text:
Der Tempel der Artemis Azzanathkona befindet sich in Dura Europos im Osten des heutigen Syrien. Er ist vor allem wegen eines Militärarchives  der Cohors XX Palmyrenorum bekannt, das sich in einem der Tempelräume fand. Das Archiv besteht aus zahlreichen Papyri und Pergamenten. Es handelt sich um den wichtigsten Fund, der Licht auf die Organisation römischer Militäreinheiten wirft.

Die Tempelanlage wurde 1931–32 ausgegraben. Kleinere Nachuntersuchungen fanden zwischen 2007 und 2010 statt. Der Tempel war schon seit dem Beginn des ersten Jahrhunderts n. Chr. in Betrieb. Die älteste Inschrift im Tempel datiert 13. n. Chr. Eine Inschrift aus dem Jahr 161 n. Chr. bezeugt, dass hier Artemis, die Göttin, die Azzanathkona genannt wird, verehrt wurde. Azzanathkona ist sonst nicht bezeugt. Ihr Name deutet jedoch an, dass sie aus Anath, einer Insel im Euphrat, stammt. Es ist möglich, dass im Tempel auch ihr Gemahl, dessen Name nicht überliefert ist, verehrt wurde.

Der Tempelbezirk liegt im Norden der Stadt direkt an der Stadtmauer und besteht aus einem Hof, der im Osten einen Eingang hatte, der mit Säulen geschmückt war. Im Westen des Hofes stehen die eigentlichen Tempelgebäude, die mesopotamischen Typen folgen. Das südliche besteht aus einem Vorraum und zwei dahinter liegenden Längsräumen, von denen der hintere nochmals unterteilt ist. Hier stand wohl auch einst ein Kultbild. Der nördliche Tempel besteht aus zwei Längsräumen, wobei wiederum der hintere in zwei Räume unterteilt ist. Hinter diesen beiden Tempelbauten befinden sich weitere Räume, deren Funktion nicht immer gesichert ist. In römischer Zeit wurden diese Räume in das Militärlager einbezogen, das im Norden von Dura Europos eingerichtet wurde. Einer der Räume war mit Graffiti und Zeichnungen bedeckt und es wurde vermutet, dass der Raum von Militärschreibern genutzt wurde. In römischer Zeit wurde auch ein zweiter Eingang in die bestehende Westmauer des Komplexes gebrochen und dazu extra Vorraum gebaut.

Literatur
 Simon James: The Roman Military Base at Dura-Europos, Syria, Oxford 2019. ISBN 978-0-19-874356-9, S. 70–78

Dura Europos
Dura Europos
Archäologischer Fundplatz (Römisches Reich)
Parthischer Tempel

redpajama_set_name: RedPajamaWikipedia


text:
Ben Adlin
Connecticut Governor Renews Pledge To Pursue Marijuana Legalization In 2021 State Of The State Speech
The governor of Connecticut reiterated his support for legalizing marijuana during his annual State of the State address on Wednesday, pledging to cooperate with lawmakers to advance the issue in 2021.
"I am working with our neighboring states and look forward to working with our tribal partners on a path forward to modernize gaming in our state, as well as the legislature on legalization of marijuana," the Gov. Ned Lamont (D) said in the speech, delivered in a video on the first day of the new session. "Sports betting, internet gaming and legalized marijuana are happening all around us. Let's not surrender these opportunities to out-of-state markets or, even worse, underground markets."
Lamont also pushed for legalization of cannabis in State of the State speech last year, and in a budget address the prior year.
But lawmakers in the state have repeatedly declined to advance legalization measures in recent years, including most recently a bill that Democrats put forward last year on Lamont's behalf.
Despite the failures, new House Speaker Matt Ritter (D) said in November that legalization in the state is "inevitable," adding later that month: "I think it's got a 50–50 chance of passing [in 2021], and I think you should have a vote regardless."
If the effort to pass legalization through the state legislature fails to get traction, Ritter has said, he will attempt to put a constitutional question on the state's 2022 ballot that would leave the matter to voters. A poll published last March found that nearly two-thirds of voters (63.4 percent) either "strongly" or "somewhat" supported legalization for adult use.
Supportive lawmakers have stressed that the state needs to update its cannabis policy in light of legalization in nearby states. "It's now legal in New Jersey, New York is coming, and it's legal in Massachusetts," Ritter said late last year. "Connecticut cannot fortify its border."
"Folks literally take something called a car," he quipped at a late November press conference, "and they drive in their car and they buy it."
Lamont, meanwhile, likened the need for regional coordination on marijuana issues to the coronavirus response, saying officials have "got to think regionally when it comes to how we deal with the pandemic—and I think we have to think regionally when it comes to marijuana, as well."
He added that legalization in Connecticut could potentially reduce the spread of COVID-19 by limiting out-of-state trips to buy marijuana.
Marijuana Moment is already tracking more than 100 cannabis bills in state legislatures and Congress this year. Patreon supporters pledging at least $25/month get access to our interactive maps, charts and hearing calendar so they don't miss any developments.
In Connecticut, Democrats will have bigger majorities in the legislature this term than in years past, but Ritter has predicted "a very, very close vote in the House."
Incoming House Majority Leader Jason Rojas (D) and Rep. Michael D'Agostino (D), chairman of the House General Law Committee, joined Ritter at November's press event to encourage support for the policy change.
"This is not the most pressing issue we're facing as a state," Rojas said at the time, but "perhaps it's the most nagging one."
New York Governor Unveils Updated Marijuana Legalization Plan For 2021
The post Connecticut Governor Renews Pledge To Pursue Marijuana Legalization In 2021 State Of The State Speech appeared first on Marijuana Moment.
Ben Adlin, KahliBuds, 420GrowLife

redpajama_set_name: RedPajamaCommonCrawl


text:
Washington Governor Intervenes in Teachers Strike
Washington Gov. Chris Gregoire, frustrated that a teachers strike has forced the cancellation of seven days of school in Tacoma, called both sides to her office Wednesday in hopes of brokering a deal.
OLYMPIA, Wash. – Washington Gov. Chris Gregoire, frustrated that a teachers strike has forced the cancellation of seven days of school in Tacoma, called both sides to her office Wednesday in hopes of brokering a deal.
Negotiators were unable to reach an agreement Wednesday afternoon, so they traveled to Olympia to continue discussions under Gregoire's watch, said Karina Shagren, a spokeswoman for the governor.
Gregoire has no direct control of schools in Washington, but she has been pressuring both sides for a deal.
"She is incredibly anxious," Shagren said. "She wants to get those kids back in school."
Wednesday was the seventh day classes have been canceled in the state's third-largest school district. The two sides have been disputing issues including pay and class size, but the major sticking point is how the district handles teacher transfers. The district wants to consider some factors in addition to seniority.
Gregoire said in a statement that she wants district and union negotiators to stay in her office "until their differences are reconciled and the school doors reopen."
The Tacoma Education Association, the union for 1,900 teachers, is defying a court order for them to return to work. Pierce County Superior Court Judge Bryan Chushcoff has said he's considering giving the district the option of replacing teachers who are on the picket line, and the next court hearing is set for Tuesday.
State and local public employees, including teachers, have no legally protected right to strike, according to a 2006 state attorney general's opinion. But that opinion also noted state law lacks specific penalties for striking public employees.
For Pope Francis, Fake News Goes Back to the Garden of Eden
Vietnamese Forged a Community in New Orleans. Now It May Be Fading.
Wash. residents warned of 'bloodthirsty' dog pack
17-year-old arrested in killing of Georgia deputy
Wife of Accused Email Hacker Refutes Claims She Allowed Husband Access to Account
Border Officials Suspend Handing Over Migrant Families to Prosecutors


