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Benefits Of Pumpkin Seeds For Males
When a person is within the mood to get it on, sometimes his body simply doesn’t agree. Xerosis equally impacts each men and women though it is extra frequent in elderly folks because of the diminishing amount of oil within the pores and skin because of the normal getting old course of. IV.A.three.b. After contact with blood, physique fluids or excretions, mucous membranes, nonintact skin, or wound dressings.
IV.B.2.a. Put on gloves when it can be reasonably anticipated that contact with blood or different probably infectious materials, mucous membranes, nonintact pores and skin, or potentially contaminated intact skin (e.g., of a patient incontinent of stool or urine) could occur.
The health benefits of consuming rum is, however, fraught with controversies because of the medical and social consequences of excessive alcohol use. Foods loaded with lean protein, antioxidants and plenty of healthy nutrients are greatest. 1) The protein in meat helps construct and repair body tissues.
I’ve some drawback which appears like a mixture of a diabetic reaction and anxiety but feel very drained and on the identical time crave that meals or badly want one thing to eat about and hour to two hours after eating it. The meals is a selected cereal and it’s the only cereal the place I’ve had this problem.
I’he always been a healthy individual a part from some digestive issues; born to a Brazilian family who used to reside in a farm,i realized the way to eat healthly and even nowadays with all the processed food accessible and even cheaper than the health ones,i still respect the natural sources.


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domain: artistic


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Would you take off the stickers an silicone the recesses flush or higher or stickers this thing binds well only after three wraps around the axle. I knew it was going to be hard to bind but enough is enough I need some response. ???
PGMs are meant to be dead unresponsive. My pgm binds well stock ??? If you need response, you can remove the spacers on the bearing, then thick lube the bearing.
removing the spacers would not be a good idea as then the gap will be way to small to do anything.
your best bet is to just add some lube to the bearing to make it a bit more responsive, thats what i do to one of my PGMs when im doing 3a.
I guess I was warned now I have it I wish it played like my DM
You use PGM’s for 3A?!? If you are going to use it for any other division other than 1A, you should do 5A. They’re not meant for 3A.
They’re not “not” meant for 3a. There is no rule saying you can’t do 3a with PGM’s. Also, I think Sumna knows what he is talking about ;D He’s been in the community for a long time…
I have no interest other than 1a at this time
I know. But the size of the PGM is a little big and it doesn’t really have long spin times because of the hubstacks and the spec bearing. Its something wrong with the yoyo design. I’m sure you will say thats not true, but yours might be in better condition that others.
I’m not sure about you, but I can definitely get more spin time with my PGM then a lot of other yoyos. I can get almost 3 minutes with the hubstacks alone.
Also, can you elaborate whats wrong with the design? I don’t really understand whats wrong with it.
Additionally, the SPEC bearing does NOT decrease spin time. Its a bearing upgrade, and actually increases spin time.
I can honestly get at least 20 people to argue with you there…
Oh, I know.
i mainly do 3a with my PGMs cuz it is the only plastic i have 2 of and i dont dare do 3a with my metals =P also i do use my PGMs for 5a, they are my main 5a players.
also it is a great yoyo, it is by far my favorite plastic.
Oh darn, forgot to add that you have to put the spacers back on ;D
Hate to agree with him but I too think the walls are too high. But other than that its a total steal for only 20 bucks.
im with samad on this one
get some thick lube… you can buy it here at yoyoexperyt for only $4
ps why would you want to make your pmg responcive? My pmg binds slightly better than any yoyojam yoyo and i think has one of the bestest responce evur. :o (no offence yoyjam, your yoyos respond great, and the new ones with silicone respond just as good as the k pad on my pmg.)
I don’t know but the kpads on my pgm or just my pgm will not bind . I wanted to know if a thin layer or silicone would give it just a little response with out slowing it down and I do mean just a little. My DM binds just fine and maybe even better with those silicone pads I just saw to replace the O ring?
Oddly enough, with my PGM it actually became more responsive to binds after around 8 full hours of play. Originally I had to make between 2 and 3 wraps to get it back. Now I’m fine with just one, and it’s still dead unresponsive to anything else. I wonder if it has to do with wearing down the slightly raised bumps that come on the rubber k-pads. Did anyone else have this experience?
Hey I like that answer I guess it’s just to get it to bind enough times.
Tip: If you want tighter binds, change your string more often.
I jumped too early when I got my Silk because of the loose binds because of an old string, so I thick lubed it and it overly responsive. So the fresher the string, the better the bind.

domain: hobby


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Scott Shenk writes about transportation issues affecting Fredericksburg-area residents. You can email him at firstname.lastname@example.org.
Lane shift set for U.S. 17 work zone
A traffic shift into temporary lanes along the widening work zone on U.S. 17 in Stafford will probably cause delays Tuesday night.
Southbound 17 between Cardinal Forest Drive and International Parkway will be intermittently reduced to a single lane between 8 p.m. Tuesday and 5:30 a.m. Wednesday for the shift.
Cones, barrels and signs will direct traffic into the temporary travel lanes, to the right of the existing lanes, the Virginia Department of Transportation said.
The $48.9-million project is widening a 2-mile stretch of the highway to six lanes. Work is expected to be completed by December 2016.
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domain: news


Internet of Things (IoT) devices, networks and
infrastructure shall be deployed, used, maintained and disposed of in an
efficient, responsible and secure manner to maximize public benefit.
3.1: To support Town of Newmarket wide coordination of IoT deployments, the Town will maintain an inventory of IoT devices that they deploy using a standardized format. The Town will also maintain an inventory of the public or private assets on which devices are installed and the networks used by these IoT devices including details on the network type (e.g. LTE), security protocol (e.g. WPA), location, service level agreements, and contact information for the network and system operator.
3.2: The Town should accumulate and publish, via the Town website, public information on IoT systems, such as the Soofa bench network, including but not limited to examples of deployed IoT devices (e.g. pedestrian traffic pattern sensors) and the different types of public assets (e.g. street furniture) on which they are deployed.
3.3: The Town should make public, via the Town website, a standardized protocol, including points of contact, for requesting access to, and approving use of, Town assets for IoT deployments. Where appropriate, the Town will detail restrictions on particular types of public assets and/or siting restrictions (e.g. rules for landmark or historic districts).
3.4: IoT deployments shall, where possible, leverage or repurpose existing conduit and public assets, maximize energy efficiency, and adhere to sustainable device disposal procedures.
3.5: The Town should leverage their own, secure, existing wireless and fixed networks where possible and appropriate. Networks for IoT deployments should be selected to best support the specific use case. This should include but is not limited to ensuring appropriate security protocols, bandwidth, pricing models, and service level agreements (SLAs).
3.6: All IoT devices and network equipment installed by the Town, on the Town's behalf, or on Town property should have clear agreements and established terms of service governing who is responsible for ongoing operations, maintenance, and the secure disposal of equipment. IoT devices and network equipment should be labelled clearly with the name and contact information for the responsible party.
3.7: Public assets should be instrumented in an orderly and organized manner that minimizes clutter and allows for ease of access for replacement, repair and addition of new equipment or devices.
3.8: IoT systems should be designed to maximize resiliency in the event of a natural disaster (e.g. severe flooding) or other emergencies (e.g. electrical outages). Critical systems should have established emergency response plans to ensure the appropriate continuity of service.


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Over the past few years, I’ve found myself reading more and more Golden Age Mysteries: crime fiction mysteries written from 1900 to 1969.
For me, the journey started in January 2017 with Agatha Christie’s (rather disappointing) ‘Elephants Can Remember’. Eighteen Christie books later, I still have a long way to travel down that road but I soon found myself exploring byways that included not just the big names like Dorothy L Sayers and Ngaio Marsh but lesser-known writers some of whom are being brought back into print and popularity by publishers like the British Library Crime Classics with their gorgeous covers and loving research.
The more of these books that I read, the more context I gain, both for the genre and for times that they flourished in. I’m attracted by the freshness of the writing in many of the books. I also find myself constantly being made aware of my own points of irritation with the entitlement expected by and accorded to the upper classes in these books and by the casual but relentless xenophobia, misogyny and racial prejudice that they embody. They remind me of how recently these views were unremarkable and how much pressure there is in Britain at the moment to return to them.
I’m going to use this post to keep track of the non-Agatha Christie Golden Age books I’ve reviewed and the reflections that they’ve prompted.
The first section is where I’ll post links to reflections sparked by reading Golden Age Mysteries.
The second section has links to reviews of Golden Age Mysteries written by people other than Agatha Christie. These are sorted alphabetically by the surname of the author and listed in the order that I read them.

