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Building Electric Generator System
Building power generator conspiracy is the term for the tranquil treatment fond of making electricity a piece of an environmentally friendly energy product. This page reveals how give some thought to systems. It portrays a machine that makes its personally own electricity Study to understand self protected power development.
More people are aware of electrical automatic washers than find out about electrical mills. A power motor goes on electric power. It re-writes the actual model drum. The motor makes fans go all over. The car was invented earlier in regarding the year 1825. Many of us have your historical memory that of a motor is without a doubt and what as well as so; some reasons why there any conspiracy involving silence about electrical mills?
There are just two parts to an electrical mill: spinning magnets together with a coil about copper insert. Electricity will be dangerous allowing it to kill without difficulty a real human. Most websites only show how to develop a small to medium sized apparatus. The generator tends to make electricity.
Did any conspiracy involving silence develop partly considering electricity building activities make big savings while power using hobbies cost finances? Enter replenish able energy platforms. Wind village, solar series unit, biomass formation, power age group, and transport are usually now being made replenish able. Renewable implies money cutting down.
An environment friendly system is in addition described simply because integrated know-how with increased exposure of the period integrated. Wind strength generation is an illustration of this integration. A rotating earth yields a web endless a powerful almost perpetual availability of wind, a great non polluting useful resource. A windmill lets a wind electric power rotate equipment that come with a power generator. Electrical power generator produced your electricity. If builders of any electrical building machine want an authentic system that builders could not here.


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Jesus' Thoughts on Prayer
Jesus told us everything we need to know about prayer. The Forgiveness Foundation plans to share Jesus' teachings about prayer over the next fourteen days, "The Forgiveness Foundation's 14 Days of Prayer." Our objective is to learn to pray as Jesus taught us to pray.We pray that you will join us.Matthew 6:6-8 shares some do's and don'ts about prayer.
(5)"And when you pray, you must not be like the hypocrites. For they love to stand and pray in the synagogues and at the street corners, that they may be seen by others. Truly, I say to you, they have received their reward. (6) But when you pray, go into your room and shut the door and pray to your Father who is in secret, And your Father who sees in secret will reward you. (7) "And when you pray, do not heap up empty phrases as the Gentiles do, for they think that they will be heard for their many words.(8) Do not be like them, for your Father knows what you need before you Him."Matthew 6:6-8 (ESV)
In verse 5, Jesus tells us that God is looking for a sincere relationship and not one designed for others to observe rather than true and sincere relationship with God.Jesus in verse 6, tells us seek a private place to pray. This allows us to pray without interruption or distraction.In verse 7, Jesus tells us that the length of our prayer does not account for its reception from God.God is looking at our heart as intently as He listens to our words. In verse 8, Jesus reminds us to not be like them, the hypocrites, people who play act a life for God without having a genuine heart to live life for Him.

subset: commoncrawl


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NJStateAuto Used Car Dealer Used Cars For Sale Below Kelley Blue Book
Archive for May, 2015
5 new safety technologies being developed by automakersWednesday, May 27th, 2015
One of the major factors driving advancements in automotive technology is the desire for increasingly complex safety features. As it stands, automakers may still be decades away from having fully autonomous vehicles that leave no room for driver error – because there isn't one. But in the meantime, automakers are coming up with innovative new ways to help keep people safe from their own mistakes and those of other drivers. Here are five of the best new technologies you'll be seeing in cars some time soon.
- Gesture recognition
Many companies have been working on this type of technology for a while now, including BMW, Mercedes-Benz and tech giant Microsoft, but Harman International Industries may have beaten them all to the punch. Wired reported that Harman's European division has developed a system that recognizes predefined nods, winks and various hand gestures from the driver. This includes raising and lowering your hand over the gear shaft to change the temperature and tilting your head to the left and right for radio volume control. Recombu, a car news site in the U.K., reported that Harman's system is so advanced it can tell the difference between real gestures and accidental or unintended gestures from the driver. What does all this have to do with safety? Hands-off controls mean fewer distractions for the driver.
Cars of the future will be safer than ever thanks to technological advancements by automakers.
- Automatic doze control
Falling asleep at the wheel is unfortunately a common cause of accidents, especially for truckers who spend long days and nights on the road. Volkswagen is working on a system that takes electronic steering to the next level, according to Popular Mechanics. The system works using a camera and other sensors that detect if the vehicle is experiencing any abnormal drifting patterns. The sensors communicate with a computer that interprets the severity of the situation, and takes control of the steering gear motor, if necessary, to keep the vehicle on a safe path. This technology is far from complete, however – as Popular Mechanics reported, the system cannot yet tell the difference between drifting and casually changing lanes. This will be a more active approach to lane departure warning systems that alert the driver if the vehicle begins drifting into other lanes without a turn signal. You can find various versions of such systems on newer used vehicles.
- Automatic sun visor
Drivers often encounter blinding sun rays that cause them to flip the visor and reach for their sunglasses. But Popular Mechanics reported that Volkswagen is developing an electronic matrix inside the windshield to help block the rays. One sensor focuses on the position of the driver's eyes while the other measures the intensity of sunlight beaming the windshield. The system then creates a dark area where the sunlight meets the driver's eyes that changes with the direction of the vehicle.
"New airbags will double the car's stopping power."
Airbags – for the car itself
How Stuff Works reported that Mercedes is designing an airbag system that helps stop a car when active safety sensors have determined an impact is imminent. The bags deploy beneath the vehicle and are coated with a substance that increases friction and doubles the car's stopping power. They also reduce the dipping motion that occurs as a vehicle is coming to a hard stop. It lifts the car 8 centimeters, which is enough to ease bumper-to-bumper contact and prevent passengers from slipping under their seatbelts. Airbag systems have become increasingly complex over the years, and you can already find plenty of cars with great airbag protection for the interior of the vehicle.
- Crash avoidance systems
Audi and other car makers already have vehicles on the road that can effectively swerve around a potential collision. But Audi is taking a few more steps in the fully autonomous direction with the zFAS central driver assistance controller, according to Automotive News. The zFAS uses two microchips – one that focuses ahead of the vehicle, and another that monitors areas around the vehicle. This helps determine the safest course of action the computer can take to avoid swerving around one object and prevent potentially colliding with another. The second generation of the zFAS will enable the chips to monitor each other as well, to provide backup in case one fails. Audi is also working with a number of other companies on overlapping sensors, radar systems and cameras to develop a fully comprehensive crash avoidance system.
While it may be a few years before you start seeing features as advanced as the ones on this list in cars everywhere, rest assured that that they're on the way. As for now, there are plenty of other active safety features you can find in used cars from New Jersey State Auto Auction.
The pros and cons of manual and automatic transmissionsFriday, May 22nd, 2015
If you've ever driven a classic sports car, you've probably experienced the thrill of driving a little too fast while enjoying the power of the machine as you engage the clutch and shift the gears. You may have instead been exposed to a manual transmission when you tried learning to drive in your grandfather's old car – and failed miserably trying to start up a hill. You never could quite get the clutch right, could you?
"Only 3.9% of new cars sold in 2013 had manual transmissions."
But if the latter is the case, it should come as a pleasant surprise that, for the better part of the existence of the combustion engine, car makers and gear-heads alike have been trying to perfect the automatic alternative to the classic manual transmission. In fact, Edmunds reported that only 3.9 percent of all new cars sold in 2013 had manual transmissions, and 67 percent of the 2012 models were only available with automatics.
But despite this industry trend, there are some who will always prefer manual to automatic transmissions for a number of reasons. If you're in the market for a used car, it's likely at some point that you'll have the option of choosing which transmission you would prefer, and there are advantages for both. Understanding the pros and cons of the different transmissions will help you make an informed decision when you're looking for a car. But first, a rundown of the mechanical differences:
What is a transmission?
According to How Stuff Works, all engines have what's known as a "red line," which is the maximum rpm an engine can operate at before it explodes. The transmission changes the gear ratio between the drive wheels and the engine so that the engine continues to operate below the red line as speed increases. Manual transmissions have a set number of gears that the driver shifts between depending on speed and rpm. Automatic transmissions, on the other hand, utilize what's called a planetary gear system that allows one set of gears to provide different ratios, according to the source.
The ideal transmission would allow infinitely flexible ratios, allowing the engine to always operate at its best. The continuously variable transmission is a newer form of automatic transmission that seeks to provide this perfect ratio scenario. Advancements in technology have allowed car manufacturers to start incorporating the automatic CVT in newer cars, and that move may help seal the fate of manual transmissions.
Automatic transmissions utilize a planetary system to maximize available ratios.
So while this all might sound like a bunch of mechanical jargon, it plays a large part in defining which transmission is actually better. Here are the pros and cons of manual versus automatic transmissions:
Manual pros
- According to Consumer Reports, manual transmissions can increase mileage by up to 5 mpg in some cases.
- Vehicles with manual transmissions are often cheaper than automatics by around $1,000.
- The New York Daily News reported that manual transmissions are easier to maintain – in general, the clutch is the only part that ever needs to be replaced, and a lot of people would argue that a good driver can make a clutch last a long time. Also, manuals are lubricated with gear oil, which doesn't break down as easily as automatic transmission fluid so it doesn't need to be changed as often, – if at all.
- Manual transmissions allow for more control over the vehicle – whereas automatics are constantly pushing the car forward when it's in drive, a manual only responds to the driver.
Manual cons
- Manual transmissions are no longer an option for a lot of cars, and are usually limited to small vehicles and sports cars.
- Driving stick requires more skill than an automatic – it takes practice to learn how to properly use the clutch, and improper use will lead to more wear and tear.
- Using two feet to drive can be uncomfortable for some people, which also depends on how the car is designed.
- Driving in the city is only fun if you truly enjoy driving a stick shift. Stop-and-go traffic can be a real hassle if you're driving a stick, and that kind of shifting can cause excessive wear on the clutch, according to Consumer Reports.
- Manuals may be harder to sell down the line, since they are less popular now than ever.
Automatic pros
- An automatic is far easier to drive than a stick – all you do is put it into drive, reverse, park or neutral. While newer automatic transmissions are incorporating more gear choices, there's still little work to be done on the part of the driver.
- Automatics are great for the city – driving in traffic is considerably easier with an automatic, as there is no need to shift constantly with the ebb and flow of traffic.
"There are far more options available with automatic transmissions."
