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Alzheimer’s and the Complex Scientific Inquiry Process

This webcast provides an interesting look at the complex scientific inquiry process: An Alzheimer’s Drug That Doesn’t Treat Alzheimer’s?

Medical research is complex. Once we figure out what is most critical and discover effective treatments often the explanations can then make it seem fairly simple. But that process is often decades of efforts that include years of frustration and confusion.

For long term medical impacts we often need to guess at important biomarker indications that may be closely related to health outcomes. But that process often isn’t as easy as it sounds.

Much Alzheimer’s research for the last few decades has focused on amyloid plaque reduction.

A new Alzheimer’s drug has been approved. But should you take it?

Aducanumab (brand name Aduhelm) is a monoclonal antibody engineered in a laboratory to stick to the amyloid molecule that forms plaques in the brains of people with Alzheimer’s. Most researchers believe that the plaques form first and damage brain cells, causing tau tangles to form inside them, killing the cells. Once aducanumab has stuck to the plaque, your body’s immune system will come in and remove the plaque, thinking it’s a foreign invader. The hope and expectation are that, once the plaques are removed, the brain cells will stop dying, and thinking, memory, function, and behavior will stop deteriorating.

I personally do not think the drug should have been approved. Continued research would be fine, but approving an extraordinarily expensive drug without strong evidence of significant positive health outcomes is very poor public policy.

Related: The Amazing Reality of Genes and The History of Scientific InquiryScientific Inquiry Leads to Using Fluoride for Healthy TeethIntroduction to Fractional Factorial Designed ExperimentsBenefits of a Mediterranean Diet May Include Reduced Risk of Cognitive Impairment As We Age

mRNA Vaccine Targets Ticks to Allow Us to Avoid Diseases Ticks Carry

A lab-stage mRNA vaccine targeting ticks may offer protection against Lyme and other tick-borne diseases

A new laboratory-stage mRNA vaccine that teaches the immune system to recognize the saliva from tick bites could prevent these bugs from feeding on and transmitting tick-borne diseases to people

What’s unique about the 19ISP mRNA vaccine is that instead of directly targeting the pathogen that causes the disease like traditional vaccines, 19ISP was able to stimulate resistance to the carrier of the disease, ticks, and prevent them from transmitting the pathogen in the first place. Our study also suggests that this form of tick-based vaccination – teaching the body to rapidly recognize and react to being bitten by a tick – may be sufficient to prevent infection.

mRNA vaccines have been in the news a great deal due to the covid19 mRNA vaccines. The potential for mRNA solutions is very promising. If this research can be confirmed and brought to market it could save us from Lyme disease and other diseases transmitted via ticks.

Related: New and Old Ways to Make Flu Vaccines (2007)Vaccines Can’t Provide Miraculous Results if We Don’t Take ThemScientific Illiteracy Leads to Failure to Vaccinate Which Leads to Death (2012)US Fish and Wildlife Service Plans to Use Drones to Drop Vaccine Treats to Save Ferrets

Toyota Mirai – Hydrogen Fuel Cell Electric Car

I am curious, even skeptical, about the potential for hydrogen fuel cell versus battery passenger cars. I do respect Toyota and so am wondering if they do indeed see something that most others are missing.

The current production Toyota Mirai has a range of 650 km.

I do think hydrogen fuel cells may provide a better option for larger vehicles (maybe even shipping), but I have done next to no research on this so I may be wrong.

It seem unlikely to me that hydrogen fuel cell passenger cars are going to make it but I would be happy to be wrong. Perhaps the advantages will overcome what seem to me to be challenges that are going to prevent them from being successful. I am confused about how committed to this strategy Toyota is (which makes me question my belief that hydrogen fuel cell passenger cars are not going to be successful).

Related: Toyota Engineering Development ProcessToyota Develops Thought-controlled WheelchairHow to Develop Products like Toyota (2011)Innovation at ToyotaElectric Cars (post on our blog in 2007)Toyota Scion iQ: 37 MPG (2011)Toyota Engineers a New Plant: the Living Kind (2005)

Science Explained: Wind Powered Vehicle Traveling Faster Than the Wind

This is an interesting explanation of a the physics involved with vehicle propulsion. And it is a great video showing the scientific method at work.

