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Dispensaries typically generate a profit margin of between 10% and 30%.Dispensaries typically generate between $1 million and $4 million in annual revenue.We came to this conclusion based on a couple of key assumptions: If you are the 100% owner of your dispensary, then you can expect to earn between $100k and $1.2 million in annual income as a dispensary owner. The average dispensary can generate between $100,000 and $1.2 million in annual profit. How much profit can a dispensary generate? Average profit margin for a dispensary = 15%. ![]()
![]() CD40 ligation, resulting from interactions between CLL cells and follicular T-helper cells, induces NFκB and mTOR activation, resulting in increased expression of antiapoptotic Bcl-2 family members and resistance to apoptosis-inducing agents such as fludarabine and the Bcl-2 antagonist venetoclax ( 32–35). Malignant B cells, including CLL cells, interact with nonmalignant immune cells within the lymph node tumor microenvironment ( 31), which results in inhibition of apoptosis and induction of proliferation. CD40 functions as a costimulatory molecule on healthy B cells, and CD40 stimulation results in maturation and improved antigen-presenting function ( 30). In contrast to toxicity concerns associated with pan-CD3–based strategies, clinical trials have demonstrated the safety of Vγ9Vδ2 T cell–based immunotherapy in hematologic malignancies ( 23–25).ĬD40 is an attractive target for antibody-based antitumor strategies due to its expression on the surface of many B-cell malignancies (i.e., CLL, MM, non-Hodgkin lymphoma, Hodgkin disease, and acute lymphoblastic leukemia) and certain solid malignancies (e.g., renal cell carcinoma, breast carcinoma, melanoma, pancreatic carcinoma refs. Vγ9Vδ2 T cells have also been shown to be cytotoxic to MM and other malignant B cells ( 22). Although we have previously shown that Vγ9Vδ2 T cells can be activated by and subsequently lyse CLL cells, the cytotoxic function of CLL-derived Vγ9Vδ2 T cells is often impaired in a CLL-mediated manner ( 21). Upon activation, Vγ9Vδ2 T cells function as cytotoxic T cells that efficiently produce proinflammatory cytokines and in addition possess antigen-presenting capacity. The Vγ9Vδ2 TCR detects high expression of phosphorylated antigens in the context of butyrophilin (BTN) 3A1, which are commonly upregulated in malignant cells and can be pharmacologically increased using aminobisphosphonates ( 18–20). Vγ9Vδ2 T cells comprise 1% to 10% of peripheral blood T cells and possess a conserved T-cell receptor (TCR) that allows MHC-independent recognition of malignant cells ( 17). The use of a restricted T-cell subset with inherent antitumor properties, such as Vγ9Vδ2 T cells, may circumvent these issues. The current bispecific antibody approaches engage T cells via their CD3 antigen, which is expressed by all T cells, leading to toxicity ( 6–9) as well as the activation of regulatory T cells (Treg), thereby impeding effective T-cell responses ( 13–16). The major challenges associated with these strategies include toxicity and limited response rates (complete response rate in CLL for CAR T-cell therapy: 17%–29% for immune-checkpoint blockade: 0% refs. Current autologous T cell–based strategies include chimeric antigen receptor (CAR) T cells, immune-checkpoint blockade, and bispecific antibodies. Besides targeted therapies, T cell–based therapy represents a promising antitumor approach, specifically in B-cell malignancies ( 3, 4). It may, therefore, represent a potential candidate for the development of novel treatments for B-cell malignancies.ĭespite major improvements in the treatment of B-cell lineage malignancies such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) brought about by novel agents, long-term treatment is required, eventually eliciting toxicity and resistance ( 1, 2). Taken together, our CD40 bispecific γδ T-cell engager increased the sensitivity of leukemic cells to apoptosis and induced a potent Vγ9Vδ2 T cell–dependent antileukemic response. The CD40-bispecific γδ T-cell engager demonstrated lysis of leukemic cells by autologous Vγ9Vδ2 T cells present in patient-derived samples. ![]() Selective activation of Vγ9Vδ2 T cells in the presence of CD40 + tumor cells induced potent Vγ9Vδ2 T-cell degranulation, cytotoxicity against CLL