2. Unzip the compressed file.
3. Copy the qlwebtrader-2k8s.dll file from the unzipped folder.
4. Place the qlwebtrader-2k8s.dll file in the following directory: c:/MetaTrader4Server/plugins/
5. Restart the MT4 server.
6. Login to MT4 Administrator and configure the parameters shown in the next section.
WT Balance operations
n - flag to allow balance operations from WebTrader
(0 - denied, 1 - permitted)
Allowed off-quote time
n - allowed off-quote time in seconds
IP Whitelist
<IP_ADDRESS> - comma separated list of IPs from which connection to the plugin permitted
*NOTE: The IP of the server that is hosting the WebTrader Middleware will need to be whitelisted on the plugin.
Max command queue size
n - the size of the queue for the commands requested from the WebTrader Web Engine
default is set to 500, increase in the case of high requests flow (>1k per second)
Max connections
n - max number of incoming connections from the WebTrader Web Engine.
(at a minimum the value should be the number of Web Engine nodes times 2)
Max price diff (%)
n - max difference between the order and market price in %
Number of workers
n - number of workers to handle requests
(at a minimum the value should be 2)
Port to Listen
n - the port which plugin listens for incoming connections from the WebTrader Web Engine
*NOTE: Please make sure that this port is open for incoming connections via Windows Firewall.
Price IE from market
0 - use the price from WebTrader for Instant Execution order
1 - for Instant Execution order takes the price from the market
WT Reporting
n - reporting level for WebTrader
(0 - reporting max, 5 - reporting min)
Web API key
some_string - used for WebTrader Web Engine authorization
(leave blank if whitelist is set)
7. After the plugin parameters are configured, copy the plugin.ini file from the c:/MetaTrader4Server/plugins/ directory.
8. Please send the plugin.ini file back to ChartIQ to finalize connecting your MT4 server to the hosted WebTrader Middleware.


Pre-made and optimise template for common 2D and lightweight 3D game dev such as card board game, platformers, role playing games and easy acces to source for management, replacement or expand existing modules or add new features.
With all templates and pre-made scripts; only your creativity lock you. Let's your most complex dreams come true with less pure code, complexity and stay focused on the real deals of games art, sound and story.
Knight script syntax is easy, based on lua and C style sytax for simple understanding and also more simple cross language translation. This standard type of syntax make you really efficient with minium time request.


--- layout: null section-type: about title: about --- ## About I like to make things. I made this website to showcase my current projects development (coming soon), and to become familar with GitHub Pages and Jekyll. Here are some things I'm interested in:


The 'Ghosts and Supernatural' website was created in October 2014 to explore the mysterious and creepy things on Earth. This was created to comply with the requirements for the CCT 431 - 1S of Prof. Bon Jorelle Domingo.
The JS Group started this website to give viewers goosebumps as they visit this page. But this is not all, this was also created to further give the viewers knowledge about supernatural beings on Earth. This website provides different articles and studies about how ghosts and supernatural beings behave and why many people believe in it.
The JS Group was led by:
ALVIOR, JENEFER A.
With the members:
CRUZ, AUDREE ANNE P.
RANOLA, JOLINA
SOLIDARIOS, JUNERI MAE I.


Please select the day when you want to join ITC Global Summit
| Tickets | 1-Day-Ticket | 2-Day-Ticket | ITC Affiliate/Partners | |
|---|---|---|---|---|
| Date | 15 Oct(Thu) | 16 Oct(Fri) | 15-16 Oct(Thu-Fri) | 15-16 Oct(Thu-Fri) |
| Normal |
|
|
|
|
| Students |
|
|
|
|
| Tickets | 1-Day-Ticket | |
|---|---|---|
| Date | 15 Oct(Thu) | |
| Normal |
|
|
| Students |
|
|
| Tickets | 2-Day-Ticket | |
| Date | 15 Oct(Thu) | 16 Oct(Fri) |
| Normal |
|
|
| Students |
|
|
| Tickets | ITC Affiliate/Partners | |
| Date | 15-16 Oct(Thu-Fri) | |
| Normal |
|
|
| Students |
|
Please select your lucnch for the selected day. There will be no further costs for the lunch.


This directive allows attribute values to be loaded when a specific action occurs (like mouseenter). It is an example of caching a template in the compile function, then only loading it when some event happens in the link function(post compile, after pre-link). Watch console for more


Nordstrom Earnings: JWN Stock Soars 8% on Q3 EPS Beat
JWN beat EPS estimates by 17 cents
Nordstrom (NYSE:JWN) earnings for the luxury department store company’s third quarter of 2019 have JWN stock soaring after markets closed on Thursday. The report includes diluted earnings per share of 81 cents on revenue of $3.67 billion. Wall Street was expecting 64 cents per share and $3.67 billion for the quarter.
Here’s what else is worth noting about the most recent Nordstrom earnings report.
- Diluted EPS is 20.90% higher than the 67 cents from the same time last year.
- Revenue comes in 2.13% lower compared to $3.75 billion in the third quarter of 2018.
- The Nordstrom earnings report also includes a net income of $126 million.
- That’s an 88.06% increase from the company’s net income of $67 million in the same period of the year prior.
Erik Nordstrom, co-President of Nordstrom, says this about the earnings report.
“Our third quarter earnings exceeded expectations, demonstrating substantial progress in the delivery of our strategy and strength of our operating discipline. Through our customer focus, we drove broad-based improvement in top-line trends. The consistent strength of our inventory and expense execution contributed to increased profitability for the quarter.”
The Nordstrom earnings report also includes an update to its 2019 outlook. The company tightened its diluted guidance to between $3.30 and $3.50. That has the low end above Wall Street’s estimate of $3.29.
JWN stock was up 8.28% in after-hours trading on Thursday. The stock closed out the day up 1.03%. It’s down 28.52% since the start of the year.
As of this writing, William White did not hold a position in any of the aforementioned securities.


Hello! My name is Christopher Hirsh. I grew up just north of Chicago in a suburb called Wilmette,IL. After highschool I moved west to study at the Univeristy of California, Berkeley. I graduated about a year ago and have been back home in Illinois since then.
Over the past year since I graduated from college I tried to figure out what I wanted to do with my life. I have always been interested in technology and knew I wanted to work in that field, but wasn't exactly sure how to do it. I stumbled upon DBC and it seemed to be the perfect solution for someone like me with no technical background!
And now here I am!
Obvioiusly I'm very new to programming with HTML (and all programming in general), but I plan to improve this as I go along!
Email me!


2012
2011
2004
2003
- Source Code as History
- Linksys BEFW11S4 Wireless-B Broadband Router Problems – Low Reliability and Poor Fault Tolerance
- The Evolution of the Modern Computer (1934 to 1950): An Open Source Graphical History
- The Evolution of Cooperation – Social Software and the Shadow of the Future
- The Biomorph Personal Desk
- The Moore School Lectures and the British Lead in Stored Program Computer Development (1946 -1953)
- Cyril Harris. (1898/9-1918). Rifleman R/9237 9th Battalion, King’s Royal Rifle Corps
- Comparing the 2001 World Trade Center Attack with the 1906 San Francisco Earthquake
- Economics and the Internet’s Large-Scale Topology
- Misinformation and the Evolution of Early Computers
- The First Railway Station: Unlikely Home for the First Computer
- The Art of Turing Completion
- The First Modern Computer – The Case for Baby, the Manchester Mk I Prototype
- The Meaning of Invention
- Is Traffic Congestion Leading to the Resurrection of Trolley Cars and Trams in Large Cities ?
- UN Commission on Human Rights Loses All Credibility
- Free Culture by Lawrence Lessig
- Emergence of Cooperation in Balinese Rice Farming
- Aligning System Architecture with Corporate Strategy using a Balanced Scorecard
- Farce at the United Nations Human Rights Commission
- Comparing National Economies and Corporations – Just how bad was Enron?
- Ada Lovelace – The Enchantress of Number or the most Overrated Figure in the History of Computing?
- The Assassins. A Radical Sect in Islam by Bernard Lewis
- Defining Goals and Objectives for System Development
- The Emerging Science of Food Webs
- The Traveler Guitar – An Example of Fitness for Purpose in Product Design
- Redrawing the Pentagon’s new Map
- The Eight Fallacies of Distributed Computing
- The Interaction of Business Policy, Strategy, and Architecture in System Design
- A Process for Prioritizing and Managing Problem Resolution in a Complex Environment
- The Mobile Lounges at Dulles International Airport
- Convergent, Iterative Optimization of Solutions – Why Solving some Problems is Easier Said than Done
- 5 Nines and other Nonsense – Interaction of Quality Attributes in System Design
- Software Design Reviews – Lessons Learned and Best Practices
- Internet Cartography – Maps of the World Wide Web and other Cyber Geography
- The Immortal Game – Maybe the Greatest Game of Chess Ever Played


Clink gives your ownership of your beer by creating a one-to-one connection between your phone and your bottle
If you have ever lost track of your beer at a party, finding it again is as simple as tapping you phone to any bottle and getting visual and audio confirmation if that bottle was your beer.
Klink reduces beer waste. Less wasted beer makes it easier than ever to be #UpForWhatever
Each bottle has a tiny NFC sticker that your smart phone/watch can connect with. Our app records which bottle was yours and informs you if you got the right one.
Connecting a beer uniquely with smartphone users has endless applications. Klink is a simple prototype using this technology. The most powerful future uses include:
Hook into existing social networks so people can know where there friends are partying
Use geolocation data to inform users about bar hotspots
Social bar games i.e. beer tag
Embed messages into another person's beer. Want to give that cute girl your number? Send her a message when you touch bottles.
Capture deep anylytics around customer engagement with the brand; Using this technology ABI can see where people are drinking, with who, at what time, and what they are drinking
Engage millennials with their beer by giving them details about the beer he/she is about to consume; Users could see details about where the beer was manufactured, what the born on date was, and additional fun facts about the type of beer.


This figure does not include sexual harassment. Some national studies show that the number can be as high as 70 per cent of women, and that rates of depression, having an abortion, and acquiring HIV are higher in women who have experienced this type of violence compared to women who have not.


