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Theresa (Terry) Kessler's appointment as the KREFT ENDOWED CHAIR for the Advancement of Nursing Science will have a greater impact on her students than on herself. As she has since joining the faculty of the College of Nursing and Health Professions in 1994, Terry's personal scholarship, accomplishments, and professional development are directed toward enhanced learning experiences for nursing students.
Whether teaching within the College's bachelor, master, or doctorate-level nursing programs, Terry has always emphasized the importance of research and created opportunities for students to be engaged in research projects. The resources provided through the Kreft Chair will allow an expansion of research opportunities and provide Valpo's nursing students with real hands-on experience that is not found at most nursing programs. "The endowed chair gives me the freedom to move forward with my research ideas and to engage more students in the research process," she says. "That's the exciting part to me."
Terry was appointed to the Kreft Chair at the start of the 2015–2016 academic year and officially inducted to the position during the Winter Commencement ceremony on Dec. 13, 2015. She holds a Ph.D. from the University of Kentucky, an MSN from Indiana University, and a BSN from Purdue University. Terry received the 2014 Distinguished Teaching Award from the Valparaiso University Alumni Association and previously received the Caterpillar Award for Excellence in Teaching from Valpo.
Shirley and Karl Kreft provided the support to establish the endowed chair in 2007, with the purpose of attracting and retaining high quality faculty for the College of Nursing and Health Professions. Terry is only the second faculty member to hold the position. Kristen Mauk was the inaugural Kreft Chair, holding the position from 2007–2015.
Importance of Endowment
Endowed faculty chairs are just one part of Valparaiso University's overall endowment. While frequently described as if it was a single fund, an endowment is actually the aggregate of many different funds, most of which have terms and restrictions on how they can be used. Established with the preference of the donor, restricted endowed funds provide support for designated scholarships, programs, and Colleges.
Unrestricted endowed funds, consisting of a smaller portion of Valpo's overall endowment, are a critical source of income and allow the University leadership to respond to the most immediate needs. The flexibility to allocate the resources generated from the unrestricted endowment fund can make the difference in whether a faculty member can continue with their research or a student is able to attend Valpo.
Whether restricted or unrestricted, there may be no better measure of a university's financial health than the strength of its endowment. A strong endowment ensures long-term financial stability, reduces dependence on student tuition dollars to balance the budget, and improves institutional agility, making it possible to take advantage of new opportunities as they arise.
Valpo's endowment is quite small when compared to aspirants, peers, and competitors. With a value of just more than $202 million, as of June 30, 2015, it does not provide the financial foundation the University needs to advance its vision.
"A strong endowment is critical to Valpo's future," says Susan D. Scroggins, CPA '04 MBA, Valpo's vice president for finance and administration. "The reliable long-term support generated from endowed funds allows the University to engage in long-term planning with confidence that the resources will be available in the future."
Considering the endowment's importance to Valpo's future, the University will be setting ambitious goals for increasing the size of the endowment during the next several years. Great strides have already been made, as evidenced by the commitments listed below to support student scholarships, faculty development, and programs of strategic significance.


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Apparently Joseline Hernandez Thinks The Kardashians Take Their Fashion Cues From Her Style [Video]
- By Bossip Staff
Joseline thinks Kim, Kylie, and crew are scrolling through her feed and jotting down outfit ideas for their upcoming red carpet appearances.
You've seen how Joseline dresses to step out on the town…do you agree?
YouTube/The Real
More Stories From Bossip

subset: commoncrawl


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Full Tomorrowland in HD QualityNow you can enjoy Tomorrowland in best video format with duration 130 Min and has been aired on 2015-05-22 and MPAA rating is 473.
- Original Title : Tomorrowland
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- Year of movie : 2015
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- Release date of movie : 2015-05-22
- Companies of movie : Walt Disney Pictures, Babieka, A113,
- Countries of movie : United States of America,
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Movie synopsis of Tomorrowland :
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Story : Brad Bird, Story : Damon Lindelof, Producer : Damon Lindelof, Original Music Composer : Michael Giacchino, Director : Brad Bird, Screenplay : Brad Bird, Screenplay : Damon Lindelof, Animation : Kyle Dunlevy, Animation : Yuhon Ng, Visual Effects : Mike Marcuzzi, Story : Jeff Jensen, Director of Photography : Claudio Miranda, Editor : Walter Murch, Editor : Craig Wood, Casting : Corinne Clark, Casting : Jennifer Page, Casting : April Webster, Casting : Alyssa Weisberg, Art Direction : Dídac Bono, Art Direction : Todd Cherniawsky, Art Direction : Steven Christensen, Art Direction : Luke Freeborn, Art Direction : Kelvin Humenny, Art Direction : Martina Javorova, Art Direction : Jeremy Stanbridge, Art Direction : Geoff Wallace, Supervising Art Director : Ramsey Avery, Supervising Art Director : Don MacAulay, Production Design : Scott Chambliss, Set Decoration : Lin MacDonald, Costume Design : Jeffrey Kurland, Hairstylist : Anne Carroll, Makeup Department Head : Monica Huppert, Script Supervisor : Kimi Webber
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Tags: inventor, apocalypse, destiny, dreamer, drone, futuristic car, futuristic city,


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Monday Miscellaney
- We (meaning Dr. M) set up my home office over the weekend. I mostly sat around & read a book while he moved all the furniture & got the internet sorted out. And now that it's all set up I probably won't actually use it for work for several weeks. I was reviewing my calendar & realized that I'm going to be away from home for the next three weekends! Land sakes! I'm not cut out for all this gallivanting (I got new boots last week, which explains my turns of phrase here). Next weekend we're headed to a conference in Tennessee. The weekend after we'll be in Louisville. And the weekend after THAT I'll be at a Vestry retreat. November doesn't look any less crazy. Eep.
- Today was "wear purple" day at work. I admit that I went onto the interwebs last night to figure out an interesting way to wear my scarf. Fun & easy! (My hair is a bit wild - lots of running my fingers through it while I figured out a problem at work.)
- However, Dr. M wins the day. It's homecoming week at his school, so he got to wear pajamas to work today!


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Movement Disorders
The area of movement disorders is a subspecialty of neurology focusing on a variety of conditions that are characterized by hypokinetic, hyperkinetic, or abnormally coordinated movements.These conditions include tremor, parkinsonism, dystonia, myoclonus, chorea, ballismus, ataxia, tic disorders, dyskinesia, akathisia, restless limbs, and others. The term movement disorders may be used to refer to either abnormal movements or to syndromes that cause these abnormal movements. The classification of movement disorders is based on phenomenology, individual syndromes, or etiology.
- Track 1-1 Dyskinesias
- Track 2-2 Pediatric Movement Disorders
- Track 3-3 Chorea
- Track 4-4 Stereotypies
- Track 5-5 Myoclonus


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Something you have been struggling with on a mental level will resolve itself to your complete satisfaction today. Your mind will come up with the right explanation and you will no doubt kick yourself for not having thought of it sooner. Never mind. Some people never understand what's going on in their lives.
As brilliantly logical as you are, there is a lot to be said for turning off your mind and doing what feels right. Pro-and-con lists will only make you more confused. When you know, just go.
This is a good day to get creative, Virgo. Start recording your brilliant ideas. However, don't be quick to share them with others just yet. Wait till you formulate them more before inviting other people's positive or negative input. Working independently allows you more freedom to achieve concepts just the way they're envisioned in your mind's
Friday, November 16, 2007
Today's horrorscope:
Posted by Joe Pennant at 5:07:00 AM
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-She did everything to get her dreams come true even undergoing risky illegal procedure.
-She didn't know the price she has to pay to fulfill this dream.
-The beautiful look she's been dying to get could have almost caused here life.
- KAMI posts her story to warn our readers.
Read more: South Korea Leads The World With The Fastest Internet Speed. Philippines Falls Behind At The Least.
Andressa Urach dreams to become a popular model, and so, she trained extremely hard for it. She did everything she could to achieve her dreams, even undergoing a risky illegal procedure to enhance her behind. Fortunately, she won a place in the beauty contest. However, Andressa learned the hard way that artificial beauty has a huge price.
After winning the contest, she began to feel an intolerable pain in her legs. So, she directed to the hospital to have her legs check by the doctors. They found out that the gel injected in her thighs was not properly absorbed in her body. Hence, her muscles got rotten that has caused her unbearable pain.
Read more: "I Miss You" A Heart-Wrenching Message That Will Make You Weep.
The doctors immediately cut her legs open and place a specific foam into the cuts. Though, the cuts get infected easily that left Andressa with the chances of losing her legs. Fortunately, the doctors resolved the problem and saved her legs.
Read more: Is It Alright To Fit The Wedding Gown Before The Big Day? A Question Raised By A Bride-To-Be On Facebook That Received Different Reactions & Comments.
Now, Andressa has fully recovered after series of surgical procedures. With this, she wrote a book where she talks about her whole experience. In a way, giving everyone a warning about the risk and danger of getting into this kind of surgery.
KAMI saw the post on Facebook through Kusina Master Recipes and Daily Health Guide.
Source: Kami.com.ph


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I usually tend to spend time between Christmas and New Years thinking about goals. I was really glad when my friend contacted me to setup a video chat to discuss our fibery goals for 2018. I'm glad I dialed back last year to focus on learning and quality, rather than sheer quantity. That said, I feel like I could have been more productive in 2017. So this year I want to be more productive without going overboard. My friend had the best idea – her word for 2018 is FOCUS and I couldn't agree more. I want to be focused with my time and focused with what I work on.
Review of last year:
- Write and submit one article – Nope, will try again this year
- Develop and teach two new classes – Beat this with three new classes
- Design and publish two new patterns – Met this with my cowl for Malabrigo and my Cathay Williams Shawl
- Learn how to knit entrelac – Nope
- Learn how to knit brioche – I not only learned but completed a brioche cowl
- Learn to spin with beads – Nope, will try again this year
- Spin a consistent worsted weight yarn – Nope. I really haven't been interested or motivated in spinning a thicker yarn.
About setting goals:
I posted year before last about setting SMART goals, particularly as they rely to fiber artists. That post is here. SMART goals are specific, measurable, attainable, realistic and time relevant. While I think its a valid method, its not what I used this year.
2018 goals:
FloofyMoose Fibers
- Write and submit one article
- Develop and teach two new classes
- Design and publish three new patterns
- Learn and complete one project using Portuguese Knitting
- Complete 57 blanket squares for a total of 100 (approximately one per week)
- Finish a pair of socks
- Spin 4 ounces of yarn every other month
- Finish two in-process spinning projects
- Complete a 1-2 ounce spinning project with beads.


