.82).
IL-29 treatment with and without chemotherapy increases apoptosis in the human melanoma cell line F01. A, the proapoptotic effects of IL-29 were evaluated by Annexin V/propidium iodide (PI) staining in the human melanoma cell line F01 after a 48-h treatment. Columns, mean from three separate experiments; bars, SE. B, F01 cells were cultured with IL-29 (10–1,000 ng/mL) combined with bortezomib (10–20 nmol/L) for 48 h. Cells treated with PBS served as a negative control in each assay. Apoptosis was measured using Annexin V/PI staining. Columns, mean of three separate experiments; bars, SE. C, lysates from IL-29 and bortezomib-stimulated F01 cells were evaluated for poly(ADP-ribose) polymerase cleavage expression via immunoblot analysis. β-actin served as a loading control. D, similarly, treatment with temozolomide (0–150 μmol/L) and IL-29 (100–1,000 ng/mL) at 48 h led to synergistic apoptosis as measured by Annexin V/PI staining. Columns, mean from three separate experiments; bars, SE.
Primary Melanomas Express the IL-29 Receptor
Paraffin-embedded tissue samples of benign nevi and primary melanoma lesions were evaluated for expression of the IL-29R components by in situ PCR (Fig. 5). Seven benign nevi were examined and all were negative for both components of the IL-29R. Six of eight primary melanoma lesions were positive for both receptor components and two primaries were negative for both components of IL-29R (P = 0.007 versus benign nevi). The signal localized primarily to the cytoplasm of the neoplastic cells.
Melanoma cells show increased transcription of the IL-29 receptors. The cDNA of the mRNA of IL-10R2 and IL-28R1 were detected via in situ PCR amplification. Benign nevi were negative for IL-10R2 and IL-28R1. Cytoplasmic signals for IL-10R2 and IL-28R1 were present in melanoma lesions but not in benign nevi. Left, receptor staining; right, negative control. Magnification, ×40; scale bars, 25 μ.
It is shown in the present study that the receptor components needed for IL-29 signal transduction are present on several human melanoma cell lines. In cells with intact IL-29R signaling machinery (IL-28R1 and IL-10R2), IL-29 treatment led to phosphorylation of STAT1 and STAT2 and an increase in the expression of genes involved with the antiviral response, immune response, and regulation of transcription. IL-29–induced apoptosis in a melanoma cell line was synergistically enhanced following the addition of temozolomide or bortezomib. Additionally, the receptor for IL-29 was found to be present on human melanoma primaries but not on benign nevi.
The receptor components for IL-29 are present on dendritic cells, T cells, intestinal epithelial cells, and several human cancer cell lines (6–12). Brand et al. evaluated signal transduction of intestinal epithelial cells stimulated with IL-29. They found that IL-29 activated the ERK-1/2, SAPK/c-JUN, AKT, and Jak-STAT pathways (6, 8). Other authors have shown Jak-STAT pathway signaling in neuroendocrine tumors (12), human keratinocytes (35), and hepatoma cells following treatment with IL-29 (9, 36). In a murine model, Sommereyns et al. found that IFN-λ (mouse ortholog of IL-29) was strongly induced in the liver in response to viral infections. They also showed that mice with systemic viral infections expressed IFN-λ and this resulted in a marked increase in IFN-stimulated genes in the stomach, intestines, and lungs (37). The present article is the first to report the presence of IL-29R in human melanoma cells and delineate the signal transduction pathways that are initiated in response to this cytokine. The induction of P-STAT1, P-STAT2, P-STAT3, and P-STAT5 in response to IL-29 suggests a complex yet robust effect. The lack of MAP-kinase activation in IL-29–treated melanoma cells was unexpected and is being confirmed in additional cell lines.
Prior studies have evaluated the response of lymphoma and hepatocellular carcinoma cells to IL-29 stimulation via microarray analysis and have shown an upregulation of multiple ISGs (9, 38). Using Affymetrix S130 high-density microarray chip analysis, Zhou et al. showed lower induction of ISGs in IFN-λ–stimulated Raji cells (10 ng/mL) compared with IFN-α–stimulated cells (38). In contrast, ISG induction by IL-29 was stronger than that of IFN-α in human hepatitis C virus-transfected hepatoma cells (36). Our studies showed an increase in antiviral proteins such as OAS and Mx1 along with many other immune and antiproliferative proteins. A prior study by our group evaluating the effects of high-dose IFN-α treatment on the expression levels of genes in the peripheral blood mononuclear cells of patients with malignant melanoma showed a pattern of gene induction that was similar to that observed in the present study (39). These results lend support to the idea that IL-29 and IFN-α induce a similar set of genes and therefore could have similar antitumor effects. Several studies have shown that type III IFNs and IFN-α have overlapping antiviral activity (9, 14, 40, 41). Overall, the antiviral effects of IL-29 are slower in onset, weaker, and last longer than those of IFN-α (7, 35, 36). IL-29 acts in an additive manner when combined with IFN-α in blocking the replication of vesicular stomatitis and hepatitis C virus (42). The precise role of IL-29 in host antitumor responses and immune surveillance has yet to be defined in the context of malignant melanoma, but the available data suggest that its effects are similar to those of IFN-α. Studies by other groups have shown that IL-29 inhibits proliferation in glioblastoma cells (7) and both inhibits proliferation and induces apoptosis in a human neuroendocrine cell line (12). Whether IL-29 has unique antitumor effects or can exert additive effects with IFN-α in the setting of malignant melanoma is currently under investigation.
Only a limited amount of in vivo work has been done to evaluate the effects of IL-29 in melanoma. In a transient transfection model, Sato and colleagues showed that overexpression of the murine IFN-λ receptor ligand in B16F10 cells caused increased expression of MHC class I. Additionally, they found that the transfected cell line had lower levels of proliferation and exhibited significantly enhanced activation of caspase 3 and caspase 7 at 36 hours. The induction of p21 and dephosphorylated Rb was also enhanced (as compared with mock transfected cells; ref. 41). Administration of IFN-λ–expressing B16F10 cells to mice via tail vein injection led to decreased pulmonary metastases at 14 days and reduced mortality as compared with control mice. This effect was dependent on NK cells, but not on CD4+ and CD8+ T-cells (41). In a separate study, Sato et al. showed that systemic overexpression of IFN-λ by hydrodynamic injection of IFN-λ cDNA resulted in increased numbers of NK and NKT cells in the livers of mice and resulted in antitumor activity against a colon cancer cell line (41). The applicability of these findings to the clinical situation is unclear as there are no reports of IL-29 being produced by human melanoma cells, although it might be present in the tumor microenvironment under certain conditions. Our analysis of primary melanomas indicates that these lesions routinely express the receptor components for IL-29 and would likely respond to IL-29 treatment with the induction of ISG transcription.
Like IFN-α, IL-29 activates several components of the immune system. IL-29 stimulates monocytes and macrophages to release cytokines (e.g., IL-6, IL-8, and IL-10) resulting in a shift from a type II T helper cell response to a type I T helper cell response (11). Similarly, exposure of lipopolysaccharide-treated monocytes to IL-29 enhances the release of IL-12 (43, 44). IFN-λ treatment resulted in increased expression of the MHC class I proteins in human keratinocyte and murine melanoma cell lines (14, 41), an effect that could enhance their recognition by T cells. Of note, IL-29 treatment of NK cells did not enhance their cytotoxicity against melanoma cells nor did IL-29 treatment of melanoma target cells render them more susceptible to lysis by NK cells (data not shown).
We hypothesized that IL-29 could render melanoma cells more susceptible to proapoptotic therapies such as chemotherapy or radiation therapy. Temozolomide has documented activity against metastatic melanoma and bortezomib has been tested in this setting as well (24, 45). IL-29 enhanced the apoptotic effects of both drugs, which suggests that combination therapies might be clinically effective. Of note, not all melanoma cell lines responded equally well to these combinations. Additional studies are underway to determine the cause of this variation.
We have shown that the receptor for IL-29 is expressed on melanoma cell lines and that activation with this cytokine leads to Jak-STAT signal transduction, expression of multiple genes, and an increase in apoptosis. The addition of either bortezomib or temozolomide resulted in a synergistic enhancement of apoptosis. Primary melanomas showed increased expression of the genes for IL-29R as compared with benign nevi. The present data suggest that the IL-29 can exert direct effects on melanoma cells.
No potential conflicts of interest were disclosed.
We thank the Ohio State University Comprehensive Cancer Center Analytic Cytometry, Centers for Biostatistics, Microarray, and the Nucleic Acid Shared Resources for their assistance.
Grant Support: NIH Grants P01 CA95426 (M. Caligiuri), P30 CA16058 (M. Caligiuri), CA84402, K24 CA93670 (W.E. Carson, III); K22 CA134551 (G.B. Lesinski), The Valvano Foundation for Cancer Research (G.B. Lesinski), T32 CA009338.
Revision received December 8, 2009.
Accepted December 21, 2009.
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. SOCS-1 inhibits expression of the antiviral proteins 2′,5′-OAS and MxA induced by the novel interferon-lambdas IL-28A and IL-29. Biochem Biophys Res Commun 2005;331:543–8.
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Kondadasula SV,
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. Colocalization of the IL-12 receptor and FcγRIIIa to natural killer cell lipid rafts leads to activation of ERK and enhanced production of interferon-γ. Blood 2008;111:4173–83.
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. The activation of natural killer cell effector functions by cetuximab-coated, epidermal growth factor receptor positive tumor cells is enhanced by cytokines. Clin Cancer Res 2007;13:6419–28.
Benninger K,
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. Bortezomib pre-treatment prolongs interferon-α-induced STAT1 phosphorylation in melanoma cells. Cancer Immunol Immunother 2009;58:2031–7, Epub 2009 Apr 26.
Crespin T,
. Multiparametric flow cytometric analysis of inter-patient variation in STAT1 phosphorylation following interferon Alfa immunotherapy. J Natl Cancer Inst 2004;96:1331–42.
Trefry J,
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. Melanoma cells exhibit variable signal transducer and activator of transcription 1 phosphorylation and a reduced response to IFN-α compared with immune effector cells. Clin Cancer Res 2007;13:5010–9.
Lehman A,
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. Interleukin-21 enhances NK cell activation in response to antibody-coated targets. J Immunol 2006;177:120–9.
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. Psychological, behavioral, and immune changes after a psychological intervention: a clinical trial. J Clin Oncol 2004;22:3570–80.
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. IFN-α and bortezomib overcome Bcl-2 and Mcl-1 overexpression in melanoma cells by stimulating the extrinsic pathway of apoptosis. Cancer Res 2008;68:8351–60.
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. In situ detection of mature microRNAs by labeled extension on ultramer templates. Biotechniques 2009;46:115–26.
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. In situ detection of precursor and mature microRNAs in paraffin embedded, formalin fixed tissues and cell preparations. Methods 2008;44:39–46.
Loewe S,
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Burdelya L,
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. Stat3 activity in melanoma cells affects migration of immune effector cells and nitric oxide-mediated antitumor effects. J Immunol 2005;174:3925–31.
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. Regulation of the innate and adaptive immune responses by Stat-3 signaling in tumor cells. Nat Med 2004;10:48–54.
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. STAT5 contributes to interferon resistance of melanoma cells. Curr Biol 2005;15:1629–39.
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. Activation of stat3 in human melanoma promotes brain metastasis. Cancer Res 2006;66:3188–96.
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. Stat3 activation regulates the expression of matrix metalloproteinase-2 and tumor invasion and metastasis. Oncogene 2004;23:3550–60.
Uze G,
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. IL-28 and IL-29: newcomers to the interferon family. Biochimie 2007;89:729–34.
Maher SG,
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. IFN-α and IFN-λ differ in their antiproliferative effects and duration of JAK/STAT signaling activity. Cancer Biol Ther 2008;7:1109–15.
Marcello T,
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. Interferons α and λ inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics. Gastroenterology 2006;131:1887–98.
Sommereyns C,
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. IFN-λ (IFN-λ) is expressed in a tissue-dependent fashion and primarily acts on epithelial cells in vivo. PLoS Pathog 2008;4:31000017.
Zhou Z,
Hamming OJ,
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. IFN-α-2b-induced signal transduction and gene regulation in patient peripheral blood mononuclear cells is not enhanced by a dose increase from 5 to 10 megaunits/m2. Clin Cancer Res 2008;14:1438–45.
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. Antitumor activity of IFN-λ in murine tumor models. J Immunol 2006;176:7686–94.
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. Interleukin-29 functions cooperatively with interferon to induce antiviral gene expression and inhibit hepatitis C virus replication. J Biol Chem 2008;283:30079–89.
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. Modulation of the human cytokine response by interferon λ-1 (IFN-λ1/IL-29). Genes Immun 2007;8:13–20.
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You are going to email the following Interleukin-29 Binds to Melanoma Cells Inducing Jak-STAT Signal Transduction and Apoptosis
Mol Cancer Ther February 1 2010 (9) (2) 510-520; DOI: 10.1158/1535-7163.MCT-09-0461


