text:
Powered by Amortization Calculator Loan Calculator
Powered by TN Mortgage Rate
Tax Information in this widget is based on information given by the listing agent. All information should be verified by the recipient and none is guaranteed as accurate. For more information please contact the listing agent.
MLS ID: 1838146Request InformationMap ItPrint Listing
Price: $72,000
Address: 0 Grooms Rd
City: Holladay
County: Other
Address: 0 Grooms Rd
City: Holladay
County: Other


text:
A day in the life
The NGO through which I have been taking bangla classes, the HEED Language Center, is a Christian organization. However the one Hindu teacher in the program took myself and my buddy John Mark down to see the Durga Puga festival down at the main Hindu temple this week, called Dhakeswari Temple. Apparently the tradition is to build these gorgeous statues and then at the end of weeklong Durga Puga celebration all the staues are taken down nto the Buringaga river and submerged. There are many aspects of Hinduism that I like… it is very welcoming to people of other religions. Approximately 12% of Bangladeshis are hindus, with a majority living in Dhaka.
Street Food
Wish I had more pics of this but this is your standard iftar food stalls, that pop up everywhere, right around 5 or 5:30pm. Mmmm... gelapi is this amazing deep fried doughy fatty pretzel looking thing dripping with guey sugary syrup inside... i guess kind of like fried dough you get at an amusment park.... mmmm...
Basket Seller
Dinner at Syed's seems pretty standard Bangladeshi food. Dhal (lentils), boiled potatoes and cauliflower or beans, beef or chicken curry, Bangladeshi salad (cucumbers, onions, green chilis)... and you always pub lemon on everything... oh, and if you don't eat rice at every meal a kitten is killed somewhere...
Regular Dinner at Syed's
Granted they don't look that great for the most prestigious Engineering school (and probably the most difficult school to get into in the country) but a dorm is a dorm... I had considered living in the dorms, but will probably lean away from it. Some of my buddies live there and I am offered a place to crash whenever I'm down there... But I'm working almost full time in Gulshan and am only down at the campus a couple times a week.

subset: commoncrawl


text:
Customer Reviews
What You'll Get
Soccer players spend so much time concentrating on the ball that they grow obsessed with hexagons, which explains why they're constantly trying to kick bees' nests. Study the shape of an exciting game with today's GrouponLive deal: for $140, you get one season-ticket package to see Chivas USA soccer games at the Home Depot Center in Carson (a $281 total value). Each package includes the following:
- One pass for reserved sideline seating in section 129–130 or 134–135 at each of Chivas USA's home games, which begin on Sunday, March 11, and run through Saturday, October 20 (a $256 value). Click here for a full 2012 schedule. A ticket to a bonus game, which has not been scheduled, is also included.
- One Chivas USA souvenir scarf (a $25 value)
- An invitation to the 2012 "Meet the Team" event<p>
Chivas USA dribbles into a fresh season determined to seize control over Major League Soccer's Western Conference and rouse hometown fans during 17 games at the Home Depot Center plus a to-be-determined bonus game. Now in his second season, head coach Robin Fraser presides over a roster that showcases talent from across the globe, such as newly signed defender John Alexander Valencia, whose lanky gait and uncanny ability to read a compass led the way to a pair of Colombian League titles during his time with Atlético Junior. Forward Juan Pablo Angel aims to build on last season's 10-goal performance, as goalkeeper Dan Kennedy traps headers and bicycle kicks with sprawling dives and catcher's mitts.
From their sideline seats, Chivas USA season-ticket holders can enjoy an array of fast-paced matchups, including two battles against the David Beckham–led MLS defending champion LA Galaxy on May 19 and August 12. Additionally, team mascot ChivaFighter joins forces with the ChivaGirls to entertain fans during breaks in foot-to-foot combat, and souvenir scarves keep cheer cords warm and help lasso hot dogs away from unsuspecting vendors.
The Fine Print
Promotional value expires Oct 21, 2012. Amount paid never expires. Reservation required. Redeem starting 2/11 for a ticket at Home Depot Center box office. Must show valid ID matching name on Groupon at Home Depot Center. Must provide first and last name at checkout, which will be provided to Home Depot Center. Refundable only on day of purchase. Must redeem together to sit together. Discount reflects Chivas USA's current ticket prices-price may differ on day of the event. Merchant is solely responsible to purchasers for the care and quality of the advertised goods and services.


text:
October is Fire Prevention Month.
This year's theme is "Every second counts, plan 2 ways out". This is a reminder for all of us to have a plan if there was ever a fire emergency in your home. We should not only have an exit plan but also practice that exit plan with your entire family so they know how to get out of the house and meet in a safe location. The following link will give you some tips and ideas from our friends at the Massachusetts Firefighting Academy. Remember…have a plan and practice your plan. Be safe everyone!
The Cheshire Fire Department, also known as the Hoosac Hose Company, is a well-equipped community support department ready to respond with a variety of emergency services and equipment never envisioned by the originating fathers.


text:
March 20, 2017 @ 10:00 AM - 12:00 PM
Announcing the Final Examination of Lauren Elizabeth Wright for the degree of Doctor of Philosophy in Sociology
The discussion of race and crime has been a long standing research interest, with statistics consistently showing an overrepresentation of non-white offenders compared to their white counterparts – specifically in relation to violent crimes such as murder and rape. Prior research has found that about 46 percent of serial rapists are black, a fact that correlates with other sensationalized violent crimes such as mass murder and serial murder. The news media are the primary sources of this kind of information for the general public, with prior research acknowledging that the media primarily focus on discussing non-white offenders in their crime-based news stories. With the majority of Americans receiving their information about crime from the news media, it is important to increase our understanding of how their representations might influence the general public. The current study explores the print media representations of serial rapists, from 1940-2010, from five newspapers: The Los Angeles Times, The New York Times, The Boston Globe, The Washington Post, and the Chicago Tribune. A content analysis was conducted on 524 articles covering 297 serial rape offenders from the data compiled by Wright, Vander Ven, and Fesmire (2016) in which race of the offender was known. Results show that newspaper articles tend to report about fear-related topics and anxiety surrounding offenders when the offenders are non-white. Results also indicate that while newspapers dehumanize both white and non-white offenders, white offenders tend to have their behavior neutralized using techniques to garner more sympathy.
Committee in Charge: Lin Huff-Corzine (Chair), Jay Corzine, Melanie Hinojosa, Tom Vander Ven


text:
About love and relationships, centers on a college student Joo Yeon Ae who has both good looks and personality, but she′s actually a novice in relationships, and always fails at getting her man. Meanwhile, Cha Ki Dae is a skilled dating coach who expert at reading women′s minds. He comes to coach Yeon Ae over SNS, but despite the experience he boasts about, however, he also always fails at getting his own girl.
More info : Get it here
- Genre: Romance
- Episodes: 2
- Broadcast network: KBS2
- Broadcast period: 2013-Sep-11 to 2013-Sep-12
- Air time: Wednesday & Thursday 21:55
RAW Episode 01 - [ DL Link ]
RAW Episode 02 - [ DL Link ] [ End ]
Note : Click Link >> Wait 5 Seconds >> Skip Ad
Eng|!sh Subt!t|e - [ DL Link ]


text:
(CNN) -- Two men entered a restaurant at Borough Market, just south of London Bridge, and stabbed two people inside, a witness told CNN on Saturday.
The patrons sheltered in the basement and police have arrived at the scene, the witness said.
"As well as #LondonBridge officers have also responded to an incident in #BoroughMarket. We have armed police at the scenes," London's Metropolitan Police tweeted.
This BBSNews article was syndicated from News | WPLG, and written by News | WPLG. Read the original article here.


text:
Remailder is a startup that see email is increasingly used for sending/assigning action items and reminders to receiver. So they have a vision of building an intelligent automatic reminder with email as the interface.
The challenge for this task involves high requirement on technical expertise, as the underlying backend software architecture as well as their features need to be implemented.
They came to WTF Studio and we chose to use Ruby on Rails for this project due to its agile nature. Integrated with various gems, we and client form an agile team that drafted up the requirement together in one week, assigned to our implementation team for another week, and then reviewed the progress on the following week. We then iterated based on their feedback, together with new set of user stories.
The development cycle of quick feedback loop and integration helped delivers this project to our client on time, with features of exactly what they want, and no surprises.


text:
ST. LOUIS — IBEW/NECA contractor prowess in delivering enormously complex projects was honored with several awards in the 2016 Associated General Contractors (AGC) of Missouri AGC Keystone Awards. The IBEW/NECA contractors swept the Mid-America Class for subcontracting work in which they competed. The winners included PayneCrest Electric, Inc. for its work on the Flint Creek Power Plant in Gentry, Ark. and Guarantee Electric, which earned two awards for their work on the William H. Danforth Wing expanding the Donald Danforth Plant Science Center and the Metropolitan Sewer District (MSD), Flood Mitigation Project. Guarantee was also named 2016 specialty contractor of the year for electrical. The awards were presented at the AGC's annual construction gala on Thursday, Nov. 10, 2016 at the River City Casino & Hotel in St. Louis.
PayneCrest Electric, Inc.'s foresight and ingenuity was saluted for its environmental retrofit of the Flint Creek plant — a project that was also spotlighted in Electric TV. American Electric Power Corp. Southwestern Electric Power Co. (AEP SWEPCO) and Arkansas Electric Corp. (AECC) relied on PayneCrest to optimize a $408 million retrofit to the 528-megawatt, coal-fueled Flint Creek Power Plant to comply with new stringent U.S. environmental regulations. PayneCrest was also required to elevate the skills of the local workforce to serve Arkansas' future power needs. In all, PayneCrest installed more than 1.3 million feet of cable, 10,000 feet of cable tray, 80,000 feet of conduit, and 1,200 light fixtures. The two-year-long project was completed on time and within budget with no injuries in 205,000 manhours on the job.
Guarantee's work on the 79,000-square-foot William H. Danforth Wing to expand the Donald Danforth Plant Science Center emphasized a strategy of building flexibility into the capacity of the space to support 21st Century plant science research. The project entailed building in four levels, three of which contain new state-of-the-technology plant science laboratories including 34 controlled environment growth chambers and collaboration spaces in open-office configurations. The new wing brings expanded computing and imaging capabilities to support the center's expanding team of research scientists.
Guarantee's work for MSD came in response to a devastating deluge of winter rain closing out December 2015 that flooded and shutdown wastewater treatment plants in Valley Park and Fenton, Mo. For the Fenton plant, the Guarantee team had to perform an in-depth diagnostic of every piece of equipment and traced and tested wiring throughout the plant, most of it submerged under water. Guarantee and its partners designed and constructed a replacement scheme for the Fenton plant, building an entirely new electrical infrastructure throughout the facility. It diligently advanced a 12-week schedule to meet an environmental compliance deadline requiring restoration of wastewater decontamination operations by April 1, 2016.
In all IBEW/NECA contractors placed seven projects as finalists in the 2016 AGC Keystone Awards including one project from Bell Electrical Contractors, four projects from Guarantee and two projects from PayneCrest.
Since 1999, more than 90 IBEW/NECA projects have been honored in the AGC Keystone Awards. All of the 2016 honorees are members of the Electrical Connection, a partnership of the International Brotherhood of Electrical Workers (IBEW) Local 1 and the St. Louis Chapter, National Electrical Contractors Association (NECA).
The AGC Keystone Awards salute building excellence in a number of categories. The finalists, spanning 10 categories, represent the highest level of professionalism, craftsmanship and quality in construction by Missouri's general and specialty contractors.
Recent News