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labmonkie (lab' muhng-kee) n., 1. A series of experiments distinguishing living organisms from dead organisms and inanimate matter such as reality show contestants. 2. Your personal guide to Nothing in Particular. Enjoy.
Wednesday, December 15, 2004
I love Tim Burton.
And Johnny Depp.
And chocolate.
And anyone who is actually reading this sentence right now.
Coming July 2005, it's "Charlie and the Chocolate Factory." Boy o boy o @#$%in' boy! I personally can't wait. "Big Fish" made me squall like a baby.
Even though I'm not crazy about remakes, this looks like a good one that I'll actually get in line to see. I didn't see the "Cat in the Hat" because (Scott pointed this one out, and it's true) Mike Myers made The Cat talk like his Jewish bubbala character from "Coffee Talk", and man, don't get me wrong: Even though I thought his verklempt schtick was past funny/it was addictive, I really need to keep what little warm and cherished childhood memories* I have left in tact, mint and unopened, with the original boxes and tags. Ya know? It's cheaper than therapy. Plus, I hear they're worth more on eBay that way.
This is the same reason I did not see "The Grinch" with Jim Carrey. I was afraid it would include fart noises and talking butt jokes that weren't in the original Suess story.
Although I am not against fart noises as long as they aren't real. Computerized and handmade flatuence welcomed.
I'm such a contradiction, huh? "Oy, do not even ASK. Here's a topic...the Moral Majority is neither...discuss-s-s-s."
Someone please tell me if I'm wrong about those two movies and I'll netflix them with an open mind. Swear ta ya, my lil boopkafinkle mensches!
*Or as Grandma would say "them memories which ain't rurnt with taint on 'em."
ps: (Let's erase that last image, shall we?) And I love zefrank and his carol maker so I hope you do, too. Enjoy.
Posted by me at 7:03:00 AM
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West Vancouver Timeline
Our WV Timeline will always be "a work in progress". We welcome suggestions regarding historical events not yet included in the Timeline.
Pre contact: Squamish and Burrard peoples lived on the North Shore for centuries.
1791: First European sighting of West Vancouver. Pilot Don Jose Narvaez passed through English Bay and explored the northwest to Jervis Inlet in the 36-foot sloop Santa Saturnia.
1792: On July 3 Captain George Vancouver entered First Narrows and explored Burrard Inlet. First Nations peoples from the village of Holmulchesun greeted him, which was located at the mouth of the Capilano River.
1858: The B.C. mainland was proclaimed a British Colony. Surveyor S.J. Dawson recommended to the Canadian Government that the West Vancouver area be the terminus for the Transcontinental Railway.
1859: Captain Richards surveyed from the H.M.S. Plumper and recommended the Burrard Inlet as a more protected harbour for settlement and the railway. He pointed out that the South Shore was more accessible by land. Richards selected Point Atkinson as a British Naval Reserve.
1863: Corporal Turner of the British Royal Engineers completed a survey setting out the boundaries of Reserve No.5, home of the Squamish Nation, at the mouth of the Capilano River.
1868: John "Navvy Jack" Thomas, who began the first ferry service across the Burrard Inlet, began extracting sand and gravel from the west side of the Capilano River. This material was used in the making of concrete and was transported in his five-ton sloop to construction sites in Moodyville, Hastings and Gastown.
1869: Sewell Moody obtained timber leases for both sides of the Capilano.
1870: Sewell Moody, who had purchased the Pioneer Mill in 1864, acquired two timber leases west of the Capilano River. The smaller lease extended along the shore west of Cypress Creek to Point Atkinson and was soon exhausted of available timber. The larger lease extended east from 22nd Street to the Capilano River and north to the headwaters of Brothers Creek. Moody's main camp at Ambleside operated into the 1880's.
1872: James Blake became the first non-native landowner in West Vancouver, pre-empting 160 acres on either side of Lawson Creek (l7th Street).
1873: John "Navvy Jack" Thomas, who had married the granddaughter of Chief Capilano, sold his half interest in the Granville Hotel and arranged to take over Blake's preemption and built a house for his bride.
1874: Arthur Finney began construction of a wooden lighthouse on May 4th at Point Atkinson. The lantern for Point Atkinson arrived in January and in March the first Light Keeper, Edwin Woodward began work for an annual salary of $800. First pre-emption on Bowen Island by William Eaton.
1876: The first settlers' children were born in West Vancouver; Christine Thomas at Navvy Jack Point and James Atkinson Woodward at Point Atkinson.
1877: Josias Charles Hughes pre-empted 121 acres at Ambleside, the territory between Blake's property and the Capilano Indian Reserve. Isaac Fisher, a New Westminster banker, filed a pre-emption and mineral claim in the Whytecliff area.
1882: The B.C. Government suspended the pre-emption privileges and cancelled those on which the required improvements had not been made - to prevent land speculation until the location of the railway terminus had been determined.
1885: The first commuter, "Navvy Jack" Thomas, used a rowboat to commute to Vancouver from his home on the West Vancouver waterfront.
1886: The railway terminus was established and the City of Vancouver incorporated in April. On June 13th everything west of Hastings Mill burnt to the ground. The shoreline of West Vancouver was rapidly pre-empted. This pattern of settlement along the water was dictated by the early settlers dependency on the water and lack of access by land. A road survey crew ran a preliminary trail from Capilano to Eagle Harbour but this was quickly overgrown. Construction began on the first Capilano Dam.
The first land pre-emptors in West Vancouver were:
J.P. Hughes "Navvy Jack" Thomas J.R. Chapman J. McCormack A.N.C. King P.A. Allen Stan James Murray Thain Peter Larson Ed Collett Nils Frolander Capt. Westerlunder A. Nelson Capt. Alcock Richard Gosse J.C. Wilson
Lack of access to land discouraged further pre-emption activity until 1891.
1890: Canessas Fish Smokehouse operating on Eagle Island. Pilot Cutter "Claymore" based in Pilot Cove.
1891: The City of North Vancouver was established which included all of the present West Vancouver. The total population was 300. The promise of a road to Eagle Harbour stimulated a new surge of pre-emption and other land speculation. A syndicate headed by the Burrard Inlet Coal Co. promoted the sale of residential lots in the City of Newcastle. This was the name used to describe early West Vancouver; the company also claimed the existence of a substantial coal deposit. Like many promotions of the time, the scheme evaporated, as did the proposed road construction. The severe depression of the 1890's dried up the land speculation.
1892: In an effort to attract settlers, North Vancouver negotiated a loan ($40,000 for 50 years at 8%) to build a road or wagon trail from Deep Cove to Eagle Harbour. Fourteen years will pass before this road reaches West Vancouver. J.C. Keith who underwrote the loan gave his name to the road.
1893: The first school was opened on Bowen Island; Mr. William Acheson was hired to teach for $50 a month.
1897: The Whiteside and Burnham Cannery erected at Eagle Harbour at August Nelson's unfinished mill site. This cannery continued as late as 1918. John Cates ran a ferry service to Bowen Island.
1898: The Defiance Cannery was erected at Sandy Cove and was operated by several owners into the 1950's. It is now a Fisheries Research Station. Francis Wm. Caulfeild bought acreage around Skunk Cove from Balfor Ker. Ker acquired the property from Nils Frolander, the original pre-emptor. Ker allowed the Pilot Boat Captains to erect the "Pilot House" just outside the Cove. Caulfeild charged the Pilots $1 a month rental so that the pilots would have no claim on the land.
1902: A few early residents in West Vancouver. Some were earning a living providing farm products to the lumber mill at Moodyville in North Vancouver. Others worked for the Great Northern Cannery (although the work was seasonal and most employees itinerant). Others came simply to enjoy the beauty and the solitude of their recreational cottages.
1905: The order of sale in default of $1320 mortgage issued against the estate of John "Navvy Jack" Thomas. J.C. Keith then purchased the property. An eight-mile shingle bolt flume down the Capilano was completed.
1906: In November John Lawson purchased the Navvy Jack Thomas property from J.C. Keith. On December 6th, Lawson leases part of his new waterfront property to the McNair Timber Co. Ltd. For use as a railway log dump and booming ground. The yearly rent was $35.
1907: McNair-Fraser Lumber Co. built a logging railway that ran from the pier on the 16th Street waterfront north east through the middle of the 1200 block Inglewood to approximately 11th Street where it turned north, then curved north east crossing Brothers Creek. There were two camps; the lower was near 11 th Street and the upper approximately 1-mile beyond. The lower camp had a large stable, a cookhouse and a bunkhouse. The upper had a blacksmith's shop, 3 bunkhouses and a combination cookhouse, store and dining hall.
1908: The McNair-Fraser Lumber Company needed something better than a locomotive to cope with West Vancouver's steep hills to get to the logging sites so purchased a unique cable engine called the "Walking Dudley". The Dudley made 4 round trips in a 10-hour day trailing 10 to 16 logs each time. The first Presbyterian and Methodist Church services were held in John Lawson's home.
1907-1913: The provincial government divided the land into parcels with road allowances at _ mile intervals. Unlike the divisions in Caulfeild and later the British Properties, the grid does not consider topography. As a result many roads go straight up hill instead of following contours this results in steep grades and a propensity to flood.
1909: John Lawson began the development of the Hollyburn area (near the waterfront). A ferry service between West Vancouver and Vancouver harbour was initiated. Also a daily ferry service to Bowen Island from Vancouver. A dynamite plant opens on Bowen Island and a number of accidental explosions lead to an inquest and juries recommendation that books of rules be printed in Chinese as the Chinese workers cannot read the English warnings and instructions.
