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Reactive oxygen species

In chemistry and biology, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (O2), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (O2H), superoxide (O2-), hydroxyl radical (OH.), and singlet oxygen. ROS are pervasive because they are readily produced from O2, which is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O2, which is central to fuel cells. ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations.

Inventory of ROS
ROS are not uniformly defined. All sources include superoxide, singlet oxygen, and hydroxyl radical. Hydrogen peroxide is not nearly as reactive as these species, but is readily activated and is thus included. Peroxynitrite and nitric oxide are reactive oxygen-containing species as well.
 * Hydroxyl radical (HO*) is generated by Fenton reaction of hydrogen peroxide with ferrous compounds and related reducing agents:
 * Fe(II) + H2O2 -> Fe(III)OH +  HO*

In its fleeting existence, the hydroxyl radical reacts rapidly irreversibly with all organic compounds.
 * superoxide (O2-) is produced by reduction of O2. Several grams are produced per day in the human body within the mitochondria.
 * O2 + e- -> O2-

Competing with its formation, superoxide is destroyed by the action of superoxide dismutases, enzymes that catalyze its disproportionation:
 * 2 O2- + 2H+ ->  O2  +  H2O2

 * hydrogen peroxide (H2O2) is also produced as a side product of respiration.
 * Peroxynitrite (ONO2-) results from the reaction of superoxide and nitric oxide.

 * Singlet oxygen (^{1}O2) is sometimes included as an ROS. Photosensitizers such as chlorophyll may convert triplet (^{3}O2) to singlet oxygen: Singlet oxygen is highly reactive with unsaturated organic compounds. Carotenoids, tocopherols, and plastoquinones contained in chloroplasts quench singlet oxygen and protect against its toxic effects. Oxidized products of β-carotene arising from the presence of singlet oxygen act as second messengers that can either protect against singlet oxygen induced toxicity or initiate programmed cell death. Levels of jasmonate play a key role in the decision between cell acclimation or cell death in response to elevated levels of this reactive oxygen species.

Biological function
In a biological context, ROS are byproducts of the normal metabolism of oxygen. ROS have roles in cell signaling and homeostasis. ROS are intrinsic to cellular functioning, and are present at low and stationary levels in normal cells. In plants, ROS are involved in metabolic processes related to photoprotection and tolerance to various types of stress. However, ROS can cause irreversible damage to DNA as they oxidize and modify some cellular components and prevent them from performing their original functions. This suggests that ROS has a dual role; whether they will act as harmful, protective or signaling factors depends on the balance between ROS production and disposal at the right time and place. In other words, oxygen toxicity can arise both from uncontrolled production and from the inefficient elimination of ROS by the antioxidant system. ROS were also demonstrated to modify the visual appearance of fish. This potentially affects their behavior and ecology, such as their temperature control, their visual communication, their reproduction and survival. During times of environmental stress (e.g., UV or heat exposure), ROS levels can increase dramatically. This may result in significant damage to cell structures. Cumulatively, this is known as oxidative stress. The production of ROS is strongly influenced by stress factor responses in plants, these factors that increase ROS production include drought, salinity, chilling, defense of pathogens, nutrient deficiency, metal toxicity and UV-B radiation. ROS are also generated by exogenous sources such as ionizing radiation generating irreversible effects in the development of tissues in both animals and plants.

Endogenous sources
ROS are produced during the processes of respiration and photosynthesis in organelles such as mitochondria, peroxisomes and chloroplasts. During the respiration process the mitochondria convert energy for the cell into a usable form, adenosine triphosphate (ATP). The process of ATP production in the mitochondria, called oxidative phosphorylation, involves the transport of protons (hydrogen ions) across the inner mitochondrial membrane by means of the electron transport chain. In the electron transport chain, electrons are passed through a series of proteins via oxidation-reduction reactions, with each acceptor protein along the chain having a greater reduction potential than the previous. The last destination for an electron along this chain is an oxygen molecule. In normal conditions, the oxygen is reduced to produce water; however, in about 0.1–2% of electrons passing through the chain (this number derives from studies in isolated mitochondria, though the exact rate in live organisms is yet to be fully agreed upon), oxygen is instead prematurely and incompletely reduced to give the superoxide radical (•), most well documented for Complex I and Complex III.

Another source of ROS production in animal cells is the electron transfer reactions catalyzed by the mitochondrial P450 systems in steroidogenic tissues. These P450 systems are dependent on the transfer of electrons from NADPH to P450. During this process, some electrons "leak" and react with O2 producing superoxide. To cope with this natural source of ROS, the steroidogenic tissues, ovary and testis, have a large concentration of antioxidants such as vitamin C (ascorbate) and β-carotene and anti-oxidant enzymes.

If too much damage is present in mitochondria, a cell undergoes apoptosis or programmed cell death.

In addition, ROS are produced in immune cell signaling via the NOX pathway. Phagocytic cells such as neutrophils, eosinophils, and mononuclear phagocytes produce ROS when stimulated.

In chloroplasts, the carboxylation and oxygenation reactions catalyzed by rubisco ensure that the functioning of the electron transport chain (ETC) occurs in an environment rich in O2. The leakage of electrons in the ETC will inevitably produce ROS within the chloroplasts. ETC in photosystem I (PSI) was once believed to be the only source of ROS in chloroplasts. The flow of electrons from the excited reaction centers is directed to the NADP and these are reduced to NADPH, and then they enter the Calvin cycle and reduce the final electron acceptor, CO2. In cases where there is an ETC overload, part of the electron flow is diverted from ferredoxin to O2, forming the superoxide free radical (by the Mehler reaction). In addition, electron leakage to O2 can also occur from the 2Fe-2S and 4Fe-4S clusters in the PSI ETC. However, PSII also provides electron leakage locations (QA, QB) for O2-producing O2-. Superoxide (O2-) is generated from PSII, instead of PSI; QB is shown as the location for the generation of O2•-.

Exogenous sources
The formation of ROS can be stimulated by a variety of agents such as pollutants, heavy metals, tobacco, smoke, drugs, xenobiotics, microplastics, or radiation. In plants, in addition to the action of dry abiotic factors, high temperature, interaction with other living beings can influence the production of ROS.

Ionizing radiation can generate damaging intermediates through the interaction with water, a process termed radiolysis. Since water comprises 55–60% of the human body, the probability of radiolysis is quite high under the presence of ionizing radiation. In the process, water loses an electron and becomes highly reactive. Then through a three-step chain reaction, water is sequentially converted to hydroxyl radical (•OH), hydrogen peroxide (H2O2), superoxide radical (•), and ultimately oxygen (O2).

The hydroxyl radical is extremely reactive and immediately removes electrons from any molecule in its path, turning that molecule into a free radical and thus propagating a chain reaction. However, hydrogen peroxide is actually more damaging to DNA than the hydroxyl radical, since the lower reactivity of hydrogen peroxide provides enough time for the molecule to travel into the nucleus of the cell, subsequently reacting with macromolecules such as DNA.

In plants, the production of ROS occurs during events of abiotic stress that lead to a reduction or interruption of metabolic activity. For example, the increase in temperature, drought are factors that limit the availability of CO2 due to stomatal closure, increasing the production of ROS, such as O2·- and 1O2 in chloroplasts. The production of 1O2 in chloroplasts can cause reprogramming of the expression of nucleus genes leading to chlorosis and programmed cell death. In cases of biotic stress, the generation of ROS occurs quickly and weakly initially and then becomes more solid and lasting. The first phase of ROS accumulation is associated with plant infection and is probably independent of the synthesis of new ROS-generating enzymes. However, the second phase of ROS accumulation is associated only with infection by non-virulent pathogens and is an induced response dependent on increased mRNA transcription encoding enzymes.

Superoxide dismutase
Superoxide dismutases (SOD) are a class of enzymes that catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide. As such, they are an important antioxidant defense in nearly all cells exposed to oxygen. In mammals and most chordates, three forms of superoxide dismutase are present. SOD1 is located primarily in the cytoplasm, SOD2 in the mitochondria and SOD3 is extracellular. The first is a dimer (consists of two units), while the others are tetramers (four subunits). SOD1 and SOD3 contain copper and zinc ions, while SOD2 has a manganese ion in its reactive centre. The genes are located on chromosomes 21, 6, and 4, respectively (21q22.1, 6q25.3 and 4p15.3-p15.1).

The SOD-catalysed dismutation of superoxide may be written with the following half-reactions:

where M = Cu ($n = 1$); Mn ($n = 2$); Fe ($n = 2$); Ni ($n = 2$). In this reaction the oxidation state of the metal cation oscillates between $n$ and $n + 1$.

Catalase, which is concentrated in peroxisomes located next to mitochondria, reacts with the hydrogen peroxide to catalyze the formation of water and oxygen. Glutathione peroxidase reduces hydrogen peroxide by transferring the energy of the reactive peroxides to a sulfur-containing tripeptide called glutathione. The sulfur contained in these enzymes acts as the reactive center, carrying reactive electrons from the peroxide to the glutathione. Peroxiredoxins also degrade H2O2, within the mitochondria, cytosol, and nucleus.

Damaging effects
Effects of ROS on cell metabolism are well documented in a variety of species. These include not only roles in apoptosis (programmed cell death) but also positive effects such as the induction of host defence genes and mobilization of ion transporters. This implicates them in control of cellular function. In particular, platelets involved in wound repair and blood homeostasis release ROS to recruit additional platelets to sites of injury. These also provide a link to the adaptive immune system via the recruitment of leukocytes.

Reactive oxygen species are implicated in cellular activity to a variety of inflammatory responses including cardiovascular disease. They may also be involved in hearing impairment via cochlear damage induced by elevated sound levels, in ototoxicity of drugs such as cisplatin, and in congenital deafness in both animals and humans. ROS are also implicated in mediation of apoptosis or programmed cell death and ischaemic injury. Specific examples include stroke and heart attack.

In general, the harmful effects of reactive oxygen species on the cell are the damage of DNA or RNA, oxidation of polyunsaturated fatty acids in lipids (lipid peroxidation), oxidation of amino acids in proteins, and oxidative deactivation of specific enzymes by oxidation co-factors.

Pathogen response
When a plant recognizes an attacking pathogen, one of the first induced reactions is to rapidly produce superoxide or hydrogen peroxide  to strengthen the cell wall. This prevents the spread of the pathogen to other parts of the plant, essentially forming a net around the pathogen to restrict movement and reproduction.

