TL DR, either just explicitly state consent between both parties when "capturing" someone or instead take a game idea including hunting and capturing others where they express consent at the very start of the game then allow the fun of hunting and capturing as expressed by others to commence. Though, I think that this would be a fairly decent idea since it's fairly solid off the bat with a game idea and plot, and with what you've done now, you can use the scenery as the map for hunting/hiding, and even battling to prevent capture to capture someone! At least in my eyes, it seems like something easy to implement now with what you've done, then you can add all the good kinky stuff after. Something would probably be needed to differentiate these two though since 's an inspired idea based off of it at best and a stolen idea at worst. With the decision to play the game should also mean consent, which can also be emphasized in the game by players having to state their will to participate and consent to capture and what comes with such a thing. Much like how Bogrim did in his After School series. Like, the game is all about the main character and a group of friends playing a game, which ends in one person capturing the rest, then everything else ensues. This, in my opinion, is probably the quickest way out since you can just easily produce the game in any way, then just generate the dialogue between characters providing clear consent between both parties.Īnother idea that, in my opinion, suits a playable game more, is actually having a game in which you capture people, but everyone's in on it. maybe asking someone off the street, a friend, anyone, with a yes. Of course, however, it wouldn't really be "capture." More just like. Well, you can just outright state consent from the moment the character is captured. So what can be done to allow the capturing of characters, but also keep it consensual? Most of these games are hardcore yaoi in video game format and include CGs. These games allow the player to interact with a storyline as a male character and end up with one of the other various male characters in the game by selecting the right 'options' for their play path throughout the game. The main concern I've seen a lot from your end is the consensual part, which is entirely reasonable. Bara, Shounen-ai and Yaoi games include a range of formats yet are normally visual novel games. There's a couple ideas in here about capturing in-game characters, which then leads to some kind of master/slave, bdsm type situation. Okay so, after misunderstanding the post completely and commenting ignorantly and now returning after some thought, I think I might have some kind of solution, given that this discussion is till open
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These episodes tend to be more chronic than those of major depressive disorder and only have partial remission between episodes. while in high school) of their depressive episodes. Individuals with features of atypical depression tend to report an earlier age of onset (e.g. Ītypical depression is four times more common in females than in males. The reason for its name is twofold: it was identified with its "unique" symptoms subsequent to the identification of melancholic depression and its responses to the two different classes of antidepressants that were available at the time were different from melancholic depression (i.e., MAOIs had clinically significant benefits for atypical depression, while tricyclics did not). ĭespite its name, "atypical" depression does not mean it is uncommon or unusual. Atypical depression also often features significant weight gain or an increased appetite, hypersomnia, a heavy sensation in the limbs, and interpersonal rejection sensitivity that results in significant social or occupational impairment. In contrast to those with atypical depression, people with melancholic depression generally do not experience an improved mood in response to normally pleasurable events. Melancholic depression, anxiety disorder, bipolar disorderĪtypical depression is defined in the DSM IV as depression that shares many of the typical symptoms of major depressive disorder or dysthymia but is characterized by improved mood in response to positive events. Primary anxious, primarily vegetative īipolar disorder, anxiety disorder, female sex Low mood, mood reactivity, hyperphagia, hypersomnia, leaden paralysis, interpersonal rejection sensitivity MDSCs and TAMs were isolated from all tumor models by generating a single-cell suspension from the tumor by using collagenase I (1 mg/mL) and DNase (100 μg/mL) for 1 hour with shaking at 37☌. Tumors were utilized for studies starting at 100 mm 3 for the start-of-treatment studies and harvested at a size of 600–800 mm 3 for nontreatment studies, unless otherwise specified Cell lines Outgrowth of the tumor was monitored by length versus width measurements for solid flank tumors. RM-1 tumors were additionally implanted as an intraperitoneal tumor by injecting 1 × 10 6 cells into the intraperitoneal space and allowing to grow for 7 days. Myc-Cap tumors were implanted orthotopically in the prostate of male FVB mice at a dose of 1 × 10 5 cells per mouse. EMT6, MB49, RM-1, TRAMP-C2, and CT26 were implanted on the flank of the animals at a dose of 1 × 10 6 cells per mouse. 