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A Q&A with Caleb GrimmEdit
I was born and raised in Sioux Falls, South Dakota
Somehow I've been lucky enough to avoid any embarrassing nicknames. My family calls me "kaygup " a lot. In high school a lot of people called me "Grimmy."
Describe yourself in 5 words or less:
Passionate, Loyal, and Driven
Favorite Bible verse/passage:
Philippians 4:13 "I can do all things through Christ, who strengthens me." That's tough to beat.
Childhood hero?
My older brothers, Scott and Micah. I wanted to be just like them. I still do.
Best advice from Mom or Dad that still is with you today?
When I was younger, anytime I'd leave the house, my mom would remind me, "Remember who you are and remember WHOSE you are." I still think about those words all the time.
What do you know now that you wish you knew 5 years ago?
I only have to be good at being me. I don't need to act/look/sound like anyone else, because God has made me a distinct individual with different gifts and talents. Once I realized that, I didn't have to measure myself by others and things started to come easier for me.
Who do you consider to be your greatest musical influences?
Gavin DeGraw, Justin Timberlake, Jody McBrayer, Billy Joel and my brother Scott Grimm
Who did you imitate singing when you were a kid?
Justin Timberlake
What artist(s) would you love to collaborate with someday?
I've always secretly dreamed of recording with Kelly Clarkson. Her vocals are stunning. I'd also love to collaborate with writer/producers Max Martin or David Foster.
What is the most embarrassing song or album on your iPod?
Probably the My World albums by Justin Bieber. Let's be honest...he's got game.
What's the first album you remember buying?
Avalon's In a Different Light. I listened to that album from front to back probably a hundred times.
What is one of your all-time favorite TV shows and why?
Friends. The premise of the show is six best friends sitting around a coffee house talking about life, and that's easy for me to relate to. Not to mention it's hilarious.
Favorite movies?
I'm a big Alfred Hitchcock fan (Vertigo, Rear Window, Psycho). I love thrillers with a lot of twists. I also like dramas and any movie involving a Marvel superhero.
Favorite sports teams?
Dallas Cowboys and Oklahoma Sooners. I'm an NBA fan too, but I don't really have a favorite team.
Beverage of choice?
Diet Dr Pepper is the best drink ever. I also drink a lot of coffee. Like...a lot.
Favorite breakfast cereal(s)?
I'm a firm believer that cereal is good to eat at any time of the day, not just for breakfast. I typically like to switch it up every time I go shopping, but I tend to lean toward flakes of some sort (Corn, Frosted, Grape-nut, etc.)
Favorite late-night snack(s)?
Popcorn. It has to have real butter or movie theater butter on it though. Otherwise, it's no good.
Who do you recommend people follow on Twitter?:
I recommend @CSLewisDaily [1]. They post quotes from C. S. Lewis and his books. They're always really challenging and thought-provoking. If you weren't in Anthem Lights, what might you be doing?
I'd be doing music in some other capacity. If I weren't doing music, I'd be a writer.
Biggest strength besides singing or unusual talent?
I'm a pretty committed person. If I'm passionate about something, I'm determined to see it through to the end.
What's a little-known or fun fact about someone else in Anthem Lights that people should know?
Chad is a dominant fantasy football player.
Anything else you'd like to share about yourself?
Playing LEGOs was my favorite childhood pastime. As a kid, I used to collect almost everything. Baseball cards, stamps, rocks...you name it, I collected it. I play fantasy football religiously. I can't watch TV shows or movie series out of sequence.

subset: commoncrawl


text:
Mine is Abbey Road, mainly because my mum had it on vinyl and up until then I'd only really listened to compilation tapes of their stuff, never a proper body of work. I also love rubber soul and Revolver, Fantastic albums. The earlier stuff I don't really care for, although there's some classics hidden in there.
Also obligatory:


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Business & Finance
answered questions
Parent Category:
This category deals with all questions about unemployment: statistics, how you deal with it, and eventually how to rise above it.
Unemployment Benefits
Unemployment Extensions
Is it possible that you can be granted sole custody if your boyfriend provides more care because he is unemployed so he has more time with child?
Yes. It is possible you can be granted sole custody. An unemployed father is not necessarily the best person for a child to live with. You need to consult with an attorney who specializes in custody issues and can review your situation and explain your options. In the US an unmarried mother has sol…
Popularity: 19
What was the unemployment rate in Chicago in the 1930s?
The Census Bureau's Regional Fun Facts page for the Chicago region notes the unemployment rate for each year from 1900 to 1999. It is located at the Related Link below.
Popularity: 124
Can you receive unemployment benefits based on employment in another state?
Yes, at least in Oregon and New Jersey. Go to the unemployment office and ask about it.
Popularity: 1
If you were laid off and getting unemployment in Wisconsin can you collect unemployment from Wisconsin while searching for a job in another state?
YES, but if you do start a new job, ANYWHERE, you have to notify the state office that you are working and the exact date you started working again and where you are working. If you don't notify them, and continue to accept payment, you are committing a felony fraud.Jim Bunting. Toronto. Canada.
Popularity: 37
If you are unemployed and want your car voluntarily repossessed in Texas what dollar charges do you face?
You "face" the unpaid balance due on the loan. PLUS repo fees, attorney fees, auction fees, fees fees, ect. TRY your best to sell the car even if you have to borrow some money to complete the payoff. It will be MUCH cheaper than any repo.<><>You also face the long-term consequences of a …
Popularity: 52
If you cosigned for your ex and he is unemployed will Ford garnish your wages?
MOST LIKELY...they go where the MONEY is. Would CU ignore this?": Ask THEM.
Popularity: 42
Can you collect disability insurance while recovering from surgery if you have been working for 35 years but are currently unemployed?
That would depend if you live in a state that provides disability insurance.The type of disability insurance would also depend on the seriousness of the surgery, i.e. is it short-term, work injury related (workers comp); longer term, permanent (SSDI); private insurance (depends on the insurance poli…
Popularity: 132
Can you collect disability while on a trial medication for kidney cancer?
If you meet the policy defintions of being disabled.Broadly, there are two main policy definitions of "disability" found in policies. The first is an "any occupation" definition, which essentially requires the insured to be unable to perform any job for which he/she is suited by knowledge, skills an…
Popularity: 128
If you still have not been released by your doctor can you be denied continuance of claim?
What state are you in? How long has it been since you changed plans or the MD quit the Network? What is the medical condition? Are you disabled? I think it's a different "term" that we are looking for in your question.Here's an answer that says 3 months.http://www.firstcare.com/ers/2004/custserv/mhb…
Popularity: 58
How much is reasonable to pay for a fiberglass or vinyl pool in upstate New York from excavation to swimming?
low to mid 20's should get you swimming w/a 4ft. deck around the pool and the site graded.All is dependant on how big and the site and the xtras(auto cleaners etc.) The figure should be good for an 18x36ft. pool 3x5ft. deep on a reasonably flat lot.
Popularity: 173
What was the solution for unemployment after World War 1?
There was unemployment on a very small scale in the United Kingdom during world war one. Even though most of the men were away fighting and the women were in the factory or in clerical jobs, there was unemployed due to a vast number of reasons.
Popularity: 74
How much will you have to pay for a 74 in a 55 zone in Ca?
72 in a 45 cost me 115.00 on 2/06
Popularity: 40
If someone marries someone who is here with an expired visa will they need a co-sponsor to get a green card if the citizen is unemployed?
The citizen has to sponsor n is always the primary sponsor but, yes, co-sponsors are allowed.
Popularity: 61
Could an illegal immigrant who married a US citizen be deported if he files the i-485 and the INS sees he's illegal?
It depends on how the immigrant entered the U.S. If they entered legally, then no they do not have to leave the country. However, if they entered ilegally, they would have to their country of origin. What will happen here: Since you filed an i-485, I imagine that you have a lawyer (stupid not to hav…
Popularity: 35
How do you answer 'What do you know about our company' in a job interview?
The WORST thing you can say is "Not much." or "Nothing." RESEARCH the company first. Yep, whether you are applying at McDonald's or applying at a Fortune 500 Company. Do a search online. Look at their website. Find out who they are, what they do and why you'd want to work there. The WORST thing you…
Popularity: 42
Does your husband no longer have a credit history if he has been unemployed for 10 years even though you have joint credit accounts?
If you have joint accounts that have been open and active in the past 7-10 years, your husband has a credit history. Credit history has nothing to do with the status of his employment.
Popularity: 34
What do you do when your Chapter 13 is dismissed due to job loss?
%REPLIES% Answer Refile in 180 days. Answer In Indiana you don't need to wait 180 days unless your case is dismissed "with prejudice," which is rare. You can normally re-file immediately after dismissal as long as the court doesn't think you're acting in bad faith by doing so. Please no…
Popularity: 43
Can an H1B sponsored employee file for personal bankruptcy without involving the sponsoring company?
Yes. Personal banruptcy does not relate to the company where the person is employed.
Popularity: 88
If a person files Chapter 7 in 2000 and it was discharged how long to they have to wait to file a Chapter 13?
There are no time limits for filing a Chapt. 13.
Popularity: 36
In California after you have filed bankruptcy how long do you have to wait before you can file again?
