MitoPedia: Oroboros QM

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high-resolution terminology - matching measurements at high-resolution

MitoPedia: Oroboros QM

The MitoPedia terminology is developed continuously in the spirit of Gentle Science.

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Oroboros quality management


The Oroboros Quality Management (Oroboros QM) was initiated in the project K-Regio MitoFit to develop and implement standards in respirometric OXPHOS analysis. QM is required for a high-quality data repository based on a consistent and accessible terminology.


Examples of definitions that require improvement are listed below:
  1. Project
  2. Experiment
    1. Assay, Experimental assay
    2. Replica
    3. Repetitions
  3. Population (or group)
    1. Sample
    2. Subsample
    3. Sample type
    4. Sample size
    5. Dataset
  4. MitoFit protocols
    1. Harmonization protocols (Begley, Ioannidis 2015)
    2. Normalization protocols
    3. Subprotocols
    4. Laboratory protocols
    5. Solution protocols: media, substrates, uncouplers, inhibitors used in SUIT protocols, permeabilization agents, etc.
    6. Instrumental performance protocols
    7. Mitochondrial preparation protocols including biopsy sampling, tissue storage, cell preparation protocols, etc.
    8. Respirometric OXPHOS data acquisition and analysis protocols
  5. MitoFit registered project
    1. MitoFit pre-registered project
    2. Publicly deposited protocols (Begley, Ioannidis 2015)
    3. Prespecified protocols (Begley, Ioannidis 2015)
    4. Time-stamped protocols (Begley, Ioannidis 2015)
  6. Standardization
    1. Standard operating procedures
    2. Harmonization
  7. MitoFit proficiency test
    1. SUIT reference protocol
    2. Performance Estimation
Oroboros quality management

MitoPedia terms and definitions: Oroboros Quality Management

AccuracyThe accuracy of a method is the degree of agreement between an individual test result generated by the method and the true value.
Air calibrationR1Air calibration of an oxygen sensor (polarographic oxygen sensor) is performed routinely on any day before starting a respirometric experiment. The volume fraction of oxygen in dry air is constant. An aqueous solution in equilibrium with air has the same partial pressure as that in water vapour saturated air. The water vapour is a function of temperature only. The partial oxygen pressure in aqueous solution in equilibrium with air is, therefore, a function of total barometric pressure and temperature. Bubbling an aqueous solution with air generates deviations from barometric pressure within small gas bubbles and is, therefore, not recommended. To equilibrate an aqueous solution ata known partial pressure of oxygen [kPa], the aqueous solution is stirred rigorously in a chamber enclosing air at constant temperature. The concentration of oxygen, cO2 [碌M], is obtained at any partial pressure by multiplying the partial pressure by the oxygen solubility, SO2 [碌M/kPa]. SO2 is a function of temperature and composition of the salt solution, and is thus a function of the experimental medium. The solubility factor of the medium, FM, expresses the oxygen solubility relative to pure water at any experimental temperature. FM is 0.89 in serum (37 掳C) and 0.92 in MiR06 or MiR05 (30 掳C and 37 掳C).
AssayAn experimental assay is a method to obtain a measurement with a defined instrument on a sample or subsample. Multiple assay types may be applied on the same sample or subsample, if the measurement does not destroy it. For instance, the wet weight of a permeabilized muscle fibre preparation can be determined based on a specific laboratory protocol (gravimetric assay), maintaining the functional integrity of the sample, which then can be used in a respirometric assay, followed by a spectrophotometric assay for measurement of protein content. The experimental design determines which types of assays have to be applied for a complete experiment. Destructive assays, such as determination of protein content or dry weight, can be applied on a sample only after performing a respirometric assay, or on a separate subsample. The experimental variability is typically dominated by the assay with the lowest resolution or signal to noise ratio. The signal to noise ratio may be increased by increasing the number, n, of repetitions of measurements on subsamples. Evaluation of procedural variation ('experimental noise') due to instrumental resolution and handling requires subsampling from homogenous samples.
AttributeAttribute in general is a characteristic or property. In databases an attribute describes a column in a table. Rows then represent the according attribute values.
BiasThe bias is defined as the difference between the mean of the measurements and the reference value. In general, the measuring instrument calibration procedures should focus on establishing and correcting it.
Biological reference intervalBiological reference interval or reference interval is the central 95 % interval of the distribution of reference values.
CECECE marking is a mandatory conformity marking for certain products sold within the European Economic Area (EEA).
Cell count and normalization in HRRNceThe cell count Nce is the number of cells, expressed in the abstract unit [x] (1 Mx = 106 x). The elementary entity cell Uce [x] is the real unit, the 'single individual cell'. A cell count is the multitude or number N of cells, Nce = NUce (Gnaiger MitoFit Preprints 2020.4). Normalization of respiratory rate by cell count yields oxygen flow IO2 expressed in units [amol路s-1路x-1] (=10-18 mol路s-1路x-1).
DatLab oxygen flux: performance and data analysisThe quality of the results are strongly affected by the performance and data analysis. Therefore, we provide guidelines for performing and evaluating respirometric assays.
DatasetA dataset is a collection of data. In the context of databases a dataset represents the collection of entries in a database-table. In this table columns represent attributes and rows display the according values of the entries.
DetectorA detector is a device that converts the light falling upon it into a current or voltage that is proportional to the light intensity. The most common devices in current use for fluorometry and spectrophotometry are photodiodes and photodiode arrays.
DirectiveA directive is a legal act of the European Union, which requires member states to achieve a particular result without dictating the means of achieving that result.
Energy saving in researchEnergy saving in research must rank as a priority of social responsibility 鈥 ever since the Club of Rome published 50 years ago the seminal book on The limits to growth (1972) [1], and more so today in face of the global threat of climate change and the russian war in aggression against Ukraine.

