New CRISPR Technology Offers Unrivaled Control of Epigenetic Inheritance (Biology)

Scientists have figured out how to modify CRISPR’s basic architecture to extend its reach beyond the genome and into what’s known as the epigenome – proteins and small molecules that latch onto DNA and control when and where genes are switched on or off.

In a paper published April 9, 2021, in the journal Cell, researchers at UC San Francisco and the Whitehead Institute describe a novel CRISPR-based tool called “CRISPRoff,” which allows scientists to switch off almost any gene in human cells without making a single edit to the genetic code. The researchers also show that once a gene is switched off, it remains inert in the cell’s descendants for hundreds of generations, unless it is switched back on with a complementary tool called CRISPRon, also described in the paper.

Because the epigenome plays a central role in many diseases, from viral infection to cancer, CRISPRoff technology may one day lead to powerful epigenetic therapies. And since this approach doesn’t involve any DNA edits, it’s likely to be safer than conventional CRISPR therapeutics, which have been known to cause unwanted and potentially harmful changes to the genome.

“Though genetic and cellular therapies are the future of medicine, there are potential safety concerns around permanently changing the genome, which is why we’re trying to come up with other ways to use CRISPR to treat disease,” said Luke Gilbert, PhD, a professor at the UCSF Helen Diller Family Comprehensive Cancer Center and co-senior author of the new paper. 

From Genome to Epigenome Editor

Conventional CRISPR is equipped with two pieces of molecular hardware that make it an effective gene-editing tool. One component is a DNA-snipping enzyme, which gives CRISPR the ability to alter DNA sequences. The other is a homing device that can be programmed to zero in on any DNA sequence of interest, imparting precise control over where edits are made.

To build CRISPRoff, the researchers dispensed with conventional CRISPR’s DNA-snipping enzyme function while retaining the homing device, creating a stripped-down CRISPR capable of targeting any gene, but not editing it. Then they tethered an enzyme to this barebones CRISPR. But rather than splicing DNA, this enzyme acts on the epigenome.

The new tool targets a particular epigenetic feature known as DNA methylation, which is one of many molecular parts of the epigenome. When DNA is methylated, a small chemical tag known as a methyl group is affixed to DNA, which silences nearby genes. Although DNA methylation occurs naturally in all mammalian cells, CRISPRoff offers scientists unprecedented control over this process. Another tool described in the paper, called CRISPRon, removes methylation marks deposited by CRISPRoff, making the process fully reversible.

“Now we have a simple tool that can silence the vast majority of genes,” said Jonathan Weissman, PhD, Whitehead Institute member, co-senior author of the new paper and a former UCSF faculty member. “We can do this for multiple genes at the same time without any DNA damage, and in a way that can be reversed. It’s a great tool for controlling gene expression.”

‘Major Surprise’ Upends A Basic Tenet

Based on previous work by a group in Italy, the researchers were confident that CRISPRoff would be able to silence specific genes, but they suspected that some 30 percent of human genes would be unresponsive to the new tool.

DNA consists of four genetic letters – A, C, G, T – but, in general, only Cs next to Gs can be methylated. To complicate matters, scientists have long believed that methylation could only silence genes at sites in the genome where CG sequences are highly concentrated, regions known as “CpG islands.”

Since nearly a third of human genes lack CpG islands, the researchers assumed methylation wouldn’t switch these genes off. But their CRISPRoff experiments upended this epigenetic dogma.

“What was thought before this work was that the 30 percent of genes that do not have CpG islands were not controlled by DNA methylation,” said Gilbert. “But our work clearly shows that you don’t require a CpG island to turn genes off by methylation. That, to me, was a major surprise.”

Enhancing CRISPRoff’s Therapeutic Potential

Easy-to-use epigenetic editors like CRISPRoff have tremendous therapeutic potential, in large part because, like the genome, the epigenome can be inherited.  

When CRISPRoff silences a gene, not only does the gene remain off in the treated cell, it also stays off in the descendants of the cell as it divides, for as many as 450 generations.