domain: library


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The cost and savings of digital payments
One of our most common questions is, “How much does Earnnest cost?” Earnnest is absolutely free for real estate agents and escrow holders to use with a convenience fee charged to homebuyers. Not only does Earnnest not cost real estate professionals anything to use — it actually provides savings! Below are the most common ways Earnnest users see the savings stack up.
Added value for agents
Agents using Earnnest see savings in time and resources. They’ll eliminate the hours spent scheduling meetups with clients for the earnest check handoff. (Not to mention the gas savings.) No more driving to pick up and drop off paper checks. Sending a digital earnest payment request with the free Earnnest App takes an average of 90 seconds to complete. And agents can request from anywhere: the office, home, or even on vacation.
Remember the time it used to take to coordinate earnest deposit paperwork like copies of checks and receipts? Now those documents are handled automatically by Earnnest. We email receipts to buyers, escrow holders, and anyone else agents indicate leading to even less time spent pushing around piles of paper. Plus, the Earnnest App lets agents track the progress of each buyer’s earnest payment from initiated to deposited all from their smartphone. That means a lot less follow up needed on the agent's end.
Added value for escrow businesses
Businesses who hold escrow — such as attorneys, title companies, and brokerages — will also reap the benefits of digital payments. It doesn’t cost anything for an escrow-holding business to register their accounts with Earnnest, but the savings start immediately.
As the saying goes: “time is money”. One of the ways Earnnest users recapture time is by drastically simplifying their bank reconciliation process. Earnnest provides detailed payment information (like address and unique payment ID) with each transaction. This means reconciliation can be completed more quickly and accurately than with check payments where the memo lines are often left blank.
In addition, many banks charge fees for receiving earnest deposits via incoming wire. By using Earnnest’s digital payments, escrow-holding businesses completely eliminate wires and thus incoming wire fees. Escrow businesses can look forward to saving on every transaction paid using Earnnest.
Added value for homebuyers
Earnnest charges a convenience fee to homebuyers to move their real estate payment from their bank to the escrow holder’s account. This fee is comparable to a cashier’s check and less than the cost of most wires which generally range from $25-30 according to BusinessInsider.com. Plus, with Earnnest, homebuyers don‘t need to leave work or home to initiate their payment at the bank. Paying their earnest money deposit from anywhere is a way to add convenience and save buyers time.
The biggest way homebuyers save is by removing the risk of check fraud and wire fraud. A transaction compromised by check or wire fraud can cost the buyer everything. Earnnest’s secure digital payment system verifies both sending and receiving accounts so that criminals cannot insert themselves in the payment process. By eliminating checks and wires completely, Earnnest’s digital payments eliminate the possibility of check and wire fraud for the homebuyer. We’ve completed over 180,000 transactions, moving more than $1 billion, with zero instances of fraud. It can be hard to place a value on security, but from the homebuyer’s perspective, that level of peace of mind is priceless.

domain: finance


Day after day we hear horrible stories of what goes on in high schools and how students cope with bullying. The cyber world, which I celebrate as it keeps me in touch with almost-lost high school friends and newly-minted grandchildren, is not always put to work for the good.
I read, aghast, about the way twitter and FB are used to isolate and terrify kids. I wonder whether Twitterverse isn’t the island that William Golding talked about in Lord of the Flies. When I read that book in college in the 70s I rolled my eyes, secure in my knowledge of humanity’s basic goodness. There’s nothing quite like privilege, is there? After all, I’d been growing up during the 60s in the years of the most heinous race riots and somehow still believed that clapping for Tinkerbelle was what it took.
Years later, I still cling to my Pollyanna worldview. I believe, when encouraged, we move toward the best in us. (it was only slightly discouraging when referencing pollyanna to have one group of information about Eleanor Porter’s 1915 novel and the other bit about “disambiguation” which is a synonym for my preternatural cheery optimism.) Once more with feeling “Let’s all look on the bright side of life…”
But looking away doesn’t help anything, especially our bullied and frightened kids. So it was a lovely thing to read about a 17 yo kid in Osseo MN taking to Twitter to shut down the mean girls and boys in his school who were using social media to terrorize and traumatize. Kudos for Kevin Curwick (and his parents who raised a great kid!). A cute, popular kid, leading the kindness brigade. Or as he says, OsseoNiceThings — goodness gracious are we going to rehabilitate the word nice, make it more than icky-sweet? He just set about noticing kids and posting what was great about them. Day after day, tweet after tweet. A young man doing his kindness reps. And Hurrah! for the kids at other schools are doing the same thing to combat bullying. If we’re going to trend and hashtag, let’s do it for the good. Hop on that bus, my dears.
And while we’re cheering, let’s hear it for the kids who are participating in Lady Gaga’s Kindness Campaign and for Office Depot and their president Patrick Schwartzenegger’s support and Cyndi Lauper’s “Give a Damn” campaign. It’s good to see people with klout taking a lead on this issue.
Makes me wonder what you’re doing for the good about bullying. Wander over to our FB page, like us, and tell me what you’re up to.
In the meantime give it up for Kevin. Thanks to him, at least in Osseo, MN, we’re no longer listening to the sound of one hand clapping, we’re listening to a rousing round of applause from every student in his school. (Although someone might want to know if was using his cell in school, but that’s the principal’s problem! I’m just happy someone’s doing what’s right. ) So, while I’ll keep working for change, I’m going to keep clapping for Tinkerbelle. Sometimes the light just shines brighter. I do believe the more you focus on what is right, the more we move toward that. But we should stop once in a while to see who’s not in the parade with us and invite them to come along. Go Kevin!


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- 2019 Financial CalendarJanuary 2, 2019 - 12:30 am
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Monday, November 20, 2006
The Mets and Marlins are at it again. The Mets have traded Henry Owens and Matt Lindstrom for Jason Vargas and Adam Bostick. Jason Vargas could be on the MLB roster while Lindstrom, who shows potential, will need some time in the minors. "Vargas started 13 games at Albuquerque (AAA) of the Pacific Coast League in 2006 going 3-6 with a 7.43 ERA. He struck out 51 batters and walked 28 over 69.0 innings pitched. In the Dominican Winter League, he has appeared in four games and not allowed a run in 6.1 innings, with two walks and five strikeouts." Bostick pitched 115.0 innings allowing 100 hits, 58 runs, 45 earned, with 67 walks and 109 strikeouts. With Albuquerque, he gave up 39 hits, 20 runs, 14 earned, with 13 walks and 30 strikeouts over 27.0 innings pitched. The Marlins acquire two young pitchers who may break the roster this year, but will probably see more action in 2008.
Also, the Angels traded Kevin Gregg to the Marlins for Chris Resop


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This time no words.
Posts tagged ‘colour’
One of my favourite spots in London, the ruins of St Dunstan in the East, used to be a church, built in the 12th. century and was bombed during the Second World War. The atmospheric ruins and gardens of St Dunstan are so full of peace and silence, I can’t help visiting this place whenever I am in London. Although being just at the heart of the busy City of London, in between the London Bridge and the Tower of London, the tranquility and the quietness of this place fascinates me. The moss on the walls, freely growing ivies, old tombstones, lacy windows, the decayed, the worn-out…
Hidden between the office blocks, St Dunstan is the perfect secret garden that won’t reveal itself unless you look for it. And this is the reason of my love for it.
Not quite close to yellow, definitely not red; warm enough but serene at the same time. Orange is hope, in a strange way reminding me of Van Gogh. But of course his orange was also a lot of other things.
Photographs are from Verona. This city has the perfect tones of orange all around.
“Let everything that’s been planned come true. Let them believe. And let them have a laugh at their passions. Because what they call passion actually is not some emotional energy, but just the friction between their souls and the outside world. And most important, let them believe in themselves. Let them be helpless like children, because weakness is a great thing, and strength is nothing.”
I know it’s not the perfect quality, but I just love remembering that moment, and what it tells me.
She was wandering alone in a mosque in Sarajevo.

domain: geography


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IMAGE: To better understand cell “plasticity ” in breast cancer, Salk scientists study how different cell types are generated in its tissue of origin, the mammary gland. From left: Christopher Dravis, Chi-Yeh… view more
LA JOLLA–(August 30, 2018) A team at the Salk Institute has identified a master switch that appears to control the dynamic behavior of tumor cells that makes some aggressive cancers so difficult to treat. The gene Sox10 directly controls the growth and invasion of a significant fraction of hard-to-treat triple-negative breast cancers.
Recently, the Salk lab led by Professor Geoffrey Wahl discovered that aggressive breast cancers return to a flexible, earlier state found in fetal breast tissue. This cellular reprogramming may be the key to cancer’s ability to form new cell types, evolve drug resistance and metastasize to other locations in the body. The new work documenting Sox10’s role in this process, which was reported in the journal Cancer Cell on August 30, 2018, represents a major milestone in researchers’ understanding of cancer and could open new avenues for diagnosing and treating aggressive breast cancer as well as other types of intractable cancers.
“Two things that make triple-negative breast cancers so hard to treat are their
Article originally posted at

domain: medical


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Chef's Choice Coconut Milk is available in different packaging sizes, including cans and tetra packs, offering convenience and versatility in the kitchen. The product is typically free from artificial additives or preservatives, ensuring a natural coconut milk experience.

