If its storytelling worked, "Natural Shocks" would land potently on multiple levels.
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Stand up, join in, speak out and - most potently of all - come out!
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Potently, "Incitement" depicts Amir as just one member of a self-reinforcing fringe.
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The bites that contained peppers were potently hot, while those that didn't were decidedly not.
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Workplace unity, despite differences, is an ideal which comes across rather potently in the movie.
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But having the "old" campaign chief doing that doesn't fit the most potently persuasive narrative.
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Namely, we know that CBD interacts with an enzyme system in the liver particularly potently.
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I would consider them to be nerve agents that selectively and very potently engage pain nerves.
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What emerges is a potently ambiguous sound world that conveys human warmth and chill in equal measure.
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The film is brief, at eighty minutes, and all the more potently wrathful for being so restrained.
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Some have theorized that the juniper berries in gin combine potently with a substance in the raisins.
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Russia's interest, post-1990, was in the dismemberment of the European-American bond, most potently expressed in NATO.
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So, these days, the anti-Enlightenment view is countered most potently by a set of parallel popular enthusiasms.
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GIOVANNI RUSSONELLO A tremendously infectious, potently throbbing, deliriously up-tempo song that blends mellow hyphy and mellow crunk.
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A flag is a potent symbol, and the act of altering or defacing one is itself potently symbolic.
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"Artificial sweeteners bind the sweet taste receptor hundreds to thousands of times more potently than sugar itself," Ludwig says.
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Those who know this music well, of course, knew they'd linked previously and potently a handful of times already.
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She puns with gusto, potently and unabashedly, until one begins reading double meanings, allusions and ulterior motives into everything.
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Eccentric contractions involve lengthening a muscle while contracting it and are known to potently build muscle strength and size.
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The thirteen months that Davis spent in Paris, starting in 1928, yielded flattened, potently charming cityscapes in toothsome colors.
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Most potently, Snap added fewer users and made less in ad revenue than expected, citing the redesign as a culprit.
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More potently, Metro again embraces his nearly avant-garde production side to properly convey the bleakness of 21's world.
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And it could be potently destabilizing in a world where nations' nuclear doctrines are shaped more by posture than by policy.
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Their aspirations for the future are a potently practical reminder of existence outside a cage and a future free from bondage.
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Inspired by neoclassical sculpture, this composition of two lovers resting in each other's arms is potently political as well as unapologetically romantic.
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There's an autobiographical component to Mr. Acconci's plainly but potently worded monologues: When he's breaking up with a girlfriend, names are named.
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"That may be a benefit to addicted adult smokers, but it also makes it potently addictive to nicotine-naive teenagers," Jackler said.
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But it was also the most puzzling: Why was an immune-response region so potently shaping the risk of a mental illness?
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Now it appears the Trump administration could throw its weight into the case or, even more potently, launch its own lawsuit against university policies.
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But it was Michelle Obama who most potently delivered on this theme, which may be why her speech served as the night's emotional highpoint.
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But in the best cases they offer a chance to find potently timely surprises in works that seemed to live only in one era.
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As the virus makes its way into dozens of countries, the economic shockwaves will still flow most potently from what is happening in China.
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James can be figurative in one painting and, in another, rub a surface with paint, make a palpable, potently suggestive smear on the surface.
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With skin slaked with enough of the potently neurotoxic batrachotoxin (BTX) to kill a staggering 20,000 mice, the golden poison frog somehow doesn't poison itself.
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Frank Bruni Watching the Democrats' smoothly staged, potently scripted convention last week, voters could easily think that Hillary Clinton has this election in the bag.
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Again, the designer — here, Mr. Taylor's long-term colleague Santo Loquasto — has provided much more vitality than the choreography, as does Ibert's potently colorful music.
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And you feel it very potently sitting here in between the USS Arizona and the USS Missouri where the Japanese signed their surrender on the deck.
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Mercury is still potently dangerous through indirect exposure -- children and infants were poisoned simply by interacting with family members who had used the mercury-tainted cream.
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Mr. Andrianomearisoa said that combining fabrics that has been made in different countries was potently symbolic, and showed that beautiful things could emerge from cross-cultural exchange.
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Evins noted, however, that kids absorb synthetic, cannabis-based drugs like dronabinol*, which helps tamp down nausea and vomiting caused by chemotherapy, more potently than adults do, too.
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But it's Graham as a speaker that Move most potently embodies, delivering that great choreographer's grand pronouncements, boasts and digs in a girlish voice that hides sharp teeth.
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The fact that we don't know which drugs CBD could interact with most potently is a major issue, especially given its frequent popular use in conjunction with other medications.
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As she did so potently in Hugo Blick's marvelous 2014 mini-series, "The Honorable Woman," Gyllenhaal forces us to search her face for clues to motives left purposely unarticulated.
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"Someone You Loved," which is at the peak of its reign, is pleasant enough and potently effective — emotionally abusive piano, resonant singing, a swell that could cause a tsunami.
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Do yourself a favor and kick off the holiday TV season not with heavy drama or days-long binges, but with Netflix's potently excellent Astronomy Club: The Sketch Show.
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The music — "Immerse," by Nils Frahm — abounded in subdued hints of tango; Ms. Ferri showed her characteristic blend of bravery and adult vulnerability; Mr. Cornejo's grace and chivalry registered potently.
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The difference comes from the music: Mr. Shchedrin's score — engaging kitsch, potently conducted here by Alexei Repnikov — is a robust romp, whereas Stravinsky's score is a masterpiece of poetic ambiguity.
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Rarely have I seen fury and sadness and residual love so potently brewed as in Irene Poole's blistering performance here, under the direction of Martha Henry, a noted Shakespearean herself.
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"Tales" has always sat so comfortably and so potently in both lanes, and it's what gave it the impact that it had in '93 and why those books are so important.
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Although I can't help wishing the two stories had worked together more potently, that doesn't detract from the deep emotional impact of "The Great Believers," nor does it diminish Makkai's accomplishment.
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But Louis has written elsewhere, potently and with great alarm, about the rise of the right in Europe, and the left's complicity through its failure to address fundamental problems of class.
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The overarching narrative of La La Land, as parroted at last night's awards (and only slightly less potently throughout its press tour), is that it's a wonder the film was ever made.
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These remained pure-dance creations, with ingeniously inventive choreography, but their music, costumes and décor made them potently theatrical: Each had a strong atmosphere in which visual effects and music made contributions.
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There are only six characters total in Lewiston/Clarkston (not counting the fellow patrons I shared a meal with), and they are some of the most potently developed I saw onstage in 2018.
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Boundary-pushing in its day, the play still has plenty to say — about tyranny and greed and corruption, sure, but more potently about our culture's long history of race-based violence and degradation.
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Some are so potently calming that, if you pound them back fast enough, instead of getting the shakes there's a good chance you slip into what some tea aficionados refer to as tea drunkenness.
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A brilliant little play in itself, "Exorcise" is as wrenching a portrait of moral gridlock as anything in Arthur Miller, as weirdly lyrical as Tennessee Williams and as potently heightened as Suzan-Lori Parks.
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It stomps on the empathy you'd been encouraged to extend to Eminem, who's long rapped potently about battling his personal demons, making it unclear if you've been commiserating with a sociopath the whole time.
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Such gruesome tragedy is unlikely material for a holiday show, let alone one as delicate, haunting and winsomely comic as "Burning Bluebeard," a play that has become a potently enchanting annual tradition in Chicago.
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This decline has been en route for a dozen years, according to the Freedom House monitors, and there have been moments of progression when some countries have seen their democratic forces return, at times potently.
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"That may be a benefit to addicted adult smokers, but it also makes it potently addictive to nicotine-naive teenagers," Dr. Robert Jackler, founder of Stanford Research into the Impact of Tobacco Advertising, previously told CNN.
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But a new study co-authored by Myburgh and published Monday found one compound that could be used to develop a type of drug to tackle all three diseases more potently, and with fewer side effects.
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The composer Laura Schwendinger and the librettist Ginger Strand achieve something similar in their potently claustrophobic opera "Artemisia," which received its staged premiere at Trinity Wall Street's St. Paul's Chapel on Thursday (and repeats on Saturday).
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Bell could not say precisely how pollution from fires might affect a person's health differently -- or more potently -- than pollution from cars, say, or factories, only that the chemical interaction with the human body would be unique.
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Even though these early sequences are beautifully filmed, with differing aspect ratios and palettes and a sensitive performance by Juan Minujin as young Jorge, what could be an intense, potently distilled argument becomes a hybridized Francis biopic.
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First, allow me to apologize for being forced to string together some of the dullest words in the English language, as few industries manage to deaden the soul and glaze over the eyes as potently as business consulting.
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"That may be a benefit to addicted adult smokers, but it also makes it potently addictive to nicotine-naive teenagers," study author Dr. Robert Jackler, founder of Stanford Research into the Impact of Tobacco Advertising, previously told CNN.
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She has always aroused a quasi-aesthetic repulsion within the metropolitan class; and, indeed, it is that continued detestation of what Jonathan Miller in the 1980s sneeringly called "her odious suburban gentility" that most potently keeps her memory alive.
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Image: Dave LonsdaleLast Friday Harding Stowe, the owner of Brooklyn Kava, stopped by the Gizmodo offices to offer us a sample of kava tea—a tea so potently relaxing people have been said to have driven off roads after drinking it.
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Mr. Vuong can create startling images (a black piano in a field, a wedding-cake couple preserved under glass, a shepherd stepping out of a Caravaggio painting) and make the silences and elisions in his verse speak as potently as his words.
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There are multitudes in Okja—for my money, the best science fiction film of the year—beyond even the oddly touching girl-and-her-superpig buddy story, or the dark, electric sendup of corporate conniving, or the potently earnest takedown of the industrial meat complex.
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The argument that the public should think of the effect on children before granting gay people basic human rights was most potently spearheaded by Anita Bryant, a Christian singer best known for her successful repeal of a 1977 Miami ordinance that barred anti-gay discrimination.
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The most potently delivered has been one of the non-Taylor works: the Dayton Contemporary Dance Company's account of Donald McKayle's "Rainbow 'Round My Shoulder" (1959), which had its first Taylor's American Modern Dance performance on Tuesday, at the start of the season's second week.
