A simulation of dark matter filaments across the universe. Zarija Lukic/Lawrence Berkeley National Laboratory Dark matter is an enigmatic beast. We can’t see it, yet we know it makes up most of our universe. Finding the mysterious particle (or particles) the exotic matter is composed of has puzzled and intrigued scientists for decades. On June 6 at the Planck 2019 conference, an international meeting highlighting frontier physics research, John Terning and Christopher Verhaaren, theoretical physicists at the University of California, Davis, presented a new theory for what makes up dark matter and how we might detect it. A preprint paper of their study was uploaded to the arXiv directory on May 31. Dark matter and dark energy, two theoretical forms of matter, are thought to make up more than 85% of the known universe. When we look out into space, the evidence for the existence of dark matter is plentiful — we can see the effect it has on gravity and the expansion of the universe. We know something, an invisible particle perhaps, is lurking out of sight and responsible for the way our universe works. Scientists have long struggled to find the elusive, exotic particle that makes up dark matter, and more theories abound every year. In December, an Oxford scientist proposed that the universe was made up of a dark fluid. Others have suggested hunting for dark matter in cutting-edge new ways. Still, we have failed to detect it.Which brings us to Terning and Verhaaren’s idea. They argue for a new “type” of dark matter and a way to detect it, a one-two punch of theory and experimental validation. However, the authors of the study caution that verifying it could take quite some time. The new type of dark matter is different from previous theories, which suggest the exotic, invisible particles may be made up of weakling interacting massive particles, or WIMPs. No experiments have been able to find these particles, though scientists have built large, shielded laboratories that hope to reveal them. “We still don’t know what dark matter is,” said Terning in a press release. “The primary candidate for a long time was the WIMP, but it looks like that’s almost completely ruled out.” The private rocket company trying to send Australia to… See SLAC, a two-mile particle accelerator next to Stanford 2 3:17 Share your voice Comments The researchers looked at an opposing theory for dark matter with an equally fantastical name: “dark electromagnetism.” It says there’s a subatomic particle known as a dark photon which sometimes interacts with regular photons that we can already detect. The duo added their own spin to the idea by showing dark matter might be caused by “dark monopoles,” which are based on quantum theory.It all gets very tangled here, especially for us mere mortals struggling with everyday physics. The bottom line? We’ve got a new theory which proposes the “dark monopole” could be detected in an experiment thanks to its interactions with regular photons and the Aharonov-Bohm effect, which has been proven experimentally. However, the observable effect would be incredibly small — even smaller than gravitational waves — and we don’t yet have the technology to detect such minute signals right now. Alan Duffy, a dark matter researcher at Swinburne University in Australia, notes how the first detection of gravitational waves (itself only a theory until recently) took “a century of heroic scientific and engineering effort” suggesting that might be “a worry for the testability of the [new] prediction.”Where does that leave Terning and Verhaaren’s theory? Well, as a theory, of course. But that’s where all good science starts. Tags 33 Photos Now playing: Watch this: Sci-Tech
State minister Nasrul Hamid on Wednesday termed the current problem in gas supply to CNG stations temporary saying that the situation will get normal within a day.He made the remark as CNG refuelling stations in the city have been shut following the start of maintenance work at Sylhet’s Bibiyana gas field, the country’s largest gas field.Nasrul was talking to reporters at his office.Titas Gas transmission and Distribution Company suddenly asked all the CNG stations to keep their operation suspended for 24 hours from zero hour Wednesday to facilitate maintenance works at Bibiyana, causing trouble to many in refuelling their cars.Many public transports also faced the similar problem as they could not refuel their vehicles.Nasrul said the CNG stations will remain off for 24 hours until zero hour Thursday. “So, this is for a very short period of time.”About the trouble being experienced by the CNG-run motor vehicles in refuelling, the junior minister said it was scheduled much earlier to keep the CNG station closed and a notice was also served to the stations concerned apart from informing the public through media.He advised those using CNG in their vehicles to use liquid fuel like petrol, octane or diesel.
