Journal Reference: Hossein J. Sadaei, Aldo Cordova-Palomera, Jonghun Lee, Jaya Padmanabhan, Shang-Fu Chen, Nathan E. Wineinger, Raquel Dias, Daria Prilutsky, Sandor Szalma, Ali Torkamani. Genetically-informed prediction of short-term Parkinson’s disease progression. npj Parkinson’s Disease, 2022; 8 (1) DOI: 10.1038/s41531-022-00412-w Now, Scripps Research scientists have developed a tool that analyzes Parkinson’s disease patients’ genetic and clinical ... Read more

Journal Reference:

Hossein J. Sadaei, Aldo Cordova-Palomera, Jonghun Lee, Jaya Padmanabhan, Shang-Fu Chen, Nathan E. Wineinger, Raquel Dias, Daria Prilutsky, Sandor Szalma, Ali Torkamani. Genetically-informed prediction of short-term Parkinson’s disease progression. npj Parkinson’s Disease, 2022; 8 (1) DOI: 10.1038/s41531-022-00412-w

Now, Scripps Research scientists have developed a tool that analyzes Parkinson’s disease patients’ genetic and clinical data to predict who is most likely to rapidly progress. The approach, described in npj Parkinson’s Disease, will let clinical researchers select the most at-risk patients and design shorter, more powerful trials to assess Parkinson’s drugs, they say.

“If clinicians are able to enroll in trials only those patients predicted to progress, they can get much faster results and move this field along more quickly,” says senior author Ali Torkamani, PhD, professor and director of Genomics and Genome Informatics at the Scripps Research Translational Institute.

Parkinson’s disease is a progressive disorder of the nervous system and affects about one million people in the United States. The earliest symptoms are often barely noticeable tremors, and over the course of many years the disease progresses, eventually impacting movement, posture, facial expressions, speech and eating, as well as causing pain and dementia. However, the order and speed at which these symptoms worsen varies greatly between people. Over a single year, for instance, many patients won’t get worse, making it difficult and time-consuming to study the effectiveness of drugs at slowing this progression.

Torkamani, along with Scripps Research colleagues and collaborators at Takeda — who are developing investigational Parkinson’s Disease treatments — set out to better predict this short-term progression in patients considered for inclusion in clinical studies to slow down this disease. They analyzed the progression over 12, 24 and 36 months of patients enrolled in two existing cohorts — the Parkinson’s Progression Markers Initiative and the Parkinson’s Disease Biomarkers Program. In all, the team used data including genetics, clinical exam information, brain scans and treatments, on 879 patients.

Overall, 529 patients were found to be “progressors” over the first 12 months of the study, with their symptoms significantly worsening, while 350 were grouped as “non-progressors.” Torkamani’s group used a machine learning approach to develop a model that could predict, with 77% accuracy, which group patients belonged to.

“This model worked by combining different aspects of comprehensive disease profiling,” says Torkamani. “Genetic risk factors were the most powerful predictor, but other factors were important to include as well.”

Some of the strongest signals, he says, included whether a patient had a mutation in LRRK2 — this known risk factor for Parkinson’s disease makes patients more likely to develop early onset disease, but then their symptoms progress more slowly.

For now, the model doesn’t have clinical value for individual patients, since there are no drugs that have been shown to slow the progression of Parkinson’s. However, the researchers hope that being able to choose “progressors” for clinical trials makes it easier and faster to pinpoint these kinds of drugs as the field moves forward.

“Right now, these clinical trials are large and tend to take two to three years,” says Torkamani. “We’re hoping to empower smaller trials that are on the order of a one-year time frame.”

The Scripps Research scientists also plan to expand their model to try to predict other aspects of Parkinson’s. For instance, can genetic markers predict which Parkinson’s patients will develop psychosis or depression? The same approach they took in the current study — integrating clinical and genetic information — could also be useful in analyzing the progression of other neurodevelopmental disorders.

This work was supported by funding from Takeda Development Center Americas, Inc., and the National Institutes of Health (R01HG010881).

Journal Reference:

Hossein J. Sadaei, Aldo Cordova-Palomera, Jonghun Lee, Jaya Padmanabhan, Shang-Fu Chen, Nathan E. Wineinger, Raquel Dias, Daria Prilutsky, Sandor Szalma, Ali Torkamani. Genetically-informed prediction of short-term Parkinson’s disease progression. npj Parkinson’s Disease, 2022; 8 (1) DOI: 10.1038/s41531-022-00412-w

“Right now, these clinical trials are large and tend to take two to three years,” says Torkamani. “We’re hoping to empower smaller trials that are on the order of a one-year time frame.”