text:
Congratulations Lu Lu Kellogg from Coastal Sisters, you are the winner of our Southern Sweet Give~Away!! Please Contact me with your address Sweetie!!
Huggs, Nancy
CHALLENGE #31 - 2017 - *HAVEN OF HOPE* *Red Wing, Minnesota* *In January, 2011, The Pink Slipper Project sent slippers to Haven of Hope. They said at the time, "We would be honor...
3 weeks ago


text:
Juan Scruggs was looking for 15 new employees—part- and full-time—to fill out his staff at the 24/7 McDonalds on Whalley Avenue. Allen Smith may fit the bill.
Smith was one of scores of job seekers and other help seekers who converged on the Green Thursday for a five-hour resource fair organized by the city's Re-Entry Roundtable. Twenty-nine sponsors contributed a total of $5,000 for the privilege of setting up tables with information aimed at anyone with "a barrier to employment," as Re-Entry coordinator Amy Meek (pictured with Smith) put it: first and foremost, anyone with a felony record. (Click here and here for background stories.)
"We actually went to employers, emailed them, followed up with phone calls—a very aggressive campaign to reach out to employers," said Lisa Fluker, who helped Meek organize the fair. "Although the economy at this time, across the board, is fairly slow, we did have some favorable response."
Smith said he was on his way to the library to search for jobs on the computer when he saw the hubbub on the Green. "Unfortunately, I do have many barriers that's a hindrance to my job search, but I don't let it deter me from looking, because I know a door will open as long as I'm persistent in looking. If there's such a thing as a plus [in this situation], I don't have a violent history, just a drug history."
He has multiple convictions for drug sales and use, and served "a few" stints in prison. The most recent was for a year, and he got out two years ago. He said he's been putting in job applications all over the city and beyond, but no luck so far.
Smith (right in top photo) approached the table where Juan Scruggs sat in the hot sun, still looking spiffy in his McDonald's uniform. Scruggs said he owns the franchise at 250 Whalley Ave., and he was looking to hire ten part-time and five full-time employees. He currently has 47 workers, but to run his business around the clock he's been advised to have up to 65. Starting pay is minimum wage—$8.25 an hour in Connecticut—and there are no benefits, but he said he has openings in all areas: food prep, food serving (at the counter), cashier and maintenance.
Smith said he'd worked at a McDonalds in another state, and was head of maintenance. Scruggs was impressed, and the two chatted for awhile, ending with a handshake. Scruggs gave everyone who stopped by a yellow sheet with information about how to apply on-line. "And I give them all my cell phone and tell them to call me to follow up," he added, "or just stop in if they want to check on their application."
Raymond Rosario (pictured) heard about the fair from his mother, a city employee. He said he has a history of being in the wrong line of work—drug sales—and the felony record to go along with it.
"I visited about eight tables," he said. "There's a lot of resources here. It's up to us to use it. Finally, we're being reached out to.I felt [before] we were being pushed under the table. We weren't being recognized, and now I feel our voice has been heard, and people do care and are doing something about it."
Asked how confident he was he'd be able to get a job in this still struggling economy, he responded firmly, "Very confident." Why? "Because the motivation these people give me, and the resources that I've gotten, I think there's about a 90 to 95 percent [chance] that I'll find employment soon."
Former State Rep. Bill Dyson, who volunteers as co-chair of the Re-Entry Roundtable, was perched at a table on the edge of the stage. He said he had "a good feeling" about the day. He used the same term as Rosario, saying that people long excluded from society—either by prison walls or by discrimination upon their release from jail—"have been recognized."
Other tables were staffed by individuals from New Haven Adult Education, New Haven Legal Assistance, Free Forever Prison Ministry, Strive and many more.


text:
Do you want to make a meaningful difference in the lives of developing athletes and teams?
Are you coaching community or club soccer for the first time and need to get up to speed quickly?
Are you an experience (or new) coach who wants to learn new skills and proven evidence-based methods that inspires players to be their best and play as a team?
Are you ready to learn the skills and knowledge that leads to both on and off field success for yourself and your athletes?
Yes?! Great. Then our Inspired Coaching Clinics are just the ticket for you.
Charles – the owner and founder of SoccerGenius, delivers all SoccerGenius Inspired Coaching Clinics. You can read a lot more about him here (link to the Who We Are page under the About Us Nav)
Charles is known for being a master of technical teaching and breaking down skills, strategy, and drills in a way that works for all types of learning styles. His patient and friendly style, combined with his ability to inspire and challenge, will have you discovering coaching skills and abilities just waiting to be unleashed.
Start your coaching journey with us and receive certification in the International SoccerGenius Association.
Our clinics are offered in a series of progressive levels to help instill the confidence, skill, and ability to put your learning into practice. Each level leads to the next and coaches can repeat a level for a discounted fee.
Clinics are offered throughout the year on evenings and weekends at the SoccerGenius Development Centre.
Inspired Coaching for
Players 3-6 years of age.
Level One & Two
Inspired Coaching for
Players 7-12 years of age.
Inspired Coaching for
Players 13-18 years of age.
Level One & Two
Level one is the starting point in for all coaches, new and experienced. A basic understanding of soccer is helpful although not required.
Applicants must be minimum 18 years of age.
Level one covers the key SoccerGenius coaching principles and concepts that are the foundation of successful coaching leadership. It blends the practical philosophy of SoccerGenius along with core technical, physical, social, and mental skills development and abilities for the age group.
Level One is a one-day or four week evening course that includes lots of action, hands on training, and plenty of on-field time.
Applicants for the Level Two courses must be minimum 18 years of age and have completed Level One in their age group. We recommend completing a season of coaching with the Level One skills and principles prior to registering for Level Two.
The Level 2 qualification builds upon the platform provided by the level 1 award, providing more advanced technical, tactical, and skill progression knowledge. It also provides the success keys, habits, and practices for personal development that is essential for all coaches leading today's children and youth.
Level Two is a two day or 8 week evening course that features a great amount of on field time to practice and develop the leadership, player and team organization, and technical skills for success.


text:
Somewhat lost among the enthusiastic critical reception to Spider-Man: Homecoming and the character's seamless entry into the Marvel Cinematic Universe was the news that Sony are still planning on developing a series of movies set in the Spider-Man universe.
In true Sony fashion, they remain undeterred by the fact that they
can't actually feature Spider-Man in any of their movies. Why? Because any appearance of Spidey instantly makes the Sony movies canon in the Marvel Cinematic Universe (which Marvel Studios don't want), which is not to be confused with Sony's Marvel Universe, which is the continuity of all of the spin-offs. Confusing, right?
Last month, the recently-revived Venom suddenly became interesting again when Tom Hardy signed on star along with rumors of an R-rating. Even more exciting was the news that fan favorite Carnage was set to be the villain, fulfilling the dreams of comic book fans across the world who had been wanting to see the character on the big screen for years.
An absolute homicidal maniac and complete and utter b*stard, Cletus Kasady is a character that could easily fall into pantomime villain material in the wrong hands.
As a brand new entity to most casual audiences, the cinematic debut of Carnage requires an actor capable of making it a memorable one that they won't forget anytime soon, which not everyone can pull off…


text:
You have no items in your shopping cart.
There is no reason why you shouldn't dive into this bomber jacket! Perfect to stay warm this winter season!
Our No Reason reversible bomber jacket will become your new staple jacket throughout the winter season! Keep it cool and casual with a pair of ripped denim and a basic bodysuit.
- Exposed zipper centre front - Fully lined - Fabric: 100% polyester - Length: 62cm / 24in- Model is wearing size 8 AUS / 4 US / 8 UK- Model's height is 164cm / 5ft 4in
Free standard shipping on orders over €60 and €7 flat-rate shipping for orders under €60
See our shipping page for more.
Sizes are based on the following body measurements, however some
items may vary due to fabric and fit. These measurements
should be used as a guide only. Please note: All garment tags are in AU sizes
Promotion ends: Hours, Minutes, Seconds.
Enter the code "EASTERBUNNY20" at cart page or checkout.
How it Works:


text:
Mad About Paris, Much more than a guide
Au pied de cochon is what you can call a myth: it opened back in 1947 and since then has never closed it doors. How come? Because it's open 24 hours a day, seven days a week. This is a nice thing, you'll agree, because night birds sometimes might get very, very hungry on their tours. Yes, it is a very touristy place but sometimes Parisians, too, to end up Au pied du cochon.
Of course, Au pied de cochon has a history – and you can feel it. Before the famous food market – le ventre de Paris – left Les Halles for Rungis, this place was one of those where market porters, food dealers and their clients used to eat their traditional onion soup in the middle of the night or a pied de cochon, a pig's foot, for breakfast, no kidding.
There is still a bit of this flair left, its côté canaille, is what the French would call it, its popular, coarse but charming dishes. But this being a mythical spot, you don't go there because the food is especially good. As so many other traditional places, Le Pied de Cochon had been bought by a big group, Les Frères Blanc. For them it's more about maximization of profits than of being loved. (Read the funny chapter "The Balzar wars" in Adom Gopnik's book "Paris to the moon" about the acquisition of the famous "Le Balzar" by the Flo group and the revolution that followed – and you get an idea how painful the change can be for regular customers).
I read a frightening description of the traditional soupe à l'oignon by food journalist Joe Ray. I, for my part, stuck to the seafood and had a lovely Assiette de l'écailler (26 €). Oysters are from the famous producer Gillardeau and at least, as long as it's fresh, you can't really ruin raw shellfish…Au Pied de Cochon 6, rue Coquillière, 75001 Paris Tel: +33 (0)1 40 13 77 00