One generally cannot file a Chapter until 6 years from the filing date of any previous Chapter 7 or Chapter 13 that received discharge. So, one usually has to wait 6 years after any previous case to file a Chapter 7, but can usually file a Chapter 13 anytime so long as no other case is pending. Plea…
Popularity: 46
Can you cosign for someone on a mortgage loan while unemployed?
As a co-signer you are taking responsibility for the loan if the signer defaults. If you are unemployed, why would you want to expose yourself to that risk?
Popularity: 104
What can you do if you are homeless and jobless but if you give your car up you will never find a job?
Answer VERY good question. Very realistic. How much intestinal fortitude do you have?? The odds get MUCH worse after you give it all up. To be honest, not very many ever get back up after that happens. Life gets much simpler then. Where do I eat today? Where do I sleep tonite? Your appearance goe…
Popularity: 43
How do you account for any time of unemployment on your resume?
Include a simple explanation for the gap, eg. full-time student, maternity leave, etc.The unemployment office would like you to earn some money before you find a full time position whatever it is you did. Work part time at a retail store or work temp agencies. You can't just stay at home and do noth…
Popularity: 59
What were the effects of the Great Depression during the 1930s?
The Great Depression (1929-1940) was a worldwide economic contraction which brought about economic hardship and in some nations, political instability. In the United States a general banking failure brought about increased government regulation of the financial sector along with the broadening of th…
Popularity: 29
How do you tell another job why you quit your last job?
It depends but I'd suggest to always speak truth to avoid issues. Well I am currently working in studytubes.co.in from last 8 months and I left my last job for betterment.
Popularity: 55
How do you answer 'Why did you choose this company' in a job interview?
The company doing the interview wants to know why you are applying for a job with them. They are trying to find out if you are submitting resumes everywhere or if you have a particular interest in their company. s like you want to work for the best company or you have heard they are on the leading e…
Popularity: 90
How does immigration to the USA affect the unemployment there?
One opinion: There are an estimated 20 million illegal immigrants in this country. They don't just pick tomatoes anymore. They have started taking over our middle jobs as well. A Mexican came over here from Mexico 9 years ago. It started slowing down. He got laid off a couple months later he gets c…
Popularity: 104
If your fiance is transferred out of state can you get unemployment if you quit to move there too?
The rule is this: If you were married it may be different. The point is that this is not absolute, and you may apply in any case. You can quit in some circumstances and receive UI benefits.
Popularity: 122
If you get a raise or another part time job while paying off a chapter 13 can they increase your payments each month?
YES, of course they can, by applying to the court for a "change of income " ruling, and a new judge's order to increase your payments per month, based on your new level of income. They will use the payroll records at the job to argue for an increase in your payments.
Popularity: 23
How do you answer 'How will you contribute to this team or job' in a job interview?
The employer wants to know how you will benefit the company on a business and financial level, as well as how you would "fit" into the team in a social way. If you've done your homework on this company, you can demonstrate how your strengths are a great fit for the position and how you will benefi…
Popularity: 93
What are your rights if you were laid off and after 3 weeks you moved and quit a job to take this job?
Answer If you mean can you get compensation from an employer who lays you off after only 3 weeks, in most cases the answer is no. It's called employment at will, and basically says an employer can fire or lay you off anytime they want to, without any reason. It's a bad deal, but the only thing yo…
Popularity: 111
Was the unemployment rate different between social groups in Chicago in the 1930's?
Unemployment was much higher for the poor in 1930s Chicago. Those in white collar jobs lost many positions, but there was simply no work for the laborers to do.
Popularity: 15
Could you get unemployment benefits if you quit your job to move to another state?
Answer: The US Dept. of Labor says that you must be unemployed Through no fault of your own and that is determined by particular State laws. Depending on that state law, to quit to move somewhere else is not "through no fault of your own". Some states do allow unemployment benefits if you quit for…
Popularity: 88
Can you collect unemployment if you are moving to a different state?
One opinion: Actually you can. I just moved from California to Colorado and EDD interviewed me again, but I still qualify for it. I explained that I could not find work where I was. Transfers: Also, I am pretty sure you can transfer the benefits. IE: if you start your claim in California and then mo…
Popularity: 53
Can you lease a car if you are unemployed?
Leasing requires income. A financial institution/leaser will likely turn you down if you are unemployed. You can try, it never hurts. I believe tht too. Leasing of a car requires your income statement and SSN. If you are not working probably you wont have any income tht month or months. But there …
Popularity: 53
Can you run Battlefield 2 on high graphics with an ATI Radeon 9550 and get a good frame rate?
the card is too oldno sorry you cant but you can put some of the graphics options on high.This card graphics card is getting very old but it still runs all thegames at the moe. I hope you did not buy this card in the last yearbecause its 4 years old now. u cant realy play this game if u have only 1…
Popularity: 39
Why do you want to work in a call center?
I want to work in a call center because of various benefits like: No Experience Needed High Income and Rewards Enhance Your Skills Get Promoted in Less Than 6 Months A Great Team To Work With Dress Code Low Work Volume Go4Customer is one of the best call centre which gives best employee…
Popularity: 58
Can you collect unemployment if you move to another state and have not found a job yet?
2009- taken from ehow.com -Scrivener answered the same question in the Related Link below. You must be approved in the state you were laid off in and the benefits will continue to be paid from that same state. Yes, it may differ state to state so I would check your states department of economical s…
Popularity: 111
What is the government doing to prevent the increasing number of unemployed people in the country?
Nothing. Anything they try to do will only increase it more. But advertisers sponsors and government corruption agents get lot out of these green garden schemes and strategies
Popularity: 5
If you got hurt at work and your employer offers you a job that you can do can you refuse the job being offered and still collect workmens comp?
Yes, if your doctor says that you are unable to perform the job being offered. Also, you cannot be fired or stop receiving workers comp for being unable to do the job.
Popularity: 5
What do you do if you move to a different state while receiving unemployment?
Because the states belong to the federal Interstate Benefit Payment Plan, all you need to do is contact your state's unemployment office with the details and they will process the claim. See the Related Link below.
Popularity: 29
Can you receive unemployment benefits if you quit your job?
Unemployment Comp if I quit my jobYou do need to check with your state's Dept of Labor and find out their rules. However, an individual may sometimes receive unemployment if they quit their job for good reasons. In Michigan, it may be allowed if the employee quit for "good reasons directly attributa…
Popularity: 16
Can you collect unemployment if you work in another state?
It is legal to collect unemployment if you work in one state and live in another. The question is, where to you collect unemployment? In which state would you file? For further information, see the Related Link below for an example of Texas' laws.You would file a claim in the state you worked.
Popularity: 19
What is the length of time that you can receive unemployment benefits?
The length and amount of benefits available varies by state and prior wage of the unemployed person.
Popularity: 16
Can a person receive disability insurance benefits when they are unemployed?
There's always unemployment insurance. For CA see the link below. If the query is in regards to Social Security Disability benefits, all necessary information concerning eligibility and filing (including down loadable forms) can be found on the related link below. Another thing to consider is, if y…
Popularity: 62
What causes unemployment?
Unemployment is caused by economical collapse, such as the Great Depression of the 1930's. Since Supply & Demand is the sole factor on the economical scale, if items are not sold or bought within a country, then that country will literally close businesses since nothing is being purchased and wo…
Popularity: 43
What are the causes of unemployment?
Unemployment can be caused by many things. Loss of employment can come from layoffs due to down sizing, or tough competition for job openings, as well as a candidate being overqualified.
Popularity: 3
How do you answer 'Why do you feel you will be an asset to the company' in a job interview?
You could say that you feel you will be an asset to the company by stating why in an interview. You cannot get this question wrong.
Popularity: 6
How does illegal immigration affect unemployment?
the immigrants take job spaces that would otherwise go to legal workers, in exchange for cheap labor.
Popularity: 2
What should you do if you have 70K in credit card debt and a house that is not paid off and your spouse is unemployed?
It would appear that the person's options are limited.Refinancing the home if one could get a lower payment and interest and perhaps cash out could be considered but that could prove difficult given the circumstances.There are debt consolidation and other such agencies, but one must be extremely cau…
Popularity: 49
How do you answer 'Why did you leave your last company' in a job interview?
Whatever you answer, always turn a negative into a positive. You could say you left your job due to lack of job advancement, want to provide a better life for yourself and/or family, want better pay benefits. Ask yourself -- why did you leave your job in the first place. All about common sense and h…
Popularity: 31
What do you do if you are unemployed and can't pay your credit card?
The credit card company will report the incident to the credit bureaus and you cost of credit will go up. You will be referred to a collections agency if the amount is large enough. This is a very bad path to start down. You may be able to negotiate with the credit card company for a settlement if …
Popularity: 17
How do you answer 'What are your expectations from the company' in a job interview?
The best way to answer this type of question is to frame your response as if you were already part of the company team. The key word here is "team," because you want to convey the strength of your ability to achieve team or company goals and fit within the company culture. In this regard, please do …
Popularity: 74
What is the unemployment and poverty rate in the US?
i dont know ask ur stupid mom or teacher
Popularity: 0
In the state of Georgia can you collect unemployment benefits for the week you will be unable to work following surgery for a workman's comp claim?