Energy saving in research does not and must not clash with quality in research. Application of high-quality and predefined experimental protocols combined with evaluation of repeatability and reproducibility represents primary strategies for energy saving in research. Publication of irreproducible results 鈥 adding to the reproducibility crisis 鈥 is the most wasteful aspect of research in terms of resources including energy (more properly: exergy). Paywall journalism is wasteful in terms of financial resources. Dramatically increasing numbers of scientific publications is a pathway towards waste of energy [2].

Besides large-scale strategies on e(n)xergy saving in research 鈥 quality versus quantity 鈥, everybody's everyday contributions to energy saving count: to cut greenhouse gas emissions, save biological and geological diversity, and improve equality across societies, gender, continents, and countries.

Do scientists take responsibility for energy saving? Or does biomedical research merely find excuses? Scientific institutions in academia and industry must implement energy saving strategies to reduce waste according to the European Union's Energy efficiency directive, and to consume less energy (exergy) by using it more efficiently (Energy efficiency targets).

Possible 鈥 important but much neglected 鈥 contributions include:

  • Re-use materials as a superior strategy than recycling, and reduce application of disposable items.
  • Reduce waste in cleaning procedures, but do not compromise the quality of cleaning procedures.
  • Replace inefficient equipment (e.g. water baths) by efficient electronic Peltier temperature control.
  • Select conferences that you attend by evaluating their 'green deal' strategy. Combine in a single trip participation in a conference and possibly offered satellite events.
  • Turn off non-essential equipment; reduce energy-wasting stand-by modes; turn off computer screens and other equipment at the mains when not in use. The monitor consumes over half of the energy used by the average computer. Lower your screen brightness.
  • Turn off the lights when you do not gain from extra illumination, when you leave the lab during the day or at the end of every day.
  • Reduce heating of the rooms to 19 掳C, cooling of rooms to 25 掳C. Apply energy-efficient heating and cooling strategies.
  • Define your personal energy saving targets at homeoffice and in your workplace.
  • Contact your energy quality manager, to suggest improvement of infrastructure and guidelines that help you and other members in the team to comply with energy saving targets.
ExaminationAn examination' is a set of operations having the object of determining the value or characteristics of a property. In some disciplines (e.g. microbiology) an examination is the total activity of a number of tests, observations or measurements.
Exclusion criteriaThe Exclusion criteria include factors or characteristics that make the recruited population ineligible for the outcome parameter. With the Inclusion criteria, this factor must be a cofounder for the outcome parameter
ExperimentA number of replica, N, of experiments on one sample type is designed to obtain statistical information about the involved population(s) and to test hypotheses about a population and about differences between populations, when experiments are carried out on different sample types. An experiment may involve various assays, e.g., a respirometric assay and an assay for protein determination.
GroupSee population.
HarmonizationHarmonization is the process of minimizing redundant or conflicting standards which may have evolved independently. To obtain a common basis in reaching a defined objective, critical requirements are identified that need to be retained.
Harmonized European normEN-normHarmonized European norms are norms valid for all members of the European Union. They are mandatory parts of the individual national collections of norms.
Harmonized standardA harmonized standard is a European standard developed by a recognized European Standards Organisation: CEN, CENELEC, or ETSI.
ISO 10012:2003 Measurement management systemsISO 10012:2003ISO 10012:2003 Measurement management systems 鈥 Requirements for measurement processes and measuring equipment: An effective measurement management system ensures that measuring equipment and measurement processes are fit for their intended use and is important in achieving product quality objectives and managing the risk of incorrect measurement results. The objective of a measurement management system is to manage the risk that measuring equipment and measurement processes could produce incorrect results affecting the quality of an organization鈥檚 product. The methods used for the measurement management system range from basic equipment verification to the application of statistical techniques in the measurement process control.