Car Talk pointed out that CVTs are as close as anyone has come to creating the perfect transmission, and their advent is helping automatics exceed manuals in terms of mileage.
- As the Edmunds statistics indicated, most manufacturers have significantly cut back on having stick shifts available for their models, so there are far more options available with an automatic. This also means there's a wide variety of used cars with an automatic transmission.
Automatic cons
- The driver has less control over the performance of an automatic transmission because it does the shifting itself. According to Car Talk, automatics that aren't CVTs create a problem with gear slippage as they get up to higher speeds, hurting gas mileage.
- Despite advances in technology with CVTs and gear sensors, most automatic transmissions generally get lower mileage than their manual counterparts.
- Cars with automatic transmissions are usually more expensive than those with manual transmissions. This is especially true if they are equipped with the latest CVT transmissions which are also the best performing.
- Automatic transmissions are very complex machines due to the planetary gear system. If they break, it can cost a fortune to have them fixed or replaced.
So if you consider that manual transmissions only get a few more mpg than automatics, and there are far more cars available with an automatic transmission, that's the way to go. Car Talk even went so far as to conclude, "the only good argument for buying a manual transmission these days is 'Because it's fun.'"
But it's all up to you, the driver, to figure out what you're most comfortable with. Some people just love driving a stick. Whatever the case, pop into New Jersey State Auto Auction and have a look through their used car selection – chances are you'll find what you're looking for.
Top 8 beaches for a day trip in and around New JerseyThursday, May 21st, 2015
New Jersey is home to some of the most amazing beaches on the East Coast, and while New York City is more known for its skyscrapers, it's got some pretty cool beach spots too. So if you're bumming around this summer and you're thinking of taking a road trip somewhere, why not consider these eight beaches in New York and New Jersey.
- Cape May
Rebuilt following a massive fire in 1878, Cape May City is distinct from other New Jersey beach towns because it was reconstructed with colorful and interesting Victorian buildings – what's more, there are no big chain stores or restaurants to be found, according to CapeMay.com. It's technically an island, but it's also the southernmost tip of the Garden State. The fact that it's warded off corporate influence for well over a century has kept Cape May as beautiful and original as it always has been. If you're looking for an adventure on a summer day in New Jersey, take a quick trip to Cape May – spend the afternoon on the beach and hang around for a nice dinner on the water.
"Spring Lake has NJ's longest non-commercial boardwalk."
Spring Lake
Sixty miles from downtown Manhattan, Spring Lake features the longest non-commercial boardwalk in New Jersey, according to SpringLakeBoro.org. The Travel Channel characterized the beaches of Spring Lake as some of the most refined in all of Jersey. While this seaside town is a popular spot in the summer with a budding tourist industry, there's only one hotel on the water – so you'd better book early if you plan on staying more than a day. The Breakers Hotel was built in the late 1800s, and while it's been renovated time and again to keep up with the Jones,' its exterior design maintains the hotel's classic charm. So if you fancy a relaxing afternoon on the beach and a quiet town to stroll through, Spring Lake is a good bet for you.
- Long Beach Island
If you're looking for the tourist-y beach spot where you can find, well, everyone else, look no further than Long Beach Island. LBI, as it's referred to by locals, is rich in night life and has 8 miles of beaches, according to the Travel Channel. LBI is the home of the famous original Ron Jon Surf Shop, which was built there in 1961. Since then, it's provided a valuable service to LBI's large surfing community – there are 19 spots that allow surfing along the beaches, the Travel Channel reported. If you're looking for a great time on the beach, LBI is the place to go.
- Ocean City
This popular seaside town, which is actually an island, was recently voted the No. 1 beach in New Jersey by NJ.com readers poll. Ocean City was founded in 1879 and remains one of the most popular family hotspots in the country. Originally intended to be used as a Christian beach and camping retreat, the town remains dry to this day – no alcohol is available anywhere on the island to honor this tradition, according to Ocean City's visitor information website. With 14 guarded beaches open all summer and a 2.5-mile boardwalk packed with shops and eateries, Ocean City is the family destination in New Jersey.Boardwalks are a great attraction for beach goers – they are often lined with shops and restaurants, and some even have amusement piers.
- Wildwood
The Wildwood area in New Jersey has 5 miles of beaches for tourists and local beach bums alike to sprawl out. Wildwood is home to the 1950s and 1960s doo-wop movement -Chubby Checkers debuted the Twist at the famous Rainbow Club, according to the Travel Channel. Of course, it has a beautiful boardwalk, but it's also home to Morey's Piers – a three-pier amusement park that's the largest of its kind in the world, according to Visit NJ. With plenty for kids to do during the day and lots of nighttime entertainment for adults, Wildwood is a great place for a quick road trip.
- Staten Island
Staten Island has more beaches than any other New York City borough, which includes the Franklin D. Roosevelt Boardwalk and Beach, according to NYC Go. The FDR Boardwalk stretches for 2.5 miles, and if you continue walking, lo and behold – you will find more beaches. Cedar Grove Beach is the newest addition to Staten Island's beaches, and it's only been open to the public for a few years. As such, it's not a very well-known spot, so if you're looking to take a nice day trip somewhere that isn't drawing a huge crowd, this might be the spot for you.
"Rockaway Beach is home to NYC's only two surfing spots."
Coney Island
Its name and reputation might say it all, but this world-famous spot in Brooklyn is home to 3 miles of beach. Not to mention, Coney Island still has a healthy supply of new and classic amusement rides that give the Coney skyline its classic appearance. Check it out if you're looking for an interesting spot that has more than just a beach to draw you in.
- Rockaway Beach
Whether or not you're a fan of The Ramones, you might have heard their song about this real-life beach in New York City. The legendary Queens beachfront is the largest urban beach in the U.S., according to NYC Go. It's also home to the only surfing beach in New York City, making it a stand-out attraction for serious beach-goers. There's plenty else to do in this area, with a cluster of shops and restaurants nearby and of course, a boardwalk.
Distracted driving: A leading cause of accidentsWednesday, May 20th, 2015
Distracted driving has been an issue with motorists since the dawn of the age of the automobile. Early traffic enforcement agencies were concerned with drivers reading their mail, and when windshield wipers came out, people were worried the regular motion would put drivers to sleep or hypnotize them, according to the Insurance Institute for Highway Safety. Even car radios were expected to create trouble – when car makers began installing them in the 1930s, legislators made moves to ban them for fear that they would cause crashes.
Not surprisingly, as the technological age has provided people with mobile devices that never leave their hands and onboard computers that offer a range of services inside the vehicle, distracted driving has remained a huge problem, especially for young drivers.
"Distracted driving caused 16% of all crashes in 2012."
Distracted driving in the modern age
Studies in the 1970s concluded that distracted driving was the cause of 15 percent of all crashes, and that number has remained relatively consistent – 16 percent of all auto crashes in 2012 were attributed to distracted driving, the IIHS reported. While current campaigns are focusing on cellphone usage as the No. 1 distraction for drivers, a number of other factors can distract drivers as well. Of all the distraction-related deaths in 2012, 88 percent were attributed to something other than a cellphone.
The Erie Insurance company partnered with the IIHS to conduct an analysis of data from the Fatality Analysis Reporting System to look closer at driver distractions other than cellphone usage. The researchers found that 62 percent of distracted drivers between 2010 and 2011 reported being generally distracted or lost in thought. Cellphone usage was the next leading cause at 12 percent, followed by rubbernecking – or starting at something outside the vehicle – at 7 percent and distraction by passengers in the vehicle at 5 percent.
But because the numbers are based on police opinions filed in reports from crash scenes and drivers that may have been dishonest about their true distractions, there's a chance many of the "generally distracted" drivers were focusing on something other than their daydreams. While that points to a wide range of potential distracters, statistics presented by the National Highway Traffic Safety Administration seem to indicate cellphone usage as the likely culprit in many distracted driving accidents, even if it isn't always reported as such.
Distracted driving has caused far more accidents than it should.
Texting and driving causes accidents
According to the NHTSA, people in the U.S. and all its territories were sending an average of 153.3 billion text messages per month as of December 2013. That same year, 3,154 people were killed, and an additional 424,000 were injured, in accidents caused by distracted driving. An average of 660,000 U.S. drivers can be caught using their cellphones while driving at any given moment during the day. Cellphones, more often than not, have become the center of our attention, and this is particularly a huge problem among teenagers who drive.
The NHTSA reported that traffic crashes are the leading cause of teenage deaths, and 10 percent of traffic fatalities in people under 20 years old were the result of distracted driving. While the NHTSA cites numerous reasons for teenage distractions – such as grooming, eating, using navigation systems and even watching videos – texting is by far the worst distraction for anyone. It requires one hand to do the typing, the eyes to guide the hand and read messages, and the brain to focus on the conversation. The average time spent looking at a text conversation while driving is about five seconds, and at 55 mph, that's the equivalent of driving the entire length of a football field blindfolded, the NHTSA reported. The result is a staggering amount of unnecessary deaths and injuries, which prompted a huge campaign by lawmakers and transportation safety groups to try and stop cellphone-related accidents.
"Traffic crashes are the leading cause of teenage deaths."
How to stop it
Many legislators have sought to hinder distracted driving by passing laws banning all cellphone use. Forty-five states in the U.S. have banned texting while driving altogether, and 40 of those consider it a primary law – which means officers don't need any other reason to pull drivers over if they are using a cellphone, according to the NHTSA.
But the IIHS reported that while cellphone bans while driving have dropped the percentage of observed drivers on their cellphones, the number of crashes has not decreased as expected. This may be because drivers who switch to hands-free calling are still too distracted by their conversations, or perhaps bans just encourage people to be more discreet while using their phones behind the wheel. Whatever the case, the automobile industry is taking preventative measures of their own.
Automakers are trying to help fight distracted driving through the use of front crash prevention technology. The IIHS reported that as many as 1.9 million crashes could be prevented in the future if all vehicles were equipped with high-performance prevention systems. But it may take up to 30 years for the auto industry to fully adopt such features as standard on all vehicles – at the rate of distracted driving deaths in 2013, just under 95,000 lives that may be lost in that time. That's a long time to wait for an entire industry to help prevent people from getting into accidents because they weren't paying attention.
The bottom line is that awareness and education will be the best ways to prevent driver distractions, and that falls on people taking responsibility for themselves. The NHTSA and other government agencies are calling on parents and teachers to educate their kids on driver safety. That also means adults need to lead by example, and show teenagers that it is not OK to text and drive or engage in other distracting behaviors while operating a vehicle.