text:
|Home | About | Journals | Submit | Contact Us | Français
We determined the molecular mechanisms underlying apolipoprotein E (ApoE)-isoform-dependent lipid efflux from neurons and ApoE-deficient astrocytes in culture. The ability of ApoE3 to induce lipid efflux was 2.5- to 3.9-fold greater than ApoE4. To explore the contributions of the amino- and carboxyl-terminal tertiary structure domains of ApoE to cellular lipid efflux, each domain was studied separately. The amino-terminal fragment of ApoE3 (22-kDa-ApoE3) induced lipid efflux greater than 22-kDa-ApoE4, whereas the common carboxyl-terminal fragment of ApoE induced very low levels of lipid efflux. Addition of segments of the carboxyl-terminal domain to 22-kDa-ApoE3 additively induced lipid efflux in a length-dependent manner; in contrast, this effect did not occur with ApoE4. This observation, coupled with the fact that introduction of the E255A mutation (which disrupts domain–domain interaction) into ApoE4 increases lipid efflux, indicates that interaction between the amino- and carboxyl-terminal domains in ApoE4 reduces the ability of this isoform to mediate lipid efflux from neural cells. Dimeric 22-kDa or intact ApoE3 induced higher lipid efflux than monomeric 22-kDa or intact ApoE3, respectively, indicating that dimerization of ApoE3 enhances the ability to release lipids. The adenosine triphosphate–binding cassette protein A1 (ABCA1) is involved in ApoE-induced lipid efflux. In conclusion, there are two major factors, intramolecular domain interaction and intermolecular dimerization, that cause ApoE-isoform-dependent lipid efflux from neural cells in culture.
The lipoprotein found in the central nervous system (CNS) is the high-density lipoprotein (HDL), and apolipoprotein E (ApoE) is one of the major apolipoproteins regulating lipid transport in CNS (Roheim et al., 1979; Pitas et al., 1987b; Weisgraber et al., 1994). Astrocytes and microglia synthesize and secrete ApoE (Boyles et al., 1985; Nakai et al., 1996), which interacts with adenosine triphosphate (ATP)-binding cassette protein A1 (ABCA1) (Krimbou et al., 2004) to remove cholesterol from cells and generate HDL particles in the cerebrospinal fluid and cultured media (Pitas et al., 1987a; Borghini et al., 1995; LaDu et al., 1998).
ApoE-inducible lipid efflux is ApoE-isoform dependent (Michikawa et al., 2000; Gong et al., 2002; Xu et al., 2004), and ApoE3 generates a similar number of HDL particles to but with a smaller number of ApoE molecules than ApoE4 (Gong et al., 2002). HDL synthesis mediated by ApoE contributes to cholesterol release from the cell membrane. On the other hand, HDL associated with ApoE is taken up by cells via ApoE receptors and the cholesterol in HDL is used for maintaining cholesterol homeostasis in CNS neurons. Thus, this isoform-specific action of ApoE to remove cholesterol and generate HDL may be the cause of altered cholesterol metabolism in an Alzheimer's disease (AD) brain (Demeester et al., 2000; Molander-Melin et al., 2005) and may explain how ApoE4 serves as a strong risk factor for AD development (Corder et al., 1993; Strittmatter et al., 1993). However, the molecular mechanism underlying ApoE-isoform-dependent HDL generation remains to be elucidated.
The ApoE molecule has two distinct domains, namely, the 22-kDa amino-terminal (residues 1–191) and 10-kDa carboxyl-terminal domains (residue 218–299), that unfold independently of each other (Wetterau et al., 1988; Morrow et al., 2000). It has been demonstrated that ApoE4 amino- and carboxyl-domain interaction is responsible for the ApoE-isoform dependent association with lipid particles (Weisgraber, 1990; Dong and Weisgraber, 1996; Saito et al., 2003). The domain interaction in ApoE4 under physiological conditions has also been confirmed at the cellular level (Xu et al., 2004) and in vivo (Raffai et al., 2001; Ramaswamy et al., 2005), suggesting that the presence or absence of the domain interaction can explain ApoE-isoform dependent lipid efflux. In addition, there are ApoE-isoform dependent differences in the structure and stability of the 22-kDa amino-terminal fragment (22-kDa-ApoE), which affect their binding affinities to lipids (Morrow et al., 2000, 2002; Segall et al., 2002; Hatters et al., 2005), suggesting that the 22-kDa-ApoE that lacks the domain interaction may also explain an isoform-dependent lipid efflux.
In this study, we investigated the molecular mechanisms, by which intact ApoE3 has a greater ability to induce cholesterol efflux than intact-ApoE4 by using cultured rat neurons and astrocytes prepared from ApoE knockout mouse brain to exclude the effect of endogenously generated and secreted ApoE. We found that the intramolecular amino- and carboxyl-terminal domain interaction is partially responsible for this ApoE-isoform dependency. To our surprise, 22-kDa-ApoE3 has a greater ability to induce cholesterol efflux than 22-kDa-ApoE4. This is because 22-kDa-ApoE3 forms dimers, whereas 22-kDa-ApoE4 does not. These findings suggest that cholesterol efflux induced by ApoE is regulated by two major factors: the presence or absence of intermolecular dimer formation and the intramolecular domain interaction.
All experiments were performed in compliance with existing laws and institutional guidelines. Neuron-rich cultures were prepared from rat cerebral cortices as previously described (Michikawa et al., 2001). Cerebral cortices from rat brains were dissected, freed of meninges, and diced into small fragments. Cortical fragments were incubated in 2.5% trypsin and 2 mg/ml DNase I in phosphate-buffered saline (PBS) (8.1 mM Na2HPO4, 1.5 mM KH2PO4, 137 mM NaCl, and 2.7 mM KCl; pH 7.4) at 37°C for 15 min. The fragments were then dissociated into single cells by pipetting. The dissociated cells were suspended in a feeding medium and plated onto poly-d-lysine-coated 12-well plates at a cell density of 1 × 106/ml in Dulbecco modified Eagle's medium nutrient mixture (DMEM/F-12; 50:50%) containing N2 supplements plus 7.5% bovine albumin fraction V.
Highly astrocyte-rich cultures were prepared according to a previously described method (Michikawa et al., 2001). In brief, brains of postnatal day 2 ApoE knockout mice were removed under anesthesia. The cerebral cortices from the mouse brains were dissected, freed of meninges, and diced into small fragments. Cortical fragments were incubated in 0.25% trypsin and 2 mg/ml DNase I in PBS (8.1 mM Na2HPO4, 1.5 mM KH2PO4, 137 mM NaCl and 2.7 mM KCl; pH 7.4) at 37°C for 15 min. The fragments were then dissociated into single cells by pipetting. The dissociated cells were seeded in 75-cm2 dishes at a cell density of 1 × 107 in DMEM nutrient mixture containing 10% FBS and 1% penicillin/streptomycin solution (Invitrogen Corporation, Carlsbad, CA). After 10 days of incubation in vitro, astrocytes in the monolayer were trypsinized (0.1%) and reseeded onto twelve-well dishes. The astrocyte-rich cultures were maintained in DMEM containing 10% FBS until use.
The full-length human ApoE3 and ApoE4 and their 22- and 10-kDa fragments were expressed and purified as described (Saito et al., 2001). The cDNA for full-length human ApoE3 and ApoE4, the 22-kDa fragments, or the 10-kDa fragment were ligated into a thioredoxin fusion expression vector pET32a and transformed into the Escherichia coli strain BL21 star (DE3). The transformed E. coli were cultured in LB medium at 37°C, and thioredoxin-ApoE expression was induced with isopropyl-β-d-galactopyranoside for 3 hr. After the bacterial pellet was sonicated and the lysate was centrifuged to remove debris, the fusion protein was cleaved with thrombin to remove thioredoxin from full-length ApoE3, ApoE4 or the 22- or 10-kDa fragment. For the full-length ApoE3 and ApoE4, the fusion protein was complexed with DMPC before it was cleaved with thrombin to protect the protease susceptible internal hinge region. After inactivation of the thrombin with β-mercaptoethanol, the mixture was lyophilized and delipidated, and the ApoE pellet was dissolved in 6 M guanidine–HCl, pH 7.4, containing 1% β-mercaptoethanol. The ApoE was isolated by gel filtration chromatography on a Sephacryl S-300 column. For further purification (>95%), the proteins were subjected to gel filtration with a Superdex 75 column or anion exchange chromatography with a HiTrap Q column
When we used ApoE and ApoE fragments, the recombinant ApoEs were dissolved in 5 M guanidine–HCl. The resulting solutions were dialyzed against PBS at 4°C for 16 hr. Each ApoE level was determined with a BCA protein assay kit (Pierce, Rockford, IL).
Astrocytes plated in twelve-well dishes were cultured in DMEM containing 10% FBS and 1% penicillin/streptomycin solution for 72 hr. The cultures were then treated with 37 kBq/ml [14C]acetate (Moravek Biochemicals Inc., Brea, CA) for 48 hr. The astrocytes were washed in DMEM two times and treated with 0.3 µM ApoE in DMEM for 24 hr. To analyze dose-dependent effects, the astrocytes were treated with 0.03 µM, 0.1 µM, 0.3 µM and 1.0 µM ApoE; to analyze time-dependent effects, the astrocytes were treated and maintained for 8, 24 and 48 hr. The culture medium was quickly removed and the astrocytes were dried at room temperature. 1.0 ml of the conditioned culture medium was extracted with 4.0 ml of hexane/isopropyl alcohol (3:2 v/v). For the extraction of intracellular lipids, dried astrocytes were incubated in hexane/isopropyl alcohol (3:2 v/v) for 1 hr at room temperature. The solvent from each plate was removed and dried under N2 gas. The organic phase was redissolved in 200 µl of hexane/isopropyl alcohol (3:2 v/v), and 10 µl of each sample was spotted on activated-silica-gel high- performance thin layer chromatography plates (Merck); the lipids were separated by sequential one-dimensional chromatography by using chloroform/methanol/acetic acid/water (25:15:4:2, v/v), followed by another run in hexane/diethyl ether/acetic acid (80:30:1). [14C]Cholesterol and [14C]PC were used as standards. The chromatography plates were exposed to radiosensitive films, and each lipid was visualized and quantified with BAS2500 (Fuji Film, Tokyo, Japan). The levels of [14C]cholesterol and [14C]PC efflux were calculated by the following formula: % efflux = media × 100/(media + cell).
The pure 22-kD-ApoE3 was obtained by reduction with 10 mM dithiothreitol (DTT) in 5 M guanidine–HCl buffer. The dimer was formed by incubation of the monomer in oxygenated 5 M guanidine–HCl at 10 mg/ml for 2 weeks at 4°C. Residual monomer was removed by passage of the protein solution through a thiopropyl Sepharose 6B column (GE Healthcare, Piscataway, NJ) according to the manufacturer's instructions.
The ApoE3 (1 mg/ml in 6 M urea, and 10 mM Tris-HCl) used was a mixture of monomeric and dimeric ApoEs. The mixture was reduced to generate monomeric ApoE3 by adding 10 mM DTT, incubated at 4°C for 16 hr, dialyzed against 6 M urea in 10 mM Tris-HCl solution, and oxidized by stirring at 4°C for 3 days. Then it was loaded onto a 2-ml-bed-volume prepacked 6% cross-linked beaded agarose gel column with a SulfoLink kit (Pierce, Rockford, IL) and equilibrated with PBS. Dimeric ApoE3 was eluted with PBS.
To determine the ratio of dimeric 22-kDa-ApoE3 in the solution, Western blot analysis was performed under nonreducing conditions. Dimeric 22-kDa-ApoE3 was mixed with the same volume of a 2× nonreducing Laemmli buffer consisting of 100 mM Tris-HCl (pH 7.4), 10% glycerol, 4% SDS, and 0.01% bromophenol blue, and analyzed by 4–12% Tris/Tricine sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) (Daiichi Pure Chemicals Co., Tokyo, Japan). The separated proteins were transferred onto Immobilon membranes with a semidry electrophoretic transfer apparatus (Nihon Eido, Tokyo, Japan) with a transfer buffer (0.1 M Tris-HCl (pH 7.4), 0.192 M glycine, and 20% methanol). The blots were probed for 16 hr at 4°C with a goat anti-ApoE polyclonal antibody, AB947 (1:2,000; Chemicon, Temecula, CA). Band detection was carried out with an ECL kit (GE Healthcare UK Ltd., England).
ApoE3 was dissolved in 5 M guanidine–HCl, 10 mM EDTA, 200 mM Tris-HCl (pH8.5), and half of each protein solution was reduced with 10 mM DTT at room temperature for 2 hr and alkylated with 40 mM iodoacetamide in the dark at room temperature for 30 min, as described previously (Franceschini et al., 1990). All the proteins were then purified on an Aquapore RP300 column (2.1 × 30 mm; Applied Bio-systems; Foster City, CA) by reverse-phase high-performance liquid chromatography (HPLC; model 1100 Series; Agilent Technology, Waldbronn, Germany) with a linear gradient of 36–52% acetonitrile in 0.1% trifluoroacetic acid for 16 min and a linear gradient of 52–76% acetonitrile in 0.1% trifluoroacetic acid for 1 min at a flow rate of 0.2 ml/min. The HPLC-purified ApoE3 was lyophilized and kept at −30°C until use.
Neuron cultures were prepared, maintained, and labeled with [14C]acetate, and exposed to 22-kDa-ApoE3 dimer or 22-kDa-ApoE3 monomer at a concentration of 0.3 µM in the presence of 22-hydroxycholesterol (10 µM) or glyburide (500 µM) for 24 hr. The lipids released into the media and the lipids retained in the cells were then determined. The expression level of ABCA1 in the cultures for each treatment was determined by Western blot analysis with anti-ABCA1 antibody (Santa Cruz, Santa Cruz, CA) used as a primary antibody.
To knock down the endogenous ABCA1, primary cultured neurons and astrocytes were transiently transfected with 50 nM of the synthesized small interfering RNAs (siRNAs) targeting ABCA1 or with the Stealth siRNA negative control (Invitrogen) with Lipofectamine RNAiMAX (Invitrogen) according to the manufacturer's protocol. ABCA1 siRNA sequences is as follows: ABCA1-siRNA sense (5′-CA GGAUUUCCUGGUGGACAAUGAAA-3′) and antisense (5′-UUUCAUUGUCCACCAGGAAAUCCUG-3′).
StatView computer software (Windows) was used for statistical analysis. The statistical significance of differences between samples was evaluated by multiple pairwise comparisons among the sets of data by ANOVA and the Bonferroni t-test.
Primary-cultured neurons and astrocytes were prepared and the levels of cholesterol and PC efflux were determined as described in Experimental Procedures. The levels of cholesterol and PC released from neurons in the medium treated with ApoE3 at 0.3 µM were significantly greater than those in the medium treated with ApoE4 (Fig. 1A). The level of cholesterol released by ApoE4 was 25% of that released by ApoE3. The reduced levels of cholesterol and PC efflux induced by ApoE4 increased significantly, although not to the level induced by ApoE3, when the neurons were incubated with the apoE4 (E255A) mutant (mt-ApoE4), which has altered amino- and carboxyl-terminal domain interaction because there is no electrostatic interaction between Arg61 and Glu255 (Dong and Weisgraber, 1996) (Fig. 1A). The partial recovery in the level of lipid efflux induced by mt-ApoE4 suggests that mechanisms other than the domain interaction are involved in ApoE-isoform-dependent lipid efflux from neurons in culture. Similar results were observed with cultured astrocytes. The levels of cholesterol and PC released from astrocytes in the medium treated with ApoE3 at 0.3 µM were significantly greater than those in the medium treated with ApoE4 (Fig. 1B). The levels of cholesterol and PC efflux induced by ApoE4 increased significantly, although not to the level induced by ApoE3, when the astrocytes were incubated with mt-ApoE4 (Fig. 1B).
We also examined the effect of the ApoE fragments on lipid efflux from cultured neurons and astrocytes to determine which part of the ApoE molecule is responsible for lipid efflux and ApoE isoform dependency. Interestingly, the 22-kDa fragment of ApoE (22-kDa-ApoE) induced cholesterol and PC efflux, which were ApoE-isoform-dependent (Fig. 1A,B). Unexpectedly, the carboxyl-terminal 10-kDa-ApoE and 12-kDa-ApoE, both of which contain the lipid binding site, have a very weak ability to release lipids (Fig. 1A,B).
Figure 2A shows the time-dependent cholesterol and PC efflux from neurons induced by 22-kDa-ApoE3 and 22-kDa-ApoE4 at 0.3 µM. The level of lipids released by 22-kDa-ApoE3 was significantly greater than that by 22-kDa-ApoE4 at time points of 24 and 48 hr (Fig. 2B). The level of cholesterol and PC efflux induced by 22-kDa-ApoE 24 hr after the treatment increased in an ApoE-concentration-dependent manner (Fig. 2B). The levels of cholesterol and PC efflux induced by 22-kDa-ApoE3 were greater than those released by 22-kDa-ApoE4 at 0.3 and 1.0 µM (Fig. 2B). Time- and ApoE-dose-dependent lipid efflux was also examined with ApoE-deficient astrocyte cultures, and the similar results were observed (Fig. 2C,D).
The results in Figures 1 and and22 indicate that the amino-terminal domain, the 22-kDa fragment, induces lipid efflux in an ApoE-isoform dependent manner, whereas the carboxyl-terminal domain, the 10-kDa fragment, has a very weak ability to induce lipid efflux from cultured astrocytes. These results raise the question of how the amino-terminal and carboxyl-terminal domains contribute to lipid efflux induced by intact ApoE in an ApoE-isoform-dependent manner. To answer this question, we examined whether the carboxyl-terminal domain of ApoE modifies lipid efflux caused by 22-kDa-ApoE. The ApoEs used were 22-kDa-ApoE (amino acids, 1–191) and 22-kDa-ApoE with carboxyl-terminal fragment of various lengths, that is, ApoEs harboring amino acids 1–250, 1–260, 1–272, and 1–299 (intact ApoE). As shown in Figure 3A, cholesterol and PC efflux induced by ApoE3 species from cultured neurons depended on the carboxyl-terminal fragment length; that is, ApoE3 variants with a longer carboxyl-terminal region induced progressively more lipid efflux. However, such is not the case for ApoE4. The addition of a carboxyl-terminal region ending at amino acid 250 increased the level of lipid efflux significantly more than 22-kDa-ApoE4; however, 22-kDa-ApoE4 with a carboxyl- terminal region longer than 250 amino acid residues lost the additional effect of the carboxyl-terminal region on lipid efflux. The levels of cholesterol and PC efflux induced by mt-ApoE4 recovered significantly but partially, and they did not reach those induced by intact ApoE3, similar to the result shown in Figure 1. Similar results were observed when ApoE-deficient astrocyte cultures were used (Fig. 3B).
The above results suggest that the amino-terminal domain basically determines the ability of ApoE to induce lipid efflux and that the carboxyl-terminal region enhances this ability when the amino and carboxyl domain interaction is absent. Because the absence or presence of cysteine at position 112 in the amino-terminal domain differentiates ApoE3 from ApoE4, it is possible to assume that this one-amino-acid difference results in intra- or intermolecular structural differences leading to the domain interaction or dimerization, respectively. Thus, we examined the effect of the dimer formation of 22-kDa-ApoE3 through disulfide bonds on lipid efflux from neurons and cultured astrocytes. To determine directly whether the dimeric form of 22-kDa-ApoE3 induces greater lipid efflux from astrocytes than the monomeric form, the pure dimeric form of 22-kDa-ApoE3 was prepared as described in Experimental Procedures. To obtain a solution containing the pure monomeric form of 22-kDa-ApoE3, 22-kDa-ApoE3 was dissolved in 5 M guanidine–HCl and 10 mM DTT. The resulting solutions were dialyzed against PBS at 4°C for 16 hr and used for the experiment. The purity of dimer and monomer in each sample was confirmed by Western blot analysis (Fig. 4). We also used 22-kDa-ApoE4 as monomeric ApoE molecule for the experiment that used astrocyte cultures because 22-kDa-ApoE4 contains no cysteine and it remains monomeric (Fig. 4B). The results demonstrated that dimeric form of 22-kDa-ApoE3 induced greater lipid efflux than the monomeric form of 22-kDa-ApoE3 and 22-kDa-ApoE4 in both neuron and astrocyte cultures (Fig. 4). Importantly, regardless of ApoE isoform, monomeric 22-kDa-ApoEs induces similar level of lipid efflux (Fig. 4B).
To determine whether such is the case for intact ApoEs, we examined the effect of the dimer formation of ApoE3 through disulfide bonds on lipid efflux from cultured neurons. We obtained dimer-enriched ApoE3 solutions by using a SulfoLink kit as described under Experimental Procedures. We also used ApoE3 solutions prepared without dimer enrichment, containing monomers and relatively few dimers. We also examined the effect of monomeric ApoEs, namely ApoE4 and ApoE3, whose cysteine was modified by carboxamidomethylation (ApoE3-CM). The levels of cholesterol and PC released from neurons treated with dimer-enriched ApoE3 were 2.9- and 7.6-fold greater than those released from neurons treated with ApoE3 and ApoE3 monomers (ApoE3-CM), respectively (Fig. 5). The effects of ApoE3-CM and ApoE4 on lipid efflux were similar. A Western blot analysis of each sample was performed and results show that the samples contained different amounts of dimers (Fig. 5B). The percentages of ApoE3 dimers as calculated by a densitometric analysis of the bands on the Western blot films were 64.5%, 36.9%, 1.8%, and 1.4% in the dimer-enriched ApoE3, non-dimer-enriched ApoE3, ApoE3-CM, and ApoE4 samples, respectively.
Next we determined the involvement of ABCA1 in 22-kDa-ApoEs-induced lipid efflux. The neuron cultures were treated with 22-kDa-ApoE3 dimers, 22-kDa-ApoE3 monomers, or 22-kDa-ApoE4 (monomers) concomitant with 10 µM of 22-hydroxycholesterol, an LXR ligand to up-regulate ABCA1 gene expression (Wang et al., 2001), and the cultures were maintained for 24 hr. After 24 hr incubation, the level of lipids released into the medium was determined. The ABCA1 expression level was enhanced when the neurons were treated with 22-hydroxycholesterol (Fig. 6A). The levels of lipids released by these ApoE fragments were significantly enhanced when the cultures were concomitantly treated with 22-hydroxycholesterol (Fig. 6B). These results suggest that ABCA1 plays a key role in 22-kDa-ApoEs-mediated lipid efflux in neurons. In support of this notion, we have observed that the treatment of neurons with glyburide, an inhibitor of the ABCA1 transporter, resulted in decreased levels of 22-kDa-ApoE3-mediated cholesterol efflux (Fig. 6C). We further examined the effect of ABCA1 knockdown on 22-kDa ApoEs-mediated lipid efflux by using specific siRNAs. The knockdown of ABCA1 in neurons significantly reduced lipid efflux induced by 22-kDa-ApoE3 dimers (Fig. 7).
We showed here that lipid efflux induced by ApoE is mainly mediated by the amino-terminal domain of ApoE and modified by the carboxyl-terminal domain. What we found are that the amino-terminal domain of ApoE induces lipid efflux in an isoform-dependent manner and the carboxyl-terminal domain enhances lipid efflux mediated by the amino-terminal domain of ApoE3. In contrast, the carboxyl-terminal domain does not strengthen the lipid efflux mediated by the amino-terminal domain of ApoE4 because of the domain interaction between the amino- and carboxyl-terminal domains. We also found that the lipid efflux induced by these ApoEs is mediated in an ABCA1-dependent manner.
Two of the main findings in this study are that the amino-terminal domain of ApoE, 22-kDa-ApoE, induces lipid efflux and that the extent of lipids released by the amino-terminal domain of ApoE, 22-kDa-ApoE3, is approximately 66% of that induced by intact ApoE3. The carboxyl-terminal domain synergistically and additively modifies lipid efflux mediated by 22-kDa-ApoE3. The additional contribution of the carboxyl-terminal domain is not observed in the case of ApoE4. Basically, 22-kDa-ApoE4 has a very weak ability to induce lipid efflux; moreover, the carboxyl-terminal region of ApoE does not effectively or additively enhance the lipid efflux mediated by 22-kDa-ApoE4. The lack of an additive effect by the carboxyl-terminal region on lipid efflux is likely due to the domain interaction, because an ApoE4 fragment ending at 250 (ApoE1–250) significantly gains in ability to release lipids; however, a carboxyl-terminal region longer than the amino acid 255, glutamate, which interacts with arginine at 61 (called the domain interaction; Dong and Weisgraber, 1996), does not induce any additive effect on lipid efflux induced by 22-kDa-ApoE4.
Another important finding regarding the effect of the domain interaction is that lipid efflux induced by mt-ApoE4 shows only a partial recovery toward the level exhibited by ApoE3. This indicates that the presence or absence of the amino and carboxyl domain interaction cannot completely explain ApoE-isoform-dependent lipid efflux mediated by intact ApoE and that other mechanisms are responsible for such ApoE-isoform dependency. This is supported by the finding of this study that 22-kDa-ApoE, which has no carboxyl-terminal region and thus has no domain interaction, induces lipid release in an ApoE-isoform-dependent manner.
We have already shown that α-helix formation is required for the high-affinity binding of apolipoprotein A-I to lipids (Saito et al., 2004), and that the binding capacity of 22-kDa-ApoE3 is lower than that of 22-kDa-ApoE4 for lipid particles (Saito et al., 2003). On the basis of the facts that the structural stabilities of 22-kDa-ApoE3 and 22-kDa-ApoE4 determine their binding affinity to lipids (Morrow et al., 2002; Segall et al., 2002; Weers et al., 2003) and that 22-kDa-ApoE4 is less stable than 22-kDa-ApoE3 (Morrow et al., 2000), it is reasonable to predict that the level of lipid efflux induced by 22-kDa-ApoE4 would be greater than that induced by 22-kDa-ApoE3. However, our results show the opposite, indicating that ApoE-isoform-dependent cholesterol efflux is unlikely to be explained by a simple theory linking the structural difference between these two fragments with their binding affinity to lipids.
Therefore, the question arises as to what is the mechanism underlying the isoform dependency of 22-kDa-ApoE-induced lipid efflux. It is possible to assume that 22-kDa-ApoE induces lipid efflux, because the 22-kDa domain contains an amphipathic four-helix bundle (Wilson et al., 1991), and it can bind to and reorganize phospholipid vesicles to form discoidal complexes (Lu et al., 2000; Segall et al., 2002). Surprisingly, 22-kDa-ApoE-induced lipid efflux is ApoE-isoform dependent. Such isoform dependency is likely to be caused by the presence or absence of cysteine at residue 112, which may result in intra- or intermolecular structural changes, forming dimers of 22-kDa-ApoE through disulfide bonds. More direct evidence that the dimeric form of 22-kDa-ApoE3 induces greater lipid efflux from cultured neurons and astrocytes than the monomeric form (Fig. 4) supports this idea. Previous reports have demonstrated that cellular cholesterol efflux is induced by many apolipoproteins in their lipid-free form, including ApoA-I, ApoA-II, ApoA-IV, and ApoCIII in addition to ApoE, all of which harbor multiple segments of amphiphilic helices (Segrest et al., 1992); the reaction still occurs with shorter apolipoproteins but to a lesser extent and only at high concentrations (Bielicki et al., 1992). Synthetic amphipathic helical peptides that mimic the physical properties of amphipathic helical segments of apolipoproteins can also induce cholesterol efflux as long as the peptide has at least two such helical segments (Mendez et al., 1994; Yancey et al., 1995). Consistent with these lines of evidence, when human ApoA-II, a disulfide-linked dimer, is reduced to a carboxyamidomethylation monomeric form, the ability of ApoA-II to induce cholesterol efflux is significantly decreased (Hara et al., 1992). In addition, the disulfide- linked homodimer of ApoE3 has been identified not only in cell culture medium (Gong et al., 2002), but also in human plasma (Weisgraber and Shinto, 1991). The mechanism by which the ApoE and ApoA-II dimers gain their functions to release higher amounts of lipids than ApoE and ApoA-II monomers, respectively, remains to be elucidated.
ABCA1 is involved in apolipoprotein-induced lipid efflux, including that mediated by ApoA-I (Brooks-Wilson et al., 1999; Lawn et al., 1999) and ApoE (Remaley et al., 2001; Krimbou et al., 2004). Regarding its effect on lipid efflux, the carboxyl-terminal fragment of ApoE (10-kDa-ApoE) induces a strong lipid efflux from non-CNS cells such as macrophages and ABCA1 plays a critical role in this efflux (Vedhachalam et al., 2007). Interestingly, contrary to these findings, 10-kDa-ApoE does not induce lipid efflux from the cultured neurons and astrocytes (Fig. 1). The reason for this discrepancy remains unknown; however, the cell type difference may be a likely reason. In support of this notion, even intact ApoE3 induces a very low level of lipid efflux from macrophages or fibroblasts, and ABCA1 transfection induces a marked lipid efflux mediated by intact ApoE3 in these cells (Smith et al., 1996; Remaley et al., 2001). In contrast, intact ApoE3 itself induces marked lipid efflux from astrocytes without ABCA1 transfection as shown in this study. This may be because apolipoprotein-mediated cholesterol efflux is only apparent in growth-arrested cells (Mendez, 1997).
We have observed that pretreatment with 22-hydroxylcholesterol enhanced ABCA1 expression in neurons and cholesterol efflux induced by ApoE, suggesting that ABCA1 is involved in ApoE- and 22-kDa-ApoE3-mediated cholesterol efflux (Fig. 6). The involvement of ABCA1 has been also demonstrated by the fact that the knockdown of ABCA1 significantly reduced lipid efflux induced by 22-kDa ApoEs (Fig. 7). One cannot exclude the possibility that factors other than ABCA1 that are relevant to biological mechanisms are involved because the involvement of ATP-binding cassette protein G1 has been reported previously (Karten et al., 2006; Kim et al., 2007); however, the lines of evidence in our present study suggest that lipid efflux from cultured neurons induced by ApoE or an ApoE fragment is mediated by ABCA1 function.
It is reasonable to assume that the disruption of the ApoE4 domain interaction by, for example, small molecules that create the ApoE3-like structure is a potential therapeutic target in neurodegenerative diseases including AD (Mahley et al., 2006). However, if the role of ApoE in HDL generation and its supply to neurons are critically involved in neurodegeneration in AD, other approaches that do not modulate the acceptor function, but modulate the cellular factors including ABCA1 expression and subsequent HDL generation, could also be candidate therapeutic targets.
Contract grant sponsor: Ministry of Health, Labor and Welfare of Japan (Research on Human Genome and Tissue Engineering); Contract grant number: H17-004; Contract grant sponsor: Program for Promotion of Fundamental Studies in Health of the National Institute of Biomedical Innovation (NIBIO); Contract grant sponsor: Japan Society for the Promotion of Science (JSPS); Contract grant sponsor: Naito Foundation; Contract grant sponsor: Grant-in-Aid for Scientific Research on Priority Areas—Research on Pathomechanisms of Brain Disorders, from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Contract grant number: 18023046; Contract grant sponsor: NIH; Contract grant number: HL 56083.
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.


