Look, Ukrainian Zelensky Is Ready to Go Down the Drain: Pentagon Weapons For Kyiv To Dry Up In Months --- U.S. Defense officials say $5.2 billion won't last long if U.S. Congress fails to fund Ukraine aid.

"The Pentagon has more than $5 billion remaining in its coffers to provide weaponry and other security assistance to Ukraine even after Congress declined to include more funding for the conflict in a weekend bill to keep the government open, Pentagon officials said.

The $5.2 billion is roughly equivalent to the value of the weaponry the Biden administration has sent to Ukraine over the last six months for its fight against Russia, but administration officials said it is unclear how long that money could last. 

A number of factors contribute to the rate at which security aid flows to Kyiv, and officials believe the $5.2 billion could last only for another few months.

The sum is roughly about 12% of the total $43.9 billion in security assistance that the U.S. has sent since Russia's February 2022 events, leaving a sizable amount of security assistance still available.

But another pot of money the U.S. had been using for a longer-term program to refurbish Ukraine's military and make it more compatible with North Atlantic Treaty Organization forces, the Ukraine Security Assistance Initiative, is empty, administration officials said.

What's more, an account used to replenish the Defense Department's own arsenal after the provision of U.S. arms to Ukraine is now down to about $1.6 billion -- insufficient to keep the Pentagon whole, officials said.

Aid packages have typically come every two weeks, and the next could come by the end of this week, officials said. But without knowing when Congress will approve more funds, the Pentagon might be reluctant to continue providing regular tranches of new equipment in order to save money to replenish the U.S. military's own stocks, or in case of a national security emergency, at least until Nov. 17, when the current funding bill runs out, a Senate aide said.

The short-term spending bill signed by President Biden on Saturday averted a partial government shutdown but omitted aid for Ukraine, raising questions about the future of U.S. support. The administration had sought another $24 billion in Ukraine funding.

Despite dire warnings from the Biden administration about the impact on Kyiv's conflict effort, the threat to security assistance for Ukraine is more likely to emerge in the long term, and U.S. officials said the political uncertainty in Washington sends a terrible signal to the international community that Biden has rallied in support of Kyiv's fight against Russia. Ukraine's supporters fear President Vladimir Putin of Russia will come to believe he can wait out the U.S. The Kremlin is girding for a longer conflict, making big increases to military spending.

Defense Secretary Lloyd Austin spoke Sunday with his counterpart in Ukraine, Defense Minister Rustem Umerov, to "reiterate" U.S. support for Ukraine, the Pentagon said.

The U.S. has given Ukraine a vast range of military materiel, including tanks, helicopters, advanced guided missile launchers, and millions of rounds of ammunition. The assistance enabled Kyiv to stave off and beat back Russia that many initially thought would quickly succeed in toppling the Kyiv government, and even regain some ground Russia took in its initial push.

So far, the weekend snag in funding for Ukraine hasn't forced the administration to begin rethinking the future of U.S. support for the conflict in Ukraine, officials said, even as a group of hard-right Republican lawmakers has begun to undermine the otherwise bipartisan, bicameral support for Kyiv.

"Nobody is hitting the panic button over here," one U.S. official said.

On Monday, Biden said he expected House Speaker Kevin McCarthy and the Republican House majority to pass more Ukraine aid.

"We cannot under any circumstances allow American support for Ukraine to be interrupted," Biden said. "Too many lives are at stake, too many children [1] and too many people."

McCarthy (R., Calif.) signaled on Monday he would link future Ukraine aid to strict Republican border security proposals. "I have been very clear from the very beginning, I have voted to arm Ukraine," he said. "America takes first priority here. And our border has got to be secure."

The $5.2 billion the Pentagon has remaining comes after it discovered an accounting error in May, essentially giving it more money for Ukraine than it thought it had. In addition, the Pentagon has about $1.6 billion in money it uses to draw from to replenish its own stocks of weaponry it has provided to Ukraine.