domain: food


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Authors: Riley Sager
Tags: #Thriller, #Mystery, #Horror, #Adult, #Suspense, #Contemporary
Vermont is gorgeous in October. Nothing but cerulean skies and fiery leaves and the smell of woodsmoke in the air. In the mornings, I like to sip my coffee on the front porch of Baneberry Hall and take it all in.
It’s my first Vermont autumn. It will likely also be my last.
There’s not much left to do on the house. With occasional help from Allie, I spent the rest of the summer and most of the fall renovating the place. My original plan in everything but execution. Instead of the Victorian glamour I’d envisioned, I settled for modern blandness. Open rooms and laminate floors and white everything. It seemed like the best option. Some houses don’t deserve to have their stories preserved.
It’s unclear how much Baneberry Hall will sell for when it’s listed. The house is once more all over the news—not always a good thing in the world of real estate.
Despite it being reported everywhere that the Book was all a lie to cover up what my parents thought I’d done, rumors persist that Baneberry Hall is haunted. People also continue to believe that my father
was right and that Curtis Carver never murdered his daughter before killing himself. In fact, there’s a growing suspicion that Marta herself might have done it, even though all the evidence suggests otherwise.
All of this has brought out the ghouls, who’ve returned with renewed vigor. It got so bad that Chief Alcott had to resume stationing a police cruiser outside the front gate. I bring the cops coffee each night.
But I no longer feel unsafe here. It helps that I had the crumbled section of wall rebuilt, even though it was only the Ditmers and Marta Carver who got onto the property that way. I also had the secret passage bricked over and a state-of-the-art home security system installed. No more slips of paper stuck in the door for me.
As for the armoire, I happily took a sledgehammer to it, relishing the crack of the wood that came with each blow. Even so, I no longer sleep in that room, having moved instead to my parents’ old bedroom.
It turns out that Marta Carver wasn’t the only person who snuck through that armoire to visit me during the night. Elsa Ditmer had, too. While only partially lucid when interviewed by Chief Alcott, she confirmed in a foggy, roundabout way that she had entered my bedroom at least twice when I was a child.
Only I knew her as someone else.
Not a ghost but a superstitious woman who knew of Baneberry Hall’s history and came at night to whisper a warning that almost came true.
You’re going to die here.
But now Elsa and her daughter are gone. Mrs. Ditmer’s Alzheimer’s got to be too much for Hannah alone, and she was admitted to a care facility near Manchester. Hannah went with her, moving into a studio apartment so she could be near her.
Before they left, my mother apologized to Hannah, who chain-smoked while she listened. When my mother finished, Hannah simply
said, “You caused my family twenty-five years of pain. No apology is going to make up for that.”
It was the last time I saw her, although in the days leading to her departure, I noticed more and more items missing from Baneberry Hall, including Petra’s teddy bear, Buster. Other than that, everything that’s vanished from the house has ended up on her online auction site. Thanks to renewed interest in Baneberry Hall and the Book, a lot of the things sold for five times what they’re worth.
Dane is also gone.
I stopped by his cottage shortly after we both got out of the hospital. To his credit, he listened to what I had to say, letting me spend a good ten minutes standing on his doorstep and rambling my apology.
He said nothing when I finished. He simply turned away and closed the door.
A week later, he moved out.
It strikes me as ironic that I’m the only one who’s still here. Me, who was never supposed to return in the first place. But it’s more than just work on the house that’s kept me here. I want to remain in Bartleby until all the legal issues are over.
That should come next week, when my mother is going to be sentenced for her role in covering up the death of Petra Ditmer.
It turns out that what she told me in the kitchen was wrong. She
stop me from throwing my life away—by confessing to Petra Ditmer’s murder, which is exactly what she tried to do immediately after leaving me alone in Baneberry Hall. While Marta Carver was rubbing my back and telling me how she accidentally killed Petra, my mother was talking to Chief Alcott.
After hearing my mother’s story, the chief came by the house to also bring me in for questioning. Instead, she discovered Elsa Ditmer, lost once more in an Alzheimer’s haze in the parlor, and Marta and me splayed out in front of the stairs.
Marta was dead.
I was on my way.
After having my stomach pumped, my fluids restored, and a fractured wrist bandaged, I told Chief Alcott everything. I even included the part about seeing Petra Ditmer right as Elsa pushed Marta down the stairs, although everyone agrees I was hallucinating.
I hope not.
I’d like to think it was Petra’s spirit, helping her mother save my life.
Once Chief Alcott got everyone’s story straight, it was time for my mother’s formal confession. In July, she pleaded guilty to one count of concealing a dead body. Now it’s up to the judge to decide her punishment. Although she could get up to three years in prison, her attorneys think she could escape jail time altogether.
Whenever I ask my mother if she’s scared about possibly going to prison, she tells me no.
“Even though we did what we thought was right, it was still wrong,” she said on the phone yesterday. “I’ll serve whatever time the judge sees fit. All I care about is that you forgive me.”
I forgave her the moment I heard she confessed to what we both had thought was my crime. I wouldn’t have let her go through with it, of course. If I had been the one to kill Petra, I would have admitted it. But the fact that my mother was willing to sacrifice herself like that told me I had been wrong about her. She wasn’t a monster. Neither was my father. They were just two people thrust into an unfathomable situation who were terrified about what might happen to their daughter.
It doesn’t excuse what they did.
But it sure does explain it.
Everything, it turned out, was for me. As for who that is, I am still figuring it out.
That the relationship between my mother and me is the best it’s
ever been is another irony. She likes to joke that all it took for us to get along was an impending prison sentence. Yet I still can’t help but think about what might have been. So many years have been wasted on cover-ups and lies. Now all we can do is make up for lost time. I only wish I’d been able to do the same thing with my father. But I hope he knows, wherever he is now, that he has also been forgiven.
My mother and Carl have been in Bartleby a lot these past few months, for reasons relating to her criminal case. Although she’s now fine with spending an afternoon in Baneberry Hall, she refuses to stay the night. She and Carl always book a room at the Two Pines, which, in my mind at least, is probably worse than jail.
When they’re not in town, I spend my nights roaming Baneberry Hall, thinking about all that’s happened within these walls. Sometimes, I just sit and wait for Petra to appear. Unlike everyone else, I don’t think she was a hallucination brought on by ingested baneberries and approaching death.
I believe she was real, and I’d like to see her one more time before I leave.
I want to tell her I’m sorry, and to thank her for coming to my rescue.
Maybe she already knows these things. Maybe she’s finally at peace.
Right now, I’m in the study on the third floor, standing at my father’s desk. All that sits here now is his old typewriter. I’ve spent several evenings in front of it, my fingers tripping over the keys, debating whether or not I should actually press a few of them.
Tonight, I decide that the time is right. Just because my interior design includes no traces of Baneberry Hall’s story doesn’t mean I won’t tell it. In fact, the same publisher who put out the Book all those years ago has already contacted me about writing a sequel.
At first I declined, despite the sizable advance they offered. I’m a designer, not a writer. But now I’m thinking about taking them up on
their offer. Not for the money, although that will keep Allie and me in business for years to come.
I want to do it because it’s what I think my father would have wanted.
I am, after all, his daughter.
So tonight I sit down at his typewriter and peck at the keyboard, writing what may or may not be the first sentence of what may or may not become a new version of the Book.
Every house has a story to tell and a secret to share.
THE REAL STORY
Every book is a journey that begins with the germ of an idea and ends with a finished product reflecting the hard work of dozens of people. This includes everyone at Dutton and Penguin Random House, especially the fabulous Maya Ziv, who guides me through each book with warmth, support, and a keen editorial eye. A special shout-out goes to Alex Merto and Chris Lin for continuing to give my books covers that are never less than gorgeously creepy.
At Aevitas Creative Management, I owe a million thanks to my tenacious agent, Michelle Brower, and to Chelsea Heller and Erin Files, who help my books take flight around the world.
Special thanks goes to the Rodgers & Hammerstein Organization for granting me permission to use lyrics from “Sixteen Going on Seventeen.” Being allowed to let their song drift through the halls of my haunted creation makes my heart sing.
Thank you, as usual, to Sarah Dutton for being an excellent first reader who pulls no punches, and to the Ritter and Livio families for their unflagging enthusiasm and support. Finally, I owe more than thanks to Michael Livio, who willingly accompanied me on this journey every step of the way. This is for you.
Home Before Dark
is the fourth thriller from
New York Times
bestselling author Riley Sager, the pseudonym of an author who lives in Princeton, New Jersey. Riley’s first novel,
, was a national and international bestseller that has been published in more than two dozen countries and won the ITW Thriller Award for Best Hardcover Novel. Sager’s novels
The Last Time I Lied
Lock Every Door
New York Times

domain: literature


text:
Award winning personal trainer and sports psychology student in Chicago, moving to Los AngelesChicago, Illinois USA
I received my BFA in Dance Performance from Northern Illinois University where I was an award winning dancer. I danced professionally in Chicago for 10 years. I am now a successful personal trainer in Chicago. I have been trainer of the year 2 years in a row at Chicago Athletic Clubs. I am also receiving my MS in Sports and Performance Psychology.


