US Deploys Anti-Drone Lasers In Middle East To Field Test Prototypes

 Via The Libertarian Institute,

The Department of Defense has deployed four laser systems designed to intercept drones and rockets in the Middle East. The Pentagon has been developing a laser-style interceptor to reduce the cost of shooting down UAVs and rockets. 

Army Vice Chief of Staff Gen. James Mingus announced the new deployment of Directed Energy Maneuver Short Range Air Defense (DE M-SHORAD) prototypes to the Middle East. The Army developed the weapons system in coordination with RTX, formerly Raytheon. The former employer of Defense Secretary Lloyd Austin, RTX, has received over $100 million to develop the platform. 

DE M-SHORAD, according to RTX, is a 50-kilowatt vehicle-mounted laser designed to intercept drones, missiles, and rockets at short range.

RTX and the Pentagon believe laser systems will be a cheaper alternative for downing cheap drones and rockets. The four interceptors deployed to the Middle East are mounted on Stryker armored vehicles.

The 2024 Pentagon funding bill authorized nearly $700 million in spending on the development and procurement of DE M-SHORAD systems. 

American soldiers occupying Iraq and Syria have come under rocket and drone attack over 150 times in the past five months. The strikes come in response to Israel’s onslaught in Gaza, with Shia militia groups taking responsibility for some of the attacks.

After a drone killed three American soldiers in Jordan, President Joe Biden ordered a massive round of airstrikes in Iraq and Syria. Dozens were killed, including some civilians. 

The Pentagon believes the Middle East is a good environment to test DE M-SHORAD as it will present unique challenges.

"Our high-energy lasers are so susceptible to weather. That’s why I think this is going to be a great laboratory because anytime there’s a dust storm, anytime there’s that kind of thing, it starts to alter the physics of the light particles that actually shoot that beam," Mingus explained. 

https://www.zerohedge.com/technology/us-deploys-anti-drone-lasers-middle-east-field-test-prototypes

Human Artificial Reality Is A Mortal Threat

 by Richard Porter via RealClear Wire,

The artificial reality Google’s woke programmers infused into their new AI chatbox, and the machine’s obtuse insistence on being woke even when obviously wrong, reflects a phenomenon in the First World Left that’s real – and that’s become dangerously pervasive.

On October 7, 2023, 3,000 Palestinian terrorists under the direction of Hamas entered Israel and committed heinous, inhumane atrocities as part of its surprise attack. This is the rare characterization of a public event that is a product of observation not opinion.

Nonetheless, a substantial percentage of Democrats (25% in a recent poll) expressed support for Hamas. Why? Surely not more than a handful of Democrats actually share Hamas’ worldview, which includes hatred of Jews and intolerance for abortion, women’s rights, and the LGBTQ movement.

So, roughly one in four Democrat voters simultaneously support Hamas while holding beliefs that are anathema to Hamas. While it is tempting to dismiss these people as idiots (or “low information” voters to use a term of art), that is observably not so: protestors at the most intellectually selective universities were holding signs supporting, for example, transgender rights and Hamas.

The post-10/7 transgender and Hamas supporters are useful in elucidating the phenomenon of woke Artificial Reality (AR). I do not mean the Metaverse or spatial computing or augmented reality, all of which are machine-based versions of manipulating environments or object.

Instead, Artificial Reality is when political or cultural beliefs distort sensory processing, causing the perception of reality to disconnect from observable reality.

Human beings naturally process sensory stimuli into a framework of memory, imagination and other ideas to create conceptual models that help us understand and interact with external, physical reality. Our sensory input processing empowers us to react to environmental challenges, and come up with ways to change the environment, in order to survive and thrive. Over thousands of years, imaginative problem-solvers (hunters, farmers, and eventually engineers) made the world safe and more hospitable to humans.

Artificial Reality arises when observation is supplanted, not supplemented, by ideas and our imaginations. This occurs when our pre-conceived notions of a concept, instead of the usefulness of the concept in surviving in or improving external reality, drives a person’s perceptions of reality.

Artificial Reality thrives among those who are more conceptual and less pragmatic and in areas or among groups where being right about external reality does not matter (when survival is not at risk) and where there are social benefits to accepting and espousing beliefs that are not supported by observations of external reality.

A post-October 7th pro-Hamas, pro-transgender supporter screens the external stimuli of that heinous day through the lens of intersectionality: the belief that identifiable groups systemically oppress other groups; that oppressors are inherently evil; and that oppressed have a common interest in overturning the existing dynamic.