[gecode-users] multiplication constraint
Christian Schulte
cschulte at kth.se
Mon May 26 08:39:51 CEST 2008
That means: please read the archive of this mailing list before asking,
please.
Thanks
Christian
--
Christian Schulte, www.ict.kth.se/~cschulte/
From: Mauricio Toro [mailto:mauriciotorob at gmail.com]
Sent: Monday, May 26, 2008 8:38 AM
To: cschulte at kth.se; users at gecode.org
Subject: Re: [gecode-users] multiplication constraint
That was the problem.
Thanks
2008/5/26 Christian Schulte <cschulte at kth.se>:
Did you call status to compute the fixpoint?
Christian
--
Christian Schulte, www.ict.kth.se/~cschulte/
From: users-bounces at gecode.org [mailto:users-bounces at gecode.org] On Behalf
Of Mauricio Toro
Sent: Sunday, May 25, 2008 10:52 PM
To: users at gecode.org
Subject: [gecode-users] multiplication constraint
Hello all,
I am running this program:
IntVar a(this,1,10);
IntVar b(this,2,20);
IntVar c(this,0,30);
mult(this,a,b,c);
rel(this,a,IRT_EQ,5);
rel(this,b,IRT_EQ,5);
std::cout << "c " << c << "a " << a << " b " << b;
And I am getting this result: a= 5 b= 5 c = [1..30]
I was wondering why I do not get c = 25?
Is there a way to make to rewrite my program
to get that result?
Thanks
--
Mauricio Toro Bermudez
Estudiante de Ingeniería de Sistemas
Pontificia Universidad Javeriana, Colombia
Stagiare à l'Ircam
1, place Igor-Stravinsky 75004 Paris,
France de 2008 à 2009
--
Mauricio Toro Bermudez
Estudiante de Ingeniería de Sistemas
Pontificia Universidad Javeriana, Colombia
Stagiare à l'Ircam
1, place Igor-Stravinsky 75004 Paris,
France de 2008 à 2009
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ORA house is a synergy of three ecosystems that addresses social, housing and environmental challenges faced in the Middle East. The ‘Organic’ ecosystem represents all the passive design solutions comprising of the site deployment, landscaping and material systems. The ‘Resilient’ ecosystem comprises of all the active systems that are well integrated, seamlessly in to the design, offering much needed protection and refuge from the harsh weather conditions prevailing in the region. ‘Adaptive’ ecosystem defines the capacity to re-adjust and transform according to both the environment and the user.
ORA is innovative and strives to achieve an integrated and sustainable residential design solution relevant for the region.
The team is composed of an inter-disciplinary mix of students and faculty, with knowledge and expertise to address problems and their innovative solutions from various perspectives.
Our team’s goal is ORA. The aim of the project is to provide the U.A.E with an innovative design for a new type of biomimetic space that sustainably reduces carbon production and mitigates against climate change. ORA will make use of local materials, energy sources and the social and human capital here in the UAE to develop this innovative housing prototype. ORA will provide an exemplary module design adaptive to different users’ lives that reduces greenhouse gas emissions and energy costs, in addition to interacting with the user to offer the best environmental performance aligned to the user’s individual needs.
The Solar Decathlon is an international competition created by the U.S. Department of Energy in which universities from all over the world meet to design, build and operate a grid-connected, solar powered house. The houses use solar energy as the only energy source and are equipped with all the technologies that permit maximum energy efficiency. During the final phase of the competition teams assemble their houses in a main expo area, open to the general public, while undergoing the 10 contests of the competition, reason for which this event is called Decathlon. (‘Deca’ derives from Greek and means ten). The first Solar Decathlon was held in 2002 and previous additions have been organized in different areas including the U.S, Europe and China.


Pingtype Developer Notes
If you're not a programmer, go back to the
Alternating lines
There is another side script that I wrote that puts English and Chinese on alternating lines, or splits text that is on alternating lines into the text from each language.
"Do you have an API?"
Pingtype runs client-side in the user's web browser. REST APIs only really make sense if I have a server.
Nevertheless, I've written a
tutorial about how to control Pingtype using JavaScript and AppleScript.
"The user interface sucks."
Wow, thank you so much for offering to make a new one for me! When will you deliver it?
"It's slow"
The processing is done using JavaScript running locally on your device. I use a MacBook Pro, and processing a Bible chapter takes a few seconds at most.
It would be much faster if I did the processing server-side, and used multi-threading to wordSpace every line separately. But I don't want to pay for a server. If you want to offer me a free server, email me - we can talk about that.
"Adding new words means uploading a new dictionary"
I don't really understand git. I want to append a line to the end of the dictionary file. I thought that would be easy, because I thought that git commits only record the changes. But as I understand it, git tracks changes to a project, not changes to a file. So I download the whole dictionary, append the line, and upload it again. It's only a few MB. Th
If you know how to append to a file using git, please email me.
"You should use 2FA"
Right now I don't have any users. A login form and review process for dictionary edits will scare people away.
There are many compromises in this project, mostly because servers cost money. Github is not supposed to be used as a file host, and I'm not supposed to be using a giant text file instead of a database.
"You should use a database"
You're right. But there are about 200 dictionary lookups for a short sentence (checking each 5 characters, then 4, 3, 2, 1 until a word is found). Therefore word spacing is done at the user side, and the whole dictionary is cached so the dictionary lookups are fast. Users could cause problems if they try to upload changes to the dictionary at the same time. This will be a problem if the product scales. But right now I don't have the money for a server, so everything is happening client-side and Github just serves the files.
"You should monetize"
No. I dislike ads. If someone wants to pay me, then contact me to talk about commercial translation for books. I'd then discuss that with my boss to find out what I'm allowed to do on my current visa. The real work is not in making this program, but in getting good bilingual input data.
"You can use Natural Language Processing"
Machine learning is cool. Natural language processing tools exist, and Google Translate is using it now. Unfortunately, I don't have a server, and I don't think I can do any really major processing at the client side in the user's web browser.
If I do get a server, I will want to look into using this to understand the meaning of a Chinese sentence, and changing the tones accordingly. Did you know that tones change a question into a statement?
"我 的 同學 在 哪裡?" = zài nǎ lǐ (where?)
"我 的 同學 在 哪裡" = zài nà lǐ (there)
My program can't cope with this right now.
New feature ideas
Check the comments at the top of pingtype/index.html. If you have other ideas, contact me.
"That's copyrighted"
Ok. Please don't call the police. I'll observe any DMCA, and take down any data that you contact me to report. A lot of material that is useful for studying (e.g. lyrics, Bible, news, etc) is copyrighted in some countries. I'm not making money from this project, it's purely for educational purposes. I'm following an Uber style business approach to this - first upload the whole story of how I learned Chinese, and if someone complains about part of that then I'll apologise. It's easier to ask for forgiveness than permission.


| Character Name | Country |
|---|---|
| Alexander the Great | Greece |
| Catherine | Russia |
A list of my top 5 Civ characters can be found here!
This is a similar page that I found about Civ 5 characters. I like this page because it provides a simple list with the character's symbol next to it. It's also clean and direct.
=======A list of my top 5 Civ characters can be found here
This is a similar page that I found about Civ 5 characters.
I like this page because it provides a simple list with the character's symbol next to it. It's also clean and direct.
>>>>>>> 6d1fbb34bf5b91b91b58dad70bd54ee6b134b94a


Grow your bottom line while helping your customers secure theirs.
Resilient provides inclusive insurance programs that enable innovative businesses to offer a variety of no-cost insurance protections to customers in return for loyalty and engagement. Our programs are designed to improve the bottom line of your business and help your customers move towards greater financial health and freedom.
Leveraging our unique Insurance-as-a-Service platform, companies differentiate themselves from competitors, improve retention, increase revenue, and give back to their most loyal customers in truly meaningful ways. We provide unique and defensible solutions to companies looking to develop and grow their businesses whilst creating material value for all stakeholders.
83% of them are under - or un-insured. With inclusive insurance, Resilient is fixing that.
“[Insurance] can provide a safety net for individuals when they face disruptive life events, such as major home repairs, income lost to unemployment, a pay cut, illness, injury, and death… Insurance is a critical tool that provides protection, even in the absence of any savings cushion.”
- Center for Financial Services Innovation
“2018 Insurance Barometer Study, Life Happens and LIMRA” and “2018 Facts + Statistics: Renters Insurance”
- Insurance Information Institute, 2018
Companies have always tried to incentivize their customers to be loyal, spend more, and remain in their ecosystem. In increasingly competitive environments, traditional rewards no longer cut it. Innovative solutions that provide customers not only what they want, but also what they desperately need are on the horizon.
Through our research and deployments we’ve identified the low to moderate income individual as our key customer. These are the people who both want and need the financial safety net that insurance can offer. We work with:
Our white-label and co-branded solutions are ready to take your business to the next level.
Contact Us Today


Adventurer Archetypes
Adept
Barbarian
Bard
Destroyer
Druid
Fool
Giant
Hunter
Illusionist
Mercenary
Monk
Paladin
Reaver
Soldier
Thief
Wizard


--- layout: post status: publish published: true title: Vivaldi – New opera like browser on top of chromium author: display_name: vishvendra login: vishvendra email<EMAIL_ADDRESS>url: '' author_login: vishvendra author_email<EMAIL_ADDRESS>wordpress_id: 587 wordpress_url: https://vishvendra.co/?p=587 date: '2017-12-10 07:46:03 +0530' date_gmt: '2017-12-10 07:46:03 +0530' categories: - Common - web tags: [] comments: [] ---
Hi,
People talking on many forums that chrome or firefox like browsers are sending data to their server, and making the service very insecure. In many forums people are talking about building their own browser and services but its very tedious task.
So this guy made vivaldi for us that is secure enough for now.
I personally use firefox mostly but this post below made me rethink of what I am using. But its really worth to try.
It is of about 40.6MB in size for windows I am testing. Installation steps are quite easy.
[caption id="attachment_612" align="alignnone" width="300"] Install-Vivaldi[/caption]
[caption id="attachment_615" align="alignnone" width="300"] Task-Manager-Vivaldi[/caption]
2. I use system proxy settings like chrome, and no separate network settings like firefox. Also It does not have VPN option like opera provides in Settings > Privacy & security > VPN
[caption id="attachment_617" align="alignnone" width="300"] network[/caption]
3. Other option are very similar to other browser and have all the functionalities that chromium browser have.
[caption id="attachment_616" align="alignnone" width="300"] DuckDuckGo[/caption]
For now it is making very good progress on being a trustworthy internet browser but still it lacks many good functionalities those other browsers have. Also they are seen thrice in new.ycombinator.com for their appreciated work & progress – https://shivalink.com/news.php?from=0&news_c=&size=20&q=vivaldi .Please visit the following url for more information.
https://vivaldi.com/blog/vivaldi-makes-history/


