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LD gamma radiation in a low-dose-rate LDR condition rescues photoreceptor cell apoptosis both morphologically and functionally. Multiple rounds of irradiation strengthened this neuroprotective effect. Our results demonstrate for the first time that LDR-LD irradiation has a biological effect in neural cells of living animals. The results support that radiation exhibits hormesis, and this effect may be applied as a novel therapeutic concept for retinitis pigmentosa and for other progressive neurodegenerative diseases regardless of the mechanism of degeneration involved.

Rat MSCs were isolated from the bone marrow from 6 to 8-week-old male Wistar rats and cultured in vitro. Cell proliferation was evaluated by counting total viable cell number with trypan-blue staining and MTT assay. Of course, there are fruit fly studies showing radiation hormesis. The effects of irradiation on the prolongation of the larval stage, pupa lethality, and imago whole body weight have been analyzed. The high dose irradiation 30 Gy, 0. The chronic low dose irradiation resulted in shortening of the larval development period hormetic effect was observed in wild type Oregon-R and mutant mus strains absorbed dose was 20 cGy of Drosophila.

At the same time these strains demonstrated the hormetic effect after chronic low dose irradiation. The hypersensitivity effect was found in sod and rad54 larvae 20 cGy, prolongation of the prepural period , and rad54 and mei pupa 40 cGy, increase of death rate. The larvae of hypersensitive strains and pupa of all strains under investigation did not have the adaptive response. The chronic irradiation in 6 and 60 cGy with the dose rate of 0.

The obtained results suggest the important role of free radical detoxification, of DNA damage sensing, and of DNA repair mechanisms in the whole organism radiation induced effects. The appearance of the adaptive response depends on the investigated effect and developmental stage of fly. The publication Evidence for radiation hormesis after in vitro exposure of human lymphocytes to low doses of ionizing radiation reports another of several cell-level studies. Here we investigated the possibility of gamma-ray hormesis during low-dose neutron irradiation, since a small contribution to the total radiation dose from neutrons involves gamma rays.

Using binucleated cells with micronuclei micronucleated cells among in vitro monoenergetic-neutron-irradiated human lymphocytes as a measure of residual damage, we investigated the influence of the small gamma-ray contribution to the dose on suppressing residual damage.

We used residual damage data from previous experiments that involved neutrons with five different energies 0. Total absorbed radiation doses were 0, 10, 50, and mGy for each neutron source. We demonstrate for the first time a protective effect reduced residual damage of the small gamma-ray contribution to the neutron dose.

Using similar data for exposure to gamma rays only, we also demonstrate a protective effect of 10 mGy but not 50 or mGy related to reducing the frequency of micronucleated cells to below the spontaneous level. Hormesis effects have been observed in a small study of interventional radiologists. To evaluate the effects of chronic low-dose exposure to ionizing radiation on redox state and apoptotic activatio n.

We measured reduced glutathione GSH, a marker of antioxidant response in erythrocytes and plasma generation of hydrogen peroxide a marker of oxyradical stress by ferrous oxidation-xylenol orange assay in plasma. In both groups, lymphocytes were isolated and caspase-3 activity a marker of apoptotic response measured at baseline and following 2 Gy in vitro irradiation.

Exposed subjects also showed higher values of caspase-3 activity, both at baseline and-more strikingly-following high-dose radiation challenge. Conclusion: In interventional cardiologists, chronic exposure to low-dose radiation is associated with an altered redox balance mirrored by an increase in hydrogen peroxide and with two possibly adaptive cellular responses: i an enhanced antioxidant defence increase in GSH, counteracting increased oxyradical stress and ii an increased susceptibility to apoptotic induction which might efficiently remove genetically damaged cells.

After 30 years the relevance and even existence of radiation hormesis remains controversial. Some have argued that the statistical analyses establishing radiation hormesis are faulty. Other publications suggest that not enough is known about it to justify changing current radiation safety standards..

This database includes lifetime studies of tumorigenic responses in mice, rats, and dogs to exposures to alpha, beta, gamma, neutron, or x-ray radiation. A J-shaped dose response, in the form of a significant decreased response at some low dose followed by a significant increased response at a higher dose, was found in only four datasets from three experiments. Three of these datasets involved the same control animals and two also shared dosed animals; the J shape in the fourth dataset appeared to be the result of an outlier within an otherwise monotonic dose response.

A meta-analysis was conducted to determine whether there was an excess of dose groups with decreases in tumor response below that in controls at doses below no-observed-effect levels NOELs in individual datasets. Because the probability of a decreased response is generally not equal to the probability of an increased response even in the null case, the meta-analysis focused on comparing the number of statistically significant diminished responses to the number expected, assuming no dose effect below the NOEL.

Only 54 dose groups out of the total of in the database had doses below the dataset-specific NOEL and that satisfied an a priori criterion for sufficient power to detect a reduced response. The excess in significant reductions was accounted for almost entirely by the excess from neutron experiments 10 observed, 6.

Nine of these 10 dose groups involved only 2 distinct control groups, and 2 pairs from the 10 even shared dosed animals. Given this high degree of overlap, this small excess did not appear remarkable, although the overlap prevented a formal statistical analysis.

A comprehensive post hoc evaluation using a range of NOEL definitions and alternative ways of restricting the data entering the analysis did not produce materially different results. A second meta-analysis found that, in every possible low dose range [0, d] for every dose, d of each of the radiation types, the number of dose groups with significantly increased tumorigenic responses was either close to or exceeded the number showing significantly reduced responses.

This meta-analysis was considered to be the more definitive one. Not only did it take dose into account by looking for consistent evidence of hormesis throughout defined low-dose ranges, it was also potentially less susceptible to limitations in experimental protocols that would cause individual animals to respond in a non-independent fashion. Overall, this study found little evidence in a comprehensive animal radiation database to support the hormesis hypothesis.

Results and conclusions : Very low radiation doses stimulate cell proliferation by changing the equilibrium between the phosphorylated and dephosphorylated forms of growth factor receptors. Radioadaptation is induced by various weak stress stimuli and depends on signalling events that ultimately decrease the molecular damage expression at the cellular level upon subsequent exposure to a moderate radiation dose. Ageing and cancer result from oxidative damage under oxidative stress conditions; nevertheless, ROS are also prominent inducers of autophagy, a cellular process that has been shown to be related both to ageing retardation and cancer prevention.

A balance between the signalling functions and damaging effects of ROS seems to be the most important factor that decides the fate of the mammalian cell when under oxidative stress conditions, after exposure to ionising radiation. Not enough is yet known on the pre-requirements for maintaining such a balance.

Given the present stage of investigation into radiation hormesis , the application of the conclusions from experiments on model systems to the radiation protection regulations would not be justified. There has been a Growing understanding of the epigenetic mechanisms through which radiation hormesis works.

It establishes, among other things, that the hormetic protective effects of low-level gamma ray exposure can protect against lung cancers induced by alpha-ray exposure. This system includes antioxidants, DNA repair, apoptosis of severely damaged cells, epigenetically regulated apoptosis epiapoptosis pathways that selectively remove precancerous and other aberrant cells, and immunity against cancer. We propose a novel model in which the protective system is regulated at least in part via radiation-stress-stimulated epigenetic reprogramming epireprogramming of adaptive-response genes.

Evidence is provided for low linear-energy-transfer LET radiation-activated natural protection ANP against high-LET alpha-radiation-induced lung cancer in plutonium exposed rats and radon-progeny-exposed humans. We have used underlined italics to indicate newly introduced terminology. The single most-important biological pathway responsible for radiation hormesis is probably the activation of Nrf2 by radiation-created oxidative stress.

I have written extensively about Nrf2 in this blog. Specifically, you can see the blog entries The pivotal role of Nrf2. Part 1 — a new view on the control of oxidative damage and generation of hormetic effects , The pivotal role of Nrf2.

Part 2 — foods, phyto-substances and other substances that turn on Nrf2 and The pivotal role of Nrf2. Part 3— Is promotion of Nrf2 expression a viable strategy for human human healthspan and lifespan extension?

Lending credence to this perception is the December publication Ionizing radiation activates the Nrf2 antioxidant response. Recently several types of cancers have been shown to overexpress Nrf2, but its role in the cellular response to radiation therapy has yet to be fully determined.

In this study, we report that single doses of ionizing radiation from 2 to 8 Gy activate ARE-dependent transcription in breast cancer cells in a dose-dependent manner, but only after a delay of five days. Clinically relevant daily dose fractions of radiation also increased ARE-dependent transcription, but again only after five days. Downstream activation of Nrf2-ARE-dependent gene and protein markers, such as heme oxygenase-1, occurred, whereas Nrf2-deficient fibroblasts were incapable of these responses.

Compared with wild-type fibroblasts, Nrf2-deficient fibroblasts had relatively high basal levels of reactive oxygen species that increased greatly five days after radiation exposure. Further, in vitro clonogenic survival assays and in vivo sublethal whole body irradiation tests showed that Nrf2 deletion increased radiation sensitivity, whereas Nrf2-inducing drugs did not increase radioresistance.

Our results indicate that the Nrf2-ARE pathway is important to maintain resistance to irradiation, but that it operates as a second-tier antioxidant adaptive response system activated by radiation only under specific circumstances, including those that may be highly relevant to tumor response during standard clinical dose-fractionated radiation therapy.

As a matter if fact, radiation oncologists have been mainly concerned with Nrf2 and its hormetic effects because they could reduce the traditional cancer cell killing impacts of radiation cancer therapies. We evaluated the relationship between radiosensitivity and expression of Nrf2 target genes in HSCs. The present results suggest that the antioxidant system associated with Nrf2 is involved in the radiosensitivity of HSCs.

It is interesting though that in the publication of those directly concerned with radiation hormesis, I have yet to come across a mention of Nrf2. Radiation hormesis is still not a mainline view. There is epidemiological, experimental and genetic pathway evidence for the existence of radiation hormesis. However, given political and social situations, the radiation safety establishment has chosen to view even low-level radiation as unsafe, despite a growing body of scientific evidence contrary to this view.

