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Category Archives: Evolution

Then vs Now: See the evolution of Disney World over 50 years – wflx

Posted: October 3, 2021 at 2:18 am

On Oct. 1, 1971 Walt Disney World opened its gates for the first time and Florida has never been the same.

In 1971, Disney World had just one theme park, Magic Kingdom, and a few golf courses and resorts.

Despite all the changes and advancements made in the last 50 years, some of the original rides and attractions from 1971 remain today including the Country Bear Jamboree, Dumbo the Flying Elephant, the Haunted Mansion and the Tomorrowland Speedway

Since then, three more major parks have been added. Epcot opened in 1982, Hollywood Studios in 1989 and Animal Kingdom in 1998. In addition, the water parks Typhoon Lagoon (1989 and temporarily closed) and Blizzard Beach (1995) were added to the resort.

A few of your favorite rides might be younger than you think. Space Mountain opened in 1975, but Splash Mountain didn't make an appearance until 1992.

To celebrate the occasion, we had our colleagues share their Disney photos spanning the past five decades. Click through the photos and travel in time.

Want to know what Disney has in store to celebrate the big anniversary? Click here.

Scripps Only Content 2021

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The Evolution of the House Plan in the United States: Post-war Era – ArchDaily

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The Evolution of the House Plan in the United States: Post-war Era

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Following the Second World War, United States veterans and citizens were seeking a fresh start, a rightful place to live out their modern American dream. With a significant housing shortage looming around andfast-growingfamilies, solutions had to be found to provide equitable living meansfor all.The development of new construction techniques and propagation of easy building materials promised an age of prosperity.

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This feature of the Evolution of the House Plan focuses on a few select examples that reconsidered people's way of life through a more utilitarian filter, providing the same basic luxuries and responding to the housing need. While not as directly relevant or similar to today's ideal house plan, the suggested case studies highlight failed attempts at envisioned utopias. Located in the United States, the plans include Wallace Neff's famous bubble houses in Virginia, the typical houses of Levittown, and the Pruitt-Igoe social housing project in St. Louis, Missouri.

Wallace Neff, an architect who up until that point had focused his architectural practice on building houses for celebrities, wanted to come up with a solution that would not only address the tremendous post-war housing shortage but also the worlds constant demand for low-cost housing. Hedeveloped a revolutionary system consisting of portable building equipment, no special tools, plentiful materials, modern design, low cost, and rapid construction.

Neff developed Airform construction, a type of pneumatic architecture that used an inflated balloon to give form and structure, and allowed each house to be built in less than 48 hours. This fast pace system enabled the first community of Bubble Houses to be completed in 1942 in Falls Church, Virginia. The project consisted of ten double bubble units and two single bubble houses. It was the first experiment to determine the potential for building more, paid for by the federal government and used to house government workers.

The larger houses were approximately 100 sqm, and the smaller ones were 45 sqm. On the first ones, one bubble acted as a living room while the other one, less than 2m apart, held the rooms. Both bubbles were connected by a flat roof structure, where the kitchen, bathroom, and entryway were located.The ceiling height for each bubble was 3.35m.After that, Neff was hired to buildbubble housesin Litchfield, AZ, a linen supply building, and a dormitory at Loyola Marymount University. Bubble Houses were built all around the world: from the Caribbean to Senegal.

According to the comments of former occupants, living in Fall Church's Bubble Houses was extremely isolating. The site was on a very dark road in the middle of the woods, cut off from the rest of the town, so a lot of people ignored its existence. They recognize the stigma about living in Igloo Village, as it was contemptuously called, where all domes looked the same: white paint was mixed with the gunite for the exterior finishes, and window shutters were all painted in the same dark green color.

Apart from this aspect, daily life turned out to be quite problematic for its inhabitants: Round rooms with concave walls were difficult to furnish and it was not possible to hang a picture, damp interiors allowed mold to be formed, andsome walls that separated rooms did not go all the way to the ceiling, so privacy was an issue. Eventually, this architecture that looked and functioned exactly the same everywhere, disregarding the context and not varying by region, climate, or even culture, ended up failing. All of Neffs Bubble Houses in the US were demolished, with the exception of the bubble house where he lived with his brother.

It was in the previously described post-war context, with a serious housing shortage that William J. Levitt (Levitt & Sons) started developing a new project which is nowadays recognized as a prime and almost perfected example of American suburbs and most importantly as the instigator of mass-housing. From 1947 until the late 60s, the company was responsible for eight housing developments around the United States, the first being in New York (1947-1951), then Pennsylvania (1952-1958), New Jersey (1958), Puerto Rico (1963), Maryland (1963 /1964/1970) and Virginia (1968). All of these were known as Levittown(s). The idea was to offer pre-planned, fast-built, housing units at relatively affordable costs.

The first development in New York saw the completion of 17,000 similar-looking housing units only with a few subtle variations of color, roofline, or window treatment. There were only six house models in Levittown, each in a slightly different style depending on the model year. This allowed for a streamlined production process with separated worker tasks, leading Bill Levitt to famously say "We are not builders. We are manufacturers."