No you can not. You will not be eligable for unemployement. There is a 7 day waiting period until your WC benefits kick in but once you are out for 21 days, WC will go back and pay you for the first 7 days you were out.
Popularity: 3
Can you work part time with light duty and still qualify for workmen's compensation benefits?
Maybe.State's establish laws and regulations for WCI, so it would depend upon the laws in the state in which worker lives or was injured.If the treating physician gives you restrictions,you can only work within them on any job as long as employer accepts them.
Popularity: 15
Are employees allowed to draw unemployment if company files bankruptcy?
Answer In bankruptcy, a company is obligated to pay employees and other labor first. Contract labor and suppliers fall in line somewhere after that. If the company is able to stay in business, the employees shouldn't be affected too much unless the company just can't support that many employees, …
Popularity: 10
How do you answer 'What do you expect from this company' in a job interview?
The employer wants to know what they can offer YOU. After you've told what you can do for the company, the company wants to know what can be done for you. Do you want to work alone? In a team setting? Do you want to be motivated? Do want to work upstairs/downstairs? They basically want to know what…
Popularity: 53
If you were laid off in Florida can you still collect unemployment benefits if you move to Illinois?
The Unemployment Compensation provisions have undergone many changes through the years; and, the procedures for qualifying for eligibility have been revised as well, varying in one manner or another from state to state. The best resource you have is the local unemployment office for the state in whi…
Popularity: 15
What is Ethiopia's unemployment rate?
According to the article in the Related Link below (as of 11/19/10) Ethiopia is estimated to have an unemployment rate of about 50% for 15 to 30 year olds, among the highest unemployed in the world According to the CIA's World Factbook, the 2011 estimated unemployment rate for Ethiopia was 18%. T…
Popularity: 64
How can you get a car loan when you are currently unemployed?
Cant. Cars dealers want at least the last two month of paystubs from the last two years of the same type of work, not necessarily the same place. If you were a painter in one place for a year and went to work as a painter somewhere else that would be ok. If you were a painter one year and then went …
Popularity: 13
Can you collect disability benefits right after you have collected unemployment?
Answer Certainly depends on the specific coverage your speaking of (and some private coverages may cover short periods of unemployment after certain qualifying periods of working in a field), but one basic premise of disability insurance is the disability is keeping you from doing a job that you …
Popularity: 13
Can you collect unemployment benefits from Connecticut if you move to New York?
If your most recent employer was in CT, and your employer paid unemployment taxes to the state of CT during that employment, then yes, you can collect benefits from CT while residing in ANY state in the US. Check your W-2 statement, and if your employer's state EIN is listed as CT, you're set.
Popularity: 5
What is the relationship between inflation and unemployment?
There has been an inverse relation between rate of inflation and the rate of unemployment in an economy. The more the entrepreneur extends the employment opportunity the more he has to pay to that particular factor of production and the more payment to factor of production the increase in the cost o…
Popularity: 51
Can you still collect unemployment if you have a part time job working 12 hrs a week?
State law varies, but in RI you CAN work part time and collect a portion of your full benefits.
Popularity: 17
What was the unemployment rate in the US during 1939?
17.3 %, according to the Related Link below. .
Popularity: 13
If you were laid off in Texas can you move to another state and collect unemployment benefits?
If you qualified, you can collect unemployment from Texas, the "liable state", but not from the state you move to.
Popularity: 0
If you were on unemployment and went to work for three weeks can you quit and go back on unemployment?
Answer You can't get unemployment when you quit a job. You can only receive benefits if you lose your job through no fault/decision of your own.
Popularity: 10
Is it true that in the calculation of nation's unemployment rate un-employees who stopped receiving unemployment benefits are not counted?
This is true, so the rate being thrown around is very misleading. This was made a big "talking point" in the 80s when they were also trying to downplay the recession, but I am not sure what the proper references are, although I used to. After unemployment runs out or if people change to "self-employ…
Popularity: 19
What should you do if you are 49 and unemployed?
You should network with no shame in any field you would like to work. Additionally, consider using the Related Link below but be aware this isn't 1999 anymore; 50 applicants are applying for 1 job on Monster these days and it is very possible the employer already has a person in mind for that job. I…
Popularity: 19
What is the percent of poor people unemployed?
As of 09/18/2014, the Bureau of Labor in the United States determined that the average unemployment rate is 6.1 percent. This percentage has not changed much in the past 30 days.
Popularity: 2
Can you draw unemployment if your on sick leave for going through inpatience center?
You cannot draw unemployment if you are on sick leave. You are technically and legally still employed. You may be entitled to sick pay though.
Popularity: 1
What is the result of a recession on unemployment compensation?
A recession can bring an increase of unemployed workers. This results in more unemployment compensation claims being filed and paid, meaning more people are collecting unemployment benefits.
Popularity: 2
How do you answer 'How will you contribute to our company' in a job interview?
tell them you will do your best and your talets offer alot to the company say that you can relate to people and do whatever needs to be donetell them about your strenths and weaknesses but dont say im horrible at this , this and this adress your weakness and say that you wont let your weakness get i…
Popularity: 19
How did Hitler use the problems created by inflation depression and unemployment to help him become dictator?
After the end of the First World War, political parties that came into being in Germany decided to reform German polity. This gave birth to the German Weimar Republic. However, following the signing of the Treaty of Versailles, Germany was forced to pay reparation in the form of money. When the gold…
Popularity: 12
Why did Italians come to America?
Italians like all other European immigrants came to America looking for a better opportunity in life. Specifically, they came for better economic opportunities.
Popularity: 0
What happend during the Great Depression?
Durring the great depression, the economy failed and people lost everything. Most characteristics during the great depression was the widding gape between the "haves" and "havenots". There was also alot of buying on margin or installment buying which was using "fake" money.
Popularity: 1
Why does unemployment cause illnesses?
I don't think that it causes illnesses but mostly mental deseases..
Popularity: 2
Can you collect unemployment compensation for quitting a job due to stess i have been accused of breaking a slicer which i didn't do i thought it was all settled but it keeps getting brought up?
No, you cannot qualify for unemployment for VOLUNTARILY leaving a full-time job.
Popularity: 1
What fiscal policy would cure high inflation and high unemployment?
A fiscal policy that focuses on job creation would cure high inflation and high unemployment. Implementing projects like road and bridge construction would improve employment rates.
Popularity: 4
Can you collect workmens compensation and unemployment at the same time?
Workman Comp and UnemploymentNot in the State of Michigan. Not sure about other states, but I highly doubt you can collect both at the same time anywhere. Addendum: Think about it.... No state in the Union (at least for now) would even entertain a notion of paying unemployment to someone collecting…
Popularity: 20
Can you collect New York state unemployment benefits if you have been receiving a severance?
You can collect unemployment benefits if you have been receiving a severance as well. You can only collect benefits for a certain period of time.
Popularity: 5
Can you collect unemployment while on disability?
Collecting unemployment while on disability depends on the state and the laws. However, in most states, you cannot collect both.
Popularity: 1
Is outsourcing raising the unemployment rate?
In the case of the United States, yes it does. It also contributes to the crisis by allowing the loss of capital, and if the government does not do anything about that, it ultimately could contribute to the downfall of the United States as a worldwide capital power. This should serve as an example t…
Popularity: 28
Can you be penalized for not returning to work after taking disability for maternity leave?
You were paid disability benefits because your delivery was a covered benefit. You were entitled to the benefit because you paid the premium, and your medical condition qualified for a benefit payment. Enjoy your time bonding with your baby. You are in the clear.
Popularity: 0
Is unemployment typically short-term or long-term?
neither... because it really depends on how we look at the data. most spells of unemployment are short. yet most weeks of unemployment are attributable to the small number of long term unemployed. source: Microeconomics by Mankiv
Popularity: 8
Can you receive 100 VA disability and still work full time?
I work at a VA clinic and three employees here work full time and are 100%. (ADDED by McHammer38) There are actually two ways to receive 100% VA disability. One is to be rated 100% based off the severity of your service-connected disability and the other is called Individual Unemployability (IU). I…
Popularity: 9
How long do unemployment benefits last in Illinois?
State unemployment benefits in Illinois last for twenty six weeks. It is possible to apply for an extension in certain circumstances.
Popularity: 0
What are the 4 main negative effects of unemployment?
effects the economy, brings poverty, homelessness, and hunger.
Popularity: 4
How long do you have to be employed at a job in order to be eligible for unemployment benefits in New York?
You had to have worked and be paid wages in at least two calendar quarters of your base period (of one year). Refer to the Related Link below.
Popularity: 2
What communication was there during the great depression?
by using notes and drawings
Popularity: 12
Can a custodial parent seek child support payments from the non custodial parent's new spouse if non custodial parent is unemployed?
No. She has no legal responsibility to support the children. Only the biological parents have any responsibility for child support.
Popularity: 29
Can you collect unemployment if you work part time?
Yes you can collect unemployment if you work part time. Myself and my neighbor are both working part time and we collect it. As long as you don't make too much they will pay you the balance of your weekly amount.
Popularity: 4
Can you collect unemployment and Social Security at the same time?
can you collect unemployment and social security at the same time in the state of Pa.
Popularity: 2
Can a future employer find out if you have collected unemployment?
No, a future employer does not have access to your unemployment records unless you talk about it at work. They cannot use that information to make an employment decision.