Ukrainian officials sought to temper doubts about U.S. support for its conflict effort against Russia. Foreign Minister Dmytro Kuleba of Ukraine said discussions with Republicans and Democrats were continuing and that the omission was an isolated event.

"We are now working with both sides of Congress so that it does not happen again under any circumstances," he said. "Therefore, we do not believe that U.S. support has faltered."" [2]

1. Everything we do here is for the children of Ukraine. Every cluster weapon demanded by Lithuanian Defense Minister Mr. Anušauskas is intended to kill Ukrainian children decades after the end of the conflict. Anušauskas quickly realized that children are not people, because they are easily produced with all the students that only you like. Jews have long said that a child is not born until it has received a degree as a medical doctor or a lawyer.

2. Pentagon Weapons For Kyiv To Dry Up In Months --- Defense officials say $5.2 billion won't last long if Congress fails to fund Ukraine aid. Lubold, Gordon; Wise, Lindsay.  Wall Street Journal, Eastern edition; New York, N.Y.. 03 Oct 2023: A.1.

Kodėl jūsų „Covid“ skiepai veikia: pora buvo sutikta su abejonėmis, dabar laimėjo Nobelio premiją

„Katalin Kariko ir Drew Weissman pirmadienį laimėjo Nobelio medicinos premiją už idėją, kuri anksčiau laikė juos nustūmtus į mokslo įstaigos užribį, o vėliau, pandemijos metu, išgelbėjo milijonus gyvybių.

 

     Molekulinė biologė Kariko ir imunologas Weissmanas, atsitiktinai susidūrę prie Pensilvanijos universiteto fotokopijavimo aparato 1990-aisiais, suprato, kad jie gali sujungti jų darbus ir ištirti, kaip pasiuntinio RNR gali gaminti veiksmingus vaistus ar vakcinas.

 

     Jų bendradarbiavimą kolegos sutiko skeptiškai ir abejingai mokslo bendruomenėje. Kariko veltui stengėsi užsitikrinti finansavimą jos darbui. Pennas ją pažemino ir išsiuntė dirbti į biurą universiteto miestelio pakraštyje.

 

     „Žmonės stebėjosi: „Kas po velnių jai negerai“, turi būti kažkokia priežastis, kodėl ji nebedirba profesore“, – sakė Kariko.

 

     Po daugelio metų, kai vaistų gamintojai lenktyniavo, kurdami vakcinas nuo Covid-19, būtent mRNR technologija buvo pritaikyta plačiai naudojamiems Pfizer-BioNTech ir Moderna skiepams. Nobelio komitetas pripažino, kad Kariko ir Weissman darbas išgelbėjo milijonus gyvybių.

 

     „Laureatai prisidėjo prie precedento neturinčio vakcinų kūrimo greičio per vieną didžiausių grėsmių žmonių sveikatai šiais laikais“, – sakė komitetas, įteikdamas 68 metų Kariko ir 64 metų Weissman kasmetinę premiją fiziologijos ar medicinos srityje. Kariko yra 13-oji moteris iš 227 žmonių, laimėjusi prizą.

 

     „Mes sutelkėme dėmesį į mokslą“, - pirmadienį sakė Kariko. „Štai kodėl mes ištvermingi, esame atsparūs“.

 

     Kariko, lengvai bendraujanti ir atvira mokslininkė, turinti daktaro laipsnį biochemijos srityje, beveik dešimtmetį veltui bandė įtikinti kolegas, kad mRNR gali pagaminti norimus baltymus  organizme. Tada ji susitiko su Weissmanu.

 

     Weissman, medicinos daktaras, turintis daktaro laipsnį. imunologijoje ir mikrobiologijoje beveik nesišypsojo, vaikščiodamas po universiteto miestelį, net dėl nuotraukų. Kartą jo žmona juokavo, kad jis buvo toks tylus, kad kiekvieną dieną nusistatydavo žodžių limitą. Vis dėlto jis norėjo padėti kitiems tyrinėtojams.

