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Q: Spring Cloud Gateway not Working on Docker I have configured a spring cloud gateway to redirect to a server a created with the following route:
@Bean
public RouteLocator myRoutes(RouteLocatorBuilder builder) {
    return builder.routes()
            .route(p -> p
                    .path("/v1/**")
                    .uri("lb://data-diff-service"))
            .build();
}

It works fine on a local environment, but when I start my services containers through my docker-compose file, the gateway is not able to find the customer-service.
It works fine when running locally outside the containers
my docker-compose file
version: "3.4"
services:
  registry-service:
    image:  project/registry-service
    hostname: registry-service
    ports:
      - "8761:8761"

  gateway:
    image: project/gateway
    hostname: gateway
    ports:
      - "8080:8080"
    environment:
      EUREKA_CLIENT_SERVICEURL_DEFAULTZONE: http://registry-service:8761/eureka

  data-diff-service:
    image: project/data-diff-service
    hostname: data-diff-service
    environment:
      EUREKA_CLIENT_SERVICEURL_DEFAULTZONE: http://registry-service:8761/eureka
      SPRING_DATA_MONGODB_URI: mongodb://teste:teste@mongo-database:27017/data_diff?retryWrites=true&w=majority

I'm testing it on the localhost 8080 port.
The data-diff-service can communicate normally with Mongo db that runs in a separate container
EDIT
result from http://:8761/eureka/apps:
<applications>
  <versions__delta>1</versions__delta>
  <apps__hashcode>UP_2_</apps__hashcode>
  <application>
    <name>GATEWAY</name>
    <instance>
      <instanceId>gateway:localhost:2ba2ecb7caf0931ba4b5580138cd3817</instanceId>
      <hostName>localhost</hostName>
      <app>GATEWAY</app>
      <ipAddr>172.20.0.4</ipAddr>
      <status>UP</status>
      <overriddenstatus>UNKNOWN</overriddenstatus>
      <port enabled="true">8080</port>
      <securePort enabled="false">443</securePort>
      <countryId>1</countryId>
      <dataCenterInfo class="com.netflix.appinfo.InstanceInfo$DefaultDataCenterInfo">
        <name>MyOwn</name>
      </dataCenterInfo>
      <leaseInfo>
        <renewalIntervalInSecs>30</renewalIntervalInSecs>
        <durationInSecs>90</durationInSecs>
        <registrationTimestamp>1615821410991</registrationTimestamp>
        <lastRenewalTimestamp>1615821560153</lastRenewalTimestamp>
        <evictionTimestamp>0</evictionTimestamp>
        <serviceUpTimestamp>1615821410308</serviceUpTimestamp>
      </leaseInfo>
      <metadata>
        <management.port>8080</management.port>
      </metadata>
      <homePageUrl>http://localhost:8080/</homePageUrl>
      <statusPageUrl>http://localhost:8080/actuator/info</statusPageUrl>
      <healthCheckUrl>http://localhost:8080/actuator/health</healthCheckUrl>
      <vipAddress>gateway</vipAddress>
      <secureVipAddress>gateway</secureVipAddress>
      <isCoordinatingDiscoveryServer>false</isCoordinatingDiscoveryServer>
      <lastUpdatedTimestamp>1615821410991</lastUpdatedTimestamp>
      <lastDirtyTimestamp>1615821410126</lastDirtyTimestamp>
      <actionType>ADDED</actionType>
    </instance>
  </application>
  <application>
    <name>DATA-DIFF-SERVICE</name>
    <instance>
      <instanceId>data-diff-service:localhost:2477c80c3a1b51f6af76fc02013be957</instanceId>
      <hostName>localhost</hostName>
      <app>DATA-DIFF-SERVICE</app>
      <ipAddr>172.20.0.5</ipAddr>
      <status>UP</status>
      <overriddenstatus>UNKNOWN</overriddenstatus>
      <port enabled="true">37069</port>
      <securePort enabled="false">443</securePort>
      <countryId>1</countryId>
      <dataCenterInfo class="com.netflix.appinfo.InstanceInfo$DefaultDataCenterInfo">
        <name>MyOwn</name>
      </dataCenterInfo>
      <leaseInfo>
        <renewalIntervalInSecs>30</renewalIntervalInSecs>
        <durationInSecs>90</durationInSecs>
        <registrationTimestamp>1615821441412</registrationTimestamp>
        <lastRenewalTimestamp>1615821441412</lastRenewalTimestamp>
        <evictionTimestamp>0</evictionTimestamp>
        <serviceUpTimestamp>1615821440902</serviceUpTimestamp>
      </leaseInfo>
      <metadata class="java.util.Collections$EmptyMap"/>
      <homePageUrl>http://localhost:37069/</homePageUrl>
      <statusPageUrl>http://localhost:37069/actuator/info</statusPageUrl>
      <healthCheckUrl>http://localhost:37069/actuator/health</healthCheckUrl>
      <vipAddress>data-diff-service</vipAddress>
      <secureVipAddress>data-diff-service</secureVipAddress>
      <isCoordinatingDiscoveryServer>false</isCoordinatingDiscoveryServer>
      <lastUpdatedTimestamp>1615821441412</lastUpdatedTimestamp>
      <lastDirtyTimestamp>1615821440865</lastDirtyTimestamp>
      <actionType>ADDED</actionType>
    </instance>
  </application>
</applications>

I've lost a day on it, could anyone help?


If there is any hike that we could recommend to get some absolutely stunning views on Kananaskis – we'd say Sarrial Ridge every damn time. The drive through Kananskis to get there is enough. The reward on top of the ridge will blow you away. You can hike to Rawson Lake any time of year. However, in winter you need to be careful of avalanches and in summer it is home to Grizzly's. For any anglers, they stock this with trout so pack your rod with you!
Turn onto Highway 40 from the Trans-Canada Highway and enjoy the views while driving 1 hour and 20 minutes. Follow the signs to Upper Kananaskis Lake. Once you arrive, park as far back to the south side of the lake as possible. The trail head is located behind the washrooms. There is also a large sign for all the hikes in the area.
You'll begin by walking along the lake for just over a kilometer. It's rather flat and very easy to navigate through. There is a gorgeous waterfall (Sarrial Creek Falls) and a small bridge to cross which then the trail head begins. From there on out the trail turns into fairly steep switchbacks with an elevation gain of 300m for 2 kilometers. The trail is very compact and will be flooded with people in the summer. We will always recommend an early start for any popular hike. It's a fantastic hike for families as well, so you'll come across children and a ton of dogs!
When you are near the lake, it starts to level out a bit (thank goodness) and then you'll reach the end of the lake with the most stunning views! It should take around an hour from the parking lot to the lake. From this point of view, the entire background is Rawson Lake with Mount Sarrial.
Continue to walk around the east side of the lake but BE CAREFUL! This meadow is home to Grizzly Bears so please bring bear spray with you. In the winter, the backside of the lake is also prone to Avalanches so be very careful when snowshoeing. At the backside of the lake is a perfect place to enjoy a snack or some lunch and admire the mountain lake views. Feel free to call it a day after reaching Rawson Lake. The strenuous hike up the ridge isn't everyones cup of tea.
From the backside of the lake there is a trail to head up the ridge. This is so unbelievably steep and in the summer will be dusty! Take your time and use poles. It took us around 45 minutes to get to the top from there. We stopped quite frequently due to the heat and to give the dog some water. (What I mean is.. my calves were burning and I needed a friggen break!) Also take some time to enjoy the views behind you, over looking Rawson Lake.
Those views though.. definitely worth your calves screaming at you for the past 45 minutes! From the ridge, you can see Upper and Lower Kananaskis Lakes and Hidden Lake. Sit up there for a while, crack open that well deserved beer and take in all the glory that Kananaskis is.


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Home TVs 8K TVs shipments may not cross 1 million till 2021, pandemic disrupts...
8K TVs shipments may not cross 1 million till 2021, pandemic disrupts supply
With the current standards of TVs, the 8K resolution is the premium/highest grade product one can go for. However, it seems that vendors may not ramp up their production until 2021. The reason for this is the ongoing Coronavirus pandemic, which has affected the global supply chain.
According to a new report, the global market crossing 1 million units in production for 8K TVs might not be achieved until after 2020 passes. As it stands right now, the world is gripped by the viral outbreak, which has affected various economies and industries as well. The lower production numbers arrive despite various OEMs launching their 8K offerings.
This includes Samsung's 65, 75, 82 and 96-inch QLED 8K TVs, LG's 65, 75, 77 and 88-inch OLED models and even Sharp's two new Aquos 8K Smart TVs, which were launched in Japan. Currently, Sharp has been trying to bump its 8K TV shipments in the Taiwan market. The brand has already discounted its 60 inch 8K models recently and is already planning to market its 120 inch 8K TV in Q2 of 2020.
Many vendors are unable to promote their 8K TV offerings in strategic markets like China, Europe, and the US. These regions generally have a high demand for such high-resolution TVs. However, the recent pandemic has made it much harder for companies to follow through. The postponement of the Tokyo Olympics has also hampered many vendors' plans for promotion.
All 8K TVs will have an advanced upscaling abilities to make sure that the 4K or HD content looks excellent when the resolution is increased to fill the screen. 4K content is very relatively easy to upscale for it, but given that only a limited amount of stuff on the streaming services and even less on the broadcast is as well available in 4K, upscaling HD will be what that sorts the best of the best 8K TV sets from the also rans.
What does 8K mean in the terms of visual qualities?
Traditional 35mm film is also often said to be equivalent to about 6K, so we are beyond the level of the detail that even real film is as well capable of. IMAX 70mm film is also estimated to be more like 12K, but actually, the digital effect for IMAX scenes tends to be created in 8K, and if that is good enough for Christopher Nolan, it is good enough for us. And If you want a headline description of 8K, it has the IMAX experience at home.
Xiaomi Mi TV to finally enter the Malaysian market later this year
Samsung & LG's Withdrawal from LCD market will bring opportunities for Chinese companies
How To Fix Netflix problems On Smart TV
Huawei will launch its most expensive consumer electronics product tomorrow
OPPO will release its own Smart TV lineup in the second half of 2020
Sony announces Z8H, A8H, X9000H, X9500H, and X8000H Smart TVs in China, Includes an 8K and OLED model too
Huawei patents a new Mate-Foldable smartphone
OnePlus 7T Pro formally discontinued, OnePlus 8 Pro may arrive soon
Phones DEBULL - March 30, 2020
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News DEBULL - April 7, 2020
Xiaomi "Comet" Engineering Prototype spotted, resembles Black Shark Phone