This situation is characterized in the April publication Hormesis : A peep in to the human nature. Hormesis is a concept which is involved to biphasic dose response effects of environmental agents including ionizing radiation. Proponents of anti-nuclear lobby brand the idea of hormesis as the privilege of the cranks, and the ill informed. These organizations based their recommendation by extrapolation of the studies done on atomic bomb survivors who had received higher doses of radiation.

According to LNT theory a The effect of low doses or radiation can be estimated by linear extrapolation from effects observed by high doses, and b There are not any safe doses as even very low doses of ionizing radiation produce some biological effect Mortazan. However, in reality, interpretation of results may to an extent, depend on the position of the interpreter. The frenzied debates about hormesis in radiation or global warming attest to the above assertion.

Jamea Miller observed mutation following radiation of Drosophila. He assumed a linear relation between radiation and mutation though his experiments did not include very low doses of radiation. Catastrophe following nuclear war on Hiroshima and Nagasaki has resulted in radiophobia and an aversion to the concept of hormesis. The evidence for hormesis is accumulating. And deaths due to leukemia in the sub group who received less than mSv was less than age matched controls.

Nambi and Soman in have demonstrated a significantly reduced death due to cancer in high back ground areas versus areas of low background radiation in Kerala. Abbat Thus, there is no evidence of harmful effects of radiation at lower doses.

Yet, most people tend to go by LNT model including regulatory authorities. It took a while to establish a link between administration of saturated oxygen and retrolenticular fibroblasia in neonates. It was felt that life sustaining oxygen can never harm human life even at higher concentration. Thus, establishing a casual link between retrolenticular hyperplasia and saturated oxygen took considerable time by which time innumerable neonates were affected. The biphasic action of chlorpromazine as protector and senstiser at various concentrations is yet another instance of concentration dependent behavior.

There are innumerable such examples of biphasic phenomenon. Hormesis also has played a crucial role in the evolution of life. Life had to evolve despite the harsh environmental conditions, including higher cosmic radiation that is seen now.

Cellular mechanism including signaling pathways responsible for adaptive pathways are emerging. Now, there is a mechanistic explanation for a possible hermetic response for a wide range of stimulants, including that for ionizing radiation. Men are no Drosophila or cells in the Petri dish. Complex biological systems behave much differently than most people concede. Failure to acknowledge hormesis is also a failure to realize essential realities of biological complexity.

There is a slow broadening of views in the area of radiobiology to where hormesis is being accepted. The new view incorporates concepts of hormesis , nonlinear systems, bioenergy field theory, uncertainty and homeodynamics. While the mechanisms underlying these effects and responses are still far from clear, it is very apparent that their implications are much wider than the field of radiobiology.

This reflection discusses the changing views and considers how they are influencing thought in environmental and medical science and systems biology. For years, voices have been raised calling for acknowledgement of the existence of radiation hormesis and for revision of the LNT linear no-threshold standards for radiation protection which state that radiation exposure at any dose is biologically damaging.

These calls have not gotten anywhere so far. Perceived harm to irradiated nuclear workers and the public is mainly reflected through calculated hypothetical increased cancers. The LNT-based system of protection employs easy-to-implement measures of radiation exposure. Such measures include the equivalent dose a biological-damage-potential-weighted measure and the effective dose equivalent dose multiplied by a tissue-specific relative sensitivity factor for stochastic effects.

These weighted doses have special units such as the sievert Sv and millisievert mSv, one thousandth of a sievert. Radiation -induced harm is controlled via enforcing exposure limits expressed as effective dose. Expected cancer cases can be easily computed based on the summed effective dose person-sievert for an irradiated group or population. Yet the current system of radiation protection needs revision because radiation -induced natural protection hormesis has been neglected.

A novel, nonlinear, hormetic relative risk model for radiation -induced cancers is discussed in the context of establishing new radiation exposure limits for nuclear workers and the public. Given that individuals may vary significantly in their hormetic responses to radiation, establishing standards to replace LNT could be a daunting task.

It is unfortunate that radiation safety standards and therefore radiation hormesis seem to be so bound up with nuclear energy safety issues, issues of great public concern where most people want to be on the safe side. It is thought by some that radiation hormesis is mainly an argument put forward by the nuclear industry to lessen the regulatory burden on it, and this may to some extent be so. However, science is science. Radiation hormesis is ancient and evolutionary but good news, providing us with layers of protection we did not know about.

It also seems clear to me that the LNT standards for radiation safety should be revised given the presence of radiation hormesis, but how much so will require further concerted study and that in turn will require a new public safety initiative. Fully acknowledging the effects of radiation hormesis conceivably could significantly reduce public concern for radiation safety from x-rays and radon as well as nuclear power plants.

Your email:. This blog is about Mitohormesis , a different form of hormesis than that discussed in the previous blog entry Radiation Hormesis. Mitohormesis has to do with cell metabolic pathways and oxidative stress, topics I have discussed in many previous blog entries. The proper functioning of mitohormesis has to do with multiple aspects of health and with extended organism longevity in many species, quite probably including our own.

And the absence of proper mitohormesis functioning has been shown to be associated with certain disease processes and shortened lifespans in a range of animals including humans. As is the case for radiation hormesis, the concept of mitohormesis has been around for some time but has not been universally accepted.

It is only recently being widely acknowledged as an important biological phenomenon. And only relatively recently are its mechanisms of operation being unveiled. I am grateful for an intensive round of communication with James P Watson, a follower of this blog and stem cell researcher, which helped me to improve this blog entry. This is not to say that Watson, clearly a very brilliant person, will necessarily agree with all I have to say. In researching this blog entry I encountered a number of interesting recent research results having to do with topics I have discussed previously including mitochondrial metabolism, the OXPHOS system in general, mitochondrial biogenesis, frataxin , the key roles of SIRT3 in controlling ROS stress in mitochondria, and the health roles of PCG1alpha.

And I started to question whether it makes sense to supplement with PQQ. And there are pathways which seem to produce health benefits independently of motohormesis, like inhibition of TOR. Because of the great complexity involved I decided to cover most of those topics in subsequent blog entries — even though they all bear on mitohormesis. So, my intent is to keep this present blog entry focused on mitohormesis itself, what turns it on and off, and the direct health implications of mitohormesis.

In particular, I deal with the important practical topic of mitohormesis and exercise, and how some antioxidants nullify the health benefits of regular exercise. Hormesis in General. The first section of the previous blog entry Radiation Hormesis is a short introduction to the topic of hormesis in general, and I will not repeat that introduction here.

What is Mitohormesis? Consistently, abrogation of this mitochondrial ROS signal by antioxidants impairs the lifespan-extending and health-promoting capabilities of glucose restriction and physical exercise, respectively. In summary, the findings discussed in this review indicate that ROS are essential signaling molecules which are required to promote health and longevity.

Hence, the concept of mitohormesis provides a common mechanistic denominator for the physiological effects of physical exercise, reduced calorie uptake, glucose restriction, and possibly beyond. This review aims to summarize published evidence that several longevity-promoting interventions may converge by causing an activation of mitochondrial oxygen consumption to promote increased formation of reactive oxygen species ROS.

These serve as molecular signals to exert downstream effects to ultimately induce endogenous defense mechanisms culminating in increased stress resistance and longevity, an adaptive response more specifically named mitochondrial hormesis or mitohormesis. Consistently, we here summarize findings that antioxidant supplements that prevent these ROS signals interfere with the health-promoting and life-span-extending capabilities of calorie restriction and physical exercise.

And, in fact, suppression of ROS by taking antioxidants can be health-damaging and life-shortening ref. These points were also made in the publications related to radiation hormesis cited in the previous blog entry. They are also articulated in several of the publications that will be cited here as relevant to mitohormesis. Hormesis, Nrf2 and Antioxidant supplementation — a unifying framework. Before proceeding further with specific findings reported in the literature, I would like to outline a framework for viewing these findings, findings which otherwise sometimes seem inconsistent.

The major points of this framework are:. And, in reviewing the literature of hormesis I likewise find that the keap1-Nrf2 pathway is mentioned only rarely. Yet my research suggests that everything that is known to happen associated with hormesis is completely explainable by the operation of keap1-Nrf2 pathway, without reference to other pathways normally associated with hormesis such as the heat-shock response.

In stressing the role of the keap1-Nrf2 pathway in hormesis, I of course acknowledge that this is a simplification and far from tells the whole story. L-proline catabolism can also be involved ref. HDAC inhibition and histone-dependent gene silencing can be involved. And of course there are other largely independent body stress-response pathways like the UPR unfolded protein response ref and the various kinds of DNA repair machinery.

A key to understanding what is going on in hormesis is understanding how the hormetic dose-response curve works, and this can be formulated in terms of NRF2 expression. In my interpretation, the horizontal axis depicts level of stress, say as driven by ROS load. The vertical axis represents relative risk , level of probable pathological organismic response where normal level is 1.

To the left of the first axis crossing in the diagram point D the Keap1-Nrf2 pathway is progressively kicking in but not sufficiently so as to overcome the direct negative effects of ROS stress. Phantom risk is theoretical risk for low stress levels that would apply if the linear model were extrapolated for low stress dosages. According to this model, supplementation with radical-scavenging supplements like vitamins C and E inhibits the ROS which triggers the release of Nrf2 which produces hormesis when the stress is in the hormesis range, i.

The result of such supplementation is a lower health state. That is, supplementation with such antioxidants when the stress is within the hormesis range of stress can turn off the stress that activates the keap1-Nrf2 pathway therefore turning off hormesis and can do more harm than good. It appears, for example, that this is what happens with exercise where taking antioxidants eliminates the hormetic health benefits of the exercise. Some of the earlier research on free radicals and their damaging effects appears to be concerned with high dosages in this beyond-hormesis region.