To the researchers’ surprise, this held true even in maturing stem cells. Though the transition from stem cell to differentiated adult cell involves a significant rewiring of the epigenome, the methylation marks deposited by CRISPRoff were faithfully inherited in a significant fraction of cells that made this transition.

These findings suggest that CRISPRoff would only need to be administered once to have lasting therapeutic effects, making it a promising approach for treating rare genetic disorders – including Marfan syndrome, which affects connective tissue, Job’s syndrome, an immune system disorder, and certain forms of cancer – that are caused by the activity of a single damaged copy of a gene.

The researchers noted that although CRISPRoff is exceptionally promising, further work is needed to realize its full therapeutic potential. Time will tell if CRISPRoff and similar technologies are indeed “the future of medicine.”

The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. UCSF Health, which serves as UCSF’s primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area.


Reference: Nuñez, James K. et al., “Genome-wide programmable transcriptional memory by CRISPR-based epigenome editing”, Cell, 2021. DOI: https://doi.org/10.1016/j.cell.2021.03.025


Provided by University of California San Francisco

How A Tangled Protein Kills Brain Cells, Promotes Alzheimer’s (Neuroscience)

Look deep inside the brain of someone with Alzheimer’s disease, most forms of dementia or the concussion-related syndrome known as chronic traumatic encephalopathy (CTE) and you’ll find a common suspected culprit: stringy, hairball-like tangles of a protein called tau.

Such conditions, collectively known as “tauopathies” strike scores of people across the globe, with Alzheimer’s alone affecting six million people in the United States.

But more than a century after German psychiatrist Alois Alzheimer discovered tau tangles, scientists still have much to learn about them.

A University of Colorado Boulder study, published this week in the journal Neuron, shows for the first time that tau aggregates gobble up RNA, or ribonucleic acid, inside cells and interfere with an integral mechanism called splicing, by which cells ultimately produce needed proteins.

“Understanding how tau leads to neurodegeneration is the crux of not just understanding Alzheimer’s disease but also multiple other neurological diseases,” said senior author Roy Parker, a professor of biochemistry and director of the BioFrontiers Institute at CU Boulder. “If we can understand what it does and how it goes bad in disease we can develop new therapies for conditions that now are largely untreatable.”

The study was led by Evan Lester, an M.D./PhD candidate in the Medical Scientist Training Program, which enables students to simultaneously work toward a medical degree from the University of Colorado Anschutz Medical Campus and a PhD from CU Boulder.

For part of his medical training, Lester worked alongside doctors and patients at the CU Alzheimer’s and Cognition Center in Denver., seeing up close how critically more research is needed.

“There is nothing we can do for these patients right now – no disease modifying-treatments for Alzheimer’s or most of the other tauopathies,” Lester said, noting that 70% of neurodegenerative diseases are believed to be at least partially related to tau aggregates.

For the study, the researchers isolated tau aggregates from cell lines and from the brains of mice with an Alzheimer’s-like condition. Then they used genetic sequencing techniques to determine what was inside.

They confirmed for the first time that tau aggregates contain RNA, or ribonucleic acid, a single-stranded molecule key for synthesizing proteins in cells. They identified what kind of RNA it is, specifically snRNA, or small nuclear RNA, and snoRNA, or small nucleolar RNA.

They also discovered that tau interacts with pieces of cellular machinery known as nuclear speckles, sequestering and displacing proteins inside them and disrupting a process called RNA splicing in which the cell weeds out unneeded material to generate new, healthy RNA.

“The tau aggregates appear to be sequestering splicing-related RNA and proteins, disrupting their normal function and impairing the cell’s ability to make proteins,” said Lester.

Notably, scientists examining the brains of Alzheimer’s patients after death have discovered evidence of splicing-related defects in cells.

The paper is the first in a series out of Parker’s lab to explore the mechanism of action by which tau aggregates gum up the works inside brain cells.

Evan Lester © University of Colorado

Already, several companies have clinical trials underway testing drugs that would do away with tau entirely in patients with neurodegenerative diseases. But that could potentially have unintended consequences, said Lester.