This work was supported by funding from Takeda Development Center Americas, Inc., and the National Institutes of Health (R01HG010881).

Journal Reference: Alexander J. Fairchild, Varghese A. Chirayath, Randall W. Gladen, Ali R. Koymen, Alex H. Weiss, Bernardo Barbiellini. Photoemission Spectroscopy Using Virtual Photons Emitted by Positron Sticking: A Complementary Probe for Top-Layer Surface Electronic Structures. Physical Review Letters, 2022; 129 (10) DOI: 10.1103/PhysRevLett.129.106801 Researchers from the Positron Lab in the UTA Department of Physics ... Read more

Journal Reference:

Alexander J. Fairchild, Varghese A. Chirayath, Randall W. Gladen, Ali R. Koymen, Alex H. Weiss, Bernardo Barbiellini. Photoemission Spectroscopy Using Virtual Photons Emitted by Positron Sticking: A Complementary Probe for Top-Layer Surface Electronic Structures. Physical Review Letters, 2022; 129 (10) DOI: 10.1103/PhysRevLett.129.106801

Researchers from the Positron Lab in the UTA Department of Physics utilized a process called auger-mediated positron sticking (AMPS) to develop a novel spectroscopic tool to measure the electronic structure of the surface of materials selectively.

A new article, “Photoemission spectroscopy using virtual photons emitted by positron sticking: A complementary probe for top-layer surface electronic structures,” published in the journal Physical Review Letters (PRL), details the new technique. In addition, the online magazine Physics published a Viewpoint article on the publication, titled “Spectroscopy That Doesn’t Scratch the Surface,” which explains why the paper is important to the field. Viewpoint articles are commissioned by PRL editors for papers they believe will draw broad interest.

Alex Fairchild, postdoctoral scholar in the Positron Lab, is the study’s lead author. Co-authors include Varghese Chirayath, assistant professor of research; Randall Gladen, postdoctoral researcher; Ali Koymen, professor of physics; and Alex Weiss, professor and chair of the UTA Department of Physics. Bernardo Barbiellini, professor of physics at LUT University in Finland, also contributed to the project.

The AMPS process, in which positrons (antimatter of electrons) stick directly to surfaces followed by electron emission, was first observed and described by Saurabh Mukherjee, a graduate student, along with Weiss and other colleagues, in 2010 at UTA. Those results were published in a paper in PRL.

“Alex (Fairchild) and Varghese figured out how to use this phenomenon that we discovered in 2010 to measure the top layer and get information about the electronic structure and the behavior of the electrons in the top layer,” Weiss said. “That will determine a material’s many properties, including conductivity, and can have important implications for building devices.”

Fairchild said the AMPS process is unique because it uses virtual photons to measure the topmost atomic layer.

“This is different from typical techniques like photoemission spectroscopy, where a photon penetrates multiple layers into the bulk of a material and therefore contains the combined information of the surface and subsurface layers,” Fairchild said.

“Our AMPS results showed how virtual photons emitted following positron-sticking interact preferably with electrons that extend further into the vacuum than with electrons that were more localized to the atomic site,” Chirayath said. “Our results are thus essential to understand how positrons interact with surface electrons and are extremely important to understand other similarly surface-selective, positron-based techniques.”

Weiss noted that the UTA Positron Lab is currently the only place this technique could have been developed, due to the capabilities of its positron beam.

“At present, UTA probably has the only lab in the world that has a positron beam that can get down to the low energies needed to observe this phenomenon,” Weiss said.

The study was supported by funding from the Welch Foundation and the National Science Foundation.

Journal Reference:

Alexander J. Fairchild, Varghese A. Chirayath, Randall W. Gladen, Ali R. Koymen, Alex H. Weiss, Bernardo Barbiellini. Photoemission Spectroscopy Using Virtual Photons Emitted by Positron Sticking: A Complementary Probe for Top-Layer Surface Electronic Structures. Physical Review Letters, 2022; 129 (10) DOI: 10.1103/PhysRevLett.129.106801

Fairchild said the AMPS process is unique because it uses virtual photons to measure the topmost atomic layer.

Weiss noted that the UTA Positron Lab is currently the only place this technique could have been developed, due to the capabilities of its positron beam.

“At present, UTA probably has the only lab in the world that has a positron beam that can get down to the low energies needed to observe this phenomenon,” Weiss said.

The study was supported by funding from the Welch Foundation and the National Science Foundation.

