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Random number generation is a process in which a sequence of numbers or symbols that cannot be predicted better than by random chance is generated. The outcome sequence will contain some patterns that are impossible to see in hindsight. Hardware random-number generators (HRNGs) can be true random number generators, since each generation is a function of the current value of a physical environment’s attribute that is almost impossible to model. Random number generations done by pseudorandom number generators can be reproduced by knowing the state of the PRNG, unlike this. Various applications of randomness have led to the development of different methods for generating random data Rolling of dice, coin flipping, the shuffling of playing cards, and the use of yarrow stalks for divination are just some of the techniques that have been around for a long time. The mechanical nature of these techniques required a lot of time and work. Random number tables would be used to collect and distribute results. There are several methods for pseudorandom number generation. All fall short of the goal of true randomness, although they may meet with varying success, some of the statistical tests for randomness intended to measure how unpredictable their results are. They are generally not usable for applications such as cryptography. Special features designed for use in cryptography are included in the carefully designed.

Summary: The company’s decades-long effort to bring a non-opioid pain medicine to market was a major milestone when the drug reduced acute, post- surgical pain without the risk of addiction. The drug works by blocking pain signals at their origin before they reach the brain, and the company plans to file for approval in the U.S. by mid-2024. According to analysts, it could achieve annual sales of more than $5 billion. In two late-stage studies, the drug was more effective in reducing the intensity of pain than a placebo was.

The treatment, however, failed to meet the secondary goal of reducing pain when compared to hydrocodone and acetaminophen. The drugmaker’s shares fell to $433.75 in early trading, down more than 3% from their previous close. Analysts hailed the results as a win for Vertex and said the drug was likely to gain approval for treatment of acute pain, offering a much-needed alternative to addictive painkillers that have fueled a national crisis.

“Investors and the company didn’t expect superiority over the drug as there is a huge safety and addiction advantage even without that,” said an analyst. While Vertex’s drug works by blocking pain signals at source, the brain’s reward centers are triggered by the opioids as they travel through the blood. They attach to the brain, causing addiction and abuse. The company said the drug was well-tolerated and safe in trials that tested a total of 2,400 patients. There were a lot of side effects, including nausea and constipation. Attempts to bring new alternatives to the market by drug makers such as Eli Lilly have failed in trials.

This article was inspired by: https://www.reuters.com/business/healthcare-pharmaceuticals/vertex-non-opioid-pain-drug-succeeds-late-stage-trials-2024-01-30/

A new study by physicists and neuroscientists from the University of Chicago, Harvard and Yale shows how networking and self-organization can lead to better connections among neurons. The research, which was published in Nature Physics on January 17, 2024, accurately describes neuronal connections in a variety of model organisms and could apply to non-biological networks. “When you’re building simple models to explain biological data, you expect to get a good rough cut that fits some but not all scenarios,” said the author of the paper. When we did that here, it ended up explaining things in a way that was really satisfying, because you don’t expect it to work as well when you dig into the mundane. A web of connections between brain cells is formed.

While the vast number of connections may seem random, networks of brain cells tend to be dominated by a small number of strong connections. The way the distribution of connections looks when plotted on a graph is called a “heavy-tailed” distribution of connections. Scientists were unsure if the heavy-tailed pattern was due to biological processes specific to different organisms or if it was due to basic principles of network organization.

Palmer and Lynn analyzed connectomes, or maps of brain cell connections, to answer the questions of how the brain works. Fruit flies, roundworms, marine worms and the mouse retina are some of the classic lab animals. They developed a model based on Hebbian dynamics, a term used by Canadian psychologist Donald Hebb in 1949, to understand how the brain works. The stronger the connection becomes, the more the two neurons are activated. The researchers found that the Hebbian dynamics produce strong connection strengths just like they saw in the different organisms.

The results show that this kind of organization is a result of general principles of networking, not specific to the biology of fruit flies, mice, or worms. The model provided an explanation for clustering, a phenomenon in which cells link with each other via connections they share. In social situations, clustering occurs. One person introducing a friend to a third person is more likely to become friends with that person than if they met separately. “These are mechanisms that everyone agrees are going to happen in neuroscience,” he said. The data can give rise to many different effects in clustering and distributions if you treat it carefully.

Palmer pointed out that biology doesn’t always fit a neat and tidy explanation, and there is still a lot of randomness and noise involved in brain circuits. Weak connections can be formed elsewhere, and stronger connections can be formed with the help of a nervy network. This randomness checks the kind of Hebbian organization the researchers found in this data, without which strong connections would grow to dominate the network.