In the mammalian host, ROS is induced as an antimicrobial defense. To highlight the importance of this defense, individuals with chronic granulomatous disease who have deficiencies in generating ROS, are highly susceptible to infection by a broad range of microbes including Salmonella enterica, Staphylococcus aureus, Serratia marcescens, and Aspergillus spp.

Studies on the homeostasis of the Drosophila melanogaster’s intestines have shown the production of ROS as a key component of the immune response in the gut of the fly. ROS acts both as a bactericide, damaging the bacterial DNA, RNA and proteins, as well as a signalling molecule that induces repair mechanisms of the epithelium. The uracil released by microorganism triggers the production and activity of DUOX, the ROS-producing enzyme in the intestine. DUOX activity is induced according to the level of uracil in the gut; under basal conditions, it is down-regulated by the protein kinase MkP3. The tight regulation of DUOX avoids excessive production of ROS and facilitates differentiation between benign and damage-inducing microorganisms in the gut.

The manner in which ROS defends the host from invading microbe is not fully understood. One of the more likely modes of defense is damage to microbial DNA. Studies using Salmonella demonstrated that DNA repair mechanisms were required to resist killing by ROS. A role for ROS in antiviral defense mechanisms has been demonstrated via Rig-like helicase-1 and mitochondrial antiviral signaling protein. Increased levels of ROS potentiate signaling through this mitochondria-associated antiviral receptor to activate interferon regulatory factor (IRF)-3, IRF-7, and nuclear factor kappa B (NF-κB), resulting in an antiviral state. Respiratory epithelial cells induce mitochondrial ROS in response to influenza infection. This induction of ROS led to the induction of type III interferon and the induction of an antiviral state, limiting viral replication. In host defense against mycobacteria, ROS play a role, although direct killing is likely not the key mechanism; rather, ROS likely affect ROS-dependent signalling controls, such as cytokine production, autophagy, and granuloma formation.

Reactive oxygen species are also implicated in activation, anergy and apoptosis of T cells.

Oxidative damage
In aerobic organisms the energy needed to fuel biological functions is produced in the mitochondria via the electron transport chain. Reactive oxygen species (ROS) with the potential to cause cellular damage are produced along with the release of energy. ROS can damage lipids, DNA, RNA, and proteins, which, in theory, contributes to the physiology of aging.

ROS are produced as a normal product of cellular metabolism. In particular, one major contributor to oxidative damage is hydrogen peroxide (H2O2), which is converted from superoxide that leaks from the mitochondria. Catalase and superoxide dismutase ameliorate the damaging effects of hydrogen peroxide and superoxide, respectively, by converting these compounds into oxygen and hydrogen peroxide (which is later converted to water), resulting in the production of benign molecules. However, this conversion is not 100% efficient, and residual peroxides persist in the cell. While ROS are produced as a product of normal cellular functioning, excessive amounts can cause deleterious effects.

Impairment of cognitive function
Memory capabilities decline with age, evident in human degenerative diseases such as Alzheimer's disease, which is accompanied by an accumulation of oxidative damage. Current studies demonstrate that the accumulation of ROS can decrease an organism's fitness because oxidative damage is a contributor to senescence. In particular, the accumulation of oxidative damage may lead to cognitive dysfunction, as demonstrated in a study in which old rats were given mitochondrial metabolites and then given cognitive tests. Results showed that the rats performed better after receiving the metabolites, suggesting that the metabolites reduced oxidative damage and improved mitochondrial function. Accumulating oxidative damage can then affect the efficiency of mitochondria and further increase the rate of ROS production. The accumulation of oxidative damage and its implications for aging depends on the particular tissue type where the damage is occurring. Additional experimental results suggest that oxidative damage is responsible for age-related decline in brain functioning. Older gerbils were found to have higher levels of oxidized protein in comparison to younger gerbils. Treatment of old and young mice with a spin trapping compound caused a decrease in the level of oxidized proteins in older gerbils but did not have an effect on younger gerbils. In addition, older gerbils performed cognitive tasks better during treatment but ceased functional capacity when treatment was discontinued, causing oxidized protein levels to increase. This led researchers to conclude that oxidation of cellular proteins is potentially important for brain function.

Cause of aging
According to the free radical theory of aging, oxidative damage initiated by reactive oxygen species is a major contributor to the functional decline that is characteristic of aging. While studies in invertebrate models indicate that animals genetically engineered to lack specific antioxidant enzymes (such as SOD), in general, show a shortened lifespan (as one would expect from the theory), the converse manipulation, increasing the levels of antioxidant enzymes, has yielded inconsistent effects on lifespan (though some studies in Drosophila do show that lifespan can be increased by the overexpression of MnSOD or glutathione biosynthesizing enzymes). Also contrary to this theory, deletion of mitochondrial SOD2 can extend lifespan in Caenorhabditis elegans.

In mice, the story is somewhat similar. Deleting antioxidant enzymes, in general, yields shorter lifespan, although overexpression studies have not (with some exceptions) consistently extended lifespan. Study of a rat model of premature aging found increased oxidative stress, reduced antioxidant enzyme activity and substantially greater DNA damage in the brain neocortex and hippocampus of the prematurely aged rats than in normally aging control rats. The DNA damage 8-OHdG is a product of ROS interaction with DNA. Numerous studies have shown that 8-OHdG increases with age (see DNA damage theory of aging).

Cancer
ROS are constantly generated and eliminated in the biological system and are required to drive regulatory pathways. Under normal physiological conditions, cells control ROS levels by balancing the generation of ROS with their elimination by scavenging systems. But under oxidative stress conditions, excessive ROS can damage cellular proteins, lipids and DNA, leading to fatal lesions in the cell that contribute to carcinogenesis.

Cancer cells exhibit greater ROS stress than normal cells do, partly due to oncogenic stimulation, increased metabolic activity and mitochondrial malfunction. ROS is a double-edged sword. On one hand, at low levels, ROS facilitates cancer cell survival since cell-cycle progression driven by growth factors and receptor tyrosine kinases (RTK) require ROS for activation and chronic inflammation, a major mediator of cancer, is regulated by ROS. On the other hand, a high level of ROS can suppress tumor growth through the sustained activation of cell-cycle inhibitor and induction of cell death as well as senescence by damaging macromolecules. In fact, most of the chemotherapeutic and radiotherapeutic agents kill cancer cells by augmenting ROS stress. The ability of cancer cells to distinguish between ROS as a survival or apoptotic signal is controlled by the dosage, duration, type, and site of ROS production. Modest levels of ROS are required for cancer cells to survive, whereas excessive levels kill them.

Metabolic adaptation in tumours balances the cells' need for energy with equally important need for macromolecular building blocks and tighter control of redox balance. As a result, production of NADPH is greatly enhanced, which functions as a cofactor to provide reducing power in many enzymatic reactions for macromolecular biosynthesis and at the same time rescuing the cells from excessive ROS produced during rapid proliferation. Cells counterbalance the detrimental effects of ROS by producing antioxidant molecules, such as reduced glutathione (GSH) and thioredoxin (TRX), which rely on the reducing power of NADPH to maintain their activities.

Most risk factors associated with cancer interact with cells through the generation of ROS. ROS then activate various transcription factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), activator protein-1 (AP-1), hypoxia-inducible factor-1α and signal transducer and activator of transcription 3 (STAT3), leading to expression of proteins that control inflammation; cellular transformation; tumor cell survival; tumor cell proliferation; and invasion, angiogenesis as well as metastasis. And ROS also control the expression of various tumor suppressor genes such as p53, retinoblastoma gene (Rb), and phosphatase and tensin homolog (PTEN).

Carcinogenesis
ROS-related oxidation of DNA is one of the main causes of mutations, which can produce several types of DNA damage, including non-bulky (8-oxoguanine and formamidopyrimidine) and bulky (cyclopurine and etheno adducts) base modifications, abasic sites, non-conventional single-strand breaks, protein-DNA adducts, and intra/interstrand DNA crosslinks. It has been estimated that endogenous ROS produced via normal cell metabolism modify approximately 20,000 bases of DNA per day in a single cell. 8-oxoguanine is the most abundant among various oxidized nitrogeneous bases observed. During DNA replication, DNA polymerase mispairs 8-oxoguanine with adenine, leading to a G→T transversion mutation. The resulting genomic instability directly contributes to carcinogenesis. Cellular transformation leads to cancer and interaction of atypical PKC-ζ isoform with p47phox controls ROS production and transformation from apoptotic cancer stem cells through blebbishield emergency program.

Cell proliferation
Uncontrolled proliferation is a hallmark of cancer cells. Both exogenous and endogenous ROS have been shown to enhance proliferation of cancer cells. The role of ROS in promoting tumor proliferation is further supported by the observation that agents with potential to inhibit ROS generation can also inhibit cancer cell proliferation. Although ROS can promote tumor cell proliferation, a great increase in ROS has been associated with reduced cancer cell proliferation by induction of G2/M cell cycle arrest; increased phosphorylation of ataxia telangiectasia mutated (ATM), checkpoint kinase 1 (Chk 1), Chk 2; and reduced cell division cycle 25 homolog c (CDC25).

Cell death
A cancer cell can die in three ways: apoptosis, necrosis, and autophagy. Excessive ROS can induce apoptosis through both the extrinsic and intrinsic pathways. In the extrinsic pathway of apoptosis, ROS are generated by Fas ligand as an upstream event for Fas activation via phosphorylation, which is necessary for subsequent recruitment of Fas-associated protein with death domain and caspase 8 as well as apoptosis induction. In the intrinsic pathway, ROS function to facilitate cytochrome c release by activating pore-stabilizing proteins (Bcl-2 and Bcl-xL) as well as inhibiting pore-destabilizing proteins (Bcl-2-associated X protein, Bcl-2 homologous antagonist/killer). The intrinsic pathway is also known as the caspase cascade and is induced through mitochondrial damage which triggers the release of cytochrome c. DNA damage, oxidative stress, and loss of mitochondrial membrane potential lead to the release of the pro-apoptotic proteins mentioned above stimulating apoptosis. Mitochondrial damage is closely linked to apoptosis and since mitochondria are easily targeted there is potential for cancer therapy.

The cytotoxic nature of ROS is a driving force behind apoptosis, but in even higher amounts, ROS can result in both apoptosis and necrosis, a form of uncontrolled cell death, in cancer cells.