and MM cells in vitro, and in vivo control of MM in a xenograft model. The CD40-targeting moiety of the bispecific antibody was selected because it can prevent CD40L-induced prosurvival signaling and reduce CD40-mediated resistance of CLL cells to venetoclax. Here, we describe the generation of a bispecific Vγ9Vδ2 T-cell engager directed against CD40, which, due to its overexpression and biological footprint in malignant B cells, represents an attractive target. Tumor targeting by Vγ9Vδ2 T cells, a conserved T-cell subset with potent intrinsic antitumor properties, mediated by a bispecific antibody represents a novel approach promising high efficacy with limited toxicity. Progress, however, has been hampered by low efficacy and high toxicity. Novel T cell–based therapies for the treatment of B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), are thought to have strong potential. ![]() Heavy gardening (e.g.Less Than or Equal To is an essential mathematical concept that plays a vital role in helping us compare numbers and understand their relationship.Doing exercises that use your body weight for resistance (e.g., push-ups, sit-ups).There are many ways you can strengthen your muscles, whether it’s at home or the gym. You can do activities that strengthen your muscles on the same or different days that you do aerobic activity-whatever works best for you. To gain even more benefits, do 2 or 3 sets. Try to do at least 1 set of muscle-strengthening activities. Try to do 8-12 repetitions per activity, which counts as 1 set. A repetition is one complete movement of an activity, like lifting a weight or doing a sit-up. To gain health benefits, you need to do muscle-strengthening activities to the point where it’s hard for you to do another repetition without help. Muscle-strengthening activities should be done in addition to your aerobic activity. Activities should work all the major muscle groups of your body-legs, hips, back, chest, abdomen, shoulders, and arms. Physical activities to strengthen your muscles are recommended at least 2 days a week. Want more tips on how you can add a variety of activities to your life? Check this out. Learn more about additional types of physical activity that are right for you. You need to feel comfortable doing moderate-intensity activities before you move on to more vigorous ones. If you have a history of a chronic disease, consider telling your doctor you are planning to increase your physical activity, including moving to more vigorous activity. If you haven’t been very active lately, however, increase your physical activity level slowly. Some people like to do vigorous activity because it gives them about the same health benefits in half the time. A rule of thumb is that 1 minute of vigorous-intensity activity is about the same as 2 minutes of moderate-intensity activity. You can do moderate- or vigorous-intensity aerobic activity, or a mix of the two, each week. Learn more about getting started with physical activity to improve health. If you want to do more vigorous-level activities, slowly replace those that take moderate effort like brisk walking with more vigorous activities like jogging. If you are doing moderate-intensity physical activity, such as walking or hiking, you can talk, but not sing during the activity. Here are some examples of activities that require vigorous effort: If you’re being active at a vigorous level, you won’t be able to say more than a few words without pausing for a breath. You may use the Talk Test to gauge the intensity of your aerobic physical activity. Vigorous-intensity aerobic activity means you’re breathing hard and fast, and your heart rate has gone up quite a bit. Riding a bike on level ground or with few hills.Here are some examples of activities that require moderate effort: One way to tell if it’s a moderate-intensity aerobic activity is that you’ll be able to talk, but not sing the words to your favorite song. Moderate-intensity aerobic physical activity means you’re working hard enough to raise your heart rate and break a sweat. Intensity is how hard your body is working during a physical activity. As long as you’re doing aerobic physical activities at a moderate- or vigorous-intensity, they count toward meeting the aerobic guideline. From pushing a lawn mower, to taking a dance class, to walking or biking to the store – these types of activities and more count. Aerobic activity or “cardio” gets you breathing harder and your heart beating faster. The Power of Destruction is in Your Hands! FEATURES- New Demon Battle Card Game: Fight your 9 Demons! " Now I can unleash my wraith upon the world." " You'll have to use your creativity…ruthlessly addictive." – Slide2Play “ Discovering each new element was an utter delight." – AppSafari Discover the seven deadly sins and watch as the world crumbles at your fingertips as you create thousands of dastardly deeds.