ISO 13528:2015 Statistical methods for use in proficiency testing by interlaboratory comparisonISO 13528:2015ISO 13528:2015 Statistical methods for use in proficiency testing by interlaboratory comparison: Proficiency testing involves the use of interlaboratory comparisons to determine the performance of participants (which may be laboratories, inspection bodies, or individuals) for specific tests or measurements, and to monitor their continuing performance. There are a number of typical purposes of proficiency testing ISO/IEC 17043:2010. These include the evaluation of laboratory performance, the identification of problems in laboratories, establishing effectiveness and comparability of test or measurement methods, the provision of additional confidence to laboratory customers, validation of uncertainty claims, and the education of participating laboratories. The statistical design and analytical techniques applied must be appropriate for the stated purpose(s).
ISO 15189:2012 Medical laboratories 鈥 Particular requirements for quality and competenceISO 15189:2012ISO 15189:2012 Medical laboratories 鈥 Particular requirements for quality and competence: This International Standard is for use by medical laboratories in developing their quality management systems and assessing their own competence, and for use by accreditation bodies in confirming or recognising the competence of medical laboratories. While this International Standard is intended for use throughout the currently recognised disciplines of medical laboratory services, those working in other services and disciplines could also find it useful and appropriate.
ISO 17511:2003 In vitro diagnostic medical devicesISO 17511:2003ISO 17511:2003 In vitro diagnostic medical devices -- Measurement of quantities in biological samples -- Metrological traceability of values assigned to calibrators and control materials: For measurements of quantities in laboratory medicine, it is essential that the quantity is adequately defined and that the results reported to the physicians or other health care personel and patients are adequately accurate (true and precise) to allow correct medical interpretation and comparability over time and space.
ISO 9001:2015 Quality management systems - requirementsISO 9001:2015ISO 9001:2015 Quality management systems - requirements: The adoption of a quality management system is a strategic decision for an organization that can help to improve its overall performance and provide a sound basis for sustainable development initiatives. Consistently meeting requirements and addressing future needs and expectations poses a challenge for organizations in an increasingly dynamic and complex environment. To achieve this objective, the organization might find it necessary to adopt various forms of improvement in addition to correction and continual improvement, such as breakthrough change, innovation and re-organization.
ISO/IEC 17025:2005 Competence of testing and calibration laboratoriesISO/IEC 17025:2005ISO/IEC 17025:2005 General requirements for the competence of testing and calibration laboratories: The use of this International Standard will facilitate cooperation between laboratories and other bodies, and assist in the exchange of information and experience, and in the harmonization of standards and procedures. This International Standard specifies the general requirements for the competence to carry out tests and/or calibrations, including sampling. It covers testing and calibration performed using standard methods, non-standard methods, and laboratory-developed methods.
ISO/IEC 17043:2010 General requirements for proficiency testingISO/IEC 17043:2010ISO/IEC 17043:2010 Conformity assessment 鈥 General requirements for proficiency testing: The use of interlaboratory comparisons is increasing internationally. This International Standard provides a consistent basis to determine the competence of organizations that provide proficiency testing.
Improvement scoreRISThe relative improvement score, RIS, provides a measure of improvement of a trait from a value measured at baseline, B, to a value measured after treatment, T, expressing the total improvement, T-B, in relation to the theoretical scope of improvement and the level of the trait observed at baseline. RIS incorporates the concept of diminishing returns and consideres maintaining a high value of a trait as an improvement relative to the potential loss.
In vitro diagnostic medical deviceIVDA medical device is an in vitro diagnostic medical device (IVD) if it is a reagent, calibrator, control material, kit, specimen receptacle, software, instrument, apparatus, equipment or system, whether used alone or in combination with other diagnostic goods for in vitro use.
Inclusion criteriaThe Inclusion criteria are based on key features of the target population that the researchers will use to answer their question. These criteria should identify the study population in a consistent, reliable, uniform, and objective manner. With the Exclusion criteria, this factor must be a cofounder for the outcome parameter
Interlaboratory comparisonAn interlaboratory comparison is the organization, performance and evaluation of measurements or tests on the same or similar items by two or more laboratories in accordance with predetermined conditions.