Popularity: 1
Can you draw unemployment if you quit your job?
Popularity: 1
Why is full employment not a good thing for the economy?
Full employment is not good for the economy as it may result in an inflationary period where workers have more disposable income and as a result would drive prices upwards. This would take a while to happen though. Also, a lot of central banks base their policies around controlling inflation (The EC…
Popularity: 4
If an unemployment hearing decision in employee's favor are benefits retroactive?
Yes, as long as you continued to call in your claim each week you were unemployed. Even if you were originally denied, filed an appeal and had your hearing; resulting in an overturn of the original decision, you will collect all weeks you were unemployed except for the one week waiting period which …
Popularity: 6
How long do you have to be employed at a job in order to be eligible for unemployment benefits in Rhode Island?
Popularity: 2
How long do you need to be employed to collect NY state unemployment benefits?
26weeks (Half of 52 weeks) NYS Department of Labor web site: http://www.labor.state.ny.us/ui/faq.shtm Q: What employment do I need in order to qualify for benefits? A: To qualify for benefits: You must have worked and been paid wages for employment in at least two calendar quarters in your base per…
Popularity: 3


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The 2008 Honda Civic Coupe once again rides high on its reputation as a reliable vehicle that maintains its edge as sporty and fun to drive.
From the base model's 140-hp, 1.8-liter, four-cylinder engine to the 197-hp, 2.0-liter, four-cylinder engine found in the Civic Si Coupe, the 2008 Civic offers fuel-saving engines and sporting choices.
Car and Driver cites the 2008 Honda Civic Coupe's smaller four-cylinder engine as a bit slow: "You need to wind the engine up to find the power." This is in line with Kelley Blue Book, who says that although the "refined" 140-hp powerplant "never overwhelms you with power…even when you run the tachometer up to its redline you don't feel like you're bullying the car." Motor Trend says this Civic "failed to impress us as energetic." The Si version, however, is the key to enthusiasts' hearts. Its 197-hp engine has an energetic feel, and it motivates the Civic Coupe with authority. "When you slam on the gas the tachometer flies to an 8,000-rpm redline — that's high — and it doesn't feel like it will stop there," Cars.com says of the engine. Edmunds calls it "delightfully fizzy."
A pair of five-speed transmissions is offered on the Civic Coupe, while only a six-speed manual comes with the Si. Cars.com feels the "five-speed automatic mitigates the performance penalty normally associated with combining a small four-cylinder engine and an automatic transmission." They add, "Performance fans who can't work a manual gearbox are shut out of the Si." Car and Driver likes the "slick-shifting five-speed manual" in base cars, but Motor Trend notes, "Further, the Civic lacks a true manual mode -- just Drive, D3, 2, and 1 -- making it impossible to lock in fourth gear and difficult to easily exploit the power."
Fuel economy performance of the 2008 Honda Civic Coupe is just as strong, according to J.D. Power, which rates the Civic Coupe with a fuel economy range of "21 mpg city to 36 mpg highway." According to Automobile, "The real bonus is at the pumps, where the Civic Coupe's estimated fuel economy rates at 26 mpg in the city and 34 mpg on the highway, making it easy on the pocketbook." The latter numbers apply to a Civic with the smaller four-cylinder and a manual transmission; with an automatic, the Civic gets 25/36 mpg, and the Si, 21/29 mpg.
In terms of handling, the 2008 Honda Civic Coupe's performance is, according to Cars.com, "nimble, with tight steering that also adds to the fun-to-drive factor." Car and Driver refers to its "somewhat sporty driving experience" in base versions. Edmunds praises how in the 2008 Civic, the "suspension, steering and brakes all work together seamlessly" and calls "even the mainstream models…somewhat sporty to drive." It goes on to note that the 2008 Honda Civic Si provides "nimble handling"; the Si, it says, "is one of the few cars available in any price range that makes you want to drive it just for the sake of driving." Cars.com wraps up its review of the 2008 Honda Civic Coupe by declaring, "The Civic still rules -- in statistical categories as well as in the real world of commuting and soaring gas prices."


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GN Photos Photographer
lexusbrookeModel Female Elizabethton, Tennessee, US
My Website: Facebook
Mayhem # 2794913
About MeHello! I'm a Alexis a 19 year old Tennessee girl. I am very interested in modeling it's a passion of mine. I am interested in all types of modeling, but I am not accepting any offers for nude work. I am very interested in underwater modeling. I swim like a fish and believe it's a very beautiful genre of modeling. I have big eyes and really pretty teeth, that's what most people compliment me on as well as my long legs and pretty tan. I'm a very competitive person and i work hard to reach my goals. I strive to do my best at whatever I am given the opportunity to accomplish. Please contact me if you're interested in working with me. I look forward to building my portfolio with you to explore an exciting career as a model!
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Need a Fertility Test in Gustine, CA? Simply order online 24/7 and get a fast, affordable Fertility Test at a lab near you (Find More Locations):
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Councils are exclusive groups of Efma members that meet three times a year to benchmark themselves against their peers, share best practices and collaborate in a constructive spirit.
This format offers a unique opportunity for participants to interact with their global peers on the same subject and build the future together.
Check out the Efma councils flyer to learn more about this unique service dedicated to Efma member institutions. Being part of a council is free of charge, please contact email@example.com for more info.
You want to become an Efma member? Send us an email!
To get more information regarding the terms and application conditions to join the Efma Advisory Councils, please contact:
Maïlys Mertian
Councils Manager
+33 1 47 42 66 39


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Overview Edit
The Future Attribute Screening Technology (FAST) (originally titled Project Hostile Intent) is a Department of Homeland Security project that seeks to improve the screening process at transportation and other critical checkpoints by developing behavior-based screening techniques that will provide additional indicators to screeners to enable them to make more informed decisions. FAST is not intended to provide "probable cause" for law enforcement processes, nor would the FAST technology, once deployed operationally, replace or preempt the decisions of human screeners.
The baseline for the project is the development and validation of the Theory of Malintent. "Malintent" is the intent to cause harm. Although individuals may experience malintent in a variety of situations, the specific focus of FAST is identifying individuals who exhibit physiological indications, which in the specific screening settings, are determined to be associated with malintent. Behavioral scientists hypothesize that someone with malintent may act strangely, show mannerisms out of the norm, or experience extreme physiological reactions based on the extent, time, and consequences of the event. The FAST technology design capitalizes on these indicators to identify individuals exhibiting characteristics associated with malintent.
The scope of malintent has three distinguishing factors: the extent of planned harm, the future time horizon of the event, and the consequences to the individual who is planning the event. The extent of harm can range from individuals planning to cause a disturbance or use false documents to individuals who are planning an assassination or terrorist attack. The future time horizon can range from planning an event years in advance to planning to carry out the act immediately after passing through screening. The consequences to the actor (perceived as either positive or negative) can range from none to being temporarily detained to deportation, prison, or death.
The FAST research seeks to (1) identify and validate indicators of malintent; (2) develop a prototype incorporating sensors that measure these indicators; and (3) test the performance of the prototype using volunteers. During the experimental research, the volunteer participant (as notified during the informed consent process) may be explicitly instructed to carry out a disruptive act, so that the researchers and the participant (but not the experimental screeners) already know that the participant has malintent. So in the experimental setting, these three factors would be known (i.e., the participant is told the time horizon, the extent of harm, and the consequences).
Source Edit
- Department of Homeland Security, Privacy Impact Assessment for the Future Attribute Screening Technology (FAST) Project (Dec. 15, 2008) (full-text).


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Lyrics Depot is your source of lyrics to From Fluff To You (Speech) by The Beatles. Please check back for more The Beatles lyrics.
From Fluff To You (Speech) Lyrics
Artist: The Beatles
Album: Live At The BBC (Live)
Alan Freeman: Paul?
Paul: Yes?
Alan: Now, listen--
Paul: Yes?
Alan: Are you singing?
Paul: Mmm...
Alan: Do you have any particular idol that you've ever copied your singing style from?
John: What about my book?
Alan: John, go away.
John: What about my--
Paul: Used to be sort of influenced by Elvis in the old days, I think.
Alan: Really?
Paul: Yeah, used to love him.
John: What about my book, then?
Paul: Chuck Berry, Chuck Berry, Carl Perkins, and, eh, Marvin Gaye and things. Can't really sing like them, you know. I like them, though, love them.
John: What about it?
Alan: Paul, what about singing "Till There Was You"?
The Beatles Lyrics
The Beatles Live At The BBC (Live) Lyrics
More The Beatles Music Lyrics:
The Beatles - Anna Go To Him Lyrics
The Beatles - Bad Boy Lyrics
The Beatles - Honey Don't Lyrics
The Beatles - I Want You (She's So Heavy) Lyrics
The Beatles - Leave My Kitten Alone Lyrics
The Beatles - Magical Mystery Tour Lyrics
The Beatles - Polythene Pam Lyrics
The Beatles - What's The New Mary Jane Lyrics


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Events - 20 Apr 17
Festive Champagne Dinner At The Hay-Adams
Mon, Apr 10 - Wed, May 31
The Hay-Adams is pleased to debut a new spring time prix fixe, three-course menu available exclusively in the Lafayette Room. The menu features contemporary American cuisine prepared by Executive Chef Nicolas Legret complemented by a half bottle of Taittinger Brut Champagne. $85 per person. This special offering is available Monday through Saturday, from 5:30 p.m. to 10:00 p.m. 800 16 Street NW. For more information and reservations, please click here.