Ĭombine fire, earth, wind & air to create demons, beasts, zombies. The same addictive, puzzle game play that made Doodle God a hit is back but with an evil twist. While Doodle God was busy creating the universe, Doodle Devil was also having some fun. God DLC, Doodle God Blitz - Doodle Devil DLC, Doodle God: Genesis Secrets, Doodle God Blitz - The Angel and the Imp DLC, Doodle God Blitz - Starter Pack DLC, Doodle God Blitz: Let there be light DLC, Doodle God Blitz: Doodle Kingdom DLC, Charm Tale, Adventure Hero, Varenje - Soundtrack DLC, Varenje - Full Game DLC, Trumpy Wall, Doodle God Blitz: The Necromancer`s Uprising DLC, Doodle God Blitz: The Return of the King DLC, Doodle God Blitz: Train Your Dragon DLC, Shoot'n'Scroll 3D, Jewel Tree, Doodle God Blitz: Hidden Object DLC, Doodle Farm, Mahjong Secrets, Our Worst Fears, Charm Tale 2: Mermaid Lagoon, Solitaire Mystery: Four Seasons, Doodle Creatures, Doodle TanksĪbout This Game If You Love Doodle God…Embrace Your Dark Side with Doodle Devil! Includes 46 items: Doodle God, Proto Raider, Doodle Kingdom, Doodle God: 8-bit Mania, Fiber Twig: Midnight Puzzle, Charm Tale Quest, Doodle Mafia, Doodle Devil, Solitaire Mystery: Stolen Power, Doodle God - Soundtrack, The Surprising Adventures of Munchausen, Doodle God Blitz - Greatest Inventions DLC, Chop Chop Princess!, Doodle God Blitz - The Rise of Egypt DLC, Doodle God Blitz - World of Magic DLC, Doodle God Blitz - Complete OST Collection, Doodle God: Alchemy Jam, Doodle God Blitz - Survivor DLC, Castle Secrets: Between Day and Night, Doodle God: Mighty Trio - Rocket Boost DLC, Doodle God Blitz - Save the Princess DLC, Doodle God Blitz - Devil vs. Challenging journey, Thanksgiving Day Mosaic, Trumpy Wall, Picross Fairytale - nonogram: Red Riding Hood secret, Koi Solitaire, Sakura Day Mahjong, Crystal Path, Fiber Twig 2, Dark Asylum, Mahjong Magic Journey 3, Christmas Mahjong 2, Sakura Day 2 Mahjong, Mahjong Magic Journey 2, Christmas Mahjong, Mahjong Valentine's Day, Shoot'n'Scroll 3D, Jewel Tree, Royal Roads, Gnomes Garden: Halloween, Gnomes Garden: Christmas Story, Lost Artifacts: Time Machine, Mahjong Secrets, Our Worst Fears, Solitaire Mystery: Four Seasons, Doodle Tanks, Doodle Creatures T.E.S.T: Expected Behaviour, Medieval Defenders, Castle Secrets: Between Day and Night, Doodle God: Genesis Secrets, DayD: Through time, Katy & Bob: Cake Café, Charm Tale, Adventure Hero, Varenje - Full Game DLC, Mosaics Galore. Match 2 Cards, Doodle Kingdom, Iron Sea Defenders, Day D - Ice Age, Solitaire Beach Season, Doodle God: 8-bit Mania, Fiber Twig: Midnight Puzzle, Charm Tale Quest, Mahjong Magic Journey, Katy and Bob: Safari Cafe, Katy and Bob Way Back Home, Mosaics Galore 2, Doodle Devil, Solitaire Mystery: Stolen Power, The Surprising Adventures of Munchausen, Lost Artifacts, Chop Chop Princess!, Phantom Signal. The team built several systems to enable this multiplayer gaming, all running on the Google Cloud Platform, including integrating Open Match, a highly-scalable, open source matchmaking framework cofounded by Google Cloud and Unity.Includes 59 items: Doodle God, Portal of Evil, Proto Raider, Chronicles of the Witches and Warlocks, Contract With The Devil, Gnomes Garden, Solitaire Christmas. Players can choose to host a game with up to seven friends and family via a custom invitation link OR just play with randomized players around the globe. But beware! - Opponents can intercept spirits from one another as they bring them back to homebase. After time’s up, the team that has collected the most spirit flames wins. There are even more unpredictable tricks and treats this time around-including new characters, game maps, special powers-ups, and more!