text:
Q: How to create a delayed queue in RabbitMQ? What is the easiest way to create a delay (or parking) queue with Python, Pika and RabbitMQ? I have seen an similar questions, but none for Python.
I find this an useful idea when designing applications, as it allows us to throttle messages that needs to be re-queued again.
There are always the possibility that you will receive more messages than you can handle, maybe the HTTP server is slow, or the database is under too much stress.
I also found it very useful when something went wrong in scenarios where there is a zero tolerance to losing messages, and while re-queuing messages that could not be handled may solve that. It can also cause problems where the message will be queued over and over again. Potentially causing performance issues, and log spam.

A: FYI, how to do this in Spring 3.2.x.
<rabbit:queue name="delayQueue" durable="true" queue-arguments="delayQueueArguments"/>

<rabbit:queue-arguments id="delayQueueArguments">
  <entry key="x-message-ttl">
    <value type="java.lang.Long">10000</value>
  </entry>
  <entry key="x-dead-letter-exchange" value="finalDestinationTopic"/>
  <entry key="x-dead-letter-routing-key" value="finalDestinationQueue"/>
</rabbit:queue-arguments>

<rabbit:fanout-exchange name="finalDestinationTopic">
  <rabbit:bindings>
    <rabbit:binding queue="finalDestinationQueue"/>
  </rabbit:bindings>
</rabbit:fanout-exchange>

A: NodeJS implementation.
Everything is pretty clear from the code.
Hope it will save somebody's time.
var ch = channel;
ch.assertExchange("my_intermediate_exchange", 'fanout', {durable: false});
ch.assertExchange("my_final_delayed_exchange", 'fanout', {durable: false});

// setup intermediate queue which will never be listened.
// all messages are TTLed so when they are "dead", they come to another exchange
ch.assertQueue("my_intermediate_queue", {
      deadLetterExchange: "my_final_delayed_exchange",
      messageTtl: 5000, // 5sec
}, function (err, q) {
      ch.bindQueue(q.queue, "my_intermediate_exchange", '');
});

ch.assertQueue("my_final_delayed_queue", {}, function (err, q) {
      ch.bindQueue(q.queue, "my_final_delayed_exchange", '');

      ch.consume(q.queue, function (msg) {
          console.log("delayed - [x] %s", msg.content.toString());
      }, {noAck: true});
});

A: You can use RabbitMQ official plugin: x-delayed-message .
Firstly, download and copy the ez file into Your_rabbitmq_root_path/plugins
Secondly, enable the plugin (do not need to restart the server):
rabbitmq-plugins enable rabbitmq_delayed_message_exchange

Finally, publish your message with "x-delay" headers like:
headers.put("x-delay", 5000);

Notice:
It does not ensure your message's safety, cause if your message expires just during your rabbitmq-server's downtime, unfortunately the message is lost. So be careful when you use this scheme.
Enjoy it and more info in rabbitmq-delayed-message-exchange

A: I found this extremely useful when developing my applications. As it gives you an alternative to simply re-queuing your messages. This can easily reduce the complexity of your code, and is one of many powerful hidden features in RabbitMQ.
Steps
First we need to set up two basic channels, one for the main queue, and one for the delay queue. In my example at the end, I include a couple of additional flags that are not required, but makes the code more reliable; such as confirm delivery, delivery_mode and durable. You can find more information on these in the RabbitMQ manual.
After we have set up the channels we add a binding to the main channel that we can use to send messages from the delay channel to our main queue.
channel.queue_bind(exchange='amq.direct',
                   queue='hello')

Next we need to configure our delay channel to forward messages to the main queue once they have expired.
delay_channel.queue_declare(queue='hello_delay', durable=True,  arguments={
  'x-message-ttl' : 5000,
  'x-dead-letter-exchange' : 'amq.direct',
  'x-dead-letter-routing-key' : 'hello'
})

*

*x-message-ttl (Message - Time To Live)
This is normally used to automatically remove old messages in the
queue after a specific duration, but by adding two optional arguments we
can change this behaviour, and instead have this parameter determine
in milliseconds how long messages will stay in the delay queue.

*x-dead-letter-routing-key
This variable allows us to transfer the message to a different queue
once they have expired, instead of the default behaviour of removing
it completely.

*x-dead-letter-exchange
This variable determines which Exchange used to transfer the message from hello_delay to hello queue.
Publishing to the delay queue
When we are done setting up all the basic Pika parameters you simply send a message to the delay queue using basic publish.
delay_channel.basic_publish(exchange='',
                      routing_key='hello_delay',
                      body="test",
                      properties=pika.BasicProperties(delivery_mode=2))

Once you have executed the script you should see the following queues created in your RabbitMQ management module.

Example.
import pika

connection = pika.BlockingConnection(pika.ConnectionParameters(
               'localhost'))

# Create normal 'Hello World' type channel.
channel = connection.channel()
channel.confirm_delivery()
channel.queue_declare(queue='hello', durable=True)

# We need to bind this channel to an exchange, that will be used to transfer
# messages from our delay queue.
channel.queue_bind(exchange='amq.direct',
                   queue='hello')

# Create our delay channel.
delay_channel = connection.channel()
delay_channel.confirm_delivery()

# This is where we declare the delay, and routing for our delay channel.
delay_channel.queue_declare(queue='hello_delay', durable=True,  arguments={
  'x-message-ttl' : 5000, # Delay until the message is transferred in milliseconds.
  'x-dead-letter-exchange' : 'amq.direct', # Exchange used to transfer the message from A to B.
  'x-dead-letter-routing-key' : 'hello' # Name of the queue we want the message transferred to.
})

delay_channel.basic_publish(exchange='',
                      routing_key='hello_delay',
                      body="test",
                      properties=pika.BasicProperties(delivery_mode=2))

print " [x] Sent"

A: Message in Rabbit queue can be delayed in 2 ways
     - using QUEUE TTL
     - using Message TTL
If all messages in queue are to be delayed for fixed time use queue TTL.
If each message has to be delayed by varied time use Message TTL.
I have explained it using python3 and pika module.
pika BasicProperties argument 'expiration' in milliseconds has to be set to delay message in delay queue.
After setting expiration time, publish message to a delayed_queue ("not actual queue where consumers are waiting to consume") , once message in delayed_queue expires, message will be routed to a actual queue using exchange 'amq.direct'
def delay_publish(self, messages, queue, headers=None, expiration=0):
    """
    Connect to RabbitMQ and publish messages to the queue
    Args:
        queue (string): queue name
        messages (list or single item): messages to publish to rabbit queue
        expiration(int): TTL in milliseconds for message
    """
    delay_queue = "".join([queue, "_delay"])
    logging.info('Publishing To Queue: {queue}'.format(queue=delay_queue))
    logging.info('Connecting to RabbitMQ: {host}'.format(
        host=self.rabbit_host))
    credentials = pika.PlainCredentials(
       RABBIT_MQ_USER, RABBIT_MQ_PASS)
    parameters = pika.ConnectionParameters(
       rabbit_host, RABBIT_MQ_PORT,
        RABBIT_MQ_VHOST, credentials, heartbeat_interval=0)
    connection = pika.BlockingConnection(parameters)

    channel = connection.channel()
    channel.queue_declare(queue=queue, durable=True)

    channel.queue_bind(exchange='amq.direct',
                       queue=queue)
    delay_channel = connection.channel()
    delay_channel.queue_declare(queue=delay_queue, durable=True,
                                arguments={
                                    'x-dead-letter-exchange': 'amq.direct',
                                    'x-dead-letter-routing-key': queue
                                })

    properties = pika.BasicProperties(
        delivery_mode=2, headers=headers, expiration=str(expiration))

    if type(messages) not in (list, tuple):
        messages = [messages]

    try:
        for message in messages:
            try:
                json_data = json.dumps(message)
            except Exception as err:
                logging.error(
                    'Error Jsonify Payload: {err}, {payload}'.format(
                        err=err, payload=repr(message)), exc_info=True
                )
                if (type(message) is dict) and ('data' in message):
                    message['data'] = {}
                    message['error'] = 'Payload Invalid For JSON'
                    json_data = json.dumps(message)
                else:
                    raise

            try:
                delay_channel.basic_publish(
                    exchange='', routing_key=delay_queue,
                    body=json_data, properties=properties)
            except Exception as err:
                logging.error(
                    'Error Publishing Data: {err}, {payload}'.format(
                        err=err, payload=json_data), exc_info=True
                )
                raise

    except Exception:
        raise

    finally:
        logging.info(
            'Done Publishing. Closing Connection to {queue}'.format(
                queue=delay_queue
            )
        )
        connection.close()

A: Depends on your scenario and needs, I would recommend the following approaches,

*

*Using the official plugin, https://www.rabbitmq.com/blog/2015/04/16/scheduling-messages-with-rabbitmq/, but it will have a capacity issue if the total count of delayed messages exceeds certain number (https://github.com/rabbitmq/rabbitmq-delayed-message-exchange/issues/72), it will not have the high availability option and it will suffer lose of data when it runs out of delayed time during a MQ restart.

*Implement a set of cascading delayed queues just like NServiceBus did (https://docs.particular.net/transports/rabbitmq/delayed-delivery).


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Warriors' Klay Thompson on Buddy Hield: "He's Next Big Thing"
Klay Thompson is no NBA general manager, but he doesn't shy away from assessing college talent – particularly that of Oklahoma guard Buddy Hield.
Thompson is a huge fan of Hield, the Oklahoma guard who is lighting up the NCAA Tournament while leading the Sooners into the Final Four this weekend in Houston.
"He'll be a great scorer," Thompson told CSNBayArea.com on Monday. "He works so hard. He'll be a tenacious defender. He's physically gifted. He's going to help somebody. He's going to make a big impact.
READ >> The latest news on Buddy Hield.