“A big problem in the field is that no one really knows what tau does in healthy people and It likely has important functions when not in tangles,” he said.

By better understanding precisely what it does to harm and kill cells, Parker and Lester hope to bring a different approach to the table.

“The idea would be to intervene in the abnormal functions while preserving the normal functions of tau,” Lester said.

While it’s unlikely his current patients will benefit from his discovery, someday his future patients just might.


Reference: Evan Lester, Felicia K. Ooi et al., “Tau aggregates are RNA-protein assemblies that mislocalize multiple nuclear speckle components”, Neuron, 2021. DOI: https://doi.org/10.1016/j.neuron.2021.03.026


Provided by University of Colorado Boulder

COVID-19: Scientists Identify Human Genes That Fight Infection (Medicine)

Research pinpoints interferon stimulating genes that control SARS-CoV-2 replication.

Scientists at Sanford Burnham Prebys have identified a set of human genes that fight SARS-CoV-2 infection, the virus that causes COVID-19. Knowing which genes help control viral infection can greatly assist researchers’ understanding of factors that affect disease severity and also suggest possible therapeutic options. The genes in question are related to interferons, the body’s frontline virus fighters.

The study was published in the journal Molecular Cell.

“We wanted to gain a better understanding of the cellular response to SARS-CoV-2, including what drives a strong or weak response to infection,” says Sumit K. Chanda, Ph.D., professor and director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys and lead author of the study. “We’ve gained new insights into how the virus exploits the human cells it invades, but we are still searching for its Achille’s heel so that we can develop optimal antivirals.”

Soon after the start of the pandemic, clinicians found that a weak interferon response to SARS-CoV-2 infection resulted in some of the more severe cases of COVID-19. This knowledge led Chanda and his collaborators to search for the human genes that are triggered by interferons, known as interferon-stimulated genes (ISGs), which act to limit SARS-CoV-2 infection.

Based on knowledge gleaned from SARS-CoV-1, the virus that caused a deadly, but relatively brief, outbreak of disease from 2002 to 2004, and knowing that it was similar to SARS-CoV-2, the investigators were able to develop laboratory experiments to identify the ISGs that control viral replication in COVID-19.

“We found that 65 ISGs controlled SARS-CoV-2 infection, including some that inhibited the virus’ ability to enter cells, some that suppressed manufacture of the RNA that is the virus’s lifeblood, and a cluster of genes that inhibited assembly of the virus,” says Chanda. “What was also of great interest was the fact that some of the ISGs exhibited control across unrelated viruses, such as seasonal flu, West Nile and HIV, which leads to AIDS”.

“We identified eight ISGs that inhibited both SARS-CoV-1 and CoV-2 replication in the subcellular compartment responsible for protein packaging, suggesting this vulnerable site could be exploited to clear viral infection,” says Laura Martin-Sancho, Ph.D., a senior postdoctoral associate in the Chanda lab and first author of this study. “This is important information, but we still need to learn more about the biology of the virus and investigate if genetic variability within these ISGs correlates with COVID-19 severity.”

As a next step, the researchers will look at the biology of SARS-CoV-2 variants that continue to evolve and threaten vaccine efficacy. Martin-Sancho notes that they have already started gathering variants for laboratory investigation,

“It’s vitally important that we don’t take our foot off the pedal of basic research efforts now that vaccines are helping control the pandemic,” concludes Chanda. “We’ve come so far so fast because of investment in fundamental research at Sanford Burnham Prebys and elsewhere, and our continued efforts will be especially important when, not if, another viral outbreak occurs.”

