Molecular neuroscience

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https://en.wikipedia.org/wiki/Molecular_neuroscience

Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied to the nervous systems of animals. The scope of this subject covers topics such as molecular neuroanatomy, mechanisms of molecular signaling in the nervous system, the effects of genetics and epigenetics on neuronal development, and the molecular basis for neuroplasticity and neurodegenerative diseases. As with molecular biology, molecular neuroscience is a relatively new field that is considerably dynamic.

Locating neurotransmitters

In molecular biology, communication between neurons typically occurs by chemical transmission across gaps between the cells called synapses. The transmitted chemicals, known as neurotransmitters, regulate a significant fraction of vital body functions. It is possible to anatomically locate neurotransmitters by labeling techniques. It is possible to chemically identify certain neurotransmitters such as catecholamines by fixing neural tissue sections with formaldehyde. This can give rise to formaldehyde-induced fluorescence when exposed to ultraviolet light. Dopamine, a catecholamine, was identified in the nematode C. elegans by using this technique. Immunocytochemistry, which involves raising antibodies against targeted chemical or biological entities, includes a few other techniques of interest. A targeted neurotransmitter could be specifically tagged by primary and secondary antibodies with radioactive labeling in order to identify the neurotransmitter by autoradiography. The presence of neurotransmitters (though not necessarily the location) can be observed in enzyme-linked immunocytochemistry or enzyme-linked immunosorbent assays (ELISA) in which substrate-binding in the enzymatic assays can induce precipitates, fluorophores, or chemiluminescence. In the event that neurotransmitters cannot be histochemically identified, an alternative method is to locate them by their neural uptake mechanisms.

Voltage-gated ion channels

Structure of eukaryotic voltage-gated potassium ion channels

Excitable cells in living organisms have voltage-gated ion channels. These can be observed throughout the nervous system in neurons. The first ion channels to be characterized were the sodium and potassium ion channels by A.L. Hodgkin and A.F. Huxley in the 1950s upon studying the giant axon of the squid genus Loligo. Their research demonstrated the selective permeability of cellular membranes, dependent on physiological conditions, and the electrical effects that result from these permeabilities to produce action potentials.

Sodium ion channels

Sodium channels were the first voltage-gated ion channels to be isolated in 1984 from the eel Electrophorus electricus by Shosaku Numa. The pufferfish toxin tetrodotoxin (TTX), a sodium channel blocker, was used to isolate the sodium channel protein by binding it using the column chromatography technique for chemical separation. The amino acid sequence of the protein was analyzed by Edman degradation and then used to construct a cDNA library which could be used to clone the channel protein. Cloning the channel itself allowed for applications such as identifying the same channels in other animals. Sodium channels are known for working in concert with potassium channels during the development of graded potentials and action potentials. Sodium channels allow an influx of Na⁺ ions into a neuron, resulting in a depolarization from the resting membrane potential of a neuron to lead to a graded potential or action potential, depending on the degree of depolarization.

Potassium ion channels

Potassium channels come in a variety of forms, are present in most eukaryotic cells, and typically tend to stabilize the cell membrane at the potassium equilibrium potential. As with sodium ions, graded potentials and action potentials are also dependent on potassium channels. While influx of Na⁺ ions into a neuron induce cellular depolarization, efflux of K⁺ ions out of a neuron causes a cell to repolarize to resting membrane potential. The activation of potassium ion channels themselves are dependent on the depolarization resulting from Na⁺ influx during an action potential. As with sodium channels, the potassium channels have their own toxins that block channel protein action. An example of such a toxin is the large cation, tetraethylammonium (TEA), but it is notable that the toxin does not have the same mechanism of action on all potassium channels, given the variety of channel types across species. The presence of potassium channels was first identified in Drosophila melanogaster mutant flies that shook uncontrollably upon anesthesia due to problems in cellular repolarization that led to abnormal neuron and muscle electrophysiology. Potassium channels were first identified by manipulating molecular genetics (of the flies) instead of performing channel protein purification because there were no known high-affinity ligands for potassium channels (such as TEA) at the time of discovery.

Calcium ion channels

Calcium channels are important for certain cell-signaling cascades as well as neurotransmitter release at axon terminals. A variety of different types of calcium ion channels are found in excitable cells. As with sodium ion channels, calcium ion channels have been isolated and cloned by chromatographic purification techniques. It is notable, as with the case of neurotransmitter release, that calcium channels can interact with intracellular proteins and plays a strong role in signaling, especially in locations such as the sarcoplasmic reticulum of muscle cells.

Receptors

Various types of receptors can be used for cell signaling and communication and can include ionotropic receptors and metabotropic receptors. These cell surface receptor types are differentiated by the mechanism and duration of action with ionotropic receptors being associated with fast signal transmission and metabotropic receptors being associated with slow signal transmission. Metabotropic receptors happen to cover a wide variety of cell-surface receptors with notably different signaling cascades.

Ionotropic receptors

Prototypical depiction of ionotropic receptor in the case of Ca²⁺ ion flow

Ionotropic receptors, otherwise known as ligand-gated ion channels, are fast acting receptors that mediate neural and physiological function by ion channel flow with ligand-binding. Nicotinic, GABA, and Glutamate receptors are among some of the cell surface receptors regulated by ligand-gated ion channel flow. GABA is the brain's main inhibitory neurotransmitter and glutamate is the brain's main excitatory neurotransmitter.