Numerous studies have shown the pathways and associations between ROS levels and apoptosis, but a newer line of study has connected ROS levels and autophagy. ROS can also induce cell death through autophagy, which is a self-catabolic process involving sequestration of cytoplasmic contents (exhausted or damaged organelles and protein aggregates) for degradation in lysosomes. Therefore, autophagy can also regulate the cell's health in times of oxidative stress. Autophagy can be induced by ROS levels through many pathways in the cell in an attempt to dispose of harmful organelles and prevent damage, such as carcinogens, without inducing apoptosis. Autophagic cell death can be prompted by the over expression of autophagy where the cell digests too much of itself in an attempt to minimize the damage and can no longer survive. When this type of cell death occurs, an increase or loss of control of autophagy regulating genes is commonly co-observed. Thus, once a more in-depth understanding of autophagic cell death is attained and its relation to ROS, this form of programmed cell death may serve as a future cancer therapy. Autophagy and apoptosis are distinct mechanisms for cell death brought on by high levels of ROS. Aautophagy and apoptosis, however, rarely act through strictly independent pathways. There is a clear connection between ROS and autophagy and a correlation seen between excessive amounts of ROS leading to apoptosis. The depolarization of the mitochondrial membrane is also characteristic of the initiation of autophagy. When mitochondria are damaged and begin to release ROS, autophagy is initiated to dispose of the damaging organelle. If a drug targets mitochondria and creates ROS, autophagy may dispose of so many mitochondria and other damaged organelles that the cell is no longer viable. The extensive amount of ROS and mitochondrial damage may also signal for apoptosis. The balance of autophagy within the cell and the crosstalk between autophagy and apoptosis mediated by ROS is crucial for a cell's survival. This crosstalk and connection between autophagy and apoptosis could be a mechanism targeted by cancer therapies or used in combination therapies for highly resistant cancers.

Tumor cell invasion, angiogenesis and metastasis
After growth factor stimulation of RTKs, ROS can trigger activation of signaling pathways involved in cell migration and invasion such as members of the mitogen activated protein kinase (MAPK) family – extracellular regulated kinase (ERK), c-jun NH-2 terminal kinase (JNK) and p38 MAPK. ROS can also promote migration by augmenting phosphorylation of the focal adhesion kinase (FAK) p130Cas and paxilin.

Both in vitro and in vivo, ROS have been shown to induce transcription factors and modulate signaling molecules involved in angiogenesis (MMP, VEGF) and metastasis (upregulation of AP-1, CXCR4, AKT and downregulation of PTEN).

Chronic inflammation and cancer
Experimental and epidemiologic research over the past several years has indicated close associations among ROS, chronic inflammation, and cancer. ROS induces chronic inflammation by the induction of COX-2, inflammatory cytokines (TNFα, interleukin 1 (IL-1), IL-6), chemokines (IL-8, CXCR4) and pro-inflammatory transcription factors (NF-κB). These chemokines and chemokine receptors, in turn, promote invasion and metastasis of various tumor types.

Cancer therapy

Both ROS-elevating and ROS-eliminating strategies have been developed with the former being predominantly used. Cancer cells with elevated ROS levels depend heavily on the antioxidant defense system. ROS-elevating drugs further increase cellular ROS stress level, either by direct ROS-generation (e.g. motexafin gadolinium, elesclomol) or by agents that abrogate the inherent antioxidant system such as SOD inhibitor (e.g. ATN-224, 2-methoxyestradiol) and GSH inhibitor (e.g. PEITC, buthionine sulfoximine (BSO)). The result is an overall increase in endogenous ROS, which when above a cellular tolerability threshold, may induce cell death. On the other hand, normal cells appear to have, under lower basal stress and reserve, a higher capacity to cope with additional ROS-generating insults than cancer cells do. Therefore, the elevation of ROS in all cells can be used to achieve the selective killing of cancer cells.

Radiotherapy also relies on ROS toxicity to eradicate tumor cells. Radiotherapy uses X-rays, γ-rays as well as heavy particle radiation such as protons and neutrons to induce ROS-mediated cell death and mitotic failure.

Due to the dual role of ROS, both prooxidant and antioxidant-based anticancer agents have been developed. However, modulation of ROS signaling alone seems not to be an ideal approach due to adaptation of cancer cells to ROS stress, redundant pathways for supporting cancer growth and toxicity from ROS-generating anticancer drugs. Combinations of ROS-generating drugs with pharmaceuticals that can break the redox adaptation could be a better strategy for enhancing cancer cell cytotoxicity.

James Watson and others have proposed that lack of intracellular ROS due to a lack of physical exercise may contribute to the malignant progression of cancer, because spikes of ROS are needed to correctly fold proteins in the endoplasmatic reticulum and low ROS levels may thus aspecifically hamper the formation of tumor suppressor proteins. Since physical exercise induces temporary spikes of ROS, this may explain why physical exercise is beneficial for cancer patient prognosis. Moreover, high inducers of ROS such as 2-deoxy-D-glucose and carbohydrate-based inducers of cellular stress induce cancer cell death more potently because they exploit the cancer cell's high avidity for sugars.

Positive role of ROS in memory

ROS are critical in memory formation. ROS also have a central role in epigenetic DNA demethylation, which is relevant to learning and memory

In mammalian nuclear DNA, a methyl group can be added, by a DNA methyltransferase, to the 5th carbon of cytosine to form 5mC (see red methyl group added to form 5mC near the top of the first figure). The DNA methyltransferases most often form 5mC within the dinucleotide sequence "cytosine-phosphate-guanine" to form 5mCpG. This addition is a major type of epigenetic alteration and it can silence gene expression. Methylated cytosine can also be demethylated, an epigenetic alteration that can increase the expression of a gene. A major enzyme involved in demethylating 5mCpG is TET1. However, TET1 is only able to act on 5mCpG if an ROS has first acted on the guanine to form 8-hydroxy-2'-deoxyguanosine (8-OHdG), resulting in a 5mCp-8-OHdG dinucleotide. However, TET1 is only able to act on the 5mC part of the dinucleotide when the base excision repair enzyme OGG1 binds to the 8-OHdG lesion without immediate excision. Adherence of OGG1 to the 5mCp-8-OHdG site recruits TET1 and TET1 then oxidizes the 5mC adjacent to 8-OHdG, as shown in the first figure, initiating a demethylation pathway shown in the second figure.

The thousands of CpG sites being demethylated during memory formation depend on ROS in an initial step. The altered protein expression in neurons, controlled in part by ROS-dependent demethylation of CpG sites in gene promoters within neuron DNA, are central to memory formation.

title: Reactive oxygen species


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Switchblade Symphony

Switchblade Symphony was an American gothic rock band from San Francisco, California. Their music combined orchestral sounds with heavy synth sequences and ethereal vocals to create a union of classical music and gothic rock.

History
Switchblade Symphony was formed in 1989 by composer Susan Wallace and vocalist Tina Root. The band's name refers to the cutting up elements of classical music to mix them with harder sounds.

They released their first album in 1995 on the Cleopatra Records label. They also had two live guitarists, first Robin Jacobs (who later joined Razor Skyline) and then George Earth (most recently of Small Halo, also with Tina Root), and three live drummers, first Eric Gebow (now with Blue Man Group), Justin Clayton, and then Scott van Shoick.

The band's second album, Bread and Jam for Frances, was released in 1997. The album peaked at #119 on the CMJ Radio Top 200.

Switchblade Symphony disbanded in November 1999. Subsequently, Tina Root started Tre Lux. In 2008, Tina Root and George Earth formed Small Halo, a band based out of Los Angeles, California.

Their song "Clown" was featured in the 1998 film Wicked starring Julia Stiles. Their song "Gutter Glitter" was also featured in an episode of The Boulet Brothers' Dragula.

Albums and EPs

 * Serpentine Gallery (1995)
 * Scrapbook (1997) (EP) (out of print)
 * Bread and Jam for Frances (1997)
 * The Three Calamities (1999)
 * Sinister Nostalgia (2001) (remixes)
 * Sweet, Little Witches (2003) (live performances and video track)
 * Serpentine Gallery Deluxe (2005)

Singles

 * "Clown" (1996)
 * "Drool" (1997)

Other

 * Fable (1991) (out of print demo cassette)
 * Elegy (1992) (out of print demo cassette)
 * "Girlscout" (single) (recorded with Jack Off Jill) (1998)

Compilation albums

 * From the Machine, featured the song: "Mine Eyes" (Index Records, 1990)
 * Gothic Rock Volume 2: 80's Into 90's (1995)
 * Gothik (1995) (re-released in 2006)
 * Wired Injections (1996)
 * Gothic Divas Presents: Switchblade Symphony, Tre Lux, and New Skin (Cleopatra, 2006)
 * Psycho Tina's Hell House Of Horrors, featured the song "Witches (Live)" (Cleopatra, )
 * Burning From the Outside: Retail Slut, featured the song "Clown (Razed In Black Vs. Transmutator Remix) " (Cleopatra, 2007)
 * The Devil's Songbook, featured the song "Wicked" (2010)
 * Virgin Voices 2, A Tribute to Madonna, featured the song "Lucky Star"

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Switchblade Symphony


text:
Rennell

Rennell may refer to:

People

 * Baron Rennell
 * Rennell Rodd, 1st Baron Rennell (1858–1941), British diplomat, poet and politician
 * Francis Rodd, 2nd Baron Rennell (1895–1978), British army officer and diplomat
 * Tremayne Rodd, 3rd Baron Rennell (1935–2006), Scottish rugby union player
 * James Rennell (1742–1830), British geographer and pioneer oceanographer
 * Paul Rennell, New Zealand soccer player
 * Thomas Rennell (1754–1840), British clergyman
 * Thomas Rennell (scholar) (1787–1824), British theologian and author

Places

 * Rennell Island, Solomon Islands
 * Rennell and Bellona Province
 * Rennell Glacier, Antarctica
 * Rennell Sound, Canada
 * North Rennell Island, Chile
 * South Rennell Island, Chile

Animals

 * Rennell fantail
 * Rennell flying fox
 * Rennell shrikebill
 * Rennell starling
 * Rennell Island monitor

title: Rennell


text:
Charles Rodman Campbell

Charles Rodman Campbell (October 21, 1954 – May 27, 1994) was an American serial killer who was executed by hanging in 1994 by the state of Washington for a 1982 triple murder committed in Clearview. He was later posthumously linked to an earlier 1975 murder via DNA.

Crimes
In December 1974, Campbell attacked 23-year-old Renae Wicklund while she was doing yard work outside her Clearview, Washington home. He demanded that she perform oral sex on him at knifepoint, threatening to kill her infant daughter, Shannah, if she did not comply. Wicklund submitted to his demands and then called police after he left. Campbell was not apprehended until 1976, when she picked him out of a police line-up. Local law enforcement were not surprised, as they had been familiar with Campbell since his childhood.