LinearityLinearity is the ability of the method to produce test results that are proportional, either directly or by a well-defined mathematical transformation, to the concentration of the analyte in samples within a given range. This property is inherent in the Beer-Lambert law for absorbance alone, but deviations occur in scattering media. It is also a property of fluorescence, but a fluorophore may not exhibit linearity, particularly over a large range of concentrations.
Measurement processA measurement process or a measurement is a set of operations to determine the value of a quantity.
Measuring equipmentA measuring equipment is a measuring instrument, software, measurement standard, reference material or auxiliary apparatus, or a combination thereof, necessary to realize a measurement process.
Medical deviceA medical device is an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including a component part, or accessory which is (1) intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man or other animals, or (2) intended to affect the structure or any function of the body of man or other animals, and which does not achieve any of its primary intended purposes through chemical action within or on the body of man or other animals and which is not dependent upon being metabolized for the achievement of any of its primary intended purposes.
MetrologyMetrology is the science of measurement, including all aspects both theoretical and practical with reference to measurements, whatever their uncertainty, and in whatever fields of science or technology they occur [SOURCE: VIM:1993, 2.2].
MitoFit protocolsMitoFit protocols are moderated by the MitoFit moderators (MitoFit team), either as protocols with direct reference to publications available to the scientific communicty, or protocols additionally described and made available in Bioblast with full information on authors (including contact details), author contributions, and editor (moderator) in charge. This aims at a comprehensive MitoFit data repository, which will require global input and cooperation.
MitoFit registered projectMitoFit-RPMitoFit registered projects are announced with reference to MitoFit protocols as publicly deposited protocols. Project registration is a two-phase process. Guidelines will be defined. (1) Pre-registration of a project requires submission to a MitoFit moderator (editor), including protocol details with reference to MitoPedia protocols, or with submission of protocols for publication (Open Access) in MitoPedia. The MitoFit (Bioblast) editors will edit the submitted protocols (layout) and insert into Bioblast submitted pre-registrations and protocols. (2) MitoFit moderators (editors) will set up a MitoFit accreditation panel, in which the registrant will be included (perhaps not in the long run, to avoid conflict of interests) and/or for which the registrant can suggest delegates (compare peer review). Accredited MitoFit protocols are labelled as MitoFit accredited, and the pre-registered MitoFit project becomes labelled and listed as MitoFit registered project (MitoFit accredited). This is possible before (advance registration), during progress, and after completion of a study (post-registration). A MitoFit registered project receives a code for feeding data into the MitoFit data repository.
ModelA model regarding databases is the representation of a real world object in a computer understandable language. A model can be defined by the structure of its dataset and the relations to other models.
National Standards BodyA National Standards Body is the national member of the International Organization for Standardization (ISO).
NoiseIn fluorometry and spectrophotometry, noise can be attributed to the statistical nature of the photon emission from a light source and the inherent noise in the instrument鈥檚 electronics. The former causes problems in measurements involving samples of analytes with a low extinction coefficient and present only in low concentrations. The latter becomes problematic with high absorbance samples where the light intensity emerging from the sample is very small.
NormA norm is a rule that is enforced by members of a community.
Notified BodyA Notified Body is an organisation designated by an EU country to assess the conformity of certain products before being placed on the market.
OutlierAn outlier is a member of a set of values which is inconsistent with other members of that set. An outlier can arise by chance from the expected population, originate from a different population, or be the result of an incorrect recording or other blunder. Many schemes use the term outlier to designate a result that generates an action signal. This is not the intended use of the term. While outliers will usually generate action signals, it is possible to have action signals from results that are not outliers [SOURCE: ISO 5725鈥1:1994, modified].
Outlier-skewness indexOSI, OIAn outlier-skewness index OSI is defined for evaluation of the distribution of data sets with outliers including separate clusters or skewness in relation to a normal distribution with equivalence of the average and median. The OSI is derived from Pearson鈥檚 coefficient of skewness 2:
Pearson 2 coefficient = 3 路 (average-median)/SD