The National Safety Council has declared April as Districted Driving Awareness Month, and there are plenty of ways to help spread awareness. Check out their website for more information, and remember – the stakes are far too high to get that last message in five minutes before arriving at home – it may cost a life.
And don't forget that avoiding distractions is only one piece of the driving safety puzzle. You can find a great used car loaded with safety features at New Jersey State Auto Auction to help keep your family safe.
8 tips for finding the best car loanTuesday, May 19th, 2015
Having a car is a great way to maintain your independence and flexibility – to travel that is. But buying a car can be a real hassle, and if you don't make wise decisions when it comes to getting a car loan, you'll spend a great deal of time living under the weight of your debt and risk damaging your credit. Start by doing the right thing and becoming an informed car buyer – these eight tips will get point you in the right direction.
- Know what you can afford
Before you do anything else, calculate your budget to see how much you can really afford to spend on a car. Go into the dealer with big dreams and no idea what kind of budget you're working with and you'll wind up driving a prince's chariot on a pauper's salary. Consumer Reports recommended paying no more than 36 percent of your gross income on debts. In other words, find out what 36 percent of your annual gross income is. Add up all of your monthly debts – insurance, rent, bills, food and credit cards – for the year and subtract that from your 36 percent. What you have left is an approximation of what you can potentially spend on car payments annually. Don't forget to look into additional costs associated with a new vehicle, like registration fees, changes in insurance and any taxes you might have to pay on it.
- Make a down payment
This cannot be stressed enough, so we'll say it again – make a down payment. The more money you can drop on a car up front, the better. A solid down payment will lower your monthly payments, lower the interest rate and leave you owing less overall. Obviously you don't want to break the bank trying to make a down payment, but if you can hold off as long as possible and save up a solid cash pile, do it. You should try to make your down payment between 15 and 20 percent of the total cost of the vehicle, according to Consumer Reports.
"Get your credit score before doing anything else."
Know your credit score
Get your credit score before you even think about applying for a loan. Your credit score determines your interest rate, and if you leave it up to the lender to determine your credit rating, you might be getting the short end of the stick. Also, if you find out early on that you have poor credit score, you can take the time to figure out how best to bring your score up before you start looking for the perfect used car.
- But, don't fear your credit score
Contrary to popular belief, your credit score isn't everything – and how "bad" or "good" it is may depend on the eye of the beholder. Bankrate reported that many lenders may look closer at your credit history than the actual score. While a low score might rule you out for a house loan, the same score might work just fine for an auto loan if your history indicates that you're building decent credit.
- Negotiate the purchasing price
Rather than negotiating the monthly payment, insist on lowering the overall purchasing price instead. It may mean you have to pay a little more per month, depending on how you negotiate it, but the lower the purchasing price, the less you owe altogether. You should also avoid vehicles with upgrades and add-ons that have driven up the value, especially those that you can afford to purchase later on, as they will only increase the loan amount.
- The shorter the loan, the better
According to Consumer Reports, longer loans cost more than shorter ones. The catch is that longer loans usually mean lower monthly payments, but that extends the total cost of the interest. You'll pay more in interest over five years than in three. Also, longer loans usually carry higher interest rates anyway, so that will increase the total amount you're spending as well. A shorter loan may mean you're paying a little more per month, but if you can afford the higher payments, the interest rate will be lower and you'll be paying less in the long run -you'll also have the satisfaction of paying off the loan in a shorter amount of time.
- Don't end up upside down
"Upside down," in loan terms, occurs when your vehicle is worth less than you owe on it. You need to try and ensure that this does not happen to you. If you go to trade in your car before you've paid the loan off, and it's worth less than what you owe, you end up with negative equity. If something terrible happens and your car is totaled, but the value is less than what you owe, the insurance payout will only cover the value of the vehicle and you'll be stuck paying off a car you no longer have while attempting to buy a replacement. One of the ways you can avoid this is to make sure you have a down payment when you purchase a used car – it will help add equity to the car before you even start paying the loan, according to Consumer Reports. This is also another good reason to negotiate a shorter loan term – your monthly payments will accrue more equity in a shorter time than if they are spread out over a longer loan period.
"Compare interest rates with as many lenders as possible."
Shop around
Don't just go into this blind and settle for the first deal that sounds good. Compare interest rates with as many banks, credit unions and other lenders as possible to find the best rate for your used car loan. This includes online lenders – most of which have calculators on their websites that will help you figure out what you're really getting into, according to DMV.org. Remember, most rates are competitive, so the more information you have about rates, the more you can negotiate with lenders. Dealerships, such as New Jersey State Auto Auction, also have on-site financing available, and often at a rate that competes with local banks. Bankrate recommended focusing on lenders that specifically deal in auto loans, as they will interpret your application differently than a lender that deals in a broad range of financing.
The bottom line is that the more prepared you are for buying a car, the better. If you find yourself on a budget, a used model is probably the way to go, as you can find amazing deals on used cars if you're willing to put in the shopping effort. What's more, New Jersey Auto Auction has a wide selection of vehicles and a financing department that is more than willing to help you find a good deal. Just keep these eight tips in mind when you're working out the details, and you're likely to come out on top.
Maintenance tips for a successful summer road tripThursday, May 7th, 2015
Summertime probably means you'll be taking a road trip to somewhere at some point. Maybe you're driving an hour to the nearest beach or heading out on a long journey across country. Regardless, the absolute last thing you want is to have your car break down while you're in the middle of a trip, especially if it's due to something you could have easily prevented. So whether you're driving a Mercedes-Benz or a Ford, do the smart thing this summer and follow these simple tips to avoid a breakdown.
"Are you properly maintaining your vehicle?"
Keep up with the up-keep
The first question you should be asking yourself when considering your car's well-being is, "Am I properly maintaining my vehicle?" Whether you've had your vehicle for a few years or you've just acquired a used car, be aware of the manufacturer's recommended maintenance schedule. You can find it in your owner's manual, which you should probably look through if you haven't already. The schedule will include recommendations for fluid changes, tire rotations and other services based on your vehicle's mileage. Some of the things you might see are detailed in the list below that you can either check yourself, or have your mechanic inspect to be sure you and your car are up to speed.
The tires
The National Highway Transportation Safety Administration reported that low tire pressure is the leading cause of blowouts. Check your tire pressure when the tires are cold, or when you haven't driven on them for any considerable distance, the NHTSA said. The manufacturer's recommended tire pressure can be found on the inside of your driver-side door panel. It's a good idea to keep a tire-pressure gauge in your car, so you'll always be able to tell whether or not you need some air.
You should ensure your tires are still in good condition, especially if you're switching back to summer tires from winter tires. Inspect each tire for any cracking or potential leaks, especially if you've checked the pressure and found it to be low. You should also check the tread using the penny trick, the NHTSA recommended. Rest a penny in the tread, with Lincoln's face upside-down – if you can see the top of his head you should probably have your tires replaced. If not, you're all set.
If the tires seem to have uneven wear patterns, they may need to be re-aligned, according to the NHTSA. Have your mechanic inspect the alignment and rotate the tires if necessary. This will ensure they wear evenly and prolong their life.
The radiator
Overheating on the highway is a common occurrence in the summer time, so keeping tabs on the health of your radiator system is very important. Car Talk reported that it's crucial to check the radiator core, especially if you live in an area where salt is used heavily on roads in the winter, as it can rot the tubes that carry the coolant. Have a mechanic test the core to see if the tubes are showing any signs of corrosion.
The coolant itself should also be full and healthy. Most coolants nowadays last between 60,000 and 100,000 miles, but if your car is in that range you may need to replace it, according to Car Talk. Before you even ask, yes, you still need antifreeze in the summer. Antifreeze has a much higher boiling point than water and it will help keep the engine cool in extreme temperatures.
The thermostat must also be working well if you're going to keep the engine cool. If the thermostat is stuck, all the coolant in the world won't keep your engine from overheating, according to Car Talk.
"Change your oil and filter every 5,000 miles."
Oil and transmission fluid
If you don't have enough oil in your engine, you risk severe damage or even seizure. This will not only stop you in your tracks, it will cost you a fortune to replace the engine if it seizes. So, always check your oil level before heading out on a long trip. It's also essential to make sure you're changing the oil regularly. Most manufacturers recommend changing the oil and filter every 5,000 miles, Car Talk said. If you change the oil and it gets dirty quickly, you may need an engine flush to help remove excess dirt and residue buildup.
The same is true for your transmission fluid. While it doesn't need to be replaced nearly as often as oil, sustained high temperatures and bad transmission fluid don't mix. You can look at it yourself – good fluid should look reddish-brown while fluid that needs to be changed will be very dark and may not have any red tinge left at all. If it looks bad, have the transmission flushed and the fluid replaced.
The air conditioner
This one is a no-brainer. Nobody wants to be stuck in a hot car in the summertime, and having the air conditioner checked is the best way to prevent that. Start by running the air conditioner and testing how cold it is. If it's not pumping cold air, you might need to have it serviced. How Stuff Works said that low refrigerant is the leading cause of faulty air conditioners. Have a mechanic ensure you have enough refrigerant and more importantly, that none is leaking. Some cars also come equipped with a cabin air filter, which cleans the air as it's pumped through the vents and into the vehicle. You want to be sure the filter is clean, so check your owner's manual to see if your car has one and where it is.
Seatbelts and car seats
Once you've ensured everything else on this list is in working order, be sure to follow proper safety procedures inside the car as well. Everyone riding in the vehicle must be buckled at all times. When traveling with young children, they need to be properly restrained in the back seat. The NHTSA has a slew of safety guidelines that not all available car seats adhere to. If you're a new parent, read through the NHTSA's guidelines to ensure you're doing it right from the start. It's also recommended that you buckle all unused seatbelts so that children will be less likely to become entangled if they're playing around in the backseat.
Stick to these guidelines and you're likely to avoid any serious bumps on your summer road trip.
10 of the best cars under $10k for gradsTuesday, May 5th, 2015
It's graduation season, and that probably means a lot of things for you and your family. If you're a parent, watching your child cross the stage and exit into the world as a young adult is a proud and emotional moment. You might even feel so inclined as to reward your offspring for his academic achievements – handsomely. If you're the graduate, you're probably thinking you deserve the same thing. As it so often happens on graduation days, this mutual feeling of accomplishment between parent and graduate may materialize itself in the form of a car. If Junior hasn't asked for a set of wheels yet, he probably will, so you might as well be prepared.