At the subsequent trial, Wicklund and her neighbor, Barbara Hendrickson, testified in detail about the assault, and Campbell was sentenced to 40 years in prison for first-degree rape. Unknown to Wicklund, Campbell's sentences ran concurrently, not consecutively. This meant that he could in theory be paroled in seven years. Ultimately, Campbell ended up being released in 1981 for good behavior. His victims were not informed of his release. During the intervening years, Wicklund had separated from her husband, Jack, due to the lingering stress of the assault and devoted herself to raising her daughter, supporting herself and Shannah with an in-home business as an accountant for local beauty parlors, as well as helping students obtain loans for beautician school.

Jack Wicklund meanwhile fell victim to a bizarre incident in December 1977, when he was found tied to a chair in his West Seattle home with massive third-degree burns. After receiving medical treatment, he said that a complete stranger visited his house, tied him up, doused him with gasoline, and set him on fire. Wicklund was required to wear a rubber bodysuit to protect his damaged skin. Five months later, he died when his car crashed into a tree. The exact circumstances surrounding Jack Wicklund's death are unclear, and police never satisfactorily determined whether he had been murdered or had committed suicide.

On April 14, 1982, Barbara Hendrickson's husband, Don, walked over to Wicklund's house and discovered Renae, her nine-year-old daughter Shannah, and his wife, all with their throats cut. Charles Campbell, then residing at a halfway house, was arrested the following week and charged with first-degree murder and second-degree theft (he had attempted to sell some of Renae Wicklund's jewelry only hours after the killings). Police described the crime scene as "resembling a massacre". Wicklund's body was naked, and she had been severely beaten, strangled, and raped with a blunt instrument in addition to having her throat slit (the murder weapon and the object used to rape her were never found). She was covered with bruises, and had a broken nose, jaw, and ribs, a testament to her attacker's aggression. Wicklund also had bruising on her knuckles, suggestive of defensive wounds. Barbara Hendrickson had been attacked and her throat cut after going over to the house to check on Wicklund, who had been ill with the flu that week. Shannah suffered the same fate when she came home from school. She had been choked, and her throat cut so deep that she was nearly decapitated. One of her earlobes was also torn, as the killer had made off with a pair of earrings she was wearing that day. The same day of the murders, Campbell also tried to rape another woman.

Police were told by a neighbor girl that she saw Campbell sneaking around Wicklund's yard with a knife that morning, and other neighbors observed him heading towards the house with a large blanket roll in his hands. It was also obvious that Campbell's getaway from the crime scene was extremely sloppy, with no attempt to conceal anything. A bloody hand print was found on a drinking glass in the Wicklunds' kitchen that matched his fingerprints, and a trail of Renae Wicklund's jewelry was running from the front door of the house down the walkway. Campbell's car had dried blood on the driver's side door handle, and the above-mentioned earring of Shannah's was found in the back seat. A pair of earrings belonging to Renae were found in Campbell's pants pockets when he was arrested. In addition, a fellow work-release resident directed police to a location along the banks of the Snohomish River, where he and Campbell had been on the evening of April 14. Divers retrieved more jewelry and knick-knacks taken from the Wicklund's home. When questioned by police, Hendrickson stated that "the man who'd attacked Renae eight years earlier" was the only possible perpetrator he could think of.

Campbell was arrested at the Monroe Reformatory on April 19, and charged with first degree murder. Held in the Snohomish County Jail, he was unpopular with other prisoners, since he had murdered a child, and because the circumstances of his crime meant that stricter rules would be imposed on the freedoms of inmates on parole.

In 2023, DNA evidence showed that Campbell was likely responsible for the April 1975 murder of University of Washington student Hallie Ann Seaman, whose murder has previously been unsolved.

Trial
At Campbell's November 1982 trial, he refused to testify in his defense or discuss the murders at all. Testifying for the prosecution were neighbors who had seen him sneaking around the house on the afternoon of April 14, and his girlfriend Judy Dirks, who said that on the morning of the killings, he'd been at her home, where he consumed an entire six pack of beer. The next day, she noticed one of her kitchen knives was missing. Dirks testified that Campbell had "considerable resentment" towards Renae Wicklund and had driven past her home a couple of times while on work release. Campbell took the unusual step of cross-examining his girlfriend himself, and got her to admit that he had never told her he wanted to harm Renae Wicklund.

The defense did not call any witnesses or present any evidence other than that the case was a miscarriage of justice because investigators immediately focused on Campbell and did not search for any other potential suspects. Numerous citizens of Clearview had signed a petition demanding the death penalty for him, and the jury agreed, arguing that he showed no signs whatsoever of remorse for killing the Wicklunds and Barbara Hendrickson. During the trial, Campbell remained for the most part detached, and said little. Even the crime scene and autopsy photos (see below) did not arouse much noticeable emotion in him. Renae Wicklund's mother and sister, who lived in North Dakota, were particularly shocked by the murders because she had never told them about being raped eight years earlier.

During the trial, Campbell's attorneys argued that he could not be charged with rape, since the wound in Renae Wicklund's vagina was a post-mortem injury that had not bled. Snohomish County Coroner Dr. Clayton Haberman, who performed the autopsies, pointed out that brain death does not occur until a few minutes after circulation ceases, and she could technically have still been alive when the assault happened, but it may just as easily have been hours later. He also noted that Shannah lost so much blood that it was difficult to collect a sample from her. Judge Dennis Britt thus ordered the jury to disregard the rape allegations. The defense also protested the prosecution's decision to display graphic autopsy photos of the Wicklunds and Barbara Hendrickson. Judge Britt allowed this, but said that the jurors could decide for themselves whether they wanted to see their blood-splattered clothing.

Because the only living witness to the murders would not speak of or recount what happened, investigators had to roughly piece together the sequence of events on April 14. Renae Wicklund had obviously been attacked first. Shannah was found lying in the bedroom next to her, and it was believed that Campbell may have shown the girl her mother's lifeless body prior to slitting her throat. They were probably both dead by the time Barbara Hendrickson entered the home. Knocked-over furniture in the living room indicated that she could have run into Campbell and attempted to flee, but was caught. The bodies were all positioned in such a way that "the effect seems to have been to intentionally shock whoever came across them".

Incarceration and appeals
Campbell's prison record showed that he had not committed anything more than relatively minor offenses there, but one inmate, who was fearful of being labeled a prison snitch and so had his identity hidden, testified that he had terrorized fellow prisoners into submitting to sex and to get him drugs. Several guards at the Monroe Reformatory attested to being afraid of him as well, and had put in a request to have him transferred to the state penitentiary at Walla Walla, which ultimately went nowhere. Campbell's ex-wife told police that he went to her house and raped her on Christmas Day 1981 and on two subsequent occasions. Police told her that there was insufficient evidence to charge Campbell with anything.

Campbell's mother claimed that he had sex with a pet dog that he adopted, and after learning of his arrest for first-degree murder told investigators that, "It was inevitable. I never believed he was going to end up anywhere but the electric chair." His father and sisters could not be located. As a condition of his parole, he was also required to attend rape counseling sessions, but he ended up becoming romantically involved with his counselor, which led to the therapy being terminated (she became pregnant and gave birth to Campbell's second child). Campbell's mother did not live to see his execution.

In the aftermath of the trial, there were numerous lawsuits. His ex-wife sued the State of Washington for negligence in allowing him to go free on work release and rape her two times. Hilda Ahlers filed a lawsuit seeking damages for the same negligence that led to the death of her daughter and granddaughter. The state also agreed to pay Don Hendrickson $950,000 in damages.

In 1985, a still more damning report emerged alleging that Monroe Reformatory staff had not only covered up for Campbell, but were actively conspiring with him. Inmate counselor Roger Button kept certain inmates on his "payroll", which included Charles Campbell. The inmates supplied Button with sexual favors in exchange for his covering up their prison infractions; and in addition, he used them as extortion agents to beat up prisoners he disliked, collect debts, or protect prisoners he did like. Button denied all of these allegations.

The judge sentenced Campbell to death on December 17, 1984. By 1989, the case had gone through the entire state court system. Campbell's lawyers appealed his conviction and sentence for 12 years (a total of three appeals). The Washington Supreme Court affirmed the conviction and sentence.

The state offered inmates the choice of execution by lethal injection or hanging. If the inmate did not choose, execution would be by hanging. Campbell declined to choose how he would be executed, arguing that participating in the decision on how he would die was akin to his committing suicide, which Campbell's lawyers argued violated Washington public policy. While his case was at various stages of appeal, he remained a much-feared figure in Walla Walla's death row for the next decade, even spitting at then-Governor Booth Gardner when he peered into his cell.

On November 7, 1988, Campbell petitioned the U.S. Supreme Court to review his case. The Supreme Court denied his petition, but that did not end the appeals. There was now debate over whether hanging, fearing decapitation due to Campbell's obesity, was cruel and unusual punishment, and thus unconstitutional. This time, it was Washington State appealing to the Supreme Court in 1993, because the state wanted the case concluded, instead of dragging on for years. Campbell's repeated appeals showed that he would prefer to spend the rest of his life behind bars, rather than face execution.

Interviews with Campbell by prison psychologists concluded that he had "a near-total lack of empathy" for other human beings and felt that it was his right to live life and act however he pleased, and he also had the right to destroy anyone who angered him. He told them, "The world has created me, and I am free to do what I want. There is no right or wrong, or anyone to tell me what to do."

Execution
On April 14, 1994, the United States Court of Appeals for the Ninth Circuit lifted the stay of execution. On May 3, 1994, Campbell asked the U.S. Supreme Court to put another stay on his execution, and to rule on his claim that hanging was unconstitutional, but his request went unanswered. His execution was set for May 27. Then-governor Mike Lowry was an opponent of the death penalty, but upon hearing the details of Campbell's crimes, he refused to commute his sentence to life in prison.

Twenty-four hours before the execution, Campbell was given his last shower. His last meal was served two hours before the hanging took place, and he refused to eat most of it. The family members of the victims asked to watch the execution, but this request was turned down.

The day prior to his execution, Campbell was non-compliant when officers went to transport him to a holding cell near the execution chamber. Officers found him faint, lying on the floor of his cell, and ultimately subdued him using pepper spray. Campbell spent his final hours talking to friends and relatives, including his ex-counselor and son. Campbell's was the second hanging in two years, after serial child killer Westley Allan Dodd.