The outlier-skewness index OSI introduces the absolute value of the arithmetic mean, m = ABS(average + median)/2, for normalization:

OSI = (average-median)/(m + SD)
OSI = (average-median)/[ABS(average+median)/2 + SD]

At the limit of a zero value of m, the OSI equals the Pearson 2 coefficient (without the multiplication factor of 3). At high m with small standard deviation (SD), the OSI is effectively the difference between the average and the median normalized for m, (average-median)/m.

The outlier index in DatLab: Outlier index threshold
OverfittingOverfitting in statistics is the act of mistaking noise for a signal. Overfitting makes a model look 鈥樷檅etter鈥欌 on paper but perform 鈥樷檞orse鈥欌 in the real world. This may make it easier to get the model published in an academic journal or to sell to a client, crowding out more honest models from the marketplace. But if the model is fitting noise, it has the potential to hurt the science (quoted from Silver 2012 Penguin Press).
Oxygen flux - instrumental backgroundJO2Instrumental background oxygen flux, JO2, in a respirometer is due to oxygen consumption by the POS, and oxygen diffusion into or out of the aqueous medium in the O2k-chamber. It is a property of the instrumental system, measured in the range of experimental oxygen levels by a standardized instrumental O2 background test. The oxygen regime from air saturation towards zero oxygen is applied generally in experiments with isolated mitochondria, and living or permeabilized cells. To overcome oxygen diffusion limitation in permeabilized fibers and homogenates, an elevated oxygen regime is applied, requiring instrumental background test in the same range of elevated oxygen.
Oxygen sensor testPOS testThe O2 sensor test is an important component of Oroboros Quality Management. The OroboPOS test is described in detail in MiPNet06.03 POS-calibration-SOP, is performed after switching on the Oroboros O2k, and is required as a basis of technical service of the instrument.
Performance EstimationPerformance estimation
PopulationA population (or group) defines the sample type of an experiment, before sample preparation. The population (or group) size represents the upper limit of the sample size, N.
Post-examination proceduresPost-examination procedures, in the postanalytical phase, are processes following the examination including systematic review, formatting and interpretation, authorization for release, reporting and transmission of the results, and storage of samples of the examinations.
Pre-examination proceduresPre-examination procedures, in the preanalytical phase, are steps starting, in chronological order, from the clinician鈥檚 request and including the examination requisition, preparation of the patient, collection of the primary sample, and transportation to and within the laboratory, and ending when the analytical examination procedure begins.
PrecisionPrecision of measurement is the closeness of agreement between independent results of measurements obtained under stipulated conditions [SOURCE: ISO 3534-1:1993, 3.14]. Precision of measurement cannot be given a numerical value in terms of the measurand, only descriptions such as 'sufficient' or 'insufficient' for a stated purpose. The degree of precision is usually expressed numerically by the statistical measures of imprecision of measurements, such as standard deviation and coefficient of variation, that are inversely related to precision. "Precision" of a given measurement procedure is subdivided according to the specified precision conditions. "Repeatability" relates to essentially unchanged conditions and is often termed "withinserial" or "within-run precision". "Reproducibility" relates to changes in conditions, e.g. time, different laboratories, operators, and measuring systems (including different calibrations and reagent batches).
Primary sampleThe primary sample or specimen is a set of one or more parts initially taken from an object. In some countries, the term 鈥渟pecimen鈥 is used instead of primary sample (or a subsample of it), which is the sample prepared for sending to, or as received by, the laboratory and which is intended for examination.
Proficiency testPTProficiency testing PT is an evaluation of participant performance against pre-established criteria by means of interlaboratory comparisons. Some PT providers in the medical area use the term 鈥淓xternal Quality Assessment (EQA)鈥 for their proficiency testing schemes, or for their broader programmes, or both. Internal PT strategies may be implemented into laboratory science as practical steps towards PT to achieve reproducibility.
ProjectThe following definition lacks quality control and is not applied as such in the Oroboros QM.

A scientific project is a collection of experiments designed to proof or disproof a specific hypothesis. The experiments will follow the logic of the scientific discovery [1] on which a hypothesis will support a prediction and this will be tested by experimental assays (i.e., observations under controlled conditions). The result of these experiments will proof or disproof the specific hypothesis and, usually, provide new hypotheses to test. A scientific project must be carefully designed to obtain relevant statistical information through enough data collection.