Ferry stranded without Portuguese subsidy?
Earlier this week all seven of the companies interested in re-introducing the ferry link between Madeira and mainland Portugal announced that they could not submit viable offers to run the operation without direct subsidies. At a press conference on Wednesday, Eduardo Jesus, Regional Secretary for Economy, Tourism and Culture, explained that the Madeiran Government had already offered "a highly attractive package" of incentives including relief port taxes (with full exemption in the first year), as well as passenger subsidies covering up to half of the ticket price. In addition the Regional Government were prepared to fund an advertising campaign worth €80,000. However all seven of the bidders still found that in order to make the numbers add up they required additional direct compensation. It is not clear whether the companies are acting jointly or independently, but none made a concrete proposal before the deadline for submissions expired at the year-end.
In an effort to keep the project alive President of the Regional Government, Miguel Albuquerque, has apparently written to the Portuguese Prime Minister requesting further support for the resumption of the ferry service – specifically a legal change that would qualify the transport link to be of "national public interest" and thereby qualify for state compensation.Despite the outcome, Eduardo Jesus said that "the Government does not end the process. It starts now a new phase….which will build on the work done in recent months", He did not indicate the amount of compensation required to make the service viable, but Naviera Armas, the previous ferry operators, reportedly made a loss of €6 million during the last year of operation, although oil prices have subsequently plummeted.
Management company ANA will invest over €74 million during 2016 at its five airports in Lisbon, Faro, Porto, Madeira and the Azores according to today's Journal. The biggest spend will be in Lisbon, where €33.5 million will be invested in improving baggage check-in and security at Terminal 1 – this is already underway and will be completed in May. €2.6 million will be spent as a "quick fix" at Terminal 2, where there is a bottleneck as a result of the increase in low-cost flights.
Faro airport will receive the second largest investment this year, at €25 million, and the Azores €5.9 million. Porto and Funchal come last with a spend of €4 million each – in the case of Funchal this may include work recently undertaken.
It is not often that crime makes the news on this island, but there seems to have been a bit of an outbreak just recently. The Diario reports that in the first instance a taxi driver was robbed and stabbed by a passenger in the early hours of Tuesday in Boa Nova on the outskirts of Funchal. The offender was quickly apprehended and remains in custody. In the second case a Dutch couple had a wallet containing around €2000 snatched whilst walking in the Lido area yesterday afternoon. A young man and woman made off by car, but witnesses noted the registration and they were subsequently arrested in Camacha. €1500 was recovered after the couple had reportedly been to a restaurant, bought drugs and put some new tyres on the car.
You have to question the sense behind going for a stroll with a wallet containing passports and other documents, debit cards and €2000 in cash, even in the safest of locations.
Porto Santo Ferry. Mega Bolo Rei. New Boeing 737.
If the Portuguese government keeps a passive approach to drug taking the situation will develop rapidly.
It's a lot easier to contain this situation whilst in its infancy, if it gets out of hand control is impossible.
Short sharp penalties would be the best option for young offenders.
Bad news re recent crime. Do we know where the perpetrators come from? Hard to believe that natives would have turned to crime.
I don't believe I am as I am not Madeiran.
I said I felt it hard to believe that any Madeirans would turn to crime.
Didn't want to pay for the deposit box in the hotel room, perhaps.
Armas run their boats between the various Canary islands and also between Huelva on the south coast of Spain to the Canaries. I would have thought it possible for one of these to stop off in Funchal. Huelva isn't too far from the Portuguese border.
As someone with rose tinted specs where Madeira is concerned. Just wish details of bad areas had been listed.
Have visited many times. But must admit this last time, i.e April 2016 did notice the number of stray dogs and saw a man surrounded in Camara do Lobos, luckily he had walking poles and fought them off.
We are wanting to buy in Madeira, because of how safe we feel there. Had always thought there was virtually no crime.


text:
Jay-Z, Justin Timberlake and Popeye cartoons helped make this East Village eatery happen
"One day, I got offered a gig with Jay-Z and Justin Timberlake and I turned it down and the next day, I went to culinary school."
Jay-Z, Justin Timberlake and Popeye cartoons helped make this East Village eatery happen "One day, I got offered a gig with Jay-Z and Justin Timberlake and I turned it down and the next day, I went to culinary school." Check out this story on dmJuice.com: https://www.desmoinesregister.com/story/entertainment/dining/2019/11/01/clydes-fine-diner-new-east-village-eatery-serves-modern-takes-on-comfort-food-classics-near-me/4097874002/
Brian Taylor Carlson, Des Moines Register Published 12:22 p.m. CT Nov. 1, 2019 | Updated 2:53 p.m. CT Nov. 13, 2019
A new restaurant now open in the East Village features fun takes on comfort food classics.
Clyde's Fine Diner, which opened Oct. 16 and is located in the new building at 111 East Grand Ave., serves a variety of appetizers, soups and salads, sandwiches, entrees and desserts.
Owned by chef Chris Hoffmann, 41, the 78-seat restaurant pays homage to Hoffmann's grandfather, a major culinary influence in his life.
A "Fried Green Tomato BLT" at Clyde's Fine Diner. The sandwich includes fried green tomatoes, bacon, pimento cheese, braised collard greens and dill garlic aioli. (Photo: Special to the Register)
"Clyde is my grandfather on my mother's side," Hoffmann said. "He was originally from Valdosta, Georgia, and he was a big, big foodie. My earliest memories of cooking are being in the kitchen with him. Every single morning, he would cook biscuits, sausage and eggs. He loved breakfast. He was amazing."
Hoffmann said back in the days before online ordering, his grandfather would send money to his favorite company in Georgia for his favorite milled grits. "He was already sourcing ingredients around the country," Hoffmann said.
Many of the design elements in the restaurant such as branding were inspired by Clyde's doodles Hoffmann kept over the years.
Clyde's Fine Diner on East Grand Avenue in Des Moines. (Photo: Bryon Houlgrave/The Register)
"He was what was called an 'in-betweener' on the Popeye cartoon," Hoffmann said. "The main artist would draw a cell and then he would draw the ones in between to smooth out the transition."
A neon sign in the space was inspired by a comic strip Clyde wrote for a G.I. newspaper when he was stationed in San Juan, Puerto Rico.
Anna Squier of Modern Studio and architect Jeff Rains of Rains Architecture partnered to make the 2,500-square-foot restaurant into a stunning addition to the Des Moines foodscape.
"We wanted to reflect the building that it's in, because it's a beautiful building with the architectural quality of the (cross-laminated) timber and to try and create a place that is classic and timeless," Squier said. "It's kind of an older school diner feel. There are notions that you see at a classic diner in there but with a modern take."
Squier said she wanted to bring a touch of Chicago to the space. Another main design focus was the bar area with comfortable seating and views of the pass-through area of the open kitchen.
"I think the blues and teal really resonated with (Hoffmann's) brand," Squier said. "It was a little more casual and playful and they went with the black and white really well. It's a nice contrast."
"Tuna Noodle Ravioli" at Clyde's Fine Diner. The dish is a play off of tuna casserole. (Photo: Special to the Register)
The menu is full of recognizable and approachable dishes with creative presentations and cultural influences. Vegetarian and vegan options also are available.
"I come from a more upscale fine dining background, and I am using that traditional technique to elevate comfort food and things I really enjoy cooking," Hoffmann said. "This menu is reflective of how I like eating at home and how I like to feed my family."
Sous chef Tom Kelly, 30, also moved with his family to Des Moines from Chicago to help with the restaurant. Kelly and Hoffmann met in culinary school seven years ago.
Not Nashville Hot Chicken at Clyde's Fine Diner on East Grand Avenue in Des Moines. (Photo: Bryon Houlgrave/The Register)
French fries are made from scratch using a method that took Hoffmann years to perfect. And the bread for all of the menu items is made in-house like the potato bun for the CFD Burger with a house burger sauce, American cheese, shaved onion and pickles ($12).
"The vision for this place has been 'everything from scratch,'" Hoffmann said. "Everything is done the hard way, basically, but the hard way yields some delicious results."
Here are a few of Hoffmann's highlights:
Tempura Shishitos - Served with miso mayo, Japanese barbecue sauce, toasted sesame seeds, chili flakes and bonito ($9)
CFD Party Dip - A caramelized onion dip served with housemade Kennebec chips ($7)
Beets salad - Beet yogurt, roasted beets, pickled beets and beet chips tossed with shave fennel, pistachios and shaved sweet onion ($12)
Caesar salad - Romaine, boquerones (fresh anchovies), Kennebec potato chips and shaved Parmesan ($13; add chicken, $5 extra)
Beet Reuben - Corned beets, vegan cheese, sauerkraut and Russian dressing served on rye bread ($14)
Not Nashville Hot - Chicken thigh with chili oil, fermented bean paste, scallion beignets, kimchi creamed collard greens, cucumber quick pickles and chili threads ($19)
Curried Lentils - Over easy duck egg with everything bagel seasoning, marinated mushrooms, yogurt, crispy shallots, pickled dill and pomegranate molasses ($16)
Look for daily blue plate specials like Tuesday's Verde Burger with salsa verde, refried beans, Oaxacan string cheese and poblano peppers served with fries ($14) and Saturday's fried chicken with chicken gravy, mashed potatoes, roasted green beans and pickled okra ($18).
Desserts include soft-serve ice cream with a choice of toppings ($4; toppings, $1 each) and a brownie sundae with hot fudge, whipped cream, nuts and a cherry ($8).
Clyde's Fine Drinks
C.J. Ryherd, formerly of Django, is heading the dining room and bar, putting his spin on the beverage program that includes seasonal cocktails
"The cocktails we do have a lot of ingredients with more complex flavors," Ryherd said. "It's a nice balance of bold flavors, variety and a little something for everybody."
Disorderly Mob is a fall seasonal cocktail at Clyde's Fine Diner on East Grand Avenue in Des Moines. (Photo: Bryon Houlgrave/The Register)
Here are a few of Ryherd's favorites (all $12):
Born on the Bayou - Old Overholt Rye, sweet vermouth, green chartreuse and bitters
Disorderly Mob - Suntory Toki Whiskey (Japanese) with allspice-infused port wine syrup, bitters and a charred orange slice
Temperature's Rising - Havana Club Añejo Rum, lime, Szechuan peppercorns, orange bitters and cinnamon
Ryherd is currently working on a barrel-aged bitters recipe for the restaurant flavored with cherry bark, cinnamon and almond.
Tango in the Night, a house cocktail at Clyde's Fine Diner on East Grand Ave. in Des Moines. (Photo: Bryon Houlgrave/The Register)
Five beers on tap with four local beers and Pabst Blue Ribbon, of course, and an assortment of bottled beers ($5-$8). Wines include red, white, rose and prosecco by the glass an bottle (by the glass, $9-$15; by the bottle, $38-$60)
How Clyde's came to be
"When I was scouting around for places in Des Moines, I was drawn to the East Village," Hoffmann said. "It felt most like my neighborhood in Chicago did and I liked all the foot traffic around here." Hoffmann said he was drawn to the building, as well.
Photos: Clyde's Fine Diner in the East Village
Chris Hoffmann, chef and owner of Clyde's Fine Diner on East Grand Ave. in Des Moines. Bryon Houlgrave/The Register
Not Nashville Hot Chicken at Clyde's Fine Diner on East Grand Ave. in Des Moines. Bryon Houlgrave/The Register
Clyde's Fine Diner on East Grand Ave. in Des Moines. Bryon Houlgrave/The Register
Gyro sausage at Clyde's Fine Diner on East Grand Ave. in Des Moines. Bryon Houlgrave/The Register
Curried lentils at Clyde's Fine Diner on East Grand Ave. in Des Moines. Bryon Houlgrave/The Register
Disorderly Mob, a fall seasonal cocktail at Clyde's Fine Diner on East Grand Ave. in Des Moines. Bryon Houlgrave/The Register
Tango in the Night, a house cocktail at Clyde's Fine Diner on East Grand Ave. in Des Moines. Bryon Houlgrave/The Register
Hoffmann grew up in Ames and spent 18 years in Chicago as a touring live sound engineer for such acts as the Rolling Stones, Wilco and many others.
But about eight years ago, he switched gears and started cooking. "While traveling the world, I got to eat in some of the best restaurants around," Hoffmann said.
Wherever the tour stopped, he would eat his way around the city or devour cooking media. And when he got back home to Chicago, he would create dishes on his own using local ingredients.
Gyro Sausage at Clyde's Fine Diner on East Grand Avenue in Des Moines. (Photo: Bryon Houlgrave/The Register)
After he got married and his wife, Shannon Jencks, 41, a native of Canton, Ohio, was promoted at her job, Hoffmann saw his chance to become a chef and own his own business. "One day, I got offered a gig with Jay-Z and Justin Timberlake and I turned it down and the next day, I went to culinary school."
After graduating from the Art Institute of Chicago, Hoffmann worked his way around restaurants in the city like Vistro under James Beard Award-nominated chef Paul Virant. Hoffmann even ran a food truck.
A "Not Nashville Hot Chicken" at Clyde's Fine Diner. The dish is a breaded chicken thigh, fermented bean paste, chili oil, creamed kimchi collard greens, scallion beignets, cucumber quick pickles and chili threads. (Photo: Special to the Register)
Hoffmann and Jencks live in Des Moines with their two children. In fact, one of their children was born on Oct. 18 — on Friday of the restaurant's opening week.
Takeout is available and lunch service will begin in about a month. The restaurant employs 17 people.
Clyde's Fine Diner on East Grand Ave. in Des Moines. (Photo: Bryon Houlgrave/The Register)
Clyde's Fine Diner
Location: 111 E Grand Ave., Suite 111, Des Moines
Hours: Tuesday-Saturday, 5-11 p.m.; closed Sundays and Mondays.
Contact: (515) 243-3686; clydesfinediner.com; Facebook
Don't miss an opening or closing. Sign up now and we'll email you with big news.
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redpajama_set_name: RedPajamaCommonCrawl


