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Assam NRC List 2017 – The state government has released the Assam NRC list / National Register of Citizens (NRC) draft list at the official website of Assam NRC at nrcassam.nic.in. The draft list of Assam NRC includes the name of 1.9 crore legal citizens out of the total 3.29 crore citizens in Assam. This is the draft of National Register of Citizens (NRC) and the citizens, whose name or whose family members name not appeared in the list, needs not to worry because it is possible that some of the name may left out in the list which may be included after completion of verification process which is under process.
Candidates can check their name in Assam NRC list from NRC Seva Kendras (NSKs), NRC automatic receipt through SMS, NRC on demand SMS, Toll Free Number or through online mode. Any one of process can be selected to check your name in draft list of NRC Assam.
Check Name in National Register of Citizens Assam
You can choose any one of the methods to check your name in the list.
NRC Seva Kendras (NSKs): Candidates can visit the nearest NRC Seva Kendras between 10 AM to 4 PM. There you can search your name in the printed copies of Part Draft NRC and the list is available till 31 January 2018.
Automatic Receipt of SMS to include your name in PART Draft – For this, candidates needs to send an SMS to 9765556555 or 9108464438 / 9108464450 and the SMS which to sent by you should be in the format, "ARN
On Demand SMS – Candidates can also check your their name through On-Demand SMS. For this option, no-pre registration is required. Candidates just have to send an SMS, ARN
Toll Free Numbers – It is the easy way to check your name by just making a call on the toll free number. The Toll free number for NRC Assam is 15107 (for Assam residents) and 18003453762 (outside Assam candidates).
NRC Online Check Portals – It is self service of NRC Assam. For this Candidates can make login to www.nrcassam.nic.in, assam.mygov.in, assam.gov.in or homeandpolitical.assam.gov.in.
For more details candidates can download the NRC Quarters Page Ad (English)


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Although this is the third book in The Cruisers series, it can be read without reading the other two books because enough background information is provided. This novel focuses primarily on LaShonda and some new opportunities after her success with the fashion designs for the Cruisers' play.
Torn on this review. Everything else I read gave it glowing recommendations, but while I liked the idea it was just okay, not great. To me, the author tried to squish too much into one book rather than focusing on the plot line originally created. That is not normal for this author and really surprised me. One thing I love about Walter Dean Myers is the well developed characters. I did appreciate the multiple forms of literature though, and that they were presented in an approachable way. Would be easy to use in the classroom because of the style but has some sensitive issues.
No quotes that really hit home on this one.
Recommended Ages: Grades 7-12 Main audience reluctant readers.
Genre: YA Realistic Fiction
Overall Opinion: Average
Source: Book

subset: commoncrawl


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Forgiveness. The Only Way to Heal part 2Written by Super User
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When we are hurt it is normal to react in anger and forgiveness is contrary to the 'get even' attitude of our society. For many victims the idea of forgiving those who have caused them pain seems absurd and even impossible.
So why should we forgive? We should forgive because it is essential to our own freedom and wellbeing. In Mathew 18: 34 and 35 we are warned by the Lord that holding onto unforgiveness, we open ourselves up to the inner torturers of inner turmoil and depression. Unforgiveness leads to attitudes of anger, bitterness and hatred and even murder and holds us captive to what was done to us. We need also to forgive ourselves for things that we too have done wrong. Over and over again forgiveness has been proven to be the first step in our inner healing process.
The question then often arises: 'How can I forgive?'
It helps us to forgive when we understand what forgiveness is and is not. When we forgive, we are not declaring a person 'not guilty' rather we recognize their guilt and give to God our right to punish them.
Forgiveness is a choice. We choose to release the other person and ourselves from anger, bitterness and the desire for revenge.
We probably will never feel like forgiving, but we can and indeed we must, forgive and we can do so by choosing to release ourselves and the other person because it is the only way to wholeness and freedom.
So, no matter whether you are upset with the Christmas gift you will receive this Christmas or whether you need healing for some deep hurt and offense choose to forgive and walk in forgiveness going forward. The benefits will be peace and freedom.
It really is worth the cost of giving up your right to punish and focusing on the wrong done in order to be forgiven and to be set free.
Should you find it very difficult to forgive, but would like help to do so, please call us or visit our website and one of our team would be happy to discuss this further with you.
God bless and stay free,
"Equipping the compassionate and setting the captives free." - Isaiah 61: 1-4