[1] Popper K (2002) The logic of scientific discovery. Routledge Classics. ISBN: 978-0-415-27843-0
Publicly deposited protocolsPDPResearchers need to be introduced into adhering to publicly deposited protocols. Prespecified and time-stamped protocols that are publicly deposited may help to save Millions of Euros that may otherwise be wasted on research that is lacking coherent standards.
Quality auditA Quality Audit is the process of systematic examination of a quality system carried out by an internal or external quality auditor or an audit team.
Quantities, symbols, and unitsIn the context of quantities, symbols, and units, a code is required to convert terms defining physicochemical quantities into symbols (encoding) and to decode symbols as used in equations, text, and figures. Then symbols and abbreviations gain meaning. Simple symbols 鈥 such as Q or N 鈥 are used with different meanings depending on context (think of Q for heat and Q for electric charge; or N for number of cells and N for number of O2 molecules). The context provides the code. When the context is extended, the symbols have to be expanded too, including more detail to avoid confusion (Qth versus Qel; Nce versus NO2). Then symbols may appear too complicated, loosing the function of sending their message quickly. There is no single best way to design the right symbol or to replace meaningful symbols (Qel) by ambiguous abbreviations (Q) 鈥 all depends on context. We need to use the adequate medium (words, symbols, and abbreviations; equations, text, and figures; videos and slide presentations) and provide the code to achieve communication. The medium is the message, the message is the meaning 鈥 from Marshall McLuhan to Hofstadter.
QuantityQA quantity is the attribute of a phenomenon, body or substance that may be distinguished qualitatively and determined quantitatively. A dimensional quantity is a number (variable, parameter, or constant) connected to its dimension, which is different from 1. {Quote} The value of a quantity is generally expressed as the product of a number and a unit. The unit is simply a particular example of the quantity concerned which is used as a reference, and the number is the ratio of the value of the quantity to the unit. {end of Quote: Bureau International des Poids et Mesures 2019 The International System of Units (SI), p. 127)}.
Raw signal of the oxygen sensorRThe raw signal of the polarographic oxygen sensor is the current Iel [碌A], 1 碌A = 10-6 C路s-1, (DatLab 8) or the electric potential difference (voltage) [V], 1 V = 1 J路C-1, obtained after a current-to-voltage conversion in the O2k (DatLab 7 and previous versions).
Reference materialRMReference material (RM) is material or substance one or more of whose property values are sufficiently homogeneous and well established to be used for the calibration of an apparatus, the assessment of a measurement procedure, or for assigning values to materials (adapted from VIM: 1993, 6.13). The adjective 'homogeneous' refers to the physical homogeneity between macroscopic parts of the material, not to any microheterogeneity between molecules of the analyte.Primary reference material is reference material having the highest metrological qualities and whose value is determined by means of a primary reference measurement procedure. The concept "primary calibrator" is subordinate to "calibrator" (see 3.7) and to "primary reference material".
ReliabilityReliability relates the magnitude of the measurement error in observed measurements (i.e., precision or intermediate precision) to the inherent variability in the 鈥榚rror-free鈥, 鈥榯rue鈥, or underlying level of the quantity between subjects. The value of the reliability takes a value between 0 and 1. When the variability value is zero, indicates that all the variability in the measurements is due to measurement error. And, on the contrary, when the value is 1 indicates that there is a zero error in the measurement error. It is also known as the intraclass correlation, as it equals the correlation between any two measurements made on the same subject.
RepetitionsnRepetitions of an experiment or assay are designed to obtain statistical information on the methodological precision of the measurements. A number of repetitions, n, of measurements are performed on the same sample, applying an identical experimental protocol to subsamples, without providing any information on variability between samples.
ReplicaNReplica are designed in scientific studies to evaluate the effect of uncontrolled variability on a result obtained from an experiment on a single sample, to describe the variability and distribution of experimental results, and to obtain statistical information such as the median or average for a defined sample size. It may be useful to make a terminological distinction between replica of experiments, N, designed to obtain statistical information on the population, and repetitions of experiments or assays, n, designed to obtain statistical information on the methodological precision of the measurements. The terms study, experiment and assay have to be defined carefully in this context.
Reproducibility crisisThe reproducibility crisis is alarming.1 An experiment or study is reproducible or replicable when subsequent experiments confirm the results. This is re-search. However, we can define different types of reproducibility depending on the conditions that we use to replicate the previous work or in the information available. Our aim is to focus mostly on two different kinds2: 1. Direct: is when we obtaining the same results using the same experimental conditions, materials, and methods as described in the original experiment. This would be the ideal reproducibility of an experiment. However, it requires a very accurate description of how the original experiment was performed. Some journals are trying to resolve the reproducibility crisis improving the rigor and the excellence on the reported methods and results (e.g. STAR Methods in Cell Press). 2. Systematical: refers to obtaining the same results, but under different conditions; for example, using another cell line or mouse strain or humman study, or inhibiting a gene pharmacologically instead of genetically. This opens the door to subsequent studies to find the conditions under which an initial finding holds.