The model was changed to account for randomness. Lynn said that the model would fail without that noise aspect. It wouldn’t work, which was surprising to us. You have to balance the Hebbian snowball effect with the randomness to get everything to look like real brains. The team hopes they can extend the work beyond the brain since these rules arise from general networking principles.

The way the science got done is another cool aspect of this work. There is a lot of knowledge on this team, from big data analysis to biochemical and evolutionary networks. We were focused on the brain here, but now we can talk about other types of networks.

This article was inspired by: https://biologicalsciences.uchicago.edu/news/simple-model-brain-cells-connect

Explorers haven’t been able to find the fountain of youth. The magic anti-aging elixir might have been in us all along. T cells can be reprogrammed to fight aging according to Cold Spring Harbor Laboratory Assistant Professor Corina Amor Vegas. White blood cells can attack senescent cells if they have the right set of genes. These cells are thought to be the cause of many diseases later in life. Senescent cells stop replicating. They build up in our bodies as we age, leading to inflammation. Several drugs are currently available that can eliminate these cells, but many must be taken repeatedly over time.

As an alternative, they turned to a drug called CAR, which is a “living” drug. They found that CAR T cells could be manipulated to eliminate senescent cells. The mice lived healthier lives as a result. They had lower body weight and increased physical activity. No tissue damage or toxicity came from the benefits. Las Vegas says:

If we give it to old mice, they will use it again. Young mice age slower if we give it to them. Right now no other therapy can do this. CAR T cells have the greatest longevity of any cell type. One dose at a young age can have long-term effects. It is possible to protect against conditions that occur later in life. Amor Vegas explains. T cells can persist in your body for a long time, which is different from a chemical drug. If you have CAR T cells, you have a chance of getting this one treatment. That is a huge advantage for chronic pathology. If you think about patients who need treatment multiple times per day, then you’re good to go for multiple years.

The FDA approved the use of CAR T cells to treat blood cancers. One of the first scientists to show that CAR T cells can be used for more than just cancer is Amor Vegas. The CAR T cells are being investigated to see if they let mice live longer. Society will be one step closer to the fountain of youth if that is the case.

This article was inspired by: https://www.cshl.edu/the-fountain-of-youth-is-a-t-cell/

We want to kill it with hand washing, antiseptic wipes, hand sanitizer, bleach, and even robot zapping hospital rooms. According to most scientists, we have been working to kill something that isn’t alive.

Viruses have rarely been considered alive. metabolism is a set of chemical reactions that produce energy. Viruses can’t metabolize. They do not fit some of the other criteria. They don’t have cells. They cannot reproduce by themselves. A host cell can’t replicate a Viruses can’t replicate without a host cell A coronaviruses is a sphere made up of genes wrapped in a coat and bedecked with spike proteins.

Viruses have a lot of living things. They are the same building blocks. They grow and change. Once inside a cell, viruses engineer their environment to suit their needs – constructing organelles and controlling which genes and proteins the cell makes Recently discovered giant viruses, which rival the size of somebacteria, have been found to contain genes for proteins used in metabolism.

Almost every rule that excludes viruses from the land of the living has its own exceptions. Rickettsiabacteria are classified as living but can only grow in other cells. Living things rely on other living things. A single rabbit can’t replicate on its own, but a rabbit is still alive, right?

The debate over whether viruses are alive or not continues today. There was a group of people in 2004. The University of Strasbourg in France and the U.S. Centers for Disease Control and Prevention defined viruses as “non living infectious entities that can be said to lead a kind of borrowed life.”

There is a possibility that a virus can be both living and dead. Patrick Forterre, a Biologist at the Pasteur Institute in Paris, argued that viruses can be either an inactive state outside a cell or a living state inside a cell.

Viruses are like seeds for Forterre. They have the potential to do something, but can’t. That is in line with our experience of investing endless time and money trying to kill a lot of diseases.

While debates over classification can feel frivolous, in reality how we talk about viruses affects how they are treated and eradicated.

Colin Hill is an infectious disease specialist at University College Cork in Ireland. The benign nature of the most successful viruses is due to the fact that they remain inactive in cells or reproduce slowly, so as to not damage the cell’s replication machinery. “Viruses and their prey are dancing,” says Hill. That isn’t how we see them.