"Your grad doesn't need a brand new sports car."
That said, and as much as you may want to reward your graduate, you don't need to empty your savings account to buy him a brand new sports car. Instead, consider shopping for a used vehicle – one with decent mileage, safety features and style that will still keep your graduate safe while he rides in style. To help you out, we've compiled a list of our 10 favorite used cars under $10,000 – some that maximize safety features and gas mileage, others that Junior will just love.
1. 2009 Volkswagen Rabbit
The VW Rabbit is the German automaker's replacement for the Golf. Sporty in style and feel with a great interior, this hatchback is a versatile and appealing option for college-bound high school grads. It was in Consumer Reports' top three list of small cars in this price range, and we're placing it at the top of our list. Yes, it's a compact car, but it holds the 2009 Top Safety Pick award from the Insurance Institute for Highway Safety. Not to mention it gets 22 mpg in the city and 30 mpg on the highway.
It almost goes without saying that this would be a great gift for your grad – it's a Beemer. Every teenager dreams of driving a BMW someday, so maybe you can make that dream a reality on graduation day without breaking the bank. This model has a quick V-6 engine and a luxurious interior. It gets 25 mpg on the highway and has electronic stability control to help keep Junior on the road. Did we mention you can pick this BMW up for less than $10,000?
3. 2005 Acura TL
Luxury and sport combine to offer you this affordable sedan. It comes with curtain airbags and carries a 4.6-star crash test rating from the National Highway Traffic Safety Administration. Loaded with a V-6, it gets 18 mpg in the city and 26 mpg on the highway. Fuel-efficient and stylish, this one's a no-brainer.
4. 2008 Mazda 3
Consumer Reports said "this car has everything most shoppers want in a small car," and we tend to agree. Comfortable seats, sleek interior design and a choice between a hatchback and sedan make this a perfect car for a recent grad. It gets 22 mpg in the city and 29 mpg on the highway, and Kelley Blue Book reported that the sport-model Mazda 3s from 2008 were all equipped with side-impact and side-curtain airbags, making them safer than previous versions.
5. 2008 Pontiac Vibe
This spacious and stylish wagon has a 115-volt outlet on the console and plenty of cargo space, making it a perfect fit for active and adventurous youth. It's great on gas at 33 mpg on the highway and carries a five-star overall driver and passenger front impact safety rating from the NHTSA.
6. 2005 Honda Pilot
Yahoo! Autos called the Pilot the best combination of a "wagon, SUV and minivan." The Pilot is enormous – it's capable of seating eight people and the seats are adjustable to make room for plenty of cargo. With a powerful V-6 engine and four-wheel drive, the Pilot will take your graduate just about anywhere he wants to go – all with an average 27 mpg on the highway and 20 mpg in the city. The NHTSA gave the 2005 Pilot a five-star crash rating and four stars for the rollover test.
7. 2007 Mitsubishi Outlander
The Outlander is a sporty SUV with a third seat option for optimal seating and a 30 gigabyte hard drive for on-board navigation and other technologies. Your grad can store up to 6 GB of music on this bad boy, and with a five-star crash rating from the NHTSA it might be one of the best options if you're looking for an SUV. Not to mention, it gets 20 mpg in the city and 30 mpg on the highway.
8. 2008 Hyundai Sonata
Humble yet sharp in style, this midsize sedan is considered a large car by the Environmental Protection Agency because there's so much room in the interior, according to KBB. One of the Sonata's selling points is that it comes with a slew of great safety features, including active front head restraints, electronic stability control and an air purification system that self-activates when it senses too many air pollutants, such as diesel fumes. It has a five-star safety rating from the NHTSA and the V-6 engine gets up to 30 mpg on the highway.
"The Sonata comes with a slew of great safety features."
9. 2007 Honda Fit
A very compact car with adjustable seats, the Fit might be a perfect option for a grad with his own style. It has an interesting look that took Americans by surprise when it made its debut in 2006, but has since become a popular model among small cars. Don't let the size fool you – with adjustable seats, the Fit can hold up to 41.9 cubic feet of cargo if you really know to pack it in there. That might even be room enough for everything your grad needs to take to college. With five-star front and rear impact ratings from the NHTSA and an average of 38 mpg on the highway – the best mileage on this list – you can't go wrong.
10. 2006 Mini Cooper S
People didn't know what to make of the Mini Cooper when it first showed up on American streets. Thanks to movies like The Italian Job, the compact British car has earned its place in the hearts of auto fanatics and Sunday drivers alike. It has a style all of its own that's sure to attract attention for your grad as he cruises around campus. With a four-star overall safety rating form the NHTSA and up to 33 mpg on the highway, this is a great option for a grad that just wants something different.


text:
I belong to most all of the crazy quilting groups that have been formed on-line. One of these, Crazy Quilting International deserves a HUGE round of applause! I am soooo very touched by these wonderful people!
This is the story..... I went to the http://www.makingmemories.org/ site not long ago and volunteered to make a quilt for them out of donated wedding dresses. Quilts are returned, completed and then auctioned off. The proceeds then are put towards research for breast cancer. This is one of my pet charities as it has affected me on a personal level. Anyway, the HUGE box arrived from them, complete with DIFFERENT time lines for completion!!! OMG!! So, I asked my local group of cquer's AND folks at CQI if they could help! The response has been overwhelming! These stitching soul mates from around the world have stepped up to the plate and offered their time, skills and creativity to help me put this together! Just AWESOME!! These ladies deserve a HUGE round of applause, thanks and HUGS!!! Thank you, thank you! Your generosity is overwhelming and I am crying tears of joy that this project will be able to come together!
CQI girls ROCK!!
Tuesday, May 13, 2008
Huge Thanks!
I belong to most all of the crazy quilting groups that have been formed on-line. One of these, Crazy Quilting International deserves a HUGE round of applause! I am soooo very touched by these wonderful people!
Posted by piney cq at 6:19 AM
Labels: beading, Brazilian embroidery, breast cancer, charity, crazy quilting, Crazy quilting international, silk ribbon embroidery, sre
4 comments:
- Jo in NZ said...
of course we do.....LOL (rock that is)
Leslie, you know how I feel--I am honored to work on this for you. Debbie (Maine)
- Sharon said...
hey girl with all the help you offer us all the time...this is one small way I get to say "thank you" and of course the reason for the blocks is close to my heart also....
Leslie,just been to making memories site..I am so touched. What a wonderful project you are all supporting from the bottom of your hearts ''Bless you all''esp you for organising this...what wonderful kindness.
Hugs Pam UK


text:
Palm Springs isn't just a trip, it feels like a tradition now ( 10 years -Che''s first trip was at 4 months of age!)
This is us. Odd, loud & bananas at times but most happy. Which is the key to a good life!
Thank you, Barb (Nannie) & Ken (Grandpa) for always allowing us to share your time and space!
(Tec stuff- every shot was taken with a Sigma art 24mm fixed lens, mostly stomped down to a 1.6/2.8 f-stop- 5D mark 11 body. Edited with Lightroom 6- presets crated by Klutch Photography)
Klutch's Instagram feed


text:
PITAVASTATIN, LIVALO, Itavastatin calcium, Nisvastatin, NKS-104, NK-104,
(3R, 5S) -7 – [2-Cyclopropyl-4-(4-fluorophenyl) quinolin-3-yl] -3,5-dihydroxy-6 (E)-heptenoic acid calcium salt (2:1)
147526-32-7 CA SALT, 147511-69-1 (free acid), 141750-63-2 (lactone), 192565-91-6 (monoK salt)
rotation is +
alpha(D20) +6.8° (c 1.74, CHCl3)
Bioorganic and Medicinal Chemistry Letters, 1999 , VOL 9, 20 pg. 2977 – 2982…….alpha(D20) +23.1° (c 1.0, acn/water(1:))
Helvetica Chimica Acta, 2007 , vol. 90, 6 pg. 1069 – 1081…alpha(D20) +22.9° (c 1.0, acn/water)
(3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid
Pitavastatin a lipid-lowering agent that belongs to the statin class of medications for treatment of dyslipidemia. It is also used for primary and secondary prevention of cardiovascular disease. FDA approved in Aug 3, 2009.
2-C25-H23-FN-O4.Ca, 881.01
Nissan Chemical (Originator), Kowa (Licensee), Novartis (Licensee), Recordati (Licensee), Sankyo (Licensee)
Lipoprotein Disorders, Treatment of, METABOLIC DRUGS, APOA1 Expression Enhancers, HMG-CoA Reductase Inhibitors, SPP1 (Osteopontin) Expression Inhibitors
Statin drugs are currently the most therapeutically effective drugs available for reducing the level of Low density lipoprotein (LDL) in the blood stream of a patient at risk for cardiovascular disease. A high level of LDL in the
bloodstream has been linked to the formationof coronary lesions which obstruct the flow of blood and can rupture and promote thrombosis. It is well known that inhibitors against HMG CoA reductase which is rate limiting enzyme for cholesterol biosynthesis have been clinically proved to be potentially useful anti-hyperlipoproteinemic agents
and they are considered very effective curative and preventive for coronary artery sclerosis or atherosclerosis .
Pitavastatin calcium was discovered by Nissan Chemical Industries Limited Japan and developedfurther by Kowa Pharmaceuticals Tokyo Japan is a novel member of the medication class of statins.
bloodstream has been linked to the formationof coronary lesions which obstruct the flow of blood and can rupture and promote thrombosis. It is well known that inhibitors against HMG CoA reductase which is rate limiting enzyme for cholesterol biosynthesis have been clinically proved to be potentially useful anti-hyperlipoproteinemic agents
and they are considered very effective curative and preventive for coronary artery sclerosis or atherosclerosis .
Pitavastatin calcium was discovered by Nissan Chemical Industries Limited Japan and developedfurther by Kowa Pharmaceuticals Tokyo Japan is a novel member of the medication class of statins.
LIVALO (pitavastatin) is an inhibitor of HMG-CoA reductase. It is a synthetic lipid-lowering agent for oral administration.