GABA receptors

GABA_A and GABA_C receptors are known to be ionotropic, while the GABA_B receptor is metabotropic. GABA_A receptors mediate fast inhibitory responses in the central nervous system (CNS) and are found on neurons, glial cells, and adrenal medulla cells. It is responsible for inducing Cl⁻ ion influx into cells, thereby reducing the probability that membrane depolarization will occur upon the arrival of a graded potential or an action potential. GABA receptors can also interact with non-endogenous ligands to influence activity. For example, the compound diazepam (marketed as Valium) is an allosteric agonist which increases the affinity of the receptor for GABA. The increased physiological inhibitory effects resulting from increased GABA binding make diazepam a useful tranquilizer or anticonvulsant (antiepileptic drugs). On the other hand, GABA receptors can also be targeted by decreasing Cl⁻ cellular influx with the effect of convulsants like picrotoxin. The antagonistic mechanism of action for this compound is not directly on the GABA receptor, but there are other compounds that are capable of allosteric inactivation, including T-butylbicyclophorothionate (TBPS) and pentylenetetrazole (PZT). Compared with GABA_A, GABA_C receptors have a higher affinity for GABA, they are likely to be longer-lasting in activity, and their responses are likely to be generated by lower GABA concentrations.

Glutamate receptors

Ionotropic glutamate receptors can include NMDA, AMPA, and kainate receptors. These receptors are named after agonists that facilitate glutamate activity. NMDA receptors are notable for their excitatory mechanisms to affect neuronal plasticity in learning and memory, as well as neuropathologies such as stroke and epilepsy. NDMA receptors have multiple binding sites just like ionotropic GABA receptors and can be influenced by co-agonists such the glycine neurotransmitter or phencyclidine (PCP). The NMDA receptors carry a current by Ca²⁺ ions and can be blocked by extracellular Mg²⁺ ions depending on voltage and membrane potential. This Ca²⁺ influx is increased by excitatory postsynaptic potentials (EPSPs) produced by NMDA receptors, activating Ca²⁺-based signaling cascades (such as neurotransmitter release). AMPA generate shorter and larger excitatory postsynaptic currents than other ionotropic glutamate receptors.

Nicotinic ACh receptors

Nicotinic receptors bind the acetylcholine (ACh) neurotransmitter to produce non-selective cation channel flow that generates excitatory postsynaptic responses. Receptor activity, which can be influenced by nicotine consumption, produces feelings of euphoria, relaxation, and inevitably addiction in high levels.

Metabotropic receptors

G-protein-linked receptor signaling cascade

Metabotropic receptors, are slow response receptors in postsynaptic cells. Typically these slow responses are characterized by more elaborate intracellular changes in biochemistry. Responses of neurotransmitter uptake by metabotropic receptors can result in the activation of intracellualar enzymes and cascades involving second messengers, as is the case with G protein-linked receptors. Various metabotropic receptors can include certain glutamate receptors, muscarinic ACh receptors, GABA_B receptors, and receptor tyrosine kinases.

G protein-linked receptors

The G protein-linked signaling cascade can significantly amplify the signal of a particular neurotransmitter to produce hundreds to thousands of second messengers in a cell. The mechanism of action by which G protein-linked receptors cause a signaling cascade is as follows:

1. Neurotransmitter binds to the receptor
2. The receptor undergoes a conformational change to allow G-protein complex binding
3. GDP is exchanged with GTP upon G protein complex binding to the receptor
4. The α-subunit of the G protein complex is bound to GTP and separates to bind with a target protein such as adenylate cyclase
5. The binding to the target protein either increases or decreases the rate of second messenger (such as cyclic AMP) production
6. GTPase hydrolyzes the α-subunit so that is bound to GDP and the α-subunit returns to the G protein complex inactive

Neurotransmitter release

Structure of a synapse where neurotransmitter release and uptake occurs

Neurotransmitters are released in discrete packets known as quanta from the axon terminal of one neuron to the dendrites of another across a synapse. These quanta have been identified by electron microscopy as synaptic vesicles. Two types of vesicles are small synaptic vessicles (SSVs), which are about 40-60nm in diameter, and large dense-core vesicles (LDCVs), electron-dense vesicles approximately 120-200nm in diameter. The former is derived from endosomes and houses neurotransmitters such as acetylcholine, glutamate, GABA, and glycine. The latter is derived from the Golgi apparatus and houses larger neurotransmitters such as catecholamines and other peptide neurotransmitters. Neurotransmitters are released from an axon terminal and bind to postsynaptic dendrites in the following procession:

1. Mobilization/recruitment of synaptic vesicle from cytoskeleton
2. Docking of vesicle (binding) to presynaptic membrane
3. Priming of vesicle by ATP (relatively slow step)
4. Fusion of primed vesicle with presynaptic membrane and exocytosis of the housed neurotransmitter
5. Uptake of neurotransmitters in receptors of a postsynaptic cell
6. Initiation or inhibition of action potential in postsynaptic cell depending on whether the neurotransmitters are excitatory or inhibitory (excitatory will result in depolarization of the postsynaptic membrane)

Neurotransmitter release is calcium-dependent

Neurotransmitter release is dependent on an external supply of Ca²⁺ ions which enter axon terminals via voltage-gated calcium channels. Vesicular fusion with the terminal membrane and release of the neurotransmitter is caused by the generation of Ca²⁺ gradients induced by incoming action potentials. The Ca²⁺ ions cause the mobilization of newly synthesized vesicles from a reserve pool to undergo this membrane fusion. This mechanism of action was discovered in squid giant axons. Lowering intracellular Ca²⁺ ions provides a direct inhibitory effect on neurotransmitter release. After release of the neurotransmitter occurs, vesicular membranes are recycled to their origins of production. Calcium ion channels can vary depending on the location of incidence. For example, the channels at an axon terminal differ from the typical calcium channels of a cell body (whether neural or not). Even at axon terminals, calcium ion channel types can vary, as is the case with P-type calcium channels located at the neuromuscular junction.

Neuronal gene expression

See also: Computational neurogenetic modeling

Sex differences

Differences in sex determination are controlled by sex chromosomes. Sex hormonal releases have a significant effect on sexual dimorphisms (phenotypic differentiation of sexual characteristics) of the brain. Recent studies seem to suggest that regulating these dimorphisms has implications for understanding normal and abnormal brain function. Sexual dimorphisms may be significantly influenced by sex-based brain gene expression which varies from species to species.

