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Nobody wants to take their vehicle in for repairs or maintenance more often than they actually need to. But having a dashboard light switch on can be scary if you're not sure what it means.
Luckily, it doesn't have to be. You have lots of resources available to you — namely your car's user manual — that can help you understand what's an emergency and what can wait.
Simply: yes. The manual is the guide to your car. It should be the go-to when you have a question about your vehicle.
While lots of information is available online, it's not all vehicle-specific. The manual is your source for information specific to your vehicle — the make, model and year. Cars can change pretty dramatically year over year, so you want information accurate to your car.
The type of oil you need
If you've ever tried to purchase your own engine oil, you were probably at least a little overwhelmed. There are so many options. There are different types — organic, semi-synthetic and full synthetic — as well as different viscosities.
Checking your owner's manual will tell you exactly what type your car was meant to run on.
Maintenance schedule
Ever wonder whether you're being talked into maintenance you don't need? Your owner's manual will clearly break down the vehicle manufacturer's recommended maintenance schedule. It will tell you recommended time intervals for new filters, fluids and even things like timing belts and spark plugs.
Dash light meanings
Have you ever had a light pop up on your dash and you had no idea what it meant? The owner's manual has your back. It explains each light in easy-to-understand terms. Here's a primer:
Tire pressure light
Normally this light goes off for one of three reasons:
1. Your tire pressure is low. This can happen because of fluctuations in air pressure outside or because your tire picked up a nail. Put some air in your tire and the light should turn off in five to 10 miles of driving in most vehicles. If the light comes back on, get your tire checked out, because there might be a slow leak.
2. Your tires are overinflated. Yes, surprise! If you put too much air in your tires — which is very unsafe — your tire pressure light should come on. Checking your tire pressure with a tire gauge is fairly straightforward. Let some air out if it's overinflated.
3. Your tire pressure monitor is broken. If this is the case, check your tire pressure regularly by hand.
Oil change/maintenance needed light
This light coming on is a reminder that your oil change is due. Make sure to get your oil changes done per the maintenance schedule in your owner's manual.
Check engine light
This light can come on for hundreds of different reasons. One thing is for certain: If the light is flashing, stop driving and get your vehicle towed. Driving with a flashing check engine light can cause catastrophic damage.
The check engine light is your indicator that something is wrong with an electrical part of your car. In most cars, it won't come on for brake problems or suspension issues.
Turning this light off won't work for long, as it will reset as you drive. Take the vehicle in to get diagnosed to determine if it's something you need to take care of right away.
Oil pressure light
If this light comes on, get it checked out right away. It could mean a number of different things, but it often comes on when the oil in a car is really low. It could mean your vehicle is burning oil or that you have a major oil leak.
Oil pressure is necessary for proper engine functioning. The oil pressure light should not simply be turned off without a check of what's going on under the hood.
[ICYMI: Is it Time to Get Rid of Your Old Car?]
You should take your vehicle in for regular oil change services. If you get the maintenance and repairs done during your regularly scheduled appointment, you can save yourself time and a trip to the shop by taking care of things right away.
There are two standard intervals for oil changes:
These are some common problems that should be checked out by a mechanic right away:
1. Brakes are squeaking when stopping or the brake pedal feels low when you are stopping. Brakes are no joking matter and should be handled immediately. Not only is this for your safety, it's also for your pocketbook. Brakes can quickly go from a simple job to an expensive repair.
2. Flashing check engine light. As mentioned above, a flashing check engine light means serious damage is happening to your engine. The less you drive it and the sooner it gets into the shop, the less money you are going to spend overall.
3. Your vehicle cuts off while driving. Often folks will get their car jump-started in this situation and keep driving. Here's the thing: the battery is not meant to keep your vehicle running. That's the alternator's job. If your car cuts off, one of the most common reasons is a bad alternator. It will drive temporarily until it uncharges the battery and then you are back to square one. Get the car checked out right away so you don't end up stranded.
4. Your car is overheating. If your car is overheating, stop driving it. Get a tow and get the vehicle checked out.
Figuring out your vehicle can be a bit of a puzzle. Using your owner's manual as a guidebook will help you learn the best ways to take care of it.
I can't stress enough how important it is to listen and feel how your car is driving. You are the driver. If you pay attention, you can feel when something is going wrong with your vehicle. If you like listening to loud music while driving, commit to driving for five minutes once a week with the music off so you can hear your car.
If something feels wrong, go get it checked out. Many car repairs become super expensive because they aren't handled at the outset of the problem.
Chaya Milchtein is an automotive speaker and writer. She's made it her mission to educate people about their cars. Find her on Twitter @mechanicfemme.
Up Next