So these early anti-ROS and pro-antioxidant papers are valid in their own domains and not in fact contradicted by later papers that show positive health effects associated with lower levels of ROS stress. I believe serious nuclear plant radiation overexposure and accidental ingestion of heavy metals are excellent reasons for taking heavy doses of radical-scavenging antioxidants.

They work by activating Nrf2 and triggering a hormesis response which lowers ROS and produces a wide range of positive health effects. I discuss these and other substances which activate Nrf2 in the blog entry The pivotal role of Nrf2. Part 2 — foods, phyto-substances and other substances that turn on Nrf2. Now, moving on to some results reported in the literature:.

In some lower organisms, inducing enhanced ROS signaling can lead to mitohormesis and significantly extended lifespans. By contrast, acute impairment of daf-2 in adult C. Consistent with the concept of mitohormesis, this ROS signal causes an adaptive response by inducing ROS defense enzymes SOD, catalase , culminating in ultimately reduced ROS levels despite increased mitochondrial activity.

IIIS upregulates mitochondrial L-proline catabolism, and impairment of the latter impairs the life span-extending capacity of iIIS while L-proline supplementation extends C. Taken together, iIIS promotes L-proline metabolism to generate a ROS signal for the adaptive induction of endogenous stress defense to extend life span. Many substances can promote mitohormesis at low doses, even poisons which are highly toxic at higher doses.

An example is the highly toxic pesticide rotenone. We investigated the effects of rotenone Compared with controls, rotenone ROS production was continually increased in cells treated with rotenone. These data indicate that low concentrations of rotenone can induce mitohormesis, which may be attributed to ROS production.

Again, more proof of mitohormetic dose-response curve. One of several substances that promotes mitohormesis in nematodes is the phytochemical glaucarubinone. We have found that glaucarubinone induces oxygen consumption and reduces body fat content of C.

Moreover and consistent with the concept of mitohormesis, glaucarubinone extends C. Taken together, glaucarubinone is capable of reducing body fat and promoting longevity in C. Yet another substance that appears to induce a hormetic-like effect in muscle tissues is Stanozolol. Since muscle fatigue has been related to oxidative stress caused by an exercise-linked reactive oxygen species ROS production, we investigated the potential effects of a treatment with the anabolic androgenic steroid stanozolol against oxidative damage induced on rat skeletal muscle mitochondria by an acute bout of exhaustive exercise.

Mitochondrial ROS generation with complex I- and complex II-linked substrates was increased in exercised control rats, whereas it remained unchanged in the steroid-treated animals. Stanozolol treatment markedly reduced the extent of exercise-induced oxidative damage to mitochondrial proteins, as indicated by the lower levels of the specific markers of protein oxidation, glycoxidation, and lipoxidation, and the preservation of the activity of the superoxide-sensitive enzyme aconitase.

This effect was not due to an enhancement of antioxidant enzyme activities. Acute exercise provoked changes in mitochondrial membrane fatty acid composition characterized by an increased content in docosahexaenoic acid.

In contrast, the postexercise mitochondrial fatty acid composition was not altered in stanozolol-treated rats. Our results suggest that stanozolol protects against acute exercise-induced oxidative stress by reducing mitochondrial ROS production, in association with a preservation of mitochondrial membrane properties.

The aim of the study was to test whether pharmaceutical concentrations of the glycolytic inhibitor lonidamine are capable of extending lifespan in a nematodal model organism for aging processes, the roundworm Caenorhabditis elegans. Several hundreds of adult C. Lonidamine was applied to test whether it may promote longevity by quantifying survival in the presence and absence of the compound.

In addition, several biochemical and metabolic assays were performed with nematodes exposed to lonidamine. Moreover, the compound increases paraquat stress resistance, and promotes mitochondrial respiration, culminating in increased formation of reactive oxygen species ROS.

Extension of lifespan requires activation of pmk-1, an orthologue of p38 MAP kinase, and is abolished by co-application of an antioxidant, indicating that increased ROS formation is required for the extension of lifespan by lonidamine. Consistent with the concept of mitohormesis, lonidamine is capable of promoting longevity in a pmk-1 sensitive manner by increasing formation of ROS. I Mitohormesis appears to be a pathway response preserved by evolution over many species, ranging from yeast cells to nematode worms to humans.

This, in turn, produces an adaptive mitochondrial ROS signal that extends worm life span. These findings further bolster the concept of mitohormesis as a critical component of conserved aging and longevity pathways. Using the yeast chronological aging model, researchers have identified conserved signaling pathways that affect lifespan by modulating mitochondrial functions.

Caloric restriction and a genetic mimetic with reduced target of rapamycin signaling globally upregulate the mitochondrial proteome and respiratory functions. Mitohormesis involves a variety of ROS during several growth stages and extends lifespan in yeast and other organisms. Here we recap recent advances in understanding of ROS as signals that decelerate chronological aging in yeast. We also discuss parallels between yeast and worm hypoxic signaling.

In sum, this mini-review covers mitochondrial regulation by nutrient-sensing pathways and the complex underlying interactions of ROS, metabolic pathways, and chronological aging. Exploitation of mitohormesis could become an important strategy for prevention and control of heart diseases. Reactive oxygen and nitrogen species are the most common electrophiles formed during lipid peroxidation and lead to the formation of both stable and unstable LPP. Of the LPP formed, highly reactive aldehydes are a well-recognized causative factor in ageing and age-associated diseases, including cardiovascular disease and diabetes.

Numerous studies have found that there are functional consequences in the heart following exposure to specific aldehydes acrolein, transhexanal, 4-hydroxynonenal and acetaldehyde. Because these LPP are known to form in heart failure, cardiac ischaemia-reperfusion injury and diabetes, they may have an underappreciated role in the pathophysiology of these disease processes.

Lipid peroxidation products are involved in the transcriptional regulation of endogenous anti-oxidant systems. Recent evidence demonstrates that transient increases in LPP may be beneficial in cardioprotection by contributing to mitohormesis i. Thus, exploitation of the cardioprotective actions of the LPP may represent a novel therapeutic strategy for future treatment of heart disease. Mitochondrial metabolism appears critical to sustain cardiac function to counteract aging.

In this study, we generated mice transgenically over-expressing the mitochondrial protein frataxin, which promotes mitochondrial energy conversion by controlling iron-sulfur-cluster biogenesis and hereby mitochondrial electron flux. Hearts of transgenic mice displayed increased mitochondrial energy metabolism and induced stress defense mechanisms, while overall oxidative stress was decreased.

Following standardized exposure to doxorubicin to induce experimental cardiomyopathy, cardiac function and survival was significantly improved in the transgenic mice. Activation of this cascade is markedly inhibited in the hearts of wild-type mice following induction of cardiomyopathy. Taken together, these findings suggest that increased mitochondrial metabolism elicits an adaptive response due to mildly increased oxidative stress as a consequence of increased oxidative energy conversion, previously named mitohormesis.

This in turn activates protective mechanisms which counteract cardiotoxic stress and promote survival in states of experimental cardiomyopathy. Thus, induction of mitochondrial metabolism may be considered part of a generally protective mechanism to prevent cardiomyopathy and cardiac failure.

The chemotherapy drug is a common FDA approved drug that causes cardiomyopathy when patients are treated with too much of this drug. In the frataxin-over expressed mice, there was an induction of mitochondrial metabolism and ROS defense. Statins induce mitohormesis, mitochondrial biogenesis and associated positive health effects in cardiac tissue but do not induce mitohormesis and instead induce excessive ROS stress and negative health effects in skeletal muscles.

To investigate mechanisms of statins, we tested the hypothesis that statins optimized cardiac mitochondrial function but impaired vulnerable skeletal muscle by inducing different level of reactive oxygen species ROS. However, in deltoid biopsies from patients with statin-induced muscular myopathy, oxidative capacities were decreased together with ROS increase and a collapse of PGC-1 mRNA expression. Several animal and cell culture experiments were conducted and showed by using ROS scavengers that ROS production was the triggering factor responsible of atorvastatin-induced activation of mitochondrial biogenesis pathway and improvement of antioxidant capacities in heart.

Conversely, in skeletal muscle, the large augmentation of ROS production following treatment induced mitochondrial impairments, and reduced mitochondrial biogenesis mechanisms. Quercetin, an antioxidant molecule, was able to counteract skeletal muscle deleterious effects of atorvastatin in rat. The report highlights the importance of dosage in determining whether ROS stress is in the range where the positive effects of hormesis are realized where the hormetic response curve is above the line , or the stress is too great where the hormetic response curve is below the line , and the net health result is negative.

The dose response curve must be scaled different for cardiac and muscle tissue. Apparently, a dose of statins with a response above the line for cardiac tissue produces a result below the line for muscle tissue. A second point of the above publication is the importance of the ROS. PGC-1 signaling pathway in regulation of mitochondrial biogenesis and functions. This protein interacts with the nuclear receptor PPAR-gamma , which permits the interaction of this protein with multiple transcription factors.

It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity ref.

Regarding this article, James P Watson had some very interesting comments which he communicated to me privately, as follow. This is very convincing evidence of an ROS-mediated mitohormetic mechanism in the heart for statins and an opposite mitodestructive mechanism in skeletal muscles with statin therapy. Here are the results summarized:.

N uclear co-activators and gene expression ;. ROS production. This study did not include anti-oxidants. It was just a skeletal muscle vs cardiac muscle biopsy study, done during open heart surgery. My comment James P Watson, continuing on this article and diagram:. Another publication relating exercise, ROS and the impact of statins is the publication Atorvastatin treatment reduces exercise capacities in rats: involvement of mitochondrial impairments and oxidative stress.

Mitochondrial impairments may play an important role in the development of muscular symptoms following statin treatment. Our objective was to characterize mitochondrial function and reactive oxygen species ROS production in skeletal muscle after exhaustive exercise in atorvastatin-treated rats.