They only touch on it a little bit but the need for creating 4 versions of the small treadmill device to illustrate the principles in action is a great example of how science inquiry and engineering work. There are often many failed attempts before an engineering solution to the issue involved can be properly created (video on Xyla Foxlin’s efforts: Building the Vehicle Physicists Called Impossible).

Enjoy the videos.

Veritasium is also offering 3 prizes to split the $10,000 for 1 minute videos that highlight science communicators with his Veritasium Science Communication Contest.

Related: The Amazing Reality of Genes and The History of Scientific InquiryScience Explained: Momentum For String of Metal BeadsCircumhorizontal Arcs – Fire Rainbows – Cloud RainbowsScientific Inquiry Leads to Using Fluoride for Healthy Teeth

Benefits of a Mediterranean Diet May Include Reduced Risk of Cognitive Impairment As We Age

Medical studies about healthy living are very complex and not easy to draw clear conclusions from. But the evidence continues to grow on the benefits of a healthy Mediterranean diet.

Mediterranean diet may prevent memory loss and dementia, study finds

The true diet is simple, plant-based cooking, with the majority of each meal focused on fruits and vegetables, whole grains, beans and seeds, with a few nuts and a heavy emphasis on extra-virgin olive oil. Fats other than olive oil, such as butter, are consumed rarely, if at all. And say goodbye to refined sugar or flour.

Meat can make a rare appearance, but usually only to flavor a dish. Instead, meals may include eggs, dairy and poultry, but in much smaller portions than in the traditional Western diet. However, fish, which are full of brain-boosting omega-3’s, are a staple.

“Eating a healthy plant-based diet is associated with better cognitive function and around 30% to 35% lower risk of cognitive impairment during aging,” lead author Claire McEvoy, assistant professor at Queen’s University Belfast

I am skeptical of the size of the risk reduction. It is seems decades of health studies show that precise measures are not that trustworthy. But it does seem that there are many benefits to a Mediterranean diet.

photo of fish dish

This is actually a photo of a dinner I enjoyed while in Malaysia (which just is one I had easy access to add to this post)

I have been taking this into account in my eating. I try to eat much more green leafy vegetable (though more is from my very low levels before). I try to reduce the amount of meat and increase the amount of fish and nuts. I try to eat enough fiber and I eat yogurt. I try to eat more fruits and vegetables in general. I try to reduce the amount of processed foods and sugar. My diet is far from great but it is much better than is was 20 years ago. I have probably been focused on doing better for over 10 years (post from 9 years ago: Healthy Diet, Healthy Living, Healthy Weight).

Related: Eat food. Not too much. Mostly plants.Big Fat LiePhysical Activity for Adults: Inactivity Leads to 5.3 Million Early Deaths a YearHow Healthy Is Squid for Us?Obesity Epidemic Explained – Kind Of

Huge Proposed Increases in USA Government Science and Engineering Support

The Biden administration has proposed greatly increasing USA government spending on science and engineering. They are proposing levels last seen in the 1960s when the USA was most committed to science and engineering spending (as most visibly seen in support for NASA).

Advance U.S. leadership in critical technologies and upgrade America’s research infrastructure. U.S. leadership in new technologies—from artificial intelligence to biotechnology to computing—is critical to both our future economic competitiveness and our national security. Based on bipartisan proposals, President Biden is calling on Congress to invest $50 billion in the National Science Foundation (NSF), creating a technology directorate that will collaborate with and build on existing programs across the government. It will focus on fields like semiconductors and advanced computing, advanced communications technology, advanced energy technologies, and biotechnology. He also is calling on Congress to provide $30 billion in additional funding for R&D that spurs innovation and job creation, including in rural areas. His plan also will invest $40 billion in upgrading research infrastructure in laboratories across the country, including brick-and-mortar facilities and computing capabilities and networks. These funds would be allocated across the federal R&D agencies, including at the Department of Energy. Half of those funds will be reserved for Historically Black College and Universities (HBCUs) and other Minority Serving Institutions, including the creation of a new national lab focused on climate that will be affiliated with an HBCU.

