Lifestyle, Zeit, Geld, Karriere: Hund statt Kind

Auch ein Thema, dass seit mehreren Jahrzehnten immer wieder aufgegriffen wird.

"Regen, Kälte, Wind. Noch einmal sich hochraffen, um mit dem Hund Gassi zu gehen, eine letzte Runde vor dem Schlafen. Für jeden Menschen ohne Vierbeiner klingt das womöglich schon wie eine Last, viel Mühe und Einschränkung. Für Menschen mit Kindern muss es lächerlich wirken. ..."

Große Teile der Wirtschaft setzen nicht mehr auf Bundesregierung

13-jähriger Irakischer Jugendlicher prügelt 62 Jahre alten Busfahrer in Leipzig ins Koma plus Schlaganfall

Schlagzeilen aus der Bananenrepublik D!

"In Leipzig hat ein 62-jähriger Busfahrer nach einer Auseinandersetzung mit einer störenden migrantischen Jugendgruppe schwere Kopfverletzungen erlitten. Der Mann liegt im Koma. Zuvor hatte er einen Schlaganfall im Nachgang der Tat erlitten und musste notoperiert werden. Der mutmaßliche Täter ist erst 13 Jahre alt – und damit strafrechtlich nicht zu belangen."

Große Teile der Wirtschaft setzen nicht mehr auf Bundesregierung

Across the social sciences, half of research doesn’t replicate | Science | AAAS

Nothing new! This too has been studied and reported frequently over the past several decades!

"A sweeping project involving hundreds of researchers in several dozen countries showed that across the social sciences, the findings of roughly half of all papers cannot be replicated independently, and there’s no reliable way to tell in advance which ones will falter. Called Systematizing Confidence in Open Research and Evidence (SCORE), the effort investigated more than 100 papers published in dozens of leading journals in business, economics, education, political science, psychology, and sociology. The replication success rate—49% for the 164 papers evaluated, reported today in Nature—is consistent with findings from previous studies in individual fields such as psychology, suggesting the problem is pervasive in the social sciences. ..."

From the abstract:

"Pursuing replicability — independent evidence for previous claims — is important for creating generalizable knowledge. Here we attempted replications of 274 claims of positive results from 164 quantitative papers published from 2009 to 2018 in 54 journals in the social and behavioural sciences. Replications were high powered on average to detect the original effect size (median of 99.6%), used original materials when relevant and available, and were peer reviewed in advance through a standardized internal protocol.

Replications showed statistically significant results in the original pattern for 151 of 274 claims (55.1% (95% confidence interval (CI) 49.2–60.9%)) and for 80.8 of 164 papers (49.3% (95% CI 43.8–54.7%)), weighed for replicating multiple claims per paper.

We observed modest variation in replication rates across disciplines (42.5–63.1%), although some estimates had high uncertainty. The median Pearson’s r effect size was 0.25 (95% CI 0.21–0.27) for original studies and 0.10 (95% CI 0.09–0.13) for replication studies, an 82.4% (95% CI 67.8–88.2%) reduction in shared variance. Thirteen methods for evaluating replication success provided estimates ranging from 28.6% to 74.8% (median of 49.3%). Some decline in effect size and significance is expected based on power to detect original effects and regression to the mean because we replicated only positive results.

We observe that challenges for replicability extend across social–behavioural sciences, illustrating the importance of identifying conditions that promote or inhibit replicability."

Across the social sciences, half of research doesn’t replicate | Science | AAAS (no public access)

Investigating the replicability of the social and behavioural sciences (no public access)

Dendritic cells power down inside tumors—re-energizing them could help treat cancer

Good news! Cancer is history (soon)!

"Dendritic cells ... By using their long projections to display fragments of protein, they summon other immune cells to attack invaders and destroy diseased cells. But when dendritic cells find themselves inside a tumor, they tend to run out of steam. According to new research, these cells stop working because their mitochondria ... become degraded.

When scientists examined mice with melanoma, they found that some dendritic cells within the animals’ tumors had perfectly healthy mitochondria, while others were debilitated.

As the tumors grew, the number of cells with active mitochondria dwindled. Although it’s unclear exactly why these organelles go on the fritz, the team did determine that a protein called OPA1 appears to be essential to their functioning. Dendritic cells that possessed this protein were much better at rallying other immune cells, while those engineered to lack it were far less effective—leading to more tumor growth.

When the researchers injected the rodents’ dendritic cells with lots of additional mitochondria, the animals were able to mount a strong antitumor response and fared better when treated with a type of immunotherapy. ..."

From the Perspective abstract:

"Dendritic cells are innate immune cells that regulate the quality, magnitude, and duration of antitumor responses. Conventional type 1 dendritic cells (cDC1s) are crucial in this capacity but are paradoxically rare and functionally impaired in most solid tumors. This is a major barrier to effective immunotherapy. The molecular underpinnings of cDC1 dysfunction within the tumor microenvironment are poorly understood. On page 55 of this issue, You et al. (1) report that mitochondrial fitness is important for cDC1 function. They also demonstrate the therapeutic rescue of cDC1 function within the tumor microenvironment in mice, which provides a framework for metabolically reprogramming dendritic cells to restore antitumor immunity."

From the editor's summary and abstract:

"Editor’s summary

Type 1 conventional dendritic cells (cDC1s) promote CD8+ T cell–mediated antitumor responses. However, cDC1s can become dysfunctional in the tumor microenvironment, and the mechanisms governing cDC1 function versus dysfunction in cancer remain unclear. You et al. report that mitochondrial metabolic states and signaling direct cDC1 function in antitumor immunity (see the Perspective by Molina and Haldar). Loss of the mitochondrial protein OPA1 disrupted nuclear respiratory factor 1 (NRF1) activity and electron transport chain integrity, leading to defects in mitochondrial bioenergetics and redox balance in cDC1s, accompanied by reduced tumor control. OPA1-NRF1 signaling progressively declined during tumor progression, and tumor-bearing mice receiving cDC1s with high mitochondrial fitness had improved antitumor responses, especially in combination with immunotherapy. Therefore, “metabolic engineering” of cDC1s may provide a mechanism for cancer immunotherapy. —Priscilla N. Kelly

Structured Abstract

INTRODUCTION

Conventional type 1 dendritic cells (cDC1s) are essential for cytotoxic CD8+ T cell responses in cancer immunity and immunotherapy. Although previous studies have suggested that mitochondrial oxidative phosphorylation (OXPHOS) is dispensable for DC maturation in vitro and represents a hallmark of tolerance in human monocyte–derived DCs, whether and how mitochondrial metabolism regulates cDC1-CD8+ T cell interactions in antitumor immunity remain largely unknown. In this study, we reveal that intratumoral cDC1s have discrete mitochondrial states and that mitochondrial fusion protein OPA1 dictates cDC1 antitumor immunity by facilitating mitochondrial energy and redox metabolism.