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The best cat sitters near Newton
As the UK's most popular cat sitter service, we've helped well over 200,000 pet owners since we started Tailster. We've got plenty of cat sitters in and around Newton who can help you regardless of your requirements - whether its ongoing or repeat, for your small dogs or large dogs. As we know how difficult it is to find the perfect cat sitter, we've made it easy at Tailster. Simply click find a carer and let us know your requirements - it takes less than 30 seconds to tell us what you require from a cat sitter. All we need to know is your postcode, your dates and requirements and we will ping this out to all the suitable cat sitters in Newton and if they are available and want to help, you'll receive personalised quotes (often within the hour). You can see in the map below, all the cat sitters in Newton and can view their profiles and let us do that hard work for you!
Hi, I'm Cass. I have two dogs: a Collie-Staffie cross and a Collie-Labrador cross. I also have two cats and have had rabbits, hamsters and gerbils in …
Witherford Whiskers
We are two young professionals aiming to make your life easier by caring for your cat(s). We have a lovely cat of our own and understand their needs a…
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chloe's paggent
I am a verry loving, bubbly person. I love animals and am happy with all diffrent sizes. I currently have 2 barn owls, 2 dogs one is a english mastive…
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I have lived with dogs my whole life and love all shapes and sizes. I am currently studying to be a dog trainer and am looking for lots of experience.…
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Ghost Rider. This sculpture is by a Belgian artist at the Goldwell Open Air Museum in Beatty, Nevada. It is right near the ghost town of Rhyolite. The artist wrapped a person in a sheet with plaster to achieve this effect.
well done
3 Dec 2015 5:05pm
bien cette cape de plâtre et on dirait l'homme invisible
4 Dec 2015 3:25pm
Add your comment ...
ghost rider bike sculpture art goldwell open air museum beatty nv rhyolite
Photography by Fran © 2020
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Hlavní nabídka:
Vod fšeho kousek
Hallo, ich bin Hilde aus Barzdorf bei Braunau!
Hilde from Božanov near by Broumov is saying Hello. She wears dress model of folk costume, which is typical for the region of Broumov. I had kept the idea to make dress model of this Broumov folk costume since the exhibiton of Broumov folk costume in 2009 yet, but it took me long time of seven years. Because I had an idea either, but I didn´t want to make. Or I wanted to make, but I didn´t have an idea, or I had an idea and I wanted to make, but I didn´t have the cloth, which would remember all of the old materials and colours using for origin old folk costumes. But I realised it at the end. Maybe, it is the only dress model copy of Broumov folk costume in the world.
I would like to say, too, that Hilde is a rubber doll made in the company Gumotex in the Czech Republic in eighties. Hilde loved discovering of our yard and house and enjoyed the Broumov beer Opat as well as her living adult women foregoer surely did in the past.


text: Bucko Report post Posted August 3, 2013 It's a nice looking gun outside. Same can't be said inside... The previous owner beat the hell out of it and lied through his teeth to me about the gun. I'll be kicking in his door shortly if he doesn't respond to me on Facebook... Share this post Link to post Share on other sites


text:
Rm.Shanmugam Chettiar.
Rm.Shanmugam Chettiar. (June 15,1942 / Aravayal, karaikudi, Tamil Nadu, South India)
Poems by Rm.Shanmugam Chettiar. : 3241 / 10126
In Glow Without Makeup. - Poem by Rm.Shanmugam Chettiar.
Makeup heavily coats the skin,
And makes it impermeable,
And blocks the hormone osmosis,
Responsible for the skin glow.
See the woman in the kitchen
Or from the bath to note difference.
Listen to this poem:
Poems by Rm.Shanmugam Chettiar. : 3241 / 10126
Poet's Notes about The Poem
Comments about In Glow Without Makeup. by Rm.Shanmugam Chettiar.
Wahab Abdul (5/30/2013 12:21:00 AM)
Rudyard Kipling
Read this poem in other languages
This poem has not been translated into any other language yet.
I would like to translate this poem »
Poem Submitted: Wednesday, May 29, 2013
Poem Edited: Thursday, September 5, 2013
Rm.Shanmugam Chettiar.'s Other Poems
Famous Poems
- Still I RiseMaya Angelou
- The Road Not TakenRobert Frost
- If You Forget MePablo Neruda
- DreamsLangston Hughes
- Annabel LeeEdgar Allan Poe
- Stopping By Woods On A Snowy EveningRobert Frost
- IfRudyard Kipling
- Do Not Stand At My Grave And WeepMary Elizabeth Frye
- I Do Not Love You Except Because I Love YouPablo Neruda
- TelevisionRoald Dahl


text:
TWA Fly Israel (1964 - LB)
TWA Fly Israel vintage 1964 travel poster
Beautiful painting of a Jewish menorah by David Klein advertising flights to Israel. Poster is linen backed
- Year: 1964
- Poster Origin: US
- Format & Size: 25x40 (64x102 cm)
- Condition: Near Mint
- Comments: Linen-backed. Rolled
Warning: Last items in stock!
1item in stockitems in stock


text: By Miguel Corrales InspirationApril 11, 2015 Alive and Healthy A beautiful day begins with a beautiful mindset. When you wake up, take a second to think about what a privilege it is to simply be alive and healthy. Share on Facebook Twitter Pinterest Google + LinkedIn Email Bio Latest Posts Miguel Corrales Web Designer Latest Posts By Miguel Corrales June Wellness Alive and Healthy The Simple Moments Previous articleThe Simple Moments Next articleBecome an instrument You may also like Pete Seeger Joanna Gaines Trevor Noah