By blocking mitohormesis, regular supplementation with antioxidants may block the beneficial effects of regular exercise. This is a sobering revelation for those who both regularly exercise and take antioxidant supplements, believing that these interventions work synergistically. A publication Antioxidants prevent health-promoting effects of physical exercise in humans speaks as to how by blocking mitohormesis, supplementation with Vitamins C and E nullifies the health-producing effects of physical exercise.

However, exercise also increases mitochondrial formation of presumably harmful reactive oxygen species ROS. Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown. Before and after a 4 week intervention of physical exercise, GIR was determined, and muscle biopsies for gene expression analyses as well as plasma samples were obtained to compare changes over baseline and potential influences of vitamins on exercise effects.

Molecular mediators of endogenous ROS defense superoxide dismutases 1 and 2; glutathione peroxidase were also induced by exercise, and this effect too was blocked by antioxidant supplementation. Consistent with the concept of mitohormesis, exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity.

Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans. Notably, by blocking exercise-dependent formation of reactive oxygen species due to ingestion of antioxidant supplements, health promoting effects of physical exercise are abolished, and physical exercise fails to promote insulin sensitivity and antioxidant defense in the presence of vitamin C and vitamin E.

The patterns of coupling the taking of antioxidants along with regular physical exercise in the interest of general health is, for many people, deeply entrenched, encouraged by much advertising, and only recently being seriously questioned. The August publication Does vitamin C and e supplementation impair the favorable adaptations of regular exercise? However, controversy has risen regarding the potential outcomes associated with vitamins C and E, two popular antioxidant nutrients.

Recent evidence has been put forth suggesting that exogenous administration of these antioxidants may be harmful to performance making interpretations regarding the efficacy of antioxidants challenging. The available studies that employed both animal and human models provided conflicting outcomes regarding the efficacy of vitamin C and E supplementation, at least partly due to methodological differences in assessing oxidative stress and training adaptations. Long-term antioxidant supplementation, specifically with Vitamin C and alpha-lipoic acid, reduces mitochondrial biogenesis in skeletal muscle tissue by interfering with ROS signaling that triggers mitohormesis.

However, exercise-induced ROS may regulate beneficial skeletal muscle adaptations, such as increased mitochondrial biogenesis. METHODS: Male Wistar rats were divided into four groups: 1 sedentary control diet, 2 sedentary antioxidant diet, 3 exercise control diet, and 4 exercise antioxidant diet. Experimental Evidence also shows absence of research support for the popular idea that antioxidant supplementation is a good thing to do associated with fitness exercising.

This has provoked expansion of the supplement industry which responded by creation of a plethora of products aimed at facilitating the needs of the active individual. However, what does the experimental evidence say about the efficacy of antioxidants on skeletal muscle function? Are antioxidants actually as beneficial as the general populous believes? Or, could they in fact lead to deleterious effects on skeletal muscle function and performance? This Mini Review addresses these questions with an unbiased look at what we know about antioxidant effects on skeletal muscle, and what we still need to know before conclusions can be made.

On the contrary, studies with antioxidant supplementations generally show no effect on muscle function during and after exercise. The exception is NAC treatment, which has been found to improve performance during submaximal exercise. It appears that muscle fibers are in some way protected against deleterious effects of oxidants during exercise and fibers are generally much more sensitive to exposure to oxidants in the rested state than during fatigue. The molecular mechanisms leading to sarcopenia are not completely identified, but the increased oxidative damage occurring in muscle cells during the course of aging represents one of the most accepted underlying pathways.

In fact, skeletal muscle is a highly oxygenated tissue and the generation of reactive oxygen species is particularly enhanced in both contracting and at rest conditions. It has been suggested that oral antioxidant supplementation may contribute at reducing indices of oxidative stress both in animal and human models by reinforcing the natural endogenous defenses. Aim of the present paper is to discuss present evidence related to possible benefits of oral antioxidants in the prevention and treatment of sarcopenia.

In fact, a large body of evidence may indicate extreme cautiousness in taking antioxidant supplementation as preventive measures against aging process and age-related conditions. Further studies are needed to support the widespread practice of oral antioxidant supplementation and to determine appropriate recommendations in elderly. Instead, seemingly puzzled, the authors suggest a need for more research to relate sarcopenia to antioxidant use.

In acknowledgement of the existence of mitohormesis, metabolic researchers are beginning to think in terms not only of oxidative stress but also in terms of antioxidant stress, especially associated with the consumption of antioxidants.. ROSs were considered traditionally to be only a toxic byproduct of aerobic metabolism.

However, recently, it has become apparent that ROS might control many different physiological processes such as induction of stress response, pathogen defense, and systemic signaling. Thus, the imbalance of the increased antioxidant potential, the so-called antioxidative stress, should be as dangerous as well.

Oxidative stress is not necessarily an un-wanted situation, since its consequences may be beneficial for many physiological reactions in cells. Antioxidants can neutralize ROS and decrease oxidative stress; however, this is not always beneficial in regard to disease formation or progression of, e.

The normal balance between antioxidants and free radicals in the body is offset when either of these forces prevails. The available evidence on the harmful effects of antioxidants is analyzed in this review. Negative health effects due to inhibition of ROS and consequent inhibition of mitohormesis applies to classical antioxidants, substances like vitamins C and E that act as free radical scavengers. Regarding this point, see the blog entry The pivotal role of Nrf2.

Speaking also directly to this point is the March publication Oligomerized lychee fruit extract OLFE and a mixture of vitamin C and vitamin E for endurance capacity in a double blind randomized controlled trial. The study aimed to investigate the effects of a polyphenol mixture and vitamins on exercise endurance capacity.

Seventy regularly exercising male participants were randomly assigned to receive oligomerized lychee fruit extract, a mixture of vitamin C mg and E IU , or a placebo for 30 consecutive days. The adjusted mean change was 3. Oligomerized lychee fruit extract significantly increased the anaerobic threshold by 7.

On the other hand, vitamins significantly attenuated VO 2 max by Their effects on plasma free radical amount, however, were similar. Our results suggest that a polyphenol-containing supplement and typical antioxidants may have different mechanisms of action and that the endurance-promoting effect of oligomerized lychee fruit extract may not directly come from the scavenging of free radicals but may be attributed to other non-antioxidant properties of polyphenols, which requires further investigation.

Consistant with the above discussions regarding mitohormesis, researchers are continuing to discover additional important biological roles played by oxidative stress, even extending to sexual signaling. In , von Schantz et al. Their suggestion has been enthusiastically tested, with over studies citing their paper, but most effort has concerned carotenoid-based and to a lesser extent melanin-based visual signals, predominantly in birds and fishes. Today, we know a great deal more about oxidative stress and related physiology, in both a pathological and regulatory sense, than we did in We revisit von Schantz et al.

In particular, we argue that differences between individuals in their ability to regulate physiology related to oxidative stress may be an important factor influencing the production of sexual signals and the costs that are incurred from investment. Wrapping it up. Mitohormesis, like radiation hormesis exists and is important. Here I have been able to discuss some key aspects of mitohormesis, but there is probably much more to come.

My experience in writing this blog entry was the usual one of more questions being raised than answered. The leading edges of science are never neat and nicely wrapped up. James P Watson has argued with me privately, for example, that most all scientifically proven lifespan extension phenomena are due to a mitohormetic principle. And I hope that some combination of he and I will be able to lay that argument out in a blog posting to come.

Me, working up a little mitohormesis in the gym. I also benefit from blogohormesis: Working to get my mind around the subject of this blog entry initially produced a similar experience of nearly-impossible weight and stress. This was slowly replaced by a feeling of wellbeing, one that will be good hopefully until I get deeply into the next blog entry. There appears to be a Great Divide in the world when it comes to health, manifest most clearly in Western Countries and in the US in particular.

The divide is between two major paradigms of thinking, philosophies, methods and institutions used to maintain health and treat diseases. On one side of the divide we have what today is popularly called Health Care.

On the other side of the Divide we have the paradigm I will call Wellness - which is actually the current form of Folk Health. This blog entry updates and amplifies on the theme of my May blog entry Shift to the wellness-longevity paradigm. I reiterate some of the key points in that blog entry and focus particularly on the dynamics that keep the Great Divide in place. I discuss how new scientific knowledge of certain plant-based substances can contribute to bridging the Great Divide.

And I express concern about how that can happen. This is a long blog entry and if you want to go first to conclusions and suggestions you can scroll down to the final section entitled Wrapping it all up — bridging the Great Divide.

The two paradigms of Health Care and Wellness encompass behavior patterns, educational approaches, major institutions, government policies and agencies. The divide is to some extent also between old and new, between East and West, and between how a person decides on what to do about his or her wellness and health. It involves who people trust for health advice, and between what educated people think they are supposed to do and what they actually do.

Though operating in very different spheres, there is some evidence that these two paradigms are increasingly overlapping and moving together. I believe this is a very good thing. In this blog entry I discuss the strengths and weaknesses of each paradigm. I talk about how the two paradigms complement and require each other, and how the process of bringing them together might be accelerated. My primary reference here is the situation in the US, although similar patterns exist in other advanced countries.

Health Care. First, let me outline the paradigm of Health Care as I see it. Health Care is based mainly on Allopathic Medicine and goes on to encompass vast institutions. At the periphery lie health insurance companies, nursing homes and secondary care facilities, government bureaucracies and countless university and private laboratories and research institutions. The numbers involved in US health care are mind-numbing.

And these costs do not include suffering from diseases, lost time from work for individuals and employers, loss of productivity, and care provided by unpaid caregivers. The Health Care system facilitates progress in many important dimensions. But the relationships among central players also limits progress in overall public health. What drives or limits progress in Health Care? What is the source of innovation?

What inhibits innovation? MD doctors and the medical schools and boards that train and discipline them, 2. The pharmaceutical, biotech and medical technology industries that convert research knowledge into practical drugs and educate doctors about these, and 3. Government agencies, especially the FDA which sets the rules for how new drugs are developed and released to the public. Only doctors and a few other highly licensed practitioners can prescribe legally-sanctioned drugs.