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City of Tempe, AZHome Menu
Tempe Newsroom
Get your city news emailed to you. Sign up now.
Donate now: Together Tempe transforms lives across the city
A ride to a doctor's appointment. A bag packed with nutritious food. A hot shower. An after-school activity.
Small actions, big impact – all supported by the Tempe Community Council.
What began in 1972 as a grassroots effort to tackle human service issues in Tempe has grown into a vital operation that plays a critical role in addressing immediate and long-term needs throughout the city.
This year alone, Tempe Community Council (TCC) is administering more than $1.2 million in human services funding to 47 nonprofit organizations that serve Tempe residents. This Saturday, Mayor Mark Mitchell's Annual State of the Neighborhood Address will focus on giving back. A Care Fair hosted by TCC will immediately follow his speech, allowing people to both give and receive a variety of services. The events begin at 8 a.m. at Tempe History Museum, 809 E. Southern Ave., Tempe. www.tempe.gov/stateoftheneighborhoods for details.
TCC's mission – "Connecting those in need with those who care" – means Timothy Mindrup has a safe place to live, eat and shower as he moves from homelessness to a brighter future with assistance from the Interfaith Homeless Emergency Lodging Program (I-HELP).
That mission means 89-year-old Elsie Mulligan can get to her medical appointments with volunteers from Tempe Neighbors Helping Neighbors. And it means Erica Leasure, a homeschooling mom of six, can shop the shelves at Tempe Community Action Agency's food pantry for fruits, veggies and other staples for her family.
"There are people from all walks of life here," said Leasure during a recent visit to the food pantry. "The community is using this. We need it."
Meeting critical needs
As human service needs continue to grow in the city, a new initiative – Together Tempe – aims to support even more programs to help individuals and families.
Together Tempe is building on the generosity of residents who, for two decades, have helped people in need by donating $1 a month through their water bills.
The original program, "Project H20," initially used homeowner donations to pay others' past due water bills. Then the program evolved, becoming "Help to Others," with a mission to support human service needs instead. TCC, in partnership with the city, became the program administrator.
In the past 20 years, those two programs have generated more than $1.1 million in donations. But awareness and donations have dropped due, in part, to the shift toward electronic billing and the high numbers of people in multi-family housing who don't receive water bills.
Together Tempe seeks to re-engage homeowners who previously donated, connect with people living in apartments and condos, and appeal to businesses that generally don't donate through the water bill.
If all 42,000 utility bill recipients donated $1 per month, the program could raise $504,000 annually to support human service needs. Every dollar goes to direct services.
"There are extensive needs in our community," said Elizabeth Cling, TCC's board president,
"Almost 22 percent of residents in Tempe live below the poverty line," she said. "Whether it's an after-school program, a shelter for homeless youth and families, or assistance for homebound seniors, these are some of the critical services that receive funding from TCC."
Easy to give back
Here's how you can support Together Tempe:
•Donate at www.togethertempe.org. Give throughout the year or make a one-time gift.
•Add $1 to the Together Tempe Voluntary Donation line on your utility bill.
•Not all bills include the donation line but the city's customer service representatives can assist with donations, and can also increase the amount you wish to give each month beyond $1. Call 480-350-8361 for assistance.
Human service needs in the city continue to grow. This year, nonprofit organizations requested more than $2.1 million in funding, up from more than $1.8 million in 2017 and nearly $1.2 million in 2016.
TCC focuses on six target populations: youth, seniors, the working poor, people with disabilities, people who are homeless, and domestic violence victims. Community volunteers with TCC vet funding requests and recommend grants through the Agency Review process.
In addition to distributing funds, TCC operates several programs such as free tax preparation services for low- and moderate-income taxpayers and clothing closets that provide free clothing, hygiene items and school supplies to students in need.
Changing lives across the city
The impact of Tempe's human services funding is easy to see in the faces of the people receiving help every day.
When they spot each other, Elsie Mulligan and Kay Slaven exchange smiles - the kind that friends share. Slaven volunteers three times a week with Tempe Neighbors Helping Neighbors (TNHN), which matches volunteers with seniors in the community who need transportation, basic home and yard maintenance, friendly visits, and more.
"I don't have a car anymore," said Mulligan. "Without this (TNHN), I'd have to call a taxi or one of my kids, and they're busy. So it's just nice to have someone available and reliable…Kay's just been a very good friend."
Not far away, kids spill into the Ladmo branch of the Boys & Girls Clubs of the East Valley after school, filling the place with a chorus of laughter and chatter. They split off for computer time, art activities, sports, and snacks, spending the next several hours in a safe and welcoming place.
"The club is a window of opportunity," said Jevin D. Hodge, a former staff member who grew his leadership skills at the branch and now is heavily involved in the community. "It's nourishment for the mind, body and soul."
At 47, Timothy Mindrup is thankful for new opportunities. He looks hopeful.
The road has been long from well-paid security consultant to drug and alcohol addict to lost soul sleeping in the park. Hungry and dirty, he welcomed help from the City of Tempe's homeless outreach team. That led to shelter, regular meals and a mobile trailer where he could shower and do his laundry through I-HELP.
Operated by Tempe Community Action Agency (TCAA), I-HELP provides immediate assistance and resources to find employment and regain self-sufficiency. Mindrup needed it all, starting with the shower.
"If you can stay clean, you can wipe the stink off you, the despair," he said. "You can get the street off you."
Newly employed as a transportation specialist, Mindrup is grateful for I-HELP.
"It meant everything in the world to me," he said. "It was literally a ray of hope."
To learn more about Together Tempe and make a donation, visit Tempe Community Council. See how human services funding impacts the community in this video.


text: The quantification and integration of hydrological and biological processes at the basin scale is based on the assumption that abiotic factors are of primary importance when become stable and predictable, then biotic interactions start to manifest themselves. The quantification covers the key elements of hydrological cycle (precipitation, evapotranspiration), patterns of hydrological pulses along the river continuum and monitoring of point and nonpoint source pollution, erosion, habitat degradation. The integration of information about hydrological cycle inputs and economical distribution provide a template to regulate processes toward sustainable water and ecosystem resources use. IHP will support research and capacity building initiatives aimed to improve the understanding of the inter-linkages of ecohydrological processes at the catchment scale with special emphasis on implementation at UNESCO EH demonstration sites.


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Organomanganese reagents easily react with conjugated enones to give the 1,4-addition products in excellent yields in the presence of copper salts.
The reaction compares favorably to the classical reactions involving copper-catalyzed Grignard reagents or cuprates. The difference is especially impressive with unreactive b,b-disubstituted enones such as isophorone.
Excellent results are obtained by using Grignard reagents under manganese/copper-catalysis.
Copper-catalyzed organomanganese reagents are also clearly superior in the case of conjugated ethylenic aldehydes.
On the other hand, we have shown that the copper-catalyzed alkylation of Grignard reagents led to excellent yields in the presence of NMP. Moreover the reaction is chemoselective.
Recently, we have undertaken a careful mechanistic study of this reaction and we have discovered that it is possible to obtain excellent yields without using any ligand by adding the Grignard reagents very slowly to the reaction mixture.
The copper-catalyzed reaction of Grignard reagents with 1-haloalkynes was known to give poor yields. We have reinvestigated this reaction and we have found that a slow controlled addition of the Grignard reagent allows to obtain excellent yields of substitution products.
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In case you've missed it, one of UW-Green Bay's most famous alumni, Tony Bennett, has been humbly leading his team, the Virginia Cavaliers to the Final Four, and tonight (April 7, 2019) they play Texas Tech for the NCAA Championship! You can read more, here. Tip-off is 8:20 (CST) and coverage will be on CBS. A quick scan reveals "watch parties" at most local bars and restaurants to cheer for one of Green Bay's most-favored sons. See some of the favorite University Archives' photos from Bennett's playing days and join in on the facebook conversation, here.
Inside UW-Green Bay News
The official site for UW-Green Bay News and Features
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UW-Green Bay, 2420 Nicolet Drive
Green Bay, WI 54311-7001
- (920) 465-5502
Department Info
- University of Wisconsin-Green Bay
2420 Nicolet Drive
Green Bay, WI 54311, USA
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- Connect with UWGB: facebook twitter flickr youtube
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(920) 465-2000 or firstname.lastname@example.com
- Report a website issue
- Privacy Policy
- Emergency Information: emergency.uwgb.edu


