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Мацуно хочет вернуться к Vagrant Story

Мацуно сейчас продолжает работать с ЁСидой над фф14: в конце сюжетки Return to Ivalice была зацепка на будущее: там появлялся имперский командир Габрант. Сейчас это ружьё выстрелило: сюжетку релик-оружия из Shadowbringers пишет Мацуно, и она про Ноа Башевича Габранта. Я сам не возвращался ещё в фф14 после того, как этот патч вышел, так что ничего сказать не могу - но там явно лучше дождаться выхода всей сюжетки, чтобы оценивать. Арка Return to Ivalice была крутой.

Тем интереснее, что Мацуно пытался вернуться в Ивалис до того, как в 17-м году его взял к себе Ёсида. Решив узнать в твиттере, как западная аудитория относится к Save the Queen, его новой сюжетной арке из фф14, Мацуно разоткровенничался.

По его словам, использованная в этой арке концепция "разум обманывает себя, чтобы справляться с травмой" изначально предлагалась для продолжения Vagrant Story, которое Мацуно придумал в 2002-м и предложил Скваре в 2013-м.




Я просто хочу напомнить, что кроме команды фф14, у Сквари сейчас нет толковых сценаристов)





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It’s time for Seder, which is Zeder, in our modern-day-plague ravaged Passover

Last week I received a very long email with instructions for Zeder. This year millions of Jews around the world will log into Zoom, and try to continue a 2000-year tradition of not changing the tradition. We will recall plagues of past like infestation of locusts and raining frogs and we’ll silently scoff that Egypt […]

The post It’s time for Seder, which is Zeder, in our modern-day-plague ravaged Passover appeared first on Penelope Trunk Careers.




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Editorial: How do we keep coronavirus from ravaging L.A.'s homeless encampments?

Los Angeles wants to move thousands of homeless people inside. But is crowding indoors actually less dangerous than letting them stay on the streets?




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Amid coronavirus shutdown, NBA hasn't given up on salvaging the regular season

The NBA continues to review its options for resuming play, and that includes some form of finishing the regular season ahead of the playoffs.




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With the live music industry ravaged by coronavirus, Travis Scott turns to 'Fortnite'

In this coronavirus climate, Travis Scott's "Fortnite" collaboration is something of an experiment for our new reality. Games are our new social spaces.




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Bop to Beyoncé and Megan Thee Stallion's new 'Savage' remix for coronavirus relief

Proceeds from Megan Thee Stallion and Beyoncé's new "Savage" remix will go toward coronavirus relief efforts in the artists' hometown of Houston.




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Vladimir Putin's savage EU swipe exposed: 'You're so weak!'



VLADIMIR PUTIN appeared to mock the EU in an eye-opening documentary, claiming Russia is "the only independent nation" whereas countries depending on the bloc become weak and "unpredictable".




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Celtic hero Chris Sutton bites back at Robbie Savage trolling as Hoops leapfrog Rangers



Celtic legend Chris Sutton has bitten back Robbie Savage on Twitter, as the Hoops finished the week top of the Scottish Premiership table, after Rangers’ 1-1 draw against Hearts.




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Retro Indy: Fire ravaged circus and elephants roamed the streets of Fulton County

Animals were burned alive in a fire that swept the winter quarters of Cole Bros. Circus in Fulton County, Indiana, on Feb. 20, 1940.

      




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‘Journey to the Savage Planet’: Forgettable for so many reasons

Cheeky behavior can be a cover for inadequacy.