Animal models such as rodents, Drosophila melanogaster, and Caenorhabditis elegans, have been used to observe the origins and/or extent of sex bias in the brain versus the hormone-producing gonads of an animal. With the rodents, studies on genetic manipulation of sex chromosomes resulted in an effect on one sex that was completely opposite of the effect in the other sex. For example, a knockout of a particular gene only resulted in anxiety-like effects in males. With studies on D. menlanogaster it was found that a large brain sex bias of expression occurred even after the gonads were removed, suggesting that sex bias could be independent of hormonal control in certain aspects.

Observing sex-biased genes has the potential for clinical significance in observing brain physiology and the potential for related (whether directly or indirectly) neurological disorders. Examples of diseases with sex biases in development include Huntington's disease, cerebral ischemia, and Alzheimer's disease.

Epigenetics of the brain

See also: Epigenetic priming

Many brain functions can be influenced at the cellular and molecular level by variations and changes in gene expression, without altering the sequence of DNA in an organism. This is otherwise known as epigenetic regulation. Examples of epigenetic mechanisms include histone modifications and DNA methylation. Such changes have been found to be strongly influential in the incidence of brain disease, mental illness, and addiction. Epigenetic control has been shown to be involved in high levels of plasticity in early development, thereby defining its importance in the critical period of an organism. Examples of how epigenetic changes can affect the human brain are as follows:

• Higher methylation levels in rRNA genes in the hippocampus of the brain results in a lower production of proteins and thus limited hippocampal function can result in learning and memory impairment and resultant suicidal tendencies.
• In a study comparing genetic differences between healthy people and psychiatric patients 60 different epigenetic markers associated with brain cell signaling were found.
• Environmental factors such as child abuse appears to cause the expression of an epigenetic tag on glucocorticoid receptors (associated with stress responses) that was not found in suicide victims. This is an example of experience-dependent plasticity.
• Environmental enrichment in individuals is associated with increased hippocampal gene histone acetylation and thus improved memory consolidation (notably spatial memory).

Molecular mechanisms of neurodegenerative diseases

Excitotoxicity and glutamate receptors

Excitotoxicity is phenomenon in which glutamate receptors are inappropriately activated. It can be caused by prolonged excitatory synaptic transmission in which high levels of glutamate neurotransmitter cause excessive activation in a postsynaptic neuron that can result in the death of the postsynaptic neuron. Following brain injury (such as from ischemia), it has been found that excitotoxicity is a significant cause of neuronal damage. This can be understandable in the case where sudden perfusion of blood after reduced blood flow to the brain can result in excessive synaptic activity caused by the presence of increased glutamate and aspartate during the period of ischemia.

Alzheimer's disease

Alzheimer's disease is the most common neurodegenerative disease and is the most common form of dementia in the elderly. The disorder is characterized by progressive loss of memory and various cognitive functions. It is hypothesized that the deposition of amyloid-β peptide (40-42 amino acid residues) in the brain is integral in the incidence of Alzheimer's disease. Accumulation is purported to block hippocampal long-term potentiation. It is also possible that a receptor for amyloid-β oligomers could be a prion protein.

Parkinson's disease

Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease. It is a hypokinetic movement basal ganglia disease caused by the loss of dopaminergic neurons in the substantia nigra of the human brain. The inhibitory outflow of the basal ganglia is thus not decreased, and so upper motor neurons, mediated by the thalamus, are not activated in a timely manner. Specific symptoms include rigidity, postural problems, slow movements, and tremors. Blocking GABA receptor input from medium spiny neurons to reticulata cells, causes inhibition of upper motor neurons similar to the inhibition that occurs in Parkinson's disease.

Huntington's disease

Huntington's disease is a hyperkinetic movement basal ganglia disease caused by lack of normal inhibitory inputs from medium spiny neurons of the basal ganglia. This poses the opposite effects of those associated with Parkinson's disease, including inappropriate activation of upper motor neurons. As with the GABAergic mechanisms observed in relation to Parkinson's disease, a GABA agonist injected into the substantia nigra pars reticulata decreases inhibition of upper motor neurons, resulting in ballistic involuntary motor movements, similar to symptoms of Huntington's disease.

Nuclear propulsion

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https://en.wikipedia.org/wiki/Nuclear_propulsion 

Pressurised water reactors are the most common reactors used in ships and submarines. The pictorial diagram shows the operating principles. Primary coolant is in orange and the secondary coolant (steam and later feedwater) is in blue.

Nuclear propulsion includes a wide variety of propulsion methods that use some form of nuclear reaction as their primary power source. Many aircraft carriers and submarines currently use uranium fueled nuclear reactors that can provide propulsion for long periods without refueling. There are also applications in the space sector with nuclear thermal and nuclear electric engines which could be more efficient than conventional rocket engines.

The idea of using nuclear material for propulsion dates back to the beginning of the 20th century. In 1903 it was hypothesized that radioactive material, radium, might be a suitable fuel for engines to propel cars, planes, and boats. H. G. Wells picked up this idea in his 1914 fiction work The World Set Free.

Surface ships, submarines, and torpedoes

Main article: Nuclear marine propulsion

USS Nimitz (CVN-68), lead ship of the Nimitz-class of nuclear-powered aircraft carriers

A Delta-class nuclear-powered submarine

Nuclear-powered vessels are mainly military submarines, and aircraft carriers. Russia is the only country that currently has nuclear-powered civilian surface ships, mainly icebreakers. The US Navy currently (as of 2022) has 11 aircraft carriers and 70 submarines in service, that are all powered by nuclear reactors. For more detailed articles see:

Civilian maritime use

• See Nuclear marine propulsion
• List of civilian nuclear ships

Military maritime use

• Nuclear navy
• List of United States Naval reactors
• Soviet naval reactors
• Nuclear submarine

Torpedo

Main article: Status-6 Oceanic Multipurpose System

Russia's Channel One Television news broadcast a picture and details of a nuclear-powered torpedo called Status-6 on about 12 November 2015. The torpedo was stated as having a range of up to 10,000 km, a cruising speed of 100 knots, and an operational depth of up to 1000 metres below the surface. The torpedo carried a 100-megaton nuclear warhead.