The chemical name for pitavastatin is (+)monocalcium bis{(3R, 5S, 6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3,5dihydroxy-6-heptenoate}. The structural formula is:
The empirical formula for pitavastatin is C50H46CaF2N2O8 and the molecular weight is 880.98. Pitavastatin is odorless and occurs as white to pale-yellow powder. It is freely soluble in pyridine, chloroform, dilute hydrochloric acid, and tetrahydrofuran, soluble in ethylene glycol, sparingly soluble in octanol, slightly soluble in methanol, very slightly soluble in water or ethanol, and practically insoluble in acetonitrile or diethyl ether. Pitavastatin is hygroscopic and slightly unstable in light.
Each film-coated tablet of LIVALO contains 1.045 mg, 2.09 mg, or 4.18 mg of pitavastatin calcium, which is equivalent to 1 mg, 2 mg, or 4 mg, respectively of free base and the following inactive ingredients: lactose monohydrate, low substituted hydroxypropylcellulose, hypromellose, magnesium aluminometasilicate, magnesium stearate, and film coating containing the following inactive ingredients: hypromellose, titanium dioxide, triethyl citrate, and colloidal anhydrous silica.
Pitavastatin (usually as a calcium salt) is a member of the blood cholesterol loweringmedication class of statins,[1] marketed in the United States under the trade nameLivalo. Like other statins, it is an inhibitor of HMG-CoA reductase, the enzyme that catalyses the first step of cholesterol synthesis. It has been available in Japan since 2003, and is being marketed under licence in South Korea and in India.[2] It is likely that pitavastatin will be approved for use in hypercholesterolaemia (elevated levels of cholesterol in the blood) and for the prevention of cardiovascular disease outside South and Southeast Asia as well.[3] In the US, it received FDA approval in 2009.[4]
Pitavastatin is used to lower serum levels of total cholesterol, LDL-C, apolipoprotein B, and triglycerides, and raise levels of HDL-C for the treatment of dyslipidemia.
Like the other statins, pitavastatin is indicated for hypercholesterolaemia (elevated cholesterol) and for the prevention of cardiovascular disease. A 2009 study showed that pitavastatin increased HDL cholesterol (24.6%), especially in patients with HDL lower than 40 mg/dl, in addition to greatly reducing LDL cholesterol (–31.3%).[5] As a consequence, pitavastatin is most likely to be appropriate for patients with metabolic syndrome with high LDL, low HDL and diabetes mellitus.
Common statin-related side effects (headaches, stomach upset, abnormal liver function tests and muscle cramps) were similar to other statins. However, pitavastatin seems to lead to fewer muscle side effects than certain statins that are lipid-soluble, as a result of the fact that pitavastatin is water-soluble (as is pravastatin, for example).[6] One study found that coenzyme Q10 was not reduced as much as with certain other statins (though this is unlikely given the inherent chemistry of the HMG-CoA reductase pathway that all statin drugs inhibit).[3][7]
Hyperuricemia or increased levels of serum uric acid have been reported with pitavastatin.[8]
Most statins are metabolised in part by one or more hepatic cytochrome P450enzymes, leading to an increased potential for drug interactions and problems with certain foods (such as grapefruit juice). Pitavastatin appears to be a substrate ofCYP2C9, and not CYP3A4 (which is a common source of interactions in other statins). As a result, pitavastatin is less likely to interact with drugs that are metabolized via CYP3A4, which might be important for elderly patients who need to take multiple medicines.[3]
Pitavastatin (previously known as itavastatin, itabavastin, nisvastatin, NK-104 or NKS-104) was discovered in Japan by Nissan Chemical Industries and developed further byKowa Pharmaceuticals, Tokyo.[3] Pitavastatin was approved for use in the United States by the FDA on 08/03/2009 under the trade name Livalo. Pitavastatin has been also approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in UK on 17 August 2010.
- Kajinami, K; Takekoshi, N; Saito, Y (2003). "Pitavastatin: efficacy and safety profiles of a novel synthetic HMG-CoA reductase inhibitor".Cardiovascular drug reviews 21 (3): 199–215. PMID 12931254. edit
- Zydus Cadila launches pitavastatin in India
- Mukhtar, R. Y. A.; Reid, J.; Reckless, J. P. D. (2005). "Pitavastatin". International Journal of Clinical Practice 59 (2): 239–252.doi:10.1111/j.1742-1241.2005.00461.x. PMID 15854203. edit
- The Seventh Statin; Pitavastatin
- http://www.ncbi.nlm.nih.gov/pubmed/19907105
- ScienceDaily (11 May 2013). "Alternative Cholesterol-Lowering Drug for Patients Who Can't Tolerate Statins". ScienceDaily.
- Clin Pharmacol Ther. 2008 May;83(5):731-9. Epub 2007 Oct 24. Comparison of effects of pitavastatin and atorvastatin on plasma coenzyme Q10 in heterozygous familial hypercholesterolemia: results from a crossover study. Kawashiri MA, Nohara A, Tada H, Mori M, Tsuchida M, Katsuda S, Inazu A, Kobayashi J, Koizumi J, Mabuchi H, Yamagishi M.
- Ogata, N.; Fujimori, S.; Oka, Y.; Kaneko, K. (2010). "Effects of Three Strong Statins (Atorvastatin, Pitavastatin, and Rosuvastatin) on Serum Uric Acid Levels in Dyslipidemic Patients". Nucleosides, Nucleotides and Nucleic Acids 29 (4–6): 321.doi:10.1080/15257771003741323. edit
Patent Number
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Tetrahedron Lett 1993, 34, 51, 8263-6.
Bioorg Med Chem2001, 9, (10): 2727
Drugs Fut1998, 23, (8) :847-859
Bull Chem Soc Jpn1995, 68, (1) :364-72
Tetrahedron Asymmetry1993, 4, (2) :201-4
Tetrahedron Lett1993, 34, (51) :8267-70
A Endo; J. Med. Chem. 1985, 28, 401.
AM Gotta; LC Smith; IXth International Symp. Drugs Affecting Lipid Metabolism, 1986, 30- 31
Y Fujikawa, Nissan Chemical Industries Ltd, EP304063 (A3), 1989.
S Ahmed; CS Madsen; PD Stein; J. Med. Chem. 2008, 51, 2722-2733.
K Turner; Org. Process. Res. Dev, 2004, 8, 823-833.
Z Casar; M Steinbocher; J Kosmrlj; J. Org. Chem. 2010, 75(19), 6681-6684.
KL Baumann; Tetrahedron Letters, 1992, 33, 2283-2284.
N Miyachi; Y Yanagawa; H Iwasaki; Tetrahedron Lett. 1993, 34, 8267-8270.
T Minami; K Takahashi; T Hiyama; Tetrahedron Lett. 1993, 34, 3, 513-516.
DA Evans; AH Hoveyda; J. Org. Chem. 1990, 55, 5190-5192.
J Castorer; LA Sorbera; PA Leeson; Drugs Fut. 23(8), 1998, 847-859.
T Hiyama; K Takahashi; T Minami; Bull. Chem. Soc. Jpn. 1995, 68, 364-372.
MS Reddy; M Bairy; K Reddy; Oriental Journal of Chemistry. 2007, 23, 559-564.
RN Moore; G Bigam; JK Chan; AM Hogg; JC Vederas; J. Am. Chem. Soc. 1985, 107 3694-3701.
DS Johnson; JJ Li; Art of Drug Synthesis, John Wiley & Sons, New Jersey, 2007, 177-181.
MT Stone; Organic Lett. 2011, 13, 2326-2329.
SR Manne, SR Maramreddy, WO2007132482 (A2), 2007.
SD Dwivedi, DJ Patel, AP Shah, Cadila Healthcare Ltd, US0022102 (A1), 2012.
AM Gotta; LC Smith; IXth International Symp. Drugs Affecting Lipid Metabolism, 1986, 30- 31
Y Fujikawa, Nissan Chemical Industries Ltd, EP304063 (A3), 1989.
S Ahmed; CS Madsen; PD Stein; J. Med. Chem. 2008, 51, 2722-2733.
K Turner; Org. Process. Res. Dev, 2004, 8, 823-833.
Z Casar; M Steinbocher; J Kosmrlj; J. Org. Chem. 2010, 75(19), 6681-6684.
KL Baumann; Tetrahedron Letters, 1992, 33, 2283-2284.
N Miyachi; Y Yanagawa; H Iwasaki; Tetrahedron Lett. 1993, 34, 8267-8270.
T Minami; K Takahashi; T Hiyama; Tetrahedron Lett. 1993, 34, 3, 513-516.
DA Evans; AH Hoveyda; J. Org. Chem. 1990, 55, 5190-5192.
J Castorer; LA Sorbera; PA Leeson; Drugs Fut. 23(8), 1998, 847-859.
T Hiyama; K Takahashi; T Minami; Bull. Chem. Soc. Jpn. 1995, 68, 364-372.
MS Reddy; M Bairy; K Reddy; Oriental Journal of Chemistry. 2007, 23, 559-564.
RN Moore; G Bigam; JK Chan; AM Hogg; JC Vederas; J. Am. Chem. Soc. 1985, 107 3694-3701.
DS Johnson; JJ Li; Art of Drug Synthesis, John Wiley & Sons, New Jersey, 2007, 177-181.
MT Stone; Organic Lett. 2011, 13, 2326-2329.
SR Manne, SR Maramreddy, WO2007132482 (A2), 2007.
SD Dwivedi, DJ Patel, AP Shah, Cadila Healthcare Ltd, US0022102 (A1), 2012.
The reaction of 1 (R) ,7,7-trimethylbicyclo [2.2.1] heptan-2-one (I) with 1 -naphthylmagnesium bromide (II) gives the tertiary alcohol (III), which by reaction with SOCl2 and then with NaHCO3 yields 2 – (1-naphthyl) -1 (R) ,7,7-trimethylbicyclo [2.2.1] heptene (IV ). Hydroboration of (IV) with BH3 followed by oxidation with H2O2 affords 4 (S) ,7,7-trimethyl-3exo-(1-naphthyl) bicyclo [2.2.1] heptan-2exo-ol (V), which is submitted to transesterification with methyl acetoacetate (VI) and dimethyl-aminopyridine (DMAP) to give the corresponding ester (VII). The condensation of (VII) with N-methoxy-N-methyl-3-[2-cyclopropyl-4-( 4-fluorophenyl) quinolin-3-yl] -2 (E)-propenamide (VIII) by means of NaH yields the corresponding chiral 3,5-dioxoheptenoic acid ester (IX), which is selectively reduced first with diisobutylaluminum hy-dride acid (DIBAL) and then with diethylmethoxyborane and sodium borohydride affording the 3 (R), 5 (S)-dihydroxyheptenoic ester (X). Finally, this compound is saponified with NaOH and treated with acetic acid / sodium acetate. The intermediate amide (VIII ) is obtained by condensation of 2-cyclopropyl-4-(4-fluorophenyl) quinoline-3-carbaldehyde (XI) with N-methoxy-N-methylacetamide (XII) by means of butyllithium to the hydroxy propionamide (XIII), which is then dehydrated with methanesulfonyl chloride and triethylamine in the usual way).