Pottery Pop Up Shop At Centrolina
Sat, Apr 15 - Sun, May 14
Join Centrolina for their pottery pop-up shop happening over the next month. Chef and owner Amy Brandwein – a supporter and patron of local artisans – welcomes ceramic artist Olivia Di Benigno, founder of Studio North Ceramics in Springfield, Va., to showcase her hand-thrown tableware in the specialty market at Centrolina. Items displayed will be available for purchase, and forms for custom orders will also be available. 974 Palmer Alley NW. For more information, please click here.
Bethesda Row Restaurant Week
Mon, Apr 17 - Sun, Apr 23
Bethesda Row is a dining destination with inventive, chef-driven restaurants by the likes of José Andrés and Mike Isabella, plus a variety of casual, family-friendly hotspots. Enjoy special three-course menus from your favorite Bethesda Row Restaurants, such as Jaleo, American Tap Room, Mon Ami Gabi, Mussel Bar, and more. Three-course lunches are $18, and three-course dinners are $34. Please click here for more details and a full list of restaurants.
Tax Relief Wine Special At The Grill Room
Tue, Apr 18 - Sun, Apr 30
The Grill Room is pleased to debut its tax relief wine special beginning on Tax Day, April 18th, through the end of April. Guests will have the opportunity to enjoy Télégramme by Domaine du Vieux Télégraphe, a standout wine from Châteauneuf du Pape in Southern Rhone, for a special discounted price. Normally $25 a glass and $98 a bottle, this delicious wine will be priced at $15 a glass and $60 a bottle. This will be available during lunch service daily, from 11:30 a.m. to 2:30 p.m., and dinner service Sunday to Thursday, from 5:30 p.m. to 10 p.m. and Friday and Saturday, from 5:30 p.m. to 10:30 p.m. 1050 31 Street NW. For more information, please click here.
Addie's Menu To Pop-Up At Black Salt
Thu, Apr 20
Prior to Addie's Grand opening, Addie's will takeover the private dining space at Black Salt Fish Market & Restaurant. Travel with Black through ghosts of menus past and taste dishes of the future. In addition to a preview dinner, you will receive an exclusive invite to the grand opening party for Addie's at Park Potomac. The seven-course, prix fixe menu will draw on seasonal seafood and highlight the spring harvest. $100 per person, not including tax and gratuity. 5:30 p.m. until 9:30 p.m. 4883 MacArthur Boulevard. Please call 202.342.9101 to reserve your spot.
Happy Hour At BKK Thai Cookshop
Thu, Apr 20
Enjoy happy hour at BKK, the Thai noodle restaurant from the folks behind Beau Thai. (Fun fact: "BKK" is the airport abbreviation for Bangkok, capital of Thailand). BKK features unique appetizers (like steamed buns, gyoza, pork shoulder sliders, and pomelo salad) and Thai noodle dishes (noodle stir fries and noodle bowls), all made from scratch. BKK offers a cocktail on draft and a nice wine, beer, and sake selection. Happy hour specials include half-price Singha, spring rolls, and fried tofu, and all wines by the glass are priced at $5. Happy hour is available daily from 4:00 p.m. to 7:00 p.m. 1700 New Jersey Ave NW. For more information, please click here.
L'Auberge Chez François' 41st Anniversary Celebration Dinner
Thu, Apr 20
Please join Chef Jacques, Paul Haeringer and the entire team at L'Auberge Chez Francois as they celebrate 41 years in Great Falls, Virginia with a festive anniversary dinner featuring the wines of Jean-Marc Brocard. They welcome Etienne Verdier from Domaine Brocard to guide us through the wonderful Chardonnays of Chablis. $140 per person, including tax and gratuity. 6:30 p.m. 332 Springvale Road, Great Falls, Va. For more information and registration, please click here.
Unaddressed: Mess Hall Pop-Up Dinner
Thu, Apr 20
Unaddressed Pop-Up Dinners will host its first event to benefit Miriam's Kitchen. Co-founders, chef Manuel Rodriguez and restauranteur Spenser McKenna, will serve a seasonally inspired tasting menu including Canpe, award-winning 'Back to Life Ceviche' (Manny's Seafood Ceviche), and more. $49 per person. 7:00 p.m. until 10:30 p.m. 703 Edgewood Street NE. For tickets and more information, please click here.
Yes Way ROSÉ! At Righteous Cheese
Thu, Apr 20
Come to "Yes Way Rosé" to learn the tasty basics of cheese and pink wine pairing; wine styles; cheese profiles; and how to differentiate between different types. You'll delve into the story behind each cheese, as well as give advice about selecting, serving, pairing, and more. You'll leave class with a full belly and a full brain – armed with all the info you'll need to navigate the cheese counter and recreate your favorite wine & cheese boards at home. Tickets are $49 per person and the event will begin at 7:00 pm. 1309 5th Street NE. For more information or to purchase tickets click here.
DC Mimouna Mania At Local 16
Thu, Apr 20
Join Israeli House Washington, Moishe House DC, Sephardic Jews in DC, FuelforTruth DC and JScreen for a Mimouna Party to celebrate the end of Passover at Local 16. They'll have the hottest music from Tel Aviv, drink specials all night, lots of Moroccan/Israeli sweets and pastries. $5 in advance, $10 at the door. 6:30 p.m. until 11:30 p.m. 1602 U Street NW. For more information, please click here.


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The Classic & Sports Car London Show
At the end of October, Classic & Sports Car is holding its inaugural London show at Alexandra Palace (October 30th to November 1st 2015), and Hagerty is offering you the chance to win five pairs of tickets for the Sunday of the event.
Show highlights will include the magazine's Best British Car Ever display – a ten classics, handpicked by experts including Gordon Murray, designer of the McLaren F1, Dire Straits front man and classic car collector, Mark Knopfler, and Lotus designer Russell Carr. Including such greats as the Jaguar E-type, Mini Cooper S, Range Rover and the Bentley Speed Six, the shortlist has been put to the public vote, and the winner will be announced at the show.
The show also features a celebration of the Aston Martin brand, with a selection of cars from all eras, and a display of single seaters driven by Stirling Moss OBE.
There's also a Live Stage with celebrity guests such as ex-Ferrari and Mercedes F1 boss, Ross Brawn, and For The Love of Cars presenter Ant Anstead. With loads of other stands including dealers and accessory vendors, this should be a really fun day out!
For a chance of winning one of five pairs of tickets for Sunday 1st November, just answer the following question:
Stirling Moss and Ross Brawn will both feature at the show. They have a car in common- the Ferrari 250 GT SWB that Moss won the 1960 Goodwood TT by two laps, and which is now owned by Brawn. But for which team was Moss driving in this race? (Hint: read our other newsletter article this week!)
For a chance of winning, email firstname.lastname@example.com with your answer by midday on Friday 9th October. The winners will be selected at random from all entries, and informed by email shortly afterwards. And remember- the competition is for the tickets only and don't include travel, accommodation or other costs. Good luck!
Classic & Sports Car – The London Show
October 30th – November 1st
For more information and to buy tickets, go to:
I've had the good fortune over the last 50 or so years to visit and participate in a great many events for contemporary and historic racing cars plus tours and … More
The Midlands was once home to literally hundreds of car and motorcycle manufacturers, from Austin to Wolseley cars and BSA to Velocette bikes, which were parked … More
The Goodwood Revival should be on every petrolhead's bucket list. Each September since 1998, the Earl of March's Sussex estate turns into the stellar racetrack … More
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Hinges Boat Seat Pedestals & Hardware
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by shelia johnson
(cartersville va 23027)
This is my baby sister she has been attack with cancer at least three times. I am asking all of you to pray for her. She is standing on God word. But she does not want to talk about it yet.
Join in and write your own page! It's easy to do. How? Simply click here to return to Daily Devotional .
Click for Inspiration
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Help Sell Me on an XD-40c (Please!)
Hello All!
I am in desperate need (well, that's what I tell the wife) of a DISCRETE sub-compact firearm in .40 S&W, and I absolutely detest Glock. Also, my budget is ~$500, but the closer to $400 I can get that, the better off I will be. That said, I have pretty much narrowed my decision down to 4 pistols: the M&P 40c, the Taurus 24/7c Gen2, the Ruger SR40c, and, of course, the XD 40c. I am comfortable CC'ing a compact without frame safeties (a la Block), but the added safeties on all of them but the S&W are added bonuses. I do like the grip safety on the XD. In all reality, I am pretty close to the XD, but my concerns are whether the higher bore axis makes accuracy difficult, quality and longevity, and if the fact that the added thickness makes EDC uncomfortable. That said, I usually carry a Witness (full-size frame, compact bbl) or my CZ SP-01, but I really, REALLY need something that I can carry without any fear of flashing. Minor printing would be bad, but not necessarily catastrophic.
Pros of the S&W? Thinner, lower bore axis
Taurus Pros? Thinner, higher capacity (unless I'm mistaken)
Ruger? Thinner, bore axis, but it's BIG for a "compact"
XD? Price, great company, trigger feels nice...