One of the suggestions emerging in the summer of 1958 from the first meeting of the scientific advisory group that became JASON was for "a nuclear-powered torpedo that could roam the seas almost indefinitely".

Aircraft and missiles

Main article: Nuclear-powered aircraft

A picture of an Aircraft Nuclear Propulsion system, known as HTRE-3 (Heat Transfer Reactor Experiment no. 3). The central EBR-1 based reactor took the place of chemical fuel combustion to heat the air. The reactor rapidly raised the temperature via an air heat exchanger and powered the dual J47 engines in a number of ground tests.

Research into nuclear-powered aircraft was pursued during the Cold War by the United States and the Soviet Union as they would presumably allow a country to keep nuclear bombers in the air for extremely long periods of time, a useful tactic for nuclear deterrence. Neither country created any operational nuclear aircraft. One design problem, never adequately solved, was the need for heavy shielding to protect the crew from radiation sickness. Since the advent of ICBMs in the 1960s the tactical advantage of such aircraft was greatly diminished and respective projects were cancelled. Because the technology was inherently dangerous it was not considered in non-military contexts. Nuclear-powered missiles were also researched and discounted during the same period.

Aircraft

• Convair X-6
• Myasishchev M-50 – Aviation Week hoax
• Aircraft Nuclear Propulsion – General Electric's project to build a nuclear-powered bomber
• Tupolev Tu-95LAL

Missiles

• Project Pluto – which developed the SLAM missile, that used a nuclear-powered air ramjet for propulsion
• Burevestnik nuclear-powered cruise missile announced by Vladimir Putin in 2018.

Spacecraft

Main article: Nuclear power in space

The attraction of nuclear propulsion and power in space is built on the high efficiency and theoretical capability that can be delivered with a nuclear system, namely energy efficiency of the system and endurance/capacity of the system to function over long distances. In balance, the systems needed to protect humans in both the space-lift and operations phase are significant detriments. Many types of nuclear propulsion have been proposed as follows.

Nuclear pulse propulsion

Main article: Nuclear pulse propulsion

• Project Orion, first engineering design study of nuclear pulse (i.e., atomic explosion) propulsion
• Project Daedalus, 1970s British Interplanetary Society study of a fusion rocket
• Project Longshot, US Naval Academy-NASA nuclear pulse propulsion design
• AIMStar, a proposed Antimatter-catalyzed nuclear pulse propulsion craft that uses clouds of antiprotons to initiate fission and fusion within fuel pellets
• ICAN-II, a proposed crewed interplanetary spacecraft that used the antimatter-catalyzed nuclear pulse propulsion engine as its main form of propulsion
• External Pulsed Plasma Propulsion (EPPP), a propulsion concept by NASA that derives its thrust from plasma waves generated from a series of small, supercritical fission/fusion pulses behind an object in space.

Nuclear thermal rocket

Main article: Nuclear thermal rocket

Bimodal nuclear thermal rockets conduct nuclear fission reactions similar to those employed at nuclear power plants including submarines. The energy is used to heat the liquid hydrogen propellant. The vehicle depicted is the "Copernicus" an upper stage assembly being designed for the Space Launch System (2010).

Bimodal nuclear thermal rockets conduct nuclear fission reactions similar to those employed at nuclear power plants including submarines. The energy is used to heat the liquid hydrogen propellant. Advocates of nuclear-powered spacecraft point out that at the time of launch, there is almost no radiation released from the nuclear reactors. Nuclear-powered rockets are not used to lift off the Earth. Nuclear thermal rockets can provide great performance advantages compared to chemical propulsion systems. Nuclear power sources could also be used to provide the spacecraft with electrical power for operations and scientific instrumentation. Examples:

• NERVA (Nuclear Energy for Rocket Vehicle Applications), a US nuclear thermal rocket program.
• Project Rover, an American project to develop a nuclear thermal rocket. The program ran at the Los Alamos Scientific Laboratory from 1955 through 1972.
• Project Timberwind (1987–1991), part of the Strategic Defense Initiative
• RD-0410, a Soviet nuclear thermal rocket engine developed from 1965 through the 1980s
• Demonstration Rocket for Agile Cislunar Operations (DRACO), under development in the 2020s

Ramjet

• Bussard ramjet, a conceptual interstellar fusion ramjet named after Robert W. Bussard.

Direct nuclear

• Fission fragment rocket
• Fission sail
• Fusion rocket
• Gas core reactor rocket
• Nuclear salt-water rocket
• Radioisotope rocket
• Nuclear photonic rocket

Nuclear electric

Main article: Nuclear electric rocket

Nuclear electric propulsion is a type of spacecraft propulsion system where a nuclear reactor generates thermal energy which is converted to electrical energy, that drives an ion thruster or other electrical spacecraft propulsion technology. Examples of nuclear electric systems:

• SNAP-10A, launched into orbit by USAF in 1965, was the first use of a nuclear reactor in space and of an ion thruster in orbit.
• US-A satellite series, launched by into orbit by the USSR, included Kosmos 1818 and Kosmos 1867 in 1987, using the TOPAZ nuclear reactor and a "Plazma-2 SPT" Hall-effect thruster.
• Project Prometheus, NASA development of nuclear propulsion for long-duration spaceflight, begun in 2003.
• Transport and Energy Module (TEM). In April 2011, Anatoly Perminov, head of the Russian Federal Space Agency, announced that it is going to develop a nuclear-powered spacecraft for deep space travel. Preliminary design was done by 2013, and 9 more years are planned for development (in space assembly). The price is set at 17 billion rubles (600 million dollars). The nuclear propulsion would offer mega-watt class power and would consist of a space nuclear power and a matrix of ion engines According to Perminov, the propulsion will be able to support human mission to Mars, with cosmonauts staying on the Red planet for 30 days. This journey to Mars with nuclear propulsion and a steady acceleration would take six weeks, instead of eight months by using chemical propulsion – assuming thrust of 300 times higher than that of chemical propulsion.

