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Advanced planning can better prepare your business, following is some points to consider and six clever ideas that may save costs if you're thinking of selling your business
Pitfalls & Possibilities
The sale of a small business can potentially provide owners with once-in-a-lifetime opportunities to access available capital gains tax (CGT) concessions. Through these concessions it is possible to completely eliminate tax on a gain of $2million.
It is imperative to seek professional Financial Planner and Accounting/Tax advice in the planning stage of the sale, rather than waiting until the sale has happened, particularly as the tax office has advised its intention to increase the number of audits on business sales to ensure there is no incorrect claims on the available concessions. We may be able to suggest changes to the sales contract for allocation of money that will not only reduce tax payable but also give benefits to the buyer, thereby helping secure the best sales price.
Advance planning may enable further savings by taking advantage of changes to superannuation for contributions resulting from the sale of small business and ensure you get the maximum benefit from your years of hard work.
There are four specific small business CGT concessions, in additional to the general 50% discount that applies to individuals & trusts for assets held for more than 12 months;
- A 50% gain reduction on the sale of 'active' assets used in the business (includes business premises, but only if owned by the same entity/individuals that operated the business);
- A 15-year business ownership exemption, when the owner is over 55 and the sale is in connection with retirement;
- A Lifetime $500,000 retirement exemption, when owner is over 55 or if under 55 and the gain is paid into superannuation;
- Rollover relief if a replacement asset is purchased within 1 year before the gain or within 2 years after.
For accessing any of the concessions there is a total 'net asset test' that must not be exceeded, currently set at $6million of net worth (assets less liabilities). This includes all business assets, investment properties, shares, cash, managed funds and the like. Excluded from the threshold is the main residence, superannuation and private use assets such as cars and boats.
Six clever ideas for a small business sale
- Aim to maximise the sale price by maximising the tax advantages for the purchaser
- Try to reduce your capital gain to Nil by combining various concessions and the general discount
- If you are likely to exceed the $6million net asset test for eligibility there may be scope to contribute cash savings to super, which can be made by the business or business owner
- Consider waiting until July 2007 to sell, as the net asset test threshold goes up from $6million to $6million at that date
- Obtain specialist advice about whether to contribute a sizable portion of the sale proceeds into super
- Think well ahead, and contact Cliftons.


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These laugh in the face of pie.
19 Pumpkin Muffins Your Fall Mornings Need
Satisfy your pumpkin cravings with these easy homemade cheesecake recipes.More
So it's fall happiness in bar form. (And that shortbread crust is killer.)
Get the recipe from Delish.
A pull-apart bread stuffed with a creamy pumpkin filling? Yes, please.
Get the recipe from Delish.
27 Spooktacular Halloween Pumpkin Carvings

subset: commoncrawl


text:
"Map is broken! RTV-iew!!!"
This article about a map is a stub missing many key information.
No don't RTV yet! You can help completing it by referring to the map page setup example.
ze_Hypernova is a Zombie Escape map created by Eddie.
Overview Edit
Development Edit
First release. It crashed some servers
Supposed to fix crash and fps.
Detail for this version is unknown.
Current and maybe final version since 2011. But a new version could come.


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The Certified I'm Possible Facility
Directing an "I'm Possible Facility" allows I'm Possible trainers the opportunity to have an economical training program for their communities. When a player or parent isn't quite serious enough or possibly can't afford personal training services, the Certified Facility option gives trainers the ability to have an economical offering for their players.
Are You Eligible?
Don't have your own facility? No problem! Opening an I'm Possible Facility in your area, DOES NOT REQUIRE owning your own gym. To gain the rights to own and operate a Certified I'm Possible Facility within the US, a trainer must simply have consistent access to facilities to run their program and guarantee to I'm Possible Training that ALL trainers directing their programs be active certified I'm Possible Trainers. With those two items in mind, every trainer is eligible to open an I'm Possible Training Facility and offer I'm Possible Training programs in their community.
Premium Placement and Maximum Exposure
The power of having an I'm Possible Facility is found in our global reputation and our Facility landing page. When people are looking for training in their area, they are either looking for personal training or a program to enroll for. Therefore, it's to any trainer's advantage to provide both offerings. With the addition of our new Certified Facility Landing page, our I'm Possible Facilities will gain maximum exposure for every parent and player looking for consistent programming. Not only that, quarterly email blasts to I'm Possible's Global database will highlight your facility for your entire community to see.
|Brand Freedom
|Creative Flexibility
|I'm Possible Support
|Maximum Exposure
"By operating a certified I'm Possible Facility, our trainers are able to provide more economical options for players and build a better local business model for themselves."
Micah Lancaster, I'm Possible Founder
No Need to Change Your Brand
When you open an "I'm Possible Certified Facility" you DO NOT need to change your brand. Your brand can operate exactly as it currently does with the added benefit of I'm Possible Training endorsing your program on our site!
Creative Flexibility
Operating your own I'm Possible Certified Location, otherwise known as a Certified Facility, is all about flexibility. All I'm Possible Trainers and Coaches have access to the I'm Possible Certified Facility Complete Player Program curriculum. Many of our locations utilize those benefits, follow the I'm Possible curriculum, and use the printable PDF workouts. As a certified facility, you are welcome to use those handouts at your leisure and offer your customers the exact I'm Possible System.
Be Powered by I'm Possible Training
If you don't have your own brand, and you want to develop a brand that is Powered by I'm Possible Training, we will work with you to develop that custom identity. If do you have your own brand you are completely welcome to continue using it. If you want to keep it even more simple and utilize the I'm Possible brand for your program, then just pick a name for your Certified Facility such as I'm Possible South Beach and you're ready to roll! The choice is yours.
For ONLY $395 per year
When a trainer has a Facility program to offer at a lower price point and personal training to offer at a higher price point there is simply something for everybody! At $395 per year, the I'm Possible Facility model is a must!
- A simple annual fee of $395 covers everything!
- Complete editable facility profile on www.PossibleTraining.com
- Enhanced exposure from our Facility landing page.
- Option to utilize I'm Possible's Complete Curriculum of drills, videos, and workouts!


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HP P650G2U56300UQX500FIWNN08NNUES US (1BD11UP#ABA)Item#: 40493865 | Model#: 1BD11UP#ABA
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Click here for full warranty and support information
- HP logos are registered trademarks of HP. All others trademarks and copyrights mentioned herein are the property of their respective owners.


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Tuesday 20th December 2016
18:30 -21:00
The Griffin
This is a Public event
Come to our Xmas Party and experience a reality you've never experienced before!
We are very lucky to have Jay, the mobile tech expert on hand to let you experience the HTC Vive, Google Daydeam, Gear VR and a whole lot more. He will be on hand to discuss your mobile technology needs whilst giving some fun demonstrations.
An event not to be missed if you feel like transporting yourself to another world this Christmas!
All are welcome. Free entry. Refreshments will be served. Meet the committee and network with fellow members in a relaxed, informal atmosphere. No booking is necessary, just turn up.
A full write-up of the event is on the Social Tech Group page


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The mission of The Charity Ball Association of San Antonio, Inc. is to support and enhance the quality of life for children of Bexar County.
Children Benefit Always through the CBA
With your help, the CBA serves countless children in Bexar County, through grants awarded to 501-c3 organizations meeting those children's needs.
There are two wonderfully easy ways to join in creating resources for the children in our community. As in past years, we are conducting a fabulous PRIZE RAFFLE with a wide range of exclusive prizes.
And, new in 2017, we are offering an incredible ONLINE AUCTION, with the opportunity to bid on unique items and distinctive opportunities. Item values range from $1,000-$3,999. Online bidding starts Sunday, October 15, 2017 at 9:00 AM and closes on Sunday, October 22, 2017 at 9:00 PM. You won't want to miss the chance to own or enjoy one of these irresistible packages!
Listen to a Podcast Interview with CBA President, Betty Venson, which details our history and mission
View the Ribbon Cutting for the New Kitchen at River City Christian School! Funding Provided by The Charity Ball Association!
Here's Our Story
How To Help
You see thousands of San Antonio's children facing life without basic support and protection. You want to be part of the solution. The Charity Ball does the footwork for you.
Click here to download a pdf version of the 2016 Rotogravure.
Learn more about the annual Rotogravure.
Morgan's Wonderland, Advocacy Event


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- 2015 38th International Convention on Information…
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This paper presents a simple architecture for clock-fault detection in high-speed applications. The overall principle consists in converting a possible error of time to a logic voltage level. When a high voltage level is present at the output, a reliable clock is detected whereas a low voltage level implies a clock error. This detection system is intended… (More)
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5 years ago
i am a wallflower
Posted by Mrs. West at 7:40 AM Labels: conversation, party, wallflower
Over the holidays, it's common to go to several different events, whether with family or with friends. I love it, but this year I've finally come to the conclusion that I much more enjoy smaller get-togethers than big parties.
With bigger crowds, I tend to blend into the wood-work a little more than usual. I find it hard to concentrate on one conversation or even to have one at all. I find I'm overwhelmed a little bit by the amount of people and miss the intimacy of a small group. Big parties are too loud, but I also find myself in awkward conversations with people that I don't really want to be talking to in the first place.
And then there's that awkward-ness I feel with big crowds, especially those containing people I'm not as familiar with. I want to be sociable - and I am a sociable person - but I find my conversational skills lacking big time.
At my family Christmas party, I watched my brother as he just talked to everyone about anything and was able to carry on an interesting conversation. I always say the same things: "I'm in my last year at university," "Yes, married life it great," "I read a lot for school." Bo-oring.
I'd really like to work on my conversational skills, especially with people that I tend not to feel as comfortable with. I want to be interesting and witty. I know I am those things - but only with certain people.
I wish I wasn't such a wallflower.
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text:
Welcome to ABC Radio National. Skip to:
RN Navigation
RN Search
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Lee Kofman seemed to have the perfect marriage. But despite plenty of love and kindness, there was very little desire.
Robyn Arrowsmith has spent a decade researching the lives of Australia's war brides.
This [series episode segment] has
Lee Kofman had the perfect marriage, with plenty of love and kindness, but very little desire.
Kristina Olsson has untangled the story of her long-lost brother Peter, who was stolen from their mother's arms as a baby.
Dr Robyn Arrowsmith has spent the past ten years researching the lives of Australia's war brides.
Monica Bradley is a high-flying corporate strategist and problem solver.
Tuesday to Saturday 12am and Saturday at 4pm
Presented by Richard Fidler