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COVID-19 has ravaged ride-hailing companies, but an industry watcher says the crisis could make Uber stronger (UBER)

  • While ride-hailing has suffered from the impact of COVID-19, Uber is in a good position to survive the crisis, three analysts who cover the company told Business Insider.
  • Uber is in no danger of running of out money anytime soon, said Mark Mahaney, a managing director at RBC Capital Markets.
  • And a series of cost-cutting moves should make the company profitable by next year, said Dan Ives, a managing director of equity research at Wedbush Securities.
  • Uber's food-delivery service, Uber Eats, gives the company an advantage over ride-hailing competitors, since it allows homebound consumers to keep using its app, said Tom White, a senior research analyst at DA Davidson.
  • Are you a current or former Uber employee? Do you have an opinion about what it's like to work there? Contact this reporter at mmatousek@businessinsider.com. You can also reach out on Signal at 646-768-4712 or email this reporter's encrypted address at mmatousek@protonmail.com.
  • Visit Business Insider's homepage for more stories.

The ride-hailing industry has taken a major hit from COVID-19 as potential customers remain confined to their homes, but Uber is in a good position to survive the crisis, three analysts who cover the company said.

"Their business model will be intact on the other side of this," said Dan Ives, a managing director of equity research at Wedbush Securities.

A strong cash reserve will help. After ending the first quarter with $9 billion in cash and short-term investments, Uber has the resources to survive a scenario in which the prevalence of COVID-19 and its effect on consumer behavior last for the next two years, said Mark Mahaney, a managing director at RBC Capital Markets.

On Thursday, Uber disclosed its first-quarter financial results, reporting an adjusted loss of $2.9 billion on revenue of $3.5 billion during the first three months of this year. Uber CEO Dara Khosrowshahi said on a call with analysts that the ride-hailing company would cut $1 billion in fixed costs. The company has recently removed its food-delivery service — Uber Eats — from eight unprofitable markets, folded its electric bike and scooter business into Lime (Uber recently led a $170 million investment round in the company), and announced it will lay off about 14% of its workforce.

Those moves should help Uber become profitable in 2021 (the company predicted in February that it would turn a profit by the end of this year), Ives said. Uber's management, which had struggled in the wake of the company's 2019 IPO, has performed well in the current crisis by being transparent with investors and quickly moving to reduce expenses, Ives said. Investors signaled their approval of the company's strategy by sending shares up as much as 8% in after-hours trading on Thursday.

Uber Eats was one of the highlights of the company's first-quarter results, said Tom White, a senior research analyst at DA Davidson, as gross bookings grew 52% from the first quarter of 2019 to $4.7 billion. Eats gives Uber an advantage over ride-hailing competitors that don't have a similar service, as it allows the company to keep homebound consumers using its app, White said. Even after the toll of COVID-19 begins to subside, demand for online food delivery could see continued growth, he added.

But there are still challenges ahead for Uber. The company said rides fell by as much as 80% in April, and Ives projects that 30% of the customers for gig-economy companies like Uber, Airbnb, and Lyft won't use a ride-hailing service until there's a vaccine for COVID-19. Yet the pandemic could leave Uber better off in the long run, White said.

"I saw and heard enough [during Uber's first-quarter earnings call] that makes it harder and harder for me to think that these guys don't emerge from this pandemic probably in a stronger competitive position and a healthier and leaner operating position," he said.

Are you a current or former Uber employee? Do you have an opinion about what it's like to work there? Contact this reporter at mmatousek@businessinsider.com. You can also reach out on Signal at 646-768-4712 or email this reporter's encrypted address at mmatousek@protonmail.com.

SEE ALSO: Elon Musk's theater of the absurd is a sign of the times for tech

Join the conversation about this story »

NOW WATCH: Why Pikes Peak is the most dangerous racetrack in America




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Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI

JE Hixson
Mar 1, 1990; 31:545-548
Articles




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Mapping prostate cancer lesions pre/post unsuccessful salvage lymph node dissection using repeat PSMA-PET