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Village of Lincolnshire Police Pension Fund Board met Feb. 6.
Here is the agenda provided by the Board:
I. Call to Order
II. Roll Call of Trustees (by Secretary)
III. Review/Approval of Minutes
a. November 7, 2017, Quarterly Meeting
b. November 28, 2017, Special Meeting
IV. Treasurer's Report
a. Reports from Lauterbach and Amen (email)
b. Pension Treasurer Michael Peterson
V. Review of Investment Activity
a. Legacy report, Doug Krapf
b. Discussion, motion and vote on investments
c. Mid-quarter rebalancing review
d. Future mid-quarter rebalance discussions and approval
VI. Presentation of Bills and/or Disbursements
a. Puchalski Goodloe Marzullo, LLP, Legal Bill, $847.50
b. Village of Lincolnshire, Forkes/Bethel Physical 50/50 Split, $902.00
VII. Old Business
a. Legal monitoring reports
b. 2018 Village Tax Levy/Contribution Program, Michael Peterson
c. Beneficiary member forms and certification status, Mr. Hyde
VIII. New Business
a. Creditable Service Forms and Salary Data, 2017
b. 2017 Year End Contributions
c. 2017 Annual Pensionable Salary Data
d. 2018 Mayor Appointment, Mr. Herst
e. Open Meetings Act Officer appointment
f. FOIA Officer appointment
g. FOIA Requests
h. Scott Alm disability physical discussion
i. Other new business
j. Met Life Check, $4.00
IX. Applications for Membership
a. Roy E. Bethel, January 8, 2018
b. Dillon M. Forkes, January 8, 2018
X. Applications for Benefits
a. None
XI. Pension Board Compliance
a. 2017 Continuing Education – Year End
i. Steven Lee, 16+ hours
ii. Adam Hyde, 16+ hours
iii. Jamie Watson, 16+ hours
iv. Mickey Herst, 16+ hours
v. Patrick Quillinan, 16+ hours
b. 2018 Continuing Education
i. None
c. Open Meetings Act/FOIA Training
XII. Executive Session Matters
a. Review and discuss – No Execution Session Minutes as of current meeting
XIII. General Public Comments
XIV. Adjournment
a. Next Meeting: May 15, 2018


text:
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We regret to inform you that this product (Cheeks leggings in big hole Mesh and PU accent) is either temporarily out of stock or not in stock in the desired quantity. Please submit your email address if you would like to be notified when new stock arrives for this product.
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Golden currant tomato (Solanum pimpinellifolium)
2.29 € *
apx. $2.54 - $2.54selection
{"list_position":0,"systype":"article","name":"Golden currant tomato (Solanum pimpinellifolium)","id":"MA-LYC23","list_name":"tree-181"}
Wild tomato 'Rote Murmel' (Solanum pimpinellifolium) Organic
2.29 € - 37.34 € *
apx. $2.54 - $41.48selection
{"list_position":1,"systype":"article","name":"Wild tomato 'Rote Murmel' (Solanum pimpinellifolium) Organic","id":"MA-0001","list_name":"tree-181"}
Wild tomatoes are usually even smaller than cherry tomatoes, but taste similar and do not require rain protection, which means that they can actually be grown anywhere in the garden - but you should allow enough space, because wild tomatoes can grow very lush and sometimes carry literally thousands of fruits.


text:
Covariate Balancing Propensity Score.
Implements the covariate balancing propensity score (CBPS) proposed by Imai and Ratkovic (2014; JRSSB). The propensity score is estimated such that it maximizes the resulting covariate balance as well as the prediction of treatment assignment. The method, therefore, avoids an iteration between model fitting and balance checking. The package also implements several extensions of the CBPS beyond the cross-sectional, binary treatment setting. The current version implements the CBPS for longitudinal settings so that it can be used in conjunction with marginal structural models (Imai and Ratkovic, 2014), treatments with three- and four-valued treatment variables, continuous-valued treatments (Fong, Hazlett, and Imai, 2015), and the situation with multiple distinct binary treatments administered simultaneously. In the future it will be extended to other settings including the generalization of experimental and instrumental variable estimates.
Christian Fong
Author(s): Christian Fong <email@example.com>, Marc Ratkovic <firstname.lastname@example.com>, Chad Hazlett <email@example.com>, Kosuke Imai <firstname.lastname@example.com>
License: GPL (>= 2)
Uses: MASS, MatchIt, nnet, numDeriv
Reverse suggests: cobalt, WeightIt
Reverse enhances: optmatch
Released over 4 years ago.