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By weaponizing and politicizing a medium so typically associated with the 'feminine,' one that is in and of itself intricately linked to the storied Mexican textile tradition of elaborate embroidery and needlework, these collectives potently condemn Mexican impunity while lending a voice to the silenced.
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It's the first lady, Michelle Obama, who has delivered the two most powerful speeches of the general election: the rousing pep talk at the Democratic National Convention and, perhaps even more potently, her excoriation of Donald Trump's sexism during a speech in New Hampshire last Thursday.
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Haim (it rhymes with time), emerged in 2013 with the critical favorite "Days Are Gone," and quickly made its name as a potently dreamy, hooky California group, with a Hollywood-worthy back story — the sisters started performing as children, in a family act with their parents.
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" On "Aeroplane," she potently captures the heavy beauty of the middle-of-the-night silence of a city as she draws listeners breath-close with lines like "The roses that you came with sure did have a thorn or two / But still this blood runs blue.
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As legendary scribe George Kimball once said of Patterson, he was "the owner of the uneasiest head to wear a crown this side of Henry IV." Floyd was successful despite his insecurity about himself and compassion towards others—two things that generally don't mix potently inside a boxing ring.
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As much as music can be, and is, a source of escapism and joy, so it is also an art form that can galvanize—it communicates in a way that can cut through color and creed, spreading a message more potently and swiftly than a painting or poem.
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Art or not then, all of these collectives, by weaponizing and politicizing a medium so typically associated with the 'feminine,' one that is in and of itself intricately linked to the storied Mexican textile tradition of elaborate embroidery and needlework, potently condemn Mexican impunity while lending a voice to the silenced.
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In the end, nothing that Rodrigues says resonates as deeply as Inoue's terrifying, teasing whine, which conveys the larger cultural and political stakes; nothing imparts the mystery of creation as potently as the flicker of a darting emerald lizard or an eerie parade of cats prowling through a spookily deserted village.
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While her sections about cancer offer unruly testimonies to sickness and dying (and, frankly, living), it's in the sections about Lessing where Diski's idiosyncratic mind — and her bravery as a human confronting both imminent obliteration as well as certain vexing questions that, years later, she's still rolling around in her head — is most potently on display.
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And this, I think, was brought out by a variety of writers, but most potently by Adam Serwer in the Atlantic, in his long piece on race and racism in the 22014 election, which is that a certain portion of the electorate voted the way they voted precisely to express a kind of racialism or racism.
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The DJs from South Africa's Gauteng Province revel in Muajva's first release in a long time with "Sgubhu Dance," an adrenalized cut from the EP. Paired potently with piercing snare syncopation, the song's melody is a raw, very-distant relative from the main riff from "Kernkraft 400," and you can easily imagine it chanted in a soccer arena.
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We'll be learning more in the hours and days to come, including just how potently homophobia in particular factored into his actions, how much ideological influence the Islamic State or other extremists had, how extensive his planning was, how far back he began plotting this, and how much he knew about Pulse itself and the specific composition of its crowd on different nights of the week.
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" That melody does not stay with a viewer as potently as the deadpan relationship advice declaimed in a halting, automated voice on an app that the actors download to help them understand sex in Germany: "The clitoris is very sensitive in Germany; in Germany, men and women satisfy themselves; be careful not to hurt yourself in Germany; people do not show emotions in Germany.
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Among many anthocyanidins studied, cyanidin most potently stimulated activity of the sirtuin 6 enzyme.
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The neuronal Kv1.1 channel and the T lymphocyte Kv1.3 channel are most potently inhibited by ShK.
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This flower works well cut in floral arrangements. Beekeepers sometimes use the Canterbury Bell for making potently sweet honey.
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3-MMC is a monoamine transporter substrate that potently inhibits norepinephrine uptake and displays more pronounced dopaminergic vs. serotonergic activity.
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Kava extract has been shown to potently inhibit a wide range of hepatic enzymes, suggesting a very high potential for interactions with many pharmaceuticals and herbal medications.
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The substance potently inhibits Src and Bcr-Abl kinases including many common imatinib-resistant Bcr-Abl mutations. AP23464 does not inhibit the T315I mutation, however, whereas ponatinib does.
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The triazole group coordinates with the heme group (Fe2+) at the active binding site of the aromatase enzyme and potently inhibits the hydroxylation that aromatase is responsible for .
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3β-HSD is potently inhibited by azastene, cyanoketone, epostane, and trilostane. Medroxyprogesterone acetate and medrogestone are weak inhibitors of 3β-HSD which may substantially inhibit it at high dosages.
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A. carneus produces other cytotoxic compounds, including sterigmatocystin, isopropylchaetominine and asteltoxin E, which are potently active against the mouse lymphoma cell line L5178Y and may have therapeutic potential as anti-cancer agents.
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Mohamad et al. (2005) found that the curcuminoids 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one, demethoxycurcumin, and 16-hydroxylabda-8(17),11,13-trien-15,16-olide inhibit lipid peroxidation more potently than does alpha-tocopherol.
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LXA4, LXB4, AT-LXA4, and AT-LXB4 are specialized proresolving mediators, i.e. they potently inhibit the progression and contribute to the resolution of diverse inflammatory and allergic reactions (see specialized proresolving mediators#lipoxins and Lipoxins).
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10R,17S-dihydroxy-7Z,11E,13E,15Z,19Z-docosapentaenoic acid (10R,17S-diHDPAEEZ) has been found in inflamed exudates of animal models and possesses in vitro and in vivo anti-inflammatory activity almost as potently as PD1.
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Amphetamines, including amphetamine, methamphetamine, MDMA, cathinone, methcathinone, mephedrone, and methylone, are all DRIs as well, but are distinct in that they also behave, and potentially more potently as dopamine releasing agents (DRAs) (due to Yerkes–Dodson's law, 'more potently stimulated' may not equal more optimally functionally stimulated). There are very distinct differences in the mode of action between dopamine releasers/substrates & dopamine re-uptake inhibitors; the former are functionally entropy-driven (i.e. relating to hydrophobicity) and the latter are enthalpy-driven (i.e. relating conformational change).. Page 928 (4th of article) 1st paragraph.
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Esketamine inhibits the dopamine transporter about 8-fold more potently than does arketamine, and so is about 8 times more potent as a dopamine reuptake inhibitor. Arketamine and esketamine possess similar potency for interaction with the muscarinic acetylcholine receptors.
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Glycogenolysis is regulated hormonally in response to blood sugar levels by glucagon and insulin, and stimulated by epinephrine during the fight-or-flight response. Insulin potently inhibits glycogenolysis. In myocytes, glycogen degradation may also be stimulated by neural signals.
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Tricin is a chemical compound. It is an O-methylated flavone, a type of flavonoid. It can be found in rice branThe rice bran constituent tricin potently inhibits cyclooxygenase enzymes and interferes with intestinal carcinogenesis in ApcMin mice and sugarcane.
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Purpurogallin is an orange-red, crystalline compound, and the aglycone of several glycosides from nutgalls and oak barks. It can inhibit 2-hydroxy and 4-hydroxyestradiol methylation by catechol-O-methyltransferase. It potently and specifically inhibits TLR1/TLR2 activation pathway.
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Strychnine may be introduced into the body orally, by inhalation, or by injection. It is a potently bitter substance, and in humans has been shown to activate bitter taste receptors TAS2R10 and TAS2R46. Strychnine is rapidly absorbed from the gastrointestinal tract.
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KN-62 is a derivative of isoquinolinesulfonamide, it is a selective, specific and cell permeable inhibitor of Ca2+/calmodulin-dependent kinase type II (CaMK II) with IC50 of 900nM, charactered by hydrophobicity. KN-62 also potently inhibits the purinergic receptor P2X7.
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Nocodazole stimulates the expression of LATS2 which potently inhibits the Wnt signaling pathway by abrogating the interaction between the Wnt-dependent transcriptional co-factors beta-catenin and BCL9. It is related to mebendazole by replacement of the left most benzene ring by thiophene.
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The assembly process includes a Diels-Alder reaction to give the fully protected eldecalcitol. In order to get the parent molecule, the hydroxyl groups have to be deprotected. The chemistry of eldecalcitol allows for its binding 2.7-fold more potently than calcitriol.
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KLF2 is a negative regulator of adipocyte differentiation. KLF2 is expressed in preadipocytes, but not mature adipocytes, and it potently inhibits PPAR-γ (peroxisome proliferator-activated receptor-γ) expression by inhibiting promoter activity. This prevents differentiation of preadipocytes into adipocytes, and thus prevents adipogenesis.
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Biguanides were first noted to be active against influenza in the 1940s. Further studies confirmed their antiviral activity in vitro. Buformin, especially, was potently antiviral against vaccinia and influenza. Buformin is a metabolic antiviral that inhibits the mTOR pathway which the influenza virus uses to infect an animal.
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Glial cell-derived neurotrophic factor (GDNF) is a protein that, in humans, is encoded by the GDNF gene. GDNF is a small protein that potently promotes the survival of many types of neurons. It signals through GFRα receptors, particularly GFRα1. It is also responsible for the determination of spermatogonia into primary spermatocytes i.e.
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All species of Ureaplasma appear as gram-negative bacteria that utilize the hydrolysis or urea to produce energy for growth. Products of urea hydrolysis include carbon dioxide and ammonia. This reaction is coordinated by the enzyme urease, which Ureaplasma species potently secrete. Unlike most microorganisms, species of Ureaplasma lack a cell wall.
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As of 2017, CBC is under laboratory research to identify its possible pharmacological properties. No in vivo human studies exist as of 2019. In vitro, CBC is not active at CB1 or CB2 receptors, but is an agonist of TRPA1 and less potently, an agonist of TRPV3 and TRPV4. CBC has two stereoisomers.
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The expression of this protease has been associated with breast, colon, prostate, and ovarian tumors, which implicates its role in cancer invasion, and metastasis. Matriptase and HAI expression are frequently dysregulated in human cancer, and matriptase expression that is unopposed by HAI-1 potently promotes carcinogenesis and metastatic dissemination in animal models.
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Despite having only 4 out of 11 amino acids in common, both the porcine and human fungicidal peptide on MSMB's C-terminus are potently fungicidal in the absence of calcium ions. The protein inhibits growth of cancer cells in an experimental model of prostate cancer, though this property is cell line specific.