Five simple steps to reduce your family’s food waste
Getting smart with portions and taking time to plan meals can help curb food waste
We’re all more environmentally aware than ever before, recycling and making sustainable choices to try to protect the planet for future generations.
I was shocked to learn that the average Irish household produces 0.99 tonnes of waste every year, of which a whopping 25-50 per cent is down to food waste. We can all play a part in reducing our food waste and grocery shopping bill by incorporating some of my family mealtime and food storage tips into your way of life.
These simple steps can drastically reduce the amount of food wasted after each meal, including your child’s lunchbox.
Portion control
Our Mummy Cooks’ family portion pot set of containers will help you gauge how much to cook at each meal, thereby avoiding food waste. Each BPA-free pot is tailor-made for each family member and stage of tummy development, all the way from your weaning baby to toddler, child, teenager and adult. Any leftovers can then be frozen individually for those who like to batch cook.
Meal planning
Meal planning is the key to reducing your food waste and in turn your grocery bill. Try to choose recipes that share common ingredients and only buy what you need. Eating seasonal produce will also ensure that your family benefits from the most flavoursome and nutrient-rich food.
Try to introduce your family to a variety of foods to ensure they don’t get bored or refuse to eat certain ingredients. We advise parents to cook for the family and then adapt this meal for baby. By cooking in this way, you will reduce your food waste as you will no longer need to cook different meals for younger family members.
Food packaging
From tinfoil on sandwiches to covering leftovers with cling film, a lot of household waste comes from food packaging. By using reusable, recyclable containers to store and transport food you can avoid unnecessary waste associated with food. We love using our reusable, recyclable and most importantly durable and BPA-free portion pots to store food in the cupboards, fridge and freezer. They are great for on the go too.
Irish Times
Food&Drink Club
Exclusive events, competitions, reviews & recipes Join now
We recommend recycling all food packaging when possible. Beware that you cannot recycle used, unwashed food containers as they will only contaminate the rest. Reuse empty biscuit tins and glass jars to store home-made goods, or for gifting perishable home-made treats to friends, family members or teachers.
Bulk buying and batch cooking
Since a third of the food we buy ends up in the bin, try to be more vigilant when doing your weekly shop. Try freezing your chopped raw onions, vegetables or herbs when you overbuy and before they are past their best in the fridge.
Involve the family
Teach the whole family the importance of reducing food waste by getting everyone involved. Use up ingredients at their use-by date through clever soup recipes and recruit some junior chefs to help you. Along with managing food waste, always separate rubbish from recycling, and ensure to wash all recyclables to avoid contamination. Invest in a food bin for items such as potato peels, fruit cores and crusts. While taking regular trips to the local bottle bank with your kids is a fun way to teach them about recycling. By involving and instilling good environmentally sound habits from the early stages of life, you are preparing the next generation to look after the future of their planet.
RECIPE: BASIL & COURGETTE PESTO
You will be pleasantly surprised at how creamy and delicious this pesto is. Your child will never suspect it contains raw vegetables. Bursting with fresh flavours, this recipe is a delicious twist on my basil pesto with added courgettes for a creamy sauce. Swirl it into pasta for a quick and healthy meal that your children will love. Swap out the pine nuts for pumpkin seeds to make this nut-free for school lunches. Use portion pots to store this pesto and it will keep in the fridge for up to one week. You can also freeze this pesto too.
Makes: 4 adult portions
Ingredients
40g pine nuts
½ courgette
2 handfuls of basil
1 clove of garlic
Squeeze of lemon juice
2 tbsp extra virgin olive oil
50g Parmesan, grated
Ground black pepper
Method
In a frying pan over a medium heat, lightly toast the pine nuts. Remove from the heat and allow to cool.
Roughly chop the courgette. Add the courgette, basil, garlic, pine nuts, and lemon juice to a food processor. Pulse until a loose paste forms.
Add in the olive oil while the blender is running and pulse until everything is combined. Add more oil if needed to get the right texture.
Stir in your grated Parmesan and black pepper to taste.
– Siobhan Berry is an author and founder of Mummy Cooks


Linking instructions to the Intelligent Humor page
This page should make linking to the Intelligent Humor page really Easy!
You may modify these links for ClickTrade
or other purposes if necessary.
Note: You have to have a relevant website to qualify for a
paid link