On the execution platform, Campbell refused to stand. Corrections officers had to forcefully strap him to a board. Campbell then repeatedly moved his head so that neither the cloak nor noose could be put on easily. It took prison officials 90 seconds to place a hood on his head, and to fix the noose before the trap was opened. The execution took place, and Campbell was pronounced dead about two minutes later. An autopsy confirmed that he had died of a fracture of the cervical spine, and that his death was quick.

Later, while cleaning out Campbell's holding cell, authorities found a four-inch piece of metal that he had been sharpening into a knife.

General references

 * Washington Hangs Murderer; Texas Executes Officer-Killer May 28, 1994
 * Federal Court Upholds Execution by Hanging February 9, 1994
 * Inmate Faces 1st Hanging in U.S. Since 1965 March 27, 1989
 * The State of Washington, Respondent, v. Charles R. Campbell, Appellant.

title: Charles Rodman Campbell


text:
Talk:Lorentz National Park

DEAD LINK
The link for "Lorentz National Park Conservation Project" (http://lorentzpark.org) is dead, and hasn't worked since I've been checking it, once a month or so, for the last six months. Does anyone know if this site is still operational? Thanks. Arjuna 20:36, 8 August 2006 (UTC)

Is there any permanent human population?
I would like to know if theres human population in this park not counting temporary people like researchers or exsplorers but year round permanent population. if so how many people live here? 99.164.52.125 (talk) 23:10, 13 November 2010 (UTC)
 * Apparently quite significant. Added some info to the article. --Elekhh (talk) 00:44, 18 November 2010 (UTC)

History of the Park
Quite interesting:

Apparently this place was established as "Lorentz nature monument in 1923 to protect indigenous tribes people from sudden contact with western civilisations." See: Histories of Protected Areas: Internationalisation of Conservationist Values and their Adoption in the Netherlands Indies (Indonesia) PAUL JEPSON* AND ROBERT J. WHITTAKER Environment and History 8 (2002): 129–72

But then there's this slightly conflicting info on the park, which does not mention its history as a reserve for indigenous peoples:

1919 The first protection status (the Lorentz Nature Monument) was given by the Dutch Colonial Government; 1956 The protected status was abolished due to conflicts with Indigenous people over unresolved land ownership; 1970s Freeport Indonesia begins operations on Indigenous land; 1978 Established as a Strict Nature Reserve by the Indonesian Government; 1990 The Directorate General of Forest Protection and Natural Resource Management formally approached the WWF Indonesia Program to request assistance in conducting research and designing a management plan. In co-operation with PHPA, WWF prepared a framework park management system that takes into account the traditional land tenure and resource use systems of the tribal communities living within the park; 1990 (Onwards) WWF has gathered basic social and human ecological information on the Indigenous groups in the park as a first step in the process of developing the management plan; 1996 A group of scientists, including WWF and PHPA staff were abducted in the north eastern part of the reserve and due to the political unrest in the Lorentz area, surveys were restricted to the buffer zone and the Asmat area of the park. Despite the hostage crisis, WWF and PHPA in cooperation with the Government have started a participatory resource mapping program to rationalize land use planning in the buffer zone and involve local people in boundary delineation, park zonation, and buffer zone development, particularly since the status changed from Strict Nature Reserve to National Park in 1997. 1997 Declared National Park by the Ministry of Forestry (including the Eastern extension).

Source: Gabriel, J. A. (2007) Cooperative Conservation: Beyond the Rhetoric. A report highlighting International Best Practice recommendations for World Heritage Protected Areas: Identifying ‘best practice’ models and practical solutions that could be applied in the Wet Tropics. Report to the Marine and Tropical Sciences Research Facility. Reef and Rainforest Research Centre, Cairns (144pp.).

Somebody else, please feel free to write this up. I'm not much for that sort of thing. 108.35.251.135 (talk) 02:17, 9 November 2013 (UTC) R.E.D.

File:Lorentz National Park map-en.svg
Hello! This is a note to let the editors of this article know that File:Lorentz National Park map-en.svg will be appearing as picture of the day on May 30, 2014. You can view and edit the POTD blurb at Template:POTD/2014-05-30. If this article needs any attention or maintenance, it would be preferable if that could be done before its appearance on the Main Page. Thanks! — Crisco 1492 (talk) 01:02, 11 May 2014 (UTC)

Error in the Fauna Section
There is an error in the second paragraph of the fauna section. It states "The mammal species include the Long-beaked echidna, Short-beaked Echidna, and four species of cuscus as well as wallabies, wildcats and tree-kangaroos.[3]" The error is in where it states "wildcats" however if you follow the reference to the original link the article referenced states "forest-cats". I was at first confused by this difference because "forest-cats" doesn't refer to wildcats (and after a small amount of research I believe there are no wildcats in New Guinea apart from in some urban areas) but instead, I believe, refers to quolls. This would make sense anyway because quolls are found in the area. Jubblubs (talk) 20:49, 16 January 2015 (UTC)

I have now edited the article to say "The mammal species include the Long-beaked echidna, Short-beaked Echidna, and four species of cuscus as well as wallabies, quolls and tree-kangaroos.[3]" (changing the word "wildcats" that was writted previously to "quolls") Jubblubs (talk) 20:53, 16 January 2015 (UTC)
 * Thanks. Indeed there seems to be some confusion on the website of the Ministry of Forestry, where the description in Indonesian is "kucing hutan" that was probably translated word-by-word to "forest cat" and is used for or range of species including Flat-headed cat, but none of these have their range extend to New Guinea. Possibly a better reference is the WHS description that doesn't indicate any cat, but the New Guinean quoll (aka. New Guinea native cat). -- ELEKHHT 00:27, 17 January 2015 (UTC)

There are much more errors. The numbers of aves species are pure fantasy numbers. 500 species of parrots in a family only containing 21 species. Just as an example! This outdated site from 2010 should be treated as curiosity, not as a source. The correct numbers have to be researched and corrected. Horst Emscher (talk) 08:21, 29 September 2018 (UTC)

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title: Talk:Lorentz National Park


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Firestorm (character)

Firestorm is a fictional superhero appearing in American comic books published by DC Comics. He was created by Gerry Conway and Al Milgrom. Ronnie Raymond and Martin Stein first fused together to become Firestorm in Firestorm, the Nuclear Man #1 (March 1978). Jason Rusch debuted as a modern update of the character in Firestorm (vol. 3) #1 (July 2004), and was created by Dan Jolley and ChrisCross.

Firestorm was featured in The CW's Arrowverse, portrayed by Robbie Amell, Victor Garber, and Franz Drameh (as Jax Jackson) mainly in The Flash and Legends of Tomorrow.

Creation
In an interview Conway discussed his reasoning and influences while creating the character "I always loved the idea of the hair on fire, I think it goes back to Johnny Storm, The Human Torch, an entire flaming character, of course." Conway further elaborated, "I’d been playing around with the idea of a teenage superhero for DC, who could sort of fill the hole that had been left in my heart by leaving Spider-Man behind. I’d been thinking about the tropes — one of which was the meek, mild alter ego, the brainy kid who, in wish fulfillment, gets superpowers, is extremely powerful… able to do things that he hadn’t been able to do before. That was, I think, the major motivating force—I wanted to play on that trope. To do that, I wanted to flip it around: create a guy who wasn’t the brightest guy in the room, the not-terribly-smart guy who became a superpowered character. The way I’d make that work: I’d bring him into contact with the smarter person, who would also share the powers. This led to… the multiple-people-in-one, Professor Stein/ Ronnie Raymond dynamic."

Jack Kirby's 1971 design for Lightray's costume influenced the look of artist Al Milgrom's creation of Firestorm in 1978. In an interview from 2019, Milgrom admitted: "The facemask on Firestorm, the way it comes around the chin, was probably inspired by Lightray more than anything... I liked the [Lightray] head-covering thing; I said, "I'm stealin' it!"

Publication history
The first Firestorm series was short-lived, canceled after issue 5, a victim of the company-wide "DC Implosion". The sixth issue was included in Cancelled Comic Cavalcade.

Writer Gerry Conway added Firestorm to the roster of Justice League of America. This led to a series of eight-page stories in the back of The Flash (issues 289–304; with art by George Pérez, Jim Starlin and others), and a revival of a monthly Firestorm comic in 1982. The Fury of Firestorm (later called Firestorm the Nuclear Man) lasted from 1982 until 1990.

Another Firestorm series began in 2004 with a new character in the role of Firestorm, Jason Rusch after Ronnie Raymond was killed off in the pages of Identity Crisis. Rusch was poorly received and his book was canceled after 30 issues and the Ronnie Raymond Firestorm was resurrected in the pages of Blackest Night.

Yet another Firestorm title was launched in 2011. Starring both Ronnie and his successor Jason, it was one of The New 52 titles launched in the wake of DC's Flashpoint crossover event. The series, The Fury of Firestorm the Nuclear Men, was initially written by Gail Simone and Ethan Van Sciver and drawn by Yıldıray Çınar. Joe Harris replaced Simone starting in issue #7, while co-writer Van Sciver also provided the art for issues #7 and 8 before Çınar returned. Veteran writer/artist Dan Jurgens took over the series with issue #13 in 2012, until the series' end with issue #20 in 2013.

In 2016, Firestorm was one of the features in the Legends of Tomorrow TV series, which united Martin Stein and Jefferson Jackson as Firestorm.

Ronnie Raymond / Martin Stein
The original Firestorm was distinguished by his integrated dual identity. High school student Ronnie Raymond and Nobel Prize-winning physicist Martin Stein were caught in an accident that allowed them to fuse into Firestorm the Nuclear Man. Due to Stein being unconscious during the accident, Raymond was prominently in command of the Firestorm form with Stein a voice of reason inside his mind, able to offer Raymond advice on how to use their powers without actually having any control over their dual form. Banter between the two was a hallmark of their adventures. Stein was initially completely unaware of their dual identity, leaving him concerned about his unusual disappearances and blackouts, but Ronnie was eventually able to convince him of the truth, allowing them to bond as separate individuals rather than as parts of a whole.

Ronnie Raymond / Martin Stein / Mikhail Arkadin
When Conway left the series in 1986, John Ostrander (with artist Joe Brozowski) began writing the Firestorm stories. His first major story arc pitted Firestorm against the world as the hero, acting on a suggestion from a terminally ill Professor Stein, demanded that the United States and the Soviet Union destroy all of their nuclear weapons. After confrontations with the Justice League and most of his enemies, Firestorm faced the Russian nuclear superhero Pozhar in the Nevada desert, where an atomic bomb was dropped on them. A new Firestorm resulted, a fusion of the two heroes: this new Firestorm was composed of Ronnie Raymond and the Russian Mikhail Arkadin but controlled by the disembodied amnesiac mind of Martin Stein.