text:
Together Alone is an album by American jazz saxophonists Joseph Jarman and Anthony Braxton recorded in 1971 and released on the Delmark label.

Reception

Scott Yanow, in his review for AllMusic calls the album a "disappointment considering the talents involved". He states "not a lot of magic or close communication occurs, and the improvisations tend to ramble."

Track listing
 "Together Alone" (Joseph Jarman) - 5:39
 "Dawn Dance One" (Jarman) - 13:46
 "Morning [Including Circles]" (Jarman) - 2:18
 "Ck7 (GN) 436" - (Anthony Braxton) - 6:10
 "SBN-A-1 66k" (Braxton) - 14:53

Personnel
Anthony Braxton - alto saxophone, contrabass clarinet, flute, piano, vocals
Joseph Jarman - sopranino saxophone, soprano saxophone, alto saxophone, flute, synthesiser, bells, vocals

References

Delmark Records albums
Anthony Braxton albums
Joseph Jarman albums
1974 albums
Albums produced by Bob Koester

redpajama_set_name: RedPajamaWikipedia


text:
Bernard Silver ( - ) est un développeur du code-barres qui travailla aux côtés de Norman Joseph Woodland.

Biographie

Bernard Silver a obtenu sa licence de sciences en génie électrique à l'Institut Drexel de technologie en 1947. En 1948, avec Norman Joseph Woodland, il invente un moyen automatisé de lire les données du produit après avoir entendu la conversation d'un épicier.

Leurs premiers résultats, un système de lignes et de cercles basés sur le code morse, a été remplacé par un modèle "cible" afin qu'il puisse être balayé dans toutes les directions. Silver et Woodland ont déposé un brevet pour leur système le . Le brevet US  est accordée le 7 octobre, 1952. Les deux hommes ont finalement vendu leur brevet à Philco pour  $.

Au cours de sa carrière, Silver a servi comme professeur de physique à Drexel et comme vice-président de Electro Nite Inc. Il est décédé le  d'une bronchopneumonie due à la leucémie myéloïde aiguë à l'âge de 38 ans.

En 2011, Silver et Woodland, ont été intronisés au National Inventors hall of Fame.

Lien externe

Naissance en septembre 1924
Décès en août 1963
Décès à 38 ans
Étudiant de l'université Drexel


Threat intelligence is evidence-based knowledge, including context, indicators, implications, and actionable advice, that can provide information about an existing or emerging threat to an asset that can be used to inform decisions as to how the organization should respond to that threat. Common forms of threat intelligence data include security threats, threat actors, exploits, malware, vulnerabilities, and compromise indicators.
Figure 1 – A threat intelligence system architecture.
Figure 1 shows collection, analysis, distribution and use of analysis information in a threat intelligence system. The data is automatically distributed to attack mitigation components in the enterprise, providing automatic updates of security configurations. The automatic updates can extend to cloud consumers' browser protection systems.
Attackers commonly attempt to take advantage of web browsers and their vulnerabilities. Threat intelligence can provide whitelists and blacklists of safe and compromised websites that can alert for new vulnerabilities and when security patches are available.


The Air Tactical Assault Group - Team Fusion - Cliffs of Dover > IL2 Cliffs of Dover > Full Mission Builder and Scripts > Example missions?
View Full Version : Example missions?
Cliffs seems completely different to other games that I've mission built in, namely the ARMA series, in that people seem very reluctant to share their code and there seems to be very few decent tutorials for mission building out there. I didn't come from IL2 so don't have that knowledge base behind me and I am struggling to manage what I'd consider to be fairly simple things.
Is there a repository of multiplayer missions out there that can be downloaded and examined? I learn best from seeing something similar and then adapting it for my own needs, but this is hard with no examples around.
I guess with a small pool of people playing CloD and an even smaller set of those making missions that it's not unsurprising that people don't want to release their work or unique tools/resources for others to benefit from although it is quite disappointing and ultimately not very good for the community at large.
If anyone knows of any decent resources for this sort of thing, please let me know.
I can help you out. Trust me in saying I wish I had more people wanting to make missions and add to the small variety of missions out there.
I'll PM you some stuff when I get off work, but you'll need to hop on TS so we can chat, to have it all make sense.
Bliss, that'd be really helpful. What time's best to catch you on TS? I've kept meaning to try and grab you but only seen you on once just as I HAD to leave - d'oh!
~S~ Bliss, I've some knowledge of IL-2's FMB and understand basic scripting concepts, have downloaded and installed MS Studio Express 2010 and would certainly enjoy any amount of guidance you'd share in putting it all together so I will be able to teach others in the years ahead of us... ty.


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A People-First U.S. Assistance Strategy for the Middle East
Washington, June 10, 2021 — In a new CNAS report, "A People-First U.S. Assistance Strategy for the Middle East," authors Ilan Goldenberg, Daphne McCurdy, Kaleigh Thomas, and Sydney Scarlata posit that the current U.S. assistance mix in the Middle East must be rebalanced away from security assistance and toward development, democracy, humanitarian, and stabilization programs as part of a broader strategy emphasizing civilian rather than military tools. The report builds on CNAS' work over the past year, which has focused on a strategy that demilitarizes U.S. policy in the Middle East.
While security assistance can be a useful tool, it must be used sparingly to achieve clear and narrow objectives, rather than making it the centerpiece of U.S. assistance policy in the Middle East. Meanwhile, the problem of nonresponsive governance, which is one of the core challenges facing the region, is much better addressed through democracy and development programs reinforced by principled diplomacy. In countries where governance challenges have already led to conflict, stabilization and humanitarian programs can help mitigate the worst consequences of violence.
Beyond these broad recommendations, the authors also make a series of concrete proposals for how the United States can improve its Middle East assistance strategy. But ultimately, they recognize that real change will have to be led by the people of the region themselves—not the United States.
To request an interview with the authors, contact Shai Korman at comms@cnas.org.