Ground vehicles

Automobiles

The idea of making cars that used radioactive material, radium, for fuel dates back to at least 1903. Analysis of the concept in 1937 indicated that the driver of such a vehicle might need a 50-ton lead barrier to shield them from radiation.

In 1941, a Caltech physicist named R. M. Langer espoused the idea of a car powered by uranium-235 in the January edition of Popular Mechanics. He was followed by William Bushnell Stout, designer of the Stout Scarab and former Society of Engineers president, on 7 August 1945 in The New York Times. The problem of shielding the reactor continued to render the idea impractical. In December 1945, a John Wilson of London, announced he had created an atomic car. This created considerable interest. The Minister of Fuel and Power along with a large press contingent turned out to view it. The car did not show and Wilson claimed that it had been sabotaged. A later court case found that he was a fraud and there was no nuclear-powered car.

Despite the shielding problem, through the late 1940s and early 1950s debate continued around the possibility of nuclear-powered cars. The development of nuclear-powered submarines and ships, and experiments to develop a nuclear-powered aircraft at that time kept the idea alive. Russian papers in the mid-1950s reported the development of a nuclear-powered car by Professor V P Romadin, but again shielding proved to be a problem. It was claimed that its laboratories had overcome the shielding problem with a new alloy that absorbed the rays.

In 1958, at the height of the 1950s American automobile culture there were at least four theoretical nuclear-powered concept cars proposed, the American Ford Nucleon and Studebaker Packard Astral, as well as the French Simca Fulgur designed by Robert Opron and the Arbel Symétric. Apart from these concept models, none were built and no automotive nuclear power plants ever made. Chrysler engineer C R Lewis had discounted the idea in 1957 because of estimates that an 80,000 lb (36,000 kg) engine would be required by a 3,000 lb (1,400 kg) car. His view was that an efficient means of storing energy was required for nuclear power to be practical. Despite this, Chrysler's stylists in 1958 drew up some possible designs.

In 1959 it was reported that Goodyear Tire and Rubber Company had developed a new rubber compound that was light and absorbed radiation, obviating the need for heavy shielding. A reporter at the time considered it might make nuclear-powered cars and aircraft a possibility.

Ford made another potentially nuclear-powered model in 1962 for the Seattle World's Fair, the Ford Seattle-ite XXI. This also never went beyond the initial concept.

In 2009, for the hundredth anniversary of General Motors' acquisition of Cadillac, Loren Kulesus created concept art depicting a car powered by thorium.

Other

The Chrysler TV-8 was an experimental concept tank designed by Chrysler in the 1950s. The tank was intended to be a nuclear-powered medium tank capable of land and amphibious warfare. The design was never mass-produced.

The X-12 was a nuclear powered locomotive, proposed in a feasibility study done in 1954 at the University of Utah.

The Mars rovers Curiosity and Perseverance are powered by a radioisotope thermoelectric generator (RTG), like the successful Viking 1 and Viking 2 Mars landers in 1976.

Renaissance humanism

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Renaissance_humanism

Leonardo da Vinci's Vitruvian Man (c. 1490) shows the correlations of ideal human body proportions with geometry described by the ancient Roman architect Vitruvius in his De Architectura.

"In his explicit turn back to an ancient model in search of knowledge and wisdom, Leonardo follows early humanist practice. What he finds in Vitruvius is a mathematical formula for the proportions of all parts of the human body, which results in its idealized representation as the true microcosmic measure of all things. [...]The perfection of this ideal human form corresponds visually to the early humanist belief in the unique central placement of human beings within the divine universal order and their consequent human grandeur and dignity, expressed in the philosopher Pico della Mirandola's Oration on the Dignity of Man (1486), known as the manifesto of the Renaissance."

— Anne Hudson Jones

Renaissance humanism is a worldview centered on the nature and importance of humanity that emerged from the study of Classical antiquity.

Renaissance humanists sought to create a citizenry able to speak and write with eloquence and clarity, and thus capable of engaging in the civic life of their communities and persuading others to virtuous and prudent actions. Humanism, while set up by a small elite who had access to books and education, was intended as a cultural movement to influence all of society. It was a program to revive the cultural heritage, literary legacy, and moral philosophy of the Greco-Roman civilization.

It first began in Italy and then spread across Western Europe in the 14th, 15th, and 16th centuries. During the period, the term humanist (Italian: umanista) referred to teachers and students of the humanities, known as the studia humanitatis, which included the study of Latin and Ancient Greek literatures, grammar, rhetoric, history, poetry, and moral philosophy. It was not until the 19th century that this began to be called humanism instead of the original humanities, and later by the retronym Renaissance humanism to distinguish it from later humanist developments.

During the Renaissance period most humanists were Christians, so their concern was to "purify and renew Christianity", not to do away with it. Their vision was to return ad fontes ("to the pure sources") to the Gospels, the New Testament and the Church Fathers, bypassing the complexities of medieval Christian theology.

Definition

Medieval and Renaissance Italian writers portrayed by Giorgio Vasari in Six Tuscan Poets (1544). From left to right: Cristoforo Landino, Marsilio Ficino, Francesco Petrarca, Giovanni Boccaccio, Dante Alighieri, and Guido Cavalcanti.