text:
The owner of a flooded business who lost some of her chickens in rapidly rising floodwaters on Friday is questioning why her property was inundated when others nearby were not.
Lesley Limbe, who owns The Tin Shed retail business and small farmyard at Rangitata, 20 minutes south of Ashburton, said the floodwaters climbed "very suddenly" on Friday morning.
Limbe said her daughter had managed to rescue rabbits from "deep water" on the property, but some of her chickens could not be saved.
Her larger animals, which include a donkey, alpaca, sheep and kune-kune pigs, were safe and able to access higher ground.
* Timaru state of emergency lifted
* State of emergency declared in Timaru and Oamaru
Waist-deep water meant the site was still cut off from the road on Saturday evening.
Limbe said although the property had flooded before, water had never got into her shop.
Properties on either side of The Tin Shed did not seem to be greatly affected, she said.
"We don't know why it's done this.
"The council should really be coming to have a look at it."
The first sign The Tin Shed was in trouble was water returning to an old water race on the property, which had not been used for years.
"Within five minutes it had got right to the top," she said.
"By 11am there was water in the shop."
Most of her staff had already been sent home due to the heavy rain which lashed South Canterbury on Friday and caused a state of emergency to be declared.
Patchy rain and high winds continued on Saturday, before the state of emergency was lifted in the afternoon.
However, floodwater still appeared to be running down the side of the road and pooling at The Tin Shed on Saturday evening.
The driveway, an orchard and garden, and a small paddock beside the driveway, all flooded.
Limbe's house, on a neighbouring section, was not damaged and most of the merchandise inside her store was safe as well.
She predicted the water would "take a while" to subside and the business would be closed for several days.
– The Timaru Herald


text:
The Wishing Tree At The Harpur Centre, Bedford
'Tis the season to start shopping! Whether it's for Christmas presents or for the perfect party outfit, Harpur Centre in Bedford has everything you need for a festive shopping spree.
The Wishing Tree is now back at the Harpur Centre, up until Friday 20th December 2019, helping to give children across Bedfordshire a better Christmas.
So while you're choosing presents for your family, why not add an extra gift to your basket to pop under the tree to make a child's day extra special? All the gifts collected will be distributed by organisations that support underprivileged children and families in Bedfordshire and delivered in time for Christmas Day.
How does it work?
1. Head to the Wishing Tree in the Harpur Centre, Bedford
2. Choose a 'Boy' or 'Girl' tag
3. Have fun selecting an appropriate gift from the Harpur Centre's stores
4. Attach the tag to the unwrapped gift
5. Drop the gift back at the tree by Friday 20th December 2019
6. Enjoy the warm feeling from making a child's Christmas more special!
The Wishing Tree with the Harpur Centre
Giving a child a magical Christmas
The Harpur Centre in Bedford's premier shopping centre and is home to well-known high street names where you're sure to find the perfect presents. There's everything you need under one roof to make Christmas shopping easier, not to mention warmer!
With gifts to buy and social gatherings to attend - not to mention the feast of all feasts to plan for, it's easy to get caught up in the rush of the preparations for Christmas Day. At the Harpur Centre, there are stores from Argos to EE, Starbucks, to Smiggle, Pandora to Primark, DW Sports to Boots, so you're sure to find something for everyone.
The Harpur Centre is open seven days a week, just metres from the bus station and a 10-minute walk from the train station. Enjoy FREE parking after 6pm every late night and all day on Sundays in the public basement car park.
Have a Magical Christmas at Harpur Centre!
Harpur Centre, Horne Lane, Bedford MK40 1TJ


text:
Why I think these healthcare shares are top buy and hold options
With the global population both growing and ageing, I think the healthcare sector is a great place to look for buy and hold investment options.
Three of the best in my opinion are listed below. Here's why I like them:
ResMed Inc. (ASX: RMD)
Over the last decade this sleep treatment specialist's shares have provided an average annual total return of approximately 23.7%. That would make a $10,000 investment 10 years ago worth almost $84,000 today. While the returns may not be quite as impressive over the next decade, I believe the company's industry-leading products and the growth of the sleep treatment market have put ResMed in a position to deliver earnings growth that could allow it to outperform the market. Because of this, I think it is a great buy and hold option for Australian investors.
Sonic Healthcare Limited (ASX: SHL)
This international medical diagnostics company's shares have performed better than most over the last 10 years. During this time Sonic Healthcare's shares have produced an average annual total return of approximately 9.6%, turning a $10,000 investment into $25,000. If demand for its pathology, radiology and clinical services rises as populations grow and age, then Sonic Healthcare could benefit greatly and continue its strong run. I think that this could make it worth a closer look.
Zenitas Healthcare Ltd (ASX: ZNT)
I think that recently listed Zenitas Healthcare is one of the more promising small cap shares in the healthcare sector. It provides home care and health services across Australia. Which I believe is a market that could grow significantly in the future, especially after the recent Federal Budget pledged to support older Australians that want to remain at home instead of going into aged care. In light of this, I would sooner buy Zenitas shares than aged care providers like Estia Health Ltd (ASX: EHE).
4 Stocks for Building Wealth After 50
Renowned investor Scott Phillips just released a brand-new report detailing his 4 favorite stocks to buy right now.
And I don't know about you, but I always pay attention when some of the best investors in the world give me a stock tip.
This is your chance to get in at the very beginning of what could prove to be very special investments.
Motley Fool contributor James Mickleboro has no position in any of the stocks mentioned. The Motley Fool Australia has recommended ResMed Inc. and Zenitas Healthcare Ltd. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy. This article contains general investment advice only (under AFSL 400691). Authorised by Scott Phillips.