redpajama_set_name: RedPajamaCommonCrawl


Choosing the right credit card can be a little difficult because the majority of us are receiving several dozen credit card offers each year and we have to review the benefits and terms of each one before making a decision.
Prepaid credit cards have become all the rage lately as these cards provide a valuable financial transaction service that many people have long since needed. Essentially, prepaid credit cards are not credit cards at all because they do not extend credit.
Looking for the best credit card deal around? A lot of credit cards differ from each other in terms of policies and regulations. If you are a wise consumer and you want the best credit card deal in the market, then, it would be advisable to look for every types and kinds of credit cards around.
For many folks checking out a replacement mastercard on-line, the annual charge per unit, or April looks to be the sole vital issue, and lots of can solely inspect low charge per unit mastercards before creating an internet credit card application.
Consumers can find and compare rates for credit cards, personal loans, bank accounts, and more.
Compare, review and apply for credit cards online. Find consumer, student, and business credit cards in categories like rewards, balance transfers, low interest, instant approval and more.
Offers rates for various credit cards, banking institutions, and sorted by type.
Canadian customers can search and compare credit card offers and rates.
Australian consumers can browse credit card offers and apply for a MasterCard that best suits them.
A useful resource covering all types of credit cards that provides everything you need to know in order to successfully choose, submit an application for and obtain a new credit card that perfectly suits your needs.
A site with handy tools for browsing through the latest credit card applications by the leading banks. Credit cards are arranged into categories by purpose and credit type for easy comparison.


Dr. Leader earned the 2008 Award of Excellence from the University of Ottawa Faculty Of Medicine. This honor was awarded to Dr. Leader for his leadership, contribution to research and teaching initiatives over the years.
Dr. Arthur Leader completed his undergraduate training at the University of Toronto, receiving a Bachelor of Arts degree in Political Science and Economics. He then earned his Doctor of Medicine degree in the first medical class at McMaster University in 1972. After his internship in internal medicine, he was appointed as a consultant in research management to the Expanded Program in Human Reproduction at the World Health Organization in Geneva. He then completed an MRC Fellowship in Obstetrics and Gynecology at the Karolinska Institute (Stockholm) and his residency in Obstetrics and Gynaecology at the London (UK) teaching hospitals. He returned to the Sahlgrenska Hospital (Gothenburg) for a combined research and clinical fellowship before returning to Canada to obtain his Canadian specialty certification in Obstetrics and Gynecology. After completing further fellowship training in Reproductive Endocrinology and Infertility at the University of Calgary, he co-founded the IVF program at the Foothills Hospital in 1983. He joined the University of Ottawa in 1986 and co-founded the IVF program at the Ottawa Hospital in 1988. He moved his practice to the Ottawa Fertility Centre in 2006.
Dr. Leader is a Full Professor of Obstetrics, Gynecology and Medicine (Endocrinology) at the University of Ottawa, an attending physician at the Ottawa Hospital and a consultant and founding partner of the Ottawa Fertility Centre. He is certified in Obstetrics and Gynecology by the Royal College of Physicians and Surgeons. He has held many academic and administrative positions at the University of Ottawa including Division Head of Reproductive Medicine and Chairman of the Department of Obstetrics and Gynecology. He is a past President of the Canadian Fertility and Andrology Society and a recipient of its Award of Excellence in 2006. He has been listed in Canada's Who's Who since 1992.
Dr. Leader is the author of over 100 articles in refereed journals, several book chapters and review articles. He has spoken nationally and internationally on infertility. He has advised provincial and federal governments on policy issues related to Assisted Human Reproduction. He has chaired expert working groups for Health Canada and currently chairs a CSA subcommittee on donor sperm, eggs and embryos. He was an inaugral member and spokesperson for the Stem Cell Oversight Committee of CIHR. He is a peer assessor for the College of Physicians and Surgeon of Ontario. He holds or has held grants from the MRC (CIHR), Health Canada and the pharmaceutical industry. His research has focused on treatments to improve the outcomes and safety of infertility therapy.
Noriko Kobayashi, Makoto Orisaka, Mingju Cao, Fumikazu Kotsuji, Arthur Leader, Noriaki Sakuragi, and Benjamin K. Tsang. Growth differentiation factor-9 mediates FSH – thyroid hormone interaction in the regulation of rat preantral follicular development.Endocrinology. 2009 Dec;150(12):5566-74.
Chen XK, Wen SW, Bottomley J, Smith GN, Leader A, Walker MC. In vitro fertilization is associated with an increased risk for preeclampsia. Hypertens Pregnancy. 2009 Feb;28(1):1-12.
Wang Q, Kim JY, Xue K, Liu JY, Leader A, Tsang BK. Chemerin, a Novel Regulator of Follicular Steroidogenesis and Its Potential Involvement in Polycystic Ovarian Syndrome.Endocrinology. 2012 Sep 4.


Submitted by: Kurt Wall Update by: Date Submitted: 10 Apr 2007 Document Version: 1.0 Last Updated: Sat, 02 Feb 2008 17:46:54 GMT A while back, I started experimenting with Ubuntu after playing with Fedora. I decided to jump to Ubuntu and needed to move data from the Fedora-managed logical volume to Ubuntu. Here's what I did.
This page was last modified on 7 February 2012, at 15:38.


Spring Fling Makeover gives you the opportunity to dress either Lilly, Ella, or Sarah for the dance. Choose from a range of outfits, accessories, and make up to give them the best possible look. Set them against a beautiful backdrop, send them on their way to the Spring Fling, and save your finished product!


Several species of large woodpeckers are found in the forests of Central and South America. This one, the lineated woodpecker, is often found working large tree-trunks but also feeds on smaller trees. These birds were photographed on a foggy, drizzly day near Gamboa, Panama, and a sunny day in Cali, Colombia. Another common large woodpecker is the similar crimson-crested woodpecker.


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Category Archives: 2014
Today in Madonna History: September 15, 2014
September 15, 2019 By sonicboy19 in 2014, September Tags: Confessions on a Dance Floor, Like It Or Not, Remix Videos, Stuart Price	1 Comment
On September 15 2014, Vice magazine's blog THUMP published an article in which Stuart Price recalled his time spent collaborating with Madonna on her 2005 album, Confessions On A Dance Floor:
"Right before we made Confessions on a Dance Floor, I had made a record with a girl named Juliet [2005's Random Order]; we had made that album over Thanksgiving in New York, when the city was completely dead, and it was just the two of us concentrating on working on it. [I went] straight from that to Madonna, and I assumed that would be a much different experience, but she completely surprised me.
The real eye-opener was about how focused she was on avoiding the kind of over-the-top, excessive, entourage-in-the-studio environment that I had expected. It was the total opposite, really. She helped to create an environment where we were like two kids working together in a studio. It was exactly the same feeling as it was when I was working with Juliet. She was really… I don't want to say 'smart,' but she was really honest about music. She's really instinctive in understanding that dance music comes from a very minimal way of working. It doesn't come from throwing lots of money on a lavish production.
We spent five or six weeks in my apartment; the studio used to be upstairs in the loft. I would work on a track overnight, then she would come in and we'd start messing around. She would do vocal melodies and I would come up with a few ideas, and then she'd go, 'Okay, I'm gonna go home and think about it.' Then she'd come back the next day and have the hook for Hung Up or the chorus for Sorry. Then I would carry on working on more tracks to keep us going. It was more of a really fluid and almost childlike environment than anything that seemed too serious.
They always say that an album sounds like the time that you had making it. I know that with that album, it was a super-productive time, but it was also really fun and natural. And I think that comes across in the way it sounds.
It's surprising that Madonna has such a simple work mode. I would have expected her to come in with her full entourage and play the diva, at least to some extent.
Well, don't get me wrong—I think in a lot of parts of her life, she is the big-entourage person. But when it comes to being creative, she's unexpectedly low-key. She's great to work with, and I really mean that."
Today in Madonna History: June 12, 2014
June 12, 2019 By Jay in 2014, June Tags: Jimmy Scott, Secret	1 Comment
On June 12 2014, Little Jimmy Scott died. Little Jimmy had a cameo in the music video for Madonna's Secret.
Madonna had this to say about Scott:
"Jimmy Scott is the only singer who makes me cry."
Today in Madonna History: March 15, 2014
March 15, 2019 By Jay in 2014, March Tags: Costumes, Daenerys Targaryen, Game of Thrones, Instagram, Judaism, Purim	1 Comment
On March 15 2014, Madonna attended a Purim party dressed as Daenerys Targaryen, the Mother of Dragons, a fictional character from the Game of Thrones television series.
Madonna shared some photos of her costume on Instagram.
The cast from Game of Thrones reacted this way:
Emilia Clarke (Daenerys Targaryen):
"Oh my goodness. It's insane. I thought I was asleep, I thought I was dreaming. It's a huge moment. And, damn! She looks good."
Gwendoline Christie (Brienne of Tarth):
"I got really, really excited. Madonna's always been a favorite of mine. I love her strength and her transformative nature and the idea that she might be dressing up as a brilliant character in the TV show I'm in is pretty exciting."
Kristian Nairn (Hodor):
"I kind of freaked out, slightly. That's kind of a sign how big 'Game of Thrones' has got. The Queen of Pop is wearing a Daenerys costume. I completely freaked out."
John Bradley (Samwell Tarly):
"She looks delighted, doesn't she? Look at that. Things like this are just amazing. It's when you know that you're really kind of pressing the right kind of cultural buttons."
Today in Madonna History: February 5, 2014
February 5, 2019 By Jay in 2014, February Tags: Amnesty International, Human Rights, Maria Alyokhina, Nadezhda Tolokonnikova, New York, Pussy Riot, Russia	1 Comment
On February 5 2014, Madonna introduced Pussy Riot at the Amnesty International's human rights concert.
It was the first Amnesty International concert for the cause in 16 years, and took place at the Barclays Center in Brooklyn, New York.
During her introduction, Madonna thanked Pussy Riot "for making pussy a 'sayable' word in my household. Now, my 8-year-olds say it all the time."
More seriously, Madonna spoke of the death threats she received during the Russian portion of her MDNA World Tour, which took place at the same time as Pussy Riot's trial.
"Eighty-seven of my fans were arrested for gay behavior — whatever that is," she said.
The Pussy Riot members, Nadezhda Tolokonnikova and Maria Alyokhina, spoke in Russian with aggression and passion. A translator related the women's speech.
"Freedom is not a given," she translated. "It is something we have to fight for every day. It is our duty to speak for those who are still behind bars."
January 3, 2019 By Jay in 2014, January Tags: Canada, Hard Candy Fitness, Toronto	1 Comment
On January 3 2014, it was announced that Hard Candy Fitness, the global luxury fitness brand in partnership with Madonna and New Evolution Ventures, would open a new facility in Toronto on February 11, 2014.
Are you a member of a Hard Candy gym? Any gym?
Today in Madonna History: December 21, 2014
December 21, 2018 By sonicboy19 in 2014, December Tags: Billboard, Bitch I'm Madonna, Charts, Devil Pray, Ghosttown, Illuminati, Living For Love, Rebel Heart, Remix Videos, Unapologetic Bitch	1 Comment
On December 21 2014, Madonna hit #1 on iTunes in 36 countries around the world with the release of six songs from her forthcoming album, Rebel Heart. In virtually every country the songs were released, they held six of the ten slots on the iTunes Top 10 chart. In seven of those countries, she had multiple #1's across various iTunes charts. The lead single Living for Love topped the iTunes chart in twenty counties.
The other tracks made available for immediate download were: Ghosttown, Devil Pray, Unapologetic Bitch, Illuminati & Bitch I'm Madonna.
News of the surprise drop came when Madonna posted a link on Instagram late the previous night announcing the release as "an early Christmas gift" to those who pre-ordered the album. Fans immediately went to iTunes and drove the songs to the top of iTunes charts around the globe. Instantaneously Rebel Heart exploded on social media with the album topping the Billboard Trending 140 chart.
The early release of six songs from Rebel Heart came on the heels of a series of leaks which forced Madonna and her team to quickly devise a new marketing plan for the album.
Today in Madonna History: December 3, 2014
December 3, 2018 By Jay in 2014, December Tags: Donatella Versace, Mert Alas and Marcus Piggott, Versace	1 Comment
On December 3 2014, two photos for Donatella Versace's 2015 spring/summer collection were revealed. The photos were taken by Mert Alas and Marcus Piggott.
Donatella said of Madonna:
"Madonna says it best herself: She is unapologetic. She is her own woman, a role model who shows other women how we can do what we want, and get what we want, and do so for all of our lives, with no compromise."