text:
Troy GOB-1200 Power Bar
This Troy Olympic Power Bar has a large 32 mm shaft, giving it a 1200 lb tensile strength, equal to that of a much more expensive power bars on the market. Bronze bushings allow the sleeves to spin freely, making it ideal for Olympic lifts such as dead lifts, cleans and snatches. Each end is secured by dual snap rings, a feature often found on the highest performing Olympic bars.
This Troy VTX Power Bar offers a high tensile strength at an affordable price. It is designed to handle any or commercial fitness application, such as training studios, public workout rooms, military and commercial gyms.
- Weight: 44 lbs
- Length: 7 ft.
- Finish: Hard Chrome
- Bronze Bushings
- Grip: 32 mm
- Center Knurl: No
- Static Tensile Strength: 1200 lbs
- No Assembly Required
- Commercial Grade
Delivery Info:
- Ships: UPS Ground
- Leaves Warehouse: 2-4 Business Days
- Average Delivery from Order Date: 5-9 Business Days
- Shipping Cost to Lower 48 United States: $0.00
- Condition:
- New


text:
Lobachevsky University
Lobachevsky University
Knyazev A.V.,Lobachevsky University |
Somov N.V.,Lobachevsky University |
Shipilova A.S.,Lobachevsky University |
Gusarova E.V.,Lobachevsky University |
And 3 more authors.
Journal of Molecular Structure | Year: 2017
The crystal structures of methylprednisolone aceponate were determined by X-ray diffraction analysis at temperatures 90 K and 150 K: space group P212121, a = 14.8592(2), b = 19.6844(5), c = 26.1626(4) Å, Z = 12; R = 0.0598 (T = 90 K); space group P212121, a = 6.57348(14), b = 14.8295(3), c = 26.2214(5) Å, Z = 4; R = 0.0518 (T = 150 K). Features of structural changes in the phase transition were revealed. The abrupt change in the unit cell parameters in the phase transition was shown by low-temperature X-ray powder. The methods of degree of invariance of crystal electron density and molecular Voronoi−Dirichlet polyhedra were used for the analysis of polymorphism in methylprednisolone aceponate. The atomic structure at 90 K have a translational pseudosymmetry of electron density η = 0.329(1). The decrease of number of intermolecular contacts in the high-temperature modification due to rupture of intermolecular non-valence contacts C/O was observed. © 2017 Elsevier B.V.
Sokolova E.,RAS Shemyakin Ovchinnikov Institute of Bioorganic Chemistry |
Guryev E.,Lobachevsky University |
Yudintsev A.,Lobachevsky University |
Vodeneev V.,Lobachevsky University |
And 2 more authors.
Oncotarget | Year: 2017
Immunotoxin 4D5scFv-PE40 is a recombinant protein that comprises 4D5scFv antibody as a targeting module and fragment of Pseudomonas exotoxin A as an effector (toxic) one. The immunotoxin has shown pronounced antitumor effect on cancer cells overexpressing HER2 receptor in vitro and on HER2-positive experimental tumors in vivo. We clarified the mechanism of 4D5scFv-PE40 activity that is of particular importance in the case of targeted therapeutic agent aimed at personalizing treatment of disease in relation to molecular genetic characteristics of each patient. After specific binding to HER2 on the cell surface and clathrin-mediated endocytosis the immunotoxin passes through retrograde trafficking route. During this route the immunotoxin molecule is supposed to undergo enzymatic processing that ends in separation of C-terminal and N-terminal fragments of the immunotoxin. Finally, C-terminal functionally active fragment of 4D5scFv-PE40 arrests protein synthesis in cytoplasm followed by cell death via apoptosis.
Es'kin V.A.,Lobachevsky University |
Ivoninsky A.V.,Lobachevsky University |
Kudrin A.V.,Lobachevsky University |
Popova L.L.,Lobachevsky University
Journal of Experimental and Theoretical Physics | Year: 2017
Electromagnetic radiation from filamentary electric-dipole and magnetic-current sources of infinite length in the presence of gyrotropic cylindrical scatterers in the surrounding free space is studied. The scatterers are assumed to be infinitely long, axially magnetized circular plasma columns parallel to the axis of the filamentary source. The field and the radiation pattern of each source are calculated in the case where the source frequency is equal to one of the surface plasmon resonance frequencies of the cylindrical scatterers. It is shown that the presence of even a single resonant magnetized plasma scatterer of small electrical radius or a few such scatterers significantly affects the total fields of the filamentary sources, so that their radiation patterns become essentially different from those in the absence of scatterers or the presence of isotropic scatterers of the same shape and size. It is concluded that the radiation characteristics of the considered sources can efficiently be controlled using their resonance interaction with the neighboring gyrotropic scatterers. © 2017, Pleiades Publishing, Inc.
Perova T.V.,Lobachevsky University |
Kustov T.V.,Saint Petersburg Electrotechnical University l
2015 4th Forum Strategic Partnership of Universities and Enterprises of Hi-Tech Branches (Science. Education. Innovation) | Year: 2015
The article deals with the most current students' career development and employment promotion technologies. The paper describes the experience of the career center Lobachevsky university. The structure and main activities of the student council's Potential activity of the Career Centre. © 2015 IEEE.
Buntov E.,Ural Federal University |
Zatsepin A.,Ural Federal University |
Slesarev A.,Ural Federal University |
Mikhailovich A.,Ural Federal University |
Mikhaylov A.,Lobachevsky University
Physica Status Solidi (A) Applications and Materials Science | Year: 2015
SiO2 films, grown on a Si substrate and implanted with Li, Na, and K ions were studied by means of optically stimulated electron emission spectroscopy (OSEE). Interference effects of exciting light were observed in OSEE spectra. Application of original normalization technique allowed to compensate interference fringes in the experimental results. Three categories of defect states were identified and studied: intrinsic luminescent, emission-active silica defect centers, and implanted cation-related localized states. © 2015 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim.
PubMed | Lobachevsky University and RAS Institute of Macromolecular Compounds
Type: | Journal: Journal of biophotonics | Year: 2016
Efficient drug delivery can be assigned to tasks that attract the most acute attention of researchers in the field of anticancer drug design. We have reported the first case of using amphiphilic polymer brushes as nanocontainers for photosensitizer delivery to cancer cells. Regular graft-copolymers of hydrophobic polyimides with hydrophilic polymethacrylic acid side chains were loaded with photosensitive dye tetra(4-fluorophenyl)tetracyanoporphyrazine (Pz) providing a sufficiently stable homogeneous fraction of fluorescent Pz-loaded nanoparticles with a size of 100-150 nm. Pz-loaded polymer brushes were substantially more efficient for Pz delivery into cells compared with other types of particles examined, Pz-polyethyleneglycol and Pz-methylcellulose. In vivo, an efficient Pz delivery to tumor can also be expected since the Pz-PB particle size is in the optimal range for passive targeting. Pz-PB showed pronounced photodynamic activity, while, that is important, in the absence of irradiation the PB carrier itself was significantly less toxic than the dye itself. Summing up, water-soluble polymer brushes with polyimide backbones and polymethacrylic acid side chains can be regarded as a novel type of nanocontainers providing efficient intracellular drug delivery for photodynamic therapy of cancers.
Agrba P.D.,Lobachevsky University |
Kirillin M.Y.,RAS Institute of Applied Physics
Photonics and Lasers in Medicine | Year: 2016
Optical coherence tomography (OCT) is a modern technique for imaging of internal structures of biotissue of up to several millimeters in depth with a resolution of several micrometers. However, various external conditions can distort the diagnostic capabilities of an OCT image. Mechanical compression and temperature regime are the two conditions which mostly affect the diagnostic OCT images obtained with a contact probe. It is shown here that the application of compression to human skin induces a decrease in contrast of the stratum corneum-epidermis junction and an increase in contrast of the epidermis-dermis junction. With regard to these junctions, a preliminary change of biotissue temperature induces additional changes in the contrast, with opposing effects in case of heating and cooling. © 2016 by De Gruyter 2016.
Konakov A.A.,Lobachevsky University |
Filatov D.O.,Lobachevsky University |
Korolev D.S.,Lobachevsky University |
Belov A.I.,Lobachevsky University |
And 3 more authors.
AIP Advances | Year: 2016
Using the envelope-function approximation, the single-particle states of electrons and holes in spherical GaN nanocrystals embedded in different amorphous dielectric matrices (SiO2, Al2O3, HfO2 and Si3N4) have been calculated. Ground state energies of electrons and holes in GaN nanocrystals are determined using the isotropic approximation of the k · p -Hamiltonian. All the ground state energies are found to increase with lowering the nanocrystal size and are proportional to the R-n, where R is the nanocrystal radius, n =1.5-1.9 for electrons and 1.7-2.0 for holes. The optical gap of GaN nanocrystals changes from 3.8 to 5 eV for the nanocrystal radius ranging from 3 to 1 nm. © 2016 Author(s).
Kudrin A.V.,Lobachevsky University |
Kudrina O.A.,Lobachevsky University |
Petrov E.Y.,Lobachevsky University
Journal of Experimental and Theoretical Physics | Year: 2016
We consider electromagnetic nonlinear normal modes in cylindrical cavity resonators filled with a nonlinear nondispersive medium. The key feature of the analysis is that exact analytic solutions of the nonlinear field equations are employed to study the mode properties in detail. Based on such a nonperturbative approach, we rigorously prove that the total energy of free nonlinear oscillations in a distributed conservative system, such as that considered in our work, can exactly coincide with the sum of energies of the normal modes of the system. This fact implies that the energy orthogonality property, which has so far been known to hold only for linear oscillations and fields, can also be observed in a nonlinear oscillatory system. © 2016, Pleiades Publishing, Inc.
Bareev D.D.,Lobachevsky University |
Gavrilenko V.G.,Lobachevsky University |
Grach S.M.,Lobachevsky University |
Sergeev E.N.,Lobachevsky University
Advances in Space Research | Year: 2016
It is shown experimentally that the relaxation time of the stimulated electromagnetic emission (SEE) after the pump wave turn off decreases when frequency of the electromagnetic wave, responsible for the SEE generation (pump wave f0 or diagnostic wave fdw) approaches 4th harmonic of the electron cyclotron frequency fce. Since the SEE relaxation is determined by the damping rate of plasma waves with the same frequency, responsible for the SEE generation, we calculated damping rates of plasma waves with ω∼ωuh (ω is the plasma wave frequency, ωuh is the upper hybrid frequency) for frequencies close to and distant from the double resonance where ωuh∼4ωce (ωce=2πfce). The calculations were performed numerically on the base of linear plasma wave dispersion relation at arbitrary ratio between |Δ|=ω-4ωce and |k|||VTe (VTe is the electron thermal speed and k|| is the projection of the wave vector onto the magnetic field direction. A comparison of calculation and experimental results has shown that obtained frequency dependence of the SEE decay rate is similar to the damping rate frequency dependence for plasma waves with wave vectors directed at the angles 60-70° to the magnetic field, and gives a strong hint that oblique upper hybrid plasma waves should be responsible for the SEE generation. © 2015 COSPAR.