Dalam hidup jika tidak ditunjang oleh kondisi kesehatan mental dan fisik yang prima. Shoot I have never exercised in 6 weeks and got here online in search of my favourite fitness fashions for inspiration and glad to read that Lisa is glad along with her family. I'm wondering if Lisa ever developed a niche following within the form of a online fan club that someone may have wished to start out if she had placed much greater in at the very least some of the fitness contests she was in such because the Olympia. Fitness is all the pieces from correct vitamin to emphasize reduction to the flexibility to sleep soundly.
Slide the drill up and down in the holes a number of instances to get smooth edges, then test to ensure that the dowel rod will slide in smoothly. That method, it is not out of website out of thoughts, you see those items of worthwhile info and it'll function an necessary visible reminder to diligently follow your fitness routine. Encouraging clients to mix up their fitness program and try different activities is what retains us energetic and healthy. Just as a fitness professional would by no means simply advocate target firming, so too, a fitness professional would continue to encourage correct kind. She was trained by bodybuilder Augustine Lee and in 2005, she and Augustine went into business together and opened Fitness Factory in the Boat Quay space in Singapore.
So too, along with your well being, do go to your medical skilled after which start your fitness program targeting firming your stomach muscle tissues in tandem with an train program that takes into consideration your whole physical wants from nutrition to exercise to the train that your heart and lungs need.
I believe its good to see more female fitness fashions out there doing the job right! Not everyone available in the market for an excellent fitness app wants to depend energy or get coached by way of a fast workout. After you've been cleared, do give these many actions a attempt to dedicate yourself each day to a fitness challenge to target tone your belly muscular tissues. Proving that good issues actually do come in small packages we have now Filipino fitness magnificence Khay Rosemond. She has also been featured in featured in Oxygen, Muscle and Fitness, FLEX and Ironman fitness magazines. I feel Jennifer Nicole Lee is probably one of the vital lovely fitness models on the market. Vixen Workout's intense Hip-Hop cardio has taken the dance fitness scene by storm.
Having greater muscle energy enhances bodily fitness as a result of it permits you to extra easily carry out tasks similar to pushing, pulling and lifting. She has had first place wins at the 2016 IFBB Australasia Bikini Model Masters Champion 35s+, Arnold Traditional Australian Bikini Masters 35s+, IFBB Gold Coast Traditional Bikini Masters 35s+, and the INBA Fitness Bikini Model 30s+ just to name just a few. Fitness professional and avid fitness purchasers choose the stability ball due to the added challenge to the core – it's important to use your core to stabilize the ball – you do not have interaction your core muscle groups as much with a chair or weight bench. Di space fitness terdapat ruang kelas tambahan, ruang ganti pakaian, kamar mandi, dan health bar. As a fitness model, Trish first showed up in the pages of MuscleMag Worldwide.


