Comment

Comment by Dr. Krishna Kumari Challa on April 26, 2023 at 8:50am

For this paper, the researchers modified those particles by adding a chemical group that would react with a tag placed on the second component in the system, which they call the crosslinker. Those crosslinkers, made of either PEG or PEG-PLGA, bind to the targeting particles that have accumulated at a wound site and form clumps that mimic blood clots. 

The idea is that with both of these components circulating inside the bloodstream, if there is a wound site, the targeting component will start accumulating at the wound site and also bind the crosslinker. When both components are at high concentration, you get more cross-linking, and they begin forming that glue and helping the clotting process.

To test the system, the researchers used a mouse model of internal injury. They found that after being injected into the body, the two-component system was highly effective at stopping bleeding, and it worked about twice as well as the targeting particle on its own.

Another important advantage of the clots is that they don't degrade as fast as naturally occurring clots do. When patients lose a lot of blood, they are usually given saline intravenously to keep up their blood pressure, but this saline also dilutes the existing platelets and fibrinogen, leading to weaker clots and faster degradation. However, the artificial clots are not as susceptible to this kind of degradation, the researchers found.

The researchers also found that their nanoparticles did not induce any significant immune reaction in the mice compared to a glucose control. They now plan to test the system in a larger animal model.

Celestine Hong et al, Engineering a Two‐Component Hemostat for the Treatment of Internal Bleeding through Wound‐Targeted Crosslinking, Advanced Healthcare Materials (2023). DOI: 10.1002/adhm.202202756

Part 2

Comment by Dr. Krishna Kumari Challa on April 26, 2023 at 8:47am

Two-component system could offer a new way to halt internal bleeding

Blood loss from traumatic events such as car crashes contributes to more than 2.5 million deaths per year worldwide. This kind of blunt trauma can cause internal bleeding from organs such as the liver, which is difficult to detect and treat. In such cases, it's critical to stop the bleeding as soon as possible, until a patient can be transported to the hospital for further treatment. Finding ways to prevent internal bleeding could have an especially significant impact in the armed services, where delayed treatment for internal hemorrhage is one of the largest causes of preventable death.

Engineers have now designed a two-component system that can be injected into the body and help form blood clots at the sites of internal injury. These materials, which mimic the way that the body naturally forms clots, could offer a way to keep people with severe internal injuries alive until they can reach a hospital.

When internal injuries occur, platelets are attracted to the site and initiate the blood clotting cascade, which eventually forms a sticky plug of platelets and clotting proteins, including fibrinogen. However, if patients are losing a lot of blood, they don't have enough platelets or fibrinogen to form clots. The engineer team wanted to create an artificial system that could help save people's lives by replacing both of those clotting components.

In a mouse model of internal injury, the researchers showed that these components—a nanoparticle and a polymer—performed significantly better than hemostatic nanoparticles that were developed earlier.

What was especially remarkable about these results was the level of recovery from severe injury they saw in the animal studies.

Unlike previously developed hemostatic systems, the new technology mimics the actions of both platelets—the cells that initiate blood clotting—and fibrinogen, a protein that helps forms clots. The idea of using two components allows selective gelation of the hemostatic system as the concentration is enhanced in the wound, mimicking the end effect of the natural clotting cascade.

What researchers in this area have been doing in the past is trying to either recapture the therapeutic effects of platelets or recapture the function of fibrinogen. This new one tried to capture the way they interact with each other.

To achieve that, the researchers created a system with two types of materials: a nanoparticle that recruits platelets and a polymer that mimics fibrinogen.

Part 1

Comment by Dr. Krishna Kumari Challa on April 25, 2023 at 1:36pm

The network "remembered" previous signals for at least seven steps. Curiously, seven is often regarded as the average number of items humans can keep in working memory at one time.

When researchers used reinforcement learning, they saw dramatic improvements in the network's memory performance.

In tehir nanowire networks, they found the formation of synaptic pathways depends on how those synapses have been activated in the past. This is also the case for synapses in the brain, where neuroscientists call it "metaplasticity".

Synthetic intelligence

Human intelligence is still likely a long way from being replicated.

Nonetheless, this research on neuromorphic nanowire networks shows it is possible to implement features essential for intelligence – such as learning and memory – in non-biological, physical hardware.

Nanowire networks are different from the artificial neural networks used in AI. Still, they may lead to so-called "synthetic intelligence".