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Life's moments are precious and fleeting. The art of photography is in the ability to capture the people and memories that mean the most to us so that we can keep them displayed on our walls, in our minds, and in our hearts forever.
It is my honor to be part of this beautiful art and service.


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Government to give auto permitsSharad Vyas | TNN | Apr 1, 2013, 07.36 PM IST
MUMBAI: The Maharashtra government will introduce a policy in four months for streamlining the permit systems of auto rikshaws, keeping in mind the increasing population and limits of a town.
The issue of rapid growth of illegal vehicles in Solapur was raised by legislator Vijay Kumar Deshmukh during the morning Question Hour session. To this Patil replied saying that this was the problem of the entire state from the time permits to new rickshaws was stopped in 1997.
Wherever required, number of vehicles will be increased as per the requirement of the city, Patil said. Deputy chief minister Ajit Pawar said permit were still being allotted in the city areas. "In Baramati, two years back nearly 200 permits were allotted," he said.
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|Also Known As:
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|April 3, 1962
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text:
Contact Qdos Contractor:
0116 269 0999
Find a Qdos Company
Although you may have left the contracting community, we still have products which may benefit your new lifestyle.
See below for the products we can offer and get a quote today.
Anyone with a portable electronic device can benefit from this policy, covering your gadgets in the event of accidental damage or breakdown, as well as optional cover for loss or theft.
Not just for the business traveller, our travel insurance policy also includes personal holidays. You can even add family members and cover for high risk activities and winter sports.
Now open weekdays until 7pm and 9am-12pm
on Saturdays for Sales & Customer Service
Qdos Contractor is a trading style of Qdos Broker & Underwriting Services Ltd
Qdos Broker & Underwriting Services Ltd trading as Qdos Underwriting - Registered in England No. 6012716
Qdos Legal Services Limited - SRA Number 611754 is the only Qdos company regulated by the Solicitors Regulation Authority
Registered office - Windsor House, Troon Way Business Centre, Humberstone Lane, Thurmaston, Leicester, LE4 9HA
Qdos Broker & Underwriting Services Limited is authorised and regulated by the Financial Conduct Authority (Firm Reference Number: 460886).
© Qdos Consulting Limited, Qdos Vantage Limited and Qdos Accounting Limited are appointed representatives of Qdos Broker & Underwriting Services Limited. All Rights Reserved | Privacy Policy |
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text:
A bee tale
Today came with its own bee tale. I was reading on and off peacefully, when I started hearing a woman wail about her turkeys from the adjacent compound, I was there wondering what the brouhaha was all about. The she screamed, "si lekun si lekun", repeatedly. I then decided to go do gbeborun. I went… Read More A bee tale


text:
In this Issue:
In this Issue:
Indaba 2013 has come and gone. We were thrilled to meet so many new faces, renew old friendships and conduct business, as usual. After Indaba, we traveled on to Botswana for supplier workshops and educational travel to visit camps, lodges and tourism attractions throughout the country. We were introduced to several new suppliers, and we look forward to sharing their adventures with you during these summer months. First up: Okavango Air Rescue, featured in our "Spotlight on" segment.
Back to top
Piece of Mind for Your Clients – Okavango Air Rescue
We were delighted to meet with the team from Okavango Air Rescue while at Indaba. A medical emergency can be a terrifying experience, even when you're at home. But if you or your clients are on vacation and are traveling in a foreign country, it can be that much more frightening. And though it's unlikely that a medical emergency will occur while you're away, it is very reassuring to know that Okavango Air Rescue is there, if you need them, providing supplemental medical emergency evacuation services. Okavango Air Rescue provides around the clock service, transporting medical assistance to clients directly, by helicopter, if that medical emergency should arise. A fully equipped helicopter with an emergency doctor who can treat and stabilize on the spot, then transport to the nearest appropriate medical facility for further treatment or medical evacuation arrangements if needed, provides that extra level of "peace of mind" so your clients can have a truly worry-free vacation.
Okavango Air Rescue also offers an affiliate program for tour operators and travel agents so you can build this service into your clients' travel packages. For more information on their services, please visit www.okavangorescue.com.
Okavango Expeditions – A Luxury Mobile Safari with Real Bite
Get closer to nature and experience the best of Botswana with a mobile safari. Okavango Expeditions offers tailor-made and scheduled mobile safaris to suit all interests and budgets. Join the team of talented guides for an incredible introduction to some of Botswana's most game-rich areas and journey into a wilderness where the only neighbors will be a remarkable density of wildlife. Experience the call of the wild, campfire camaraderie, and sunsets that truly have to be seen to be believed in some of Botswana's finest national parks and game reserves. Choose from a variety of pre-planned itineraries or allow Okavango Expeditions' friendly reservations team to plan a custom-made trip just for your clients.
Okavango Expeditions' owner, Clint Gietlink, has built himself an enviable reputation for guiding standards, overall safari experience and also value for money. Kathryn Haylett, a Namibia-based travel professional, recently joined Okavango Expeditions on a mobile safari to Botswana's Moremi, Khwai and Savuti areas. Here's what she had to say: "As a safari specialist, I know first-hand just how wielding a client can be – expecting wall-to-wall wildlife and an ever-patient professional guide who knows the area intimately, who drives a photo-friendly vehicle and understands how to position for the ultimate shot. Okavango Expeditions truly recognizes all this and delivered on all of the above." Kathryn will be using the company regularly for her clients' wanting to travel to Botswana, as she and her team are often asked for Botswana combos.
For more information, please visit www.okavangoexpeditions.com.
Wilderness Safaris – 30 Years of Changing Lives
Last month marked Wilderness Safaris' 30th anniversary as Africa's leading ecotourism and conservation company. From humble beginnings in 1983, the company has grown substantially over the last 30 years – not only in size but also in its ability to positively impact Africa.
Check out Wilderness' video highlighting its incredible journey through the eyes of a few special people who helped make it all happen. We want to congratulate Wilderness Safaris on 30 years of amazing conservation and community efforts that they have undertaken in Botswana…and here's to 30 more!
For more information, please visit www.wilderness-safaris.com.
Tuli Safari Lodge Update on Planned Reopening
Following the damage sustained in the January floods, Tuli Safari Lodge will be extensively refurbished and will reopen mid-2014 in what will be the lodge's 50th anniversary year. Although the lodge is currently closed, the community joint project at Molema Bush Camp remains fully operational.
For more information, please visit www.tulilodge.com.
Up Close and Personal with Desert & Delta Safaris
Desert & Delta Safaris' portfolio brings together some of Botswana's most historic lodges including the iconic Chobe Game Lodge, Savute Safari Lodge, Camp Moremi, Camp Okavango, Xugana Island Lodge and Leroo La Tau. Together these lodges offer an outstandingly diverse safari experience throughout Botswana while providing personalized service and attention to detail. This year Desert & Delta Safaris has taken sharing their passion of their destinations to the next level, by launching a channel on the wildly popular video-sharing website, Vimeo.com. These videos bring an "up close and personal" view of Desert & Delta Safaris' products and destinations, and are the perfect "extra" to share with clients! Check out their channel here.
For more information, please visit www.desertdelta.com.
Up, Up and Away with Roger Dugmore Safaris
No more long road transfers. During Botswana's peak game viewing season, Roger Dugmore Safaris has two fully inclusive 7-night fly-in Moremi safaris available for couples or single travelers to join. Starting at $6,037 per person, guests are flown in and out of camp to maximize the time spent in the wilderness. Game drives and a day of boating on the Okavango Delta are included. Dates are:
For more information, please visit www.rogerdugmoresafaris.com.
Get Away with Umpengu Tours & Safaris
Your adventure-minded clients can experience a 15-day mobile safari like no other with Umpengu Tours & Safaris. Starting at $4,425 per person sharing, this safari includes unforgettable stops in the Okavango, Maun, Savuti and Chobe, to name a few. Interact with the local San people and learn more about their culture, discover the wilderness in the Okavango and enjoy sundowners while sharing exciting stories of the day… all included!
For more information, please visit www.umpengu.com.
Get Wild at Molema Bush Camp
Molema Bush Camp is pleased to share their Wildside packages with your clients. As a joint project from Tuli Safari Lodge, Molema is a self-catering bush camp offering en-suite chalets and campsite accommodations in a beautiful, shaded location on the banks of the Limpopo River. Ranging from 2-4 night stays, the Wildside packages are applicable to both the Molema chalet and Molema campsite and include a range of activities. From morning walking safaris to community visits to sunset drives, these Wildside packages have your clients covered.
For more information, please visit www.tulilodge.com or email firstname.lastname@example.com for reservations.
Green Season Specials at Sanctuary Retreats
This green season, save $290 per couple with Sanctuary Retreats. Green season offers wonderful sightings of newborn animals both big and small, exceptional bird watching and unforgettable adventures. Spend a minimum of 6 nights at a combination of selected lodges and camps in Botswana and/or Zambia and pay only $450 per person per night. Lodges and camps in Botswana include Stanley's Camp and Chobe Chilwero, with Chief's Camp available at a rate of $850 per person per night. Valid for travel from November 1 – March 31, 2014, with the exception of December 20 – January 5, 2014. Other terms and conditions apply.
For more information, please visit www.sanctuaryretreats.com.
Botswana's Makgadikgadi Pans are home to the largest zebra population in southern Africa. When the rain rolls into the Kalahari, the striped herds begin an epic journey across the vast pans, overcoming Mother Nature's obstacles and putting family ties to the test. Watch as this migration story, set against the backdrop of Botswana's breathtaking landscapes, unfolds before your very eyes. Click here to watch.
We hope you enjoyed the latest updates from Botswana Tourism and that you will share this newsletter with your colleagues.
Yours in travel,
Botswana Tourism – U.S. Office
Contact Us - Trade Website - Travel Offers - Previous Trade Newsletter Issues.
You are receiving this newsletter because you have either signed up for the Botswana Tourism - North America Trade enewsletter site or you have requested information on international destination news.
127 Lubrano Drive, Suite 203 - Annapolis, MD 21401