Very broadly, the project of the Italian Renaissance humanists of the fourteenth and fifteenth centuries was the studia humanitatis: the study of the humanities, "a curriculum focusing on language skills." This project sought to recover the culture of ancient Greece and Rome through its literature and philosophy and to use this classical revival to imbue the ruling classes with the moral attitudes of said ancients—a project James Hankins calls one of "virtue politics." But what this studia humanitatis actually constituted is a subject of much debate. According to one scholar of the movement,

Early Italian humanism, which in many respects continued the grammatical and rhetorical traditions of the Middle Ages, not merely provided the old Trivium with a new and more ambitious name (Studia humanitatis), but also increased its actual scope, content and significance in the curriculum of the schools and universities and in its own extensive literary production. The studia humanitatis excluded logic, but they added to the traditional grammar and rhetoric not only history, Greek, and moral philosophy, but also made poetry, once a sequel of grammar and rhetoric, the most important member of the whole group.

However, in investigating this definition in his article "The changing concept of the studia humanitatis in the early Renaissance," Benjamin G. Kohl provides an account of the various meanings the term took on over the course of the period.

• Around the middle of the fourteenth century, when the term first came into use among Italian literati, it was used in reference to a very specific text: as praise of the cultural and moral attitudes expressed in Cicero's Pro Archia poeta (62 BCE).
• Tuscan humanist Coluccio Salutati popularized the term in the 1370s, using the phrase to refer to culture and learning as a guide to moral life, with a focus on rhetoric and oration. Over the years, he came to use it specifically in literary praise of his contemporaries, but later viewed the studia humanitatis as a means of editing and restoring ancient texts and even understanding scripture and other divine literature.
• But it was not until the beginning of the quattrocento (15th century) that the studia humanitatis began to be associated with particular academic disciplines, when Pier Paolo Vergerio, in his De ingenuis moribus, stressed the importance of rhetoric, history, and moral philosophy as a means of moral improvement.
• By the middle of the century, the term was adopted more formally, as it started to be used in Bologna and Padua in reference to university courses that taught these disciplines as well as Latin poetry, before then spreading northward throughout Italy.
• But the first instance of it as encompassing grammar, rhetoric, history, poetry, and moral philosophy all together only came when Tommaso Parentucelli wrote to Cosimo de' Medici with recommendations regarding his library collection, saying, "de studiis autem humanitatis quantum ad grammaticam, rhetoricam, historicam et poeticam spectat ac moralem" ("concerning studies of the humanities, insofar as they [consist of] grammar, rhetoric, history and poetry, and also ethics").

And so, the term studia humanitatis took on a variety of meanings over the centuries, being used differently by humanists across the various Italian city-states as one definition got adopted and spread across the country. Still, it has referred consistently to a mode of learning—formal or not—that results in one's moral edification.

Under the influence and inspiration of the classics, Renaissance humanists developed a new rhetoric and new learning. Some scholars also argue that humanism articulated new moral and civic perspectives, and values offering guidance in life to all citizens. Renaissance humanism was a response to what came to be depicted by later whig historians as the "narrow pedantry" associated with medieval scholasticism.

History

In the last years of the 13th century and in the first decades of the 14th century, the cultural climate was changing in some European regions. The rediscovery, study, and renewed interest in authors who had been forgotten, and in the classical world that they represented, inspired a flourishing return to linguistic, stylistic and literary models of antiquity. There emerged a consciousness of the need for a cultural renewal, which sometimes also meant a detachment from contemporary culture. Manuscripts and inscriptions were in high demand and graphic models were also imitated. This "return to the ancients" was the main component of so-called "pre-humanism", which developed particularly in Tuscany, in the Veneto region, and at the papal court of Avignon, through the activity of figures such as Lovato Lovati and Albertino Mussato in Padua, Landolfo Colonna in Avignon, Ferreto de' Ferreti in Vicenza, Convenevole from Prato in Tuscany and then in Avignon, and many others.

By the 14th century some of the first humanists were great collectors of antique manuscripts, including Petrarch, Giovanni Boccaccio, Coluccio Salutati, and Poggio Bracciolini. Of the four, Petrarch was dubbed the "Father of Humanism," as he was the one who first encouraged the study of pagan civilizations and the teaching of classical virtues as a means of preserving Christianity. He also had a library, of which many manuscripts did not survive. Many worked for the Catholic Church and were in holy orders, like Petrarch, while others were lawyers and chancellors of Italian cities, and thus had access to book copying workshops, such as Petrarch's disciple Salutati, the Chancellor of Florence.

In Italy, the humanist educational program won rapid acceptance and, by the mid-15th century, many of the upper classes had received humanist educations, possibly in addition to traditional scholastic ones. Some of the highest officials of the Catholic Church were humanists with the resources to amass important libraries. Such was Cardinal Basilios Bessarion, a convert to the Catholic Church from Greek Orthodoxy, who was considered for the papacy, and was one of the most learned scholars of his time. There were several 15th-century and early 16th-century humanist Popes one of whom, Aeneas Silvius Piccolomini (Pope Pius II), was a prolific author and wrote a treatise on The Education of Boys. These subjects came to be known as the humanities, and the movement which they inspired is shown as humanism.

The migration waves of Byzantine Greek scholars and émigrés in the period following the Crusader sacking of Constantinople and the end of the Byzantine Empire in 1453 was a very welcome addition to the Latin texts scholars like Petrarch had found in monastic libraries for the revival of Greek literature and science via their greater familiarity with ancient Greek works. They included Gemistus Pletho, George of Trebizond, Theodorus Gaza, and John Argyropoulos.

There were important centres of Renaissance humanism in Bologna, Ferrara, Florence, Genoa, Livorno, Mantua, Padua, Pisa, Naples, Rome, Siena, Venice, Vicenza, and Urbino.