RequirementA requirement is a singular documented physical or functional need that a particular design, product or process must be able to perform.
ResearchResearch is a term composed of search and re. What does this tell us? The best comparison of the English with a German word is Untersuchung, composed of suchung (search) and unter (below). The term search (suchen) is straightforward to understand and comparable in both languages. The prefix re and unter are more difficult to reconcile, yet in both languages these perfixes reveal complementary if not nearly identical messages. re means {Quote} back to the original place; again, anew, once more {end of Quote} [1], whereas unter means below or underneath. Re-search, therefore, is not simply the search or investigation of some topic or problem, it means essentially doing the search again and again (re -> re-producibility) and penetrating below a simple search by reaching out for an underlying level of the search. The re in re-search and re-producibility has to be extended ultimately from a single re-search group to inter-laboratory re-investigation. This tells us, therefore, that while search is valuable, re-search provides the necessary validation. This re-evaluation of confirmative re-search should be re-cognized as the most important strategy to address the reproducibility crisis.
ResolutionSpectral resolution is a measure of the ability of an instrument to differentiate between two adjacent wavelengths. Two wavelengths are normally considered to be resolved if the minimum detector output signal (trough) between the two peaks is lower than 80 % of the maximum. The resolution of a spectrofluorometer or spectrophotometer is dependent on its bandwidth.
Risk managementRisk management is the identification, assessment, and prioritization of risks.
SamplesA sample is one or more parts taken from an ensemble that is studied. A sample is either stored for later quantification or prepared and possibly separated into subsamples, which are enclosed in a system for qualitative or quantitative investigation. A pure sample S is a pure gas, pure liquid or pure solid of a defined elementary entity-type. A pure biological sample is a cell type, tissue, or organism without its solid, liquid or gaseous environment. Then the system used to investigate sample S contains only entities of entity-type S, and the volume VS [L] and mass mS [kg] of the pure (sub)sample S are identical to the volume V and mass m of the experimental system. A pure sample S may be mixed with other components to be investigated as a solution, mixture, or suspension, indicated by the symbol s in contrast to the pure sample S. A sample s is obtained in combination with other components, such that the volume Vs [L] and mass ms [kg] of the sample s are larger than the volume VS and mass mS of the pure sample S. For example, the number of cells Nce [Mx] can be counted in a sample s of a cell suspension, whereas the mass mce [mg] of cells requires a pure sample S of cells to be measured on a mass-balance. Clarity of statistical representation is improved, if the symbol N is used for the number of primary samples taken from a study group, and the symbol n is used for the number of subsamples studied as technical repeats.
Sample sizeSample size is an ambiguous term. (1) Size can be measured as an extensive quantity in terms of mass mS [kg], volume VS [m3], or energy ES [J] of a pure sample S. If the sample consists of countable entities X, the count NX [x] in sample S is an elementary quantity, in contrast to the extensive quantities used as indicators of sample size. (2) In statistics, however, the term 'sample size' does not refer to the individual sample, but indicates on the contrary the number of samples investigated or sampled from a study group. N is the number of samples collected and assayed to obtain representative statistical information on the population. The population size defines the upper limit of the statistical sample size.
Sample typeAn experimental sample type is the object of an experiment. A sample type is defined by the specifications of the population and by a specific sample preparation (see MitoPedia: Sample preparations).
SelectivitySelectivity is the ability of a sensor or method to quantify accurately and specifically the analyte or analytes in the presence of other compounds.
SensitivitySensitivity refers to the response obtained for a given amount of analyte and is often denoted by two factors: the limit of detection and the limit of quantification.
SmoothingVarious methods of smoothing can be applied to improve the signal-to-noise ratio. For instance, data points recorded over time [s] or over a range of wavelengths [nm] can be smoothed by averaging n data points per interval. Then the average of the n points per smoothing interval can be taken for each successively recorded data point across the time range or range of the spectrum to give a n-point moving average smoothing. This method decreases the noise of the signal, but clearly reduces the time or wavelength resolution. More advanced methods of smoothing are applied to retain a higher time resolution or wavelength resolution.
Solution protocolsThe following definition lacks quality control and is not applied as such in the Oroboros QM. Solution protocols contain media, substrates, uncouplers, inhibitors used in SUIT protocols, permeabilization agents, etc.
StabilityStability determines the accuracy of intensity and absorbance measurements as a function of time. Instability (see drift introduces systematic errors in the accuracy of fluorescence and absorbance measurements.