Actor Ben Castle is a phony singing cowboy who cannot ride, sing, or act, is afraid of guns and horses, and is the first one out the door when trouble breaks out. His studio hires attorney Abigail Furnival to get him out of trouble with a big-time gambler because he cannot pay off a gambling debt. The next thing she knows, she has married him. The gambler decides to write off the debt when he learns that Abigail is the daughter of an old friend. But the gambler is murdered, and Ben appears to be involved.

Journal Reference: Haiming Li, Yufeng Sun, Ying Yang, Yifu Cui, Lele Ren, Hu Li, Guoke Chen, Petra Vaiglova, Guanghui Dong, Xinyi Liu. Water and soil management strategies and the introduction of wheat and barley to northern China: an isotopic analysis of cultivation on the Loess Plateau. Antiquity, 2022; 1 DOI: 10.15184/aqy.2022.138 But the story gets ... Read more

Journal Reference:

Haiming Li, Yufeng Sun, Ying Yang, Yifu Cui, Lele Ren, Hu Li, Guoke Chen, Petra Vaiglova, Guanghui Dong, Xinyi Liu. Water and soil management strategies and the introduction of wheat and barley to northern China: an isotopic analysis of cultivation on the Loess Plateau. Antiquity, 2022; 1 DOI: 10.15184/aqy.2022.138

But the story gets more complex from there. Wheat and barley arrived on the scene at about the same time, but early farmers only used water management techniques for wheat. The results, reported Nov. 9 in the journal Antiquity, raise awareness that the dispersal of domesticated crops and the knowledge of best using them can be traced independently across time and space.

“Pioneering farmers who cultivated wheat in this region managed water to meet the higher demand of this newly introduced grain,” said Xinyi Liu, an associate professor of archaeology in Arts & Sciences, who collaborated on this study with researchers from several prominent institutions in China and Australia, including Guanghui Dong from Lanzhou University, who led the field expedition on the Loess Plateau. “The water management may have been achieved either by deliberate watering or by strategic planting in soils with higher water retention.”

On the other hand, early farmers were able to grow the other new grain, barley, in a rainfed system as if it were just another kind of millet — the locally domesticated and most commonly grown grain in northern China at the time — without using any form of irrigation.

Liu published the study with Washington University graduate student Yufeng Sun. Other co-authors include Haiming Li and Petra Vaiglova, former members of Liu’s lab group.

Introducing irrigation

Both wheat and barley were domesticated in an area known to archaeologists as the hilly flanks of the Fertile Crescent in southwest Asia, where they originally were grown as winter crops. Traditionally, farmers there sowed their seeds in autumn — to avoid the summer drought period — and harvested them in late spring or early summer before the next drought season.

When these Fertile Crescent crops, wheat and barley, were introduced to East Asia about 4,000 years ago, they would have encountered a markedly different climate compared with where they originated.

“Every summer, the East Asian monsoon brings rains from the Pacific Ocean to a region otherwise arid throughout the rest of the year. This environment is perfect for rainfed millet cultivation as these local grains are drought tolerant but need considerable water in the summer growing season,” Liu said. “But it is a different story if you try to grow wheat there, not only because it is water demanding, but also the growing cycle doesn’t match the rainy season.”

Liu and his colleagues wanted to know: Did the farmers who sought to grow the new grains in northern China also introduce new systems of irrigation to support them?

“The introduction of a new irrigation system is something that scholars have speculated about, but now we have the technology to seek direct evidence,” Liu said.

Using relatively new techniques, the actual growing conditions of past crops — including past water and soil conditions during plant growth — can be measured using the stable carbon and nitrogen isotope compositions of charred plant remains. These methods initially were established in plant science for research concerning environmental conditions of modern-day agriculture and have been subsequently applied to archaeological research.

Previous studies using similar approaches have shed significant light on early crop management in Europe and the Middle East. This research is one of the first attempts to apply it to East Asian monsoon environments with innovative questions.

For this study, the scientists identified more than 35,000 charred seed remains of cereal plants, including wheat, barley and millet, from more than 50 archaeological sites excavated on the Loess Plateau of China spanning a timeframe over eight millennia. Selected plant remains from this collection were radiocarbon dated and isotopically measured.

The results showed major differences between wheat and barley.

Despite the arid local environment, the majority of the wheat samples from all time periods had isotopic values above an optimal watering threshold, indicating that their growth was not limited by water availability.

“We see this in the Qijia culture period, when wheat and barley were just introduced to this region,” Liu said. “The isotopic data of wheat show a significant level of water manipulation unambiguously since 4,000 years ago, indicating the new crop was introduced with water management strategies to support it.”