text:
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Gibson's version of the humbucking pickup, the PAF ("Patent Applied For"), was first used on the Les Paul in 1957 and is still sought after for its sound. With declining guitar sales in the early 1960's, due primarily to competition from Fender, Gibson did a major revamping of the Les Paul and found themselves with another winner and future rock icon: the SG.
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Founded in Kalamazoo, Michigan in 1902, the Gibson Mandolin-Guitar Manufacturing Company is a giant in the world of modern guitars. Originator of the archtop guitar, Gibson's early success was due to the popularity, particularly among jazz guitarists, of its hollow-body electrics such as the ES-150 and ES-335.
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In 1957, Gibson bought its main rival, Turkish musical instrument manufacturer Epiphone. Epiphone guitars built by Gibson up until 1969 were, in fact, identical to actual Gibson guitars in everything but name. In 1970 Gibson decided to make Epiphone their budget line, changing the models and having them built by Aria in Japan. In fact, for a few years Epiphone guitars were actually re-branded Aria models.
Video Interview: Jason Hook
The 21st century finds Gibson to be a giant in the musical instrument world, producing brands such as Baldwin, Kramer, Slingerland, Steinberger and Wurlitzer.
Legendary Guitarists
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text:
Archive for the 'Drug Discovery Chemistry' Category
Drug Repurposing Hub Library @broadinstitute @MIT @Harvard
Posted in Drug Development Process, Drug Discovery Chemistry, drug repurposing, Pharmaceutical Drug Discovery on February 14, 2019| Leave a Comment »
Reporter: Aviva Lev-Ari, PhD, RN and Irina Robu, PhD
CLAIMER: most valuable information for Drug Repurposing is found in the following LPBI Group three Intellectual Property Asset Classes
Our intellectual property "IP" consists of three classes of assets as described in detail within live links in the below, listed article.
First, the Journal, an ongoing journal of curated, current biomedical research;
Second, the books, a collection of 16 volumes of e-books available via Amazon in five specialties of Medicine: Cardiovascular, Genomics, Cancer, Immunology and Precision Medicine; and
Third, real-time curation of biotech and medical conferences yielding an e-Proceedings at the end of the conference in One-click operation.
These three IP asset classes are described in details with live links in
eScientific Publishing a Case in Point: Evolution of Platform Architecture Methodologies and of Intellectual Property Development (Content Creation by Curation) Business Model
https://pharmaceuticalintelligence.com/2019/02/04/escientific-publishing-a-case-in-point-evolution-of-platform-architecture-methodologies-and-of-intellectual-property-development-content-creation-by-curation-business-model/
The Drug Repurposing Hub: A next-generation drug library and information resource
M Corsello, Steven & A Bittker, Joshua & Liu, Zihan & Gould, Joshua & McCarren, Patrick & E Hirschman, Jodi & E Johnston, Stephen & Vrcic, Anita & Wong, Bang & Khan, Mariya & Asiedu, Jacob & Narayan, Rajiv & C Mader, Christopher & Subramanian, Aravind & R Golub, Todd. (2017). The Drug Repurposing Hub: A next-generation drug library and information resource. Nature Medicine. 23. 405-408. 10.1038/nm.4306.
… Published on January 3, 2018 as DOI: 10.1124/mol.117. Downloaded from additional source, we used data from the Broad repurposing hub ( Corsello et al, 2017), which employed high throughput screening to characterize drug-target interactions of approved drugs, natural products and nutraceuticals along with other entities. Our analysis yielded a list of currently 'druggable' GPCRs and the drugs that target them. …
… Using a range of ~500 (conservative estimate) to ~700 GPCR-targeted drugs, we estimate that between ~25% and ~36% of approved drugs target GPCRs, with the upper figure the more likely. As additional studies such as the Broad repurposing initiative ( Corsello et al, 2017) characterize GPCR-drug interactions in more detail, we anticipate a growth in this number, as secondary interactions between GPCRs and drugs are defined ( Allen and Roth, 2011). IUPHAR lists more druggable GPCRs than CHEMBL or DRUGBANK but has the smallest number of GPCR-related and overall approved drugs ( Figure 3C shows the number of GPCR-targeted drugs based on target-ligand interactions annotated by either IUPHAR or CHEMBL; of the 476 such drugs listed in one or both sources, only a portion are common to both (50%). …
To date there has not been a systematic effort to identify such opportunities, limited in part by the lack of a comprehensive library of clinical compounds suitable for testing. To address this challenge, we hand-curated a collection of 4,707 compounds, experimentally confirmed their identity, and annotated them with literature-reported targets. The collection includes 3,422 drugs that are marketed around the world or that have been tested in human clinical trials. Compounds were obtained from more than 50 chemical vendors and the purity of each sample was established. We have thus established a blueprint for others to easily assemble such a repurposing library, and we have created an online Drug Repurposing Hub (www.broadinstitute.org/repurposing) containing detailed annotation for each of the compounds.
Nat Med. Author manuscript; available in PMC 2017 Aug 23.
Published in final edited form as:
Nat Med. 2017 Apr 7; 23(4): 405–408.
doi: 10.1038/nm.4306
PMCID: PMC5568558
NIHMSID: NIHMS893143
Steven M. Corsello,1,2,3 Joshua A. Bittker,1 Zihan Liu,1 Joshua Gould,1Patrick McCarren,1 Jodi E. Hirschman,1 Stephen E. Johnston,1 Anita Vrcic,1Bang Wong,1 Mariya Khan,1 Jacob Asiedu,1 Rajiv Narayan,1Christopher C. Mader,1 Aravind Subramanian,1 and Todd R. Golub1,3,4,5,*
Cancer based pharmacogenomics network supported with scientific evidences: from the view of drug repurposing.[BioData Min. 2015]
Open-source approaches for the repurposing of existing or failed candidate drugs: learning from and applying the lessons across diseases.[Drug Des Devel Ther. 2013]
The Resource Hub: an innovative e-information service delivery model addressing mental health knowledge management.[Australas Psychiatry. 2009]
A weighted and integrated drug-target interactome: drug repurposing for schizophrenia as a use case.[BMC Syst Biol. 2015]
Drug Repurposing Is a New Opportunity for Developing Drugs against Neuropsychiatric Disorders.[Schizophr Res Treatment. 2016]
Record Innovations in Drug Discovery by Koch Institute @MIT Members and Affiliates
Posted in BioTechnology - Venture Creation, BioTechnology - Venture Creation, Venture Capital, CANCER BIOLOGY & Innovations in Cancer Therapy, DNA repair, Drug Delivery Platform Technology, Drug Development Process, Drug Discovery Chemistry, MHC Repertoires for Antigen Prediction, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Discovery on February 6, 2019| Leave a Comment »
Reporter: Aviva Lev-Ari, PhD, RN
Trovagene announced a new patent for the use of the drug onvansertib in combination with other anti-androgen drugs for the treatment of prostate cancer. Last fall, Trovagene secured exclusive rights to develop combination therapies and clinical biomarkers for prostate cancer based in part on Bridge Project-funded research. Read more.
Lyndra Therapeutics, co-founded by KI member Bob Langer, raised $55 million in its Series B round, with new investors including the Bill and Melinda Gates Foundation and Gilead Sciences. Phase 2 trials for its ultra long-acting drug delivery capsule are expected to begin next year. Read more.
Dragonfly Therapeutics, co-founded by KI director Tyler Jacks, has committed $10 million to launch the first clinical studies of its TriNKETs (Tri-specific, NK cell Engager Therapies) platform for both solid tumor and hematological cancers. Read more.
Following its record-breaking IPO, Moderna Therapeutics (co-founded by KI member Bob Langer) published preclinical data in Science Translational Medicine demonstrating the promise of its mRNA-2752 program in several cancers. Read more.
Dewpoint Therapeutics launched with a $60 million Series A, aims to translate recent insights into biomolecular condensates from the laboratory of co-founder and KI member Rick Young to drug discovery. Read more.
KI member Bob Langer and collaborator Omid Farokhzad co-founded Seer— combining nanotechnology, protein chemistry, and machine learning—to develop liquid biopsy tests for the early detection of cancer and other diseases. Read more.
Epizyme, co-founded by KI member Bob Horvitz, is submitting a New Drug Application to gain accelerated approval of tazemetostat for patients with relapsed or refractory follicular lymphoma. Read more.
Ribon Therapeutics, founded by former KI member Paul Chang, launched with $65 million in a Series B funding round with Victoria Richon, a veteran of Sanofi and Epizyme, at the helm. Ribon focuses on developing PARP7 inhibitors for cancer treatment. Read more.
From: MIT Koch Institute for Integrative Cancer Research <cancersolutions=mit.edu@cmail19.com> on behalf of MIT Koch Institute for Integrative Cancer Research <cancersolutions@mit.edu>
Reply-To: <ki-communications@mit.edu>
Date: Wednesday, February 6, 2019 at 3:15 PM
To: Aviva Lev-Ari <AvivaLev-Ari@alum.berkeley.edu>
Subject: Lung Microbiome Corrupted in Cancer; Angelika Amon wins 2019 Vilcek Award; Lunch Lines of Inquiry
In 2018 Cardiovascular PharmacoTherapy Market: Anti-thrombotic Drug Class Segment will continue to bring in the biggest profit and dominate production
Posted in Drug Development Process, Drug Discovery Chemistry, Pharmaceutical Analytics, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Value-based Drug Pricing on February 27, 2018| Leave a Comment »
Who were the top players in cardiovascular disease in 2017?
By GlobalData Healthcare
The total revenue from branded cardiovascular drugs in 2017 is projected to be just over $40 billion. Top companies in this space are putting a heavy focus on the anti-thrombotic segment, as these drugs continue to bring in the biggest profit and dominate the cardiovascular market.
Figures ($M) represent projected 2017 global sales of cardiovascular products. Credit: GlobalData.
Bayer currently holds the top spot in the market with 2017 sales of $5.4 billion; however, Sanofi and BMS come in a close second and third with sales of $5.1 and $4.7 billion, respectively.
Overall, apart from the anticoagulants segment, companies are investing less frequently due to the heavily genericized and mature nature of the cardiovascular market. This and the high cost of drug development makes the cardiovascular market hard to penetrate, especially for smaller, less established companies.
The clear leaders in sales of cardiovascular drugs are Eliquis and Xarelto (NOACs). These two drugs currently represent over 30% of the total cardiovascular market and their shares will continue to expand.
Despite high clinical unmet needs, this market is not expected to grow significantly in the near future, with the exception of the NOACs class.
Figures ($M) represent projected 2017 global sales. Credit: GlobalData.
https://www.pharmaceutical-technology.com/comment/top-players-cardiovascular-disease-2017/
CHI's Discovery on Target, Sheraton Boston, Sept. 25-28, 2018
Posted in Conference Coverage with Social Media, Drug Delivery Platform Technology, Drug Development Process, Drug Discovery Chemistry, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Informatics, Pharmaceutical R&D Investment, Pharmacodynamics and Pharmacokinetics, Pharmacogenomics, Pharmacologic toxicities on February 21, 2018| Leave a Comment »
Leaders in Pharmaceutical Business Intelligence (LPBI) Group is a selected CHI Business Partner for Media Communication for this event as well a provider of REAL TIME PRESS COVERAGE for this cardinal event in the domain of Drug Discovery and Drug Delivery.
Dr. Aviva Lev-Ari, PhD, RN, Editor-in-Chief, PharmaceuticalIntelligence.com will be in attendance covering this event for the Press using Social Media via 12 Channels
LOGO of LPBI Group
Follow us on ALL our Media Communication Channels:
Channels for e-Marketing of Biotech Conferences
Our Journal has 1,373,977 eReaders on 1/29/2018, for All Time and 7,283 Scientific Comments
http://pharmaceuticalintelligence.com
Aviva's – +6,430 BIOTECH Followers on LinkedIn
http://www.linkedin.com/in/avivalevari
Aviva is a Member of +60 LinkedIn Groups in Biotech related fields
https://www.linkedin.com/groups/my-groups
LPBI Group's FaceBook Page
http://www.facebook.com/LeadersInPharmaceuticalBusinessIntelligence
https://pharmaceuticalintelligence.com/2016/05/12/preliminary-agenda-available-and-exclusive-discount-to-attend-understanding-crispr-mechanisms-to-applications-symposium-in-boston-september-19-2016
LPBI Group's Twitter Account
http://twitter.com/pharma_BI
LinkedIn (LI) Group Launcher and Manager of Three LI Groups
Cardiovascular Biotech & Pharma UK & US Networking Group
918 members (1/2018)
Leaders in Pharmaceutical Business Intelligence
Innovation in Israel
LPBI Group's Company's Page on LinkedIn
https://www.linkedin.com/company/9325543?trk=tyah&trkInfo=clickedVertical%3Acompany%2CclickedEntityId%3A9325543%2Cidx%3A1-1-1%2CtarId%3A1439226813927%2Ctas%3ALeaders%20in%20Pharmaceutica
For UPDATES on this Cardinal Conference and for REGISTRATION, go to
http://www.discoveryontarget.com/?utm_source=partner
For PROGRAMS, go to
http://www.discoveryontarget.com/programs
Small Molecules for Cancer Immunotherapy
NK Cell-Based Cancer Immunotherapy
Autoimmune and Inflammation Drug Targets
Targeting Tumor Myeloid Cells
Targeting the Ubiquitin-Proteasome System
CNS and Neurodegenerative Targets
Constrained Peptides and Macrocyclics
Target Identification & Validation – Part 1
Kinase Inhibitor Discovery
GPCR-Based Drug Discovery
Lead Generation Strategies
Antibacterial Discovery and Development
NASH and Fibrosis
Targeting Gram Negative Pathogens
Targeting the Microbiome
Antibody Discovery Forum – Part 1
Antibodies Against Membrane Protein Targets – Part 1
Antivirals: Targeting HBV and Beyond
Targeting Autophagy
What is the Role of the Editor-in-Chief at PharmaceuticalIntelligence.com
Editor-in-Chief's Roles and Accomplishments
1 Curation Methodology Development
Leadership we provide on curation of scientific findings in the eScientific publishing for Medical Education contents.
In Section 1, the Leadership we provide on curation of scientific findings in the eScientific publishing for Medical Education contents is demonstrated by a subset of several outstanding curations with high electronic Viewer volume. Each article included presents unique content contribution to Medical Clinical Education.
· These articles are extracted from the list of all Journal articles with >1,000 eReaders, 4/28/2012 to 1/29/2018.
Article Title, # of electronic Viewers, Author(s) Name
Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View? 16,114 Larry H. Bernstein, MD, FCAP
Do Novel Anticoagulants Affect the PT/INR? The Cases of XARELTO (rivaroxaban) and PRADAXA (dabigatran) 11,606 Vivek Lal, MBBS, MD, FCIR,
Justin D. Pearlman, MD, PhD, FACC and
Aviva Lev-Ari, PhD, RN
Clinical Indications for Use of Inhaled Nitric Oxide (iNO) in the Adult Patient Market: Clinical Outcomes after Use, Therapy Demand and Cost of Care
5,865 Aviva Lev-Ari, PhD, RN
Peroxisome proliferator-activated receptor (PPAR-gamma) Receptors Activation: PPARγ transrepression for Angiogenesis in Cardiovascular Disease and PPARγ transactivation for Treatment of Diabetes 1,919 Aviva Lev-Ari, PhD, RN
Bystolic's generic Nebivolol – Positive Effect on circulating Endothelial Progenitor Cells Endogenous Augmentation 1,059 Aviva Lev-Ari, PhD, RN
Triple Antihypertensive Combination Therapy Significantly Lowers Blood Pressure in Hard-to-Treat Patients with Hypertension and Diabetes 1,339 Aviva Lev-Ari, PhD, RN
Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination? 1,472 Aviva Lev-Ari, PhD, RN
Treatment of Refractory Hypertension via Percutaneous Renal Denervation 1,085 Aviva Lev-Ari, PhD, RN
2 Content Creation and Key Opinion Leader (KOL) Recognition
2.1 Volume of Articles in the Journal and in the 16 Volume-BioMed e-Series
Aviva Lev-Ari, PhD, RN 2012pharmaceutical
· All (5,288) avivalev-ari@alum.berkeley.edu Administrator 3064
1. Volume of Articles in the Journal since Journal inception on 4/28/2012:
· Total articles by ALL authors in Journal Archive on 1/29/2018 = 5,288
· ALL articles/posts Authored, Curated, Reported by Aviva Lev-Ari, PhD, RN = 3,064
2. Volume of Articles in the 16 Volume-BioMed e-Series
· Editorial & Publication of Articles in e-Books by Leaders in Pharmaceutical Business Intelligence: Contributions of Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/2014/10/16/editorial-publication-of-articles-in-e-books-by-leaders-in-pharmaceutical-business-intelligence-contributions-of-aviva-lev-ari-phd-rn/
· LPBI Group's Founder: Biography and Bibliographies – Aviva Lev-Ari, PhD, RN
https://pharmaceuticalintelligence.com/founder/
2.2 Digital Presence measured by eViews: Clicks on article by Author Name
Top Authors for all days ending 2018-01-29 (Summarized)
Author Name electronic Views
Aviva Lev-Ari, PhD, RN [2012pharmaceutical]
Our TEAM 5,934
Founder 3,257
BioMed e-Series 3,140
Journal PharmaceuticalIntelligence.com 2,214
About 2,054
VISION 2,803
LPBI Group 1,201
2.3 Digital KOL Parameters
Key Opinion Leader (KOL) – Aviva Lev-Ari, PhD, RN, as Evidenced by