text:
Ariston Andris LUX 15
Sorry, this product is currently unavailable.
Product Details
Experience the stunning synthesis of form and function. The Italian Ariston Lux is made with super ecologic insulation materials and energy can be better conserved through its improved titanium enamel tank. Its shell technology a perfect balance of geometry and assembly promises intuitive design and enduring performance. Its strong resistance to pressure and corrosion makes it a permanent fixture in the house.


text:
So here we are, a very small independent production company sitting with an Emmy award-winning actress and accomplished author, yet Carolyn was more concerned with our comfort level than receiving any type of preferential treatment. Carolyn is truly one of a one of a kind woman with her own views on the world. To many, the term 'broad' can be offensive, but somehow Carolyn described it in a way that left you aspiring to achieve the title. Everything from Carolyn's eccentric rings, huge smile and photos by Jonathan Mannion spoke directly to her energetic, charismatic and infectious personality. Carolyn is a beautiful person and a 'class act' that was an absolute pleasure to work with.
I Am...Carolyn Hennesy
We really enjoyed the time we had with LisaRaye, and some of the things you hear about her are true. Yes, she showed up on time and was dressed in all white, she even had a wardrobe change and returned to set wearing…all white. Yes, she is very strong, extremely stunning in person and definitely has a presence that demands respect. However, it's the things that aren't talked about as often that come to mind when I think about her now. I see someone who was able to find her self-worth while being teased as a child and a woman who is strong enough to ask herself tough questions during the most vulnerable moments of her life. After our time together, we are very comfortable saying that LisaRaye is a rare individual who would be the same remarkable woman if the cameras of Hollywood never found her.
I Am...LisaRaye
I Am...Niecy Nash
This interview is a very special one to us at AWJ. Niecy was the first woman to lend her name to the I Am…web series and our first interview. Honestly speaking, there is no way I can verbally express my gratitude to you Niecy. Your short time with us has made us better and opened numerous doors of opportunity and growth for AWJ. For this we are forever grateful. I literally can't thank you enough. The first words that come to mind when thinking about Niecy Nash would have to be 'very professional' followed by 'extremely genuine.' Niecy showed up at least 20 minutes early with very detailed questions about our shoot. Once the interview started it became very clear that we were talking to a rare woman. It's not too often you meet people who are able to articulate the perspective they've gained from the challenges that life has presented as candidly as Niecy. Niecy has played many roles to entertain us all, but none were as meaningful as the role she played in mother's life after loosing her brother to a violent crime. Her honesty and strength captivated our entire crew, and even brought tears to her friend and our second interviewee's (Tatyana Ali) eyes.
I Am...Tatyana Ali
Most of us fell in love with childhood character, Ashley Banks from The Fresh Prince of Bel-Air, but it is just as easy to fall in love with Tatyana, the woman. Tatyana is extremely pleasant, genuine, humble and very sweet. She had a sincere interest in touching the lives of other women and believed in AWJ's message of changing lives. We were very humbled when Tatyana complimented us on the work we were doing and the ascetics of the site prior to our interview. Tatyana described herself as a 'friend' in her I Am… statement, and after spending time with her, we'd all be fortunate to be able to call her just that. We wish Tatyana and her sister, Anastasia, continued success with their production company, HazraH Entertainment, which they named after their grandmother.
I Am...Sheryl Lee Ralph
Sheryl Lee Ralh has truly made the word 'DIVA' her own. 'Divinely Inspired Victoriously Anointed' is a perfect description of what she embodied during our time together. She had the grace of an angel, the inspiration to change the lives of others, has found victory in trying times and the gift of leaving a lasting impression on those around her. She wanted to make sure the crew was very comfortable, and offered small nuggets of knowledge to help spread the word of AWJ. We all feel very fortunate for the pleasure of meeting Sheryl Lee Ralph and are honored to have worked with her.


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Articles tagged "Chute Boxe"
Thomas Almeida: Reawaking the Dominance of Chute Boxe
Like Wanderlei Silva and Shogun Rua before him, Thomas Almeida's aggressive Chute Boxe style is sure to please fans for years to come. Full story
Fabricio Werdum: The Heir of Chute Boxe
Fabricio Werdum's extensive work with Rafael Cordeiro seems to have resulted in a vastly improved striker on the feet. How much of it is in his technique, and how much is in his mind? Full story
I Trained With Rafael Cordeiro In Mexico
Accompanying Fabricio Werdum at his UFC 180 bout against Mark Hunt in Mexico City, Rafael Cordeiro gave a seminar to a group of lucky fighters. Full story
The Mixed Martial Arts of Victorian London
Before BJJ, there was Bartitsu.
Jonathan Maicelo: The Last Inca
Peru's up-and-coming boxing star.
Kron Gracie on Jiu-Jitsu, Skateboarding, Older Brothers, and Famous Fathers
The ties that bind are strong.
Joel Tudor on the Art of Surfing, Fighting, and Style
A surf icon helps MMA keep its sense of tradition.
Japan's Karate Kid: Kyoji Horiguchi
Japan's brightest MMA prospect.