Police officers detaining Kremlin critic Alexei Navalny during an unauthorised anti-corruption rally in central Moscow. Photo: AFPHundreds of people including top Kremlin critic Alexei Navalny were arrested on Sunday as thousands of Russians defied bans to stage protests across the country against corruption.Navalny had called for the marches after publishing a detailed report this month accusing Prime Minister Dmitry Medvedev of controlling a property empire through a shadowy network of nonprofit organisations.The report has been viewed over 11 million times on YouTube, but so far Medvedev has made no comment on the claims.Sunday’s march in Moscow was one of the biggest unauthorised demonstrations in recent years, with police putting turnout at 7,000-8,000 people.Police detained Navalny, who has announced plans to run for president in the 2018 election, as he was walking to the protest, putting him in a police minibus.The crowd briefly tried to block it from driving off, shouting “Shame!” and “Let him out!”“Guys, I am all right, go on along Tverskaya,” Navalny tweeted from the van, referring to Moscow’s main central street.Police said about 500 people had been arrested in Moscow, while OVD-Info, a website that monitors the detention of activists, said at least 933 had been detained, as well as dozens in other cities.The Interfax news agency said 130 people were arrested in Saint Petersburg, where about 4,000 people gathered in the city centre.“We’re tired of the lies, we have to do something,” Sergei Timofeyev, a 23-year-old protester in Saint Petersburg, told AFP.A spokeswoman for Navalny’s Anti-corruption Foundation (FBK) said on Twitter than he would be held overnight before being brought before a judge on Monday.He will face charges of calling a rally that disrupted public order, and could be held for up to 15 days.From his cell, Navalny posted on Twitter that he was “proud” of the protesters and said the mass detentions were “understandable”.“The thieves defend themselves this way. But you cannot arrest everyone who is against corruption. There are millions of us,” he wrote.The United States condemned the arrests as an affront to democracy.“Detaining peaceful protesters, human rights observers, and journalists is an affront to core democratic values,” acting State Department spokesman Mark Toner said in a statement.‘They steal and lie’Thousands of people filled central Pushkin Square, some shouting “Russia without (President Vladimir) Putin”. Some climbed on to lamp posts and the monument to poet Alexander Pushkin, shouting “impeachment!”Dozens of police vans and rows of riot officers were lined up as a police helicopter hovered overhead.“We have all seen the movie, it gives specific examples of corruption, and there has been no reaction,” Nikolai Moisey, a 26-year-old factory worker, said of the claims against Medvedev.“They steal and they lie but still people will be patient to the end. The protest is a first push for people to start acting.”Police officers moved to detain protesters and clear the square, with some using truncheons and pepper spray to disperse the crowd, AFP correspondents said.Police also searched FBK offices over alleged incitement to hatred, and “Everyone was detained and brought to the police,” the organisation’s spokeswoman Kira Iarmych said.‘99 cities’Despite the dramatic scenes in Moscow, state TV did not cover the protests, instead showing soap operas and nature films.“The whole country is tired of corruption on such a scale,” 50-year-old Natalia Demidova said. “Medvedev should be fired once such exposes come to light.”Elsewhere, about 2,000 gathered in the Siberian city of Novosibirsk, carrying signs such as “No to corruption,” according to local news website Sib.fm.Some held up images of yellow rubber ducks, following reports that Medvedev has a special house for a duck on one of his properties.Local media estimated about 1,500 people turned out in each of the Siberian cities of Krasnoyarsk and Omsk.The Russian constitution allows public gatherings, but recent laws have criminalised protests unauthorised by city authorities, who frequently refuse to grant permission for rallies by Kremlin critics.Navalny said on his website that 99 Russian cities planned to protest, but that in 72 of them the local authorities did not give permission, citing reasons such as street cleaning, a bell-ringing concert and rival events by various pro-Kremlin groups.There were also protests in Vladivostok and Yekaterinburg, according to local reports.Navalny, a 40-year-old lawyer by training announced plans to run for the presidency after he won a surprise 27 percent of the vote in the Moscow mayoral election in 2013.But he has been the subject of several legal prosecutions in recent years, and in February he was found guilty of embezzlement and given a five-year suspended sentence which could make him ineligible to run in next year’s vote.