Help push me over the edge guys, or steer me in a better direction. I won't be buying it this month, but I am putting money down on one of them next week, one way or another.
I appreciate your help!
After 17 years of daily CCW I do not think anything in your list will fill your need. No double stack auto will be a "no printing" option.
If you lime .40 check out the Kahr line of single stack autos...personally, we I in the market, I'd be dropping 5 bills on the new XD's .45 ACP.
Not trying to bust your selections, just sharing my experience.
My EDC is a XD40SC and I love it. About 6K rounds down the pipe without a failure of any type. It replaced a S&W M&P 9mm compact .
Tack? Thanks for the input. Perhaps I'll price those... For all the others, thanks a ton! As I said, I am pretty close to getting the XD, so unless the Kahr is super well-priced, it will very likely be the XD. And if it does print, well, maybe I'll end up "being forced, against my will no less" into buying a Kahr or other single stack a few months down the road... :)
Hey, does anyone here have a Walther PK380 and an XD compact? I know the XD is significantly wider, but how does the XD measure up as far as height and lenghth? I can look at the specs online and compare them, but I would love a comparison by feel from real people. My Witness P-S (full frame, compact bbl) is only about .4" greater in height, but in terms of carry, the difference is huge...
Thanks again, gents!
I have both the XD40 and XDm40. If I buy another handgun it will be the XD40sc. I have recently seen them for sale for $399 new. That is $100 under your budget.
That's a great price. But my guy had a Ruger SR40c when I went to get the XD and I liked it lots more, so I bought it... I wouldn't mind a FS XD40 though... Hopefully one of those is in my near future
2 Attachment(s)
I have a 40SC and a PK.380. Here are side by side pics.
Attachment 59373
Attachment 59374
Thanks for the comparison!
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What is JotForm?
JotForm is a free online form builder which helps you create online forms without writing a single line of code. No sign-up required.
At JotForm, we want to make sure that you're getting the online form builder help that you need. Our friendly customer support team is available 24/7.
We believe that if one user has a question, there could be more users who may have the same question. This is why many of our support forum threads are public and available to be searched and viewed. If you'd like help immediately, feel free to search for a similar question, or submit your question or concern.
Send Post Data: How to get values for checkboes?Asked by lafototeca on July 19, 2014 at 09:33 AM
Fine tutorial, thank you.
How can I work with a checkbox if I want to pass the result to the variable 5?
Can you help me with this?
Thank you.
This is a re-post of a comment on Send Submission Data via Post Method and Thank You Settings
JotForm Support
First you must find out the actual Variable Names and PHP codes in the POST result.
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Chefs Chris Curtiss, James Porter Return to the Valley
Chris Curtiss making pasta at North Arcadia in 2012.
Nikki Buchanan
It's been almost a year since chef Chris Curtiss, former (and original) executive chef at Noca, left the Valley to take a job in Northern California. But now the chef, whose résumé also includes opening Sam Fox's North Italia in Arcadia and serving as executive chef of Michael Mina's Bourbon Steak, has returned, according to the Arizona Republic .
Curtiss, who was working in Santa Clara as executive chef of Mina'a restaurants at Levi's Stadium, is now working as a corporate chef for Fox Restaurant concepts. He'll be developing recipes for use throughout the Scottsdale-based company's restaurants, and will be in the kitchen for pop-up dinner events at Little Cleo's Seafood Legend starting in the new year.
Also back in town is chef James Porter, mostly recently known as the chef/owner of Petite Maison in Scottsdale. Around the same time as Curtiss' departure, Porter sold that restaurant and moved with his wife, Wendy, to Wisconsin to help renovate and reopen the Hotel Northland in Green Bay. Porter's still involved with that project, but has relocated back to Arizona and will be announcing his plans soon.
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Tell Us More About Your Mazda B2500. View all models
AutoZone carries hundreds of thousands of parts and accessories.
Select your Year, Make, Model and Engine to find those that fit your vehicle.
For extreme payloads and the ability to handle the toughest conditions on the road, you cannot get much better than your Mazda B2500. This sporty pick-up truck is excellent for any rugged outdoorsman. You just need to make sure you have a working Mazda B2500 timing belt, so shop with AutoZone when you're in need of quality replacements.
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Serious issues occur if you drive around with a broken belt, and fortunately, a B2500 timing belt replacement is easily acquired. Engine oil is capable of leaking onto the belt, and there is always the risk of there being improper tension. For peace of mind on the road, head over to AutoZone to get your vehicle checked out. Trustworthy advice provided by a helpful staff points you where you need to go. You're also able to get Same Day Store Pickup and home shipping when you order from us online.


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Conceived and designed the experiments: AH HV BS CV. Performed the experiments: CV EB NW. Analyzed the data: AH HV CV NW. Contributed reagents/materials/analysis tools: CV. Wrote the paper: AH HV BS CV.
The prolonged time course of Huntington's disease (HD) neurodegeneration increases both the time and cost of testing potential therapeutic compounds in mammalian models. An alternative is to initially assess the efficacy of compounds in invertebrate models, reducing time of testing from months to days.
We screened candidate therapeutic compounds that were identified previously in cell culture/animal studies in a C. elegans HD model and found that two FDA approved drugs, lithium chloride and mithramycin, independently and in combination suppressed HD neurotoxicity. Aging is a critical contributor to late onset neurodegenerative diseases. Using a genetic strategy and a novel assay, we demonstrate that lithium chloride and mithramycin remain neuroprotective independent of activity of the forkhead transcription factor DAF-16, which mediates the effects of the insulin-like signaling pathway on aging.
These results suggest that pathways involved in polyglutamine-induced degeneration are distinct from specific aging pathways. The assays presented here will be useful for rapid and inexpensive testing of other potential HD drugs and elucidating pathways of drug action. Additionally, the neuroprotection conferred by lithium chloride and mithramycin suggests that these drugs may be useful for polyglutamine disease therapy.
Drug discovery for late onset neurodegenerative diseases is a major challenge. In large part, the complexity of treating these disorders results from our insufficient understanding of the contributions of multiple pathways on disease pathophysiology. Furthermore, since the pathology of these disorders is often only discernable in aged populations, testing the therapeutic value of small molecules in vertebrate disease models requires time consuming and costly experimental designs. The development of rapid and inexpensive in vivo assays to evaluate the numerous candidate compounds identified in high-throughput screens is therefore of paramount importance.
Invertebrate model organisms such as C. elegans provide an attractive alternative for prioritizing lead compounds in the early stages of drug development for age-related diseases [1]–[3]. C. elegans has several characteristics that make it ideal for drug testing- including a short lifecycle, small size and the ease of culturing in liquid. Furthermore, decades of neurobiological and antiparasitic drug studies in C. elegans provide a strong foundation for use of this organism in therapeutic compound identification [1]–[3].
Huntington's Disease (HD) is caused by expansion of a polyglutamine (polyQ) tract in the huntingtin protein leading to neurodegeneration that is age and polyQ tract length dependent [4]. In this study, we use a C. elegans model of polyQ neurotoxicity in which the N-terminal 171 amino acid fragment of human huntingtin protein containing an expanded polyglutamine tract (150Qs) is expressed in neurons. Degeneration and cell death in this model is dependent on both age and polyglutamine tract length, recapitulating these aspects of the human disease [4]–[6].
We tested a collection of compounds that have been previously described to decrease degeneration in cell culture/animal models of polyQ toxicity for their ability to protect C. elegans neurons from the toxic effects of an expanded huntingtin polyglutamine fragment. We developed, optimized and validated new assays for use in rapid assessment of drug efficacy using C. elegans HD models. Of the compounds tested, we found that two FDA approved drugs, mithramycin (MTR) and lithium chloride (LiCl), reduced polyQ toxicity in the C. elegans model.
An important determinant of neurodegenerative diseases is the aging process. However, the mechanistic links between aging and the cellular pathways leading to neurodegeneration are not well understood. The forkhead transcription factor DAF-16, which mediates the effects of the insulin-like signaling pathway on aging, has been shown to play a role in polyQ aggregation. Mutations that reduce insulin signaling, derepress DAF-16 leading to an increase in lifespan and stress resistance [7], [8], whereas RNAi based knockdown of daf-16 accelerates polyQ aggregation and toxicity [9] suggesting that DAF-16 transcriptional targets not only promote longevity but also prevent polyQ aggregation. Despite the pivotal role that growth and aging play in neurodegenerative disease, we found that LiCl and MTR protect C. elegans neurons in the absence of growth and through a daf-16 independent pathway suggesting that these compounds may target pathways that are specific to neurodegeneration. Thus, the integration of pharmacological and genetic examination of drugs, in C. elegans HD models that we describe, should accelerate the identification of interventions for HD along with insight into mechanism of drug action.