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PCA statement, online 23 May 2016
"Palliative Care Australia (PCA) CEO Liz Callaghan looks forward to the review of the palliative care resolution at the sixty-ninth World Health Assembly which starts today in Geneva, Switzerland. "Two years ago a palliative care resolution was passed unanimously at the World Health Assembly to ask governments around the world to make palliative care a priority for their health systems." "This week is Australia's 20th National Palliative Care Week, and in the lead up to the Federal election we are calling on political parties to make palliative care a National Health Priority," Ms Callaghan said."
Find statement and election policy here.
Palliative care on World Health Assembly agenda
PCA statement, online 23 May 2016


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PK, GW, ML, WE, and SP conceived and designed the experiments. PK performed the experiments. PK, GW, ML, IH, and BM analyzed the data. IH, UW, WA, and SP contributed reagents/materials/analysis tools. PK, ML, and SP wrote the paper.
The authors have declared that no conflicts of interest exist.
Microarray technologies allow the identification of large numbers of expression differences within and between species. Although environmental and physiological stimuli are clearly responsible for changes in the expression levels of many genes, it is not known whether the majority of changes of gene expression fixed during evolution between species and between various tissues within a species are caused by Darwinian selection or by stochastic processes. We find the following: (1) expression differences between species accumulate approximately linearly with time; (2) gene expression variation among individuals within a species correlates positively with expression divergence between species; (3) rates of expression divergence between species do not differ significantly between intact genes and expressed pseudogenes; (4) expression differences between brain regions within a species have accumulated approximately linearly with time since these regions emerged during evolution. These results suggest that the majority of expression differences observed between species are selectively neutral or nearly neutral and likely to be of little or no functional significance. Therefore, the identification of gene expression differences between species fixed by selection should be based on null hypotheses assuming functional neutrality. Furthermore, it may be possible to apply a molecular clock based on expression differences to infer the evolutionary history of tissues.
Analysis of differences in gene expression between primate species suggests that the majority of them are selectively neutral and likely to have little or no functional consequences.
Advances in microarray technology have made the systematic study of expression levels of thousands of transcripts possible. This has been heralded as a major step forward in understanding the function of genomes, since transcript expression levels are expected to correlate with biological functions. Although this is clearly the case for many genes that change their expression in response to environmental stimuli (e.g.,
To test whether this may be the case, we have investigated whether a neutral model can describe transcriptome differences observed among primate and mouse species as well as among various brain regions within a species.
If the majority of evolutionary changes are caused by historical accidents rather than by natural selection, they will accumulate mainly as a function of time rather than as a function of morphological or behavioral change of organisms. Applied to transcriptome evolution, a neutral model therefore implies that the rate of transcriptome change is proportional to time. In particular, if we assume that mutations cause changes in the relative amounts of transcripts independently of the absolute expression level of the gene, then the squared difference of the logarithm of the expression level is expected to increase linearly with divergence time (
Average expression differences within and between primates in brains (A), in liver (B), and for genes in brain for genes with high (red) and low (blue) variation among six humans (C). Colors: red, comparisons between and with humans; blue, comparisons between and with chimpanzees; purple, comparisons between humans and chimpanzees; orange, comparisons between orangutan and rhesus macaque; black, comparisons between experimental duplicates. Vertical error bars for expression indicate 95% confidence intervals calculated by 10,000 bootstraps over genes. Divergence times are according to
Since oligonucleotide-based microarrays are sensitive to DNA sequence differences and the orangutan and rhesus macaque genome sequences are not yet known—so that we cannot delete oligonucleotides carrying mismatches between the species—we used arrays containing around 28,000 cDNAs ranging in length from 500 to 1,500 nucleotides to assay gene expression patterns in the prefrontal cortex of six humans, five chimpanzees, five rhesus macaques, and five crab-eating macaques
Colors and symbols as in
In a recent study of gene expression in the brains of humans, chimpanzees, and orangutans, we found that the rate of expression change on the human lineage has been larger than on the chimpanzee lineage (
The clocklike accumulation of expression differences between species observed for primates is in agreement with the recent observation that differences in gene expression are consistent with phylogenetic relationships among
In addition to the clocklike accumulation of evolutionary changes, the neutral theory states that the same forces determine the rate of evolution both within and between species (
We further considered the correlation between the average diversity within humans and chimpanzees and the divergence between the species for the 2,926 genes. This correlation is highly significant (
To investigate whether gene expression differences accumulate as a function of time also in another group of mammals, we analyzed three mouse species. An advantage in this case is that post mortem artifacts are less likely to influence the results than in the case of autopsy material of humans and great apes. We determined differences in gene expression levels for around 9,000 genes in the frontal cortex of six outbred