Quaternary-ammonium-salt linkers can be proteolytically or reductively cleaved on cell entry and tracelessly release tertiary and heteroaryl amines. Credit: (c) Nature Chemistry (2016) doi:10.1038/nchem.2635 (Phys.org)—Beyond designing a drug that will attack cancer cells or bacterial cells, drug design also involves figuring out how the drug can safely enter the body and find its target before doing its work. However, many drugs never make it to their desired target either because of solubility issues or inability to access certain parts of the cell. That is where carriers come in. Carriers are like molecular taxis that latch onto a small-molecule drug and transport it to its target location. Journal information: Nature Chemistry Citation: Targeted drug therapy with carrier links to tertiary and heteroaryl amines (2016, November 3) retrieved 18 August 2019 from https://phys.org/news/2016-11-drug-therapy-carrier-links-tertiary.html These molecular taxis need to connect to the drug in such a way that they safely take it to the location, but the connection must also be reversible so the carrier can eventually release the drug. There are very few types of chemical bonds that can do this and the ones that can are limited in scope.A group of scientists from Genentech, Inc. have devised a synthetic scheme that is generalizable, protecting-group free, and allows for a carrier linker to attach to tertiary or heteroaryl amines via a quaternary ammonium salt. Additionally, because it is a charged species, it is more water soluble than typical carrier molecules and, therefore, may alleviate the problems associated with aggregation. These linkers can be set up to be cleaved either by proteases in the lysosome or reducing agents in the cytosol. This work appears in Nature Chemistry.”Enabling the reversible connection of tertiary and heteroaryl amines allows us to consider many new drugs, previously unamenable for targeted therapy,” Dr. Thomas Pillow told Phys.org.The ability to attach a linker to a tertiary amine or a heteroaryl amine is of interest because there are several known anticancer and antibacterial drugs that that have these functional groups. These groups often cannot be converted to a secondary or primary amine because of synthetic complexities or diminished drug potency. These drugs require a carrier molecule in order to be most effective in the body, but most carrier molecules previously could only be connected to primary or secondary amines.Additionally, many anticancer and antibacterial drugs are hydrophobic. But, the body is a predominantly aqueous environment. This means that, upon entering the body, the hydrophobic molecules tend to aggregate, which can cause problems with bodily systems or protein uptake. Notably, when the Genentech scientists attached a tertiary amine to a linker via a quaternary ammonium salt, it became more hydrophilic suggesting that this might be a good option for countering the aggregation problem. The first step was to determine if a tertiary amine could be reversibly attached to a chemical linker. To test their proposed linker connection, a p-aminobenzyl quarternary ammonium salt, they chose a known dipeptide-cleavable trigger: valine-citrulline (ValCit) which cleaves in the presence of cathepsin B. Incubation of their linker in buffer demonstrated that the quaternary ammonium salts were stable, and exposure to cathepsin B resulted in cleavage at the aniline amide and generation of the tertiary amine as expected. Carbon-carbon bond formation at selective aliphatic carbon sites More information: Leanna R. Staben et al. Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody–drug conjugates, Nature Chemistry (2016). DOI: 10.1038/nchem.2635AbstractThe reversible attachment of a small-molecule drug to a carrier for targeted delivery can improve pharmacokinetics and the therapeutic index. Previous studies have reported the delivery of molecules that contain primary and secondary amines via an amide or carbamate bond; however, the ability to employ tertiary-amine-containing bioactive molecules has been elusive. Here we describe a bioreversible linkage based on a quaternary ammonium that can be used to connect a broad array of tertiary and heteroaryl amines to a carrier protein. Using a concise, protecting-group-free synthesis we demonstrate the chemoselective modification of 12 complex molecules that contain a range of reactive functional groups. We also show the utility of this connection with both protease-cleavable and reductively cleavable antibody–drug conjugates that were effective and stable in vitro and in vivo. Studies with a tertiary-amine-containing antibiotic show that the resulting antibody–antibiotic conjugate provided appropriate stability and release characteristics and led to an unexpected improvement in activity over the conjugates previously connected via a carbamate. Explore further This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. The next step was to optimize their synthesis to make it simple and generalizable so it can be used for drug screening. In particular, the synthesis could not involve the use of protecting groups and the carrier molecule needed to preferentially react with the tertiary amine on the small molecule drug. After developing the experimental conditions for their reaction, Staben et al. then tested the stability and release of their protease-cleavable linker with a variety of molecules containing tertiary and heteroaryl amines. Good stability and drug release was demonstrated with several of these conjugates.Thus far, Staben et al. have been looking at the cleavage of peptide bonds. Disulfide bonds are another bond that can be set up as a bioactive trigger that is reduced by intracellular GSH. They tested their system by cleaving the disulfide bond and were able to generate the free tubulysin drug. In the field of targeted therapies, antibody-drug conjugates have gained ground as a way to target cancer cells or invading bacteria. Prior research by this team demonstrated that an antibody-antibiotic conjugate was able to successfully clear methicillin-resistant S. aureus (MRSA) infections. For the current research, they linked the tertiary amine of a rifamycin analog to their quaternary ammonium salt linker and found that in vitro tests showed a large reduction in the number of intracellular MRSA bacteria, a typically difficult-to-treat bacterial infection. According to Dr. Pillow, “This novel linker connection expands the universe of drugs for targeted therapy, opening up new possibilities for the treatment of cancer and infectious disease.” © 2016 Phys.org