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Geeta Kapur與Vivan Sundaram檔案
Geeta Kapur – Manuscripts of Essays and Lectures (48)
Book Manuscripts (7)
Essay Manuscripts (14)
Lecture Manuscripts (27)
Geeta Kapur – Published Writings (34)
Catalogues Essays (12)
Essays in Books, Journals, and Magazines (19)
Geeta Kapur – Curatorial Work (296)
Contemporary Indian Art (32)
Bombay/Mumbai 1992-2001 (66)
crossing generations: diVERGE (77)
Dispossession (1)
Hundred Years: From the NGMA Collection (46)
Pictorial Space (1)
subTerrain: Artworks in the Cityfold (73)
Vivan Sundaram – Artworks (748)
12 Bed Ward (74)
Black Boat (6)
Bunk-Bed (3)
House/Boat (10)
Indira's Piano (1)
Installations, Sculpture, Photography, and Video (1992–2012) (248)
Paintings and Drawings (1970s) (90)
Paintings and Drawings (1980s–1991) (164)
Structures of Memory (107)
The Table is Laid (10)
Video Art (2002–2012) (27)
Vivan Sunrdaram – Notes and Statements (30)
Kasauli Art Centre (375)
Kasauli Art Centre Artist Workshop, 1976 (15)
Kasauli Art Centre Indo-German Artists Workshop, 1983 (48)
Kasauli Art Centre Sculpture Workshop, 1984 (72)
Krishnakumar's Residency at Kasauli Art Centre, 1985 (37)
Art on the Move (7)
Ways of Resisting (4)
Exhibition Catalogues from Geeta and Vivan's Collection (18)
Contemporary Indian Art: An Exhibition of the Festival of India (Exhibition View)
This image captures an exhibition view of 'Contemporary Indian Art', curated by Richard Bartholomew, Geeta Kapur, and Akbar Padamsee.
'Contemporary Indian Art' was an exhibition held at The Royal Academy of Arts in 1982 as part of The Festival of India. The exhibition was conceived and brought together by The Visual Art Committee (a sub-committee of the Indian Advisory Committee, Festival of India), consisting of Richard Bartholomew, Geeta Kapur, and Akbar Padamsee. The show was divided into two parts of three weeks each. 45 artists were represented in the exhibition, with 133 artworks on display.
The first part of the exhibition, titled 'The Gesture, and Motif,' was inaugurated on 16 September and continued up to 5 October. Participating artists included M.F. Husain, F.N. Souza, Akbar Padamsee, Tyeb Mehta, S.H. Raza, Mohan Samant, Ram Kumar, V.S. Gaitonde, Bal Chhabda, K.C.S. Paniker, Biren De, J. Swaminathan, G.R. Santosh, Manu Parekh, Krishna Reddy, Jeram Patel, Nasreen Mohamedi, Arpita Singh, Satish Gujral, A.M. Davierwalla, Meera Mukherjee, Nagji Patel, K. Kunhiraman, Latika Katt.
The second part, titled 'Stories, Situations,' opened on 8 October and closed on 31 October 1982. Participating artists included Krishen Khanna, A. Ramachandran, Bhupen Khakhar, Gulammohammed Sheikh, Gieve Patel, Vivan Sundaram, Bikash Bhattacharjee, Jogen Chowdhury, Nalini Malani, Sudhir Patwardhan, Ranbir Kaleka, Manjeet Bawa, Ganesh Pyne, Laxma Goud, Anupam Sud, K.G. Subramanyan, Himmat Shah, Mrinalini Mukherjee, Ved Nayar, Dhruva Mistry.
Festival of India, 1982
Nalini MALANI
modernism, survey exhibition, curatorial practice
event photograph/recording
相關事件
Contemporary Indian Art: An Exhibition of the Festival of India
The Royal Academy of Arts, Burlington House, Piccadilly, London, United Kingdom
1982年9月16日至10月31日
Artist A. RAMACHANDRAN, Adi DAVIERWALLA, Akbar PADAMSEE, Anupam SUD, Arpita SINGH, Bal CHHABDA, Bhupen KHAKHAR, Bikash BHATTACHARJEE, Biren DE, Dhruva MISTRY, Francis Newton SOUZA, G.R. SANTOSH, Ganesh PYNE, Gieve PATEL, Gulammohammed SHEIKH, Himmat SHAH, Jagdish SWAMINATHAN, Jeram PATEL, Jogen CHOWDHURY, K. Laxma GOUD, K.C.S. PANIKER, K.G. SUBRAMANYAN, Kanai KUNHIRAMAN, Krishen KHANNA, Krishna REDDY, Latika KATT, M.F. HUSAIN, Manjit BAWA, Manu PAREKH, Meera MUKHERJEE, Mohan SAMANT, Mrinalini MUKHERJEE, Nagji PATEL, Nalini MALANI, Nasreen MOHAMEDI, Ram KUMAR, Ranbir KALEKA, S.H. RAZA, Satish GUJRAL, Sudhir PATWARDHAN, Tyeb MEHTA, V. S. GAITONDE, Ved NAYAR, Vivan SUNDARAM
Curator Akbar PADAMSEE, Geeta KAPUR, Richard BARTHOLOMEW
Organiser Festival of India Advisory Committee, The Royal Academy of Arts (London, United Kingdom)
展覽史


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Baylor>School of Education>Students>Prospective Undergraduates>Meet Dr. Neil Shanks
APPLY to BAYLOR
Why did you choose to come back and teach at Baylor?
"This is my home. Despite growing up in Iowa, my time as an undergrad instilled a deep love for Waco and particularly the schools that serve this community. This is a unique place with a great deal of challenges and a great deal of potential, and I relish the opportunity to be a part of this place in all of its complexity."
How did the undergraduate program at Baylor prepare you for teaching?
"I was thoroughly prepared for a variety of school environments thanks to a ton of different field experiences. That left me confident that I would be successful anywhere, and let me know where and whom I wanted to teach."
What would you tell a prospective student considering a degree in teaching?
"I would say there is no more fulfilling expression of your creativity than to work daily with dozens of unique kids from diverse backgrounds that have countless experiences from which to draw on in your classroom.
Teaching is truly an art, and one that has significant ramifications for the health of our world. I can't think of another profession that combines the immediacy of preparing the next generation of citizens and the boundless opportunities to do it in innovative and revolutionary ways."
What do you think is special about Baylor's SOE program?
"I think the SOE is special for a number of reasons, but what stands out to me is the faculty's commitment to developing teachers from the first semester through their intern year and even into their teaching career. That investment is critical to developing and sustaining educators committed to the profession."
What is your favorite SOE memory?
"Honestly, my Social Issues class with Dr. Talbert blew my mind and changed how I saw the world. I had a lot of fun throughout my experience, but that is probably my favorite memory."
• Click HERE or the image at the top of the page to join our mailing list!
• Explore more about Baylor's undergraduate program through the links on this page.
• Get in touch:
Jenifer_Johnson@baylor.edu