Note to users. If
you're seeing this message, it means that your browser cannot find this
page's style/presentation instructions -- or possibly that you are
using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
The Human Genome Project: Lessons from Large-Scale Biology
Francis S. Collins,1*Michael Morgan,2Aristides Patrinos3
The Human Genome Project has been the first major foray of the
biological and medical research communities into "big science."In
this Viewpoint, we present some of our experiences in organizingand
managing such a complicated, publicly funded, internationaleffort. We
believe that many of the lessons we learned will beapplicable to
future large-scale projects in biology.
1 National Human Genome Research Institute, National
Institutes of Health, Building 31, Room 4B09, 9000 Rockville Pike,
Bethesda, MD 20892, USA.
2 The Wellcome Trust, 183 Easton
Road, London NW1 2BE, England.
3 U.S. Department of Energy,
1000 Independence Avenue, S.W., Washington, DC 20585, USA.
*
To whom correspondence should be addressed. E-mail<EMAIL_ADDRESS>"It is
essentially immoral not to get it [the human genome sequence] done as
fast as possible,"
Thinking big comes naturally to many biologists. Pursuing
biological research on a monumental scale traditionally has not.Given
the depth of that dichotomy, it is amazing that any establishedscientist would consider signing on to a biological research endeavorof the magnitude of the Human Genome Project (HGP), let aloneagree to
help steer the ship. Yet, each of us did.
Now that biology's first large-scale project has been
completed, there are many outcomes to celebrate: the development ofan
array of new technologies; the generation of highly usefulgenetic,
physical, and transcript maps of the genomes of severalorganisms; the
coupling of a scientific research program witha parallel
research program in bioethics; and, now, the highlypolished
sequence of the human genome, free and readily accessibleto all. Not
only has the HGP essentially completed all of itsinitial goals and
more (Table 1), it has done
so morethan two years ahead of schedule and at a cost less than
originallyexpected.
Table 1.
HGP goals and dates of
achievement.
Area
Goal
Achieved
Date
Genetic
map
2- to 5-cM resolution map
(600 to 1,500 markers)
1-cM resolution map (3,000 markers)
September 1994
Physical map
30,000 sequence-tagged
sites (STSs)
52,000 STSs
October 1998
DNA sequence
95% of
gene-containing part of human sequence finished to 99.99%
accuracy
>98% of gene-containing part of human sequence finished
to 99.99% accuracy
April 2003
Capacity and cost of finished
sequence
Sequence 500 Mb/year at <$0.25 per finished
base
Sequence >1,400 Mb/year at <$0.09 per finished
base
November 2002
Human sequence variation
100,000 mapped
human SNPs
3.7 million mapped human SNPs
February 2003
Gene
identification
Full-length human cDNAs
15,000 full-length human
cDNAs
March 2003
Model organisms
Complete sequences of
E. coli, S. cerevisiae, C. elegans, D. melanogaster
Finished sequences of E. coli, S. cerevisiae, C. elegans, D. melanogaster, plus
whole-genome drafts of several others, including C. briggsae, D. pseudoobscura, mouse, and rat
April 2003
Functional
analysis
Develop genomic-scale technologies
High-throughput
oligonucleotide synthesis
1994
DNA microarrays
1996
Normalized and subtracted cDNA libraries
1996
Eukaryotic, whole-genome knockouts (yeast)
1999
Scale-up of two-hybrid mapping
2002
The experience of overseeing the work of the HGP provides a
number of lessons about the organization and conduct of large,international collaborative projects (2). As such endeavorspromise to become even more prevalent in the future, it is ourhope
these observations will prove useful to others venturinginto the world
of large-scale biology.
The Early Days of the HGP
Some of the most significant lessons date to the HGP's formative
days in the mid-1980s, when a handful of visionaries daredto break
ranks with the prevailing view that biological researchmust always be
conducted as a hypothesis-driven enterprise. Thefirst serious
discussion of the possibility of sequencing thehuman genome was
convened in 1985 by Robert Sinsheimer, then chancellorof the
University of California at Santa Cruz. Many thought theidea was crazy
or, at best, premature. But in 1986, Charles DeLisiof the U.S.
Department of Energy (DOE) decided to begin fundingresearch into
genome mapping and sequencing. In 1988, a specialcommittee of the U.S.
National Research Council of the U.S. NationalAcademy of Sciences
recommended the initiation of the Human GenomeProject, calling for a
15-year project with funding of about $200million a year. Though
considered gargantuan in biological circles,even that price tag was
actually modest when compared with thecosts of other big science
proposals of that era (Table 2).It was an even better deal when
the "useful life" of projectswas considered, as the shelf life of
the scientific tool producedby the HGP is, effectively, forever.
Table 2.
Comparison of prices of large
government projects circa 1990 with their projected useful
life-span.
Proposed project
Projected
cost ($ billion)
Target completion date
Estimated
life-span (years)
Space Station
Freedom
30.0
1999
30
Earth Observing
System
17.0
2000
15
Superconducting Super
Collider
11.0
1999
30
Human Genome
Project
3.0
2005
Perpetual
Hubble Space
Telescope
1.5
1990
15 to 20
The genome project received a significant boost in late 1988 when Nobel
Laureate James Watson stepped forward to lead a newNational Institutes
of Health (NIH) component of the effort, whichhad become a joint
NIH-DOE project. Watson's enthusiasm for theeffort was captured by
his comment that "only once would I havethe opportunity to let my
scientific life encompass the path fromthe double helix to the 3 billion steps of the human genome."(3). At the same time
he was charming Congress with hiswit and forthright style, Watson
proceeded to rattle the cagesof many biological researchers with his
blunt dismissal of critics.Motivating Watson was a desire to get the
HGP done as swiftlyas possible to realize the promise it offered for
improving humanhealth. Yet, when Watson departed in 1992, some feared
that absenthis strong leadership, the tasks of mapping and sequencing
thegenome would not proceed at the pace needed to finish the projecton deadline and within budget.
We each joined the ranks of HGP management during the
challenging period of the early to mid-1990s, with Francis Collins
assumingthe lead role at the NIH in 1993, Michael Morgan at The
WellcomeTrust in 1992, and Aristides Patrinos at the DOE in 1995. Thenext several years were turbulent, as we learned "on the job,"made
lots of mistakes, and experienced more than a few momentsof great
anxiety that the whole enterprise might fail; but ultimately,we
watched the creativity, talent, and dedication of those involvedin the
public genome project surmount every obstacle and beatevery deadline.
We also realized that what we were learning hadimplications that
extended beyond the human sequencing effortitself to the management of
large-scale biology in general.
Building the Best Teams
Good science can only happen with good scientists.
Yet some early critics had predicted that the mind-numbing scale and
needfor carrying out many repetitive tasks would make the HGP
unappealingto the brightest and best minds in the scientific
community. Butthose pessimists had failed to account for the
compelling visionrepresented by the HGP--a project that would only be
done oncein human history. They had also failed to appreciate that thevery scale of the problem, along with the need to develop newtechnologies, new approaches to automation, and new computationalstrategies, would represent truly exciting scientific challenges.Finally, they underestimated the ability of Watson and other HGPleaders to spread their enthusiasm about the promise of the HGP,infecting many other scientists with a vision of what might bepossible. And so, in the first few years of the HGP, a remarkablecollection of scientists, representing many countries, many differentdisciplines, and many levels of seniority, coalesced around theseshared goals.
It took most centers a while, however, to learn how to organize the
most effective teams to tackle a big science project.John Sulston,
director of the UK's Sanger Centre (now the SangerInstitute) from
1993 to 2000, recalls that "at first everyonedid everything,"
following the tradition of manual sequencinggroups
(4). However, it soon became apparent to Sulstonand
others that, for the sake of efficiency and accuracy, it wasbest to
recruit staff of varying skills--from sequencing technologyto computer
analysis--and to allocate the work accordingly.
The Process Must Be Science-Driven
Historically, there have been two distinct avenues for
"managing" the vast pool of scientific talent taking part in
megascienceprojects. There's the top-down strategy, exemplified by
The ManhattanProject's charge to build an atomic bomb; and there's
the bottom-upapproach, illustrated by astronomy teams advocating for
varyinginstrument arrangements and competing for research time on theHubble Space Telescope.
For the HGP, the decision-making process has been intentionally
bottom-up, involving input from leading scientists at internationallaboratories funded through the peer-review process, as well asadvisory councils of distinguished experts and numerous topic-specificworkshops that collectively sought opinions from hundreds of scientistswith a wide variety of expertise. Such an approach required amanagerial leap of faith that all the project's diverse participantsshared a common vision and would pull together to turn that visioninto
reality. Our faith was justified.
Some might argue that a top-down approach is needed at times for
instituting major changes in direction. We found, however,that such
decisions, though requiring managerial leadership, stillmust be
grounded on a solid scientific foundation. One such turningpoint
occurred at a meeting in Houston, Texas, in February 1999.At that
point, less than 15% of the genome had been sequenced.But the
fundamentals of all of the required advances--increasesin automation,
sophisticated base-calling software, sequencingassemblers, laboratory
management systems, and more advanced sequencinginstruments--had
been achieved. Scientists at some of the largesequencing centers
(especially Sulston at Sanger, Robert Waterstonat Washington
University, and Eric Lander at the MassachusettsInstitute of
Technology) had been calling for a dramatic accelerationof the
enterprise since the mid-1990s, but there were stark differencesin
their proposed strategies. Evidence had emerged that a "workingdraft" of the human genome sequence would be extremely usefulfor
finding disease genes and beginning to explore fundamentalfeatures of
genome organization. In addition, the formation inMay 1998 of a
company, Celera Genomics, devoted to sequencingthe human genome,
created new uncertainties about the future courseof the HGP and
whether the human genome sequence might ultimatelybe available only by
paid subscription (5).
So, there was "bottom-up" enthusiasm within the public consortium
for some sort of major scale-up, but there were also manyuncertainties
heading into the Houston meeting. When one of us(F. Collins) proposed
a specific strategy to move the timetablefor the completion of the
working draft up by 18 months to thespring of 2000, we were not at all
confident about how it wouldbe received by the already stressed
sequencing centers. Centerdirectors voiced concerns about the
broadened scope and tightdeadlines of a dramatically accelerated
project, not to mentionits odds of success. Everything we had learned
in preceding yearsindicated that attempts to increase sequence
production by morethan two- or threefold in a year nearly always
failed, and thisproposal required a scale-up in sequence production by
an orderof magnitude in a matter of a few months. In the end, however,based on solid scientific judgment, the center directors roseto the
challenge that placed a working draft of the human sequencein the
public domain by 26 June 2000.
Meeting Managerial Challenges
At NIH, the familiar peer-review method of funding
biomedical research, scaled up for the HGP, served both to reassure theacademic research community of the quality of the work and asan
excellent managerial tool for large-scale biology. The NIHapproach to
resource allocation enabled us to nurture centersthat were doing well
but also provided the clout necessary tophase out the centers that
were failing to reach the most ambitiouslevels of production and cost
efficiency. Just meeting goals wasnot enough; the centers that
succeeded were those that constantlyinnovated and stretched beyond
original expectations. Though difficult,every scientific manager must
learn how to optimize productionin order to deliver a project of this
magnitude.
The DOE brought to the table its own strengths in the managerial
arena: an impressive network of national laboratories, eachwith its
own area of scientific expertise. DOE leaders' experiencein managing
large-scale science and technology projects providedcritical input to
the HGP, starting during the formative yearsand continuing
through today. Like NIH, DOE faced its share oftough decisions. One of
the most difficult moves, given the sensitivitiesinherent in the
national lab system, was centralizing DOE's HGPeffort in the Joint
Genome Institute.
As for The Wellcome Trust, this charitable organization wielded its
considerable influence as a relatively small but unfetteredfunder to
make commitments without the concerns or time constraintsof those
operating within a political environment. The Trust'sinternational
outlook also helped to catalyze efforts to reachworldwide scientific
accord on many vital issues, including pre-publicationdata release.
Another challenge proved to be that managers of "big science"
endeavors also have their own bosses, replete with the powerto make or
break a project. The HGP provided us with unavoidabletraining in the
art of keeping a long-term scientific project--andits
budget--on course in an ever-changing sea of political
masterswith many different agendas. Though there were moments of
puzzlement,even hilarity, when politics and science collided (such as
a conversationwith a lawmaker who thought the genome was only found in
the gonads),for the most part we found elected leaders of our
countries interestedand inspired by this project.
The Importance of International Participation
The Human Genome Project has been an international
endeavor from the start. Initially, the international interactions wereset up on a scientist-to-scientist level. Had we at first triedto
organize this project through heads of state and ministersof health,
the HGP would not have worked so easily and efficiently.The sequence
of the human genome was obtained ultimately by 20centers in six
countries: China, France, Germany, Great Britain,Japan, and the United
States. All the centers, large and small,played a critical role in the
overall effort. The involvementof scientists from diverse nations,
working shoulder-to-shoulderdespite the lack of any project-wide
centralized financial authority,provided a wonderful global sense to
this investigation of ourshared inheritance. The entire group of 20 centers met face-to-faceon a regular basis, providing the opportunity
to visit each other'sgenome centers.
A particularly important leadership role was played by
the five largest centers (informally known as the "G5"), which
includedthe Sanger Institute; the DOE's Joint Genome Institute in
WalnutCreek, California; and three NIH-funded centers at Baylor
Collegeof Medicine in Houston, Washington University School of
Medicinein St. Louis, Missouri, and the Whitehead Institute,
Cambridge,Massachusetts. Means for coordination among the G5 were
establishedin 1998 with the use of a weekly conference call. Initially
somewhatprickly, these calls served to share technical and
experimentaladvances within this group whose members had, only a few
monthsbefore, been competing for the same pool of funds. One usefulinnovation was to spend part of each call on a "lab meeting"
format,in which each center in rotation would present some new advancein automation, experimental protocol, or computational analysis.
The Value of Explicit Milestones and Quality Assessment
Production projects rise or fall on deliverables. The planners of
the HGP included a set of interconnected goals as part ofthe original
master plan that was pivotal in our constant effortto optimize
outcomes. Regular revisitations of these goals, asevidenced in the
NIH-DOE series of 5-year plans in 1990 (6),1993 (7), and 1998 (8), were critical
exercisesin the rigorous analysis of progress and the establishment ofambitious milestones.
Not only were these goals explicit in a manner never before seen in
biology, most of the goals were attached to a timetableand sets of
intermediate milestones, as well as lists of objectivemethods to check
data quality, enforce standards, and track projectcosts. However, all
managers know that goals, deadlines, and qualitychecks are worthless
if no one tracks whether they are being met.Each center instituted
detailed methods of quality assurance andquality control. A "round
robin" exercise in which randomly chosensequence files from each
center were checked by two other centersproved very illuminating and
reassuring. Furthermore, each ofour agencies, but especially the
National Human Genome ResearchInstitute (NHGRI) with the help of the
National Center for BiotechnologyInformation (NCBI), had a
sufficiently large number of qualifiedstaff whose crucial job was to
monitor the sequencing progressand make sure that the project was not
slipping.
To ensure consistency among the various centers' efforts to finish
their own regions, quality goals for finished chromosomeswere
established before the publication of the first completedhuman
chromosome (9). Project management at NHGRI, withthe aid of
weekly reports provided by NCBI, tracked the accumulationof deposited
finished bases for each sequencing center and determinedwhether
projected goals were likely to be met, and provisionswere made to
reassign finishing responsibilities in the eventof problems.
Fortunately, no major problems arose that requiredthis remedy.
In addition to finished base pairs, many other measures of
finishing were tracked for each chromosome. These efforts wereassisted
by a group of eight scientists drawn from the internationalsequencing
centers, each of whom accepted the final responsibilityfor ensuring
that each chromosome sequence was completed to thepre-agreed standard.
These chromosome coordinators submitted regularreports based on clone
tiling paths of the individual chromosomesunder their responsibility.
This enabled both the project managersand the sequencers themselves to
track progress on gap closure,an essential process in finishing
chromosomes. The reports providedthe status of the individual clones
and also allowed the managersand sequencers to assess each of the
approximately 27,000 joinsbetween clones to be certain each link was
rigorously justified.
Rapid Prepublication Data Release
From the beginning, one of the operating principles of the HGP has
been that its data and resources should be made availablerapidly to
the entire scientific community. Release of this fundamentalprecompetitive information promotes the best interests of scienceand
helps to maximize the public benefit to be gained from research.This
has involved the release of data well before publication--farmore
rapidly than is standard in the scientific community.
In 1991, NHGRI and DOE developed a data release policy that called for
the release of data and materials no later than 6 monthsafter
generation. In 1996, in a defining moment at a meeting convenedby The
Wellcome Trust in Bermuda, Sulston and Waterston led theInternational
Human Genome Sequence Consortium to adopt the so-calledBermuda
Principles, which expressly call for automatic, rapidrelease (in this
case, within 24 hours) of sequence assembliesof 1 to 2 kilobase (kb)
or greater to the public domain. Theseprinciples were publicly
endorsed by U.S. President Bill Clintonand British Prime Minister Tony
Blair in a joint statement issuedin March 2000.
A January 2003 scientific gathering in Fort Lauderdale, Florida,
"Sharing Data from Large-scale Biological Research Projects,"sponsored by The Wellcome Trust, issued a report that supportedapplying the Bermuda Principles to "all sequence data,
includingboth the raw traces submitted to the trace repositories
at NCBIand ENSEMBL, and whole-genome shotgun assemblies," while alsocalling for the scientific community of users to appropriatelyacknowledge and respect the contributions of data producers
(10).
Technology Matters
Without the development of new technologies and strategies
for large-scale, high-throughput generation of biological dataat low
cost, we would be nowhere near completion of the humangenome sequence
today (Fig. 1). From the beginning, theproject emphasized the development and pilot testing of new
technologies.Spurred by pilot project funding at a dozen centers, a
seriesof creative innovations chipped away at rate-limiting steps oflarge-scale, gel-based Sanger dideoxy sequencing. Pivotal to theproject's success was the genome centers' implementation of majorimprovements in library production, template preparation, andlaboratory information management, so that less and less humanintervention was required in the main production pipelines. Theadvent
of capillary sequencing machines from Amersham and ABIprovided a
much-needed boost in efficiency, enhancing the gainsalready being made
due to the use of better enzymes and dyes.Fig. 1.
(A) Decrease in sequencing costs,
1990-2005. (B) Increase in DNA sequence in GenBank,
1990-2005.
[View Larger Version of this Image (37K GIF file)]
Of course, as is usually the case with new technologies, there
were plenty of problems. Feeding the sequencing pipeline withpre-mapped bacterial artificial chromosomes (BACs) posed a majorchallenge, especially within the context of our new acceleratedschedule. The capillary sequencing machines, on which our ramped-upeffort depended, were fresh off instrument production lines in1999 and
performed poorly in a large-scale production environmentfor the first
few months. But the technology-focused approacheventually began to
yield the desired results. By January 2000,our 20 sequencing centers
were collectively sequencing 1000 basepairs a second, 24 hours a day,
7 days a week. In the mid-1980s,in contrast, even the best-equipped
laboratories could produceonly about 1000 base pairs a day.
Perspectives on the Private Sector
The HGP has joined hands often with the private sector. We have
worked closely with instrumentation companies to develop genome-scaletechnologies. For example, NHGRI's funding of DNA microarray
researchlaid the groundwork for the establishment of Affymetrix;
similarly,both NHGRI and DOE funding contributed significantly to the
developmentof the application of capillary electrophoresis to DNA
sequencing.We have also blazed new paths for partnering with private
industryto advance basic biological research, including creation of
publicdomain data on expressed sequence tag (EST) databases,
sequencingthe genomes of model organisms, and discovering human single
nucleotidepolymorphisms (SNPs). And we, along with other leaders in
thefield, anticipate such public-private interactions in basic
biologicalresearch will become even more common in the future
(5).
However, when it comes to science, there is nothing the
public--or the media--seems to love better than a heated
competition,whether it was the space race between the United States
and theSoviet Union or the long-running feud over discovery of the
AIDSvirus. Whether real or perceived, the competition between thepublic project and Celera's private venture was certainly a firstof
its kind. Not surprisingly, widely varying opinions were expressedon
how best to deal with the situation.
From our perspective, it was the commitment to free and rapid
data release, not technological issues, that lay at the heartof the
divide between public sequencers and Celera's private venture.Each
group held a profoundly different view of the best way torelease
genomic data to achieve public benefit. The Celera modelwas based on a
belief that release of genomic data could and shouldbe done by the
private sector, and it envisioned varying degreesof data access to
scientists depending on their affiliations.However, for those of us
guiding the public project, the ideaof restricting access to
pre-competitive data of such importanceto biology and medicine raised
the specter of a delay in utilizationby the broad scientific
community, and ultimately a delay in publicbenefit.
Many outside observers, concerned that the contentious aspects of
the relationship between the HGP and Celera were damagingthe
credibility of all parties, urged that a collaborative approachbe
sought. Many serious attempts at such models were undertaken,but
ultimately all failed. Nonetheless, though it proved impossibleto
merge the two enterprises, an agreement was brokered, withthe help of
the negotiating skills of one of us (A. Patrinos),leading to the joint
announcements of the working draft in June2000 and simultaneous
publications in February 2001.
Social Consequences
Becoming the first large scientific undertaking to dedicate a
portion of its budget for research into social, legal, and ethicalimplications, the HGP under Watson's guidance set aside 3 to 5%of
its budget to study how our exponential increase in knowledgeabout
humans' genetic makeup may affect humankind. The ethical,legal, and
social implications (ELSI) program at NHGRI and DOEhas provided an
effective base from which to assess the implicationsof genome
research. An example of how ELSI research has helpedto inform public
policy is the fact that more than 40 states inthe United States have
passed genetic nondiscrimination bills,many based on model language
that grew out of such research. Anotherexample is the training of more
than 3000 judges through 20 workshopson the fundamentals of
genetics that are becoming increasinglyimportant in their courtrooms.
The HGP's forward-looking approachto ethical, legal, and social
implications is now being used asa model in other research endeavors.
Beyond the Human Genome Project
While the HGP is drawing to its conclusion, we
fully expect its heirs, the new disciplines of genomics and
genomics-basedmedicine, to carry on its tradition of pushing the
envelope ofbiological thinking. At least for the foreseeable future,
thereis a pressing need for similar large-scale, coordinated effortsthat provide early and unrestricted release of key biologicaldata to
the scientific community. Among the enterprises that havealready
headed down this road are comparative genomics, with thegenomic
sequencing and analysis of key model organisms being doneby some
of the centers that worked on the human genome. Large-scalegenomic
enterprises now extend well beyond straightforward sequencing,as
witnessed by the recent launch from our own funding agenciesof other
large-scale biology initiatives involving functionalgenomics
(11), structural biology (12), microbialgenomics
and proteomics (13), and haplotype mappingfocusing on human
populations (14). Other candidatesfor the "big
science" approach to biology include interagencyand international
approaches to biological database creation andmaintenance, the
construction of public small-molecule librariesfor use by basic
scientists in their efforts to chart biologicalpathways, and the
large-scale application of microarray technologieswith the potential
for applications in a wide range of biologicalresearch settings.
The millions of people around the world who supported
our quest to sequence the human genome did so with the expectation thatit would benefit humankind. Now, at the dawning of the genomeera, it
is critical that we encourage the same intensity towardderiving
medical benefits from the genome that has characterizedthe historic
effort to obtain the sequence. If research supportcontinues at
vigorous levels, we imagine that genome science willsoon begin
revealing the mysteries of hereditary factors in heartdisease, cancer,
diabetes, schizophrenia, and a host of otherconditions. Genomics holds
the promise of "individualized medicine,"tailoring prescribing
practices and management of patients toeach person's genetic profile.
These revelations should also leadus to develop and target drugs in a
rational fashion to genes,protein pathways, and networks shown to be
involved in primarydisease pathogenesis. Furthermore, a better
understanding of thegenetic factors that influence susceptibility
and/or responseto various infectious diseases could have an enormous
impact onhealth in the developing world. Genomics also has the
potentialto help agricultural researchers develop better crops and
livestock,environmental scientists create better methods of cleaning
uptoxic material, production experts streamline industrial processes,and energy researchers work toward sustainable, nonpolluting energysources.
For this grand vision (15) to come true, however, we in the
biologic research community need to pursue the nextgeneration of
research projects with the same determination andcreativity that the
dedicated scientists of the HGP used to spellout the human genetic
code. This Herculean challenge is by nomeans limited to biologists. We
call on leaders across scienceand society, across academia and
industry, and across politicaland geographic boundaries to join us on
this exciting voyage tounderstanding ourselves. If the past 50 years
of biology is anyindication of the future, the best is certainly yet
to come.
W. H. Lambright, Managing "Big
Science": A Case Study of the Human Genome Project (The Price
Waterhouse Coopers Endowment for the Business of Government, Arlington,
VA 2002). Available at
www.endowment.pwcglobal.com/pdfs/LambrightReport2.pdf.
J. Sulston, G. Ferry, The Common Thread: A
Story of Science, Politics, Ethics and the Human Genome
(Joseph Henry Press, Washington, DC, 2002), pp.
73-76.
U.S. Department of Health and Human Services,
U.S. Department of Energy, Understanding Our Genetic Inheritance.
The U.S. Human Genome Project: The First Five Years (Government
Printing Office, Washington, DC, 1990).
"Sharing Data from Large-scale Biological Research
Projects," meeting sponsored by The Wellcome Trust, Fort Lauderdale,
FL, January 2003. Available at
www.wellcome.ac.uk/en/1/awtpubrepdat.html.
We express our profound gratitude to leaders of all
of the sequencing centers involved in the International Human Genome
Sequencing Consortium, along with all other participants in the HGP,
1990 to
2003.
10.1126/science.1084564 Include this information when citing this paper.
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WEST IS WEST A film review by Thomas E. Billings Copyright 1989 Thomas E. Billings
Synopsis: A young man from Bombay arrives in San Francisco, hoping to gain admission to college. However, his sponsor has left the U.S., and the Immigration and Naturalization Service thinks he is a Sikh terrorist. He has only 24 hours to get married to a U.S. citizen -- or be deported. Naturally, he asks the only American woman he has met -- a thoroughly obnoxious punkette! A comedy/drama of culture shock.
U.S.A., color, 1989, 80 minutes.
Director/Writer/Film Editor: David Rathod Producer: Cristi Janaki Rathod Principal cast: Ashutosh Gowariker, Heidi Carpenter, Pearl Padamsee
The film is the story of Vikram, a nerdish young man from Bombay, who comes to San Francisco in anticipation that he will be admitted to U.C. Berkeley. As things turn out, his sponsor has left the U.S. for an indefinite period (returned to India). Vikram goes to one of the city's better hotels, only to find that a single room costs $175/night, rather more than he can afford.
He eventually ends up in a seedy hotel in the Tenderloin district (perhaps the city's worst neighborhood). The hotel is owned by one Mrs. Shah, a spirited ("salty" or "seedy" might be more accurate) immigrant from India. She gives Vikram a menial job, and he begins to explore America.
In his explorations, Vikram visits a supermarket, and develops a taste for junk food. He meets Sue, an obnoxious redheaded punkette, when she shows up at the hotel with a punk rock band and some groupies, trying to rent a single room for a "party." Later he runs into her at the movie theater where she works. Sue then introduces Vikram to the San Francisco punk scene.
Vikram is soon visited by a zealous agent of the INS, the Immigration and Naturalization Service. It seems that the INS thinks he might be a terrorist, and they want him out of the country. Mrs. Shah seizes the opportunity to offer to sponsor Vikram in the U.S., if only he will marry her niece. In an act of desperation, Vikram asks the only U.S. citizen he knows, the thoroughly vile Sue, to marry him, and the story continues from there.
This is the first feature film by its director, David Rathod, and it shows at times. Additionally, of the 3 principal cast members, only one has extensive acting experience, and this is apparent also. It's really not a bad movie; perhaps the best description would be "weak."
The film is weak in the following sense. It is advertised as a comedy, yet there is very little humor or comedy in the film. As a drama, it fares better, although it has a rather slow pace (obviously it's not an "action film"). The culture shock angle is used extensively in the film, but it is not handled very well -- it generates very few laughs.
Overall evaluation: only fair. Consider for matinee price; really not worth full price.
Reviewer: Thomas E. Billings, Department of Statistics University of California, Berkeley Reviewer contact<EMAIL_ADDRESS>.
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Kedar Hanuman Aitawdekar
304/M3A, Shiv-Sneh CHS, Sion, Mumbai - 400 022 | (+91)<PHONE_NUMBER>
<EMAIL_ADDRESS><EMAIL_ADDRESS>To be involved creatively in work and system where, I can utilize my skill and efforts that effectively contributes to the growth of organization.
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: Python , Java , C# , C++ , C |
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: MongoDB, Oracle 10g , SQL Server , JSON |
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: HTML5 , CSS3 , JavaScript , AJAX, Servlet , JSP , Drupal |
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: jQuery , D3.js , Leaflet.js (Maps) , Django, Django-Mongokit |
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: Emacs, NetBeans , MS Visual Studio , Corel Draw |
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IT Experience :
Non - IT Experience :
Overall, I believe that the various skills and maturity I learned in this role will be very helpful for my future success.
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Viral detection and classification¶
IMPORTANT: It is strongly recommended that you complete section 1.1 below (setting up the computing environment) prior to the practical session. Depending on your available network it can take some time (1-2 hrs) to download the necessary files.
1.1. To run this tutorial first we need to set up our computing environment in order to execute the commands as listed here. First, download and the virify_tutorial.tar.gz file containing all the data you will need using any of the following options:
wget http://ftp.ebi.ac.uk/pub/databases/metagenomics/mgnify_courses/biata_2021/virify_tutorial.tar.gz
or
rsync -av --partial --progress rsync://ftp.ebi.ac.uk/pub/databases/metagenomics/mgnify_courses/biata_2021/virify_tutorial.tar.gz .
Once downloaded, extract the files from the tarball:
tar -xzvf virify_tutorial.tar.gz
Now change into the virify_tutorial directory and setup the environment by running the following commands in your current terminal session:
cd virify_tutorial
docker load --input docker/virify.tar
docker run --rm -it -v $(pwd)/data:/opt/data virify
mkdir obs_results
All commands detailed below will be run from within this current working directory. Note: if there are any issues in running this tutorial, there is a separate directory exp_results/ with pre-computed results.
1. Identification of putative viral sequences¶
In order to retrieve putative viral sequences from a set of metagenomic contigs we are going to use two different tools designed for this purpose, each of which employs a different strategy for viral sequence detection: VirFinder and VirSorter. VirFinder uses a prediction model based on kmer profiles trained using a reference database of viral and prokaryotic sequences. In contrast, VirSorter mainly relies on the comparison of predicted proteins with a comprehensive database of viral proteins and profile HMMs. The VIRify pipeline uses both tools as they provide complementary results:
VirFinder performs better than VirSorter for short contigs (<3kb) and includes a prediction model suitable for detecting both eukaryotic and prokaryotic viruses (phages).
In addition to reporting the presence of phage contigs, VirSorter detects and reports the presence of prophage sequences (phages integrated in contigs containing their prokaryotic hosts).
1.2 In the current working directory you will find the metagenomic assembly we will be working with (ERR575691_host_filtered.fasta). We will now filter the contigs listed in this file to keep only those that are ≥500 bp, by using the custom python script filter_contigs_len.py as follows:
filter_contigs_len.py -f ERR575691_host_filtered.fasta -l 0.5 -o obs_results/ERR575691_host_filtered_filt500bp.fasta
1.3. The output from this command is a file named ERR575691_host_filtered_filt500bp.fasta which is located in the obs_results diretory. Our dataset is now ready to be processed for the detection of putative viral sequences. We will first analyse it with VirFinder using a custom R script:
VirFinder_analysis_Euk.R -f obs_results/ERR575691_host_filtered_filt500bp.fasta -o obs_results
1.4. Following the execution of the R script you will see a tabular file (obs_results/ERR575691_host_filtered_filt500bp_VirFinder_table-all.tab) that collates the results obtained for each contig from the processed FASTA file. The next step will be to analyse the metagenomic assembly using VirSorter. To do this run:
wrapper_phage_contigs_sorter_iPlant.pl -f obs_results/ERR575691_host_filtered_filt500bp.fasta --db 2 --wdir obs_results/virsorter_output --virome --data-dir /opt/data/databases/virsorter-data
VirSorter classifies its predictions into different confidence categories:
Category 1: “most confident” predictions
Category 2: “likely” predictions
Category 3: “possible” predictions
Categories 4-6: predicted prophages
1.5. While VirSorter is running, we have prepared an R script so you can inspect the VirFinder results in the meantime using ggplot2. Open RStudio and load the Analyse_VirFinder.R script located in the /virify_tutorial/data/scripts/ directory. Run the script (press Source on the top right corner) to generate the plot. (If you don’t have RStudio, or don’t care to run this you can just look at the resulting plot in the image below)
As you can see there is a relationship between the p-value and the score. A higher score or lower p-value indicates a higher likelihood of the sequence being a viral sequence. You will also notice that the results correlate with the contig length. The curves are slightly different depending on whether the contigs are > or < than 3kb. This is because VirFinder uses different machine learning models at these different levels of length.
1.6. Once VirSorter finishes running, we then generate the corresponding viral sequence FASTA files using a custom python script (parse_viral_pred.py) as follows:
parse_viral_pred.py -a obs_results/ERR575691_host_filtered_filt500bp.fasta -f obs_results/ERR575691_host_filtered_filt500bp_VirFinder_table-all.tab -s obs_results/virsorter_output -o obs_results
Following the execution of this command, FASTA files (*.fna) will be generated for each one of the VIRify categories mentioned above containing the corresponding putative viral sequences.
The VIRify pipeline takes the output from VirFinder and VirSorter, reporting three prediction categories:
High confidence: VirSorter phage predictions from categories 1 and 2.
Low confidence:
Contigs that VirFinder reported with p-value < 0.05 and score ≥ 0.9.
Contigs that VirFinder reported with p-value < 0.05 and score ≥ 0.7, but that are also reported by VirSorter in category 3.
Prophages: VirSorter prophage predictions categories 4 and 5.
2. Detection of viral taxonomic markers¶
Once we have retrieved the putative viral sequences from the metagenomic assembly, the following step will be to analyse the proteins encoded in them in order to identify any viral taxonomic markers. To carry out this identification, we will employ a database of profile Hidden Markov Models (HMMs) built from proteins encoded in viral reference genomes. These profile HMMs were selected as viral taxonomic markers following a comprehensive random forest-based analysis carried out previously.
2.1. The VIRify pipeline uses prodigal for the detection of protein coding sequences (CDSs) and hmmscan for the alignment of the encoded proteins to each of the profile HMMs stored in the aforementioned database. We will use the custom script Generate_vphmm_hmmer_matrix.py to conduct these steps for each one of the FASTA files sequentially in a “for loop”. In your terminal session, execute the following command:
for file in $(find obs_results/ -name '*.fna' -type f | grep -i 'putative'); do Generate_vphmm_hmmer_matrix.py -f ${file} -o ${file%/*}; done
Once the command execution finishes two new files will be stored for each category of viral predictions. The file with the suffix CDS.faa lists the proteins encoded in the CDSs reported by prodigal, whereas the file with the suffix hmmer_ViPhOG.tbl contains all significant alignments between the encoded proteins and the profile HMMs, on a per-domain-hit basis.
2.2. The following command is used to parse the hmmer output and generate a new tabular file that lists alignment results in a per-query basis, which include the alignment ratio and absolute value of total E-value for each protein-profile HMM pair.
for file in $(find obs_results/ -name '*ViPhOG.tbl' -type f); do Ratio_Evalue_table.py -i ${file} -o ${file%/*}; done
3. Viral taxonomic assignment¶
The final output of the VIRify pipeline includes a series of gene maps generated for each putative viral sequence and a tabular file that reports the taxonomic lineage assigned to each viral contig. The gene maps provide a convenient way of visualizing the taxonomic annotations obtained for each putative viral contig and compare the annotation results with the corresponding assigned taxonomic lineage. Taxonomic lineage assignment is carried out from the highest taxonomic rank (genus) to the lowest (order), taking all the corresponding annotations and assessing whether the most commonly reported one passes a pre-defined assignment threshold.
3.1. First, we are going to generate a tabular file that lists the taxonomic annotation results obtained for each protein from the putative viral contigs. We will generate this file for the putative viral sequences in each prediction category. Run the following:
for file in $(find obs_results/ -name '*CDS.faa' -type f); do viral_contigs_annotation.py -p ${file} -t ${file%CDS.faa}hmmer_ViPhOG_informative.tsv -o ${file%/*}; done
3.2. Next, we will take the tabular annotation files generated and use them to create the viral contig gene maps. To achieve this, run the following:
for file in $(find obs_results/ -name '*annot.tsv' -type f); do Make_viral_contig_map.R -t ${file} -o ${file%/*}; done
3.3. Finally, we will use the tabular annotation files again to carry out the taxonomic lineage assignment for each putative viral contig. Run the following command:
for file in $(find obs_results/ -name '*annot.tsv' -type f); do contig_taxonomic_assign.py -i ${file} -o ${file%/*}; done
Final output results are stored in the obs_results/ directory.
The gene maps are stored per contig in individual PDF files (suffix names of the contigs indicate their level of confidence and category class obtained from VirSorter). Each protein coding sequence in the contig maps (PDFs) is coloured and labeled as high confidence (E-value < 0.1), low confidence (E-value > 0.1) or no hit, based on the matches to the HMM profiles. Do not confuse this with the high confidence or low confidence prediction of VIRify for the whole contig.
Taxonomic annotation results per classification category are stored as text in the *_tax_assign.tsv files.
Let’s inspect the results. Do:
cat obs_results/*tax_assign.tsv
You should see a list of 9 contigs detected as viral and their taxonomic annotation in separate columns (partitioned by taxonomic rank). However, some do not have an annotation (e.g. NODE_4… and NODE_5…).
Open the gene map PDF files of the corresponding contigs to understand why some contigs were not assigned to a taxonomic lineage. You will see that for these cases, either there were not enough genes matching the HMMs, or there was disagreement in their assignment.