Simple ditches can be powerful

This evidence alone does not necessarily imply large-scale irrigation, Liu is quick to point out; instead, wheat crops may have been strategically sown in areas with the best water availability, either close to local springs or in soils with high water retention.

“In those locations, small ditches to diffuse water is sufficient,” Liu said. “This explains why there is no archaeological evidence of channels or other irrigation installations in the area until much later.”

Barley, on the other hand, appears to have been grown on the dry hills of the Loess Plateau without a special water management approach — a landscape and cultivation strategy that had been familiar to the Neolithic millet farmers since 8,000 years ago.

This and other evidence suggest to Liu and his collaborators that ancient farmers sought to optimize land use and crop yield by taking advantage of the different water demands of these two crops.

“Our results raise an awareness that the dispersal of domesticated crops and the knowledge of best using them can be traced independently across time and space,” Liu said.

“Central to our inquiry is the tension between non-native crops and indigenous farming practices,” he said. “When non-native innovations were adopted in another cultural and physical environment, they would have been transformed within the local context. How this happens is an enduring question that is relevant to globalization in the past and present.”

This study resonates with other archaeological investigations led by Liu’s research group, the Laboratory for the Analysis of Early Food-Webs at Washington University. For example, co-author Sun’s previous work with Washington University graduate student Melissa Ritchey demonstrated a similar geographic decoupling of the dispersal of grains and cuisines, such that wheat and barley dispersed into ancient China 4,000 years ago, but the western grinding-and-baking cuisines did not. The eastern movement of these grains involved selections of phenotypic traits adapted to ancient China’s cooking tradition of using steaming-and-boiling.

It has been a long time since some scholars assumed the association between the origin of bureaucracy and irrigation, and ancient China had been used as an example of “oriental despotism,” according to Liu. The “hydraulic empire” hypothesis speculated that a centralized government structure that maintained power would have been derived from the need for flood control and irrigation.

“Our results suggest otherwise, such that irrigation was a much more localized practice, which did not necessarily require central coordination and a specialized bureaucracy,” Liu explained. “Simple ditches and strategic planting can be as powerful as monopoly empires.”

Journal Reference:

Haiming Li, Yufeng Sun, Ying Yang, Yifu Cui, Lele Ren, Hu Li, Guoke Chen, Petra Vaiglova, Guanghui Dong, Xinyi Liu. Water and soil management strategies and the introduction of wheat and barley to northern China: an isotopic analysis of cultivation on the Loess Plateau. Antiquity, 2022; 1 DOI: 10.15184/aqy.2022.138

Liu published the study with Washington University graduate student Yufeng Sun. Other co-authors include Haiming Li and Petra Vaiglova, former members of Liu’s lab group.

Introducing irrigation

When these Fertile Crescent crops, wheat and barley, were introduced to East Asia about 4,000 years ago, they would have encountered a markedly different climate compared with where they originated.

Liu and his colleagues wanted to know: Did the farmers who sought to grow the new grains in northern China also introduce new systems of irrigation to support them?

“The introduction of a new irrigation system is something that scholars have speculated about, but now we have the technology to seek direct evidence,” Liu said.

The results showed major differences between wheat and barley.

Simple ditches can be powerful

This and other evidence suggest to Liu and his collaborators that ancient farmers sought to optimize land use and crop yield by taking advantage of the different water demands of these two crops.

“Our results raise an awareness that the dispersal of domesticated crops and the knowledge of best using them can be traced independently across time and space,” Liu said.

Journal Reference: Josefine Ruder, María José Docampo, Jordan Rex, Simon Obahor, Reza Naghavian, Antonia M.S. Müller, Urs Schanz, Ilijas Jelcic, Roland Martin. Dynamics of T cell repertoire renewal following autologous hematopoietic stem cell transplantation in multiple sclerosis. Science Translational Medicine, 2022; 14 (669) DOI: 10.1126/scitranslmed.abq1693 Every day, one person in Switzerland is diagnosed with multiple ... Read more

Journal Reference:

Josefine Ruder, María José Docampo, Jordan Rex, Simon Obahor, Reza Naghavian, Antonia M.S. Müller, Urs Schanz, Ilijas Jelcic, Roland Martin. Dynamics of T cell repertoire renewal following autologous hematopoietic stem cell transplantation in multiple sclerosis. Science Translational Medicine, 2022; 14 (669) DOI: 10.1126/scitranslmed.abq1693

Every day, one person in Switzerland is diagnosed with multiple sclerosis. MS is an autoimmune disease in which the body’s own immune system attacks the myelin sheath of the nerve cells in the brain and spinal cord. The disease leads to paralysis, pain and permanent fatigue, among other symptoms. Fortunately, there have been great advances in therapies in recent decades. A study by the Department of Neuroimmunology and MS Research at the University of Zurich (UZH) and the Department of Medical Oncology and Haematology Clinic at the University Hospital Zurich (USZ) has now pinpointed why the most effective currently available therapy — a stem cell transplant — works so well.

