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NNadir
NNadir's Journal
NNadir's Journal
July 29, 2022
While we're all waiting smugly for the grand so called "renewable energy" transition that did not come, is not here, and won't come, we're burning coal, recently resurgently. We often think of the carbon dioxide in coal, but we seldom pay attention to the volatile elements it releases on combustion, notably lead, mercury and cadmium. (Soils in China have significant natural cadmium, although the mining of cadmium for batteries and other electrical devices has greatly exacerbated the levels found in Chinese soils.)
The point is that a huge fraction of soil is "contaminated," and realistically, we don't actually know where those soils are and what's growing in them.
Bad news I think.
Some rather sobering info on heavy metals in biomass and its fate in pyrolytic systems.
For various reasons, I'm way behind in reading this journal, but I came across a paper published in March that I find a bit unsettlng.
By way of full disclosure, I'm a big fan of biomass pyrolysis - "waste biomass" - as a tool for capture of CO2 from the air.
I won't have the time to go into any detail about this, and it is after all a review article, but here it is:
Roles of Heavy Metals during Pyrolysis and Gasification of Metal-Contaminated Waste Biomass: A Review Abdul Raheem, Qing He, Fareed Hussain Mangi, Chinnathan Areeprasert, Lu Ding, and Guangsuo Yu Energy & Fuels 2022 36 (5), 2351-2368.
This table from the paper is for lack of a better word, disturbing:
This figure is also troubling.
The caption:
Figure 2. Proportions of heavy metals in char (a), liquids (b), and gases (c). Reproduced with permission from Zhang et al. (46)
While we're all waiting smugly for the grand so called "renewable energy" transition that did not come, is not here, and won't come, we're burning coal, recently resurgently. We often think of the carbon dioxide in coal, but we seldom pay attention to the volatile elements it releases on combustion, notably lead, mercury and cadmium. (Soils in China have significant natural cadmium, although the mining of cadmium for batteries and other electrical devices has greatly exacerbated the levels found in Chinese soils.)
The point is that a huge fraction of soil is "contaminated," and realistically, we don't actually know where those soils are and what's growing in them.
Bad news I think.
July 28, 2022
Figure 1:
The caption:
For the period covered by the graphic, with the largest number of accidents taking place in 2017, around 180, probably of the result of more and more of this future trash being built because of a mentality that is reminiscent of a cargo cult, in "percent talk" fires had declined to around 14 percent, around 40 in real numbers.
The paper continues:
I think the need would be less "urgent" if we simply stopped building these unicorn chimeras that have proved to be a phantasm, at least for anyone serious about climate change. That's just my opinion though.
I often remark that wind turbines, because of their low capacity utilization, require redundant back up systems, and as almost all of these are dangerous fossil fueled power plants, the wind industry does nothing more to entrench fossil fuel abuse. The next paragraph gives a rather stark account of the other dangerous fossil fuel dependence on these systems:
I added the bold.
A table from the paper:
The TGA (thermogravimetric analysis) curves:
The caption:
The caption:
Another table based on this data of the combustion of this stuff:
Here's a cool equation from the paper, posted as a graphics object, with which I was unfamiliar (I'm not much of a student of fire science) :
Additional figures from the paper:
The caption:
There's a lot of stuff discussed in this fine, detailed paper, but I've run out of time to comment on it.
It would be acceptable, of course, had all the decades of cheering for wind energy had done something to address climate change. It didn't. It isn't. It won't.
Of course, the point of the wind and solar industry as is often demonstrated, the nation of Germany being the most egregious case, was never even remotely interested in addressing climate change. It was always about the willful destruction of valuable nuclear energy infrastructure. It was always about indulging the dopey fantasies thrown about lazily anti-nukes that exposure to low level radiation would be extremely deadly, a malign embrace of the LNT that has ended up causing tens of millions, hundreds of millions of deaths, because nuclear energy saves lives that would otherwise be lost to air pollution, and now, extreme temperatures.
Nuclear energy is not risk free. I would note that this paper describes instantaneous deaths - which count for more on a disability lost years of life (DALY) calculation - from the wind industry that is higher than the instanteous deaths attributed to radiation from the big boogeyman at Fukushima.
But the biggest risk of the wind industry has nothing to do with fires or other wind accidents. The biggest risk is that the wind industry generates more complacency than energy, the bizarre and demonstrably false belief that everything will be OK, so long as we worship the wind and the sun.
Everything is not OK. It hasn't been OK for a long time. It won't be OK as long as we continue of this path of fantasy.
Have a nice day.
Flammability hazards of typical fuels used in wind turbine nacelle
The paper I'll discuss briefly comes from the Wiley journal Fire and Materials: Wang Zhenhua, You Fei, Guillermo Rein, Jiang Juncheng, Han Xuefeng, Han Junhua, Sun Wei, Flammability hazards of typical fuels used in wind turbine nacelle Fire and Materials. 2018; 42: 770–781.
The paper caught my eye because I have been interested, for sometime in thermal analysis techniques, although quite honestly I have never been able to convince my management to buy a TGA/DSC system, although we've looked at several such units and have had presentations from a number of companies that make them. (There isn't much call for it immediately.)
As I frequently point out, often with appeal to the : Master Register of Wind Turbines the lifetime of wind turbines is short. In this comprehensive database, one can follow the decline in performance of wind turbines and learn that an average lifetime for a wind turbine is less than 18 years. Some last considerably longer than that, others revert to landfill in less than 5 years, some even in less than a year.
Most of the wind turbines that fail simply wear out and become useless hulks, but accidents are well known: I'll show a graphic below giving some real numbers.
I often point out that wind turbine plants are often situated in wilderness rendered into industrial parks. When they are located in once virgin forest, some of the forest, that not needed for access roads for huge diesel trucks, some of the forest is left intact.
It should surprise no one that the grotesque failure of so called "renewable energy" to address climate change has left forests all over the world in flames, particularly in the last several years where desiccating extreme heat events are observed where never seen previously.
Ignition sources are to be, um, discouraged, not that the "renewable energy will save us" - so called "renewable energy" has not and is not saving us - crowd really cares about huge networks of wires to hook all this crap us, or the fact that these units do catch fire.
Most wind turbine accidents are not fires, but one can easily insert the search term, wind turbine fires, into Google, click on images, and see lots and lots of them.
A favorite of mine is one in which the burning vanes trace out beautiful helices of smoke in the sky; a video can be found on the internet.
Anyway, the introductory text from the paper:
Wind power has become a globally recognized and vigorously developed source of renewable energy.1, 2 Until 2016, the global newly added and cumulative installed capacities of wind turbine have been 54.6 and 486.8 GW, respectively.3
For double-fed induction generator–type wind turbines, the main components usually include rotor (hub and blades); nacelle (generator, gearbox, brake, electronic controller, transformer, and control system); tower; and base,4 among which the nacelle is regarded to be core. Until now, the nacelles of modern wind (MW capacity) turbines have reached dimensions of a small single-family dwelling room.5 However, a traditional wind turbine nacelle is generally a small, confined, and crowed space, in which high-value electrical equipment and the 4 flammable materials, such as sound-insulation polyurethane foam, glass fiber-reinforced polymer shell, electric cables, transformer oil, hydraulic oil, gear oil, and other lubricants, are housed.6 Therefore, oil leakage, hot work, bad ventilation, high-speed braking, overheating of electrical components, aging and breakdown of cables, and poor maintenance could cause a fire. An extensive documentation of wind turbine accidents is provided by the Caithness Windfarm Information Forum database (see Figure 1).7 This database includes all documented cases of wind turbine–related accidents that can be found and confirmed through press reports or official releases. By the end of 2017, among 2186 documented cases, there were nearly 316 fires (14.5%), rating second after blade failure (17.2%). Actually, there is a growing trend of wind turbine fires due to increasing installations of wind power equipment.
For double-fed induction generator–type wind turbines, the main components usually include rotor (hub and blades); nacelle (generator, gearbox, brake, electronic controller, transformer, and control system); tower; and base,4 among which the nacelle is regarded to be core. Until now, the nacelles of modern wind (MW capacity) turbines have reached dimensions of a small single-family dwelling room.5 However, a traditional wind turbine nacelle is generally a small, confined, and crowed space, in which high-value electrical equipment and the 4 flammable materials, such as sound-insulation polyurethane foam, glass fiber-reinforced polymer shell, electric cables, transformer oil, hydraulic oil, gear oil, and other lubricants, are housed.6 Therefore, oil leakage, hot work, bad ventilation, high-speed braking, overheating of electrical components, aging and breakdown of cables, and poor maintenance could cause a fire. An extensive documentation of wind turbine accidents is provided by the Caithness Windfarm Information Forum database (see Figure 1).7 This database includes all documented cases of wind turbine–related accidents that can be found and confirmed through press reports or official releases. By the end of 2017, among 2186 documented cases, there were nearly 316 fires (14.5%), rating second after blade failure (17.2%). Actually, there is a growing trend of wind turbine fires due to increasing installations of wind power equipment.
Figure 1:
The caption:
Statistics of the total number of wind turbine accidents involving fires since 1970s
For the period covered by the graphic, with the largest number of accidents taking place in 2017, around 180, probably of the result of more and more of this future trash being built because of a mentality that is reminiscent of a cargo cult, in "percent talk" fires had declined to around 14 percent, around 40 in real numbers.
The paper continues:
n over 90.0% of reported wind turbine fires, a total loss of the wind turbine or, at least, a severe structural failure of the major components (eg, blades, nacelle, and mechanical or electrical components)8 as shown in Figure 2. Moreover, even in the case of early detection, there is no possibility for the fire brigade to fight the fire because of the considerable height of the nacelle and limited accessibility. Even worse is that burning fragments and molten metal can fall from the turbine housing to ignite nearby vegetation and start forest or grassland fires. The guides of “VdS Schadenverhütung GmbH” and “VdS 3523en : 2008-07 (01) Wind turbines: Fire protection guideline,” publications by the German Insures (GDV e.V.) on the issue of loss prevention, estimate a loss of €5000 per week if a 20-year-old 2-MW wind turbine is out of operation.9 Therefore, there is an urgent demand to conduct fundamental research on wind turbine fires...
I think the need would be less "urgent" if we simply stopped building these unicorn chimeras that have proved to be a phantasm, at least for anyone serious about climate change. That's just my opinion though.
I often remark that wind turbines, because of their low capacity utilization, require redundant back up systems, and as almost all of these are dangerous fossil fueled power plants, the wind industry does nothing more to entrench fossil fuel abuse. The next paragraph gives a rather stark account of the other dangerous fossil fuel dependence on these systems:
As mentioned above, flammable fuels of different phases are present in a nacelle in significant quantities. For example, up to 900 L of lubricating oil is contained in the nacelle of a single 1.5-MW offshore wind turbine.8 Diverse fuels in an 8-MW offshore wind turbine are estimated to be 200 L of grease, 1100 L of hydraulic oil, 2000 L of gear oil, and 3000 kg of transformer oil.11 When exposed to sustained heating or fire conditions, these fuels will decompose, vaporize, generate heat and flame, and produce smoke and toxic gases. As a result, these typical fuels inevitably pose a high threat of initiating and spreading a fire, which may be dangerous and even deadly to operators and maintenance workers. Several severe injuries and deaths linked to wind turbine fires have been reported. For example, 3 workers were injured8, 9 in 2008 and 1 in 2012, and 2 were killed in 2013. Apparently, concerns about the fire performance of these typical fuels have adversely affected their widespread applications in wind turbine nacelles where fire risk is high.
Presently, few studies have been done on wind turbine fires, especially those regarding fire behavior of typical fuels inside nacelles and assessments of their fire hazard. Some work only focused on fire causes and relevant fire protection systems from the viewpoint of engineering, such as the selection of proper and a high-efficiency automatic fire-fighting system...
Presently, few studies have been done on wind turbine fires, especially those regarding fire behavior of typical fuels inside nacelles and assessments of their fire hazard. Some work only focused on fire causes and relevant fire protection systems from the viewpoint of engineering, such as the selection of proper and a high-efficiency automatic fire-fighting system...
I added the bold.