text:
Q: PlatformNotSupportedException when trying to create a TransactionScope with multiple DbContext with same connection string I have multiple DbContext in the same ASP.NET Core website with Entity Framework Core and I want to create a transaction so that if SaveChanges fails in one context any changes on the other contexts are rolled back. These DbContext all have the same connection string, therefore they are connected to the same database.
However, when I try to create a TransactionScope, I get a PlatformNotSupportedException that says distributed transactions are not supported. But all DbContext are connected to the same database! Is there any way to create a TransactionScope with multiple DbContext connected to the same database without creating a distributed transaction?

redpajama_set_name: RedPajamaStackExchange


text:
Month 1 - Exploring how and why 'giving' makes us happy
Zoe Flint
Life Coach, Hypnotherapist and Founder of the Colchester Happiness Project, ZoeFlint.com
"Am I in the right place?"
"I have no idea, Heidi" I said as I shovelled my remaining sandwich into my mouth "I haven't even left the house yet. What's the time?"
"Quarter to"
"Crap…I'm on my way"
That was how my first happiness club began. I would love to be able to tell a story of how organised and prepared I was, of how the lead up to Sunday was all beautifully and effortlessly managed; but that's just a fantasy. It's just not me. I am and will forever be (as my mother would say) a 'last minute Minnie'.
Thankfully I did manage to get to our meeting point, the gorgeous Castle Park in Colchester, in time to meet this months happiness explorers to talk about and trial how 'giving' can make us happy.
Prior to meeting, we had all chosen a book that had impacted on us in a positive way, and registered it on the Bookcrossing.com website. Discovering bookcrossing was like uncovering a whole new world. If you haven't heard of it, it's a way of donating your preloved books but also of tracking the journey they make across their lifetime. You register your book and are given an ID number. You write this on the inside cover with a little message and release it into the wild (leave it somewhere) a park bench; a café; a train station, for example. Then sit back and wait for a little alert that your book has been 'caught' and read messages from the person who caught it. It's joyous and took me back to a long forgotten and childlike feeling of the wonder of magical lands and treasure trails.
A group of eight of us (plus one gorgeous two year old) shared details of the books we had chosen and why they were important to us. The two year old didn't; she can't read. As people shared their stories a kind of stillness fell over the group as we listened to each other intently. There's something so powerful about really listening to each other, it was almost tangible.
We then had some more tea (well, we are British) and started to talk in depth about the power of giving, how it makes us feel and in what ways we can take action to give more during the following month. This is where the discussion got really interesting. We talked about the things we had done and the things others had done for us that made us really happy, and a three key themes emerged as the ingredients for giving with joy:
1. Have no expectation of the gift being reciprocated
Be it time, money or even just a phone call, giving feels best when we do it without any expectations and purely for the joy of making someone else's day.
2. Give small things - preferably through the post!
This isn't about grandiose gestures, but tapping in to that feeling of getting a postcard or a note from a friend, for no reason, other than to let them know you think they are great.
3. Give things with real thought
Remembering your friend has a hospital appointment and sending them a text to check how they got on; the sorts of day to day stuff we forget about but that's really important.
We all agreed that when we give in this way, we are filled with a genuine and lasting sense of happiness that's hard to beat.
Before we all left to release our books into the wild we each made a pledge; something we would do in the month ahead to give more. It was at this point it dawned on me that in all the planning and preparation for the group, it hadn't occurred to me to think about how I would give more. Suddenly on the spot, I pledged to give a little more of my thoughts and time to those closest to me; the odd text or call just to say hi. I know I can be guilty of taking for granted some of my nearest and dearest and want to remedy this, and see what difference it makes.
Some of the other club members had clearly given this much more thought than me, and came up with some wonderful pledges. Eddie (who happens to have a very large garden) pledged to create a community gardening project, allowing people to use his land to grow and share produce. But my favourite was from Bronwyn, who pledged to make a pack of little postcards saying something very simple and along the lines of 'I think you are Ace' and sending them to her friends.
We left our little happiness club in a bit of a happy bubble, grateful of the reminder of the things that are truly important in life, and how the gift of giving just keeps on giving.
Look out for next months happiness club blog for the results of our experiment in giving and follow the Colchester Happiness Project on Facebook.
Facebook ZoeFlintHypno
Twitter zoeflintcoach
Website zoeflint.com
Donna Booth
Love this Zoe! I would love to know where all your books ended up x x
Yes, Yes And Yes!
Psychologies Ambassadors , Self, 360me, The Happiness Club , The Great Wake Up, How To Achieve Your Goals, Happiness Book Club
Gaelle Berruel
Guided Visualisation | Vision for 2022 | Shamanic Journey | Connecting with Our Higher Self
Barefoot Coaches' Channel , Self, 360me, The Happiness Club , The Great Wake Up, Work, How To Achieve Your Goals, Money, Family & Relationships , Women in Business Expo TV
Verónica Moreno
It May Be Your Word For 2022
Psychologies Ambassadors , Self, 360me, The Happiness Club , The Great Wake Up, Work, How To Achieve Your Goals
The power of progesterone – why you need it and how to get it!
360me, The Happiness Club , The Great Wake Up
Nicki Williams


Former U.S. Attorney-General Ramsey Clark, along with LaRouche's wife Helga Zepp-LaRouche while defending the "LaRouche case" at the CSCE conference on "Human Rights" in Copenhagen, on June 21, 1990.
1. 1983 WORLD WAR III THREAT IS A HOAX, by Lyndon H. LaRouche, Jr.; EIR; October 28, 1988.
2. THE DANGER OF GENERAL WAR, by Lyndon H. LaRouche, Jr.; Pamphlet; July 18 1976.
3. HOW A SOCIALIST QUARTERLY DRIFTS TOWARD FASCISM, by Lyndon H. LaRouche, Jr.; The CAMPAIGNER, Vol. 14, n°2; April 1981.