Establish the United States as a leader in climate science, innovation, and R&D. The President is calling on Congress to invest $35 billion in the full range of solutions needed to achieve technology breakthroughs that address the climate crisis and position America as the global leader in clean energy technology and clean energy jobs. This includes launching ARPA-C to develop new methods for reducing emissions and building climate resilience, as well as expanding across-the-board funding for climate research. In addition to a $5 billion increase in funding for other climate-focused research, his plan will invest $15 billion in demonstration projects for climate R&D priorities, including utility-scale energy storage, carbon capture and storage, hydrogen, advanced nuclear, rare earth element separations, floating offshore wind, biofuel/bioproducts, quantum computing, and electric vehicles, as well as strengthening U.S. technological leadership in these areas in global markets.

Eliminate racial and gender inequities in research and development and science, technology, engineering, and math. Discrimination leads to less innovation: one study found that innovation in the United States will quadruple if women, people of color, and children from low-income families invented at the rate of groups who are not held back by discrimination and structural barriers. Persistent inequities in access to R&D dollars and to careers in innovation industries prevents the U.S. economy from reaching its full potential. President Biden is calling on Congress to make a $10 billion R&D investment at HBCUs and other MSIs. He also is calling on Congress to invest $15 billion in creating up to 200 centers of excellence that serve as research incubators at HBCUs and other MSIs to provide graduate fellowships and other opportunities for underserved populations, including through pre-college programs.

This text is from The White House Infrastructure Plan (The American Jobs Plan). Likely this link will stop working in several years (once a new administration takes over.
photo of NASA's Mars Rover: Curiosity
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I Just Finished Statistics for Experimenters and I Cannot Praise it Enough

Guest post by Michael Betancourt.

I just finished Box, Hunter, and Hunter (Statistics for Experimenters) and I cannot praise it enough. There were multiple passages where I literally giggled. In fact I may have been a bit too enthusiastic about tagging quotes beyond “all models are wrong but some are useful” that I can’t share them all.

photo of Statistics for Experimenters with many blue bookmarks shown

I wish someone had shared this with me when I was first learning statistics instead of the usual statistics textbooks that treat model development as an irrelevant detail. So many of the elements that make this book are extremely relevant to statistics today. Some examples:

  • The perspective of learning from data only through the lens of the statistical model. The emphasis on sequential modeling, using previous fits to direct better models, and sequential experiments, using past fits to direct better targeted experiments.
  • The fixation on checking model assumptions, especially with interpretable visual diagnostics that capture not only residuals but also meaningful scales of deviation. Proto visual predictive checks as I use them today.
  • The distinction between empirical models and mechanistic models, and the treatment of empirical linear models as Taylor expansions of mechanistic models with covariates as _deviations_ around some nominal value. Those who have taken my course know how important I think this is.
  • The emphasis that every model, even mechanistic models, are approximations and should be treated as such.
  • The reframing of frequentist statistical tests as measures of signal to noise ratios.
  • The importance of process drift and autocorrelation in data when experimental configurations are not or cannot be arbitrarily randomized.
  • The diversity of examples and exercises using real data from real applications with detailed contexts, including units everywhere.

Really the only reason why I wouldn’t recommend this as an absolute must read is that the focus on linear models and use of frequentist methods does limit the relevance of the text to contemporary Bayesian applications a bit.

Texts like these make me even more frustrated by the desire to frame movements like data science as revolutions that give people the justification to ignore the accumulated knowledge of applied statisticians.

Academic statistics has no doubt largely withdrawn into theory with increasingly smaller overlap with applications, but there is so much relevant wisdom in older applied statistics texts like these that doesn’t need to be rediscovered just reframed in a contemporary context.

Oh, I forgot perhaps the best part! BHH continuously emphasizes the importance of working with domain experts in the design and through the entire analysis with lots of anecdotal examples demonstrating how powerful that collaboration can be.

I felt so much less alone every time they talked about experimental designs not being implemented properly andthe subtle effects that can have in the data, and serious effects in the resulting inferences, if not taken into account.

Michael Betancourt, PhD, Applied Statistician – long story short, I am a once and future physicist currently masquerading as a statistician in order to expose the secrets of inference that statisticians have long kept from scientists. More seriously, my research focuses on the development of robust statistical workflows, computational tools, and pedagogical resources that bridge statistical theory and practice and enable scientists to make the most out of their data.
Twitter: @betanalpha
Website: betanalpha
Patreon: Michael Betancourt

Related: Statistics for Experimenters, Second EditionStatistics for Experimenters in SpanishStatistics for Experimenters ReviewCorrelation is Not Causation

Molecular Motor Proteins

Webcast on amazing processes inside cells by Ron Vale.