A table from the paper:
The TGA (thermogravimetric analysis) curves:
The caption:
Figure 4: Thermogravimetric curves (pyrolysis in air at 40°C/min) of the 4 fuels
The caption:
Differential thermogravimetric curves (pyrolysis in air at 40°C/min) of the 4 fuels
Another table based on this data of the combustion of this stuff:
Here's a cool equation from the paper, posted as a graphics object, with which I was unfamiliar (I'm not much of a student of fire science) :
Additional figures from the paper:
The caption:
Figure 12: Variations of average smoke release rate (SRR) values of the 4 fuels at different radiant heat fluxes
Figure 13: Schematic of temperature development with time during a potential wind turbine nacelle fire. The dashed line means there exist multiple potential burning behaviors or special fire properties since the nacelle housing is burnt through and ventilation conditions are varied much, say, from originally confined space to semiconfined and even completely open space
There's a lot of stuff discussed in this fine, detailed paper, but I've run out of time to comment on it.
It would be acceptable, of course, had all the decades of cheering for wind energy had done something to address climate change. It didn't. It isn't. It won't.
Of course, the point of the wind and solar industry as is often demonstrated, the nation of Germany being the most egregious case, was never even remotely interested in addressing climate change. It was always about the willful destruction of valuable nuclear energy infrastructure. It was always about indulging the dopey fantasies thrown about lazily anti-nukes that exposure to low level radiation would be extremely deadly, a malign embrace of the LNT that has ended up causing tens of millions, hundreds of millions of deaths, because nuclear energy saves lives that would otherwise be lost to air pollution, and now, extreme temperatures.
Nuclear energy is not risk free. I would note that this paper describes instantaneous deaths - which count for more on a disability lost years of life (DALY) calculation - from the wind industry that is higher than the instanteous deaths attributed to radiation from the big boogeyman at Fukushima.
But the biggest risk of the wind industry has nothing to do with fires or other wind accidents. The biggest risk is that the wind industry generates more complacency than energy, the bizarre and demonstrably false belief that everything will be OK, so long as we worship the wind and the sun.
Everything is not OK. It hasn't been OK for a long time. It won't be OK as long as we continue of this path of fantasy.
Have a nice day.
July 28, 2022
I added the bold.
Source: Derek P. Gregory "Electrochemistry and the Hydrogen Economy," Ch.5 in MODERN ASPECTS OF
ELECTROCHEMISTRY J. O'M. Bockris, and B.E. Conway Eds. Plenum Press, NY © 1975. Excerpt pages 239-240.
No it wasn't Amory Lovins idea; Amory has always been short on original thinking. He may have come across this book while cutting classes; it was published the year before he was declared a genius for saying that energy conservation and solar energy would dominate the world by the year 2000.
Anybody have a hydrogen station near them?
By the way this text has an interesting graphic prediction on the supply of US dangerous natural gas:
The author had nice things to say about nuclear power, the tenor of it being, "we'd better use nuclear power or we'll be in trouble..."
Well, we stopped the high volume building nuclear plants about 1990. Most of them are still running, but we forgot how to build them because of public pressure.
That worked out well, didn't it?
It was 34°C (93°F) today in Portland, Oregon, tomorrow it will be 37°C (99°F) and Friday close to 40°C (103°F). The idea of needing an air conditioner in that area is a new concept but everyone has to keep up with the times, no?
Don't worry, be happy.
"Renewable energy" nirvana will break out "by 2050," just like it did "by 1990," "by 2000," "by 2010," and "by 2020."
Have a nice day tomorrow.
Over the past three years...there has been a surge of interest in...the hydrogen economy...
I had to truncate the text to put in the title space. Let me fix that.
The full text of the excerpt:
"Just imagine," many of us must have often thought, "how much easier our job would be if hydrogen came out of a pipe in the wall like natural gas, or was available by the gallon at the corner gasoline station."
Over the past 3 years (1970-1973), there has been a dramatic surge of interest in a concept that could indeed make this dream a reality. The concept has come to be known as "The Hydrogen Economy"9,11,12.16 and concerns the ultimate replacement of our conventional fossil-fuel economy with a synthetic-fuel system, in 239 240 Electrochemistry and the Hydrogen Economy which hydrogen produced from water by nuclear or solar energy plays the role of oil, gas, and coal in our present energy system and coexists with electric power as a clean, flexible, and universal secondary energy form. Since the universal availability of hydrogen could make such a great difference to the potential role of the fuel cell, and since one of the most attractive processes for producing hydrogen from water is by electrolysis, the development of the hydrogen economy could have a major and positive impact on the field of electrochemistry. At the same time, a negative impact could occur if the hydrogen fueled, internal-combustion-engine-powered vehicle proved to be a more easily realizable goal than the battery- or fuel-cell-powered electric car, or if the bulk storage of electric power as hydrogen proved to be more attractive than the storage battery. It seems appropriate, therefore, to explore the present status of the hydrogen-economy concept to acquaint the electrochemist not only with the direct implications of such a system to his field, but also with the broader issues involved which could have far-reaching ramifications for the entire energy-conversion field.
Over the past 3 years (1970-1973), there has been a dramatic surge of interest in a concept that could indeed make this dream a reality. The concept has come to be known as "The Hydrogen Economy"9,11,12.16 and concerns the ultimate replacement of our conventional fossil-fuel economy with a synthetic-fuel system, in 239 240 Electrochemistry and the Hydrogen Economy which hydrogen produced from water by nuclear or solar energy plays the role of oil, gas, and coal in our present energy system and coexists with electric power as a clean, flexible, and universal secondary energy form. Since the universal availability of hydrogen could make such a great difference to the potential role of the fuel cell, and since one of the most attractive processes for producing hydrogen from water is by electrolysis, the development of the hydrogen economy could have a major and positive impact on the field of electrochemistry. At the same time, a negative impact could occur if the hydrogen fueled, internal-combustion-engine-powered vehicle proved to be a more easily realizable goal than the battery- or fuel-cell-powered electric car, or if the bulk storage of electric power as hydrogen proved to be more attractive than the storage battery. It seems appropriate, therefore, to explore the present status of the hydrogen-economy concept to acquaint the electrochemist not only with the direct implications of such a system to his field, but also with the broader issues involved which could have far-reaching ramifications for the entire energy-conversion field.
I added the bold.
Source: Derek P. Gregory "Electrochemistry and the Hydrogen Economy," Ch.5 in MODERN ASPECTS OF
ELECTROCHEMISTRY J. O'M. Bockris, and B.E. Conway Eds. Plenum Press, NY © 1975. Excerpt pages 239-240.
No it wasn't Amory Lovins idea; Amory has always been short on original thinking. He may have come across this book while cutting classes; it was published the year before he was declared a genius for saying that energy conservation and solar energy would dominate the world by the year 2000.
Anybody have a hydrogen station near them?
By the way this text has an interesting graphic prediction on the supply of US dangerous natural gas:
The author had nice things to say about nuclear power, the tenor of it being, "we'd better use nuclear power or we'll be in trouble..."
Well, we stopped the high volume building nuclear plants about 1990. Most of them are still running, but we forgot how to build them because of public pressure.
That worked out well, didn't it?
It was 34°C (93°F) today in Portland, Oregon, tomorrow it will be 37°C (99°F) and Friday close to 40°C (103°F). The idea of needing an air conditioner in that area is a new concept but everyone has to keep up with the times, no?
Don't worry, be happy.
"Renewable energy" nirvana will break out "by 2050," just like it did "by 1990," "by 2000," "by 2010," and "by 2020."
Have a nice day tomorrow.
July 27, 2022
I added the bold.
The Germans think they can store anything indefinitely through weeks of Dunkelflaute. And let's get serious, they have zero intent to phase out coal, particularly because they pissed off Putin by objecting to his war on Ukraine that they financed. They are killing people right now because they shut their nuclear plants to burn coal.
Now they plan to store chlorine because their energy supplies, much as they did in the 18th century, depend on the weather.
One should recognize whence the "alkyl" in "alkyl ammonium" comes. It comes "alkane" carbon compounds from petroleum and dangerous natural gas, the stuff for which they've sent boatloads of money to Putin, supervised by former Chancellor Gerhardt Schroeder, Gazprom employee. The "ammonium" comes from hydrogen generated by reforming dangerous natural gas, Schroeder/Putin's product.
No kidding.
No kidding...
I just came across this paper:
Alkyl Ammonium Chloride Salts for Efficient Chlorine Storage at Ambient Conditions Patrick Voßnacker, Nico Schwarze, Thomas Keilhack, Merlin Kleoff, Simon Steinhauer, Yuliya Schiesser, Maxime Paven, Sivathmeehan Yogendra, Rainer Weber, and Sebastian Riedel, ACS Sustainable Chemistry & Engineering 2022 10 (29), 9525-9531.
It contains this delicious text:
With a production of 75 million tons per year, chlorine is one of the most important base chemicals. It is used in numerous reactions and involved in the synthesis of roughly 50% of all industrial compounds, 20% of small-molecule pharmaceutical products, and 30% of agrochemicals. (1) Primarily, chlorine is applied in the synthesis of precursors for polymers, e.g., vinyl chloride for PVC and phosgene for polyurethanes and polycarbonates. (2)
However, the production of chlorine by chloralkali electrolysis is an extremely energy-demanding process requiring, for instance, 2% of the entire electrical energy production in Germany. (3) To realize the vision of an exit of coal and nuclear energy, the production of renewable energy (e.g., solar and wind energy) is currently expanded, which results in a more inconsistent energy supply depending on local weather circumstances. Therefore, achieving higher flexibility for energy-intensive processes is a key challenge. (4) Currently, the flexibilization of chlorine production is mainly limited by the lack of techniques for efficient chlorine storage. (5,6)
However, the production of chlorine by chloralkali electrolysis is an extremely energy-demanding process requiring, for instance, 2% of the entire electrical energy production in Germany. (3) To realize the vision of an exit of coal and nuclear energy, the production of renewable energy (e.g., solar and wind energy) is currently expanded, which results in a more inconsistent energy supply depending on local weather circumstances. Therefore, achieving higher flexibility for energy-intensive processes is a key challenge. (4) Currently, the flexibilization of chlorine production is mainly limited by the lack of techniques for efficient chlorine storage. (5,6)
I added the bold.
The Germans think they can store anything indefinitely through weeks of Dunkelflaute. And let's get serious, they have zero intent to phase out coal, particularly because they pissed off Putin by objecting to his war on Ukraine that they financed. They are killing people right now because they shut their nuclear plants to burn coal.
Now they plan to store chlorine because their energy supplies, much as they did in the 18th century, depend on the weather.
One should recognize whence the "alkyl" in "alkyl ammonium" comes. It comes "alkane" carbon compounds from petroleum and dangerous natural gas, the stuff for which they've sent boatloads of money to Putin, supervised by former Chancellor Gerhardt Schroeder, Gazprom employee. The "ammonium" comes from hydrogen generated by reforming dangerous natural gas, Schroeder/Putin's product.
No kidding.
July 26, 2022
The Kairos reactor is Per Peterson's design (UC Berkeley) It's a kind of hybrid reactor, with features of a pebble bed reactor and features of a molten salt reactor with FLIBE coolant.
I'm no longer as enthusiastic as I was about FLIBE, say 10 or 15 years ago, for various reasons, one being it's a thermal spectrum reactor, but even a less than ideal nuclear reactor is better than any dangerous fossil fuel plant and in fact, the so called "renewable energy" junk that entrenches dangerous fossil fuels.
Kairos and Materion commission molten salt purification plant
[link:https://www.world-nuclear-news.org/Articles/Kairos-and-Materion-commission-molten-salt-purific|Kairos and Materion commission molten salt purification plantThe plant, designed by Kairos Power and based at the Materion campus in Elmore, Ohio in the USA, will produce high-purity fluoride salt coolant to be used in high-temperature molten salt reactors.
Kairos Power's fluoride salt-cooled high-temperature reactor (KP-FHR) is cooled by a mixture of lithium fluoride and beryllium fluoride salts known as Flibe, which is chemically stable and operates at low pressure. The molten salt coolant will be used in Karios's engineering test unit and proposed Hermes demonstration reactor as well as future commercial KP-FHR reactors.