1910: The North Vancouver District Council built a wharf at Hollyburn (l7th Street) at a cost of $9,000. The wharfs exposed situation made it unsuitable for ferries it was also too short and did not extend into deep water. This did not prevent it from still being used by ferries between 1909 and 1912. It became an attraction for tourists and young fishermen. The foundations for the Presbyterian Church were laid at the southeast corner of 18th and Marine Drive. On April 24 a two-day forest fire threatens the upper camp of McNairs logging operation.
1911: Scattered tents and summer cottages dotted the shore of West Vancouver. Miss Mary Reid came from Ontario to teach the 14 boys and girls who were of school age in West Vancouver. The students were between the ages of 5 and 14. Before she arrived the children had to hike over the Keith Road to North Vancouver. Before the Presbyterian Church is complete the services were held in a makeshift tent. But one day the tent collapsed under the weight of a heavy snowfall, so a more sturdy, temporary building had to be constructed. To help pay the costs of the new building a decision was made that it would be rented to the school board as a schoolhouse.
1912: West Vancouver becomes a separate District Municipality. The split between North and West Vancouver was amicable-even as terms were discussed the North Shore Council approved a by-law for $100,000 to improve Keith Road and to build Marine Drive. Charles Nelson was elected first Reeve (Mayor) and the first Municipal Hall was built at a cost of $3500. At separation West Vancouver assumed $156,000 of North Vancouver's debt of $54,300,000 (a heavy load for a population of 700). The debt was accumulated for development costs and services. By the end of 1912 the school population was 44. The Council tried to encourage industry (fish canneries, logging). The Clachan hotel is built by the Stevenson sisters at the east side of 25th Street and the waterfront. David Rogers built a timber mill above McNairs upper camp and the Walking Dudley's track was extended to serve the mill.
1912: The first lighthouse at Pt. Atkinson was torn down and replaced by a new tower. Col. Wm. P. Anderson, Chairman of the Dominion Lighthouse Board designed a concrete hexagonal tower, 65' high, embracing six buttresses, which stood 108' high above sea level.
1913: The Conservative Hall is built at Dundarave. The first classes for children in the Dundarave area were held in the Conservative Hall with Miss MacKay as Principal. They moved into a new two-room schoolhouse in 1918 at the site of the West Vancouver Care Centre. A two-room schoolhouse called Hollyburn is built and Miss Lillian Smith became principal. In July the ferry service moved to the foot of 14th Street, where a new pier, freight shed and ticket office were built. (Today the ticket office is known as the Ferry Building Gallery). The first St. Stephens Church was built. Campbell and O'Conner opened a lumber mill at 3rd Street and Mathers. F.W. Cardinell Shingle Mill builds at 27th Street and Marine.
1913: First Reported (toll station) telephones in West Vancouver.
1914: First telephone switchboard with 35 magneto 'phones located in John Lawson's real estate office.
1914: The Pacific Great Eastern (P.G .E.) passenger service had its first run to Dundarave on January 1. On January 2 the train derailed at 24th Street. The original Methodist Church was at 2200 Fulton. A pier was built at Dundarave to provide transportation for those living in the area. McNair and Fraser Lumber Co. ceased to operate. Hollyburn Lumber Company opened a mill at 14th Street and Fulton.
1915: Marine Drive to Caulfeild was officially opened.
1916: The Dundarave pier built in 1914 was not well used and was discontinued in favour of a bus system. The bus service was inaugurated to 25th Street, the bus held 12 people and ran on an hourly basis.
1917: Logging was still a major industry with seven operators and several small contractors establishing shingle mills, lumber mills and logging operations in West Vancouver.
1917: Telephone exchange opened at 1718 Marine Drive with 65 magneto 'phones connected.
1918: The Council decided to obtain foreshore rights in Horseshoe Bay, Copper Cove and Fisherman's Cove. The Council now wanted to control all the foreshores and faced the problem of expropriating established housing. A 10,877 foot timber flume was built from the McNair, Fraser Lumber Co. mill on Hollyburn Ridge to the P.G.E. Station at Sharon Drive.
1918-1920: The number of schools was growing with the opening of Cypress Park School and the 22nd Street School (Pauline Johnson).
1919: The West Vancouver Courier, the first regularly published paper came into existence. It was printed until 1921.
1921: A one-roomed school in a rented private house was opened in the Whyte Cliff area.
1922: The introduction of electric power, before this time coal, oil lamps, wood stoves were used.
1924: Telephones converted from magneto to manual service - 418 telephones in service.
1925: A new St. Stephens Church was built. The old church became the parish hall. A small amount of logging continued as an element of land clearing. Skiing on Hollyburn Mountain was started by three Scandinavian who used the deserted logging bunkhouses as their cabins. The area around the cabins had been previously logged and provided open areas for cross-country skiing. By the Fall of 1926 they had moved up the hill to ski camps at First Lake. A ski jump was also built on the east side of First Lake.
1926: The Council initiated the Town Planning Act and zoning By-laws to ensure a quality residential area free of major industry. West Vancouver becomes a strictly residential community. The Library was moved from its old home, in Gemmill's Drug Store on the corner of 14th Street and Bellevue, to a more modern home at the corner of 14th Street and Marine. Hollyburn Theatre opened with five vaudeville acts and a "Great War Play" entitled 'The Dark Angel'. A large shingle mill was demolished to clear a site for the Inglewood School.
1927: Gleneagles Golf Course opened. Hollyburn Pacific Ski Club was formed. Inglewood School was opened as the West Vancouver High School. The first apartment block was built in West Vancouver, called "Appleton Court". (The west end of the current West Vancouver Municipal Hall is situated on this property at 17th Street and Esquimalt.
1931: The British Pacific Properties Limited company was formed. The Sewell family arrived in Horseshoe Bay to set up a boat rental business. The first May Day was celebrated in West Vancouver and the first Queen, Peggy Barker was chosen. May Day continued until 1973.
1938: Lions Gate Bridge opened to traffic. The official opening in 1939 was presided over by H.M. King George VI. The population of West Vancouver at that time was 8,324.
1938: New telephone exchange opened at 6093 Marine Drive to serve 52 customers in the Caulfeild and Horseshoe Bay area.
1950: West Vancouver Memorial Library opened (November 11, 1950) at its present location.
1956: New telephone exchange opened at 1651 Inglewood Avenue providing dial service to over 7400 customers.
1958: West Vancouver Recreation Centre opened at 22nd and Marine Drive
1963: Ice Arena constructed
1964: The new West Vancouver Municipal Hall opened November 20, 1964 at 750 17th Street
1977: West Vancouver Memorial Library expansion completed with official opening of new premises on November 14, 1977.
1979: July 23, 1979 – Tribute to Rupert A Harrison on his retirement after 42 years of service to the Municipality of West Vancouver having served 36 of those years as Municipal Clerk. September 30, 1979 – Municipal Parks and Public Works Yard opened on Cypress Bowl Road.
1981: Opening of the West Vancouver Seniors Centre at 21st and Marine Drive. The Centre was awarded the 1981 Canadian Architects' Award of Excellence and the 1985 Canadian Parks and Recreation Association Facility Excellence Award.
1982: March 22, 1982 – endorsement of the formation of the West Vancouver Historical Society for the purpose of preserving West Vancouver's historical heritage for the knowledge and benefit of all the citizens of West Vancouver.
1985: Negotiations underway with the Squamish Band to allow development of Ambleside Park and the Centennial Seawalk. Horseshoe Bay Revitalization initiated.
1987: District of West Vancouver 75th Anniversary Celebrations
1992: Official Presentation of the Patent of Registration for the Coat of Arms of the District of West Vancouver.
1994: Gertrude Lawson House opened as the Municipal Museum and Archives on July 1, 1994. Through cooperation with BC Rail, preservation of almost all usable land along Seaview Walk for recreational community development became a reality. Dedication of certain municipal lands above Upper Levels Highway as old growth wilderness park.
1994: Pt. Atkinson was designated a National Historic site in recognition of its crucial role in navigation and life saving to B.C's marine trade.
1995: Expanded Seniors' Centre opened. Citizen Survey of 1995 awarded the municipal organization a 97 percent approval rating.
1996: Lightkeeper services were terminated at Pt. Atkinson on May 31st, and the station was automated with solar panels and batteries to power a rotating beacon and electronic foghorns. The horns were permanently removed two years later.
1997: West Vancouver Court House officially amalgamated with North Vancouver and moved to that district. District of West Vancouver wins Communities In Bloom Award.
1999: BC Ferries/Horseshoe Bay development issues escalate. Recreation Facilities Master Plan developed.
2000: Celebration of the Millennium with completion of the Millennium Clock and Millennium Tree projects.
2010: February 12 to 28 - 2010 Winter Olympics, snowboarding and freestyle skiing events on "Cypress Mountain".
2010: May 23, 2010 - Commemoration of the Lions Gate Bridge as a National Historic Site.
Content originally from the West Vancouver Museum & Archives. Compiled from material collected by: Hugh Johnston and Dave Barker, West Vancouver Historical Society, Rupert Harrison, District of West Vancouver, and the West Vancouver Museum and Archives. This version (Pre contact to 1938) was written and adapted by Gallery Guide Volunteer Yvonne Wilson, March 2003, and reformatted for the WVHS website, October, 2009