RATIONALE

Despite the success of immunotherapy in cancer treatment, therapeutic resistance or relapse occurs in a large subset of patients. cDC1s determine antitumor effects and therapeutic benefits upon immune checkpoint blockade (ICB) by orchestrating CD8+ T cell activation and function. However, cDC1s often experience metabolic stress and exhibit decreased functional fitness within the tumor microenvironment. ...

RESULTS

We established, from both mouse and human tumors, that cDC1s exhibit discrete mitochondrial states.

One subpopulation, referred to as [TMRM/MG]hi cells, contained polarized mitochondria, as demonstrated by the ratio of mitochondrial membrane potential [measured with tetramethylrhodamine methyl ester perchlorate (TMRM)] compared with mitochondrial mass [measured with MitoTracker Green (MG)]; whereas the 

other subpopulation, [TMRM/MG]lo cells, had depolarized mitochondria. Intratumoral cDC1s with polarized mitochondria more effectively primed CD8+ T cell responses than those with depolarized mitochondria.

Using unbiased profiling approaches and experimental validations, we uncovered that OPA1 orchestrates the mitochondrial states and morphology in intratumoral cDC1s.

Notably, OPA1 deletion in cDC1s led to increased tumor growth and impaired antitumor CD8+ T cell responses, corresponding to defective antigen presentation by cDC1s. Mechanistically, we established that OPA1 supports nuclear respiratory factor 1 (NRF1) activity and expression to sustain mitochondrial OXPHOS in cDC1s. OPA1-NRF1 axis–mediated OXPHOS inhibited autophagy and lysosome–dependent degradation of major histocompatibility complex I (MHC-I) and antigen. In addition, OPA1-mediated electron transport chain (ETC) flow contributed to cDC1 immunogenicity by facilitating NADH-to-NAD+ conversion (i.e., conversion from the reduced to the oxidized form of nicotinamide adenine dinucleotide). These OPA1-dependent effects were antagonized by mitochondrial fission protein DRP1.

During tumor progression, intratumoral cDC1s experienced a progressive mitochondrial dysfunction, as revealed by reduction of the [TMRM/MG]hi subpopulation as well as decreased mitochondrial volume and OPA1-NRF1 signaling.

Intratumoral administration of tumor antigen–pulsed cDC1s with polarized mitochondria into tumor-bearing mice resulted in superior tumor control compared with cDC1s with depolarized mitochondria, particularly when combined with ICB therapies. Indeed, a substantial proportion of mice receiving cotreatment of tumor antigen–pulsed cDC1s with polarized mitochondria plus ICB completely rejected tumors and developed durable immune memory responses upon tumor rechallenge.

CONCLUSION

We uncovered discrete mitochondrial states and the underlying mitochondrial metabolic signaling programs in cDC1s that support their functional fitness in antitumor immunity and the establishment of durable ICB responses. These discoveries provide opportunities to reinvigorate cDC1s for improved cancer immunotherapy."

ScienceAdviser

Mitochondria power immunity against cancer (Perspective, no public access)

Mitochondrial metabolism and signaling direct dendritic cell function in antitumor immunity (no public access)

Mitochondrial metabolism and signaling orchestrate cDC1 antitumor responses.

Global human population is pushing Earth past its breaking point. Really!

Such or similar false apocalyptic claims have been made frequently for the past 50 years or so!

Human ingenuity has already defeated many of those and other apocalyptic claims in the past!

Look at the chart below, this is primitive trend extrapolation. Yes, the growth of human population since about 1800 AD was extreme and a miracle, but it will not continue like this!

This is superstition, not science! Alarmism and hysteria! Perhaps very lucrative for these pseudo scientists behind this study!

When scientists call for authoritarian central government watch out!

I am not sure why any journal today would publish such rubbish again!

Actually, world population may even decrease over the next several decades. The population of e.g. China and Japan is already shrinking. E.g. Germany's German population may also be shrinking. I bet also India's population growth is already slowing and so on.

"Earth has already exceeded its ability to support the global population sustainably, with new research warning of increasing pressure on food security, climate stability, and human well-being. However, slowing population growth and raising global awareness could still offer humanity some hope. ..."

From the abstract:

"The ecological concept of human carrying capacity is necessarily complicated because human beings are the ‘ultimate ecosystem engineers’ who moderate the environment for their benefit.

For at least the last few hundred years, human ingenuity, access to massive stocks of fossil fuels, and technological development have driven facilitation whereby increasing human abundance has promoted higher population growth rates.

However, this positive relationship broke down during the 1950s, and by 1962, the global human population entered a phase where the growth rate consistently declined as population increased.

The onset of this negative phase occurred 8 years before a global biocapacity deficit began in 1970. The onset of the negative phase also varies regionally, with the lowest-income and highest fertility regions entering this phase later than higher-income regions.

A Ricker logistic model fitted to the negative phase predicts that the global population could reach 11.7–12.4 billion people between 2067 and 2076. The same model fitted to the facilitation phase predicts a maximum population of 2.5 billion people that Earth might be able to maintain [???]. 

The negative phase also correlates strongly with the trend in global temperature anomaly, ecological footprint, and total emissions, with more of their variation explained by increasing population size rather than increasing per-capita consumption.

The Earth cannot sustain the future human population, or even today’s, without a major overhaul of socio-cultural practices [???] for using land, water, energy, biodiversity, and other resources."

Global human population is pushing Earth past its breaking point

Global human population has surpassed Earth's sustainable carrying capacity

Figure 1. Global human population size from 1000 to present (main figure) and from 1800 to present

Thirty previously unpublished verses by Empedocles discovered on a papyrus from Cairo

Good news!