New drugs are developed typically through the course of an years period of research and development, culminating with Phase 1, Phase2 and Phase 3 clinical trials. These trials are overseen by the FDA and alone may cost from one to several hundred million dollars. No wonder that big drug companies aim new drugs at massive markets and the business model is like that for blockbuster movies. Medical doctors are highly trained, regulated and respected in our society.

They function within practice frameworks prescribed by law and by rule-setting professional associations like the American College of Cardiology, the American Association for Thoracic Surgery, the American Academy of Pediatrics, etc. Few doctors will administer or prescribe treatments that have not gone through the FDA approval process and that are not mainline in their professional subspecialty. One reason is that straying beyond FDA and association-approved medications engenders a risk of ruinous lawsuits.

If a treatment prescribed is not an established standard of medical practice and someone claims to be harmed by that treatment, the doctor is at risk of ruin. Use of standard and government approved drugs provides badly needed legal coverage in case of such commonly-occurring lawsuits. Another reason, sadly, is that doctors, being extremely busy as they are, may simply not know about highly effective alternative treatments in Wellness which have been highly researched and found effective but which are not FDA sanctioned.

Including what are the correct dimensions? For example, materialization the precomputation and storage of inferred triples is an expensive process which may not contribute to desired results. Another contribution to this debate is the Billion Triple Challenge run in conjunction with the International Semantic Web Conference see below in Related Resources [60].

Finally, Orri Erling has an interesting database-centric blog on this in [76]. From the beginning, the Semantic Web was seen as a necessary platform for supporting agents which could carry out tasks on behalf of human users. Within the seminal Semantic Web paper [6], a scenario is presented at the start where a Semantic Web agent books an important medical appointment checking the online diaries of a woman, her two grown-up children, and a number of hospitals satisfying geographic and quality constraints.

The motivation for creating the Semantic Web is based on the functionality provided by software agents, which rely on the combination and exchange of content from diverse sources. The Semantic Web would allow agents to read the content of pages because the data are coded in a machine-readable representation. The underlying ontological basis for the data supports semantic interoperability by coding meaning in a way that supports semantic mediation. Given the early motivations, however, the amount of agent research based on Semantic Web technology has been relatively small.

There were two main reasons for this. Firstly, more emphasis than initially envisioned was required for creating a robust, usable, and scalable data layer. Also the majority of agent research was founded on FIPA protocols [67] rather than the stack of Web standards. It is hard to know who first had the idea of creating a language on the World Wide Web that could be used to express the domain knowledge needed to improve Web applications. However, by or so, it was clear that the Web was going to be around for some time, and there was a burst of energy going on.

This historical event is mentioned here as it is sometimes said that the Semantic Web was created to improve search. This is partly true, but it is important to note that search as known back then, pre-Google, was not the same as the current keyword search that powers so much of the modern Web today. Around this effort, a number of tools were created within the project including a semantic annotator for HTML pages and a semantic search tool.

These two early projects looked at what is now called Web ontology languages, and were driven less by the AI-inspired push for expressive languages, and more by the needs of the emerging Web — what would now be called semantic annotation or tagging. Approximately 18 months later the OntoWeb [70] network of excellence started, which was the birthplace for the Knowledge Web project [71]. In parallel with this Web representation work, W3C had begun to explore whether some sort of Web markup language could be defined to help bring data to the Web.

There was at this time a split between XML and RDF, which we do not have space here to recount but suffice to say that this added confusion to the overall story. It is also worth noting here the dialogue that began in the late s within the Knowledge Acquisition Workshop Series in Banff [72] on the relationship between knowledge acquisition, modeling, and the Web.

One of the projects that came out of this discussion was IBROW3 [4], which examined how knowledge components could be reused through the Web. To help sell the US government on funding this research area, the techniques pioneered in Ontobroker and SHOE were used to build some demos showing the potential for these new languages. In fact, in a talk Web Conference, Geneva he said: " Documents on the web describe real objects and imaginary concepts, and give particular relationships between them.

For example, a document might describe a person. The title document to a house describes a house and also the ownership relation with a person. This means that machines, as well as people operating on the web of information, can do real things. For example, a program could search for a house and negotiate transfer of ownership of the house to a new owner. The land registry guarantees that the title actually represents reality. As this work grew, it was decided that an effort was needed to bring together the key players in this emerging area.

The outcome of this was a Dagstuhl Seminar held in [62]. The workshop was quite successful and led to a dramatic increase in funding especially in Europe. Knowledge and Content Unit in Luxembourg by type and funding, color coded according to the areas of semantic annotation, modeling, search, inference, and Semantic Web Services. The change in name relates to the conference series covering topics related to the application of semantics to mobile platforms, cloud computing, sensor networks, as well as the Web.

The event usually attracts around participants and includes a research and in-use track as well as workshops and tutorials. This con- ference traditionally includes a Semantic Web track. It often includes papers though related to the Semantic Web. A number of videos and websites exist that outline the basic notions behind the Semantic Web. Pollock Wiley Inc. Moreover, a number of commercial announcements have been made recently, which indicate that one is moving from an early adopters phase to more mainstream markets for semantic technologies.

However, of interest here is the fact that. One of the main reasons for this is that as with many commercial shifts, this was a requirement from Oracle customers, particularly in the areas of pharmaceutics, life sciences, and health care, who need to integrate large amounts of data from many different sources. This type of data integration at scale and across many heterogeneous sources which cannot be changed is one where semantic repositories cope well.

Additionally, in these areas, reasoning capabilities are useful in supporting the mining and analysis of the data. Here, the focus is on the impact of the announcement. In short, the Open Graph protocol facilitates the integration of Web resources into a Facebook social graph.

It is seen in the figure that three readers have expressed that they like the story. These preferences also allow site owners to track the demographic data of users visiting their site. In the last few months, a number of commercial companies have built sites around this feature. Also, Amazon have integrated their recommendation system to use Facebook pro- files through Open Graph. There are two main reasons for highlighting this deployment of semantic technology. The probability is that this will in the short to medium term be a major source for semantic data.

In July , Google bought Metaweb, the company which maintains Freebase. Currently, Freebase has around 12 million items including movies, books, and organizations. From a linked data viewpoint, one interesting aspect of this purchase is that Google intends to maintain Freebase as a free and open resource. The Website included over pages describing the 32 teams, 8 groups, and the associated hundreds of footballers that took part in the event.

The Web pages were dynamically aggregated using a football ontology describing concepts associated with the World Cup e. One can see the page describing the England midfielder Frank Lampard. The use of semantic technology was deemed to be successful and the website proved popular dealing with several million page requests every day throughout the World Cup.

User requests, which can be typed or spoken, are given through a dialog interface customized for smart phone screens. The currently supported tasks include booking a table at a restaurant, for a movie, or for an event, and requesting a local taxi or finding local businesses. In addition to the sophisticated dialog system, domain and task models are used to support the combining of online services to fulfill the requested task.

The main benefit that Siri provides for the end user is that a simple conversation replaces the effort of combining either a sequence of Web searches or a sequence of mobile phone App interactions. It can be seen above that semantic technology is beginning to enter the mainstream. Also, by and large, it is the simpler technologies which are data-centric that have been taken up. There are a number of views that one could take on this.

One is that it should be expected that by their very nature, real-world Web applications will be dom- inated by data rather than conceptual structures. Second, even with the successes emerg- ing now, the Semantic Web is still in a preliminary phase of commercialization and it will take time to progress to Web applications, which require more complex conceptual reasoning. The acquisition of Siri runs somewhat counter to the reasoning above and indicates that there may be space for more complex forms of reasoning, as is required to deal with services and Web APIs.

Reflecting on the last decade of research into the Semantic Web, two issues seem clear. Firstly, as outlined above, at this point semantic technology is becoming mainstream and we will continue to see deployment of semantics in the commercial sector. It is envisaged that in the near term, organizations will make significant portions of their data available on the Web using semantic technologies.

Moreover, the emergence of data will grow in a way analogous to the way in which the Web grew. At the beginning of the Web, it was often asked what would motivate individuals and organizations to put resources into creating and developing websites.

Over the history of the Web, we have seen a progressive escalation in this effort. Corporations will now have entire departments dedicated to maintaining their presence on the Web. Web presence is seen as a requirement rather than a luxury, and the Google ranking of an organization can determine its success. As a first step toward the vision outlined in the Scientific American paper [6], a semantic data presence will soon become a requirement rather than a luxury.

Thus, linked data moves the effort of creating and maintaining websites and Web applications over organizational data to external parties. Secondly, the Web is changing in a number of ways. It is expected to see a growth in platforms for Web applications based upon combinations of social networking and semantic technologies, harnessing the power of human networks and automated reasoning.

A discussion is currently taking place related to which forces will dominate the way the Internet is used. In this article, the authors saw three trends emerging. Firstly, that video and peer-to-peer network traffic are beginning to take a large proportion of Internet traffic when compared to pure Web communication.

Secondly, that as predicted in several places, the number of users accessing the Internet from mobile devices will soon surpass the number who access it from PCs. A consequence of the shift to mobile devices such as the iPhone and iPad is that specialist Apps designed for a single purpose will be used more than general-purpose Web browsers. A third trend from the commercial perspective is that the Internet will be dominated by a relatively small number of large players, such as Apple, who will act like the media empires of the third quarter of the twentieth century.

These claims are not agreed by all however. One thing that can be assumed safely is that the debate will continue for some time. After a decade of research and as shown in the rest of this book, the Web is a global infrastructure that benefits significantly from the use of semantics. Semantics supports a broad range of tasks including data sharing and data integration at scale, knowledge management, decision making, data analysis, search, and the use and management of Web applications based on Web APIs and services, as well as a variety of vertical sectors such as government, science, business, and media.