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Pequea Families,
Sunday, March 1 is the day
for read Read Across America
You can also click here
so don't shed a tear
for activities to celebrate
Dr. Seuss' birth date.
Celebrating reading
is something we're needing
this winter has been bleak
so the PRIDE team organized a spirit week!
Monday, March 2 – Seuss Character Day: Students are encourage to dress like their favorite Seuss character.
Tuesday, March 3 – Foxiest Sock Day: Students are encourage to wear crazy socks! This idea is from the book, Fox in Socks.
Wednesday, March 4 – Mustache Day: Students are encouraged to wear a mustache like the Lorax from the book, The Lorax.
Thursday, March 5 – Greenie Grinch Day: Students are encouraged to wear green like the famous Grinch from How the Grinch Stole Christmas.
Friday, March 6 – Crazy Hat Day: Students are encouraged to wear a crazy hat like The Cat in the Hat from the book, The Cat in the Hat.


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Katherine Heigl.
Photos by Michael Thompson
Summer Of Love.
Model: Amber Valletta.
Photos by Patrick Demarchelier
The New Bob.
Model: Alison Nix.
Photos by Michael Thompson
Ocean Shades.
Models: Kastyn Reid, Veranika Antsipava
Photos by Michael Thompson
Broken Flowers.
Models: Kastyn Reid
Photos by Patrick Demarchelier
Anna Paquin. Nataliya Gotsiy.
Saturday, October 4, 2008
Allure June 2007
Posted by Kokobombon at 1:02 PM
Labels: Alison Nix, Allure, Amber Valletta, Celebs, Michael Thompson, Nataliya Gotsiy, Patrick Demarchelier
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Million Dollar Quiz and Tax
The Tax Office wasn't going to comment on how much tax Rob Fulton owes following his win in the popular TV game show "Who wants to be a Millionaire".
The tax rate in Australia is 48.5% and 1.5% medicare. Rob could see up to half his winnings being pocketed by the Treasurer, and hopefully shared with the other 17 million Australians.
Under Australian Tax law, Rob has two ways to find out how much he owes:
1. He can obtain a Private Binding Ruling, detailing legal points for and against why he should not be taxed. For such a large winnings, he'll need to get a pretty good tax lawyer
2. He can pay up 50% of his winnings
3. He can elect not to pay, but risk an audit, which under Australia's tough self assessment laws can see him paying 50% penalty plus 14% interest. This could easily add up to more than 75% of his winnings.
The problem is Rob has been diligently preparing for his quiz shows for several years by studying magazines and reference books. Now one could term his winning as speculative but taxable income nontheless, similar to day traders who speculate on the stock market. In contrast, winnings due to raffles aren't taxable.
On the other hand, Rob could argue that he was able to participate in the game show only by chance, and all those studying would have come to nothing.
Maybe the Capital Gains tax would apply, since he has to give back a cheque worth $468,000 in order to take a chance on the million dollars.
Who knows? The tax legislation is heavy enough to kill someone.


text: barefut Posted November 19, 2006 I am a childcare provider and I have a preschool out of my home. I have been very specific in my preschool handbook about NOT bringing children to school sick. I will tolerate a runny nose as long as its running clear - no green mucuos- because some kids have allergies and have a constant sniffle but I've had parents bring their kids here with a nasty loose cough. I am fanatical about hand washing here and I disinfect all surfaces and door knobs before and after kids are here. I teach kids to cough into their elbow rather than their hands and I have them wash their hands after they blow their noses. I even spray disinfectant into the air after sick kids leave here. BUT my kids and I have STILL gotten sick. Here I sit with a sore throat and a stuffy head. It makes me so mad not only because I'm on immunosuppressant medication, but because when I'm sick I lose income. ARG! :angry: Just as I don't want sick kids here, I can't have kids come here when I'm sick, even if I feel up to teaching. That would be hypocritical and wrong. I realize that anyone can catch a germ from anywhere and that my kids can catch stuff from other kids at their schools but it just makes me mad when I do all I CAN do to keep us healthy and then it's all for naught. Can anyone help me compose a friendly reminder to parents to keep their kids home when they are sick? Should I or should I not mention my compromised immune system? If I do mention it, how do I do that without having to go into great detail? I'm afraid any mention of my health issues will alarm parents if they don't have all the details. Even if they do have all the details, they may not understand. I'm afraid some parents may not want to bring their children here and I live in a small gossipy town so it could ruin my business.....help?! Maybe I ought to just give it up and sell stuff online????? :unsure: Thanks, Barefut Take care, Barefut Serena Justis ISN Blogger International Scleroderma Network (ISN) Share this post Link to post Share on other sites


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ASUS A8R32-MVP Deluxe - King of Xpress 3200?
ATI has now started to mass ship its Xpress 3200 Crossfire chipsets and it has picked up quite a following for the Crossfire crowd, mostly because of its dual PCI Express x16 interfaces for graphics cards. Whatever it is, it's clear that the battle between ATI and nVidia is heating up even more. ATI has one major advantage over nVidia and that is ATI has given support to Intel with the 975X chipset to support Crossfire. Though Intel only offers twin PCI-E x8 ports, we can expect to see this change with the next chipset revision - 985X will most likely give the Crossfire platform another dual PCI-E x16 partner.
ASUS is the motherboard manufacturer to watch these days. Beginning as a desktop and workstation only manufacturer, ASUS has pulled all the stops to become the most well known and most trusted motherboard platform on the market.
ASUS has put out more motherboards than any other company out there, with support for every chipset that comes on the market of value, including ones like SiS and ULi. ASUS can be a truly valuable partner.
ASUS has now adopted the latest Crossfire chipset, the Xpress 3200 onto its new high-end Crossfire platform, known as the A8R32-MVP. ASUS has clams that this is the ultimate in Crossfire boards. Will these big, bold claims hold true?
PRICING: You can find products similar to this one for sale below.
United States: Find other tech and computer products like this over at Amazon's website.
United Kingdom: Find other tech and computer products like this over at Amazon UK's website.
Canada: Find other tech and computer products like this over at Amazon Canada's website.
- Page 1 [Introduction]
- Page 2 [Specifications]
- Page 3 [Package and Contents]
- Page 4 [The Motherboard]
- Page 5 [Overclocking]
- Page 6 [Benchmarks - Test System Setup and Sandra]
- Page 7 [Benchmarks - PCMark05]
- Page 8 [Benchmarks - 3DMark03]
- Page 9 [Benchmarks - 3DMark05]
- Page 10 [Benchmarks - 3DMark06]
- Page 11 [Benchmarks - Doom 3]
- Page 12 [Benchmarks - Quake 4]
- Page 13 [Benchmarks - F.E.A.R.]
- Page 14 [Benchmarks - Far Cry]
- Page 15 [Final Thoughts]
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Many adults wish to incorporate power play into their intimate moments, and the fantasy of being helpless before a much more dominant personality, of submitting to a will more powerful than your own and having no choice in the matter, is becoming a once-forbidden subject that is finally being brought out into the light for discussion and consideration.
Part of exploring this darker side of your personality is the appropriate attire - after all, your day-to-day denim-jeans-and-worn-tee-shirt combination might not be appropriate for enacting a power play scenario. This is where fetish clothing can come into play. By incorporating the edgier outfits available into the bedroom, you can explore your more dominant side - or, perhaps, finally submit to the will of your partner. Combining the fantastic elements of the traditional costume with the eroticism of the forbidden, fetish clothing can take a physical relationship to the next level.
Do not instantly leap to a stereotypical conclusion - fetish clothing does not necessarily consist of a leather hood with a zipper over the mouth and a pair of manacles dangling from the ceiling. Rather, they provide an edgy, fantastic element that allows one to explore their darker side. Some fetish clothing borrows elements from other fantasy costumes, such as a cowboy assless chaps (with a jockstrap to prolong the anticipation). Others adapt "traditional" lingerie with different materials and cuts to emphasize the edgy nature, such as a vinyl miniskirt (with or without complementary fishnet stockings). Still others take the fantasy further, such as a cupless teddy in black leather and thigh-high boots. See-through fabrics can be used to add a titillation factor, and fishnets with weaves ranging from the tight to wide diamonds can be added to display just how saucy you actually are. The point is not to dress as though you just escaped from the set of a BDSM video shoot, but rather to add a spicy edge to your play in the bedroom.
Of course, for those couples for whom vaguely edgy just won't do, there are even more extreme outfits that leave little to the imagination and much to the fantastic play. For him you can find edgy tormentor outfits with a collar and a jock for those times in which their partners are helpless in their grasp, while dominant lady can display her power with a fishnet bustier and vinyl front-zip shorts. And of course what self-respecting Dom or Domme would be without a collar and a leash to make sure their favored pet doesn't wander too far astray?
Conversely, the submissive in you can opt to don a vinyl strappy teddy, or a collar with a set of chains firmly attached to a pair of cuffs. And it's not just for the women - today there is a wide range of chastity belts, complete with locks and keys, for those men who thrill to being under the control of those they love.
There are bondage harnesses available for both men and women that provide just the right amount of constriction and restraint while still providing a free range of movement. And best of all, for those who are seeking a public-yet-discrete domination, these harnesses can be worn underneath clothing to create a situation where both partners knows EXACTLY what's going on under that prim-and-proper attire to the exclusion of everyone else at the party.
Fetish clothing can be used to add a bit of edgy spice to a vanilla relationship, or it can be used to explore the darker side of one's own soul. Today, the only limits are those of your imagination.