While looking at the Levittown plans, one can easily distinguish the familiar traits of what is now referred to as a midcentury-modern house layout that was slightly larger than earlier house plans and suggesting a more comfortable setting. The open plan was adopted, making the most of the limited living area that was oriented to focus on the main fireplace; not an ideal implementation seen as the heating and cooling methods were veering towards the electric. Also in the name of space-saving, the tiny modern kitchens were completely fitted with all built-in appliances and accessories. Just enough picture windows were placed to provide some natural light; well-positioned to maintain a bit of privacy from the neighboring dwelling.

The small pitched roof houses were decorated to hint at the beach-lodge or small ranch style with some use of natural-looking materials such as wood shiplap on the living room walls or ceiling and brick cladding fireplace. Carpet flooring went along the bedrooms, over the radiantly heated cement slabs. Cost-saving considerations also reflected on the finishing with Levitt substituting some conventional quality natural materials with cheaper alternative imported products.

However, all of these considerations did not ensure the promise the project held at providing affordable quality housing for All, most notably due to the blatant racial segregation practiced by the managers of Levittown. In fact, the project was contested for explicitly refusing to sell to certain demographics of different ethnicities. Along with other Levittown regulations that made it harder for inhabitants to have certain flexibilities in the way they led their day-to-day lives; the development became more limiting as the housing model explicitly suggested and influenced the way you had to behave in order to live there. While the models and regulations have changed since then, Levittown houses still reflect the expected post-war conformity through their identical plans.

The Pruitt-Igoe social housing project was originally built for low- and middle-income groups in the United States in the 1950s. It was born as a social tool in the years after World War II. Nonetheless, due to a public decision, it was demolished after 20 years for reasons of vandalism and assault. The article AD Classics: Pruitt-Igoe Housing Project reviews the history of the Minoru Yamasaki Associates project from its inception to the time of its demolition in 1972. A closer look at the project reveals further interpretations about the architectural design, beyond the initial bad press.

Pruitt-Igoe brought together a group of design features championed by modern architects: semi-detached laminar block buildings of various heights; wide access galleries in the apartment blocks that functioned as play areas, porches, laundry drying areas, and nurseries; duplex units with paternoster lifts; and a river of free space that winds through the site, a concept proposed by urban planner Harland Bartholomew. The chief architect, Yamasaki believed that a low-density row-house type was closer to a Human space than one that features crowded high-rise buildings. The different floors show the architect's desire to create variety in the blocks thanks to minimal variations in length and height. The basic building combines two units called the "end" and the "rib" (that contains the elevators). The larger buildings have a lengthened distance between the end units due to an added apartment at the center and larger ribs.

Unfortunately, this housing design proposal was not approved by the Public Housing Administration (PHA) due to a limited budget. Hence, some changes occurred such as the reduction of the site area, along with a decrease in blocks construction and the total number of housing units. In addition to that, some of the important services such as bathrooms and play areas located on the ground floors were eliminated. Upon the project's completion, many technical details were missing, including proper landscaping, painting of the concrete walls in the galleries and staircases, insulation of steam pipes, and implementation of mosquito nets on the gallery windows.

As it was already inhabited, the rents of the housing units increased in contradiction to the low-income profile of the project. Maintenance expenses and other public servicesdepended on the complete collection of rent. Yet, neither Pruitt Homes nor Igoe Apartments were operating at full capacity during this period. Consequentially, not enough money was raised to convert them into self-sufficient public housing projectsand the units could not receive the necessary services.

The resulting malfunction of the project was popularly attributed to the building'smodern architectural designrather than the political and social context or policies. The fairest solution was therefore demolition. "Demolition is assumed as the solution to social problems when in reality it only moves them geographically."There is an urgent need to overcome the criticism attributed to the architectural object and the blame based on its conception as a product of modern architecture in order to analyze the context in which it was built, inhabited, and demolished.

Rosero, Vernica (2017). Modernity, guilty? The role of architecture in social housing. Pruitt-Igoe as a symbol. Rita n8, pp. 126-135.

This article is part of the ArchDaily Topic: Equity. Every month we explore a topic in-depth through articles, interviews, news, and projects. Learn more about our monthly topics. As always, at ArchDaily we welcome the contributions of our readers; if you want to submit an article or project, contact us.

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The Chiefs Showed Evolution on Offense Against the Chargers – Chiefs Digest

Posted: at 2:18 am

Despite the loss, it is okay to be encouraged by the Kansas City Chiefs' offense and their performance against the Los Angeles Chargers on Sunday.

Well, other than the four turnovers.

Going forward, one would expect the Chiefs will not commit four turnovers in one game. However, there were very repeatable strengths shown by the Chiefs against an opponent that has given them trouble recently that show the offense has developed a few new wrinkles this year.

In looking at the last four times the Chiefs have played the Chargers with Patrick Mahomes starting at quarterback since the 2019 season, last Sunday was probably the offense's best outing against their division rival. It is crazy that on a day with four turnovers that was the case, but it's true.

Compared to both Chargers games in 2019 and the first Chargers game in 2020 (the Chiefs rested starters in the second Chargers game last year), the Chiefs offense on last Sunday had:

While the turnovers should not be ignored, everything around them was an improvement. The crux of the last few years against the Chargers has been that the Chiefs have struggled to move the ball consistently down the field.

The 2020 matchup with the Chargers famously featured Tyrod Taylor having his lung punctured pregame, which led to Justin Herbert starting his first NFL game. What many forget about that day was the Chiefs started the game with three straight three-and-outs and only got it together in the fourth quarter to send the game into overtime. The offense was inconsistent and struggled.