 

     Kaip ir dauguma to meto mokslininkų, Weissmanas iš pradžių buvo atsargus dėl mRNR – molekulės, kuri buvo laikoma per trumpaamže ir sunkiai pagaminama laboratorijoje, kad suteiktų daug naudos. Kariko įtikino jį naudoti mRNR jo eksperimentuose.

 

     „Jei tau pavyks ją padaryti, aš ją pabandysiu“, – prisiminė Weissmanas, sakydamas jai su abejonėmis.

 

     Prieš naudojant mRNR technologiją, vakcinos buvo gaminamos iš neaktyvios arba nekenksmingos virusinės medžiagos. Tokie gydymo būdai gali užtrukti daugiau, nei 10 metų, nes virusams auginti reikalingas daug pastangų reikalaujantis ląstelių auginimas. Kariko ir Weissmanas norėjo rasti būdų, kaip į organizmą įšvirkšti mRNR, nesukeliant kūno apsaugos reakcijos.

 

     „Nuo pat pradžių žinojome, kad RNR turi neįtikėtiną potencialą, tik nežinojome, kada“, – pirmadienį sakė Weissmanas, sužinojęs, kad laimėjo Nobelio apdovanojimą 4 val. ryte iš pokalbio telefonu.

 

     Devintajame dešimtmetyje mokslininkai atrado mRNR gamybos be ląstelių kultūros metodą, vadinamą in vitro transkripcija. Tačiau mRNR, pagaminta šiuo metodu, sukėlė imuninį atsaką, kuris sukėlė uždegimą, ir tai nesukėlė veiksmingos baltymų gamybos organizme. Kariko ir Weissmano atradimai padėjo įveikti šias kliūtis.

 

     Jie įrodė, kad gali modifikuoti mRNR – tam tikrą molekulinę bitę darbuotoją, kuri turi DNR užkoduotas instrukcijas, todėl ją būtų galima saugiai ir efektyviai naudoti. Tyrėjai dabar išbando mRNR vakcinas, kad būtų nukreiptos į kitas ligas, įskaitant gripą ir kai kurias vėžio formas.

 

     Weissmanas dirbo su dalimi imuninės sistemos, vadinamos dendritinėmis ląstelėmis, o Kariko eksperimentavo su mRNR švirkštimu į vėžio ląsteles. Jiedu nusprendė suleisti mRNR į dendritines ląsteles, kad pamatytų, ar mRNR sukels tam tikrų baltymų gamybą. Tai padarė. Weissmanas kartą pasakė, kad rezultatai buvo „nepaprasti“. Tačiau mRNR sukėlė uždegiminį atsaką, nes ląstelės traktavo ją kaip svetimą įsibrovėlį, paneigdamos bet kokią naudą.

 

     Duetas išsiaiškino, kad jei jie pakeistų mRNR bazinius komponentus arba nukleozidus, jie galėtų išvengti uždegiminio atsako [1].

 

     Modifikacijos veiksmingai padarė mRNR „imuninę tylią“, leidžiančią jai patekti į ląsteles ir atlikti savo darbą. Mokslininkai taip pat išsiaiškino, kad modifikuota mRNR žymiai padidino baltymų gamybą.

 

     2005 m. paskelbę šį perversmą, Kariko ir Weissman manė, kad juos užplūs biotechnologijų įmonių ir kitų mokslininkų susidomėjimas. Taip neatsitiko. Poros startas toli nenuėjo. Jie vis tiek to laikėsi.

 

     Bartas Andersonas, dirbęs su Kariko ir Weissman Penne kaip mokslų aspirantas 2000-taisiais, prisimena Kariko sakiusi, kad jos siekis buvo pamatyti bent vieną žmogų, kuriam per jos gyvenimą padėtų mRNR terapija.

 

     „Jie turėjo įžvalgumo ir ryžto pamatyti terapinės mRNR vertę, nepaisant to, ką galvoja platesnė mokslo bendruomenė“, – sakė Andersonas, dabar dirbantis Vokietijos farmacijos įmonėje Grunenthal ir kuriantis RNR pagrindu pagamintus vaistus nuo skausmo.