Materion is an industry leader in the production and manufacturing of beryllium-based materials and the decision to locate the Molten Salt Purification Plant (MSPP) at its Elmore facility is said to "reinforce a long-term, strategic commitment by both companies to demonstrate leadership in molten salt production".
Ed Blandford, Chief Technology Officer and co-founder, Kairos Power, said: "We are thrilled to announce the commissioning of MSPP, a critical milestone to produce Flibe for KP-FHR technology and the cornerstone of our collaboration with Materion Corporation. MSPP represents a major investment in Kairos Power’s vertical integration strategy to achieve cost certainty by establishing commercial Flibe production. We have confidence in our ability to produce Flibe that meets our nuclear specification for Kairos Power’s testing programme at the scale necessary to supply our major hardware demonstrations..."
Kairos Power's fluoride salt-cooled high-temperature reactor (KP-FHR) is cooled by a mixture of lithium fluoride and beryllium fluoride salts known as Flibe, which is chemically stable and operates at low pressure. The molten salt coolant will be used in Karios's engineering test unit and proposed Hermes demonstration reactor as well as future commercial KP-FHR reactors.
Materion is an industry leader in the production and manufacturing of beryllium-based materials and the decision to locate the Molten Salt Purification Plant (MSPP) at its Elmore facility is said to "reinforce a long-term, strategic commitment by both companies to demonstrate leadership in molten salt production".
Ed Blandford, Chief Technology Officer and co-founder, Kairos Power, said: "We are thrilled to announce the commissioning of MSPP, a critical milestone to produce Flibe for KP-FHR technology and the cornerstone of our collaboration with Materion Corporation. MSPP represents a major investment in Kairos Power’s vertical integration strategy to achieve cost certainty by establishing commercial Flibe production. We have confidence in our ability to produce Flibe that meets our nuclear specification for Kairos Power’s testing programme at the scale necessary to supply our major hardware demonstrations..."
The Kairos reactor is Per Peterson's design (UC Berkeley) It's a kind of hybrid reactor, with features of a pebble bed reactor and features of a molten salt reactor with FLIBE coolant.
I'm no longer as enthusiastic as I was about FLIBE, say 10 or 15 years ago, for various reasons, one being it's a thermal spectrum reactor, but even a less than ideal nuclear reactor is better than any dangerous fossil fuel plant and in fact, the so called "renewable energy" junk that entrenches dangerous fossil fuels.
July 26, 2022
The caption:
The caption:
The caption:
The caption:
Figure 4. Temporal variation in eaq– availability during a 24 h UV/sulfite experiment. (A) Measured MCAA degradation (symbols) as a function of time in Ohio River (20 μM [MCAA]0 spiked into reactor prior to each time point). The best linear fit (line) is also shown. (B) Re–,UV, (C) Rf,teaq–, and (D) kS,t′ (eq 3.6) as function of time for all waters (20 μM [MCAA]0 spiked into reactor prior to each time point). Legend in panel (B) applies to panels (C) and (D). Reported kS,t′ values in panel (D) are within the eaq– scavenging capacity measurement limit established by the probe compound. All experiments include the following conditions: 10 W low-pressure Hg lamp, pH0 = 9.4–9.7, 20 °C, [MCAA]0 spikes = 20 μM, [SO32–]0 = 10.0 mM, [PFOS]0 = 20.0 μM, and [borate] = 1.0 mM (ultrapure water only). All chemicals were spiked into the waters at time 0. Markers represent the mean of duplicate measurements and error bars represent the range between the duplicates.
The conclusion:
These kinetics suggest that these systems will not work well, except through multiple passes in continuous flow systems, and that the solid phase extraction/elution system might be better, except in situations where water is being conditioned for use, such as in the case of drinking water restored from contaminated bodies of water.
Kinetics Over Extended Periods of Solvated Electrons in the Remediation of PFAS and Halocarbons.
I envision a system in which our energy production cleans up, via continuous flows of the contaminated media - air and water, and by extraction, indirectly, land - the pollution left by our generation. I'm not trying to be glib, there is a long and extremely difficult - and possibly expensive path to such a world - but it strikes me as just on the edge of feasibility.
Among the most serious pollutants are the halocarbons, with the most actively discussed set of compounds being the PFAS, per(poly)fluorinated alkyl substances.
I discussed the radiolytic degradation of these a little over two years ago in this space: A Nice Scientific Review Article on the Destruction of Persistant Perfluoroorganic Pollutants.
The system I discussed then was really relevant to destruction in processed water, which is not entirely unrealistic in a scenario where solid phase extraction/elution is utilized to capture the PFAS from a natural matrix such as river water, groundwater or seawater. My vision for this kind of system would be to elute the contaminants into highly radioactive water whereupon they would be mineralized into a fluorite analog - fluorite is the mineral CaF2 - BaF2 is similar.
I came across a paper tonight that discusses the properties of electrons in natural (unprocessed) water, this one: Quantifying Hydrated Electron Transformation Kinetics in UV-Advanced Reduction Processes Using the Re–,UV Method Benjamin D. Fennell, Adam Odorisio, and Garrett McKay Environmental Science & Technology 2022 56 (14), 10329-10338.
Regrettably I don't have a lot of time to discuss this paper in a lot of detail, but perhaps a brief excerpt and some pictures will give the flavor. MCAA here is a model compound, monochloroacetic acid. Chlorinated carbons are also a serious matter; although they've been banned largely, we still have huge quantities of many of these remaining, DDT and PCBS for just two examples.
The introduction to the paper:
The rate of contaminant degradation in ultraviolet advanced reduction processes (UV-ARP) is directly related to the available concentration of hydrated electron (eaq–). Acting as a powerful reductant (E° of −2.9 V), (1) eaq– is produced through the illumination of a chemical sensitizer (e.g., sulfite) and has been explored for the treatment of a wide range of contaminants, such as oxyanions, (2−6) high-valence transition metals and metalloids, (7,8) and halogenated organic compounds, (9−12) including per- and polyfluoroalkyl substances (PFAS). (13−26) Furthermore, extensive laboratory studies within the past decade (13−22) and a recent pilot-scale study (23) suggest that eaq–-based UV-ARP are a promising technology for degrading PFAS, which are resistant to direct photolysis and ultraviolet advanced oxidation processes (UV-AOP). (13,14,27) Despite the growing success of eaq–-based UV-ARP treatment, a method to determine the available eaq– concentration for contaminant degradation has yet to be developed.
Quantifying the time-based hydrated electron concentration ([eaq–]t) is important in UV-ARP treatment due to the varied treatment times required for contaminant degradation and the potential for eaq– formation and scavenging conditions to change over these time scales. For instance, nitrate, which has high reactivity with eaq–, completely degrades on the time scale of minutes in UV-ARP systems, (2,28,29) whereas degradation half-lives of hours are typical for more recalcitrant contaminants like PFAS. (15,22) It is likely that the [eaq–]t experienced by nitrate and PFAS at early treatment times is not the same as at later treatment times. This contrasts with UV-AOP in which hydroxyl radical (•OH)-mediated contaminant transformation kinetics occur on much shorter time scales, (30) such that the [•OH] in these systems is assumed to be at a steady state. The [eaq–]t available for contaminant degradation is impacted by eaq– scavengers present in water. Past studies have demonstrated the inhibitory impacts eaq– scavengers such as dissolved oxygen, (6,31) nitrate, (10) dissolved organic matter (DOM), (8,11) and bicarbonate (11) have on contaminant degradation. While these studies highlight the importance of individual eaq– scavengers, the combined, long-term impact of eaq– scavengers most often present in natural waters has not been considered.
The purpose of this paper is to develop a method for characterizing the key properties of eaq–-mediated transformation kinetics in UV-ARP, namely, [eaq–]t and kS,t′ (eaq– scavenging capacity). To this end, we deployed a probe compound selective for eaq– in the UV/sulfite system, monochloroacetate (MCAA), and developed the Re–,UV method (defined as the eaq– exposure per UV fluence) in analogy to ROH,UV previously used for the UV/H2O2 system. (32) We then use the Re–,UV method to model the degradation rates of two contaminants─nitrate (NO3–) and perfluorooctane sulfonate (PFOS)─in four source waters with varying water quality. The results demonstrate that a water’s initial eaq– scavenging capacity does not necessarily determine the ultimate treatability of PFOS. Rather, the extent of PFOS degradation is determined by the total eaq– exposure as measured by the Re–,UV method...
Quantifying the time-based hydrated electron concentration ([eaq–]t) is important in UV-ARP treatment due to the varied treatment times required for contaminant degradation and the potential for eaq– formation and scavenging conditions to change over these time scales. For instance, nitrate, which has high reactivity with eaq–, completely degrades on the time scale of minutes in UV-ARP systems, (2,28,29) whereas degradation half-lives of hours are typical for more recalcitrant contaminants like PFAS. (15,22) It is likely that the [eaq–]t experienced by nitrate and PFAS at early treatment times is not the same as at later treatment times. This contrasts with UV-AOP in which hydroxyl radical (•OH)-mediated contaminant transformation kinetics occur on much shorter time scales, (30) such that the [•OH] in these systems is assumed to be at a steady state. The [eaq–]t available for contaminant degradation is impacted by eaq– scavengers present in water. Past studies have demonstrated the inhibitory impacts eaq– scavengers such as dissolved oxygen, (6,31) nitrate, (10) dissolved organic matter (DOM), (8,11) and bicarbonate (11) have on contaminant degradation. While these studies highlight the importance of individual eaq– scavengers, the combined, long-term impact of eaq– scavengers most often present in natural waters has not been considered.
The purpose of this paper is to develop a method for characterizing the key properties of eaq–-mediated transformation kinetics in UV-ARP, namely, [eaq–]t and kS,t′ (eaq– scavenging capacity). To this end, we deployed a probe compound selective for eaq– in the UV/sulfite system, monochloroacetate (MCAA), and developed the Re–,UV method (defined as the eaq– exposure per UV fluence) in analogy to ROH,UV previously used for the UV/H2O2 system. (32) We then use the Re–,UV method to model the degradation rates of two contaminants─nitrate (NO3–) and perfluorooctane sulfonate (PFOS)─in four source waters with varying water quality. The results demonstrate that a water’s initial eaq– scavenging capacity does not necessarily determine the ultimate treatability of PFOS. Rather, the extent of PFOS degradation is determined by the total eaq– exposure as measured by the Re–,UV method...
The caption:
Figure 1. Re–,UV at initial conditions. (A) Measured MCAA degradation (symbols) as a function of time with variable [SO32–]0 in ultrapure water. Lines represent a linear fit to the data. (B) Re–,UV with variable [SO32–]0 for all waters. All experiments in panels (A) and (B) include the following conditions: 10 W low-pressure Hg lamp, pH0 = 9.1–9.7, 20 °C, [MCAA]0 = 20 μM, and [borate] = 1.0 mM (ultrapure water only). Markers represent the mean of duplicate measurements and error bars represent the range between the duplicates.
The caption:
Figure 2. Measured (eq 3.6) and estimated (eq 3.7) and kS,0′ for each source water. Adjusted bimolecular rate constants accounting for ionic strength were used to calculate kS,0′. Nonadjusted bimolecular rate constants (M–1 s–1) used are as follows: kSO32–,eaq– = 1.3 × 106, kMCAA,eaq– = 1.0 × 109, kCO32–,eaq– = 3.9 × 105, kHCO3–,eaq– = 1.0 × 106, kDOC,eaq– = 1.97 × 104 L mgC–1 s–1, kNO2–,eaq– = 3.5 × 109, and kNO3–,eaq– = 9.7 × 109. (38) Formation of NO2– was observed in the Ohio River and LWC RBF source waters due to direct photolysis of NO3– (see SI Text S12). Experimental conditions include 10 W low-pressure Hg lamp, pH0 = 9.4–9.7, 20 °C, [MCAA]0 = 20 μM, [SO32–]0 = 10.0 mM, and [PFOS]0 = 20.0 μM (Simsboro Aquifer [PFOS]0 = 16.3 μM). All chemicals were spiked into the waters at time 0. Markers represent the mean of duplicate measurements and error bars represent the range between the duplicates.