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Getting Rich with Comparison Methods
10:15 AM - 11:00 AM on August 16, 2014, Room 704Matt Story
- Audience level:
- intermediate
- Watch:
- http://youtu.be/RcVQveUjq8U
Description
Matt's obsession with Python's rich comparison methods started about 6 years ago with a gnarly bug and some bad assumptions. A few long nights and a lot of reading later, the docs corrected my assumption:
There are no implied relationships among the comparison operators. The truth of x==y does not imply that x!=y is false.
Mind == blown and mind != blown. In Getting Rich with Comparison Methods we'll start by learning how to avoid common and costly bugs in your rich comparison methods, learn a bit about which methods are executed in comparisons and why, and then go beyond symmetrical comparisons exploring some of the ways we can take full advantage of asymmetrical comparison methods.
Abstract
"Getting Rich with Comparison Methods" starts with what most engineers are trying to do when they first read the data model documentation for rich comparison methods, make comparisons function "as expected", returning truthy and falsey values. A common case is an object with an id attribute, and rather than: self == other being translated into: self is other, you'd prefer it to turn into self.id == other.id. Conversely you'd like self != to translate to: self.id != other.id, and you might go so far as to define '>', '>=', '<' and '<=' too. Straight-forward as this seems there are some pitfalls to avoid, and (of course) some standard library goodies that make avoiding these pitfalls as easy as decorating your class.
Once you've handled this basic use-case, you'll eventually compare your object to an object of a different type, and you'll start to wonder exactly how Python chooses the rich comparison method of record. Grasping how order and inheritence of objects in a comparison play into the resolution of the rich comparison method will allow you to write more resiliant c ode, and will lead you to understand the importance of extensive testing whenever rich comparison methods are involved.
Once again, the standard library saves us, this time with the operator module providing us with the ability to write simple (and non-ugly) tests for our rich comparison enabled classes. The final step in our rich comparison journey is to begin to understand how to harness the power of asymmetrical and non-boolean comparisons to build powerful and expressive fu nctionality (like the kind found in SQLALchemy, just to name one).
By the time you leave "Getting Rich with Comparison Methods" you should be comfortable using rich comparison methods to solve a variety of problems, you should be able to write elegant tests for your comparison method code, and you'll know what they say about assumptions.