In their Artificial Reality, the intersectional ideologue sorts all humans into dualities of good vs evil, oppressed vs oppressors, poor vs rich, Arabs vs Jews, gay vs straight, black and brown vs white and so forth, and believe that overturning the present power dynamic, even via murder and mayhem, is a social virtue.

After Oct. 7, people who are not wedded to intersectionality would either drop the theory or drop Hamas from the framework. For example, many Israelis share common beliefs with progressive American Democrats, but after 10/7 they didn’t pigeon-hole the facts into a narrative that excused Hamas atrocities: They re-examined their previous views.

Only those who live far away from Hamas are sanguine about the militants’ approach to human rights. Neighboring Egypt won’t accept refugees from Gaza, Hamas’s home base. Neither will any other nation in the region, including those who aim to destroying Israel. Why would that be?

The First World is so rich, generous and remote from external threats that we increasingly indulge impractical things, like high heels, pants without belts, the metaverse -- and AR -- because practicality does not matter. In some ways impracticality (manicured nails, gender ideology) conveys status: the rich and safe are more likely to indulge the fanciful.

Those living in their AR bubbles also support other policies that are observably dangerous, such as defunding police and releasing repeat offenders from jail without bail.

Human Artificial Reality is a mortal danger when it flourishes, leading people or governments to pursue policies at odds with external reality. The safer and richer we are, the lower the personal cost of AR, which increases the risk of AR spreading socially and impacting policies and leaders. Artificial Reality is not just Google’s problem; it is a first world problem with real world consequences.

When leaders act on AR, when they contextualize murder and mayhem, or act on the belief that the inhumane are just and evildoers are good, then death, destruction and misery will become all too real for us yet again.

Richard Porter is a lawyer in Chicago and National Committeeman to the RNC from Illinois.

https://www.zerohedge.com/technology/human-artificial-reality-mortal-threat

Israeli Jet Intercepts Inbound Drone From Syria In Escalation

 While Israel has over the past months and even years regularly attacked Syria - especially in Damascus and its environs - with airstrikes, it remains extremely rare for projectiles to be fired the other way, from Syria onto Israel.

But that very rare event appears to have taken place Tuesday, as an Israeli Air Force fighter jet was scrambled and shot down a "suspicious aerial target" that flew into Israeli airspace from Syria. 

Israeli media citing the IDF believes that it was a drone, however, few details were given and the military says it is unclear precisely who was behind the attack.

Israel has said that both Hezbollah and Iranian officers and troops have long been present in Syria, and the Israel Defense Forces (IDF) strikes their positions at least on a weekly basis at this point. Syria did near the start of the Gaza war, within days after the Hamas Oct.7 attack, fire rockets into the occupied Golan Heights territory, but that was essentially a one-off.

Fears persist that the ongoing Hezbollah-Israel fighting along the southern Lebanese border could at any moment spill over into a bigger regional conflict that would certainly have immediate impact on Syria and the Golan.

As for fighting in Lebanon, Israeli media has tallied, "Hezbollah has named 232 members who have been killed by Israel during the ongoing skirmishes, mostly in Lebanon but some also in Syria. In Lebanon, another 37 operatives from other terror groups, a Lebanese soldier, and at least 30 civilians, three of whom were journalists, have been killed."

On Sunday, Arab media sources did claim a new development which suggests escalation. Hezbollah said it struck Israeli ground forces on Lebanon's own territory, which suggests an 'invasion' or border breach of some kind was attempted: 

Hezbollah claimed to thwart two separate Israeli attempts to enter Lebanese territory late Sunday evening, saying it struck Israeli soldiers "directly" with rockets and artillery shells.

According to a statement by the group, two groups of Israeli forces attempted to cross into Lebanese territory from the town of Ramya along the central part of the Lebanese border and the town of Rmeish in the west.

The two infiltration attempts occurred within half an hour of one another.

If accurate, this would mark the first instance of Israeli troops attempting to enter Lebanon since that start of the conflict which began in the aftermath of Oct.7.

Fresh Hezbollah missile attacks have left towns across northern Lebanon without power...

Any potential scenario where Israel were to move ground troops into southern Lebanon would likely spark a bigger war with Hezbollah, which could engulf all of Lebanon. Already Israel has launched airstrikes deep into Lebanese territory, including all the way up to the Bekaa Valley. 

https://www.zerohedge.com/geopolitical/israeli-jet-intercepts-apparent-inbound-drone-syria-escalation

Stress hormones can lead to enhanced cognitive abilities in children

 Researchers at the Max Planck Institute of Psychiatry have investigated how stress hormones affect the early development of brain cells in the cerebral cortex of the fetus. The cortex is the crucial area of the brain for thinking. The team was able to demonstrate causal links between stress hormones and altered brain structure, which relate to higher levels of educational attainment later in life.