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Sirt6 deacetylation activity can be stimulated by high concentrations (several hundred micromolar) of fatty acids, and more potently by a first series of synthetic activators based on a pyrrolo[1,2-a]quinoxaline scaffold. Crystal structures of Sirt6/activator complexes show that the compounds exploit a SIRT6 specific pocket in the enzyme's substrate acyl binding channel.
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Since physical exercise induces temporary spikes of ROS, this may explain why physical exercise is beneficial for cancer patient prognosis. Moreover, high inducers of ROS such as 2-deoxy- D-glucose and carbohydrate-based inducers of cellular stress induce cancer cell death more potently because they exploit the cancer cell's high avidity for sugars.
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NAN-190 is a drug and research chemical widely used in scientific studies. It was previously believed to act as a selective 5-HT1A receptor antagonist, but a subsequent discovery showed that it also potently blocks the α2-adrenergic receptor. The new finding has raised significant concerns about studies using NAN-190 as a specific serotonin receptor antagonist.
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Morales, R., Buytaert-Hoefen, K.A., Gonzalez-Romero, D., Castilla, J., Hansen, E.T., Hlavinka, D., Goodrich, R.P. and Soto, C. (2008) Reduction of prion infectivity in packed red blood cells. Biochem.Biophys.Res.Commun., 377, 373-378.Orem, N.R., Geoghegan, J.C., Deleault, N.R., Kascsak, R. and Supattapone, S. (2006) Copper (II) ions potently inhibit purified PrPres amplification. J Neurochem 96, 1409-1415.
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Wortmannin is a commonly used cell biology reagent that has been used previously in research to inhibit DNA repair, receptor-mediated endocytosis and cell proliferation.Liu Y, Shreder KR, Gai W, Corral S, Ferris DK, Rosenblum JS. Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase. Chem Biol. 2005;12:99–107.
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The combination of these two features could provide a novel mechanism for treating colon cancer. Steamed American ginseng extract has been reported to "potently kill colorectal cancer cells". Specifically, derivatives of protopanaxadiol Rg3 and Rh2, are the key ginsenosides found in the extract. In colorectal cancer cell lines, HCT116, cytosolic vacuolization has been induced by Rh2.
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In molecular biology, ecotin is a protease inhibitor which belongs to MEROPS inhibitor family I11, clan IN. Ecotins are dimeric periplasmic proteins from Escherichia coli and related Gram-negative bacteria that have been shown to be potent inhibitors of many trypsin-fold serine proteases of widely varying substrate specificity, which belong to MEROPS peptidase family S1. Phylogenetic analysis suggested that ecotin has an exogenous target, possibly neutrophil elastase. Ecotin from E. coli, Yersinia pestis, and Pseudomonas aeruginosa, all species that encounter the mammalian immune system, inhibit neutrophil elastase strongly while ecotin from the plant pathogen Pantoea citrea inhibits neutrophil elastase 1000-fold less potently. Ecotins all potently inhibit pancreatic digestive peptidases trypsin and chymotrypsin, while showing more variable inhibition of the blood peptidases Factor Xa, thrombin, and urokinase-type plasminogen activator.
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However, the production of carcinogenic nitrosamines can be potently inhibited by the use of the antioxidants Vitamin C and the alpha-tocopherol form of Vitamin E during curing. A 2007 study by Columbia University suggests a link between eating cured meats and chronic obstructive pulmonary disease. Nitrites were posited as a possible cause. The use of either compound is carefully regulated.
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While lack of VEGF-C results in lymphedema, VEGF-C production is implicated in tumor lymphangiogenesis and metastasis. Expression of VEGF-C by tumors induces peri-tumoral and intratumoral lymphangiogenesis what potently promotes metastatic dissemination of tumor cells. VEGF-C primarily stimulates lymphangiogenesis by activating VEGFR-3, yet under certain conditions it can also act directly on blood vessels to promote tumor angiogenesis.
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In an in vitro mixed culture system, 5-(S)-HETE is released by monocytes to stimulate, at sub-nanomolar concentrations, osteoclast-dependent bone reabsorption. It also inhibits morphogenetic protein-2 (BMP-2)-induced bone- like nodule formation in mouse calvarial organ cultures. These results allow that 5-(S)-HETE and perhaps more potently, 5-oxo-ETE contribute to the regulation of bone remodeling.
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When oxygen is bound to hemocyanin, the molecule takes on a distinctive transparent, opalescent blue color, due to the Cu2+ state of the copper. In the absence of oxygen, the bound copper is found as Cu1+ and hemocyanin is colorless. The KLH protein is potently immunogenic, but does not cause an adverse immune response in humans. It is therefore highly prized as a vaccine carrier protein.
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The mechanism behind this inhibition is still unknown. Thirdly, kalkitoxin blocks the electron transport chain (ETC) complex 1, one of the protein complexes involved in mitochondrial respiration. By blocking the ETC complex 1, kalkitoxin potently inhibits hypoxia-inducible factor-1 (HIF-1) activation. HIF-1 is a transcription factor, which enhances the expression of genes that increase oxygen availability, as well as genes that decrease oxygen consumption.
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Bile acid diarrhea (also called bile acid malabsorption) can be secondary to Crohn's disease or be a primary condition. Reduced median levels of FGF19, an ileal hormone that regulates increased hepatic bile acid synthesis, have been found in this condition. FGF19 is potently stimulated by bile acids and especially by OCA. A proof of concept study of OCA (25 mg/d) has shown clinical and biochemical benefit.
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Interleukin 33 (IL-33) is a protein that in humans is encoded by the IL33 gene. Interleukin 33 is a member of the IL-1 family that potently drives production of T helper-2 (Th2)-associated cytokines (e.g., IL-4). IL33 is a ligand for ST2 (IL1RL1), an IL-1 family receptor that is highly expressed on Th2 cells, mast cells and group 2 innate lymphocytes.
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The atmosphere is one of hushed disclosure: the music implies more than it says. What emerges is a potently ambiguous sound world that conveys human warmth and chill in equal measure. Above all, it is a transparent medium in which singing actors can speak instead of shout." Heidi Waleson described Spears' compositional style in her Wall Street Journal review of the opera O Columbia: "Mr.
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PRX-07034 is a selective 5-HT6 receptor antagonist. It has cognition and memory-enhancing properties and potently decreases food intake and body weight in rodents. PRX-07034 was under development by Epix Pharmaceuticals for the treatment of obesity and cognitive impairment associated with Alzheimer's disease and schizophrenia but upon the company collapsing due to lack of funds the compound was auctioned to another corporation.
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A range of primates rub millipedes onto their fur and skin; millipedes contain benzoquinones, compounds known to be potently repellent to insects. Tufted capuchins (Cebus apella) rub various parts of their body with carpenter ants (Camponotus rufipes) or allow the ants to crawl over them, in a behaviour called anting. The capuchins often combine anting with urinating into their hands and mixing the ants with the urine.
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In addition, Artesunate potently inhibits the essential Plasmodium falciparum exported protein 1 (EXP1), a membrane glutathione S-transferase. As a result, the amount of glutathione in the parasite is reduced. In 2016, artemisinin has been shown to bind to a large number targets, suggesting that it acts in a promiscuous manner. There is evidence suggesting DHA inhibition of calcium-dependent ATPase on endoplasmic membrane, which disrupts protein folding of parasites.
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MCD peptide has immunotoxic as well as neurotoxic properties due to different active sites of the MCD peptide. The MCD peptide has an immunotoxic effect on mast cells by releasing histamine from these cells. MCD peptide has also been described as a potent modulator of voltage-gated ionic channels. It binds to several subclasses of voltage-gated potassium channels (Kv channels), including Kv1.1, Kv1.6, and less potently to Kv1.2.
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Capeserod (INN; development code SL65.0155) is a selective 5-HT4 receptor partial agonist with Ki = 0.6 nM and IA = 40–50% (relative to serotonin). It potently enhances cognition, learning, and memory, and also possesses antidepressant effects. Capeserod was in phase II clinical trials around 2004–2006 for the treatment of memory deficits and dementia but no new information has surfaced since and it appears to have been abandoned.
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This situation was further aggravated by patriarchal practices which gave girls no traditional rights to succession. Therefore, the same patriarchal practices encouraged preference to be given to the education of a boy rather than a girl. The Nigerian society (both historical and contemporary) has been dotted with peculiar cultural practices that are potently hurtful to women's emancipation, such as early/forced marriage, wife-inheritance and widowhood practices.Nmadu, T. (2000).
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Like 7,8-DHF, administration of R7 has been found to activate the TrkB in vivo in the mouse brain. Moreover, R7 was found to potently activate the TrkB and the downstream Akt signaling pathway upon oral administration, an action that was tightly correlated with plasma concentrations of 7,8-DHF. As such, R7 has shown in vivo efficacy as an agonist of the TrkB, including central activity, similarly to 7,8-DHF.
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Most intriguingly, a recent study identified that TNF-induced canonical signalling subverts non-canonical RelB:p52 activity in the inflamed lymphoid tissues limiting lymphocyte ingress. Mechanistically, TNF inactivated NIK in LTβR‐stimulated cells and induced the synthesis of Nfkb2 mRNA encoding p100; these together potently accumulated unprocessed p100, which attenuated the RelB activity. A role of p100/Nfkb2 in dictating lymphocyte ingress in the inflamed lymphoid tissue may have broad physiological implications.
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The muscarinic M3 receptor regulates insulin secretion from the pancreas and are an important target for understanding the mechanisms of type 2 diabetes mellitus. Some antipsychotic drugs that are prescribed to treat schizophrenia and bipolar disorder (such as olanzapine and clozapine) have a high risk of diabetes side-effects. These drugs potently bind to and block the muscarinic M3 receptor, which causes insulin dysregulation that may precede diabetes.
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Endostatin is a 20 kDa fragment of collagen XVIII. The major role of endostatin is in its ability to potently inhibit endothelial cell migration and induce apoptosis. These effects are mediated by interacting and interfering with various angiogenic related proteins such as integrins and serine/threonine-specific protein kinases. Numerous studies have demonstrated that tropoelastin, the soluble precursor of elastin, or proteolytic elastin fragments have diverse biological properties.