Additional study authors include Lars Pache, Anshu P. Gounder, Courtney Nguyen, Yuan Pu, Heather M. Curry, Paul D. De Jesus, Ariel Rodriguez-Frandsen and Xin Yin at Sanford Burnham Prebys. Other authors include Mary K. Lewinski, Charlotte A. Stoneham, Aaron L. Oom, and John Guatelli at the University of California at San Diego and the VA San Diego Healthcare System; Mark Becker, Thomas J. Hope and Judd F. Hultquist at the Northwestern University Feinberg School of Medicine; Dexter Pratt, Christopher Churas, Sara B. Rosenthal, Sophie Liu, Fan Zheng, Max W. Chang, Christopher Benner, Trey Ideker and Alan M. O’Neill at the University of California San Diego; Lisa Miorin, Matthew Urbanowski, Megan L. Shaw and Adolfo García-Sastre at the Icahn School of Medicine at Mount Sinai; Stuart Weston and  Matthew B. Frieman at the University of Maryland School of Medicine; and Chunxiang Wu and Yong Xiong at Yale University.

The study’s DOI is https://doi.org/10.1016/j.molcel.2021.04.008.

Research reported in this press release was supported by DoD grants W81XWH-20-1-0270; DHIPC: U19 AI118610; and Fluomics/NOSI: U19 AI135972. It was also supported by generous philanthropic donations from Dinah Ruch and Susan & James Blair, from the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611 (5384)) and anonymous donors. Additional support has been provided by DARPA grant HR0011-19-2-0020 and by CRIP (Center for research on Influenza Pathogenesis), a NIAID-funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C). This work was additionally supported by the following grants to Northwestern University Feinberg School of Medicine: a CTSA supplement to NCATS: UL1 TR002389; a CTSA supplement to NUCATS with the generous support of the Dixon family: UL1 TR001422; and a Cancer Center supplement: P30 CA060553. Additional support was provided by the following grant to JG at UC San Diego: NIH grant R37AI081668. This work was also supported by a generous grant from the James B. Pendleton Charitable Trust.


Provided by SBP Medical Discovery Institute

A Brainwave From Social Networks (Neuroscience)

The statistics used to understand social networks reveal the diversity of functional connections in the brain.

Analyzing brain activity across multiple subjects using sophisticated statistics has produced a model that better captures the diversity and dynamics of brain function. The method, developed by KAUST researchers, could help us better understand human cognition and identify the abnormal brain states that underlie many neurological diseases.

Neuroscientists use a noninvasive technique called functional magnetic resonance imaging (fMRI) to measure the activation of neurons in the brain by detecting localized changes in blood flow and blood oxygen in different brain regions. This has allowed researchers to see networked “communities” of neuronal clusters or nodes that are densely connected and respond to the same stimuli.

“The current state-of-the-art approach is to use a stochastic ‘block model’ to explain brain networks, which gives only a static description of brain function and is not realistic because brain function changes dynamically as the brain responds to new stimuli,” says group leader Hernando Ombao. “So we set out to develop a new unified statistical framework that can characterize the community structure of brain functional networks and help understand how they vary across individuals.”

Current models of the brain’s community network structure suggest that much of brain function is assortative, meaning that brain function is segregated into separate specialized information-processing regions in the brain. Although the integration of information from specialized brain regions is also known to be important in brain function, this has been very difficult to observe.

“The problem has been that brain function is traditionally analyzed by fitting models to individual subjects, which can capture localized or ‘assortative’ community structures,” explains Ombao. “But this is not well suited to picking the nonassortative integration functions, which require information to be mapped and compared among different subjects under different stimuli.”

To solve this problem, the research team — including KAUST student Meini Tang, long-time collaborator Chee-Ming Ting from Monash University in Malaysia and former KAUST postdoctoral fellow Balqis Samdin, who led the study — used a “multilayer modularity maximization method.” Recently proposed for social networks, the method has been adapted by the team to detect common brain community structures that are shared across subjects.

“Our model has revealed a more diverse community organization in addition to the typical assortative structure in brain networks associated with language processing and motor functions,” says Samdin.

“For example, we found a core-like community in the language network that seems to serve an integrative function between periphery communities in the left and right hemispheres during language comprehension,” says Samdin. “Our model is able to capture more complex intercommunity interactions related to a wider functional repertoire of brain function.”