 

     Praėjus keleriems metams po to, kai Kariko ir Weissmanas paskelbė savo pagrindinį darbą, Harvardo universiteto kamieninių ląstelių mokslininkas Derrickas Rossi, atlikdamas savo tyrimus, rėmėsi tuo, todėl jis tapo „Moderna“ įkūrėju.

 

     „Retai kada esminis atradimas daro tokį didžiulį klinikinį poveikį“, – pirmadienį sakė Rossi.

 

     Pennas užpatentavo jų mRNR technologiją, o šis Filadelfijoje įsikūręs universitetas vėliau licencijavo ją „Moderna“ ir „BioNTech“. „Moderna“ ir „BioNTech“ moka dalį savo mRNR vakcinos pardavimo lėšų, kaip honorarą Pennui.

 

     Kariko buvo BioNTech vyresnioji viceprezidentė nuo 2013 m. iki 2022 m., o dabar konsultuoja bendrovę. Ji taip pat yra Segedo universiteto profesorė savo gimtojoje Vengrijoje ir docentė Penne. Weissmanas yra Penno profesorius.

 

     Nobelio fiziologijos ar medicinos premijos laureatai gauna 11 milijonų Švedijos kronų, ty maždaug 1 milijoną dolerių.

 

     „Didelė privilegija priklausyti visiems mokslininkams, kurie gavo šią premiją“, – sakė Kariko." [2]

 

1. Kariko pastebėjo, kad jos kontrolė, transporto RNR, nesukelia stiprios imuninės reakcijos organizme. Bandydama suprasti kodėl, ji išsiaiškino, kad pagrindinė priežastis buvo dažniausia uridino nukleotido modifikacija gamtoje, kai cukraus likutis yra prijungtas prie bazės C-Cryšiu vietoj uridino C-N jungties, todėl  susidaro pseudouridinas. Tokios modifikacijos pakanka, kad mūsų susintetinta iRNR liktų organizme pakankamai ilgai, kad pagamintų pakankamai baltymų, kuriuos norime susintetinti.

 

 2.  Pair Met With Doubts, Now Win Nobel Prize. Mosbergen, Dominique; Loftus, Peter; Zuckerman, Gregory.  Wall Street Journal, Eastern edition; New York, N.Y.. 03 Oct 2023: A.1.

Why Do Your Covid Shots Work: Pair Met With Doubts, Now Win Nobel Prize.

"Katalin Kariko and Drew Weissman won the Nobel Prize in medicine on Monday for an idea that pushed them to the fringes of the scientific establishment before it saved millions of lives during the pandemic.

Kariko, a molecular biologist, and Weissman, an immunologist, realized during a chance encounter at a University of Pennsylvania photocopy machine in the 1990s that they could combine their work to explore how messenger RNA might produce effective drugs or vaccines.

Their collaboration was met with skepticism by their colleagues and indifference in the scientific community. Kariko struggled to secure funding for her work. Penn demoted her and sent her to work in an office on the outskirts of campus.

"People wondered, 'What the hell is wrong with her,' there must be some reason she's not on the faculty," Kariko has said.

Years later, as drugmakers raced to develop vaccines against Covid-19, it was mRNA technology that powered widely used shots from Pfizer-BioNTech and Moderna. The Nobel committee credited Kariko's and Weissman's work with saving millions of lives.

"The laureates contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times," the committee said in awarding Kariko, 68 years old, and Weissman, 64, the annual prize in physiology or medicine. Kariko is the 13th woman among 227 people to win the prize.

"We focused on doing the science," Kariko said Monday. "That's why we persevere, we are resilient."

Kariko, a gregarious and outspoken scientist with a Ph.D. in biochemistry, had tried for nearly a decade to convince colleagues that mRNA could deliver desired proteins to the body. Then she met Weissman.

Weissman, a medical doctor with a Ph.D. in immunology and microbiology, hardly smiled around campus, even for photos. His wife once joked that he was so taciturn he set a self-imposed word limit each day. He was eager to help other researchers, though.