Introduction: The aim of this study was to analyze patterns of persistent versus recurrent or new PET lesions in a selected patient cohort with PSA persistence following salvage lymph node dissection (SLND) and pre/post procedure prostate-specific membrane antigen ligand positron emission tomography (PSMA-PET). Material and Methods: 16 patients were included in this multicenter study. Inclusion criteria were: a) PSMA-PET performed for biochemical recurrence before SLND (pre-SLND PET) and b) repeat PSMA-PET performed for persistently elevated PSA level (≥0.1 ng/mL) ≥6 weeks after SLND (post-SLND PET). Image analysis was performed by three independent nuclear medicine physicians applying the molecular imaging TNM system PROMISE. Lesions were confirmed by histopathology, presence on correlative CT/MRI/bone scan or PSA response after focal therapy. Results: post-SLND PET identified PCa-lesions in 88% (14/16) of patients with PSA persistence after SLND. Median PSA was 1.2 ng/mL (IQR, 0.6-2.8 ng/mL). Disease was confined to the pelvis in 56% of patients (9/16) and most of these men had common iliac (6/16, 38%) and internal iliac lymph node metastases (6/16, 38%). Extrapelvic disease was detected in 31% of patients (5/16). In pre- and post-SLND PET comparison, 10/16 had at least one lesion already detected at baseline (63% PET persistence); 4/16 had new lesions only (25% PET recurrence); 2 had no disease on post-SLND PET. All validated regions (11 regions in 9 patients) were true positive. 9/14 (64%) patients underwent repeat local therapies after SLND (7/14 radiotherapy, 2/14 surgery). Conclusion: SLND of pelvic nodal metastases was often not complete according to PSMA-PET. About two thirds of patients had PET positive nodal disease after SLND already seen on pre-SLND PSMA-PET. Notably, about one quarter of patients had new lesions, not detected by pre-surgical PSMA-PET.




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ADAM10 and ADAM17 proteases mediate proinflammatory cytokine-induced and constitutive cleavage of endomucin from the endothelial surface [Membrane Biology]

Contact between inflammatory cells and endothelial cells (ECs) is a crucial step in vascular inflammation. Recently, we demonstrated that the cell-surface level of endomucin (EMCN), a heavily O-glycosylated single-transmembrane sialomucin, interferes with the interactions between inflammatory cells and ECs. We have also shown that, in response to an inflammatory stimulus, EMCN is cleared from the cell surface by an unknown mechanism. In this study, using adenovirus-mediated overexpression of a tagged EMCN in human umbilical vein ECs, we found that treatment with tumor necrosis factor α (TNF-α) or the strong oxidant pervanadate leads to loss of cell-surface EMCN and increases the levels of the C-terminal fragment of EMCN 3- to 4-fold. Furthermore, treatment with the broad-spectrum matrix metalloproteinase inhibitor batimastat (BB94) or inhibition of ADAM metallopeptidase domain 10 (ADAM10) and ADAM17 with two small-molecule inhibitors, GW280264X and GI254023X, or with siRNA significantly reduced basal and TNFα-induced cell-surface EMCN cleavage. Release of the C-terminal fragment of EMCN by TNF-α treatment was blocked by chemical inhibition of ADAM10 alone or in combination with ADAM17. These results indicate that cell-surface EMCN undergoes constitutive cleavage and that TNF-α treatment dramatically increases this cleavage, which is mediated predominantly by ADAM10 and ADAM17. As endothelial cell-surface EMCN attenuates leukocyte–EC interactions during inflammation, we propose that EMCN is a potential therapeutic target to manage vascular inflammation.




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What is vaginal seeding - and is it safe?

How should health professionals engage with this increasingly popular but unproved practice? Aubrey Cunnington, a consultant paediatrician from Imperial College London joins us to discuss. Read the full editorial: http://www.bmj.com/content/352/bmj.i227




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What's it like to live with a vaginal mesh?

What can we learn from the shameful story of vaginal mesh? That thousands of women have been irreversibly harmed; that implants were approved on the flimsiest of evidence; that surgeons weren’t adequately trained and patients weren’t properly informed; that the dash for mesh, fuelled by its manufacturers, stopped the development of alternatives;...




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Doctor alleged to have performed “designer vagina” surgery won’t be prosecuted




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Decreased Vagal Activity and Deviation in Sympathetic Activity Precedes Development of Diabetes

OBJECTIVE

The objective of this study was to examine whether altered heart rate variability (HRV) could predict the risk of diabetes in Asians.