https://pharmaceuticalintelligence.com/2016/07/21/key-opinion-leader-kol-aviva-lev-ari-phd-rn-as-evidenced-by/
3 Team building: Editors and Expert, Authors, Writers
Aviva Lev-Ari, PhD, RN, Director and Founder
Experts, Authors, Writers (EAWs)
Business Development & Private Equity Investment
Scientific Delegation Members & Patent Holders
Inventors: Biologics
Inventors: Medical Devices
Selection of Journal's Chief Scientific Officer (CSO) and BioMed e-Series Content Consultant (CC): Series B, C, D, E
L.H. Bernstein, MD, FCAP
Editorial & Publication of Articles in e-Books by Leaders in Pharmaceutical Business Intelligence: Contributions of Larry H Bernstein, MD, FCAP
https://pharmaceuticalintelligence.com/2014/10/16/editorial-publication-of-articles-in-e-books-by-leaders-in-pharmaceutical-business-intelligence-contributions-of-larry-h-bernstein-md-fcap/
4 Book Title Generation and Cover Page Design
As BioMed e-Series Editor–in-Chief, I was responsible for the following functions of product design and product launch
· 16 Title creations for e-Books
· Designed 16 Cover Pages for a 16-Volume e-Books e-Series in BioMed
· Designed Series A eTOCs and approved of all 16 electronic Table of Contents (eTOCs), working in tandem with all the Editors of each volume and all the Author contributors of article contents in the Journal.
· Commissioned Articles by Authors/Curators per Author's expertise on a daily basis
Below, see Volume Titles and Cover Pages:
13 LIVE results for Kindle Store: "Aviva Lev-Ari"
The VOICES of Patients, Hospitals CEOs, Health Care Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures … E: Patient-Centered Medicine Book 1)
Oct 16, 2017 | Kindle eBook
by Larry H. Bernstein and Aviva Lev-Ari
Subscribers read for free.
$49.00$ 49 00 to buyKindle Edition
Get it TODAY, Jan 29
Sold by: Amazon Digital Services LLC
Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery (Series C Book 2)
May 13, 2017 | Kindle eBook
by Larry H. Bernstein and Demet Sag
$100.00$ 100 00 to buyKindle Edition
The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications: VOLUME 2: Infectious Diseases and Therapeutics and VOLUME 3: The … (Series D: BioMedicine & Immunology)
Sep 4, 2017 | Kindle eBook
Perspectives on Nitric Oxide in Disease Mechanisms (Biomed e-Books Book 1)
Jun 20, 2013 | Kindle eBook
by Margaret Baker PhD and Tilda Barliya PhD
Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders (Series E)
Dec 9, 2017 | Kindle eBook
Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics
Nov 28, 2015 | Kindle eBook
by Justin D. Pearlman MD ME PhD MA FACC and Stephen J. Williams PhD
Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation: The Art of Scientific & Medical Curation
by Larry H. Bernstein MD FCAP and Aviva Lev-Ari PhD RN
Medical 3D BioPrinting – The Revolution in Medicine Technologies for Patient-centered Medicine: From R&D in Biologics to New Medical Devices (Series E: Patient-Centered Medicine Book 4)
Dec 30, 2017 | Kindle eBook
by Larry H. Bernstein and Irina Robu
Metabolic Genomics & Pharmaceutics (BioMedicine – Metabolomics, Immunology, Infectious Diseases Book 1)
Jul 21, 2015 | Kindle eBook
by Larry H. Bernstein MD FCAP and Prabodah Kandala PhD
Cancer Biology and Genomics for Disease Diagnosis (Series C: e-Books on Cancer & Oncology Book 1)
Aug 10, 2015 | Kindle eBook
by Larry H Bernstein MD FCAP and Prabodh Kumar Kandala PhD
Genomics Orientations for Personalized Medicine (Frontiers in Genomics Research Book 1)
by Sudipta Saha PhD and Ritu Saxena PhD
Milestones in Physiology: Discoveries in Medicine, Genomics and Therapeutics (Series E: Patient-Centered Medicine Book 3)
by Larry H. Bernstein MD FACP and Aviva Lev-Ari PhD RN
Regenerative and Translational Medicine: The Therapeutic Promise for Cardiovascular Diseases
by Justin D. Pearlman MD ME PhD MA FACC and Ritu Saxena PhD
5 Style Setting: Instruction manuals for Journal, Articles, Books
As BioMed e-Series Editor–in-Chief, Aviva Lev-Ari, PhD, RN was responsible for
· All the documentation (Instruction manuals) on Style setting, and for
· Training all team members
· Journal Articles Format
· Journal Comment Exchange Format
· e-Books Production Process:
1. Volume creation from Journal's Article Archive,
2. Format Translation from HTML to .mobi for Kindle devices,
3. Proof reading process,
4. Title release,
5. Book electronic Upload to Amazon.com Cloud.
6. Connection of all articles and e-Books to Social Media, Ping back generation by mentioning other related articles published in the Journal
Lastly, 6, below
6 Annual Workflow Management of Multiple eTOCs – Multi-year Book Publishing Scheduling Plan, 2013 – Present
Title Date of Publication Number of Pages
Perspectives on Nitric Oxide in Disease Mechanisms 6/21/2013 895
Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation 11/30/2015 11039 KB
Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics 11/29/2015 12333 KB
Regenerative and Translational Medicine: The Therapeutics Promise for Cardiovascular Diseases 12/26/2015 11668 KB
Genomics Orientations for Personalized Medicine 11/23/2015 11724 KB
Cancer Biology & Genomics for Disease Diagnosis 8/11/2015 13744 KB
Cancer Therapies: Metabolic, Genomics, Interventional, Immunotherapy and Nanotechnology in Therapy Delivery 5/18/2017 5408 pages
Metabolic Genomics and Pharmaceutics 7/21/2015 13927 KB
The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications 9/4/2017 3747 pages
The VOICES of Patients, Hospitals CEOs, Health Care Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures 10/16/2017 826 pages
Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders 12/9/2017 2862 pages
Milestones in Physiology: Discoveries in Medicine, Genomics and Therapeutics 12/27/2015 11125 KB
Medical 3D BioPrinting – The Revolution in Medicine, Technologies for Patient-centered Medicine: From R&D in Biologics to New Medical Devices 12/30/2017 1005 pages
Pharmacological Agents in Treatment of Cardiovascular Disease
Work-in-Progress, Expected Publishing date in 2018 ???
Interventional Cardiology and Cardiac Surgery for Disease Diagnosis and Guidance of Treatment Work-in-Progress, Expected Publishing date in 2018
Novartis' Kymriah (tisagenlecleucel), FDA approved genetically engineered immune cells, would charge $475,000 per patient, will use Programs that Payers will pay only for Responding Patients
Posted in Drug Delivery Platform Technology, Drug Development Process, Drug Discovery Chemistry, Patient-centered Medicine, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Informatics, Pharmaceutical R&D Investment, Pharmacogenomics, Value-based Drug Pricing on August 31, 2017| Leave a Comment »
UPDATED on 9/1/2017:
This Pioneering $475,000 Cancer Drug Comes With A Money-Back Guarantee
Novartis defends the eye-popping price of its pioneering gene therapy with arguments about its $1 billion expenditure—and novel "value-based" pricing.
https://www.fastcompany.com/40461214/how-novartis-is-defending-the-record-475000-price-of-its-pioneering-gene-therapy-cancer-drug-car-t-kymriah
On 8/30/2017 we wrote:
FDA has approved the world's first CAR-T therapy, Novartis for Kymriah (tisagenlecleucel) and Gilead's $12 billion buy of KitePharma, no approved drug and Canakinumab for Lung Cancer (may be?)
https://pharmaceuticalintelligence.com/2017/08/30/fda-has-approved-the-worlds-first-car-t-therapy-novartis-for-kymriah-tisagenlecleucel-and-gileads-12-billion-buy-of-kite-pharma-no-approved-drug-and-canakinumab-for-lung-cancer-may-be/
The Price for the Treatment was published on 8/31/2017, a Value-based Pricing Payment Model of a $475,000 per patient charge for the responding patients after ONE month of treatment. Novartis says it takes an average of 22 days to create the therapy, from the time a patient's cells are removed to when they are infused back into the patient. Kymriah will initially be available at 20 U.S. hospitals within a month, Novartis says. Eventually, 32 total sites will offer the therapy.
CAR-T gained national attention three years ago when Carl June, a researcher at the University of Pennsylvania, used to put a young girl's acute lymphoblastic leukemia. Genetically altering the girl's immune cells had made her deathly ill, but June had used a Roche drug, Actemra, to treat the side effects. She lived, and the results were published in The New England Journal of Medicine. Novartis bought the rights to the Penn treatment for just $20 million up front.
Pharma Buying the right to use from an Academic Institution is a known route to leap frog the R&D lengthy process of Drug discovery.
"I've told the team that resources are not an issue. Speed is the issue," says Novartis' Chief Executive Joseph Jimenez, told Forbes in a cover story about the work then.
The FDA calls this CAR-T therapy treatment, made by Novartis, the "first gene therapy" in the U.S. The therapy is designed to treat an often-lethal type of blood and bone marrow cancer that affects children and young adults. The FDA defines gene therapy as a medicine that "introduces genetic material into a person's DNA to replace faulty or missing genetic material" to treat a disease or medical condition. This is the first such therapy to be available in the U.S., according to the FDA.
Two gene therapies for rare, inherited diseases have already been approved in Europe.
To further evaluate the long-term safety, Novartis is also required to conduct a post-marketing observational study involving patients treated with Kymriah.
The FDA granted Kymriah Priority Review and Breakthrough Therapy designations. The Kymriah application was reviewed using a coordinated, cross-agency approach. The clinical review was coordinated by the FDA's Oncology Center of Excellence, while CBER conducted all other aspects of review and made the final product approval determination.
The FDA granted approval of Kymriah to Novartis Pharmaceuticals Corp. The FDA granted the expanded approval of Actemra to Genentech Inc.
FDA commissioner Scott Gottlieb in a statement.
"We're entering a new frontier in medical innovation with the ability to reprogram a patient's own cells to attack a deadly cancer,"
"Kymriah is a first-of-its-kind treatment approach that fills an important unmet need for children and young adults with this serious disease," said Peter Marks, M.D., Ph.D., director of the FDA's Center for Biologics Evaluation and Research (CBER). "Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials."
https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm574058.htm
A patient's T cells are extracted and cryogenically frozen so that they can be transported to Novartis's manufacturing center in New Jersey. There, the cells are genetically altered to have a new gene that codes for a protein—called a chimeric antigen receptor, or CAR. This protein directs the T cells to target and kill leukemia cells with a specific antigen on their surface. The genetically modified cells are then infused back into the patient.
In a clinical trial of 63 children and young adults with a type of acute lymphoblastic leukemia, 83 percent of patients that received the CAR-T therapy had their cancers go into remission within three months. At six months, 89 percent of patients who received the therapy were still living, and at 12 months, 79 percent had survived.
https://www.technologyreview.com/s/608771/the-fda-has-approved-the-first-gene-therapy-for-cancer/?utm_campaign=add_this&utm_source=email&utm_medium=post
CAR-T Therapies: Product/Molecules/MOA under Development:
Similar CAR-T treatments were being developed at other institutions including
Memorial Sloan-Kettering Cancer Center,
Seattle Children's Hospital, and
The National Cancer Institute.
The Memorial and Seattle work was spun off into a startup called Juno Therapeutics, which has fallen behind. Juno Therapeutics ended a CAR-T study earlier this year after patients died from cerebral edema, or swelling in the brain.
The NCI work became the basis for the product being developed by Kite Pharma. Kite Pharma, which is awaiting FDA approval for its CAR-T therapy to treat a form of blood cancer in adults, was this week bought out by Gilead in a deal worth $11.9 billion.
On Cambridge Healthtech Institute's 4th Annual Adoptive T Cell Therapy, Delivering CAR, TCR, and TIL from Research to Reality, August 29 – 30, 2017 | Sheraton Boston | Boston, MA
TUESDAY, AUGUST 29 – I covered in Real Time the talk on Juno Therapeutics: Building Better T Cell Therapies: The Power of Molecular Profiling by Mark Bonyhadi, Ph.D., Head, Research and Academic Affairs, Juno Therapeutics
https://pharmaceuticalintelligence.com/2017/08/29/live-829-chis-oncolytic-virus-immunotherapy-and-adoptive-cell-therapy-august-28-29-2017-sheraton-boston-hotel-boston-ma/
Precision Medicine is Costly and not a Rapid manufacturing process
All of the CAR-T products are expensive to make, and must be manufactured on an individual basis for each new patient from the patient's own T-cells, a type of white blood cells, a process that takes weeks.
How quickly companies can speed up manufacturing.
Kymriah will be manufactured at a facility in Morris Plains, N.J.
CAR-T technology, which has so far been used only in patients with blood cancers that have not been cured by other treatments, can be used earlier in the disease or for solid tumors: Breast, Prostate, Melanomas.
https://www.forbes.com/sites/matthewherper/2017/08/30/fda-approves-novartis-treatment-that-alters-patients-cells-to-fight-cancer/#2aecb25b4400
Prediction How Patients will Far Well – Researchers use a big-data approach to find links between different genes and patient survival.
https://www.technologyreview.com/s/608666/a-cancer-atlas-to-predict-how-patients-will-fare/?set=
A pathology atlas of the human cancer transcriptome
Mathias Uhlen1,2,3,*,
Cheng Zhang1,
Sunjae Lee1,
Evelina Sjöstedt1,4,
Linn Fagerberg1,
Gholamreza Bidkhori1,
Rui Benfeitas1,
Muhammad Arif1,
Zhengtao Liu1,
Fredrik Edfors1,
Kemal Sanli1,
Kalle von Feilitzen1,
Per Oksvold1,
Emma Lundberg1,
Sophia Hober3,
Peter Nilsson1,
Johanna Mattsson4,
Jochen M. Schwenk1,
Hans Brunnström5,
Bengt Glimelius4,
Tobias Sjöblom4,
Per-Henrik Edqvist4,
Dijana Djureinovic4,
Patrick Micke4,
Cecilia Lindskog4,
Adil Mardinoglu1,3,6,†,
Fredrik Ponten4,†
+ See all authors and affiliations
Vol. 357, Issue 6352, eaan2507
DOI: 10.1126/science.aan2507
Modeling the cancer transcriptome
Recent initiatives such as The Cancer Genome Atlas have mapped the genome-wide effect of individual genes on tumor growth. By unraveling genomic alterations in tumors, molecular subtypes of cancers have been identified, which is improving patient diagnostics and treatment. Uhlen et al. developed a computer-based modeling approach to examine different cancer types in nearly 8000 patients. They provide an open-access resource for exploring how the expression of specific genes influences patient survival in 17 different types of cancer. More than 900,000 patient survival profiles are available, including for tumors of colon, prostate, lung, and breast origin. This interactive data set can also be used to generate personalized patient models to predict how metabolic changes can influence tumor growth.
FDA has approved the world's first CAR-T therapy, Novartis for Kymriah (tisagenlecleucel) and Gilead's $12 billion buy of Kite Pharma, no approved drug and Canakinumab for Lung Cancer (may be?)
Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, CAR-T, Drug Development Process, Drug Discovery Chemistry, Immuno-Oncology & Genomics, Immunotherapy, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmacogenomics on August 30, 2017| Leave a Comment »
UPDATED on 5/3/2019
Gilead Sciences tapped new CEO Daniel O'Day in part because of his cancer expertise. But he's not planning to lead the company's oncology ramp-up alone.
The Roche veteran intends to bring on a CEO for Gilead's Kite unit, responsible for key CAR-T drug Yescarta. The new chief will report to O'Day and operate Kite as a separate business unit, JPMorgan analyst Cory Kasimov wrote in a Thursday note to clients.
RELATED: Gilead, looking for cancer sales, swipes Roche pharma chief Daniel O'Day for CEO post
Gilead acquired Kite in 2017 for $12 billion as its hepatitis C revenues, once its bread and butter, crashed. But so far, both Yescarta and Novartis' rival CAR-T player, Kymriah, have struggled, thanks to a mix of reimbursement and manufacturing challenges.
Kite underperformed expectations once again in the first quarter, with Yescarta's $96 million in sales for the period checking in below Wall Street consensus of $105 million.
O'Day doesn't expect to see that trend continue, though. On Gilead's earnings conference call, he "proclaimed his confidence in cell therapy, noting that it was a critical element of the company's long term strategy," Kasimov wrote.
Getting Gilead's commercial business in order is just one of O'Days three main priorities as he settles into the CEO role, though. After taking the reins March 1, he decided to zero in on strengthening Gilead's pipeline, in part through M&A. And he'll also be making organizational tweaks to "ensure the right people are in the right place," as Kasimov put it.
Gilead is "continuing to scan the entirety" of the M&A landscape and "acknowledges they will continue to 'look at late stage pipeline,'" while keeping an eye on the company's areas of expertise—oncology, HIV and hepatitis B and nonalcoholic steatohepatitis, Jefferies analyst Michael Yee wrote to his own clients. And the Big Biotech will be "accelerating internal" candidates in addition to adding bolt-on buys.
RELATED: Gilead executives predict patience—and some deal scouting—from new CEO Daniel O'Day