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This rich and creamy casserole is the best way to use extra produce from your summer garden! A tasty side dish!
Summer squash, zucchini, egg, garlic powder, Italian seasoning, cream cheese, salt, black pepper, cheddar, Ritz crackers, Parmesan, and butter
Peel and slice the zucchini and squash into thin rounds. Salt and let sit for 15 minutes then pat dry and pour into a large bowl.
In a separate bowl, whisk together the egg, salt, pepper, Italian seasoning, and cream cheese together, then pour over the squash.
Add the cheese and combine then pour into the baking dish. In a separate bowl, mix together the butter, Parmesan, and cracker crumbs.
Spread cheese over the squash mixture, then top with the cracker crumble and bake until golden brown and bubbling.
This side dish is ideal any time of year, but perfect for those summer and fall extra batches of squash and zucchini from your garden.


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Updated: Sep 30, 2022
Here's Steve's first reaction and rough review.
These “Bird” scooters can be found all over the resort of Caleta de Fuste and are available to ride through a phone app.
In short, the idea is great but the scooters probably need to be more rugged to cope with the less-than-perfect road surfaces around the resort! There are scooter hire companies in town offering more robust looking machines but I haven’t tested these. Let me know if you would like me to!
Prices: Total was €7.80 broken down below.
Startup charge: €1

domain: travel


text:
- What is the best thing to feed chickens for eggs?
- Do hens miss their eggs?
- Can a chicken lay 2 eggs a day?
- Do older chickens lay eggs?
- How much light do chickens need to keep laying?
- What breed of chickens live the longest?
- Can you eat hens after they stop laying?
- How do you tell if a hen has stopped laying?
- Can chickens stay in the coop all day?
- Why do chickens stop laying eggs?
- What is the average lifespan of a laying hen?
- Do chickens stop laying eggs when it gets cold?
- How cold is too cold for chickens?
- What to do with hens when they stop laying?
- Does rain affect chickens laying eggs?
- Do chickens die of old age?
- Is keeping chickens easy?
What is the best thing to feed chickens for eggs?
5 Chicken Treats for Better Quality Backyard EggsVery Good Greens.
Vibrant leafy green vegetables like spinach, pak choi, silverbeet, kale or millet are a great treat for your laying hens.
Fruits for Feathers.
Adding goodies to your chooks’ water supply is a cluckin’ good way to keep your chickens happy and healthy..
Do hens miss their eggs?
The simplest answer to this is ‘no’. Laying eggs is as instinctive to hens as perching and scratching. It’s something they need to do, but they are not doing it with thoughts of hatching chicks, and will leave their egg as soon as it has been laid.
Can a chicken lay 2 eggs a day?
Can a chicken lay two eggs a day? Yes! A chicken can lay two eggs a day, however it is uncommon.
Do older chickens lay eggs?
A: Chickens usually don’t simply “stop” laying eggs when they get to a certain age, but they will lay fewer as they get older. That said, most laying breeds will lay more or less productively in backyard terms for five or seven years.
How much light do chickens need to keep laying?
Hens need about fourteen hours of light a day to produce eggs, and in many areas of the country the sun is only giving about eight hours of light in these winter months. Since most chickens trace their heritage back to equatorial regions, their systems just aren’t adapted to continuing egg production in winter light.
What breed of chickens live the longest?
Plymouth RocksPlymouth Rocks are hybrid chickens that are known for being some of the longest-lived of all of their flock mates. They can live for ten to twelve years if they are raised in the proper conditions!
Can you eat hens after they stop laying?
When your hen’s egg-producing days are done, send her off humanely with one last meal. When layer hens no longer lay eggs, chicken keepers can consider culling them from the flock to be used as meat.
How do you tell if a hen has stopped laying?
4 ways to know if a Chicken has stopped Laying Eggs Comb Color – The comb should be a nice, rich red color. If it’s pale or light-colored, you might have an non-egg laying chicken. Vent Moisture – The vent should be moist and in a chicken that isn’t laying, she’ll have a very dry almost dusty-looking vent.
Can chickens stay in the coop all day?
From our experience raising laying hens, I can say chickens can stay in their coop all day on occasion, but not for days on end. This will also depend on the size of your coop and the number of chickens housed in it. This also assumes you have food and water available for them inside the coop.
Why do chickens stop laying eggs?
Chickens stop laying eggs for a variety of reasons. Hens may lay fewer eggs due to light, stress, poor nutrition, molt or age. … As the days become shorter and temperatures drop, you may notice fewer eggs when you go out to the chicken coop.
What is the average lifespan of a laying hen?
Chicken: 5 – 10 yearsLaying hen/Lifespan
Do chickens stop laying eggs when it gets cold?
Many hens stop or slow down egg production during the fall and winter. The lack of daylight and cooler temperatures tell their bodies to rest. Extension Poultry Specialist Jesse Lyons at the University of Missouri says if you want to convince your hens to keep laying, they’ll need supplemental daylight.
How cold is too cold for chickens?
Chickens are quite hardy and can tolerate temperatures below freezing, but they prefer a warmer climate. The ideal temperature for chickens is about 70-75 degrees Fahrenheit.
What to do with hens when they stop laying?
When Chickens Stop Laying for the Winter. … One option, especially if you have very few chickens, is to allow the older hen to contribute to the farm in other ways. … Another option is to cook your chickens as meat chickens. … The third option is to humanely dispose of a chicken.
Does rain affect chickens laying eggs?
In fact, there doesn’t seem to be much of a change in the number of eggs they lay regardless if the day is sunny, rainy, snowy, hot, or cold. The only time it usually drops off is when the chickens are molting.
Do chickens die of old age?
That’s old, very old, for chickens. … Chickens die from respiratory ailments. They mysteriously die around the age of three. They die from egg-laying screw-ups, like internal laying and prolapse.
Is keeping chickens easy?
As mentioned previously, keeping chickens is a relatively easy job, so long as you establish a strong routine. Here are some of the things you’ll need to do for your flock each day… Ensure that they have plenty of food and water. Spot check the coop to make sure it is clean and sanitary.


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Mubadala Petroleum is a leading international, upstream oil and gas exploration and production company. We manage assets and operations spanning 10 countries with a primary geographic focus on the Middle East and North Africa, Russia and and Southeast Asia.
We are a wholly-owned subsidiary of Mubadala Investment Company (Mubadala), which is owned by the Government of Abu Dhabi. Established in 2012, incorporating and building on the success of Mubadala’s existing investments in the oil and gas sector, we are today one of the strategic companies in the petroleum and petrochemicals portfolio within Mubadala, targeting growth and building a world class business.
Our success is built on a clear purpose, strong partnerships, the passion and capability of our people, and our focus on performance.
Core to Mubadala Petroleum’s business is being a responsible corporate citizen and operator with a strong commitment to health, safety and the environment to safeguard our employees, contractors and communities in the vicinity of our operations. We operate the majority of our assets in Southeast Asia where we are recognized for an excellent track record of safe and efficient operations.
We are participants in a number of major projects including the world-class Dolphin Gas Project, which is central to meeting the energy needs of the UAE, enhanced oil recovery in Oman, the giant Zohr gas project in Egypt and the Gazpromneft-Vostok joint venture in Russia to develop and produce oil reserves in Western Siberia. In Southeast Asia, we are the operator of the majority of our exploration, development and production assets across Thailand, Indonesia, Malaysia and Vietnam. Utilizing our experience and strong track record of safe and efficient operations from Southeast Asia across our entire business, has seen us emerge as a very active partner in all of our projects, including those where we are not the operator.See more


text:
Think of it as a safety helmet for your outfit – this bicycle lapel pin is a small and quirky touch to an outfit in need of saving. Not only is vélo the French word for bike, it is also an anagram for love. Coincidence? We think not.
The pin is made out of brass with a polished finish and is a great quirky addition to your outfit that will make anyone smile. It is delivered beautifully packaged in a gift box for protection and storage.