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U46619 is a stable synthetic analog of the endoperoxide prostaglandin PGH2 first prepared in 1975, and acts as a thromboxane A2 (TP) receptor agonist. It potently stimulates TP receptor-mediated, but not other prostaglandin receptor-mediated responses in various in vitro preparations. and exhibits many properties similar to thromboxane A2, including shape change and aggregation of platelets and smooth muscle contraction. U46619 is a vasoconstrictor that mimics the hydroosmotic effect of vasopressin.
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Prokineticin is a secreted protein that potently contracts gastrointestinal smooth muscle. Recently, prokineticins have been recognized in humans and other vertebrates. They are thought to be involved in several important physiological processes like neurogenesis, tissue development, angiogenesis, and nociception. Other important physiological roles the Bv8/Prokineticins (PKs) are involved in may include cancer, reproduction, and regulating physiological functions that influence circadian rhythms like hormone secretion, ingestive behaviors, and the sleep/wake cycle.
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INH1 controls the biological activity of Hec1/Nek2 mitotic pathway. It specifically disrupts the Hec1/Nek2 interaction by directly binding to Hec1, resulting in defective Hec1 kinetochores localization and low-level cellular Nek2 protein. INH1 induces a transient mitotic arrest, exhibiting metaphase chromosome misalignment, spindle abnormality, and consequently cancer cell apoptosis. Experiments show that INH1 potently inhibits the proliferation of multiple human breast cancer cell lines, cervical HeLa cells, and colon cancer cells in vitro.
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During his tenure as commander-in-chief in the Caucasus, Yermolov (by that time promoted to the rank of full artillery general) was responsible for robust Russian military policies in Caucasus, where his name became a byword for brutality. In a reply to the outraged Alexander I, he wrote, "I desire that the terror of my name shall guard our frontiers more potently than chains or fortresses."Lesley Blanch The Sabres of Paradis; p.
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BMP-2 like other bone morphogenetic proteins, plays an important role in the development of bone and cartilage. It is involved in the hedgehog pathway, TGF beta signaling pathway, and in cytokine-cytokine receptor interaction. It is also involved in cardiac cell differentiation and epithelial to mesenchymal transition. Like many other proteins from the BMP family, BMP-2 has been demonstrated to potently induce osteoblast differentiation in a variety of cell types.
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Finasteride inhibits two 5α-reductase isoenzymes (II and III), while dutasteride inhibits all three. Finasteride potently inhibits 5α-R2 at a mean inhibitory concentration IC50 of 69 nM, but is less effective with 5α-R1 till an IC50 of 360 nM. Finasteride decreases mean serum level of DHT by 71% after 6 months, and was shown in vitro to inhibit 5α-R3 at a similar potency to 5α-R2 in transfected cell lines.
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Dideoxyverticillin A, also known as (+)-11,11’-dideoxyverticillin A, is a complex epipolythiodioxopiperazine initially isolated from the marine fungus Penicillium sp. in 1999. It has also been found in the marine fungus Bionectriaceae, and belongs to a class of naturally occurring 2,5-diketopiperazines. Dideoxyverticillin A potently inhibits the tyrosine kinase activity of the epidermal growth factor receptor (median inhibitory concentration = 0.14 nM), exhibits antiangiogenic activity, and has efficacy against several cancer cell lines.
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It has been observed that the hyperactivity, inattention, and impulsivity in ADHD is related to abnormal DAT function and regulation. Dopaminergic hypofunction in the frontal cortex and basal ganglia is a neurobiological feature observed in ADHD. Psychostimulants that potently inhibit DAT, such as methylphenidate and amphetamine, are efficacious in treating ADHD. Methylphenidate (Ritalin) inhibits both DAT and NET, which results in an increase in extracellular dopamine and norepinephrine that can readily bind postsynaptic cells.
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He has also developed a series of compounds that potently and effectively inhibit TDP-43 aggregation in multiple neuronal models. In 2014, Dr. Wolozin combined forces with Glenn Larsen, Ph.D. to co-found the biotechnology company, Aquinnah Pharmaceuticals. Aquinnah Pharmaceuticals Inc. is dedicated to developing novel medicines to treat neurodegenerative diseases, and using a technology platform that focuses on the roles of RNA binding proteins, RNA metabolism and stress granules in neurodegenerative diseases.
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REST levels are highest in the brains of people who lived up to be 90 - 100s and remained cognitively intact. Levels stayed high specifically in the brain regions vulnerable to Alzheimer's, suggesting that they might be protected from dementia. It is assumed that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity.
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Several findings indicate that high levels of FICZ can exert ROS-dependent toxicity, whereas low doses can transiently elevate local levels ROS/Ca2+, thereby promoting cellular adaptation, survival, and proliferation. FICZ has proven to be potently embryotoxic toward fish and birds. Zebrafish embryos demonstrated a dramatically increased mortality and severe toxicity, however only when CYP1A1 was inhibited.FICZ can also act as a nanomolar photosensitizer potentiating UVA-induced oxidative stress irrespective of AHR ligand.
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In contrast, it has been posited by Guggenbühl-Craig that it is precisely through disaffirmation that we grow and move towards our ideal-selves. This is because it is through disaffirmation that we are made aware of our flaws and can overcome them. Much like the Michelangelo phenomenon, this growth-as-hell model of self-growth and movement towards the ideal self is understood to occur most potently in close, romantic relationships.
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200px Allium polyanthum, called the many-flowered garlic, is a Mediterranean species of wild onion native to Spain, France, Italy, Morocco, and Tunisia.Kew World Checklist of Selected Plant Families It is widely cultivated for its edible and potently aromatic bulbs and foliage.Altervista Flora Italiana, Aglio con molti fiori, Allium polyanthum Allium polyanthum produces an egg- shaped bulb, often with small bulblets around the base. Scape can be up to 80 cm tall.
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Unlike other racetams, nefiracetam shows high affinity for the GABAA receptor (IC50) = 8.5 nM), where it is presumed to be an agonist. It was able to potently inhibit 80% of muscimol binding to the GABAA receptor, although it failed to displace the remaining 20% of specific muscimol binding. Nefiracetam is able to reverse the amnesia caused by the GABAA receptor antagonists picrotoxin and bicuculline in mice, although it failed to prevent seizures induced by these drugs.
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Like Hoiamide A, Hoiamide B stimulated sodium influx in mouse neocortical neurons with an EC50 value of 3.9 micromolar. Because hoiamide B is so structurally similar to hoiamide A, research currently predicts that B is also a site 2 VGSC inhibitor. Though the mechanism of inhibition of calcium oscillations in mouse neocortical neurons is unknown for hoiamide A and B, both compounds potently suppress spontaneous calcium oscillations with EC50 values of 45.6 and 79.8 nanomolar, respectively.
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Compounds from a quinazoline series can be considered as conformationally restricted analogs of a biarylamide series. In terms of activity 5-isoquinoline was found the most active among and ranked in the order of 5-isoquinoline > 8-quinoline > 8-quinazoline > 8-isoquinoline ≥ cinnoline > phthalazine > quinoxaline > 5-quinoline e.g. AMG517 (fig. 8b), although it lacks any recognizable carbonyl motif it still potently blocks capsaicin, proton, and heat activation of TRPV1 in vitro and shows a good tolerability profile.
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The film received positive reviews from critics. It currently holds a 100% "Certified Fresh" score on the review-aggregator site Rotten Tomatoes. Rolling Stone called it "a piercing cry from the heart""Edward II" 2 April 1992 Retrieved 29 March 2010 and The Washington Post praised Jarman for "keeping the story streamlined and potently clear while retaining Marlowe's poetic period language"."Edward II" 10 April 1992 Retrieved 29 March 2010 The Observer called it one of "Derek Jarman's most accomplished films".
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3,4-Dimethylmethcathinone (3,4-DMMC) is a stimulant drug first reported in 2010 as a designer drug analogue of mephedrone, apparently produced in response to the banning of mephedrone, following its widespread abuse in many countries in Europe and around the world.EMCDDA Annual Report 2010 3,4-DMMC has been seized as a designer drug in Australia. In vitro, 3,4-DMMC was shown to be a monoamine transporter substrate that potently inhibits norepinephrine and serotonin reuptake, and to a lesser extent dopamine reuptake.
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Sometimes cross-tolerance occurs between two drugs that do not share mechanisms of action or classification. For example, amphetamine and amphetamine-like stimulants have been shown to exhibit cross-tolerance with caffeine, and it is likely the mechanism of cross-tolerance involves the dopamine receptor D1. Amphetamines also have cross-tolerance with pseudoephedrine, as pseudoephedrine can block dopamine uptake in the same manner that amphetamines do, but less potently. Alcohol is another substance that often cross-tolerates with other drugs.
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Galanin is an important neuromodulator present in the brain, gastrointestinal system, and hypothalamopituitary axis. It is a 30-amino acid non-C-terminally amidated peptide that potently stimulates growth hormone secretion, inhibits cardiac vagal slowing of heart rate, abolishes sinus arrhythmia, and inhibits postprandial gastrointestinal motility. The actions of galanin are mediated through interaction with specific membrane receptors that are members of the 7-transmembrane family of G protein-coupled receptors. GALR2 interacts with the N-terminal residues of the galanin peptide.
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The threat to Scotland's independence seem to come most potently from France, not England... And absorption by France was not a future that appealed to Scots.David Ditchburn and Alastair MacDonald, "Medieval Scotland: 1100–1560," in R.A. Houston, ed., The New Penguin History of Scotland: From the Earliest Times to the Present Day (2001). p. 175. Queen Elizabeth I, whose own legitimacy was challenged by Mary Queen of Scots, worked with the Protestant Scottish Lords to expel the French from Scotland in 1560.
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The lead compound in this series, IMP-1088, very potently inhibited host myristoylation of viral capsid protein and prevented infectious virus formation, rescuing the viability of cells in culture which had been exposed to a variety of rhinovirus serotypes, or to related picornaviruses including poliovirus and foot-and-mouth-disease virus. Because these compounds target a host factor, they are broadly active against all serotypes, and it is thought to be unlikely that they can be overcome by resistance mutations in the virus.