Unsurprisingly, analysts trained their attention on the call to O'Day's strategy comments, and "there were literally minimal to no questions about financials," Yee noted. But that doesn't mean Gilead turned in a bad quarter. On the contrary, the first quarter was "fairly clean," he wrote, with revenues of $5.28 billion meeting expectations and earnings per share of $1.76 topping forecasts by 15 cents.
New HIV hotshot Biktarvy stole the show on the revenue side, blowing the $648 million consensus prediction out of the water with $793 million in quarterly sales.
In the quarter, "about 80% of Biktarvy revenue came from switches with 25% from dolutegravir-containing regimens in the U.S.," Kasimov wrote, referencing key combinations from Gilead's HIV archrival, GlaxoSmithKline.
https://www.fiercepharma.com/pharma/new-gilead-chief-plots-kite-ceo-hire-pipeline-m-a-and-organizational-tweaks?mkt_tok=eyJpIjoiTTJRM1pUY3pZMkUwWmpkayIsInQiOiJwZTgzWVMwcjhlWUR4Z2RCc1VyalU4ck9GMWh1UUIzamZYbUJGclFhTjZibG1aN05Db0VQRVorWTI2UjdlM1ozcjhIKzVhTzJTVlwvbzlnVFwvRE1uMmpkYnUybXdnbnNrRWxpSTV4UWtyTkJHRWNpVjl6cW5BWGtBemxGM3VoNnh4In0%3D&mrkid=993697
Here's the inside account of Gilead's 11-week sprint to its $12B Kite buyout – ENDPOINTS NEWS
Gilead-Kite: A New Transformative Deal For Biotech, AUG 30, 2017
Gilead has made a big bet on new technology in Kite's immunotherapy platforms and has reduced the number of credible large players in the space.
With a reputation for intense diligence and dynamism in its business development efforts, Gilead's management team will only bolster the immunotherapy field as it prepares to face off with Novartis, its immediate competitor, and enters squarely in the province of Merck and Bristol Myers Squibb, two of the leaders in immuno-oncology.
Gilead has reinvented the transformative transaction for the sector.
https://www.forbes.com/sites/stephenbrozak/2017/08/30/gilead-kite-a-new-transformative-deal-and-maybe-the-new-future-of-healthcare-deals/#fc64fca65d49
I attended this week the Cambridge Healthtech Institute's 4th Annual
Adoptive T Cell Therapy
Delivering CAR, TCR, and TIL from Research to Reality
August 29 – 30, 2017 | Sheraton Boston | Boston, MA
The following talks on 8/29/2017 presented the frontier of CAR-T Therapies and Technologies from lab to bed side:
Building Better T Cell Therapies: The Power of Molecular Profiling
Mark Bonyhadi, Ph.D., Head, Research and Academic Affairs, Juno Therapeutics
Tricked-Out Cars, the Next Generation of CAR T Cells
Richard Morgan, Ph.D., Vice President, Immunotherapy, Bluebird Bio
The Generation of Lentiviral Vector-Modified CAR-T Cells Using an Automated Process
Boro Dropulic, Ph.D., General Manager and CSO, Lentigen Technology, Inc.
I covered this event in Real Time for the Press
LIVE – 8/29 – CHI's Oncolytic Virus Immunotherapy and ADOPTIVE CELL THERAPY, August 28-29, 2017 Sheraton Boston Hotel | Boston, MA
One year ago we published the following:
What does this mean for Immunotherapy? FDA put a temporary hold on Juno's JCAR015, Three Death of Celebral Edema in CAR-T Clinical Trial and Kite Pharma announced Phase II portion of its CAR-T ZUMA-1 trial
https://pharmaceuticalintelligence.com/2016/07/09/what-does-this-mean-for-immunotherapy-fda-put-a-temporary-hold-on-jcar015-three-death-of-celebral-edema-in-car-t-clinical-trial-and-kite-pharma-announced-phase-ii-portion-of-its-car-t-zuma-1-trial/
Lydia Ramsey reported on Aug. 28, 2017 that Gilead just handed a revolutionary kind of cancer treatment a $12 billion endorsement.
For Gilead, which is known for its HIV and hepatitis C medications, this is an entirely new area of cancer development.
"The field of cell therapy has advanced very quickly, to the point where the science and technology have opened a clear path toward a potential cure for patients," Gilead CEO John Milligan said in a news release. "We are greatly impressed with the Kite team and what they have accomplished, and share their belief that cell therapy will be the cornerstone of treating cancer."
In July, a Food and Drug Administration panel voted in favor of approving one of these treatments made by Novartis. One of the panelists called it "most exciting thing I've seen in my lifetime." The FDA is expected to decide whether to approve that therapy, a treatment for pediatric acute lymphoblastic lymphoblastic leukemia, by October.
Gilead won't have to wait long to see if the FDA will approve Kite's leading cell therapy, which is called axicabtagene ciloleucel or axi-cel. In November, Kite is expected to get an answer from the FDA regarding its CAR-T treatment for a type of blood cancer called aggressive B-cell non-Hodgkin lymphoma. In data Kite released in February, the company found that out of 101 patients, 36% had a complete response to the treatment after six months.
The one-time treatments won't come cheap. While companies might price the drug based on how well it works, axi-cel's price tag could still be $325,000. Analysts expect the therapy to generate $1.7 billion in sales by 2022.
While its axi-cel program is the farthest along, Kite's also working on another CAR-T cell therapy that's in clinical trialsto treat multiple myeloma, another form of blood cancer. The company's also working on cell therapies to treat solid tumors that are still in early clinical trials.
On August 30, 2017, John Carroll writes:
[A]pproval marks a major shift in oncology, with a truly revolutionary approach to treating cancer.
The FDA has approved the world's first CAR-T therapy, giving a green light to Novartis for Kymriah (tisagenlecleucel) in what regulators themselves describe as an historic event.
The accelerated approval — about a month ahead of the PDUFA date — came through for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia
Novartis, the leader in the field, which will set the price on this therapy and likely those to come. Novartis' investigators registered a game-changing 83% remission rate in its pivotal study.
CAR-T, though, is also associated with severe and potentially deadly side effects, including lethal instances of cytokine release syndrome with some patients dying from brain swelling in separate studies from the Novartis drug.
Regulators noted that they will require special training for anyone involved in delivering this therapy, while expanding the approval of Actemra (tocilizumab) to treat CAR T-cell-induced severe or life-threatening CRS in patients 2 years of age or older. "In clinical trials in patients treated with CAR-T cells," the FDA reported, "69% of patients had complete resolution of CRS within two weeks following one or two doses of Actemra."
Said Joseph Jimenez, CEO of Novartis:
"Five years ago, we began collaborating with the University of Pennsylvania and invested in further developing and bringing what we believed would be a paradigm-changing immunocellular therapy to cancer patients in dire need. With the approval of Kymriah, we are once again delivering on our commitment to change the course of cancer care."
This approval marks a major shift in oncology, with a truly revolutionary approach to treating cancer. That hasn't escaped the notice of big players and small, with a host of developers looking to do much better, more safely, with new drugs in the pipeline.
From: "John Carroll [Endpoints News]" <john@endpointsnews.com>
Reply-To: <john@endpointsnews.com>
Date: Wednesday, August 30, 2017 at 11:27 AM
Subject: BREAKING: FDA ushers in a new era in cancer treatment with 'historic' CAR-T approval for Novartis
Novartis' Canakinumab – NEW Inflammation hypothesis of lung cancer
When researchers looked at the safety profile of canakinumab, they found something amazing — a major reduction in the risk of fatal cancers. This was driven by an effect of the highest dose of the drug to prevent lung cancer. The 300 mg dose reduced the occurrence of lung cancer by 67% and death from lung cancer by 77%. It was Viagra all over again.
Is Canakinumab the Next Viagra?
In this Revolution and Revelation, Milton Packer explains how safety data can sometimes trump a primary endpoint
by Milton PackerAugust 30, 2017
https://www.medpagetoday.com/Blogs/RevolutionandRevelation/67605
Genomic Diagnostics: Three Techniques to Perform Single Cell Gene Expression and Genome Sequencing Single Molecule DNA Sequencing
Posted in Analytical Instruments Industry, Bio Instrumentation in Experimental Life Sciences Research, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Cell Biology, Cell Biology, Signaling & Cell Circuits, Computational Biology/Systems and Bioinformatics, DNA repair, Drug Discovery Chemistry, Gene Regulation and Evolution, Genetics & Innovations in Treatment, Genome Biology, Genomic Testing: Methodology for Diagnosis, Meta-analysis of transcriptome data, Microfuidics, Transcriptomics, tagged ancestor's germline cells, Cell-free nucleic acid sequencing, Immune repertoire sequencing, microfluidic large-scale integration, Single-cell sequencing, Single-neuron genome sequencing on July 4, 2017| Leave a Comment »
Related stories and links From nature.com
Single-cell genome sequencing: current state of the science
Genomics: The single life
Single-cell analysis: The deepest differences
Single-cell genomics
This article presents Three Techniques to Perform Single Cell Gene Expression and Genome Sequencing Single molecule DNA sequencing
Stephen Quake, Quake Lab @Stanford University
Ido Amit, AmitLab @Department of Immunology at the Weizmann Institute of Science, Rehovot, Israel
Gilad Evrony – EPPENDORF 2016 GRAND PRIZE WINNER
Quake Lab @Stanford University
Immune repertoire sequencing
Single-cell sequencing
Cell-free nucleic acid sequencing
https://quakelab.stanford.edu/research/overview
Quake Lab Publications
https://quakelab.stanford.edu/quake-lab-publications
The Amit lab studies the genomic code enabling immune cells to differentiate to specific subtypes and devise a specific response to invading pathogens. Our main focus is to understand how gene regulatory networks activate this code. We develop and apply state of the art high throughputgenomic tools and interdisciplinary approaches to address these critical biological and therapeutic questions. We believe that elucidating the underlying principles of the regulatory code will allow us to impact the future of personalized medicine. We are currently seeking highly motivated individuals who want to join us on this quest.
https://www.weizmann.ac.il/immunology/AmitLab/front
Immunology, one cell at a time
Amir Giladi
& Ido Amit
Basic lessons – "Single-cell genomics will soon be commonplace in basic and applied immunology research."
It is early days for single-cell genomics. But already, a number of important lessons can be learnt from the experiences of our lab and those of others.
First, it is clear that many of the current categories of immune cells, such as T cells or monocytes, encompass heterogeneous populations. To probe cellular complexity, researchers must therefore cast their nets wide, and try to collect all immune cells within a tissue or region of interest. This is a very different approach from that used with methods based on cell-surface markers, which aim to obtain as pure a sample as possible.
Second, success will depend, in part, on the extent to which researchers preserve the states of cells and the original composition of a tissue. Cell stress or death should be minimized to ensure that tissue preparation does not favour specific cell types. (Some are more sensitive to heat stress, for example, than others.)
Third, bioinformaticians will need to develop scalable and robust algorithms to cope with greater numbers of cells, conflicting or overlapping programs of gene expression and fleeting developmental stages.
Fourth, after researchers have characterized all of the immune cells in a sample, they will need to find molecular markers that can be used to either enrich or deplete certain cell types in further samples. Tissues comprise trillions of cells with myriad molecular characteristics and functions, and the types or states of these cells may vary in abundance by many orders of magnitude. For instance, in the brains of healthy mice, our newly identified population of DAM makes up less than 0.01% of cells15. Thus, repeated unbiased sampling to characterize rare populations will keep on accumulating cells that are not those of interest.
Nature 547, 27–29 (06 July 2017) doi:10.1038/547027a
http://www.nature.com/news/immunology-one-cell-at-a-time-1.22232?WT.ec_id=NEWSDAILY-20170703
Ido Amit – Selected References
Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses.
Lavin Y, Kobayashi S, Leader A, Amir ED, Elefant N, Bigenwald C, Remark R, Sweeney R, Becker CD, Levine JH, Meinhof K, Chow A, Kim-Shulze S, Wolf A, Medaglia C, Li H, Rytlewski JA, Emerson RO, Solovyov A, Greenbaum BD, Sanders C, Vignali M, Beasley MB, Flores R, Gnjatic S, Pe'er D, Rahman A, Amit I, Merad M.
Cell. 2017 May 4;169(4):750-765.e17. doi: 10.1016/j.cell.2017.04.014.
Select item 284714805.
MicroRNA-142 controls thymocyte proliferation.
Mildner A, Chapnik E, Varol D, Aychek T, Lampl N, Rivkin N, Bringmann A, Paul F, Boura-Halfon S, Hayoun YS, Barnett-Itzhaki Z, Amit I, Hornstein E, Jung S.
Eur J Immunol. 2017 May 4. doi: 10.1002/eji.201746987. [Epub ahead of print]
Single-cell transcriptome conservation in cryopreserved cells and tissues.
Guillaumet-Adkins A, Rodríguez-Esteban G, Mereu E, Mendez-Lago M, Jaitin DA, Villanueva A, Vidal A, Martinez-Marti A, Felip E, Vivancos A, Keren-Shaul H, Heath S, Gut M, Amit I, Gut I, Heyn H.
Genome Biol. 2017 Mar 1;18(1):45. doi: 10.1186/s13059-017-1171-9.
Select item 2816653811.
Single-cell spatial reconstruction reveals global division of labour in the mammalian liver.
Bahar Halpern K, Shenhav R, Matcovitch-Natan O, Tóth B, Lemze D, Golan M, Massasa EE, Baydatch S, Landen S, Moor AE, Brandis A, Giladi A, Stokar-Avihail A, David E, Amit I, Itzkovitz S.
Nature. 2017 Feb 16;542(7641):352-356. doi: 10.1038/nature21065. Epub 2017 Feb 6. Erratum in: Nature. 2017 Mar 30;543(7647):742.
Gilad Evrony, MD, PhD
EPPENDORF 2016 GRAND PRIZE WINNER
Gilad Evrony
One brain, many genomes
Gilad D. Evrony
DOI: 10.1126/science.aak9761
We each begin life as a single cell harboring a single genome, which—over the course of development—gives rise to the trillions of cells that make up the body. From skin cells to heart cells to neurons of the brain, each bears a copy of the original cell's genome. But as anyone who has used a copy machine or played the childhood game of "telephone" knows, copies are never perfect. Every cell in an individual actually has a unique genome, an imperfect copy of its cellular ancestor differentiated by inevitable somatic mutations arising from errors in DNA replication and other mutagenic forces (1). Somatic mutation is the fundamental process leading to all genetic diseases, including cancer; every inherited genetic disease also has its origins in such mutation events that occurred in an ancestor's germline cells. Yet how many and what kinds of somatic mutations accumulate in our cells as we develop and age has long been unknown and a blind spot in our understanding of the origins of genetic disease.
E. Shapiro,
T. Biezuner,
S. Linnarsson
, Nat. Rev. Genet. 14, 618 (2013).
CrossRefPubMed
http://science.sciencemag.org/content/354/6312/557
http://science.sciencemag.org/content/sci/354/6312/557.full.pdf
The author of the prize-winning essay, Gilad Evrony, received his undergraduate degree from the Massachusetts Institute of Technology. He served in the Intelligence Division of the Israel Defense Forces and completed an M.D. and Ph.D. at Harvard Medical School, with graduate research in the laboratory of Dr. Christopher Walsh at Boston Children's Hospital. Dr. Evrony is currently pursuing clinical training in pediatrics at Mount Sinai Hospital and continuing his research developing novel technologies for studying the brain and neuropsychiatric diseases.
https://www.sciencemag.org/prize/eppendorf/gilad-evrony
Single-neuron genome sequencing is revealing clues about what goes wrong in the brain
https://www.technologyreview.com/lists/innovators-under-35/2015/pioneer/gilad-evrony/
Gilad Evrony – PubMed Selected Publications
Integrated genome and transcriptome sequencing identifies a noncoding mutation in the genome replication factor DONSON as the cause of microcephaly-micromelia syndrome.
Evrony GD, Cordero DR, Shen J, Partlow JN, Yu TW, Rodin RE, Hill RS, Coulter ME, Lam AN, Jayaraman D, Gerrelli D, Diaz DG, Santos C, Morrison V, Galli A, Tschulena U, Wiemann S, Martel MJ, Spooner B, Ryu SC, Elhosary PC, Richardson JM, Tierney D, Robinson CA, Chibbar R, Diudea D, Folkerth R, Wiebe S, Barkovich AJ, Mochida GH, Irvine J, Lemire EG, Blakley P, Walsh CA.
Genome Res. 2017 Jun 19. doi: 10.1101/gr.219899.116. [Epub ahead of print]
One brain, many genomes.
Evrony GD.
Science. 2016 Nov 4;354(6312):557-558. No abstract available.
Resolving rates of mutation in the brain using single-neuron genomics.
Evrony GD, Lee E, Park PJ, Walsh CA.
Elife. 2016 Feb 22;5. pii: e12966. doi: 10.7554/eLife.12966.
Somatic mutation in single human neurons tracks developmental and transcriptional history.
Lodato MA, Woodworth MB, Lee S, Evrony GD, Mehta BK, Karger A, Lee S, Chittenden TW, D'Gama AM, Cai X, Luquette LJ, Lee E, Park PJ, Walsh CA.
Science. 2015 Oct 2;350(6256):94-8. doi: 10.1126/science.aab1785.
Single-cell, genome-wide sequencing identifies clonal somatic copy-number variation in the human brain.
Cai X, Evrony GD, Lehmann HS, Elhosary PC, Mehta BK, Poduri A, Walsh CA.
Cell Rep. 2015 Feb 3;10(4):645. doi: 10.1016/j.celrep.2015.01.028. Epub 2015 Feb 3. No abstract available.