One of the most common reasons that leads people to seek counselling is in response to a bereavement or a loss in their life. This could be the death of a friend or loved one, a much loved pet, loss of a job, a relationship or sudden change in one's financial or health circumstances. The common denominator for all of these is that something central to one's life has been lost or altered and that it's a struggle to come to terms with it.
What causes my nails to grow thick and discoloured?
There are many reasons, let's look at a few.
A lifetime of trauma. Many sporting activities cause repetitive damage to the nails and over time the area where the nails are formed (the matrix) decides it needs to toughen up the nails to compensate. Thicker nails refract the light differently so you no longer see the pinkish normal nail colour.
If you are pregnant have you ever asked yourself any of the following questions?
Is there anything that can help with this morning sickness?
What can I do about the aches and pains I have, that are only getting worse as the baby gets bigger?
Will I go into labour spontaneously or will I need help?
Is there anything my partner and myself can do to help me during labour?


text:
Q: SocketIO – connection issues and clustering I have a really simple NodeJS app that I want to run on Heroku. This is how the index.js file looks like:
Server (port 3030)
const http = require('http');
const os = require('os');
const express = require('express')
const throng = require('throng'); // For cluster management
const { port, env, isProduction } = require('./config/vars');
const SocketIO = require('socket.io');

// Setting up a simple express app and wrapping it with http server
const setupServer = () => {
  const app = express();

  app.use(express.static(path.join(__dirname, '../public')));

  const server = http.createServer(app);
  return server;
};

const setupSocket = (server) => {
  const io = new SocketIO(server);
  io.on('connection', (socket) => {
    console.log(`[Socket] Connection established: ${socket.id}`);
    socket.on(msg.rooms.join, (room) => {
      socket.join(room);
      socket.to(room).emit(msg.rooms.joined);
      console.log(`[Socket] User ${socket.id} joined '${room}' room`);
    });
    socket.on('disconnect', () => {
      console.log(`[Socket] Distonnected: ${socket.id}`);
    });
  });
  return io;
};

const WORKERS = (() => {
  if (!isProduction) return 1;
  return process.env.WEB_CONCURRENCY || os.cpus().length;
})();

async function master() {
  console.log(`Preparing ${WORKERS} workers...`);
  console.log('Master started.');
}

// There should be one server instance for each worker
const start = () => {
  const server = setupServer(); // Returns and `http` server instance
  const socket = setupSocket(server);
  server.listen(port, async () => {
    Logger.info(`Server – listening on port ${port}`);
  });
  return server;
};

const instance = throng({
  workers: WORKERS,
  lifetime: Infinity,
  start,
  master,
});

module.exports = instance;

Client (port 3000)
const setupSocket = ({ room }) => {
  // Fallback if already setup
  if (window.sockets[room]) {
    return window.sockets[room];
  }
  const socket = io('http://localhost:3030');
  socket.on('connect', () => {
    console.log('[Socket] Connection established!', socket.id);
    socket.emit('room.join', room);
  });
  socket.on('room.joined', () => {
    console.log(`[Socket] Connected to ${room} room!`);
  });
  window.sockets[key] = socket;
  return socket
};

The problem – the connection is sometimes established properly but most of the time I get an error
Error during WebSocket handshake: Unexpected response code: 400

What might be the problem here? Is it because I have it on two different ports or is it because of the clusters?
I've tried removing the throng part of the code, and just calling start() method without any cluster setup, but the problem remains :(

A: why would you use http module? The server instance that you send in the socketIO constructor should be the return object of the expressInstance.listen
Something more like this:
const express= require('express')
const app = express()
const socketio = require('socket.io')

app.use(express.static(__dirname + '/public'))

const server = app.listen('4000',()=>{
   console.log('Listening to port:4000')
})
const io = socketio(server)

io.on('connect',(socket)=>{

   socket.broadcast.emit('new_user')

   socket.on('new_message',(message)=>{
      io.emit('new_message',message)
   })

})

source code: socket-io chat


At St Anne's we are an all through primary school and therefore only admit children to Y3 as out of rounds/in year admissions. Places for September 2018 will be decided after 11th June 2019.
Return SIF to the school office together with a copy of your child's baptismal certificate and proof of address by Friday 8th June 2019 latest.


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1. SSSRA reserves the right to determine participant appropriateness for programs and special events.
2. When arriving and departing a program, parents/guardians/group home staff are required to notify the program supervisor.
3. If a participant cannot attend a program, he/she cannot send a substitute in their place.
4. When participants of varying ages and ability levels are in the same program, SSSRA will group them appropriately.
5. SSSRA provides an approximate 1:4 staff-to-participant ratio.
6. While SSSRA staff will assist participants with their belongings at programs, SSSRA cannot be responsible for lost or stolen property. Participants should not bring valuables to programs.
7. Vacation Trips, Weekend Trips, and Overnights: Participants must have independent self-help skills, be able to function in a 1:4 staff to participant ratio, and have participated in SSSRA weekly programs.
8. With your child's best interest in mind, parents are invited to their child's first program meeting. Our instructors have found that parent and/or sibling distractions during the program time affects the quality of their instruction. Our instructors always welcome the opportunity to discuss a participant's progress with parents at any time.