We tested a collection of compounds that have demonstrated therapeutic value in either cell culture and/or animal models of polyQ toxicity for screening in our C. elegans HD models (Table 1). These candidates represent compounds that may protect against polyQ toxicity by affecting a variety of cellular pathways. To efficiently evaluate the effects of these candidates on neurodegeneration and neuronal cell death, we first established a systematic method for selecting optimal drug concentrations to assess in our C. elegans HD models (see Methods). Compounds were tested in a dose dilution series in the food clearance assay (Figure 1 and Figure S1) starting at the highest soluble concentration. Taking advantage of the short life cycle and the ability of C. elegans to grow in liquid culture of E. coli, we evaluated compounds by monitoring the rate at which the E. coli suspension (food source) was consumed. Each adult is capable of producing hundreds of progeny that rapidly consume the limited E. coli supply. As a result, the OD of wells without compound drastically decreases in 3 days. Any drug that decreases C. elegans growth, survival or fecundity would result in a dose dependent reduction of the rate at which food is cleared (consumed) in a well. For example, addition of 5 mM LiCl to the culture showed no effect on food clearance compared to control animals, whereas animals exposed to 10 mM or 25 mM LiCl had delayed food clearance (Figure 1B). Visual inspection confirmed that animals treated with 10 mM and 25 mM LiCl were smaller in size compared to untreated animals whereas animals treated with 5 mM LiCl were unaffected (Figure 1C and data not shown). Furthermore, animals exposed to 50 mM and 100 mM LiCl did not produce progeny over the time course of the experiment (data not shown), which correlated with the lack of clearance of the E coli food source. For all compounds, optimal concentrations for C. elegans were similarly assessed using the food clearance assay (Table 1). This simple assay for determining a compound's concentration range to test in C. elegans uses a small amount of compound and is amenable to high-throughput format, making it applicable to any C. elegans drug study.
In order to test compounds in an efficient manner, we decided to reduce the amount of time required to test drug efficacy. Relatively long assay duration may also be unsuitable for testing compounds that are unstable under assay conditions. We utilized a genetic mutant background (pqe-1 loss of function) that accelerates polyQ mediated neurodegeneration and cell death in C. elegans from 7 days to 2–3 days. We evaluated neuronal death by monitoring loss of expression of a GFP reporter construct in the bilateral ASH sensory neurons in pqe-1;Htn-Q150 animals, a genetically enhanced model of polyQ toxicity [10] (Figure S2). In pqe-1;Htn-Q150 animals, the vast majority (>90%) of ASH neurons undergo cell death in less than three days (Figure S2).
Synchronized pqe-1;Htn-Q150 L1 larvae were treated with and without drug for three days, then GFP expression was monitored to assess ASH neuronal viability (Figure 2A). Of the candidates tested, we identified three protective compounds, mithramycin (MTR), trichostatin A (TSA) and lithium chloride (LiCl) (Table 1). All three compounds caused a dose-dependent neuroprotection in the pqe-1 sensitized background (Figure 2B). MTR and TSA affect transcriptional activity [11], [12] and LiCl is a drug used clinically to treat individuals with bipolar disorders and is a potential inhibitor of GSKβ [13]. Previous studies in C. elegans demonstrated that TSA reduced polyQ mediated neurodegeneration [14], validating this approach. Htn-Q150 transgene expression was not altered by drug treatment based on RT-PCR (Figure S3). Based on these results, we conclude that a genetically sensitized background (e.g. pqe-1) can be used to dramatically reduce the amount of time required to accurately assess effects of drugs on neuronal cell death.
To determine if neuroprotection was dependent on pqe-1, we tested candidates in the Htn-Q150 only background that exhibits age-dependent neurodegeneration but no cell death. Late onset degeneration of ASH sensory neurons was monitored by defects in dye uptake, a previously described assay [6] (Figure S2).
One limitation due to the prolonged duration (7 days) of the aging assay is the production of progeny (200–300 per adult) by the aging animals. Since the progeny grow to adulthood in 3 days, they are difficult to distinguish from the aged parent by day 7. A novel genetic strategy was employed to prevent progeny development. We crossed Htn-Q150 into a genetic background (pha-1) in which progeny fail to feed and grow at the restrictive temperature of 25°C [15]. Introducing pha-1(e2123) to eliminate progeny development permits the use of liquid cultures and facilitates any C. elegans aging study (see Methods).
To assay compound efficacy, synchronized pha-1;Htn-Q150 L1 larvae were treated with and without drug for seven days, then scored for degeneration using the dye-filling assay (Figure 3A). Introducing the pha-1 mutation had no effect on the dye-filling of ASH neurons or the polyQ dependent neurodegeneration (data not shown and Figure S2). LiCl decreased polyQ neurodegeneration in a dose dependent manner (Figure3B) while equivalent concentrations of sodium chloride (NaCl) had no effect (data not shown), showing the specificity of LiCl's effect. Consistent with previous findings [14], the HDAC inhibitor trichostatin A (TSA) also suppressed neurodegeneration in the aging assay format (Figure S4). The confirmation of compound activity in the age dependent Htn-Q150 model validated the utilization of the pqe-1 sensitized strain as a rapid means of identifying HD therapeutic compounds.
Since the aging process is a critical but poorly understood contributor to late onset neurodegenerative diseases [9], [16], [17], compounds that affect aging may indirectly affect degeneration. To distinguish drug effects on neuronal cell death from those on growth, development and aging rates, we applied two strategies: (i) we modified our assay format to prevent growth of animals for the duration of the assay (ii) we genetically altered the well characterized insulin signaling pathway that affects aging. To modify our assay, we took advantage of the growth arrest induced by starvation of L1 stage C. elegans larvae. When embryos hatch in the absence of food, their development is arrested until food is available [18], [19]. Since starved L1 animals do not grow, the effects of compounds on neuronal cell death can be evaluated independent of their effects on growth and development. A further advantage is that drugs can be tested in the absence of bacteria (E. coli food source) that could degrade or metabolize compounds under analysis. Using a starvation assay format (Figure 4A), we found that ASH neurons continue to undergo neuronal cell death in pqe-1;Htn-Q150 animals that are growth arrested by the absence of food (data not shown). This finding suggests that certain pathways that affect polyQ neurodegeneration are distinct from pathways that effect growth and development.
We tested LiCl and MTR in this starvation assay format. Both LiCl and MTR protected ASH neurons of starved animals in a dose-dependent manner (Figure 4B). Equivalent concentrations of NaCl as that of LiCl had no effect on neuronal cell death demonstrating specificity of the compound's effect (data not shown). Using this assay modification, higher concentrations of compounds that interfere with C. elegans development and growth were tested in the starvation assay (Figure 1C and Figure 4B). Therefore, testing drugs in the L1 arrest assay can distinguish contributions of specific drugs on organismal development and aging, providing a clearer demonstration of the neuroprotective properties of compounds.
The insulin signaling pathway, a critical regulator of longevity in C. elegans, is also a modifier of polyQ toxicity. RNAi mediated knockdown of daf-16 decreases lifespan and leads to early onset of polyQ aggregation [9]. To determine if the neuroprotective effects of LiCl and MTR are dependent on components of the insulin signaling pathway, we crossed a daf-16 null mutation into pqe-1;Htn-Q150 animals and tested the effects of LiCl and MTR on neuronal cell death in the starvation assay. We found that both compounds remained neuroprotective in the daf-16 mutant animals in a dose dependent manner (Figure 4C), suggesting that LiCl and MTR suppress polyQ mediated neuronal cell death independent of DAF-16 activity. The dissociation of the neuroprotective effects of compounds from growth and specific aging pathways allows a mechanistic classification of therapeutic compounds.
A number of therapies for complex diseases use combinations of drugs that allow targeting of multiple mechanisms and allow therapeutic efficacy at lower compound concentrations, limiting toxicity of single agents. We also investigated the utility of our C. elegans assay in drug combinatorial studies by testing LiCl in combination with MTR on C. elegans polyQ toxicity in the starvation assay. Combining 25 mM LiCl and 0.5 mM mithramycin in the starvation assay format increased ASH neuron survival compared to the protection afforded by either compound alone (Figure 4D).
In this study, we have devised strategies for efficiently assessing therapeutic efficacy of compounds in C. elegans HD models (Figure 5). Our methods exploit the strengths of C. elegans model for drug discovery, including convenient and precise visualization of live neurons, small-scale liquid cultures that significantly reduce the amount of drug required for testing as well as genetic approaches to implicate specific cellular pathways in a compound's mechanism of action. These assays could be utilized for prioritizing the large numbers of hits already identified by high-throughput screens for HD and other polyQ diseases [20]–[23].
The normal aging process is intricately linked to late onset neurodegenerative diseases. However, the influence of aging on cellular events that impact neurodegeneration is unclear. To dissect the interplay of pathways involved in neurodegeneration from those involved in aging, we combined genetic manipulations with a novel assay that utilizes growth-arrested animals. Our studies demonstrate that LiCl and MTR exert their neuroprotection in a daf-16 independent manner. However, starvation of animals may activate additional stress responsive transcription factors such as heat shock factor (HSF1). HSF1 regulates the heat shock response and also influences longevity [17], [24], [25]. Furthermore, HSF1 RNAi enhances polyQ aggregation [26] raising the possibility that HSF1 or other stress activated pathways may function as molecular targets of these compounds. However, the fact that neurons continue to die under conditions of starvation suggests that the stress responses induced by starvation are insufficient to abrogate the neurodegenerative process. Thus, the combination of strategies outlined in the study allows the separation of drug effects on neurodegeneration from those on growth and stress related aging pathways.
