As COVID-19 wreaks havoc across the globe, one characteristic of the infection has not gone unnoticed. The disease is heterogeneous in nature with symptoms and severity of the condition spanning a wide range. The medical community now believes this is attributed to variations in the human hosts’ biology and has little to do with the virus per se. Shedding some light on this conundrum is Associate Professor SUMI Tomonari from Okayama University, Research Institute for Interdisciplinary Science (RIIS), and Associate Professor Kouji Harada from the Toyohashi University of Technology, the Center for IT-based Education (CITE). The duo recently reported their findings on imbalances in the host immune system that facilitate persistent or severe forms of the disease in some patients.

The researchers commenced their study by supercomputer simulations with models based on a host’s immune system and its natural response to SARS-CoV-2 exposure. Mathematical equations for the dynamics of cells infected by SARS-CoV-2 were plugged in to predict their behavior. Now, the immune system has messenger cells known as dendritic cells (DCs). These cells report information (in the form of antigens) about the invaders to the warriors, or T cells, of the immune system. The model showed that at the onset of infection, DCs from infected tissues were activated, and then antibodies to neutralize SARS-CoV-2 gradually started building.

To investigate long-term COVID-19, the behavior of DCs 7 months after infection was evaluated by the supercomputer simulation. the baseline model simulation revealed that DCs drastically decreased during the peak of infection and slowly built up again. However, they tended to remain below pre-infection levels. These observations were similar to those seen in clinical patient samples. It seemed like low DC levels were associated with tenacious long-term infection.

The subsequent step was to understand if DC function contributed to disease severity. It was found that a deficiency of the antigen-reporting function of DCs and lowered levels of chemicals known as interferons released by them were related to severe symptoms. A decrease in both these functions resulted in higher amounts of virus in the blood (viral load). What’s more, the researchers also found two factors that affected the virus’s ability to replicate in the host, namely, antigen-reporting DCs and the presence of antibodies against the virus. Anomalies in these functions could hamper viral clearance, enabling it to stay in the body longer than expected, whereas a high ability of these immune functions suppresses viral replication and yields prompt viral clearance.

Components of immune signaling that directly affect the outcome of COVID-19 infection were revealed in this study. “ Our mathematical model predicted the persistent DC reduction and showed that certain patients with severe and even mild symptoms could not effectively eliminate the virus and could potentially develop long COVID,” concludes the duo. A better understanding of these immune responses could help shape the prognosis of and therapeutic interventions against COVID-19.

A recent document acquired by Atlas VPN reveals that a federal watchdog chastised the US agency in charge of maintaining and modernizing the country's nuclear arsenal for lax cybersecurity procedures that jeopardize both IT and operational technology networks.

The United States Government Accountability Office (GAO) issued an 81-page report on September 24th, 2022, outlining the National Nuclear Security Administration's (NNSA) cybersecurity failings.

The NNSA is a separate agency within the Department of Energy (DOE) tasked with managing U.S. nuclear weapons at eight laboratory and production sites across the country.

According to the GAO, the NNSA and its contractors have not completely adopted six legally mandated cybersecurity standards, including basic risk management techniques and others.

NNSA failed to fully implement two out of six mandatory cybersecurity measures, including the development and maintenance of an organization-wide continuous monitoring strategy as well as the documentation of cybersecurity policies and plans.

NNSA contractors responsible for the management and operational activities have to adhere to the same strict standards, but they failed on multiple fronts as well. Most notably, they were unable to implement the same organization-wide monitoring strategy that NNSA struggled with.

Out of seven M&O (management and operating) contractors, four implemented the monitoring policy substantially, one partially, and two barely improved the cybersecurity measure.

Unlike NNSA, all contractors were able to document and maintain cybersecurity policies and plans according to the outlined standards.

However, four contractors were assigned most, but not all, cybersecurity management roles and responsibilities. One M&O partner assigned only about half of the roles and duties. 

The last area where some M&O contractors struggled was the establishment and maintenance of a cybersecurity strategy for the organization. Two partners implemented the measure substantially, while one only partially, which is around 50%.

Why GAO did this study

NNSA and its site contractors incorporate information systems into nuclear weapons, automate production equipment, and develop warheads using supercomputer modeling.

To read the full article, head over to:

https://atlasvpn.com/blog/report-us-nuclear-security-body-failed-to-implement-cybersecurity-measures

Brazilian researchers have created an innovative and agile computational tool to link and analyze different health databases with millions of patient records. Called Tucuxi-BLAST, the platform encodes identification records in a database, such as patient name, mother’s name, and place of birth, using letters that represent the nucleotides in a DNA sequence (A, T, C, or G). This “conversion” of individuals to DNA enables accurate record linkage across databases despite typographical errors and other inconsistencies. The tool can be used in research, epidemiological analysis, and public policy formulation.