Italian humanism spread to Spain, with Francisco de Vitoria becoming its first great exponent. He founded the School of Salamanca, of which Antonio de Nebrija became one of its main members. A circle of humanists also formed around King of Spain and Holy Roman Emperor Charles I and V, with names like Alfonso and Juan de Valdés, Juan Luis Vives and Luisa Sigea. Charles appointed another noted humanist, Mercurino di Gattinara, his chancellor. The Valdés brothers, Gattinara and Antonio de Guevara were proponents of working towards the restoration of a Christian, universal Roman Empire, an idea originally inspired by Dante Alighieri in his Monarchia. Spain's participation in the Italian Wars and the Ottoman-Habsburg conflicts also gave birth to a militant strain of humanism known as las armas y las letras, first codified in Charles' court by Baldassare Castiglione.

Humanism also spread northward to France, Germany, the Low Countries, Poland-Lithuania, Hungary and England with the adoption of large-scale printing after 1500, and it became associated with the Reformation. In France, pre-eminent humanist Guillaume Budé (1467–1540) applied the philological methods of Italian humanism to the study of antique coinage and to legal history, composing a detailed commentary on Justinian's Code. Budé was a royal absolutist (and not a republican like the early Italian umanisti) who was active in civic life, serving as a diplomat for Francis I and helping to found the Collège des Lecteurs Royaux (later the Collège de France). Meanwhile, Marguerite de Navarre, the sister of Francis I, was a poet, novelist, and religious mystic who gathered around her and protected a circle of vernacular poets and writers, including Clément Marot, Pierre de Ronsard, and François Rabelais.

Paganism and Christianity in the Renaissance

Many humanists were churchmen, most notably Pope Pius II, Sixtus IV, and Leo X, and there was often patronage of humanists by senior church figures. Much humanist effort went into improving the understanding and translations of Biblical and early Christian texts, both before and after the Reformation, which was greatly influenced by the work of non-Italian, Northern European figures such as Erasmus, Jacques Lefèvre d'Étaples, William Grocyn, and Swedish Catholic Archbishop in exile Olaus Magnus.

Description

The Cambridge Dictionary of Philosophy describes the rationalism of ancient writings as having tremendous impact on Renaissance scholars:

Here, one felt no weight of the supernatural pressing on the human mind, demanding homage and allegiance. Humanity—with all its distinct capabilities, talents, worries, problems, possibilities—was the center of interest. It has been said that medieval thinkers philosophised on their knees, but, bolstered by the new studies, they dared to stand up and to rise to full stature.

In 1417, for example, Poggio Bracciolini discovered the manuscript of Lucretius, De rerum natura, which had been lost for centuries and which contained an explanation of Epicurean doctrine, though at the time this was not commented on much by Renaissance scholars, who confined themselves to remarks about Lucretius's grammar and syntax.

Only in 1564 did French commentator Denys Lambin (1519–72) announce in the preface to the work that "he regarded Lucretius's Epicurean ideas as 'fanciful, absurd, and opposed to Christianity'." Lambin's preface remained standard until the nineteenth century. Epicurus's unacceptable doctrine that pleasure was the highest good "ensured the unpopularity of his philosophy". Lorenzo Valla, however, puts a defense of epicureanism in the mouth of one of the interlocutors of one of his dialogues.

Epicureanism

Charles Trinkhaus regards Valla's "epicureanism" as a ploy, not seriously meant by Valla, but designed to refute Stoicism, which he regarded together with epicureanism as equally inferior to Christianity. Valla's defense, or adaptation, of Epicureanism was later taken up in The Epicurean by Erasmus, the "Prince of humanists:"

If people who live agreeably are Epicureans, none are more truly Epicurean than the righteous and godly. And if it is names that bother us, no one better deserves the name of Epicurean than the revered founder and head of the Christian philosophy Christ, for in Greek epikouros means "helper". He alone, when the law of Nature was all but blotted out by sins, when the law of Moses incited to lists rather than cured them, when Satan ruled in the world unchallenged, brought timely aid to perishing humanity. Completely mistaken, therefore, are those who talk in their foolish fashion about Christ's having been sad and gloomy in character and calling upon us to follow a dismal mode of life. On the contrary, he alone shows the most enjoyable life of all and the one most full of true pleasure.

This passage exemplifies the way in which the humanists saw pagan classical works, such as the philosophy of Epicurus, as being in harmony with their interpretation of Christianity.

Neo-Platonism

Renaissance Neo-Platonists such as Marsilio Ficino (whose translations of Plato's works into Latin were still used into the 19th century) attempted to reconcile Platonism with Christianity, according to the suggestions of early Church Fathers Lactantius and Saint Augustine. In this spirit, Pico della Mirandola attempted to construct a syncretism of religions and philosophies with Christianity, but his work did not win favor with the church authorities, who rejected it because of his views on magic.

Evolution and reception

The historian of the Renaissance Sir John Hale cautions against too direct a linkage between Renaissance humanism and modern uses of the term humanism: "Renaissance humanism must be kept free from any hint of either 'humanitarianism' or 'humanism' in its modern sense of rational, non-religious approach to life ... the word 'humanism' will mislead ... if it is seen in opposition to a Christianity its students in the main wished to supplement, not contradict, through their patient excavation of the sources of ancient God-inspired wisdom."

Individual freedom

Historian Steven Kreis expresses a widespread view (derived from the 19th-century Swiss historian Jacob Burckhardt), when he writes that:

The period from the fourteenth century to the seventeenth worked in favor of the general emancipation of the individual. The city-states of northern Italy had come into contact with the diverse customs of the East, and gradually permitted expression in matters of taste and dress. The writings of Dante, and particularly the doctrines of Petrarch and humanists like Machiavelli, emphasized the virtues of intellectual freedom and individual expression. In the essays of Montaigne the individualistic view of life received perhaps the most persuasive and eloquent statement in the history of literature and philosophy.

Two noteworthy trends in some Renaissance humanists were Renaissance Neo-Platonism and Hermeticism, which through the works of figures like Nicholas of Kues, Giordano Bruno, Cornelius Agrippa, Campanella and Giovanni Pico della Mirandola sometimes came close to constituting a new religion itself. Of these two, Hermeticism has had great continuing influence in Western thought, while the former mostly dissipated as an intellectual trend, leading to movements in Western esotericism such as Theosophy and New Age thinking. The "Yates thesis" of Frances Yates holds that before falling out of favour, esoteric Renaissance thought introduced several concepts that were useful for the development of scientific method, though this remains a matter of controversy.