The caption:
Figure 3. PFOS transformation in the UV/sulfite system in ultrapure water and four source waters. (A) PFOS degradation and (B) defluorination as a function of time. Legend in panel (A) applies to panel (B). All experiments include the following conditions: 10 W low-pressure Hg lamp, pH0 = 9.4–9.7, 20 °C, [MCAA]0 spikes = 20 μM, [SO32–]0 = 10.0 mM, [PFOS]0 = 20.0 μM (Simsboro Aquifer [PFOS]0 = 16.3 μM), and [borate] = 1.0 mM (ultrapure water only). All chemicals were spiked into the waters at time 0. Markers represent the mean of duplicate measurements and error bars represent the range between the duplicates.
The caption:
Figure 4. Temporal variation in eaq– availability during a 24 h UV/sulfite experiment. (A) Measured MCAA degradation (symbols) as a function of time in Ohio River (20 μM [MCAA]0 spiked into reactor prior to each time point). The best linear fit (line) is also shown. (B) Re–,UV, (C) Rf,teaq–, and (D) kS,t′ (eq 3.6) as function of time for all waters (20 μM [MCAA]0 spiked into reactor prior to each time point). Legend in panel (B) applies to panels (C) and (D). Reported kS,t′ values in panel (D) are within the eaq– scavenging capacity measurement limit established by the probe compound. All experiments include the following conditions: 10 W low-pressure Hg lamp, pH0 = 9.4–9.7, 20 °C, [MCAA]0 spikes = 20 μM, [SO32–]0 = 10.0 mM, [PFOS]0 = 20.0 μM, and [borate] = 1.0 mM (ultrapure water only). All chemicals were spiked into the waters at time 0. Markers represent the mean of duplicate measurements and error bars represent the range between the duplicates.
Figure 5. Modeling contaminant transformation rates in the UV/sulfite system using Re–,UV. (A) Measured nitrate (symbols) and modeled nitrate degradation (lines) based on measured [eaq–]t and eq 3.2. (B) Measured PFOS degradation (symbols) and modeled PFOS degradation (lines) based on measured [eaq–]t and eq 3.2. Experimental conditions include: 10 W low-pressure Hg lamp, pH0 = 9.4–9.7, 20 °C, [PFOS]0 = 20.0 μM (Simsboro Aquifer [PFOS]0 = 16.3 μM), [MCAA]0 spikes = 20 μM, [SO32–]0 = 10.0 mM, and [borate] = 1.0 mM (ultrapure water only). All chemicals were spiked into the waters at time 0. kNO3–,eaq– = 9.7 × 109 M–1 s–1 and kPFOS,eaq– fitted = 5.7 × 106 M–1 s–1. Markers represent the mean of duplicate measurements and error bars represent the range between the duplicates.
The conclusion:
In this study, we used MCAA as an eaq– probe compound to demonstrate that the eaq– exposure (Re–,UV) varies significantly in a set of diverse source waters. Notably, the factors that determine eaq– availability are shown to vary considerably over 24 h, which is a typical treatment time in UV-ARP. The Re–,UV method allows for the characterization of [eaq–]t and other key parameters (e.g., Rf,teaq– and kS,t′ ) that can be used to compare and optimize UV-ARP for any source water. Treatment of contaminants with fast bimolecular rate constants will be most impacted by other eaq– scavengers with fast bimolecular rate constants. On the other hand, more recalcitrant contaminants requiring longer treatment times such as PFOS will be inhibited by eaq– scavengers with slower bimolecular rate constants (e.g., bicarbonate).
Our results suggest that high alkalinity may inadvertently increase the treatment time or amount of sensitizer chemical required for complete PFOS degradation when applying UV-ARP treatment to groundwaters. Furthermore, DOC was shown to both increase the eaq– scavenging capacity by having a moderately fast eaq– bimolecular rate constant (∼108 MC–1s–1) and decrease Rf,teaq– by shielding sulfite from incoming photons. The role of DOC in eaq– scavenging deserves further attention. For example, we observed that Lake Bryan (with an initial [DOC] of almost 10 mgC L–1) exhibited a higher eaq– scavenging capacity than other source waters after ∼12 h of treatment. This is particularly relevant for UV-ARP treatment of concentrated PFAS sources such as ion exchange regenerate and reverse osmosis concentrate. Effective UV-ARP treatment in waters with high DOC may require pretreatment to lessen the impacts of this eaq– scavenger.
Our results suggest that high alkalinity may inadvertently increase the treatment time or amount of sensitizer chemical required for complete PFOS degradation when applying UV-ARP treatment to groundwaters. Furthermore, DOC was shown to both increase the eaq– scavenging capacity by having a moderately fast eaq– bimolecular rate constant (∼108 MC–1s–1) and decrease Rf,teaq– by shielding sulfite from incoming photons. The role of DOC in eaq– scavenging deserves further attention. For example, we observed that Lake Bryan (with an initial [DOC] of almost 10 mgC L–1) exhibited a higher eaq– scavenging capacity than other source waters after ∼12 h of treatment. This is particularly relevant for UV-ARP treatment of concentrated PFAS sources such as ion exchange regenerate and reverse osmosis concentrate. Effective UV-ARP treatment in waters with high DOC may require pretreatment to lessen the impacts of this eaq– scavenger.
These kinetics suggest that these systems will not work well, except through multiple passes in continuous flow systems, and that the solid phase extraction/elution system might be better, except in situations where water is being conditioned for use, such as in the case of drinking water restored from contaminated bodies of water.
July 24, 2022
Mr. Piller is an investigative journalist. Science is not generally - primarily - involved in "Investigative Journalism;" it is a well-respected prominent scientific journal published by the American Association for the Advancement of Science, the AAAS. I am a member of the AAAS by virtue of being a subscriber to Science; no evaluation of my credentials was required to become a member, but I am a working scientist, generally in a management role. One also gets a nice tee shirt every year when one renews one’s subscription to Science with the AAAS logo on it. My favorite is the one from a few years back that reads:
Somehow this tautology has become a controversial political statement.
I logged out of Science to ascertain that the full article is open sourced. Thus I will limit the number of excerpts of the full article; anyone who is seriously interested in the facts of the case can read it themselves. It is a compelling article and makes a very solid case that fraud may well have occurred. I certainly make a number of comments from time to time criticizing journalistic interpretations of science, making sweeping jokes that I apply to all journalists. My critique would not apply to Mr. Piller, from what I can tell. He is very fair and does a fine job engaging in the science underlying his piece; it does however, overall, read like investigative journalism. Of course, he has the benefit of producing his work in an organization led and supervised by scientists.
A post here at DU links has a more hyperbolic title than the Science article, Two decades of Alzheimer's research may be based on deliberate fraud that has cost millions of lives, however the author of the post was simply reproducing the title found in article at Daily Kos, to which the post referred, adding a tweet on the subject.
The Daily Kos article, which was written by a sometime Geologist who apparently now writes Syfy novels, and who has as well as a written popular science book, Mark Summer, a staffer at Daily Kos.
Two decades of Alzheimer's research may be based on deliberate fraud that has cost millions of lives.
Several other posts have appeared at DU with the same title. This stuff is getting a lot of air time.
Daily Kos is owned by a journalist, but I’ll make no further comment.
I commented on the Tweet in the DU post: The tweet may be a considerable overstatement.
I hadn't read the Daily Kos diary as of the time I read the post and responded to the "tweet" referring to the Daily Kos diary; I quickly read through it at this morning, an easy read with very little technical detail. Mr. Summer seems to have taken a look at the Science news article on which I will comment here, and has provided a link to the original Nature paper, whether he fully accessed and read either is not clear from what he wrote. Whether he did or not does not come through the innuendo clearly present, although he does make several brief statements which are clearly true, if superficial. The post is consistent with how I personally view as a Daily Kos level discussions of issues in science.
I have downloaded and looked through the Nature paper. It is here: Lesné, S., Koh, M., Kotilinek, L. et al. A specific amyloid-β protein assembly in the brain impairs memory. Nature 440, 352–357 (2006). I have highlighted the name of the scientist under suspicion who is discussed at length in the Science news feature. Another scientist discussed in the news article is Dr. Karen Ashe. As I understand it, she developed the transgenic mice.
The Nature article now comes with an "Expression of Concern" dated July 14, 2022:
For full disclosure: I read the Science article, before reading anything on political blogs, this past Friday because I have been involved, peripherally, in supporting three different Alzheimer's projects for three different (gasp) pharmaceutical companies. I am not an expert in any sense of the word on the mechanism or physiology of Alzheimer's, although I make a serious effort to at least familiarize myself with the basic tenets of the science. As I am an old man, I also have some personal interest in dementia, since anyone my age should consider themselves as under a sword of Damocles in this respect. The work in which I am participating is involved with conducting analytical support, in two cases, measuring pharmacokinetic pathways, including in one case of monitoring certain biomarkers, in another, properties of a formulation. I cannot say much about this work; I am bound by CDA's, but none of the projects on which I am working is involved with Cassava Science, a company which comes up in the Science article. I have nevertheless also read the statement on this topic written by the Cassava CEO for general interest; their lead drug has followed the appropriate regulatory pathway and is about to enter Phase III clinical trials, although the company has lost over a billion dollars of valuation based on the issues discussed in this report. (Failures of Phase III clinical trials of Alzheimer's drugs are legion, but this does not rule out that anyone's phase III clinical trial, including that being conducted by Cassava, will not fail.) For the record and further full disclosure, one study in which I am involved will utilize the αβ generating transgenic mice - I have no idea whether these are the mice developed by Dr. Ashe - that have been engineered to produce the Amyloid beta precursor like protein 2 as well as the plaques resulting from their hydrolysis, however, the mode of action of the drug does not depend on the αβ oligomer subtype hypothesis intimately. Thus none of the projects on which I am working are at risk, at least in the absence of hysteria.
The CEO of Cassava Sciences is not a scientist. He's an investment type, and plainly confesses he doesn't know much about Western blots. His comments on the use of a "Citizens Petition" are well taken. I can recall no instance in my long career, in which a "Citizen's Petition" has been employed for clinical trials on an NCE (New Chemical Entity) for the treatment of human disease. I am aware of "Citizen's Petitions" involved with approved drugs, generally for patent cases as well as a number involved with the opioid crisis. I was involved with one filed in the latter category, and have been involved, indirectly, in producing data for the former case. I also fully credit the CEO of Cassava's note that money changed hands; that there was a financial position involved, something the Science news feature fully discloses in its generally and I think appropriately laudatory description of Dr.Matthew Schrag of Vanderbilt University. None of this of course has merit as to whether fraud has taken place or not, however.
I am in no position to state that the Cassava Sciences drug will fail either. The Citizens Petition filed by short selling scientists as described clearly, but anomalously in the Science news feature, has been rejected by the FDA.
I do have a scientific opinion on Western blots, although I have never run one or even actively interpreted one. I know how they work and what they are, and have occasionally looked at them in papers, without all that much sophistication. This said, I believe that overall the Western Blot technique should ultimately go the way of the dinosaur, dinosaurs being subject on which Mr. Summer apparently, from his bio, has some professional experience, although I strongly suspect his familiarity with Western Blots is not a sophisticated as even my very limited experience with them. Here's what I said about the subject in my comment in the DU post:
This said, Western blots are cheap and easy to run and do not require the very expensive equipment and sophisticated software that are required for the technologies I have implied might supplant them. They are, and have been, good scientific tools, particularly where cost is an issue, and, especially now, as the Science investigative journalism article shows, there are very sophisticated tools to determine or at least suggest whether one is cheating and manipulating images of their output.
About cost:
I recently screened for a potential purchase of a high end TIMS-TOF (Trapped Ion Mobility Spectroscopy Time of Flight) Mass Spec, which is said to offer unprecedented ion utilization efficiency along with an added degree of analytical orthogonality. A single instrument, which may have a run time as long as three minutes, or perhaps very much longer depending on the use chromatographic separations, thus placing limits on the number of samples that can be screened will run roughly at a million dollars, plus ancillary costs, not the least of which is reagents, obtaining samples and preparing them, as well as, most importantly, the cost and time involved in training staff to run the instrument and further, most importantly to interpret the results.