It's the weekend before Easter and Earth Day.
That means you can find events and things to do across the Treasure Coast celebrating these holidays before they happen.
The 15th annual Earth Day Festival is 10 a.m. to 3 p.m. Saturday at Oxbow Eco-Center at 5400 N.E. St. James Drive in Port St. Lucie.
The festival features exhibitions that include the Treasure Coast Wildlife Center, animal handler Reptile Riff, the Friends of Savannas Preserve State Park, the Florida Fish and Wildlife Conservation Commission, Florida's aquatic preserves, the Treasure Coast Beekeepers Association, Tinkergarten children's activities, the University of Florida's Institute of Food and Agricultural Sciences Extension, the St. Lucie Cultural Alliance, St. Lucie County's Environmental Resources Department, Florida Atlantic University's Harbor Branch Oceanographic Institute, the Smithsonian Marine Station at Fort Pierce and the Florida Oceanographic Society. Plus, there is live entertainment, as well as food and beer for sale.
Admission is free. Carpool, kayak or bicycle to the event to reduce your ecological footprint. Trolley service to and from the event is available from 8 a.m. to 4 p.m. at Calvary PSL at 5555 N.W. St. James Drive. The event is rain or shine. No dogs allowed. For more information, call 772-785-5833 or go to www.stlucieco.gov.
The Spring Community Mixer and Egg Hunt is 10 a.m. to noon Saturday at the 10th Street Community Center at Guy Davis Sports Complex at 724 S.E. 10th St., in Stuart. Hunt areas are divided into four groups: ages 4 and younger, ages 5-7, ages 8-10 and ages 11-12. The event also includes golden eggs, face painting, carnival games, inflatable games, popcorn, snow cones and a free hot dog lunch. Admission is free. For more information, call 772-288-5340.
The City of Vero Beach Recreation Department's 59th annual Easter Egg Hunt is 10-11 a.m. Saturday at Mulligan's Beach House at 1025 Beachland Blvd. The event includes a beachside egg hunt, golden egg winners, a jellybean guessing contest and a visit from the Easter Bunny. The hunt for kids ages 9 and younger is free. Bring six empty plastic eggs for donation. For more information, call 772-770-6517 or go to www.covb.org.
The Easter Eggstravaganza is 10:45 a.m. to 2 p.m. Sunday at the First United Methodist Church at 1500 S. Kanner Highway in Stuart. The event includes an Easter egg hunt starting at 12:30 p.m., a bounce house, games and crafts, as well as barbecue and snow cones for sale. Admission is free. For more information, go to www.facebook.com/fumcstuartkids.
Hopping for a Cure is noon to 4 p.m. Sunday at Walking Tree Brewery at 3209 Dodger Road in Vero Beach. The event includes a petting zoo, crafts, games, pony rides and a visit from the Easter Bunny, as well as beer discounts for parents. Admission is a $5 donation to benefit the St. Baldrick's Foundation of Indian River County. For more information, call 772-217-3502 or go to www.facebook.com/walkingtreebrewery.
The 16th annual Hibiscus Festival is 10 a.m. to 6 p.m. Saturday and 10 a.m. to 4 p.m. Sunday along 14th Avenue in downtown Vero Beach. The Miss Hibiscus Pageant is 7-9 p.m. Thursday at the Heritage Center at 2140 14th Ave.
The festival, which is celebrating the city's centennial this year, features more than 50 artists displaying art, a children's art show, live music, entertainment, food for sale and children's activities. Plus, the 10th annual Shopping Cart Parade food drive starts at 1 p.m. Friday and benefits United Against Poverty.
Also, the fifth annual Hibiscus Ride starts at 9 a.m. Saturday and travels from American Icon Brewery to Ocean Grill to Waldo's to McKee Botanical Garden. It features speakers and local historians sharing interesting facts and information at each destination.
The cost for the ride is $25 and includes a shirt. To register, go to hibiscusbikeride.eventbrite.com. For more information, call 772-299-1383 or go to mainstreetverobeach.org/hibiscus-festival.
Citizen Science Day is noon to 4 p.m. Saturday at the Environmental Learning Center at 255 Live Oak Drive, north of Vero Beach.
The day includes quick canoe trips, seining activities, making birdhouses and rain barrels, rescued wild birds, booths showcasing projects, demonstrations, and science talks and workshops. Researchers explain why they need citizens to help with critical projects, such as spotting otters, tracking bats and birds or identifying invasive plants and reptiles.
Admission is free. Canoe trips and seining require close-toed water shoes. Seining is from 1-3 p.m. For more information, go to www.discoverelc.org/citizen-science-day.
Sailfish Brewing Company's sixth anniversary block party starts at 2 p.m. Saturday and lasts until midnight at 130 N. Second St., in downtown Fort Pierce. Kegs are tapped when doors open at 11 a.m.
Four live bands play at different times throughout the day on a stage set up on Second Street, which is shut down between Marina Way and Orange Avenue. Plus, there are beer releases, outdoor bars, street games, artists, vendors, children's activities and food for sale from The Crafted Pie and 2nd Street Bistro.
Plant City Poptart kettle sour treated with strawberries from Plant City, vanilla and lactose.
An unnamed blueberry kettle sour treated with blueberries from Double C Bar Ranch in Kenansville and cinnamon.
Blackberry Bramble kettle sour treated with blackberries from Bramble Creek Farms in Brooksville, limes from the Florida Research Center for Agricultural Sustainability in Vero Beach and mint.
Passing Lane kettle sour treated with pineapples from Nature Farms in Sebastian, limes from the Florida Research Center for Agricultural Sustainability in Vero Beach and honey from Hani Honey Company in Stuart.
Zest-A-Peel kettle sour treated with honeybells and Rangpur limes from the Florida Research Center for Agricultural Sustainability in Vero Beach.
PBS kettle sour treated with blackberries from Bramble Creek Farms in Brooksville, blueberries from Double C Bar Ranch in Kenansville and peaches from Vero Beach.
Admission is free. For more information, go to www.facebook.com/sailfishbrewingcompany.
The Winery Comedy Tour is 7-9 p.m. Friday at Summer Crush Vineyard & Winery at 4200 Johnston Road, north of Fort Pierce. Gates open at 5:30 p.m. Food is for sale from 6-7 p.m. Tickets are $15 each.
Then, the Horsin' Around in the Vineyard: Mustang and All-Ford Car, Truck & Art Show is noon to 4 p.m. Sunday. Admission is free to spectators. Food trucks are available. For more information, call 772-460-0500 or go to www.summercrushwine.com.
St. Andrew's Episcopal Academy Community Family Day is 12:30-4 p.m. Sunday at 210 S. Indian River Drive in Fort Pierce.
The riverfront campus is filled with children's sports, an obstacle course challenge, arts and crafts, food and drinks, raffles, prizes and a silent auction. Admission is peanut butter and jelly to benefit Mustard Seed Ministries. For more information, go to www.facebook.com/standrewsepiscopalacademy.
The Niña and Pinta replicas of Christopher Columbus' ships are open for self-guided tours from 9 a.m. to 6 p.m. every day this weekend at the Vero Beach City Marina at 3611 Rio Vista Blvd.
The ships arrived Monday and opened Tuesday, and they will be docked in Vero Beach until their departure April 18. Admission is $8.50 for adults, $7.50 for seniors, $6.50 for kids ages 5-16 and free for kids ages 4 and younger. For more information, go to www.ninapinta.org.
The Vero Beach Arts & Crafts Expo Spring Edition is 10 a.m. to 5 p.m. Saturday and 10 a.m. to 4 p.m. Sunday at the Indian River County Fair Grounds at 7955 58th Ave., north of Vero Beach. Admission is free. For more information, go to www.artandcraftexpo.com.
The 22nd annual Downtown Stuart Craft Festival is 10 a.m. to 5 p.m. Saturday and Sunday at 26 S.W. Osceola St., in Stuart. Admission is free. For more information, go to www.artfestival.com.
The Jensen Beach Art League's art show is 10 a.m. to 4 p.m. Sunday at Indian RiverSide Park at 1707 N.E. Indian River Drive. For more information, call 772-486-5240 or go to jensenbeachartleague.yolasite.com.
A DJ and teen-only access to the waterpark is 6-8 p.m. The movie, "Avengers: Infinity War" plays on the big screen from 8-10 p.m. while teens watch from inner tubes in the pool. Admission is free. For more information, call 772-334-1954 or go to www.martin.fl.us/teens.
The fourth annual PSL Taste of the Islands Caribbean food and live music festival is noon to 10 p.m. Sunday at Causeway Cove Marina at 601 Seaway Drive in Fort Pierce.
The festival also features craft vendors, a talent showcase and a children's zone. Admission is $10 for adults and free for kids younger than 12. For more information, go to www.facebook.com/psltasteoftheislands.
Laurie K. Blandford is TCPalm's entertainment reporter and columnist dedicated to finding the best things to do on the Treasure Coast. Read her weekly column, Laurie's Stories, on TCPalm.com. Follow her on Twitter at @TCPalmLaurie or Facebook at faceboook.com/TCPalmLaurie.