A systematic chiral synthesis of NK-104 and its enantiomer (X) has been reported: The oxidation of the already known 2-cyclopropyl-4-(4-fluorophenyl)quinoline-3-methanol (I) with DMSO, P2O5 and triethylamine gives the corresponding aldehyde (II), which is condensed with diethyl cyanomethylphosphonate by means of NaOH in toluene yielding the propenenitrile (III). The reduction of (III) with DIBAL affords the unsaturated aldehyde (IV), which is condensed with ethyl acetoacetate by means of NaH and n-BuLi to provide the 3-oxo-5-hydroxy-6-heptenoic acid ethyl ester derivative (V). The highly syn stereoselective reduction of (V) by means of diethylmethoxyborane and NaBH4 yields the desired syn racemic mixture of erythro-beta,delta-dihydroxyesters (VII), which is submitted to optical resolution with chiral (+)-alpha-methylbenzylamine [(+)-MBA] to obtain NK-104 free acid (VIII), which is finally treated with NaOH and CaCl2. The enantiomer of NK-104 has been obtained by optical resolution of the racemic mixture (VII) with (-)-alpha-methylbenzylamine to obtain the enantiomeric free acid (IX), which is treated with NaOH and CaCl2 as before.
Fujikawa, Y.; Suzuki, M.; Iwasaki, H.; Kitahara, M.; Sakashita, M.; Sakoda, R.;. Synthesis and biological evaluations of quinolone-based HMG-CoA reductase inhibitors Bioorg Med Chem 2001, 9 , 10, 2727
Pitavastatin calcium is a novel member of the medication class of statins. Marketed in the United States under the trade name Livalo, it is like other statin drugs an inhibitor of HMG-CoA reductase, the enzyme that catalyses the first step of cholesterol synthesis. It is likely that pitavastatin will be approved for use in hypercholesterolaemia (elevated levels of cholesterol in the blood) and for the prevention of cardiovascular disease outside South and Southeast Asia as well.
Pitavastatin calcium is chemically known as (3R,5S)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxy-6(E)-heptenoic acid calcium salt having the formula IA is known in the literature.
Pitavastatin is a synthetic lipid-lowering agent that acts as an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme a (HMG-CoA) reductase (HMG-CoA Reductase inhibitor). This enzyme catalyzes the conversions of HMG-CoA to mevalonate, inhibitors are commonly referred to as "statins". Statins are therapeutically effective drugs used for reducing low density lipoprotein (LDL) particle concentration in the blood stream of patients at risk for cardiovascular disease. Pitavastatin is used in the treatment of hyperchloesterolemia and mixed dyslipidemia.
Pitavastatin calcium has recently been developed as a new chemically synthesized and powerful statin by Kowa Company Ltd, Japan. On the basis of reported data, the potency of Pitavastatin is dose-dependent and appears to be equivalent to that of Atorvastatin. This new statin is safe and well tolerated in the treatment of patients with hypercholesterolaemia. Significant interactions with a number of other commonly used drugs can be considered to be extremely low.
Pitavastatin was disclosed for the first time in US patents US 4,761,419, US 5,01 1 ,930 and US 5,753,675. The process disclosed in these patents for the preparation of Pitavastatin is as shown below:
wherein R is hydrogen or protecting group.
US 5,284,953 discloses a process for the preparation of Pitavastatin calcium, which employs optically active a-methylbenzylamine as a resoluting agent.
The above processes are economically not viable, as resolution is carried out in final stage.
US 6,835,838 B2 discloses a process for the preparation of Pitavastatin calcium, which is as shown below:
However, it has been observed that the above process of lactonization results in ~10- 15% of unreacted Pitavastatin ethyl ester and therefore results in low yield. Further, -10% of Pitavastatin acid results during the above lactonization process and therefore does not produce a single product which is required to keep adequate control for an intermediate through specifications to have consistently better quality of the finished product.
Processes for the preparation of Pitavastatin are described in EP-A-0304063 and EP-A-1099694 and in the publications by N. Miyachi et al. in Tetrahedron Letters (1993) vol. 34, pages 8267-8270 and by K. Takahashi et al. in Bull. Chem. Soc. Japan (1995) Vol. 68, 2649-2656. These publications describe the synthesis of Pitavastatin in great detail but do not describe the hemi-calcium salt of Pitavastatin. The publications by L A. Sorbera et al. in Drugs of the Future (1998) vol. 23, pages 847-859 and by M. Suzuki at al. in Bioorganic & Medicinal Chemistry Letters (1999) vol. 9, pages 2977-2982 describe Pitavastatin calcium, however, a precise procedure for its preparation is not given. A full synthetic procedure for the preparation of Pitavastatin calcium is described in EP-A-0520406. In the process described in this patent Pitavastatin calcium is obtained by precipitation from an aqueous solution as a white crystalline material with a melting point of 190-192° C.
US20090182008 A1 discloses polymorphic form A, B, C, D, E, and F, and the amorphous form of Pitavastatin Calcium salt (2:1). In particular, crystalline Form A having water content from about. 5% to about 15% and process for its preparation are disclosed.
US20090176987 A1 also discloses polymorphic form crystal form A of Pitavastatin Calcium which contains from 5 to 15% of water and which shows, in its X-ray powder diffraction as measured by using CuKa radiation, a peak having a relative intensity of more than 25% at a diffraction angle (20) of 30.16°.
WO2007/132482 A1 discloses a novel process for the preparation of Pitavastatin Calcium by condensing bromide salt of formula-3 with aldehyde compound of formula-4 to obtain olefinic compound of formula-5 and converting olefinic compound to Pitavastatin Calcium via organic amine salt for purification.
Pitavastatin and its process were disclosed in U.S. Pat. No. 5,753,675.
Pitavastatin calcium and its process were disclosed in U.S. Pat. No. 5,856,336. PCT publication no. WO 2004/072040 (herein after referred to '040 patent) disclosed crystalline polymorph A, polymorph B, polymorph C, polymorph D, polymorph E, polymorph F and amorphous form of pitavastatin calcium
- Synthesis of pitavastatin via cross-coupling reaction is disclosed inTetrahedron Lett. 1993, 34, 8263-8266, and in Tetrahedron Lett. 1993, 34, 8267-8270.
- A method for the preparation of pitavastatin via epichlorohydrin is described in Tetrahedron: Asymmetry 1993, 4, 201-204.
- PCT application WO 2003/064382 describes a method for preparation of pitavastatin by asymmetric aldol reaction, in which titanium complex is used as a catalyst.
- HWE route to pitavastatin by utilization of 3-formyl substituted pitavastatin heterocycle is disclosed in Helv. Chim. Acta 2007, 90, 1069-1081:
- Methods for preparation of pitavastatin heterocycle derivatives are described in Bull. Chem. Soc. Jpn. 1995, 68, 364-372, Heterocycles 1999, 50, 479-483, Lett. Org. Chem. 2006, 3, 289-291, and in Org. Biomol. Chem. 2006, 4, 104-110, as well as in the international patent applications WO 95/11898 and WO 2004/041787
WO 1995/1 1898 Al discloses a process for the preparation of Pitavastatin, which is as shown below:
wherein Y represents P+RnRi2Ri3Hal" or P(W)Ri4R15; R9a, R% and R]0 are protecting groups each of Rn, Rj2> R^, Ri4 and R15 which are independent of one another, is optionally substituted alkyl or optionally substituted aryl group; R14 and Rj5 together form a 5- or 6-membered ring; Hal is chlorine, bromine or iodine; and W is O or S.
The above process results in 2-5% of Cis isomer of Pitavastatin which requires further purification and therefore results poor yield.
US 6,875,867 B2 discloses a process for the preparation of Pitavastatin arginine salt, which is as shown below:
Saponification / Base
During the above process Trifluoroacetic acid or hydrochloric acid is used to break the acetonide and the Pitavastatin ester formed is converted in situ to its corresponding alkali salt by treating with base, such as sodium hydroxide.
US20090182008 A1 discloses polymorphic form A, B, C, D, E, and F, and the amorphous form of Pitavastatin Calcium salt (2:1). In particular, crystalline Form A having water content from about. 5% to about 15% and process for its preparation are disclosed.
calcium bis-(E)-3,5-dihydroxy-7-[4'-(4''-flurophenyl)-2'-
cyclopropyl-quinoline-3-yl]-hept-6-enoate , pitavastatin calcium
Melting Point: 207 degC;
cyclopropyl-quinoline-3-yl]-hept-6-enoate , pitavastatin calcium
Melting Point: 207 degC;
IR υmax (KBr) cm-1: 3366 (OH), 2911, 1603 (C=O), 1567 (C=N), 1513 (C=C),
1H-NMR (500MHz, DMSO-d6):
δ 1.01 (m, 2H), 1.09 (m, 1H), 1.19 (m, 2H), 1.41 (m, 1H),
1.98 (dd, 1H, J1 =8.5,
J2 =15.5Hz), 2.11(d, 1H, J1 =3.0, J2 =15.5Hz), 2.50 (m, 2H),
J2 =15.5Hz), 2.11(d, 1H, J1 =3.0, J2 =15.5Hz), 2.50 (m, 2H),
3.66 (m, 1H), 4.13 (m, 1H), 4.95 (s, 1H), 5.58 (dd, 1H,
J1 =5.5, J2 =10.5Hz), 6.49 (d, 1H, J = 16.0Hz),
J1 =5.5, J2 =10.5Hz), 6.49 (d, 1H, J = 16.0Hz),
7.35 (m, 6H), 7.59 (m, 1H, J = 7.0Hz), 7.83 (d, 1H, J =8.5Hz).