Many types of viral infections, especially when they colonize a host in a persistent, lifelong manner without causing acute illness, are overlooked as “backwater” science. He says that it is like having dirt on your shoe. Like that dirt, some scientists don’t consider persistent viral infections urgent to study. Polyomaviruses are used in laboratories to study how cancer can be caused by viruses. Because the rhesus macaque hosts rarely, if ever, get tumors from it, little is known about how and why polyomaviruses persist in an animal population.

Understanding such infections is important to humankind. “A persistent virus in one host is frequently nasty in another host, and that’s what we’re experiencing with COVID,” says Villarreal.

There are other ways in which viruses have been ignored. The tree of life is a model used to depict evolution. The Interactive Tree of Life is one of the popular versions that does not include viruses. Hill says one cannot fully understand evolution without viruses.

There are a lot of Viruses. In the ocean, where they work as a gigantic recycling network, they rip apart 20 percent of thebacteria and other microbes there each day to release tons of carbon, which is then used by other organisms.

Across the globe, viruses leave behind genetic material. It is possible for a single viral particle to be transmitted to other viruses and other species. We rely on the viral genetic sequences that have taken up residence in our genomes. The human innate immune system is made up of ancient viral proteins, which are required for the formation of the mammalian placenta, the growth of early embryos, and the growth of the human fetus. When a person is fighting COVID-19, they are doing it with the help of viruses that colonized our cells long ago.

Viruses are considered to be the world’s leading source of genetic innovation. Viruses are woven into every limb and leaf of a tree.

The importance of viruses to life is something scientists can hopefully agree on, even if they disagree on whether they are alive or dead. “However you want to think about life,viruses will be there.”

This article was inspired by: https://www.sciencenews.org/article/viruses-alive-coronavirus-definition

The confidence intervals tell you how well you have determined the mean. Assume that the data is random. If you do this many times, you’d expect about 95 percent of the intervals to include the true value of the population mean. The key point is that the confidence interval tells you the location of the true population.

Predicting intervals tell you where you can expect to see the next data point. The data might be from a random distribution. Take a sample of data and make a prediction interval. You should sample one more value from the population. The key point is that the prediction interval tells you about the distribution of values, not the uncertainty in determining the population mean, if you do this many times.

Predicting intervals have to account for the uncertainty in knowing the population mean and scatter. A prediction interval is bigger than a confidence interval.

The study of the universe is called cosmology. The whole universe is a single object. Scientists try to understand the origins, history, evolution, contents, and ultimate fate of this place that we call our home. About a hundred years ago, astronomer Edwin Hubble discovered that there are two remarkable things: that the universe is very far away from us and that some of the universe are moving away from us. He discovered that the universe is expanding and that it is very large.

Our universe was smaller, hotter, and denser a long time ago, according to the big bang theory. We have a lot of evidence to back up this simple statement, but that doesn’t mean we know everything about the universe. There are two glaring holes in our understanding. Dark matter was discovered in the 1970s. As far as we can tell, dark matter is made of a new particle with a mysterious identity. Dark matter takes up most of the mass in the universe, even though it doesn’t interact with light or normal matter.

Dark energy is the other giant hole. The expansion of the universe was discovered in the late 1990s by two teams of astronomer. Our universe is getting bigger and bigger every day, and it is also getting bigger and faster every day. We named the effect dark energy because we had no idea what was happening. Dark energy takes up 70% of all the mass energy in the entire universe, completely dominating everything else. There is a weird place where modern cosmology is located.

We understand the general picture of the big bang, and we are able to make some really cool statements, like the age of the universe is 13.77 billion years old, or that all the hydrogen atoms were formed when the universe was only a dozen minutes old. We know that we are on solid ground because we can back up all those statements. We don’t have an understanding of the vast majority of the contents of our universe. We know how they act, but they are not what they are. The name of the game in modern cosmology is to keep measuring the properties of dark matter and dark energy as precisely as possible and hope that something interesting pops up. The latest result is from the PANTHEON+ survey, which measured the precise positions of about 1,500 supernovae. The team behind the study used the data to find that the universe is made up of dark energy and dark matter. We’re going to have to keep digging because PANTHEON+ didn’t find any surprises when it came to the twin mysteries.

Mercury is the smallest of the four inner rocky planets of the solar system. It’s a big ball of rock. Why did NASA send a probe to the planet in 1974? The MESSENGER was a decade ago. Why did the Japanese and European space agencies join forces to develop BepiColumbo? There is a secret to Mercury. Mercury is a dead world. By its craters, you can tell. Worlds that are capable of active resurfacing, like from plate tectonics, will eventually erase their scars. A lot of craters on the surface of the Earth are not visible. Mercury hasn’t been molten in a long, long time.