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text:
H.R.3781 - Improving National Safety by Updating the Required Amount of Insurance Needed by Commercial Motor Vehicles per Event (INSURANCE) Act of 2019116th Congress (2019-2020)
Rep. Garcia, Jesus G. "Chuy" [D-IL-4] (Introduced 07/16/2019)
House - 07/17/2019 Referred to the Subcommittee on Highways and Transit. (All Actions)
Text: H.R.3781 — 116th Congress (2019-2020)All Information (Except Text)
There is one version of the bill.
XML/HTML
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To increase the minimum levels of financial responsibility for transporting property, and to index future increases to changes in inflation relating to medical care.
Mr. García of Illinois (for himself, Mr. Cartwright, Mr. Espaillat, Ms. Meng, Mr. Cohen, Mr. Payne, and Mr. Soto) introduced the following bill; which was referred to the Committee on Transportation and Infrastructure
A BILL
Be it enacted by the Senate and House of Representatives of the United States of America in Congress assembled,
This Act may be cited as the "Improving National Safety by Updating the Required Amount of Insurance Needed by Commercial Motor Vehicles per Event (INSURANCE) Act of 2019".
SEC. 2. Findings.
(1) In passing the Motor Carrier Act of 1980, Public Law 96–296, Congress intended for the minimum insurance levels to maintain safety. According to the House Report No. 96–1069, "the action of the Committee in increasing financial responsibility is to encourage the carriers to engage in practices and procedures that will enhance the safety of their equipment so as to afford the best protection to the public.".
(2) The National Transportation Policy Study Commission (which consisted of six Members of the Senate, six Members of the House of Representatives, and seven public members appointed by the President) recommended mandatory minimum insurance requirements of $1,000,000, in its 1979 Final Report to the Congress, National Transportation Policies through the Year 2000. The Report stated: "As an example, all certificated motor carriers operating upon the highways should be obligated to carry adequate insurance (or proof of financial responsibility equal to such insurance) to protect the public. The insurance should cover public liability, property, damage, cargo and environmental restoration with a $1 million for single occurrence, or another minimum amount sufficient to require periodic 'on site' inspection by the insurance company, with the minimum to be updated regularly. Non-certificated motor carriers should be subject to similar standards.".
(3) According to the U.S. Bureau of Labor Statistics, the amount of $750,000, set in 1980 (the year of enactment), would have the same purchasing power as $4,923,153.29 in 2019, if the amount was raised to account for medical-cost inflation.
SEC. 3. Minimum financial responsibility for transporting property.
(a) In general.—Section 31139(b) of title 49, United States Code, is amended—
(1) in paragraph (2), by striking "$750,000" and inserting "$4,923,154"; and
"(3) ADJUSTMENT.—The Secretary, in consultation with the Bureau of Labor Statistics, shall adjust the minimum level of financial responsibility under paragraph (2) quinquennially for inflation relating to medical care.".
(b) Effective date.—The amendments made by subsection (a) shall take effect on the date that is 1 year after the date of enactment of this Act.