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I am blessed with a man who continues to love me even with all my faults. Here a few pictures that remind me I am forever grateful for my man!
He loves and supports my family!
He is an excellent grill master and now smoker master! That means I have it easy in the kitchen.
He took in my animals when he didn't have to.
He is an amazing uncle which only means he will be an extraordinary dad one day.
When he gets flowers he also gives my students flowers so they feel loved too.
He eats my cake and food even when it doesn't turn out the way I planned.
He goes to my friends weddings and their children's birthday parties.
He waited for me at the baseball field as I visited with 7 of my students.
He is the hardest worker and I couldn't be more proud when things go great for him.
I pray each day that God continues to strengthen our marriage and prepare us for what he has planned for our lives together.


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Payne likes to sift through my diaper bag contents while in the stroller. Just before this he was leafing through an old People Magazine.
I suppose it's good he didn't have a stuffed animal or something with him or he probably would have pretended to nurse it under the cover. At least he's modest. Heh.
Oh, and when I was loading them up on the way into the mall today I told Payne, as he was climbing slooowly out of his car seat, "Hurry up! Baby sister is baking out here!" (the highs have been above 105 this week) and he responded in a truly indignant manner "No! Her not bacon!". I love that he thought I referred to his sibling as a cured pork product.
And one more "One month" photo. Dan took this last night and I love it so much!


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this blog post -- they came back with an astounding price of approximately $500! (More or less, depending on the thickness of the material.)
I describe it as "astounding" because the cases available on Sideshow, which light up by the way, run about $300.
So, basically, it looks like I'll try my hand at building a display case of some sort. I already have a vision in my head as to what it will look like. Now it's just a matter of measuring and cutting, gluing and swearing.
That last item tends to go hand in glove when I attempt DIY projects. What initially begins so simply and easily... well, that's the warning sign that something is about to go completely sideways. I'm a realist when it comes to this. The only thing one can do sometimes is just stammer, throw down a hammer, and fire invective at the walls (which are hopefully thick enough to shield people walking by the house).
And a lot of the time that old nugget from Jurassic Park springs forward.
You were "so preoccupied with whether or not [you] could, that [you] didn't stop to think if [you] should."
DIY enthusiasts take note.


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The Best Raspberry Fudge Brownie Recipe
Raspberry Fudge Brownies Recipes
Try this Raspberry Fudge Brownies Recipe, it's a bit of a challenge with a larger ingredients list, but they taste fantastic!
I remember my Grandmother making brownies. You could smell them cooking outside when the windows were open and the cool breezes blew through the house.
I think you will love this recipe, it is a variation of the original brownie but very, very delicious.
History of the Brownie...or so it seems!
I probably had my first brownie as a child in the high chair. My Mother was a great cook and I can almost bet that my love of chocolate came from the very early years.
The brownie has a controversial history. There are various stories on where they originated. All of the stories, however, have one thing in common, that the brownies were created by accident. It is also believed that they started somewhere in New England.
They actually class them as a cookie, and not cake although according to an early 20th Century Betty Crocker Cookbook, it stated that they started as cake that was cooked, accidentally, without yeast. Instead of throwing them away, they were served...and the brownie was born.
Now, let's have a brownie and sit back and enjoy the website!
33 of the most Amazing Brownie Recipes of all Time!
Some of the most spectacular brownies that will ever melt in your mouth!
There are recipe books with hundreds of brownies in them. Why try to figure it out for yourself when they have been narrowed down to the tastiest morsels available - all tried and tested and I am ready for that package where you send me some!
Cook Time
Prep Time: 20-25 minutes
Total Time: Approximately 3 hours
Serves: (30) - (32) Brownies
- (1) cup sugar - white
- (2) large eggs
- (1/2) tsp vanilla or extract
- (1/2) cup butter - you can use margerine but I prefer butter - melted
- (1/2) cup flour
- (1/3) cup cocoa powder - unsweetened
- (1/4) tsp baking powder
- (1/4) tsp salt
- (1/2) cup chocolate chips - miniature are preferred
- (1/2) cup evaporated milk
- (1) yolk of egg
- (4) (1 oz) semi-sweet baking chocolate squares - chopped
- (6) oz cream cheese - softened
- (2) tbsp raspberry jam - seedless
- (1) cup frozen whipped topping - thaw before use
- (16) chocolate curls ( these are optional)
- 1. Prepare oven by pre-heating to 350F
- 2. Prepare a square baking pan by covering with aluminum foil
- 3. Put the following ingredients in a large mixing bowl; eggs, sugar, vanilla and mix thoroughly. Let the butter soften and mix it in also.
- 4. In a separate bowl, mix the cocoa powder, baking powder, salt and flour. Take this mixture and stir into the first bowl. Before pouring into the pan, fold the chocolate chips into the mixture.
- 5. Put the pan in the preheated oven for about 25-30 minutes. A good test to see if ready is to cook with a toothpick in the center. When you remove the pick, it should have crumbs attached. When ready, remove the pan and let them cool.
- 6. In a small saucepan, whisk the evaporated milk and egg yolk. Use medium heat and only whisk until the mixture is hot and thickens. DO NOT allow this mixture to go to a boil.
- 7. Put the semi-sweet chocolate in a small mixing bowl and pour the hot milk/yolk mixture in until the chocolate is melted. When melted, pour this mixture over the brownies and cool in refrigerator for about 2 hours.
- 8. Put the raspberry jam and cream cheese in a large bowl and beat together until they are very smooth. When smooth, put in the whipped topping by folding and add food coloring if you would like.
- 9. Cover the cooled brownies with the topping and be artistic, if you would like and put designs on them.
- 10. Cut the brownies and garnish with the chocolate curls if you don't think there is already enough chocolate! Ha!
Leave a Comment! - About this Raspberry Fudge Brownies Recipe!
Seems I've found yet another recipe that I'd like to make.
This raspberry fudge recipe looks absolutely amazing Mmmmm!!
Merry Christmas and Happy New Year!!
Sounds good, I have a raspberry brownie, too but it doesn't have cream cheese. Sharing on my Facebook page, Culinary Favorites From A to Z.
Wow! I am going to have to try this! I love chocolate and raspberries!!!! Blessed!
Oh, great lens, delicious recipes.
Wanna try to make at home!
those brownies look extra tastey, just makes me wont to make this recipe even more!