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As one of the industry's leading tissue data and image analysis services providers, Flagship Biosciences was recently selected as a Top Image Analysis Solution Provider for 2020. With advanced tissue image analysis solutions that give pharmaceutical and diagnostics clients distinct advantages, Flagship acts as the scientific bridge between therapeutic development and real world results to accelerate the process of drug development and clinical diagnostics.
Flagship Biosciences offers an end- to-end tissue analysis service, starting with specimen collection, slide prep, in situ assay, scanning, and image capture, all the way to tissue image analysis, pathologist review, tissue data analytics, and custom reporting. The company's proprietary technology delivers high-quality tissue data, using exclusive, cell-based analysis processes.
As Flagship CEO Trevor Johnson shares in the article, Flagship Biosciences' identity runs deeper than its solutions, with a very hands-on, end-to-end approach to working with their clients.
"We are more than just a technology company," said Johnson. "We are a services company – a combination of technology, an expert multi-disciplinary team of pathologists, biologists, analysts, software engineers, and technicians who are committed to helping create life-saving drugs."
Flagship's technology takes tissue context, in digital form, to measure how different cell types, particularly immune cells and tumor cells, interact and change on a patient-by-patient basis.
"Flagship Biosciences can show real world evidence that demonstrates an effect, the way and where you'd want to see it," said Johnson, in the article.
He provided an example, that if a company is developing a drug to boost the immune system for an oncology application, Flagship Biosciences can show that the drug is increasing the number of macrophages within the tumor nests that are being targeted.
The article continues to share insights on the elements that make Flagship a Top Image Analysis Solution Provider for 2020.
Human tissue analysis is an extremely vital discipline that helps pharmaceutical scientists and drug developers explore the very nature of human pathology. The role of this analysis varies depending on the type and stage of drug development. At its most fundamental, it is used to verify if a drug in development will achieve its intended (or unintended) objectives. The processes associated with tissue image study and examination are incredibly complex, with challenges at every step of the process. The analyses must be able to reveal evidence of the drug's efficacy or enable patient selection for each specific drug, to make it successful.
Flagship Biosciences' analysis platform can also be used for both existing and novel diagnostic testing, using highly precise and accurate measurements, to deliver more detailed results. The company collects an enormous amount of data under the supervision of pathologists, while adhering to College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments of 1988 (CLIA) standards, to produce better diagnostic results for patients.
Flagship Biosciences' cell-based image analysis technology provides improved results over the variability implicit within traditional, pixel-based image analysis. Flagship's clients have access to one of the most accurate tumor and immune cell identification services in the world.
Flagship's process includes industry-leading image analysis, machine learning, and artificial intelligence (AI) capabilities, and every sample is reviewed by a human pathologist who has final say on accuracy. "We always use the highest level of review, which is by the pathologist- the gold standard in pathology, on every single sample we run," says Johnson.
The company can receive digital images of the samples from across the globe, run the analysis remotely, and send back results, including the Flagship pathologist's analysis and review of the resulting data. Clients with prospective clinical trials, where individual patient data is used to make an enrollment decision, or those needing clinical diagnostic testing at the Flagship Biosciences CAP/CLIA lab, can get additional insights into diagnostic biomarkers from a digital image.
The company is always improving and adapting its technology to the of the pharmaceutical development space. Flagship Biosciences is also building out its clinical diagnostics capabilities. The company's long-term goal is to be the world leader in digital tissue diagnostics.
"We want to have a digital analytical version of almost every manual pathology biomarker test to give a more accurate, precise, and informative result. To maintain the highest level of precision, we will ensure that a pathology team supervises all results to give patients the best testing possible," said Johnson.
Download a PDF of the story here
Read the entire Pharma Tech Outlook cover story on Flagship Biosciences – Accelerating Drug Development on the magazine's website.


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text:
Q: I want gird lines of x-axis and y-axis in highcharts but i don't want x-axis value and y-axis value https://jsfiddle.net/Kondaldurgam/7kLkh7ya/8/
i want show gridines only x and y axis but but i don't have any data of x and y axis its possible to showing without data
$(function() {
Highcharts.chart('container', {

    chart: {
        type: 'bubble',
        plotBorderWidth: 1,
        zoomType: 'xyz'
    },
    legend: {
        enabled: false
    },
    credits: {
        enabled: false
    },

    title: {
        text: 'Using X Y Z Coordinates'
    },

    xAxis: {
        type: "category",
        gridLineWidth: 1
    },
    yAxis: {
        startOnTick: false,
        endOnTick: true,

        title: {
            text: ''
        },
    },
 });
});

A: May be this will help you.. use this logic in it..fiddler
$(function () {
    var chart = new Highcharts.Chart({
        chart: {
            renderTo: 'container',
          ignoreHiddenSeries : false
        },

        xAxis: {
        },

        series: [{
            data: [29.9, 71.5, 106.4, 129.2, 144.0, 176.0, 135.6, 148.5, 216.4, 194.1, 95.6, 54.4]
        }, {
            data: [129.2, 144.0, 176.0, 135.6, 148.5, 216.4, 194.1, 95.6, 54.4, 29.9, 71.5, 106.4]
        }]
    });

    // the button action
  var series = chart.series[0];
  series.hide();
  series = chart.series[1];
  series.hide();
});

A: If you have no data, you need to set axis.showEmpty to true and set axis min/max. You also need at least one series - it might be without data.
    Highcharts.chart('container', {

    chart: {
        type: 'bubble',
        plotBorderWidth: 1,
        zoomType: 'xyz'
    },
    legend: {
        enabled: false
    },
    credits: {
        enabled: false
    },

    title: {
        text: 'Using X Y Z Coordinates'
    },

    xAxis: {
        type: "category",
        gridLineWidth: 1,
        showEmpty: true,
        min: 0,
        max: 10
    },
    yAxis: {
        startOnTick: false,
        endOnTick: true,
                    showEmpty: true,
        title: {
            text: ''
        },
        min: 0,
        max: 10
    },

    series: [{}]

});

example: https://jsfiddle.net/7kLkh7ya/9/

redpajama_set_name: RedPajamaStackExchange


text:
var keystone = require('keystone');

var Types = keystone.Field.Types,
    Enquiry = new keystone.List('Enquiry', {
        nocreate: true,
        noedit: true,
        defaultSort: '-createdAt'
    });

Enquiry.add({
    name: { type: Types.Text },
    email: { type: Types.Email, required: true },
    message: { type: Types.Markdown, required: true },
    createdAt: { type: Date, default: Date.now }
});

Enquiry.schema.pre('save', function(next) {
    this.wasNew = this.isNew;
    next();
});

Enquiry.schema.post('save', function() {
    if (this.wasNew) {
        this.sendNotificationEmail();
    }
});

Enquiry.schema.methods.sendNotificationEmail = function(callback) {

    if ('function' !== typeof callback) {
        callback = function() {};
    }

    var enquiry = this;

    keystone.list('User').model.find().where('isAdmin', true).exec(function(err, admins) {

        if (err) return callback(err);

        new keystone.Email('enquiry-notification').send({
            to: admins,
            from: {
                name: 'Contre Pensées',
                email: 'contact@contre-pensees.com'
            },
            subject: 'New Enquiry for Contre Pensées',
            enquiry: enquiry
        }, callback);
    });
};

Enquiry.defaultSort = '-createdAt';
Enquiry.defaultColumns = 'name, email, message';
Enquiry.register();

redpajama_set_name: RedPajamaGithub


text:
NS_ASSUME_NONNULL_BEGIN

@interface NCShoppingList (CoreDataProperties)

@property (nullable, nonatomic, retain) NSString *name;
@property (nullable, nonatomic, retain) NSSet<NCShoppingGroup *> *shoppingGroups;

@end

@interface NCShoppingList (CoreDataGeneratedAccessors)

- (void)addShoppingGroupsObject:(NCShoppingGroup *)value;
- (void)removeShoppingGroupsObject:(NCShoppingGroup *)value;
- (void)addShoppingGroups:(NSSet<NCShoppingGroup *> *)values;
- (void)removeShoppingGroups:(NSSet<NCShoppingGroup *> *)values;