In the second Chargers game of 2019, the Chiefs scored two touchdowns off two monster plays from Mecole Hardman (kick return) and Damien Williams (84-yard run). Mahomes threw for a shockingly low 174 yards and generated the lowest passing EPA of the four games in the last three years in which he played against the Chargers.

In the first Chargers game of 2019, the Chiefs actually had negative passing EPA their worst yards per play of the four games mentioned and were a paltry 6-for-13 on third down. The only reason the Chiefs did not get blown out was because Philip Rivers threw four interceptions. This was the game in Mexico City, so that could have been a factor, but it was still a disappointing day from the offense nonetheless.

The reason the 2021 game, a loss compared to three wins before, was better for the offense was the balance. The passing and rushing game both looked good at the same time. Why? Well, it is hard not to credit the Chiefs' revamped offensive line.

Running back Clyde Edwards-Helaire and the Chiefs' offensive line had a really nice day Sunday (other than the fumble for Edwards-Helaire). The Chiefs' run game with Edwards-Helaire generated four runs of at least five yards on first-and-10, and it also had five runs that generated a first down. Considering there were 17 total attempts by Edwards-Helaire, that is a very productive day.

The reason this is important against the Chargers, and important going forward for the Chiefs, is that the blueprint is out to at least mitigate the Chiefs offense's big plays. Brandon Staley is a disciple of Vic Fangio and their coaching tree is all about Cover 2 defenses that mitigate explosive plays. Staley takes this even further and loves to play with light boxes, daring opposing offenses to run.

While running the ball more does play into the point of the defense, if you cannot run against the light boxes at all, it's a double-whammy. Sometimes, you do need to take what the defense gives you and the Chiefs' offense of the last two years hasn't been able to even do that. If Williams 84-yard touchdown run is taken out of the second Chargers game of 2019, the Chiefs 141 yards of rushing by running backs and wide receivers (excluding Mahomes scrambles) on Sunday is easily higher than any other total by the Chiefs in the other three games. The second-highest total was 71 yards.

The Chiefs passing game also delivered a solid game on Sunday, and pairing that with an efficient run game really allowed the offense to move the ball against an opponent that they had struggled against before.

No one believes Mahomes will continue to throw terrible interceptions or that the Chiefs will continue fumbling at the rate they have so far this season. The Chiefs were tied for the fourth-least giveaways last year in the NFL. There will be some regression in that area as the team makes it a priority.

The new offensive line, however, is a change from previous seasons and has been playing well to start the year. With its continued growth and integration into the offense, the offense should surely continue to prosper. This new dimension, an offensive line that pairs quality pass blocking with much-improved run blocking, could provide a boost to a Chiefs offense that needs an equalizer against some defenses.

The Chargers game proved this Chiefs offense is evolving, despite the result being less than ideal.

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Minimal Consciousness and the Cambrian Explosion – Discovery Institute

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Photo: Fossil of Opabinia regalis, a Cambrian animal, by Jstuby at English Wikipedia, Public domain, via Wikimedia Commons

Eva Jablonkais one of the worlds foremost experts in epigenetic inheritance and evolution but she has also had a longstanding interest in consciousness studies. She was author, withMarion J. Lamb, ofEvolution in Four Dimensions:Genetic, Epigenetic, Behavioral, and Symbolic Variation in the History of Life(MIT Press 2006/rev. 2014).

She and neurobiologistSimona Ginsberg,along with illustrator Anna Zeligowski, offer a new approach to the origin of consciousness in an essay at IAI.TV one with an interesting departure from many approaches to consciousness.

Taking their inspiration from Hungarian chemistTibor Gnti(19332009), who posited achemoton the minimal life form or protocell as the origin of life, they first attempt to defineminimal consciousness,listing many requirements.

A minimal life form must show the ability to learn but it must also be a subject of experience. After all, as Ginsberg et al. point out, the MuZero algorithm can beat humans at any number of games but it is as conscious as your washing machine. Theyargue thatThe evolution of learning drove the evolution of consciousness and the cognitive architecture of complex learning in living organisms constitutes basic consciousness.

Where their approach differs from many is that they do not try to identify a mechanism of consciousness. In fact, they write,

The next step we took was search for an evolutionary transition marker that requires that all the characteristics we listed are in place. We looked at genes, proteins, anatomical brain regions and neurophysiological processes, but none of the many possibilities we examined entailed all the characteristic of consciousness.

They are looking, rather, fortransition markersbetween one stage of consciousness and the next, in terms of actual behavior. They settled on the concept ofunlimited associative learning (UAL). Thats an interesting shift in emphasis if we recall a 1998science wagerbetween two big names in consciousness studies:

TWENTY years ago this week [1998], two young men sat in a smoky bar in Bremen, northern Germany. Neuroscientist Christof Koch and philosopher David Chalmers had spent the day lecturing at a conference about consciousness, and they still had more to say. After a few drinks, Koch suggested a wager. He bet a case of fine wine that within the next 25 years someone would discover a specific signature of consciousness in the brain. Chalmers said it wouldnt happen, and bet against.

Well, the wager has only two years to run now and, barring a sudden, dramatic discovery, it looks as though consciousness may not be a specific signature at all.