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text:
Colonizing Animals
A blog about beasts, Burma and British imperialism
#animalhistory
#histcrime
#histmed
#histsci
Beastly Bibliography
Gharry Drivers and Armoured Dog Coats
On my way back from a trip to London, I was able to get a couple of hours in the Newsroom of the British Library to take a look at some colonial-era newspapers. Scanning through the microfilm of the English-language daily The Times of Burma for the year 1905, I stumbled across an odd story….
Darwin's Empire of Emotions
Recently I've found myself interested in Charles Darwin's 1872 book The Expression of Emotions in Man and Animals. This is in no small part because of its charming illustrations of cats and dogs in a variety of emotional states. In the book, Darwin closely describes the bodily signs of emotion shown in different species to…
Theories of Evolution in Colonial Burma
Historians of natural history have long explored the emergence of evolutionary theory. Most of the studies that I have read on the subject tend to discuss its development and influence within an Imperial framework. The colonized world appears in these histories as a site in which key figures, such as Alfred Russell Wallace and Charles…
Colonial Canicide, Cruel to be Kind?
One of the ways in which British colonizers sought to distinguish themselves from the colonized populations that they ruled over, and to justify that rule, was through claiming that they treated animals more humanely than the 'natives'. In Burma this claim was also made, but it was not always straight-forward. Buddhism was viewed by imperial…
Prisoners and Pariah Dogs
Many things have changed in Yangon since I first visited as a wide-eyed PhD student back in 2008, but the city's street dogs remain a ubiquitous presence. Although, they have had their own share of difficulties since then. In 2013 the city's authorities were accused of poisoning them in order to beautify the streets in…
A Dog's Life in Colonial Burma
I have just finished reading a traveller's account of Burma published in 1909 and purportedly written by a dog. The dog, called 'John', travelled the northern-most reaches of the colony with his master, 'the Colonel', the Colonel's wife, the 'Mem Sahib', their female friend, referred to only as 'Missy Sahib', and their entourage of Indian…
Reporting Reports
Race, Racism and Some Rhinos
King Thibaw's Elephants
(Natural) Historical Haircuts
Costly Cats, Neglected Lepers
History of Crime
Follow Colonizing Animals on WordPress.com