@end

NS_ASSUME_NONNULL_END


text:
Tag: neural progenitor cells
McMaster Scientists Convert Blood into Neural Cells With One Gene
McMaster University stem cell scientists have discovered a way to adult sensory neurons from human patients simply by having them roll up their sleeve and provide a blood sample. The McMaster scientists directly converted adult human blood cells to both central nervous system (brain and spinal cord) neurons and peripheral nervous system (rest of the body) neurons responsible for pain, temperature and itch perception. This means that how a person's nervous system cells react and respond to stimuli can be determined from their blood.
This breakthrough was published online recently and was also featured on the cover of the journal Cell Reports. The leader of this research, Mick Bhatia, serves as the director of the McMaster and Cancer Research Institute and holds the Canada Research Chair in Human stem Cell Biology and is a professor in the Department of Biochemistry and Biomedical Sciences in the Michael G. DeGroote School of Medicine.
Scientists do not have a robust understanding of pain and how to treat it. Neurons in the peripheral nervous system is composed of different types of nerves that detect mechanical forces like pressure or touch, and others and detect temperature, such as heat. Pain is perceived by the brain when signals are sent by peripheral pain receptors.
"The problem is that unlike blood, a skin sample or even a tissue biopsy, you can't take a piece of a patient's neural system. It runs like complex wiring throughout the body and portions cannot be sampled for study," said Bhatia.
"Now we can take easy to obtain blood samples, and make the main cell types of neurological systems — the central nervous system and the peripheral nervous system — in a dish that is specialized for each patient," said Bhatia. "Nobody has ever done this with adult blood. Ever.
"We can actually take a patient's blood sample, as routinely performed in a doctor's office, and with it we can produce one million sensory neurons, that make up the peripheral nerves in short order with this new approach. We can also make central nervous system cells, as the blood to neural conversion technology we developed creates neural stem cells during the process of conversion."
This new protocol uses a gene called "Oct4" to directly reprogram blood cells. Additionally, if two proteins (SMAD and GSK-3) are inhibited with small molecules while the cells are transfected with the Oct4 gene, then the resultant cells transdifferentiate into blood-derived induced neural progenitor cells (BD-iNPCs). Now the direct conversion of skin cells called fibroblasts into neural progenitor cells that look a great like neural crest cells. However, these BD-iNPCs have the ability to differentiate into glial cells (support cells in the nervous system, multiple central nervous system neurons, and pain receptors, which are normally found in the peripheral nervous system.
Using OCT-4-induced direct reprogramming, Lee et al. convert human blood to neural progenitors with both CNS and PNS developmental capacity. This fate alternation is distinct from fibroblasts that are primed for neural potential. Furthermore, human sensory neurons derived from blood phenocopy chemo-induced neuropathy in formats suitable for drug screening.
This new, revolutionary protocol that directly converts white blood cells into neurons with one gene has not only been patented, but has "broad and immediate applications," according to Bhatia. He also added that it allows researchers to start asking questions about understanding disease and improving treatments. These cells could be used to determine why certain people feel pain instead of numbness, or whether or not the degree to which people perceive pain is genetically determines, or whether or not diabetic neuropathy ca be mimicked in a culture dish? Bhatia's new protocol also provides a slick, new model system to find new pain drugs that don't just numb the perception of pain, but completely block it.
"If I was a patient and I was feeling pain or experiencing neuropathy, the prized pain drug for me would target the peripheral nervous system neurons, but do nothing to the central nervous system, thus avoiding non-addictive drug side effects," said Bhatia. "You don't want to feel sleepy or unaware, you just want your pain to go away. But, up until now, no one's had the ability and required technology to actually test different drugs to find something that targets the peripheral nervous system and not the central nervous system in a patient specific, or personalized manner."
Bhatia's team successfully tested their protocol by using fresh blood and frozen blood. This is an important piece of research since blood samples are usually taken and frozen. Freezing blood samples allows scientists or even physicians to create a kind of "time machine" that can show the evolution of a patient's response to pain over a period of time.
For future studies, Bhatia and his colleagues would like to examine patients with Type 2 Diabetes to determine if his technique can help predict whether they will experience neuropathy by running tests in the lab using their own neural cells derived from their blood sample.
"This bench to bedside research is very exciting and will have a major impact on the management of neurological diseases, particularly neuropathic pain," said Akbar Panju, medical director of the Michael G. DeGroote Institute for Pain Research and Care, a clinician and professor of medicine.
"This research will help us understand the response of cells to different drugs and different stimulation responses, and allow us to provide individualized or personalized medical therapy for patients suffering with neuropathic pain."
Posted on May 28, 2015 Categories Model Systems, Neurological treatments, ReprogrammingTags Direct reprogramming, neural progenitor cells, Oct4, Pain receptors
An Improved Way to Make Motor Neurons in the Laboratory from Stem Cells
A research team from the University of Illinois at Urbana-Champaign has reported that they can produce human motor neurons from stem cells much more quickly and efficiently than previous methods allowed. This finding was published in the journal Nature Communications and it will almost certainly provide new ways to model human motor neuron development, diseases of the nervous system, and ways to treat spinal cord injuries.
The new protocol described in the Nature Communications paper includes adding critical signaling molecules to precursor cells a few days earlier than specified by previous methods. This innovation increases the proportion of healthy motor neurons derived from stem cells from 30 to 70 percent. It also cuts in half the time required to make motor neurons.
"We would argue that whatever happens in the human body is going to be quite efficient, quite rapid," said University of Illinois cell and developmental biology professor Fei Wang, who led the study with visiting scholar Qiuhao Qu and materials science and engineering professor Jianjun Cheng. "Previous approaches took 40 to 50 days, and then the efficiency was very low – 20 to 30 percent. So it's unlikely that those methods recreate human motor neuron development."
The new method designed by Qu generated a larger population of mature, functional motor neurons in 20 days. According to Wang, this new approach will allow scientists to induce mature human motor neuron development in cell culture, and to identify the factors that drive this process
Because stem cells can differentiate into a wide variety of cell types, they are unique compared to mature, adult cells. Making neurons from either embryonic stem cells or induced pluripotent stem cells requires the addition of signaling molecules to the cells at critical moments in culture.
Previously, Wang and his colleagues discovered a molecule called compound C that converts stem cells into "neural progenitor cells," or NPCs. NPCs represent an early stage in neuronal development, and further manipulation of NPCs can drive them to become neurons, but differentiating NPCs into motor neurons presents another set of problems.
Other published studies have established that the addition of two important signaling molecules, six days after exposure to compound C, to NPCs in culture can generate motor neurons, but at rather poor efficiencies. In this newly published study, Qu showed that adding the signaling molecules at Day 3 worked better: The NPCs differentiated into motor neurons quickly and efficiently. Thus, Day 3 represents a previously unrecognized NPC cell stage.
This new approach has immediate applications in the laboratory. Amyotrophic lateral sclerosis or ALS is a neurological disease that causes motor neurons to die off. By using Wang and Qu's cell culture system to make neurons from the skin cells of ALS, and watching them develop into motor neurons, scientists and physicians will divine other new insights into disease processes. Therefore, any method that improves the speed and efficiency of generating the motor neurons will be a boon to neuroscientists. These cells can also be used to screen for drugs to treat motor neuron diseases, and might even be used to therapeutically restore lost function in patients someday.
"To have a rapid, efficient way to generate motor neurons will undoubtedly be crucial to studying – and potentially also treating – spinal cord injuries and diseases like ALS," Wang said.
Posted on April 18, 2014 Categories Embryonic Stem Cells, Induced Pluripotent Stem Cells, Model Systems, Neurological treatmentsTags amyotrophic lateral sclerosis, Compound C, motor neurons, neural progenitor cells, stem cell culture, stem cell differentiation
Tumor Suppressor Gene is Required For Neural Stem Cells to Differentiate into Mature Neurons
Cancer cells form when healthy cells accumulate mutations that either inactivate tumor suppressor genes or activate proto-oncogenes. Tumor suppressor genes work inside cells to put the brakes on cell proliferation. Proto-oncogenes work to drive cell proliferation. Loss-of-function mutations in tumor suppressor genes remove controls on cell proliferation, which causes cells to divide uncontrollably. Conversely activating mutations in proto-oncogenes removes the controls on the activity of proto-oncogenes, converting them into oncogenes and driving the cell to divide uncontrollably. If a cell accumulates enough of these mutations, they can grow in such an uncontrollable fashion that they start to gain extra chromosomes or pieces of chromosomes, which contributes to the genetic abnormality of the cell. Accumulation of more mutations allows the cell to break free from the original tumorous mass and spread to other tissues.
There are over 35 identified tumor suppressor genes and one of these, CHD5, has another role besides controlling cell proliferation. Researchers at Karolinska Institutet in Stockholm, Swede, in collaboration with other laboratories at Trinity College in Dublin and BRIC in Copenhagen has established a vital role for CHD5 in normal nervous development.
Once stem cells approach the final phase of differentiation into neurons, the CHD5 protein is made at high levels. CHD5 reshapes the chromatin structure into which DNA is packaged in cells, and in doing so, it facilitates or obstructs the expression of other genes.
Ulrika Nyman, postdoc researcher in Johan Holmberg's laboratory, said that when they switched of CHD5 expression in stem cells from mouse embryos at the time when the brain develops, the CHD5-less stem cells were unable to turn off those genes that are usually expressed in other tissues, and equally unable to turn on those genes necessary for making mature neurons. Thus these CHD5-less stem cells were trapped in a nether-state between stem cells and neurons.
retinoic
The gene that encodes the CHD5 protein is found on chromosome 1 (1p36) and it is lost in several different cancers, in particular neuroblastomas, a disease found mainly in children and is thought to arise during the development of the peripheral nervous system.
Neuroblastomas that lack this part of chromosome 1 that contains the CHD5 gene are usually more aggressive and more rapidly fatal.
Treatment with retinoic acid forces immature nerve cells and some neuroblastomas to mature into specialized nerve cells. However, when workers from Holmberg's laboratory prevented neuroblastomas from turning up their expression of CHD5, they no longer responded to retinoic acid treatment.
Holmberg explained, "In the absence of CHD5, neural tumor cells cannot mature into harmless neurons, but continue to divide, making the tumor more malignant and much harder to treat. We now hope to be able to restore the ability to upregulate CHD5 in aggressive tumor cells and make them mature into harmless nerve cells."
Posted on August 30, 2013 Categories Cancer Stem Cells, Cancer Treatments, Model SystemsTags cell proliferation, CHD5, chromatin structure, genetic abnormality, johan holmberg, mature neurons, mouse embryos, neural progenitor cells, neural stem cells, neuroblastoma, Neuronal gene expression, oncogenes, Polycomb, postdoc researcher, proto oncogenes, retinoic acid, tumor suppressor genes
FDA Approves the First Stem Cell Clinical Trial for Multiple Sclerosis
The Tirsch Multiple Sclerosis (MS) Research Center of New York has received Investigational New Drug (IND) approval from the Food and Drug Administration to launch a Phase I trial that uses a patient's own neural stem cells to treat MS.
MS is a chronic disease that results when a patient's own immune system attacks the myelin insulation that covers many nerves. This damages the myelin sheath and causes degeneration of the nervous system. Some 2.1 million people worldwide are afflicted with MS.
"To my knowledge, this is the first FDA-approved stem cells trial in the United States to investigate direct injection of stem cells into the cerebrospinal fluid of MS patients, and represents an exciting advance in MS research and treatment," said Saud A. Sadiq, senior research scientist at Tisch and the study's principal investigator.
The groundbreaking study will evaluate the safety of using stem cells harvested from the patient's own bone marrow. Once harvested, these stem cells will be injected into the cerebrospinal fluid that surrounds the spinal cord in 20 participants who meet the inclusion criteria for this trial.
Since this is a phase 1 study, it is an open safety and tolerability study. The Tisch MS Research Center and affiliated International Multiple Sclerosis Management Practice (IMSMP) will host all the activities associated with this study.
The clinical application of autologous neural precursors in MS is the culmination of a decade of stem cell research headed by Sadiq and his colleague Violaine Harris, a research scientist at Tisch.
Preclinical testing found that the injection of these cells seems to decrease inflammation in the brain and may also promote myelin repair and neuroprotection. In a 2012 publication in the Journal of the Neurological Sciences, Harris and others showed that mesenchymal stem cell-derived neural progenitor cells could promote repair and recovery after intrathecal injection into mice with EAE (experimental autoimmune encephalitis), which is a MS-like disease in mice. They were able to ascertain that intrathecal injection of mesenchymal stem cell-derived neural progenitor cells significantly correlated with reduced immune cell infiltration in the brain, reduced area of demyelination, and increased number of neural progenitor cells in EAE mice. This successful preclinical study was the impetus for this clinical trial.
Sadiq said, "This study exemplifies the Tisch MS Research Center's dedication to translational research and provides a hope that established disability may be reversed in MS." All study participants will undergo a single bone marrow collection procedure, from which mesenchymal stem cell-derived neural progenitor cells (MSC-NPs) will be isolated. expanded, and tested prior to injection.
All patients will receive three rounds of injections at three-month intervals. Safety and efficacy parameters will be evaluated in all trial participants throughout their regular visits with their attending physicians.
Posted on August 28, 2013 Categories Alternatives to Embryonic Stem Cells, Bone marrow stem cells, Mesenchymal Stem Cells, Neurological treatmentsTags Clinical Trials, Demyelination, food and drug administration, inclusion criteria, Investigational New Drug, mesenchymal stem cells, Mesenchymal stem cells-derived neural progenitors, Multiple Sclerosis, myelin sheath, neural precursors, neural progenitor cells, neural stem cells, stem cell research