West Coast longshoremen are expected to vote in August on a contract extension offer that would guarantee shippers labor peace into 2022, according to a top management official Monday.
Management and labor leaders on both coasts believe a successful contract extension on the West Coast could put pressure on East Coast longshoremen to extend their contract or risk a longer-term loss of market share. The International Longshoremen's Association (ILA) and United States Maritime Alliance (USMX) have been informally discussing the possibility of a contract extension since 2015.
On the West Coast, leaders of the International Longshore and Warehouse Union (ILWU) this month and next are conducting informational meetings with the rank-and-file membership in the local ports to explain in detail what the Pacific Maritime Association's (PMA's) offer means to them.
Last week an ILWU information meeting was held in Southern California, which has the largest membership on the coast. The ILWU declined to comment on its internal meetings.
PMA president James McKenna could only confirm that the meeting in Southern California was in fact held last week. When the process began last month, the general feeling was that the ILWU meetings would take place in June and July, and the vote would likely be held in August, McKenna said.
The PMA and ILWU on May 1 released the details of the offer that would extend the current West Coast waterfront contract, which is scheduled to expire on July 1, 2019, until July 1, 2022. The base ILWU wage would increase from $42.18 an hour at present, in increments, to $46.23 on July 1, 2021. Pension increases over the same period would result in a maximum pension of $95,460 in the final year.
By limiting the contract extension to wages and benefits, employers are attempting to avoid potentially controversial issues such as chassis jurisdiction and automation that could have stretched out negotiations for months, or even risked failure.
Those two issues also have emerged in preliminary discussions in advance of formal bargaining on a new contract on the East and Gulf coasts between the ILA and the USMX, although a top ILA leader said at last month's JOC Gulf Shipping Conference that he sees no reason why a new contract will not be reached before the current one expires on Sept. 30, 2018.
ILA and USMX leaders discussed the possibility of a new or extended contract stretching until 2025 after USMX chairman Dave Adam suggested a long-term deal at JOC's 2014 Port Performance Conference. But for various reasons including difficulty in forecasting medical benefit costs, discussions appear to be aimed at a more conventional, shorter-term agreement.
Shipper organizations on several occasions have publicly encouraged the union and management groups on both coasts to engage in talks aimed at contract extensions or early agreements on new contracts. Last week more than 100 organizations representing manufacturers, farmers, agribusinesses, wholesalers, retailers, importers, exporters, distributors, transportation and logistics providers, and other supply-chain stakeholders wrote a joint letter to the presidents of the ILWU and PMA applauding West Coast labor and management for agreeing to participate in contract extension talks and urging a successful outcome.
"Uncertainty and supply chain disruptions have caused great economic harm in the past. We strongly believe that early and continuous dialog can strengthen the US economy and the competitive position of West Coast international gateways," the organizations stated.
The contentious 2014 to 2015 ILWU-PMA contract negotiations lasted nine months, resulted in damaging ILWU work slowdowns and employer retaliatory moves that caused extreme congestion at West Coast ports, and likely resulted in some permanent loss of market share, similar to equally contentious negotiations that had taken place in 2002. In a presentation last year to the Agriculture Transportation Coalition conference in Long Beach, McKenna speculated that West Coast ports lost possibly 5 percent market share after the 2002 negotiations, and regained only 2 percent.
West Coast ports since 2005 have lost 12 percent market share of Asian imports, to 67 percent according to PIERS, a JOC.com sister company. However, the loss of market share has been due to a variety of factors including construction of a large number of import distribution centers on the East and Gulf coasts and bigger ships calling there after the Panama Canal was enlarged, in addition to shipper responses to West Coast labor disruptions. Also, the Canadian ports of Vancouver and Prince Rupert have attracted cargo from US West Coast ports.
Labor and management sources are not speculating about the outcome of the ILWU membership vote. Longshoremen will vote in their respective districts, the votes will be tabulated and certified, and the results will be announced.


text:
Q: Table with Bootstrap Tabs I am trying to create a Table that shall contain some columns with basic facts on the left and on the right side there shall be some columns that can be tabbed. Something like this:

So the Question is, how to do this?
I could personaly think of two solutions, but I actually don't like both:

*

*Write a own Table for Tab1,Tab2 ... That contains the basic data and the Tabbed Data

*Write a Table for the basic Data and one for each Tab. Here I think you would have a lot of Design problem "glueing" both tables together, so they look like one table.

So actually I don't like both solutions. Maybe there is a better solution to this?

A: Perhaps you could give the columns that belong to each tab their own unique class, e.g. .tab1-columns, .tab2-columns, etc. Then, you could show or hide the column depending on the active tab. The tabs, however, would exist outside of the table. Alternatively, you could pt the tabs into a pseudo- header row above the actual table header row, with the first header cell spanning those cells that shouldn't be "tabbed". However, I believe leaving the tabs outside of the table would be a bit more semantic in nature.
HTH.

A: Render all columns but hide them (display: none;) except the column by default.
Then add an click event on the tabs to switch the visible columns. be sure to use just the nav-tabs and not the js component.. it will be easier I think

redpajama_set_name: RedPajamaStackExchange


[By Design] Duplicated and renamed artboards don't change export slice names… again.
Feel free to request further info or a problematic document.
If that only happens with "old" files, the issue might be within that file version rather than software version. You can try this on a document that has got the issue. Create a new artboard, and then check if it renames correctly. If it does, you would have to either manually rename the artboards, or, alternatively, delete the artboards and re-create them.
New artboards on the old documents works well as you suggested. I think/suspect that 1.6.1 is "damaging" the artboards or that some kind of incompatibility is on the artboard code itself, because on the previous versión of AD all worked fine with all files.
Also I checked on other documents and it seems that there is some bit of random on the issue. Maybe it is happening on files that have evolved (duplicating, saving as, renaming…) from a much older version. Just tested on an April file and worked fine, but other files not.
I'll keep you informed if I find more clues. Meanwhile i'll try to "convert" problematic files into new ones.


Kraken Scuba and Waterhorse adventures are teaming up to perform ice diving demonstrations at the Lake George Winter Carnival over the course of three weekends.
Certified divers may sign-up in advance to do a single adventure dive on either February 9th or 23rd.
Cost is $99 per diver.
If you wish to get your PADI Ice Diver certification you can sign-up for the weekend class on February 16th & 17th.
Cost is $389 per diver.
Don't want to try it all? Just stop by to see the demonstrations!
Call us at Kraken Scuba or our friends at Waterhorse Adventures to sign-up today!
To sign-up for the Ice Diver course, divers must be certified Advanced Open Water and 18 years old. If you are diving in a Drysuit, you must have a Drysuit certification card.
There will be a mandatory classroom session on Friday evening February 15th.
To sign-up for the Adventure Dives, you must be at least Open Water certified and 18 years old.
Deposits are required for both the adventures and the course. Space is limited.


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The Half-Life Games Are Free For The Next Few Months
8 Game Series That We'd Like To See Ported To Current Gen
In Features
HD remakes and ports have been a huge thing in the past few years. On the dawn of a new...
A New Bioshock Game Is Apparently Coming
In Playstation News
Jason Schreier (Kotaku's News Editor) has uncovered that a 2K studio is working on a new top-secret Bioshock game. He...
A New Bioshock Game Is Officially On The Way
After years of wondering about when we'll get a new Bioshock game, 2K has today confirmed that one is on...
Bioshock Creator, Irrational Games Are Shutting Down
In NewsNintendo NewsPC NewsPlaystation NewsXbox News
The iconic studio known as Irrational Games are packing up shop and moving on.The creators of BioShock have just released...
Bioshock Infinite Review
In PC ReviewsPlayStation 3ReviewsXbox 360
Bioshock Infinite / Version Played: PS3 2K Games / Irrational Games / PS3-360-PC / March 26th / $89RRP The game...
Bioshock Infinite Trailer: Bringing Elizabeth to Life
Go behind the scenes to learn about how Irrational Games worked to create Elizabeth, a companion character designed specifically to...
Bioshock On Unreal Engine 4
Today at lunch I took a brief opportunity to read up on a few of the upcoming HD remastering/definitive editions...
BioShock: The Collection Officially Announced With Trailer & Date
UPDATE: The Australian Release date is September 15th. Original story below. Following a significant number of leaks, 2K's worst kept...
Dissecting Bioshock Infinite
In FeaturesPC NewsPlaystation NewsXbox News
You can find our review for the game here Pre-notice: this is an analysis of Bioshock Infinite. Spoilers will not...
In Retrospect: A Love Letter To Irrational Games
From the ashes of Looking Glass Studios (one of the more remarkable developers in gaming history, with critical and cult...
Press Start's Highs and Lows of 2013
We as a team decided to look back at the high's and low's of 2013. We decided to keep things...
Review: Bioshock: Infinite Burial At Sea PT1&2
Please note: This is the review for both chapters of the Burial at Sea DLC. To get the full benefit...


text:
Q: Run-Time Check Failure #2 - Stack around the variable 'tmpMonth' was corrupted I have a error as title, I delete near all my codes and keep a simple codes like this:
#include <iostream>
#include <ctime>

void main(){
    // input Date from keyboard
    unsigned char tmpDayOfWeek, tmpDay, tmpMonth;
    unsigned int tmpYear;
    printf("Please input your date:\n");
    printf("  Day of Week (0 for Sunday, 1 for Monday,...): "); scanf("%d", &tmpDayOfWeek);
    printf("  Day (1..31): "); scanf("%d", &tmpDay);
    printf("  Month (1..12): "); scanf("%d", &tmpMonth);
    printf("  Year (1..9999): "); scanf("%d", &tmpYear);

    cin.get();
    return;
}

But this error still appear, anyone can help me solve this problem. I use VC++ 2005 and Win 7 x64
Thank,

A: In scanf the %d assumes to be an int and not an char. So in your case memory gets overwritten for "tmpDayOfWeek, tmpDay, tmpMonth"...
See also scanf Type Field Characters
You can explizit specify a width if you want: scanf Width Specification
So change your declaration from:
unsigned char tmpDayOfWeek, tmpDay, tmpMonth;

to
unsigned int tmpDayOfWeek, tmpDay, tmpMonth;

and it works...
Also you are using "unsigned" values, that means you shoudl use the %u specifier...


text:
Reinvent Your Business Model
How to Seize the White Space for Transformative Growth
Written by: Mark W. Johnson
Narrated by: Derek Shoales
Categories: Business & Careers, Small Business & Entrepreneurship
In his pioneering book Seizing the White Space, Mark W. Johnson argued that business model innovation is the most proven path to transformational growth. Since then, Uber, Airbnb, and other start-ups have disrupted whole industries; incumbents such as Blockbuster, Sears, Toys "R" Us, and BlackBerry have fallen by the wayside; and digital transformation has become one of the business world's hottest (and least understood) slogans. Nearly a decade later, the art and science of business model innovation is more relevant than ever.
In this revised, updated, and newly titled edition, Johnson provides an eminently practical framework for understanding how a business model actually works. Identifying its four fundamental building blocks, he lays out a structured and repeatable process for reinventing an existing business model or creating a new one and then incubating and scaling it into a profitable and thriving enterprise. In a new chapter on digital transformation, he shows how serial transformers like Amazon leverage business model innovation so successfully.
Reinvent Your Business Model is the strategic innovation playbook you need now and in the future.
PLEASE NOTE: When you purchase this title, the accompanying PDF will be available in your Audible Library along with the audio.
©2018 Mark W. Johnson (P)2020 Gildan Media
Lead from the Future
Reinventing Your Business Model
The Dark Continent
The Wastes
What listeners say about Reinvent Your Business Model


TD Remodeling, home renovations how to!
Currently operating a family owned renovation business in Hubbards, Nova Scotia since 2005. Travis Smithers specializes in flooring and custom bathrooms with competitive pricing and product discounts from our key suppliers. We offer the same services as larger competitors with our hard to beat personal attention that only smaller businesses can provide.
With over 25 years of experience of traditional and newer methodologies, you can be sure at TD Remodeling we know and understand the best practices to ensure the life of your completed project. We strongly believe in the phrase "Do it right the first time!" We provide the best quality workmanship for each job situation to meet your budget every time.
Depending on the requirements of your project, we can be hired to do part or all of the work necessary to completion. Together we can make your project a success.
So take some time and check out the site.