Average expression differences within and between the mouse species (A) and for genes with high (red) and low (blue) variation among
One way to test whether gene expression differences between species accumulate at a rate consistent with neutral expectation is to compare them to the expression differences observed for a class of genes that can reasonably be expected to not be the direct targets of positive or negative selection. Since expressed pseudogenes do not produce any functional gene products, they can be viewed as such a class of genes. Thus, if a substantial proportion of intact genes accumulate expression differences faster than pseudogenes, this would indicate that they are positively selected. Such an observation would falsify a neutral model.
To test this, we considered the expression patterns in four regions of the brain in three humans and three chimpanzees using the Affymetrix U95 array set interrogating approximately 40,000 genes (Philipp Khaitovich, unpublished data). In order to identify all probe sets on these arrays that interrogate expressed pseudogenes, we aligned the probe sequences, as well as published lists of human pseudogenes, to the human genome (
We compared the distributions of the squared differences between the mean expression levels of each gene in humans and in chimpanzees for the 23 pseudogenes and 12,647 intact genes for each of the four brain regions. In each case, only the genes detected in a given brain region were used for the calculation. In all four brain regions the distribution of expression distances among intact genes did not differ significantly from that among pseudogenes in either a Kolmogorov-Smirnov test or a Wilcoxon rank sum test. These tests would have been significant if more than 5% (1/23) of the genes had a distribution radically different from that of the pseudogenes. When the data for four brain regions were combined, no visual difference between the two distributions was apparent (
(A) shows the distributions of expression divergence between humans and chimpanzees for intact genes and pseudogenes. (B) shows the distributions of the ratio of expression divergence between humans and chimpanzees and expression diversity within humans for intact genes and pseudogenes.
Thus, we failed to detect any significant excess of intact genes that diverged faster in expression than pseudogenes. This indicates that the fraction of gene expression differences between the species that are fixed by positive selection is small. Interestingly, there was also no detectable excess of intact genes that diverged slower than pseudogenes. This may seem unexpected, since the expression of many intact genes might be thought to be stabilized by negative selection and therefore to change more slowly than pseudogenes. This may indicate that purifying selection as well is a weak force affecting gene expression. However, it should be noted that the small number of expressed pseudogenes analyzed limits the power to detect positive and negative selection. A targeted effort to study expressed pseudogenes in closely related species would be a worthwhile undertaking.
The fact that the overall accumulation of expression differences conforms to a selectively neutral model does not mean, of course, that all expression differences between species are selectively neutral. As for nucleotide changes, some changes in gene expression will have had phenotypic consequences and some of these will have become fixed due to positive selection. To identify such gene expression differences, we propose to use the ratio of divergence between species to diversity within species, akin to the tests suggested for quantitative genetic traits (
Since we are unable to tease apart genetic and environmental contributions to expression diversity, we instead used pseudogenes to estimate the distribution of divergence to diversity ratios observed in the absence of selection and compared these ratios to intact genes. No significant difference was found (Kolmogorov-Smirnov test,
Different anatomical brain structures appeared at different times during vertebrate evolution. These time points can be viewed as divergence times between brain regions extending millions of years back in the past (
(A) Schematic evolutionary tree for six human brain regions: B.44, Brodmann's area 44; PFC, prefrontal cortex; ACC, anterior cingulate cortex; PVC, primary visual cortex; CN, caudate nucleus; and CB, cerebellum. Numbers indicate approximate divergence time in millions of years (
(B) Average expression differences among brain regions in humans (red) and in chimpanzees (blue).
(C) Average expression differences among brain regions in
If gene expression differences between the brain regions were largely adaptive, one would expect them to correlate with tissue function and not with evolutionary divergence time. Our data show that tissues that diverged recently have very similar gene expression profiles irrespective of the differences in function. For instance, the transcriptome of Brodmann's area 44 in the left hemisphere (Broca's area) is very similar to that of the prefrontal cortex in both humans and chimpanzees, although it is known to be involved in speech processing in humans while it must have another function in chimpanzees (
A noteworthy finding is that the accumulation of expression differences between brain regions within a species is much slower than the accumulation of expression differences within a brain region between species. In fact, the expression differences that have accumulated among the primate species over 20 million years (see
A possible alternative explanation for the correlation between differences in gene expression and evolutionary divergence time among brain regions could be that differences in gene expression do not correlate with evolutionary divergence time, but instead with divergence time during fetal development. Our observations would then result from the fact that both developmental divergence times and expression differences correlate with evolutionary divergence. A correlation between developmental and evolutionary divergence times has been hypothesized before (for a review, see
We show that a neutral model of evolution can predict the main features of transcriptome evolution in the brains of primates and mice. A neutral model is also in agreement with published observations in