Stand alone applicationA Stand alone application is computer software that can work offline, i.e. does not necessarily require network connection to function or does not even provide the possibility to connect to a network.
StandardA standard is an established norm or requirement in regard to a defined system. It can consist of a formal document that establishes uniform criteria, methods, processes and practices.See also Harmonized standard.
Standard operating proceduresSOPThe following definition is incomplete. Standard operating procedures are a set of step-by-step instructions to achieve a predictable, standardized, desired result often within the context of a longer overall process.
Steady stateA system is in a steady state if the state variables of a dynamic system do not change over time due to exchange processes with the environment, which compensate for internal dissipative transformations 鈥 such as chemical reactions or diffusion 鈥 and thus prevent any changes of the system and externalize dissipative changes to the environment. The dynamic nature of the steady state differentiates it from the thermodynamic equilibrium state. {Quote} Steady states can be obtained only in open systems, in which changes by internal transformations, e.g., O2 consumption, are instantaneously compensated for by external fluxes across the system boundary, e.g., O2 supply, thus preventing a change of O2 concentration in the system (Gnaiger 1993). Mitochondrial respiratory states monitored in closed systems satisfy the criteria of pseudo-steady states for limited periods of time, when changes in the system (concentrations of O2, fuel substrates, ADP, Pi, H+) do not exert significant effects on metabolic fluxes (respiration, phosphorylation). Such pseudo-steady states require respiratory media with sufficient buffering capacity and substrates maintained at kinetically-saturating concentrations, and thus depend on the kinetics of the processes under investigation. {end of Quote: BEC 2020.1}. Whereas fluxes may change at a steady state over time, concentrations are maintained constant. The 'respiratory steady state' (Chance and Williams 1955) is characterized by constant fluxes (O2 flux, H2O2 flux) and measured variables of state (cytochrome redox states, Q redox state, NADH redox state, mitochondrial membrane potential). High-resolution respirometry allows for the measurement of several parameters (e.g. O2 flux, H2O2 flux, mitochondrial membrane potential) at pseudo-steady states, when changes of concentrations in the closed system do not exert any control on fluxes. Combination with the Titration-Injection microPump (TIP2k) allows operation with programmable titration regimes at steady-state ADP concentration (Gnaiger 2001), oxygen concentration (oxystat mode; Gnaiger et al 2000, Harrison et al 2015) or steady-state pH (pH-stat more), yielding an expanded flexibility in experimental design by combining the technical advantages of closed and open systems approaches.
SubsamplenSubsamples can be obtained (1) from a homogenous sample (e.g. cell suspension, tissue homogenate, isolated mitochondria), (2) as subsamples obtained by splitting a sample into comparable parts (e.g. permeabilized muscle fibres from a biopsy split into different chambers for repeated measurements), or (3) repetitive sampling (e.g. taking multiple biopsies) at a single time point. Subsamples may be used for (i) application of different types of assay (e.g. for measurement of respiration and enzyme activities), and (ii) a number of repetitions, n, of the same assay on the same sample.
Time resolutionTime resolution in respirometric measurements is influenced by three parameters: the response time of the POS, the data sampling interval and the number of points used for flux calculation.
TraceabilityTraceability is the property of the result of a measurement or the value of a standard whereby it can be related to stated references, usually national or international standards, through an unbroken chain of comparisons all having stated uncertainties [SOURCE: VIM:1993, definition 6.10].
TruenessTrueness is understood as the lack of bias and the instrument calibration procedures are the key factor on establishing and correcting it.
Trueness of measurementTrueness of measurement is the closeness of agreement between the average value obtained from a large series of results of measurements and a true value (adapted from ISO 3534-1:1993, definition 3.12). The degree of trueness is usually expressed numerically by the statistical measure bias that is inversely related to trueness and is the difference between the expectation of the results of measurement and a true value of the measurand.
Uncertainty of measurementUncertainty of measurement is a parameter, associated with the result of a measurement, that characterizes the dispersion of the values that could reasonably be attributed to the measurand. The parameter can be, for example, a standard deviation (or a given multiple of it), or the half-width of an interval having a stated level of confidence. The components of uncertainty are evaluated experimentally from statistical distributions (Type A) or evaluated from assumed probability distributions based on experience or other information (Type B). All components are expressed as standard uncertainties that are combined into one final expression.
Uncoupler titrationsIn uncoupler titrations various uncouplers, such as CCCP, FCCP or DNP are applied to uncouple mitochondrial electron transfer from phosphorylation (ATP synthase, ANT and phosphate carrier), particularly with the aim to measure ET capacity. ET capacity is maximum oxygen flux measured as noncoupled respiration with optimum uncoupler concentration.
Web applicationA Web application is a computer software where the user interface gets accessed by the user through a web browser.
Working measurement standardA working measurement standard is a standard that is used routinely to calibrate or check material measures, measuring instruments or reference materials [SOURCE: VIM:1993, 6.7].
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