text:
Windows 10 is the latest version of Windows from Microsoft, looking to win back customers, largely in the business area, that were disappointed with various aspects of Windows 8 and its modern Live Tile interface.
Windows 10 addresses these issues, producing a faster cleaner version of Windows and one which sees the return of the Desktop as the default for traditional form factor PCs and laptops, and a Start Menu which although more sophisticated than in Windows 7 is familiar enough to appease those who were vocally opposed its removal.
Microsoft has confirmed that computers with a licensed copy of Windows 7 or Windows 8.1 will receive a free upgrade to Windows 10, for one year from release, for the lifetime of that device. So the upgrade license is not transferable from the installed device (as per OEM license restrictions) and you have a year from release to perform the upgrade.
Initial wording quoted "consumers" leading many businesses to believe they would not be included in the free upgrades. This is not the case however, and Microsoft has confirmed any machine with a Standard and Professional license will be upgradable for free. Only businesses running Enterprise editions won't receive the free upgrade, however most of those larger customers are most likely running Software Assurance which covers them for the upgrade anyway.
A condition for receiving a free license is the tightened security from Microsoft. Outside of Enterprise environments, updates to the core operating system were received via Windows Update directly from Microsoft. Traditionally users could select whether to receive all updates, critical updates only, or turn updates off all together. Under Windows 10 this option is removed completely, updates are downloaded automatically, and notification of when they will be installed is presented to the user when they are available. You can choose to install them immediately, but you cannot delay installing them past the determined time.
Overall I'm in favour of this, the reason behind the move is to try and keep customers computers up to date and secure, something the delayed or turned off Windows Updates option prevented. Its no good complaining about Microsoft having an insecure operating system when you refuse to let it fix vulnerabilities and make itself more secure.
Another new feature that businesses should welcome is a new web browser. Internet Explorer has so many negative associations Microsoft has introduced a new browser, codenamed Spartan, which will be the default browser in Windows 10. IE will still remain available for back compatibility purposes, so don't worry if you have a legacy applications you need to run in IE, they will still work.
Spartan uses a new "Edge" layout engine that is faster and designed for the "modern web" and one of its key new features is the ability to annotate webpages and store and share them for later discussion – something that could be very useful in a sales environment.
There have been preview builds of Windows 10 available since the first Windows Technical Preview released 1st October 2014. The final release date unconfirmed at this point, its likely to be Released To Manufacturing (RTM) around the middle of the year to allow computers running Windows 10 to be on the shelves around late August/September time – to meet Microsoft's reported desire to have units available in time for 'back to school'.
If you're a business that only last year finally removed Windows XP from your environment, it may seen daunting to consider another upgrade now. This upgrade will be free, which removes the direct financial impact, but the in-place upgrade from Windows 7 or 8 to Windows 10 is better than ever, meaning unlike Windows XP you don't necessarily have to erase and reinstall everything from scratch.
Pingback: Windows 10 – Both Fresh and Familiar | TechOven()