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Student Organizations
There are many student organizations on campus whose focus is either community service, philanthropy, or political/social action. To search and find organizations of interest to you, visit the HUB.
The Office of Community Engagement and Service advises and has formal partnerships with several student organizations on campus. For more information, feel free to reach out to any of the officers listed at the HUB pages below:
- Circle K International
- Student United Way
- Multifaith Engagement for Transformative Action Collective (META)
- Alpha Phi Omega
Event/Program Co-Sponsorship
Is your student organization planning an event or program which needs monetary, marketing, or other support? We are happy to co-sponsor programming that is aligned with our mission. If you are interested in co-sponsorship, please email us at firstname.lastname@example.com.


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Still a very short story of lived life, left us by Bruno in his notebook of notes.
This time it is a particular practice concerning the sheep that every peasant family possessed, mainly for their own use, but in some cases also as a source of income.
The story is closely linked to our territory and its natural resources.
click here to read or download the story


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If you're looking for a series of short films that explain economic concepts or key features of the modern economy, it's hard to go past "We the Economy". Each of the 22 films in the series is directed by a leading filmmaker, and each film focuses on some aspect of the U.S. economy or on some economic concept, answering a key question (like "What causes a recession?", "What is money?", or "What are the causes of inequality?"). The films are grouped into five 'chapters' covering the basics of the economy, money, the role of government, globalisation, and inequality. Every 5-8 minute video is well worth watching, regardless of whether you are new to economics, or a seasoned lecturer looking for something to use in your teaching.
My personal favourite was "Supply and Dance, Man!", although "The Unbelievably Sweet Alpacas" is also hard to beat. The human shadow puppets in the "Recession" video are pretty cool also. Thanks to Vulcan Productions and Cinelan for putting this collection of shorts together for us. And there is more bonus content available on YouTube.
[HT]: Jodi Beggs at Economists Do It With Models, who has a starring role in one of the videos, and an uncredited cameo in at least one other.


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Components. Available glyphs Includes over 250 glyphs in font format from the Glyphicon Halflings set.
Glyphicons Halflings are normally not available for free, but their creator has made them available for Bootstrap free of cost. As a thank you, we only ask that you include a link back to Glyphicons whenever possible. How to use For performance reasons, all icons require a base class and individual icon class. Complex Navigation Patterns for Responsive Design. The most frequently asked question I get since posting my responsive navigation patterns article is: How do I handle complex navigation for responsive designs?"
Great question, but before we get down to brass tacks, I urge you: use mobile as an excuse to revisit your navigation. Look at your analytics. Online Flat Icon Generator. Flat Icon Generator is Licensed Under Apache License v2.0 As far as the Redistribution goes, refer Point 4 "Redistribution" You may reproduce and distribute copies of the Work or Derivative Works thereof in any medium, with or without modifications, and in Source or Object form, provided that You meet the following conditions: You may add Your own copyright statement to Your modifications and may provide additional or different license terms and conditions for use, reproduction, or distribution of Your modifications, or for any such Derivative Works as a whole, provided Your use, reproduction, and distribution of the Work otherwise complies with the conditions stated in this License.
Better, Simpler Grid Systems — Solved By Flexbox — Cleaner, hack-free CSS. Can I use... Support tables for HTML5, CSS3, etc. Little Big Details - Your daily dose of design inspiration. Single Element CSS Spinners. Top 5…Photo stock sites. iStockphoto www.istockphoto.com UK: Starts with six credits for £7US: Starts with six credits for £9.99 There's much more to iStockphoto.com than just royalty-free stock images, as the website also provides illustrations, video, Flash animations and even audio files, amounting to over ten million resources in all.
Free membership includes access to special offers and hand-picked stock, chosen for its superior quality. The Vetta Collection holds the best of the best from a range of artists, priced slightly higher for its premium quality. Scratch the surface even further and you'll find iStockphoto.com's The Steel Cage design competition, which gives artists an opportunity to win free credits. Prices at first appear steep, but reflect the quality on offer. Fotoliawww.fotolia.com. Introduction - Material Design - Google design guidelines. Lovely ui. Mobile Awesomeness. Advertisement.
The Future of Wireframes - Articles - MIX Online. As we move into the next decade of web design, it's time for us to reevaluate our understanding of wireframes—a tried and tested user experience staple Riddle me this: How do you piss of a UX professional?
The answer: Call him a "designer". These days, user experience professionals look down on the word "designer" because it implies that their primary role is to paint pretty pixels. UX is more than that, they clarify. Web.without.words. Wireframe Showcase - Home. I ♥ wireframes - The ultimate source of inspiration and collection of resources for wireframes.
Mobile-First Responsive Web Design. What Is Mobile-First Responsive Web Design?
Mobile-First Responsive Web Design is a combination of philosophies/strategies, and ultimately boils down to a broader application of good ol' web best practices. As the digital landscape gets increasingly complex, we need to design experiences that work across the entire spectrum of digital devices. Sounds like fun, right? Mobile First Mobile First Mobile First is a philosophy created by Luke Wroblewski that highlights the need to prioritize the mobile context when creating user experiences. Design Your Own Android Apps Without Programming Skills » Web Design » SitePoint Blogs. This article was written in 2010 and remains one of our most popular posts.
If you're keen to learn more about Android development, you may find this recent article on free web development apps of great interest. If you like the idea of creating your own App but don't have any coding skills, you may be very interested to hear about Google's new offering. The App Inventor (with the obligatory BETA in the title) is a new tool which allows non-programmers to build fully working applications for Android. Google announced the availability of the App Inventor on its blog earlier this week.
To use App Inventor, you do not need to be a developer. Google has been working on the tool for over a year and it has been tested in schools and colleges. Here's a 60-second video (with jazzy, xylophone background music) showing how a simple app can be created using the App Inventor. You can learn more about the App Inventor and see tutorials and sample apps here. UX Design. Blog. The State of In-Car UX We are surrounded by bad design.
You witness it when you're taking cash out of an ATM. Written by Geoff Teehan on April 9,2014 in Design iOS 7 GUI templates will ship inside of Sketch 3 I'm really excited today to share the news that our iOS 7 GUI template is going to ship natively in Sketch 3 (Sketch 2 shown above). Written by Geoff Teehan on March 31,2014 in Design, News Zen and the Art of Insight Generation It's not even really up for debate. Written by Kyra Aylsworth on February 25,2014 in How We Work, Strategy Don't go chasing waterfalls Waterfall. UX.