Įxploring one of several spooky maps, players must collect as many wandering spirit flames as they can in two minutes and return them to their homebase. ![]() In this multiplayer interactive sequel to the 2018 Great Ghoul Duel Doodle, players around the world join a team of four to compete and collect the most wandering spirit flames before the moon is gone. This Halloween, we’re revisiting an old haunt, but with some extra flare. ![]() ![]() BOO-lieve it or not, the Great Ghoul Duel is back and spookier than ever! ![]() Objective To evaluate the outcomes and safety of a history-based screening, no-test approach to medication abortion care.ĭesign, Setting, and Participants This retrospective cohort study included patients obtaining a medication abortion without preabortion ultrasonography or pelvic examination between February 1, 2020, and January 31, 2021, at 14 independent, Planned Parenthood, academic-affiliated, and online-only clinics throughout the US.Įxposures Medications for abortion provided without preabortion ultrasonography or pelvic examination and dispensed to patients in person or by mail. However, few US-based studies have been conducted on the outcomes and safety of this novel model of care. To reduce physical contact during the COVID-19 pandemic, many clinicians stopped requiring tests before medication abortion and instead screened patients for pregnancy duration and ectopic pregnancy risk by history alone. Importance Screening for medication abortion eligibility typically includes ultrasonography or pelvic examination. Shared Decision Making and Communication. ![]()
![]() On your one day in Bologna, wander around its medieval porticoes-filled city center, climb up the Asinelli tower for great views, check out the world’s first university, and, of course attend a cooking class. The next day, wake up bright and early for another day trip, this time to Bologna. Take a day trip to Pisa, Siena, or San Gimignano, or even better opt for a full-day tour that’ll show you the best of Tuscany in one day. For the best sunset views, head to Piazzale Michelangelo.Īre you ready to explore more of Tuscany? That’s what’s up on day 7. Art lovers can’t miss the Uffizi Gallery and the David of Michelangelo. Don’t rush it, you’ll have another two full days in Florence.Ī few of the things you can’t miss in Florence are visiting the incredible Duomo and climbing up the Dome, and walking down Ponte Vecchio. ![]() On your fourth day, transfer from Rome to Florence and wander around the beautiful city center. Now, Rome doesn’t really need an introduction, right? 3 days in Rome is enough time to check out all the major attractions such as the Colosseum, the Vatican and the Sistine Chapel, and the Trevi Fountain. Start your two weeks in Italy itinerary in Rome, where you’ll spend day 1 to 3. Discover the fashion capital of Italy, Milan.Visit the charming villages by the sea at Cinque Terre.Get your art fill at the Uffizi Gallery in Florence.Go back to the gladiators’ era in Rome.This not-too-packed two weeks in Italy itinerary will show you all the highlights. Italy offers everything from charming cities, a long history, delicious food, and natural wonders. The D-Day Landing Beaches Road Trip in Normandy, FranceĪ road trip through Italy is at the top of many people’s bucket list, and it’s not difficult to understand why.Zurich to Grindelwald Road Trip, Switzerland.Catalunya & Costa Brava Road Trip from Barcelona, Spain.Eastern Europe Road Trip Through the Baltics.Slovenia Road Trip through Triglav National Park.Austria Road Trip, from Vorarlberg to Vienna.Athens to Thessaloniki Road Trip, Greece. ![]() ![]() Plus, it’s super user-friendly, and has some pretty cool features, like outdoor gear contests and forums to connect and seek advice from fellow campers, that you won’t find on any other camping app. With the largest database of campgrounds (44,000+ campsites and counting!) and over 1 million user-submitted reviews, we’re not the only ones that love this app! Our favorite campsite locating app is The Dyrt app and we personally use this to compare and book campsites in Washington. So without further ado, let’s dive in! How to find campsites in Washington We tried to include a good mix from all over the state, as well as a blend of all types of campgrounds: free, backcountry, and National or State Parks. Plus, we asked our fellow travel bloggers to share their top recommendations. We rounded up a couple of our very favorite campsites in Washington