The temperatures on Mercury are very cold. Because it is the closest planet to the Sun, it gets blasted in the daytime, with temperatures reaching up to 800 degrees. On the night side, away from the Sun, the temperatures can plunge to -270 degrees. There is water ice on the surface. craters are deep enough that they stay in the shadows all day long, even in the daytime, without much atmosphere to speak of. Mercury’s magnetic field is a big mystery. It is barely 1% of the Earth’s strength. Mercury is not supposed to have a magnetic field.

Planets have magnetic fields in their cores. Iron and nickel are the heaviest elements of a planet, found in those cores. The metals will melt if the cores are too hot. As the planet spins, the metal, molten core, which is exactly the conditions you need to power up a magnetic field, swooshes around. Mercury doesn’t have much of a molten core. It is so small that its inner core has cooled off and is now rock solid. It still has a liquid outer core, but it is not quite large.

Mercury is barely rotating. A day on Mercury lasts 58 Earth days. Astronomers and planetary geologists assumed that Mercury couldn’t form a magnetic field because it wasn’t able to get its act together. It was staring them in the face. The purpose of BepiColumbo and MESSENGER is to understand the origins of the magnetic field.

Inspired by Paul M. Sutter: https://www.discovery.com/space/mercury

For more than 2 years, Johnson & Johnson has been working on its future. In the wake of the consumer healthcare spinoff last summer, the company’s fourth-quarter results offer plenty of signs of life. J&J ended the year with a total haul of $85.2 billion, with multiple catalysts for growth, according to the company’s fourth quarter and full-year earnings conference call. In the fourth quarter of the year, the company’s innovative medicines portfolio generated the lion’s share of sales, helping the unit achieve operational growth in the U.S. The pharma business of J&J grew 4% to $13.72 billion during the fourth quarter of the year.

J&J said in an earnings presentation that its immunology blockbuster, Stelara, grew its market share and demonstrated continued strength in IBD. Thanks to market growth, the company’s plaque psoriasis and psoriatic arthritis med was able to enjoy gains. In the fourth quarter, J&J’s Oncology group turned in another top performance. J&J’s multiple myeloma injection Darzalex had a sales increase of 22%, thanks to “strong share gains in all regions.” J&J credited the ongoing launch of the CAR-T med Carvykti, plus gains from manufacturing capacity improvements, for its continued success.

The CAR-T manufacturing boost is worldwide, from J&J doubling its cell processing capacity at its New Jersey plant to making progress at its European cell facilities and contracting external capacity to scale up production, according to the call. J&J is confident that the additional supply will lead to increased sales for Carvykti. J&J is about to launch a new multiple myeloma contender. While Carvykti often takes the spotlight in the company’s multiple myeloma franchise, it’s important to recognize the market performance of the two new bispecific antibodies.

The growth of J&J’s innovative medicines was partially offset by the loss of exclusivity for the leukemia and lymphoma drug Imbruvica. Despite the current strength of J&J’s innovative portfolio, the New Jersey-based pharma giant isn’t shying away from potential deals in 2024. The company is in a good position to entertain a lot of different types of deals. The company spent more than $3 billion in capital for smaller deals in the way of licenses or partnerships, and signed more than 50 deals, according to Duarto. Our appetite is still interested in moving into spaces that complement our existing portfolio, whether that be in the near or long term.

Looking ahead to the rest of the year, J&J is still filling in some of the details, but the company expects 5% to 6% operational growth. J&J expects to deliver its 13th year of above-market growth in innovative medicines, with the performance driven by a handful of medicines. In the first half of the year, the growth of innovative medicines is expected to be slightly stronger. J&J expects to face generics in Europe in the back half of the 20th century. The recent launches of our products will partially offset this headwind.

Inspired by: https://www.fiercepharma.com/pharma/jj-reveals-new-face-major-oncology-bent-after-last-summers-healthcare-spinoff?itm_source=parsely-api

The FDA investigation into secondary T-cell cancers following treatment with existing CAR-T therapies is poised to lead to a class wide black box warning. The FDA requires label updates to include T-cell malignancies in the boxed warning section of all CAR-T therapies. A black box warning is the most serious alert on a medication’s label.

J&J’s Legend Biotech-partnered Carvykti and Novartis’ Kymriah are among the products involved. Multiple myeloma, large B-cell lymphoma and other blood cancers are treated with the products. The boxed warnings should include a paragraph stating that T-cell malignancies may occur following treatment with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including. The same language is required in the warning section of a drug’s label.