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We sell, market and distribute standard and tailor-made
dairy products and related ingredients.
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HOME was last modified: November 22nd, 2019 by


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Leading the forefront in local Surveying firms, Geosurv have been servicing Sydney since 2005 offering a complete surveying solution for commercial and residential high rise, roads and civil infrastructure, industrial, health, government, education, hotels and clubs, and home and land.
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- We minimise our impact on the environment by using sustainable resources and engaging in proper recycling and waste reduction measures.
What we've done in Wollongong
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Kivik is the heart of apple producing in Österlen. Once a year, in September, there is a famous Apple Market. Kivik is surrounded by orchards and gardens, the Baltic sea, and the most beautiful sandy beaches. MORE
Starhouse in Kivik
A special day at Stjärnhuset in Kivik. A transit of Mercury accros the sun, and everybody was welcome to witness this rare astronomical event with a help of many good advices and equipment. MORE
Apple Market in Kivik
Thousands of visitors and tons of apples this year on the opening of Apple Market, or famous "Äpplemarknad" in Kivik. This festival of apple is one of the biggest events in Österlen. MORE
Esperöd Arboretum
Once forgotten, Kivik´s Arboretum shines today in its beauty and natural richness.There are trees from all over the world, many species with different variations, and they all seem to have it really nice. MORE
King´s Grave
For few thousand of years, this place was a mystery for local people. In 1748, two farmers discovered an ancient stone grave. It turned out to be one of the most important archeology findings in Sweden. MORE
Stenshuvud National Park
Stenshuvud is a national park spreading on 390 hectares. An ancient forest with a stone mountain, just a mile south from Kivik. According to legend, the mountain got its name from the stone giant. MORE
Bo Hultén´s Art of Nature
"Soon after I bought Esperöd property, I found out that the impenetrable forest on it contained a highly interesting collection of trees. It has become my passion and inspired me to my long study of nature." MORE
Cake Cowboy - A Little Kingdom of Chocolate
Cake Cowboy is a pastry and chocolate saloon we found in Kivik, driven by internationally acknowledged chef, Markus Lundquist. MORE
Killegården, located centrally in Kivik is a four-winged old farm dating back to the 1850s, turned into a cozy Bed & Breakfast. MORE
Esperods Herrgard or Esperöd Manor is settled on the slopes of national park Stenshuvud. and overlooking Kivik with long sandy beaches. MORE
read more about towns & villages in Österlen
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One brand that really embraces the the idea of Podcasting is Argand Solutions, based in Totnes. We are creating a whole series called "Power Generation and Storage" Fraser Durham at Argand along with other members of the team come over to my studio for a coffee before we get on with the recording. We have a good Content Plan in pace which means that it all goes very smoothly… usually.
The results? Well how about this for feedback: "I listened to the two podcasts the other day from your website – brilliant idea. Concise, informative and engaging." Alan Rees, Metering Solutions Manager, Schneider Electric.