Fire Elemental
The Firestorm with Arkadin proved to be a transitional phase, as in 1989 Ostrander fundamentally changed the character of Firestorm by revealing that Firestorm was a "Fire Elemental". Firestorm now became something of an environmental crusader, formed from Ronnie Raymond, Mikhail Arkadin, and Svarozhich, a Soviet clone of the previous Firestorm, but with a new mind. Professor Stein, no longer part of the composite at all, continued to play a role, but the focus was on this radically different character. New artist Tom Mandrake would create a new look to match. It was during this phase that Firestorm met and befriended Sango and the Orishas, the elemental gods of Nigeria. He also met their chief deity and Sango's older brother Obatala, Lord of the White Cloth.

By the series' 100th issue, Stein learned that he was destined to be the true Fire Elemental and would have been being it not for Raymond also being there by circumstance. Raymond and Arkadin were returned to their old lives, and Stein as Firestorm was accidentally exiled to deep space in the process of saving the Earth. He thereafter spent many years traveling through space as a wanderer, returning to Earth only rarely.

After the transition to the elemental Firestorm, all of the main characters from the series vanished from the comics for some time after the cancellation of the Firestorm comic in 1990. Raymond eventually returned in the pages of Extreme Justice. Raymond, at the time undergoing treatment for leukemia, regained his original powers after a chemotherapy session. It took the combined might of the Justice League led by Captain Atom, and the returned elemental Firestorm, to restore Ronnie's health. Firestorm began to appear regularly in a number of DC titles, though lacking the guidance and knowledge necessary to use his skills wisely. Firestorm was drafted by Batman into a "replacement" Justice League that was commissioned in case something befell the original team (in this case, being stranded in the distant past in "The Obsidian Age" storyline). After the original team returned, Firestorm stayed on as a reserve member and participated in events such as a team-up with the Justice Society of America (in JLA/JSA: Virtue and Vice) and the intercompany crossover JLA/Avengers. He was also briefly a member of the Power Company.

Jason Rusch
In 2004, DC revived the Firestorm comic for the second time, with writer Dan Jolley and artist Chris Cross, but instead of the original Firestorm, Ronnie Raymond, there was a new protagonist; the teenager Jason Rusch.

Jason was a 17-year-old living in Detroit who wanted nothing more than to escape his home city. He lived with his father, who had turned abusive after he lost his hand in an industrial accident. His mother left the family sometime after the accident. With the loss of a job he needed for college tuition, Jason turned to a local thug for money, accepting a job as a courier. It was on that job that he encountered the Firestorm Matrix, searching for a new host after Ronnie Raymond's death. In the aftermath, Jason struggled to cope with his new identity and powers—a struggle that led to the death of the man who had hired him.

Jason Rusch / Martin Stein
In the 2006 miniseries Infinite Crisis, it was revealed that Martin Stein, alive in space as the "Elemental Firestorm", had sensed the presence of Jason Rusch within the Firestorm Matrix, but was unaware of Ronnie Raymond's death. When Jason, as Firestorm, was gravely wounded in the line of duty, Stein linked with him in a variation of the merge, promising Jason a new Firestorm body to let him return into battle (although Martin had been unable to save Mick) and asking him about Ronnie's fate.

Accepting Martin's proposal, Jason asked Stein to become the permanent second member of the Firestorm Matrix. Sensing his "errors" (including Mick's death) were the result of his youth and lack of experience, he sought the experience and maturity of Stein. Stein refused at first, but later accepted Jason's request, thus ensuring both a new Firestorm body and the reconstruction of human bodies for both Rusch and Stein.

It was revealed in Infinite Crisis that if the Multiverse had survived up to the present, Jason would have been a native of Earth-Eight.

Jason Rusch / Firehawk
As the storyline jumped ahead one year (and the series itself was now re-titled as Firestorm the Nuclear Man from issue #23 on), Professor Stein has mysteriously vanished, and Jason Rusch has been merging with Firehawk to become Firestorm, allowing him to use her powers as well. The two decided to look for Stein together. Stein had been kidnapped and tortured by the Pupil, a former teaching assistant of Stein's. Flanked by the D.O.L.L.I.s, a group of cyborg soldiers of limited cognitive ability, the Pupil (formerly known as Adrian Burroughs) questioned the nearly dead Stein about the secrets of the universe. Jason and Lorraine, along with the mysterious teleporter Gehenna, freed the captured Stein and restored him to full health. Jason is a college freshman at New York City's Columbus University and seems to have ties with Dani Sharpe, a member of the senior staff at LexCorp.

The Firestorm team of Jason and Firehawk made several appearances across the DC Comics Universe before the search for Martin Stein ended. This included dealing with the latest OMAC and teaming up with Superman in the "Back in Action" story arc in Action Comics. Firehawk later introduced Jason to Pozhar, a Russian superhero who was once a part of the Firestorm Matrix; together, the trio takes on a newly reborn Tokamak. This series ended with Firestorm the Nuclear Man #35 (April 2007).

Jason Rusch / Ronnie Raymond
In the 2009–2010 Blackest Night miniseries, Ronnie Raymond is called by a black power ring to join the Black Lantern Corps. Like other Black Lanterns, the undead Firestorm mimics the personality of Ronnie Raymond, often wisecracking and exhibiting other stereotypical teenage behavior.

In the 2010–2011 Brightest Day miniseries, Ronnie Raymond arrives at Jason Rusch's apartment with Professor Stein and Ray Palmer to attend Gehenna's funeral. When Ronnie is actually unable to remember Gehenna's name, Jason angrily lashes out and punches him in the face. This causes the two young men to merge into Firestorm, and they begin arguing inside the Matrix. Palmer manages to separate Jason and Ronnie, but not before the Firestorm matrix causes a huge explosion. It is revealed that Deathstorm intends to create enough emotional instability between Ronnie and Jason that the Matrix will trigger another Big Bang, thereby destroying all life in the universe. Ronnie and Jason must find a way to contain their Firestorm matrix from the explosion in less than 90 days.

After the events of the 2011 Flashpoint storyline, The New 52 reality altered Firestorm's personal history to the point of it being completely restarted. Ronnie Raymond is now introduced as a high school senior and the captain of the football team. During a terrorist attack on their school, classmate Jason Rusch produces a vial given to him by Professor Stein, which contains the "God Particle", one of Stein's creations. The God Particle transforms both Jason and Ronnie into Firestorm, and the two teens briefly battle each other before accidentally merging into a hulking creature known as the Fury. Sharing the identity of Firestorm, with Ronnie being the brawn and Jason being the brains, Firestorm is considered for recruitment into the Justice League along with several other heroes.

DC Rebirth
In the Watchmen sequel Doomsday Clock, Firestorm becomes a subject of controversy after claims arise stating that he was created by the American government. Firestorm profanely denounces the "Superman Theory" and insults his Russian counterpart Pozhar, much to the dismay of Martin Stein. Firestorm subsequently becomes embroiled in a fight with several Russian superheroes before appearing to inadvertently turn a crowd of civilian protesters into a glass (a feat previously deemed beyond his capabilities). Firestorm flees with the body of an affected child and is found in hiding at the Chernobyl Nuclear Power Plant in Ukraine by Superman. With Superman's encouragement, Firestorm returns the child to normal. Firestorm and Superman return to the affected crowd and are engaged by the Russian military. The area then becomes engulfed in an explosion of blue light. Subsequent discoveries reveal that the 'Superman Theory' is actually partially correct, as Stein deliberately engineered the creation of Firestorm to make himself a superhuman, even if Raymond genuinely had no idea of this until recently.

Powers and abilities
Firestorm has the ability to rearrange molecular or particle structures of any substance into most anything else, creating different atomic structures of equal mass. He can transmute the basic composition of an object (e.g., transmuting lead into gold) and can also change its shape or form at will. Much like Green Lantern's limitations, Firestorm can only create items whose workings are understood by the "driver" of the Firestorm Matrix, through he can make more complex sentient constructs out of the Matrix's energies. Unlike Green Lantern's creations, Firestorm's alterations are permanent unless he reverses them.

Initially, he could not affect organic matter without painful, even lethal, feedback (i.e., fatal biophysical disruption or even localized particle motion phenomena like extreme changes in the weather). It was later revealed that Firestorm could always change organic matter, but opted not to. As Jason Rusch became Firestorm, however, this weakness appeared to have dissipated. With old and new variations, the organic limitation does not extend to his own person, as its users can molecularly change their driver self at will, allowing them to regenerate lost or damaged bodily tissue, boost immune systems, shape-shift, increase physical capabilities and survive indefinitely without food, sleep, water or air. Capacities as such produce superhuman levels of strength, durability, stamina and resistance to injury great enough to challenge the New Gods—the likes of Orion, Lashina, or an empowered Kalibak—or surviving the rigors of outer space and sitting near the inner corona above the Sun's photosphere without discomfort. Stein has stated Firestorm's power to be theoretically infinite, harnessing the spark of creation, the Big Bang itself. However, infinite power runs the risk of burning out its host.

While the Firestorm Matrix can be utilized by a single host, it is not recommended. The Matrix functions best with two people, a pilot and secondary, to comprehend and master it. Martin instructed Jason on how to study current and potential powers available to them within the Matrix and to manually adjust them on the fly at a later date. Its main source of energy stemmed from the ambient stellar energies of native stars and suns but could also use its co-pilot as a power source, though they will burn out over time and genetically disintegrate if not properly adjusted to its power.

The merging aspect of the Matrix can enable outside fusions which assimilate any inherent abilities these others might possess. However, this can diminish its effectiveness and stability. Rusch has shown he can spontaneously warp himself and others he had previously merged with to his specific location, triggering the neural pathway connection and allowing the gestalt to access each other's knowledge and memories to better utilize Firestorm's capabilities. Users of the Firestorm Matrix can access a type of ancestral memory from the continuum of past Matrix users, allowing them to access the latest knowledge of the atoms comprising it. This also translates into a form of time-space sight in which the Matrix user can glimpse the past, present, future, and alternate lives of every other Firestorm throughout reality using a collective of subatomic wormholes which exist as a part of the Matrix. This power is too complex to properly control; thus, it has been highly unreliable as an ability.