Given the success thus far, it is clear that semantic technology will also play a major role in other global network infrastructures based on, for example, mobile devices and sensor nets. Whatever form future planet-scale networks take, it has certainly been an exhilarating journey so far and we look forward to the next decade.

Acknowledgments We thank Ian Horrocks and Michael Kifer from preventing mistakes in the sections of the chapter related to logic. We also thank Neil Benn for his help in the final formatting stages. References 1. Adida, B. Accessed Aug ing Group Note Oct 6.

Berners-Lee, T. Antoniou, G. Scientific American Magazine, pp. Baader, F. Bizer, C. Web Inf. Cambridge University 1—22 Press, Cambridge 8. Brachman, R. Benjamins, V. Morgan Kaufmann, Studer, R. Brickley, D. W3C world-wide web. Brin, S. ISDN Syst. Bush, V.

The Atlantic Monthly, 5. Cerf, V. Gruber, T. Accessed Aug Chen, W. Log Program 15 3 , — consumer experience on the phone. Keynote Clocksin, W. Springer, New York tomgruber. Codd, E. Addison-Wesley Halpin, H. Dean, M. Hedman, S. Horrocks, I. Feigenbaum, E. In: Proceedings of the gence: themes and case studies of knowledge Sixth International Conference on Principles of engineering.

Fensel, D. Schnurr, H. Web Semant. Isaac, A. Jurafsky, D. Processing, 2nd edn. Kelly, J. Prentice Hall, Stollberg, M. Kifer, M. Springer, 42, — Berlin , 2nd edn. Springer Lausen, H. Garcia-Molina, H. Prentice Hall, New Jersey Lloyd, J. Giarratano, J. Springer, Berlin Principles and Programming, 4th edn.

PWS, Luke, S. In: Proceedings of Manning, C. Accessed University Press, Cambridge 6 Sept Manola, F. Accessed Maslow, H. Mauritius National Assembly: The constitution. Accessed 6 Accessed 6 Sept Sept Mead, G. The Univer- Moens, M. Accessed 6 Sept rithms and Prospects in a Retrieval Context.

Accessed 6 Sept Motik, B. Lutz, C. Nelson, T. In: Proceedings Accessed 6 Sept of the 20th National Conference, Association for Patel-Schneider, P. Accessed 6 Sept OWL web ontology language semantics and abtrsct syntax. Section 5.

RDF-compatible Pingdom: Internet in numbers. Accessed Jan 6 Sept Reynolds, D. Accessed 6 Sept Group Note June Robinson, A. Elsevier Science, on-building-britains-digital-future, Amsterdam Accessed 6 Sept Russell, S. Accessed 6 Sept A Modern Approach, 2nd edn. Prentice Hall, Accessed 6 Sept New Jersey Schreiber, G. Accessed 6 Sept Hoog, R. Tomasello, M.

MIT Press, Cambridge Wikipedia: Semantics. Wikipedia: Tag cloud. Wikipedia: Taxonomies. Wikipedia: Controlled vocabulary. Wikipedia: Tower of Babel. Accessed 6 Accessed 6 Sept Sept Wikipedia: Energy. Wiktionary: Device. Wikipedia: Equipment.

Accessed 6 Sept logy language reference, W3C Recommenda- Wikipedia: Idea. Idea Accessed 6 Sept Accessed 6 Sept Accessed 6 Sept Recommendation. Wikipedia: Machine. World Wide Web Consortium: The global Wikipedia: NLS computer system. Accessed 6 Sept global. Wikipedia: OSI model. Accessed 6 Sept W3C Standard. Wikipedia: Purpose. Yeates, G. Te Ara — the encyclope- Wikipedia: Second-order logic. Maciej Janik2. Abstract: The Semantic Web extends the existing Web, adding a multitude of language standards and software components to give humans and machines direct access to data.

The chapter starts with deriving the architecture of the Semantic Web as a whole from first principles, followed by a presentation of Web standards underpinning the Semantic Web that are used for data publishing, querying, and reasoning. Further, the chapter identifies functional software components required to implement capabilities and behavior in applications that publish and consume Semantic Web content. One of the key goals of Semantic Web technologies is to provide machines with a more sapient understanding of data.

Given a wider availability of quality data online, applications can leverage a common data access and integration layer for providing elaborate services to users. The chapter derives the architecture of the Semantic Web from first principles, gives an overview of the architecture of Semantic Web applica- tions, and covers building blocks of the Semantic Web in more detail.

The information required to answer these questions is available on the Web. In fact, a large amount of such information already exists in formats amenable to machine processing on the Semantic Web. The reason that Web search engines fail at answering such questions is that they are limited to analyzing Web content — mostly documents in natural language — one page at a time, while the Semantic Web allows for combining data that are distributed across many different sources and described in a machine-interpretable manner.

For example, how may one pursue answering the questions related to playlists of UK radio stations? MusicBrainz knows about band members, such as Benny Andersson, and about genre of artists and songs. MusicBrainz aligns its information with Wikipedia, for example, to be able to include the biography of an artist, or to add facts from DBpedia [2], a version of Wikipedia in Semantic Web formats.

The meaning of such relationships are explained online, too, using a set of ontologies available on the Web, such as Dublin Core, for describing general properties of information resources, SKOS for covering taxonomic descriptions, and specialized ontologies covering the music domain. Given the available data, one may answer questions such as the frequency of certain music genres played on UK radio stations, radio stations playing Swedish composers, and many many more.

However, having access to and leveraging such data does not come for free. The outlined scenario and likewise other use cases require generic software components, languages, and protocols that must interact in a seamless manner to be able to satisfy such requests. The chapter investigates the construction of the required infrastructure at large, that is, the Semantic Web architecture, and analyzes the requirements that come from the technical need to identify and relate data, and the organizational needs to maintain the Semantic Web as a whole — even if single compo- nents shake or break.

Achieving such functional capabilities requires an unprecedented growth of openly available data covering a wide range of domains and involving large amounts of people and organizations. Such phenomenal and fast growth is a nonfunctional i. Thus, the first consideration is the architec- ture of the Web, to be able to learn from its design considerations, and to derive additional nonfunctional requirements later on. Its explosive growth is tightly associated with its underlying software architecture.

The fact that each individual system has been coupled only very loosely with the other one and that document creation, document delivery, and document browsing could happen in isolation in each of the many individual nodes was of key importance for enabling the fast adoption of the early Web.

The lesson to be learned is that a state-of-the-art system that produces higher quality output e. Furthermore, a distributed system without the need for a central coordinator is inherently robust. While there are many potential problems that may affect individual nodes in the World Wide Web, the only problem leading to brittleness in the World Wide Web as a whole is the hierarchical control of the IP addresses and the Domain Name System of the Internet.

Many requirements were derived from the design decisions that worked well for the World Wide Web and led to its phenomenal growth, but which had yet to be realized for data and knowledge systems. In fact, traditional knowledge systems have already exhibited some of the functional requirements sought from the Semantic Web. However, traditional knowledge systems exhibited a lack of flexibility, robustness, and scalability. To quite some extent the problem had been a lack of maturity in the face of algorithmic methods with high computational complexity.

For instance, description logics systems, which are now the backbone of Web Ontologies, were severely limited in scale, typically capable of handling not more than a few hundred concepts in the mids cf. Such problems have been assuaged using much increased computational power and better understood and optimized algorithms. However, several bottlenecks remain, which are akin to the problems that the architecture solved for the domain of hypertext documents. Remaining barriers for managing data and semantics revolve around issues concerning the large number of data sources with varying 1 underlying technologies, 2 geographically dispersed locations, 3 authorities, 4 service quality, and 5 adop- tion rate.

These are exactly the dimensions that had and have to be considered for the design of the World Wide Web. Thus, in analogy to the World Wide Web, the Semantic Web requires a computing mega system with the following five characteristics: 1. Explicit, Simple Data Representation: A common data representation should hide the underlying technologies and only capture the gist of the underlying data representa- tions. Here, the analogy may be drawn with HTML documents that have served as simple, yet effective representations of what constitutes a document.

Distributed System: The system should be fully distributed, comprising of data sources without a centralized instance that controls who owns what type of information. Distrib- uted ownership and control, if done properly, facilitates adoption and scalability, which is in analogy to websites and Web pages that are under full control of their producers.

Cross-referencing: In order to benefit from the network beyond the mere sum of its parts, the data must be cross-linked, allowing for reuse of existing data and existing data definitions from different authorities, analogous to hyperlinks allowing for the reuse of text in the hypertext space. Loose Coupling with Common Language Layers: In a mega system, the components have to be only loosely coupled.

The loose coupling is achieved by communicating in standardized languages. The standardized languages must come with great flexibility such that they may be customized for specific systems, but the overall communication must not be jeopardized by such specialization. The requirement should be seen in analogy to the coupling between different Web clients and servers, where dependency is reduced to understanding HTTP as transport protocol and producing and interpreting HTML content.

Ease of Publishing and Consumption: The mega system should allow for easy publishing and consumption of simple data and for comprehensive publishing and consumption of complex data. The requirement is in analogy to the Web page description language HTML that provides a simple means of conveying textual information, but that can be viewed, managed, and composed using elaborate browsers and powerful content man- agement systems.

Given these requirements, two points of view for a Semantic Web architecture emerge. One viewpoint is focused on the Semantic Web languages and protocols and is mentioned several times in the above list.

Another viewpoint concentrates on the functionalities to be contributed by Semantic Web components. Requirements for a Semantic Web Language Architecture. At high level of abstraction, Semantic Web languages must address the listed requirements. Below, mandatory objec- tives are presented, accompanied by examples and, in parenthesis, the requirement they refer to.

Second, such a data model must be serializable in a standardized manner such that data become easily exchangeable between different computing nodes 1, 2, 4. Wikipedia or DBpedia cannot be easily joined. A merge of such datasets may lead into forming interesting connections between playlists, music groups, artists, and their origin that span across datasets. While combining data is possible in conventional systems, such as relational databases, the emphasis on the Semantic Web is on the ease of joining such separate pieces of information.