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400 W Main Street
Benson, NORTH CAROLINA 27504
Price: $269,900
4 Bedrooms, 3 Total Baths
2969 SqFt
Listing # 2109152
Take a step back in time as you enter this beautiful home! Boasting much of the original character with hardwood floors, incredible trim, unique built-ins, cedar closets & more. Meander thru the huge family room into the office/den area, pass the incredible dining room with crystal chandelier, into the renovated kitchen. Although this home has retained much of its original splendor, it has been wonderfully update with new a new kitchen, new roof, & new HVAC! All Nestled on a corner lot in downtown Benson!
Basic Features:
Acres: 0.47
Area: 325 - Johnston County
City Name: Benson
County: Johnston
Schools: Johnston - Benson, Johnston - S Johnston
State: NORTH CAROLINA
Sub Area: 325 - Johnston County/K
Subdivision: Not in a Subdivision
Property Type: RESIDENTIAL
Postal Code: 27504
Total Baths: 3
Bedrooms: 4
Partial Baths:
SqFt: 2969
Additional Features:
Air Conditioning: Central Air, A/C Age 0-3 Years
Attached Description: Single Family
Attic Description: Pull Down
Basement: No
Bath Features: Ceramic Bath Wall, Tub/Shower
Bedroom 2 Dimensions: 12x15
Bedroom 2 Floor: Second
Bedroom 3 Dimensions: 12x15
Bedroom 3 Floor: Second
Bedroom 4 Dimensions: 11x13
Bedroom 4 Floor: Second
Bedrooms 1st Floor: No
Design: 2 Story
Dining: Eat-in Kitchen, Separate Dining Room
Dining Room Dimensions: 14x16
Dining Room Floor: Main
Elementary School 1: Johnston - Benson, Johnston - S Johnston
Entrance Hall Dimensions: 8x7
Entrance Hall Floor: Main
Equipment: Electric Range, Range Hood
Exterior Features: Fenced Yard, Porch, Warranty Program
Exterior Finish: Aluminum
Family Room Dimensions: 15x31
Family Room Floor: Main
Fireplace: 1
Fireplace Description: In Family Room
Flooring: Hardwood, Tile Floor
Foundation: Basement
Fuel Heat: Natural Gas
Full Baths: 3
Garage: 2
Garage Dimensions: 20x28
Garage Floor: Main
Heating: Forced Air, Heat Age 0-3 Yrs
High School 1: Johnston - S Johnston
HO Fees Include: None Known
HUD Compliant Sr. Housing: No
Inside City: Yes
Kitchen Dimensions: 12x15
Kitchen Floor: Main
Living Area Above Grade: 2969
Lot Description: Corner Lot, Landscaped
Lot Dimensions: see plat
Lot Number: 2
Master Bedroom 1st Floor: No
Master Bedroom Dimensions: 13x15
Master Bedroom Floor: Second
Middle School 1: Johnston - Benson
New Construction: No
Number of Rooms: 8
Other Area Below Grade: 200
Other Area/Room 2 Description: UnFinBase
Other Area/Room 2 Dimensions: 15x15
Other Area/Room 2 Level: Lower
Other Area/Room 4 Description: ScreenPorc
Other Area/Room 4 Dimensions: 16.9x6
Other Area/Room 4 Level: Main
Other Rooms: Office, Walk In Pantry, Utility Room
Parking: Garage
Porch Dimensions: 11x36.8
Porch Floor: Main
Status: ACTIVE
Roof: Roof Age 0-5 Years
Screened Porch Dimensions: 16.8x11.7
Screened Porch Floor: Main
Property Type: Detached
Status Category: Active
Style: Traditional
Total Other Area SqFt: 200
Utility Room Dimensions: 5x9
Utility Room Floor: Main
Washer Dryer Location: 1st Floor
Water Heater: Electric WH
Water/Sewer: City Sewer, City Water
Year Built: 1937
Data services provided by IDX Broker
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text: Whenever i start to warm up after like a few throws i feel that my elbow kinda hurts. and then when i finish pitching my elbow hurts. as in i cant barely lift anything with it until like a day or two! is this normal? am i pitching wrong? please help?


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Kip Moore
Pre Sale Info for Kip Moore at Hampton Beach Casino Ballroom
If you want in on the pre-sale for Kip Moore, here's the info you need.
Win Tickets to See Kip Moore!
I got tickets to see Kip Moore at the Hampton Beach Casino Ballroom!
Kip Moore Tackles Racism, Media and Police in America
Country singer Kip Moore shares his thoughts about police, media, protests and racism in America. You really should check it out.
Kip Moore, Sam Hunt and Charlie Worsham Close Out 2014 Concert Season at Hampton Beach
What a way for the Hampton Beach Casino Ballroom to close out their 2014 concert season. A sold out show featuring Kip Moore, Sam Hunt and Charlie Worsham!
MWC Daily: Where Will the MWC Be This Weekend?
The Morning Waking Crew will be out and about this weekend.
Go Inside Kip Moore's Tour Bus (His Mama Won't Be Happy!)
CMT on Tour Lands at Hampton Beach Casino Ballroom in November with Kip Moore, Charlie Worsham and Sam Hunt
Country music fans, listen up! The Hampton Beach Casino Ballroom is closing out their 2014 concert season with the CMT on Tour with Kip Moore, Charlie Worsham and Sam Hunt!
Kip Moore Releases Surprise EP
How To Enjoy Homemade Apple Pie
I found the easiest way to enjoy homemade apple pie!


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Marvel Comics Best Covers – December 2010
Marvel has recently released the info on comics they will be putting out in December, here are what I think are the best covers. I decided to organize them alphabetically and not by date because I couldn't find the date that some of them were releasing.
The above cover was done by Humberto Ramos. Check below for the rest.
Cover by Marko Djurdjevic
Cover by Clayton Crain
Cover by Jae Lee
Cover by Daniel Acuna
Cover by Salvador Larroca Martinez
Cover by Juan Doe
Cover by Patrick Scherberger
Cover by Mike Mayhew
Cover by Skottie Young
Cover by Pasqual Ferry
Cover by Greg Land
Cover by Jae Lee
Cover by Leinil Francis Yu


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African American Men Hairstyles
African American Men Hairstyles
Graduated, elevated hair with partitions, fades, afro, and long with edgy outlines are some of the cool black men haircuts and black boys haircuts for 2017. Whatever type of black mens hairstyles you are looking for, we've got the best classic, sporty, trendy, business, retro, casual, and all around amazing haircuts for black men and boys. Get comfortable and join us for a journey through various hairstyles so you can find that special haircut to make your own.
African American Men Hairstyles
Getting the best black men haircuts can be tricky. Because black men have a number of haircuts to choose from, with options for short, medium, or long hair, picking just one cut and style at the barbershop can be hard. However, the top hairstyles for black men seem to incorporate a low or high fade haircut with some kind of styling on top.
African American Men Hairstyles
If you want to look clean and fresh for the new year, check out the latest, coolest and hottest black men's hairstyles, including the flat top, frohawk, faux hawk, curls and the line up haircut. Combine all these styles on top with a taper fade and you'll have one of the most popular hairstyles of any black guy.
African American Men Hairstyles
Black men hairstyles don't often involve hair dye. But why not? Warm colors like orange, red, and gold look great against dark skin. Of course, you can't pair wild hair colors with just any haircut, but a Mohawk fade is a safe choice for sure.
African American Men Hairstyles
Black men's hairstyles often rely heavily on the cut. If you are thinking of trying a new style, talk it over with your barber and get his or her opinion. There are some seriously cool styles to try, so try one or try them all!
African American Men Hairstyles
Are you a black man and considering things like relaxing and permanent hair styling? You should take pride of your stunning natural hair texture. Your unique hair structure allows you to achieve a lot of hairstyles that no other race can achieve. There are many ways to style black mens hairstyle. They can choose to go for natural, afro, dreads, long, short, shaved, tapered and many more. If you have been contemplating on changing your haircut, you would find this list very helpful. Here we have listed and shared 40 Best Black Haircuts for Men. Do not just stand out with your hairstyle this fall, nail the best look for your all year round.
African American Men Hairstyles
Shaved, short, long, fro or natural, there are several different ways for black men to style their hair. Considering a style change? Check out these varied (and handsome!) black men haircuts to try next time you're at the barber.
African American Men Hairstyles
If you give some highlights in the kinky texture of curls, it will accentuate your looks. Moisturizing gel right after the shower, will help fight frizz and you don't need anything else to maintain this hairstyle. Any man looking for cute hairstyles for naturally curly hair must try this haircut.
Black men haircuts are typically known for the different hair textures and sometimes the color too. Each hairstyle or cut is recognized for the special characteristics. Why? Well, it is because many haircuts take time and fine finishing which can't be achieved by any hair stylist off the street. It takes a certain, skilled eye and hand to craft the more intricate hair masterpieces. Let's get to the list:
Above all, curls are a cute hairstyle for black men. It not only looks natural, but also professional and elegant at the same time. You even don't need to comb your hair, running your fingers through it will be just fine.
Gradual smoothed reduction of hair length in fades can be paired with edgy outlines at the temples, patterned sides, or a shaped top. As you can see, fade haircuts look equally awesome on boys, young guys and older men. For every setting where extremely short hair is a requirement, a fade will look better than a simple close cut or complete baldness.
Black men often opt for a high fade haircut, featuring complete disappearing of hair much higher than the natural lines of hair growth at the temples and back of the head. With a low fade hair disappears about an inch above the lines of hair growth, while a regular fade is something in between these two. As a rule, when you are going to have your first fade, they recommend to start from its regular type.
Low fades for black men are a great option because natural hair lies flat when cropped close and that gives a super clean look on the sides. A low fade simply means that it starts to taper somewhere near the eyebrow, not higher up on the head. The carved line gives it something extra, without being over the top.
A high fade is one of the best haircuts for black men. With this cut, you will have very low maintenance each day, but you will need to go to the barber twice per month to keep it looking clean.
Today's black men haircuts are anything but boring. This clean look is the perfect combination of retro and modern. For this style, don't get the back cut to the skin. Instead, leave it at a medium length for a faux hawk effect. An afro fade is a style that always exudes creativity.
When you're looking for a fresh haircut, a fade is definitely a go-to. This cool, clean style is very sharp. Plus, it's easy to pull off. Some men look their best with high fades, others prefer their fade to start lower on the head. This high-to-medium fade is classic. Pair it with a beard, and you're golden.
Black men haircuts are synonymous with shaved designs and shaved parts. The texture of black hair, especially when it's short, lends itself to all sorts of creative designs, the most common ones being different lines. Some designed styles can get a little wild and crazy, but a side part is always a wearable option.
This afro fade is a great simple and flattering option: a high and tight with fade, perfectly lined up hairline, and thin beard that helps to enhance the masculine bone structure. Black boys and men positively can rock this haircut with confidence.
A high fade is one of the favorite black haircut styles for men who want to look fashionable. While a low fade tends to look more like a classic cut, a high fade is a younger, more modern style.
For men who want that old school pompadour look, opt for a high top that is lower towards the back. This look is all about the shape, and can be a challenge to describe. Be sure to bring in pictures, especially when you're after something unique or retro.
This high top fade is a good option for men who want to exude a strong, powerful appearance. To keep it from being too retro, hair is not polished all around. The sharp part also gives it a modern edge.