text:
Germany was covered by glaciers 450,000 years ago
March 26, 2018 by Infinite
– Germany was covered by glaciers 450,000 years ago:
The timing of the Middle Pleistocene glacial-interglacial cycles and the feedback mechanisms between climatic shifts and earth-surface processes are still poorly understood. This is largely due to the fact that chronological data of sediment archives representing periglacial, but also potentially warmer climate periods, are very sparse until now.
"The Quaternary sediments in central Germany are perfect archives to understand the climate shifts that occurred in the region during the last 450,000 years", says co-author Tobias Lauer, a geochronologist at the Max Planck Institute for Evolutionary Anthropology. "This is because all sediments representing the ice advances and retreats of Scandinavian glaciers into Europe are preserved here." The sediments in the region, and especially in the area around the city Leipzig, are extremely well documented due to tens of thousands of drillings over the past few decades and open pits related to brown-coal mining.
Read moreGermany was covered by glaciers 450,000 years ago
Categories Environment, Global News, Science Tags Climate Change, Environment, Germany, glaciers, Global News, Science Leave a comment
Trying to explain New Zealand's 'unusual' growing glaciers
Trying to explain New Zealand's 'unusual' growing glaciershttps://t.co/hxYQnnGuVd
— Infinite Unknown (@SecretNews) February 19, 2018
Categories Environment, Global News Tags Climate Change, Environment, glaciers, Global Cooling, Global News, Global Warming, New Zealand Leave a comment
2 Recent Papers Further Confirm That Natural Cycles Are Indisputable, Powerful Climate Drivers
March 2, 2017 by Infinite
– 2 Recent Papers Further Confirm That Natural Cycles Are Indisputable, Powerful Climate Drivers:
Two recent papers dispelling claims often made by global warming alarmists have been presented by the Die kalte Sonne site. here.
Insidious preindustrial warm phase: 4000 years ago glaciers in Norway had almost completely melted away
By Dr. Sebastian Lüning and Prof. Fritz Vahrenholt
(German text translated/edited by P Gosselin)
The University of Bergen in Norway reported 14 February 2017 on the climate in Norway 4000 years ago, when in the summertime it was on average two to three degrees warmer than today. Most glaciers in the country at the time had almost completely melted away and gone. Instead of examining these what for many are unexpected warm phases, the team of authors in the press release chose to focus the public's attention on concern and fear for the future.
Read more2 Recent Papers Further Confirm That Natural Cycles Are Indisputable, Powerful Climate Drivers
Categories Global News, Politics Tags Climate Change, Environment, glaciers, Global Cooling, Global News, Global Warming, Norway, Science Leave a comment
SUMMER Snow Australia and 58 Glaciers Growing Across New Zealand (Video)
Categories Environment, Global News Tags Australia, Climate Change, Environment, glaciers, Global Cooling, Global News, Global Warming, Meteorology, New Zealand, Snow 10 Comments
Ice Bridge Collapses At GROWING Argentina glacier (Video)
– Ice bridge collapses at GROWING Argentina glacier – Video:
You might mistakenly assume the collapse came about because of global warming. That's because articles about the collapse fail to mention that the glacier is growing. Yes, GROWING.
So how did ABC News handle it? They spun it this way:
"Experts said the collapse has nothing to do with climate change and was instead all to do with physics."
Funny, isn't it? The glacier is receding? Oh my God, it's global warming! The glacier is advancing? Oh, that's just "physics."
Read moreIce Bridge Collapses At GROWING Argentina glacier (Video)
Categories Environment, Global News Tags Argentina, Climate Change, Environment, glaciers, Global Cooling, Global News, Global Warming Leave a comment
90% Of The World's Glaciers Are GROWING
November 2, 2015 by Infinite
– 90 percent of the world's glaciers are growing:
NASA admits Antarctic Ice Sheet is growing – Confirms what I've been saying all along.
A new NASA study, released on Friday, admits that ice is accumulating in Antarctica.
Satellite measurements show an 82-112 gigaton-a-year net ice gain. That's 82-112 billion tons per year! Nine zeroes!
112,000,000,000 tons. Per year.
Read more90% Of The World's Glaciers Are GROWING
Categories Environment, Global News Tags Antarctica, Environment, glaciers, Global News, NASA Leave a comment
Glaciers advancing on Mt Baker, Washington, says renowned geologist
– Glaciers advancing on Mt Baker, Washington, says renowned geologist:
"Photos and maps prove that all of Mt. Baker glaciers are significantly more extensive today than they were in 1950," says geologist Dr. Don J. Easterbrook.
Not only are the glaciers larger today than in 1950, some have recently begun to advance, says Easterbrook, Emeritus Professor of Geology at Western Washington University.
Categories Environment, Global News Tags Environment, glaciers, Global News Leave a comment
Glaciers On K-2, The 2nd Highest Peak On Earth, Are … Growing
October 23, 2014 by Infinite
– Glaciers on K-2, the 2nd highest peak on Earth, are growing (Ice Age Now, Oct 21, 2014):
Scientists struggle to explain it (Look out! Here comes the spin!)
In the mountainous Karakoram region of Asia the glaciers aren't melting. If anything, some are expanding, says this article on LiveScience.
"It's been a source of controversy that these glaciers haven't been changing while other glaciers in the world have," said study researcher Sarah Kapnick, a postdoctoral researcher in atmospheric and ocean sciences at Princeton University.
Read moreGlaciers On K-2, The 2nd Highest Peak On Earth, Are … Growing
Categories Environment, Global News Tags Climate Change, Environment, glaciers, Global Cooling, Global News, Global Warming, Science Leave a comment
Volcanic eruption begins under Iceland's (and Europe's) largest glacier
– Volcanic eruption begins under Iceland's (and Europe's) largest glacier (Ice Age Now, Aug 23, 2014):
Dyngjujokull eruption begins – It's all subglacial for now
Iceland's Dyngjujokull volcano began erupting today, prompting the country to raise its aviation alert level to red, the country's Meteorological Office said. However, the eruption is still just considered a minor event at this point
Dyngjujokull volcano is not far from Bárðarbunga, which gave us the largest eruption of the Holocene (this era).
An alert level of red — the highest level — indicates the threat of "significant emission of ash into the atmosphere." Meanwhile, the National Commissioner of the Icelandic Police has raised the alert phase to emergency phase.
Seismic data indicates that hot magma is melting the ice beneath the Dyngjujokull icecap on the Vatnajokull glacier, said Met Office vulcanologist Melissa Pfeffer.
Read moreVolcanic eruption begins under Iceland's (and Europe's) largest glacier
Categories Environment, Global News, Science Tags Environment, glaciers, Global News, Iceland, Science, Volcano 1 Comment
Evidence Of New, Present-Day Glaciation In Scotland
– Evidence of new, present-day glaciation in Scotland (Ice Age Now, Aug 22, 2014):
A team of experts investigating the North Face of Scotland's Ben Nevis mountain have found snowfields remaining in many gullies and upper scree slopes.
On these snowfields, the team – which included mountaineers, geologists and botanists – came across compacted, dense, ice hard snow call neve.
Neve is the first stage in the formation of glaciers, the team said.
Read moreEvidence Of New, Present-Day Glaciation In Scotland
Categories Environment, Global News, Science Tags Climate Change, Environment, glaciers, Global News, Science, Scotland, U.K. Leave a comment
Volcanoes Melting West Antarctic Glaciers, Not Global Warming
– Volcanoes Melting West Antarctic Glaciers, Not Global Warming (Ice Age Now, Aug 11, 2014):
"Geothermal heat under the glaciers is likely a key factor in why the ice sheet is currently collapsing."
The edge of the Thwaites glacier – NASA photo by Jim Yungel
"A new study by researchers at the University of Texas, Austin found that the West Antarctic Ice Sheet is collapsing due to geothermal heat, not man-made global warming," says this article in The Daily Mail.
"Researchers from the UTA's Institute for Geophysics found that the Thwaites Glacier in western Antarctica is being eroded by the ocean as well as geothermal heat from magma and subaerial volcanoes.
Read moreVolcanoes Melting West Antarctic Glaciers, Not Global Warming
Categories Environment, Global News Tags Antarctica, Climate Change, Environment, glaciers, Global News, Global Warming, Volcano 1 Comment
IPCC Chairman Rajendra Pachauri was told of false Himalayan glacier melting claims before Copenhagen
Add that to Climategate! Global warming is a scam.
Most experts believe that the Himalayan glaciers will take centuries to melt
The chairman of the leading climate change watchdog was informed that claims about melting Himalayan glaciers were false before the Copenhagen summit, The Times has learnt.
Rajendra Pachauri was told that the Intergovernmental Panel on Climate Change assessment that the glaciers would disappear by 2035 was wrong, but he waited two months to correct it. He failed to act despite learning that the claim had been refuted by several leading glaciologists.
The IPCC's report underpinned the proposals at Copenhagen for drastic cuts in global emissions.
Dr Pachauri, who played a leading role at the summit, corrected the error last week after coming under media pressure. He told The Times on January 22 that he had only known about the error for a few days. He said: "I became aware of this when it was reported in the media about ten days ago. Before that, it was really not made known. Nobody brought it to my attention. There were statements, but we never looked at this 2035 number."
Asked whether he had deliberately kept silent about the error to avoid embarrassment at Copenhagen, he said: "That's ridiculous. It never came to my attention before the Copenhagen summit. It wasn't in the public sphere."
However, a prominent science journalist said that he had asked Dr Pachauri about the 2035 error last November. Pallava Bagla, who writes for Science journal, said he had asked Dr Pachauri about the error. He said that Dr Pachauri had replied: "I don't have anything to add on glaciers."
The Himalayan glaciers are so thick and at such high altitude that most glaciologists believe they would take several hundred years to melt at the present rate. Some are growing and many show little sign of change.
Dr Pachauri had previously dismissed a report by the Indian Government which said that glaciers might not be melting as much as had been feared. He described the report, which did not mention the 2035 error, as "voodoo science".
Read moreIPCC Chairman Rajendra Pachauri was told of false Himalayan glacier melting claims before Copenhagen
Categories Environment, Global News, Politics Tags Climate Change, Copenhagen, Environment, glaciers, Global Warming, Himalaya, IPCC, Politics, Rajendra Pachauri, Science Leave a comment
Mile-thick glaciers found on Mars
November 21, 2008 by Infinite
A mountain in the eastern Hellas region of Mars
Huge glaciers up to half a mile thick have been discovered close to the equator of Mars and are thought to be the remnants of an ice age on the planet.
The glaciers are thought to have been formed up to 100 million years ago and are the "most dramatic" evidence yet of climate change on Mars.
Hundreds of glaciers have been identified by researchers using ground-penetrating radar that allows them to see through a rocky layer of debris covering the ice.
The biggest of the glaciers are up to 13 miles long and more than 60 miles wide and represent a potential source of water for astronauts on missions to Mars.
Read moreMile-thick glaciers found on Mars
Categories Science Tags Climate Change, glaciers, Ice Age, Mars, Science, Scientists Leave a comment