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DNA dC->dU-editing enzyme APOBEC-3C is a protein that in humans is encoded by the APOBEC3C gene. A3C belong to the A3 family of cytidine deaminases that act as restriction factors against diverse retroviruses. A3C was reported to inhibit simian immunodeficiency deficiency virus potently rather than HIV-1, in absence of viral infectivity factor, Vif. Enhancing A3C's catalytic activity had only a marginal effect on HIV-1 replication (in absence of Vif), the counteractive viral mechanism is unclear.
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Dapagliflozin inhibits subtype 2 of the sodium-glucose transport proteins (SGLT2) which are responsible for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter mechanism causes blood glucose to be eliminated through the urine. In clinical trials, dapagliflozin lowered HbA1c by 0.6 versus placebo percentage points when added to metformin. Regarding its protective effects in heart failure, this is attributed primarily to haemodynamic effects, where SGLT2 inhibitors potently reduce intravascular volume through osmotic diuresis and natriuresis.
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They have since been labeled "steroidal microneurotrophins", due to their small- molecule and steroidal nature relative to their polypeptide neurotrophin counterparts. Subsequent research has suggested that DHEA and/or DHEA-S may in fact be phylogenetically ancient "ancestral" ligands of the neurotrophin receptors from early on in the evolution of the nervous system. The findings that DHEA binds to and potently activates neurotrophin receptors may explain the positive association between decreased circulating DHEA levels with age and age-related neurodegenerative diseases.
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It was also shown that cortistatin A potently inhibits growth of acute myeloid leukemia cells and AML in two in vivo mouse models. Identification of dominant drug-resistant alleles of CDK8 and CDK19 demonstrate that these kinases mediate the activity of cortistatin A in AML cells. Thus, inhibition of CDK8 and CDK19 is a new therapeutic approach to AML. Cortistatin A caused selective and disproportionate up-regulation of super-enhancer-associated genes in AML cells which contributed to its anti- leukemic activity.
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The TCAs also have varying but typically high affinity for antagonising the H1 and H2 histamine receptors, as well as the muscarinic acetylcholine receptors. As a result, they also act as potent antihistamines and anticholinergics. These properties are often beneficial in antidepressants, especially with comorbid anxiety, as it provides a sedative effect. Most, if not all, of the TCAs also potently inhibit sodium channels and L-type calcium channels, and therefore act as sodium channel blockers and calcium channel blockers, respectively.
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It inhibits glucocorticoid biosynthesis and hence circulating levels of glucocorticoids, thereby treating Cushing's syndrome. In addition to its increased potency, the drug is 12-fold less potent than racemic ketoconazole in inhibiting CYP7A1 (cholesterol 7α-hydroxylase), theoretically resulting in further reduced interference with bile acid production and metabolite elimination and therefore less risk of hepatotoxicity. Levoketoconazole has also been found to inhibit CYP11A1 (cholesterol side-chain cleavage enzyme) and CYP51A1 (lanosterol-14α-demethylase), similarly but more potently relative to ketoconazole.
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Though cleverly marketed, the Euphoria mixes are - to coin a slightly cringeworthy phrase - more about the music. Ambient music. They are not guilty of genre snobbery: inclusion of tracks by Groove Armada (lounge) and Kruder & Dorfmeister (dub) and Autechre (pure techno) is adequate proof of that. But these albums do suggest a recognition that, in the club music of the 90's and beyond, old-school ambient music's legacy has emerged most potently in the subtle, lush, psychedelic qualities of progressive trance and house.
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Angiogenesis is a physiological process involving the growth of new blood vessels from pre-existing vessels. Under normal physiological conditions angiogenesis is tightly regulated and is controlled by a balance of angiogenic stimulators and angiogenic inhibitors. Tumor growth is dependent upon angiogenesis and during tumor development a sustained production of angiogenic stimulatory factors is required along with a reduction in the quantity of angiogenic inhibitory factors tumor cells produce. The cleaved and latent form of antithrombin potently inhibit angiogenesis and tumor growth in animal models.
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For example, the Spanish dancer nudibranch (genus Hexabranchus), among the largest of tropical marine slugs, potently chemically defended, and brilliantly red and white, is nocturnal and has no known mimics. Other studies of nudibranch molluscs have concluded they are aposematically coloured, for example, the slugs of the family Phylidiidae from Indo-Pacific coral reefs. Nudibranchs that feed on hydrozoids can store the hydrozoids' nematocysts (stinging cells) in the dorsal body wall, the cerata. These stolen nematocysts, called kleptocnidae, wander through the alimentary tract without harming the nudibranch.
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AZD 1305 also acts on voltage gated sodium channels (Nav1.5) by attenuating the peak (INapeak) and late sodium current (INalate), though the latter current is more potently inhibited. Attenuation of INalate by AZD1305 is concentration-dependent and decreases the slope of depolarization and delays repolarization. INalate blockade by AZD1305 depressed the threshold of sodium channel excitation and prolongs APD. Blockade of IKr may lead to excessive prolongation of APD and repolarization instability, which may promote arrhythmic conditions in the heart, including EAD and Torsade de Pointes (TdP).
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Edogestrone (, ) (developmental code name PH-218), or edogesterone, also known as 17α-acetoxy-3,3-ethylenedioxy-6-methylpregn-5-en-20-one, is a steroidal progestin and antiandrogen of the 17α-hydroxyprogesterone group which was synthesized in 1964 but was never marketed. Similarly to the structurally related steroid cyproterone acetate, edogestrone binds directly to the androgen receptor and antagonizes it, displacing androgens like testosterone from the receptor, though not as potently as cyproterone acetate. The drug has also been found to suppress androgen production, likely via progesterone receptor activation-mediated antigonadotropic activity.
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Angiogenesis is controlled by a local balance between stimulators and inhibitors of new vessel growth and is suppressed under normal physiologic conditions. Angiogenesis has been shown to be essential for growth and metastasis of solid tumors. In order to obtain blood supply for their growth, tumor cells are potently angiogenic and attract new vessels as results of increased secretion of inducers and decreased production of endogenous negative regulators. BAI1 contains at least one 'functional' p53-binding site within an intron, and its expression has been shown to be induced by wildtype p53.
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The image of the crucifixion recurs in religious sacraments, and the proliferation of symbols of the cross in homes and churches potently reinforces the wide array of Christian memes. Although religious memes have proliferated in human cultures, the modern scientific community has been relatively resistant to religious belief. Robertson (2007) reasoned that if evolution is accelerated in conditions of propagative difficulty, then we would expect to encounter variations of religious memes, established in general populations, addressed to scientific communities. Using a memetic approach, Robertson deconstructed two attempts to privilege religiously held spirituality in scientific discourse.
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Several cultural explanations for social cleansing in Africa are related to religion. One that has been offered by scholars is the presence of Pentecostalists, whose focus on the occult has been spread by the media and increased social anxiety. Pentecostalists have been recorded as preaching connections between illness and the devil, which has combined potently with existing indigenous beliefs, most notably in Kenya, Ghana, Nigeria, and Tanzania. In Tanzania, a positive correlation exists between witch killing and areas where populations practice traditional religions, where the belief in witchcraft is strong.
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Their name is a reference to Spica, the brightest star in the constellation of Virgo. On January 10, 2012, the group released their first digital single, "Doggedly" (독하게; also translated "Potently"). The music video sparked high interest, as their fellow label-mate Lee Hyori made an appearance.열애중 이효리, 그 치명적 매력 어디갈까. OSEN (January 3, 2012). Retrieved on March 23, 2012. On January 31, B2M Entertainment announced that the group would have their formal debut with a mini-album, titled Russian Roulette. The full-length music video was released on February 7.
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Many scholars highlighted the potently ideological nature of The Malachite Box, especially regarding the stories created at the end of the Great Patriotic War (1941–1945) and in the post-war years. Bazhov's work was supported by the Party. It was in high demand from the very beginning due to the shortage of the "workers' folklore", which should have represented the so- called class consciousness of the proletariat. The book conveys certain ideological concepts common for that time period, such as emphasis on the hard life of the working class before the Russian Revolution.
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Other positive reviews included Charles Spencer of The Telegraph, who raved, "this is Lloyd Webber's finest show since the original Phantom, with a score blessed with superbly haunting melodies and a yearning romanticism that sent shivers racing down my spine." He gave the show four stars out of five, but cautioned that "The show may ultimately prove too strange, too dark, too tormented to become a massive popular hit, but I suspect its creepy allure will linger potently in the memory when frothier shows have been long forgotten".Spencer, Charles.
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Gastric inhibitory polypeptide (GIP), also called glucose-dependent insulinotropic polypeptide, is a 42-amino acid polypeptide synthesized by K cells of the duodenum and small intestine. It was originally identified as an activity in gut extracts that inhibited gastric acid secretion and gastrin release, but subsequently was demonstrated to stimulate insulin release potently in the presence of elevated glucose. The insulinotropic effect on pancreatic islet beta-cells was then recognized to be the principal physiologic action of GIP. Together with glucagon-like peptide-1, GIP is largely responsible for the secretion of insulin after eating.
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The close interaction of mTOR with the PI3K pathway has also led to the development of mTOR/PI3K dual inhibitors. Compared with drugs that inhibit either mTORC1 or PI3K, these drugs have the benefit of inhibiting mTORC1, mTORC2, and all the catalytic isoforms of PI3K. Targeting both kinases at the same time reduces the upregulation of PI3K, which is typically produced with an inhibition on mTORC1. The inhibition of the PI3K/mTOR pathway has been shown to potently block proliferation by inducing G1 arrest in different tumor cell lines.
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Plasma nitrite is reduced in persons with endothelial dysfunction. The use of nitrites in food preservation is controversial due to the potential for the formation of nitrosamines when nitrites are present in high concentrations and the product is cooked at high temperatures. The effect is seen for red or processed meat, but not for white meat or fish. Nitrates and nitrites may cause cancer and the production of carcinogenic nitrosamines can be potently inhibited by the use of the antioxidants Vitamin C and the alpha-tocopherol form of Vitamin E during curing.