"A 2,000-year-old papyrus fragment, discovered in the archives of the French Institute of Oriental Archaeology in Cairo, reveals 30 previously unpublished verses by Empedocles, a pre-Socratic philosopher of the fifth century BCE. This discovery offers researchers direct access to a body of thought previously known only through quotations from later authors. The very first edition, translation, and commentary on these verses are published in the book "L'Empédocle du Caire," ... 

a papyrologist ... identified papyrus P. Fouad inv. 218 as an unknown fragment of the "Physica," the poem by the philosopher Empedocles of Agrigentum. ...

The text that has come to light deals with the theory of particle effluvia and sensory perceptions, particularly vision. Analysis of the text has revealed unexpected connections, including the probable direct source of a passage by Plutarch (2nd century), as well as a dialogue by Plato and a text by Theophrastus, a disciple of Aristotle, both from the 4th century BCE. Unnoticed echoes of Empedocles have also been detected in the comic poet Aristophanes and in the Latin philosopher Lucretius. The study further suggests that Empedocles could be regarded as a precursor of the atomist philosophers, foremost among whom is Democritus of Abdera. ..."

Thirty previously unpublished verses by Empedocles discovered on a papyrus from Cairo

Thirty previously unpublished verses by Empedocles discovered on a papyrus from Cairo (original news release) "A two-thousand-year-old papyrus fragment, discovered in the archives of the French Institute of Oriental Archaeology in Cairo, reveals thirty previously unpublished verses by Empedocles, a pre-Socratic philosopher of the 5th century BCE. This discovery offers researchers direct access to a body of thought previously known only through quotations from later authors. The very first edition, translation and commentary on these verses are published in the book L'Empédocle du Caire ..."

Why solid-state batteries keep short-circuiting

Good news!

"... Faster dendrite growth was associated with lower stress levels in a commonly used battery electrolyte material. Using a new technique that allowed them to directly measure the stress around growing dendrites, the researchers found cracks formed at stress levels as low as 25 percent of what would be expected under mechanical stress alone.

The experiments ... instead revealed another culprit: chemical reactions caused by high electrical currents that weaken the electrolyte and make it more susceptible to dendrite growth. Researchers had previously proposed that such reactions cause dendrite growth, but the new study provides the first experimental data on the interplay between chemical and mechanical stress in dendrite formation. ..."

From the abstract:

"Charging rates, cycling performance and safety of solid-state batteries using metal negative electrodes are often limited by dendrites, the growth of which depends on coupling between electrochemical and mechanical driving forces.

Previously, it has been assumed that dendrites propagate when plating-induced stresses reach the fracture stress of the solid electrolyte.

Here we show that dendrites can propagate at far lower stresses. Using operando birefringence microscopy, we directly measure stresses around growing dendrites in garnet Li6.6La3Zr1.6Ta0.4O12, a highly stable solid electrolyte.

Plating-induced stresses are present throughout growth and approach the mechanical fracture stress for the slowest-growing dendrites.

As current densities and dendrite velocities increase, the stresses accompanying dendrite growth surprisingly decrease, with dendrite propagation occurring at stresses up to 75% lower than under mechanical load alone.

Cryogenic scanning transmission electron microscopy (STEM) of dendrites propagated at high current reveals electrolyte decomposition to new phases, associated with which is a net molar volume contraction.

The electrochemically induced mode of embrittlement may be mitigated through understanding and control of the nature of phase transitions accompanying instability."

Why solid-state batteries keep short-circuiting | MIT News | Massachusetts Institute of Technology "New insights into metallic cracks that harm battery performance could advance the longstanding quest to develop energy-dense solid-state batteries."

Electrochemical corrosion accompanies dendrite growth in solid electrolytes (no public access)

Researchers used a new visualization technique to measure stress in a battery material as a dendrite crack grows. This video shows two different rates of charging, with brighter colors corresponding to higher stress. A bowtie-shaped pattern can be seen at the crack tip. Less stress is required to break the material under fast-charging conditions.

The foreign gig workers who are training humanoid robots in the US

Amazing stuff! $15 per hour is not so bad!

"The gig workers who are training humanoid robots at home

Zeus, a medical student living in Nigeria, has a bizarre side gig: He straps an iPhone to his forehead and films himself doing chores, like making the bed, and then sends this footage to a Silicon Valley company called Micro1. If the footage is good, the company will pay him an average of $15 an hour. 

Zeus is one of thousands of gig workers—particularly in India, Nigeria, and Argentina—who are now building a massive training data set for humanoid robots to learn from. While large language models can get better by learning from the whole internet, robots need more particular videos to train on. Micro1, among other companies, is setting up a gig economy to supply just that. " (Source)

Physics - How Hair Cells in the Ear Actively Respond to Sound

Amazing stuff! There is a lot going on inside of ears!

"... Previous research has shown that hair bundles aren’t simply passive entities. They actively oscillate to amplify weak audio signals or to tune into specific frequencies. Biologists have also observed bundles oscillating in the absence of stimuli. Models have tried to capture this bundle behavior, but the connection between active oscillation and the audio response has not been made clear.

A new thermodynamic model of energy flow within hair bundles suggests that they work like tiny machines. Depending on the stimulus, the bundles either extract power from incoming sound waves or inject power into them—corresponding, respectively, to sensing or amplifying a stimulus.

In the inner ear, an active process called cochlear amplification helps humans (and other mammals) hear the faintest of sounds. When a faint whisper enters the ear, for example, the outer rows of hair cells respond to the weak signal by moving in a way that amplifies the sound waves for the inner hair cells, which are the ones that send a message to the brain. Molecular motors propel the movement or twisting of hair bundles required for these functions.

Previous work has explored how much energy a hair cell consumes to drive bundle oscillations, but the resulting models have typically assumed that bundles are moving spontaneously—that is, in the absence of external stimuli.

... [This work] have developed a stochastic thermodynamic model that includes an energy input from sound waves.  ...

The model featured three energy channels: an external environment acting like a heat reservoir, an external signal representing the sound stimulus, and an internal energy source driving active processes. The researchers found that the simulated hair bundle operated in one of four different thermodynamic regimes, depending on the amplitude and the frequency of the signal.