One reason for doubt about such a signature is provided by Ginsbergs teams findings: Were a physical signature the explanation of consciousness, we might expect to find that consciousness follows simple rules of heredity. But when the team tried to determine, from behavior, which life forms over evolutionary time have demonstrated at least minimal consciousness, they found,

Our survey of the vast (yet very patchy) learning literature of the last 100 years revealed no evidence of UAL [unlimited associative learning] in most animal groups, including medusa, flat worms and slugs. It has, so far, been found only in three groups: most of the vertebrates (fish, amphibians, reptiles, birds and mammals), some of the arthropods (e.g., crabs, bees, crickets, cockroaches) and some mollusks (the cephalopod squid, cuttlefish and octopus).. We discovered that although the brains of these animals are anatomically very different, they have similar functional units that generate models of the world, the body, and prospective actions, a memory system that can store composite representations, and an integrating and flexible system that evaluates and updates them. This cognitive architecture gives us a clue to the function of consciousness: it enables the organism to make context-dependent decisions that are based on its subjectively-experienced perceptions and motivations.

If the life forms brains are anatomically very different, it makes more sense to track consciousness by evidence from behavior, as the researchers are doing, than by the long-sought evidence from anatomy. But that entails decoupling consciousness from a specific physical structure. Thats a different direction from the 1998 wager.

Ginsbergs team argues for the Cambrian explosion as the first evidence for minimal consciousness.

Read the rest at Mind Matters News, published by Discovery Institutes Walter Bradley Center for Natural and Artificial Intelligence.

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Evolution of Q: Goldfinger-spec DB5 vs 2021 recreation – Autocar

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The standard DB5 is truly special, but we suspect that future buyers will all wish theircars could feature similar enhancements to this one. Our only substantive complaint is with the cars Fern Green paintwork; we struggle to see such a drab hue catching on.

While this car hasnt caused us to substantially revise the conclusion we reached inour earlier DB5 road test, its impressive arsenal has given cause to amend it slightly. Because this is a mans mans car: one that savages, chastises and frequently bites.

Fast-forward to 2021...

While earlier Aston Martin Continuation cars were designed to be almost exact copies of the hallowed originals, the DB5 Goldfinger Continuation threw up a much greater challenge. The gadgets that made the original film car famous were theatrical props that neededto work only once; those fitted to the Continuation had to be able to operate repeatedly. They would also need tobe non-lethal. Gaydons lawyers were apparently very insistent on that point.

Theres an almost full set of gadgets, created under the supervision of Chris Corbould, an Oscar-winning special-effects designer who has worked onno fewer than 15 James Bond films, including No Time to Die. They include machine guns, rotating numberplates, on-board radar, a bulletproof rear screen, an oil slick and a smokescreen, plus the front and rear bumper rams,which were referenced but not used in 1964s Goldfinger film.

The original film car used blank-firing guns, which were an impractical solution for the Continuation, because they would be too loud and indeed illegal in many territories. Instead,its barrels simulate fire with ultra-bright LEDs and a motorised recoil action, accompanied by a loudspeaker soundtrack thats much more subdued than real gunfire. For similar reasons,the oil slick actually fires water andthe tyre-slashers come in a display case and cant actually be fitted tothe car. And although the asymmetric sunroof aperture is present, the Continuation doesnt feature an ejector seat. Disappointingly, pressing thered button beneath the gearlevers folding flap doesnt do anything;some passenger-startling under-seat vibration would have been a nice touch.

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MIT Scientists Zero In on the Origins of Earths Single Most Important Evolutionary Innovation – SciTechDaily

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A new study shows oxygenic photosynthesis likely evolved between 3.4 and 2.9 billion years ago.

Some time in Earths early history, the planet took a turn toward habitability when a group of enterprising microbes known as cyanobacteria evolved oxygenic photosynthesis the ability to turn light and water into energy, releasing oxygen in the process.

This evolutionary moment made it possible for oxygen to eventually accumulate in the atmosphere and oceans, setting off a domino effect of diversification and shaping the uniquely habitable planet we know today.

Now, MIT scientists have a precise estimate for when cyanobacteria, and oxygenic photosynthesis, first originated. Their results were published on September 29, 2021, in the Proceedings of the Royal Society B.

They developed a new gene-analyzing technique that shows that all the species of cyanobacteria living today can be traced back to a common ancestor that evolved around 2.9 billion years ago. They also found that the ancestors of cyanobacteria branched off from other bacteria around 3.4 billion years ago, with oxygenic photosynthesis likely evolving during the intervening half-billion years, during the Archean Eon.

MIT scientists estimate that oxygenic photosynthesis the ability to turn light and water into energy, releasing oxygen first evolved on Earth between 3.4 and 2.9 billion years ago. Credit: MIT News, iStockphoto

Interestingly, this estimate places the appearance of oxygenic photosynthesis at least 400 million years before the Great Oxidation Event, a period in which the Earths atmosphere and oceans first experienced a rise in oxygen. This suggests that cyanobacteria may have evolved the ability to produce oxygen early on, but that it took a while for this oxygen to really take hold in the environment.

In evolution, things always start small, says lead author Greg Fournier, associate professor of geobiology in MITs Department of Earth, Atmospheric and Planetary Sciences. Even though theres evidence for early oxygenic photosynthesis which is the single most important and really amazing evolutionary innovation on Earth it still took hundreds of millions of years for it to take off.