Perhaps a neuromorphic nanowire network could one day learn to have conversations that are more human-like than ChatGPT, and remember them.

https://www.science.org/doi/10.1126/sciadv.adg3289

https://theconversation.com/networks-of-silver-nanowires-seem-to-le...

Part 3

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Comment by Dr. Krishna Kumari Challa on April 25, 2023 at 1:34pm

New work uses this nanowire system to explore the question of human-like intelligence. Central to the investigation are two features indicative of high-order cognitive function: learning and memory.

This study demonstrates we can selectively strengthen (and weaken) synaptic pathways in nanowire networks. This is similar to "supervised learning" in the brain.

In this process, the output of synapses is compared to a desired result. Then the synapses are strengthened (if their output is close to the desired result) or pruned (if their output is not close to the desired result).

Researchers expanded on this result by showing they could increase the amount of strengthening by "rewarding" or "punishing" the network. This process is inspired by "reinforcement learning" in the brain.

Part 2

Comment by Dr. Krishna Kumari Challa on April 25, 2023 at 1:31pm

Networks of Silver Nanowires Appear to Learn And Remember Like The Human Brain

New research explores non-biological systems that are more like human brains. In a new study published in Science Advances, researchers found self-organizing networks of tiny silver wires appear to learn and remember in much the same way as the thinking hardware in our heads.

This is a part of a field of research called neuromorphics, which aims to replicate the structure and functionality of biological neurons and synapses in non-biological systems.

The work focuses on a system that uses a network of "nanowires" to mimic the neurons and synapses in the brain.

These nanowires are tiny wires about one thousandth the width of a human hair. They are made of a highly conductive metal, such as silver, typically coated in an insulating material like plastic.

Nanowires self-assemble to form a network structure similar to a biological neural network. Like neurons, which have an insulating membrane, each metal nanowire is coated with a thin insulating layer.

When we stimulate nanowires with electrical signals, ions migrate across the insulating layer and into a neighboring nanowire (much like neurotransmitters across synapses). As a result, we observe synapse-like electrical signaling in nanowire networks.

Part 1

Comment by Dr. Krishna Kumari Challa on April 25, 2023 at 1:17pm

HOW Does Carbon Dioxide Trap Heat?

Comment by Dr. Krishna Kumari Challa on April 25, 2023 at 11:36am

Why do transversions not expand and accumulate with age? And why do transversion and transition mutations behave differently?

Despite using a duplex sequencing approach, it is possible that the transversions they detect might have been potentially generated in vitro from real in vivo DNA damage.

The researchers built a model to understand this: there are two broad classes of mtDNA molecules (Figure 1): a ‘stem subpopulation’ of actively replicating mtDNAs which are responsible for renewing the mtDNA pool, and a ‘worker subpopulation’ which are located in actively respiring mitochondria. ‘Stem’ mtDNAs reside in mitochondria that respire less and are therefore protected from reactive oxygen species. Consequently, transversions primarily occur on ‘worker’ mtDNA molecules which rarely replicate, which prevents these mutations from being able to clonally expand and accumulate with age. 

https://elifesciences.org/articles/87194?utm_source=content_alert&a...

Part 3

Comment by Dr. Krishna Kumari Challa on April 25, 2023 at 11:33am

The team studied eight different tissues – ranging from the kidney, to the brain and the heart – in young and old mice which were 4.5 and 26 months old. This resulted in an unprecedently large dataset consisting of around 80,000 somatic mtDNA mutations, showing that the rate of accumulation and the composition of mutations vary between different tissues. The highest accumulation rate was in the kidney, where mutations reached the level of one in five mtDNA molecules.

In agreement with previous studies, Sanchez-Contreras et al. observed a high proportion of transition mutations, in which purine (adenine and guanine) and pyrimidine (thymine and cytosine) nucleotide bases are only exchanged for other purines or pyrimidines, respectively. An unusually high proportion of transversion mutations – where a purine changes to a pyrimidine, or vice versa – were also detected. However, unlike the transition mutations, these transversions did not clonally expand and did not accumulate with age in any of the tissues studied. Because new transversions are constantly being generated (mostly through damage caused by reactive oxygen species), lack of accumulation with age implies that these mutations are excluded from being propogated in somatic cells.