RESEARCH DESIGN AND METHODS

A cohort study was conducted in 54,075 adults without diabetes who underwent 3-min HRV measurement during health checkups between 2011 and 2014 at Kangbuk Samsung Hospital. We analyzed the time domain (SD of the normal-to-normal interval [SDNN] and root mean square differences of successive normal-to-normal interval [RMSSD]) and the frequency domain (total power, normalized low-frequency power [LF], and normalized high-frequency power [HF] and LF/HF ratio). We compared the risk of diabetes until 2017 according to tertiles of heart rate and HRV variables, with tertile 1 serving as the reference group.

RESULTS

During 243,758.2 person-years, 1,369 subjects were diagnosed with diabetes. Both time and frequency domain variables were lower in the group with diabetes, with the exception of those with normalized LF and LF/HF ratio. In Cox analysis, as SDNN, RMSSD, and normalized HF tertiles increased, the risk of diabetes decreased (hazard ratios [95% CIs] of tertile 3: 0.81 [0.70–0.95], 0.76 [0.65–0.90], and 0.78 [0.67–0.91], respectively), whereas the risk of diabetes increased in the case of heart rate, normalized LF, and LF/HF ratio (hazard ratios [95% CIs] of tertile 3: 1.41 [1.21–1.65], 1.32 [1.13–1.53], and 1.31 [1.13–1.53), respectively) after adjusting for age, sex, BMI, smoking, drinking, systolic blood pressure, lipid level, CRP, and HOMA of insulin resistance.

CONCLUSIONS

Abnormal HRV, especially decreased vagal activity and deviation in sympathovagal imbalance to sympathetic activity, might precede incident diabetes.




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Des vices de conformation de l'utérus et du vagin et des moyens d'y remédier / par Leon Le Fort.

Paris : Delahaye, 1863.




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Du manuel opératoire de l’hystérectomie vaginale / par M. Malapert.

Paris : Société d’éditions scientifiques, 1893.




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Epithélioma primitif du vagin / par Félix Bernard.

Paris : G. Carre, 1895.




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Esperienze e riflessioni sopra la carie de'denti umani, coll'aggiunta di un nuovo saggio su la riproduzione dei denti negli animali rosicanti / di Francesco Lavagna.

Genova : G. Bonaudo, 1812.




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Poligny (Jura), France: an ancient mosaic floor at the villa of Estavage (Chambrettes), including figures of gryphons and centaurs. Line engraving.




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Got junk Yellowknife? Salvagers Unite wants to hear about it

From bikes to vinyl records to a remote controlled airplane, Yellowknifers looking to get rid of or find second-hand treasures have a new place to look.



  • News/Canada/North

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Journey through Congo. A new chance for Africa's ravaged heart




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'The Vagina Monologues' coming to Penn State Beaver on Feb. 13

Penn State Beaver students will give a special performance of Eve Ensler’s "The Vagina Monologues" at 5 p.m. Feb. 13 in the Penn State Beaver auditorium. The event is open to the public.




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Locked out of galleries, Londoners find Caravaggio street art

The Italian baroque master’s 'Supper at Emmaus' is usually exhibited at London's National Gallery but, with that shut, Stanhope’s giant interpretation is now on show in Ladywell, southeast London




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News18 Urdu: Latest News Sivaganga

visit News18 Urdu for latest news, breaking news, news headlines and updates from Sivaganga on politics, sports, entertainment, cricket, crime and more.




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CES Veteran Chris Dragon on the Show’s Evolution; from Simple Audio to a Tech Extravaganza

HARMAN is excited and ready to head to Las Vegas in the New Year, once again, for the Consumer Electronics Show or CES. Without a doubt, CES is one of the most prominent and strategic events for the technology, automotive and the broader business...