Fourniers MIT co-authors include Kelsey Moore, Luiz Thiberio Rangel, Jack Payette, Lily Momper, and Tanja Bosak.

Estimates for the origin of oxygenic photosynthesis vary widely, along with the methods to trace its evolution.

For instance, scientists can use geochemical tools to look for traces of oxidized elements in ancient rocks. These methods have found hints that oxygen was present as early as 3.5 billion years ago a sign that oxygenic photosynthesis may have been the source, although other sources are also possible.

Researchers have also used molecular clock dating, which uses the genetic sequences of microbes today to trace back changes in genes through evolutionary history. Based on these sequences, researchers then use models to estimate the rate at which genetic changes occur, to trace when groups of organisms first evolved. But molecular clock dating is limited by the quality of ancient fossils, and the chosen rate model, which can produce different age estimates, depending on the rate that is assumed.

Fournier says different age estimates can imply conflicting evolutionary narratives. For instance, some analyses suggest oxygenic photosynthesis evolved very early on and progressed like a slow fuse, while others indicate it appeared much later and then took off like wildfire to trigger the Great Oxidation Event and the accumulation of oxygen in the biosphere.

In order for us to understand the history of habitability on Earth, its important for us to distinguish between these hypotheses, he says.

To precisely date the origin of cyanobacteria and oxygenic photosynthesis, Fournier and his colleagues paired molecular clock dating with horizontal gene transfer an independent method that doesnt rely entirely on fossils or rate assumptions.

Normally, an organism inherits a gene vertically, when it is passed down from the organisms parent. In rare instances, a gene can also jump from one species to another, distantly related species. For instance, one cell may eat another, and in the process incorporate some new genes into its genome.

When such a horizontal gene transfer history is found, its clear that the group of organisms that acquired the gene is evolutionarily younger than the group from which the gene originated. Fournier reasoned that such instances could be used to determine the relative ages between certain bacterial groups. The ages for these groups could then be compared with the ages that various molecular clock models predict. The model that comes closest would likely be the most accurate, and could then be used to precisely estimate the age of other bacterial species specifically, cyanobacteria.

Following this reasoning, the team looked for instances of horizontal gene transfer across the genomes of thousands of bacterial species, including cyanobacteria. They also used new cultures of modern cyanobacteria taken by Bosak and Moore, to more precisely use fossil cyanobacteria as calibrations. In the end, they identified 34 clear instances of horizontal gene transfer. They then found that one out of six molecular clock models consistently matched the relative ages identified in the teams horizontal gene transfer analysis.

Fournier ran this model to estimate the age of the crown group of cyanobacteria, which encompasses all the species living today and known to exhibit oxygenic photosynthesis. They found that, during the Archean eon, the crown group originated around 2.9 billion years ago, while cyanobacteria as a whole branched off from other bacteria around 3.4 billion years ago. This strongly suggests that oxygenic photosynthesis was already happening 500 million years before the Great Oxidation Event (GOE), and that cyanobacteria were producing oxygen for quite a long time before it accumulated in the atmosphere.

The analysis also revealed that, shortly before the GOE, around 2.4 billion years ago, cyanobacteria experienced a burst of diversification. This implies that a rapid expansion of cyanobacteria may have tipped the Earth into the GOE and launched oxygen into the atmosphere.

This new paper sheds essential new light on Earths oxygenation history by bridging, in novel ways, the fossil record with genomic data, including horizontal gene transfers, says Timothy Lyons, professor of biogeochemistry at the University of California at Riverside. The results speak to the beginnings of biological oxygen production and its ecological significance, in ways that provide vital constraints on the patterns and controls on the earliest oxygenation of the oceans and later accumulations in the atmosphere.

Fournier plans to apply horizontal gene transfer beyond cyanobacteria to pin down the origins of other elusive species.

This work shows that molecular clocks incorporating horizontal gene transfers (HGTs) promise to reliably provide the ages of groups across the entire tree of life, even for ancient microbes that have left no fossil record something that was previously impossible, Fournier says.

Reference: The Archean origin of oxygenic photosynthesis and extant cyanobacterial lineages by G. P. Fournier, K. R. Moore, L. T. Rangel, J. G. Payette, L. Momper and T. Bosak, 29 September 2021, Proceedings of the Royal Society B.DOI: 10.1098/rspb.2021.0675

This research was supported, in part, by the Simons Foundation and the National Science Foundation.

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A Snapshot Of SARS-CoV-2 Evolution: Observed Increase Of Infectivity In The Covid-19 Virus – Forbes

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A sports car today is far more advanced than those from the 20th century.

A recent scientific report underscores how rapidly SARS-CoV-2 adapts to selective pressure. The experiments examine how rapidly the virus can adapt to life in a Petri dish. The results are startling, explaining in part the emergence of an entire Greek alphabet of variants over that past year and a half. No matter what the original source, the virus becomes 100 times more infectious, and does so in short order. No wonder new variants seem to pop up no matter where or when we look.

The experiments follow a hallowed tradition of medical science: passaging dangerous human pathogens multiple times through non-natural hosts to derive altered viruses that may be used as a vaccine. That is what Louis Pasteur did to develop the first Rabies vaccine and what Max Theiler did to develop the first and only vaccine for Yellow Fever. It does not always work that way. Sometimes the virus that emerges from multiple passages in animals in Petri dishes is more dangerous than the original. For example, serial passaging of alphaviruses results in mutations that, in some cases, result in higher neurovirulence in mice. The same can be said for feline enteric coronavirus, which when passaged multiple times, results in furin cleavage mutations that correlate with transformation to a more pathogenic biotype.