Featured image: KAUST scientists have developed a method that will help to describe brain function and identify many neurological diseases. © SCIEPRO/ SHUTTERSTOCK IMAGES


Reference

  1. Ting, C.-M. Samdin, S.B., Tang, M. & Ombao, H. Detecting dynamic community structure in functional brain networks across individuals: A multilayer approach. IEEE Transactions on Medical Imaging 40 (2020).| article

Provided by Kaust

Study Shows Past COVID-19 Infection Doesn’t Fully Protect Young People Against Reinfection (Medicine)

Although antibodies induced by SARS-CoV-2 infection are largely protective, they do not completely protect against reinfection in young people, as evidenced through a longitudinal, prospective study of more than 3,000 young, healthy members of the US Marines Corps conducted by researchers at the Icahn School of Medicine at Mount Sinai and the Naval Medical Research Center, published April 15 in The Lancet Respiratory Medicine.

“Our findings indicate that reinfection by SARS-CoV-2 in health young adults is common” says Stuart Sealfon, MD, the Sara B. and Seth M. Glickenhaus Professor of Neurology at the Icahn School of Medicine at Mount Sinai and senior author of the paper. “Despite a prior COVID-19 infection, young people can catch the virus again and may still transmit it to others. This is an important point to know and remember as vaccine rollouts continue. Young people should get the vaccine whenever possible, since vaccination is necessary to boost immune responses, prevent reinfection, and reduce transmission.”

The study, conducted between May and November 2020, revealed that around 10 percent (19 out of 189) of participants who were previously infected with SARS-CoV-s (seropositive) became reinfected, compared with new infections in 50 percent (1.079 out of 2,247) of participants who had not been previously infected (seronegative). While seronegative study participants had a five times greater risk of infection than seropositive participants, the study showed that seropositive people are still at risk of reinfection.

The study population consisted of 3,249 predominantly male, 18-20-year-old Marine recruits who, upon arrival at a Marine-supervised two-week quarantine prior to entering basic training, were assessed for baseline SARS-CoV-2 IgG seropositivity (defined as a 1:150 dilution or greater on receptor binding domain and full-length spike protein enzyme-linked immunosorbent [ELISA] assays.) The presence of SARS-CoV-2 was assessed by PCR at initiation, middle and end of quarantine. After appropriate exclusions, including participants with a positive PCR during quarantine, the study team performed three bi-weekly PCR tests in both seronegative and seropositive groups once recruits left quarantine and entered basic training.

Recruits who tested positive for a new second COVID-19 infection during the study were isolated and the study team followed up with additional testing. Levels of neutralising antibodies were also taken from subsequently infected seropositive and selected seropositive participants who were not reinfected during the study period.

Of the 2,346 Marines followed long enough for this analysis of reinfection rate, 189 were seropositive and 2,247 were seronegative at the start of the study. Across both groups of recruits, there were 1,098 (45%) new infections during the study. Among the seropositive participants, 19 (10%) tested positive for a second infection during the study. Of the recruits who were seronegative, 1,079 (48%) became infected during the study.

To understand why these reinfections occurred, the authors studied the reinfected and not infected participants’ antibody responses. They found that, among the seropositive group, participants who became reinfected had lower antibody levels against the SARS-CoV-2 virus than those who did not become reinfected. In addition, in the seropositive group, neutralising antibodies were less common (neutralising antibodies were detected in 45 (83%) of 54 uninfected, and in six (32%) of 19 reinfected participants during the six weeks of observation).

Comparing new infections between seropositive and seronegative participants, the authors found that viral load (the amount of measurable SARS-CoV-2 virus) in reinfected seropositive recruits was on average only 10 times lower than in infected seronegative participants, which could mean that some reinfected individuals could still have a capacity to transmit infection. The authors note that this will need further investigation.

In the study, most new COVID-19 cases were asymptomatic – 84% (16 out of 19 participants) in the seropositive group vs 68% (732 out of 1,079 participants) in the seronegative group – or had mild symptoms and none were hospitalised.