Less than two months after the FDA launched an investigation into secondary T-cell malignancies among patients who received CAR-Ts, the required label update comes. The risk was labeled as serious by the agency because of cases it had received from clinical trials and postmarketing research. The potential risk was deemed applicable to all CAR-T products by the FDA from the beginning. Industry watchers believe that a classwide boxed warning is likely to come next.

The FDA has decided that the T-cell malignancy safety signal should be included in the labeling of all genetically modified autologous T cell immunotherapies. Even future CAR-T hopefuls that fit the description will be subject to a boxed warning. Gracell has a dual-targeting GC012F that is the centerpiece of the $1 billion acquisition of the Chinese biotech. The FDA distinguishes between autologous therapies and off-the-shelf CAR-T therapies.

The companies can either file a supplement with different wording or meet the FDA’s demand and submit it. A rebuttal statement detailing their disagreements can be submitted. The companies must submit a response within 30 days if they want to avoid enforcement action. J&J will work with the FDA to update the Carvykti prescription information. J&J is confident in the favorable benefit-risk profile of Carvykti with more than 2,000 patients having been treated.

A month ago, Carvykti was updated with a boxed warning about secondary hematological malignancies, including myelodysplastic syndrome and acute myeloid leukemia, following treatment with the BCMA CAR-T.

Fierce pharma was told by the company that it will update the label in accordance with FDA guidance. The Swiss pharma pointed to 10,000 patients that have received Kymriah worldwide, saying it has not found sufficient evidence to declare a causality between CD19 therapy and T-cell malignancies. The company that got the CAR-T therapies from its acquisition of Celgene said it hasn’t found a relationship between its products and T-cell cancer.

The company will determine appropriate next steps in the interest of patients and healthcare providers as it reviews FDA’s changes. The latest analysis of more than 15,500 patients treated with Yescarta and more than 2,700 patients treated with Tecartus didn’t establish a role for the drug in the development of T-cell malignancies, a spokesman said. The FDA is allowing the products to stay on the market because of their benefit-risk profiles.

In a commentary published in Nature Medicine a few days ago, several cell therapy experts, including CAR-T pioneers Bruce Levine, PhD, and Carl June, M.D., suggested that treatment centers should continue to use those commercial CAR-T products. The rate of T-cell malignancies observed is far lower than that seen with some other treatments. The FDA is currently reviewing J&J and Legend’s application for Carvykti as a second-line multiple myeloma therapy, and the agency will convene an advisory committee meeting to discuss Bristol’s bid to move AbeCMa into the third-line setting. Yescarta is being tested in patients with high-risk large B-cell lymphoma.

Inspired by:

https://www.fiercepharma.com/pharma/fda-wants-classwide-boxed-warning-all-commercial-car-t-therapies-amid-secondary-cancer

For many people a new year means new resolutions. The best exercise people can do to be healthy was supposed to be covered in this story. There is a small problem. Stamatakis says that there is no such thing as the best exercise. He says it is probably clickbait if you see that headline. Scientists know that regular physical activity pays off in long-term health benefits. Recent work is showing a clearer picture of all the activities that can help. You don’t have to build a body like Arnold or crush marathons like Tigst. Not everyone has the time or money to join a gym or use special equipment. Stamatakis says that you don’t need to.

It might seem obvious that physical activity is good for you. News reports tout the benefits of exercise and governments worldwide try to get citizens to move. The United States has physical activity guidelines that show that 80% of adults aren’t doing enough. The guidelines suggest that adults need at least 150 minutes of moderate physical activity or 75 minutes of vigorous activity per week. How long should these sessions last? Lee says that they don’t know. Even a small amount of physical activity can be helpful. Lee and colleagues wrote in October that most of the studies underpinning the recommendations relied on self-reported data. Lee says people tend to remember exercises like running or swimming. It was difficult to document the many movements we take in a day that can improve health. Wearable technology has taken those missing movements out of the shadows. Scientists can collect mountains of in-depth data throughout a person’s day, such as step count, acceleration and heart rate, with fitting participants with tracking devices.

It would be easier for people to rack up physical activity if there were more sidewalks, trails, and bike paths. Stamatakis says the role of the environment is important. Lee agrees with it. She says that physical activity is more than a choice. Government policies affect how much we can do. She emphasizes that it doesn’t take much to get substantial health benefits. People are able to start at any level.

This article was inspired by: https://www.sciencenews.org/article/physical-activity-exercise-health-benefits