Shiliaev et al. use two different sources of virus. The first was a sample as close to the original Wuhan strain they could find, designated WA1/2020. It had been grown successively (passaged) four times on cells in Petri dishes. The second source was derived from a DNA copy of the GenBank sequence NC_045512.2, a clone closely related to the Wuhan strain. To recover infectious virus, the DNA was first transcribed into RNA thenintroduced into a cell that constitutively produced the N protein.

In both cases, bothvirus stocks wereremarkably heterogeneous. The first evidence of heterogeneity is dramatic variation in plaque size, the dimensions of the clear area of dead cells surrounding infection of a single virus particle. Figure 1A and 1B show the variation in plaque of the Wuhan strain (1A) and the cloned strain (1B) when grown on Vero E6 cells. Moreover, the ratio of total virus particles (the genome equivalents-GE) to those viruses capable of infecting cells in culture and in forming a plaque (The plaque forming units PFU) was low, roughly 27.6 compared to over 1000 in the unpassaged viruses.

FIGURE 1: Increase in plaque size after five passages for the (A) natural virus and (B) cloned ... [+] virus.

The viruses were then passaged. Viruses were introduced to Vero E6 cells with the human ACE2 receptor in five rounds. They infected the cells, were allowed to spread, then diluted and reintroduced. They repeated this process for the two different viruses five times.

Through several of these passages, the researchers noted that infectivity rose dramatically, as demonstrated by the ratio of genome equivalent to plaque-forming units (GE:PFU) decreasing starkly. In original virus stocks, the great majority of the viruses were incapable of infecting and forming plaques, whereas in the passaged viruses, the GE:PFU ratio was much closer to one, a 100-fold increase in the particle to infectivity ratio. Both virus stocks when passaged only five times became far more infectious, as measured by the plaques forming test.

FIGURE 2: Decrease in genome equivalent to plaque forming units (GE:PFU) ratio in the (A) natural ... [+] virus and (B) cloned virus after five passages. Decreases in GE:PFU correlate with increases in infectivity. Note that the natural virus received by the lab before experimental passaging had already previously been passaged. Vero E6 cells with and without ACE2 receptors were used in testing the cloned virus.

Mutations Found Post-Passaging

The mutations resulting in the 100-fold more infectious viruses were dramatic changes in the structure of the gene that encodes the Spike protein. After the final passage of the live virus, they find a high prevalence of an insertion of 21 nucleotides in the N-terminal domain coding sequence. This insertion added the peptide GLTSKRN (glycine-leucine-threonine-serine-lysine-arginine-asparagine) between Spike protein positions 214 and 215. Additionally, they found S247R (serine to arginine) downstream in the N-terminal domain and H655Y (histidine to tyrosine) in the furin cleavage region.

FIGURE 3: Mutation selection in the natural virus after five passages.

The seven amino acid insertion introduces two positive charges to an otherwise neutral or negative region of the Spike protein. The other N-terminal domain mutation also introduces a positive charge.

Measurements of the ratio of the full-length genome to the cleaved protein show that the changes in and around the furin cleavage site decrease the efficiency of cleavage by the furin, but do not eliminate the site altogether. However, the mutations still allow the passaged viruses to be fully infectious as they do not change the second cleavage site earlier in the Spike genome.

FIGURE 4: Spike protein domains with cleavage sites (noted in green), mutations in the natural virus ... [+] (noted in blue), and mutations in the cloned virus (noted in red).

Notably, the researchers found that the mutations were already present in low frequencies. After five rounds of passaged, those mutations were selected as favorable for the virus.

In the cDNA passaged virus, different mutations were observed. Before passaging, there was a collection of small and large plaques, but then after five passages, all large plaques were observed. The GE:PFU ratio dropped dramatically, as in the live virus. Though the researchers found different mutations: the S686G mutation directly following furin cleavage and the I68R and N74K mutations in the in vitro N-terminal domain.

FIGURE 5: Mutation selection in the cloned virus after seven passages.

As demonstrated by Figure 5, the researchers found that in the clone, mutations were again found in low frequencies among the early rounds of passaging. Those mutations that conveyed significant advantages to the virus were selected in greater frequency as passages advanced while those that were not advantageous were left behind.

FIGURE 6: Mutations in natural viruses (noted in blue) and cloned viruses (noted in red).

Consequences of the Mutations

These mutations impose similar results on the passaged cDNA virus. The N-terminal domain mutations increase the overall positivity of the region, albeit less so than the live virus insertion, and the furin cleavage mutation reduces furin cleavage. We can therefore conclude that SARS-CoV-2, whether naturally passaged or passaged in vitro, will replicate and mutate rapidly in Vero E6 cells containing the human ACE2.

The authors then speculate that the N-terminal domain mutations allow the virus to bind more tightly to negatively charged glycans on the surface of cells. They test that by testing the binding affinity of the virus to bind to negatively-charged molecules that resemble the glycans called heparin. The passaged viruses bound to heparin more tightly, and thus the cell surface glycan. Binding to these negatively-charged glycans can facilitate infection, as facilitated by the N-terminal domain mutations.