How Neural Stem Cells Create New and Varied Neurons
A new study in fruit flies has elucidated a mechanism in neural stem cells by which these types of stem cells generate the wide range of neurons that they form.
Chris Doe, a professor of biology from the Institute of Neuroscience at the University of Oregon, and his co-authors have used the common fruit fly Drosophila melanogaster to investigate the cellular mechanism by which neural stem cells make their distinctive progeny.
As Doe put it, "The question we confronted was 'How does a single kind of stem cell, like a neural stem cell, make all kinds of neurons?"
Researchers have known for some period of time that stem cells have the capacity to produce new cells, but the study by Doe's group shows how a select group of stem cells can create progenitor cells that can generate numerous subtypes of cells.
Doe's study builds on previous studies in which Doe and his colleagues identified the specific set of stem cells that generated neural precursors. These so-called "intermediate neural progenitors" or INPs can expand to form several different new cell types. However, this study did not account for the diversity of the cells generated even if it did account for the number of cells generated (see Boone JQ, Doe CQ, Dev Neurobiol. 2008 Aug;68(9):1185-95).
"While it's been known that individual neural stem cells or progenitors could change over time to make different types of neurons and other types of cells in the nervous system, the full extent of this temporal patterning had not been described for large neural stem cell lineages, which contain several different kinds of neural progenitors," according to this study's first author Omar Bayraktar.
The cell types discovered in this study have analogs in the developing human brain and the research has potential applications for human biologists who want to know how neurons form in the human brain.
The paper from Doe's lab was published along another study on the generation of diverse neurons by a group from New York University. These two papers provide new insight into the means by which neural stem cells generate the wide range of neurons found in the brains of fruit flies and humans.
In their study, Bayraktar and Doe specifically examined stem cells in fruit fly brains known as type II neuroblasts, which generate INPs. However, in this study, the type II neuroblasts were shown to generate INPs, which then go on to form distinct neural subtypes. Even though previous work showed that INPs went on to form about 100 new neurons, in this paper, the INPs were shown to make about 400-500 new neurons.
Another interesting finding was that the gene expression patterns of INPs, which began with three different transcription factors (Dichaete, Grainy Head, and Eyeless). These transcription factors lay the groundwork for INP differentiation, but once INP formation occurs, a new transcriptional program is extended that extends the types of neurons that INPs can form. Such nested transcriptional programs are also common during the specification of neural stem cell progeny in humans brains, with many of the same transcription factors playing a central role in neuron specification.
"If human biologists understand how the different types of neurons are made, if we can tell them 'This is the pathway by which x, y, and Z neurons are made,' then they may be able to reprogram and redirect stem cells to make these precise neurons," Doe said.
However, the mechanism described in this paper has its limits. Eventually the process of generation new cells stops. One of the next questions to answer will be what makes the mechanism turn off, according to Doe.
"This vital research will no doubt capture the attention of human biologists," said Kimberly Andrews Espy, who is vice-president for research and innovation and the dean of the UP graduate school. "Researchers at the University of Oregon continue to further our understanding of the processes that undergird development to improve the health and well-being of people throughout the world."
See Bayraktar OA, Doe CQ. Combinatorial temporal patterning in progenitors expands neural diversity. Nature. 2013 Jun 27;498(7455):449-55. doi: 10.1038/nature12266.
Posted on July 15, 2013 July 15, 2013 Categories Stem Cell BiologyTags cell lineages, Chris Doe, Dichate, Eyeless, Grainy head, human biologists, Institute for Neuroscience, neural progenitor cells, Neural progenitor differentiation, neural stem cell, neural stem cells, neurogenesis, science, Transcription factors, types of stem cells, University of Oregon
Making Brain Cells from Urine
Every day people flush large quantities of cells down the toilet. We think nothing of it because these cells are sloughed into our urine and there is little that can be done about it. However, Chinese scientists have used cells from urine to make neurons that could eventually be used to treat neurodegenerative diseases.
The technique is described in a study that was published in the journal Nature Methods (Wang, et al., Nature Methods (2012) doi:10.1038/nmeth.2283). Unlike embryonic stem cells, which are derived through the destruction of embryos and have the potential to cause tumors, these neural progenitor cells do not form tumors and are made quickly and without the destruction of human embryos.
Stem cell biology expert Duanqing Pei and his co-workers from China's Guangzhou Institutes of Biomedicine and Health, which is part of the Chinese Academy of Sciences, previously published a paper that showed that epithelial cells from the kidney that are sloughed into urine can be reprogrammed into induced pluripotent stem cells (iPSCs) (Ting Zhou, et al., Journal of the American Society of Nephrology 2011 vol. 22 no. 7 1221-1228, doi: 10.1681/ASN.2011010106). In this study, Pei and his colleagues used retroviruses to insert pluripotency genes into kidney-based cells to reprogram them. Retroviruses are efficient vectors for genes transfer, but they insert their virus genomes into the genomes of the host cell. This insertion event can cause mutations, and for this reason, retroviral-based introduction of genes into cells are not the preferred way to generate iPSCs for clinical purposes.
Researchers use retroviruses to routinely reprogram cultured skin and blood cells into iPSCs, and these iPSCs can be differentiated into any adult cell type. However, urine is a much more accessible source of cells.
In this present study, Pei's team used a different technique to introduce genes into the cells from urine; they used "episomal vectors," which is an overly fancy way of saying that they placed the pluripotency genes on small circles of DNA that were then pushed into the cells. Episomal vectors can reprogram adult cells into iPSCs, but they do so at lower levels of efficiency. Nevertheless, episomal vectors have an added advantage in that the vectors transiently express the pluripotency genes in cells and then are lost without inserting into the host cell genome. This makes episomal vectors inherently safer for clinical purposes.
In one of their experiments, perfectly round colonies of reprogrammed cells from urine that resembled pluripotent stem cells after only 12 days. This is exactly half the time typically required to produce iPSCs. When cultured further, the colonies assumed a rosette shape that is common to neural stem cells.
When Pei and others cultured his urine-derived iPSCs in a culture conditions that normally used for cultured neurons, these cells formed functional neurons in the lab. Could these cells work in the brain of a laboratory animal? Transplantation of these cells into the brains of newborn rats showed that, first of all, they did not form tumors, and, secondly, they took on the shape of mature neurons and expressed the molecular markers of neurons.
The beauty of this experiment is that neural progenitors cells (NPCs) grow in culture and researchers can generate buckets of cells for experiments. However, when cells are directly reprogrammed to neurons, even though they make neurons faster than iPSCs.
James Ellis, a medical geneticist at Toronto's Hospital for Sick Children in Ontario, Canada who makes patient-specific iPSCs to study autism-spectrum disorders, said: "This could definitely speed things up."
Another plus of this study is that urine can be collected from nearly any patient and banked to produce instant sources of cells from patients, according to geneticist Marc Lalande, who creates iPSCs to study inherited neurological diseases at the University of Connecticut Health Center in Farmington. Lalande is quite intrigued by the possibility of making iPSCs and NPCs from urine draw from the same patient. Lalande added: "We work on childhood disorders," he says. "And it's easier to get a child to give a urine sample than to prick them for blood."
Posted on December 12, 2012 Categories Alternatives to Embryonic Stem Cells, Embryonic stem cell debate, Induced Pluripotent Stem Cells, Model Systems, Neurological treatments, Stem Cell BiologyTags Embryonic stem cells, neural progenitor cells, pluripotent stem cells, research, science, stem cell biology2 Comments on Making Brain Cells from Urine
Induced Pluripotent Stem Cells Form Layered Retina-Like Structure in Culture
Embryonic stem cells can form several different types of eye-specific cells. In the early years of the 21st century, reproducible and efficient methods for differentiating embryonic stem cells into lens cells, retinal neurons, and retinal pigment epithelial (RPE) cells were developed (Haruta M., Embryonic stem cells: potential source for ocular repair. Semin Ophthalmol. 2005 Jan-Mar;20(1):17-23).
Other experiments showed that embryonic stem cells could be differentiated into neural progenitor cells (NPCs). These NPCs differentiated in culture and some of them even expressed genes characteristic of developing retinal cells. Although it must be noted that this was uncommon and cells expressing markers of mature photoreceptors were not observed. Implantation of these differentiated NPCs into the retinas of laboratory animals allowed them to survive for at least 16 weeks, migrate over large distances, and form photoreceptor-like cells that made blue-absorbing pigments. These cells also integrated into the host retina (Banin E, Retinal incorporation and differentiation of neural precursors derived from human embryonic stem cells. Steem Cells. 2006 Feb;24(2):246-57).
These early experiments were followed by several others that showed equally remarkable promise. Workers in Takahashi's laboratory in Kobe, Japan found that embryonic stem cells could form retinal precursors, but that they rarely formed photoreceptors unless they were treated with extracts from embryonic retinas. However in a follow-up paper in 2008, Takahashi, research group found that specific cocktails of small molecules and/or growth factors could push retinal precursors to form photoreceptors (Osakada, et al., Nat Biotechnol. 2008 Feb;26(2):215-24). Kunisada's lab in Gifu, Japan used various techniques to differentiate embryonic stem cells in culture so that they would form an elaborate retinal-like structure. When this structure was transplanted into the eyes of rodents with inherited eye diseases, these transplanted cells regenerated the ganglion cells in the retina (Aoki H, et al., Graefes Arch Clin Exp Ophthalmol. 2008 Feb;246(2):255-65). Yu's lab from Seoul National University, Seoul, South Korea made pure RPE cell cultures from embryonic stem cells and then transplanted them into the eyes of rodents with RPE-based retinal degeneration diseases (Park UC, et al., Clin Exp Reprod Med. 2011 Dec;38(4):216-21). The transplanted cells formed RPEs and integrated into the retinas of the laboratory animals. Sophisticated functional assays definitively showed that the RPEs made from embryonic stem cells gobbled up the old segments from photoreceptors and recycled the components back to the photoreceptors (Carr AJ, et al., Mol Vis. 2009;15:283-95).
Using embryonic stem cells to make retina-like structures in culture can provide a model for testing new drugs and procedures to treat degenerative eye diseased such a macular degeneration. Also, such structures might be used to transplant sections of retina into the eyes of individuals where the retina has died off.
With this goal in mind, researchers at the University of Wisconsin-Madison have succeeded in making made early retina structures that contain growing neuroretinal progenitor cells. The novelty in this experiment is that they did it using induced pluripotent stem (iPS) cells that were derived from human blood cells.
In 2011, the laboratory, of David Gamm lab, pediatric ophthalmologist and senior author of the study whose lab is at the Waisman Center, created structures from the most primitive stage of retinal development using embryonic stem cells and iPS cells derived from human skin. These structures generated the major types of retinal cells, including photoreceptors, they did not possess the layered structure found in more mature retina. Clearly something was missing t form a retinal-like structure.
The iPS cells used in this study were made by scientists at a biotechnology company called Cellular Dynamics International (CDI) of Madison, Wisconsin. CDI pioneered the technique to convert blood cells into iPS cells, and they extracted a type of blood cell called a T-lymphocyte from donor samples. These T-lymphocytes were reprogrammed into iPS cells (full disclosure: CDI was founded by UW-Madison stem cell pioneer James Thomson).
With these iPS cells, Gamm and postdoctoral researcher and lead author Joseph Phillips, used their previously-established protocol to grow retina-like tissue from iPS cells. However, this time, about 16% of the initial retinal structures developed distinct layers, which is the structure observed in a mature retina. The outermost layer primarily contained photoreceptors, whereas the middle and inner layers harbored intermediary retinal neurons and ganglion cells, respectively. This particular arrangement of cells is reminiscent of what is found in the back of the eye.
At 72 days, stem cells derived from human blood formed an early retina structure, with specialized cells resembling photoreceptors (red) and ganglion cells (green) located within the outer and inner layers, respectively. Nuclei of cells within the middle layer are shown in blue. These layers are similar to those present during normal human eye development.
These retinal structures also showed proper connections that could allow the cells to communicate information. In the retina, light-sensitive photoreceptor cells along the back wall of the eye produce impulses that are ultimately transmitted through the optic nerve and then to the brain, and this allows. Because these layered retinal structures not only had the proper cell types, but also the proper connections, these findings suggest that it is possible to assemble human retinal cells into the rather complex retinal tissues found in an adult retina. This is extremely stupefying when one considers that these structures all started from a single blood sample.
There are several applications to which these structures might be subjected. They could be used to test drugs and study degenerative diseases of the retina such as retinitis pigmentosa (a major cause of blindness in children and young adults). Also, it might be possible one day to replace multiple layers of the retina in order to help patients with more widespread retinal damage.
Gamm said, "We don't know how far this technology will take us, but the fact that we are able to grow a rudimentary retina structure from a patient's blood cells is encouraging, not only because it confirms our earlier work using human skin cells, but also because blood as a starting source is convenient to obtain. This is a solid step forward." He also added, "We were fortunate that CDI shared an interest in our work. Combining our lab's expertise with that of CDI was critical to the success of this study."
This work was published in the March 12, 2012 online issue of Investigative Ophthalmology & Visual Science. The research is supported by the Foundation Fighting Blindness, the National Institutes of Health, the Retina Research Foundation, the UW Institute for Clinical and Translational Research, the UW Eye Research Institute and the E. Matilda Ziegler Foundation for the Blind, Inc.
Posted on March 16, 2012 March 16, 2012 Categories Induced Pluripotent Stem Cells, Model Systems, Stem Cell Biology, Stem Cell Eye TreatmentsTags Embryonic stem cells, gifu japan, human embryonic stem cells, neural progenitor cells, research, science