Wiping out unwanted immune cells

“80 percent of patients remain disease-free long-term or even forever following an autologous hematopoietic stem cell transplant,” says recently retired Professor Roland Martin, study lead and last author. The treatment is particularly suitable for younger people with aggressive forms of the disease. Four years ago, thanks to the high effectiveness of the treatment and the now low mortality rate, Martin’s department together with the USZ clinic were granted approval to administer the therapy. It is the only clinic in Switzerland approved for this treatment.

During the treatment, several chemotherapies completely destroy the patients’ immune system — including the subset of T cells which mistakenly attack their own nervous system. The patients then receive a transplant of their own blood stem cells, which were harvested before the chemotherapy. The body uses these cells to build a completely new immune system without any autoreactive cells.

Systematic analysis of immune cells

“Previous studies have shown the basic workings of the method, but many important details and questions remained open,” says Martin. Some unclear aspects were what exactly happens after the immune cells are eliminated, whether any of them survive the chemotherapy, and whether the autoreactive cells really do not return.

In the recently published study, Martin’s team systematically investigated these questions for the first time by analyzing the immune cells of 27 MS patients who received stem cell therapy in Zurich. The analysis was done before, during and up to two years after treatment. This allowed the researchers to track how quickly the different types of immune cells regenerated

Successful reset of immune system

Surprisingly, the cells known as memory T cells, which are responsible for ensuring the body remembers pathogens and can react quickly in case of a new infection, reappeared immediately after the transplant. Further analysis showed that these cells had not re-formed, but had survived the chemotherapy. These remnants of the original immune system nevertheless pose no risk for a return of MS: “They are pre-damaged due to the chemotherapy and therefore no longer able to trigger an autoimmune reaction,” explains Martin.

In the months and years following the transplant, the body gradually recreates the different types of immune cells. The thymus gland plays an important role in this process. This is where the T cells go to school, so to speak, and learn to distinguish foreign structures, such as viruses, from the body’s own. “Adults have very little functioning tissue left in the thymus,” says Martin. “But after a transplant, the organ appears to resume its function and ensures the creation of a completely new repertoire of T cells which evidently do not trigger MS or cause it to return.”

Further studies needed for wider approval

These findings have enabled the researchers to understand why stem cell transplants are usually so successful. But lamentably, says Martin, the treatment is not approved in many countries, as phase III studies are lacking. “Phase III studies cost several hundred million euros, and pharmaceutical companies are only willing to conduct them if they will make money afterward.” This is not the case with stem cell therapy, as the drugs used are no longer patent-protected.

“I am therefore very pleased that we have succeeded in obtaining approval for the treatment from the Federal Office of Public Health and that health insurers are covering the costs,” Martin says. In the past, many MS sufferers from Switzerland had to travel to Moscow, Israel or Mexico to receive transplants.

Journal Reference:

Josefine Ruder, María José Docampo, Jordan Rex, Simon Obahor, Reza Naghavian, Antonia M.S. Müller, Urs Schanz, Ilijas Jelcic, Roland Martin. Dynamics of T cell repertoire renewal following autologous hematopoietic stem cell transplantation in multiple sclerosis. Science Translational Medicine, 2022; 14 (669) DOI: 10.1126/scitranslmed.abq1693

Wiping out unwanted immune cells

Systematic analysis of immune cells

Successful reset of immune system

Further studies needed for wider approval

Colorized Western Movie: Colorado Sundown - Rancher helps a friend claim a spread he's inherited, only to get involved in his murder. The Hurley's own a lumber mill and want to harvest all the timber in the valley. They kill…

Colorized Western Movie: Colorado Sundown – Rancher helps a friend claim a spread he’s inherited, only to get involved in his murder. The Hurley’s own a lumber mill and want to harvest all the timber in the valley. They kill the Forester and substitute their brother Dusty in his place.

Colorado Sundown (1952)
Director: William Witney
Writers: Eric Taylor (screenplay), William Lively (screenplay)
Stars: Rex Allen, Koko, Mary Ellen Kay
Genre: Western
Country: United States
Language: English
Release Date: 8 February 1952
Filming Location: Shay Ranch, Big Bear Valley, San Bernardino National Forest, California, USA

Storyline:
The Hurley’s own a lumber mill and want to harvest all the timber in the valley. They kill the Forester and substitute their brother Dusty in his place. Dusty then says all the trees are infected and must be cut down. But Rex Allen is suspicious and writes to the Forestry Department.