Third, individual entities must be referable in such a data model across borders of ownership or computing systems, thus allowing also for the cross-linking of data 1, 2, 3, 4. Fourth, the data model should have an expressive, machine-understandable data description language. In a global data space, having an expressive data description language is of major concern because users and developers can no longer manually inspect and make use of data descriptions due to the sheer size and heterogeneity of data on the Web 1, 5.

Furthermore, such a data description language also allows for a refinement of the basic data model, providing levels of specialization needed in the application domains 4. For instance, the richness of BBC program descriptions is hard to understand given long chains of data leading from radio stations, over shows, versions of shows, to the songs which are connected to artists.

Fifth, such a data model requires a query and manipulation language allowing for selections of data or aggregations of data, such as the number of Swedish composers being broadcasted on specific programs 5. Sixth, reasoning is desirable to facilitate querying, as it provides shortcuts for complex data situations, for example, turning the chain of relationships between a program and a song into a direct relationship using inference rules 5.

Seventh, the transport of data and the transport of queries and results need commonly agreed-upon protocols. While many protocol details are still under discussion, the usage of HTTP is agreed and even refined, for example, for the transport of queries. Eighth, such a transport requirement may also include encrypted data requests and data transport. Security of data transmission is typically addressed by encrypting the data transmission channel. Beyond the increased security of transport, further security functionality is required, for example, for signing data items.

Such features call for a completely distrib- uted authentication system to establish the authenticity of a user request and control access to resources. All require- ments for Semantic Web languages imply corresponding requirements on functionality to be delivered by software components.

However, some software components are not standardized and should not be , but should be customizable to every individual user needs — up to a point where the community may recognize new chores to be carried out in the stack of software components that should be moved out into a joint language or joint computational model or structure. Core requirements that are not yet included in the language architecture comprise the following.

First, versatile means for user interaction. A Web of Data is not merely a Web of Documents and understanding cross-linked data is different to reading a document. Hence, early means of tabular interfaces constitute a stepping stone, which however is rather a crutch than a full-fledged solution for making the content of the Web accessible to users.

Broad accessibility requires viewing, searching, browsing, and querying for data, while at the same time abstracting from the intricacies underlying the distributed origin of the content. The users need the ability to assemble information from a multitude of sources without a priori knowledge about the domain or structure of data. Such on-the-fly integration of multiple data sources enables new interesting scenarios for searching and interacting with the data, but may require software that is oblivious to the underlying structure.

Likewise, interaction should facilitate data production and publishing. Crucial to the success of the Web of Data is that metadata creation and migration of data are made convenient, no matter whether the data originate from the content management systems, relational databases, or competing metadata representations, such as microformats. Second, the issue of provenance and trust is even more important in a Web of Data than in a Web of Documents.

While documents still convey provenance and trust via indications such as authorship and website ownership, corresponding notions for data are watered down once data are processed and aggregated with other data. Hence, notions of origin, reliability, and trustworthiness need to be reconsidered for making them applicable to individual data items and for aggregated datasets.

Furthermore, such notions are connected to faithful authentication working at Semantic Web scale. Third, in exploring the data and weighing their provenance and trustworthiness, one must be able to align unconnected sets of data. Only with such an alignment, the full picture of a Web of Data may emerge. A software architecture describes the structure of a software system and serves the purpose of dividing the software into components that may be developed and maintained — and may be used — independently of each other.

Thus, a software architecture gives developers, maintainers, and users the possibility to care about their part of the system while being able to communicate system properties with other people. Unlike traditional information systems design, both the Web and the Web of Data do not emphasize the specific application, but rather generic needs that can be realized in many different components, which only agree on a core set of standards.

Therefore, the first architectural viewpoint presented is the famous Semantic Web layer cake which is actually a Semantic Web protocols and languages layer cake. Most of the parts in the layer cake are related to data publishing and exchange. The second architectural viewpoint considered is a functional view; thus, a description of software components that provide certain functionality, such as supporting language standards or user interaction is given, followed by a discussion of alternative architectural choices for Semantic Web applications.

The remainder of the section first briefly introduces each language component, starting at the bottom and progressing to the top; more detailed discussions follow later on. Given the decentralized nature of the Semantic Web, data publishers require a way to unambiguously refer to resources. The ability to unambiguously point to resources and dereference them is a first step. Next, required is a language to exchange description of resources.

The Extensible Markup Language XML is used for encoding documents and provides means for specifying and serializing structured documents which can be parsed across operating systems. Building on a referencing and a document exchange mechanism, means to encode descriptions about resources are required. Given that the data on the Semantic Web are highly distributed, the description of resources should be encoded in a way that facilitates integration from a large number of sources.

A graph-structured data format [61] achieves the easy integration of data from multiple sources. RDF graphs can be serialized in multiple ways; one of the most commonly used is the XML serialization. Having integrated data, mechanisms for querying the integrated graphs are necessary.

Encoding data as graph covers only parts of the meaning of the data. Often, constructs to model class or property hierarchies provide machines and subsequently humans a more comprehensive understanding of data. To more comprehensively model a domain of interest, so-called ontology languages can be employed. RDF Schema RDFS is a language which can be used to express, for example, class and property hierarchies as well as domain and range of properties.

Since data originate from multiple sources and are thus highly heterogeneous, means to reconcile data from different sources and to check consistency of combined data are required. The Web Ontology Language OWL allows for specifying the equality of resources or cardinality constraints of properties, for example. Ontology languages allow for auto- mated inferences, that is, drawing conclusions based on existing facts. An alternative way to specifying logical inferences is via rules.

Often, users require means to express logical rules which transform data or enrich data with additional specifications. Another view is via software applications and components that implement func- tionality based on the standards and languages. For a survey of Semantic Web applications described in the literature and the components they implement, see [41].

The basic infrastructure components enable the publishing RDF and the dereferencing of content. The Semantic Web inherits the basic infrastructure for referencing and lookup from the Web. Similarly, rule engines allow for processing rules exchanged in RIF. A crucial point for transmitting sensitive personal data is to ensure that data trans- missions cannot be intercepted, read, or altered. Crypto-tools cover encryption and authen- tication technologies to ensure the secure exchange of data.

Crypto-modules, such as SSL processors, verify digital certificates and provide cryptographic privacy and authentication. Given that content aggregated from a large number of sources often uses multiple identifiers to denote the same real-world object, an integration and alignment layer provides for consolidation and the tighter integration of data. The provenance and trust layer analyzes the data in conjunction with additional information to provide the user with a notion of trust associated to individual data items.

Finally, the user interface enables users to interact with Semantic Web data. From a functionality viewpoint, some user interfaces are generic and operate on the graph structure of the data, while others are tailored to a certain domain and ontology. In the preprocessing approach, Web crawlers or scripts collect large amounts of data and indexers prepare the entire corpus for fast lookups. The architecture of Web crawlers has been adapted to the intricacies of Semantic Web data e.

In some of the warehousing systems, reasoning modules ensure that all inferences on the gathered data are computed a priori, and then the queries are answered against the materialized version of the dataset.

Typical large-scale Semantic Web search engines [20, 22, 24, 43, 58] use the precomputed approach where all data are collected and preprocessed. The on-demand query model, on the other hand, is used in meta-search engines [72] and distributed query-processing systems, which start with the query or goal and iteratively collect the required data from a set of distributed sources. Meta-search engines collect and integrate results from several search engines during query execution time.

Distributed query-processing systems [39, 49] use source descriptions to decide which source can answer parts of a given query and delegate parts of the initial query to the appropriate source. In a similar vein, reasoning systems that employ so-called backward- chaining used in, e. Deciding on which architecture to select for applications depends on the requirements of the use case. The warehousing model provides fast query—response times due to the large amount of preprocessing involved, but suffers a number of drawbacks.

First, the aggregated data are never fresh as the process of collecting and indexing vast amounts of data is time consuming. Second, from the viewpoint of a single requester with a particular query, there is a large amount of unnecessary data gathering, processing, and storage involved since a large portion of the data might not be used for answering that particular query.

Furthermore, due to the replicated data storage, the data providers have to give up their sole sovereignty on their data e. On-demand query processing offers several advantages: the system is more dynamic with up-to-date data and new sources can be added easily without time lag for indexing and integrating the data, and the system requires less storage and processing resources at the query-issuing site.

The drawback, however, is that such systems cannot give guarantees about query performance since the integration system relies on a large number of possibly unreliable sources, and that potentially the same work has to be done repeatedly.

The successful traditional client—server model has been adapted to the Web at a grand scale where clients can easily connect to and transfer data from a multitude of servers. Documents on servers are interlinked with each other in a decentralized manner, and clients use these links to navigate from server to server. The model has been condensed to the necessary function- ality, and loose coupling between one server and another is achieved by unilaterally linking from a document on one server to a document on another server.

Actually, whether the referenced document is located on the same server or a server on a different continent does not make a fundamental difference in the process of linking. Having the ability to reference things via URIs forms the basis for identity on the Web. Sources other than the authoritative source i. A URI starts with a scheme name e.

HTTP allows for mechanisms to specify additional parameters when requesting content. For example, clients can ask for content in certain formats to be returned from the Web server using the Accept header, which specifies the preference for certain formats.

Data publishers on the Semantic Web typically use linked data principles [6]: 1. Include links to other URIs, so that they can discover more things. Assuming that all the data publishers use these standards, data consumers can use those standards as clients to access the data and further process the data.

The so-called linked data cloud of Semantic Web data [21] has been growing considerably in the past years and provides a foundation upon which applications leveraging that data can be built. Wrappers a special case of mediators [80] allow for accessing legacy data as linked data. For example, D2R [10] provides a mechanism for exposing data stored in relational databases as linked data. This model decouples data providers from data consumers, allowing clients to use uniform interfaces for accessing and querying data stored on remote servers.