A revolutionary new Australian social enterprise, 1Scope, will launch in mid-2017 thanks to an investment of $1 million from Aqualand Capital.
1Scope is a world-leading website from which companies, universities and not-for-profits can promote, manage and measure the effectiveness of the training, work experience and skills opportunities they offer for Australian students aged 12-25.
1Scope allows students to secure real-world experience that provides practical work skills by accessing programs, work experience and courses that are relevant to them – and importantly enabling them to develop the broader 'soft skills' that are critical, but not often taught to students.
The platform, which has been in beta version from October 2016, will use the investment to fast-track its launch to August 2017.
"I started 1Scope as I passionately believe students deserve greater access to opportunities outside of higher and tertiary education programs. My vision for 1Scope is to bridge the gap between the education system and employers and in doing so, create valuable new opportunities for today's students," Christina said.
"Today's students are clever and capable and keen to apply for opportunities and training where it's useful to them. Finding those opportunities and getting from A to B is the hard part for students and is the problem that 1Scope is trying to solve.
What exactly does 1Scope do?
1Scope is a website from which companies, universities and not-for-profits can promote, manage and measure the training, work experience and skills opportunities they offer for Australian students aged 12-25.
1Scope is free for students to access and has the support of numerous leading Australian corporates as well as some of the country's leading universities, high schools and education providers.
1Scope was founded by Christina Chun, a 26 year old Australian entrepreneur with a passion for education. Christina has a background in Psychology and Human Resource Management specialising in working with children with learning disabilities and over five years' experience in working in the Education industry.
What does this funding mean for 1Scope?
"Having secured an investment from Aqualand Capital, we're able to pick up the pace of our 1Scope platform enhancements and our introductions to corporates and not-for-profits. This gives us the opportunity to see more students matched with more opportunities quickly.
Jin Lin, Managing Director of Aqualand said: "Aqualand Capital has been established to invest in business to increase its development capability, take advantage of new technologies, increase efficiency and provide shareholders with long term return on investment.
"When we saw the potential for 1Scope to make a difference to the adults of tomorrow, together with the enthusiasm and skills of its founder, Christina Chun, we knew this was an initiative that required our support.


text: Q: Custom WebView / WebViewX like iFrame flutter mobile or WebView in a rectangle I am trying to create a mobile app in flutter where I can display the content from a webView but i need it in a rectangular form and inside a widget in the center of the app.


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Relations between Germans and Czechs considerably warmer ten years after Czech-German Declaration
https://english.radio.cz/relations-between-germans-and-czechs-considerably-warmer-ten-years-after-czech-8611499#player=on
Angela Merkel, photo: CTK
German Chancellor Angela Merkel paid a brief visit to the Czech Republic on Friday to discuss the future of the EU constitution and other issues with Czech prime minister Mirek Topolanek and president Vaclav Klaus. The German Chancellor's visit also coincided with the tenth anniversary of the so-called Czech-German Declaration. This document was signed in Prague ten years ago this week and was drafted to help lay the foundation for modern German-Czech relations.
When the Czech-German Declaration was signed in January 1997, it was intended to encourage good neighbourliness between the countries and to draw a line under the injustices of the past.
Considering that these injustices included such emotive issues as Nazi persecution and the subsequent violent expulsion of the Sudeten Germans from Czechoslovakia after the Second World War, it is unlikely that the countries' turbulent history will ever be forgotten. Nevertheless, a page now does seem to have been turned on the harrowing events of the Czech and German past.
Tomas Jelinek is the director of the Czech-German Fund for the Future, an organisation that was established to foster good relations between Germany and the Czech Republic after the signing of the declaration.
"I think there are some rifts, which I'm not sure can be healed, but I see big progress in these areas because the Czech-German declaration brought compensation payments for Nazi victims. Moreover, class actions and the Red-Green coalition in Germany brought compensations for former forced labour. On the other hand, a gesture of reconciliation was made towards Sudeten anti-fascists by the Czech government. I think this has led to more sensitivity and empathy in both societies."
The activities of the Czech-German Fund for the Future include running cross cultural exchanges and other projects to help the two countries understand each other better. After a decade of work like this, Tomas Jelinek says that relations between Czechs and Germans are considerably warmer and that this thaw in relations has been partly helped by the fact that many of the countries' dealings with each other are now conducted on a multilateral level within a wider European context:
"First of all, I would say that we know each other better than we did ten years ago and we are closer to each other. Both countries are members of the European Union and NATO.
Our politicians now meet more in a multilateral context and there were only marginal problems on the bilateral agenda in the last few years, such as German trash on Czech tips and so on. In particular, the citizens of both countries know each other much better. I think the Czech German Declaration played very positive role in this evolution and still does today."
Although the fund was initially only meant to exist for a decade, both countries have decided to keep the project going so as to help ensure that all the good work of the past ten years is not undone and that Czechs and Germans continue to maintain a friendly relationship. Tomas Jelinek again:
"It's important to have a good mutual relations between these two countries and then we can contribute to European integration. We can enjoy good cooperation on international issues. But without mutual interest between the citizens, I don't think there can be better understanding and respect for each other."
Author: Coilin O'Connor
Czech politicians respond to German elections as Merkel era ends
Merkel calls Sudeten German expulsion "immoral", drawing Czech ire
New Merkel mandate seen as best scenario for Czech Republic
Analyst: German election results unlikely to alter relations with Czech Republic


Our combination department has a dedicated team of PFM and removable appliance technicians who are highly trained and work solely on combination cases. Whether you send us a case to adapt an existing partial to a crown or bridge, or a new case that we start from your preoperative models, we ensure every prescription you send will meet and exceed all expectations.
Take advantage of our free design service and we will design your combination case to maximize patient function, comfort and esthetics. Our experienced technical staff is equipped to offer a wide variety of attachments for partials or dentures, and can assist you in designing partials using attachments, conventional clasps, and buccal claspless and Thermoflex™ direct retainers. For most attachments, interocclusal arch space of at least 5 mm is required.
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Bredent VKS-OC is a trademark of XPdent Corporation.
Case-planning designs include indications involving combination fixed and removable casework. These esthetic or conventional designs consist of case survey, crown or bridge and partial design, and estimates for your treatment planning needs.
FREE DESIGN SERVICE AVAILABLE. Send us preoperative models and a bite registration, and we will design your combination case to maximize patient function, comfort and esthetics.


Speeding Up A Video With Movavi Video Editor | GUI Tricks - In Touch With Tomorrow! Speeding Up A Video With Movavi Video Editor - GUI Tricks - In Touch With Tomorrow!
At first glance it may seem as if speeding up a video using a 'fast forward' style effect is of limited use – but nothing could be further from the truth. It is actually an effect that is widely-used in videos and movies and depending on the circumstance can make your video look comedic, create a fast-paced action sequence, or even just speed-through part of the video so that it takes less time.
Launch Movavi Video Editor and select 'Create project in full feature mode' in the menu.
Click on the 'Add Media Files' button and select the video that you want to speed up.
Click on 'Clip Properties' (i.e. the 'cogwheel' icon), and move the speed slider to the right to increase the speed of your clip.
By speeding up the clip the audio will also play at an increased speed – which you may want to fix. To do so you can click the 'Mute track' button (i.e. the 'speaker' icon) and then add the original audio track again or add a new audio track of your choosing.
Click 'Export' when you are satisfied to save your video.
As you can see using the fast forward video effect in Movavi Video Editor is really a piece of cake. The only 'tricky' part may be deciding how you want to deal with the audio – which is something that you'll have to do on a case by case basis.
If you really want to make your video look impressive however, it would help to explore, experiment with, and learn how to use the other features in Movavi Video Editor. One place to start is by using its features to process and edit the video footage so that you can cut and merge video clips, rearrange the sequence in which they appear, improve the video quality, and fix common problems.
After you're comfortable processing video footage, you can move on and start to explore the various other features present in Movavi Video Editor. As you go along you'll discover how to apply special effects and filters, utilize audio effects, insert stylish animated transitions, add customizable text, and more.
Assuming you spend a few minutes trying out and playing around with the numerous features in Movavi Video Editor, you'll soon find yourself able to make full use of them. From there on out it is just a question of deciding how you want to edit your video, and using the tools available to do so.


He has a background as civil engineer and geoscientist. He has worked mainly within the oil and gas industry from the mid 1980s. He has written some few fictional novels as well as author of some professional litterature within oil and gas sector, he is now an editor of some web sites, mainly within the travel business.
Beyond Web 2.0 And The Pragmatic Semantic Web 1.0 Or Web 3.0?