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Here we go again. It has been discovered by the guys at SupraMKV.com that Toyota has trademarked
This latest development could be a hint that a flagship sports car from the world's largest carmaker is on the way, and the desire to create a 'new Supra' is still alive. It could be that Toyota is keeping its options open with regards to the name of the future sports car. Or it could be nothing, for now.
What we know is that Toyota is working together with BMW to develop a sports car, a collaboration that was announced in 2012. BMW's version of the car is rumoured to be the 'Z5', a replacement for today's Z4. Toyota rolled out the much-praised FT-1 concept at the 2014 Detroit Motor Show.
Industry gossip, shared by Motor1.com, say that production of both sports cars is set to start in 2018 at Magna Steyr's factory in Graz, Austria, to the tune of 60,000 units per annum. Apparently, both cars will use BMW engines, but there will be a hybrid version powered by Toyota. Spyshots of the 'Z5' have shown a soft top, but a coupe is also in the plan, they say. Same platform, unique exterior and interior design.
"Big brother will have amazing performance," Tetsuya Tada, chief engineer of Toyota's Sport Vehicle Mangement Division was quoted as saying last year, referring to TMC's plan to have 'three brothers' in its sports car family. The Toyota 86 will be the middle child, the 'Supra' the big brother and the cute S-FR Coupe from Tokyo 2015 the little brother.
If the 2018 production start rumour is true, an official reveal of the much-anticipated sports car shouldn't be too far away. By the way, Toyota registered the 'S-FR' name in the US last year, so it might not necessarily be called 'Supra'. The burden of carrying such an iconic name could be very heavy…
GALLERY: Toyota FT-1 Concept
GALLERY: Toyota Supra, through the years
GALLERY: The late Paul Walker's 1993 Toyota Supra


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Alistair Banham: pureLiFi CEO profile
Alistair Banham talks about what it takes to grab the reigns of a promising young technology company
In the latest issue of Land Mobile Magazine, our CEO Alistair Banham talked about what it takes to grab the reigns of a promising young technology company and drive an innovative team towards unleashing truly disruptive wireless communications.
Alistair Banham is not the new kid on the block. He comes with more than 30 years of experience in the semiconductor industry taking leading roles at companies like Philips, and Wolfson Semiconductors. He has a strong vision and the experience to take the company there. Read about Alistair's approach to growing the prueLiFi team, keeping focused and overcoming challenges. Enjoy this pureLiFi CEO profile.


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Thursday, October 13, 2011
Jazz Festival Weekend in Rehoboth Beach, DE
Some things are planned and arranged far in advance, others happen at a moments notice. Our appearance in Rehoboth for Jazz Festival weekend is more like the latter. This weekend, you will find music to suit many a taste all over town. It's really worth the trip. In addition to the ticketed events, most all of the restaurants and clubs feature live jazz all weekend. I am with Shore Jazz and the Eddie Sherman Show at Cilantro's. Click on the above poster to enlarge. Hope to see you!
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Thursday, August 23, 2007
Clubbing (or not)
These days it seems that I don't get around to writing about my weekend until the next one is almost upon me. I suppose that is the life of a busy adult. On Saturday, I went to the birthday celebration of a new friend. Happy works with a woman by the name of Mandy. Mandy is from South Africa, and for her birthday, she wanted to go clubbing in Salt Lake. For those of you who don't know me well, I don't particularly like to go clubbing. The music is usually so loud that you can't talk to people, the club usually has cigarette smoke in it, and half the people have had an alcoholic drink or two. The last time I went clubbing, which was two years ago, a strange man started kissing my neck while I was dancing. It freaked me out and I haven't been since. The only thing Mandy wanted for her birthday was to go clubbing. After much cajoling by Mandy and by Happy, I said yes. I did put time limits on it though. I didn't want to stay out too late since I had church and a family party the next day. Happy drove the two of us to Mandy's house and we waited for some of Mandy's other friends to join us. We left for Salt Lake at 10pm and proceeded to go to a club called Bliss. After waiting in line for a half an hour, we got up to the front. That was when Mandy realized that she didn't have her ID. Since clubs serve alcoholic drinks, you can't get in unless you have a picture ID. We went to several other clubs to see if they would let her in and they all said no. I must admit that I was relieved. I didn't have to go into a club and I got to walk around Salt Lake with some friends. Brandon, Happy, and I left at 12:30am and had an interesting discussion about marriage on the way home. I had fun, even though I don't know that Mandy did.
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Property Location
The D feringghi and Restaurant is conveniently located at 66 - 15 - 0 Jalan Batu Feringghi, Пенанг.
About Property
Selamat Datang – you are welcome! This boutique budget hotel, D'feringghi Hotel and Restaurant, is the perfect hideout for small groups who intend to build up something together. The relaxing atmosphere once you enter already suggests the feeling of being far away in a cosy and homely place.Cosy rooms suiting all budgets, from standard and superior - accommodating 2 persons - to deluxe and suite - beds for 3 persons - D'feringghi Hotel and Restaurant's family room offering 2 bedrooms in a private area.In the evenings there are plenty of entertainment and shopping facilities just in front D'feringghi Hotel and Restaurant's place and along the stretch of the famous night market.
Property Amenities
Please inquire us about the business and other amenities at this property by email@example.com
Мы гарантируем для Вас лучшие цены. Стоит немного подождать.


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by admin • September 24, 2010 • * Safe for Work *, Fear, Lost Love, Short -n- Sweet • 0 Comments
I think I wanted you back because I am terrified of being alone. The only thing I am afraid of.
That, and I had to confirm that you never truly wanted me. Confirmed. And facing my fear.
Promises and love are just words.


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Tuesday, April 3, 2012
Have I mentioned how much I love riding?
The last four months have been pretty hectic at the Kelly house. From the holidays until now there have been visitors, weekend commitments, home projects and generally more ways to keep me busy than I really would like. But it is part of life as they say. My only real riding has been to and from the office and to various work projects for photography sessions. No canyons, no trips, just grinding out the day to day. Know what? I am still loving being on my bike. The ride to work, identical each morning, is still 35 or so minutes of fun. Coming home, even better. Still to this day, almost 42 years of being on a bike and I get that little tickle of excitement as it warms up in the driveway. It's not about the ride, the destination, how fast you went, did your knee touch ground, was your chrome sony enough....it's just about the blending of you and your bike into a single entity....and choosing the bike over the car all the times possible.
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Five Things Friday: 1.30.15Monday, February 2, 2015
It's week two of Five Things Friday and I'm only one week behind :)
This week was so good! And these are the top five things that happened:
- I FINALLY finished my sewing project from forever ago. I took it home for the break and still didn't finish it, but it turned out nicely.
- I was accepted to law school! I'm still waiting to hear back from several schools but at least I got into one and I'll be going in the fall!
- I rediscovered my love for country music and have been listening to George Strait and the like all week long.
- I got tickets to a Walk The Moon concert down in NC which means I get to go home in a few weeks AND go to a concert with my baby sister. Win-win!
- I drove in the snow and didn't crash Jarvis. I've been stressed about this for weeks so it's definitely going down as a win.
PS--The playlist I'm currently addicted to:


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Cell division cycle 7-kinase inhibitor PHA-767491 hydrochloride suppresses glioblastoma growth and invasiveness
Genomic instability is a hallmark of cancer cells, and this cellular phenomenon can emerge as a result of replicative stress. It is possible to take advantage of replicative stress, and enhance it in a targeted way to fight cancer cells. One of such strategies involves targeting the cell division cycle 7-related protein kinase (CDC7), a protein with key roles in regulation of initiation of DNA replication. CDC7 overexpression is present in different cancers, and small molecule inhibitors of the CDC7 have well-documented anti-tumor effects. Here, we aimed to test the potential of CDC7 inhibition as a new strategy for glioblastoma treatment.
PHA-767491 hydrochloride was used as the CDC7 inhibitor. Two glioblastoma cell lines (U87-MG and U251-MG) and a control cell line (3T3) were used to characterize the effects of CDC7 inhibition. The effect of CDC7 inhibition on cell viability, cell proliferation, apoptosis, migration, and invasion were analyzed. In addition, real-time PCR arrays were used to identify the differentially expressed genes in response to CDC7 inhibition.
Our results showed that CDC7 inhibition reduces glioblastoma cell viability, suppresses cell proliferation, and triggers apoptosis in glioblastoma cell lines. In addition, we determined that CDC7 inhibition also suppresses glioblastoma cell migration and invasion. To identify molecular targets of CDC7 inhibition, we used real-time PCR arrays, which showed dysregulation of several mRNAs and miRNAs.
Taken together, our findings suggest that CDC7 inhibition is a promising strategy for treatment of glioblastoma.
KeywordsGlioblastoma Cell division cycle 7 CDC7 inhibitor Cathepsin S Kinase inhibitor
adenosine monophosphate-activated protein kinase
- BrdU
cell division cycle 7-related protein kinase
- cDNA
complementary deoxyribonucleic acid
cerebrospinal fluid
cathepsin S
Dulbecco's Modified Eagle's Medium
deoxyribonucleic acid
fetal bovine serum
glyceraldehyde 3-phosphate dehydrogenase
half maximal inhibitory concentration
isocitrate dehydrogenase 1
mitogen-activated protein kinase 8
minichromosome maintenance protein 2
- p-MCM2
phospho-minichromosome maintenance protein 2
O6-methylguanine-DNA methyltransferase
- mRNA
messenger ribonucleic acid
- miRNA
micro ribonucleic acid
- mTOR
mechanistic target of rapamycin
- p53
tumor protein 53
- p70s6k
phosphoprotein 70 ribosomal protein S6
phosphate-buffered saline
polymerase chain reaction
phosphoinositide 3-kinase
reactive oxygen species
Glioblastoma is the most common malignant primary brain tumor. At the molecular level, glioblastoma is characterized by unique genomic alterations, which are used to define four molecular subtypes [1]. The existence of distinct tumor subtypes creates a structural complexity, together with inherent resistance, limits the efficacy of available treatment strategies. These findings highlight the unmet need to develop novel therapeutic strategies for glioblastoma.
Conventional treatment strategies aim to inhibit cell cycle progression to attenuate tumor growth. An alternative approach involves enhancing replicative stress in a targeted manner, which can be exploited for therapeutic purposes [2]. One of the direct ways to accomplish this goal is to target cell division cycle 7-related protein kinase (CDC7). CDC7 is a serine/threonine kinase that phosphorylates minichromosome maintenance protein 2 (MCM2) of the eukaryotic pre-replication complex [3], and this step is required for initiation of DNA replication [4, 5]. Moreover, CDC7 overexpression is present in different cancer types [6, 7, 8, 9, 10]. Based on these findings, targeting CDC7 kinase was suggested as a new approach for cancer therapy [11].
Small molecule inhibitors of CDC7 were shown to have anti-tumor activity in different cancer types [12, 13, 14]. PHA-767491 hydrochloride is one of the first-generation CDC7 inhibitors, and its anti-tumor activity is well characterized. Here, we report that CDC7 inhibition by PHA-767491 hydrochloride inhibits cell proliferation and induces apoptosis in glioblastoma cells. In addition, we found that CDC7 inhibition suppresses glioblastoma cell migration and invasion. By using real-time PCR arrays, we found that CDC7 inhibition alters the expression of several mRNAs and miRNAs in glioblastoma cells. In particular, CDC7 inhibition results in a significant decrease in cathepsin S mRNA and protein expression. Overall, our results indicate that CDC7 inhibition suppresses glioblastoma growth and invasiveness.
Cell culture
U87-MG, U251-MG, and 3T3 cells were obtained from American Tissue Culture Collection (ATCC). All cell lines were cultured in Dulbecco's Modified Eagle's Medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 2% l-glutamine, and 1% penicillin–streptomycin. Cells were maintained at 37 °C and in 5% CO2 atmosphere.
CDC7 inhibitor
PHA-767491 hydrochloride (Sigma-Aldrich, Germany) was used as the CDC7 inhibitor. Lyophilized PHA-767491 hydrochloride was dissolved in nuclease-free water to achieve a final concentration of 5 mM, and aliquoted in 100 µl volume. Aliquots were stored at −20 °C, and a fresh aliquot was used for each experiment.
Cell viability assay
5×103 U87-MG and U251-MG cells were seeded in a 96-well plate 24 h before treatment. Next day, cells were treated with inhibitor (10 µM final concentration), solvent control (water), or left untreated. Seventy-two hours after treatment, 10 µl of PrestoBlue cell viability reagent (Invitrogen, Thermo Fisher Scientific, USA) was added onto the cells to assess cell viability. Relative cell viability was calculated by setting the viability of solvent control as 100%. Experiments were repeated at least three times.
Cell proliferation assay
For synchronization, U87-MG and U251-MG cells were maintained in culture medium supplemented with 1% FBS for 24 h. Then, 1 × 104 U87-MG and U251-MG cells were seeded in a 96-well plate. Next day, cells were treated with inhibitor (2.5 or 10 µM final concentration), solvent control (water), or left untreated. Seventy-two hours after treatment, bromodeoxyuridine (BrdU) cell proliferation ELISA kit (Cell Signaling, #5492) was used according to the manufacturer's instructions. Rate of proliferation in cells treated with solvent control was set as 100% to calculate relative cell proliferation rate.
Detection of cell death
To analyze total MCM2 and p-MCM2 (S40 + S41) protein levels, U87-MG and U251-MG cells were treated with PHA-767491 hydrochloride (10 µM final concentration) for 12 h. To analyze CTSS protein expression, U87-MG and U251-MG cells were treated with CDC7 inhibitor (2.5 µM final concentration), and cells were harvested at three different time points (24, 48, and 72 h). Afterwards, cells were lysed in a cocktail (RIPA buffer supplemented with protease and phosphatase inhibitors). Equal amount (50 µg) of protein samples were separated on 4–10% Tris–Cl polyacrylamide gel, and proteins were transferred to polyvinylidene difluoride (PVDF) membranes. The following antibodies were used in Western blotting experiments: p-MCM2 (S40/S41) antibody (1:2000, abcam, ab70371); MCM2 antibody (1:1000, abcam, ab108935); cathepsin-S (1:1000, abcam, ab134157) and beta-actin antibody (1:10,000, abcam, ab8227). After incubation with primary antibodies, membranes were subsequently incubated with HRP-labeled goat-anti-rabbit immunoglobulins (Santa Cruz). SuperSignal West Pico Chemiluminescent Substrate (Thermo Scientific) was used for protein detection.
RNA isolation
miRNeasy kit (#217004; Qiagen GmbH, Hilden, Germany) was used according to the manufacturer's protocol to isolate total RNA from glioblastoma cells. RNA samples were eluted in nuclease-free water, and stored at −80 °C until further analysis.
RevertAid First Strand cDNA Synthesis Kit (#K1622; Thermo Scientific Fisher) was used to reverse-transcribe RNA samples for mRNA expression analysis. miScript RT II kit (Qiagen GmbH, Hilden, Germany) was used to reverse-transcribe RNA samples for miRNA expression analysis. Equal amount (1 μg) of RNA samples were used for reverse transcription. cDNA samples were diluted with nuclease-free water, and stored at −20 °C until analysis.
Real-time PCR
All real-time PCR experiments were performed on a LightCycler 480 instrument (Roche). In each experiment, three technical replicates per sample and a no-template control (NTC) were used. The following primer sequences were used: CTSS-F: GCCTGATTCTGTGGACTGG, CTSS-R: GATGTACTGGAAAGCCGTTGT; GAPDH-F: GCAAATTCCATGGCACCGT; GAPDH-R: TCGCCCCACTTGATTTTGG. GAPDH was used as a housekeeping gene to normalize mRNA expression. Relative mRNA expression was calculated by using the formula 2−ddCt [15].
Migration assay
U87-MG and U251-MG cells were seeded at a density of 2.5 × 105 cells/well in 6-well plates, and incubated in DMEM supplemented with 10% FBS for 24 h. A confluent monolayer of each well was scratched with a 200 μl pipette tip, and cells were washed twice with 1× PBS. Then, fresh growth medium containing 10% FBS, with or without CDC7 inhibitor (final concentration: 2.5 or 10 µM) was added onto the cells. For each well, the wound area was marked, and images were acquired immediately after the scratch (0 h), and at 48 h on a phase-contrast inverted microscope (Olympus, CKX41; magnification: 10×). At each time point, the same wounded area was selected for image acquisition. The number of migrated cells was counted on ImageJ v.1.42 software as described previously [16]. All experiments were performed in triplicate, and each experiment was repeated at least three times.
Invasion assay
Cell invasion experiments were performed using 24-well invasion chambers (pore size: 8 µm, 24 well; Greiner) coated with 250 µg/ml Matrigel (#356234; BD Bioscience). U87-MG and U251-MG cells (2 × 104/well) were plated in medium without FBS, and 10% FBS in the bottom chamber served as chemoattractant. Twenty-four hours after seeding, cells were stained with Diff-Quick Staining Set (#NC0674866; Siemens) and cells that did not cross the transfilter were removed with cotton swabs. Invaded cells were visualized by phase-contrast microscopy, and counted on Image J v.1.42 software.
Real-time PCR arrays
Human Cancer Drug Targets PCR Array (PAHS-507ZF-12; Qiagen GmbH, Hilden, Germany) and Brain Cancer miRNA PCR Array (MIHS-108Z; Qiagen GmbH, Hilden, Germany) were used to analyze the changes in cellular mRNA and miRNA expression profiles upon CDC7 inhibitor treatment. Twenty-four hours before treatment, 1 × 105 U87-MG cells were seeded in 6-well plates. Next day, cells were treated with inhibitor (final concentration: 2.5 µM) or solvent control (water). Total RNA isolation was performed as described previously. miScript RT II kit (Qiagen GmbH, Hilden, Germany) and RT2 First Strandt kit (Qiagen GmbH, Hilden, Germany) were used for reverse-transcription reactions. Input RNA amount was 400 ng for Human Cancer Drug Targets PCR array, and 500 ng for Brain Cancer miRNA PCR Array.
Three biological replicates were used for each real-time PCR experiment. All real-time PCR experiments were performed on a LightCycler 480 instrument (Roche). A cut-off value of 1.5-fold was used to identify the significant hits.
Statistical analysis