Reviews:
“B-westerns almost always have a baddie. It’s usually some guy bent on taking over the county and he secretly controls a gang of thugs who are terrorizing the countryside. However, “Colorado Sundown” is quite different. While the plot has the usual attempt to practically steal everyone’s land, it’s by a trio of evil siblings–and the most evil and conniving is a woman! And, to make things even more different, the woman is even more brutal and vicious than usual! And, instead of a gang, they use trickery and murder to make their plans work and a gang is only recruited when their plan starts to unravel.

When the movie begins, three different groups of people think they are inheriting a ranch. In reality, they ALL are inheriting a third. While this may not sound so bad, one group (the Hurleys) are vicious thieves and want it all–and they’ll get it one way or another. Their plan is to convince everyone that the land is infested with a bark beetle–and then get all the property for a tiny fraction of what it’s worth. Then, they’ll do the same thing for all the surrounding land that supposedly is infested.

As for Carrie Hurley (June Vincent), she is the boss in her family and specializes in poisonings. The first victim is a forestry official who KNOWS the land is beetle-free. The second is a fake forest ranger who Carrie brought in–and to make matters worse, it’s her own younger brother!! In addition to these killings, one Hurley shoots an innocent maid (Louise Beavers) and even a tiny dog!! Could it get worse? Well, she even shoots poor Rex Allen and then claims she shot him AFTER Rex beat the ‘ranger’ to death–when she actually poisoned him! Can the good guys uncover the plot and dispatch the evil Hurleys? Because the villains are so bad, this is a dynamite B-western. It also helps that the plot is quite original in many ways and Louise Beavers was great as one of the spunkiest women of the old west I’ve ever seen. Surprisingly good.

It is interesting that in this film Rex Allen plays a character named Rex Allen and Slim Pickens played a guy named Slim Pickens! This sort of thing was quite popular in Roy Rogers films, as Roy and Gabby were often referred to by their stage names. Odd. Also odd is that Pickens really was a cowboy and rodeo star–and so playing a cowboy is pretty natural.”
– written by “planktonrules” on IMDb.com

Also Known As (AKA):
(original title) Colorado Sundown
Brazil Cavaleiro do Colorado
Canada (English title) Colorado Sundown
Romania Apus de soare în Colorado
UK Colorado Sundown
USA Colorado Sundown

COPYRIGHT: All of the films published by us are legally licensed. We have acquired the rights (at least for specific territories) from the copyright holders by contract. If you have questions please send an email to: info@amogo.de, Amogo Networx – The AVOD Channel Network, www.amogo-networx.com.

Also Known As (AKA):
(original title) Colorado Sundown
Brazil Cavaleiro do Colorado
Canada (English title) Colorado Sundown
Romania Apus de soare în Colorado
UK Colorado Sundown
USA Colorado Sundown

A young man troubled by his past finds comfort playing basketball alone, until a persistent homeless man claiming a love for basketball disrupts his summer. Teaming up they take on street games for cash and their unlikely friendship develops both on and off the court. He discovers answers to his past both touching and tragic, as basketball becomes more than a game.

Directors: Kylie Claude, Rody Claude
Stars: Ek Harris, Adam T. Perkins, Alex McTavish

Journal Reference: Yann LeCun, Yoshua Bengio, Geoffrey Hinton. Deep learning. Nature, 2015; 521 (7553): 436 DOI: 10.1038/nature14539 Aspiring bakers are frequently called upon to adapt award-winning recipes based on differing kitchen setups. Someone might use an eggbeater instead of a stand mixer to make prize-winning chocolate chip cookies, for instance. Being able to reproduce a ... Read more

Journal Reference:

Yann LeCun, Yoshua Bengio, Geoffrey Hinton. Deep learning. Nature, 2015; 521 (7553): 436 DOI: 10.1038/nature14539

Aspiring bakers are frequently called upon to adapt award-winning recipes based on differing kitchen setups. Someone might use an eggbeater instead of a stand mixer to make prize-winning chocolate chip cookies, for instance.

Being able to reproduce a recipe in different situations and with varying setups is critical for both talented chefs and computational scientists, the latter of whom are faced with a similar problem of adapting and reproducing their own ”recipes” when trying to validate and work with new AI models. These models have applications in scientific fields ranging from climate analysis to brain research.