50% of all business waste is composed of paper. The most obvious reasons for ditching paper transactions is, of course, reducing paper waste and moving towards eco-friendlier operations. More than that, however, going paperless provides a more convenient, faster, and more secure way of doing transactions and may even have the added benefit of growing your revenue and productivity! Most businesses these days are digitizing the majority of their processes, including accounting, filing, payroll, and even human resource processes.
Despite all the advances in communication technology, it has not gotten and perhaps will never get to the point where artificial intelligence will beat the importance and effectivity of personalized interaction. And it cannot get any truer in 2019 when everything is digitized. Even while you work towards going paperless, strive to keep the personal and human touch for your services especially in direct communications with your customers.
2018 was rocked by cybersecurity attacks and controversies, one after the other. Even the biggest names in the corporate world were not spared. The coming year is not looking too great either, with predictions about e-security concerns involving increased threats, smarter attackers, and breaches that are increasingly more difficult to guard against. These attacks spare no one and it goes without saying that cybersecurity should be one of your top priorities for this year, especially if you are planning to go digital or expand your digital horizons.
Whether you're running a digital office or a physical one, there are many ways to change things up to boost creativity, improve equality, and open more opportunities for growth for your employees and your business alike. One of those aspects that you should focus more on this year is employee engagement. It is one facet of your organization that is as important as sales performance, revenues, productivity, etc. Engaged employees are proven to be more proactive, more willing to go the extra mile, and become leaders instead of just passive followers in your organization.
5. Outsource more parts of your operations.
"If you want to do small things right, do them yourself. If you want to do great things and make a big impact, learn to delegate." John Maxwell's quote has become truer than ever in the age of outsourcing. There are many minor parts of business operations that you are better off delegating to a third-party service provider – for reasons that include but are not limited to convenience, efficacy, cost-efficiency and better business focus. These things can include uniform services, facility services, bookkeeping, and a whole host of other big and small services.
The new year always comes with bigger changes and even bigger challenges and the best way to embrace them is to prepare for them. Happy new year from your friends at Ideal Linen!