Sixteenth century and beyond

Though humanists continued to use their scholarship in the service of the church into the middle of the sixteenth century and beyond, the sharply confrontational religious atmosphere following the Reformation resulted in the Counter-Reformation that sought to silence challenges to Catholic theology, with similar efforts among the Protestant denominations. Some humanists, even moderate Catholics such as Erasmus, risked being declared heretics for their perceived criticism of the institutional church.

A number of humanists joined the Reformation movement and took over leadership functions, for example, Philipp Melanchthon, Ulrich Zwingli, Henry VIII, John Calvin, and William Tyndale. Others, like Jacques Lefèvre d'Étaples, were favorable to it although they remained Catholic.

With the Counter-Reformation initiated by the Council of Trent (1545–1563), positions hardened and a strict Catholic orthodoxy based on scholastic philosophy was imposed. However the education systems developed by Jesuits ran on humanist lines.

Historiography

Baron thesis

Hans Baron (1900–1988) was the inventor of the now ubiquitous term "civic humanism." First coined in the 1920s and based largely on his studies of Leonardo Bruni, Baron's "thesis" proposed the existence of a central strain of humanism, particularly in Florence and Venice, dedicated to republicanism.

As argued in his chef-d'œuvre, The Crisis of the Early Italian Renaissance: Civic Humanism and Republican Liberty in an Age of Classicism and Tyranny, the German historian thought that civic humanism originated in around 1402, after the great struggles between Florence and Visconti-led Milan in the 1390s. He considered Petrarch's humanism to be a rhetorical, superficial project, and viewed this new strand to be one that abandoned the feudal and supposedly "otherworldly" (i.e., divine) ideology of the Middle Ages in favour of putting the republican state and its freedom at the forefront of the "civic humanist" project. Already controversial at the time of The Crisis' publication, the "Baron Thesis" has been met with even more criticism over the years.

Even in the 1960s, historians Philip Jones and Peter Herde found Baron's praise of "republican" humanists naive, arguing that republics were far less liberty-driven than Baron had believed, and were practically as undemocratic as monarchies. James Hankins adds that the disparity in political values between the humanists employed by oligarchies and those employed by princes was not particularly notable, as all of Baron's civic ideals were exemplified by humanists serving various types of government. In so arguing, he asserts that a "political reform program is central to the humanist movement founded by Petrarch. But it is not a 'republican' project in Baron's sense of republic; it is not an ideological product associated with a particular regime type."

Garin and Kristeller

Two renowned Renaissance scholars, Eugenio Garin and Paul Oskar Kristeller collaborated with one another throughout their careers. But while the two historians were on good terms, they fundamentally disagreed on the nature of Renaissance humanism.

• Kristeller affirmed that Renaissance humanism used to be viewed just as a project of Classical revival, one that led to great increase in Classical scholarship. But he argued that this theory "fails to explain the ideal of eloquence persistently set forth in the writings of the humanists," asserting that "their classical learning was incidental to" their being "professional rhetoricians." Similarly, he considered their influence on philosophy and particular figures' philosophical output to be incidental to their humanism, viewing grammar, rhetoric, poetry, history, and ethics to be the humanists' main concerns.
• Garin, on the other hand, viewed philosophy itself as being ever-evolving, each form of philosophy being inextricable from the practices of the thinkers of its period. He thus considered the Italian humanists' break from Scholasticism and newfound freedom to be perfectly in line with this broader sense of philosophy.

During the period in which they argued over these differing views, there was a broader cultural conversation happening regarding Humanism: one revolving around Jean-Paul Sartre and Martin Heidegger.

• In 1946, Sartre published a work called "L'existentialisme est un humanisme," in which he outlined his conception of existentialism as revolving around the belief that "existence comes before essence"; that man "first of all exists, encounters himself, surges up in the world – and defines himself afterwards," making himself and giving himself purpose.
• Heidegger, in a response to this work of Sartre's, declared: "For this is humanism: meditating and caring, that human beings be human and not inhumane, "inhuman", that is, outside their essence." He also discussed a decline in the concept of humanism, pronouncing that it had been dominated by metaphysics and essentially discounting it as philosophy. He also explicitly criticized Italian Renaissance humanism in the letter.

While this discourse was taking place outside the realm of Renaissance Studies (for more on the evolution of the term "humanism," see Humanism), this background debate was not irrelevant to Kristeller and Garin's ongoing disagreement. Kristeller—who had at one point studied under Heidegger—also discounted (Renaissance) humanism as philosophy, and Garin's Der italienische Humanismus was published alongside Heidegger's response to Sartre—a move that Rubini describes as an attempt "to stage a pre-emptive confrontation between historical humanism and philosophical neo-humanisms."  Garin also conceived of the Renaissance humanists as occupying the same kind of "characteristic angst the existentialists attributed to men who had suddenly become conscious of their radical freedom," further weaving philosophy with Renaissance humanism.

Hankins summarizes the Kristeller v. Garin debate as:

• Kristeller conceives of professional philosophers as being very formal and method-focused. Renaissance humanists, on the other hand, he viewed to be professional rhetoricians who, using their classically-inspired paideia or institutio, did improve fields such as philosophy, but without the practice of philosophy being their main goal or function.
• Garin, instead, wanted his "humanist-philosophers to be organic intellectuals," not constituting a rigid school of thought, but having a shared outlook on life and education that broke with the medieval traditions that came before them.

I. R. Grigulevich

According to Russian historian and Stalinist assassin Iosif Grigulevich two characteristic traits of late Renaissance humanism were "its revolt against abstract, Aristotelian modes of thought and its concern with the problems of war, poverty, and social injustice."