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11β-HSD1 is inhibited by carbenoxolone, a drug typically used in the treatment of peptic ulcers. Moreover, 18alpha- glycyrrhizic acid from the root of glycyrrhiza glabra was discovered as an inhibitor. Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and hence may explain why aspirin improves glycemic control in type 2 diabetes. Epigallocatechin gallate from green tea can also potently inhibit this enzyme; green tea is a complex mixture of various phenolics with contents varying with production and processing, and some of the phenolics are known HDAC inhibitors that alter genetic expression.
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Similarly to μ-opioid receptor (MOR) agonists, KOR agonists are potently analgesic, and have been employed clinically in the treatment of pain. However, KOR agonists also produce side effects such as dysphoria, hallucinations, and dissociation, which has limited their clinical usefulness. Examples of KOR agonists that have been used medically as analgesics include butorphanol, nalbuphine, levorphanol, levallorphan, pentazocine, phenazocine, and eptazocine. Difelikefalin (CR845, FE-202845) and CR665 (FE-200665, JNJ-38488502) are peripherally restricted KOR agonists lacking the CNS side effects of centrally active KOR agonists and are currently under clinical investigation as analgesics.
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In addition, similar findings have been found in mice deficient in BMAL1, the mammalian ortholog of CYC, but without the sexual dimorphism exhibited by drosophila. Cyc is also involved in Drosophila's responses to starvation, which also directly affect life span. Starvation in Drosophila potently suppresses sleep, suggesting that the homeostatically regulated behaviors of feeding and sleep are integrated in flies. Clk and cyc act during starvation to modulate the conflict of whether flies sleep or search for food, thus playing a critical role for proper sleep suppression during starvation.
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There is abundant irrefutable physiological, experimental, pharmacological, and clinical evidence that in many migraine sufferers the pain originates in painfully dilated extracranial terminal branches of the external carotid artery. That vasodilatation is an important factor in migraine is further confirmed by the fact that the most widely used migraine rescue medications, the ergots, the triptans, and the promising newer drugs, the gepants, possess one significant common denominator: they all potently constrict abnormally dilated extracranial arteries while simultaneously reducing or eliminating migraine pain. Furthermore, to date all migraine-provoking agents have had vasodilating properties.
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Methallenestril () (brand names Cur-men, Ercostrol, Geklimon, Novestrine, Vallestril), also known as methallenoestril () and as methallenestrol, as well as Horeau's acid, is a synthetic nonsteroidal estrogen and a derivative of allenolic acid and allenestrol (specifically, a methyl ether of it) that was formerly used to treat menstrual issues but is now no longer marketed. It is a seco-analogue of bisdehydrodoisynolic acid, and although methallenestril is potently estrogenic in rats, in humans it is only weakly so in comparison. Vallestril was a brand of methallenestril issued by G. D. Searle & Company in the 1950s. Methallenestril is taken by mouth.
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The functions of FPR3 and the few ligands which activate it have not been fully clarified. Despite its homology to FPR1, FPR3 is unresponsive to many FPR1-stimulating formyl peptides including FMLP. However, fMMYALF, a N-formyl hexapeptide derived from the mitochondrial protein, NADH dehydrogenase subunit 6, is a weak agonist for FPR3 but >100-fold more potent in stimulating FPR1 and FPR2. F2L is a naturally occurring acylated peptide derived from the N-terminal sequence of heme-binding protein 1 by cathepsin D cleavage that potently stimulates chemotaxis through FPR3 in monocytes and monocyte-derived dendritic cells.
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Wild wedge- capped capuchin monkeys (Cebus olivaceus) self-anoint with millipedes (Orthoporus dorsovittatus). Chemical analysis revealed these millipedes secrete two benzoquinones, compounds known to be potently repellent to insects and the secretions are thought to provide protection against insects, particularly mosquitoes (and the bot flies they transmit) during the rainy season. Millipede secretion is so avidly sought by the monkeys that up to four of them will share a single millipede. The anointment must also involve risks, since benzoquinones are toxic and carcinogenic, however, it is likely that for capuchins, the immediate benefits of self-anointment outweigh the long-term costs.
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At a conference of German physicians and natural scientists, most of the speakers rejected his doctrine, including the celebrated Rudolf Virchow, who was a scientist of the highest authority of his time. Virchow's great authority in medical circles contributed potently to Semmelweis' lack of recognition. Ede Flórián Birly, Semmelweis's predecessor as Professor of Obstetrics at the University of Pest, never accepted Semmelweis's teachings; he continued to believe that puerperal fever was due to uncleanliness of the bowel. August Breisky, an obstetrician in Prague, rejected Semmelweis's book as "naïve" and he referred to it as "the Koran of puerperal theology".
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58-68 MMA was largely forgotten until being reassayed by David E. Nichols as a non-neurotoxic MDMA analogue in 1991, and has subsequently been sold as a designer drug on the internet since the late 2000s (decade). In animal studies, MMA fully substitutes for MDMA and MBDB, partially substitutes for LSD, and does not substitute for amphetamine. Additionally, it has been shown to potently inhibit the reuptake of serotonin and does not produce serotonergic neurotoxicity in rodents. These data appear to confer a profile of MMA as a selective serotonin releasing agent (SSRA) and 5-HT2A receptor agonist.
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Dr. O'Day encouraged her apply for graduate school where she eventually chose to join the laboratory of Richard Lewis at Stanford University. For her graduate studies, Dr. Bautista used electrophysiology and calcium imaging to characterize how plasma-membrane calcium-ATPase (PMCA) and Ca(2+) release-activated Ca(2+) (CRAC) channels regulate calcium levels in T-cells. As a post-doctoral fellow in David Julius's lab, she characterized the response profiles of TRPA1 and TRPM8 and the molecular target of Szechuan peppers. Previously, Dr. Bautista helped show that allyl isothiocyanate, a pungent chemical found in wasabi and other mustard plants, potently activates TRPA1.
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A woman with locked collar Woman wearing collar in public at Folsom Street Fair Collars have varying degrees of significance for people in the BDSM community. A person wearing a collar may wish by doing so to make it known that he or she is submissive. Wearing a collar may similarly be a signal to others that the submissive is "owned" by or is in a relationship with a dominant, and that the wearer has been formally collared. It may also be a potently tangible symbol of the relationship itself or of the ownership the submissive is held in.
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The side effects of ketoconazole are sometimes harnessed in the treatment of non-fungal conditions. While ketoconazole blocks the synthesis of the sterol ergosterol in fungi, in humans, at high dosages (>800 mg/day), it potently inhibits the activity of several enzymes necessary for the conversion of cholesterol to steroid hormones such as testosterone and cortisol. Specifically, ketoconazole has been shown to inhibit cholesterol side-chain cleavage enzyme, which converts cholesterol to pregnenolone, 17α-hydroxylase and 17,20-lyase, which convert pregnenolone into androgens, and 11β-hydoxylase, which converts 11-deoxycortisol to cortisol. All of these enzymes are mitochondrial cytochrome p450 enzymes.
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In primary cultures of rat cortical neurons, the inhibition of PDE2A by EHNA potentiates NMDA (N-methyl-D- aspartate) receptor activated increase in cGMP, but has no effect on cAMP concentrations. EHNA is also a very potent adenosine deaminase inhibitor with an IC50 ~2 nM. This dual inhibition would lead to the accumulation of the two inhibitory metabolites, adenosine and cGMP, which may act in synergy to mediate diverse pharmacological responses including anti-viral, anti-tumour and anti-arrhythmic effects. Although EHNA potently inhibits adenosine deaminase, it has been successfully used with the proper controls as a tool to probe PDE2 functions.
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This gene encodes a protein involved in G protein- mitogen-activated protein kinase (MAPK) signaling cascades. When overexpressed in mammalian cells, this gene could potently suppress a RAS- and MAPK-mediated signal and interfere with JNK activity, suggesting that the function of this gene may be signal repression. The encoded protein is an integral subunit of the NCOR1-HDAC3 (nuclear receptor corepressor 1-histone deacetylase 3) complex, and it was shown that the complex inhibits JNK activation through this subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP1 (activator protein 1) function.
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For spiritual and social resources, in addition to the Chaplain, the College engages a social worker to help address the needs of all community members. Because St. George's is of an Anglican foundation it welcomes students of all backgrounds, without proselytization, and requires the respectful participation of all boys in the nurturing of the spiritual life. Student leadership is expressed most potently in the Student Council, the Junior School Captains, the Stewards, and the lead boys in the graduating class, the Prefects, under the Head Prefect. Students compete with each other on four teams, or houses, named for the four great cathedrals of England which collectively supply the school colours.
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These analyses suggest that an integrated NF-κB system network underlies activation of both RelA and RelB containing dimer and that a malfunctioning canonical pathway will lead to an aberrant cellular response also through the non- canonical pathway. Most intriguingly, a recent study identified that TNF- induced canonical signalling subverts non-canonical RelB:p52 activity in the inflamed lymphoid tissues limiting lymphocyte ingress. Mechanistically, TNF inactivated NIK in LTβR‐stimulated cells and induced the synthesis of Nfkb2 mRNA encoding p100; these together potently accumulated unprocessed p100, which attenuated the RelB activity. A role of p100/Nfkb2 in dictating lymphocyte ingress in the inflamed lymphoid tissue may have broad physiological implications.
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At proposed therapeutic concentrations, this molecule lacks anti-inflammatory activity, and does not inhibit either cyclooxygenase 1 (COX-1) or cyclooxygenase 2 (COX-2) enzymes. Only the S-enantiomers of arylpropionic acid NSAID can potently inhibit COX, whereas the R-enantiomers exert almost no COX activity. R-Flurbiprofen is inefficiently converted into S-flurbiprofen, with 1.5% of the R-enantiomer undergoing bioinversion to the S-form. Although this compound lacks activity against COX, studies have shown that this drug is a potent reducer of levels of beta amyloid, the main constituent of amyloid plaques in Alzheimer's disease, and therefore there was interest in this drug as a therapeutic agent.
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Wolfgang Amadeus Mozart, circa 1780 The musicologist Stanley Sadie reviewed the album on LP in Gramophone in September 1979. It had a very strong roster of soloists, he thought, even if they did not mine quite as much meaning from Lorenzo da Ponte's libretto as they would have done if they had been Italian. Tom Krause was the more successful of the Almavivas, singing with "plenty of weight and virility", powerfully conveying the "rage, frustration and wounded social pride" that consumed the priapic Count after his failure to seduce his servant's fiancée. Sadie could not recall another artist who had expressed the Count's lust so potently.