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Thousands attend the Oyster Festival
ARCATA – Arcata Main Street's Oyster Festival brought in thousands of fest goers. Major features at the event range from the local aquaculture and tons of oysters.
California being the oyster capital is not only a fun-filled time for the crowd but, a way to showcase the culture, eateries, locally made and grown foods and the unique pieces of art you can't find anywhere else.


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Lady GaGa's "Bad Romance" Video Meets The Sims (VIDEO)
The original version of Lady GaGa's "Bad Romance" video wasn't unsettling enough for you? First of all, seek professional help. Secondly, feast your eyes on this recreation of the clip, featuring characters generated with the popular life-simulation game The Sims.
So technically impressive. So mesmerizing. So nightmare-inducing.
Dig in, and try to make good use of the extra time you'll have on your hands, now that it will be impossible for you to Ever. Sleep. Again.


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The months from May through to October are the autumn and winter months in Africa. Generally, inland safari areas receive their rainfall from summer thundershowers, which means these are also the drier months and conditions are pleasant all round.
Dry months are the best times to go on a safari in Africa for excellent viewing of big game. Little rainfall has allowed the bush lands to thin out, making spotting and tracking of game notably easier. The lack of water during the dry winter also drives animals toward rivers and waterholes, where they congregate in search of much needed drinking water.
In East Africa, the herds of Wildebeest in the great game migration make their way northward in search of water, moving into the northern Serengeti and then into the Maasai Mara reserve in Kenya. Temperatures are mild, conditions pleasant, and wildlife plentiful. It is also the season for some of the more famous scenes of the migration crossing the Grumeti and Mara Rivers, so position yourself well for this.
In Southern Africa these are very much the premium months for viewing of game in the Okavango Delta, Selinda, Linyanti and Chobe National Park areas of Botswana. The high water season from June through October is a great season for animal action here (as well as boating and canoeing on the Delta) and the drier, cooler climate with very few mosquitoes makes for a very comfortable time with exciting wildlife experiences, such as lions hunting buffalo in two feet of water! Toward the end of this season - around September and October - game viewing conditions are at their peak in these areas.
Albeit slightly cooler, these months are also the best for game viewing in the Kruger National Park, Sabi Sand and Thornybush reserves in South Africa. Temperatures are moderately cool, there are no afternoon thundershowers, game is easier to spot, and this only improves as the winter moves on toward September.
This is also a good time to visit KwaZulu Natal in South Africa, as well as the Etosha Pan in northern Namibia, when it is less humid than during the summer months.
Whilst the breathtaking experiences around Sossusvlei and Sesriem in Namibia can be enjoyed all year, the spring months between August and October are excellent months to visit, for more moderate temperatures, hiking, clear skies, and outstanding photography opportunities.
Our recommendations at this time of year:


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Since 1956, Montrose Travel a Travel Partner of LAVETTE'S BLESSED TRAVEL has been a leader with the majority of the world's top travel suppliers, within the travel industry itself and within our own community. Check us out at www.lbt.mtravel.com.
We pride ourselves on our accomplishments and the awards we've earned. Never accepting the status quo, we constantly strive to attain new goals within our field and continuously search new ways to be a leader in our community. One of the greatest features that www.lbt.mtravel.com has to offer is the email updates on the latest and best deals, travel updates and more. By taking advantage of this single source of travel specials and information, you will never have to look anywhere else. So don't wait, subscribe now!


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ruby polka-dot embellished silk midi dress
click to zoom
ruby polka-dot embellished silk midi dress
Polka Kaffir
Size (US)
Choose your size
view item's measurements
- Fits true to size, take your normal size
- Cut for a slim fit
- Non-stretch fabric
- Model is 176cm / 5'7" and is wearing a US size 2
Unexpected details elevate a classic print for a ladylike piece with creative flair by Saloni. Polka-dot printed silk featured a blouson top with halter neckline and pencil skirt with ruffled hem. A banded waist offers a universally flattering fit, embellished by a beaded pendant.
- 100% Silk
- Beaded ladybug adornment
- Invisible back zip closure with hook-and-eye
- Lined
- Dry clean only
- Item Code : 2926
- View More :
- Saloni
- Midi
- More styles from Saloni


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The Chinese government has been denounced in the past for human rights issues, censorship and oppression. However I think we can all agree #bacongate should be front and center.
The city of Chongqing has banned the smoking of bacon in an effort to reduce pollution and cut down on carbon emissions. The ban includes a possible fine of more then $800 US. This is an affront to bacon loving people around the world. When one person is banned from enjoying the crispy fatty glory which is Bacon, we are all oppressed.
We all agree that Climate Change is a global issue with drastic solutions which will effect the whole world. Without working together towards global solutions our children will be living in a world dramatically different then ours. Sacrifices must be made, with new solutions required in transportation, energy production, and industry. But this is a step too far, well beyond the pale. Would I want my children to live in a post-apocalyptic Mad Max world or a idyllic Utopian world living in harmony with nature?
My only question is: in which world does bacon still exist?... I rest my case.


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AJAX Developers
Expert AJAX Developers
AJAX is a set of XHTML, CSS, DOM, XML HTTP Request and XML. Or more simply stated; it reduces the number of clicks, updates the screen without taking that extra step, and adds animation/movement that increases the usability of a web page. It's not new tech but it's cool for your end users.
WBD AJAX developers use the technology to make your users experience more engaging and interactive. This includes items such as auto-complete forms, single page "tab" menus, visual effects, animations, calendars, and interactive graphs.
Get Started!
Let our expert teams create your next technology project.


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Each month, Rated People connects over 50,000 homeowners with quality tradesmen - simply enter your job details in the form above to get started.
We'll match your job to the relevant tradesmen in your area - those interested will pay to see your contact details and call you to quote.
As each tradesman expresses interest in quoting on your job, we'll send you their profile and ratings to help you choose the right one for you.
After the work is complete, return to the site and rate your tradesman based on their quality of work, reliability and value for money.
Added 06/12/2016
new locks needed, noon front door 1 on garage door. new handle on internal door.
Searching for tradespeople
Added 30/06/2016
Recently bought a house and the patio door has no key
Searching for tradespeople
Added 28/06/2016
Replace door lock in back door
Added 26/04/2016
Fit 2 key locks on bedroom doors to match door furniture and maybe change licking mechanism...
Searching for tradespeople
Added 31/01/2016
Lost key so need lock replacing.
Searching for tradespeople
Added 06/01/2016
Lost key for mailbox and ow moved out of rented accommodation. I have to replace key and l...
Searching for tradespeople
Went the extra mile to make good my old gate and made sure I was able to unlock without any difficulty. He will be boarding my loft in a week's time as well.
Managing your job is easier with the Rated People Homes App, download it today.


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The RowBlack Leather Spaghetti Strap Tank Top
Sleek and sexy leather tank top by The Row. Soft and smooth leather makes a great layering piece. Seamed details throughout with thin, spaghetti straps. Straight neckline and a fitted silhouette. Side zipper with hook and eye closure. Tank is fully lined. Size: Unknown, see measurements.
Made in: USA Color: Black Fabric Content: Unknown, appears to be genuine leather. Condition: Pre-owned. This item is in good condition. Minor loose threads throughout. Some tiny holes/nicks on back left side. Light marks on lining. Number "4" drawn onto interior hemline. No other visible signs of wear and tear.
Measurements & Sizing
- Total Length: 20.5"
- Bust: 29.5"
- Waist: 28"
- Hips: 32"
Returns & Shipping
Luxury Garage Sale guarantees that all items sold on our site are 100% authentic. All products we accept are inspected for brand-specific guidelines and are put through a rigorous authenticity test process.
LGS is not affiliated with The Row. We guarantee this The Row item to be authentic. The Row® is a registered trademark of The Row.
Item #: 129018


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Thursday, December 1, 2011
Delicious Emilys True Love Premium Edition
Share in Emily's search for true happiness with Delicious - Emily's True Love Premium Edition, a
wonderful new chapter in the amazing series.A year after Emily opens her own restaurant, business continues to boom though her personal life is completely non-existent. Shades of promise appear when she receives a rose, but she is too shy to act on it. Then one day an old love letter from a summer romance arrives that turns Emily's world upside down. Will she act upon either of these to find her true love?
Thanks Velocity
Posted by Wendy at 12:38 PM
Labels: Dash / Time Management
Subscribe to: Post Comments (Atom)


text: Family & Relationships Great Gifts For All Dad's – Father's Day Is Near – 10 Great Gifts Bucket List Adventures Guide | May 23, 2017 Father's Day is coming. It will be here before you know it. Need some gift ideas for Dad? I've been thinking about that too. Father's Day is Sunday, Read More