For example, people who have been vaccinated by the SUS, Brazil’s national health service, can be cross-referenced to other datasets to find vaccinated patients with a specific disease. Even if a vaccination record contains errors or uncompleted fields, Tucuxi-BLAST is able to link it to the same patient in another database because it treats inconsistencies as if they were DNA mutations. Genomics tools routinely need to compare fragments in order to decide whether they are more similar than different and whether to link the base pairs in question. If each individual corresponds to a sequence of letters, data from different repositories can be cross-referenced and linked by the tool.

“The SUS is a valuable source of information for medical and epidemiological research because it stores health data for millions of patients. However, records relating to diseases and other types of data are stored in different databases that don’t always talk to each other. The method we’ve developed is able to effect record linkage accurately and at great speed,” Helder Nakaya, corresponding author of an article on the study published in the journal PeerJ, told Agência FAPESP. 

Nakaya is an immunologist affiliated with the University of São Paulo’s School of Pharmaceutical Sciences (FCF-USP), the Albert Einstein Jewish Hospital (HIAE), the Scientific Platform Pasteur-USP, and Todos pela Saúde institute. He also belongs to the Center for Research on Inflammatory Diseases (CRID), one of the Research, Innovation, and Dissemination Centers (RIDCs) funded by FAPESP. 

The study was also supported by FAPESP via two other projects (18/14933-2 and 19/27139-5).

Using the tool in practice

Even before the article was published, Tucuxi-BLAST began to be deployed in practice. It was used, for example, to cross-reference four years of data from the Ministry of Health’s Malaria Surveillance System with clinical data from the Dr. Heitor Vieira Dourado Tropical Medicine Foundation (in Manaus, Amazonas state), a branch of Oswaldo Cruz Foundation (Fiocruz), another arm of the ministry. 

The result showed that being HIV positive is a risk for Plasmodium vivax malaria patients, representing an additional challenge for public policy. Given the lack of single identifiers, Tucuxi-BLAST used the patient's name, mother’s name, and date of birth. The findings were described in an article published in May 2022 in Scientific Reports. 

The study was led by researchers at Amazonas State University (UEA). Nakaya and FCF-USP’s José Deney Alves Araújo, the first author of the PeerJ article, also participated. Araújo named the tool Tucuxi in honor of Sotalia fluviatilis, a freshwater dolphin that inhabits the rivers of the Amazon Basin.

BLAST (Basic Local Alignment Search Tool) refers to a suite of programs used in bioinformatics to generate alignments between nucleotides or protein sequences across large databases.

How it works

To develop the new method, the scientists translated patient data into DNA sequences using a codon wheel that changed dynamically over different runs without impairing the efficiency of the process. Codons are sequences of three nucleotides that code for a specific amino acid in a DNA or RNA molecule. Codon wheels are used to identify the amino acids encoded by any DNA or RNA codon.

This encoding scheme enabled real-time data encryption, thus providing an additional layer of privacy during the linking process. “It used DNA to encrypt the information and guarantee privacy,” Nakaya said.

The DNA-encoded identification fields were compared using BLAST, and machine learning algorithms automatically classified the final results. 

As in comparative genomics, where genes from different genomes are compared to determine common and unique sequences, Tucuxi-BLAST also permits the simultaneous integration of data from multiple administrative databases without the need for complex data pre-processing. 

In the study, the group used Tucuxi-BLAST to test and compare a simulated database containing 300 million records, as well as four large administrative databases containing data for real cases of patients infected with different pathogens.

The conclusion was that Tucuxi-BLAST successfully processed record linkages for the largest dataset (200,000 records), despite misspellings and other errors and omissions, in a fifth of the time: 23 hours, compared with 127 hours (five days and seven hours) for the state-of-the-art method.

The researchers set up a website where users can translate words, phrases, and names into DNA.

Several countries, such as the UK, Canada, and Australia, have invested in successful initiatives to integrate databases and develop novel data analysis strategies, Nakaya noted.

A Brazilian example is the Center for Health Data and Knowledge Integration (CIDACS/Fiocruz), which has integrated administrative and health databases to assemble records for 114 million people.

Subtropical gyres are enormous rotating ocean currents that generate sustained circulations in the Earth’s subtropical regions just to the north and south of the equator. These gyres are slow-moving whirlpools that circulate within massive basins around the world, gathering up nutrients, organisms, and sometimes trash, as the currents rotate from coast to coast.

For years, oceanographers have puzzled over conflicting observations within subtropical gyres. At the surface, these massive currents appear to host healthy populations of phytoplankton — microbes that feed the rest of the ocean food chain and are responsible for sucking up a significant portion of the atmosphere’s carbon dioxide.