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Artificial Intelligence has a gender problem — why it matters for everyone
To fight the rise of bias in AI, more representation is critical in the computing workforce, where only 26 percent of workers are women, 3 percent are African-American women, and 2 percent are Latinx.
EqualAI executive director Miriam Vogel and author of "Weapons of Math Destruction" Cathy O'Neil during a discussion at Boundary Breakers in Brooklyn on Thursday.Celeste Martearena for Julian Ribinik Photography
Dec. 6, 2019, 6:03 PM UTC
By Halley Bondy
More women and minorities must work in tech, or else they risk being left behind in every industry.
This grim future was painted by Artificial Intelligence (AI) equality experts who spoke at a conference Thursday hosted by LivePerson, an AI company that connects brands and consumers.
In that future, if AI goes unchecked, workplaces will be completely homogenous, hiring only white, nondisabled men.
"In this bleak depiction of our future, decades of fights for civil rights and equality have been unwritten in a few lines of code," said EqualAI executive director Miriam Vogel at the conference in Brooklyn, N.Y., called "Boundary Breakers: Women Driving The Future of Tech."
Women and minorities are not building AI, and therefore, they are not being represented in popular algorithm-based products, according to Vogel. Algorithms find patterns throughout history, and essentially make predictions based on stereotyping, she said. Already, facial recognition technology perceives white men more easily than women and minority features, Vogel said. Minorities are being denied credit cards due to where they live [and] due to their area's history of poor credit.
The future of A.I. is in the hands of nine companies. It's time to take it back.
Large companies are using AI in their hiring practices, which leads to inevitable implicit bias that is difficult to detect, Vogel said to the crowd of about 55 tech thinkers.
"The people employing these AI products probably don't even know their outcomes are discriminatory," said Vogel. "AI becomes a mirror. It reflects and it magnifies the biases in our society."
Guest speaker Cathy O'Neil, who authored "Weapons of Math Destruction," explained how hiring bias works with AI: company algorithms are created by (mostly white male) data scientists, and they are based on the company's historic wins. If a CEO is specifically looking for hirees who won't leave the company after a year, for example, he might turn to AI to look for candidates based on his company's retention rates. Chances are, most of his company's historic wins only include white men, said O'Neil.
"Algorithms are presented to us as objective truth that will solve problems that seem unsolvable. But what we really have is people who have their definition of success who are hiding behind the authority of mathematics," O'Neil said. "The truth is, it's not that mathematically complicated...It's about pattern matching, and the presumption that what worked before will work again. And guess what, we don't actually want to repeat history, do we?"
'Be comfortable with being uncomfortable': See how this scientist is openings doors for women in STEM
Speaker Judith Spitz said only around 18 percent of computer science graduates are female, and that this number has been static since 2008. Spitz built an internship program called Women in Technology and Entrepreneurship in New York (WiTNY), which finds paid computer science internships for low income, female high school freshman and sophomores.
"The confidence they got from having met with executives, the experience that they'd been there, and project they worked on...I can tell you, the confidence they get from one paid summer tech internship, they're off and running...One of our students is sitting on five offers this summer. It's really transformational."
Panelist Lisa Kay Davis, a journalist and social strategist at IBM, credits her mentors and her ability to speak up for her rise.
"I've been groomed to be the type of person who speaks up and advocates, and ask 'is this really true?'" said Davis. "Especially in tech, you get to ask that question all the time. I like to push people...there are always ways to create opportunities for other women."
Davis encouraged women to negotiate for their worth.
"Be greedy about getting access to information," said Davis. "...I relish sharing that information and asking 'how much do you make?' It makes some people uncomfortable, but you have to know. Sometimes there is a $20,000 gap between what you're making and what the person next to you is making, and you're doing the same job"
For Vogel, closing the gap between men and women in tech is not just a moral imperative. It could curb economic disaster for women and minorities. She said she was alarmed that her two daughters were not learning to code in middle school.
"I'm used to being the only woman in the room...but I thought it would be different for my two daughters," she said. We all need to ask if our daughters, nieces and neighbors are being exposed to the modern language of coding, computational thinking, and data literacy."


text:
Le France est un projet de paquebot français mené par Didier Spade. Depuis 2015, ce projet pour un navire  est à la recherche d'un financement.

Le siège social de l'armateur se situe à Paris dans le port de Grenelle au bord de la Seine.

Histoire

Naissance du projet
Ce projet, monté par l'armateur Didier Spade, patron de Paris Yacht Marina, est né d'une vocation familiale dans le design et l'exploitation de bateaux. Une équipe de professionnels de la croisière, de la finance, du design et de l'architecture navale a été constituée afin de mener ce projet jusqu'à son terme. En 2010, des obligations ont été émises pour financer les études, et des relations ont été engagées avec les Chantiers de l'Atlantique à Saint-Nazaire, qui ont déjà travaillé à la construction et à l'aménagement de prestigieux navires. Pour autant, en 2022, faute de financement, le début de construction du nouveau paquebot France n'est pas envisagé avant 2024.

Conception et construction
En 2011, le projet initial s'articule autour d'un navire de moyenne capacité conçu et construit aux chantiers STX de Saint-Nazaire :  de long, 640 passagers et environ 600 membres d'équipage, 300 suites réparties sur 17 ponts, 8 restaurants, un casino et de nombreux autres lieux de loisir. La mise à l'eau était envisagée en 2015.

En 2017, faute de financement, Didier Spade est contraint de revoir ses ambitions fortement à la baisse. Il envisage désormais un navire aux dimensions très modestes : ,  de long sur  de large, avec à peine 450 passagers. Son architecture rappellerait néanmoins celle de son célèbre et illustre prédécesseur, le France, avec deux cheminées rouge et noire. Il serait la propriété de la société par actions simplifiée « Le Nouveau France » et battrait pavillon français. La livraison est alors estimée vers 2021/2022, si commande en 2018.

En mars 2020, en conséquence de la pandémie de Covid-19 et sans certitude sur la reprise du marché de la croisière, la levée de fonds est annulée et aucune date n'est avancée pour l'actualisation et la reprise de celle-ci.

Caractéristiques

Aspects techniques

Architecture de la coque
La proue du paquebot serait élancée, tandis que la poupe serait entièrement ouverte sur la mer. La coque blanche serait surmontée de deux superstructures noires rayées de rouge, en référence aux cheminées du France. Elles seraient aménagées et abriteraient divers espaces de vie et seront la particularité du design extérieur du navire.

Propulsion
Malgré un faible tirant d'eau de 6,80 mètres, la vitesse du navire serait de 13 nœuds. Sa propulsion serait assurée par une machinerie à bicarburation (gazole et gaz naturel liquéfié), participant aux efforts d'économie d'énergie.

Installations

Aménagements intérieurs
Un design moderne habillerait le navire. Cependant, le pont 8 offrira aux nostalgiques des grands paquebots transatlantiques des répliques de certaines cabines historiques.

Le paquebot serait, entre autres, doté d'un théâtre immersif et d'un spa d'environ 1300 m².

Aménagements extérieurs
Un jardin palmeraie s'étendrait sur plus de  au cœur du navire.