FIGURE 7: Heparin efficiently inhibiting infectivity of high passage, but not low passage natural ... [+] and cloned viruses.

Let us pause to understand exactly what was happening in these experiments. When we describe a virus, such as Wuhan, Alpha, Beta, we are not measuring a pure collection of viruses. Viruses exist as a swarm, or quasi-species as described by Manfred Eigen, each of which contains slightly different mutations from the set, despite originating from the same strain. This is why some viruses from the same strain can form small plaques versus large plaques. This is a critical distinction, as the population of viruses in an infected person are not uniform, but represent a collection of slightly different viral genomes.

Passaging in culture has a powerful selection of the properties of the virus that emerge. Pre-existing variants emerge rapidly under these conditions. If that is the case, what then does the sequence of a variant mean? The published sequence is an average of the viruses in the collection. The description of any particular variant is the average of the predominant mutations in that particular viral isolate, whether derived from patient blood samples or culture passaging.

We have seen this process in immunosuppressed patients that developed long Covid-19. The virus continues to adapt to the patients weakened immune systems, selecting mutations continuously to avoid detection and expulsion.

The cDNA experiment additionally allows us to conclude that even in cloned viruses, the RNA polymerase used to transcribe the clone makes transcription errors. These errors may occur in low probability, but if present are selected and propagated throughout a virus swarm.

Conclusions

Both the natural and cloned viruses adapt rapidly to cell culture. They adapt by selecting from mutations that appeared at a low-frequency in the quasi-species to become high-frequency mutations. The low-frequency mutations originate from polymerase mistakes when copying the virus. In the cloned virus, the authors suggest errors occur when the DNA clone is copied by an error prone polymerase in vitro. In both viruses, RNA virus particles emerge that are heterogeneous. Through cell culture passage, low-frequency mutations that confer enhanced viral characteristics are selected under the conditions used.

This same phenomenon occurs in nature as well. When SARS-CoV-2 infects a host, they begin to make copies of themselves. Each copy has, on average, three different mutations. In nasal fluids, the concentration of virus per milliliter in the Wuhan strain is 108 particles/mL (100,000,000). For the Delta variant, it is 1,000 times larger (1011 or 100,000,000,000 particles/mL). Therefore, there are between 300 million and 300 billion mutations per mL in an infected person.

These mutations are selected via passage for viability, stability, infectivity, and replication capability, meaning each passaging infection selects a more virulent virus. This is how variants arise. Given these numbers, it should be no surprise that variants arise so frequently.

Three final questions on this research:

First, is the SARS-CoV-2 virus selected in tissue culture also more infectious in animals, including humans? That could be tested in mice, hamsters, and primates, and those answers would be instructive.

Second, the authors only examine the Spike protein. Under natural selective conditions, the virus varies along the entire length of the genome, both synonymous and nonsynonymous mutations in the Orf1ab proteins, structural proteins, and regulatory (accessory) proteins. Does viral selection mutate amino acids in the 29 other viral genes? Might some of the changes in infectivity be attributed to these changes?

Finally, there has been controversy over potential gain of function experiments. The live SARS-CoV-2 in these experiments is far more infectious, at least in human cells, than some of those strains circulating around the world. There is a history of these viruses being even more pathogenic in animals than in cell culture.

For instance, deletions in the furin cleavage site in the feline enteric coronavirus increase pathogenicity in animals. There are some strains that emerge from passage that acquire neurotropism, causing brain disease. The natural and clone viruses in Shiliaev et al. both contain furin cleavage mutations that may have a similar proclivity.

The authors describe conducting their experiments under P3 containment conditions. Such a dramatic increase in infectivity as they noted causes us to wonder whether these experiments should be done under more restrictive containment conditions.

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A Snapshot Of SARS-CoV-2 Evolution: Observed Increase Of Infectivity In The Covid-19 Virus - Forbes

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The evolution of top Mets prospects Brett Baty, Mark Vientos, and Tylor Megill | Mets Prospective – Yahoo Sports

Posted: at 2:18 am

In this Mets Prospective extra content presented by Verizon, hosts Jacob Resnick and Joe DeMayo are joined by Mets Director of Player Development Jeremy Barnes to discuss the evolution of Tylor Megill from Double-A to the majors in 2021, and what it took for him to get there. Barnes also explains why they plan to work top prospects Brett Baty and Mark Vientos at different positions other than third base and the thought process on their development going forward as well as the challenge of improving the talent at the minor league level outside of the top ranked prospects in the organization. Watch more Mets Prospective: https://next.sny.tv/shows/mets-prospective-top-mets-minor-league-prospects About Mets Prospective: Mets Prospective features Jacob Resnick and Joe DeMayo profiling the top minor league prospects in the New York Mets organization, focusing on up-and-coming talent like Francisco Alvarez, Ronny Mauricio, Matt Allan, Brett Baty, Khalil Lee, and more. About SNY: SNY is an award winning, multiplatform regional sports network serving millions across the country through unparalleled coverage of all things New York sports. SNY delivers the most comprehensive access to all of the Tri-State area's professional and collegiate sports teams through nightly sports and entertainment programs. SNY.tv is the "go-to" digital communal home for New York sports fans to get succinct, easy-to-read updates, video highlights and features, recaps, news, opinion, rumors, insight and fan reaction on their favorite New York sports teams. Check out more from SNY at https://sny.tv Subscribe to SNY on YouTube: https://on.sny.tv/S5RYeWN Like SNY on Facebook: https://on.sny.tv/rBYAHLi Follow SNY on Twitter: https://on.sny.tv/nOn1uq1 Follow SNY on Instagram: https://on.sny.tv/lEArPVp

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The evolution of top Mets prospects Brett Baty, Mark Vientos, and Tylor Megill | Mets Prospective - Yahoo Sports

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30 Years of Evolution and Excellence – School Transportation News

Posted: at 2:18 am

I called my parents Bill and Colette Paul recently to wish them a happy anniversary. What? Its not our anniversary! they responded. Oh, but it is. School Transportation News was born September 1991 in Redondo Beach, California.