text:
VacLance cleans up as you do surface preparation
Add vacuum recovery to any NLB rotating water jet lance with a VacLance attachment and vacuum source. Model DM32283 works vertically, horizontally and in corners.
Corrosion Coatings for Protection and Repair
Buy POLYURETHANE or POLYUREA coatings and spray surfaces for years of proven chemical resistance, water- and weather-proofing, and structural improvements.
NO FLASH RUST -
Our HoldTight®102 salt remover & flash rush inhibitor prevents flash rust by removing surface contaminants.
Contact us for your nearest distributor. (800) 319.8802 email@example.com
GOING PLACES YOU ONLY DREAM ABOUT!
We custom design.
We sell new & used.
What are your equipment needs?
Cleverly simple. Clearly ADI.
Surface Prep & Material Removal
CS Unitec’s Floor Planers remove coatings & corrosion from concrete & metal surfaces. Produce keyed profiles for waterproofing applications. firstname.lastname@example.org
The Next Generation
• Most Comfortable
• Most Dependable
POLYGON - Temporary Humidity Control
We specialize in innovative climate control solutions for industrial painting, utilizing alternative energy sources and combining desiccants with heating or cooling.
Portable Power from Absolute Equipment
Sales • Rental • Service
Over a century of

domain: chemistry


Local government units are important income-generating entities. They play a crucial role in the economic development of their respective regions, as they have the power to create and implement policies that promote business growth and attract investments.
One of the primary sources of income for local governments is through taxation. They have the authority to impose various taxes, such as property tax, business tax, and franchise tax, among others. By levying these taxes, local government units generate revenue that can be used to fund public services such as infrastructure development, healthcare, education, and social welfare programs.
Apart from taxation, local government units engage in income-generating activities such as providing basic services, collecting fees, and managing assets. For instance, they can charge fees for permits and licenses, thereby generating income to finance the operations of their respective offices. Local governments also manage public resources and properties, such as public lands, marketplaces, and entertainment venues, and can generate revenue through leasing or renting these assets. Moreover, they may create business enterprises such as public transportation systems, utilities, and tourism services, generating additional income for the local government.
With these in mind, local government units can engage in public-private partnerships (PPP) as a means of further generating income. A PPP allows the government to collaborate with private entities in providing public services and infrastructure, while also generating revenue. For example, a local government unit can partner with a private company to build and operate a toll road, with the government receiving a share of the toll revenues. This form of collaboration not only generates income for the government, but also enhances efficiency and service delivery.
Local government units, then, are essential income generating entities that play a vital role in the economic development of their regions, hence their need to activate. Through taxation, fees, managing assets, and engaging in public-private partnerships, they can generate income to fund public services and infrastructure development. By maximizing their revenue sources, local government units can contribute significantly to the overall well-being and progress of their communities.


text:
bierkoning (11403) - La Tropica, NETHERLANDS - SEP 10, 2007
4 AROMA 9/10 APPEARANCE 3/5 TASTE 8/10 PALATE 4/5 OVERALL 16/20
3rd LCRBM. 2003 bottle. Aroma of malt whisky mixed with raisin. The very sweet flavor has raisin and banana and is very brandy-like. Very malty, very alcoholic, but somehow this is very well integrated in this malt beverage (I don’t know if I can call this a beer). Magic stuff, extreme in al ways thinkable.
Jerre (3019) - Waregem, BELGIUM - SEP 9, 2007
3.7 AROMA 7/10 APPEARANCE 4/5 TASTE 8/10 PALATE 4/5 OVERALL 14/20
Bottle @ LCRBM, Kulminator. Black color, no head. Aroma very strong alcoholic. This is like liquor.
Medium body. Taste = complex, very caramel, port, strong alcoholic.
jbrus (4991) - Delft, NETHERLANDS - SEP 9, 2007
4 AROMA 8/10 APPEARANCE 4/5 TASTE 8/10 PALATE 4/5 OVERALL 16/20
Bottle@LCRBM. Cognac aroma. Red brown color, no head. Very sweet, varnish, grapes, very alcoholic. What to do? Is this a beer, no way! Did I like it? Yeah. So I decided to rate it and as a beer but as a cognac or something. I wouldn’t mind if this was removed from the website though.
Buddahchild (28) - Littleton, Colorado, USA - SEP 6, 2007
4.4 AROMA 8/10 APPEARANCE 4/5 TASTE 9/10 PALATE 5/5 OVERALL 18/20
Dark amber with no carbonation. Sweet caramel, candied fruits, and vanilla. Rich thick body, with tastes of vanilla, port, caramel, light dark fruit and sweet toffee. The sweet finish seems to go forever. Enjoy like a port, have a cigar or some creme brulee. i think I’ll keep mine in my cellar a while.
kp (10884) - Woodstock, Georgia, USA - SEP 1, 2007
4.3 AROMA 8/10 APPEARANCE 4/5 TASTE 9/10 PALATE 5/5 OVERALL 17/20
UPDATED: JUN 7, 2008 Name: Utopias
Source: Freakin Frog
Appearance: clear amber, headless,
Aroma: rich sweet alcoholic fruity aroma with caramel, vanilla, oak, and licorish, aroma gets a bit syrupy sweet after a while,
Body: thick body,
Flavor: flavor is a much richer version of the incredible aroma, fumey alcohol the quickly fades replaced by the richest most wonderful elixar ever
Appearance: clear brown, headless, thick and viscous with lots of legs,
Aroma: sweet hot caramel aroma, sweet maple, alcohol comes in waves,
Body: big thick body,
Flavor: lots of rich caramel flavor, nice maple and vanilla sweetness, light bitterness, alcohol comes and goes but generally stays out of the way,
Aroma: 8/10; Appearance: 8/10; Flavor: 9/10; Palate: 9/10; Overall: 17/20
mikey (503) - farmington, Utah, USA - AUG 31, 2007
2.5 AROMA 5/10 APPEARANCE 2/5 TASTE 5/10 PALATE 1/5 OVERALL 12/20
Poured a deep amber/ruby with no head or lace. The nose was bourbon-esque with massive dark fruits, tons of alcohol, malt and caramel. A touch of maple syrup like character is also noticed. The flavor is vinous and ripe. Full of raisin, plum, butterscotch, sweet carmel and brown sugar. The finish is full bodied, bitter and all alcohol. This burnt like hell going down. Every sip steals your breath (not in a good way). Fortunatly I was able to sample it for free at the 2005 Great American Beer festival. At $100 a bottle you should try it; if anything to say, you’ve had the strongest beer in the world.
WeeHeavySD (3361) - Portland, Oregon, USA - AUG 28, 2007
3.8 AROMA 7/10 APPEARANCE 4/5 TASTE 7/10 PALATE 4/5 OVERALL 16/20
Few Ounce taste @ Downton Bar and Grill courtesy of super cool bartender Matt Byrne, normally the tastes go for $20 and the bottles are $400, so I have to give major props to Matt. Shared coincidentally with a friend named Matt. Pours brown and viscous looking. It looks quite thick overall, this however changes as it goes on it seems more thin it opens up. The nose is pretty damn insane its very hardcore with a supreme kick of alchol thats bigger than I’d expect but than again it is 25%. Also there is some big maple syrup smell in there too. The taste is like dessert wine on crack cocaine. Sweet maple and caramel. It also has a huge mouth punch, with a grappa kick. Its sharp on the palate but it also is intriguing as it changes as I drank it. Memorable.
LyndaNova (532) - Manchester, New Hampshire, USA - JUL 29, 2007
2.9 AROMA 5/10 APPEARANCE 3/5 TASTE 7/10 PALATE 2/5 OVERALL 12/20
Copper brew kettle: Pours a clear cola color with no bubbles. Rich, refined malts with notes of whiskey, wood, fruit, spice, grass and earth. Very robust, complex and strong. Heavy bodied and crisp, without carbonation. Ending contains brown sugar notes. Thanks, Bruce!! :)
bager (2120) - Copenhagen N, DENMARK - JUL 12, 2007
4.1 AROMA 8/10 APPEARANCE 3/5 TASTE 8/10 PALATE 4/5 OVERALL 18/20
Copper kettle thanks to my man Chris. 2003. Very complex with notes of malt, raisins, prunes, caramel, coffee, syrup, pine, alcohol and a somewhat dry finish.
ryan (3186) - Beltsville, Maryland, USA - JUN 26, 2007
2.9 AROMA 5/10 APPEARANCE 3/5 TASTE 6/10 PALATE 3/5 OVERALL 12/20
Sample provided by Jeffin7. Clear amber body is still. Uber hot and boozy nose is very sweet with toffee and raisins. The flavor is rum-like, very sweet, raisins, toffee and booze. Full body is sticky and still.