Notes et références

Voir aussi
 Liste des navires construits aux Chantiers de l'Atlantique
 Histoire de la construction navale dans l'estuaire de la Loire

Liens externes
 Site du projet
 Site Mer et Marine - Nouveau paquebot France

Nom de bateau
Paquebot de croisière


This month we are launching a new monthly series called Scratch in Practice (SiP) to share ideas and strategies with other educators. We're interested in hearing your thoughts. How do you help learners get started with Scratch? What have you learned about how what works for your students? Visit the SiP site and join the conversation!
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text:
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SET @OLD_FOREIGN_KEY_CHECKS=@@FOREIGN_KEY_CHECKS, FOREIGN_KEY_CHECKS=0;
SET @OLD_SQL_MODE=@@SQL_MODE, SQL_MODE='TRADITIONAL,ALLOW_INVALID_DATES';

-- -----------------------------------------------------
-- Schema appsec
-- -----------------------------------------------------

-- -----------------------------------------------------
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CREATE SCHEMA IF NOT EXISTS `appsec` DEFAULT CHARACTER SET utf8 COLLATE utf8_general_ci ;
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CREATE TABLE IF NOT EXISTS `appsec`.`user` (
  `id` INT UNSIGNED NOT NULL AUTO_INCREMENT,
  `email` VARCHAR(120) NOT NULL,
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ENGINE = InnoDB;

-- -----------------------------------------------------
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CREATE TABLE IF NOT EXISTS `appsec`.`post` (
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ENGINE = InnoDB;

SET SQL_MODE=@OLD_SQL_MODE;
SET FOREIGN_KEY_CHECKS=@OLD_FOREIGN_KEY_CHECKS;
SET UNIQUE_CHECKS=@OLD_UNIQUE_CHECKS;


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text:
Nevada as a Role Model
I'm Not a Politician
By: Jared Fisher I never aspired to have a career in politics. As a life-long Republican, I was raised to value self-reliance and not to look to the government to fix the problems I could fix myself. I was also raised to appreciate entrepreneurship. I became a small business owner… [Read More]
Why the Key to Nevada's Success Starts with Strong Family Values
By: Jared Fisher I believe our state is only as strong as its families and communities. Nevada residents need to elect officials that will emphasize the value of parental involvement in schools and encourage community engagement and volunteer service. Nevada is facing a major mental health crisis. Our state currently… [Read More]
Jared Fisher Sponsors "Scale the Strat" Champion Runner, Raises Money for the American Lung Association
On a chilly Sunday morning in Las Vegas, when many Southern Nevada residents were still sound asleep in their beds, 19-year-old Fisher for Nevada Team volunteer Greg Billingsley was running up the stairs of the Stratosphere—the tallest free-standing observation tower in the United States. It took Greg only eight minutes… [Read More]
8 Reasons to Elect Me as Your Next Governor
By: Jared Fisher When I first moved to Southern Nevada over 25 years ago, I knew this state was a place for visionaries. Two years into my time at the University of Nevada Las Vegas (UNLV) and I'd already launched what would become a successful small business, thanks to the… [Read More]
Jared Talks Education, Energy and the Economy with BMX Star TJ Lavin and UFC Hall of Famer Forrest Griffin
Updated September 11, 2017: The podcast is now live! Click here: http://anythinggoestjforrest.libsyn.com/episode-13-nevada-governor-candidate-jared-fisher to hear the interview in its entirety. This week, Jared appeared on TJ Lavin and Forrest Griffin's podcast "Anything Goes" in their recording studio in Las Vegas. Jared, who has known TJ since the 90s, was invited to be a… [Read More]


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Florida Amusement Park Ride Injury Lawyers
Orlando Personal Injury Attorneys > Florida Amusement Park Ride Injury Lawyers
Every year, millions of people visit the nation's amusement parks, a wonderful form of entertainment for people of all ages. Florida is home to some of the world's most popular attractions, including Walt Disney World.
However, mechanical problems and other defects have hurt or even killed dozens of visitors at these amusement parks. Some of the most recent injuries are the following:
In June 2007, a 13 year-old girl had both of her feet severed on a ride at Six Flags Kentucky Kingdom in Louisville.
In August 2006, a 7 year-old boy from Florida was bitten on the thumb by a dolphin at SeaWorld Orlando.
In August 2006, a 6-year-old boy from Georgia was bitten on the arm by a dolphin at SeaWorld Orlando.
In July 2006, a 52-year-old man from Florida died after riding Busch Gardens Tampa's Gwazi Tiger Coaster.
In June 2006, a 12-year-old boy from Kentucky died after riding Walt Disney World's Rock 'n' Roller Coaster.
In April 2006, a 49-year-old woman from Germany died after riding Walt Disney World's Mission: Space.
In June 2005, a 4-year-old boy died after riding Walt Disney World's Mission: Space.
10 serious injuries and illnesses from Mission: Space have been reported since the ride opened in 2003.
Both Space Mountain at Disney's Magic Kingdom and the wave pool at Typhoon lagoon had reported one death and four serious injuries or illnesses since 2003.
The Consumer Protection Safety Commission estimates that the number of serious injuries on amusement park rides warranting a trip to the emergency room have risen to almost 5,000 annually. Unfortunately, the CPSC's ability to gather accurate information is seriously hampered by the loophole in the Consumer Product Safety Act in 1981 — the so-called "roller coaster loophole." This loophole prohibits the CPSC from regulating the safety of rides that are fixed to a specific site. While mobile rides, those that move from location to location – such as in carnivals and other mobile attractions – fall under their jurisdiction. Although legislation regarding amusement park rides has been introduced in Congress, it has failed to become law.
As a result, regulation and inspection of "fixed site" amusement rides are left up to the state or local municipality, and as a result, oversight varies from good to none. A majority of states and municipalities provide some type of regulation (i.e., licensing, inspection, insurance requirements); the states containing the largest number of amusement parks (i.e., California, Florida, Ohio) do have some oversight. However, consumers have no way of finding out how many guests have been seriously injured on rides at parks such as Disney World and Universal Studios Florida.
Florida's largest amusement parks, including Walt Disney World, are exempt from state regulations that require mandatory reporting of injuries and give the state authority to shut down and inspect rides. Disney voluntarily submits to safety inspections.
CPSC has stated that several factors are at fault in the amusement park accidents: consumer behavior, operator behavior, mechanical failure and design defects or limitations.
Liability for amusement park accidents and theme park injuries involves three types of law – negligence or tort law, product liability law and premises liability law. These laws are complex and require the expertise of a Florida personal injury lawyer with experience handling amusement park accident injury cases.
At Martinez Manglardi, our personal injury lawyers are committed to protecting the safety of Florida's families. We represent the injured in Orlando, Orange County, Kissimmee, Osceola County, Apopka, Seminole County, Palm Bay, Brevard County, Ocala and throughout Florida. Our cases are handled by a team of professionals, including nurses, doctors, engineers and other experts. State-of-the-art technology is utilized to effectively present claims. If you or a loved one has been a victim of personal injury, contact us today via our online contact form, or call our Orlando, Kissimmee, Apopka, Palm Bay or Ocala offices at 407-846-2240.Whether your case is settled or tried, you can be assured that Martinez Manglardi has obtained the maximum possible amount of damages in your case.


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Bivens v. Board of Review
Opinion Date: September 27, 2004
UNEMPLOYMENT COMPENSATION—It is an unemployment benefit claimant's obligation to do whatever is reasonable and necessary in order to remain employed.
An employee resigned from her job and filed a claim for unemployment benefits. The Deputy Director of the Division of Unemployment and Disability Insurance determined the employee to be eligible for benefits without disqualification. The employer appealed, and after a hearing, the Appeal Tribunal reversed, holding that the employee disqualified for benefits. The Board of Review affirmed the Tribunal's decision.
At the time of her resignation, the employee was in a high level supervisory role. At the hearing, she testified that she told her employer that she was leaving because "things seem[ed] to be changing for [her]. Jobs are being taken away… [her] position and [her] obligation ... seem[ed] to be at a stand still." She also claimed that she was told that the product line that she was working on was becoming obsolete. She admitted that she would not have resigned had her product line not been taken, and she admitted that she was told her job was secure and that neither her salary nor work hours were going to be changed. Her employer testified that she was an exemplary employee, heavily relied upon because of her experience and people skills. According to the employer, its employee had expressed a desire to relocate because her family was not in the area. In fact, less than three months after her resignation, she relocated to another state. For those reasons, the Appeal Tribunal disqualified the woman for benefits, finding that she had left work voluntarily without good cause attributable to such work.
In her appeal, the Appellate Division, the employee claimed that her supervisory and managerial abilities were slowly being taken away and that her job duties had been reduced to that of a manager-supervisor with no one to manage or supervise. She alleged that her employer was slowly, but surely, constructively discharging her. She claimed that she had no alternative but to leave and seek other employment because her termination seemed inevitable.
When an employee voluntarily quits a job, he or she has the burden of proving that the resignation was for good cause attributable to his or her work. An employee's reason for leaving his or her employment must meet the test of ordinary common sense and prudence. In fact, it is a claimant's responsibility to do whatever is necessary and reasonable in order to remain employed. The Appellate Division found that the employee's job was secure at the time of her resignation and work was available to her at her same hourly wage, with the same work hours and the same work week. For those reasons, the Court held that a factfinder could reasonably conclude that the woman had left work voluntarily without good cause attributable to such work. Therefore, it affirmed the Board of Review's decision to affirm the disqualification of benefits.