The driver can fly at supersonic speeds in an atmosphere and reach escape velocities. The driver can also adjust the driver's body's size or pull and enlarge others from the subatomic universe at will, Rusch having once dragged Ray Palmer from his microscopic size to the natural world while on Apokolips. Manipulation of the self at the subatomic level allows the driver to become intangible and pass through solid objects. This allowed Rusch to communicate with John Stewart and sift through his mind telepathically after he had been taken over by the void beast. Firestorm is also adept at absorbing and redistributing radiation or energy both harmlessly and productively (such as in Green Lantern: Circle of Fire #7, having both absorbed Zeta Radiation from Adam Strange's body and repurposed it to turn a universe-destroying quasar back onto itself and absorb the fallout from a massive nuclear detonation). ) He can generate destructive or concussive blasts of nuclear energy, through which he can also channel his transmogrification powers.

While the Matrix grants the fusers unique powers, it can also accidentally bestow them on individuals caught in the Matrix by mistake. One example is Nanette Phaedon, wife of the late Allen Phaedon, who gained the ability to change her quantum state for size-shifting and flight by her own will. Following Raymond's resurrection during Brightest Day, Firestorm gained the ability to switch "drivers" between Ronnie and Jason at will; before that, only the active driver was in control, with the dormant consciousness only able to advise the other on what action to take. One of the faults of a Firestorm fusion is that the stronger psyche will have dominance of the Matrix's power, such as when Jason fused with Luis Salvador who overpowered him from the passenger seat of the Matrix.

During The New 52, the Firestorm Matrix could be shared through multiple users at a time. Users could fuse and become stronger, but more unstable. The entity formed between Ronnie and Jason when using the Matrix in tandem created a nuclear being called "the Fury". It was also shown that The Matrix shares a kinship to the Quantum Field in some way, enabling Firestorm users to derive its power for subatomic transmutation and manipulation. Some believe it is key to the fabled God particle theory. Its merging properties can place a large burden on the user; Firestorm runs the risk of reaching critical mass and detonating. At worst, the fusion of too many users in the Matrix could trigger a second Big Bang.

Other versions
Firestorm has appeared in various alternate realities within the DC Multiverse: a gender-reversed version appears in Countdown: The Search for Ray Palmer as an inhabitant of Earth-11; a version of Ronnie Raymond appeared in JLA: The Nail, as a captive of Cadmus Labs; a Firestork of the Just'a Lotta Animals; and a merger of Ronnie Raymond and Nathaniel Adam of Earth-37 called Quantum-Storm who was summoned by Monarch in the miniseries Countdown: Arena.

We-Are-Firestorm
A version of Firestorm crafted by Anansi in Volume Two of Justice League of America, he appears to be a form of sentient red energy and is a member of that reality's Justice League.

Television

 * The Ronnie Raymond / Martin Stein incarnation of Firestorm appears in the Super Friends: The Legendary Super Powers Show, voiced by Mark L. Taylor and Olan Soule respectively.
 * The Ronnie Raymond / Martin Stein incarnation of Firestorm appears in The Super Powers Team: Galactic Guardians, voiced by Mark L. Taylor and Ken Sansom respectively.
 * The Ronnie Raymond / Martin Stein incarnation of Firestorm was planned to appear in Justice League Unlimited, with writer/producer Dwayne McDuffie stating that the series' producers had permission from DC Comics to use them. However, the series' creators could not come up with a story that they liked. Later on, it was stated that the character was intended to be the focus of "The Greatest Story Never Told", but was ultimately replaced with Booster Gold.
 * The Ronnie Raymond / Jason Rusch incarnation of Firestorm appears in Batman: The Brave and the Bold, voiced by Bill Fagerbakke and Tyler James Williams respectively. Producer James Tucker said, "...the smart kid has the body and he's got this dumb guy in his head telling him stuff...it's kind of a total flip of the original Firestorm".
 * The Ronnie Raymond incarnation of Firestorm appears in the Robot Chicken DC Comics Special segment "Real Characters From the DC Universe", voiced by Alfred Molina.
 * The Ronnie Raymond / Martin Stein incarnation of Firestorm appears in Justice League Action, voiced by P. J. Byrne and Stephen Tobolowsky respectively.

Arrowverse
Firestorm appears in media set in The CW's Arrowverse, with Martin Stein portrayed by Victor Garber, Ronnie Raymond portrayed by Robbie Amell, and Jefferson "Jax" Jackson portrayed by Franz Drameh.
 * Stein, Raymond, and Jackson first appear in the live-action TV series The Flash, with Stein and Raymond as the first incarnation of Firestorm after they were fused with the former's F.I.R.E.S.T.O.R.M. matrix during the explosion of Harrison Wells' particle accelerator. They initially lack control over their powers until Wells safely separates them, allowing the pair to master their powers and join the Flash in fighting crime until Raymond sacrifices himself to save Central City. After the F.I.R.E.S.T.O.R.M. matrix begins to destabilize and threaten Stein's life, Team Flash eventually find Jackson, who joins forces with Stein to become the new Firestorm despite initial hesitancy and leaves Central City with him to hone their powers.
 * Additionally, Jason Rusch appears in the episode "Revenge of the Rogues", portrayed by Luc Roderique.
 * Jackson and Stein appear in the animated web series Vixen, with Drameh and Garber reprising their respective roles.
 * Jackson and Stein appear in the live-action TV series Legends of Tomorrow, with Drameh and Garber reprising their respective roles and Graeme McComb portraying a younger version of Stein. Stein and Jackson join the Legends in traveling through and stopping evildoers across time until the "Crisis on Earth-X" crossover, during which Stein is killed by Nazis from Earth-X and takes a formula developed by Ray Palmer to save Jackson, who leaves the Legends to resume his life.

Film

 * The Jason Rusch incarnation of Firestorm appears in Justice League: Crisis on Two Earths, voiced by Cedric Yarbrough. Additionally, an unnamed, alternate universe version appears as a member of the Crime Syndicate.
 * The Jason Rusch incarnation of Firestorm appears in Lego DC Comics Super Heroes: The Flash, voiced by Phil LaMarr.

Video games

 * The Ronnie Raymond / Martin Stein incarnation of Firestorm appears as a playable character in Lego Batman 3: Beyond Gotham, voiced by Nolan North.
 * The Jason Rusch / Martin Stein incarnation of Firestorm appears as a playable character in Injustice 2, voiced by Ogie Banks and Fred Tatasciore respectively.
 * The Jason Rusch / Martin Stein incarnation of Firestorm appears as a playable character in Lego DC Super-Villains.

Miscellaneous

 * The Ronnie Raymond incarnation of Firestorm appears in the Justice League Unlimited tie-in comic.
 * An unidentified Firestorm makes a cameo appearance in The Order of the Stick #359.

Collected editions

 * Firestorm the Nuclear Man - collects Firestorm the Nuclear Man #1–5, the unpublished #6 and backup stories from The Flash Vol.1 #289-293
 * Firestorm the Nuclear Man: Reborn - collects vol. 3 #23–27
 * The Fury of Firestorm the Nuclear Men Vol. 1: God Particle - collects vol. 4 #1–6; 144 pages, September 2012,
 * The Fury of Firestorm the Nuclear Men Vol. 2: The Firestorm Protocols - collects vol. 4 #7–12 and #0; 160 pages, June 2013,
 * The Fury of Firestorm the Nuclear Men Vol. 3: Takeover - collects vol. 4 #13–20; 176 pages, December 2013,
 * The DC Universe by Dwayne McDuffie - collects Action Comics #847, The Demon #26-29, Impulse #60, JLA Showcase 80 Page Giant #1, Batman: Gotham Knights #27, Sins of Youth: Kid Flash/Impulse #1, Firestorm: The Nuclear Man vol. 3 #33-35; 280 pages, February 2023,

title: Firestorm (character)


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No Sweat (organisation)

No Sweat is a broad-based not-for-profit organisation with HQ in London's Kings Cross, England, which fights for the well-being and protection of sweatshop labourers, not only in developing countries but also in Britain.

History
Working with the GMB Union in London's East End, in the London Borough of Tower Hamlets in 2005, the organisation infiltrated and exposed sweatshops operating for Topshop and reported those involved to the authorities. No Sweat encourages consumers to choose ethically sourced clothing, whilst firmly rejecting boycotts which only lead to factories being moved further from the limelight, further increasing the dangers to those trapped in the cycle of wage slavery.

Partners
The organisation works variously with parts of the TUC and other trade union organisations, the National Garment Workers Federation and closely cooperates with the Ethical Threads clothing company in Britain. It is also aligned with other campaign groups like Labour Behind the Label, and with "No Sweat Apparel" in the United States. Independent of political influence, the group seeks to reach out to all parts of the global community to help stamp out sweatshop labour fullstop - often dealing directly with groups of workers that would normally have no voice and no support outside their immediate community - for example Batay Ouvriye in Haiti and individuals like jailed union official Ali Nejati in Iran.

Events
They hold numerous events in London, Sheffield, Glasgow, Brighton and elsewhere around the United Kingdom, and have a presence at many events such as Glastonbury Festival's Leftfield and many smaller counter-culture festivals and gigs.

Recently the organisation has been running a successful comedy night on the 2nd Thursday of each month in London's Cross Kings basement rooms, guest acts have included Mark Thomas, Josie Long, Rob Newman, Robin Ince and Simon Munnery as well as live podcasts from established acts such as Richard Herring and Andrew Collins and legendary punk filmmaker Don Letts.

These events all aim to publicise the plight of sweatshop workers (children and adults) around the world as well as giving a platform to other, less prominent groups where appropriate and have developed a reputation as the last bastion of genuine counter culture in the now hyper-developed Kings Cross area.

Fashion parade
In April 2009 the BBC news and Times newspapers covered a No Sweat fashion parade outside Primark's flagship Oxford St store - an event organised in response to recent outcry over the company's atrocious labour policies and relationships with subsidiary contractors who make regular use of child labour, as highlighted by the BBC's in 2006.

Goals
The group's activities are primarily two-fold, firstly to organise direct action campaigns to pressure the big brand companies that exploit people through sweatshop labour, secondly to work with independent organisations around the globe to support vulnerable people and help them to unite together and stand up to their employers, demanding safe working conditions, decent hours and a living wage as well as independent trade union rights to protect them from malicious attacks and extreme exploitation.

They are volunteer-run, and anyone can get involved.

title: No Sweat (organisation)


text:
HMS Trump (P333)

HMS Trump (pennant number P333) was a British submarine of the third group of the T class. She was built by Vickers-Armstrongs, Barrow, and launched on 25 March 1944. So far she has been the only ship of the Royal Navy (RN) to bear the name Trump. She spent the majority of her life attached to the 4th Submarine Squadron based in Australia. She was kept in service following the war and was refitted for greater underwater performance, and was the final RN submarine to be posted in Australia, departing in January 1969. She was sold off and broken up for scrap in August 1971.