But judging from what scientists know about the dynamics of gyres, they estimated the currents themselves wouldn’t be able to maintain enough nutrients to sustain the phytoplankton they were seeing. How, then, were the microbes able to thrive?

Now, MIT investigators have found that phytoplankton may receive deliveries of nutrients from outside the gyres and that the delivery vehicle is in the form of eddies — much smaller currents that swirl at the edges of a gyre. These eddies pull nutrients in from high-nutrient equatorial regions and push them into the center of a gyre, where the nutrients are then taken up by other currents and pumped to the surface to feed phytoplankton. 

Ocean eddies, the team found, appear to be an important source of nutrients in subtropical gyres. Their replenishing effect, which the researchers call a “nutrient relay,” helps maintain populations of phytoplankton, which play a central role in the ocean’s ability to sequester carbon from the atmosphere. While climate models tend to project a decline in the ocean’s ability to sequester carbon over the coming decades, this “nutrient relay” could help sustain carbon storage over the subtropical oceans.

“There’s a lot of uncertainty about how the carbon cycle of the ocean will evolve as the climate continues to change, ” says Mukund Gupta, a postdoc at Caltech who led the study as a graduate student at MIT. “As our paper shows, getting the carbon distribution right is not straightforward, and depends on understanding the role of eddies and other fine-scale motions in the ocean.”

The study’s co-writers are Jonathan Lauderdale, Oliver Jahn, Christopher Hill, Stephanie Dutkiewicz, and Michael Follows at MIT, and Richard Williams at the University of Liverpool.

A snowy puzzle

A cross-section of an ocean gyre resembles a stack of nesting bowls that is stratified by density: Warmer, lighter layers lie at the surface, while colder, denser waters make up deeper layers. Phytoplankton lives within the ocean’s top sunlit layers, where the microbes require sunlight, warm temperatures, and nutrients to grow.

When phytoplankton dies, they sink through the ocean’s layers as “marine snow.” Some of this snow releases nutrients back into the current, where they are pumped back up to feed new microbes. The rest of the snow sinks out of the gyre, down to the deepest layers of the ocean. The deeper the snow sinks, the more difficult it is for it to be pumped back to the surface. The snow is then trapped, or sequestered, along with any unreleased carbon and nutrients.

Oceanographers thought that the main source of nutrients in subtropical gyres came from recirculating marine snow. But as a portion of this snow inevitably sinks to the bottom, there must be another source of nutrients to explain the healthy populations of phytoplankton at the surface. Exactly what that source is “has left the oceanography community a little puzzled for some time,” Gupta says.

Swirls at the edge

In their new study, the team sought to simulate a subtropical gyre to see what other dynamics may be at work. They focused on the North Pacific gyre, one of the Earth’s five major gyres, which circulates over most of the North Pacific Ocean and spans more than 20 million square kilometers. 

The team started with the MITgcm, a general circulation model that simulates the physical circulation patterns in the atmosphere and oceans. To reproduce the North Pacific gyre’s dynamics as realistically as possible, the team used a MITgcm algorithm, previously developed at NASA and MIT, which tunes the model to match actual observations of the ocean, such as ocean currents recorded by satellites, and temperature and salinity measurements taken by ships and drifters.  

“We use a simulation of the physical ocean that is as realistic as we can get, given the machinery of the model and the available observations,” Lauderdale says.

The realistic model captured finer details, at a resolution of fewer than 20 kilometers per pixel, compared to other models that have a more limited resolution. The team combined the simulation of the ocean’s physical behavior with the Darwin model — a simulation of microbe communities such as phytoplankton, and how they grow and evolve with ocean conditions.

The team ran the combined simulation of the North Pacific gyre for over a decade, and created animations to visualize the pattern of currents and the nutrients they carried, in and around the gyre. What emerged were small eddies that ran along the edges of the enormous gyre and appeared to be rich in nutrients.

“We were picking up on little eddy motions, basically like weather systems in the ocean,” Lauderdale says. “These eddies were carrying packets of high-nutrient waters, from the equator, north into the center of the gyre and downwards along the sides of the bowls. We wondered if these eddy transfers made an important delivery mechanism.”

Surprisingly, the nutrients first move deeper, away from the sunlight, before being returned upwards where the phytoplankton live. The team found that ocean eddies could supply up to 50 percent of the nutrients in subtropical gyres.

“That is very significant,” Gupta says. “The vertical process that recycles nutrients from marine snow is only half the story. The other half is the replenishing effect of these eddies. As subtropical gyres contribute a significant part of the world’s oceans, we think this nutrient relay is of global importance.”