All statistical analyses were performed on GraphPad Prism v.6.0 for Mac OS X (GraphPad Software, La Jolla, California, USA). Independent samples t test was used to analyze the differences between groups. P < 0.05 were considered as statistically significant.
CDC7 inhibition decreases glioblastoma cell viability in a time- and dose-dependent fashion
Next, we aimed to determine the half maximal inhibitor concentration (IC50) of PHA-767491 hydrochloride. To do this, we treated U87-MG and U251-MG cells with different concentrations of PHA-767491 (0–10 µM) for 72 h, and analyzed cell viability. For both cell lines, the IC50 concentration was approximately 2.5 µM (Fig. 1c).
After determining the IC50 value, we aimed to analyze how glioblastoma cell viability changes in response to CDC7 inhibition. We treated U87-MG and U251-MG cells with different concentrations of CDC7 inhibitor (2.5 and 10 µM final concentration), and determined that treatment with 2.5 µM PHA-767491 hydrochloride decreased cell viability by approximately 45% in both cell lines (Fig. 1d). Similarly, treatment with 10 µM PHA-767491 hydrochloride decreased cell viability by approximately 75% in U87-MG cells, and 70% in U251-MG cells (Fig. 1e).
To explore the effects of CDC7 inhibition on non-tumorigenic cells, we used non-transformed 3T3 cells as control cell line. Treatment with PHA-767491 hydrochloride resulted in a modest decrease in cell viability (Additional file 1: Fig. S1a). On the other hand, we determined significant decrease in cell proliferation (Additional file 1: Fig. S1b). Contrary to glioblastoma cells, CDC7 inhibition did not cause a significant increase in the level of DNA fragmentation in 3T3 cells (Additional file 1: Fig. S1c). Overall, these findings indicate that PHA-767491 hydrochloride effectively decreases cell viability in glioblastoma cells in a time-dependent fashion, and CDC7 inhibition exerts limited effects on non-tumorigenic cells.
CDC7 inhibition inhibits glioblastoma cell proliferation, and induces apoptosis
CDC7 inhibition suppresses migration and invasion of glioblastoma cells
Molecular consequences of CDC7 inhibition at the transcriptomic level
To understand the molecular consequences of CDC7 inhibition, we used commercial real-time PCR arrays to analyze the changes in expression levels of several mRNAs and miRNAs.
In parallel to mRNA expression analysis, we also aimed to identify how CDC7 inhibition alters the cellular miRNA profile. By using a commercial PCR array specific to known miRNAs related to different tumors of the brain and central nervous system, we determined that CDC7 inhibition leads to upregulation of hsa-miR-451a (2.34-fold) and hsa-miR-320a (1.96-fold) in U87-MG cells. To validate the results of our profiling experiment, we used real-time PCR, and found that CDC7 inhibition results in 2.2-fold increase in miR-451a expression in U87-MG cells (Fig. 6e).
We wanted to focus on CTSS, as it was the most significantly downregulated target in the PCR array. To validate our screening results, we analyzed CTSS mRNA and protein levels after CDC7 inhibitor treatment. Treatment with CDC7 inhibitor (2.5 µM) for 48 h resulted in 55% decrease in CTSS mRNA expression in U87-MG cells, and 48% decrease in U251-MG cells (Fig. 6c). Similarly, treatment with CDC7 inhibitor (2.5 µM) for 72 h caused a decrease in CTSS protein expression in U87-MG cells (Fig. 6b, d). Taken together, these results suggest that CDC7 inhibition may suppress glioblastoma growth through CTSS.
Cancer cells override the checkpoints in cell cycle to sustain continuous growth; however, this results in replicative stress. Recently, it has been suggested that replicative stress can be enhanced in a targeted way to attenuate growth of cancer cells. In this regard, CDC7 has been suggested as a potential therapeutic target for p53-negative breast cancers [17], and other cancer types, as it is known to be overexpressed in multiple cancers [6, 18].
Commonly used inhibitors of DNA replication (including topoisomerase inhibitors, intercalating agents, alkylating agents) lead to DNA damage, and activate the S-phase replication checkpoint (Chk1/Chk2-dependent checkpoint) [11]. Contrary to these agents, CDC7 inhibitors are able to halt DNA replication, and induce apoptosis without activating the Chk1-dependent pathway [11]. This brings a therapeutic advantage to this class of agents.
PHA-767491 hydrochloride is a first-generation CDC7 inhibitor with well-characterized anti-tumor activity. In the pioneering study, Montagnoli et al. showed that PHA-767491 hydrochloride inhibits cell proliferation in a comprehensive panel of cancer cell lines at a mean IC50 value of 3.17 µM [12]. The authors also showed that PHA-767491 hydrochloride induces apoptosis in multiple cell lines [12]. In our study, we determined that PHA-767491 effectively reduces cell viability in both glioblastoma cell lines.
The IDH1 gene encodes isocitrate dehydrogenase 1, which is responsible for catalyzing the conversion of isocitrate to alpha-ketoglutarate. The most common IDH1 mutation is R132H, which produces a missense mutation that affects substrate binding ability of the enzyme. This mutation is commonly found in secondary glioblastomas, and has clinical importance, as it is associated with improved survival in glioblastoma patients [19].
The IDH1 status of experimental cell models is a crucial factor to consider when evaluating the therapeutic potential of CDC7 inhibition. The study by Ichimura et al. showed that none of the 15 glioblastoma cell lines (including U87-MG and U251-MG) has IDH1 mutations [20]. To address whether IDH1 status is associated with a differential response to CDC7 inhibition, further studies should be carried out on IDH1 wild-type and IDH1 mutant cell lines.
The methylation of MGMT promoter is another factor that is associated with survival of glioblastoma patients. The MGMT gene encodes O6-methylguanine–DNA methyltransferase, which functions as a DNA-repair protein to remove alkyl groups from guanine residues. The methylation of MGMT promoter has a direct clinical consequence, as it is associated with longer overall survival in patients with glioblastoma, who undergo a combination treatment consisting of radiotherapy and an alkylating agent (such as temozolomide) [21].
Both U87-MG and U251-MG cell lines have hypermethylated MGMT promoter [22, 23]. Considering that CDC7 inhibition with PHA-767491 does not elicit DNA damage response in recipient cells, it is possible that MGMT methylation status is not associated with a differential response to CDC7 inhibition. The consequences of CDC7 inhibition should be compared between cell lines that have normal MGMT promoter and cell lines with hypermethylated MGMT promoter to reach a better conclusion.
To analyze the effects of CDC7 inhibition on non-tumorigenic cells, we used 3T3 cell line as a model system. Our results indicate that CDC7 inhibition leads to a slight decrease in cell viability, while causing a significant reduction in cell proliferation. In addition, CDC7 inhibition does not induce apoptotic cell death in 3T3 cells, unlike glioblastoma cells. While CDC7 inhibition appears to cause selective cytotoxicity in glioblastoma cells, these results should be confirmed further in primary human astrocytes and other non-tumorigenic cells.
To understand the molecular consequences of CDC7 inhibition, we used two commercial PCR arrays, which contain probes against (1) miRNAs known to be associated with brain and central nervous system tumors, and (2) mRNAs with roles in key intracellular signaling pathways. We determined that several important genes show differential expression in response to CDC7 inhibition. Considering that the majority of these genes are classified as growth factors and receptors, it is possible that glioblastoma cells are trying to compensate the tumor suppressive effect of CDC7 inhibition by activating key genes related to cell survival. This finding is particularly important, as it may allow predicting how cells are likely to develop chemoresistance over time. By identifying upregulated gene(s) and associated pathways, it may be possible to design combined therapies for glioblastoma.
hsa-miR-451a was one of the few miRNAs, which shows differential expression in response to CDC7 inhibition. We determined that CDC7 inhibition leads to a 2.3-fold increase in hsa-miR-451a expression in U87-MG cells. Previously, hsa-miR-451/AMPK complex was shown to work as a conditional switch to regulate glioblastoma cell migration and proliferation [24]. In case of glucose deprivation, hsa-miR-451 expression is reduced, which in turn leads to enhanced cell migration and survival [25]. In a recent study, Drusco et al. found that miR-451, among several other miRNAs, is significantly upregulated in cerebrospinal fluid (CSF) sample of glioblastoma patients (>180-fold compared to normal) [26]. These findings are consistent with our results, which indicate that CDC7 inhibition results in upregulation of hsa-miR-451 expression and decreased cell migration.
Cathepsin S is a lysosomal cysteine protease, which is encoded by the CTSS gene. CTSS is overexpressed in different cancer types (including astrocytomas [27]), and is reported to be an independent prognostic factor of survival for glioblastoma [28]. Previously, Zhang et al. reported that inhibition of CTSS expression induces autophagy and apoptosis in glioblastoma cell lines, through ROS-mediated PI3K/AKT/mTOR/p70S6K and JNK signaling pathways [29]. In another study, Kenig et al. found a correlation between increased CTSS expression and invasiveness of glioblastoma cells [30]. Recently, Sevenich et al. reported that CTSS expression is significantly high in tumor cells in early stage metastases, and pharmacological inhibition of CTSS reduces experimental brain metastasis [31].
In this study, we focused on multiple aspects of glioblastoma biology to understand the consequences of CDC7 inhibition in vitro. We provided substantial evidence that CDC7 inhibition suppresses glioblastoma growth and invasiveness. In addition, our results provide preliminary evidence that CDC7 inhibition alters the glioblastoma transcriptome by upregulating and downregulating key genes involved in different cellular pathways. Notably, our results suggest that CDC7 inhibition may suppress glioblastoma growth through CTSS.
Authors' contributions
EPE designed the study. ZE, BA, and EPE performed the experiments. ZE and SE performed statistical analysis, and contributed to final editing of the manuscript. BA and EPE interpreted the data, and wrote the manuscript. All authors read and approved the final manuscript.
Not applicable.
Competing interests
The authors declare that they have no competing interests.
The study received financial support from Pharmaplus Ilac ve Saglik Urunleri Ltd. Sti. The funding body did not have any effect on study design, data analysis, interpretation of data, and writing manuscript.
Supplementary material
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Thursday, October 1, 2009
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We are so happy with the new blinds which were purchased for the preschool classroom. These custom blinds are perfect for every moment of the day as we can open them completely or just a little bit, depending on the activity at hand. For example, we can close them entirely for our naptime too. Please peek in and take a look!
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