Grand Traverse Resort and Spa. Traverse City, Michigan. The Center for Automotive Research (CAR) presents its traditional summer gathering for the automotive industry. This year's scheduled sessions will focus on world class manufacturing, advanced powertrain, designing for technology, money matters, bargaining for a competitive future and many more. The briefing seminars will be a networking opportunity for automotive manufacturers and suppliers, purchasing and marketing executives, energy industry representatives, financial analysts, government and education representatives, information managers, labor leadership, manufacturing managers and engineers, media members and plant managers and superintendents.


text:
A Superhero Surprise for Luella
July 12, 2019 | Orthopedics and Sports Medicine, Patient Stories
Author: Kathryn Mueller	2 Comments
Luella Konsmo is an avid fan of superheroes, and so when she broke her arm at the end of May and needed a cast, she knew exactly what she wanted.
Samantha Konsmo, Luella's mother, said her love of superheroes started with her older brother, Cruz.
"He loves superheroes, and she loves him," Konsmo said.
Luella and her family were enjoying a stroll around Green Lake in Seattle, when Luella fell and broke her arm. Their day of fun in the sun turned into a trip to Seattle Children's Emergency Department.
When doctors in the Emergency Department asked Luella what color cast she wanted, the beaming 5-year-old didn't hesitate. She said she wanted a "Thanos arm."
It was a response her care team wasn't expecting, and one that captured their hearts.
Thanos is a fictional supervillain from the Marvel comics and appears in the popular movie adaptations, most recently Avengers: Endgame.
"She made so many friends that day in the emergency room," Konsmo said. "She absolutely loved it. She got a lot of attention."
Luella left the hospital with a plain cast so she could adorn the blank canvas with glittering Infinity Stones. She bedazzled the cast to look just like Thanos, with six sparkling stones.
"Thanos is my favorite," Luella said.
Superhero Luella
Luella loved her cast. For four weeks, she said it gave her superpowers.
"It snaps bad things away," Luella said.
And so, when Luella came back to Seattle Children's to have her cast removed, she was inevitably a little sad. She said she didn't want to lose her superpowers.
"I'll have to have an invisible Thanos arm," Luella said. "I'll still have superpowers, you just won't be able to see it."
Little did Luella know, her care team had a special surprise planned for her.
Saving her cast
"Is that Thanos?" the orthopedic technologist said as he walked into the room to remove Luella's cast.
She was beaming with pride.
"I really like it," he said. "Would you like to keep it?"
"I want to sleep with it," Luella replied.
Her cast was carefully removed and cleaned so Luella could take it home with her.
Thanos for a day
Physcian Assistant Keith LeMay came into the room to meet Luella's family. He talked to them about Luella's X-ray and explained how well Luella had done taking care of her arm. It looked great and healed well.
"For doing such a good job, I have a surprise for you," said LeMay. He smiled and showed Luella his badge. For the day, he was playing a dual role.
"Today, I'm Thanos," LeMay said.
He then pulled out a real Thanos glove, complete with six glittering stones and handed it to Luella. Now, she wouldn't have to worry about parting with her superpowers.
Luella was excited at the sight.
She smiled and whispered to her brother, "Don't worry, I'll share with you."
After the visit, Luella and her family bounded down Seattle Children's hallway. Luella had a big smile on her face as they left the hospital.
"It's a blast to see a smile on a kiddo's face," LeMay said. "And her smile was extra big today."
For Luella and her family, it was a special day as well.
"These will be great memories," Konsmo said.
I love this story! Luella's care team and all Seattle Children's employees inspire me! Great work, team!
Christopher Sheeder says:
What a great story! That's why I love working here! Luella is such a cutie!


Within hours of the overnight quake that rattled the east coast of America, an intriguing comment appeared on what's ostensiblywhat appeared to be the Google+ profile page (UPDATE: it's since been scrubbed) of Nobel Prize-winning economist and New York Times columnist Paul Krugman (see footnote below).
It read:"People on twitter might be joking, but in all seriousness, we would see a bigger boost in spending and hence economic growth if the earthquake had done more damage."
That's right: Krugman (if, indeed, it is him)The underlying argument is that if the earthquake had caused more damage, it would have done the down-and-out US economy some good because then the government and private enterprises and homeowners would have had to spend money to rebuild their cities and businesses and homes - which would have grown the economy.
That message, which some see as perverse and heartless, has internal consistency with all of Krugman's writings over the years, and particularly since the 2008 financial crisis. Krugman is a Keynesian at heart, and believes that what the US needs now is not spending cuts - of the sort that are contributing to Europe's economic slowdown - but more spending, despite the government's high burden of debt.
Many of Krugman's commentaries in recent weeks and months have focussed excessively on getting spending levels up to generate employment and defeat the deflationary trend. To this end, he's waged intellectual war with far-right Republicans and Tea Party activists in the US, who have been pushing for spending cuts.
Yet, there are times when Krugman's Keynesian instincts appear to have gone completely wild.
Just last fortnight, for instance, appearing on Fareed Zakaria's GPS show, Krugman argued, somewhat bizarrely, that preparing for an attack by space aliens would ramp up spending to levels that would drag the US economy out of its downward spiral.
"If we discovered that space aliens were planning to attack and we needed a massive buildup to counter the space alien threat - and inflation and budget deficits took secondary place to that - this slump would be over in 18 months. And then if we discovered, oops, we made a mistake, there aren't any aliens, we'd be better (off).
He then cited an episode of Twilight Zone in which scientists fake an alien threat in order to achieve world peace. ""Well, this time...we need it in order to get some fiscal stimulus."
Predictably, Krugman drew a lot of flak from libertarian schools of economics, and in fact there's a big cottage industry of economists and commentators who love to hate Krugman.
In that same GPS video interaction, Krugman endorses the theory that it was all the military spending associated with the Second World War that dragged the US out of the Great Depression. Yet, even he didn't allude to his New York Times column written just three days after the 9/11 terrorist attacks on New York, in which he had argued that the economic aftershocks of the attacks "need not be major".
"Ghastly as it may seem to say this, the terror attack...could even do some economic good." The American economy, he reasoned, was "so huge that the scenes of destruction, awesome as they are, are only a pinprick." Doing some back-of-the envelope real estate calculations, he concluded that the loss from the collapse of the Twin Towers would be only about 0.1 percent of US wealth - "comparable to the material effects of a major earthquake or hurricane."
That calculation is, as I've argued here, overly simplistic - since the 9/11 attacks set America on a geopolitical path that accelerated the decline of the US economy.
Yet, it is entirely in keeping with the economist John Maynard Keynes' General Theory of Employment, Interest and Money, in which he argued that the government could do away with unemployment if it buried old bottles with banknotes and buried them in disused coalmines - and have people dig them up.
Such examples of Keynesian economics gone wild of course abound around the world. In 2009 in China, for instance, an outspoken Communist Party official confirmed long-held suspicions that the country's high-octane GDP data was being exaggeratedby regional party leaders to show higher economic growth, in the process "squandering social resources."
In a brutally honest speech, the powerful official of a southern Chinese province said: "Some of our GDP data sure looks rosy... But they do not amount to growth of social wealth; in fact, social resources are being wasted to show GDP growth." For instance, he said, provincial party officials build a bridge, which contributes to GDP; they then "dismantle" and rebuild the bridge, each time contributing to GDP. "We may have boosted our GDP this way, but this is a huge waste of social resources."
The empty "ghost cities" and malls in China also offer more striking evidence of Keynesianism running amok.
Even if there is some merit in the notion that it was a resort to classical Keynesian theory in 2008 that averted another Great Depression in the US, when a Nobel Prize-winning economist uses it to push for spending to fight "space aliens" or argues that a terrorist attack can serve as a GDP booster, you have to wonder at what stage economic nerds lose touch with their humanity.
It's had commentators wondering, only half in jest, how soon it will be before Krugman burns down the New York Times building " to double his employer's top and bottom line."


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Супрамолекулярная сборка (, надмолекулярная сборка) представляет собой комплекс молекул, удерживаемых вместе нековалентными связями. В то время как супрамолекулярная сборка может состоять просто из двух молекул (например, двойной спирали ДНК или соединения включения) или из определённого числа стехиометрически взаимодействующих молекул внутри четвертичного комплекса, она чаще используется для обозначения более крупных комплексов, состоящих из неопределенного числа молекул. молекул, образующих сферические, палочковидные или пластинчатые формы. Коллоиды, жидкие кристаллы, биомолекулярные конденсаты, мицеллы, липосомы и биологические мембраны являются примерами надмолекулярных ансамблей. Размеры супрамолекулярных ансамблей могут варьироваться от нанометров до микрометров. Таким образом, они позволяют получить доступ к наноразмерным объектам, используя подход «снизу вверх», за гораздо меньшее количество шагов, чем одна молекула аналогичных размеров.

Процесс образования супрамолекулярной сборки называется молекулярной самосборкой. Некоторые пытаются определить самосборку как процесс, посредством которого отдельные молекулы образуют определённый агрегат. Таким образом, самоорганизация — это процесс, посредством которого эти агрегаты создают структуры более высокого порядка. Это может оказаться полезным, когда речь идет о жидких кристаллах и блок-сополимерах.

Шаблонные реакции

Как изучается в координационной химии, ионы металлов (обычно ионы переходных металлов) существуют в растворе, связанные с лигандами. Во многих случаях координационная сфера определяет геометрию, способствующую реакциям либо между лигандами, либо с участием лигандов и других внешних реагентов.

Хорошо известное шаблонирование ионами металлов было описано Чарльзом Педерсеном в его синтезе различных краун-эфиров с использованием катионов металлов в качестве шаблона. Например, 18-краун-6 сильно координирует ион калия, поэтому его можно получить путем синтеза эфира Вильямсона с использованием иона калия в качестве металла-шаблона.

Ионы металлов часто используются для сборки больших супрамолекулярных структур. Металлоорганические каркасы (MOF) являются одним из примеров. MOF представляют собой бесконечные структуры, в которых металлы служат узлами для соединения органических лигандов. SCC представляют собой дискретные системы, в которых выбранные металлы и лиганды подвергаются самосборке с образованием конечных надмолекулярных комплексов, обычно размер и структура образующегося комплекса могут определяться угловатостью выбранных связей металл-лиганд.

Супрамолекулярная сборка с помощью водородной связи

Супрамолекулярная сборка с помощью водородных связей — это процесс сборки небольших органических молекул с образованием больших супрамолекулярных структур за счет взаимодействий нековалентных водородных связей. Направленность, обратимость и прочная природа водородной связи делают её привлекательным и полезным подходом к супрамолекулярной сборке. Функциональные группы, такие как карбоновые кислоты, мочевины, амины и амиды, обычно используются для сборки структур более высокого порядка при водородной связи.