A very large screening project may require many such instruments, and many experiments utilizing them, and the potential for honest error is high, meaning that experiments with ambiguous results may require many repetitions. It is true that these instruments will produce a deeper level of data, and many instruments today are designed with software designed to be 21CFR Part 11 compliant, a kind of IT system that is designed to disallow or track data manipulation. However, not every lab can afford such luxuries, and in any case, there are certainly instances in which they are overkill.
Mr. Summer takes time in his Daily Kos rant to complain about pricing of the only approved Alzheimer's drug, the controversial drug Aduhelm (Aducanumab). Single doses of the drug are given over periods several weeks, apparently at 21 day intervals. Thus the maximum number of doses in a year will be about 17. All of the development costs of the drug will need to be covered by very few doses compared to the doses of say, blood pressure drugs, or drug even antibiotics, which may involve hundreds, even thousands of doses, over a year. (Antibiotics are not huge money makers compared to chronic dose drugs; their economics as well as their widespread and entirely legal use and abuse will make this a problem for future generations, about whom many people my age apparently couldn't care less: All we seem to care about is our money and our convenience.)
I don't know if Mr. Summers was paid for his geological work on dinosaur fossils, or if his books are distributed for free. Writing a book, of course, is a risky enterprise if the goal is to make money, but hardly nowhere near as risky as developing an Alzheimer's drug, given the high rate of failure for many well known efforts as well as the legitimately questioned efficacy of Aducanumab. Writing a book or a blog post on Daily Kos doesn't require a one million dollar equipment investment, a computer from Best Buy or Staples or the Apple store will do, and not much training is required to use a computer.
People who develop drugs are in a morally difficult place; their products can do what was once magic, cure or at least treat the symptoms of disease. It is only human - I personally question the humanity of Republicans - to think that a sick person should be treated, and that cost should not be the only factor under consideration. Sometimes this exercises the noble altruism muscles of people who consider themselves altruistic because they bought an electric car from Elon Musk, among other things. I am proud of the projects on which I worked in my career that treated the ill, but regrettably perhaps, I do want to be paid for my work.
I do understand that there is considerable room for discussion of drug pricing, and egregious abuses are well known, but we should not isolate the cost of doing science from the potential rewards, some of which are financial, particularly if we are cherry picking only to emphasize abuses. Again, I want to be paid for what I do.
Perhaps I should apologize for that, but I won't.
One of the issues of the soundbite/tweet era is magnification of the trivial over greater good that requires critical thinking to recognize. (This is hardly limited to pharmaceuticals but also plays an important role in environmental decisions, most of which, left and right, are delusional.)
Now I'll briefly turn to the aptly named Mr. Piller's article to point to his description of the technology that can be used, from this time forward, to keep people who rely on Western Blots for their publications honest. I'll reproduce the text on the five steps that are used by PubPeer, the technology utilized by Dr. Schrag in his investigation. I'll produce the text from the news feature, as the paper is open sourced, the interested reader is invited and encouraged to look at the graphics attached. I won't reproduce them here.
The PubPeer link in this excerpt will take the reader to papers by Dr. Lesné that are under review for potential fraud.
Step One:
Step Two:
Step Three:
Step Four:
Refer to the article to see the color.
In this case a high correlation is a bad thing, not a good thing. Similarity algorithms play a large role in many areas of science, they can be displayed graphically and are in the article, to which, again, it is useful to refer, showing similar (undesirable if fraud is being investigated) and dissimilar (desirable to disprove fraud) images.
It's a very good technique, I think, and makes a good case that Dr. Lesné may be "cooking" (the scientific) "books."
But what does this mean and how does it compare what does Mr. Summers' headline implies?
Well first of all, in my view, the statement that this fraud "cost millions of lives" is a extremely dubious statement. The involvement of αβ plaques in Alzheimer's disease has been known since the early 20th century. It's what Dr. Alzheimer, for whom the disease is named, discovered. Dr. Alzheimer lived in a time where immunology was poorly understood; indeed proteomics itself was a practically non-existent science. The question is whether the plaques are a cause of the disease or whether they are a symptom of the disease. The first hypothesis, that they are a cause, was around probably when Dr. Lesné was in diapers. His highly cited paper - Google Scholar indicates 3,265 citations - was offered as evidence that the first hypothesis was correct, but if, as the Science News Feature suggests is fraudulent, this does not prove that the hypothesis is incorrect, only that it is not supported by this particular finding.
Amyloid-beta precursor protein, accession number P05067 · A4_HUMAN in the Uniprot protein database has many important cell functions, described at the accession number link. In the section on diseases in which it is involved it says this about Alzheimer's Disease 1:
I'd like to emphasize the 1. As is the case with the generic term, "cancer" it now seems possible that Alzheimer's is not just one disease. The alternate inflammatory hypothesis may account based on similarities for a relational dementia between Alzheimer's and CTE, the disease most often found in football players as the result of multiple concussions. CTE may or may not account for Georgia Senate candidate Hershel Walker; I'm not qualified to say, but I can suggest as much anyway. The inflammatory pathway results in some grousing by its supporters as noted in Mr. Piller's investigative journalism piece:
The second sentence may be a bit of an overstatement by Dr. Forsayeth. It may Ptolemaic for one "AD" and not for another if in fact, "Alzheimer's disease" is more than one disease. Let's not "jump the gun."
As for Mr. Summers, he's making a wildly unjustified assumption with his headline. He's assuming that if the αβ process had not been supported by the suspect work, lives would have been saved. In his contempt for the pharmaceutical industry, he assumes, with zero justification that if money had been spent differently, a cure would exist. The polite word for this is "bullshit." Americans, somewhat arrogantly believ based on the Manhattan Project and the Apollo project, that every problem can be solved if only enough money is thrown at it. This is not true. I personally regard the money thrown at so called "renewable energy," a policy I very strongly am inclined to believe that Mr. Summers supports, as all having been wasted. Trillions of dollars thrown at so called "renewable energy" has done nothing, zero, zilch, nada, zip, to address climate change as we can see because the planet is burning.
There is no evidence, zero, zilch, nada, zip, that spending money differently on Alzheimer's research other than the way money was spent would have "saved lives." It may have done so, or it may have not done so. I personally hope that the immune/inflammatory hypothesis will work; I have great respect for, and rather like, the people I know working on it. Full disclosure, they help finance my paycheck.
It is possible that if the same money that was thrown at the “amyloid mafia” was thrown at the inflammatory/immunomoderated hypothesis, a better treatment may have been found a "cure" or at least a moderately effective treatment, but I would suggest that Mr. Summers rather myopic view does not guarantee as much. This is a very difficult disease, and the study of the plaques is hardly a wasted effort, in particular because as indicated in the Uniprot accession document under functions it says this:
Caspases are enzymatic hydrolysis agents - about 10 are known in mammalian species - that cleave at the amino acid asparagine (Asn), in contrast to the widely used trypsin and chymotrypsin utilized in analytical chemistry to cleave proteins at, arginine or lysine residues for trypsin, and aromatic residues for chymotrpsin.
Asparagine is a rather interesting residue. It's formally a derivative of aspartic acid, it is the β amide of aspartic acid, to which it can, and does, revert via amide bond cleavage. The β nitrogen has an interesting property; it can be glycosylated (functionalized with a very complex sugar). This is called "N glycosylation." Other oxygen functionalized amino acids can also be glycosylated, serine, somewhat more rarely threonine or tyrosine (O-glycosylation). Because of the relative ease with which the amide bond can be broken in comparison to the carbon oxygen bond, it is much simpler to characterize N-glycans than O-glycans, although significant progress with the latter has been made in the last few years. Glycans are like trees, often highly branched in various ways that affect the function of proteins. One important feature of a N-glycosylated asparagine is that it is probably unavailable for hydrolysis by a caspase. It can also undergo rearrangement to form was we call β linkages.
I downloaded the sequence for the Amyloid-beta precursor protein. I count 31 asparagines in the sequence. The glycosylation of this protein has been the subject of 23,000 papers, many of which predate Dr. Lesné's famous or perhaps infamous 2006 paper in Nature. It strikes me as entirely possible - and I am not qualified to do any more than speculate wildly, perhaps not at the same level as Mr. Summers speculates - that the ultimate cause of Alzheimer's is connected with glycosylation. Again, wild speculation.
In any case, there is evidence in other papers that the Amyloid-beta precursor protein is involved in the cause of at least some cases of Alzheimer's, perhaps just one of the possible "more than one" cases of disease. This is because caspase inhibitors seem to effect the cognition of Alzheimer's model mice:
Flores, J., Noël, A., Foveau, B. et al. Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer’s disease mouse model. Nat Commun 9, 3916 (2018). None of Dr. Lesné's papers are cited in this paper.
I'm not fond of Mr. Summers rhetoric and frankly, by way of even more full disclosure, I have been banned from Daily Kos for interpreting a scientific paper by the climate scientist Jim Hansen in a way that Mr. Kos did not like. I contend that Mr. Kos's view of how to address climate change is dangerous in the extreme - I think the world is aflame because his view has clearly experimentally failed - and I further contend that Mr. Summers' view of Alzheimer's research, while not quite as dangerous as Mr. Kos's dogmatic climate views, is not helpful, inasmuch as it incites contempt for a serious and hardly disproven scientific hypothesis, albeit one that seems likely to have been supported, partially, by fraud.
I have a low opinion of discussions of science at Daily Kos.
Mr Summers, by choosing his title, has engaged in hyperbole of the type that clearly sets the internet in flames, and may do serious damage to research that may work - it also may not work - to treat this serious disease by reducing public support.
I thought I should at least comment on this.
A little critical thinking would be in order.
Have a pleasant Sunday evening.
Some remarks on purported fraud concerned with αβ oligomer hypothesis in Alzheimer's research.
The news article in the prominent scientific journal, Science, to which I will refer in this post is this one: Blots on a Field Charles Pillar, Science 21, July, 2022.
The subtitle is here:
A neuroscience image sleuth finds signs of fabrication in scores of Alzheimer’s articles, threatening a reigning theory of the disease
Mr. Piller is an investigative journalist. Science is not generally - primarily - involved in "Investigative Journalism;" it is a well-respected prominent scientific journal published by the American Association for the Advancement of Science, the AAAS. I am a member of the AAAS by virtue of being a subscriber to Science; no evaluation of my credentials was required to become a member, but I am a working scientist, generally in a management role. One also gets a nice tee shirt every year when one renews one’s subscription to Science with the AAAS logo on it. My favorite is the one from a few years back that reads:
Facts are facts.
Somehow this tautology has become a controversial political statement.
I logged out of Science to ascertain that the full article is open sourced. Thus I will limit the number of excerpts of the full article; anyone who is seriously interested in the facts of the case can read it themselves. It is a compelling article and makes a very solid case that fraud may well have occurred. I certainly make a number of comments from time to time criticizing journalistic interpretations of science, making sweeping jokes that I apply to all journalists. My critique would not apply to Mr. Piller, from what I can tell. He is very fair and does a fine job engaging in the science underlying his piece; it does however, overall, read like investigative journalism. Of course, he has the benefit of producing his work in an organization led and supervised by scientists.
A post here at DU links has a more hyperbolic title than the Science article, Two decades of Alzheimer's research may be based on deliberate fraud that has cost millions of lives, however the author of the post was simply reproducing the title found in article at Daily Kos, to which the post referred, adding a tweet on the subject.
The Daily Kos article, which was written by a sometime Geologist who apparently now writes Syfy novels, and who has as well as a written popular science book, Mark Summer, a staffer at Daily Kos.
Two decades of Alzheimer's research may be based on deliberate fraud that has cost millions of lives.
Several other posts have appeared at DU with the same title. This stuff is getting a lot of air time.
Daily Kos is owned by a journalist, but I’ll make no further comment.
I commented on the Tweet in the DU post: The tweet may be a considerable overstatement.
I hadn't read the Daily Kos diary as of the time I read the post and responded to the "tweet" referring to the Daily Kos diary; I quickly read through it at this morning, an easy read with very little technical detail. Mr. Summer seems to have taken a look at the Science news article on which I will comment here, and has provided a link to the original Nature paper, whether he fully accessed and read either is not clear from what he wrote. Whether he did or not does not come through the innuendo clearly present, although he does make several brief statements which are clearly true, if superficial. The post is consistent with how I personally view as a Daily Kos level discussions of issues in science.