For two of the thermodynamic regimes, the hair bundles acted as work-to-work machines, converting mechanical work from one source into another, with minimal heat loss.

In the first regime, mechanical energy from the signal flowed through the hair bundle into the cell.

Conversely, in the second regime, energy flowed outward from the hair cell into the signal channel.

Although the two work-to-work regimes are simplified, the team believes that they correspond to the hair cell’s main functions of sensing and amplification. The switching between regimes depends on the strength of the incoming signal, with the active cell motion (amplification) only turning on when the signal is weak, Belousov says.

The other two regimes, likely not biologically relevant, were thermodynamic peculiarities. In one, the moving hair bundle actively dissipated heat. Surprisingly, in the remaining regime, the hair bundle could “work as a tiny refrigerator cooling down the surrounding environment around the cell,” ..."

From the abstract:

"Hair cells actively drive oscillations of their mechanosensitive organelles—the hair bundles that enable hearing and balance sensing in vertebrates. Why and how some hair cells expend energy by sustaining this oscillatory motion in order to fulfill their function as sensors and amplifiers remains unknown.

Here, we develop a stochastic thermodynamic theory to describe flows of mechanical energy in a periodically driven hair bundle. Our analysis of thermodynamic fluxes associated with hair-bundle motion and external sinusoidal stimulus reveals that these organelles function as thermodynamic work-to-work machines under different operational modes.

One mode allows the cell to harvest energy of the external signal, whereas another channels the power supplied by the cell into the signal. These two regimes might represent thermodynamic signatures of signal sensing and amplification, respectively, which we further connect to the receptor currents through ion channels controlled by the hair bundles.

In addition to energy harvesting and work transduction, our model also substantiates the capability of hair cells to operate as heaters and, at the expense of external driving, as active feedback refrigerators. We quantify the performance and robustness of the mechanical work-to-work conversion by hair bundles, whose thermodynamic efficiency in some conditions exceeds 80% of the applied power."

Physics - How Hair Cells in the Ear Actively Respond to Sound "Our ability to hear relies on tiny “hair bundles” in the inner ear. A new thermodynamical model offers an explanation for the different ways that bundles oscillate."

Thermodynamic Signatures of Sensing and Amplification by Periodically Driven Hair-Cell Bundles (open access)

Left: A hair cell captured with differential interference contrast microscopy. Right: Energy can flow in and out of the cell through three channels: active driving by molecular motors in the cell, heat from the environment, and work from the external sound signal.

Fig. 1 Left: Schematic of a hair cell with its hair bundle on top. Energy is exchanged between the thermal environment, the hair bundle characterized by the position of its tallest cilium—the kinocilium—and two agents

Scientists Map Aging Across the Body of a Short-Lived Fish

Amazing stuff!

"Studying aging takes time. That’s why neuroscientists studying how brains age turn to thumb-sized fish called killifish. Within just four to six months, the fish hatch, grow to maturity, spawn and die. Their compressed lifespan has made the fish a favorite for research on this inevitable process.

Now, a team ... has created a comprehensive atlas of aging in killifish. By sequencing gene activity across 12 tissues at six life stages in male and female fish, they have documented progressive molecular changes in detail as they unfold across the fish’s body. ...

In humans, immune cells are produced in the bone marrow. In fish, that role falls to the front portion of the kidney. By examining gene activity in this organ, the researchers found a pattern reminiscent of what has been observed in aging mammals, including humans. Markers associated with B and T cells, the immune system’s precision defenders, declined with age. Meanwhile, evidence of immune cells that participate in broader inflammatory responses increased.

Interestingly, this shift was much more pronounced in females than in males. ..."

From the abstract:

"Aging is associated with progressive tissue dysfunction, leading to frailty and mortality. Characterizing aging features, such as changes in gene expression and dynamics, shared across tissues or specific to each tissue, is crucial for understanding systemic and local factors contributing to the aging process.

We performed RNA sequencing on 13 tissues at six different ages in male and female African turquoise killifish, the shortest-lived vertebrate that can be raised in captivity.

This comprehensive, sex-balanced ‘atlas’ dataset revealed varying strength of sex–age interactions across killifish tissues and age-altered genes and biological pathways that are evolutionarily conserved in mice and humans.

We discovered a female-biased myeloid shift with age in the killifish hematopoietic organ, developed tissue-specific ‘transcriptomic clocks’ and identified biomarkers predictive of chronological age.

We showed the importance of sex-specific clocks for selected tissues, validated the tissue clocks with an independent transcriptomic dataset and used them to evaluate different lifespan interventions in the killifish.

Our work provides a comprehensive resource for studying aging dynamics across tissues in the killifish, a powerful vertebrate aging model."

Scientists Map Aging Across the Body of a Short-Lived Fish "A new atlas of aging in the killifish tracks how organs change over time, revealing processes implicated in Alzheimer’s and Parkinson’s diseases. The study also creates AI-driven tools for predicting the biological age of different tissues."

Multi-tissue transcriptomic aging atlas reveals predictive aging biomarkers in the killifish (open access)

Fig. 1: A multi-tissue killifish transcriptomic aging atlas reveals shared and tissue-specific age effects on different tissues.

Neue Kampfdrohne für Deutschland? Was die Ghost Bat wirklich kann

Gute Nachrichten! Besser spät als nie! Not a ghost buster, but a ghost bat! 😊

"Die Art und Weise, wie moderne Luftstreitkräfte operieren, steht vor einem massiven Umbruch. Weg von teuren, rein bemannten Formationen, hin zu hybriden Modellen. In diesem Szenario spielen unbemannte Begleiter eine zentrale Rolle. Rheinmetall und Boeing Australia haben nun eine strategische Partnerschaft geschlossen, um genau diese Technologie nach Deutschland zu bringen.

Im Fokus steht die MQ-28 Ghost Bat. Rheinmetall und Boeing positionieren die Plattform als Lösung für eine geplante Beschaffung sogenannter Collaborative Combat Aircraft (CCA) durch die Bundeswehr bis 2029. Dabei handelt es sich um unbemannte Kampfflugzeuge, die im Verbund mit bemannten Jets operieren. Eine endgültige Beschaffungsentscheidung ist damit jedoch noch nicht gefallen. ..."