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World news story
11 July is World Population Day
- From:
- British High Commission Windhoek
- Part of:
- Namibia
- Published:
- 11 July 2013
- Last updated:
- 11 July 2013, see all updates
This was published under the 2010 to 2015 Conservative and Liberal Democrat coalition government
World Population Day 2013 raises awareness of the issue of adolescent pregnancy, health, and human rights.
11 July is World Population Day. The focus this year is on Adolescent Pregnancy.
About 16 million girls under age 18 give birth each year. Another 3.2 million undergo unsafe abortions.
The vast majority – 90 per cent – of the pregnant adolescents in the developing world are married. But for far too many of these girls, pregnancy has little to do with informed choice. Often it is a consequence of discrimination, rights violations (including child marriage), inadequate education or sexual coercion.
Adolescent pregnancy is a health issue: the youngest mothers face a heightened risk of maternal complications, death and disability, including obstetric fistula. Their children face higher risks as well.
It is also an issue of human rights. Adolescent pregnancy often means an abrupt end of childhood, a curtailed education and lost opportunities.
On this World Population Day, the UNFPA raises awareness of the issue of adolescent pregnancy in the hopes of delivering a world where every pregnancy is wanted, every childbirth is safe, and every young person's potential is fulfilled.
Document information
Published: 11 July 2013
Updated: 11 July 2013
- Wrong Worldwide Association
- First published.
From: British High Commission Windhoek
Part of: Namibia


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The links below are provided as a service to those who visit our website. These links direct you to websites that are out of our control, and we have no control over their content. If you find a link that is not working or that you feel is inappropriate, please let us know.
Health Professional Web Sites
Healthcare Project Funding
International Health
Public Health Related Sites


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Author Archives: ruhaniqalb
TV is a Shepherd
Whose Islam is Best
Hadith on Moderation
The Prophet reprimands Mu'adh for reciting too long in congregational prayer
Spread Peace
Best to Women
Nasiri Dua
This highly potent du'a by the renowned Shaykh Muhammad Ibn Nasir, was recited across Morocco and inspired resistance to the French occupation. So powerful was it that the French President had to issue an order banning its recitation from the mosques. Moroccans date the movement to return King Muhammad from that outlawing of the du'a. It is appropriate to the present state of the Muslim ummah today.
Wird Latif of Imam al-Haddad
As with all the litanies of Imam al-Haddad, al-Wird al-Latif is made up of nothing but the 'prayers' of the Prophet (peace be upon him) and the formulae that he instructed his community to recite mornings and evenings. It is therefore strictly in conformity with the sunna, and once it is well-rehearsed and becomes regular practice, one can rest assured that he is following the 'Prophetic' instructions as to which adhkar he should use to begin and end his day.
Lecture on the Wali Songo
Shaykh Abdal Hakim Murad's talk in Kuala Lumpur about the Wali Songo, who are seen as the founders of Islam in Java/Indonesia.


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As South Africans move closer and closer to the August Local Government Elections, cases of politically motivated killings are on the rise.
According to some analysts, the political violence seen ahead of the 2016 local elections is the worst since the 1994 election.
Below Councillor for ward 81 in Ekurhuleni Mthumeleni Nditha's shares about the traumatic event of having his house burnt by community members.


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Jobs in Chaddlewood
Email me jobs like this
Healthcare Assistant HCA - Weekend work
Optical Practice Manager
Posted 8 August by Inspired Selections UK Limited
Band 5 / 6 / 7 Physiotherapist - Inpatient - Plymouth
Posted 4 August by MedicsPro Limited
Healthcare Assistant HCA jobs FULL OR PART TIME
Adult Learning Tutor
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Vehicle Technician
Posted 4 August by Rise Technical Recruitment Limited Ending soon
Adult Learning Tutor
Adult learning Tutor
Print Finisher - Guillotine
Posted 5 August by GAP Recruitment (SW) Limited T/A Big Ant Group
Registered Nurse RGN RN FULL OR PART TIME
Customer Service / Collections Advisors
Posted Today by Capita
Optical Practice Manager
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Complex Care team Leader - Plymouth
Posted Today by Newcross Healthcare New
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Driver & Storesperson Plymouth
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text:
More things I hate
February 26, 2009
So earlier this week I was requested by Karmen to write about 'um'. I decided that there wasn't much to say about um except that it's used by a lot of people who don't have a lot to say.
So instead I decided to write about things I hate, just because I'm such a negative little hethen who likes putting people down :D. No jk I just hate writting about things I like 'cause there's no fun in that.
anyways let's get started.
- I hate *hate* hate hate looking at the bottoms of peoples feet. Gross. Disgusting. Revolting. So in public if ur wearin fliperfloppers cause it's the south and that's just what we do but I'm able to see the bottom part of ur foot I'll try and ignore it but end up asking you to move it. Leanne can attest to that.
- I hate dramaqueens. They're always so self-centered little brats who think the world evolves around them. Now like I understand a 6 year old dramaqueen, but to be 15 and still act like that is just ridiculous.
- Watered down sweet tea. Yeah-that's gross.. UR IN THE SOUTH! FLAVOR UP UR TEA YOU YANKEES!
- Oh yeah people who insult u for wearin flip flops in the winter. Like hey listen number 1 this is the south. That's kinda like what we do. wearing flip-flops in the winter and other such retarted stuff. Number 2 i'm to lazy to tie my shoe, so, well umm deal with it.
- EWW people who don't wear deoderent are just, umm, stupid. Let's leave it at that.
- I hate people telling me to do something I'm already doing. I dont hate the people telling, cause then I'd hate a lot of people. I just hate the act of being told something so obvious a baby would know it.
Yeah so u know writting like "Oh YEAH my life is so hunky dory!" is just so darn annoying. Soooooo instead I write about these stupid things I can't stand. Feel free to comment (duh.)


text:
24918 VINTAGE CT, Lutz, Florida
$1,3953 Beds2 BathsContract Pending
$1,3953 Beds2 BathsContract Pending
24918 VINTAGE CT, Lutz, Florida 33559 - BEAUTIFUL 3 bedroom 2 bathroom home for rent!! Living room and kitchen are spacious with an open floor plan and high ceilings which makes this home perfect for entertaining! FENCED IN YARD!!! Sliding glass doors in living room open to a covered back patio and sizable back yard with a relaxing view that over looks a small creek. Master bedroom is large and equipped with TWO walk in closets. Master bathroom hosts garden tub and separate standing shower. Located right around the corner from a dog friendly park with a playground, all located inside a nice community with elementary school. Available at the end of August. Owners are not sure if they will allow all types of pets, there will be a pet fee of $250-500. Looking for 550+ credit scores, no eviction history in the last 5 years, no major criminal issues. Looking for at least 2.5x rent amount for net income, security deposit is at least $1400. First and Last months rent may be needed if there are credit or income concerns. Owners have final approval on applications. $40/per adult to run background and credit checks on applications.
View Virtual Tour
Listing Courtesy of BLUE SUN REALTY
"Mary and her husband David did an excellent job of marketing my home, provided guidance on pricing to attract potential buyers, engaged an excellent photographer to show the home in its best light, and utilized web sites and channels to make the home visible to a very large segment of the buying community. Their service was consistently excellent. Their services could be enhanced by finding a better network of supporting services (like handymen, stagers, closers, etc.). But most importantly they got the job done, professionally and timely."


text:
Please note that the address for this place is approximate. Upon booking a stay, the rental owner will provide an exact address. First class Waipouli Beach Resort. Location: Waipouli, East Kauai, Hawaii, USA (Next to the Historic Town of Kapaa). This resort has all the modern-day amenities that you would expect in a Five-Star resort, including a lazy river-style saline poo... DVD Player, Satellite / Cable, Air Conditioning, Clothes Dryer, Hair Dryer, Internet, Iron & Board, Linens Provided, Telephone, Washing Machine, Coffee Maker, Dishes & Utensils, Dishwasher, Kitchen, Microwave, Refrigerator, Toaster, Balcony, Lanai / Gazebo, Outdoor Grill, Communal Pool, Hot Tub, non smoking only, pets not allowed, condo, outlet shopping, Beach View, ATM/bank, fitness center, groceries, medical services, golf, tennis
Waipouli #A-303: 2bdr/3 bath on Beach Front Resort
Kapaa, Hawaii 96746 USA
Waipouli #A-303: 2bdr/3 bath on Beach Front ResortReserve from $229
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Kapaa, Hawaii
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text:
First off,
Thank you for everyone that has and continues to support the new single. It is available everywhere you listen to music, but here it is (see right) if you haven't had a chance to listen to it.
Now, to the Jump. (Topic)
I had the awesome chance of speaking with a great, long time friend today. Last year, he dropped everything and took a job as a chef in Belize. Needless to say, I was shocked. I've never known him to be so bold. Let me clarify. He has always been a man pursuing growth and the desires of his heart, but this action is a bigger "jump" than I've ever seen him take.
I was so excited to hear the news, and see him follow through! I immediately made sure I was paying closer attention to his story because I knew it was going to be a big transition. I saw a friend I love taking action towards his desires and dreams. I wanted to make sure I actively provided any support I could.
He is now chillin' in Belize, and living the life HE wants.
"What does the life you desire look like?"
This is the question that comes to my mind when I witness people desperately seeking something they are so certain must be for them.
Here's my answer.
- Good friends.
- Close family.
- Happy wife.
- Financial freedom (whatever that means.)
- Kids (eventually.)
- I want to have connected listeners that I share life with through the music I create and in person performances. (That's it. Everything else is just a catalyst to achieve this goal.)
This year is dedicated to spending every second, dime, resource to reaching potential listeners. It's not about being famous. It's about filling the void there would be if I did not. I don't want to look back at my life and say I didn't risk everything to pursue my desires, and niether should you. Whatever that looks like. Don't be careless or responsible, just pray and figure out what they are.
I have no clue how to do this, or what the next steps are. I'm reading and taking action every day trying to figure this business out.
One Major Priority : Radio Play
I'm currently doing everything I can to get "Tranquilo", my current radio single (unreleased to the public yet), on radio stations. If there is a radio station (including internet stations) you want to hear it on, let me know so I can send it. Then request it like crazy. This is one way you can help.
Second Priority: Spotify Verification
I need to be verified on Spotify in order to be considered for spotlight playlist adds. Trevor Lee Spotify Artist Page has 197 monthly listners and it is growing everyday, but there are only 152 followers. If you use Spotify, please follow and share the page with others to help. It needs 250 followers to become verified.
Lastly: Listener Connection
There are a lot of people listening that I know exist because I see the purchases and stream counts of my music. I want to hear about your lives and how the music is a part of it. Let me know. Don't be shy. You can show genuine support by SHARING my music or promotional posts and saying what you like about it or why you are listening to it. This not only encourages me to keep creating for you, but exposes others to the music as well. Which, then helps me be able to create more.
At the end of the day it's not even about the music.
It's about the life connection it creates.
Take your jump and encourage others to do the same.
Live. Create. Share.
- Trevor Lee