from personal experience. We even have a free map to show you where in the state each site is located. Whether you’re tent camping or road tripping in a campervan or RV, we’re sharing a list of some of the best campsites in Washington so you can see which ones fit into your itinerary. And the best way to truly explore the outdoors is by camping. Aside from simply taking in the stunning scenery, there are endless opportunities for hiking, hot springs, and other outdoor pursuits. Washington State has some of the most diverse and beautiful nature in all of the United States. With the help of our fellow travel bloggers, we’ve put together this list of the best campsites in Washington to help you plan your next trip. For fee information, check out our camping rates page.Exploring the diverse state of Washington is best done by car and camping along the way will ensure you get to spend the most time in the outdoors. Reservations can be made online or by calling (888) CAMPOUT or (888) 226-7688. For more information, visit our cabins and yurts page. Pets are allowed in cabin 62 with a $15 (plus tax) pet fee per night. Outside is a fire ring with attached grill. Each cabin has an AC outlet, ceiling fan and heating / air conditioning unit. Restrooms are nearby in the park, cabins have no plumbing and indoor cooking is prohibited. ![]() The five cabins at Potholes are located in the primitive camp area, within a short walk of the Potholes Reservoir. There is a year-round creek adjacent to the group camp that provides excellent trout and bass fishing. Facilities include a covered picnic shelter. The group camp has a grassy section and is well-shaded. ![]() The park provides a group camp that accommodates up to 50 people. There is no camping next to the reservoir.Ĭheck-out time is 1 p.m. Maximum site length is 50 feet (limited availability). But, anyone using the full-hookup sites will pay that site fee. The park has 61 standard campsites, 60 full-hookup sites, five cabins, one dump station, four restrooms (two ADA), and four showers (two ADA).Īny tent or RV may use either site type. For more information on coverage areas and hours of service and our growing list of parks with Wi-Fi service, visit our parks Wi-Fi page. PARK WI-FI SERVICEįree, high-speed Wi-Fi access is available in limited coverage areas at Potholes. The terrain is desert with freshwater marshes.Īutomated pay stations: This park is equipped with automated pay stations for visitors to purchase a one-day or annual Discover Pass and boat launch permit. This body of water is often confused with the Pothole Lakes themselves, which are a 30- to 45-minute drive from the park. Potholes State Park is a 773-acre camping park with 6,000 feet of freshwater shoreline on O'Sullivan Reservoir. Either way, you’ll have fun and learn about natural history and geology at this fascinating park. If you have a sleeping bag, eastern Washington is the place to sleep under the stars, or you can rent a cute cabin in the primitive campground. When water levels drop in August, the mud flats beckon sandpipers, stilts, plovers and curlews. Sandhill cranes and waterfowl come through in late February raptors in April sage thrasher, lark sparrow and burrowing and long-eared owls arrive in May, along with shorebirds. More into birding than fishing? Fill your field journal on a visit to the Potholes lakes and islands. Think waterskiing, kayaking and paddleboarding. But if you would rather be in the water on a hot, eastern Washington day, water sports abound. The year-round fishing at Potholes is superb, with abundant yellow perch, crappie, largemouth bass, rainbow trout and walleye. These little lakes make up half the O’Sullivan Reservoir, and Potholes State Park lies on the other side, where visitors find the lakes deeper and welcoming to boaters and fishers. A series of Ice Age flood-carved depressions in the earth, combined with the dynamics of the O’Sullivan Dam, created hundreds of tiny islands surrounded by “pothole” lakes. The Potholes are the defining geologic feature near this eastern Washington park. ![]() Just upload or email your favorite photos for Nomi to use as reference for your custom portrait painting. Portrait artist Nomi Wagner is as close as your email, phone, and mailbox and she’s here to help you. She creates portrait paintings you can enjoy, display on the walls