Neue Kampfdrohne für Deutschland? Was die Ghost Bat wirklich kann "Kampfjet ohne Pilot: Die Ghost Bat soll Deutschlands Luftwaffe stärken. Wie die Drohne funktioniert und warum sie strategisch wichtig ist."

Rheinmetall bringt die Ghost Bat zur Bundeswehr: Autonome Kampfdrohne soll bis 2029 einsatzbereit sein. Rheinmetall AG

Scientists capture how cells trigger inflammation

Amazing stuff!

"In brief

• SLAC researchers observed a key master regulator of inflammation inside living cells, revealing a dense, gel-like structure that is much less organized than expected.
• The findings suggest this inflammation-triggering system forms a flexible cluster of proteins, which could influence the design of treatments for inflammatory diseases.
• The study also revealed a link between inflammation and the machinery that controls cell division, suggesting a possible explanation for why cells usually stop dividing while mounting an inflammatory response.

... to capture, for the first time, the formation of an immune signaling complex inside intact human cells.

The results ... provide a closer look at how the complex assembles and interacts with other parts of the cell, offering new insight into the early stages of the body’s inflammatory response to infection and other stress signals. Their work, which challenges longstanding models of the process, could help guide future efforts to develop new therapeutic approaches for inflammatory diseases. ..."

From the abstract:

"The NLRP3 inflammasome is a multiprotein molecular machine that drives inflammatory responses in innate immunity. Although its dysregulation is implicated in numerous human diseases, its structural organization in cells remains poorly understood.

Here, we used precise fluorescence-guided cryo–focused ion beam (cryo-FIB) milling and cryo–electron tomography (cryo-ET) to visualize NLRP3 inflammasomes in situ within human macrophages at various stages of activation.

After priming and activation, we observed expansion and dispersion of Golgi cisternae, along with the emergence of 50-nanometer NLRP3-associated vesicles, which likely transport NLRP3 to the MTOC.

Dense NLRP3-containing condensates then formed in and around the MTOC. In later stages, the condensates solidified, coincident with widespread mitochondrial damage, autophagy, and pyroptotic cell death."

Scientists capture how cells trigger inflammation | Stanford Report "SLAC scientists observed an immune signaling complex forming inside cells for the first time, revealing insights that could guide new treatments."

Human NLRP3 inflammasome activation leads to formation of condensate at the microtubule organizing center (open access)

Fig. 1. Progression of NLRP3 inflammasome activation.

The Justice Department declared the Presidential Records Act unconstitutional

Maybe an interesting legal case!

This could be one more reason why President Trump could go down in history as one of the most consequential US presidents in recent history since President Reagan.

Caveat: I am not familiar with the Presidential Records Act.

"The Justice Department declared the Presidential Records Act unconstitutional, saying President Trump doesn’t need to comply with the post-Watergate law requiring presidents to preserve and turn over documents when they leave office."

"The Justice Department said that a federal law enacted in the wake of the Watergate scandal that requires the president to preserve certain documents and turn them over to the National Archives at the end of his administration is unconstitutional.

The opinion from Assistant Attorney General T. Elliot Gaiser, who leads the Office of Legal Counsel, concluded that the Presidential Records Act exceeds Congress' power and "aggrandizes the legislative branch" at the expense of the independence of the executive branch. ..."

Saturday, April 4, 2026 - Join The Flyover

Justice Department says law requiring president to turn over records at end of administration is unconstitutional

Putin Confronts Pashinyan Over Election Rules and Armenia’s Westward Drift

Putin the Terrible, what a bully! Will he invade Armenia next?

"In a rare public airing of differences, Russian President Vladimir Putin pressed Armenian Prime Minister Nikol Pashinyan on Wednesday over restrictions affecting Russian passport holders and other pro-Russian figures ahead of Armenia’s June 7 parliamentary election. The televised exchange, during talks in Moscow on April 1, underscored the widening rift between the two formally allied countries. ..."

Putin Confronts Pashinyan Over Election Rules and Armenia’s Westward Drift "In a rare public airing of differences, Putin warned Pashinyan that Yerevan’s westward drift was straining ties with Moscow."

Russian President Vladimir Putin (R) speaks with Armenian Prime Minister Nikol Pashinyan during their meeting at the Kremlin in Moscow, on April 1, 2026.

Disclaimer

I  am currently blogging from behind the Great Firewall of China.

My Internet service in China is very spotty. Thus, I am not able to blog as usual.

President Trump became the first sitting president to attend Supreme Court oral arguments

What President Trump does to promote his legacy! 😊

"President Trump became the first sitting president to attend Supreme Court oral arguments, showing up on Wednesday as justices heard his challenge to birthright citizenship."

Thursday, April 2, 2026 - Join The Flyover

U.S. forces rescued the second crew member from an F-15E shot down over Iran

Absolutely stunning! Bravo! Once more, the US Military at its best and finest! Nobody left behind!

"U.S. forces rescued the second crew member from an F-15E shot down over Iran, pulling the seriously wounded colonel from a mountain crevice after 36 hours behind enemy lines.

The CIA ran a deception campaign inside Iran, spreading false reports that the airman had already been found while intelligence teams pinpointed his actual location.

Hundreds of special forces and dozens of aircraft carried out the extraction, striking Iranian forces who were closing in and destroying two transport planes that got stuck before evacuating. See the details of the mission."

Monday, April 6, 2026 - Join The Flyover

I will be travelling, no blog posts until Monday 4/6

Beginning today 4/1 (no April fool's joke)! 😊

AI completes the formal proof of higher-dimensional sphere packing

Good news!

"When Ukrainian mathematician Maryna Viazovska received a Fields Medal—widely regarded as the Nobel Prize for mathematics—in July 2022, it was big news. Not only was she the second woman to accept the honor in the award’s 86-year history ... Today, in a collaboration between humans and AI, Viazovska’s proofs have been formally verified, signaling rapid progress in AI’s abilities to assist with mathematical research. ..."

"These results, originally proved by Maryna Viazovska and collaborators, earned Viazovska the Fields Medal at the 2022 International Congress of Mathematicians. This is the only formalization of a Fields Medal-winning result from this century ..."