The hormone group of glucocorticoids is crucial for the regulation of our metabolism and immune response, but also for the development of organs such as the brain and lungs before birth. The hormones are released in response to stress and can travel from the mother to the fetus. One of the best-known stress hormones is cortisol. Synthetic forms are prescribed, for example, in pregnancies at high risk for preterm delivery in order to help the maturation of the fetal lungs.

"We found that glucocorticoids, when present early in gestation in the first or early second trimester, increase the number of a particular type of brain cells that are formed very early in development (called basal progenitor cells)", reports Anthi C. Krontira, who led the study published in Neuron. "These are cells that are important for the growth of the cerebral cortex."

The scientists used so-called brain organoids for their investigations. These are models of the developing brain that are derived from human skin or blood cells and mature in a petri dish. They reproduce early developmental stages of the maturing brain and thus provide insights into the first steps in the development of a human brain.

Glucocorticoids act via a protein called ZBTB16 to alter the development of the cortex, and this results in the production of more neurons. The researchers looked in detail at a genetic variant that leads to an increase in ZBTB16 levels in response to glucocorticoids. They found causal relationships with altered brain structure and higher educational attainment later in life. This connection was further supported by data from a study that followed pregnant women and their offspring.

Many studies in the past have shown that glucocorticoids when present late in gestation, in the third trimester, cause adverse effects for the offspring including loss of neuronal connections and increased risk for psychiatric disorders later in life. "Our study shows that the same hormones when present early in gestation can have an opposite effect," reports Krontira.

This is related to neurogenesis, the process of producing neurons from progenitor cells, which is active in early but not in late gestation. "We found that glucocorticoids early in gestation increase progenitor cells and neurons and this relates to beneficial phenotypes for the offspring such as increased cognitive abilities," explains Krontira. The same results wouldn't be possible for glucocorticoids late in gestation as then the production of neurons from progenitor cells does not happen anymore.

"Our research uncovers a pathway at the cellular and molecular level that explains how glucocorticoids influence the development of the human cortex, with potential consequences for cognitive abilities and brain structure later in life," says the Institute's director Elisabeth Binder.

Knowledge of these earliest developmental processes is significant as it could enable therapeutic approaches at such an early stage of human development via the mother.

More information: Anthi C. Krontira et al, Human cortical neurogenesis is altered via glucocorticoid-mediated regulation of ZBTB16 expression, Neuron (2024). DOI: 10.1016/j.neuron.2024.02.005

https://medicalxpress.com/news/2024-03-stress-hormones-cognitive-abilities-children.html

World-first trial of regenerative hearing drug is successfully completed

 Researchers at UCL and UCLH have successfully completed the first trial of a therapy designed to restore hearing loss. The REGAIN trial, the results of which were published in Nature Communications, was the first study of a treatment aimed at restoring lost hearing, focusing on a drug with the technical name gamma-secretase inhibitor LY3056480.

The researchers found that while the therapy did not restore hearing across the group of adults with mild to moderate hearing loss, a deeper analysis of the data showed changes in various hearing tests in some patients, suggesting the drug has some activity in the inner ear.

These so-called efficacy signals call for further development of LY3056480—using the learnings from this trial.

Trial participants were aged between 18 and 80, hailed from the UK, Germany, and Greece, and had mild to moderate hearing loss. 15 patients took part in the phase 1 trial, which showed the treatment was safe and well tolerated, and 44 patients took part in the phase 2a trial designed to establish if the drug worked.

Participants received three injections of the drug into the ear through the eardrum. Their hearing was tested with a range of tests before and after receiving the drug.

One test looked at the quietest possible sounds participants were able to hear. Another test assessed the ability to understand word sounds in a noisy background, which is the main unresolved problem for people with hearing loss.

45% of participants were able to identify some sounds that were at least 10 decibels quieter than they were previously able to hear at both 6 and 12 weeks after the start of treatment.

However, the research team set a higher bar to establish the impact of the drug—which was an average improvement of 10 decibels or more across three sound frequencies—and the hearing changes seen in the trial did not reach this more ambitious target.

Hearing loss is the most common sensory disorder in humans and an area of significant unmet need. It is primarily caused by progressive loss of inner ear sensory hair cells or their functionality. Presently, the only treatment is wearing hearing aids. These help people communicate but do not restore natural hearing or treat the underlying cause of hearing loss.

Because inner ear sensory hair cells do not naturally regenerate, hearing loss progresses with age.

Damage to these hair cells has long been considered irreversible, but various studies in animal models indicate that functioning inner ear sensory hair cells may be regenerated by a small molecule substance called a gamma-secretase inhibitor.