of your home, and pass on to future generations-custom art that reminds you of what matters most in your life-the people you love! Included in your portrait commission is a stunning portrait, hand-crafted on your choice of fine art watercolor paper or canvas, any size you wish up to 30×40 inches. Nomi Wagner is here to make it happen for you. ![]() Have you dreamed of seeing a gorgeous family portrait painting on your home or office wall? Nomi loves surprises and works closely with you to create an exciting portrait painting for your celebration. Capture favorite memories in a unique Nomi Wagner portrait for your special someone. Planning a surprise gift for a birthday, anniversary, or the holidays?Ĭustom Portrait Paintings are the perfect gift. They value the time and care she takes with every detailed artwork, capturing their loving relationships, and creating luxury heirloom paintings to be treasured for generations. Nomi Wagner’s collectors know that she puts her heart and soul into each of their custom portraits. ![]() Nomi keeps in touch for feedback as she paints your one-of-a-kind personalized portrait. She is honored to be trusted with your personal memories. Wish you had commissioned the custom portrait painting of a beloved relative or pet? Nomi often paints portraits of her clients’ family members who have passed away. Portraits are shipped to clients in the United States and internationally. She hand paints your spectacular portrait in a traditional watercolor style to enhance your home and bring you comfort. Nomi has the gift to look deeply into your reference photos and bring them to life. Your custom portrait painting by artist Nomi Wagner is an original work of fine art, designed specifically for your family to enjoy. ![]() And yes, they still brew those classic Farmhouse Ales and Fruited Saisons (such as Dog Ate My Homework, a Saison with Blackberries), but also Light Lagers, Berliner Weisses, and even a new line of fruited Hard Seltzers called Things … For Your Head. Since then, their releases have more often revolved around the growth of more malt forward Northeast or Hazy IPAs that showcase use of raw spelt such as Picnic Lightning, Starfish, Supercollider, and Dig My Earth DIPA. It was later in 2016 that Brouwerij West created their first IPAs and what has become their flagship beer, Popfuji Pilsner. For instance, their mash filter can provide 98% malt efficiency, which means 30% less water use, as well as a rooftop solar array that generates more electricity than their operation uses. Taking up residence in a former World War II naval warehouse, it encompasses 26,000 square feet, with 17,000 sq ft of that devoted to an outdoor beer garden and 8,000 sq ft for the tasting room event space where they’ve hosted concerts, weddings, beer festivals, and more.Īs for the brewhouse, now housing their own specialized equipment and a much larger capacity for experimentation & growth, it embodies an approach that puts efficiency and environmental impact at the fore. This permanent location is like no other brewery you’ll visit. And this was the entirety of their beer focus until 2016, when along with Business Operations Manager David Holop, Brouwerij West created a unique new space in Mercer’s hometown of San Pedro. And yes, “Brouwerij” (pronounced brewery) is a tribute to these Belgian-inspired beginnings. ![]() In those early days, working as a nomadic or “gypsy” brewer – contract brewing his creations at other breweries across California, Mercer focused his energy on Belgian styles. It was a concept that centered on the largest percentage of what makes a beer – malt & water – to guide raw material selection and styles, to eventually inform the brewery’s current endeavors. He became enamored by the methods utilized by Belgian brewers in making authentic beers with a simple approach. The concept and brand of the brewery was founded by Brian Mercer in 2010, who was then working as an importer of Belgian Candi Sugar. What they’ve accomplished as a result of their winding route is something akin to 40 days and 40 nights of finding one’s way in the wilderness: a difficult series of trials that only make one stronger. The path taken by Brouwerij West, a San Pedro California based brewery, is unlike many you’ll find in modern American brewing. |
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