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Progesterone has a number of physiological effects that are amplified in the presence of estrogens. Estrogens through estrogen receptors (ERs) induce or upregulate the expression of the PR. One example of this is in breast tissue, where estrogens allow progesterone to mediate lobuloalveolar development. Elevated levels of progesterone potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a reduction in extracellular fluid volume. Progesterone withdrawal, on the other hand, is associated with a temporary increase in sodium retention (reduced natriuresis, with an increase in extracellular fluid volume) due to the compensatory increase in aldosterone production, which combats the blockade of the mineralocorticoid receptor by the previously elevated level of progesterone.
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Cyclothiazide (Anhydron, Acquirel, Doburil, Fluidil, Renazide, Tensodiural, Valmiran), sometimes abbreviated CTZ, is a benzothiadiazide (thiazide) diuretic and antihypertensive that was originally introduced in the United States in 1963 by Eli Lilly and was subsequently also marketed in Europe and Japan. Related drugs include diazoxide, hydrochlorothiazide, and chlorothiazide. In 1993, it was discovered that cyclothiazide is a positive allosteric modulator of the AMPA and kainate receptors, capable of reducing or essentially eliminating rapid desensitization of the former receptor, and potentiating AMPA-mediated glutamate currents by as much as 18-fold at the highest concentration tested (100 μM). Additionally, in 2003, cyclothiazide was also found to act as a GABAA receptor negative allosteric modulator, potently inhibiting GABAA-mediated currents.
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Garcia has conducted several studies targeting cellular receptors for applications in cancer immunotherapy. In 2013, Garcia's group developed high affinity antagonists of the receptor CD47 that potently enhance the antitumor effects of established therapeutic antibodies.Engineered SIRPα variants as immunotherapeutic adjuvants to anticancer antibodies, Science (2013) Garcia later determined that the therapeutic effects of CD47 blockade require combination therapy with checkpoint blockade antibodies in immunocompetent hosts, thus proving that CD47-based therapy relies upon stimulation of the adaptive immune system.Durable antitumor responses to CD47 blockade require adaptive immune stimulation, PNAS (2016) Garcia's lab published the creation of an "orthogonal" IL-2 receptor complex to enable the selective delivery of IL-2 signals to engineered T cells during adoptive cell therapy.
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Broparestrol () (brand names Acnestrol, Longestrol; former developmental code name LN-107), also known as α-bromo-α,β-diphenyl-β-p-ethylphenylethylene (BDPE), is a synthetic, nonsteroidal selective estrogen receptor modulator (SERM) of the triphenylethylene group that has been used in Europe as a dermatological agent and for the treatment of breast cancer. The drug is described as slightly estrogenic and potently antiestrogenic, and inhibits mammary gland development and suppresses prolactin levels in animals. It is structurally related to clomifene and diethylstilbestrol. Broparestrol is a mixture of E- and Z- isomers (LN-1643 and LN-2299, respectively), both of which are active and are similarly antiestrogenic but, unlike broparestrol, were never marketed.
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The venom of M. eupeus is not as potent as that of other dangerous buthid species. Victims of stings feel intense pain, hyperemia, swelling and a burning sensation in the affected area, while numbness and itching were also reported in some cases. As in other scorpions, the venom of M. eupeus contains various neurotoxic proteins that interact specifically with ion channels. A number of unique proteins in this scorpion's venom have been identified, cloned and investigated for clinical applications. For instance, MeuKTX, structurally related to BmKTX (α-KTx3.6) from M. martensii, potently inhibits rKv1.1, rKv1.2 and hKv1.3 channels but does not affect rKv1.4, rKv1.5, hKv3.1, rKv4.3, and hERG channels even at high concentrations.
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Listing israel-opera.co.il, retrieved August 18, 2010 In a review of his work Super Straight is coming down by the Hubbard Street Dance Chicago in 1989, the reviewer wrote that it is a "coldly tormented work", and that "Ezralow has put his own manic stamp on the piece--the headlong barrel turns, the galumphing leaps, the desperate floor rolls--and has potently contrasted such excesses with moments of sullen stillness."Curtis, Cathy."Music and Dance Reviews Ezralow Work Premieres"Los Angeles Times, February 13, 1989 His works for opera include The Flying Dutchman, for the Los Angeles and Houston Opera Companies, Maggio Musicale’s Aida with Zubin Mehta as conductor, and the Paris Opera Ballet.
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Pure AR antagonists like flutamide and bicalutamide are potent progonadotropins with indirect estrogenic activity in males. This is because they block the AR in the pituitary gland and hypothalamus and thereby inhibit the negative feedback of androgens on the hypothalamic–pituitary–gonadal axis (HPG axis). This, in turn, results in increased gonadotropin secretion, activation of gonadal steroidogenesis, and an up to 2-fold increase in testosterone levels and 2.5-fold increase in estradiol levels. Conversely, AR antagonists that are also progestogens, like cyproterone acetate, are not progonadotropic, as activation of the PR is antigonadotropic and preserves negative feedback on the HPG axis, and these medications are indeed potently antigonadotropic in clinical practice.
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GDNF has been investigated as a treatment for Parkinson's disease, though early research has not shown a significant effect. Vitamin D potently induces GDNF expression. In 2012, the University of Bristol began a five-year clinical trial on Parkinson's sufferers, in which surgeons introduced a port into the skull of each of the 41 participants through which the drug could be delivered, in order to enable it to reach the damaged cells directly. The results of the double-blind trial, where half the participants were randomly assigned to receive regular infusions of GDNF and the other half placebo infusions, did not show a statistically significant difference between the active treatment group and those who received placebo, but did confirm the effects on damaged brain cells.
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As a result, imidazole engineering has been suggested as a means to specifically inhibit NO dioxygenases. In addition, genetically modified plants with heterologous flavohemoglobin-NODs are being developed to limit NO toxicity created by metabolism of nitrogen fertilizers by soil microbes and as a means towards plant self-fertilization through absorption of environmental NO. Recently a lentiviral vector that allows for expression of E. coli flavoHb in mammalian cells has been described. This approach demonstrated that flavoHb is indeed enzymatically active within human and murine cells and potently blocks exogenous and endogenous sources of nitrosative stress. This technology was then extended to interrogate the role of NO synthesis in the highly tumorigenic cancer stem cells (CSCs) from human glioblastoma (brain tumor) samples.
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The activation of protein kinase C (PKC) is likely to be responsible for the antiproliferative and tumor-promoting activities of aplysiatoxin-related compounds. Tumor promoters like PDBu and ATX bound potently to the C1 domains of both conventional and novel PKCs, while antiproliferative compounds such as aplog-1 and bryo-1 exhibited some selectivity for novel PKCs other than PKCε, that is, PKCδ, PKCη, and PKCθ. The affinity of DAT for the PKC C1 domains is quite similar to that of aplysiatoxin. The introduction of a methylgroup group into position 4 could enhance the affinity for conventional PKCs rather than for novel PKCs, and the introduction of a methyl group into position 10 would enhance the affinity for both conventional and novel PKCs.
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Nudibranch molluscs are the most commonly cited examples of aposematism in marine ecosystems, but the evidence for this has been contested, mostly because (1) there are few examples of mimicry among species, (2) many species are nocturnal or cryptic, and (3) bright colours at the red end of the colour spectrum are rapidly attenuated as a function of water depth. For example, the Spanish Dancer nudibranch (genus Hexabranchus), among the largest of tropical marine slugs, potently chemically defended, and brilliantly red and white, is nocturnal and has no known mimics. Mimicry is to be expected as Batesian mimics with weak defences can gain a measure of protection from their resemblance to aposematic species. Other studies have concluded that nudibranchs such as the slugs of the family Phyllidiidae from Indo-Pacific coral reefs are aposematically coloured.
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PAC-1 is notable for the unique path it has taken to the clinic, as it is possibly the only cancer drug to first be rigorously evaluated in pet dogs with spontaneous cancer as a prelude to the human clinical trial. In 2010, a study showed PAC-1 to be safe for dogs, and a second study published later that same year reported that a PAC-1 derivative (called S-PAC-1) was well tolerated in a small phase I clinical trial of dogs with lymphoma. More recently, in addition to this single-agent activity PAC-1 has shown to potently synergize with approved cancer drugs, for example with doxorubicin in the treatment of pet dogs with lymphoma and metastatic osteosarcoma, and with temozolomide in treating pet dogs with spontaneous glioma.
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Crenolanib besylate (CP-868,596-26 or AR-868,596-26, 4-piperidinamine, 1-[2-[5-[(3-Methyl-3-oxetanyl) methoxy]-1H-benzimidazol-1-yl]- 8-quinolinyl]-, monobenzenesulfonate) is an investigational inhibitor being developed by AROG Pharmaceuticals, LLC. The compound is currently being evaluated for safety and efficacy in clinical trials for various types of cancer, including acute myeloid leukemia (AML), gastrointestinal stromal tumor (GIST), and glioma. Crenolanib is an orally bioavailable benzamidazole that selectively and potently inhibits signaling of wild-type and mutant isoforms of class III receptor tyrosine kinases (RTK) FLT3 (FMS-like Tyrosine Kinase 3), PDGFR α (Platelet-Derived Growth Factor Receptor), and PDGFR β. Unlike most RTK inhibitors, crenolanib is a type I mutant-specific inhibitor that preferentially binds to phosphorylated active kinases with the ‘DFG in’ conformation motif.
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Romidepsin was first reported in the scientific literature in 1994, by a team of researchers from Fujisawa Pharmaceutical Company (now Astellas Pharma) in Tsukuba, Japan, who isolated it in a culture of Chromobacterium violaceum from a soil sample obtained in Yamagata Prefecture. It was found to have little to no antibacterial activity, but was potently cytotoxic against several human cancer cell lines, with no effect on normal cells; studies on mice later found it to have antitumor activity in vivo as well. The first total synthesis of romidepsin was accomplished by Harvard researchers and published in 1996. Its mechanism of action was elucidated in 1998, when researchers from Fujisawa and the University of Tokyo found it to be a histone deacetylase inhibitor with effects similar to those of trichostatin A.