The REGAIN trial (Regeneration of inner ear hair cells with gamma-secretase inhibitors) was led by Professor Anne GM Schilder (UCL Ear Institute, UCLH Royal National ENT, Eastman Dental Hospitals, and NIHR UCLH Biomedical Research Centre). It was the first study of a regenerative hearing drug worldwide, delivered by an EU Consortium with clinical partners in Germany and Greece and the company Audion Therapeutics.

Professor Schilder said, "There are many important lessons from this study which will guide future studies of its kind. For example, the study will help how we best select the patients that may benefit from these new and highly targeted hearing treatments."

"This requires a better understanding of the mechanisms behind inner ear hearing loss and better hearing tests to identify its causes in patients. Big data and AI may speed up this process."

To progress this work, the UCLH BRC team, together with other BRCs, have set up the NIHR Hearing Health Informatics Collaboration (HIC) that will bring anonymized hearing data together from NHS hospitals across the UK for analysis with advanced computational techniques.

And locally, the team have opened a new patient registry called HEDGE, which offers people with hearing loss the opportunity to participate in research to help uncover the genetic and environmental factors, molecular pathways and mechanisms that cause hearing loss.

The huge demand among patients to take part in research was revealed by REGAIN.

Professor Schilder said, "We were contacted by more than 5,000 patients with hearing loss worldwide requesting to take part, illustrating the huge unmet clinical need."

UCL Ear Institute researchers were among the first to understand the role of a protein found in inner ear hair cells, which paved the way for new hearing therapies such as the one trialed in REGAIN.

More information: Anne G. M. Schilder et al, A phase I/IIa safety and efficacy trial of intratympanic gamma-secretase inhibitor as a regenerative drug treatment for sensorineural hearing loss, Nature Communications (2024). DOI: 10.1038/s41467-024-45784-0

https://medicalxpress.com/news/2024-03-world-trial-regenerative-drug-successfully.html

Turning skin cells into limb cells sets the stage for regenerative therapy

 In a collaborative study, researchers from Kyushu University and Harvard Medical School have identified proteins that can turn or "reprogram" fibroblasts—the most commonly found cells in skin and connective tissue—into cells with similar properties to limb progenitor cells. Publishing in Developmental Cell, the researchers' findings have enhanced our understanding of limb development and have set the stage for regenerative therapy in the future.

Globally, close to 60 million people are living with limb loss. Amputations can result from various medical conditions such as tumors, infections, and birth defects, or due to trauma from industrial accidents, traffic accidents, and natural disasters such as earthquakes. People with limb injuries often rely on synthetic materials and metal prostheses, but many researchers are studying the process of limb development, with the aim of bringing regenerative therapy, or natural tissue replacement, one step closer as a potential treatment.

"During limb development in the embryo, limb progenitor cells in the limb bud give rise to most of the different limb tissues, such as bone, muscle, cartilage and tendon. It's therefore important to establish an easy and accessible way of making these cells," explains Dr. Yuji Atsuta, lead researcher who began tackling this project at Harvard Medical School and continues it as a lecturer at Kyushu University's Graduate School of Sciences.

Currently, a common way to obtain limb progenitor cells is directly from embryos, which—in the case of human embryos—raises ethical concerns. Alternatively, they can be made using induced pluripotent stem cells—adult cells that are reprogrammed into an embryonic-like state, and can later be coaxed into specific tissue types.

The new method developed by Atsuta and colleagues, which directly reprograms fibroblast cells into limb progenitor cells and bypasses induced pluripotent stem cells, simplifies the process and reduces costs. It also mitigates the concern of cells turning cancerous, which often occurs with induced pluripotent stem cells.

In the initial phase of the study, the researchers looked at which genes were expressed in the early limb buds in mice and chicken embryos. Almost all cells in the body, including fibroblasts and limb progenitor cells, contain identical genomic DNA, but the different properties and functions of each cell type emerge during development due to changes in gene expression (in other words, which genes are active, and which proteins are produced by the cell). One way that gene expression is controlled in cells is by specific proteins, called transcription factors.

The research group identified 18 genes, mostly transcription factors, that are more highly expressed in the early limb bud compared to other tissues. They cultured fibroblasts from mouse embryos and introduced these 18 genes into the fibroblasts using viral vectors so that the cells produced these 18 protein factors. They found that the modified fibroblasts took on the properties and showed similar gene expression to naturally-occurring limb progenitor cells found in limb buds.

Next, over a series of experiments, the researchers narrowed down their selection and determined that only three protein factors were essential to reprogram mouse fibroblasts into limb progenitor-like cells: Prdm16, Zbtb16, and Lin28a. A fourth protein, Lin41, helped the cultured limb progenitor cells grow and multiply more rapidly.