Molecular motor proteins are fascinating enzymes that power much of the movement performed by living organisms. The webcast provides an overview of the motors that move along cytoskeletal tracks (kinesin and dynein which move along microtubules and myosin which moves along actin). The talk first describes the broad spectrum of biological roles that kinesin, dynein and myosin play in cells. The talk then discusses how these nanoscale proteins convert energy from ATP hydrolysis into unidirectional motion and force production, and compares common principles of kinesin and myosin. The talk concludes by discussing the role of motor proteins in disease and how drugs that modulate motor protein activity can treat human disease.

Ron Vale is a Professor of Cellular and Molecular Pharmacology at the University of California, San Francisco and an Investigator of the Howard Hughes Medical Institute. He is also the founder of the iBiology project.

Related: Animations of Motor Proteins Moving Material Inside CellsScience Explained: How Cells React to Invading VirusesLooking Inside Living Cells

Popular Posts on the Curious Cat Science and Engineering Blog in the Last Decade

These were the most popular (by number of page views) posts on our blog in the last decade.

photo of John Hunter with snow covered mountain peaks in the background

John Hunter, Olympic National Park (where the mountain peaks are colder and covered in snow)

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Regeneron High School Science Talent Search 2019

$3.1 million in prizes was awarded through the Regeneron Science Talent Search 2019, including $2,000 to each of the top 300 scholars and their schools. The top award was for $250,000. If you want to watch the video without knowing the winner, watch it before reading the rest of this post.

Every year the accomplishments of high school students provide amazing hope for the future. I am glad for the organizations that highlight the efforts of these students and provide awards for a few of the most amazing accomplishments. The top 40 students all get at least $25,000 (with the top 10 getting more).

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Scientists Watch Single Cell Organisms Evolve Multicellular Trait in Response to Predation

The scientists used the ciliate predator Paramecium tetraurelia to select for the de novo evolution of multicellularity in outcrossed populations of C. reinhardtii. They show that multicellular life cycles that evolved were passed on to future generations (the change was heritable). The evolved multicellular life cycles are stable over thousands of asexual generations in the absence of predators. Because C. reinhardtii has no multicellular ancestors, these experiments represent a novel origin of multicellularity.

De novo origins of multicellularity in response to predation

Here we show that de novo origins of simple multicellularity can evolve in response to predation. We subjected outcrossed populations of the unicellular green alga Chlamydomonas reinhardtii to selection by the filter-feeding predator Paramecium tetraurelia. Two of five experimental populations evolved multicellular structures not observed in unselected control populations within ~750 asexual generations.

The control populations remained unicellular. The populations subjected to predation evolved in different ways including one that formed stereotypic eight-celled clusters (Fig. 1A), with an apparent unicellular and tetrad life stage.

electron microscope images of multicellular colonies from evolved populations

Scanning electron micrographs of representative multicellular colonies from evolved populations. (A) Shows an amorphous cluster from population B2. Cell number varies greatly between clusters in this clone and between clones in this population. (B) Shows an eight-celled cluster from population B5. Octads were frequently observed in both populations.

an external membrane is visible around both evolved multicellular colonies, indicating that they formed clonally via repeated cell division within the cluster, rather than via aggregation.

The article also provides details on the scientific inquiry process where theory meets practical realities of observation. I think these ideas are very important and we often gloss over such details. This article was shared as an open access article and is written so that those who are interested in science but are not scientists can understand, which is a valuable. The research was funded by USA National Science Foundation, the John Templeton Foundation, the NASA Astrobiology Institute, a NASA Postdoctoral Program Fellowship and a Packard Foundation Fellowship. And the researchers work at public and private universities. Such research should all be published in an open access manner.

Related: The Amazing Reality of Genes and The History of Scientific InquiryParasite Evolved from Cnidarians (Jellyfish etc.)Why Don’t All Ant Species Replace Queens in the Colony, Since Some DoScientific Inquiry Leads to Using Fluoride for Healthy TeethMechanical Gears Found in Jumping Insects