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Locked out of galleries, Londoners find Caravaggio street art

Londoners locked out of galleries can find an alternative art fix on a wall under under some railway arches after street artist Lionel Stanhope painted a Caravaggio classic, updated for the coronavirus age.




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Ecuador ravaged by coronavirus

The outbreak has ravaged the economy of the oil-producing country and overwhelmed sanitary authorities in the largest city of Guayaquil, where corpses remained in homes or for hours on the streets.




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Study Redefines What a Healthy Vagina Is

Title: Study Redefines What a Healthy Vagina Is
Category: Health News
Created: 5/2/2012 4:05:00 PM
Last Editorial Review: 5/3/2012 12:00:00 AM




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Vaginal Bacteria Could Help Predict Risk of Premature Birth: Study

Title: Vaginal Bacteria Could Help Predict Risk of Premature Birth: Study
Category: Health News
Created: 4/8/2020 12:00:00 AM
Last Editorial Review: 4/9/2020 12:00:00 AM




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Vaginal Bleeding

Title: Vaginal Bleeding
Category: Diseases and Conditions
Created: 7/4/2001 12:00:00 AM
Last Editorial Review: 2/11/2020 12:00:00 AM




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Multiplex Genetic Engineering Exploiting Pyrimidine Salvage Pathway-Based Endogenous Counterselectable Markers

ABSTRACT

Selectable markers are indispensable for genetic engineering, yet their number and variety are limited. Most selection procedures for prototrophic cells rely on the introduction of antibiotic resistance genes. New minimally invasive tools are needed to facilitate sophisticated genetic manipulations. Here, we characterized three endogenous genes in the human fungal pathogen Aspergillus fumigatus for their potential as markers for targeted genomic insertions of DNAs of interest (DOIs). Since these genes are involved in uptake and metabolization of pyrimidines, resistance to the toxic effects of prodrugs 5-fluorocytosine and 5-fluorouracil can be used to select successfully integrated DOIs. We show that DOI integration, resulting in the inactivation of these genes, caused no adverse effects with respect to nutrient requirements, stress resistance, or virulence. Beside the individual use of markers for site-directed integration of reporter cassettes, including the 17-kb penicillin biosynthetic cluster, we demonstrate their sequential use by inserting three genes encoding fluorescent proteins into a single strain for simultaneous multicolor localization microscopy. In addition to A. fumigatus, we validated the applicability of this novel toolbox in Penicillium chrysogenum and Fusarium oxysporum. Enabling multiple targeted insertions of DOIs without the necessity for exogenous markers, this technology has the potential to significantly advance genetic engineering.

IMPORTANCE This work reports the discovery of a novel genetic toolbox comprising multiple, endogenous selectable markers for targeted genomic insertions of DNAs of interest (DOIs). Marker genes encode proteins involved in 5-fluorocytosine uptake and pyrimidine salvage activities mediating 5-fluorocytosine deamination as well as 5-fluorouracil phosphoribosylation. The requirement for their genomic replacement by DOIs to confer 5-fluorocytosine or 5-fluorouracil resistance for transformation selection enforces site-specific integrations. Due to the fact that the described markers are endogenously encoded, there is no necessity for the exogenous introduction of commonly employed markers such as auxotrophy-complementing genes or antibiotic resistance cassettes. Importantly, inactivation of the described marker genes had no adverse effects on nutrient requirements, growth, or virulence of the human pathogen Aspergillus fumigatus. Given the limited number and distinct types of selectable markers available for the genetic manipulation of prototrophic strains such as wild-type strains, we anticipate that the proposed methodology will significantly advance genetic as well as metabolic engineering of fungal species.