I have downloaded and looked through the Nature paper. It is here: Lesné, S., Koh, M., Kotilinek, L. et al. A specific amyloid-β protein assembly in the brain impairs memory. Nature 440, 352–357 (2006). I have highlighted the name of the scientist under suspicion who is discussed at length in the Science news feature. Another scientist discussed in the news article is Dr. Karen Ashe. As I understand it, she developed the transgenic mice.
The Nature article now comes with an "Expression of Concern" dated July 14, 2022:
14 July 2022 Editor’s Note: The editors of Nature have been alerted to concerns regarding some of the figures in this paper. Nature is investigating these concerns, and a further editorial response will follow as soon as possible. In the meantime, readers are advised to use caution when using results reported therein.
For full disclosure: I read the Science article, before reading anything on political blogs, this past Friday because I have been involved, peripherally, in supporting three different Alzheimer's projects for three different (gasp) pharmaceutical companies. I am not an expert in any sense of the word on the mechanism or physiology of Alzheimer's, although I make a serious effort to at least familiarize myself with the basic tenets of the science. As I am an old man, I also have some personal interest in dementia, since anyone my age should consider themselves as under a sword of Damocles in this respect. The work in which I am participating is involved with conducting analytical support, in two cases, measuring pharmacokinetic pathways, including in one case of monitoring certain biomarkers, in another, properties of a formulation. I cannot say much about this work; I am bound by CDA's, but none of the projects on which I am working is involved with Cassava Science, a company which comes up in the Science article. I have nevertheless also read the statement on this topic written by the Cassava CEO for general interest; their lead drug has followed the appropriate regulatory pathway and is about to enter Phase III clinical trials, although the company has lost over a billion dollars of valuation based on the issues discussed in this report. (Failures of Phase III clinical trials of Alzheimer's drugs are legion, but this does not rule out that anyone's phase III clinical trial, including that being conducted by Cassava, will not fail.) For the record and further full disclosure, one study in which I am involved will utilize the αβ generating transgenic mice - I have no idea whether these are the mice developed by Dr. Ashe - that have been engineered to produce the Amyloid beta precursor like protein 2 as well as the plaques resulting from their hydrolysis, however, the mode of action of the drug does not depend on the αβ oligomer subtype hypothesis intimately. Thus none of the projects on which I am working are at risk, at least in the absence of hysteria.
The CEO of Cassava Sciences is not a scientist. He's an investment type, and plainly confesses he doesn't know much about Western blots. His comments on the use of a "Citizens Petition" are well taken. I can recall no instance in my long career, in which a "Citizen's Petition" has been employed for clinical trials on an NCE (New Chemical Entity) for the treatment of human disease. I am aware of "Citizen's Petitions" involved with approved drugs, generally for patent cases as well as a number involved with the opioid crisis. I was involved with one filed in the latter category, and have been involved, indirectly, in producing data for the former case. I also fully credit the CEO of Cassava's note that money changed hands; that there was a financial position involved, something the Science news feature fully discloses in its generally and I think appropriately laudatory description of Dr.Matthew Schrag of Vanderbilt University. None of this of course has merit as to whether fraud has taken place or not, however.
I am in no position to state that the Cassava Sciences drug will fail either. The Citizens Petition filed by short selling scientists as described clearly, but anomalously in the Science news feature, has been rejected by the FDA.
I do have a scientific opinion on Western blots, although I have never run one or even actively interpreted one. I know how they work and what they are, and have occasionally looked at them in papers, without all that much sophistication. This said, I believe that overall the Western Blot technique should ultimately go the way of the dinosaur, dinosaurs being subject on which Mr. Summer apparently, from his bio, has some professional experience, although I strongly suspect his familiarity with Western Blots is not a sophisticated as even my very limited experience with them. Here's what I said about the subject in my comment in the DU post:
The claim was that a specific set of small oligomers derived from the the σβ protein were responsible for inducing the plaques. The Science article indicates that there is strong suspicion of manipulated images in a technique that, in my opinion, should rapidly become obsolete, Western Blot, kind of a cross between TLC, SEC, and electrophoresis. The technique utilized to raise the doubts involved computer processing of some images.
This said, Western blots are cheap and easy to run and do not require the very expensive equipment and sophisticated software that are required for the technologies I have implied might supplant them. They are, and have been, good scientific tools, particularly where cost is an issue, and, especially now, as the Science investigative journalism article shows, there are very sophisticated tools to determine or at least suggest whether one is cheating and manipulating images of their output.
About cost:
I recently screened for a potential purchase of a high end TIMS-TOF (Trapped Ion Mobility Spectroscopy Time of Flight) Mass Spec, which is said to offer unprecedented ion utilization efficiency along with an added degree of analytical orthogonality. A single instrument, which may have a run time as long as three minutes, or perhaps very much longer depending on the use chromatographic separations, thus placing limits on the number of samples that can be screened will run roughly at a million dollars, plus ancillary costs, not the least of which is reagents, obtaining samples and preparing them, as well as, most importantly, the cost and time involved in training staff to run the instrument and further, most importantly to interpret the results.
A very large screening project may require many such instruments, and many experiments utilizing them, and the potential for honest error is high, meaning that experiments with ambiguous results may require many repetitions. It is true that these instruments will produce a deeper level of data, and many instruments today are designed with software designed to be 21CFR Part 11 compliant, a kind of IT system that is designed to disallow or track data manipulation. However, not every lab can afford such luxuries, and in any case, there are certainly instances in which they are overkill.
Mr. Summer takes time in his Daily Kos rant to complain about pricing of the only approved Alzheimer's drug, the controversial drug Aduhelm (Aducanumab). Single doses of the drug are given over periods several weeks, apparently at 21 day intervals. Thus the maximum number of doses in a year will be about 17. All of the development costs of the drug will need to be covered by very few doses compared to the doses of say, blood pressure drugs, or drug even antibiotics, which may involve hundreds, even thousands of doses, over a year. (Antibiotics are not huge money makers compared to chronic dose drugs; their economics as well as their widespread and entirely legal use and abuse will make this a problem for future generations, about whom many people my age apparently couldn't care less: All we seem to care about is our money and our convenience.)
I don't know if Mr. Summers was paid for his geological work on dinosaur fossils, or if his books are distributed for free. Writing a book, of course, is a risky enterprise if the goal is to make money, but hardly nowhere near as risky as developing an Alzheimer's drug, given the high rate of failure for many well known efforts as well as the legitimately questioned efficacy of Aducanumab. Writing a book or a blog post on Daily Kos doesn't require a one million dollar equipment investment, a computer from Best Buy or Staples or the Apple store will do, and not much training is required to use a computer.
People who develop drugs are in a morally difficult place; their products can do what was once magic, cure or at least treat the symptoms of disease. It is only human - I personally question the humanity of Republicans - to think that a sick person should be treated, and that cost should not be the only factor under consideration. Sometimes this exercises the noble altruism muscles of people who consider themselves altruistic because they bought an electric car from Elon Musk, among other things. I am proud of the projects on which I worked in my career that treated the ill, but regrettably perhaps, I do want to be paid for my work.
I do understand that there is considerable room for discussion of drug pricing, and egregious abuses are well known, but we should not isolate the cost of doing science from the potential rewards, some of which are financial, particularly if we are cherry picking only to emphasize abuses. Again, I want to be paid for what I do.
Perhaps I should apologize for that, but I won't.
One of the issues of the soundbite/tweet era is magnification of the trivial over greater good that requires critical thinking to recognize. (This is hardly limited to pharmaceuticals but also plays an important role in environmental decisions, most of which, left and right, are delusional.)
Now I'll briefly turn to the aptly named Mr. Piller's article to point to his description of the technology that can be used, from this time forward, to keep people who rely on Western Blots for their publications honest. I'll reproduce the text on the five steps that are used by PubPeer, the technology utilized by Dr. Schrag in his investigation. I'll produce the text from the news feature, as the paper is open sourced, the interested reader is invited and encouraged to look at the graphics attached. I won't reproduce them here.
Image in question Ashe uploaded this Western blot to PubPeer after Schrag said the version publishedin Nature showed cut marks suggesting improper tampering with bands portraying Aβ*56 and other proteins (black boxes added by Ashe). The figure shows levels of Aβ*56 (dashed red box) increasing in older mice as symptoms emerge. But Schrag’s analysis suggests this version of the image contains improperly duplicated bands...
The PubPeer link in this excerpt will take the reader to papers by Dr. Lesné that are under review for potential fraud.
Step One:
1 Spot the similarities. Some bands looked abnormally similar, an apparent manipulation that in some cases (not shown) could have made Aβ*56 appear more abundant than it was. One striking example (red box)ostensibly shows proteins saidto emerge later in the life span than Aβ*56.
Step Two:
2 Match contrast. Schrag matched the contrast level in the two sets of bands foran apples-to-apples comparison.
Step Three:
3 Colorize and align. Schrag turned backgrounds black to make the bands easier to see, then colorized them and precisely matched their size and orientation.
Step Four:
4 Merge He merged the sets of colorized bands. The areas of the imagethat are identical appear in yellow
Refer to the article to see the color.
5 Calculate similarity Schrag then calculated the correlation coefficient, showing the strength of the relationship between the merged bands. Identical images show a correlation of 1, and display as a straight 45° angle line. These bands show a 0.98 correlation, highly improbable to occur by chance.
In this case a high correlation is a bad thing, not a good thing. Similarity algorithms play a large role in many areas of science, they can be displayed graphically and are in the article, to which, again, it is useful to refer, showing similar (undesirable if fraud is being investigated) and dissimilar (desirable to disprove fraud) images.
It's a very good technique, I think, and makes a good case that Dr. Lesné may be "cooking" (the scientific) "books."
But what does this mean and how does it compare what does Mr. Summers' headline implies?
Well first of all, in my view, the statement that this fraud "cost millions of lives" is a extremely dubious statement. The involvement of αβ plaques in Alzheimer's disease has been known since the early 20th century. It's what Dr. Alzheimer, for whom the disease is named, discovered. Dr. Alzheimer lived in a time where immunology was poorly understood; indeed proteomics itself was a practically non-existent science. The question is whether the plaques are a cause of the disease or whether they are a symptom of the disease. The first hypothesis, that they are a cause, was around probably when Dr. Lesné was in diapers. His highly cited paper - Google Scholar indicates 3,265 citations - was offered as evidence that the first hypothesis was correct, but if, as the Science News Feature suggests is fraudulent, this does not prove that the hypothesis is incorrect, only that it is not supported by this particular finding.
Amyloid-beta precursor protein, accession number P05067 · A4_HUMAN in the Uniprot protein database has many important cell functions, described at the accession number link. In the section on diseases in which it is involved it says this about Alzheimer's Disease 1:
The disease is caused by variants affecting the gene represented in this entry
Description
A familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.
Description
A familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death.
I'd like to emphasize the 1. As is the case with the generic term, "cancer" it now seems possible that Alzheimer's is not just one disease. The alternate inflammatory hypothesis may account based on similarities for a relational dementia between Alzheimer's and CTE, the disease most often found in football players as the result of multiple concussions. CTE may or may not account for Georgia Senate candidate Hershel Walker; I'm not qualified to say, but I can suggest as much anyway. The inflammatory pathway results in some grousing by its supporters as noted in Mr. Piller's investigative journalism piece:
Scientists who advance other potential Alzheimer’s causes, such as immune dysfunction or inflammation, complain they have been sidelined by the “amyloid mafia.” Forsayeth says the amyloid hypothesis became “the scientific equivalent of the Ptolemaic model of the Solar System,” in which the Sun and planets rotate around Earth.
The second sentence may be a bit of an overstatement by Dr. Forsayeth. It may Ptolemaic for one "AD" and not for another if in fact, "Alzheimer's disease" is more than one disease. Let's not "jump the gun."