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Why We Need To Stop Shaming Each Other Over Our Milestones
Two of your friends from college post a picture on Facebook. "I can't believe they're engaged," you say to your coworker — who doesn't know them, of course, but still nods sympathetically. You launch into some diatribe about how young they are, or how they're not really right for each other, or how they don't know what they're getting into. You ritualistically stalk through their most recent pictures. You mention it on the phone to your mom. Driving home that day you're still thinking about it, feeling a little bit smug and superior to them, telling yourself that the discomfort you feel is from your concern for your friends and nothing more.
Hard truth: we're all doing this every time we scroll down our feed. Harder truth: we are not uncomfortable because we are concerned. We are uncomfortable because we are insecure, and watching people move on into different places in their lives without us, and we don't know how to express that in a way that doesn't make us feel totally lame and selfish.
So what do we do instead? We shame each other's milestones. Our friend scores a massively impressive job and a corporate firm, and we shake our heads about how their priorities are out of order for "selling out". Our friend Snapchats us a picture of their new baby and we roll our eyes about how boring and suburban they are. Our friend posts a picture of their ring with some hokey "I said yes!" caption and we basically flatline from irritation.
We feel insecure and uncomfortable with ourselves, so we project it on them. We make them the problem. It's their fault for flaunting it, for being "cliché," for "selling out". And yeah, we don't shame them to their faces, or even necessarily think of our attitude towards it as "shaming". But that doesn't make it any less damaging — not just for ourselves, but everyone around us. If you notice this bitter pattern in yourself when you log on and see someone else's good news in your feed, consider just how much it is affecting you — and just how relieving it will be to let it go.
The Milestones You Shame The Most Often Are The Ones You Feel The Most Insecure About
Dig deep the next time you feel an eye roll coming on and ask yourself why you're on edge. Is this person really so insufferable and deserving of your irritation? Or, alternately, is this person really making a decision that is a cause for concern? If you examine your feelings and can honestly answer "no" to both of those questions, then
But the truth is, the specific things that upset us wouldn't upset us at all if it weren't out of some private jealousy. If you find yourself the most bitter about friends who are realizing career goals, it is a reflection of the feelings you have in your own career. If you find yourself the most bitter about friends "spamming" your feed with wedding pictures, it is a reflection of your own discomfort with what you want or don't want out of a relationship someday. It's a different kind of upset for each person. You don't necessarily want what they have — but there is some part of your life in that related area that is working you up.
If anything, this desire to "shame" milestones of other people can be helpful to you. Let yourself feel that for a moment. Lean into it. Then decide what the hell it is that is really upsetting you. It might just be the push you need to change your priorities, whatever those priorities are.
It Really, Truly, In Perpetuity Has Nothing To Do With You
Two important pieces of advice that I've gotten that I remind myself of on the daily:
- Run your own race.
- Don't make other people's problems your problems.
The first one is especially important to remember in the age of the curated newsfeed. We are all posting our highlight reels. I personally never post to Facebook these days unless it's an article I'm proud of, or a not-so-humble brag, or a picture of myself that's so slammin' that I can't not post it. We're all the same in that regard, but we forget it when we're looking at other people's feeds. We compare our ordinary lives to their highlight reels, and it makes us feel inadequate.
Hence, the important of running your own race. You'll absolutely get lapped in some areas of adulthood. Some friends are going to be working for hedge funds while you're flipping their burgers. Some friends are going to travel the world while you make an indent on your parents' couch. Some friends are going to get married and have kids while you still feel like a kid yourself. But odds are, they're all looking at your feed and picking apart your accomplishments too. Which is ultimately a waste of time — we're all going to get to the places we need to be at our own time, at our own pace. Other people's accomplishments are not race markers. They're just scenery to enjoy on the ride.
On the flip side of this, if your discomfort at your friend's milestone really is out of concern — sit down. Take a breath. You are only responsible for what you do in this world. Unless they are in some kind of legitimate danger, the only thing you can do as a friend is be supportive of them if it works, and remain supportive of them if they fail. But it is not your job to fix them. Do not make other people's problems your problems. You've got your own hustle to focus on. Which leads me to ...
It's A Waste Of Your Precious Time And Energy
It's the psychological version of "it takes more muscles to frown than to smile". I'm not going to tell you that you have to smile over everyone's good news — (Lord knows we've been told to smile enough for one lifetime) — but actively being annoyed, badmouthing, or even just thinking negative thoughts about someone else's achievements is incredibly exhausting and unproductive. Funnel that time and energy into worthy pursuits.
It Is Sucking Joy Out Of A World That Is Already Sometimes Hard To Find Joy In
Let's get real grim, real quick: we're all gonna die someday. Everything you enjoy is going to disappear at some point or another. Most days that you spend on this planet you will do the same things over and over and over again, with a few awesome and terrible moments that punctuate it. I'm not saying this to be the Biggest Bummer On The Planet (TM), but because it just goes to show how rare and awesome opportunities for real joy are — and when you let yourself share in other people's joy, you multiply it to a staggering degree.
Someday You're Going To Hit Milestones, And Want People To Be Supportive Of You
Someday (SOON!) you're going to have the awesome breakthrough, snag the dream job, move to the big city, move in with someone you love, or get married or have some kids, if the life suits ya. If any of those are things you want, of course you have imagined in your mind's eye what it's like to achieve them — and of course in that image you have, your loved ones have been supportive and happy for you. As the saying goes, Facebook like unto others as you would want Facebook liked unto you.


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Improving service knowledge and access among older people from Culturally and Linguistically Diverse (CALD) backgrounds with dementia
National Ageing Research Institute (NARI) will be working with Aged Care Assessment Teams to trial videoconferencing technology with interpreters for aged care assessments. The interpreter will be in a different location to the assessment worker, older person and family. This project will contribute to the health and wellbeing of older Australians from Culturally and Linguistically Diverse (CALD) backgrounds through improved assessment for aged care services and dementia.
It aims to improve service access among people from CALD backgrounds and address the issue of delayed diagnosis amongst this group. A more timely diagnosis of dementia will allow for early planning, access to services and medication. It will also address the issue of shortage of interpreters, especially in new and emerging languages and rural/remote areas. It is anticipated the use of e-interpreting will be more cost-effective than face-to-face.


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#1 2014-05-21 12:40:02
- doubleailes
- Guerilla dev, the guy to hug
Removing noise in metal material
Is there is any tips for removing noise in metal material?
I tried to over sample this setting.
Direct sampling
Env sampling
indirect sampling
Philippe Llerena
#2 2014-10-01 16:30:08
- Narann
- Member
Re: Removing noise in metal material
Hi doubleailes,
It's hard to say without see any pictures. I don't remember metal create particular noises so it's maybe not metal related.
Please provide some pictures when it's fireflies related.
Don't hesitate to also provide a .gproject with simple primitives (Guerilla provide sphere, cube and a plane primitives wich are often enough to reproduce such problems).
A good way to find where the problems can come from is to create some AOVs (in "Passes" tab: Reflection, Diffuse, etc...) and look at them separately (bottom left of the render view).
Hope this help.