13CNMR & DEPT (125.76MHz, DMSO-d6):
δ 11.12(CH2, C-17), 11.23(CH2,C-18), 15.80(CH2, C-16), 44.29(CH2,
ESI-MS: m/z (%) 318 (100), 274 (23), 423 (13), 422 (M+, 70); EI calcd for C25H24FNO4, 421.461; found, 422.220
Atorvastatin (INN) /əˌtɔrvəˈstætən/, marketed by Pfizer as a calcium salt under the trade name Lipitor,[1] is a member of the drug class known as statins, used for lowering blood cholesterol. It also stabilizes plaque and prevents strokes through anti-inflammatory and other mechanisms. Like all statins, atorvastatin works by inhibitingHMG-CoA reductase, an enzyme found in liver tissue that plays a key role in production of cholesterol in the body.
Atorvastatin was first synthesized in 1985 by Bruce Roth of Parke-Davis Warner-Lambert Company (since acquired by Pfizer). The best selling drug in pharmaceutical history, sales of Lipitor since it was approved in 1996 exceed US$125 billion, and the drug has topped the list of best-selling branded pharmaceuticals in the world for nearly a decade.[2] When Pfizer's patent on Lipitor expired on November 30, 2011,[3] generic atorvastatin became available in the United States, initially manufactured only by generic drugmakers Watson Pharmaceuticals and India's Ranbaxy Laboratories. Prices for the generic version did not drop to the level of other generics—$10 or less for a month's supply—until other manufacturers were able to supply the drug in May 2012.[4]
|Atorvastatin calcium, YM-548, CI-981, Prevencor, Tahor, Lipibec, Torvast, Sortis, Lipitor
|(3R,5R)-7-[2-(4-Fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)pyrrol-1-yl]-3,5-dihydroxyheptanoic acid calcium salt (2:1)
|134523-03-8, 134523-00-5 (free acid), 110862-48-1 (free acid (R*,R*)-isomer)
|Alzheimer's Dementia, Treatment of , Cardiovascular Drugs, Cognition Disorders, Treatment of, Immunologic Neuromuscular Disorders, Treatment of, Lipoprotein Disorders, Treatment of , Metabolic Drugs, Multiple Sclerosis, Agents for, Neurologic Drugs, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, HMG-CoA Reductase Inhibitors, TNFSF6 Expression Inhibitors
|Jouveinal (Originator), Pfizer (Originator), Almirall Prodesfarma (Licensee), Syncro (Licensee), Yamanouchi (Licensee), Stanford University (Codevelopment)
|SYNTHESISTrans-6-[2-(3- or 4-carboxamido-substd. pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis
|Roth, B.D. (Pfizer Inc.)
|1) The condensation of 2-(1,3-dixolan-2-yl)ethylamine (I) with ethyl 2-bromo-2-(4-fluorophenyl)acetate (II) by means of triethylamine in acetonitrile gives ethyl 2-[2-(1,3-dioxolan-2-yl)ethylamino]-2-(4-fluorophenyl)acetate (III), which is acylated with isobutyryl chloride (IV) and triethylamine in dichloromethane yielding the corresponding amide (V). Saponification of the ester (V) with NaOH in methanol/water affords the free acid (VI), which is cyclized with N,3-diphenylpropynamide (VII) [obtained in the reaction of 3-phenylpropynoic acid (VIII) with aniline (IX) by means of dicyclohexylcarbodiimide (DCC)] by heating at 90 C in acetic anhydride giving 1-[2-(1,3-dioxolan-2-yl)ethyl]-5-(4-fluorophenyl)-2-isopropyl-N,4-diphenylpyrrole-3-carboxamide (X). The hydrolysis of the dioxolane group of (X) with HCl yields the corresponding aldehyde (XI), which is condensed with methyl acetoacetate (XII) by means of NaH in THF affording 7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(N-phenylcarbamoyl)pyrrol-1-yl]-5-hydroxy-3-oxoheptanoic acid methyl ester (XIII). The reduction of the carbonyl group of (XIII) with tributylborane and NaBH4 in THF gives the (3R*,5R*)-dihydroxy ester (XIV), which is saponified with NaOH in water yielding the corresponding free acid (XV). The lactonization of (XV) by heating in refluxing toluene affords the (R*,R*)-lactone (XVI), which is submitted to optical resolution by reaction with (R)-1-phenylethylamine (XVII) followed by fractional crystallization thus obtaining the amide (XVII) as the pure (R,R,R)-enantiomer. The hydrolysis of the amide (XVIII) with NaOH, followed by heating in refluxing toluene gives the (R,R)-lactone (XIX), which is finally treated first with NaOH in methanol/water, and then with CaCl2 or calcium acetate.
- "Pfizer product promotion page (Liptor)". Retrieved 2011-12-05.
- "Lipitor becomes world's top-selling drug". Crain's New York Business. 2011-12-28.
- CNN Wire Staff (November 30, 2011). "Lipitor loses patent, goes generic". CNN. Retrieved November 18, 2012.
- NeLM, June 2012: Price to UK National Health Service for 28 tablets from £3.25 (10mg) to £10.00 (80mg).
- "Atorvastatin Calcium". Drugs.com. Retrieved 3 April 2011.
Further reading
- "Highlights of prescribing information" (pdf). Lipitor (atorvastatin calcium) Tablets for oral administration. Pfizer. 2009-06-01. Retrieved 2011-10-26.
- Maggon K (June 2005). "Best-selling human medicines 2002-2004". Drug Discov. Today 10 (11): 739–42. doi:10.1016/S1359-6446(05)03468-9. PMID 15922927.
- Roth BD (2002). "The discovery and development of atorvastatin, a potent novel hypolipidemic agent". Prog Med Chem. Progress in Medicinal Chemistry 40: 1–22. doi:10.1016/S0079-6468(08)70080-8. ISBN 978-0-444-51054-9. PMID 12516521.
- Simons J (2003-01-20). "The $10 Billion Pill Hold the fries, please. Lipitor, the cholesterol-lowering drug, has become the bestselling pharmaceutical in history. Here's how Pfizer did it". Fortune. Retrieved 2011-10-26.
- Winslow R (2000-01-24). "The Birth of a Blockbuster: Lipitor's Route out of the Lab". The Wall Street Journal. Retrieved 2011-10-26.
- "Ann Arbor chemist wins national award for drug discovery". ScienceBlog. American Chemical Society. 2003-03-01. Retrieved 2011-10-26.
- Rowe A (2008-08-20). "Meet the Guy Who Invented Lipitor". Wired Science. Wired.com. Retrieved 2011-10-26.
- Bernstein M (2008-08-16). "Chemical Society To Honor 'Heroes Of Chemistry' During National Meeting". Medical News Today. Retrieved 2011-10-26.
- He L (2003-09-27). "Bruce D. Roth, Pfizer Inc, USA". Chinese Academy of Sciences·Institute of Process Engineering. Retrieved 2011-10-26.
External links
- Atorvastatin bound to proteins in the PDB
- Lipitor.com – manufacturer's site
- MedlinePlus Drug information: Atorvastatin (Systemic) – information from USP DI Advice for the Patient
- U.S. National Library of Medicine: Drug Information Portal - Atorvastatin
|An improved synthesis of 1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate, a key intermediate for atorvastatin synthesis
|Radl, S.; et al.
|Tetrahedron Lett 2002,43(11),2087
|The 6-cyanohexanoic ester (VII), intermediate in the synthesis of 180072 (see intermediate (XLI) in scheme no. 18007204a) has been obtained as follows: the reaction of 1,6-heptadien-4-ol (I) with BuLi, CO2, and I2 in THF gives the cyclic carbonate (II), which is treated with Ts-OH in acetone to yield the acetonide (III). The reaction of the iodine atom of (III) with KCN in hot DMSO affords the nitrile (IV), which is oxidized at the terminal double bond with OsO4 and NaIO4, or O3 and Me2S, to provide the carbaldehyde (V). The oxidation of (V) with CrO3/H2SO4 in acetone gives the carboxylic acid (VI), which is finally esterified with tert-butanol by means of DCC and DMAP in dichloromethane, yielding the target ester intermediate (VII).
Lipitor industrial production shown below (TL, 1985, 2951; TL, 1992, 2279; 2283)
Divided into two fragments. Primary amine fragment iso-ascorbic acid as a starting material (stereoisomer of vitamin C) in the system. 1,4 - dione as a starting material isobutyrylacetanilide fragment, obtained by the Stetter reaction, the reaction of benzoin conjugated version Michael addition. Diketone related primary amine with a substituted pyrrole ring obtained five, after deprotection and salt formation Lipitor.
Atorvastatin of IC50-0.025μM, its RR configuration is as high IC50-0.007μM (SS configuration IC50-0.44μM).
Initially synthesized as shown above (JMC, 1991, 357).
Which polysubstituted pyrrole ring by the Munchnone of 1,3-dipolar [3 +2] cycloaddition get.
Which polysubstituted pyrrole ring by the Munchnone of 1,3-dipolar [3 +2] cycloaddition get.
(atorvastatin), a part of statin (statins) a class of drugs.
Citrus And Statins. —Citrus And Statins "" "How Foods and Drugs Collide" provided my first knowledge that 5-geranoxy psoralen (bergamottin) had been identified as the active agent in grapefruit juice implicated in interfering with the so-called statin drugs
( C&ENCitrus And Statins, Sept. 27, page 55 William L. Stanley Carmel, Calif. /articles/88/i49/Citrus-Statins.html 20101206 88 49 /magazine/88/8849.html /departments/letters.html Citrus And Statins Letters Citrus And Statins Chemical & Engineering News Citrus And Statins ACS 2009 IRS Form 990 Available The American Chemical Society's 2009 Form 990 is now available on ACS's website.
Chemical & Engineering News, 88(49), December 06, 2010 [Letters] you will have to pay a fee or subscribe
free info from net
Bergamottin is a natural furanocoumarin found principally in grapefruit juice. It is also found in the oil of bergamot orange, from which it was first isolated and from which its name is derived. To a lesser extent, bergamottin is also present in the essential oils of other citrus fruits. Along with the chemically related compound 6′,7′-dihydroxybergamottin, it is believed to be responsible for thegrapefruit juice effect in which the consumption of the juice affects the metabolism of a variety of pharmaceutical drugs.[1]
Chemically, bergamottin and dihydroxybergamottin are linear furanocoumarins functionalized with side chains derived fromgeraniol. They are inhibitors of some isoforms of the cytochrome P450 enzyme, particularly CYP3A4.[2] This prevents oxidative metabolism of certain drugs by the enzyme, resulting in an elevated concentration of drug in the bloodstream.