Unit Testing
Single Page Applications
By @johnkpaul
johnkpaul.com/html5devs
github.com/johnkpaul/twitter-show-more-example
Unit Testing - Confidence
Domenic did an amazing job. I bet he convinced you all.
- I'm was tired of manually refreshing and manually debugging everything
- I was tired of not knowing when I've broken something
- I was tired of using my app to find all the edge cases
Imperative code is easy to test
function add(){
var sum = 0;
for(var i = 0;i<arguments.length;i++){
sum += arguments[i];
}
return sum;
}
equal(10, add(1, 2, 3, 4), "sum should be 10");
equal(100, add(50, 50), "sum should be 100");
refactoring is awesome
function add(){
return Array.prototype.slice.call(arguments)
.reduce(function(prev, current){
return prev + current;
});
}
equal(10, add(1, 2, 3, 4), "sum should be 10");
equal(100, add(50, 50), "sum should be 100");
cross browser test runners can verify that your tests pass everywhere
Imagine if you wanted to unit test
But our code doesn't look like that.
Our lives are so much easier with client side MV*
We have modularity
We have "classes"
What to test?
imperative logic & event logic
- models, collections and views each have a bit of both
- it's logic we want to test, not every nitty gritty detail
- views and templates are the most difficult to sort out
Quick App Demo
And then into the code!
First, we'll take a look at the collection
- ensure we store the last fetched id
- ensure that last fetched id is sent with every subsequent request
- ensure that when fetched, it always uses add:true option
QUnit test - sinon ajax example
Collection's fetch method
Now, onto the view
- ensure that collection is fetched when rendered
- ensure that collection is fetched periodically for update
- ensure that subview is created for each model in the collection
- ensure that new subviews are hidden when models are added to collection
- ensure that show more button is visible, if there are hidden subviews
- ensure that when clicking on show more button, hidden subviews are now visible
- ... and on and on...
collection is fetched when rendered
Complex View test - sinon timer example
Code to pass test
What exactly is a unit?
- On the client, it's a little blurry
- How do we deal with units of code with dependencies?
- is a template separately testable?
- minimize, but if necessary, integrate some pieces
template conventions
- .js- and .js-test- class prefixes
- keep templates out of the DOM for sharing between app and tests
template dependent test
event handling
- make clean separation between triggering and handling of event
- in Backbone's case, there is no need to test that view events fire correctly
- But in the case of custom events, test that they are fired when expected
How do we run all of these tests?
Grunt
Grunt is a task-based command line build tool for JavaScript projects.
grunt-junit
demo
Did I forget the router?
You know what to do
Real confidence
Jenkins
(although any continuous integration system will do)
QUnit alternatives
- Jasmine - BDD
- Chai - TDD/BDD
- BusterJS
- JSTestDriver
Cross browser testing services
- Testling
- Browserling
- Browserstack
QUESTIONS
By @johnkpaul
www.johnkpaul.com