The authors note some limitations to their study, including that it likely underestimates the risk of reinfection in previously infected individuals because it does not account for people with very love antibody levels following their past infection. They strongly suggest that even young people with previous SARS-CoV-2 infection be a target of vaccination since efforts must be made to prevent transmission and prevent infection amongst this group.

This work was supported by the Defense Health Agency through the Naval Medical Research Center and the Defense Advanced Research Projects Agency.

Featured image: Stuart Sealfon, MD, Professor of Neurology, Neuroscience, and Pharmacological Sciences, Icahn School of Medicine at Mount Sinai © Mount Sinai Health System


Reference: Letizia, Andrew G et al., “SARS-CoV-2 seropositivity and subsequent infection risk in healthy young adults: a prospective cohort study”, The Lancet Respiratory Medicine, 2021. DOI: https://doi.org/10.1016/S2213-2600(21)00158-2


Provided by Mount Sinai Hospital

A New Super-Earth Detected Orbiting A Red Dwarf Star (Planetary Science)

In recent years there has been an exhaustive study of red dwarf stars to find exoplanets in orbit around them. These stars have effective surface temperatures between 2400 and 3700 K (over 2000 degrees cooler than the Sun), and masses between 0.08 and 0.45 solar masses. In this context, a team of researchers led by Borja Toledo Padrón, a Severo Ochoa-La Caixa doctoral student at the Instituto de Astrofísica de Canarias (IAC), specializing in the search for planets around this type of stars, has discovered a super-Earth orbiting the star GJ 740, a red dwarf star situated some 36 light years from the Earth.

The planet orbits its star with a period of 2.4 days and its mass is around 3 times the mass of the Earth. Because the star is so close to the Sun, and the planet so close to the star, this new super-Earth could be the object of future researches with very large diameter telescopes towards the end of this decade. The results of the study were recently published in the journal Astronomy & Astrophysics.

“This is the planet with the second shortest orbital period around this type of star. The mass and the period suggest a rocky planet, with a radius of around 1.4 Earth radii, which could be confirmed in future observations with the TESS satellite”, explains Borja Toledo Padrón, the first author of the article. The data also indicate the presence of a second planet with an orbital period of 9 years, and a mass comparable to that of Saturn (close to 100 Earth masses), although its radial velocity signal could be due to the magnetic cycle of the star (similar to that of the Sun), so that more data are needed to confirm that the signal is really due to a planet.

The Kepler mission, recognised at one of the most successful in detecting exoplanets using the transit method (which is the search for small variations in the brightness of a star caused by the transit between it and ourselves of planets orbiting around it), has discovered a total of 156 new planets around cool stars. From its data it has been estimated that this type of stars harbours an average of 2.5 planets with orbital periods of less than 200 days. “The search for new exoplanets around cool stars is driven by the smaller difference between the planet’s mass and the star’s mass compared with stars in warmer spectral classes (which facilitates the detection of the planets’ signals), as well as the large number of this type of stars in our Galaxy”, comments Borja Toledo Padrón.

Cool stars are also an ideal target for the search for planets via the radial velocity method. This method is based on the detection of small variations in the velocity of a star due to the gravitational attraction of a planet in orbit around it, using spectroscopic observations. Since the discovery in 1998 of the first radial velocity signal of an exoplanet around a cool star, until now, a total of 116 exoplanets has been discovered around this class of stars using the radial velocity method. “The main difficulty of this method is related to the intense magnetic activity of this type of stars, which can produce spectroscopic signals very similar to those due to an exoplanet”, says Jonay I. González Hernández, an IAC researcher who is a co-author of this article.

The study is part of the project HADES (HArps-n red Dwarf Exoplanet Survey), in which the IAC is collaborating with the Institut de Ciències de l’Espai (IEEC-CSIC) of Catalonia, and the Italian programme GAPS (Global Architecture of Planetary Systems), whose objective is the detection and characterization of exoplanets round cool stars, in which are being used HARPS-N, on the Telescopio Nazionale Galileo (TNG) at the Roque de los Muchachos Observatory (Garafía, La Palma). This detection was possible due to a six year observing campaign with HARPS-N, complemented with measurements with the CARMENES spectrograph on the 3.5m telescope at the Calar Alto Observatory (Almería) and HARPS, on the 3.6m telescope at the La Silla Observatory (Chile), as well as photometric support from the ASAP and EXORAP surveys. Also participating in this work are IAC researchers Alejandro Suárez Mascareño, and Rafael Rebolo.