“When we talk about data, we have a practical understanding of the digital assets we deal with,” said Eliu Huerta, scientist and lead for Translational AI at the U.S. Department of Energy’s (DOE) Argonne National Laboratory. ”With an AI model, it’s a little less clear; are we talking about data structured in a smart way, or is it computing, or software, or a mix?”

In a new study, Huerta and his colleagues have articulated a new set of standards for managing AI models. Adapted from recent research on automated data management, these standards are called FAIR, which stands for findable, accessible, interoperable and reusable.

“By making AI models FAIR, we no longer have to build each system from the ground up each time,” said Argonne computational scientist Ben Blaiszik. ”It becomes easier to reuse concepts from different groups, helping to create cross-pollination across teams.”

According to Huerta, the fact that many AI models are currently not FAIR poses a challenge to scientific discovery. ”For many studies that have been done to date, it is difficult to gain access to and reproduce the AI models that are referenced in the literature,” he said. ”By creating and sharing FAIR AI models, we can reduce the amount of duplication of effort and share best practices for how to use these models to enable great science.”

To meet the needs of a diverse community of users, Huerta and his colleagues combined a unique suite of data management and high performance computing platforms to establish a FAIR protocol and quantify the ”FAIR-ness” of AI models. The researchers paired FAIR data published at an online repository called the Materials Data Facility, with FAIR AI models published at another online repository called the Data and Learning Hub for Science, as well as with AI and supercomputing resources at the Argonne Leadership Computing Facility (ALCF). In this way, the researchers were able to create a computational framework that could help bridge various hardware and software, creating AI models that could be run similarly across platforms and that would yield reproducible results. The ALCF is a DOE Office of Science user facility.

Two keys to creating this framework are platforms called funcX and Globus, which allow researchers to access high performance computing resources straight from their laptops. ”FuncX and Globus can help transcend the differences in hardware architectures,” said co-author Ian Foster, director of Argonne’s Data Science and Learning division. ”If someone is using one computing architecture and someone else is using another, we now have a way of speaking a common AI language. It’s a big part of making AI more interoperable.”

In the study, the researchers used an example dataset of an AI model that used diffraction data from Argonne’s Advanced Photon Source, also a DOE Office of Science user facility. To perform the computations, the team used the ALCF AI Testbed’s SambaNova system and the Theta supercomputer’s NVIDIA GPUs (graphics processing units).

“We’re excited to see the FAIR productivity benefits from model and data sharing to provide more researchers with access to high performance computing resources,” said Marc Hamilton, NVIDIA vice president for Solutions Architecture and Engineering. ”Together we’re supporting the expanding universe of high performance computing that’s combining experimental data and instrument operation at the edge with AI to increase the pace of scientific discovery.”

“SambaNova is excited to partner with researchers at Argonne National Laboratory to pursue innovation at the interface of AI and emergent hardware architectures,” added Jennifer Glore, vice president for Customer Engineering at SambaNova Systems. ”AI will have a significant role in the future of scientific computing, and the development of FAIR principles for AI models along with novel tools will empower researchers to enable autonomous discovery at scale. We’re looking forward to continued collaboration and development at the ALCF AI Testbed.”

A paper based on the study, ”FAIR principles for AI models, with a practical application for accelerated high energy diffraction microscopy,” appeared in Nature Scientific Data on Nov. 10, 2022.

In addition to Huerta, other authors of the study include Argonne’s Nikil Ravi, Pranshu Chaturvedi, Zhengchun Liu, Ryan Chard, Aristana Scourtas, K.J. Schmidt, Kyle Chard, Ben Blaiszik and Ian Foster.

The research was funded by DOE’s Office of Advanced Scientific Computing Research, the National Institutes of Standards and Technology, the National Science Foundation and Laboratory Directed Research and Development grants.

Journal Reference:

Yann LeCun, Yoshua Bengio, Geoffrey Hinton. Deep learning. Nature, 2015; 521 (7553): 436 DOI: 10.1038/nature14539

A paper based on the study, ”FAIR principles for AI models, with a practical application for accelerated high energy diffraction microscopy,” appeared in Nature Scientific Data on Nov. 10, 2022.

From a young age, Joseph believed God had destined him for greatness. In dreams, God assured Joseph that he would rise to a position of leadership over his parents and brothers. A series of memorable dramatizations from the Holy Bible,…

From a young age, Joseph believed God had destined him for greatness. In dreams, God assured Joseph that he would rise to a position of leadership over his parents and brothers.

A series of memorable dramatizations from the Holy Bible, complete with gorgeous costumes, compelling performances, and the Word of God.