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Mini Review ARTICLE
Targeting molecular networks for drug research
- 1SysBioLab, Centre for Molecular and Structural Biomedicine, Universidade do Algarve, Faro, Portugal
- 2Centre of Marine Sciences, Universidade do Algarve, Faro, Portugal
The study of molecular networks has recently moved into the limelight of biomedical research. While it has certainly provided us with plenty of new insights into cellular mechanisms, the challenge now is how to modify or even restructure these networks. This is especially true for human diseases, which can be regarded as manifestations of distorted states of molecular networks. Of the possible interventions for altering networks, the use of drugs is presently the most feasible. In this mini-review, we present and discuss some exemplary approaches of how analysis of molecular interaction networks can contribute to pharmacology (e.g., by identifying new drug targets or prediction of drug side effects), as well as list pointers to relevant resources and software to guide future research. We also outline recent progress in the use of drugs for in vitro reprogramming of cells, which constitutes an example par excellence for altering molecular interaction networks with drugs.
Over the last decade, we have witnessed impressive technological advances in the field of molecular biology. Many of them have brought us an incredible wealth of molecular data. Initially, it was hoped that large data-driven projects such as the Human Genome Project would readily pave the way for the development of new effective therapies in biomedicine. Unfortunately, the translation of these molecular data into biomedical breakthroughs has been dauntingly slow. Why is this so?
One reason for this "bottleneck" is that biological processes are highly interconnected, so their manipulation is a formidable challenge. In addition, major human diseases, such as cancer, type II diabetes, and hypertension, are genetically complex. Hence, a direct correspondence between causative genotype and disease phenotype, as observed in Mendelian disorders, is frequently obscure. Instead, these diseases are multi-factorial and seem to result from interplay between multiple genes and environmental factors, each having a relatively small effect, with few (if any) being prerequisites for the disease to occur (Manolio, 2010). This view is supported by several other lines of investigations that underline how important it is to regard causative genes not as isolated entities, but as integral parts of molecular networks or pathways (Badano and Katsanis, 2002; Oti and Brunner, 2007).
Molecular Networks: Data and Analysis
In recognition of the importance of molecular networks, researchers from different fields have begun to study them intensely through computational and experimental means. Their underlying premise has been that changes to cellular networks determine many phenotypic variations, and that such changes can be provoked, not only by alterations to a gene product's abundance, but also through perturbations of its interactions.
The intensified interest in molecular networks has resulted in systematic gathering of interaction data for biomolecules, as well as the development of computational approaches for the analysis of biological networks. Nowadays, a large number of publicly accessible databases contain various types of molecular interaction data1. Networks derived from these resources frequently contain only a specific type of molecular interaction such a protein–protein or protein–DNA interactions. Based on the type of included interaction, we distinguish between different types of interaction networks. Currently, the major types are protein–protein interaction (PPI), gene regulatory and metabolic networks. These networks are often visually represented as simple graphs, with nodes or vertices denoting molecules, and links or edges denoting interactions between them. While such drastic simplification neglects many characteristics of individual components, it facilitates the analysis and modeling of large cellular networks. Furthermore, we can profit from the rich repertoire of mathematical tools and concepts already developed in graph theory.
The most basic characteristic of a node in a graph is its degree, i.e., the number of edges attached to it. In many biological networks, the majority of nodes have a low degree, and only a few nodes have a high degree. These highly connected nodes are known as hubs, and are important for the integrity of the network (Albert, 2005). Another important concept in graph theory is modularity. A module is commonly regarded as a set of nodes that are more densely connected with each other than with other nodes in the network (Pinto, 2012). These two concepts are illustrated for biological networks in Figure 1A. Modularity has also been suggested to contribute to robustness of molecular systems (Hartwell et al., 1999). In fact, robustness of molecular processes seems to result directly from the structure of the underlying networks. Besides redundant genetic components, compensatory network structures such as alternative metabolic or signaling pathways can buffer the failure of single parts (Wagner, 2005). This feature of networks is a crucial aspect to be considered, when we want to design effective interventions in their functioning.
FIGURE 1. (A) Illustration of basic concepts in the analysis of molecular networks. Hubs are defined by their large number of interactions, whereas "bottleneck" proteins link densely connected sub-networks or modules. Both types of nodes provide prominent targets for interventions, aimed at changing the network structure and integrity. (B) Approaches for network-based drug targeting and repositioning. Different types of heterogeneous bipartite or tripartite networks have been used in the literature to identify new targets for drugs. (C) Network-oriented pharmacology in the UniHI environment. After querying for molecular interactions for central proteins, UniHI derives tissue and phenotype-specific networks, which can be scrutinized for known drug targets. In the example shown, an interaction network with GADD45A, SNCA, PARK2 as central proteins was retrieved and filtered using gene expression data from the brain. Additional filtering steps, using drug–target data and phenotypic information ("nervous system phenotype") from knock-out mice, generated a compact network of drug targets with potential relevance for neurological disorders. Information regarding the drugs and their mode of action can be interactively accessed within the displayed network.
Prime examples of popular and freely available software for network analysis are R/Bioconductor2 or Cytoscape3. While these are powerful and versatile tools, their use requires expertise in both data handling and processing. Alternatives are given by several on-line resources, which provide integrated and annotated data together with applications for analysis and visualization. For instance, our Unified Human Interactome (UniHI)4 database stores a large number of molecular interactions for the human genome, together with other types of information, and includes tools for the interactive analysis of retrieved interaction networks (Chaurasia et al., 2007; Kalathur et al., 2014). Especially for researchers less acquainted with network analysis, such integrative platforms offer convenient gateways to a wealth of interaction data.
Drugs and their Targets
Pharmaceutical drugs are a common means to modify the activity of biomolecules, making them prime candidates for altering activity and structure of molecular networks as well. The targets of drugs can be proteins, peptides or nucleic acids, whose activities can be modulated. Drugs can be sub-divided into at least three different classes: (i) chemical compounds with low molecular weight (typically referred to as small molecules) that target enzymes, receptors, transcription factors or ion channels; (ii) biologics (such as antibodies or recombinant proteins) that target extracellular proteins and transmembrane receptor; and (iii) nucleic acids that target messenger RNA by interference (Gashaw et al., 2011). Notably, small molecules are still by far the most common type of drugs, and are frequently associated with low costs and easy (i.e., oral) delivery. However, the number of proteins, which can be targeted by small molecules, appears to be fairly limited (Overington et al., 2006).