text:
SOWELL BIO
THE PEDIGREE
THE TRAINING ACADEMY
COLLEGE PREP & ADVISING
CP advising
RICK SOWELL
20 year Division I Mens Lacrosse Coach
One of only three Division I coaches to take three different teams to the NCAA tournament.
My passion for the last 20 years has been to help lacrosse players reach their athletic potential. I am excited to be able to share my knowledge and coaching acumen with dedicated middle and high school students.
In 2018, Navy captured the program's eighth Patriot League regular-season crown after posting a 7-1 record to complement a 9-5 overall mark. Among the season's highlights, the Class of 2018 became the first class to go 4-0 against Army in the annual Star Game since the Class of 2007. In 2010, Sowell led Stony Brook to the program's first America East regular-season title, a school-record 13 wins, a national ranking as high as No. 6 and a 9-7 victory over Denver in the first round of the NCAA Tournament. The Seawolves were just a game away from advancing to the school's first-ever final four, narrowly losing in to Virginia in the quarterfinals, 10-9. Stony Brook had four players earn All-America honors, including Kevin Crowley who was the school's first First-Team All-American and was named the USILA Player of the Year.
Sowell, who was an assistant coach for the gold-medal winning Team USA at the 2010 World Championships in England, led Stony Brook to a 9-6 record in 2009 and a final ranking of No. 20 in the country. It marked the school's first end-of-the-season national ranking. Stony Brook finished 4-1 in America East and stood as the regular season co-champions. Prior to Stony Brook, Sowell was tapped to head the rebirth of the St. John's lacrosse program that had been dormant since 1995. Sowell had just one season to recruit before the Red Storm took the field in 2005.
Sowell was the head coach at Dartmouth from 1999-2003 and revived the Big Green program, taking the team from last place in the Ivy League to first. In his final season at Dartmouth in 2003, Sowell's squad posted an 11-3 record and won the Ivy League with a 5-1 record. It was Dartmouth's first Ivy League title since 1965 and just the third Ivy League title in school history. During the title run, the Big Green upset No. 2 Princeton marking the first time that Dartmouth had won at Princeton since 1958. Sowell was also named the NEILA Coach of the Year that season.
Sowell served as an assistant at Georgetown from 1990-98 where the Hoyas grew from an also-ran to a national contender. In 1998, the Hoyas finished 10-5 overall and advanced to the quarterfinal round of the NCAA's.
Sowell's coaching career began at Washington College in Chestertown, Md., where he helped guide the Shoremen to the NCAA Division III national title game in 1986 and the semifinal round in 1987.
©2023 BY SOWELLAX LLC


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Citation: Proceedings ELBA NW Nanoforum XLII on Structural NanoProteomics. Part-1: Introduction and Topics–XFEL versus Synchrotron Radiation and Cryo-EM. NanoWorld J 3(Suppl 2): S1-S6.
Citation: Proceedings ELBA NW Nanoforum XLII. Part-2: Featured Presentations. NanoWorld J 3(Suppl 2): S7-S11.
Citation: Proceedings ELBA NW Nanoforum XLII. Part-3: Nanotechnology for Structural Proteomics and Conclusions. NanoWorld J 3(Suppl 2): S12-S18.


Sedum spectabile Brilliant commonly known as Ice plant, has broad flat heads of tiny, bright pink flowers held on strong stems with flesh pale green leaves.
Clump-forming perennial with upright, unbranched, green stems producing flowers to 1cm (½in) across with prominent stamens in dense, flat cymes to 15cm (6in) across.
Harmful if eaten - These will give you an upset tummy, so please don't eat any of these. May cause skin allergy or irritant, having skin or eye contact with these plants could result in an allergic reaction, burning or rash.


text:
Q: how many2many defined for custom module I tried to use many2many relational field in my custom module "notebook". Code is given below:
notebook.py:
from osv import fields, osv
import time

class notebook(osv.osv):
    _name = "notebook"
    _description = "Simple Notebook"
    _columns = {
        'title' : fields.char('Title', size=30, required=True),
        'tag_ids': fields.many2many(
                    'hello',
                    'title',
                    'name',
                    string="Tags"
                                ),
    }

notebook()

class hello(osv.osv):
    _name = 'hello'
    _columns = {
            'name':fields.char('Name',size=30),
            'note_ids': fields.many2many(
                                'notebook',
                                'name',
                                'title',
                                string="Notebooks"
                                        ),
                    }
hello()

notebook_view.xml:
<?xml version="1.0" encoding="utf-8"?>
<openerp>
    <data>
        <record model="ir.ui.view" id="notebook_form_view">
            <field name="name">notebook.form</field>
            <field name="model">notebook</field>
            <field name="type">form</field>
            <field name="arch" type="xml">
                <form string="Notebook">
                    <field name="title" />
                    <field name="tag_ids" widget="many2many_tags"/>
                </form>
            </field>
        </record>

        <record model="ir.actions.act_window" id="action_notebook_form">
            <field name="name">notebook</field>
            <field name="res_model">notebook</field>
        </record>

        <menuitem name="NotebookParent" icon="terp-project" id="NotebookParent_menu" />

        <menuitem name="NotesChild" parent="NotebookParent_menu" id="NotesChild_menu" />

        <menuitem name="Header" parent="NotesChild_menu" id="Header_menu_mainform"
            action="action_notebook_form" />
    </data>
</openerp>

hello_view.xml:
<?xml version="1.0" encoding="UTF-8"?>
<openerp>
    <data>
        <record model="ir.ui.view" id="hello_form_view">
            <field name="name">hello.form</field>
            <field name="model">hello</field>
            <field name="type">form</field>
            <field name="arch" type="xml">
                <form string="Hello Form">
                    <field name="name" select="1" />
                    <field name="note_ids" widget="many2many_list"/>
                </form>
            </field>
        </record>
    </data>
</openerp>

There is no error in installing and the fields are also displayed and data is stored in the Database.
My problem arises as inter-relationship between note_ids and tag_ids is not proper.
Example:
If I have a notebook record as :
       title = sample
       tags = tag1, tag2
 The tags are created in hello record as:
       tag1 record:
           name="tag1"
           Notebooks = ""
       tag2 record:
           name="tag2"
           Notebooks= ""

Why is the relationship not maintained?

A: Please take a look at your many2many
It should be like this
fields.many2many('that object name',
             'sql relation table name',
             'this object id',
             'that object id',
             'Field Lable')

Eg: in your case the two many2many could be like this
first many2many
'tag_ids': fields.many2many(
                'hello',
                'notebook_hello_rel',
                'notebook_id',
                'hello_id',
                string="Tags"
                            ),

Second many2many
'note_ids': fields.many2many(
                            'notebook',
                            'notebook_hello_rel',
                            'hello_id',
                            'notebook_id',
                            string="Notebooks"
                                    ),


text:
Sant Jordi de ses Salines is a small village in the south  of the Spanish island of Ibiza. The village is in the municipality of Sant Josep de sa Talaia and is located close to the islands main Airport and straddles the designated road PM-802. The village is  south west of Ibiza Town and  of Ibiza Airport.

References

Populated places in Ibiza

redpajama_set_name: RedPajamaWikipedia


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