AI Proof Verification: Gauss Tackles 24D - IEEE Spectrum

Completing the formal proof of higher-dimensional sphere packing "Using Gauss, we have helped formally verify the sphere packing problem in dimensions 8 and 24 — certifying that the E8 lattice and the Leech lattice achieve the densest possible arrangements of non-overlapping spheres in their respective dimensions."

Fields Medal–winning mathematical work about optimal sphere packing in many dimensions is now formally verified by a human-AI collaboration

AI turns electron microscopy into materials insights in minutes

Good news! This could be an important breakthrough!

"... The EMSeek platform ... streamlines materials research by identifying key features in a microscopy image, determining the crystal structure, predicting material properties, comparing results with existing scientific literature and generating a report within a single, integrated workflow. ..."

From the abstract:

"Electron microscopy (EM) reveals atomic-scale structures that underpin catalysis, energy storage, and semiconductor reliability, yet current workflows remain fragmented across segmentation, crystallographic reconstruction, property modeling, and literature review, often requiring weeks of expert effort. Although recent artificial intelligence models have assisted individual steps, the diversity of EM modalities and tasks means existing approaches remain siloed and perform poorly in complex multistage workflows.

We present EMSeek, a modular, provenance-tracked multiagent platform that connects EM to materials insight through five key units: reference-guided one-for-all segmentation, mask-aware reconstruction of crystal structures from EM data, a gated mixture of experts property predictor with uncertainty calibration, literature retrieval with citation anchoring, and physical consistency checks with audit-ready reporting. These units are orchestrated by large language models (LLMs) that automatically plan, invoke, and execute tools, minimizing human intervention.

On 20 material systems and five tasks, EMSeek delivers segmentation about twice as fast as Segment Anything with higher accuracy, achieves more than 90% structural similarity on STEM2Mat, and, with about 2% labeled calibration, matches or surpasses strong single experts on three out-of-distribution property benchmarks.

A complete query runs in 2 to 5 minutes per image, roughly 50 times faster than expert workflows. Case studies on two-dimensional lattices and nanoparticles validate EMSeek’s ability to automate complex workflows, with integrated uncertainty calibration and audit signals that provide scientists with rigorous yet actionable guidance to accelerate materials discovery."

AI turns electron microscopy into materials insights in minutes | Cornell Chronicle

Bridging electron microscopy and materials analysis with an autonomous agentic platform (open access)

Fig. 1. Interactive EMSeek multiagent framework for end-to-end EM analysis.

Fig. 2. One-click reference-patch framework for universal EM segmentation.

Fig. 4. End-to-end agentic workflow linking EM images to materials knowledge.

Italy turns away Middle East-bound US military aircraft from Sicily stopover

Bad news! What the heck is Italian Prime Minister Meloni doing?

"U.S. military aircraft heading from the United States to the Middle East have been refused permission to stop off at an air base in Italy, an Italian government source has told Defense News. ...

Italy has a longstanding deal with the U.S. to allow it to use Sigonella for regular military flights, while permission for use of the base by flights not covered by the agreement must be granted by the Italian parliament.

In a speech to parliament this month, Italian Prime Minister Giorgia Meloni said, “The bases used by the U.S. in Italy derive from agreements signed in 1954 and which have been updated since then by various governments. According to those agreements there are technical authorizations when it comes to logistics and non-kinetic operations that do not involve, put simply, bombing.” ..."

Italy turns away Middle East-bound US military aircraft from Sicily stopover

Paper tiger NATO didn’t show up — now Trump’s asking why we stay

This is very serious stuff! It may have serious consequences!

"... Trump said, when the U.S. needed cooperation, allies denied access to bases, shut down airspace, and stayed out while Washington moved forward alone. ...

He pointed to Ukraine to make the contrast unavoidable. When Russia invaded in 2022, the United States stepped in immediately despite having no obligation under NATO to do so. It didn’t wait for consensus. It didn’t hedge. “We were there for them… and we would always have been there for them,” Trump said. “They weren’t there for us.”

That’s where his long-running criticism of NATO lands differently now. “I was never swayed by NATO. I always knew they were a paper tiger, and Putin knows that too.”

Inside the administration, that thinking is no longer just Trump’s. Marco Rubio said Monday the alliance will have to be “re-examined” after several countries blocked U.S. operations during the Iran conflict. Spain, among others, reportedly refused to allow American use of its airspace and bases—decisions that didn’t just signal disagreement, but actively limited what the U.S. could do. ..."

MxM News: NATO didn’t show up — now Trump’s asking why we stay

No helium, no chips: why Australia needs to make the gas again

Recommendable!

"No helium, no chips: why Australia needs to make the gas again

Australia should restart domestic helium production. Government action will be needed for it to do so.

Iranian strikes on Qatar’s Ras Laffan gas complex have knocked out roughly a third of the world’s helium supply" (Source, I can not access aspistrategist website from China)

Scientists claim to have found evidence of a liquid-liquid critical point in supercooled water

Amazing stuff! The many wonders of water!

"Despite being the most familiar liquid, water is weird. It breaks many of the usual rules that govern the liquid state. In 1992 a team of researchers suggested why that is. Perhaps, they said, there are two types of liquid water, which become distinct only at temperatures well below freezing point, where it’s all but impossible to keep water liquid. Researchers have sought evidence for this bold conjecture ever since – and now an international team claims to have found it.

Water is weird. It has over 60 properties that mark it as rather different to other liquids, such as high surface tension, high boiling point and low compressibility. Is it because liquid water is better thought of as two different liquids? ...

used ultrafast laser pulses to rapidly melt ice at temperatures and pressures close to those at which the two deeply supercooled liquid phases of water are thought to exist. They then used x-ray scattering to see a signature of the two liquids and the liquid–liquid phase transition between them – an abrupt (first-order) transition that, like the transition between a normal liquid and gas phase, ends in a critical point where the two phases become indistinguishable. ..."

"Using x-ray lasers, researchers at Stockholm University have been able to determine the existence of a critical point in supercooled water at around -63 °C and 1000 atmosphere. Ordinary water at higher temperatures and lower pressures is strongly affected by the presence of this critical point, causing the origin of its strange properties. ..."