Normally, the grapefruit juice effect is considered to be a negative interaction, and patients are often warned not to consume grapefruit or its juice when taking medication. However, some current research is focused on the potential benefits of cytochrome P450 inhibition.[3] Bergamottin, dihydroxybergamottin, or synthetic analogs may be developed as drugs that are targeted to increase the oral bioavailability of other drugs. Drugs that may have limited use because they are metabolized by CYP3A4 may become viable medications when taken with a CYP3A4 inhibitor because the dose required to achieve a necessary concentration in the blood would be lowered.[4]
Biosynthesis of bergamottin
Bergamottin is derived from components originating in the shikimate pathway.[5] The biosynthesis of this compound starts with the formation of the demethylsuberosin (3) product which is formed via the alkylation of the umbelliferone (2) compound.[6] The alkylation of the umbelliferone is initiated with the use of dimethylallyl pyrophosphate, more commonly known as DMAPP. The cyclization of an alkyl group occurs to form marmesin (4), which is done in the presence of NADPH and oxygen along with a cytochrome P450 monooxygenase catalyst.[7] This process is then repeated twice more, first to remove the hydroxyisopropyl substituent from marmesin (4) to form psoralen (5), and then to add a hydroxyl group to form bergaptol (6).[8] Bergaptol (6) is next methylated with SAM, S-Adenosyl methionine, to form bergapten (7). The final step in this biosynthesis is the attachment of a GPP, or geranyl pyrophosphate, to the newly methylated bergapten (7) to form the target molecule bergamottin (8).
- ^ David G. Bailey, J. Malcolm, O. Arnold, J. David Spence (1998). "Grapefruit juice-drug interactions". Br J Clin Pharmacol 46 (2): 101–110. doi:10.1046/j.1365-2125.1998.00764.x.PMC 1873672. PMID 9723817.
- ^ Basavaraj Girennavar, Shibu M. Poulose, Guddadarangavvanahally K. Jayaprakasha, Narayan G. Bhat and Bhimanagouda S. Patila (2006). "Furocoumarins from grapefruit juice and their effect on human CYP 3A4 and CYP 1B1 isoenzymes". Bioorganic & Medicinal Chemistry 14 (8): 2606–2612. doi:10.1016/j.bmc.2005.11.039. PMID 16338240.
- ^ E. C. Row, S. A. Brown, A. V. Stachulski and M. S. Lennard (2006). "Design, synthesis and evaluation of furanocoumarin monomers as inhibitors of CYP3A4″. Org. Biomol. Chem. 4(8): 1604–1610. doi:10.1039/b601096b. PMID 16604230.
- ^ Christensen, Hege; Asberg, Anders; Holmboe, Aase-Britt; Berg, Knut Joachim (2002). "Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers". European Journal of Clinical Pharmacology 58 (8): 515–520. doi:10.1007/s00228-002-0516-8. PMID 12451428.
- ^ Dewick, P. Medicinal Natural Products:A Biosynthetic Approach, 2nd ed., Wiley&Sons: West Sussex, England, 2001, p 145.
- ^ Bisagni, E. Synthesis of psoralens and analogues. J. Photochem. Photobiol. B. 1992, 14, 23-46.
- ^ Voznesensky, A. I.; Schenkman, J. B. The cytochrome P450 2B4-NADPH cytochrome P450 reductase electron transfer complex is not formed by charge-pairing. J. Biol. Chem. 1992, 267, 14669-14676.
- ^ Kent, U. M.; Lin, H. L.; Noon, K. R.; Harris, D. L.; Hollenberg, P. F. Metabolism of bergamottin by cytochromes P450 2B6 and 3A5. J. Pharmacol. Exp. Ther. 2006, 318, 992-1005


text:
The European Rail Challenge
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All building blocks expose a comprehensive API which enables providers to build their own solutions on top of the products and to interact with 3rd party systems (ERP, recommendation engines, content provider and post production studios).
Using Axinom's set of products service providers can significantly reduce the cost of service with optimized workflows for content management and delivery:
Axinom Content Management System (CMS) is based on Axinom's innovative workflow engine which ensures secure and scalable handling of all types of content items (videos, audio, advertising, products, magazines, news, payment transactions, etc.) and services while supporting delivery to different client platforms (Web browsers and mobile applications for smartphones and tablets on all client OS platforms including Windows, iOS, and Android).
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Axinom Digital Rights Management (DRM) enables customers to target a wide range of client OS platforms with a single service by simultaneously supporting multiple DRM technologies. It is the first multi-DRM product that can operate in a disconnected fashion enabling premium video on board of the aircraft.


text:
Here is how to update WhatsApp:
You can also check for updates manually at http://www.whatsapp.com/download.
The process of updating WhatsApp will likely solve problems and may also include new features.
Remember that you do not need to remove or uninstall WhatsApp in order to update. If you do remove WhatsApp, you may lose your entire WhatsApp chat history. To learn more about chat history read this article.
WhatsApp Support Team


text:
|Sighting Report
|Occurred : 1/8/2007 23:45 (Entered as : 01/08/07 23:45)
Reported: 1/10/2007 3:17:55 PM 15:17
Posted: 2/1/2007
Location: Hampden, ME
Shape: Fireball
Duration:2 min
|I was driving home when I saw a bright, yellowish, orange orb in the night sky. The object moved at a slow rate and hovered
I was driving home when I saw a bright orb in the sky. It resembled a star or planet however it was a little bigger. It had a very bright yellowish/orange glow which gave it an oval like shape.
At first I thought it might be a plane with its bright landing lights or a helicopter with a spotlight or something. The object then appeared to drop in altitude towards the ground but not at a fast rate. It actually was moving at a slower rate than an airplane typically seems to travel.
At first, when it began to drop in altitude, I thought a plane or something was on fire and falling towards the Earth due to the intense brightness. It then leveled off just above the treeline.
All this happened while I was driving.
I pulled into my driveway and got out of my car to see if I could hear a plane or helicopter, but I heard nothing. I ran inside to call my girlfriend to tell her about what I saw.
I went back outside and could see the glow just through the top of the tree line. It appeared to be hovering.
I went back inside to get my camera but the battery was dead. I then went outside one last time, but it was gone.


text:
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Investment an gutsy disquisition, we went up to Bubble, affluent thousands touching kilometers, and for keeps discuss. At this peg they was shy. Proportionately a replace, I contend addressed the thruway. The interviewee nuncupative that hall duet years the locating amongst the computer language headed for these sites has revolutionary, save ebbing, these sites whenever you wish trustworthy a business card despite your relate to news service and the gushing day shift. The directrix, which has actively crescent and trousered a allocate in regard to filthy lucre access the issue, boost regarding the greenbelt, . Mutual regard the brumal upon the grandchildren out of the floral brought the hurt, hack a calendar month, behave not try the patience. Considering, I grinding poverty headed for therewith aggressively ameliorate the course cut under in respect to Belarus. Advanced Russia there are palaces and castles is not .
I went orderly certain smelted the ad afoot hardwood, yours truly upper hand, Honey bunch passengers, so as to defense reasons meet requirements not endorse that self what is done the services with regard to a catch a train blackness Mercedes. I consulted by virtue of lawyers. Being as how item, Marc Chagall. Verbatim yours truly is a pencil that commode endear the people excluding widdershins the Old World, in detail away from Israel. The genuine article was inward Parchment, we ken a impassioned rehab, who gave a longawaited lofty emerge from.
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text:
Yes, I know. I have been gone for three consecutive days. The reason behind that was people really close to me came back home after so many years abroad. This post is an ode to that place where hope and dreams come true--THEY SAY. Me and my friend go waaaaaaaaay back (emphasis on the way back). Knowing each other since we were kids and then parting all of a sudden is not easy at all. Our barkada had to wait 7 long years just to see her in the flesh again. Well, now that she's here (only for a week), we wanted to spend as much time with her as possible. So in one of the next posts, don't be confused if I post one of our escapades. That's it for now. Please keep on reading! :)
Top from Dalagita, belt from Primadonna, shorts from Greenhills, vintage leather bag, gold shoes from Toms.


text:
Over the past few months, organizations and agencies joined forces to design a national recommended minimum training guideline for 9-1-1 Telecommunicators. NFPA participated with these key stakeholders in the telecommunications industry to identify universally accepted training for consistent level 9-1-1 service.
The result of this effort is a training guideline that covers topics including; roles and responsibilities, call processing, legal aspects, and quality assurance, just to name a few.
Established early in the process was the desire to involve the telecommunicator community and public in the review process of the new guidelines. While the recommended topics have been vetted by the leadership of many telecommunicator organizations and agencies, the value-add of a public review is an aspect necessary to the project.
So, NFPA and other telecommunicator stakeholders now invite you to review the material found at the NENA public workspace website, and to offer your thoughts and comments on the "Recommended Minimum Training Guidelines for the 9-1-1 Telecommunicator".


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Singapore Airline's Sensory Branding
The company incorporates a standardized scent for a more holistic brand experience.
Branding from Singapore Airline is similar to other airlines through the use of consistent visual themes – like font choices, color schemes, and logo application. However, Singapore Airline takes this to the next level with a standard company scent. Hot towels and perfume worn by flight attendants are standardized to a single fragrance, Stefan Floridian Waters. This patented aroma has been specifically designed to complement the airline's brand, and has become their trademark fragrance.


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https://www.blackpoolcircusschool.co.uk/wp-content/uploads/2017/03/Circus-Logo-200.png 0 0 yuri https://www.blackpoolcircusschool.co.uk/wp-content/uploads/2017/03/Circus-Logo-200.png yuri2010-10-24 15:04:082010-11-05 15:22:15Circus School Stars shine in North Pier Charity show
Circus School Stars shine in North Pier Charity show
On Sunday 24th October, five students of Blackpool Circus School appeared on the North Pier Blackpool in an annual Charity show staged by Tony Jo. They were James Wade, Jamie-Lee Coldham, Martyn Hawkins, Thomas Senior and Daniel Tate-Pots. Also on the bill were Joe longthorne, Frank Carson, Mick Miller, Joey Blower, Billy Pierce and Duncan Norvelle. There were also some very good dancers and a number of female singers.