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ADAM10 and ADAM17 proteases mediate proinflammatory cytokine-induced and constitutive cleavage of endomucin from the endothelial surface [Membrane Biology]

Contact between inflammatory cells and endothelial cells (ECs) is a crucial step in vascular inflammation. Recently, we demonstrated that the cell-surface level of endomucin (EMCN), a heavily O-glycosylated single-transmembrane sialomucin, interferes with the interactions between inflammatory cells and ECs. We have also shown that, in response to an inflammatory stimulus, EMCN is cleared from the cell surface by an unknown mechanism. In this study, using adenovirus-mediated overexpression of a tagged EMCN in human umbilical vein ECs, we found that treatment with tumor necrosis factor α (TNF-α) or the strong oxidant pervanadate leads to loss of cell-surface EMCN and increases the levels of the C-terminal fragment of EMCN 3- to 4-fold. Furthermore, treatment with the broad-spectrum matrix metalloproteinase inhibitor batimastat (BB94) or inhibition of ADAM metallopeptidase domain 10 (ADAM10) and ADAM17 with two small-molecule inhibitors, GW280264X and GI254023X, or with siRNA significantly reduced basal and TNFα-induced cell-surface EMCN cleavage. Release of the C-terminal fragment of EMCN by TNF-α treatment was blocked by chemical inhibition of ADAM10 alone or in combination with ADAM17. These results indicate that cell-surface EMCN undergoes constitutive cleavage and that TNF-α treatment dramatically increases this cleavage, which is mediated predominantly by ADAM10 and ADAM17. As endothelial cell-surface EMCN attenuates leukocyte–EC interactions during inflammation, we propose that EMCN is a potential therapeutic target to manage vascular inflammation.




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Journey to the Savage Planet review: It's wacky but not in a good way

There’s nothing like crash-landing on an alien planet. Journey to the Savage Planet doesn't always get it right, but it has echoes of classic Metroid Prime, says Jacob Aron




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Piers Morgan savages Boris Johnson over coronavirus leaks - 'how many lives will it cost?'



PIERS MORGAN launched another blistering attack on Boris Johnson, accusing the prime minister of encouraging the public to break the lockdown through "absurdly reckless" leaks to the media.




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Locked out of galleries, Londoners find Caravaggio street art

Londoners locked out of galleries can find an alternative art fix on a wall under under some railway arches after street artist Lionel Stanhope painted a Caravaggio classic, updated for the coronavirus age.




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Tiger King: Sia performs Megan Thee Stallion 'Savage' parody about Joe Exotic

Sia's video stars dancer Maddie Ziegler and stylist Tonya Brewer




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As coronavirus ravages Louisiana, ‘cancer alley’ residents haven’t given up the fight against polluters

The state's African Americans face some of the country’s worst pollution — and some of its most severe COVID-19 outcomes. The two may well be linked.




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BOM issues dangerous wind warning as dust blankets drought-ravaged towns

Extreme winds are churning up dust from Broken Hill to Sydney, with some parts of the central west turning red and forcing residents to eat dinner under bedsheets so as not to spoil their food.




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Sydney news: Geoffrey Rush appeal looms, drought-ravaged areas rejoice in rain

MORNING BRIEFING: The $2.9 million awarded to Australian actor Geoffrey Rush in his defamation case will be challenged in court today, while much-needed rain has fallen in some of the state's driest areas.




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Tina Lawson’s Reaction To ‘Savage’ Remix Is Priceless



Miss Tina runs the Beyhive.




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Megan Thee Stallion Secures First Top 10 Hit With "Savage"



"I really want to cry right now like oh my god!!!!"




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CarryMinati Closes In On YouTube Records After Savage TikTok Roast & The Numbers Just Keep Rising




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Cycling tries to salvage season with overlapping Giro, Vuelta in October

Cycling's governing body responds to the coronavirus pandemic, announcing a jam-packed 100-day schedule with a string of major races — including two Grand Tours — in October alone.




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Trovagene Rebrands as Cardiff Oncology, Promotes Longtime Exec to CEO

Trovagene (NASDAQ: TROV), which started out as a diagnostics company, has renamed itself Cardiff Oncology to better reflect its focus on the cancer drug it is advancing in three clinical trials. In 2017 the San Diego area-based biotech made the first step in its transformation into a drug development-focused organization, licensing rights to an investigational […]