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HomeGEOGRAPHIC REGIONAsiaJohnson Pilton Walker wins National Workers' Memorial
Johnson Pilton Walker wins National Workers' Memorial
National Workers' Memorial winning design is by Sydney based architecture firm, Johnson Pilton Walker. A memorial is to be established in the Canberra, Australia to honour, and pay tribute to those working Australians who have lost their lives through work-related accidents, incidents or disease. The winning design was developed by Sydney based architecture firm, Johnson Pilton Walker.
The winner was selected following a national design competition held from 17 August to 6 October 2011. A total of 26 entries were received. The Memorial represents a workers' glade nestled into a small rise in the topography of the park.
It features eight slender columns clad in stone unique to the state or territory each represents. Viewed from above, the locations of the columns, laid out like a map of Australia, correspond with the locations of each state's capital city. The columns provide a place where visitors can leave tokens of remembrance for loved ones.
Concentric rings on the plaza pavement surrounding the columns represent the 'ripple effect' a work related death has on family, friends and the local community. The ripples will contain milestones and positive steps taken to improve health and safety outcomes and the prevention of work-related accidents and disease in Australia.
The elements of the Memorial include:
A meaningful place of reflection – sensitively designed with capacity for commemorative ceremonies, as well as quiet personal contemplation
This material may take many forms, such as a chronological list of actions, events, legislation, milestones and quotes relevant to each value, and can be updated over time.
The format will be inlayed metal strips, engraved with lettering, following the circular contours of the ripples. This technique encourages exploration of the memorial grounds.
Eight tall, slender columns representing the contributions and sacrifice of workers from each state in Australia set in a memorial plaza.
Viewed from above, the columns indicate a map of Australia – and the national nature of workplace death.
The columns are the tactile focus of the memorial, and provide a personal encounter for visitors.
Each column will be clad in granite or other stone, unique to the state or territory that the columns represent. 'The people of…' each state or territory will be etched into the column.
A plate at the base of each column will be engraved with a statement about work, such as 'Work and Family', 'Work and Skills' and 'Work and Safety'.
Each column provides a focus for individual reflection, and as a group, they illustrate the influence of work on our lives, communities and nation.
The columns, measuring around seven metres in height, will finish below the level of the surrounding existing tree canopy in Kings Park.
A low, curvilinear seating wall creating an informal amphitheatre.
The opportunity for wreaths and tributes to be placed at the foot of the columns or around the amphitheatre.
Images: Courtesy of National Capital Authority
AIDS Memorial new design approved by Community Board
July 24, 2012,AEST
The Rooftop Garden Climbs Down a Wall
November 20, 2009,AEST
In The Modern Context | San Mateo, CA, USA | Arterra Landscape Architects
October 10, 2017,AEST


ERUS 2018: Lymph Node Dissection: Extended is Enough or is Super Extended Mandatory?
Marseille, France (UroToday.com) Dr. Moon gave an overview of the optimal pelvic lymphadenectomy (PLND) in radical cystectomy (RC) and the comparison of extended vs. super-extended dissection.
Preoperative imaging can be used to guide us in the decision in which patients we should perform PLND. When performing PLND, the chance of benefit should be weighed against the risk of harm. The benefit is established when there is N1 disease, high risk of local recurrence, and when adjuvant chemotherapy is considered. Harm could be caused when complications arise, and when dissection is expected to be harder than expected.
The PLNDy templates can be divided into several zones (Figure 1). The median number of lymph nodes removed from each location1 is demonstrated in figure 2. Almost all lymph nodes are found up to the level of the ureter crossing the common iliac vessels (Figure 3). There are different templates for PLND, including limited, extended and super-extended (Figure 4).
The outcomes of PLND are predicted by pathological T stage, the number of positive lymph nodes removed, the density of positive lymph nodes, their location, the extent of PLND performed and the nodal yield. When comparing PLND to no PLND, studies have shown that no PLND yields increased mortality2, with 5-year cancer-specific mortality of 65% for PLND vs. 54% for no PLND3. A systematic review of 7 studies demonstrated that any PLND is better than no PLND, and extended PLND is better than standard PLND, while no benefit was seen from super extended PLND4.
Interestingly, PLND has even shown benefit in patients with no lymph node involvement. A published study demonstrated that a cutoff of 16 nodes (all negative) yielded a higher cancer-specific survival of 83% vs. 72% for a lower number of removed nodes5. Furthermore, the cancer-specific death two years post-cystectomy was higher among patients with a lower number of negative lymph nodes removed (16% for ten nodes removed vs. 5.5% for 30 nodes removed)6.
Extended PLND has been shown to be better than non-extended PLND in a meta-analysis of 6 studies, including almost 3000 patients. The recurrence-free survival was better for patients with pathological stage T3-T4 and patients with involved and uninvolved lymph nodes7. However, when comparing extended vs. super-extended PLND no improved outcomes were evident.
Dr. Moon summarized his talk by stating that there are currently two randomized controlled trials assessing the impact of PLND in RC (Figure 5). The key take-home messages should be that there is a substantial amount of evidence demonstrating the oncological benefit of PLND for both node-positive and node-negative disease. Prognostic information from resected nodes can help us guide management. Extended PLND provides optimal recurrence-free survival, and cancer-specific survival, while no additional benefit can be seen with super-extended PLND. To date, until results of level 1 evidence are published, recommendations for the optimal PLND template are limited.
Dorin RP, Daneshmand S, Eisenberg MS, et al. Lymph node dissection technique is more important than lymph node count in identifying nodal metastases in radical cystectomy patients: a comparative mapping study. European Urology 2011; 60(5): 946-52.
Konety BR, Joslyn SA, O'Donnell MA. The extent of pelvic lymphadenectomy and its impact on outcome in patients diagnosed with bladder cancer: analysis of data from the Surveillance, Epidemiology, and End Results Program database. The Journal of Urology 2003; 169(3): 946-50.
Larcher A, Sun M, Schiffmann J, et al. Differential effect on survival of pelvic lymph node dissection at radical cystectomy for muscle-invasive bladder cancer. European journal of surgical oncology: the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 2015; 41(3): 353-60.
Bruins HM, Veskimae E, Hernandez V, et al. The impact of the extent of lymphadenectomy on oncologic outcomes in patients undergoing radical cystectomy for bladder cancer: a systematic review. European Urology 2014; 66(6): 1065-77.
May M, Herrmann E, Bolenz C, et al. Association between the number of dissected lymph nodes during pelvic lymphadenectomy and cancer-specific survival in patients with lymph node-negative urothelial carcinoma of the bladder undergoing radical cystectomy. Annals of surgical oncology 2011; 18(7): 2018-25.
Crozier J, Papa N, Perera M, et al. Lymph node yield in node-negative patients predicts cancer-specific survival following radical cystectomy for transitional cell carcinoma. Investigative and clinical urology 2017; 58(6): 416-22.
Bi L, Huang H, Fan X, et al. Extended vs non-extended pelvic lymph node dissection and their influence on recurrence-free survival in patients undergoing radical cystectomy for bladder cancer: a systematic review and meta-analysis of comparative studies. BJU international 2014; 113(5b): E39-48.


A new vegan Chinese and sushi restaurant, Chef Kenny's Asian Vegan Restaurant, has opened in Las Vegas on Spring Mountain Road.
Launched by Kenny Chye, the founder of Las Vegas' first vegan drive-thru, Vege-Way, the new menu features vegan tuna, eel, salmon, and eel sauce. As well as Chye's very own spin on the Rainbow Roll, which includes avocado, cucumber, and carrots, with vegan fish. "I found out vegan sushi is a trend," the chef told Las Vegas Weekly. "No chef makes good vegan sushi," he added.
Further, some of the city's casinos, owned by major gaming brand Station Casinos, recently added vegan options to their menus. "This year we've redesigned our menus to bring you more vegan and vegetarian options. From Mexican to Italian, Station Casinos is bringing you more options than ever before," the company wrote in a blog post.
The Modern Vegan Restaurant is another new plant-based establishment to Vegas, opened in March – it was the first vegan restaurant to launch in the city of the year and offers 100 plant-based menu items, from vegan fried chicken to avocado on toast.


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Filipe de Saboia, Duque de Nemours nasceu em 1490 em Bourg-en-Bresse e morreu em Marselha a 25 de Outobro de 1533.

Foi Conde de Genebra de 1514 a 1533 e Duque de Némours de 1515 a 1533. Filho de Filipe II de Saboia e de Claudina de Brosse era  Duque de Saboia  e Príncipe do Piemonte.

Ao princípio destinado à vida monástica foi nomeado Bispo de Genebra - o quarto no século XV da Casa de Saboia nomeado para uma diocese desta importância. Depois de ter combatido ao lado do rei de França, deixa o a vida eclesiástica para se dedicar ao lado do seu irmão Carlos III de Saboia à política. Nessa altura, 1514, recebe em apanágio o Genevois e o Francigny e no ano seguinte o seu sobrinho Francisco I de França dá-lhe o Ducado de Nemours.

Casamento e descendência
Em 1528 casou com Carlota de Orleães-Longueville, filha de Luís I de Orleães-Longueville. Nessa ocasião, o seu sobrinho, o rei Francisco I de França, dá-lhe o ducado de Nemours, Deste casamento nasceram dois filhos:
Jaime de Saboia-Nemours (1531 † 1585), duque de Genève e de Nemours;
Joana de Saboia (1532 † 1568) que se casou com Nicolau de Lorena (1524-1577), duque de Mercœur.

Ver também
 Os Saboia-Nemours
 Duques de Nemours

Nobres da França
Nobres da Suíça
Duques de Némours
Condes de Genebra
Condes de Saboia