Like most scientists at the time, Weissman was originally wary of mRNA, a molecule deemed too short-lived and difficult to make in the lab to provide much value. Kariko convinced him to use mRNA in his experiments.

"If you make it, I'll try it," Weissman remembered telling her, halfheartedly.

Before mRNA technology, vaccines were made from inactive or harmless viral material. Such therapies can take more than 10 years to develop because of the laborious cell culturing required to grow the viruses. Kariko and Weissman wanted to find ways to inject mRNA into the body without setting off the body's defenses.

"We knew from the beginning that RNA had incredible potential, we just didn't know when," Weissman said on Monday, after he learned he had won the Nobel in a 4 a.m. phone call.

In the 1980s, researchers discovered a method of producing mRNA without cell culture called in vitro transcription. But mRNA made by that method triggered immune responses that caused inflammation and it didn't result in efficient protein production in the body. Discoveries by Kariko and Weissman helped overcome those roadblocks.

They proved they could modify mRNA, a kind of molecular worker bee that carries instructions encoded in DNA, so it could be used safely and effectively. Researchers are now testing mRNA vaccines to target other diseases including influenza and some cancers.

Weissman had been working with part of the immune system called dendritic cells, and Kariko had been experimenting with injecting mRNA into cancer cells. The two decided to inject mRNA into dendritic cells to see if the mRNA would cause the production of certain proteins. It did. The results were "off the wall," Weissman once said. But the mRNA triggered an inflammatory response because the cells treated it as a foreign intruder, negating any benefit.

The duo figured out that if they modified the base components, or nucleosides, of mRNA, they could avert the inflammatory response [1].

The modifications effectively rendered mRNA "immune silent," allowing it to get into cells to do its work. The scientists also discovered that modified mRNA significantly increased protein production.

After publishing a breakthrough paper in 2005, Kariko and Weissman thought they would be inundated with interest from biotechnology companies and other scientists. That didn't happen. The pair's startup didn't get far. They kept at it anyway.

Bart Anderson, who worked with Kariko and Weissman at Penn as a Ph.D. student in the 2000s, remembers Kariko saying her ambition was to see at least one person helped by mRNA therapies in her lifetime.

"They had the foresight and determination to see the value of therapeutic mRNA, regardless of what the wider scientific community thought," said Anderson, who is developing RNA-based medicines for pain at Grunenthal, the German pharmaceutical company.

A few years after Kariko and Weissman published their seminal work, a stem-cell scientist at Harvard University, Derrick Rossi, built on it in his own research, leading him to become a co-founder of Moderna.

"It is rare that a fundamental discovery makes such an enormous clinical impact," Rossi said on Monday.

Penn patented their mRNA technology, and the Philadelphia-based university later licensed it to Moderna and BioNTech. Moderna and BioNTech pay a portion of their mRNA vaccine sales as royalties to Penn.

Kariko was a senior vice president at BioNTech from 2013 until 2022, and now advises the company. She is also a professor at University of Szeged in her native Hungary and an adjunct professor at Penn. Weissman is a professor at Penn.

Winners of the Nobel Prize in physiology or medicine receive 11 million Swedish kronor, the equivalent of around $1 million.

"It's a great privilege to belong to all of those scientists who have received this prize," Kariko said." [2]

1. Kariko noticed that her control, transport RNA, did not cause a strong immune reaction in the body. While trying to understand why, she found that the main cause was most common modification of uridinenucleotide in nature is when a sugar residue is attached to a base with a C-Cbond, resulting in pseudouridine, instead of a C-N bond in uridine. Such a modification is enough to keep in the body the mRNA we have synthesized long enough to produce enough of the protein we want to synthesize.

2.  Pair Met With Doubts, Now Win Nobel Prize. Mosbergen, Dominique; Loftus, Peter; Zuckerman, Gregory.  Wall Street Journal, Eastern edition; New York, N.Y.. 03 Oct 2023: A.1.