As I reflect on our 30th anniversary, I flash back to my 11-year-old self. I was a kid in 6th grade living in my parents house and playing lots of Nintendo. I may have ridden the school bus on a field trip or two, but that was the extent of my experience. Little did I know that my life would be impacted so greatly by my parents decision to launch STN.

Starting this business took a lot of preparation, hardwork, dedication, passion, and some luck, too, Colette Paul recalled recently. It was scary to take such a huge risk. It felt like stepping off the cliff to start our family business using all our retirement money. Plus, people told us we would never make it and that we were nuts. I like to think of myself as an optimist who stays positive about the choices we make in life.

In the beginning STN was an oversized tabloid-style news format monthly magazine. I recall me and Bill working 16-hour days, since it was the two of us doing everything out of the house. I remember the ink coming off on my fingers as I flipped through pages, she added.

I recently picked up a copy of STN, like I do every month. But this particular issue was special. It was volume number one. I loved taking a walk down memory lane to check out the headlines and ads. The top news headlines back in September 1991 were about state school bus regulations, NHSTA standards, bus evacuation times, school bus driver pay, and workers comp rates. These topics sound all too familiar even 30-years later. Wouldnt you agree?

Related:Back to School and the New NormalRelated:Focus on Rider Experience: The Way ForwardRelated:The Art of Decision-Making

My stepfather Bill Paul was in the school bus business for 10 years prior as the editor and publisher of School Bus Fleet magazine. This gave him the insights, knowledge and contacts to take the leap of starting STN. I was very excited to start the magazine. My goal was to create an information source that delivered the news to school transportation professionals monthly, he recounted. I wanted to help influence public policy, government and create a global reach to make the public aware of all the good things professionals in this industry were doing. Also, my hope was the information we provided would reduce the tragic loss of life of students on and around the school bus.

Colette and I have deep love for the school bus industry. Its helped propel this business forward through all the turbulence we experienced over the years. I feel we successfully accomplished all our objectives that we set out to achieve when we started STN, he added.

STN has grown significantly over the years with digital media offerings such as the School Transportation Nation Podcast and conferences like STN EXPO and the TSD Conference. But our vision has remained steadfast over three decades. Our relentless vision to help school transportation professionals do their jobs safer and more efficiently. As a result, the kids, families and our industry benefits.

I want to give kudos to the STN team and all our contributors over the last 30 years for all the editorial excellence and creativity that has been exemplified by our magazine, website, conferences, podcast and so much more. It takes a village to make everything a success.

Also, we couldnt have done it without our loyal readers like you. Thank you for giving us your trust and time. Know that we are committed to being the voice of the school transportation industry for years to come. I truly hope we have added value to your personal and professional life, if so, we have done our job. See you next month in Indianapolis!

Related:(STN Podcast E80) Industry Buzz: Excitement for Electric School Buses & Driver Shortage SolutionsRelated:(STN Podcast E81) Strategic Student Transportation: Responding to the Pandemic & Driver ShortagesRelated:(STN Podcast E82) Back to School Efforts: National Guard Drivers, Vaccine Mandates

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30 Years of Evolution and Excellence - School Transportation News

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People Can’t Believe How Bad The New Pro Evolution Looks – Balls.ie

Posted: at 2:18 am

It was the great debate of its time: FIFA versus Pro Evolution.

Many preferred the gameplay on the Konami release, but others just couldn't get past having to use Merseyside Red or Man Red in the game.

In any case, there hasn't been much of a debate on the matter in recent times. FIFA is now clearly much more popular, with the quality of the game having long surpassed that of its once rival.

You don't get many people vouching for the newer versions of Pro Evolution, so much so that the game has undergone a complete rebrand this year.

Not only has it changed its name to the much less exciting sounding 'eFootball 2022', but it also available to download for free.

Even though it costs nothing, early reviews would suggest that it still might be overpriced.

People have been absolutely slating the game in recent days, with its brutal graphics and numerous glitches causing quite the stir.

For example, here's what the crowd in the stadium looks like.

In fairness, the crowd doesn't play much of a part in the game. Surely the players themselves look decent?

Not quite. Here are just a few of the screenshots that have been doing the rounds, with the developers absolutely butchering the likes of Lionel Messi and Cristiano Ronaldo.

Not great.

That is without even mentioning the numerous glitches that have been spotted so far. The video below sums things up pretty well.

In fact, eFootball 2022 is so bad that Konami have already apologised for the game.

We will probably be sticking to FIFA for this year.

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People Can't Believe How Bad The New Pro Evolution Looks - Balls.ie

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