Graph-structured data models e. RDF is a data format based on directed labeled graphs, which contains data items consisting of subject, predicate, object triples. The RDF specification includes a special property rdf:type which is used to relate instances e. RDF is an abstract data format which can be written in multiple serializations. These libraries also contain repositories which allow for storing and retrieving RDF. The linked data principles cf. Now, consider a query asking for singers from ABBA that were also members of other music bands, as such a situation is not unusual among musicians.

Although a software program could navigate from the URI describing ABBA to each of its members, and later to all bands she or he was a member of, iteratively dereferencing individual URIs could be too time consuming for certain use cases. Furthermore, if some of the URIs do not point to real-world Web addresses, it is not even possible to find an answer for such a query.

The repository that supports SPARQL must implement the querying of the underlying data using a specific syntax and protocol. SPARQL allows a user to specify arbitrary URIs even those not accessible on the Web and a graph pattern that should be matched against the knowledge base together with additional constraints. ABBA foaf:name. Please note that the example query shall return only the names of musicians and bands, not the URIs describing them.

Here, users define the exact graph pattern that has to be matched against Semantic Web data. A basic graph pattern consists of individual subject, predicate, object patterns which are joined by variables, forming a template that will be filled during the matching process.

In the example, joining resources include the unknown band and members of ABBA. The example query filters the names of music bands other than ABBA. Some of the repositories do not only provide storage and query access for RDF graphs, but also support querying with use of inference and rules. It is the role of the underlying repository to support a corresponding inference model.

Using such bridges, legacy relational datasets can be exposed and queried as semantic graphs. Such wrappers are of high importance, as they enable smooth transition from the relational model to graph-based processing. The access protocols enable remote access to the data and free the data from closed data silos. It is possible to remotely query MusicBrainz for information about ABBA and later send a query to DBpedia for the biography of each of the band members.

Yet to do this, two separate queries have to be asked and the user is in charge of merging the results. New language constructs are proposed in SPARQL to handle the querying of multiple remote repositories, but the federated query feature is not defined yet in the standard. Some solutions to federated queries already have been proposed to address the need of querying multiple repositories. The foundations for querying distributed RDF reposito- ries were stated by Stuckenschmidt et al.

There, the authors proposed a mediation architecture, index structures, and algorithms for executing distributed path queries. The approach was further refined and extended in Networked Graphs [69]. Networked Graphs do not only allow for the querying of remote repositories in a unified manner and building dynamic views of the remote graphs, but also for joining them together and using recursive views defined as CONSTRUCT queries , and for applying rules.

The query accesses two graphs and presents joined results to the user. The implementation of Networked Graphs takes care of distributing proper parts of a query to specific remote SPARQL endpoints depending on a configuration and joining the final result. From the user perspective, it is executed as a single query extracting data from two named RDF graphs, hiding the complexity of accessing remote repositories and creating a combined result.

With mechanisms such as Named Graphs it is possible to hide the heterogeneity of data sources and schemas, restrict access to specific resources, or redefine types of relationships between entities. The construct can serve the same purpose as SQL views in relational databases.

As the view mechanism produces RDF graphs as result, it can be later used as a single data source for constructing another view. In addition to accessing data, the newly proposed version of SPARQL Update [71] introduces methods for data and graph manipulation in the form of inserts and deletes. Until now, all updates to data in the repository had to be performed using storage-specific tools. With the SPARQL Update standardization, changes to the semantic data in repositories no longer require use of third-party applications.

The second way for encoding meaning is by the use of logical constructs. To illustrate the use of reasoning, that is, drawing conclusions from existing facts in the Semantic Web, a selection of ontology constructs are explained based on our example, namely, rdfs:subClassOf, owl:sameAs, and property chains. The rdfs:subClassOf construct can be used to model class hierarchies. Such a construct allows a reasoner to deduce that instances of mo:MusicGroup are also of type mo:MusicArtist.

Another construct is that of owl:sameAs which can be used to specify that two resources are identical. Using owl:sameAs instead of reusing the same URI across sources allows for sources being connected after they coined the URIs for the respective thing. Property chains, which have been added to the recent OWL 2 specification, are useful to collapse property paths.

To find out which show played which songs, on the original BBC data one must have access to the timeline of the show, which requires traversing a path of four properties. OWL enables also more complex modeling constructs, for example, cardinality restric- tions a predicate can only have a certain number of objects or disjoint classes the set of instances of two classes are disjoint.

Specialized software systems, so-called reasoners, are able to take OWL knowledge bases and 1 check for the consistency of the knowledge base and 2 infer new statements based on existing ones. Another mechanism for drawing conclusions from existing knowledge are logical rules e. Rules consist of two parts, antecedent and consequent: if the statement in the antecedent is true, the statement in the consequent follows. RIF is the. W3C recommendation for exchanging rule sets between rule engines.

The common subset of a large number of rules systems is standardized in RIF Core [12] which forms the basis for more expressive languages, notably Prolog-style and Production Rule languages. In addition, technology has to be in place to ensure the authenticity of documents. Further, to establish the identity of users, authentication mechanisms are required. These issues are addressed in the architecture of the Semantic Web in the crypto layer.

To make sure data are not altered during transmission, HTTPS, a secure version of HTTP, has been developed [66] using a different server port compared to HTTP and an encryption protocol to counteract man-in-the-middle attacks and eavesdropping of connections on the level of the transport layer.

Digital signing of RDF graphs ensures the authenticity of content — that the content at hand has been created by a known source and that the content has not been altered. Signing RDF documents consists of a normalization step which returns a canonical representation of RDF triples which then are signed using standard digital signature methods [17].

For establishing the identity of a user when logging into a website or service, two similar mechanisms are currently in use. With OpenID [57], users are redirected from a service provider to an identity provider which authenticates the user and returns the credentials of the user to the service provider.

Identity is related to the social meaning of semantics and concerns the question of what identifiers mean and how to ensure the authenticity of an identifier i. The issue of identity is substantial in the context of the Semantic Web, given that the system is decentralized and people may mint own identifiers for resources, which leads to a plethora of identifiers for the same real-world entity. Reusing identifiers across sources allows for discovery and navigation in such a decentralized environment.

Indications for identity in the sense of object equality can be explicitly stated via reusing identifiers across sources, either directly or via connecting an own resource with an already existing one e. To be able to consolidate information from multiple sources, the identity of URIs has to be established. In the simplest case, when two sources attach RDF descriptions to the same URI, a syntactic check can be used to merge the data.

At data creation time, the data publishers have to be aware of the existence of a URI and what entity it refers to and therefore decide that they mean the same thing, reuse the URI, and thus subscribe to the meaning of the URI.

The data publishers can then attach new descriptions to the URI. For a given identifier, if it is known to the system, they provide a list of co-referant URIs. They make it possible to locate the same entity in different sources, although an entity may be referred to by multiple different URIs.

Data publishers can also relate their identifiers to already existing ones, which is in-line with linked data principles. Interlinking data and reusing concepts already modeled in. A case of relating own identifiers to already existing ones on the data description level is the Music Ontology stating that mo:MusicArtist is an rdfs:subClassOf foaf:Agent.

By that, the creators of the Music Ontology relate their concept of MusicArtist to the more general and established concept of foaf:Agent. Another way to establish the sameness of identifiers is via reasoning. For example, OWL allows for specifying so-called inverse functional properties which uniquely identify a thing, such as an ISBN for books or passport numbers for people. Reasoners can be used to establish the sameness of two URIs if they share the same value for a property which is defined as inverse functional.

While it is desirable to have associations between available data sources, disparate sources often lack links between them. To allow for the querying and processing data from these sources in an integrated manner, mappings between identifiers have to be found.

The Silk [78] linking framework allows for a declarative specification of how resources relate to each other and thus provides a semiautomatic way of matching identifiers across sources. Other approaches, such as [18], allow for automated instance matching based on defined similarity metrics. Work on ontology matching has mostly focused on aligning class- and property-level identifiers.

For example, [27] presents algorithms to align taxonomies with each other. For a comprehensive review of state-of-the-art methods for ontology matching, see [29]. The Ontology Alignment Evaluation Initiative [56] holds annual events to evaluate systems and publish matching accuracy of participating systems.

The graph-structured nature of RDF allows for the amalgamation of data from disparate sources. If the data sources do not share identifiers between each other, instance and ontology matching can provide the tight integration that more elaborate application scenarios require.

On the Semantic Web, not all data are created equal, and in order to judge the value of the data items and how to use data appropriately, one has to know the origin of data. Data provenance can be traced back in various ways. Along formal chains of information processing, such as queries, one may trace the data lineage as data provenance is called under these specific circumstances using a formal machinery [25, 32].

These models can provide explanation to questions, such as which pieces of data were chosen and composed together, where do they come from, who created them, or which inference rules were used to create implicit statements. Along chains of data processing, where the semantics of the processing are not fully specified, one needs more abstract models to trace data provenance.

Such meta-information is crucial for understand- ing what happened in the whole chain of data manipulation, which process produced certain results, or who initiated them and when. Based on provenance one may also attribute other properties, such as trust on data. There are multiple approaches to modeling trust and trust propagation.

In data lineage, trust is related to information such as data source, authorship, certainty, and other dimensions of meta-knowledge. Queries that combine data of different certainty or from multiple data sources need a specific algebra to calculate the overall trust of a result. Such a comprehensive algebra for querying and reasoning with different dimensions of meta-knowledge is described in [26].

Using the proposed algebra, certainty can be calculated for multiple joined statements and graphs, providing a trust value for larger structures. In peer-to-peer networks, peers must decide if a node is reliable or malicious. Trust is related to the reputation of the node, and modeling requires both a notion of trust and distrust. Trust to the specific node reputation reflects the experiences of all peers in the network interacting with the node and each peer gains a view of the network that is wider than its own experience [45].

In social networks, trust follows the friendship relationship. Users define their level of trust to the direct neighbors.

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