text:
Ontario's opposition parties are pushing forward with an investigation into the controversial cancellation of gas plants, which could lead to a finding the Liberal government was in contempt of parliament.
Premier Kathleen Wynne had sought to reach a compromise with the opposition over the thorny issue, which dominated the last legislative session in the fall, to no avail.
The Progressive Conservatives, with the backing of the NDP, voted Wednesday to have the legislature's justice committee determine whether the Liberals deliberately tried to hide documents related to the facilities.
The government put the brakes on plants in Mississauga and Oakville at a cost of at least $230-million in what was widely seen as a political play to save Liberal seats in the 2011 election. Last September, in response to opposition demands, the government released 36,000 pages of paperwork on the matter. The following month, they turned over 20,000 pages more, which they said had accidentally been missed in the first search.
The opposition, however, alleges the documents were withheld in a deliberate cover-up.
"Misleading the House is a serious charge," PC MPP Todd Smith said Wednesday.
"We need to determine, and it is an open question at this point, if documents were destroyed in the course of this matter," said NDP MPP Peter Tabuns.
Government house leader John Milloy called the motion "mean-spirited" and argued against it.
"There was no political involvement or interference by the former minister, myself or political staff with the search [for documents]," he said.
The Tories rejected Ms. Wynne's compromise – which would have seen a special committee investigate the decision to cancel the plants themselves – because they said it would not have allowed a probe into the alleged cover-up, and that the premier would have compelled them to drop their contempt motion.
Ms. Wynne said she was "disappointed" with the outcome before heading in to Question Period..
"My hope would have been that we could have moved on to talk about other things," she said.
The justice committee could be set up within days. It will likely question those involved in the gas plant cancellations in public hearings. Ms. Wynne has said she would appear before the committee to answer questions, but maintains she took no part in the decision to stop the plants.