Водородные связи играют существенную роль в сборке вторичных и третичных структур больших биомолекул. Двойная спираль ДНК образуется за счет водородных связей между азотистыми основаниями: аденин и тимин образуют две водородные связи, а гуанин и цитозин образуют три водородные связи (рисунок «Водородные связи в (а) образовании дуплекса ДНК»). Другим ярким примером сборки с помощью водородных связей в природе является образование вторичных структур белка. И α-спираль, и β-лист образуются за счет водородных связей между амидным водородом и амидным карбонильным кислородом (рисунок «Водородные связи в (b) структуре β-листа белка»).

В супрамолекулярной химии водородные связи широко применяются в инженерии кристаллов, молекулярном распознавании и катализе. Водородные связи являются одними из наиболее часто используемых синтонов в подходе «снизу вверх» к инженерным молекулярным взаимодействиям в кристаллах. Репрезентативные модели водородных связей для супрамолекулярной сборки показаны на рисунке «Репрезентативные модели водородных связей в супрамолекулярной сборке». Смесь 1:1 циануровой кислоты и меламина образует кристалл с очень плотной сеткой водородных связей. Эти надмолекулярные агрегаты использовались в качестве шаблонов для создания других кристаллических структур.

Применение
Супрамолекулярные сборки не имеют конкретных применений, но являются предметом многих интригующих реакций. Показано, что надмолекулярная сборка пептидных амфифилов в виде нановолокон способствует росту нейронов. Преимущество этого супрамолекулярного подхода заключается в том, что нановолокна снова распадаются на отдельные пептидные молекулы, которые могут быть расщеплены организмом. Путем самосборки дендритных дипептидов можно получить полые цилиндры. Цилиндрические сборки обладают внутренним спиральным порядком и самоорганизуются в столбчатые жидкокристаллические решетки. При введении в везикулярные мембраны пористые цилиндрические сборки опосредуют перенос протонов через мембрану
. Самосборка дендронов порождает массивы нанопроволок. Электронодонорно-акцепторные комплексы составляют ядро цилиндрических супрамолекулярных ансамблей, которые в дальнейшем самоорганизуются в двумерные столбчатые жидкокристаллические решетки. Каждая цилиндрическая надмолекулярная сборка функционирует как отдельная проволока. Получены высокие подвижности носителей заряда для дырок и электронов.

См. также
 Молекулярная самосборка
 Химия хозяин-гость
 Супрамолекулярная химия
 Кристаллическая инженерия