As for Mr. Summers, he's making a wildly unjustified assumption with his headline. He's assuming that if the αβ process had not been supported by the suspect work, lives would have been saved. In his contempt for the pharmaceutical industry, he assumes, with zero justification that if money had been spent differently, a cure would exist. The polite word for this is "bullshit." Americans, somewhat arrogantly believ based on the Manhattan Project and the Apollo project, that every problem can be solved if only enough money is thrown at it. This is not true. I personally regard the money thrown at so called "renewable energy," a policy I very strongly am inclined to believe that Mr. Summers supports, as all having been wasted. Trillions of dollars thrown at so called "renewable energy" has done nothing, zero, zilch, nada, zip, to address climate change as we can see because the planet is burning.
There is no evidence, zero, zilch, nada, zip, that spending money differently on Alzheimer's research other than the way money was spent would have "saved lives." It may have done so, or it may have not done so. I personally hope that the immune/inflammatory hypothesis will work; I have great respect for, and rather like, the people I know working on it. Full disclosure, they help finance my paycheck.
It is possible that if the same money that was thrown at the “amyloid mafia” was thrown at the inflammatory/immunomoderated hypothesis, a better treatment may have been found a "cure" or at least a moderately effective treatment, but I would suggest that Mr. Summers rather myopic view does not guarantee as much. This is a very difficult disease, and the study of the plaques is hardly a wasted effort, in particular because as indicated in the Uniprot accession document under functions it says this:
The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.
Caspases are enzymatic hydrolysis agents - about 10 are known in mammalian species - that cleave at the amino acid asparagine (Asn), in contrast to the widely used trypsin and chymotrypsin utilized in analytical chemistry to cleave proteins at, arginine or lysine residues for trypsin, and aromatic residues for chymotrpsin.
Asparagine is a rather interesting residue. It's formally a derivative of aspartic acid, it is the β amide of aspartic acid, to which it can, and does, revert via amide bond cleavage. The β nitrogen has an interesting property; it can be glycosylated (functionalized with a very complex sugar). This is called "N glycosylation." Other oxygen functionalized amino acids can also be glycosylated, serine, somewhat more rarely threonine or tyrosine (O-glycosylation). Because of the relative ease with which the amide bond can be broken in comparison to the carbon oxygen bond, it is much simpler to characterize N-glycans than O-glycans, although significant progress with the latter has been made in the last few years. Glycans are like trees, often highly branched in various ways that affect the function of proteins. One important feature of a N-glycosylated asparagine is that it is probably unavailable for hydrolysis by a caspase. It can also undergo rearrangement to form was we call β linkages.
I downloaded the sequence for the Amyloid-beta precursor protein. I count 31 asparagines in the sequence. The glycosylation of this protein has been the subject of 23,000 papers, many of which predate Dr. Lesné's famous or perhaps infamous 2006 paper in Nature. It strikes me as entirely possible - and I am not qualified to do any more than speculate wildly, perhaps not at the same level as Mr. Summers speculates - that the ultimate cause of Alzheimer's is connected with glycosylation. Again, wild speculation.
In any case, there is evidence in other papers that the Amyloid-beta precursor protein is involved in the cause of at least some cases of Alzheimer's, perhaps just one of the possible "more than one" cases of disease. This is because caspase inhibitors seem to effect the cognition of Alzheimer's model mice:
Flores, J., Noël, A., Foveau, B. et al. Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer’s disease mouse model. Nat Commun 9, 3916 (2018). None of Dr. Lesné's papers are cited in this paper.
I'm not fond of Mr. Summers rhetoric and frankly, by way of even more full disclosure, I have been banned from Daily Kos for interpreting a scientific paper by the climate scientist Jim Hansen in a way that Mr. Kos did not like. I contend that Mr. Kos's view of how to address climate change is dangerous in the extreme - I think the world is aflame because his view has clearly experimentally failed - and I further contend that Mr. Summers' view of Alzheimer's research, while not quite as dangerous as Mr. Kos's dogmatic climate views, is not helpful, inasmuch as it incites contempt for a serious and hardly disproven scientific hypothesis, albeit one that seems likely to have been supported, partially, by fraud.
I have a low opinion of discussions of science at Daily Kos.
Mr Summers, by choosing his title, has engaged in hyperbole of the type that clearly sets the internet in flames, and may do serious damage to research that may work - it also may not work - to treat this serious disease by reducing public support.
I thought I should at least comment on this.
A little critical thinking would be in order.
Have a pleasant Sunday evening.
July 24, 2022
The authors propose using the CaCl2 molten salt to overcome these difficulties, the same molten salt as is used in the FCC process that I expect will change the world by improving on the production of many metals, most notably, titanium.
The experimental procedure:
The potentiometric separation is kinetically controlled:
The caption:
This is a high temperature process. The dangerous fantasy of providing the world's energy using wind energy - dangerous inasmuch as it has experimentally proved incapable of addressing the extreme danger of climate change - depends on access to neodymium based magnets having dysprosium doping to assure thermal stability of the magnets. The same is true for the related bourgeois fantasy of electric cars.
If you insist on believing this process can be environmentally or economically viable using intermittent energy sources, well, I'm very sorry to hear that, since the belief is pernicious given the on going collapse of the planetary atmosphere and with it minor things like say, the food supply.
This is nonetheless very interesting and, I think, vital chemistry.
I trust you're enjoying the weekend.
Molten Salt Electrochemical Separation of Dysprosium and Neodymium from Magnet Scrap.
I will very briefly refer a paper across which I've come, this one: Highly Efficient and Precise Electrolysis Separation of Dysprosium from Neodymium for Magnet Scrap Recycling in Molten Salt Hang Hua, Kouji Yasuda, and Toshiyuki Nohira ACS Sustainable Chemistry & Engineering 2022 10 (28), 9225-9231.
I am always interested in electrochemical metal separations, in particular in advanced used nuclear fuel recycling which is key to providing energy for saving humanity from itself. These separations will require the separation of the lower lanthanides - in this paper referred to with the common misnomer, "rare earth elements" - from one another. Dysprosium is a higher lanthanide and is only found in tiny traces in used nuclear fuels, but overall the process described herein may have some more general relevance. In addition, although electricity is a thermodynamically degraded form of energy, its production as a side product of high thermal processes may increase system exergy recovery: High efficiency which will allow us (in a moral universe) to provide the human right to energy to those deprived of that right. Magnets are essential to the generation of electricity, and as the paper notes, to the use of electric motors.
I will be very brief in this discussion - I'm short of time - and offer a few interesting excerpts of this interesting paper:
Rare-earth (RE) elements are not as rare as their name implies. For example, the abundance of cerium in the Earth’s crust is the highest among the RE elements and is also higher than that of nickel, copper, and lead, which are major industrial metals. Even the least-abundant RE element (except promethium) lutetium is much more abundant than silver, platinum, and gold, which are known as precious metals. However, because of the uneven distribution, over 80% of the global RE reserves are located in a few countries. (1) In addition, because of lanthanide contraction, the chemical properties of the RE elements are similar and thus extremely difficult to separate from each other. When they were first discovered, RE elements were rarely used for applications other than ignition stones and abrasives. Currently, a combination of wet leaching and solvent extraction methods is commonly used for RE separation, but it has some disadvantages, such as multistep reactions, high energy loss, and high environmental load. (2) Therefore, this method is not used in developed countries that impose strict environmental regulations due to economic rationality.
Among the 17 RE elements, neodymium (Nd) is well known as the most important component of Nd permanent magnets, which are the strongest permanent magnets commercially available. The maximum energy product of Nd magnets over 470 kJ m–3 is much higher than that of ferrite and samarium magnets. (3) In addition, because of their high mechanical strength and low manufacturing cost, Nd magnets have been widely used in mobile phones, wind turbines, and motors for battery and hybrid electric vehicles (BEVs and HEVs). Owing to the global expectation of carbon neutrality, the demand for Nd magnets used in clean energy production and transportation is expected to increase dramatically in the near future. Generally, Nd magnets can only be operated at temperatures up to 393 K, (4) but Nd magnets used in BEV and HEV motors require a higher operating temperature than this. Using the intergranular diffusion method, it is possible to replace some Nd with dysprosium (Dy) to maintain the required magnetic force at high temperatures. (5,6) Therefore, Dy is added to prevent the degradation of magnetic properties when a high operating temperature is required.
Currently, the recycling of Nd magnet scrap is only partly carried out in manufacturing plants of the magnet using the wet leaching and solvent extraction method mentioned above. However, a large amount of magnet scrap generated by end users is disposed of as garbage or accumulated in urban mines. To meet the increasing demand for Nd and Dy, the separation and recycling of these RE elements from Nd magnet scrap are expected to provide a valuable and sustainable secondary source.
Several researchers have proposed RE recycling methods. (7−18) Some of them are new smelting methods for raw ore, but their principles are also applicable for RE recycling from Nd magnet scrap. Among them, only two methods have been proposed with realistic data for RE separation using the difference in the vapor pressure of each RE complex. The first method involves a reaction with aluminum chloride vapor at high temperature to synthesize complexes containing RE elements with high vapor pressure. (7) The separation ratio of Nd/Dy varied with temperature distribution and was approximately two times higher than the original material at the position with the highest amount of precipitation. (8) The second method separates RE components using the difference in vapor pressure of chlorides or iodides of different valences. (9) The separation between Nd and Sm was very high, but the separation between Nd and Dy has not been reported. In addition, many RE extraction methods using metals, oxides, chlorides, and fluorides as extraction agents have been proposed. (10−18) Although many of them can successfully separate RE from non-RE elements, the separation of individual REs is still not sufficient to achieve high-precision RE separation.
A method based on the selective electrochemical formation of RE–Ni alloys has been proposed, which is an effective method for the individual separation of RE elements with high precision. (19) The electrochemical formation of RE–Ni (RE = Nd and Dy) alloys and the separation ability for Dy/Nd have been proven in molten LiCl–KCl, NaCl–KCl, and LiF–CaF2 systems at various temperatures. (20−22) Due to their wider potential windows than aqueous or organic solution systems, RE ions can be electrochemically reduced to RE metals in the molten salt systems. In the LiCl–KCl system at 723 K, an extremely high Dy/Nd separation ratio of 72 was obtained with a low alloy formation rate of approximately 20 μm h–1. In contrast, in the LiF–CaF2 system at 1123 K, the maximum Dy/Nd separation ratio was as low as 5.6, and the alloy formation rate was over 100 μm h^(–1)...
Among the 17 RE elements, neodymium (Nd) is well known as the most important component of Nd permanent magnets, which are the strongest permanent magnets commercially available. The maximum energy product of Nd magnets over 470 kJ m–3 is much higher than that of ferrite and samarium magnets. (3) In addition, because of their high mechanical strength and low manufacturing cost, Nd magnets have been widely used in mobile phones, wind turbines, and motors for battery and hybrid electric vehicles (BEVs and HEVs). Owing to the global expectation of carbon neutrality, the demand for Nd magnets used in clean energy production and transportation is expected to increase dramatically in the near future. Generally, Nd magnets can only be operated at temperatures up to 393 K, (4) but Nd magnets used in BEV and HEV motors require a higher operating temperature than this. Using the intergranular diffusion method, it is possible to replace some Nd with dysprosium (Dy) to maintain the required magnetic force at high temperatures. (5,6) Therefore, Dy is added to prevent the degradation of magnetic properties when a high operating temperature is required.
Currently, the recycling of Nd magnet scrap is only partly carried out in manufacturing plants of the magnet using the wet leaching and solvent extraction method mentioned above. However, a large amount of magnet scrap generated by end users is disposed of as garbage or accumulated in urban mines. To meet the increasing demand for Nd and Dy, the separation and recycling of these RE elements from Nd magnet scrap are expected to provide a valuable and sustainable secondary source.
Several researchers have proposed RE recycling methods. (7−18) Some of them are new smelting methods for raw ore, but their principles are also applicable for RE recycling from Nd magnet scrap. Among them, only two methods have been proposed with realistic data for RE separation using the difference in the vapor pressure of each RE complex. The first method involves a reaction with aluminum chloride vapor at high temperature to synthesize complexes containing RE elements with high vapor pressure. (7) The separation ratio of Nd/Dy varied with temperature distribution and was approximately two times higher than the original material at the position with the highest amount of precipitation. (8) The second method separates RE components using the difference in vapor pressure of chlorides or iodides of different valences. (9) The separation between Nd and Sm was very high, but the separation between Nd and Dy has not been reported. In addition, many RE extraction methods using metals, oxides, chlorides, and fluorides as extraction agents have been proposed. (10−18) Although many of them can successfully separate RE from non-RE elements, the separation of individual REs is still not sufficient to achieve high-precision RE separation.