Me Dee would easily rate as my favourite casual Thai eatery in Melbourne, and I have tried more than my fair share over the years. Having shopped in Springvale with my Thai wife most weekends for over two decades, Me Dee had become a regular choice for a quick lunch before heading home to cook up a storm with all the specialty Asian ingredients available in the area.
Sometimes we'll share a few small dishes like neua yang nam tok (grilled beef salad), larb gai (chicken mince with red onion, chilli, lemon, ground rice & fresh herbs), yam nor mai (bamboo shoot salad) or perhaps the por tak (seafood in a spicy clear soup).
Other times we'll just order a single item each, maybe boat noodle soup or what the Thais refer to as 'lard khao' (served over rice).
Me Dee may be a cheap & casual experience, but the food certainly hits the spot.
If driving out to Springvale is a bit of a stretch, check out their newish outpost located within the Paramount Centre food court located within the Melbourne CBD. The food court itself has seen better days, but it's worth putting up with to eat such authentic & affordable Thai food.


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def setUpProvisionLogging(vmName)
	if $vmProvisionLoggingEnabled
		currentTime = Time.now.strftime("%d-%m-%Y-%H-%M")

		logDirectoryGuest = "/vagrant/generated/vagrant/provisioning/%s/" % vmName
		logDirectoryHost = "generated/vagrant/provisioning/%s/" % vmName

		logFileGuest = "%s%s.log" % [logDirectoryGuest, currentTime]
		logFileHost = "%s%s.log" % [logDirectoryHost, currentTime]

		FileUtils.mkdir_p(logDirectoryHost)
		FileUtils.touch(logFileHost)

		return logFileGuest
	else
		return "/dev/null"
	end
end

redpajama_set_name: RedPajamaGithub