text:
Amy Lawrence
A textile designer specialising in luxury, knitted, artisan jewellery.
Amy uses a big and beautiful Italian knitting machine to create all her pieces.
Amy uses the best quality yarns such as super soft merinos and brushed cottons, sourced from Italian and UK mills, making each piece feel as good as it looks. Carefully hand finishing all her items to the highest quality ensures your knitted pieces can be treasured for years.
"Whilst studying for a Textile Design degree at Birmingham City University (former UCE), I found my first true love, a knitting machine. My final major project of machine knitted light coverings caught the eye of a Nottingham based swatch company, who saw my potential and hired me as a full time swatch designer.
I learned invaluable skills in stitch development and fabric design, as well as broadening my knowledge of yarns and trends. During my time at the swatch company I sold many of my pieces to high street retailers through to high end designers such as Julien McDonald, John Varvatos and Calvin Klein.
After leaving Nottingham for adventures in Liverpool, I bought my very own machine, sourced some great yarns, and started up my own home studio"


text:
Karnataka SSLC Results 2017 – Karnataka Secondary Education Examination Board (KSEEB) going to conduct the SSLC (10th) Examination for the session 2016-17. Large number of students appeared in the examination of Karnataka Board 10th Class Examination every year. Board will be provided the KSEEB SSLC Exam Form in the month of September / October every year. All the students must to fill up the Karnataka 10th Exam Form before the last date. Candidates who are appeared in the examination and looking for the KSEEB SSLC Result will be checking it from the official website of Karnataka Board. We are provided a platform regards KSEEB SSLC Examination 2017 such as Results, merit list, Mark sheet and other details mention below. KSEEB will release Karnataka SSLC Results 2017 expected in June 2017. You need to submit name or roll number in results portal will update here as it declare by authority.
Karnataka SSLC Exam Result 2017
Large number of candidates enrolled for the KSEEB 10th Class Examination for the session 2016-17. Karnataka Board will be conducted the KSEEB 10th Examination in the month of March / April every year. Last year it was started from 30th March 2017 to 12th of April 2017. After the examination board will be announced the KSEEB 10th Class Exam Results in the month of May / June every year. Candidates will be got their SSLC results by using their Admit card / Roll number / Name from the official result portal. Students get the good marks and percentage with hard exam preparation. We are provided all the details of Karnataka Board 10th Exam Result 2017 here, candidates need to visit to get the updates. A lot of Students have appeared in Karnataka SSLC Examination 2017. Now the Aspirants are looking and Searching the Karnataka SSLC Result 2017, As per School Board notification indicates that, Karnataka SSLC Result 2017 may be announced on 12th May 2017, Aspirants can be check out respective Results through clicking above provided official direct link
Karnataka SSLC Examination 2016-17
- Name of the Exam Authority: – Karnataka Secondary Education Examination Board (KSEEB)
- Name of the Exam: – KSEEB SSLC (Class 10th) Exam 2017
- Exam Date:- March / April 2017
- Results date:- 12th April 2017 (12:30 PM)
- Category: – Result
- Status:- Available Soon
- Official Website: – kseeb.kar.nic.in
Karnataka SSLC Results Observations: –
Passed Students %
|Boys %
|Girls %
Appeared Students
|92.50 (expected)
|91.78 (expected)
KSEEB SSLC 10th Results 2017
Karnataka Secondary Education Examination Board is also known as KSEEB. The Karnataka Board was established in 1966. The Head office is located in Malleswaram, Karnataka. The KSEEB will be provided the school education for the students of class 1st to 12th class. Every year board will be conducted the 10th and 12th class examination. Large number of private and Government schools are affiliated under the Karnataka board. The main motive of Karnataka Board is to improve the level of Education in Karnataka State.
Steps to download Karnataka 10th Results online
- Start to visit on official website of conduct body @ kseeb.kar.nic.in
- Then click on link of Exam
- Select your Category "Result" and open it
- Fill up mandatory details and submit it
- Within few second wait your Karnataka SSLC Result will be displayed
- Download it, & Save it
- Take a print out for further uses
Karnataka 10th Exam Results 2017 Date
All the students who are looking for their 10th Exam Results will be got it from the official website. Students need to get their exam syllabus for the exam preparation. Candidates can better exam preparation and get good marks and percentage. Students will be got more information of KSEEB Exam Results from the official website. We are also provided all the details of KSEBB Examination 2017 on our website as soon as possible. Best of Luck for your results.
The Karnataka SSLC Results 2017 declaration date is near. Students will be happy and excited to check online Karnataka SSLC Exam Result will be available on mention below link by mid of May 2017. Easily appear on display by name or roll number details.


text:
I don't need a piece of paper to affirm my rights. I have rights because I am a sentient, sovereign human being living within the physical realities of this universe.
Category Archives: Uncategorized
This blog will be dedicated to me. I deserve it.
Prepare yourselves for something you have never asked for: completely unfiltered me, now with more vulgarity, rudeness, substance abuse and child labor advocation.
There will not be quotes from famous intellectuals to act as verification for my own beliefs. My thoughts require no one but myself.
In the words of Jaime Lannister, "There are no men like me. There's only me."
Let's get on with it then.