Choose the right number of each place value to make
\Huge{
\color{PINK}{THOUSANDS}
\color{ORANGE}{HUNDREDS}
\color{GREEN}{TENS}
\color{BLUE}{ONES}.
\color{purple}{TENTHS}
\color{gray}{HUNDREDTHS}
\color{#a52a2a}{THOUSANDTHS}
}
Choose the right number of bills and coins to make
\Huge{$
\color{PINK}{THOUSANDS}
\color{ORANGE}{HUNDREDS}
\color{GREEN}{TENS}
\color{BLUE}{ONES}.
\color{purple}{TENTHS}
\color{gray}{HUNDREDTHS}
}
\Large{
\color{PINK}{THOUSANDS}
\color{ORANGE}{HUNDREDS}
\color{GREEN}{TENS}
\color{BLUE}{ONES}.
\color{purple}{TENTHS}
\color{gray}{HUNDREDTHS}
\color{brown}{THOUSANDTHS}
}
is the same as
\large{
\color{PINK}{THOUSANDS000} +
\color{ORANGE}{HUNDREDS00} +
\color{GREEN}{TENS0} +
\color{BLUE}{ONES} +
\color{purple}{0.TENTHS} +
\color{gray}{0.0HUNDREDTHS}
+ \color{brown}{0.00THOUSANDTHS}
}
.
\large{\color{PINK}{THOUSANDS000}}
is the same as \large{\color{PINK}{THOUSANDS}}
plural( "thousand", THOUSANDS ), the place value four places to the left of the decimal point.
Because there is no number in the thousands place, you don't need any thousands.
\large{\color{ORANGE}{HUNDREDS00}}
is the same as \large{\color{ORANGE}{HUNDREDS}}
plural( "hundred", HUNDREDS ), the place value three places to the left of the decimal point.
Because the hundreds place is \large{0}
, you don't need any hundreds.
\large{\color{GREEN}{TENS0}}
is the same as \large{\color{GREEN}{TENS}}
plural( "ten", TENS ), the place value two places to the left of the decimal point.
Because the tens place is \large{0}
, you don't need any tens.
\large{\color{BLUE}{ONES}}
is the same as \large{\color{BLUE}{ONES}}
plural( "one", ONES ), the place value one place to the left of the decimal point.
Because the ones place is \large{0}
, you don't need any ones.
\large{\color{purple}{0.TENTHS}}
is the same as \large{\color{purple}{TENTHS}}
plural( "tenth", TENTHS ), the place value one place to the right of the decimal point.
Because the tenths place is \large{0}
, you don't need any tenths.
\large{\color{gray}{0.0HUNDREDTHS}}
is the same as \large{\color{gray}{HUNDREDTHS}}
plural("hundredth", HUNDREDTHS ), the place value two places to the right of the decimal point.
Because the hundreds place is \large{0}
, you don't need any hundreds.
\large{\color{#a52a2a}{0.00THOUSANDTHS}}
is the same as \large{\color{#a52a2a}{THOUSANDTHS}}
plural("thousandth", THOUSANDTHS ), the place value three places to the right of the decimal point.
Therefore you need
\large{\color{PINK}{THOUSANDS}}
plural( "thousand", THOUSANDS ),
\large{\color{ORANGE}{HUNDREDS}}
plural( "hundred", HUNDREDS ),
\large{\color{GREEN}{TENS}}
plural( "ten", TENS ),
\large{\color{BLUE}{ONES}}
plural( "one", ONES ),
\large{\color{purple}{TENTHS}}
plural( "tenth", TENTHS ),
and \large{\color{gray}{HUNDREDTHS}}
plural( "hundredth", HUNDREDTHS ).
\large{\color{gray}{HUNDREDTHS}}
plural( "hundredth", HUNDREDTHS ),
and \large{\color{#a52a2a}{THOUSANDTHS}}
plural( "thousandth", THOUSANDTHS ).