Intriguingly, another study also found a high proportion of transversion mutations in the mtDNA of mouse egg cells , which was surprising given that the proportion of inherited mutations that are transversions is usually very low. This suggests that transversion mutations are excluded from being propagated in germ cells as well.

Part 2

Comment by Dr. Krishna Kumari Challa on April 25, 2023 at 11:31am

Mitochondrial DNA: Are some mutations more equal than others?

A large-scale study of mutations in mitochondrial DNA has revealed a subset that do not accumulate with age.

Every cell in our body contains hundreds to hundreds of thousands of mitochondria. These organelles are involved in a myriad of functions, most notably respiration (combining oxygen with food to generate energy) and controlled cell death. Mitochondria are the descendants of prokaryotic cells (similar to bacteria) that became part of primordial eukaryotic cells via a process called endosymbiosis: this means that they have their own double-stranded circular DNA (mtDNA), which is similar to the DNA found in bacteria.

The mitochondria within a cell are constantly proliferating and replicating their mtDNA to compensate for cell growth and division, as well as to offset the removal of damaged mitochondria. Because of their respiration activity, mitochondria produce large amounts of reactive molecules, most notably reactive oxygen species, which damage the mtDNA. If a damaged nucleotide in mtDNA remains unrepaired, this may lead to an incorrect nucleotide being inserted during replication, which is then copied onto the new strand during the next round of replication. This results in permanent double-stranded mutations that accumulate with age as mtDNA molecules are continuously damaged and replicated over the course of a person’s lifespan. Consequently, the mutation rates in mtDNA are about a thousand times higher than in nuclear DNA.

 In addition to accumulating with age, mutant mtDNAs are also subject to ‘clonal expansion’ within a cell . This is mostly a stochastic process in which a random mutated mtDNA molecule multiplies and replaces its peers, resulting in the same mutation appearing in most mtDNA molecules in the cell. Clonal expansions are fundamentally important. If enough mitochondria in a cell contain the same mutation, then this mutation will have a phenotypic effect on the entire cell. Moreover, in the female germline, clonal expansions allow mtDNA mutations to take over the egg cell lineage, potentially resulting in the next generation inheriting the mutation.

Most approaches used to analyze mutations in mtDNA suffer a major drawback as they typically involve in vitro DNA replication, such as PCR. This means that damaged nucleotides – which, in vivo, would have likely been repaired prior to replication or excluded from replication – end up getting erroneously copied and eventually converted into artificial double-stranded mutations that are indistinguishable from genuine ones. Now, in eLife, scientists report how they used a technique called duplex sequencing, which excludes these artificial mutations, to study how mtDNA mutations accumulate with age in mice.

Part 1 

Comment by Dr. Krishna Kumari Challa on April 25, 2023 at 10:16am

Study examines the potential of edible cutlery

Plastic waste is an increasing problem the world over, with food packaging and single-use items such as plastic knives and forks representing a significant component of the waste stream. There have been efforts to replace disposable cutlery with implements crafted from wood or bamboo, but work in the International Journal of Mathematical Modelling and Numerical Optimisation has looked at a radical alternative—edible cutlery.

Researchers think that creating edible cutlery from millet is one possibility. However, as they explain the production of such items from this unusual source material requires a lengthy step-by-step process.

the researchers recognized that such step-by-step processes lend themselves to being defined by a scientific queuing model that can be solved using supplementary variable queuing technology. They have thus developed a conceptual approach to queue theory that might be implemented in the creation of edible cutley and is displayed through a numerical and complex visual analysis.

Millet is a nutritious, gluten-free, and easily cultivable crop that is widely grown in many parts of the world, particularly in Africa and Asia. It is a general term for are small-grained, annual, warm-weather cereals in the grass family of crops. These plants are fast-growing and highly drought-tolerant. They could therefore be useful as a sustainable and accessible source material in the developing world.

If such edible cutlery were to become a sustainable alternative to plastic or wooden products, then there is a cradle-to-grave assessment to be made of energy and resource costs as well as a need for health and safety considerations. The team has surveyed potential users and found the concept largely acceptable. All that said, chewing and swallowing a millet knife and fork at the end of one's meal may not be to everyone's taste.

Vignesh Perumal et al, An Investigation on MX/G/1 Queuing Model of Interrupted Services in the Manufacturing of Edible Cutlery Process, International Journal of Mathematical Modelling and Numerical Optimisation (2022). DOI: 10.1504/IJMMNO.2023.10050913

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