From the editor's summary and abstract:

"Editor’s summary

Polyamorphism and the resulting liquid-liquid critical point (LLCP) in supercooled water are intriguing phenomena in condensed-matter science. Rapid spontaneous ice formation that the water can undergo when probed makes finding the LLCP extremely challenging experimentally.

Previously, evidence for polyamorphism relied on indirect signs such as extrapolating unusual physical properties, the presence of two amorphous ice forms, and liquid-liquid transitions in simulations.

Experiments presented by You et al. with isochoric heating of high- and low-density amorphous ices using infrared ultrafast laser pulses followed by x-ray scattering at time scales before ice formation have directly and convincingly demonstrated two liquid states near a critical point in supercooled water ...

Abstract

The search for the liquid-liquid critical point in supercooled water is challenging owing to rapid crystallization. We studied supercooled water at timescales before ice formation by heating high- and low-density amorphous ices using infrared ultrafast laser pulses, followed by x-ray scattering.

By varying the pump laser fluence, we accessed liquid states straddling the predicted critical point. We observed a crossover from a discontinuous to a continuous transition at which broad and slow structural variations occurred, consistent with critical fluctuations and slowing down.

We also observed a rapid increase in the heat capacity indicating a critical divergence at 210 ± 8 K coincident with enhanced density fluctuations. These results suggest that our experiments have directly probed the vicinity of a critical point in supercooled water."

Scientists claim to have found the two types of water that explain the liquid’s oddness | Research | Chemistry World

Experimental Discovery of a New Critical Point in Water (original news release)

Experimental evidence of a liquid-liquid critical point in supercooled water (no public access)

AI system learns to keep warehouse multiple robots traffic running smoothly

Good news!

"Inside autonomous warehouses, even small traffic jams or minor collisions can snowball into massive slowdowns. Now, MIT researchers have developed a system that keeps a fleet of robots moving smoothly. It decides which bots should get the right of way at every moment, avoiding congestion and increasing throughput."

From the abstract:

"Lifelong Multi-Agent Path Finding (MAPF) is critical for modern warehouse automation, which requires multiple robots to continuously navigate conflict-free paths to optimize the overall system throughput. However, the complexity of warehouse environments and the long-term dynamics of lifelong MAPF often demand costly adaptations to classical search-based solvers. While machine learning methods have been explored, their superiority over search-based methods remains inconclusive.

In this paper, we introduce Reinforcement Learning (RL) guided Rolling Horizon Prioritized Planning (RL-RH-PP), the first framework integrating RL with search-based planning for lifelong MAPF.

Specifically, we leverage classical Prioritized Planning (PP) as a backbone for its simplicity and flexibility in integrating with a learning-based priority assignment policy.

By formulating dynamic priority assignment as a Partially Observable Markov Decision Process (POMDP), RL-RH-PP exploits the sequential decision-making nature of lifelong planning while delegating complex spatial-temporal interactions among agents to reinforcement learning.

An attention-based neural network autoregressively decodes priority orders on-the-fly, enabling efficient sequential single-agent planning by the PP planner. Evaluations in realistic warehouse simulations show that RL-RH-PP achieves the highest total throughput among baselines and generalizes effectively across agent densities, planning horizons, and warehouse layouts.

Our interpretive analyses reveal that RL-RH-PP proactively prioritizes congested agents and strategically redirects agents from congestion, easing traffic flow and boosting throughput. These findings highlight the potential of learning-guided approaches to augment traditional heuristics in modern warehouse automation."

AI system learns to keep warehouse robot traffic running smoothly | MIT News | Massachusetts Institute of Technology "This new approach adapts to decide which robots should get the right of way at every moment, avoiding congestion and increasing throughput."

Learning-guided Prioritized Planning for Lifelong Multi-Agent Path Finding in Warehouse Automation (no public access)

Donald Trump says US strongly considering NATO exit, Telegraph newspaper says

Food for thought! Is NATO still necessary and viable? What comes next?

Donald Trump says US strongly considering NATO exit, Telegraph newspaper says | The Jerusalem Post "Trump described the alliance as a "paper tiger" and said removing the United States from the defense pact was now "beyond reconsideration," the newspaper reported."

English for trippers: Follow the fellow on fallow land

Hello, there is a fellowship for everything!

Trump EPA Ends Exorbitant Pay-Outs to Litigious Environmental Nonprofits

Good news! Bravo!

"Since 2013, millions of dollars in attorneys’ fees have been awarded to entities, usually nonprofits, to resolve environmental law litigation against the federal government. New data collected via Freedom of Information Act shows that in the first year of the Trump administration, environmental attorney fee pay outs have seen record lows.

As Open the Books has reported in the past, these fees are often part of “sue-and-settle” schemes where environmental nonprofits friendly to a presidential administration (typically Democratic) will sue the federal government to initiate a back-door rule making process that can exclude Congress and the public. ...

While Environmental Protection Agency Administrator Lee Zeldin hasn’t made many public statements about sue-and-settle practices since taking office at the head of the agency, a spokesperson told Open the Books last year:

“Outside activist groups should not dictate EPA’s agenda or federal environmental policy. The Trump Administration is keenly aware of concerns with sue-and-settle practices and commits to not engage in them. The Trump EPA will respect the rule of law and the will of the American people in setting policy based on its statutory mandates and Gold Standard Science, not based on side deals with outside activist groups dead-set on driving up costs to Americans or advancing the interests of our foreign adversaries.”

New data indicates Zeldin has kept his word, as attorney fee payouts in 2025 for litigation under the Clean Water Act, Clean Air Act, and Endangered Species Act (three of the most important laws under which most environmental litigation is filed) have been at their lowest level since 2013, when our records begin, at a little more than $510,000. ..."

Source

Why does the body deem some foods safe and others unsafe?

Amazing stuff!

"Highlights

• Scientists identify three new proteins, one each from soybean, corn, and wheat, that the body uses to determine oral tolerance—the opposite of food allergy
• They found that specialized immune cells called regulatory T cells interact with these proteins in the gut
• By understanding tolerance, researchers can better understand food allergies and begin to imagine future immunotherapies that promote tolerance rather than allergic reactions

...

identifies new bits of food proteins that tell gut immune cells when to tolerate certain foods. They found three of these protein segments, called epitopes—one each from soybean, corn, and wheat. These epitopes interact with specialized immune cells called regulatory T cells to inform that tolerance-or-rejection decision. ..."