text:
Welcome to My College
Uniport international Secondary School , is a co- educational private school, established in2004 by the College of Continuing Education, University of Port Harcourt with a firm belief that the Nigerian education system needs urgent reform. it is located at the permanent site of the college of continuing education, Nkpolu Oroworukwo, Port Harcourt.
The School is open to student of all backgrounds, and it is without religious cultural or ethic bias, it is committed to academic excellence, discipline and hard work, ensuring that the fear of God and Good character are inculcated into the children, who are leaders of tomorrow, the school is fenced round to enhance security. it has a crop of dedicated professional teachers to cater for the moral and educational needs of the students.
The Motto of the School is "Learning for Excellence"
Our Vision
Our Vision is to educate the total child with the appropriate tool to compete in the 21st century knowledge driven economy.
Our Mission
Our mission is to provide a competitive learning environment with state of the art facilities where children irrespective of tribes, races, religion, etc are continually groomed and nurtured in conformity with the norms and aspirations of the society.
Our Goal
To impact exceptional leadership and management skills in our students. thereby empowering them for future challenges, it is also our goal to develop professional competence and fulfilling career for our staff.
Core Values
- Honesty/Respect
- Self Reliance/Creativity
- Integrity
- Responsibility
- Trust
- commitment


text:
October 6, 2014
SAN DIEGO -- Daimler Trucks North America announced that it will offer Detroit medium-duty engines beginning in 2016.
Speaking to journalists attending the American Trucking Associations Management Conference and Exhibition, DTNA President and CEO Martin Daum pointed out that while the Detroit brand has grown to include not only heavy-duty engines but also transmissions and axles, "something is missing – a medium-duty engine. I am announcing today, the DD5 and the DD8 medium-duty engines to the North American market."
Detroit's new DD5 and DD8 engines are a part of Daimler Trucks' Global Excellence Strategy to have uniform production standards and processes worldwide. Global testing and validation is being undertaken in both Europe and the United States. Versions of the engine series have been produced in Europe since 2012, but the line will be customized for the North American market, much as the Detroit DT12 automated transmission was developed.
DTNA's entire product line-up, including vehicles equipped with the DD5 and DD8, will meet GHG17 standards early. The engines will be initially built and shipped from Daimler's powertrain facility in Mannheim, Germany, with further plans to industrialize the engines in North America in 2018.
"It will be a great engine, we are all excited about that," Daum said.
When asked for more details about the engines, Brad Williamson, manager of engine and component marketing for DTNA, quipped, "Stay tuned."
The new DD5 and DD8 engines will be offered throughout Daimler Trucks North America's product portfolio, which includes Freightliner, Western Star, Thomas Built Buses, and Freightliner Custom Chassis vehicles.
[ Request more info about this product/service/company ]
Fill out the form below to request more info regarding the company/product/service featured in the story.
Will other OEM's follow or do they continue to build on their relationship with Cummins? Cummins can't be too excited about this announcement!
We offer e-newsletters that deliver targeted news and information for the entire fleet industry.
Scott Sutarik from Geotab will answer your questions and challenges
Steve Carlson from Xantrex will answer your questions and challenges
On the Spot: The Inaugural NACV Show [Video]
On the Spot: Kinedyne at the NACV Show
On the Spot: The Mack Trucks Anthem Launch [Video]
Ultimate Test Drive Video: T680 With Paccar Automated Transmission
Stoneridge's ELD Solution Verified By Third-Party Analyst
Anco Wiper Blades Fit Medium- and Heavy-Duty Trucks
Stoughton Launches Platinum Series Grain Trailer
Work Light Designed for Durability


text:
Only months after Lourd Ramos opened his second Creations branch in Makati City, the renowned hair and make-up artist continues to share his expertise through the opening of not just one, but two additional branches to his name. And I'm so happy that I was invited to check out one of them, the Soho Central Podium, Greenfield District branch!
Right inside the the peaceful Greenfield District, and alongside the great selection of newly opened restaurants there, Creation by Lourd Ramos is now offering their outstanding and renowned services that are sure to be enjoyed by everyone.
Lourd Ramos and Cathy Argar
According to Lourd, he personally trains his staff to ensure professionalism, high standards, and excellence - which in turn guarantees clients that they get the best salon experience every time they visit. From haircuts and hair treatments to make-up and styling to massage and waxing services, Creations offers an extensive array of hair care and styling services that pampers guests from head to toe.
Stay beautiful, everyone!


text:
Blackberry spy phone
Mobile Spy App - Reviews for the best online solution of spy apps for android and ios. Track Messages, SMSes, Text, Calls, SnapChat, Viber, WhatsApp, Twitter IKeyMonitor Mobile Spy App is invisible mobile phone spy software that can monitor Keystrokes/Passwords, SMS text messages, calls, websites, social networks, Cell Phone Spy Software app to monitor mobile phones remotely. Track Location,Call Logs,SMS,Contacts,Photos for iPhone, Blackberry & Android. FlexiSPY lets you spy on mobile phones and tablets and has unique call interception capability. Provides SMS Tracker, Cell phone tracker, room bugging total Best cell phone software for spying SMS, Text, Calls, Messengers. Spy On A Cell Phone Without Having It In Your Possession. Learn How and Where to Immediately Download the EXACT Remote Phone Spy Software Being Sold for - , 100% Free. Learn which phones are compatible with Mobile Spy. Works with smartphones running Android, iPhone iOS, and BlackBerry OS. Mobile Spy cell phone monitoring software monitors your child or employee's smartphone activity on iPhone, Android, BlackBerry and other mobile phones. Complete Application Solution for Spy On a Cell Phone. Friendly administration panel for view SMS, Calls, Messengers: WhatsApp, Viber, Facebook, Twitter and much more
Get quick how can you spy in someones iphone information about the installation steps and how to use the program to monitor a smartphone or tablet.
Online Demo Interact with a working example of the is there an app to where i can receive my boyfriends text messages on my phone online control panel to get a feel for how easy it is to monitor your smartphone.
Purchase Now Purchase online through our secure blackberry spy phone shopping cart to get the app and start monitoring your smartphone today.
What is Mobile Spy Smartphone Monitoring Software? Mobile Spy is the next generation of smartphone monitoring software. Do you worry your child or employee is abusing their smartphone or Internet privileges? Our software can help you keep them on the right track.
First, notify your child or employee they will be monitored. Then install the tamper-proof app directly onto the compatible smartphone you own and wish to monitor. Your child or employee will also be notified they are being monitored by device notifications and a tamper-proof icon.
Mobile Spy Software - iKeyMonitor
To view the results, simply login blackberry spy phone to your secure account using any computer or mobile web browser. Logs are displayed by categories and sorted for easy browsing.
Mobile Spy blackberry spy phone does not rely on the phone's call and message database to log activities. So even if your child or employee tries to delete their usage histories, the information will still be retained and inserted to your account.
Mobile Spy constantly updates the software so that it contains the latest features as requested by our loyal customers. Many of http://nileairwayscargo.com/iphone-spy-keylogger-for-not-jailbroken-phone-2caq/ our features cannot be found anywhere else. Check out a summary of Mobile Spy's features below.
"Our daughter stole our truck, bank cards, credit cards and the phone. The only way to find her was by tracking the SMS with your software. The police were able to catch her with the messages. We would not have caught her as fast as we did without Mobile Spy." - Adam D
"I love this program it is working great and helping me monitor all the text messages from the monitored phone. I am trying to prevent pornography from getting to my child's phone." - Mike
"That far exceeds what I would consider good product support! Thank you very much and you can count on my spy wear for fone support and references on your other products, which by the way, are more stable and generally work better than those of your competitors." - Robert
Read more:


text:
Wednesday, 31 August 2011
Last week's decision not to bring the case for attempted rape and sexual assault against Dominique Strauss Kahn was hardly a shock. The whole case was a clusterfuck of supreme proportions. The prosecution went overboard trying to make Nafitassou Diallo out to a be a room cleaning representation of perfect womanhood, setting her up to fall very hard and fast if anything proved otherwise. The defence played a clever game in saying the prosecution ws biased against DSK because of who he was and hoist them with their own petard as Cyrus Vance Jr and his team did the defence's dirty work for them by digging very deep on Diallo to try and show just how unbiased they were. Diallo turned out to be a flawed victim (but then aren't we all according to the very high standards set?) and her lie on her asylum application about a gang rape in Guinea did make a fair trial tricky to ensure.
But I'm not here to re-hash the DSK case. I really don't think much else can be said about it now. What has piqued my interest is the unbelievable amount of victim blaming, rape apologism and attempts to belittle sexual assault that have floated to the surface around it. Some of it is overt and palpable, some of it is so insidious and internalised that it blows my mind and some of it is borne of ignorance, the peddling of rape myths and the perceptions that our imbalance justice system creates. But despite the different paths, it all leads to one result. Women who report rape aren't believed and their trauma and fear is minimised at every step of the way.
If we weren't talking about something so serious, I'd laugh at the increasingly desperate almost hysterical levels of denial that rape and sexual assault even exist. In a blog conversation with the fantastic Sian at crooked rib, a charmer by the name of Iain dismissed forensic evidence in the DSK case with "that it's [semen] on a wall or clothes seems totally irrelevant. I'm surprised that anyone (even those who'd never had sex with a man) would be unaware that semen ends up in all sorts of places. It shoots out, quite a long way if allowed to." So apparently in an encounter where the accused denies being in the same room or touching the victim until his bodily fliuds are found present, this can be written off further by trying to tell us that penises are a bit like a shower head dropped in the bath and make a terrible mess if not watched closely at all times.
Another peach (now deleted) on the comments below this Hadley Freeman piece on the Guardian asked how oral sex could ever be forced? I like to think this is because it's honestly never occurred to him that a rapist will threaten to kill or injure a victim (or someone close to her) unless she does his bidding or that it isn't especially difficult to overpower a smaller person who may actually be on her knees or physical prevented from getting up. But since his username was 2Sceptic, I don't think he was having a gosh-golly learning experience about the shittiness of human nature.
Also on CiF, a serial rape denier by the username of FelixKrull declared with a Poirot-esque flourish that because she went back and cleaned the room where the assault had taken place magically erased the fact she had been attacked and thus rendered her a liar, rather than a frightened confused woman simultaneously trying to come to terms with being raped (forced oral sex is rape in the UK, hence my use of the term) and worried about losing her job for not cleaning the room, let alone utterly humiliated by the fact she had someone's semen on her (at work for extra mortification) and not necessarily wanting to advertise her shame to everyone in the hotel.
Nothing, not even calm measured explanation of how trauma works and the kind of reasoning shame and degradation affects people would change their minds and those who flocked to agree with them. Rape myths got a fresh airing with people queuing up to state that if she'd been raped, she'd have been cleaning herself instead of the room. They were unable to see the close link (admittedly it did take me several years to realise why I repainted our kitchen three times in the month afterwards, but then again I was having a nervous breakdown and no one was helpfully writing internet comments explaining the link for me). I wrote a few comments trying to explain why these people are both wrong and being massively unhelpful and then went off and banged my head against a wall instead for more effect. But then again, all the rape apologists had got nicely warmed up earlier in the year trotting out the short skirt and tight tops argument over the Slutwalks, so I should have known I was on the back foot.
Two other things came to my attention in the midst of this orgy of fingerpointing. Firstly this horrifying Mumsnet survey about rape and sexual assault (which needs a trigger warning) and secondly this amazing piece about Schrodingers' Rapist which seeks to explain just how prevalent the fear of rape and the spectre of blame for such a thing is for so many women. It makes chilling reading. I mean, you've read this blog, you know how scared I am of everything? That post still shook me up when I realised some of the things that we women are just expected to give up or go out of our way to do or if we get raped it'll all be our fault. And if it can shock someone like me who is hypervigilant, hasn't worn a skirt above the knee for seven years, refuses to match her underwear and checks the locks five times everytime she goes near the door all because of being both raped and being blamed for it, then it's rocket fuel for someone who has never had to consider it. And yet it wasn't wholeheartedly followed by a lot of people saying ' wow. That's shitty. What can we all do to change this and make everyone feel safer?'
No, it was followed by a whole load of people who have obviously mistaken the rape apology bingo card for the EuroMillions on a ten week rollover and can't wait to get every square in record time by spewing bullshit and looking butt-hurt that not all single women react to them to the street like a Babycham fuelled housewife at a Tom Jones concert. But then why would they take an (albeit) brilliant blogpost so seriously when the big boys in the police and judiciary don't have to play by the same rules? Because if you want to see victim blaming taken up a notch, this is where the gloves come off and you have to glue your eyes into the sockets to prevent an injury from rolling them.
The police suggested to me with utter seriousness that the roughly 100 injuries (that took almost 2 hours to photograph in detail) on my body could have been caused by either my friend and I giving each other hickeys in the pub for fun, arm wrestling, tripping over my flip flop and long skirt more than once in the evening and landing on the backs of my hands and the tops of my feet each time or (and this is my favourite) crouching down to pee in the park and catching myself on a twig or a combination of all the above. Not being drugged, forcibly held down and raped by at least one person. No, for one night only I became an arm wrestling, body contortionist with a hitherto unknown before or since penchant for pissing in parks with 8 foot high railings and didn't remember one nanosecond of it. I was too busy crying inside to hear how they explained away my bag ending up in the street in a mile away minus only a spare pair of knickers, a library book on Ted Bundy and my debit card while my mobile phone was sold by a bloke to a man in a shebeen in Tottenham Court Road and used to call India for next few hours. No doubt, they thought I was trying to renact a entire gap year without leaving W1.
Unsurprisingly this culture of sticking their fingers in their ears and going la-la-la got in the way of them investigating my rape (or the other four ultimately believed to be connected to the same bar) and no one was ever identified, let alone questioned. Weirdly despite trotting out every excuse and myth possible they did actually seem to believe a rape had taken place and said so when I claimed compensation several years later (even if it was grudgingly and with a sting in the tail). Recent missives from the frontline of the Sapphire units don't sadly seem to show any great enlightenment amongst the Met and the sound of clutching at straws still whistles on the wind as women seek justice.
This is why the Dominique Strauss Kahn case is important. It allowed rape myths to be seen as gospel and weak excuses to be commonplace like gossip. It also showed the uphill battle to raise rape conviction rates while such attitudes are so rife. The Stern Review touched on this handicap but sorely underestimated its insidious impact on the police and jury members alike which unless tackled counteracts every other proposal to raise rape conviction rates. The DSK case shows the media is a reluctant ally, so looks like we've got to speak up for ourselves. Challenge a preconception where you can. Poke holes in people's ignorant arguments. Educate without preaching*. But speak up all the same!
*Doing this in internet comments is optional for your mental health.
Posted by gherkingirl at 11:17
Labels: blame, bullshit, lack of facts, myths, rant, rape, the guardian
Subscribe to: Post Comments (Atom)


text:
- Grant Access
- Subscribe
- Track Account
- Gift Paid Account
Whatsamatter, Cat got your tongue?
Free Account
Created on 2012-07-31 04:36:56 (#1691922), last updated 2014-04-07 (184 weeks ago)
3 comments received, 527 comments posted
5 Journal Entries, 0 Tags, 0 Memories, 22 Icons
|Ask me nicely~
|May 20
[Yet another catwoman in the sea of cats invading dreamwidth. Probably will do nothing with her, but we'll see.]
People [View Entries]
Communities [View entries]
dear_mun, dear_player, dw_maintenance, dw_news, entrancelogs, entranceooc, entranceway, entranceworks, strippers
Feeds [View Entries]
To link to this user, copy this code:On Dreamwidth:


text:
My name is Rick Flores and it is my honor and privilege to serve as the new Somerset High School Principal for the 2017-2018 school year. As I reflect on my educational journey...I am truly grateful for the opportunities that I have been afforded to enjoy and I can humbly state that I have been blessed beyond measure. As a young man, I was raised in the inner city of San Antonio where poverty and crime oftentimes dictates the future of so many of our inner-city children. From middle school and beyond, I was raised in a single-parent home where we were oftentimes plagued with many life challenges. Our family struggled so much that as soon as I turned sixteen years of age I accepted my first job as custodian at a local Handy Andy Grocery Store. Although the challenges were too many to count, I am indebted to some of my middle and high school teachers, counselors and my Project-Stay representative that crossed my path while a student at Luther Burbank High School in San Antonio. It was not until my senior year of high school that I gave serious consideration to attending a university. Like many of our children I had a desire to attend a university but had no idea how to begin this process.
In the fall of 1990, I began my university studies at Texas Luther University in Seguin, Texas. Attending and graduating from Texas Lutheran was one of the best decisions I have ever made. Without a doubt I was oftentimes pressed and challenged at every side but I was determined to not give up. Sometimes in life if you want something that you have never had...you must be willing to do what has never been done. Let me reassure our Bulldog students that hard work does pay off! Being one of the first in my family to attend the university posed its fair share of challenges but earning my education has been one of the best decisions that I have ever made. Your education is that one thing that no one can take away from once it is earned.
As principal of Somerset High
School, my expectation of all Bulldogs is that we never settle for anything less
than our absolute best. You can expect that our students will be challenged to reach higher than perhaps they would have anticipated. Our goal is to simply provide our students with a menu of options and choices beyond high school. I do not expect perfection but rather improvement from all students. I learned from an early age that our greatest competition in life lies in the individual that we observe in the mirror every morning. So the question then becomes, "Can I be a little bit better today than I was yesterday?" Perfection is not expected but improved is required of all students.
I look forward to an amazing year of learning and growing with you Bulldog Nation. As a graduate of Luther Burbank High School, I was a BULLDOG! As a graduate of Texas Lutheran University...I was a BULLDOG! Now...I have the distinct honor and privilege of serving as the proud principal of our Somerset High School BULLDOGS! Let's remain "PAWSITIVE" and have a memorable 2017-2018 school year!
Once a BULLDOG...always a BULLDOG!
Mr. Rick Flores
Somerset High School Principal


text:
Workshop: Amphibian Identification
Chuck Peterson, Idaho State University
Sponsored by: Idaho Chapter of the Wildlife Society
Location: Boise Centre
Date and Time: Half day (PM) on February 28th; 1:30 PM - 5:00 PM
Fee: $15
Maximum Number of Participants: 50
Description: The Amphibians of Idaho workshop, presented by Chuck Peterson of Idaho State University, will use live animals, preserved specimens, audio recordings, and slide presentations to show how to identify Idaho's amphibian species and learn about their distribution, habitat relationships, and activity patterns. This is a half-day, afternoon workshop.
Registration: Please visit the Registration Form to register for these workshops. It is possible to register only for a workshop and not attend the meeting, if you so choose, though you'll be missing a lot of good information. Stick around!