Ideally, drug targets should have: (i) a proven role in the pathophysiology of a disease; (ii) little impact on physiological (health) conditions when modulated; and (iii) a favorable prediction for potential side effects (Gashaw et al., 2011). To fulfill the later criterion, highly selective targeting is generally considered to be a desirable trait. To target multiple proteins, as is frequently required for treatment of complex diseases, it is therefore necessary to combine multiple drugs. Especially for cancer, combinatorial drug therapy has become a standard practice, minimizing the risk of drug resistance. However, kinase inhibitors, which target multiple pathways simultaneously, have shown efficacy in the treatment of different cancers (Al-Lazikani et al., 2012). Thus, it has been argued that multiple-target drugs might be a more favorable option, since detrimental drug–drug interactions can be avoided, and optimal dosage can be more easily determined (Hopkins, 2008).
Network-Based Approaches for Drug Research
Identification of Drug Targets
The identification of drug targets is a crucial, but laborious task in biomedical research. Nowadays, in silico methods can assist greatly. Conventional in silico methods for drug target prediction are typically receptor- or ligand-based models. Whereas receptor-based methods start with a known structure of the target, and employ docking to assess drug binding (Luo et al., 2011); ligand-based methods involve the comparison of drugs with known ligands of the target protein. A successful example of the latter method on a genomic scale is the study by Keiser et al. (2009), in which a large number of new potential targets for existing drugs were found based on chemical similarity with known ligands.
More recently, network-based methods have complemented the computational toolbox for drug target identification. They are especially helpful, if the three-dimensional structure of the target is unknown. Network-based methods are motivated by the observation that the general biological importance of a protein is at least partially linked to its location in relevant PPI networks. For instance, essential genes tend to correspond to hubs or central nodes in many PPI networks; although, in practice, such conclusions might be compromised by prevalent inspection biases (Futschik et al., 2007; Barabási et al., 2011). Consequently, drugs should target central nodes, when a lethal effect is intended, as it is the case, for example, in the treatment of cancer cells or pathogens (Figure 1A). In contrast, if a molecular process needs be adjusted, it might be preferable to target neighbors of central nodes (Csermely et al., 2013). This approach is consistent with observations that targets of approved drugs tend to have more connections on average than most proteins, but fewer connections than for those proteins that correspond to essential genes (Yildirim et al., 2007).
In addition to degree as a basic centrality measure, other more sophisticated local metrics, including bridging centrality and graphlet degree, have been proposed for the identification of drug targets in PPI networks (Hwang et al., 2008; Milenkoviæ et al., 2011). Alternatively, global network-based analyses can be used to provide cues for follow-up investigations. For example, a systematic review of major signaling pathways led to the conclusion that proteins involved in cross-talk between pathways, represent promising targets for drug (Korcsmáros et al., 2010).
While the study of the topology of PPI networks provides a valuable, general indication about the likelihood of finding drug targets; more specific predictions can be determined by evaluating local heterogeneous networks (Figure 1B). One of the first steps in this direction was taken in the work of Yamanishi et al. (2008), who transformed a bipartite network (in which two types of nodes form a network) of drugs and their known targets into a high dimensional composite "pharmacological feature space", where interacting drugs and targets were close to each other. New chemicals or targets could be mapped into this feature space, and drug–target interactions were predicted based on their spatial proximity. A simpler approach, based on diffusion of scores within the local bipartite network neighborhood, has recently been proposed. This approach outperformed predictions based on interference using either chemical similarity of drugs, or sequence similarity of targets (Cheng et al., 2012). Although several of its predicted new targets of known drugs were successfully validated, a drawback of this simpler method is that it cannot be applied to novel drugs. This limitation can be overcome through integration of the drug–target network with drug–drug (based on chemical similarity) and target–target (based on sequence similarity) networks. In the study by Cheng et al. (2012), random walks on these integrated heterogeneous networks were simulated to connect drugs with potential targets. Using drug–drug connections, new drugs, for which no target is yet known, can be linked to proteins via drugs that have known targets.
Furthermore, the use of expression responses appears to assist in the process of drug target identification. Starting with a network of functional associations between proteins, Laenen et al. (2013) evaluated whether differential gene expression upon drug treatment can pinpoint the protein targeted by a drug. Strikingly, while the expression changes of the target itself was only moderately informative, integration of differential expression observed in the target's network neighborhood resulted in a drastic increase in prediction accuracy. However, it remains to be assessed, whether it is generally the case that expression of genes functionally related to a target is altered by its corresponding drug.
Repositioning of Drugs
Closely related to drug target identification is the task of drug repositioning, i.e., finding new therapeutic uses for existing drugs (Tobinick, 2009). Since drug repositioning is based on known drugs, it provides an attractive shortcut to the lengthy development of new drugs. While the above mentioned approaches for drug target identification also can be applied to drug repositioning, several methods and software have been exclusively developed for this task. For instance, Mathur and Dinakarpandian (2011) proposed new possible disease–drug relationships through the analysis of affected biological processes. After identifying processes defined in Gene Ontology that were enriched by genes associated with a particular disease, drugs were linked to these processes, if they targeted central proteins of the PPI network representing these processes. Through comparing predicted disease–drug relationships with ones that had been reported in clinical trials, they found a statistically significant overlap. A similar, but more direct approach has been implemented in the PharmDB database, which integrates binary linkages between drug, proteins, and diseases (Lee et al., 2012). New targets of existing drugs are inferred using a method called Shared Neighborhood Scoring, which evaluates weighted connections between drug and disease nodes via their associated proteins in a tripartite network composite. An alternative software tool, which combines structural models with analysis of interaction profiles, is DRAR-CPI (Luo et al., 2011). This web-server compares the binding behavior of a candidate drug with a set of pre-determined drug–target interactions using a docking approach. Similar interaction profiles can indicate shared targets and common clinical application. The number of included reference targets for docking, however, is limited.
It is important to note, that the use of networks as computational tools is not necessary constrained to the representation of actual molecular interactions, but can be used to represent any kind of defined similarities or association between distinct entities. For instance, Iorio et al. (2010) derived a drug–drug network, where links between drugs indicated similar expression changes upon treatment; they exploited it both for drug target prediction, as well as repositioning.
Analysis of Side Effects