The researchers not only confirmed that the reprogrammed limb progenitor cells had similar gene expression to natural limb progenitor cells, but that they also had similar ability.

"These reprogrammed cells are not only molecular mimics; we have confirmed their potential to develop into specialized limb tissues, both in laboratory dishes (in vitro) and also in living organisms (in vivo)," says Atsuta. "Testing in vivo was particularly challenging, as we had to transplant the reprogrammed mouse cells into the limb buds of chicken embryos."

In these experiments, the researchers used lentiviruses, which insert genes directly into the infected cells' genome, raising the risk that the cells can become cancer. Instead, the team is considering other safer vectors, such as adeno-associated viruses or plasmids, which deliver genes to the cells without inserting genes into the genome.

Atsuta's lab group is now trying to apply this method to human cells, for future therapeutic applications, and also to snakes, whose ancestors had limbs that were subsequently lost during evolution.

"Interestingly, the reprogrammed limb progenitor cells generated limb bud-like organoids, so it seems possible to generate limb tissues in species that no longer possess them. The study of limbless snakes can uncover new pathways and knowledge in developmental biology."

More information: Yuji Atsuta et al, Direct reprogramming of non-limb fibroblasts to cells with properties of limb progenitors, Developmental Cell (2024). DOI: 10.1016/j.devcel.2023.12.010

https://medicalxpress.com/news/2024-03-skin-cells-limb-stage-regenerative.html

New research supports repurposing sildenafil (Viagra) for Alzheimer's

 New Cleveland Clinic-led research points to sildenafil (Viagra) as a potential treatment for Alzheimer's disease. The study provides evidence from computational models, insurance claims data and observations from brain cells in Alzheimer's patients.

Sildenafil is the main component of drugs used to treat erectile dysfunction (Viagra) and pulmonary arterial hypertension (Revatio).

"Our findings provide further weight to re-purposing this existing FDA-approved drug as a novel treatment for Alzheimer's, which is in great need of new therapies," said Feixiong Cheng, Ph.D., who led the research. "We used artificial intelligence to integrate data across multiple domains which all indicated sildenafil's potential against this devastating neurological disease."

Alzheimer's disease currently affects over 6 million Americans and incidence is expected to triple by 2050, underscoring the need for rapid development of new prevention and treatment strategies. Drug repurposing—use of an existing drug for new therapeutic purposes—offers a practical alternative to the costly and time-consuming traditional drug discovery process.

Published in Journal of Alzheimer's Disease, the study builds upon the researchers' earlier findings in 2021 that used computational models to initially identify sildenafil as a promising drug candidate to help prevent and treat Alzheimer's disease.

In the new study, Dr. Cheng, director of the Cleveland Clinic Genome Center, and his team analyzed millions of de-identified insurance claims from two independent patient databases, which revealed a 30–54% reduced prevalence in Alzheimer's disease diagnoses among patients who took sildenafil compared to those who did not after adjusting various possible confounding factors.

In brain cells from Alzheimer's patients, researchers also showed that sildenafil lowers levels of neurotoxic tau proteins, which are known to be associated with Alzheimer's disease when they build up. They also found that neurons treated with sildenafil expressed genes related to cell growth, improved brain function, reduced inflammation and other processes known to protect against the neural degeneration associated with Alzheimer's disease.

Dr. Cheng's findings demonstrate the feasibility of using computer models to identify potential new drug candidates in a fast, reliable way, representing a significant step forward in Alzheimer's drug discovery.

"After integrating this large amount of data computationally, it is rewarding to see sildenafil's effects in human neurons and real-world patient outcomes," said Dr. Cheng. "We believe our findings provide the evidence needed for clinical trials to further examine the potential effectiveness of sildenafil in patients with Alzheimer's disease."

Dr. Cheng's co-authors include Andrew A. Pieper, M.D., Ph.D., of Louis Stokes Cleveland VA Medical Center, Case Western Reserve University and University Hospitals Cleveland Medical Center; and Jeffrey Cummings, M.D., Sc.D., director emeritus of the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas.

Dhruv Gohel, Ph.D., and Amit Gupta, Ph.D., postdoctoral research associates in Dr. Cheng's laboratory, are co-first authors.

More information: Dhruv Gohel et al, Sildenafil as a Candidate Drug for Alzheimer's Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons, Journal of Alzheimer's Disease (2024). DOI: 10.3233/JAD-231391

https://medicalxpress.com/news/2024-03-repurposing-sildenafil-viagra-alzheimer-treatment.html