From a young age, Joseph believed God had destined him for greatness. In dreams, God assured Joseph that he would rise to a position of leadership over his parents and brothers.

A series of memorable dramatizations from the Holy Bible, complete with gorgeous costumes, compelling performances, and the Word of God.

Journal Reference: Emanuele Panatta, Alessio Butera, Eleonora Mammarella, Consuelo Pitolli, Alessandro Mauriello, Marcel Leist, Richard A. Knight, Gerry Melino, Ivano Amelio. Metabolic regulation by p53 prevents R-loop-associated genomic instability. Cell Reports, 2022; 41 (5): 111568 DOI: 10.1016/j.celrep.2022.111568 But even when there are no DNA-damaging agents around, it is an extremely difficult task for cells to ... Read more

Journal Reference:

Emanuele Panatta, Alessio Butera, Eleonora Mammarella, Consuelo Pitolli, Alessandro Mauriello, Marcel Leist, Richard A. Knight, Gerry Melino, Ivano Amelio. Metabolic regulation by p53 prevents R-loop-associated genomic instability. Cell Reports, 2022; 41 (5): 111568 DOI: 10.1016/j.celrep.2022.111568

But even when there are no DNA-damaging agents around, it is an extremely difficult task for cells to maintain their genomic (DNA) stability. Researchers have suspected that p53’s protective function also covers healthy cells. The mechanism by which the protein would gain such capabilities, however, has remained unclear. A research team led by Ivano Amelio, Professor of Systems Toxicology at the University of Konstanz, and involving his Konstanz colleague Marcel Leist, Professor of In-Vitro Toxicology and Biomedicine, has now shed new light on this mystery.

Cell division is a vulnerable process

Cells — and their DNA integrity — are particularly at risk when they divide, as they duplicate their DNA in the process. “Like in any other replication process, such as photocopying a document or copying a digital file, it is disastrous if the template moves or is changed while the copy is being made. For this reason, genes cannot be transcribed — i.e. used as templates for proteins — while the DNA is being copied,” Amelio explains. If they are transcribed anyway, serious disruptions occur, which can lead to cancer-promoting mutations. The results from Amelio and his team, now appearing as the cover story in Cell Reports, show that p53 inactivation favours such copy-related damage. They found that p53 normally acts by changing cell metabolism in a way that prevents activation of genome regions that should remain inactive.

The scientists painstakingly dissected the underlying mechanism down to the last detail. They made use of the knowledge that some parts of the genome, called heterochromatin, are packed densely to prevent transcription of genes in these regions. For this reason, such regions are called “silent,” and they are controlled by what is known as epigenetic mechanisms, i.e. processes that do not affect the genes as such, but their overall packaging and accessibility in the genome. One of the most interesting findings of the recent study was that in the absence of p53 these usually inaccessible or “silent” regions of our DNA were transcribed, leading to catastrophic consequences.

Crosstalk between p53-driven metabolism and epigenetic integrity

“Normally, transcription of these areas of the genome should be kept under tight control, and p53 is the key to keeping their information locked-away by controlling metabolism in a way that renders the heterochromatin inaccessible,” Amelio says. When p53 is absent, as in p53-inactivated tumours, the cell loses its metabolic homeostasis, and the information hidden in the heterochromatin becomes aberrantly accessible and is transcribed. This causes so much damage that it will drive cells into a state of genomic instability that favours and worsens cancer progression. “By unravelling this mechanism, we could demonstrate that there is a link between metabolism, epigenetic integrity and genomic stability. In addition, we provided evidence that p53 represents the switch controlling the on/off status of this protection system in the response to environmental stress,” Amelio summarizes the finding.

The question of how p53-inactivated tumours develop genomic instability has plagued the scientific community for quite some time. “Now we have certainty that, in these tumours, there is a problem at the metabolic level that is reflected in the integrity of the epigenome. Hence, p53 should actually be called guardian of the (epi-)genome. This essential insight can direct research to identify potential new therapeutic strategies for the very frequent forms of cancers that carry p53 inactivation,” Amelio concludes.

Journal Reference:

Emanuele Panatta, Alessio Butera, Eleonora Mammarella, Consuelo Pitolli, Alessandro Mauriello, Marcel Leist, Richard A. Knight, Gerry Melino, Ivano Amelio. Metabolic regulation by p53 prevents R-loop-associated genomic instability. Cell Reports, 2022; 41 (5): 111568 DOI: 10.1016/j.celrep.2022.111568

Cell division is a vulnerable process

Crosstalk between p53-driven metabolism and epigenetic integrity