Physiological side effects can be caused by binding of drugs to proteins ("off-targets"), in addition to their intended targets. As side effects are crucial factors in therapeutic applications, their accurate prediction is of eminent importance to avoid failure in drug trials. Notably, systematic recording of side effects represents a broad phenotying on the level of the human organism, providing valuable holistic information on the action of drugs. A unique resource, with this objective, is the SIDER database, which accumulates reported side effects for almost 1000 marketed drugs (Kuhn et al., 2010). Using this database, Mizutani et al. (2012) correlated a drug's side effects with the proteins it binds to. For this, side effects and bound proteins were represented as binary profiles and statistically associated using a modified version of canonical correlation analysis. The obtained correlation was used subsequently for the prediction of side effects, by evaluating the proteins that the drug binds to. Remarkably, it is equally possible to predict a drug's target based on its side effects. This relationship was originally explored by Campillos et al. (2008); they identified new targets of known drugs based on the similarity of their side effects with those of other drugs. There is now a database, which has implemented this approach, called PROMISCUOUS (von Eichborn et al., 2011). It enables the interactive exploration of an integrated network of drug, protein, and side effect nodes, and can be used to gain new insight into the drug's mode of action. Finally, side effects can also be indicative for drug–drug interactions, which are frequently of clinical relevance. It was recently shown that two drugs tend to interact, if their targets are in close proximity in a PPI network, or if they have similar side effects (Huang et al., 2013). Moreover, combining information on physical interaction of drug targets and recorded side effects improves the prediction accuracy for drug–drug interactions.
In Table 1, we provide a selection of publicly available databases and computational resources, which may be useful for the reader to initiate their own investigations in the field of network-based pharmacology.
New Horizons: in Vitro Reprogramming of Cells Using Small Molecules
In the network-based approaches described above, drugs mainly act within small sub-networks in order to "fix" or interfere with particular processes. This contrasts with their recent use in stem cell biology, where small molecules have been used to re-wire entire cellular networks. Their main object in this context is to convert (or reprogram) somatic cells, specific to an individual, into stem cells. These cells may eventually provide a personalized supply of tissue to replenish cells lost in degenerative diseases. Pioneering work led by Yamanaka showed that such conversion is possible through forced expression of merely four transcription factors using viral vectors (Takahashi and Yamanaka, 2006). The original combination of transcription factors used by Yamanaka comprises Octamer-binding transcription factor 4 (Oct4), Sex-determining region Y-box 2 (Sox2), Kruppel-like factor 4 (Klf4), and v-myc avian myelocytomatosis viral oncogene homolog (c-Myc). However, this approach suffers from low efficiency. Furthermore, the viral integration of exogenous transcription factors, in particular of oncogenes, such as Klf4 and c-Myc, is unlikely to offer a viable therapeutic option. Thus, efforts have been made by various groups to find small molecules that can boost reprogramming efficiency, as well as replace virally transduced transcription factors.
Two main classes of small molecules have been identified so far: (i) molecules that facilitate chromatin remodeling by inhibition of, e.g., histone deacetylase, and thereby increase the plasticity of cells (Huangfu et al., 2008); and (ii) molecules that block signaling events that induce differentiation. Examples of the latter class are inhibitors of extracellular signal-regulated kinases (ERKs) and glycogen synthase kinase 3 (GSK3; Silva et al., 2008). By combining these two classes of small molecules, it is even possible to replace all four transcription factors (Hou et al., 2013). A remaining challenge, however, is to determine the underlying molecular processes of chemically induced pluripotency. So far, only rudimentary models, which lack mechanistic details, have been proposed for the activation of key transcription factors by the applied molecules (Hou et al., 2013). Here computational methods for "reverse engineering" of gene regulatory networks can be very helpful. These methods aim to infer regulatory interactions from observed gene expression patterns and comprise a diverse set of statistical approaches such as regression, analysis of correlation or mutational information or Bayesian networks (Marbach et al., 2012). Usually, their application requires a large set of genome-wide expression measurements and might not scale up very well to the complexity of regulatory networks in higher eukaryotes. Nevertheless, a recent study identified successfully a novel regulator of stem cell differentiation through reverse engineering of gene regulatory networks from microarray expression data (De Cegli et al., 2013). We anticipate that such approaches as well as systems biology in general will help to establish a rational basis for creating chemically induced pluripotency.
Our review highlights several applications of molecular networks, in which they act as versatile interfaces between phenotypes and drugs. While these applications demonstrate the utility of network-based analyses, several major challenges still exist. Firstly, the quality and coverage of interaction data need to be improved and consolidated. Many interaction data sets suffer from both detection and selection biases, which limit their use (Futschik et al., 2007). Published drug target data also appear to be compromised by their low reproducibility (Prinz et al., 2011). Secondly, condition-specific networks need to be constructed, reflecting the dynamics of molecular processes, in contrast to the static nature of current models. In this way, it will be possible to study the effects of external and internal stimuli on network structure and function. Finally, the vast majority of available drugs target network nodes, disrupting the general activity of a specific biomolecule. Only a small number of drugs are directed towards specific interactions (Wells and McClendon, 2007). Such "link-directed" drugs, however, can provide a more precise means to modulate molecular networks.
In summary, network-based analyses offer new ways of studying targets and effects of drugs. Although challenges lie ahead, network models promise to be powerful and versatile tools in our quest to better understand and control molecular systems in health and disease.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
This work was supported by the Portuguese Fundação para a Ciência e a Tecnologia (BIA-GEN/116519/2010, SFRH/BPD/96890/2013, IF/00881/2013 and PEst-OE/EQB/LA0023/2013). We would like to thank Trudi Semeniuk for critically reading our manuscript and the reviewers for their valuable suggestions.
- ^http://www.pathguide.org
- ^http://www.bioconductor.org
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Keywords: networks, molecular interactions, drugs, diseases, stem cells
Citation: Pinto JP, Machado RSR, Xavier JM and Futschik ME (2014) Targeting molecular networks for drug research. Front. Genet. 5:160. doi: 10.3389/fgene.2014.00160
Received: 05 April 2014; Accepted: 14 May 2014;
Published online: 04 June 2014.
Edited by:Enrico Capobianco, Center for Computational Science – University of Miami, USA
Reviewed by:Subha Madhavan, Georgetown University, USA
Alexey Goltsov, University of Abertay Dundee, UK
Zahraa Naji Sabra, American University of Beirut, Lebanon
Copyright © 2014 Pinto, Machado, Xavier and Futschik. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Matthias E. Futschik, SysBioLab, Centre for Molecular and Structural Biomedicine, Campus de Gambelas, Universidade do Algarve, CBME, FCT, Ed. 8, 8005-139 Faro, Portugal e-mail: email@example.com


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Published July 2014
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