Finally, the finding that gene expression differences can be used as a molecular clock to date tissue divergences opens the prospect of reconstructing the evolutionary history of organs and tissues based on gene expression measurements in a single species.
For the primate samples, approximately 200 mg of gray matter was collected from post mortem brain samples from prefrontal cortex region corresponding to Brodmann's area 9 in the left hemisphere from six male humans who were 45, 45, 63, 65, 70, and 70 years old; five male chimpanzees that were 7, 12, 12, 12, and approximately 40 years old; one 16-year-old male orangutan; five approximately 10-year-old male rhesus macaques; and five approximately 15-year-old male crab-eating macaques. All individuals had no history of brain-related diseases and suffered sudden deaths without associated brain damage. For the mouse samples, approximately 50 mg of gray matter was collected from the frontal cortex regions of six
For Affymetrix microarrays, labeling of 5 μg of the RNA, hybridization, staining, washing steps, and array scanning were carried out following Affymetrix protocols. Expression data were collected using Affymetrix HG U95Av2 arrays for the primate samples and Affymetrix MG U74Av2 arrays for the mice samples. The Affymetrix CEL files containing expression data for the different regions of the mouse brain, including amygdala, cerebral cortex, hippocampus, hypothalamus, cerebellum, olfactory bulb, and two regions of spinal cord were provided by John Hogenesch.
Arrays containing 51,000 cDNAs corresponding to approximately 40,000 UniGene clusters were manufactured in the laboratory of W.A. as described elsewhere (Anonymous 2003). Labeling, hybridization, staining, washing, and array scanning were carried out as described by
In order to exclude all oligonucleotide probes that did not match perfectly between humans and chimpanzees, we aligned all Affymetrix target sequences (
Affymetrix microarray image data were analyzed with Affymetrix Microarray Suite v5.0 using default parameters. Arrays were scaled to the same average intensity using all probes on the array. Detected genes were defined as those with a detection
We measured the divergence between human and chimpanzee by looking at the squared difference between the mean expression values in humans and chimpanzees. This estimate of divergence includes the errors in our estimates of the two means, which is proportional to the variance in each of the species, and thus to the diversity in each species. Therefore, even if no correlation between divergence and diversity existed, our measured divergence and diversity estimates would correlate, and the smaller the divergence is relative to diversity, the stronger the correlation would be. To estimate if the observed correlation is larger than that expected from this effect alone, we performed a randomization test, in which we computed how much correlation between diversity and divergence would be generated from the above effect even if no correlation between diversity and divergence exists. To be conservative, we first generated a distribution that deliberately underestimated the real divergence between humans and chimpanzees. This was done by first generating a distribution of the expected observed differences (X) in gene expression between humans and chimpanzees if the real divergence is zero. Then using this distribution and the observed distribution of differences (Z), we generated a distribution (Y) that-added to values from X-would give Z. In order to underestimate the divergence, we generated Y assuming that the correlation of X and Y is one. We then generated random samples in the following way: For each gene (g), we chose a random difference of expression (d) from our generated distribution. We then drew six samples from a normal distribution whose mean is zero and whose variance is the diversity in humans for gene g, and three samples from a normal distribution whose mean is d and whose variance is the diversity of chimps for gene g. For these expression values we then calculated the correlation between diversity and divergence. We repeated the whole procedure 1,000 times. None of these randomizations generated a correlation that is as strong as the observed one. To make sure that the whole test is conservative, we generated 100 datasets of three types, all of which had a similar diversity, but had a "real" divergence distribution of (1) zero, (2) the underestimated divergence, or (3) the measured divergence, and had uncorrelated diversity and divergence. We then performed the whole test described above, doing just one randomization test. If the test was not conservative, one would expect the correlation in the dataset to be higher than the correlation after randomization in 50% of the cases. Instead, the correlation after randomization was higher in 98, 98, and 99 cases respectively-showing that our test is indeed conservative.
We retrieved sequences of all pseudogenes as determined by
We thank M. Przeworski for helpful discussions and critical reading of the manuscript, M. Leinweber for help with microarray data analysis and Jun Li and M. Donaldson for providing critical insights into the permutation test. This work was supported by the Bundesministerium für Bildung und Forschung and the Max Planck Society.


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Tag Archives: capacity
Odd and inconsistent product descriptions
We highlight an oddity in Waitrose product description and pricing, recently picked up in an article on msn. And no, this is not a belated April fool story. Likes(30)Dislikes(16)
Posted in Consumer affairs Tagged capacity, empty, full, jam, jars, mass, volume, Waitrose 11 Comments
The curse of conversion factors
In this article, Ronnie Cohen looks at lists of plausible conversions in both directions between imperial units still in use in the UK and metric units. Likes(1)Dislikes(0)
Posted in Consumer affairs, Education, General, Media, Road signs, Technical Tagged area, both, capacity, combination, combinations, conversion, conversions, directions, energy, factor, factors, length, mass, power, pressure, table, tables, temperature, unit, units, volume 29 Comments


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Zebra is our series of two-stage rotary vane vacuum pumps for medium vacuum. Busch also offers proven technology for higher vacuum levels: the Zebra series two-stage oil-lubricated rotary vane vacuum pumps for the fine vacuum sector.
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