Featured image: Artistic impression of the super-Earth in orbit round the red dwarf star GJ-740. Credit: Gabriel Pérez Díaz, SMM (IAC).


Article: B. Toledo-Padrón, A. Suárez Mascareño, J. I. González Hernández, R. Rebolo, et al. “A super-Earth on a close-in orbit around the M1V star GJ 740”. Astronomy & Astrophysics, April 7th, 2021. DOI: 10.1051/0004-6361/202040099


Provided by IAC

New Method to Improve Power Supply Control for High Intensity Heavy-ion Accelerator Facility (Physics)

A project team of High Intensity Heavy-ion Accelerator Facility (HIAF) from the Institute of Modern Physics of the Chinese Academy of Sciences has recently achieved great results in research on power supply control with high power, high precision and fast cycle. The results were published in IEEE Transactions on Industrial Electronics.  

HIAF will provide highest pulse current heavy ion beams in the world. In order to avoid the loss of beam caused by the avalanche effect generated by the space charge and the strong flow dynamic vacuum, the next generation of high intensity accelerators should accelerate ions quickly to high energy, which requires the extremely fast current change rate and high dynamic tracking precision of the magnet power supply. Thus, it is essential to improve the control accuracy of the magnet power supply for HIAF. 

In order to improve the tracking precision of the magnet power supply with a wide dynamic range, the researchers proposed a new analytical model with optimal control method and kinetic inductance fine-tuning method.  

They carried out the experiment on a 200 Hz triangular wave scanning magnet power supply. They then successfully identified the kinetic inductances corresponding to different triangular waves and used these kinetic inductances to calibrate the model. The current error at the end of each switching cycle is controlled from 0.5 A to 0.015 A, which is close to the measurement accuracy limit. Therefore, the method was verified.  

The new method greatly improves the control accuracy and is of great significance for the fast cycle acceleration mode of the next generation of high-current heavy ion accelerators. 

This work was supported by the national key research program “Key Beam Physics and Core Technology Pre-research for a New Generation of High Current Heavy Ion Accelerator”.

Featured image: The experiment results of 200A waveform by scanning power supply. (Image from IEEE Transactions on Industrial Electronics)


References

Analytic Modeling Optimal Control with Kinetic Inductance Fine Turning Method of Pulsed Power Supply for Accelerator Magnet

Analytic Modeling Optimal Control of Pulsed Power Supply for Accelerator Magnet


Provided by Chinese Academy of Sciences

Researchers Obtain New Results on Solar Wind Ion Charge Exchange (Planetary Science)

Researchers at the Institute of Modern Physics (IMP) of the Chinese Academy of Sciences (CAS) and their collaborators have recently obtained new results on the solar wind ion charge exchange. The results were published in The Astrophysical Journal Supplement Series

Charge exchange is one of the important mechanisms of soft X-ray emission in many celestial environments. Soft X-rays caused by charge exchange are important basic data for diagnosing plasma evolution and celestial plasma modeling, which can be used to study the temperature, abundance, and ion species of solar wind ions or stellar wind ions, and help us gain an in-depth understanding of celestial plasma and fusion.  

At present, in charge-exchange soft X-ray emission modeling, researchers usually apply the semi-classical theories to calculate the cross-section data of the state-selective capture resolved by the principal quantum number n and the angular quantum number l. However, the accuracy of the model urgently needs to be verified.  

In this study, the researchers used Reaction Microscopy to systematically measure the state-selective charge exchange of Ne(8,9)+ ions with He and H2 in the solar wind speed range, and obtained the cross-section data of the main quantum number resolution of the electron captured to the projectile ion.