text:
By MalaysiaKini (6 January 2016)
Analysis by a top audit firm, PricewaterhouseCoopers (PWC), shows that the benefits of the Trans-Pacific Partnership Agreement (TPPA) on growth may be overblown, PKR MP Wong Chen said.
"The conclusion on the matter is clear: the PWC cost-benefit report does not support any significant macroeconomic justification of signing the TPPA," Wong said at a press conference in Petaling Jaya today.
Wong and his officers perused the voluminous report which came out after the TPPA text was finalised last year, following lengthy negotiations among 12 countries.
Wong said PWC's analysis shows GDP and exports would only grow an extra 0.22 percent at most, with TPPA.
PWC came to this conclusion by comparing two scenarios - if Malaysia does not sign the TPPA and if the nation signs the deal and tariffs go down to zero over 10 years.
However, PWC found that if non-tariff measures like subsidies and quotas are removed as a result of the TPPA, GDP can grow up to 1.15 percent and exports by up to 0.9 percent.
Even then, this comes at a heavier trade-off, Wong said.
This is because the modelling finds that the same scenario will bring 30 percent dip in balance of trade.
Balance of trade refers to the difference in the value of imports and exports.
A drop in balance of trade means Malaysia will be importing goods that are of higher value than what it is exporting.
There is stiff resistance to TPPA by some opposition parties and civil society.
Critics fear damaging industry-state dispute settlements, limitations of the state's ability to introduce potentially anti-industry policy and higher cost of medicine.
The government, however, insists it will not sign the agreement if it means pricier medicine.
The agreement will be tabled in Parliament on Jan 26, after workshops with MPs and town hall meetings nationwide.