text:
One of the most powerful & honest women of our …Read More »
This Parody Of Shakespeare Tweets Song Lyrics In Archaic Language
"All the world internet is a stage." It's a valorous thing Shakespeare is n…
23 Hilarious Tweets By Indians About Valentine's Day
Valentine's Day is almost here, the day of couples spreading joy, making promises, giving thou…
25 Times Rachel Green From Friends Was Relatable, Hilarious & Savage
In the course of 10 seasons of Friends, Rachel Green's character came a long way from being ri…
Shararat Season 2 is Coming & Everyone's Psyched AF
If you grew up in the 90's, there's a very little chance that you haven't heard of…
19 Hilarious Jokes By Indian Stand-up Comedians You Don't Need Audio To Laugh At
What a great time to be alive! I'm a sucker for comedy and I couldn't be happier to see …
Recent Posts
20 Of The Most Creative & Hilarious Signs From Women's Marches Across The World
Donald Trump's inauguration being the catalyst, the world finally united …Read More »
These Tweets Will Make You Want To Punch & Hug Your Sibling Simultaneously
Sister or brother, younger or older, dumb or dumber, it's …Read More »
Twitter Reaction To Salman Khan's Verdict For Arms Act Case
Déjà bhai: From French, "acquitted", is the phenomenon of having …Read More »
This Guy Went On A Hilarious & Accurate Rant Against Bigg Boss
Disclaimer: If you don't have any idea what in the …Read More »
Hilarious Tweets Only Desi Girls Will Understand & Relate To
Life of a desi girl. We are no strangers …Read More »
This Chef Is Breaking The Internet In India As Well
Welcome to the internet, on the left side you have …Read More »
Internet Reacts To Mcdonalds Masala Dosa Burger
It's only been a few months since internet had a …Read More »
22 Jokes By Indians That Are So Bad They Are Hilarious
BAD JOKES! love them or hate them (trust me I …Read More »
People Talk About What It's Like To Have Depression In Desi Household
Living with crippling depression is hard but you know what's …Read More »
16 Jokes About Friends Series That Couldn't Be More Relatable
Over 10 seasons and 236 episodes, they made us laugh, …Read More »
MS Dhoni Stepped Down As Captain & Here's How Twitter Reacted
The day we have all been fearing has finally come. …Read More »
25 Funniest Tweets By Indian Stand-up Comedians On Twitter
If you haven't been living under a massive rock, you'd …Read More »
If You Have Forgotten How To laugh, Watch This Guy Roast KRK's Deshdrohi
It's like some people are just born to be on …Read More »
14 Genius Tweets By Salman Khan That Will Prove Bhai = Roxxx
Salman bhai often drops his pearls of wisdom on social media. …Read More »


text:
Zillow Group, Inc. (NASDAQ:Z) last session's volume of 3.94 million shares was higher than its average volume of 1.27 million shares. The stock, after opening at $45.49, hit $44.44 through the close by scoring -2.33%.Zillow Group, Inc. (Z) Analyst Opinion
Zillow Group, Inc. has a consensus outperform rating from 17 Wall Street analysts, and the number of shares currently sold short amount to at least 16.08% of shares outstanding. The stock spiked 3.11% last month and is up 21.85 this year. Wall Street is only getting more bullish on the stock, with 9 of analysts who cover Z having a buy-equivalent rating. Analysts have placed a $42 price target on Zillow Group, Inc., suggesting a -5.49% decline from recent close. It's currently trading about -3.08% below its 52-week high.Zillow Group, Inc. Earnings Surprise
Zillow Group, Inc. (Z) surprised the stock market in its last reported earnings when it earned $0.11 a piece versus the consensus-estimated $0.05. Its revenue totaled $236.02 million up 3.69% from the previous quarter.
This stock (Z) is ahead of its 52-week low with 42.34%. Its last month's stock price volatility remained 2.98% which for the week stands at 2.71%. The share price has moved forward from its 20 days moving average, trading at a distance of 2.22% and stays 12.15% away from its 50 days moving average. Over the last five days, shares have faced -1.38% losses and now is up 22.19% since hitting its 200-day moving average of $37.41. Zillow Group, Inc. (Z) has made its way to a 12-month gain of 37.67%.
Turning to Care.com, Inc. (NYSE:CRCM), its shares were trading at $15.08 a retreat of $-0.5, on the trading floor. The stock, after opening at $15.62, touched a high of $15.79 before paring much of its gains. So far, analysts are sticking with their neutral recommendations with the consensus call at 2.9. Care.com, Inc. has 0 buy ratings, 4 holds and 0 sells even after the stock tumbled -6.16% from its high of $16.07 to a $440.64 million market value through last close.Care.com, Inc. (CRCM) Consensus Price Target
The company's consensus rating on Reuter's scale improved from 2.62 to 2.86 during a month. Analysts set a 12-month price target of $13.57 a share. The target implies a -10.01% decrease from where the shares are currently trading. Also, the current price highlights a discount of 12.73% to analysts' high consensus price target.Care.com, Inc. (NYSE:CRCM) Intraday Trading
The counter witnessed a trading volume of 0.22 million shares versus an average volume of 0.28 million shares during last trading session. Its last month's stock price volatility remained 3.38% which for the week approaches 3.32%. The lowest price the stock reached in the last trading day was $14.92 and compares with the $7.51 52-week low. The stock recovered 100.8% since its low point and has performed 75.96% year-to-date.


text: animals Animals Smelling Flowers Prove Humans Are Not The Only Ones That Enjoy Them 2 years ago I find flowers enchanting. With their vibrant colors, sweet scents and beautiful shapes, I know I can't resist stopping and giving them a sniff when I see them. And based on these photos, the same goes for all sorts of animals. It's not just bees that like to get up close to flowers, but raccoons, owls, dogs, foxes and more! (Source) Facebook Prev Article Next Article


text: On Thursday, my friend Renee Wilson said she would help me out with a school project and we planned a photo shoot that would be loosely Thumbelina themed. Friday we went to the mall and she bought 3 different outfits to wear for the shoot. I took Dahlia with me to the mall and quickly learned that when you're holding a puppy, everyone smiles at you. :) Saturday we did our shoot. I made a crown out of sticks and twine. I also cut out paper stars and tied them to twine so I could hang them from a tree. We went to the county park, but this time to the other side of the park that had more trees and was less groomed. I'm pretty pleased with the results!


text:
Association of special economic zones – an all-Ukrainian public nonprofit organization established to promote investment in special economic zones (SEZ) and territories of priority development (TPD) to meet the needs of the population of Ukraine in the creation of new jobs and protect the interests of its members. UkrASEZ registered by the Ministry of Justice of Ukraine on March 3, 2000 № 1348.
President of the Association – Kunitsyn S.V., Chairman of the Council of Ministers of the Autonomous Republic of Crimea;
Vice President – Minin, L.V., Professor, Doctor of Economics;
Chairman of the Board – Pikhno S.A.
Main activities
* Preparation of proposals for the authorities on issues that are relevant to investment, scientific, technical, tax and financial-credit policy and other issues of social and economic development of FEZ and TPD;
* Social analysis and synthesis of BMS;
* Assisting in the development and dissemination of economic and legal and regulatory documentation, domestic and foreign scientific and technical developments in the field of parks and special economic zones for use in the work of members of the Association;
* Assist in the creation of a common information base SEZ, TPA and Technology Parks;
* Organizing and conducting exhibitions, conferences, symposia, seminars on the development of SEZ, TPA, and parks and on other relevant issues for members of the Association;
* Assist in the search for Ukrainian and foreign partners to build mutually beneficial cooperation;
* Search and investment in SEZs, TPA and parks.
Possible areas of cooperation
* Organizing and conducting the analysis of investment attractiveness of regions, BMS and individual enterprises;
* Preparation and dissemination of information material to investors about the features of the SEZ, TPA;
* Learning experience (organizing and conducting training courses), the preparation and publication of scientific and methodological developments in the field of regional development, the functioning of SEZs, TPA and industrial parks, attracting investments, preparation of investment projects;
* Preparing and conducting business meetings and negotiations of Ukrainian and foreign businessmen;
* Training and joint exhibitions, seminars, conferences, roundtables, etc.;
* Dissemination of information on possible directions and prospects for cooperation, concrete proposals innovation-investment nature;
* Joint participation in the preparation and conduct of visits of delegations of business circles of different levels on the promotion of innovation and investment processes in some regions and Ukraine in general.


text:
Kentucky Department of Parks offers fun and educational programs and activities throughout the majority. This weekend is Father's Day. Most dads would love just to go out with the family check out these activities and events and treat Dad to a day at the park.
Historian Cid.D. Chattopadhyay of Jawaharlal Nehru University says the archaeological record says nothing like that. There civil projects ppt is not an evidence of one's human presence in the subcontinent, he says, before roughly 250,000 to 300,000 years formerly. It is generally believed man's hominid ancestors still did not leave their African home until announced nov . million rice.
Wright finally got his divorce from Miriam medication addict in 1927. Again, he had to wait another year to marry Olgivanna. They tied the knot in 1928. Thus, in the age of 61 Wright finally was married to your love of his personal. Through the years they became more and more involved the actual world occult. Olgivanna convinced Wright that these folks were both reincarnated royalty. They held their royal architectural court at Taliesin-West near Scottsdale, California. Despite the kinky spiritualistic interests of Olgivanna, they stayed happily married until 1959, when Wright died in the age of 92. Kitty Wright, his first wife, died the same year.
It's to be able to cost just how much? What concerns the IRS-Hitman is the $150 billion price amount. That's a quite high price tag to be sure everyone gets an extra $600.
Are there MLM experts that have confidence in? Absolutely. Dale Calvert made an income in MLM and is a great trainer. He has walked the walk and continues to share the converse.
You only have one or two in order to work around. Small bugs. Like students a lot more important one one other. That is exactly what the "day at school" means! To meet up with teachers various other kids, likewise get sooth subjects. I am aware every student cannot sign on to check out. I realize that some have to have the breakfasts and lunches. I am aware there are special needs students throughout all areas, have to have "hands-on" assist of teachers repeatedly. But that will be only a low percentage of student frames. And they probably get that special help and attention when the 98% student body is at home or some office on a working computer doing homework and studying lectures, getting classes to participate in in. Within the local schools to out space, they could be learned so substantially than we are able to instruct them.
IES is probably JOB that all engineer aspire for shield . preparation of IES one need to get afflicted with determination and dedication. You will have a good time table on which you strictly follow. There are lot of good publisher who publish books for perpetrations for everything subjects and for GK. They are very good encourage. You must also have previous year question and model test papers actually type you hand in it and will assist in good way for IES Engineering Functions. If you want to join ome coaching then you can opt for similar. There are many coaching centre in this in Delhi. Good Luck to you all.


text:
We were seated on the outside deck overlooking the street, which was totally lovely on a lovely night. It appeared that most if not all the couples were seated there, with groups of younger people inside, perhaps so they could spread out more. Our service was shaky from the start, with one server (I wish I got her name) making up for it with her willingness to take our orders and for her friendliness. She was great. Our assigned server was totally perfunctory in his attitude, although he did nothing wrong per se. My husband started with 1 paella slider that he liked a lot. Then he had the jambalaya which he was totally disappointed with. The shrimp were highly seasoned for no good reason, and the rest of the dish was a meh. I had the ribs which were okay and the fries, which I hardly touched. The key lime pie was a nice dessert. Prices on St. John are just high for reasons listed elsewhere in these reviews. While I didn't think the dinners themselves warranted the prices, you've got to give the restaurant some slack for the nice ambience they provide. But would we go back? I'm pretty sure not.
Own or manage this property? Claim your listing for free to respond to reviews, update your profile and much more.