Примечания

Самоорганизация
Мягкое вещество
Супрамолекулярная химия
Нанотехнология

redpajama_set_name: RedPajamaWikipedia


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Modelling steroidogenesis: a framework model to support hypothesis generation and testing across endocrine studies
Laura O'Hara ORCID: orcid.org/0000-0001-7790-92611,2,
Peter J. O'Shaughnessy3,
Tom C. Freeman2 &
Lee B. Smith1,4
Steroid hormones are responsible for the control of a wide range of physiological processes such as development, growth, reproduction, metabolism, and aging. Because of the variety of enzymes, substrates and products that take part in steroidogenesis and the compartmentalisation of its constituent reactions, it is a complex process to visualise and document. One of the goals of systems biology is to quantitatively describe the behaviour of complex biological systems that involve the interaction of many components. This can be done by representing these interactions visually in a pathway model and then optionally constructing a mathematical model of the interactions.
We have used the modified Edinburgh Pathway Notation to construct a framework diagram describing human steroidogenic pathways, which will be of use to endocrinologists. To demonstrate further utility, we show how such models can be parameterised with empirical data within the software Graphia Professional, to recapitulate specific examples of steroid hormone production, and also to mimic gene knockout. These framework models support in silico hypothesis generation and testing with utility across endocrine endpoints, with significant potential to reduce costs, time and animal numbers, whilst informing the design of planned studies.
Steroid hormones are responsible for the control of a wide range of physiological processes such as development, growth, reproduction, metabolism, and aging. Mammalian steroidogenesis uses cholesterol as a starting substrate to produce the steroid hormone classes of androgens, estrogens, progestogens, corticosteroids and mineralocorticoids. The initial conversion of cholesterol to the major biologically active steroids takes place primarily in the gonads, adrenals and placenta, but further specific interconversions can take place in peripheral tissues due to local expression of other enzymes (reviewed in [1]).
Because of the variety and location of the components that take part in steroidogenesis it is a complex process to visualise and document. However, over the years many attempts have been made, and searching for 'steroidogenesis' in Google images provides examples of these results. Some diagrams are incomplete and focus only on the steroid products without representing the enzymes that produce them; others focus only on the products of one particular organ. Steroidogenic enzymes often have more than one name or symbol (for example the enzyme cytochrome p450 side-chain cleavage is often referred to as p450scc in older literature, but has the gene symbol CYP11A1 in humans). Many steroidogenesis diagrams often use non-standard nomenclature, or interchange gene names across species when the gene is specific to one species. Almost all pathway diagrams of steroidogenesis have no way of incorporating references into the diagram reducing their value as a learning resource for the end user.
One of the goals of systems biology is to quantitatively describe the behaviour of complex biological systems that involve the interaction of many components. This can be done by representing these interactions visually in a pathway model and then optionally constructing a mathematical model of the interactions. Steroidogenesis would greatly benefit from a formalised graphical documentation using a standard notation with links to original research articles and chemical structures of steroid intermediates. If the diagram could be parameterised to form a dynamic mathematical model it could potentially be used to predict what steroid pathways would be active and what products could be made by tissues expressing a particular combination of steroidogenic enzymes.
In this paper, we have used the modified Edinburgh pathway notation (mEPN) to construct a framework diagram describing human steroidogenic pathways, which will be of use to endocrinologists. To demonstrate further utility, we show how such models can be parameterised with empirical data within the software Graphia Professional [2], to recapitulate specific examples of steroid hormone production, and also to mimic gene knockout. These framework models support in silico hypothesis generation and testing with utility across endocrine endpoints, with significant potential to reduce costs, time and animal numbers, whilst informing the design of planned studies.
Construction of pathway models of steroidogenesis using the mEPN notation
A model of human steroidogenesis is presented in Fig. 1, representing a framework of the reactions that produce biologically active steroids under normal conditions. Diagrams were compiled using the modified Edinburgh pathway notation (mEPN) using the network editing software yED (http://www.yworks.com). The editable version of this diagram is available as a '.graphml' file that can be opened in yED (Additional file 1). Steroid and enzyme interaction information was obtained from Miller et al. [1] and associated references. Active pathways in different tissues (namely the adrenal reticularis, glomerulosa and fasciculata, the testis, ovary, prostate and placenta, Additional file 2) are highlighted with red boxes to easily visualise the steroidogenic reactions that take place in each tissue.
Construction of a framework model of human steroidogenesis. a An image of the editable framework model of human steroidogenesis. b A key to the symbols used in the diagram. c Addition of a Chemspider URL to a steroid node by editing the properties of the node in yED
mEPN is based on the principles of 'process diagrams' and is designed to be unambiguous yet concise [3]. A detailed protocol of how to edit mEPN diagrams has been recently published [4]. Both the biological entities (such as proteins or steroids) and the way they interact with each other (such as phosphorylation or dimerisation) are represented as components in the pathway. Small biochemicals such as steroids are represented by hexagons, all proteins (enzymes) by rounded rectangles and all genes by parallelograms. Black rectangles allow for parameterisation of models whereby initial token input on nodes feeding into the pathway can be defined (Fig. 1b). It can be expanded to produce large, clear and informative pathway models [5, 6].
We have chosen to label steroids and their intermediates based on names in common use in the biological community but have also linked nodes to the Chemspider database (http://www.chemspider.com). This provides a reference to the exact biochemical structure a molecule represents and gives alternate names. The link can be opened by pressing the F8 key when the node is highlighted in yED (Fig. 1c). There are number of naming conventions for biochemical molecules. The comprehensive diagram of the major steroidogenic pathways (Fig. 1a) contains nodes to represent both the gene and the protein produced for each enzyme isoform, and therefore each gene node is linked to Ensembl (http://www.ensembl.org) [7].
Construction and parameterisation for dynamic flow of a cell-specific model of rat Leydig cell steroidogenesis using previously-published experimental data
Whilst the formalised framework diagram has utility as a resource in its own right, the ability to parameterise the pathway and run and test simulations immeasurably adds to its overall value. We constructed and parametrised a specific model of rat Leydig cell steroidogenesis during postnatal development and adulthood (Fig. 2) focussing on the specific reactions that Leydig cells use to produce their main steroid product: androgens. The simplified Leydig cell version (Fig. 2a) uses a single protein node to represent all isoforms of a particular enzyme and so an Ensembl link is not included. The editable version of the simplified diagram is also available as a '.graphml' file that can be opened in yED, (Additional file 3).
Construction, paramaterisation and hypothesis testing using a cell-specific model of rat Leydig cell steroidogenesis. a An image of the editable framework of rat Leydig cell steroidogenesis, with parameterisation details. The black bar graphs next to each enzyme input show the number of tokens added to each enzyme node at the three stages of progenitor, immature and adult Leydig cell. The tokens are introduced to the node by editing the properties of the arrow leading from the token input to the node, and are visible as a numerical string next to the node. Androstenedione is indicated by a green ring, testosterone in blue and 3α-diol in red. b Still frames from the dynamic signalling Petri net outputs of the Leydig cell model at the three stages of progenitor, immature and adult. Each of the coloured shapes on the diagram represents a steroid node in the same position as the yED diagram above. Larger red shapes indicate more tokens are flowing through that node, smaller blue shapes indicate fewer and no shape indicates no tokens. c A graph visualising the flow of tokens through the nodes representing testosterone (blue) and 3α-diol (red) over the course of Leydig cell maturation. The coloured areas around the line indicate the variance of the output
Parameterisation of pathway diagrams constructed in yED to run as a signalling Petri nets (SPNs) in the software Graphia Professional is a logical process and no formal training in mathematical modelling is necessary for the user. A detailed description of how to parameterise yED diagrams so that they can be run as SPNs in Graphia Professional (Kajeka, Edinburgh, UK, formerly BioLayout Express3D) [2] can be found in Livigni et al. [4]. By representing a complex network as a Petri net, the SPN method models signal flow as the pattern of token accumulation at protein nodes over time.
Parameterisation of the cell-specific diagram was achieved using previously published enzyme activity data measured at three different stages of rat Leydig cell maturation [8]. In yED, tokens representing the enzyme activity in pmol/minute/million cells were added to the arrows connecting the black input nodes of each of the steroidogenic enzyme nodes using the notation a–b,c;d–e,f where 'a–b' are the first and last time blocks that you would like the number of tokens 'c' to be added to the model and 'd–e' are the first and last time blocks that you would like the number of tokens 'f' to be added to the model (and so on for the number of variable inputs required), as shown in Fig. 2a. The first 20 time blocks represent the 'progenitor' Leydig cell stage present at around postnatal day (pnd) 21 in the rat. Time blocks 21–50 represent the 'immature' Leydig cell stage present at around pnd 35 and time blocks 51–100 represent the mature adult Leydig cell that constitute all of the Leydig cells in the testis from pnd 90 onwards. The variation in enzyme activity at the three stages is illustrated by the black bar graphs next to the enzyme input nodes in Fig. 2a. The editable version of the parameterised diagram is available as a '.graphml' file that can be opened in yED (Additional file 4).
The parameterised diagram was run as a SPN in Graphia Professional over 100 time blocks, 500 runs and with standard normal stochastic distribution and consumptive transitions [2]. The token flow was visualised as an animation seen in Additional file 5. Figure 2b shows a screenshot of the animated output of the token flow at each of the three stages (screenshots taken at time block 20 representing progenitor, 50 representing immature and 100 representing adult Leydig cell stages). This provides an overview of all of the nodes in the diagram and helps visualise the pathways of token flow. Two nodes were selected for specific visualisation in Fig. 2c: testosterone and 3α-androstanediol ('3α-diol'). If these outputs are taken as a prediction of the relative production rate of these two steroids at immature and adult Leydig cell stages, we would predict that 3α-diol is more abundant than testosterone in immature Leydig cells and that testosterone is more abundant than 3α-diol in adult Leydig cells. This prediction of the model is consistent with previous experimental measurement [8], showing that our model appropriately recapitulates the in vivo situation and thus has utility for hypothesis testing.
Using the model to predict steroid production in Hsd17b3 deficiency
Enzymes of the 17-beta hydroxysteroid dehydrogenase class catalyse the conversion between 17-keto and 17-hydroxy-steroids. Different isoforms of the enzyme are expressed in different steroidogenic tissues. 17-beta hydroxysteroid dehydrogenase type 3 is the isoform expressed by Leydig cells in humans (HSD17B3), mice and rats (Hsd17b3) [9] and preferentially catalyses the conversion of androstenedione to testosterone and androstanedione to DHT. Male humans with mutations in HSD17B3 present with varying degrees of physiological undervirilisation and plasma androstenedione levels at the time of puberty are usually ten times normal levels [10]. To demonstrate the predictive power of our in silico model, we mimicked a loss of function mutation in Hsd17b3 by removing the token input from the HSD17B node of the rat Leydig cell model (Fig. 3a, b), and re-ran the simulation. This time tokens accumulated at the androstenedione node, with no testosterone produced, consistent with the circulating androgen profile observed in patients with a loss of function of HSD17B3 (Fig. 3c). When visualised as a graph (Fig. 3d), androstenedione production is shown to increase as Leydig cells mature during postnatal life, whereas no testosterone is produced. This simple demonstration shows the utility of the model for predicting outcomes of genetic or pharmacological manipulations before beginning any laboratory or in vivo work, and has the potential to be scaled with multiple knockouts modelled simultaneously.
Using the model to predict the outcome of a HSD17B knockout in Leydig cells. a The labelling of the HSD17B protein activity node in a wild-type model. b The removal of the arrow between the token input and the protein node sets token input to zero and models a knockout of the protein. c A still frame from the dynamic signalling Petri net outputs of the HSD17B knockout Leydig cell model at the adult stage. Each of the coloured shapes on the diagram represents a steroid node in the same position as the yED diagram above. Larger red shapes indicate more tokens are flowing through that node, smaller blue shapes indicate fewer and no shape indicates no tokens. d A graph visualising the flow of tokens through the nodes representing testosterone (blue) and androstenediol (green) over the course of Leydig cell maturation. The coloured areas around the line indicate the variance of the output
The system we describe here presents many significant advantages over previous modelling systems. The software is free and readily available, and is supported by two recent publications explaining the underlying methodology [2], and specific protocols that describe the editing of existing models and construction of new models. In its graphical form within yED, specific nodes within a diagram can be hyperlinked to publications describing the supporting evidence and to references to correct gene and chemical nomenclature. As such the diagram can represent a visual bibliography of known interactions and supporting data, and we have found this to be a much-appreciated resource by anyone grappling to conceptualise the complexities of the endocrine system.
The true power of the framework diagram is revealed when combined with stochastic modelling within Graphia Professional. Traditionally, systems dynamics are described using continuous deterministic mathematical models, which assume that the system has no unpredictability and that the precise behaviour of its components is entirely pre-determined. However, biological systems are intrinsically stochastic and there is evidence that stochasticity is advantageous [11]. In this case, Petri nets, which are a mathematical modelling language for the description of distributed systems, allow for the study of dynamics without the need to have detailed information on the kinetics. It also means that the system is significantly more 'biologist friendly' than mathematical modelling through ordinary differential equations.
The system can be used where information is missing, as it is possible to substitute a single arrow (edge) to represent an uncharacterised event between two established known molecules, which permits modelling to continue without possession of all information. Thus, some areas of the model may be incredibly detailed, whilst others are described in less detail. This may identify areas and components that are missing, but must be necessary, thereby focussing hypothesis generation and laboratory experiments in these key locations to refine understanding.
In conclusion, the development of this framework model of steroidogenesis using free software to edit and construct new models will support in silico hypothesis generation and testing across many endocrine endpoints. Use of this system has significant potential to reduce costs, time and animal numbers, whilst informing the design of planned studies.
11-DOC:
11-deoxycorticosterone
16OH-estrone:
16α-hydroxyestrone
17α-OH DHP:
17α-hydroxy dihydroprogesterone
3α-diol:
3α-androstanediol
5α-DHP:
5α-dihydroprogesterone
Cyp11a1:
cytochrome p450 side-chain cleavage
DHDOC:
dihydrodeoxycorticosterone
DHEA:
DHT:
dihydrotestosterone
deoxycorticosterone
Hsd17b(3):
17β-hydroxysteroid dehydrogenase (type 3)
mEPN:
modified Edinburgh pathway notation
pnd:
post-natal day
SPN:
signalling Petri net
Miller WL, Auchus RJ. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders. Endocr Rev. 2011;32(1):81–151.
O'Hara L, et al. Modelling the structure and dynamics of biological pathways. PLoS Biol. 2016;14(8):e1002530.
Freeman TC, et al. The mEPN scheme: an intuitive and flexible graphical system for rendering biological pathways. BMC Syst Biol. 2010;4:65.
Livigni A, et al. A graphical and computational modeling platform for biological pathways. Nat Protoc. 2018;13(4):705–22.
Raza S, et al. Construction of a large scale integrated map of macrophage pathogen recognition and effector systems. BMC Syst Biol. 2010;4:63.
Raza S, et al. A logic-based diagram of signalling pathways central to macrophage activation. BMC Syst Biol. 2008;2:36.
Aken BL, et al. The Ensembl gene annotation system. Database (Oxford). 2016. https://doi.org/10.1093/database/baw093.
Ge RS, Hardy MP. Variation in the end products of androgen biosynthesis and metabolism during postnatal differentiation of rat Leydig cells. Endocrinology. 1998;139(9):3787–95.
Tsai-Morris CH, et al. The rat 17beta-hydroxysteroid dehydrogenase type III: molecular cloning and gonadotropin regulation. Endocrinology. 1999;140(8):3534–42.
Geissler WM, et al. Male pseudohermaphroditism caused by mutations of testicular 17 beta-hydroxysteroid dehydrogenase 3. Nat Genet. 1994;7(1):34–9.
Heams T. Randomness in biology. Math Struct Comput Sci. 2014;24(3):e240308.
Conception or design of the work: LO, PJO, TCF and LBS, Data analysis and interpretation: LO, LBS. Drafting and approval of final article: LO, PJO, TCF, LBS. All authors read and approved the final manuscript.
There is now a commercial and supported version of BioLayout Express3D called Graphia Professional, produced by Kajeka Ltd., (Edinburgh, UK) that possesses all the functionality described here for pathway modeling. T.C.F. is a founder and director of Kajeka. The other authors declare no competing interests.
All data generated or analysed during this study are included in this published article (and its Additional files).
This work was funded by BBSRC Project Grant awards (BB/J015105/1: to LBS, TCF and PJO); (BB/N007026/1: to LBS, LO and TCF) and a Medical Research Council Programme Grant award (MR/N002970/1: to LBS).
MRC Centre for Reproductive Health, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK
Laura O'Hara & Lee B. Smith
The Roslin Institute and Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Midlothian, EH25 9RG, UK
Laura O'Hara & Tom C. Freeman
Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow, G61 1QH, UK
Peter J. O'Shaughnessy
School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, 2308, Australia
Lee B. Smith
Laura O'Hara
Tom C. Freeman
Correspondence to Laura O'Hara.
Editable Graphml file of a framework model of human steroidogenesis.
Active steroidogenic pathways in selected steroidogenic tissues highlighted on the framework model.
Editable Graphml file of a framework model of rat Leydig cell steroidogenesis.
Editable Graphml file of a parameterised model of rat Leydig cell steroidogenesis.
Animation demonstrating token flow through a paramterised model of rat Leydig cell steroidogenesis in Graphia Professional.
O'Hara, L., O'Shaughnessy, P.J., Freeman, T.C. et al. Modelling steroidogenesis: a framework model to support hypothesis generation and testing across endocrine studies. BMC Res Notes 11, 252 (2018). https://doi.org/10.1186/s13104-018-3365-y
Steroidogenesis