The Time Picker component allows the user to easily set a time using either an HTML5 time input or the
Fundamental
Library for Angular Time component.
The time picker supports the same keyboard navigability as the time component. The calendar can be opened by
focusing the time picker input field and closed by focusing the calendar icon button and pressing enter or space.
The Time Picker component relies on provided datetime implementation (DatetimeAdapter
)
and datetime formats (DateTimeFormats
).
Currently fundamental-ngx offer 2 kind of adapters:
FdDateTimeAdapter and MomentDateTimeAdapter.
The Time Picker component uses Time Component internally,
for internationalization configuration, check
Internationalization
section in Time
documentation


Full Stack Developent Intern at Builder India Dec 2018- Feb 2019
- Build a web app for their new startup idea.
- Technologies used: PHP, JavaScript
I'm Naman Vashistha.
Some of my specialities are:
I also have experience in MonogoDB, HTML5, CSS3 and C programming.
Bachelor In Technology


Goals
the goal is to account for all our goals, so we're not held back from achieving them due to financial reasons or saving just for the sake of saving
Professional Development
- this may involve going to conferences, networking events, etc.
- may also involve some form of education with the aim of attaining a certificate, a degree, a diploma, etc.
- attaining this education has
- a direct cost (course fees)
- an indirect cost (time spent not working)
- educating yourself may be the best investment
- set goals for your professional development, plan the costs and understand the impact on future earning potential
Family/Friends
- let's be honest, relationships cost money (kids? dates? hosting friends? birthday gifts?)
- we typically make most financial sacrifices for our family and friends
- recognize this, and understand your relationship goals
- what costs may be involved?
Retirement
- do you want to retire early?
- maybe you want to be able to maintain a similar lifestyle when you retire
- you may not neet to know just yet, but having some ideas of what you'd like doesn't hurt
- set some goals and you can always re-evaluate them
- this will likely be one of your largest financial goals
Travel/Hobbies
- recognize your hobbies and activies that makes you feel good, like travelling
- hobbies have costs, which can add up especially when we're really passionate about something
- some hobbies are more expensive than others
- set goals related to your hobbies and account for the costs
Health / Exercise
- set fitness and health related goals
- for example, playing a sport and going to the gym once a week
- consider the costs of a gym membership and joining a sports team
- also consider the costs of healthy food and taking care of yourself


Be warned, I wrote this trip report in a textpad document. It is 7:57am. I took the blotter at 3:25pm, yesterday, and haven't 'wanted' to sleep yet because i've been so overstimulated by these amazing things it has shown me, about my self, and about the world. The 'trip' peaks, for about 6-8 hours.  No Halucinations, but a way of looking at the world. It's very motivational and positive, despite all the negative clutter, as I call it, that enlightened me throughout the trip, if that makes any sense.
So enjoy, what I call, my logical psychobabble, of this trip.
Dropped @ 3:25pm
1HR IN 4:25pm
Effects slowly creeping. When I felt the drug in my system was about 45minutes-1 hour in. I then swallowed the blotter. Lots of peripherial images. I gave my friend one of the extra tabs I had and he spit it out after 10 minutes because I gave it to him while I was tripping hardcore and didn't tell him to keep it there for an hour or so. So he wasted it *facepalm* on accident, waiting to trip when I found out 4 hours later he sit it out 10 minutes in.. fail.
2hr In and for 3+ more hours. A BEGINGING of a peak, if that makes any sense. Now, personally, I've never done acid, but this was amazing. I think I basically peaked for 4-5 hours. Vivid halucinations I can say. Okay, up at this point, i'm going to be real, it was trippy. I will tell you all of the crazy things I saw to give you an idea how badass this was.
First thing I saw, when I started to peak, I saw a faint mouth in the clouds, as if God, was talking to me, and I don't even believe in god. It was intense. I knew it wasn't a spirit, but I did know it was an awesome experience. This drug makes you aware that what you see isn't really there, so you don't get carried away with it, but hell is it a full blown halucination.
 And these shotguns connected in geosymetrical lines along the earths tilt plane to the top of the atmosphere, following the earths shape. Then, at the top, there were Pentagrams, beaming down. Now, I felt like aliens, if they were there, could read ALL of my thoughts. Though, I feel 25i-nBOME makes me very introspective in the sense that I am completely aware of these crazy thoughts I am having, so I don't sound like a lunatic nut telling people the aliens are reading my thoughts >.>. Lol. Aka, I knew it wasn't real but the thought blew my mind IMMENSELY eitherway you look at it.
At one point I saw jesus in the patterns on the floor like I did with the clouds, but very very vivid, and there was skulls all over him like he was plaguing humanity as some sort of deception. Anytime I went outside.. I kept seeing Jesus in the sky, everywhere. I guess that is just my christian upbringing, which keep in mind I do not believe in any of it anymore... my deep emotional attachments I had to it as a kid or something? At one point I felt it was as if Jesus telling me I turned on him. But then I laughed at him and the idea. No offense to any christians reading this.
The 3rd thing I saw, was when I sat long enough...I entered into the matrix. I saw mathematic equations flying everywhere embeded with cryptic symbols in perfect harmony. Like a work of higher nature, showing the mathmatics of it's functioning to me. It was sick. I felt like einstine, times 10. Though I couldn't focus on any of the conceptual concepts because I was tripping... but... just maybe, I think the trip showed me how to get back to that land if I want to access that cryptic knowledge when I am sober. But shh, keep that on the down low.
Another thing that happened throughout the trip, was when I sat for more than a few seconds not doing something that changes like a conversation... Everything would turn black and neon green, red, and blue dots would be on everything in perfect symetry.  Haha it was awesome. Think of a rave club. Now multiple that times a million. That doesn't come close to this.  You notice it and kind of walk out of it so you don't get sucked too far out of reality.
One thing I saw when I was outside, most people would consider it trippy and scary, but I was hyperaware that I was tripping so it didn't phase me... All the leaves on the trees grew evil mask, and they overwhelmed my vision field and flew at me.. but I felt like it was awesome haha. At one point I saw benjamin Franklin giving me the evil eye in a tree, like his face was in the patterning of the trees leaves.
To sum the peak of this drug up. You are basically walking along the line of dreaming and reality. I was sitting having a conversation with some people, and for a moment I zapped into another realm. I was all of a sudden in the middle of nature, next to a creek, and animals. It felt 100% real. People would call this phasing into a lucid dream... but it happened mid conversation.  I made the conscious CHOICE to step out of it because I can't just leave my body in the middle of a conversation. That would be fucked, even though the land I arrived to was amazing. I think I know how to get back there also.... It's just the mind bro.
I also kept seeing cryptic ancient egyptian symbols EVERYWHERE. They were an integral part of the trip, every bit of it, they were involved someway in everything I saw.
This drug, I read someone compared it to acid as... They said acid is very extrospective(I haven't taken it so I don't know), while this is very introspective. I think it described it perfectly, because I've tripped psychedlics before, but I was never this much aware that I was trpping.
I think I had extremely high anxiety while doing this, but I think you're so introspective that anxiety is pointless because you see you have anxiety, and I mean, that's anxiety. I saw scary shit, but I wasn't afraid, because it made me realize, that its nothing but scary. It cant hurt me at all. I think this trip has pushed me in the direction of overcoming social anxiety when sober. Trip was well worth my while, very introspective into myself.
TIP:
Do not smoke weed during this, or drink caffeine. I drank caffeine at points I felt it really dumbed my trip down. Don't drink caffeine within 15 hours of tripping this. Before or after. With weed, you may think weed calms you down, which it may do... but it makes the trip very foggy. It took the fun out of it. I think... It made my thoughts foggy, but I was still halucinating for a good bit, like when smoking weed the house became a machine cyborge for a short moment, like the walls inside it.  Do you?
Experience Reports are the writings and opinions of the individual authors who submit them.
Some of the activities described are dangerous and/or illegal and none are recommended by Erowid.


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On November 21st, Super Duper is hosting an event for
children battling cancer to be team captain to build and
launch rockets! Each captain has the opportunity to be bring
a team of one to two super duper sidekick friends who together
will design, construct and launch kid-friendly rockets.
Sidekicks can be anyone -- a friend, supporter, cousin,
sister, brother, etc -- as long as they are between the
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The event will be hosted at NASAs Moffett Field. Rockets,
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We only ask that you bring one to two chaperones per child.
Applications are now open. As there are limited spots,
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