text:
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17 publication(s) depuis Septembre 2009:
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Les IF indiqués ont été collectés par le Web of Sciences en
Biol Psychiatry
CB1 Cannabinoid Receptors Mediate Cognitive Deficits and Structural Plasticity Changes During Nicotine Withdrawal.
Saravia R, Flores A, Plaza-Zabala A, Busquets-Garcia A, Pastor A, de la Torre R, Di Marzo V, Marsicano G, Ozaita A, Maldonado R, Berrendero F
BACKGROUND: Tobacco withdrawal is associated with deficits in cognitive function, including attention, working memory, and episodic memory. Understanding the neurobiological mechanisms involved in these effects is crucial because cognitive deficits during nicotine withdrawal may predict relapse in humans. METHODS: We investigated in mice the role of CB1 cannabinoid receptors (CB1Rs) in memory impairment and spine density changes induced by nicotine withdrawal precipitated by the nicotinic antagonist mecamylamine. Drugs acting on the endocannabinoid system and genetically modified mice were used. RESULTS: Memory impairment during nicotine withdrawal was blocked by the CB1R antagonist rimonabant or the genetic deletion of CB1R in forebrain gamma-aminobutyric acidergic (GABAergic) neurons (GABA-CB1R). An increase of 2-arachidonoylglycerol (2-AG), but not anandamide, was observed during nicotine withdrawal. The selective inhibitor of 2-AG biosynthesis O7460 abolished cognitive deficits of nicotine abstinence, whereas the inhibitor of 2-AG enzymatic degradation JZL184 did not produce any effect in cognitive impairment. Moreover, memory impairment was prevented by the selective mammalian target of rapamycin inhibitor temsirolimus and the protein synthesis inhibitor anisomycin. Mature dendritic spines on CA1 pyramidal hippocampal neurons decreased 4 days after the precipitation of nicotine withdrawal, when the cognitive deficits were still present. Indeed, a correlation between memory performance and mature spine density was found. Interestingly, these structural plasticity alterations were normalized in GABA-CB1R conditional knockout mice and after subchronic treatment with rimonabant. CONCLUSIONS: These findings underline the interest of CB1R as a target to improve cognitive performance during early nicotine withdrawal. Cognitive deficits in early abstinence are associated with increased relapse risk.
Mol Psychiatry
Pregnenolone blocks cannabinoid-induced acute psychotic-like states in mice.
Busquets-Garcia A, Soria-Gomez E, Redon B, Mackenbach Y, Vallee M, Chaouloff F, Varilh M, Ferreira G, Piazza PV, Marsicano G
Cannabis-induced acute psychotic-like states (CIAPS) represent a growing health issue, but their underlying neurobiological mechanisms are poorly understood. The use of antipsychotics and benzodiazepines against CIAPS is limited by side effects and/or by their ability to tackle only certain aspects of psychosis. Thus, safer wide-spectrum treatments are currently needed. Although the blockade of cannabinoid type-1 receptor (CB1) had been suggested as a therapeutical means against CIAPS, the use of orthosteric CB1 receptor full antagonists is strongly limited by undesired side effects and low efficacy. The neurosteroid pregnenolone has been recently shown to act as a potent endogenous allosteric signal-specific inhibitor of CB1 receptors. Thus, we tested in mice the potential therapeutic use of pregnenolone against acute psychotic-like effects of Delta9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis. We found that pregnenolone blocks a wide spectrum of THC-induced endophenotypes typically associated with psychotic-like states, including impairments in cognitive functions, somatosensory gating and social interaction. In order to capture THC-induced positive psychotic-like symptoms (e.g. perceptual delusions), we adapted a behavioral paradigm based on associations between different sensory modalities and selective devaluation, allowing the measurement of mental sensory representations in mice. Acting at hippocampal CB1 receptors, THC impaired the correct processing of mental sensory representations (reality testing) in an antipsychotic- and pregnenolone-sensitive manner. Overall, this work reveals that signal-specific inhibitors mimicking pregnenolone effects can be considered as promising new therapeutic tools to treat CIAPS.Molecular Psychiatry advance online publication, 21 February 2017; doi:10.1038/mp.2017.4.
A cannabinoid link between mitochondria and memory.
Hebert-Chatelain E, Desprez T, Serrat R, Bellocchio L, Soria-Gomez E, Busquets-Garcia A, Zottola AC, Delamarre A, Cannich A, Vincent P, Varilh M, Robin LM, Terral G, Garcia-Fernandez MD, Colavita M, Mazier W, Drago F, Puente N, Reguero L, Elezgarai I, Dupuy JW, Cota D, Lopez-Rodriguez ML, Barreda-Gomez G, Massa F, Grandes P, Benard G, Marsicano G
Cellular activity in the brain depends on the high energetic support provided by mitochondria, the cell organelles which use energy sources to generate ATP. Acute cannabinoid intoxication induces amnesia in humans and animals, and the activation of type-1 cannabinoid receptors present at brain mitochondria membranes (mtCB1) can directly alter mitochondrial energetic activity. Although the pathological impact of chronic mitochondrial dysfunctions in the brain is well established, the involvement of acute modulation of mitochondrial activity in high brain functions, including learning and memory, is unknown. Here, we show that acute cannabinoid-induced memory impairment in mice requires activation of hippocampal mtCB1 receptors. Genetic exclusion of CB1 receptors from hippocampal mitochondria prevents cannabinoid-induced reduction of mitochondrial mobility, synaptic transmission and memory formation. mtCB1 receptors signal through intra-mitochondrial Galphai protein activation and consequent inhibition of soluble-adenylyl cyclase (sAC). The resulting inhibition of protein kinase A (PKA)-dependent phosphorylation of specific subunits of the mitochondrial electron transport system eventually leads to decreased cellular respiration. Hippocampal inhibition of sAC activity or manipulation of intra-mitochondrial PKA signalling or phosphorylation of the Complex I subunit NDUFS2 inhibit bioenergetic and amnesic effects of cannabinoids. Thus, the G protein-coupled mtCB1 receptors regulate memory processes via modulation of mitochondrial energy metabolism. By directly linking mitochondrial activity to memory formation, these data reveal that bioenergetic processes are primary acute regulators of cognitive functions.
genes (basel)
Possible Therapeutic Doses of Cannabinoid Type 1 Receptor Antagonist Reverses Key Alterations in Fragile X Syndrome Mouse Model.
Gomis-Gonzalez M, Busquets-Garcia A, Matute C, Maldonado R, Mato S, Ozaita A
Fragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability. The cognitive deficits in the mouse model for this disorder, the Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mouse, have been restored by different pharmacological approaches, among those the blockade of cannabinoid type 1 (CB1) receptor. In this regard, our previous study showed that the CB1 receptor antagonist/inverse agonist rimonabant normalized a number of core features in the Fmr1 knockout mouse. Rimonabant was commercialized at high doses for its anti-obesity properties, and withdrawn from the market on the bases of mood-related adverse effects. In this study we show, by using electrophysiological approaches, that low dosages of rimonabant (0.1 mg/kg) manage to normalize metabotropic glutamate receptor dependent long-term depression (mGluR-LTD). In addition, low doses of rimonabant (from 0.01 mg/kg) equally normalized the cognitive deficit in the mouse model of FXS. These doses of rimonabant were from 30 to 300 times lower than those required to reduce body weight in rodents and to presumably produce adverse effects in humans. Furthermore, NESS0327, a CB1 receptor neutral antagonist, was also effective in preventing the novel object-recognition memory deficit in Fmr1 KO mice. These data further support targeting CB1 receptors as a relevant therapy for FXS.
Glutamatergic stimulation induces GluN2B translation by the nitric oxide-Heme-Regulated eIF2alpha kinase in cortical neurons.
Ramos-Fernandez E, Tajes M, Ill-Raga G, Vargas L, Busquets-Garcia A, Bosch-Morato M, Guivernau B, Valls-Comamala V, Gomis M, Grau C, Fandos C, Rosen MD, Rabinowitz MH, Inestrosa N, Maldonado R, Altafaj X, Ozaita A, Alvarez A, Vicente R, Valverde MA, Munoz FJ
The activation of N-Methyl D-Aspartate Receptor (NMDAR) by glutamate is crucial in the nervous system function, particularly in memory and learning. NMDAR is composed by two GluN1 and two GluN2 subunits. GluN2B has been reported to participate in the prevalent NMDAR subtype at synapses, the GluN1/2A/2B. Here we studied the regulation of GluN2B expression in cortical neurons finding that glutamate up-regulates GluN2B translation through the action of nitric oxide (NO), which induces the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2alpha). It is a process mediated by the NO-heme-regulated eIF2alpha kinase (HRI), as the effect was avoided when a specific HRI inhibitor or a HRI small interfering RNA (siHRI) were used. We found that the expressed GluN2B co-localizes with PSD-95 at the postsynaptic ending, which strengthen the physiological relevance of the proposed mechanism. Moreover the receptors bearing GluN2B subunits upon NO stimulation are functional as high Ca2+ entry was measured and increases the co-localization between GluN2B and GluN1 subunits. In addition, the injection of the specific HRI inhibitor in mice produces a decrease in memory retrieval as tested by the Novel Object Recognition performance. Summarizing our data suggests that glutamatergic stimulation induces HRI activation by NO to trigger GluN2B expression and this process would be relevant to maintain postsynaptic activity in cortical neurons.
Proc Natl Acad Sci U S A
Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation.
Busquets-Garcia A, Gomis-Gonzalez M, Srivastava RK, Cutando L, Ortega-Alvaro A, Ruehle S, Remmers F, Bindila L, Bellocchio L, Marsicano G, Lutz B, Maldonado R, Ozaita A
Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific cell types revealed that the CB1 receptor population specifically in dopamine beta-hydroxylase (DBH)-expressing cells is both necessary and sufficient for stress-induced impairment of memory consolidation, but CB1 receptors present in other neuronal populations are not involved. Strikingly, pharmacological manipulations in mice expressing CB1 receptors exclusively in DBH+ cells revealed that both hippocampal and peripheral receptors mediate the impact of stress on memory consolidation. Thus, CB1 receptors on adrenergic and noradrenergic cells provide previously unrecognized cross-talk between central and peripheral mechanisms in the stress-dependent regulation of nonemotional memory consolidation, suggesting new potential avenues for the treatment of cognitive aspects on stress-related disorders.
Habenular CB Receptors Control the Expression of Aversive Memories.
Soria-Gomez E, Busquets-Garcia A, Hu F, Mehidi A, Cannich A, Roux L, Louit I, Alonso L, Wiesner T, Georges F, Verrier D, Vincent P, Ferreira G, Luo M, Marsicano G
Expression of aversive memories is key for survival, but the underlying brain mechanisms are not fully understood. Medial habenular (MHb) axons corelease glutamate and acetylcholine onto target postsynaptic interpeduncular (IPN) neurons, but their role in aversive memories has not been addressed so far. We found that cannabinoid type 1 receptors (CB1R), key regulators of aversive responses, are present at presynaptic terminals of MHb neurons in the IPN. Conditional deletion of CB1R from MHb neurons reduces fear-conditioned freezing and abolishes conditioned odor aversion in mice, without affecting neutral or appetitively motivated memories. Interestingly, local inhibition of nicotinic, but not glutamatergic receptors in the target region IPN before retrieval, rescues these phenotypes. Finally, optogenetic electrophysiological recordings of MHb-to-IPN circuitry revealed that blockade of CB1R specifically enhances cholinergic, but not glutamatergic, neurotransmission. Thus, presynaptic CB1R control expression of aversive memories by selectively modulating cholinergic transmission at MHb synapses in the IPN.
Dissecting the cannabinergic control of behavior: The where matters.
Busquets-Garcia A, Desprez T, Metna-Laurent M, Bellocchio L, Marsicano G, Soria-Gomez E
The endocannabinoid system is the target of the main psychoactive component of the plant Cannabis sativa, the Delta9 -tetrahydrocannabinol (THC). This system is composed by the cannabinoid receptors, the endogenous ligands, and the enzymes involved in their metabolic processes, which works both centrally and peripherally to regulate a plethora of physiological functions. This review aims at explaining how the site-specific actions of the endocannabinoid system impact on memory and feeding behavior through the cannabinoid receptors 1 (CB1 R). Centrally, CB1 R is widely distributed in many brain regions, different cell types (e.g. neuronal or glial cells) and intracellular compartments (e.g. mitochondria). Interestingly, cellular and molecular effects are differentially mediated by CB1 R according to their cell-type localization (e.g. glutamatergic or GABAergic neurons). Thus, understanding the cellular and subcellular function of CB1 R will provide new insights and aid the design of new compounds in cannabinoid-based medicine. Also watch the Video Abstract.
Antioxid Redox Signal
Physiological Control of Nitric Oxide on neuronal BACE1 Translation by Heme-Regulated Eif2-alpha Kinase HRI Induces Synaptogenesis.
Ill-Raga G, Tajes M, Busquets-Garcia A, Ramos-Fernandez E, Vargas LM, Bosch-Morato M, Guivernau B, Valls-Comamala V, Eraso-Pichot A, Guix FX, Fandos C, Rosen MD, Rabinowitz MH, Maldonado R, Alvarez AR, Ozaita A, Munoz FJ
Aims: Hippocampus is the brain center for memory formation, a process that requires synaptogenesis. However hippocampus is dramatically compromised in Alzheimer's disease due to the accumulation of amyloid alpha-peptide, whose production is initiated by BACE1. It is known that pathological stressors activate BACE1 translation through the phosphorylation of the eukaryotic initiation factor-2alpha (eIF2alpha) by GCN2, PERK or PKR kinases leading to amyloidogenesis. However BACE1 physiological regulation is still unclear. Since nitric oxide (NO) participates directly in hippocampal glutamatergic signaling we investigated the neuronal role of the eIF2alpha kinase HRI, which can bind NO by a heme group, in BACE1 translation and its physiological consequences. Results: We found that BACE1 is expressed upon glutamate activation being NO the downstream effector by triggering eIF2alpha phosphorylation, as it was obtained by western blot and luciferase assay. It is due to the activation of HRI by NO as assayed by western blot and immunofluorescence with a HRI inhibitor and HRI siRNA. BACE1 expression was early detected at synaptic spines contributing to spine growth and consolidating the hippocampal memory as assayed with mice treated with HRI or neuronal NO synthase inhibitors. Innovation: We provide the first description that HRI and eIF2alpha are working in physiological conditions in brain under the control of nitric oxide and glutamate signaling, and also that BACE1 has a physiological role in hippocampal function. Conclusion: We conclude BACE1 translation is controlled by NO through HRI in glutamatergic hippocampal synapses where it plays physiological functions allowing the spine growth and memory consolidation.
Int J Biochem Cell Biol
New insights into the molecular pathophysiology of fragile X syndrome and therapeutic perspectives from the animal model.
Busquets-Garcia A, Maldonado R, Ozaita A
Fragile X syndrome is the most common monogenetic form of intellectual disability and is a leading cause of autism. This syndrome is produced by the reduced transcription of the fragile X mental retardation (FMR1) gene, and it is characterized by a range of symptoms heterogeneously expressed in patients such as cognitive impairment, seizure susceptibility, altered pain sensitivity and anxiety. The recent advances in the understanding of the pathophysiological mechanisms involved have opened novel potential therapeutic approaches identified in preclinical rodent models as a necessary preliminary step for the subsequent evaluation in patients. Among those possible therapeutic approaches, the modulation of the metabotropic glutamate receptor signaling or the GABA receptor signaling have focused most of the attention. New findings in the animal models open other possible therapeutic approaches such as the mammalian target of rapamycin signaling pathway or the endocannabinoid system. This review summarizes the emerging data recently obtained in preclinical models of fragile X syndrome supporting these new therapeutic perspectives.