4T1 tumors were implanted in the mammary fat pad of female BALB/cJ mice at a dose of 1 × 10 6 cells per mouse. Unless otherwise specified, mice were housed on corn cob bedding and fed complete chow. Mice were used at 8–12 weeks of age for tumor implantation studies. Materials and MethodsīALB/cJ, FVB/NJ, and C57BL/6J mice were purchased from The Jackson Laboratory and housed in accordance with Purdue Animal Use and Care Committee guidelines. We further show that a potent folate-targeted TLR7 agonist (TLR7a) that is too toxic to administer in nontargeted form can be safely and specifically targeted to myeloid cells within the TME by conjugation to folate, resulting in reprogramming of tumor myeloid cells, abrogation of MDSC/TAM immunosuppressive activities, enhancement of T-cell infiltration, induction of antitumor activity, and significant improvement in overall survival. Herein, we demonstrate that FRβ + MDSCs and TAMs freshly isolated from the TME are the dominant immunosuppressive myeloid populations and that highly specific delivery of both imaging and therapeutic agents to these cells in the TME can be achieved with folate targeting. Given that FRβ is also localized to inflammatory sites and the TME, we initiated studies to define the functional properties of FRβ + TME-derived myeloid cells. Ongoing research by our group has shown the immediate suppressive function of MDSCs to be located within inflammatory sites and the TME ( 14). Previous studies have shown that folate receptor beta (FRβ) constitutes a marker for TAMs ( 9) and other forms of activated macrophages ( 10), however, use of this marker has focused to date on imaging of autoimmune diseases ( 11, 12), with little effort devoted to exploiting it for therapeutic applications or evaluating its association with function ( 13). In fact, to date, no diagnostic marker has been identified that distinguishes immunosuppressive from nonimmunosuppressive MDSCs or TAMs. Because all solid tumors accumulate MDSCs and TAMs, a general strategy to both identify and reprogram these cells should be broadly applied in the characterization and treatment of multiple tumors.ĭespite significant advances in MDSC and TAM biology ( 1, 7, 8), both populations are still primarily defined functionally, because antigenic markers that segregate with MDSCs and TAMs are also expressed on nonimmunosuppressive myeloid populations ( 8). The data also establish FRβ as the first marker that distinguishes immunosuppressive from nonimmunosuppressive subsets of MDSCs and TAMs. These data reveal a broadly applicable strategy across tumor types for reprogramming MDSCs and TAMs into antitumorigenic immune cells using a drug that would otherwise be too toxic to administer systemically. Delivery of a folate-targeted TLR7 agonist to these cells (i) reduced their immunosuppressive function, (ii) increased CD8 + T-cell infiltration, (iii) enhanced M1/M2 macrophage ratios, (iv) inhibited tumor growth, (v) blocked tumor metastasis, and (vi) improved overall survival without demonstrable toxicity. This FRβ + subpopulation could be selectively targeted with folate-linked drugs. Here, we explore the properties of MDSCs and TAMs from freshly isolated mouse and human tumors and find that an immunosuppressive subset of these cells can be distinguished from the nonimmunosuppressive population by its upregulation of folate receptor beta (FRβ) within the TME and its restriction to the TME. Prominent among immunosuppressive cells are myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) that inhibit T cells via release of immunosuppressive cytokines and engagement of checkpoint receptors. 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I have been feeding them my koi fish food which I ground up like powder. I had put about 200 of them in my pond, but the fish ate them. Three of them have become little frogs about the size of my little fingernail. Now, how do I keep them alive? I have about 50 of them. I didn’t want to kill them so I put them in a tote with some aeration. I saved some of the peep frog baby tadpoles that I found swimming around my pool cover when I was opening it. Take a listen to the sounds of the chorus of spring peepers here! Among them, you’ll hear the chirps of these amazing little frogs. Warm weather is almost here! If you have the chance, spend an evening outside listening to the sounds of spring. Other chorus frogs have spotted or striped markings. When it comes to looks, spring peepers are easily identified by a dark X-shaped marking across their backs. Because of their minute size, these frogs feed on small bugs like ants or small beetles. Most chorus frogs are quite small - spring peepers and Western chorus frogs will grow to a maximum of 1.5 inches, while boreal chorus frogs top out at