"Editor’s summary

Immunological tolerance to dietary antigens is essential for preventing food allergies and digestive disorders such as celiac disease. However, the specific food-derived antigens that contribute to immune tolerance remain poorly described. Blum et al. mapped the dietary epitopes recognized by food-responsive T cell receptors (TCRs) derived from murine intestinal regulatory T (Treg) cells.

Seed storage proteins from corn, wheat, and soy, including the maize protein αZein, were targets of food-responsive Treg cell TCRs. αZein-specific Treg cells suppressed T cell responses to αZein ex vivo and after adoptive transfer into naive mice. These findings provide insight into the dietary components recognized by naturally occurring Treg cells that mediate oral tolerance. ...

Abstract

Food antigens elicit immune tolerance through the action of intestinal regulatory T (Treg) cells. Unlike food allergens, the proteins that mediate tolerance are mostly undescribed.

Here, we found that epitopes derived from seed storage proteins are targets of murine intestinal Treg cells, with the most frequent response targeting the C terminus of the maize protein alpha-zein.

A major histocompatibility complex (MHC) tetramer loaded with this antigen revealed that zein-specific T cells are predominantly intestinal Treg cells, develop concurrently with weaning, and constitute up to 2% of the peripheral Treg cell pool. Zein-responsive Treg cells repressed naïve T cell proliferation ex vivo, and prior dietary exposure resulted in a constrained response upon diverse inflammatory challenges in vivo, supporting a specific role for gut-resident Treg cells in suppressing systemic immune responses.

Our work reveals the development, immune-suppressive characteristics, and function of naturally occurring Treg cells that recognize dietary seed storage proteins, a previously undescribed class of antigens in oral tolerance."

Why does the body deem some foods safe and others unsafe? - Salk Institute for Biological Studies "Study co-led by scientist now at Salk Institute finds three new proteins that the body uses to determine “safe” foods, helping understand food tolerance and allergy"

Identification and characterization of dietary antigens in oral tolerance (no public access)

Tiny implantable, high density ‘cell factories’ produce drugs inside the body

Good news!

"Tiny devices containing cells engineered to continuously produce drugs could one day deliver medicines from inside the body without requiring patients to remember to administer doses.

Researchers have designed a device called hybrid oxygenation bioelectronics system for implanted therapy, or HOBIT, in a step towards realising this goal.

The system hides genetically-engineered cells from the immune system while producing its own oxygen and nutrients to keep the cells alive.

It contains a cell chamber to house the cells, an electrochemical device to generate oxygen by splitting water molecules and electronics and a battery to regulate oxygen production while wirelessly communicating with external devices.

In a proof-of-concept study the team engineered cells to produce an anti-HIV antibody, a GLP-1-like peptide used to treat type 2 diabetes and leptin, a hormone that regulates appetite and metabolism. They implanted the devices under the skin of rats and monitored drug levels in the animals’ bloodstreams for 30 days.

Levels remained stable across the study period. About 65% of the cells were still viable by the end of the experiment. ..."

From the highlights and abstract:

"The bigger picture

.... The difficulty lies in making cells potent enough to be clinically relevant and easy to administer. The hybrid oxygenation bioelectronics system for implanted therapy (HOBIT) device solves these problems: supplemental oxygen is produced at the site of implant and enables a greater density of cells in the subcutaneous space, allowing a minimally invasive procedure to deliver a complex biologic regimen in a proof-of-concept model. From here, the platform can be expanded to target a variety of diseases or cell types to maximize efficacy and feasible translation.

Highlights

• A fully implantable, subcutaneous device enables high-density cell therapy

• Complex biologic therapy regimens are enabled with the HOBIT design

• The HOBIT device demonstrates power-efficient, subcutaneous oxygen generation

Summary

Cell therapy shows promise for sustained delivery of therapeutics, allowing a single dose to replace repeated injections and lasting many months to years. As cells are typically delivered systemically, a natural progression of cell therapy is to miniaturize and compact the cells into a single device. However, the nutrient requirements, coupled with practical limits on device size, limit its application. In addition, while the subcutaneous space presents a convenient location for implantation, oxygen supply is limited and restricts the density of effective cell therapy.

To address this problem, we designed and validated a wireless, fully implantable platform to produce local oxygen and increase the maximum cell density. We demonstrate that encapsulated cells with a density of 60 million cells per mL are viable in our device for 31 days in vivo. This technology has the potential to serve as a platform for cell therapy, allowing clinically relevant doses with minimally invasive implants."

Implantable ‘cell factories’ produce drugs inside the body | News | ConnectSci

Design of a wireless, fully implantable platform for in-situ oxygenation of encapsulated cell therapies (no public access)

Graphical abstract

What changes happen in the aging brain? A comprehensive single-cell atlas to date of epigenetic changes in the aging mouse brain

Very impressive!

"Highlights

• Salk researchers create epigenetic atlas of cell type-specific changes in the aging mouse brain
• The atlas represents eight different brain regions and 36 different cell types, and shows clear epigenetic differences associated with different ages
• The new resource—available publicly on Amazon Web services—can be used to unravel age-related contributions to neurodegenerative diseases like Alzheimer’s, Parkinson’s, and ALS

...

One major mechanistic influence on aging is epigenetic change: the way small chemical tags on top of our base genetic code shift over time to alter gene expression. Salk researchers created the most comprehensive single-cell atlas to date of epigenetic changes in the aging mouse brain, revealing how DNA methylation, genome structure, and gene activity change across brain regions and cell types. The new atlas represents eight brain regions and 36 distinct brain cell types, with over 200,000 single cells profiled across methylation and chromatin conformation assays, plus nearly 900,000 cells captured with spatial transcriptomics. ..."

What changes happen in the aging brain? - Salk Institute for Biological Studies "Salk Institute scientists create atlas of cell type-specific epigenetic changes that occur in the mouse brain as it ages to better understand the basis of neurodegenerative diseases"

Salk researchers used spatial transcriptomics to map where different cell types reside in the mouse brain. Shown are excitatory neurons (left, blue), inhibitory neurons (middle, red), and non-neuronal cells (right, green), color-coded by cell type.