Design and description
HMS Trump was one of the group three of T-class submarines. She was part of the second batch of the third group to be ordered, in 1941. She was one of a number of boats which had an all-welded hull which increased diving depth to 350 ft, an increase of 50 ft. The torpedo armament was the same as the earlier group two, although by the time group three was coming into service it was realised that external torpedo tubes had major problems and affected the streamlining of the boats; the external tubes were abandoned in the following Amphion-class submarine. Due to expected use in tropical climates, boats of group three were equipped with freon blowers in order to deal with the increased temperatures.

World War II
Trump was commissioned in July 1944. After trials and a work-up in the North Sea in mid-October she was sent to Perth in Western Australia. On arrival, she joined the 4th Submarine Squadron, supported by the depot ship HMS Adamant (1940). From Perth, Trump carried out four patrols before the end of the war.

During her Far East service, Trump sank the Japanese guard boat No. 15 Shosei Maru on 13 May; a Japanese sailing vessel on 24 May; and two coasters, one on 29 May and the other on 1 June. She sank a tanker on 5 June and together with her sister boat HMS Tiptoe (P332), she sank a Japanese cargo vessel on 9 August.

Also with Tiptoe, Trump carried out an attack on a convoy on 3 August. Although it was escorted by a Japanese patrol boat, they successfully sank Tencho Maru, an army cargo ship, with the sinking credited to Tiptoe.

Post war
Trump survived the war and continued in service with the Royal Navy. Trump was one of several all-welded T-class submarines rebuilt for greater underwater performance. This "Slippery T" or "Super T" conversion involved the removal of the deck gun and the replacement of the conning tower with a streamlined "fin". Extra batteries were installed below the control room and additional electric motors were accommodated by cutting through the pressure hull and adding in a new 20 ft hull section inserted aft of the control room. The diesel engines were modified and supercharged with output increased by 300 bhp. The gun armaments and external torpedo tubes were removed, and the bow reshaped. Trump was one of two submarines, the other being HMS Tabard (P342), which had the bridge incorporated into the added fin section; and was the last to undergo this conversion.

In 1960, Trump, along with HMS Taciturn (P334) and Tabard, rejoined the 4th Submarine Flotilla at Sydney, Australia. There, they operated with units of the Far East Fleet, the Royal Australian Navy, and the Royal New Zealand Navy. In June 1964, she participated in the "NEWS EX" anti-submarine exercise in the Hauraki Gulf off the coast of New Zealand.

Trump underwent refits at Cockatoo Dockyard, between January 1962 and April 1963, and again between August 1965 and October 1966. She was the final Royal Navy submarine to be on station in Australia, departing on 10 January 1969 when the 1st Australian Submarine squadron was formed from the RN 4th Submarine Squadron. She was temporarily assigned to the Royal Australian Navy while boats of the Oberon-class submarine were under construction, but remained a Royal Navy submarine. Trump was scrapped at Newport from 1 August 1971.

title: HMS Trump (P333)


text:
Hales–Jewett theorem

In mathematics, the Hales–Jewett theorem is a fundamental combinatorial result of Ramsey theory named after Alfred W. Hales and Robert I. Jewett, concerning the degree to which high-dimensional objects must necessarily exhibit some combinatorial structure; it is impossible for such objects to be "completely random".

An informal geometric statement of the theorem is that for any positive integers n and c there is a number H such that if the cells of a H-dimensional n×n×n×...×n cube are colored with c colors, there must be one row, column, or certain diagonal (more details below) of length n all of whose cells are the same color. In other words, assuming n and c are fixed, the higher-dimensional, multi-player, n-in-a-row generalization of a game of tic-tac-toe with c players cannot end in a draw, no matter how large n is, no matter how many people c are playing, and no matter which player plays each turn, provided only that it is played on a board of sufficiently high dimension H. By a standard strategy-stealing argument, one can thus conclude that if two players alternate, then the first player has a winning strategy when H is sufficiently large, though no practical algorithm for obtaining this strategy is known.

Formal statement
Let W$H n$ be the set of words of length H over an alphabet with n letters; that is, the set of sequences of {1, 2, ..., n} of length H. This set forms the hypercube that is the subject of the theorem. A variable word w(x) over W$H n$ still has length H but includes the special element x in place of at least one of the letters. The words w(1), w(2), ..., w(n) obtained by replacing all instances of the special element x with 1, 2, ..., n, form a combinatorial line in the space W$H n$; combinatorial lines correspond to rows, columns, and (some of the) diagonals of the hypercube. The Hales–Jewett theorem then states that for given positive integers n and c, there exists a positive integer H, depending on n and c, such that for any partition of W$H n$ into c parts, there is at least one part that contains an entire combinatorial line.

For example, take n = 3, H = 2, and c = 2. The hypercube W$H n$ in this case is just the standard tic-tac-toe board, with nine positions:

A typical combinatorial line would be the word 2x, which corresponds to the line 21, 22, 23; another combinatorial line is xx, which is the line 11, 22, 33. (Note that the line 13, 22, 31, while a valid line for the game tic-tac-toe, is not considered a combinatorial line.)  In this particular case, the Hales–Jewett theorem does not apply; it is possible to divide the tic-tac-toe board into two sets, e.g. {11, 22, 23, 31} and {12, 13, 21, 32, 33}, neither of which contain a combinatorial line (and would correspond to a draw in the game of tic-tac-toe). On the other hand, if we increase H to, say, 8 (so that the board is now eight-dimensional, with 38 = 6561 positions), and partition this board into two sets (the "noughts" and "crosses"), then one of the two sets must contain a combinatorial line (i.e. no draw is possible in this variant of tic-tac-toe). For a proof, see below.

Proof of Hales–Jewett theorem (in a special case)
We now prove the Hales–Jewett theorem in the special case n = 3, c = 2, H = 8 discussed above. The idea is to reduce this task to that of proving simpler versions of the Hales–Jewett theorem (in this particular case, to the cases n = 2, c = 2, H = 2 and n = 2, c = 6, H = 6). One can prove the general case of the Hales–Jewett theorem by similar methods, using mathematical induction.

Each element of the hypercube W$8 3$ is a string of eight numbers from 1 to 3, e.g. 13211321 is an element of the hypercube. We are assuming that this hypercube is completely filled with "noughts" and "crosses". We shall use a proof by contradiction and assume that neither the set of noughts nor the set of crosses contains a combinatorial line. If we fix the first six elements of such a string and let the last two vary, we obtain an ordinary tic-tac-toe board, for instance "132113??" gives such a board. For each such board "abcdef??", we consider the positions "abcdef11", "abcdef12", "abcdef22". Each of these must be filled with either a nought or a cross, so by the pigeonhole principle two of them must be filled with the same symbol. Since any two of these positions are part of a combinatorial line, the third element of that line must be occupied by the opposite symbol (since we are assuming that no combinatorial line has all three elements filled with the same symbol). In other words, for each choice of "abcdef" (which can be thought of as an element of the six-dimensional hypercube W$6 3$), there are six (overlapping) possibilities:

 * 1) abcdef11 and abcdef12 are noughts; abcdef13 is a cross.
 * 2) abcdef11 and abcdef22 are noughts; abcdef33 is a cross.
 * 3) abcdef12 and abcdef22 are noughts; abcdef32 is a cross.
 * 4) abcdef11 and abcdef12 are crosses; abcdef13 is a nought.
 * 5) abcdef11 and abcdef22 are crosses; abcdef33 is a nought.
 * 6) abcdef12 and abcdef22 are crosses; abcdef32 is a nought.

Thus we can partition the six-dimensional hypercube W$6 3$ into six classes, corresponding to each of the above six possibilities. (If an element abcdef obeys multiple possibilities, we can choose one arbitrarily, e.g. by choosing the highest one on the above list).

Now consider the seven elements 111111, 111112, 111122, 111222, 112222, 122222, 222222 in W$6 3$. By the pigeonhole principle, two of these elements must fall into the same class. Suppose for instance 111112 and 112222 fall into class (5), thus 11111211, 11111222, 11222211, 11222222 are crosses and 11111233, 11222233 are noughts. But now consider the position 11333233, which must be filled with either a cross or a nought. If it is filled with a cross, then the combinatorial line 11xxx2xx is filled entirely with crosses, contradicting our hypothesis. If instead it is filled with a nought, then the combinatorial line 11xxx233 is filled entirely with noughts, again contradicting our hypothesis. Similarly if any other two of the above seven elements of W$6 3$ fall into the same class. Since we have a contradiction in all cases, the original hypothesis must be false; thus there must exist at least one combinatorial line consisting entirely of noughts or entirely of crosses.

The above argument was somewhat wasteful; in fact the same theorem holds for H = 4. If one extends the above argument to general values of n and c, then H will grow very fast; even when c = 2 (which corresponds to two-player tic-tac-toe) the H given by the above argument grows as fast as the Ackermann function. The first primitive recursive bound is due to Saharon Shelah, and is still the best known bound in general for the Hales–Jewett number H = H(n, c).

Connections with other theorems
Observe that the above argument also gives the following corollary: if we let A be the set of all eight-digit numbers whose digits are all either 1, 2, 3 (thus A contains numbers such as 11333233), and we color A with two colors, then A contains at least one arithmetic progression of length three, all of whose elements are the same color. This is simply because all of the combinatorial lines appearing in the above proof of the Hales–Jewett theorem, also form arithmetic progressions in decimal notation. A more general formulation of this argument can be used to show that the Hales–Jewett theorem generalizes van der Waerden's theorem. Indeed the Hales–Jewett theorem is substantially a stronger theorem.

Just as van der Waerden's theorem has a stronger density version in Szemerédi's theorem, the Hales–Jewett theorem also has a density version. In this strengthened version of the Hales–Jewett theorem, instead of coloring the entire hypercube W$H n$ into c colors, one is given an arbitrary subset A of the hypercube W$H n$ with some given density 0 < δ < 1. The theorem states that if H is sufficiently large depending on n and δ, then the set A must necessarily contain an entire combinatorial line.

The density Hales–Jewett theorem was originally proved by Furstenberg and Katznelson using ergodic theory. In 2009, the Polymath Project developed a new proof of the density Hales–Jewett theorem based on ideas from the proof of the corners theorem. Dodos, Kanellopoulos, and Tyros gave a simplified version of the Polymath proof.

The Hales–Jewett is generalized by the Graham–Rothschild theorem, on higher-dimensional combinatorial cubes.

title: Hales–Jewett theorem