Fig. 2. The normalized emission spectra of Ne7+ following single electron capture between 4 keV/u Ne8+ and He. The solid lines show the reconstructed X-ray spectra from different angular momentum models; The solid square symbol indicates the other group measured X-ray spectra. (Image from The Astrophysical Journal Supplement Series)

They then compared the experimental data with the results calculated by the multi-channel Landau-Zener method and found that the main reaction channels were consistent with theoretical expectations. 

Meanwhile, by applying charge exchange models commonly used in astrophysics, the researchers obtained the angular quantum number resolution cross-sections corresponding to different angular quantum number distribution models, developed relevant calculation programs, and obtained soft X-ray spectra in the charge exchange between Ne8+ and He atoms.

Moreover, they compared reconstructed X-ray spectra with the existing X-ray measurement spectrum and found that there were significant differences in different angular momentum distribution models, which tested the applicability of the angular momentum distribution model in astrophysics. 

This work was supported by the Key R&D Program of the Ministry of Science and Technology, the Strategic Priority Research Program of CAS, and the National Natural Science Foundation of China. 

Featured image: The measured Q-value spectra for the single electron capture in Ne8+-He collisions at different projectile velocities. (Image from The Astrophysical Journal Supplement Series)


Reference:  J. W. Xu et al., “Measurement of n-resolved State-selective Charge Exchange in Ne(8,9)+ Collision with He and H2“, 2021 ApJS 253 13. https://iopscience.iop.org/article/10.3847/1538-4365/abd020


Provided by Chinese Academy of Sciences

Scientists Predict Accurate Structure and Energy of Nanovoids in Metals (Physics)

Researchers from the Institute of Solid State Physics of the Hefei Institutes of Physical Science (HFIPS), together with their Canadian partners from McGill University, developed a new theoretical model recently, which enables accurate predictions of nanovoid structures and energetics in metals.

“This result will provide quantitative understanding and evaluation of irradiation induced damage in key components of nuclear reactors,” said LIU Changsong, who led the team.

In nuclear reactors, metal materials are constantly irradiated by high energy particles such as neutrons. These particles can easily knock metal atoms out of their stable sites, creating vacancies which then agglomerate and form nanosized voids, leading to premature failure to metal materials. Therefore, accurate prediction of nanovoid formation and evolution is of great importance. Yet, many basic properties of nanovoids, such as structure and vacancies binding energy, have never been precisely determined.

To tackle this problem, the research team did a thorough study via computer simulations based on fundamental quantum mechanics. After screening thousands of potential nanovoid structures, they finally found a simple way to predict the stable structure and determine the related energy.

First, they proposed using a special polyhedron call “Wigner-Seitz cell” to accurately describe nanovoid structures. In this way, different nanovoids structures were viewed as different stacking of these Wigner-Seitz cells, and the stable structure of a nanovoid was simply the one with the minimum Wigner-Seitz cell surface area.

Following this thread, they then calculated energies of different nanovoids, and found a perfect linear relationship between their energies and their surface area. Based on this relation, a new theoretical model was formulated, allowing precise predictions on the strength of vacancies binding nanovoids.

“The new model offers predictions that far more accurate than previous models, and shows much better agreement with recent experimental observations,” said Dr. KONG, member of the team from HFIPS, “it provides a powerful tool for evaluating irradiation damages in current nuclear reactors, and paves ways for harvesting fusion energy in the future.”

The work was supported by the National Magnetic Confinement Fusion Energy Research Project and the National Natural Science Foundation of China.

Featured image: Structures of nanovoids predicted by the new research model. Spheres indicate constituting vacancies and are colored by the number of neighboring vacancies (Image by HOU Jie)


Reference: Jie Hou, Yu-Wei You, Xiang-Shan Kong, Jun Song, C.S. Liu, Accurate prediction of vacancy cluster structures and energetics in bcc transition metals, Acta Materialia, Volume 211, 2021, 116860, ISSN 1359-6454, https://doi.org/10.1016/j.actamat.2021.116860. (https://www.sciencedirect.com/science/article/pii/S1359645421002408)


Provided by Chinese Academy of Sciences