A method based on the selective electrochemical formation of RE–Ni alloys has been proposed, which is an effective method for the individual separation of RE elements with high precision. (19) The electrochemical formation of RE–Ni (RE = Nd and Dy) alloys and the separation ability for Dy/Nd have been proven in molten LiCl–KCl, NaCl–KCl, and LiF–CaF2 systems at various temperatures. (20−22) Due to their wider potential windows than aqueous or organic solution systems, RE ions can be electrochemically reduced to RE metals in the molten salt systems. In the LiCl–KCl system at 723 K, an extremely high Dy/Nd separation ratio of 72 was obtained with a low alloy formation rate of approximately 20 μm h–1. In contrast, in the LiF–CaF2 system at 1123 K, the maximum Dy/Nd separation ratio was as low as 5.6, and the alloy formation rate was over 100 μm h^(–1)...
The authors propose using the CaCl2 molten salt to overcome these difficulties, the same molten salt as is used in the FCC process that I expect will change the world by improving on the production of many metals, most notably, titanium.
The experimental procedure:
The schematic view of the electrochemical experiment has been already described in our previous report. (24) All electrochemical experiments were conducted in an Ar atmosphere in a glovebox. First, 300 g of CaCl2 (Kojundo Chemical Laboratory Co., Ltd., 99%) was placed in a carbon crucible (Sanko Co., Ltd., IG-110, inner diameter: 90 mm, height: 120 mm) and placed at the bottom of a stainless-steel vessel in an airproof Kanthal container. After preliminary dehydration under vacuum at 453 K for more than 72 h and further dehydration at 773 K for 24 h, the container was replenished with Ar gas. The temperature was increased to 1123 K to melt CaCl2 after dehydration. Anhydrous NdCl3 or DyCl3 (Kojundo Chemical Laboratory Co., Ltd., 99.9%) was individually added directly into the melt at a concentration of 1.0 mol % for electrochemical measurements and preparation of Nd–Ni or Dy–Ni alloy samples. An electrochemical measurement system (Hokuto Denko Corp., HZ-7000) connected to a computer was used for the measurements. A Ni-plate working electrode (Nilaco Corp., >99%, width: 5 mm, length: 20 mm, thickness: 0.1 mm) was used for sample preparation. A carbon rod (Sanko Co. Ltd., diameter: 7 mm, length: 520 mm) was used as the counter electrode and a Ni wire (Nilaco Corp., >99%, diameter: 1.0 mm) immersed in molten CaCl2 containing 1.0 mol % NiCl2 (Alfa Aesar Corp., 98%) set in a mullite tube (Nikkato Corp., 56% Al2O3–40% SiO2, HB grade, outer diameter: 6 mm, inner diameter: 4 mm, length: 500 mm) was used as the reference electrode. After the individual experiments in each RECl3-added system, both NdCl3 and DyCl3 were added to the melt at 1.0 mol % each for Dy/Nd separation experiments...
The potentiometric separation is kinetically controlled:
The caption:
Figure 4. Electrochemical formation rate of RE–Ni (RE = Nd and Dy) alloy in molten CaCl2–RECl3 (1.0 mol %) at 1123 K.
This is a high temperature process. The dangerous fantasy of providing the world's energy using wind energy - dangerous inasmuch as it has experimentally proved incapable of addressing the extreme danger of climate change - depends on access to neodymium based magnets having dysprosium doping to assure thermal stability of the magnets. The same is true for the related bourgeois fantasy of electric cars.
If you insist on believing this process can be environmentally or economically viable using intermittent energy sources, well, I'm very sorry to hear that, since the belief is pernicious given the on going collapse of the planetary atmosphere and with it minor things like say, the food supply.
This is nonetheless very interesting and, I think, vital chemistry.
I trust you're enjoying the weekend.
July 22, 2022
Pickering Nuclear plant needs to be 'un-retired' if Ontario hopes to meet zero carbon goals
Pickering Nuclear plant needs to be ‘un-retired’ if Ontario hopes to meet zero carbon goalsThe hope of net zero carbon emissions will not be possible without finding more nuclear power for the grid, says the President of Canadians for Nuclear Energy.
The best way to achieve that lofty goal, added Dr. Chris Keefer, is to reverse the decision to mothball the Pickering Nuclear Generating Station, which is scheduled to shut down, beginning in 2024.
Keefer, who is an emergency room doctor when he’s not advocating for clean energy solutions, said there is “indeed hope” for Pickering to be back online as the Independent Electrical Service Operator (IESO) – which represents all the individual electricity providers in Ontario – is “panicking” because of forecasted energy shortfalls which “threatens” Ontario’s ‘Open for Business’ status.
Ontario’s electricity system is searching for more power producers as demand rises and Pickering Nuclear nears a forced retirement, a process likely to secure more natural gas generation while the government seeks to end reliance on it.
It means that for at least the next two decades, greenhouse gas emissions from the electricity sector are set to rise by as much as 400 per cent, though the IESO projects the net greenhouse gas emission reductions from electric vehicles will offset those carbon emissions by 2038...
... “Pickering B refurbishment offers the province the fastest and cheapest route to locking in 550MW of clean baseload power per unit refurbished,” Keefer said, citing the ongoing $12.8 Billion refurbishing project at the Darlington Nuclear Plant near Bowmanville that is coming in “below budget and on time” and is expected to provide emissions-free electricity for 30-plus years.
“We are quickly becoming masters of refurbishment and the supply chain and workforce is optimized. Darlington refurbs will be done in 2027 and we will be ready to move hammer in hand to Pickering.”
Johnston and the Society of United Professionals are also on board with the Pickering refurbishing project, with other trade unions also likely to support the plan.
“The cheapest sources of zero-emission energy are the refurbished Bruce and Darlington nuclear reactors. It’s time for Ontario to reconsider a similar refurbishment of Pickering Nuclear,” she said “The case for Pickering has changed drastically since it was last reviewed. Today, Ontario faces an electricity shortage, natural gas prices have spiked, and there is broad consensus on the need for a massive shift to electrification to fight climate change.”
“Nuclear got us off dirty coal and now it can keep us off dirty gas...”
The best way to achieve that lofty goal, added Dr. Chris Keefer, is to reverse the decision to mothball the Pickering Nuclear Generating Station, which is scheduled to shut down, beginning in 2024.
Keefer, who is an emergency room doctor when he’s not advocating for clean energy solutions, said there is “indeed hope” for Pickering to be back online as the Independent Electrical Service Operator (IESO) – which represents all the individual electricity providers in Ontario – is “panicking” because of forecasted energy shortfalls which “threatens” Ontario’s ‘Open for Business’ status.
Ontario’s electricity system is searching for more power producers as demand rises and Pickering Nuclear nears a forced retirement, a process likely to secure more natural gas generation while the government seeks to end reliance on it.
It means that for at least the next two decades, greenhouse gas emissions from the electricity sector are set to rise by as much as 400 per cent, though the IESO projects the net greenhouse gas emission reductions from electric vehicles will offset those carbon emissions by 2038...
... “Pickering B refurbishment offers the province the fastest and cheapest route to locking in 550MW of clean baseload power per unit refurbished,” Keefer said, citing the ongoing $12.8 Billion refurbishing project at the Darlington Nuclear Plant near Bowmanville that is coming in “below budget and on time” and is expected to provide emissions-free electricity for 30-plus years.
“We are quickly becoming masters of refurbishment and the supply chain and workforce is optimized. Darlington refurbs will be done in 2027 and we will be ready to move hammer in hand to Pickering.”
Johnston and the Society of United Professionals are also on board with the Pickering refurbishing project, with other trade unions also likely to support the plan.
“The cheapest sources of zero-emission energy are the refurbished Bruce and Darlington nuclear reactors. It’s time for Ontario to reconsider a similar refurbishment of Pickering Nuclear,” she said “The case for Pickering has changed drastically since it was last reviewed. Today, Ontario faces an electricity shortage, natural gas prices have spiked, and there is broad consensus on the need for a massive shift to electrification to fight climate change.”
“Nuclear got us off dirty coal and now it can keep us off dirty gas...”
July 22, 2022
This is definitely a kid you'd want in your lab.
Kudos.
Integrity.
This came in my Nature Briefing
This is the kind of kid I'd want in my lab:
Retraction with honor
On July 2, 2022, we retracted a paper we published last year in Evolution https://onlinelibrary.wiley.com/doi/10.1111/evo.14551. The reason I wanted to write this post is to explain what happened and how we dealt with it and thereby to help normalize honest retractions which should probably be more common. I’ll give a little detail on the experiment and then focus on the human side.
The experiment was an exciting one. We took several clones of the social amoeba we study, Dictyostelium discoideum, cured them of the bacteria that they carried symbiotically, and then let them proliferate through many generations isolated from their bacteria. We also took those same bacteria and let them proliferate on their own for many generations. If you evolve to make your partner worse when reintroduced, you would originally have been adapted to cooperate with them. And if you evolve to harm your partner less when reintroduced, you would originally have been adapted to exploit them. We feel it is a new approach using lab evolution to understand what originally happened in the wild.
We got a clear experimental response and published the paper. It was only later when we decided to sequence the lines to see what changed that we discovered the problem. Sequences from lines that should have been Paraburkholderia. hayleyella turned out to match P. agricolaris. There had been cross contamination. This was not a rare event but impacted all the P. hayleyella lines. By the time we did the final experiment mixing host and bacteria, all the bacterial lines were predominantly P. agricolaris...
...Retraction has a stigma about it... ...When I discovered the contamination, I could have quietly moved on and likely nobody would have ever known. Some selfish, anxious part of me wanted to do that. But I believe in the importance of intellectual honesty and owning my mistakes...
...The first few results that did not turn out as I expected I assumed were because I had made some mistake in my code, had failed to set some needed argument, or failed to understand one of the multitude of assumptions inherent to doing bioinformatics. Each would send me off on some tangent trying to understand some new aspect of the program I was using.
Eventually, though, the simpler, uglier explanation occurred to me: I had messed up. I had messed up bigtime. Not with a few lines of code that could be fixed with some careful Google research. I had messed up the experiment itself, many months and dollars ago...
The experiment was an exciting one. We took several clones of the social amoeba we study, Dictyostelium discoideum, cured them of the bacteria that they carried symbiotically, and then let them proliferate through many generations isolated from their bacteria. We also took those same bacteria and let them proliferate on their own for many generations. If you evolve to make your partner worse when reintroduced, you would originally have been adapted to cooperate with them. And if you evolve to harm your partner less when reintroduced, you would originally have been adapted to exploit them. We feel it is a new approach using lab evolution to understand what originally happened in the wild.
We got a clear experimental response and published the paper. It was only later when we decided to sequence the lines to see what changed that we discovered the problem. Sequences from lines that should have been Paraburkholderia. hayleyella turned out to match P. agricolaris. There had been cross contamination. This was not a rare event but impacted all the P. hayleyella lines. By the time we did the final experiment mixing host and bacteria, all the bacterial lines were predominantly P. agricolaris...
...Retraction has a stigma about it... ...When I discovered the contamination, I could have quietly moved on and likely nobody would have ever known. Some selfish, anxious part of me wanted to do that. But I believe in the importance of intellectual honesty and owning my mistakes...
...The first few results that did not turn out as I expected I assumed were because I had made some mistake in my code, had failed to set some needed argument, or failed to understand one of the multitude of assumptions inherent to doing bioinformatics. Each would send me off on some tangent trying to understand some new aspect of the program I was using.
Eventually, though, the simpler, uglier explanation occurred to me: I had messed up. I had messed up bigtime. Not with a few lines of code that could be fixed with some careful Google research. I had messed up the experiment itself, many months and dollars ago...
This is definitely a kid you'd want in your lab.
Kudos.
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