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By using a novel gene-based prime boost vaccine, Sullivan and her team were the first to demonstrate vaccine protection against Ebola infection in primates. This was followed by her discovery of a single shot vaccine that provided more immediate protection, making it a very practical vaccine that could be used in the face of an acute Ebola epidemic. As a result, this vaccination schedule is now standard in the field of Ebola vaccine research, where one of the lead Ebola vaccine candidates, ChAd3-EBOV, has been advanced to Phase I/II and III human clinical trials. More recently, Sullivan and her team discovered a potently protective monoclonal antibody, mAb114, from a human Ebola survivor that completely rescues Ebola-infected primates, even when given as a monotherapy several days after their Ebola exposure.
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Moreover, suppression of PGE2 in breast tissue is relevant because, via activation of prostaglandin EP receptors, PGE2 potently induces amphiregulin expression in breast tissue, and activation of the EGFR by amphiregulin increases COX-2 expression in breast tissue, in turn resulting in more PGE2, and thus, a self-perpetuating, synergistic cycle of growth amplification due to COX-2 appears to potentially be present in normal breast tissue. Accordingly, overexpression of COX-2 in mammary gland tissue produces mammary gland hyperplasia as well as precocious mammary gland development in female mice, mirroring the phenotype of VDR knockout mice, and demonstrating a strong stimulatory effect of COX-2, which is downregulated by VDR activation, on the growth of the mammary glands. Also in accordance, COX-2 activity in the breasts has been found to be positively associated with breast volume in women.
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Figure 4: Molecular structure of apremilast, an analog of thalidomide After finding a novel set of analogs of thalidomide, namely 3-(1,3-dioxo-1,3 dihydroisoindol-2-yl)-3-(3,4-dimethoxyphenyl) propionic acid (not shown), which had PDE4 inhibition activity the work began to optimize the activity. For that purpose the researchers used a known structure moiety, 3,4-dialkoxyphenyl, that is a recognized pharmacophore in PDE4 inhibitors such as rolipram (Figure 6) and roflumilast and added it onto the structure of the previously mentioned analog series. After tweaking the structure and testing different substitution at the 4-position of the phthaloyl ring and at the carboxyl acid the researchers finally landed at a molecule that potently inhibits PDE4 and TNF-α, which they later named apremilast (Figure 4). The S-enantiomer of apremilast was chosen since it was the more active enantiomer.
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Enraged, he tries to beat up Wes, but Darla stops them by informing Rich that he does not own her; later, Rich apologizes to Wes, saying that he should not have taken his feelings of anger out on him, and Wes accepts (while remarking that it had been a while since they "had a few rounds" with each other), and then apologizes for what he did. Rich decides to return to Megan's place, where she — fed up with fighting with her father — convinces him that her father killed her mother and that they should kill him, and run off with the money. However, Rich, blinded by the potently sexual relationship, is in two minds about what to do. The next day, Rich and Wes are shocked to find out that Darla has been killed in a horse riding accident.
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5-HEDH functions as a highly specific oxidizer of 5(S)-HETE to 5-oxo-ETE; no functional importance has yet been ascribed to its ability in similarly oxidizing other 5(S)-hydroxyl fatty acids. 5-Oxo-ETE stimulates a wide range of biological activities far more potently and powerfully than 5(S)-HETE (see 5-oxo-eicosatetraenoic acid and 5-HETE). For example, it is 30-100-fold more potent in stimulating cells that promote inflammation and allergy reactions such as neutrophils, monocytes, macrophages, eosinophils, and basophils and is more potent than 5-HETE in stimulating various types of cancer cells to grow. Furthermore, 5-oxo-ETE appears to be involved in various animal and human reactions: injected into the skin of rabbits, it causes a severe edema with an inflammatory cell infiltrate resembling an urticaria-like lesion;Int J Mol Med.
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The same has been found for ascorbic acid (vitamin C) and EE, although the significance of the interaction has been regarded as dubious. In contrast to estradiol, it is unlikely that there is a pharmacokinetic interaction between smoking (which potently induces certain cytochrome P450 enzymes and markedly increases the 2-hydroxylation of estradiol) and EE. This suggests that estradiol and EE are metabolized by different cytochrome P450 enzymes. There is, however, an increased risk of cardiovascular complications with smoking and EE, similarly to the case of smoking and other estrogens. The 19-nortestosterone progestins, gestodene and, to a lesser extent, desogestrel, have been found to inhibit cytochrome P450 enzymes and to progressively inhibit the metabolism and increase the concentrations of EE. EE has been found to significantly increase (by 38%) the AUC of omeprazole (which is metabolized by CYP2C19).
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The Camsá shamans of the Sibundoy Valley are also expert in the use of the dangerously toxic solanaceous hallucinogens Brugmansia and Iochroma and their occasional employment of Desfontainia for similar divinatory purposes (and reticence to speak of this practice) may well indicate a plant similarly toxic and difficult to use and causing a comparably unpleasant experience and after- effects. Desfontainia spinosa var. hookeri has been reported as a narcotic utilized by the Mapuche people of Chile by Carlos Mariani Ramirez, who also likened the bitterness of the plant to that of Gentian and mentioned its use as a yellow dye. The greenish-yellow, baccate fruit of D. spinosa is reputedly even more intoxicating than the foliage of the plant and is reported occasionally to have been brewed into a potently psychoactive type of chicha (see also Saliva-fermented beverages).
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He was peculiarly happy in the smiles of all the country damsels. How he would figure among them in the churchyard, between services on Sundays; gathering grapes for them from the wild vines that overran the surrounding trees; reciting for their amusement all the epitaphs on the tombstones; or sauntering, with a whole bevy of them, along the banks of the adjacent millpond; while the more bashful country bumpkins hung sheepishly back, envying his superior elegance and address. He was like a travelling gazette, carrying the whole budget of local gossip from house to house so that his appearance was always greeted with satisfaction. He was, moreover, esteemed by the women as a man of great erudition, for he had read several books quite through, and was a perfect master of Cotton Mather's History of New England Witchcraft, in which, by the way, he most firmly and potently believed.
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The town of Nassau with the castle and family seat of the imperial knights of Stein (copper engraving by Matthäus Merian 1655) In his old age, Stein would express his gratitude to his parents for the influence of their religious and truly German and knightly example. He added: > My view of the world and of human affairs I gathered as a boy and youth, in > the solitude of a country life, from ancient and modern history, and in > particular I was attracted by the incidents of the eventful history of > England. The influence of English ideas, so potent a factor in the lives of Voltaire, Rousseau, Talleyrand and many others in the 18th century, was therefore potently operative in the early career of Stein. He does not seem to have gone to any school except in 1773, when he went with a private tutor to the University of Göttingen in Hanover.
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" Derek Elley of Variety states "at times semi-impressionistic, at others gut-wrenchingly up close and personal, Nanjing massacre chronicle City of Life and Death lives up to hype and expectations." Maggie Lee of The Hollywood Reporter states the film is "Potently cinematic and full of personal stylistic bravura." Betsy Sharkey of the Los Angeles Times describes the film as "Truly a masterpiece in black and white and pain" and the film contains "some of the most affectingly choreographed battle scenes to be found, with Lu Chuan a master at moving from the micro of a face to the macro of a city in ruins." Karina Longworth of IndieWire describe the film "manages to convey the total horror of the Japanese atrocities from the perspective of both perpetrators and victims, all with exceptional nuance, sensitivity and sadness" and the film "has the feel of a lost post-War foreign classic, a masterwork implicating the viewer in the horrors of bearing witness.
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The following year, at the same venue, she starred in Repentance, as a young Muslim woman conflicted about her romantic relationship with a non-Muslim. The Daily Telegraph's Charles Spencer felt that Dhillon gave a "touching performance" in a play that "potently catches the clash between faith and sexual desire". The Financial Times called Dhillon's performance "powerfully acted", and Time Out said she was "luminous". After appearances in The Mimic (2011) and The Thick of It (2012), she starred as the character Saz Kaur, a sarcastic high school student from a strict Indian family, in Some Girls, which aired on BBC Three from 2012 to 2014. Dhillon went on to appear as a guest character in seven episodes of the 2014 TV series 24: Live Another Day, alongside Kiefer Sutherland. The low budget romantic comedy A Wonderful Christmas Time was shot over five days and released in 2014, with the actors improvising around a scripted outlines.
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His research group was the first to clone and sequence mRNAs encoding a mammalian glucose transport protein, GLUT1, and then GLUT2 and the insulin- responsive GLUT4, an anion exchange protein, a transporter for free fatty acids, the hepatic asialoglycoprotein receptors, intestinal sucrose-isomaltase, the erythropoietin receptor, two subunits of the TGFß receptor, and several adipocyte-specific proteins including adiponectin (formerly Acrp30). These have been used to define the structure, biosynthesis, and cellular functions of these and related proteins and to identify and characterize related genes that encode proteins with important physiological functions. Current efforts of his group focus on: #Erythropoiesis – activation of and signal transduction by the erythropoietin receptor in erythroid progenitor cells, and the regulation of transcription, apoptosis, cell division, and enucleation during erythropoiesis. #Hematopoietic stem cells – characterizing new marker cell surface proteins and new growth factors for their expansion in culture #The functions of adiponectin, an adipocyte-produced hormone that potently enhances glucose and fatty acid metabolism by muscle, and a family of adiponectin homologs.
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This is of particular relevance when it is considered that many progestins used in COCs have varying degrees of weak androgenic activity. A combination of 20 µg/day EE and 0.25 mg/day levonorgestrel, a progestin with relatively high androgenicity, decreases SHBG levels by 50%; 30 µg/day EE and 0.25 mg/day levonorgestrel has no effect on SHBG levels; 30 µg/day EE and 0.15 mg/day levonorgestrel increases SHBG levels by 30%; and triphasic COCs containing EE and levonorgestrel increase SHBG levels by 100 to 150%. The combination of 30 µg/day EE and 150 µg/day desogestrel, a progestin with relatively weak androgenicity than levonorgestrel, increases SHBG levels by 200%, while the combination of 35 µg/day EE and 2 mg/day cyproterone acetate, a progestin with potent antiandrogenic activity, increases SHBG levels by 400%. As such, the type and dosage of progestin contained in COCs potently moderates the effects of EE on SHBG levels.
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