domain: politics


text:
Ten years ago, Cardo et al.  showed for the first time that zidovudine (ZDV) treatment could reduce the risk of HIV infection after percutaneous exposure by 80% among healthcare workers. However, the results of this case–control study have never been confirmed, and studies of ZDV postexposure prophylaxis (PEP) in animal models have only established a reduction of plasma viral load (PVL) but no full protection from infection [2–4].
Despite the few formal evidences of PEP efficiency in humans and cases of treatment failure reported among individuals treated within 2 h of exposure to contaminated fluids [5,6], the use of PEP is nowadays largely widespread; consisting currently in highly active antiretroviral associations. In several countries, the use of PEP is not limited to occupational exposure to HIV, but is also recommended after sexual exposure to HIV .
As truly effective vaccines and topical microbicides are probably years away from commercial availability, the use of antiviral therapy is now also considered for preexposure prophylaxis (PrEP) in populations at high risk of transmission. Very recently, Garcia-Lerma et al.  showed the prevention of rectal simian/human immunodeficiency virus (SHIV) transmission in macaques by daily or intermittent prophylaxis with emtricitabine and tenofovir. Several trials based on the use of tenofovir administered as a once-daily pill alone or in combination for PrEP are also underway in various highly exposed populations .
The use of animal models to evaluate HIV-prevention strategies is indispensable, because of the difficulties involved in carrying out trials in humans. Macaques infected with pathogenic strains of simian immunodeficiency virus (SIV) or related chimeras are currently the most relevant models of human HIV infection and AIDS . This model has been used to evaluate both preexposure and postexposure chemoprophylaxis mostly after intravenous challenge. Tsai et al.  demonstrated the efficacy of tenofovir for preventing SIV infection in macaques after intravenous challenge, provided that treatment was initiated between 48 h before inoculation and 24 h after inoculation and continued for 28 days. A related study on a closely related compound (BEA-005) showed that PEP was not as effective if initiated 48 or 72 h after exposure or continued for only 3 days, demonstrating the importance of treatment timing and duration . Only a few studies have evaluated the efficacy of PEP after mucosal exposure. Böttiger et al.  showed that both of the two macaques given BEA-005 1 h after exposure were protected against rectal challenge with SIV. To date, only Otten et al.  have studied PEP after vaginal exposure. They showed that tenofovir could protect pig-tailed macaques against HIV-2 infection if treatment was initiated within 36 h of viral inoculation.
Many of the molecules tested in animal models may not be suitable for PEP in humans, and very few studies have focused on the antiretroviral drugs routinely used in HAART, although combinations of nonnucleoside and nucleoside analogues and protease inhibitors are frequently used after occupational or sexual exposure to HIV. We previously demonstrated that the combination of ZDV/lamivudine (3TC) and indinavir (IDV), initiated within 4 h of intravenous inoculation with SHIV89.6P or SIVmac251 and continued for 28 days, could not prevent infection in macaques but may have a significant impact on disease progression [10,14]. Here we demonstrate that complete prevention from infection could be nevertheless achieved with a similar treatment against the vaginal transmission of pathogenic SIVmac251 probably because of the specificity of viral dissemination after mucosal exposure. In addition, pharmacokinetics of the compounds appeared as a key factor for prevention efficiency.
Eighteen adult cynomolgus female macaques (Macaca fascicularis), each weighing 4–6 kg, were imported from Mauritius. All animals were confirmed negative for SIV, simian T-lymphotropic virus (STLV), herpes B virus, filovirus, SRV-1, SRV-2 and measles before study initiation and were housed in single cages within level 3 biosafety facilities at the Centre International de Recherches Médicales de Franceville (Franceville, Gabon). Studies were conducted in accordance with European guidelines for animal care and were approved by the CIRMF ethics committee for animal experimentation. The animals were sedated with ketamine chlorhydrate (10–15 mg/kg; Rhone-Mérieux, Lyon, France), before inoculation with the virus, blood sample collection and treatment. Female macaques were treated with a single 30 mg intramuscular injection of medroxyprogesterone acetate (Depo-provera; Pharmacia&Upjohn, St Quentin-en-Yvelines, France) 30 days before virus inoculation, to synchronize their menstrual cycles and thin the vaginal mucosa .
The vaginal vault of the animals was inoculated with 50 intravaginal AID50 (corresponding to 6 × 107 vRNA copies) of a cell-free stock of pathogenic SIVmac251 (kindly provided by A.M. Aubertin, Université Louis Pasteur, Strasbourg, France) diluted 1: 2 in human seminal fluid using a pliable French catheter . This inoculation caused no trauma.
In-vitro anti-simian immunodeficiency virus activity
Anti-SIV activities of ZDV, 3TC and IDV were evaluated in vitro on human peripheral blood mononuclear cell (PBMC). Briefly, freshly isolated PBMCs were activated for 3 days with 1 μg/ml phytohaemaglutin-P (Difco Laboratories, Detroit, Michigan, USA) and then cultivated in cell culture medium supplemented with 20 IU/ml human recombinant interleukin-2 (Roche, Meylan, France). PBMCs were treated with ZDV (0.1, 1, 10, 100 and 400 nmol/l), 3TC (0.1, 1, 10, 100 and 1000 nnmol/l), IDV (0.1, 1, 10, 100 and 1000 nnmol/l) alone or in combination (1, 10 and 100 nnmol/l of each molecule) and infected 30 min later with 360 TCID50 of SIVmac251 per 150 000 PBMC. Viral replication was assessed by quantifying RT activity in cell culture supernatants harvested 7 days after infection (RT Retrosys kit; Innovagen, Lund, Sweden). The 50, 70 and 90% effective doses (ED50, ED70 and ED90) were calculated using SoftmaxPro 4.6 software (Molecular Devices, Sunnyvale, California, USA). ED50 and ED90 of ZDV were 39 and more than 400 nmol/l, respectively, that of 3TC were 25 and 360 nmol/l, respectively, that of IDV were 3 and 81 nmol/l, respectively, and that of ZDV/3TC/IDV combination were 1.4 and 6.9 nmol/l, respectively.
Treatment of the animals
Six animals received oral ZDV (4.5 mg/kg body weight), 3TC (2.5 mg/kg) and IDV (20 mg/kg) twice daily, through a nasogastric catheter (oral group). Six macaques were given ZDV (4.5 mg/kg) and 3TC (2.5 mg/kg) subcutaneously twice daily and a higher dose of IDV (60 mg/kg), orally twice daily (subcutaneous group). Treatment was initiated 4 h after virus exposure and was continued for 4 weeks. Six macaques were treated with orally and subcutaneously administered placebo (placebo group).
Clinical, biological and virological evaluations
Plasma and cell-associated viral loads and T-lymphocyte subsets were determined as previously described [17,18]. A 1: 10 dilution of each plasma sample in calf fetal serum was assayed for the presence of SIV-specific antibodies, using a commercially available ELISA kit (Genscreen HIV 1/2 version 2; Bio-Rad Laboratories, France).
Nested PCR on lymph node mononuclear cells
Inguinal lymph nodes were collected when the animals were killed, for the detection of SIV infection. Genomic DNA was extracted from lysates of 5–10 × 106 lymphoid cells, using the DNEASY Tissue kit (Qiagen, Courtaboeuf, France) and analyzed for the presence of viral DNA. Nested PCR amplification was carried out with primers specific for SIV gag, using the outer primers GAG A: 5′-AGGTTACGGCCCGGCGGAAAGAAAA and GAG B: 5′-CCTACTCCCTGACAGGCCGTCAGCATTTCT in the first-round reaction and the inner primers GAG C: 5′-AGTACATGTTAAAACATGTAGTATGGGC and GAG F: 5′-CCTTAAGCTTTTGTAGAATCTATCTACATA in the second-round reaction. In the first-round and second-round amplifications, we used 2 U of Taq polymerase (5 U/μl; Roche Diagnostic, Meylan, France), 200 pmol of each dNTP, 200 pmol of each primer in a total volume of 100 μl. The sample was denatured by heating at 94 °C for 2 min and was then subjected to 40 cycles of 94 °C for 30 s, 55 °C for 30 s and 72 °C for 1 min. The second-round amplification was carried out using 5 μl of products from the first-round PCR and a similar cycling profile. The amplified products were analyzed by electrophoresis in 1% agarose gels.
Determination of antiretroviral drug levels
Pharmacokinetic studies were carried out on another set of animals. Four animals receiving the oral or the subcutaneous combinations were bled 15, 30, 45, 60, 120, 180 and 240 min after the first administration of the treatment. ZDV and 3TC concentrations were determined in monkey plasma using the previously described LC–MS/MS assay method [19,20]. Plasma IDV concentration was determined with a newly developed UPLC–MS/MS method. Plasma proteins were precipitated in ethanol, and UPLC (Waters) was carried out on a C18-Shield 2.1 mm × 100 mm × 1.7 μm column with a mobile phase consisting of a gradient of phase A (2 mmol/l ammonium acetate/0.1% formic acid) and phase B (0.1% formic acid in acetonitrile). The mobile phase was delivered at a rate of 0.5 ml/min, as follows: from T0 to T0.2 min, 75% A/25% B; from 0.2 to 2 min, linear gradient to 30% A; from 2 to 2.3 min, linear gradient to 0% A; from 2.3 to 2.7 min, linear gradient to 75% A; 75% A/25% B maintained until 4.5 min. Quantification was carried out by electrospray positive ionization, followed by triple quadruple MS/MS in a Quattro Premier XE (Waters). Capillary voltage reached 4 kV, cone voltage 40 and 35 V and collision energy 36 and 35 eV for methyl-IDV (internal standard) and IDV, respectively. The transitions followed were (in m/z) 628.5 → 421, 614.5 → 421.3 for methyl-IDV and IDV, respectively. With a quantification limit of 0.012 μg/ml, validation experiments showed that precision and accuracy were within the recommended ranges of about 15% (20% at the lower limit of quantification).
Statistical analysis was carried out using Stat View software (SAS Institute Inc., Cary, North Carolina, USA). In a first step, the three treatment groups were compared for the day of PVL peak, the value for PVL peak and the area under the curve of PVL (between days 28 and 170), using a nonparametric Kruskall–Wallis test for multiple group analysis. When significant, the three groups were compared one by one using a nonparametric Mann–Whitney test.
HAART protects macaques against SIVmac251 vaginal challenge
In the placebo group, all six macaques became infected with peak of viremia at day 14 after infection (median peak PVL 6.2 × 106 vRNA copies/ml) (Fig. 1a). The animals showed a rapid, severe and persistent decline in CD4 cell counts associated with AIDS. Among placebo macaques, two animals were sacrificed 125 days after infection following an acute diarrhea episode and two others were euthanized 175 days after infection subsequent to AIDS symptoms (Fig. 1d and Table 1).
In the group treated orally with ZDV/3TC/IDV combination, viral RNA remained under the quantification threshold (<60 vRNA copies/ml) and CD4 cell counts were stable in one of the six female animals (S339) (Fig. 1b and e). This animal remained seronegative and virus could not be detected by PCR in the PBMC or lymph node mononuclear cell (LNMC) (day 230 after infection) (Table 1), confirming complete protection against virus transmission. In the remaining animals of the same group, PVL peaks were significantly lower (median 2.7 × 104 vRNA copies/ml; P < 0.05) and delayed (median 21 days after infection; P < 0.05) when compared with that in controls, and a smaller decrease in CD4 cell counts was observed (nadir median at day 28 after infection 58 and 34% of baseline for the oral and placebo groups, respectively) (Fig. 1b and e). After treatment had ended, the infected animals of the oral-treated group had CD4 cell counts close to normal values and better control of viremia than the placebo group, as shown by the lower area under the curve (AUC28–170d) for PVL (oral group median 3.6 × 106 copies-day/ml versus 27.4 × 106 for placebo; P < 0.05). Corroborating the better preservation of CD4 cell count in the oral group, only two macaques of this group evolved lately toward AIDS.
In the group treated subcutaneously with ZDV/3TC and which received a triple dosage of oral IDV, four of the six animals were protected (7963, 9693, A936 and G281) as shown by persistent viremia under the quantification threshold and undetectable virus in PBMC and LNMC. No modification was observed in the CD4 cell counts and none seroconverted (Fig. 1c and f, and Table 1). The two macaques infected after intravaginal challenge and receiving subcutaneous treatment showed no detectable viremia until the end of treatment, subsequently presenting a delayed, reduced PVL peak (5.5 × 105 copies/ml at day 35 after infection and 1.7 × 105 copies/ml at day 49 after infection) (Fig. 1c). Like animals treated orally, the two infected animals treated subcutaneously presented better control of viremia than did the placebo animals (median PVL AUC28–170d 4.5 × 106 and 27.4 × 106 copies-day/ml for treated and control animals, respectively).
Pharmacokinetics of antiviral drugs could explicit difference of postexposure prophylaxis efficacy between oral and subcutaneous groups
In order to elucidate the efficiency differences of oral and subcutaneous treatment, we further determined the plasmatic drug levels in two groups of four macaques receiving the same ZDV/3TC/IDV regimens orally or subcutaneously.
Oral administration in macaques of the three-drug combination (2.5, 4.5 and 20 mg/kg for 3TC, ZDV and IDV, respectively) results in slow, weak and variable absorption (Fig. 2): mean T max and C max were 3.3 h (3–4) and 144 nmol/l (17–318) for 3TC, 2.2 h (0.7–3) and 97 nmol/l (17–195) for ZDV. Regarding IDV, two animals had plasmatic concentrations constantly under the detection threshold and two other macaques had T max and C max as 2 and 3 h and 495 and 542 nmol/l, respectively. The administration of a triple oral dose of IDV (60 mg/kg) resulted in increased C max [mean: 876 nmol/l (107–2410)]. Also, T max remained unchanged [mean 2.7 h (0.75–4)], efficient antiviral concentrations were reached as early as 30 min after treatment in 4/4 animals.
Compared with the pharmacokinetic data in humans receiving the same drugs at the same doses [mean C max and T max 6.5 μmol/l (5.7–7.8) and 0.75 h (0.5–2) for 3TC, 6.7 μmol/l (5.6–8.2) and 0.5 h (0.25–2) for ZDV, 12.5 ± 4 μmol/l and 0.8 ± 0.3 h for IDV], the absorption of antiretroviral drugs after oral administration seemed rather slow and weak in our macaque model [21–23].
Interestingly, the subcutaneous administration of 3TC and ZDV at the same dose (2.5 and 4.5 mg/kg, respectively) resulted in a better and more reproducible absorption with an early T max and a clearly increased C max [mean T max and C max 0.6 h (0.5–0.75) and 9.6 μmol/l (6.5–13) for 3TC, 0.6 h (0.5–0.75) and 1.1 μmol/l (0.8–1.4) for ZDV]. After subcutaneous injection, the plasmatic concentration of 3TC in macaque was similar to that in humans receiving the same oral dose.
Our study shows for the first time, in the macaque/SIV model of HIV infection and AIDS, that the ZDV/3TC/IDV combination may prevent infection in animals after experimental vaginal exposure to SIVmac251.
The ZDV/3TC/IDV combination protected five of the 12 animals treated after vaginal exposure, whereas the same treatment gave no protection after intravenous inoculation of the same virus [14,18]. The difference in efficacy against intravenous and intravaginal exposure is consistent with the other studies in the SIV/macaque model of HIV transmission. As shown by Zhang et al. , after the intravenous infusion of radiolabeled SIV in macaques, the circulating virus had a half-life of only 4 min and was rapidly transported to the liver, lungs and lymph nodes. It is possible that, following intravenous exposure, even if the antiretroviral drugs used have optimal pharmacokinetics, the virus may penetrate the target cells too rapidly to be blocked by the treatment. Alternatively, the initial target cells may be located in tissues inaccessible to antiviral drugs. It should also be borne in mind that ZDV and 3TC are prodrugs that require three phosphorylation steps to render them active against the viral reverse transcriptase. Defected or delayed phosphorylation in target cells may also affect the efficacy of treatment.
Although the virus can reach the target cells within a few minutes of intravenous inoculation, it must first interact with immune cells of the cervicovaginal mucosa following atraumatic vaginal inoculation, subsequently disseminating in the draining lymph nodes within 2 days and becoming detectable in the bloodstream by day 5 . These data are in favor for a larger window of opportunity for prophylaxis in individuals exposed to the virus during sexual intercourse than in individuals exposed to the virus through the blood. During this period, it may be possible to stop either the initial infection of cells or viral dissemination, by administering antiretroviral treatment.
ZDV/3TC/IDV administered orally protected one in six intravaginally inoculated macaques, whereas an optimized version of the same treatment (NRTIs administered subcutaneously and the IP administered at a triple dose) was around two-thirds effective. These results are in accordance with our pharmacokinetic data showing that, after oral administration of the ZDV/3TC/IDV combination, plasma antiretroviral drug concentrations in macaques are lower than those in human patients on the day of treatment initiation [21–23]. After subcutaneous administration in the macaque, ZDV and 3TC showed a rapid absorption and higher plasmatic concentrations associated with a much better efficiency to prevent vaginal infection. In a very recent study, Garcia-Lerma et al. showed in the same way that subcutaneous injection of tenofovir (22 mg/kg) and emtricitabine (20 mg/kg) was more effective to prevent rectal SHIV transmission than the same association administrated orally. Although the subcutaneous route is inappropriate for preexposure chemoprophylaxis or postexposure chemoprophylaxis in humans, all these data suggest to carefully consider dosage and pharmacokinetics when selecting drug combinations for PEP.
The biodistribution of antiviral drugs is also probably critical for protection . After vaginal exposure to VIH/SIV virus, we could assume that the antiretroviral drugs act mainly on the target cells of the vaginal mucosa and the adjacent tissues. As recently shown by Dumond et al. , different antiretrovial drugs display very different diffusion properties in the female genital tract. ZDV, 3TC and tenofovir concentrate in vaginal secretions, whereas protease inhibitors show genital tract concentrations lower than in plasma. Hypothesizing that antiviral drugs secreted in the vaginal lumen with high levels have also high concentrations in the surrounding cervico-vaginal tissues; ZDV, 3TC and tenofovir would be of particular interest as PrEP/PEP candidates [13,27].
In all the animals infected despite antiretroviral therapy (ART), a strong effect on viral load was observed regardless of the mode of treatment administration. In macaques treated orally, viremia remained low and peak viremia was delayed during antiviral treatment. In animals treated subcutaneously, viral load remained almost undetectable until the end of treatment. Once ART was stopped, viral load increased rapidly, suggesting that virus levels had already begun to increase before the end of treatment. In all treated animals becoming infected, the partial control of viral replication seems to be associated with the maintenance of high CD4 cell counts at least in the medium term and a lowered evolution toward AIDS. So, even if the treatment was unable to prevent infection in some animals, it had nonetheless a positive effect on the issue of the infection.
Although we have not tested resistance emergence at the end of treatment, our previous unpublished monotherapy PEP trials indicated that nonsynonymous nucleotide mutations increased in pol sequence of virus isolated from treated animals. Nevertheless, as also reported by Fournier et al. , no resistance mutations could be detected in transmitted virus. Considering these data and those of pharmacokinetics, we could suppose that the treatment failure that occurred in some animals is rather related to insufficient or late drug concentration in the initial sites of viral replication than to transmission of viruses resistant to drugs.
Postexposure prophylaxis studies in macaques are very useful for designing preventive strategies for HIV transmission in humans. Our study shows, for the first time, that one of the classical PEP treatments currently recommended in humans may prevent SIV infection after vaginal exposure, although it may not be able to prevent intravenous transmission. This study also highlights the importance for optimizing drug pharmacokinetics and the need for cautious design of prophylactic treatments.
We thank Sandrine Burton and Paul Bamba for excellent technical assistance. We also thank Christophe Joubert and the technical staff of the CEA and CIRMF for animal care.
Author's contributions: R.L.G. and O.B. conceived and designed the experiments. O.B., P.B., S.S., M.M., J.C., and F.M. performed the experiments. O.B., N.D.B., H.B., and R.L.G. analyzed the data. M.K. and H.B. contributed reagents/materials/analysis tools. O.B. and R.L.G. wrote the paper.
This work was supported by the French national AIDS agency, Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS, Paris France), EMPRO (LSH-2002-2.3.0-2), EUROPRISE European network of excellence (LSHP-CT-2006-037611) and DORMEUR foundation.
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Keywords:© 2009 Lippincott Williams & Wilkins, Inc.
antiretroviral therapy; macaque; pharmacokinetic; postexposure prophylaxis (PEP); SIV; vaginal transmission