Though we focus on neurodegeneration in HD models, similar strategies may apply to other age dependent phenotypic readouts. For example, deletion of the C. elegans dystrophin gene, the homolog of a gene involved in Duchenne's Muscular Dystrophy, in combination with a second mutation in the myogenic factor MyoD leads to progressive muscle degeneration [27], [28]. Using the strategies described in this study, the protective effect of compounds on muscle degeneration could be conducted rapidly. These C. elegans disease models should be valuable tools for rapid identification of potential therapeutic compounds for aging related human diseases and cellular pathway elucidation of any compounds that are active in these models.
C. elegans N2[wild-type] and GE24[pha-1(e2123)], E. coli food sources OP50 and HB101 (OP50 for compound efficacy and aging assays and HB101 for sensitized and food clearance assays) were obtained from the Caenorhabditis elegans Genetics Center. Htn-Q150(rtIs11) expressing strains with and without pqe-1(rt13) were previously described [6], [10]. daf-16(mgDf47) was crossed into pqe-1(rt13) mutant strain expressing Htn-Q150(rtIs11) marked with dpy-11(e224). All mutations were homozygous in the final strain for analysis. All strains were cultivated on nematode growth media (NGM) plates at 15°C [29].
E. coli were grown overnight at 37°C in Luria broth (LB) media, pelleted by centrifugation, frozen at −70°C, and then resuspended at a final OD of 0.5 (595 nm) for the aging assay or an OD of 6.6 in nematode S-medium [29] (supplemented with 100× streptomycin/penicillin (Invitrogen, #15140-122) and nystatin (Sigma, #N1638)) for all other food based assays. Note the lower OD (~0.6) in plates was due to a decreased path length of the 60 µl final suspension, in a well, compared to a 1 cm path length in a spectrophotometer.
All compounds were purchased from Sigma (St. Louis, MO). Stock solution of 1 M lithium chloride (LiCl) in water, 10 mM mithramycin (MTR) in PBS and 5 mg/ml trichostatin A (TSA) in DMSO were stored at room temperature (LiCl), 10–14 days at 4°C (MTR) and at −20°C (TSA). Compounds were diluted into E. coli suspension or S-medium (starvation assay) to the desired concentrations. 1 ml of the final mixture was added per well of a 24-well polystyrene plate for the aging assay. For the remaining assays, 50 µl of the final mixture was added per well in a 96-well polystyrene plate.
We used newly hatched C. elegans, collected as L1 larvae at 15°C. Specifically, adults were lysed, fertilized eggs were collected by hypochlorite treatment of gravid adults and suspended in S-medium for 24–30 hours at 15°C and L1 larvae were allowed to hatch overnight in the absence of food [29]. pha-1(e2123) is a temperature sensitive loss of function allele that affects normal pharyngeal development [15]. A normal pharynx forms at the permissive temperature of 15°C in newly hatched L1 animals while the pharynx fails to develop in pha-1(e2123) animals hatched at 25°C. C. elegans L1 animals do not initiate growth in the absence of food, resulting in a synchronous population of arrested L1 animals. Introduction of a food source (E. coli) results in growth; animals become adult hermaphrodites within 48 hours at 25°C. This L1 growth arrest and recovery provides an efficient means of collecting large numbers of synchronized animals for assays.
The effect of compounds on C. elegans physiology is monitored by the rate at which the E. coli food suspension was consumed, as a read out for C. elegans growth, survival or fecundity. Approximately 20–30 L1 synchronized animals per 10 µl of S-media were added to an E. coli suspension. Microtiter plates containing animals and drugs were incubated at 25°C. The absorbance (OD 595nm) was measured daily using a Vmax Kinetic microplate reader (Molecular Devices). We used N2 animals when determining compound concentration. Introduction of pha-1(e2123), pqe-1(rt13), daf-16(mgDf47) or Htn-Q150(rtIs11) had no effect on overall growth or health of the animal compared to N2 in the presence of drug at assay temperatures.
At time points indicated, animals were collected by centrifugation, washed in S-media and immobilized with 5 mM sodium azide on a 2% agarose pad. GFP fluorescence was scored using an Axioplan2 fluorescence microscope (n=100 ASH neurons). For the aging assay, degeneration was assessed by dye-filling [6]. Animals were incubated for 2 hours in 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindodicarbocyanine perchlorate (DiD) (Molecular Probes) and immobilized as above for scoring ASH dye filling (n=50 ASH neurons). To determine statistical significance, we compared the results from parallel experiments using 2×2 contingency tables comparing the number of GFP+ and GFP- neurons in control vs. specific concentrations of a compound. We determined the statistical significance using a Fisher's exact test for each of the three independent experiments and reported the largest p value of the three trials to provide a conservative estimate. In Figure 4d, Bliss Independence was assessed [30]. Neuronal survival was converted to a fractional scale with no drug treatment (17%) arbitrarily set to 0 and 100% survival set to 1. Survival for each drug and the combination was converted to a fraction and the Bliss Independence score was calculated as C=A+B−AB, where A and B are the fractional survival for LiCl and MTR and C is the predicted effect for the combination. The difference between C and the actual value (fractional) was calculated to assess synergy. LiCl had a fractional survival of 0.22, MTR 0.19 and the combination 0.51. The expected value for the combination was 0.37. The excess 0.14 was a measure of synergy.
qRT-PCR analyses were carried out using the SYBR Green method (BioRad) and the SmartCycler 1600 System by Cepheid Innovation. Total RNA was extracted using Trizol (Invitrogen), DNase treated (Ambion), followed by cDNA synthesis (BioRad) according to manufacturer's instructions. The primers used for amplification of the actin gene, act-1, are 5′-atcaccgctcttgccccatc-3′ (for) and 5′-ggccggactcgtcgtattcttg-3′ (rev). Primers for Htn transgene were previously described [3].
Concentration of compounds for testing in C. elegans was assessed using a food clearance assay. The OD of E. coli is reported daily for each concentration of TSA (A) and MTR (B). The mean OD is calculated for each day from triplicate samples and plotted over time.
C. elegans model of polyQ neurodegeneration and cell death [6], [10]. (A) An N-terminal fragment of human huntingtin with 150 glutamines (Htn-Q150) was expressed in C. elegans ASH neurons as previously described [6]. (B) A GFP reporter expressed in the ASH neurons was used to assess cell death; loss of GFP expression in ASH neurons indicates cell death as shown here in young pqe-1;Htn-Q150 animals (bottom panel). (C) The ASH neuron and 5 other sensory neurons in Htn-Q150 young (top panel) or aged (bottom panel) animals were visualized by dye filling. Sensory endings of ASH neurons expressing Htn-Q150 degenerate in aged animals and fail to take up dye (bottom panel). (D) ASH neuronal survival decreases dramatically over time based on GFP fluorescence. By day 3, 75% of ASH neurons are dead in pqe-1;Htn-Q150 animals. Error bars represent SEM. Scale bar is approximately 20 nm. (E) Only 21% of ASH neurons remain intact in aged (7 day) pha-1 animals expressing Htn-Q150 raised at 25°C compared to young (3 day) animals based on dye filling.
HtnQ150 transgene levels are not decreased in the presence of LiCl or MTR. Relative HtnQ150 transgene levels were determined using the ΔΔCt method and normalized to an act-1 control. Results are from two independent RNA collections from untreated animals (C) and animals treated with 25 mM LiCl or 0.5 mM MTR in the starved assay format for 24 hours at 15°C. The error bars indicate the standard deviation from two replicates of qRT-PCR experiments comparing untreated and drug treated samples.
HDAC inhibitor trichostatin A (TSA) decreases polyQ toxicity measuring ASH neurodegeneration or neuronal death. At least three trials for each efficacy assay were performed. Representative experiments are depicted. (A) TSA decreases polyQ toxicity in a pqe-1 independent manner in pha-1;Htn-Q150 aged animals. 30 synchronized pha-1;Htn-Q150 L1s per well were incubated at 25°C in S medium with E. coli at an OD at A595 of 0.5 with varying concentrations of TSA to a total volume of 1 ml. On day 7, animals were collected, dye filled and 100 neurons were scored for degeneration. (B) TSA increases neuronal survival in the absence of growth using the starvation assay. 50 synchronized pqe-1;Htn-Q150 L1s per well were incubated at 25°C in S medium with varying concentrations of TSA to a total volume of 60 µl. On day 2, the survival of 100 ASH neurons was evaluated by the presence or absence of GFP. Animals were treated with final concentration of TSA or vehicle (2% DMSO).
We would like to thank Sally McFall, Patrick McMullen, Daniel Stouffer, Mike Stringer and Wyndham Lathem for helpful discussions, and Gary Ruvkun and the C. elegans Genetics Center for strains.
Competing Interests: The authors have declared that no competing interests exist.
Funding: We gratefully acknowledge the support of the Hereditary Disease Foundation (C.V. and B.R.S.), Cure Huntington Disease Initiative (B.R.S.), the High Q Foundation (H.V. and B.R.S.), the Ellison Medical Foundation (A.C.H.) and the NIH (NS-040048 for A.C.H. and T32 AG20506 for C.V.). Brent R. Stockwell is supported in part by a Career Award at the Scientific Interface from the Burroughs Wellcome Fund.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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