just over an inch. Peepers especially love wooded wetlands or swampy areas near forested areas because they like to hibernate under tree bark or fallen logs. Habitat, Diet, and Other Froggy Factsīecause chorus frogs need still water to lay their eggs, you’ll find spring peepers, boreal chorus frogs and Western chorus frogs in predominately marshy areas. Scientists still aren’t sure how frozen frogs can wake up again, but once they thaw out and wake up, most frogs will go through a period of healing before they resume their normal lives. Up to 70% of the frog’s body can freeze, to the point that the heart stops pumping and the frog appears to be dead. As temperatures dip below 32 degrees, these frogs start producing their own “antifreeze” to help preserve the most essential organs. Two of these frogs are the spring peeper and the Western chorus frog. There are actually five species of frogs in North America that can freeze and survive. Not all frogs in cold climates bury themselves deeply enough to avoid freezing temperatures in the winter. Did You Know Spring Peepers Can Survive Being Frozen? The peeping sound happens as air leaves the lungs, passes over the vocal cords and into the vocal sac. To make their calls, peepers close their nostrils and mouths and squeeze their lungs, which causes the vocal sac in the throat to inflate like a balloon. This bubble is actually the frog’s vocal sac. Male Spring Peeper (Pseudacris crucifer) With vocal sac Inflated as it sings It’s not just spring peepers that can puff up their throats - many frogs can do this, but peepers are more numerous and therefore more easily spotted. If you’ve ever seen a peeper peeping, then you’ve probably noticed the peculiar bubble that seems to form under the frog’s mouth. What’s Up With the Bubble on a Frog’s Chin? Those eggs hatch in approximately 12 days. After the frogs mate, the females will lay eggs underwater. The males of this species are calling out to the females, who are drawn to their chirping suitors. That nightly chorus that you hear on warm spring nights is actually a spring peeper mating ritual. Western chorus frogs make a high pitched creaking sound, and boreal chorus frogs have a raspy chirp that sounds like the noise that you make when you run your fingernail over a fine-toothed comb. Spring peepers make a distinctive peeping noise that can sound a lot like jingling bells when there are a lot of peepers around. The easiest way is to listen to their chirping. How do you tell the difference between these frogs and regular frogs? Then there are Western and boreal chorus frogs that have a range spanning between Ohio and Arizona, and north into central Canada. In fact, spring peepers belong to a group of frogs known as “chorus frogs.” Spring peepers live in the eastern half of North America, from northern Florida up into Canada. While spring peepers, pseudacris crucifer, are the most famous of all the chirping frogs, they’re not the only species native to North America. But why do peepers peep? And are they the only frogs that sing all night long? Here are some interesting facts about this tiny frog with the big sound. If you live anywhere east of the Mississippi River, you’re probably very familiar with the sleigh bell-like sound of hundreds of these chirping frogs around swampy areas. There are unmistakable signs that spring has finally sprung-flowers blooming, the return of the robins, and the unique sound of spring peepers. Just drag the folder with your photos into the scan area. Easy photo comparisonsįind duplicate photos is a piece of cake with Duplicate Photo Cleaner. 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She's quite good, really, but my mind is other places.Mississippi Department of Archives and Historyġ973, The Optimists Daughter, Eudora Welty. The Eudora Welty Writers Symposium at Mississippi University for Women is going virtual this year, Oct. This photograph by Welty, of a home in Simpson County, reflects a folk belief that "bottle-trees" trees on whose limbs bottles have been placed will trap evil spirits that might try to get in the house. and Mississippi poet laureate Natasha Trethewey is the keynote author. This photograph, like many others taken by Welty during her work for the Works Progress Administration in the 1930s, appears in One Time, One Place: Mississippi in the Depression: A Snapshot Album (Jackson: University Press of Mississippi, 1996).Ĭenter for the Study of Southern Culture | Welty used bottle trees in her short story "Livvie," which was set near the Old Natchez Trace, a famous colonial "road" used by Indians, merchants, soldiers, and outlaws between Natchez and Nashville, Tennessee. a favorite haunt (while she was still living, that is) of Eudora Welty. Lady Gaga hits Springfield in The Simpsons season finale Lisa goes GAGA. However, two twentieth-century southern women writers often tower above the rest: Zora Neale Hurston and Eudora Welty. Padgett.Ĭopyright © 2015 The University of Mississippi English Department. 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