Knowing the Wheel and Motor RPM, especially for cars with multiple gears, is very useful for determining gear ratios used around the track and ensuring the motor is run in it’s most efficient RPM range.
Two non-latching hall effect sensors are included in the eChook kit. For the pin out, google the name printed on them to find the data sheet. They will require 5V, GND and have one output. This output goes to the Motor RMP or Wheel RPM input on the eChook. No specific pin out is given here as different sensors have been used through the various eChook hardware iterations.
Positioning the sensor on the car is the more difficult part. The hall effect sensor is triggered by magnets that need to be attached to the motor shaft/wheel. The eChook kit contains 10 5mm puck magnets for this.
The tapered side of the hall effect sensor is the ‘sensing’ side. This will only pick up one pole of the magnet, so check magnet polarity! If you use the app you can watch the RMP as you wave a magnet over the sensor to determine the correct polarity - it will give a speed or RPM reading only when the polarity is correct.
Make a useful little tool - once you've identified the correct polarity, glue another magnet to a lolipop stick or similar so that it is attracted to the sensor side of the fixed magnet. You can use this tool to quickly check all your magnets are in the correct orientation.
Magnets need to be securely mounted and evenly spaced on the motor shaft and wheel, the suggested number is three on the motor shaft and 6 on the wheel. Increasing the number will give a higher resolution reading. The number of magnets used needs to be specified in the calibration.h file. Whilst not pretty, we have found electrical tape effective in securing magnets to the motor shaft, and have used 3D Printed mounts to secure magnets to the wheel.
The hall effect sensor needs to be mounted very close to the magnets, with the tapered facing them. The distance between magnets and sensor needs to be 1-3mm for the small 1x3mm disc magnets. We have used both folded sheet aluminium and 3D printed brackets to hold the hall effect sensors. Larger magnets may allow for a larger sensing gap.


Monday, May 21, 2007
Also spotted at the stunning San Francisco Maker Fair was this amazing "e-illusion" Electric Cafe/Bobber/Motard created by Illusion Motorcycles, Using a Parilla frame this a fully electric motorcycle with regenerative braking and tipping the scales at 440 lbs. It uses a PML wheelmotor HPD-30 with a peak torque-of 368 ft lbs and a battery voltage-402 volts DC with a top speed of 140 mph and 0-60 / 3 sec time. The Quality of the work was simply stunning.
Although not made by Illusion motorcycles this electric beast is looking all the the world like it came from Mad Max Beyond Thunderdome: but sadly I could not find the artist at the time to talk to him or her and get all the details.
A full set of the Maker Fair photos can be found here (Thanks to my bro M. Christian for the pics)


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Sunday, January 14, 2007
Custom Made hp charms for Michelle
Added a number of black and dark shaded beads to the black stoned round ring. Used czech beads, acrylic hearts, flat faceted square beads and oval faceted czech glass beads. It immdiately became perfect for a night of mystery and partying.